September 2014 by McMahon Group

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Case of Large-Scale Opioid Diversion Puts Hospitals on Alert Director Charged as Drug Kingpin

he recent arrest of a former New York hospital pharmacy director for pilfering nearly 200,000 oxycodone pills underscores the need for facilities to shore up their operations, making sure there are safeguards in place so that no one employee has enough power to divert controlled substances and other indemand medications, according to pharmacists skilled in preventing the criminal activity. On July 8, Anthony D’Alessandro, former director of pharmacy services for Beth Israel Medical Center, in New York City, was arrested and indicted for stealing

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Peri-Op Protocols Enhancing Recovery After Colorectal Surgery

he goal of any perioperative protocol is to improve patient outcomes after surgery. In colorectal surgery, however, there is minimal evidence to support traditional perioperative practices, such as bowel preparation and fasting before surgery. In the mid-1990s, this gap in understanding prompted a group of surgeons, led by Henrik Kehlet, MD, PhD, from Copenhagen, to begin implementing early recovery efforts. Following Dr. Kehlet’s work, a multinational group of surgeons and anesthesiologists began collaborating as the Enhanced Recovery After Surgery (ERAS) research group. The aim of ERAS is to systematically study patients’ physiologic responses to surgery and develop a multifaceted, evidence-based approach to patient care in colorectal

see Kingpin page 20

see ERAS page 30

Med Board Uses Humor—Lamely, Critics Say—To Pitch Certification Maintenance

hile controversy and serious debate continue to surround the issue of enhanced requirements for maintenance of certification (MOC), the American Board of Pediatrics (ABP) attempted a bit of summertime humor byy emailing animated cartoons to its diplomatees as reminders to complete their MOC requuirements by year’s end. But some pediatriciaans— including those who say the ABP had threeatened them with legal action over their anti-MOC organizing efforts—found the “Nick Jr.”–style cartoons to be,

for iPad pages 4 and 14

well, juvenile and offensive. w “The cartoons appear to be designed for my youngest patients rather than their pediatrician,” said Joseph Zanga, MD, chief of pediatrics, Columbus Regional Healthcare System, in Columbus, Ga., and a former president of the American Academy of Pediatrics. “It makes me angry that they’d sppend our money on demeaning junk such as [this].” see Humor page 16

PAIN MEDICINE

The race of a patient affects pain management in surprising ways.

POLICY & MANAGEMENT

Understanding, mitigating and preventing drug shortages.

COMMENTARY

When Prosecution Replaces Prescription

CLINICAL ANESTHESIOLOGY

A vasoconstrictor may counteract anesthesiainduced hypotension.

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SEPTEMBER 2014

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FDA Approves Ryanodex, New MH Drug

Alternative to A-Line? Device Offers Noninvasive View of Pulse Pressure Variation

For Anesthesiologists, Bigger Group Practices Don’t (Necessarily) Mean Higher Pay

The $3.5 Million Anesthesiologist

VTE May Be Misleading Quality Measure

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Anesthesia_Guy @Anesthesia_Guy There is more than one type of cognitive change after GA, they don’t all start immediately, and some are long lasting http://www.eurekalert.org/pub_ releases/2014-08/ehs-apn081514.php AMA @AmerMedicalAssn @JAMAInternalMed studies chronic pain, #opioid use in US soldiers after deployment. http://goo.gl/f7lypy

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Is IV Ibuprofen the Missing Piece to Your Surgical Pain Management Puzzle?

BRIEF SUMMARY OF PRESCRIBING INFORMATION CALDOLOR ® (ibuprofen) Injection WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS Cardiovascular Risk • Non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk [see Warnings and Precautions (5.1)]. • Caldolor is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4.3) and Warnings and Precautions (5.1)]. Gastrointestinal Risk • NSAIDs increase the risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events [see Warnings and Precautions (5.2)]. 1 INDICATIONS AND USAGE: 1.1 Analgesia (Pain): Caldolor is indicated in adults for the management of mild to moderate pain and the management of moderate to severe pain as an adjunct to opioid analgesics. 1.2 Antipyretic (Fever): Caldolor is indicated for the reduction of fever in adults. 4 CONTRAINDICATIONS 4.1 HYPERSENSITIVITY: Caldolor is contraindicated in patients with known hypersensitivity (e.g., anaphylactoid reactions and serious skin reactions) to ibuprofen [see Warnings and Precautions (5.7, 5.8)]. 4.2 ASTHMA AND ALLERGIC REACTIONS: Caldolor is contraindicated in patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal anaphylactic-like reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.7, 5.12)]. 4.3 CORONARY ARTERY BYPASS GRAFT (CABG): Caldolor is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1)]. 5 WARNINGS AND PRECAUTIONS: 5.1 Cardiovascular Thrombotic Events: Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke [see Contraindications (4.3)]. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious gastrointestinal (GI) events [see Warnings and Precautions (5.2)]. 5.2 Gastrointestinal Effects: Risk of Ulceration, Bleeding, and Perforation: NSAIDs, including ibuprofen, can cause serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately

1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. These trends continue ysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the and symptoms of serious skin manifestations, and to discontinue Caldolor at the first appearance of skin rash course of therapy. However, even short-term therapy is not without risk. Prescribe NSAIDs, including Caldolor, or any other sign of hypersensitivity. 5.9 Pregnancy: Starting at 30 weeks gestation, Caldolor, and other NSAIDs, with extreme caution in those with a prior history of ulcer disease or GI bleeding. Patients with a prior history should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur [see of peptic ulcer disease and/or GI bleeding who use NSAIDs have a greater than 10-fold increased risk for devel- Use in Specific Populations (8.1)]. 5.10 Masking Inflammation and Fever: The pharmacological activity of oping a GI bleed compared to treated patients with neither of these risk factors. Other factors that increase the ibuprofen in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoag- complications of presumed noninfectious, painful conditions. 5.11 Hematological Effects: Caldolor must be ulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most diluted prior to use. Infusion of the drug product without dilution can cause hemolysis [see Dosage and reports of spontaneous fatal GI events are in elderly or debilitated patients, and therefore special care should be Administration (2.3)]. Anemia may occur in patients receiving NSAIDs, including ibuprofen. This may be due to taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with fluid retention, occult or gross GI blood loss, or an incompletely described effect on erythropoiesis. In patients an NSAID, use the lowest effective dose for the shortest possible duration. Patients and physicians should remain on long-term treatment with NSAIDs, including ibuprofen, check hemoglobin or hematocrit if they exhibit any alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate addi- signs or symptoms of anemia or blood loss. NSAIDs inhibit platelet aggregation and have been shown to protional evaluation and treatment if a serious GI event is suspected. This should include discontinuation of the long bleeding time in some patients. Unlike aspirin, their effects on platelet function are less severe quantitatively, NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve of shorter duration, and reversible. Carefully monitor patients who may be adversely affected by alterations in NSAIDs should be considered. 5.3 Hepatic Effects: Borderline elevations of one or more liver tests may occur platelet function, such as those with coagulation disorders or patients receiving anticoagulants. 5.12 Pre-existing in up to 15% of patients taking NSAIDs, including ibuprofen. These laboratory abnormalities may progress, may Asthma: Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirinremain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approxi- sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross-reactivity mately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clin- between aspirin and NSAIDs has been reported in such aspirin-sensitive patients, including bronchospasm, ical trials with NSAIDs. In addition, rare cases of severe hepatic reactions have been reported, including jaundice, Caldolor is contraindicated in patients with this form of aspirin sensitivity and should be used with caution in all fulminant hepatitis, liver necrosis and hepatic failure, some with fatal outcomes. A patient with symptoms and/or patients with pre-existing asthma. 5.13 Ophthalmological Effects: Blurred or diminished vision, scotomata, and signs suggesting liver dysfunction, or with abnormal liver test values, should be evaluated for evidence of the changes in color vision have been reported with oral ibuprofen. Discontinue ibuprofen if a patient develops such development of a more severe hepatic reaction while on therapy with ibuprofen. If clinical signs and symptoms con- complaints, and refer the patient for an ophthalmologic examination that includes central visual fields and color sistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), ibuprofen vision testing. 5.14 Aseptic Meningitis: Aseptic meningitis with fever and coma has been observed in patients should be discontinued. 5.4 Hypertension: NSAIDs, including ibuprofen, can lead to onset of new hyper- on oral ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythetension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of matosus and related connective tissue diseases, it has been reported in patients who do not have underlying CV events. Use NSAIDs, including ibuprofen, with caution in patients with hypertension. Monitor blood pressure chronic disease. If signs or symptoms of meningitis develop in a patient on ibuprofen, give consideration to closely during the initiation of NSAID treatment and throughout the course of therapy. Patients taking ACE whether or not the signs or symptoms are related to ibuprofen therapy. 5.15 Monitoring: Because serious GI tract inhibitors, thiazides, or loop diuretics may have impaired response to these therapies when taking NSAIDs. ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms 5.5 Congestive Heart Failure and Edema: Fluid retention and edema have been observed in some patients tak- of GI bleeding. Patients on long-term treatment with NSAIDs should have CBC and chemistry profiles checked ing NSAIDs. Use Caldolor with caution in patients with fluid retention or heart failure. 5.6 Renal Effects: Use cau- periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestation when initiating treatment with Caldolor in patients with considerable dehydration. Long-term administration tions occur (e.g., eosinophilia, rash), or abnormal liver tests persist or worsen, discontinue Caldolor. of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in 6 ADVERSE REACTIONS: The following serious adverse reactions are discussed elsewhere in the labeling: patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these • Cardiovascular thrombotic events [see Boxed Warning and Warnings and Precautions (5.1)] patients, administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and, sec- • Gastrointestinal effects [see Boxed Warning and Warnings and Precautions (5.2)] ondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this • Hepatic effects [see Warnings and Precautions (5.3)] reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics or ACE • Hypertension [see Warnings and Precautions (5.4)] inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment • Congestive heart failure and edema [see Warnings and Precautions (5.5)] state. No information is available from controlled clinical studies regarding the use of Caldolor in patients with • Renal effects [see Warnings and Precautions (5.6)] advanced renal disease. If Caldolor therapy must be initiated in patients with advanced renal disease, closely mon- • Anaphylactoid reactions [see Warnings and Precautions (5.7)] itor the patient’s renal function. 5.7 Anaphylactoid Reactions: As with other NSAIDs, anaphylactoid reactions • Serious skin reactions [see Warnings and Precautions (5.8)] may occur in patients without known prior exposure to ibuprofen. Caldolor is contraindicated in patients with The most common adverse reactions reported in clinical studies are nausea, flatulence, vomiting, and headache. the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or The most common reason for discontinuation due to adverse events in controlled trials of Caldolor is pruritus (<1%). without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs 6.1 Clinical Studies Experience: Because clinical trials are conducted under widely varying conditions, adverse [see Contraindications (4.2)]. 5.8 Serious Skin Reactions: NSAIDs, including ibuprofen, can cause serious skin reaction rates observed in the clinical trials of a drug cannot be compared directly to rates in the clinical trials of adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrol- another drug and may not reflect the rates observed in practice. During clinical development, 560 patients were

• Caldolor reduces surgical pain1,2,3 • Caldolor can be used prior to surgery1 • Caldolor reduces narcotic consumption1 • Caldolor offers an Anti-Inﬂammatory action3

> Caldolor offers New Price Assurance Program For more information, please contact Caldolor@CumberlandPharma.com

Caldolor is indicated in adults for the management of:3 • Mild to moderate pain • Moderate to severe pain as an adjunct to opioid analgesics • Reduction of fever • Caldolor must be diluted prior to use. Infusion of the drug product without dilution can cause hemolysis.3 • The most common adverse reactions are nausea, ﬂatulence, vomiting, headache, hemorrhage, and dizziness (>5%).3 1. Singla N, Rock A, Pavliv L. Pain Med. 2010; 11: 1284-93. 2. Data on ﬁle, Cumberland Pharmaceuticals Inc. Nashville, TN. 3. Prescribing Information for Caldolor, 2014. Cumberland Pharmaceuticals Inc. Nashville, TN.

See full Prescribing Information including Boxed Warning at www.Caldolor.com exposed to Caldolor, 438 in pain and 122 with fever. In the pain studies, Caldolor was started intra-operatively and administered at a dose of 400 mg or 800 mg every six hours for up to three days. In the fever studies, Caldolor was administered at doses of 100 mg, 200 mg, or 400 mg every four or six hours for up to 3 days. The most frequent type of adverse reaction occurring with oral ibuprofen is gastrointestinal. Pain Studies: The incidence rates of adverse reactions listed in the following table were derived from multi-center, controlled clinical studies in post-operative patients comparing Caldolor to placebo in patients also receiving morphine as needed for post-operative pain. Table 1: Post-operative Patients with Adverse Reactions Observed in ≥ 3% of Patients in any Caldolor Treatment Group in Pain Studies* Caldolor 400 mg 800 mg Placebo Event (N=134) (N=304) (N=287) Any Reaction 118 (88%) 260 (86%) 258 (90%) Nausea 77 (57%) 161 (53%) 179 (62%) Vomiting 30 (22%) 46 (15%) 50 (17%) Flatulence 10 (7%) 49 (16%) 44 (15%) Headache 12 (9%) 35 (12%) 31 (11%) Hemorrhage 13 (10%) 13 (4%) 16 (6%) Dizziness 8 (6%) 13 (4%) 5 (2%) Edema peripheral 1 (<1%) 9 (3%) 4 (1%) Urinary retention 7 (5%) 10 (3%) 10 (3%) Anemia 5 (4%) 7 (2%) 6 (2%) Decreased hemoglobin 4 (3%) 6 (2%) 3 (1%) Dyspepsia 6 (4%) 4 (1%) 2 (<1%) 4 (3%) 4 (1%) 4 (1%) Wound hemorrhage Abdominal discomfort 4 (3%) 2 (<1%) 0 Cough 4 (3%) 2 (<1%) 1 (<1%) Hypokalemia 5 (4%) 3 (<1%) 8 (3%) * All patients received concomitant morphine during these studies. Fever Studies: Fever studies were conducted in febrile hospitalized patients with malaria and febrile hospitalized patients with varying causes of fever. In hospitalized febrile patients with malaria, the adverse reactions observed in at least two Caldolor-treated patients included abdominal pain and nasal congestion. In hospitalized febrile patients (all causes), adverse reactions observed in more than two patients in any given treatment group are presented in the table below.

Table 2: Patients with Adverse Reactions Observed in ≥ 3% of Patients in any Caldolor Treatment Group in All-Cause Fever Study Caldolor 100 mg 200 mg 400 mg Placebo Event N=30 N=30 N=31 N=28 Any Reaction 27 (87%) 25 (83%) 23 (74%) 25 (89%) Anemia 5 (17%) 6 (20%) 11 (36%) 4 (14%) Eosinophilia 7 (23%) 7 (23%) 8 (26%) 7 (25%) Hypokalemia 4 (13%) 4 (13%) 6 (19%) 5 (18%) Hypoproteinemia 3 (10%) 0 4 (13%) 2 (7%) Neutropenia 2 (7%) 2 (7%) 4 (13%) 2 (7%) Blood urea increased 0 0 3 (10%) 0 Hypernatremia 2 (7%) 0 3 (10%) 0 Hypertension 0 0 3 (10%) 0 Hypoalbuminemi 3 (10%) 1 (3%) 3 (10%) 1 (4%) Hypotension 0 2 (7%) 3 (10%) 1 (4%) Diarrhea 3 (10%) 3 (10%) 2 (7%) 2 (7%) Pneumonia bacterial 3 (10%) 1 (3%) 2 (7%) 0 Blood LDH increased 3 (10%) 2 (7%) 1 (3%) 1 (4%) Thrombocythemia 3 (10%) 2 (7%) 1 (3%) 0 Bacteremia 4 (13%) 0 0 0 7 DRUG INTERACTIONS: 7.1 Aspirin: When ibuprofen is administered with aspirin, ibuprofen’s protein binding is reduced, although the clearance of free ibuprofen is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of Caldolor and aspirin is not generally recommended because of the potential for increased adverse effects. 7.2 Anticoagulants: The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that the users of both drugs together have a higher risk of serious GI bleeding than users of either drug alone [see Warnings and Precautions (5.2)]. 7.3 ACE Inhibitors: NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors. 7.4 Diuretics: Clinical studies and postmarketing observations have shown that ibuprofen can reduce the natriuretic effects of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, observe patients closely for signs of renal failure, as well as to assure diuretic efficacy [see Warnings and Precautions (5.6)]. 7.5 Lithium: NSAIDs have produced elevations of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance of lithium decreased by 20%. This effect has been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, observe patients carefully for signs of lithium toxicity. 7.6 Methotrexate: NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This indicates that NSAIDs may enhance the toxicity of methotrexate. Use caution when NSAIDs are administered concomitantly with methotrexate. 7.7 H-2 Antagonists: In studies of human volunteers, co-administration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations. 8 USE IN SPECIFIC POPULATIONS: 8.1 Pregnancy: Teratogenic effects - Pregnancy Category C prior to 30 weeks gestation; Category D starting at 30 weeks gestation. Starting at 30 weeks gestation, Caldolor, and other NSAIDs, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may

occur. Caldolor can cause fetal harm when administered to a pregnant woman starting at 30 weeks gestation. There are no adequate, well-controlled studies in pregnant women. Prior to 30 weeks gestation, Caldolor should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. 8.2 Labor and Delivery: The effects of Caldolor on labor and delivery in pregnant women are unknown. In rat studies, maternal exposure to NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, increased the incidence of dystocia and delayed parturition, and decreased pup survival. 8.3 Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Caldolor, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use: Safety and effectiveness of Caldolor for management of pain and reduction of fever has not been established in pediatric patients below the age of 17 years. 8.5 Geriatric Use: Clinical studies of Caldolor did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients are at increased risk for serious GI adverse events. 10 OVERDOSAGE: The following signs and symptoms have occurred in individuals following an overdose of oral ibuprofen: abdominal pain, nausea, vomiting, drowsiness, and dizziness. There are no specific measures to treat acute overdosage with Caldolor. There is no known antidote to ibuprofen. In case of an overdosage, discontinue Caldolor therapy and consider contacting a regional poison control center at 1-800-222-1222. Manufactured for: Cumberland Pharmaceuticals Inc., Nashville, TN 37203 US Patent Number 6,727,286

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8 I AnesthesiologyNews.com

SEPTEMBER 2014

COMMENTARY

Obamacare a Successful Failure By Samuel Metz, MD

s the Affordable Care Act a failure? For some of us, the answer is simple: If you voted for President Obama, it must be a success. If you voted against the president, it must be a failure. But if you think the legacy of Barack Obama is irrelevant to health care reform, the answer gets more complex. Will the Affordable Care Act (ACA) achieve anything at all? Maybe. More Americans will own health insurance policies, especially if they are young and employed. Government spending on health care will decrease, despite the added cost of new computer programs and 17 different state insurance exchanges. Also, the financial burden of Medicare patients who have excessively costly diseases will move from the payor (the U.S. government) to the providers (us). But these changes hardly qualify as reform. For patients, physicians and employers, none of these potential achievements has the slightest bearing on health care reform.

Patient Expectations What do patients want from reform? Simple: access, lower costs and better health outcomes. The ACA misses all three. Access?? According to the Congressional Budget Office (CBO), despite the new law, the ACA will leave 10 million to 30 million Americans under-insured, putting them at risk for bankruptcy or death if they get the wrong disease at the wrong time. Another 30 million will be left with no insurance at all. In other words, when their incomes end, so does their health care—and maybe their lives. And that’s if the ACA works perfectly. Lower costs?? Although the CBO anticipates a $100 billion annual decrease in government health care spending, it also predicts a net increase of $100 billion in total health care spending. That means patients and employers will pay $200 billion more annually than they pay now. And that’s if the ACA works perfectly. Improved outcomes?? The Massachusetts experience says no. Six years after implementing its version of the ACA ( Jonathan Gruber, the Massachusetts Institute of Technology economist who worked on both the Massachusetts program and the ACA, called them “the same [expletive deleted] bill”), 95% of state residents own insurance policies. Yet outcomes are unchanged, medical bankruptcies are 30% higher, and costs are increasing faster than anywhere else in the country. (This is not entirely true. Those Massachusetts residents newly covered by Medicaid expansion now enjoy better health and lower medical debt. The same can’t be said, however, for those with private insurance.) If you’re a patient, the ACA is a failure.

payment is not a slam dunk. It’s one thing to voluntarily perform charity care in Third World countries to prevent patients from dying of easily treatable diseases. But it’s a real tragedy to realize that without our charity work, many Americans similarly will die of easily treatable diseases. In no other industrialized country do the poor and sick get charity care—physicians caring for them get paid the same amount as the physicians would if they cared for the rich and the famous. Only in the United States do physicians go unreimbursed if they care for the wrong patients. Second, our payment should reflect the value of our services, not the value of the insurance policies of our patients. If we are paid more for patients with pearls than we are for those with tattoos, then financial motive favors care for the pearls. Lastly, physicians want easy billing and prompt payment. Most of us haven’t seen that for decades. The ACA makes no pretense of simplifying either.

‘Whether we voted for or against our current president, whether we register to vote as Republicans or Democrats, whether we are in private practice or academics, the ACA leaves our health care landscape in the same shape as before: a complete shambles.’ Physician-Employer Expectations What should health care reform provide to employers? First, employers want healthy employees. When office staff call in sick, it doesn’t matter if they are full-time or part-time—it’s lost productivity. Next, employers want out of the health benefit management business. Just to manage the complexities of employee benefits costs employers an extra 2% of payroll. Can we rid ourselves of this added cost of doing business? Employers want health care benefits removed from labor–management negotiations. To remain competitive, employers want costs for employee health care to be no more than what our competitors pay. Similarly, our employee benefits should be no worse than what our competitors offer. Lastly, employers want health care costs to be predictable and consistent. The ACA addresses none of these needs.

Health Care Basics Physician Expectations Whatever else the ACA may achieve, it completely What do physicians want from reform? fails to address the basic health care needs of patients, First, payment. Given the amount of pro bono physicians and employers. Whether we voted for or work that physicians provide, sometimes unwillingly, against our current president, whether we register to

vote as Republicans or Democrats, whether we are in private practice or academics, the ACA leaves our health care landscape in the same shape as before: a complete shambles. It’s disappointing that this massive opus strives so valiantly to make a difference, yet falls so short of achieving what we really need. Is the ACA a well-intended piece of legislation? Yes. Is it reform? Sadly, no. Maybe Congress will have better luck next time, if there is a next time. Let’s hope so. Dr. Metz is a private practice anesthesiologist who lives and works in Portland, Oregon. He can be reached at s@samuelmetz.com

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CORRESPONDENCE To the Edito or: n the storry, “Hypoxia After Surgery Much h More Common Than Previouslyy Believed—Study finds high rate of pprolonged bouts of desaturation on warrds” (Anesthesiology News, March 2014, page 1), Daniel Sessler, MD, who hellped conduct the study, described its reesults as “sobering.” As Dr. Sesssler noted, most health experts agree tthat long periods of oxygen desaturattion are not good for patients. Dr. SSessler also pointed out that physician ns need an early warning sign for respirratory distress, which is currently only possible through continuous electronicc monitoring.

‘Having lost our otherwise healthy loved ones—Amanda, John and Leah—to undetected respiratory depression, we know this all too well.’ We couldn’’t agree more with his description. A recent report from HealthGrades confirms the seriousness of these findin ngs. HealthGrades examined nearly 2288,000 life-threatening events that ooccurred among Medicare patients in U.S. hospitals from 2009 through 2011. According to the report, three ppatient safety indicators accounted for 66.7% of these adverse events: respirratory failure after surgery; deep bloood clots in the lungs or legs following surgery; and accidental punctures or llacerations during a procedure. Respirratory failure represented 60,632 (22%) of the 287,630 adverse events documeented in the report. Dr. Sesslerr stated that because hypoxia is so ccommon, he believes continuous pulse oximetry will become a standard of caare in the next five to 10 years. Howeveer, five to 10 years is too long to wait, aaccording to the Anesthesia Patient Safeety Foundation (APSF). Referring to a recently released video by the APSF, the group’s president, Robert Stoelting, MD, said there must be a “paradigm shift” in the way that we monitor receiving opioids: Continuous electronic monitoring of all patients receiving opioids with pulse oximetry for oxygenation and capnography for adequacy of ventilation, as recommended by the APSF, would be the “alert” that we need to intervene in a timely manner for better patient safety and outcomes.

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Although we fervently concur that continuous electronic monitoring needs to be R a national patientsafetyy standard, we sincerely hope this occurs far sooner than Dr. Sessler predicts. A Why? Because patients’ lives are literally at stake. We can’t afford to wait

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any longer. Having lost our otherwise healthy loved ones—Amanda, John and Leah—to undetected respiratory depression, we know this all too well. Sincerely,

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EDUCATION

Cindy and Brian Abbiehl, Founders, A Promise to Amanda Foundation;

Patricia LaChance, Wife of John Michael LaChance; Lenore Alexander, Founder and Executive Director, LeahsLegacy; Michael Wong, JD, Executive Director, Physician-Patient Alliance for Health & Safety (PPAHS) Editor’s note: Financial support for PPAHS has been received from AcelRx, CareFusion, Covidien and Masimo. Lenore Alexander has received support from Masimo.

10 I AnesthesiologyNews.com

SEPTEMBER 2014

PAIN MEDICINE

Race Matters as a Factor in Pain Management, but Why? important step toward improving patient care. “Previous research has found that providers treat black and white patients differently whenever they have chronic pain,” said Adam T. Hirsh, PhD, assistant professor of psychology at the Indianapolis institution. “We’re interested in exploring why that may be. Is it simply because the patients differ in their race? Or are

there other things at work here, too?” To help tease out these possible factors, Dr. Hirsh and his colleagues studied 110 resident physicians who made pain assessment and treatment decisions for 12 computer-simulated patients. In each vignette, a patient presented with acute pain. Patient race (white or black) and clinical ambiguity (low or high) were manipulated across

vignettes. The 110 participants also completed measures of implicit and explicit racial bias. “The explicit measure asks people point-blank how they feel toward European American and African American patients,” Dr. Hirsh said. “The implicit measure gets at the more subtle forms of racial bias, which seems to be more prominent in contemporary society and may have a stronger effect on clinical care. Few people will outwardly say they dislike black or white people. But when you give them the implicit association test, a majority of people in the U.S. actually show an implicit preference for white rather than black people.” As Dr. Hirsh reported in Tampa, Fla., at the 2014 annual scientific meeting of the American Pain Society (abstract 511), the sample demonstrated moderate to strong implicit bias favoring white patients over black patients, and indicated more explicit positive feelings toward whites than blacks. When analyzed separately, clinical ambiguity had a stronger influence on participants’ decisions than did patient race. However, when patient race and clinical ambiguity were examined together, an interesting picture emerged. Key:

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s if managing the broad spectrum of patient pain were not complex enough, results from an Indiana Universityy Purdue University Indianapolis study has found that patient race, provider bias and clinical ambiguity interact to influence providers’ assessment and treatment decisions. The researchers suggested that understanding these factors and their influence might be an

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Figures. Effect of race on physician pain rating and opioid prescribing. ED, emergency department; VAS, visual analog scale

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AnesthesiologyNews.com I 11

PAIN MEDICINE “We found an interesting interaction,” he explained. “Race mattered, but it mattered in a way that was tied to ambiguity. In the low back pain [highambiguity] conditions, black patients actually received higher pain intensity ratings and were more likely to be given an opioid, relative to whites. However, this effect reversed in the wrist fracture [low-ambiguity] situations, where white patients were given higher pain intensity ratings and more opioid medications than black patients. “So race mattered, but it mattered according to ambiguity.” Dr. Hirsh found it interesting that providers approached black patients the same way in both the wrist fracture and low back pain conditions. “So a different way of looking at this interaction is to say that providers gave black patients the same pain intensity ratings and opioid treatment regardless of their pain condition,” he explained, “whereas pain conditions seemed to influence providers’ treatment for white patients [Figures]. “Clearly the effect of race on treatment decisions is complicated,” he added. “It’s not always just black versus white. The context seems to matter, too; in our study, the clinical situation mattered. And that’s particularly important in pain management, because pain is not always a

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cut-and-dried situation.” Although these results do not shed clear light on what influences providers’ decisions, they represent an important step in informing efforts to reduce disparities and improve pain care, Dr. Hirsh said. “How do we solve this?” he asked. “First, we need to understand it better. More research allows for bettertailored solutions.” Salimah H. Meghani, PhD, associate professor of nursing at the University

of Pennsylvania, in Philadelphia, noted that 30 years of research has demonstrated that pain disparities are a very real phenomenon. “Dr. Hirsh’s study is important as it points to nuances in explaining these disparities, especially the critical role of ‘ambiguity’ in clinical decision making,” Dr. Meghani said. “The direction of some of the findings, however, is in contrast with our previous work.” Indeed, a meta-analysis conducted by Dr. Meghani and her

colleagues of analgesic treatment disparities in the United States (Pain Med 2012;13:150-174) found that black– white disparities were present for all types of pain, but were starkest for ambiguous pain types such as abdominal or low back pain. “The differences noted in Dr. Hirsh’s study may be related to the vignette nature of the study or that we don’t completely understand the relation between explicit and implicit bias,” Dr. Meghani see Race page 12

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SEPTEMBER 2014

PAIN MEDICINE

FDA Approves Buccal Buprenorphine Plus Naloxone Formulation for Treatment of Opioid Dependence

ioDelivery Sciences International, Inc. (BDSI) has received FDA approval of its New Drug Application for Bunavail (buprenorphine and naloxone) buccal film (CIII). Bunavail is indicated for the maintenance treatment of

opioid dependence as part of a complete treatment plan that includes counseling and psychosocial support. BDSI expects to launch Bunavail in the third quarter of 2014. Bunavail was designed using BDSI’s BioErodible MucoAdhesive (BEMA)

drug delivery technology. According to the company, the BEMA technology allows for the “efficient and convenient” delivery of buprenorphine. BDSI stated in a press release that Bunavail provides twice the bioavailability of buprenorphine of

other available buprenorphine/naloxone formulations. BDSI added that this may allow for lower doses, which could help reduce the potential for misuse and diversion, and potentially lessen the incidence of certain side effects. Bunavail is the first formulation of buprenorphine and naloxone for buccal administration. The ability of Bunavail to stick to the inside of the cheek allows patients to talk, swallow and go about normal daily activities while the medication is consistently absorbed. According to Gregory Sullivan, MD, principal investigator of the Phase III Bunavail safety study, and an addiction specialist and medical director of Parkway Medical Center in Birmingham, Ala., the Phase III study included 249 patients converted from Suboxone (Reckitt Benckiser; buprenorphine and naloxone) sublingual tablet or film to Bunavail. In this study, Bunavail demonstrated favorable safety and efficacy in the maintenance treatment of opioid dependence, as demonstrated by the high study retention rate and the low frequency of patients with positive urine tests for nonprescribed opioids over the 12-week period. —AN Staff

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explained. “However, the fact that white patients were given more highintensityy pain ratings and more opioid medications than black patients despite wrist fracture is consistent with our findings. This is concerning because treatment differences exist even when the cause of pain is readily verifiable.” Identifying the genesis of these types of disparities is wound tightly into social processes, she added. “Research remains scarce on successful models for health [care] provider sensitization and education to overcome these disparities.” —Michael Vlessides

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PAIN MEDICINE

Long-Term Opioid Rx Can Promote Good Patient Outcomes In Chronic Noncancer Pain—but Choose Patients Carefully

ong-term opioid treatment can produce positive outcomes in chronic noncancer pain when physicians prescribe it carefully to individuals who have low risks for addiction and overdose, according to the results of a systematic review. Andrea Furlan, MD, PhD, and her colleagues searched Medline, EMBASE, CINAHI, PsycINFO, Central and Business Source Premier for studies published since 2000 on function and quality of life (QOL) in patients taking long-term opioids for chronic noncancer pain. The studies included in the analysis involved chronic noncancer pain that lasted longer than three months, opioid use for longer than three months, and outcomes that included measures of function and QOL. Most of the studies excluded patients who had comorbidities and psychiatric diagnoses. The majority of the patients were monitored closely by health care professionals, and were on doses of opioids that were less than approximately 200 mg per day. The initial literature search by Dr. Furlan, a scientist at the Institute for Work & Health, and pain physician at University Health Network, Toronto, Canada, and her colleagues yielded 16,288 references. The studies focused on function and QOL, as well as outcomes of misuse, abuse, addiction, and falls and fractures. They then excluded all papers that lacked sufficient detail for a careful analysis. Ultimately, the researchers performed a meta-analysis of pre–post results on eight randomized controlled trials, eight open-label extension studies from randomized controlled trials and nine observational controlled studies. These 25 studies included 4,719 patients, 3,160 of whom (67%) completed the studies. The analysis focused on these latter patients. The investigators found that longterm opioid use resulted in significantly improved function, and physical and mental QOL. Mark Sullivan, MD, PhD, professor, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, said that although Dr. Furlan and her collaborators do “careful work,” he had queries about the study, which was presented at the Canadian Pain Society’s 2014 annual meeting (poster 56). “First, in pre–post studies without a

control group, estimates of efficacy are strongly related to who drops out. Since almost all patients who drop out are not doing well on the drug, the mean pre–post differences can grossly overstate efficacy. We are told 67% were completers. How did this 67% compare with those who did drop out?”

Dr. Sullivan noted in an email. He also pointed out that the populations in the studies included in the systematic review were not typical. Dr. Furlan said she and her team discussed at great length these points, and other potential critiques, while they were completing the systematic review.

She said that, for publication, the paper will include an uncertainty analysis that takes into account the worstcase scenario of a high dropout rate and the resulting underestimates of complications and overestimates of opioid effectiveness. Dr. Furlan also conceded see Opioid page 17

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PAIN MEDICINE

Small Study Examines Inflammatory Response To Combination of Acute Pain and Opioids

preliminary study has found that a larger immune response is triggered in patients who are given a dose of fentanyl while also being administered a standard experimental acute pain stimulus than in individuals receiving either fentanyl or the acute pain

stimulus alone. The investigators believe this may point to potentially salubrious effects of opioids beyond pain reduction. “How to interpret the results is the interesting part,” said lead investigator Peggy Compton, RN, PhD, after

presenting the study at the American Pain Society’s 2014 annual meeting, held in Tampa, Fla. “Do we want to say that opioids and pain together cause inflammation and so clinicians should stay away from giving opioids because it will only make things worse—or that

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by giving the two together functional, tissue-healingg inflammatory effects are enhanced, which is good? I prefer to interpret the data in the latter fashion.” Dr. Compton said this is one of only a handful of studies on the immune system effects of opioids. Some research has shown broad immunosuppressive effects of opioids (see e.g., J Pharmacol Exp Therr 2002;300:213-219), whereas other studies indicate that opioids can upregulate proinflammatory cytokine production (Clin Exp Immunol 2003;132:40-45). Dr. Compton and her co-investigators will attempt to reproduce the results in animal studies before deciding what further steps to take in the research. Lynn R. Webster, MD, immediate past president of the American Academy of Pain Medicine, who was not involved in the study, said further research is key to determining the true effects of the combination of opioids and pain. “Perhaps as [Dr. Compton] reported, there is an immediate synergistic immune response to acute pain and opioids, but we don’t know if that is a sustained effect over days or weeks,” said Dr. Webster, r who is also vice president of scientific affairs at PRA International, a contract research organization headquartered in Raleigh, N.C. “[In addition,] Dr. Compton used one pain model and only fentanyl. We don’t know if other pain models or other opioids produce the same effect.” Dr. Compton, associate dean for academic affairs and professor of nursing, Georgetown University School of Nursing & Health Studies, Washington, D.C., and her colleagues recruited 20 individuals from the University of California, Los Angeles community (age range, 21-40 years). The participants were free of pain and in overall good mental and physical health. All had refrained from caffeine and nicotine in the hour preceding the study sessions. The researchers gave each of the 11 women and nine men four randomly ordered sessions, each at least 48 hours apart: a single, 1 mcg/kg IV injection with fentanyl; a cold-pressorr test (CPT) involving immersion of the individual’s hand into an ice-water container; a simultaneous fentanyl injection and CPT; and a control session without fentanyl or a CPT. see Acute Pain page 17

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PAIN MEDICINE

Eye Color a Potential Cue to Pain Tolerance

hysicians often flag patients with red hair, given its understood role as a biomarker for resistance to anesthetics; now, new research suggests that eye color may indicate how individuals will respond to pain as well. According to the results of a recent study involving 58 pregnant, white women—24 with dark-colored eyes (brown or hazel) and 34 with lightcolored eyes (blue or green)—individuals with darker eyes showed increased anxiety (P=0.01), and trended toward increased sleep disturbance (P=0.19) and less improvement in catastrophizing/rumination (P=0.15) compared with their lighter-eyed counterparts. Those with darker eyes also showed trends toward experiencing more pain both at rest (P=0.28) and during movement (P=0.22) after receiving epidural analgesia. Inna Belfer, MD, PhD, associate professor in the Departments of Anesthesiology & Human Genetics and director of the Molecular Epidemiology of Pain Program at the University of Pittsburgh School of Medicine, presented the findings at the American Pain Society 33rd annual scientific meeting in Tampa, Fla. (poster 197). “Human pain is correlated with many factors such as gender, age and even hair color,” Dr. Belfer said. “If we can prove that eye color is another genetic biomarker, it would be great because that’s exactly what we are looking for. Biomarkers can be instantly recognized, aren’t invasive and can save time and money. We are constructing a pain genome and are figuring out how it can be used in the future, so basically the more we know the better it will make the treatment process.” To measure their response to pain, the women were assessed by using standard validated tools, including the Brief Pain Inventory, the Patient-Reported Outcomes Measurement Information System anxiety/depression/sleep scales, the Pain Catastrophizing Scale and Quantitative Sensory Testing. Dr. Belfer noted that although these distinctions in pain reduction indicate a trend, they are not clinically significant. The next step, she said, is to conduct a study with a large sample size that will encompass many patient populations. “I want to examine the eye colors individually because color is all about genes, and therefore a clear distinction between them is important,” she said. “We also want to look at the

relationship between eye color and pain in different races, in nonpregnant women and in men. Dentists are super cautious when they have patients with red hair, so there’s no reason why, if the correlation exists, that eye color can’t be another thing to look out for as well.” —Paul Bufano

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POLICY & MANAGEMENT HUMOR

CONTINUED FROM PAGE 1

“I’m glad the ABP has a sense of humor, but I was not amused by the videos,” said Victor Strasburger, MD, distinguished professor of pediatrics and chief of adolescent medicine, University of New Mexico School of Medicine, in Albuquerque. “They could be spending their time reviewing how MOC works—or doesn’t work—and make it much more palatable to the average pediatrician.” In late June, the ABP emailed links to three short musical cartoons to about 15,000 pediatricians who had MOC requirements to fulfill in 2014. “Summer’s here and we’re having some fun!” the ABP explained on its Facebook page. “We’ve created three MOC videos explaining requirements. The content in these videos may not pertain to every diplomate (so be sure to check your ABP Portfolio for YOUR specific requirement needs), but we hope you get a giggle to lighten your day.” The first animation featured “a friendly bluegrass farmer who can sure play that banjo!” The second video presented a classical motet entitled, “If ye loves being certified …” The third was a rap song, peculiarly titled, “Now this is the story ALL about how my points got flipped, turned upside down … ” Virginia A. Moyer, MD, MPH, vice president for maintenance of certification and quality at the ABP, said the idea was to remind physicians of the December deadline for completing their Part 4 MOC requirements, which involve quality improvements performance in practice. “I wanted to send a ‘Harry Potter’–style ‘howler’ but couldn’t figure out a way to do it,” Dr. Moyer explained, referring to the magical letter that screams its written message to the unfortunate recipient. “The videos were one way to get their attention,” she said. Paul M. Kempen, MD, PhD, an anesthesiologist at the Cleveland Clinic, in Ohio, and an outspoken critic of MOC, said the cartoons are evidence that “the [medical] boards have become so arrogant that they feel they can use any means to force this [MOC] down the throats of physicians.” Getting Into Trouble Over MOC In 2010, Dr. Zanga launched an Internet-based anti-MOC petition drive using his email account at Columbus Regional. “The communications director at ABP called expressing concern,” Dr. Zanga said in an interview. “She stated that the information in the petition was blatantly wrong, bordering on libelous. The hospital was not happy and told me to take it down,” he said. After moving the petition to another website, Dr. Zanga said he collected 2,000 signatures opposing ABP’s enhanced MOC requirements. Dr. Moyer said she had “no information” about the matter, but noted that ABP did not have a communications director in 2010. In the April 2010 issue of Clinical Pediatrics, Dr. Strasburger coauthored a commentary article with Donald E. Greydanus, MD, then at the Kalamazoo Center for Medical Studies, in Kalamazoo, Mich., critical of both ABP and MOC as it was then being developed. In the commentary, titled “Maintenance of Certification: The Elephant in the Room,”

The American Medical Association’s House of Delegates directed AMA to ‘oppose mandatory maintenance of certification as a condition of medical licensure....’

they proposed several less burdensome ways by which pediatricians could demonstrate that they were keeping up with developments in the field (Clin Pediatr 2010;49:307-309). “The ABP threatened to sue me personally and SAGE Publications [the journal publisher] for libel,” said Dr. Strasburger, r who was also a member of the journal’s editorial board. “They demanded a retraction. It took SAGE countless hours to review the complaint. Obviously, they were not happy.” The lawsuit never materialized, and in July 2011, Dr. Strasburger wrote another editorial, “Ain’t Misbehavin’: Is It Possible to Criticize Maintenance of Certification (MOC)?” This time, the editorial was endorsed by 10 members of Clinical Pediatrics’’ editorial board. “The ABP has tried to shut down any disagreement or even discussion about MOC,” Dr. Strasburger’s editorial said. “Several petitions to put a moratorium on the MOC process have generated >2000 signatures; yet the ABP has tried to shut down Web

sites and any discussion. Pediatricians initially train within an academic system that prides itself on questioning everything. MOC should be no exception” (Clin Pediatrr 2011;50:587-590). “I do know that the board [of directors] was very unhappy with the two editorials that Dr. Strasburger wrote,” Dr. Moyer said when asked to comment. “If there was any legal action, I know absolutely nothing about it,” she said. Formal legal action would have had to come before the board, which did not happen, she added. Dr. Moyer said she has “no access” to any informal communications that may have occurred with Dr. Strasburgerr at the time. “No one should feel threatened about speaking their mind about something,” she said. “We really want the same thing; we all want pediatricians to be keeping up and improving the quality of their care.” However, according to Dr. Strasburger, r “the threatened lawsuit shows that the ABP doesn’t have much of a sense of humor. It needs to look critically at the

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AnesthesiologyNews.com I 17

POLICY & MANAGEMENT product it’s producing, like all of the medical boards need to do, and see how to make it more user-friendly. y Making halff heartedd attempts at funny videos is not going in the right direction. Pediatricians are very upset about this but feel they are powerless,” he said. “What does a single practicing pediatrician do? They feel completely helpless.”

the American Board of Anesthesiology, approved new MOC standards that emphasize continuous learning and assessments. The new standards are to be adapted and implemented by each specialty board starting Jan. 1, 2015. Backlash in some specialties has been accelerating. For example, an ongoing petition drive protesting new MOC requirements by the American MOC Required for Licensure? Board of Internal Medicine (ABIM) In January, the American Board of had collected so many signatures that Medical Specialties (ABMS), com- in April, ABIM President Richard J. posed of 24 member boards including

OPIOID

CONTINUED FROM PAGE 13

“critical review” of the effect of MOC on physician practice and patient outcomes, and a resolution opposing mandatory participation in MOC as a condition for licensure. The delegates directed AMA to “oppose mandatory MOC as a condition of medical licensure, and encourage physicians to strive to constantly improve their care of patients by the means they find most effective.” —Ted Agres

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that the patients in the systematic review represented a minority of typical chronic pain patients, because they did not have risk factors and were monitored carefully. “It is true that most of these conditions are not followed in real-life opioid prescribing. [In clinical practice] I see a lot of careless prescribing, which can be characterized as ‘high-riskk patients’ or ‘high-riskk prescriptions.’ When you mix both, it is dangerous,” Dr. Furlan said in an interview. “But when physicians and their teams take the time to carefully screen patients, keep them on as low a dose as possible and monitor them very regularly, our results show that the outcomes can be very satisfactory.”

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Individuals who were given fentanyl with CPT had a longer time to finding the cold painful (pain threshold) or intolerable (pain tolerance) than those who were given the CPT alone (P=0.025 and P=0.002, respectively). Furthermore, they had higher intranuclear levels of activated nuclear factor-κB in peripheral blood mononuclear cells, monocytes and lymphocytes than those with the CPT alone, fentanyl alone or neither (all P<0.05). These effects were significant at both 15 and 30 minutes after the test conditions were imposed, although the effects were slightly attenuated at 30 minutes.

Baron, MD, issued a lengthy statement defending the organization’s efforts. As of July 2014, the petition had gathered 17,400 signatures. Alarmed over escalating MOC requirements, including the apparent melding of MOC with maintenance of licensure (MOL) requirements, the American Medical Association’s House of Delegates approved several resolutions in June. They included opposing mandatory MOC in favor of selff regulation, the establishment of a

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18 I AnesthesiologyNews.com

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Anesthesiologists Continue To Cope With Shortages of Needed Medications 300

Daniel S. Orlovich, PharmD Pharmacist Number of Prevented Drug Shortages

s you fumble through the anesthesia drug tray, you begin to sweat. You notice that some drugs are missing. You quickly move to open the Pyxis machine but those drugs are missing, too. You swing open the heavy door to the operating room next door. Before you can speak through your mask, your colleague frames the question as a bewildered statement: “Let me guess, where’s the succinylcholine?” Jerry A. Cohen, MD, past president of the American Society of Anesthesiologists (ASA), noted in 2012, “When I started practicing, I thought whatever drugs I needed would always be there. Now I open the drawer and occasionally something isn’t there.” In the past five years, according to the ASA, the United States has experienced shortages of an array of vital anesthetic drugs such as propofol, succinylcholine, even epinephrine. The FDA began tracking drug shortages in 1999 in anticipation of possible manufacturing interruptions that might be caused by the Y2K computer scare. During the first year of the Drug Shortage Program (DSP), the FDA recorded shortages in the supplies of 61 different drugs. At that time, the shortages were caused by disruptions in regional distribution and often could be resolved locally. Over time, however, the number of reported shortages has increased. By 2011, the DSP recorded shortages of 251 drugs, quadruple the number of drug shortages in 1999. And the drug shortages were no longer regional but national. Approximately 63% of shortages reported between January 2007 and June 2013 lasted an average of 340 days. In response to the significant increase in drug shortages, the FDA required, rather than suggested, that pharmaceutical companies report all potential discontinuances of drugs used in the prevention or treatment of serious or life-threateningg conditions. This included most anesthetic drugs.1 It appears the FDA’s actions have had some effect. Since implementation of mandatory reporting, the number of notifications to the FDA has risen sixfold. In response, the FDA has been able to prevent an increasing number of new national drug shortages (Figures 1 and 2). Even so, the number of active drug shortages has either remained steady since 2010 or has trended upward (Figure 3). In fact, 97.6% of anesthesiologists surveyed by the ASA in March 2012 reported experiencing a current shortage of at least one anesthetic drug. The anesthetic drugs most likely to be in short supply were fentanyl and neostigmine.

250

Injectables Total

250

200

150 150

100 100

2010

2011

2012

2007 2008 2009 2010 2011 2012 2013

Figure 1. Number of drug shortages prevented Figure 2. Number of new national drug by the FDA. shortages. Source: FDA Internal Drug and Biologics Shortages Databases

400

Number of Prevented Drug Shortages

Richard J. Kelly, MD, JD, MPH Anesthesiologist UC Irvine Medical Center Orange, California

300

Source: University of Utah Information Service

Average active drug shortages

350 300 250 200 150 100

Injection

Oral suspension solution Tablet/capsule

2010

2011

2012

Other

Figure 3. Average number of active drug shortages.

Figure 4. U.S. drug shortages by dosage form, July 3, 2014.

Source: University of Utah Drug Information Service

Source: FDA Drug Shortage Program

Generic injectable drugs are the most likely to be in short supply (Figure 4). These medications are 2.5 times more likely than brand-name injectable drugs to experience a shortage because approximately onethird of them are produced by only one or, at most, two manufacturers. In fact, only three manufacturers supply 71% of all generic injectable drugs.2-4 Because most injectable medications are used in the hospital and ambulatory care setting, it is not surprising that anesthesiology is among the specialties most affected by drug shortages. Propofol, for example, was the most frequently used anesthetic for outpatient surgeries in 2010, employed in nearly 70% of all procedures.5 Outside of the operating room, propofol is the most frequently used hypnotic in ICUs in the United States.6

All generic medications, not just generic injectable drugs, are more vulnerable to shortages than brandname medications, in part, because brand-name medications usually have backk up manufacturing lines that provide redundancy in the event that one of the manufacturing lines goes down.2 Generic medications, probably because of their low profit margins, often are made on a single manufacturing line that also is being used to produce other products.7 Several important reasons exist for drug shortages. The first and most common (40% of shortages) is the issue of quality. Production lines may be contaminated with bacteria or particulate matter that necessitates closure of the production line. For example, in 2010, shortly after one manufacturer permanently discontinued production of propofol, a second

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AnesthesiologyNews.com I 19

POLICY & MANAGEMENT manufacturer was affected by a quality problem that necessitated a temporary halt in production. The third and only remaining manufacturer of propofol simply was unable to meet the national demand for the drug.8 The second most common reason for drug shortages involves manufacturing delays caused by slowdowns and shutdowns for maintenance or remediation efforts (30%).4 Six of the top 10 manufacturers of sterile injectable drugs received warning letters from the FDA for serious violations of manufacturing standards between 2009 and 20129 which, in turn, required the manufacturers to address the concerns. The remediation efforts often require inspections, maintenance and equipment upgrades that either slow down or completely stop production of the drugs. For most of the generic injectable products, there is only one manufacturer that produces the majority of a particular drug in the marketplace.2 Moreover, generic drug manufacturers are operating their production lines at full production capacity,4,10 24 hours a day, using equipment that is at least 50 years old, and using their manufacturing lines to produce not just one but multiple drug products.10 Thus, it is not uncommon for the manufacture of one drug to be halted because a second drug on the same production line has documented quality issues. Only Getting Worse? Looking to the future, the drug shortage problem may get even worse. In a review of 900 generic sterile injectable applications submitted to the FDA and approved between 2000 and 2011, only 1% of the applicants had a backup facility.10 Also, between 2006 and 2010 the number of generic sterile injectable drugs being manufactured increased by 52% without a commensurate increase in manufacturing capacity.4 The majority of the older facilities in the United States that already operate at full capacity will be manufacturing an increasing number of different types of injectable drugs on their production lines without any provisions for backup production if production lines are slowed or stopped. Despite incremental steps that have been taken by the FDA, the agency does not have the authority to require a company to manufacture a drug, maintain certain levels of inventory or set drug prices. Manufacturers, therefore, do not have a strong financial incentive to upgrade their production facilities or aspire to exceed the minimum standards set forth by the FDA.2 In fact, the most common action taken by the FDA in 2011 was to ask other manufacturers to increase production. Those manufacturers already running at maximum capacity and those who did not have the necessary equipment to increase production could not act on the FDA’s request. Also, many manufacturers maintain a “just-in-time” inventory and therefore do not have a supply of their drugs on hand to respond to any drug shortages.11,12 Nationally, companies have about two to three months of inventory on hand; wholesale distributors have about one month of inventory; and providers such as hospitals only have a few weeks of inventory. Despite the availability of public information regarding the precariousness of the drug supply in the United States, hospitals and other buyers have not responded to this information by holding larger inventories of drugs.

Anesthesiologists and their patients often are the victims of these drug shortages. In a summary of critical drug shortages reported between June 2011 and June 2013, anesthetic and central nervous system drugs were shown to have the highest frequency of critical shortages.10 The detrimental effects of these drug shortages for anesthesiologists include increased patient morbidity (hypotension, apnea, aspiration, prolonged mechanical ventilation, nausea and vomiting), longer anesthesia or recovery time, postponement of surgical procedures and even death.8,13-16 Succinylcholine, the most commonly used neuromuscular blocking agent (NMBA) for managing the airway in emergency situations,17 often is in short supply. Although anesthesiologists are the paragon of adaptability, alternative NMBA such as rocuronium may nonetheless result in lifethreateningg challenges in certain clinical situations. The use of a different NMBA in the absence of succinylcholine can lead to inferior intubation conditions,18 prolonged neuromuscular blockade, and an increased risk for difficulty ventilating and intubating critically ill patients.19 The adverse consequences of drug shortages are substantial. In a Premier Health report that surveyed 311 hospitals over a sixx month period from July 2010 to December 2010, 89% of the hospitals reported drug shortages that caused a medication safety issue or error; 80% experienced a shortage that led to the delay or cancellation of care; and 98% reported a drug shortage that resulted in increased cost of care.2,20 Drug shortages also result in an increased number of “gray market” suppliers. These are suppliers who are not authorized by the manufacturer to sell the drug but, during a shortage, buy up the drug and resell it at inflated prices. Because these suppliers are not authorized by the manufacturer to buy or sell the drug, there is no assurance that the medications bought and sold in the gray market have been stored and transported properly. Although progress has been made for the prevention of new drug shortages and to decrease the number of shortages, the FDA has room for improvement. Currently, no civil or monetary penalties exist for industry noncompliance.2,9 Despite a goal to collect data with the aim of predicting drug shortages, the FDA also has no way to internally authenticate the data’s validity. The collected data, according to a report from the U.S. Government Accountability Office, often relies on memories of events, email records and meeting notes without any mechanism in place to scrutinize and verify the information.1 Instead of waiting on the FDA to deliver further actions, anesthesiology and pharmacy departments could work together to mitigate and prevent shortages. One simple way involves improved communication regarding potential drug shortages as well as current drug shortages. This approach could mean designating a committee or members to drug shortages specifically. Often, anesthesiologists are not aware of a drug shortage until informed by the pharmacy department. As part of this communication, both departments could regularly check websites dedicated to drug shortages such as that of the FDA21 or the American Society of Health-System Pharmacists.22

If an alternative product must be used, educational material from the pharmacy could be sent out to the anesthesiology department to provide information on proper dosing limits, side effects, pharmacokinetics and other salient points. The pharmacy department in particular uses publicly available information about a manufacturer’s historical ability to provide quality products and reward companies who are more dependable. Relying solely on price is shortsighted. With the above suggestions, perhaps you can help keep propofol, succinylcholine and epinephrine in your anesthesia trays. References 1. US Department of Health and Human Services. Strategic Plan for Preventing and Mitigating Drug Shortages. Silver Spring, MD: U.S. Department of Health and Human Services, FDA; 2013. 2. FDA. A review of FDA’s approach to medical product shortages. FDA Report. 2011;31. 3. IMS Institute for Healthcare Informatics. The Use of Medicines in the United States: Review of 2011. Parsippany, NJ: IMS Institute for Healthcare Informatics; 2012. 4. Haninger K, Jessup A, Koehler K. ASPE Issue Brief: Economic Analysis of the Causes of Drug Shortages. Washington, DC: Office of the Assistant Secretary for Planning and Evaluation, Department of Health and Human Services; 2011. 5. Glass PS. Preface. Anesthesiol Clin. 2010;28(2):xv-xviii. 6. Wunsch H, Kahn JM, Kramer AA, et al. Use of intravenous infusion sedation among mechanically ventilated patients in the United States. Crit Care Med. 2009;37(12):3031-3039. 7. Karlin S. Generic Rx shortage initiative stuck: too few manufacturers to pick up slack. FDC Rep Drugs Cosmet.t 2013;130708013. 8. Jensen V, Rappaport BA. The reality of drug shortages—the case of the injectable agent propofol. N Engl J Med. 2010;363(9):806-807. 9. Thomas K. Lapses at big drug factories add to shortages and danger. New York Times. 2012;18. 10. Woodcock J, Wosinska M. Economic and technological drivers of generic sterile injectable drug shortages. Clin Pharmacol Ther. 2012;93(2):170-176. 11. Gupta D, Huang S. Drug shortages in the United States: a critical evaluation of root causes and the need for action. Clin Pharmacol Ther. 2013;93(2):133-135. 12. Fox E, Tyler L. Call to action: finding solutions for the drug shortage crisis in the United States. Clin Pharmacol Ther. 2013;93(2):145-147. 13. De Oliveira GS Jr, Theilken LS, McCarthy RJ. Shortage of perioperative drugs: implications for anesthesia practice and patient safety. Anesth Analg. 2011;113(6):1429-1435. 14. McHugh SM, Ibinson JW. Anesthesiology in the era of drug shortages: use of a succinylcholine infusion for a laparoscopic sigmoid colectomy due to a shortage of neostigmine. J Clin Anesth. 2013;25(1):79-81. 15. Kosarek L, Hart SR, Schultz L, et al. Increase in venous complications associated with etomidate use during a propofol shortage: an example of clinically important adverse effects related to drug substitution. Ochsner J. 2011;11(2):143-146. 16. Moffett BS, Mossad EB. Drug shortages: implications on pediatric anesthesia practice and management resources. J Clin Anesth. 2 2012;24(8):677-679. 17. Strayer RJ. Rocuronium vs. succinylcholine revisited. J Emerg Med. 2010;39(3):345-346. 18. Perry JJ, Lee JS, Sillberg VA, et al. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev. 2008;2. 19. Mallon WK, Keim SM, Shoenberger JM, et al. Rocuronium vs. succinylcholine in the emergency department: a critical appraisal. J Emerg Med. 2009;37(2):183-188. 20. Cherici C, Frazier J, Feldman M, et al. Navigating Drug Shortages in American Healthcare: A Premier Healthcare Alliance Analysis. Washington, DC: Premier Heatlhcare Alliance; 2011. 21. www.fda.gov/Drugs/DrugSafety/DrugShortages/default.htm 22. www.ashp.org/menu/DrugShortages

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and illegally possessing oxycodone, which he allegedly began diverting in 2009. The drugs carried a street value of approximately $5.6 million, according to a statement from Bridget Brennan, New York City’s special narcotics prosecutor. The indictment charged D’Alessandro with operating as a major trafficker under New York State’s Drug Kingpin Statute. He also faces one count of grand larceny and 247 counts of criminal possession of a controlled substance. D’Alessandro was fired from the hospital at the end of April, and also was let go from Staten Island University Hospital, where he worked weekends as a per diem pharmacist. “For a pharmacist working alone, this is one of the larger cases of drug diversion,” said Carmen Catizone, RPh, executive director of the National Association of Boards of Pharmacy. Usually more than one person would have been responsible for theft of this magnitude, he said. Shortly after Beth Israel’s parent company, Continuum Health Partners, merged with Mount Sinai Medical Center to form the Mount Sinai Health System last fall, the new administration received an anonymous letter documenting D’Alessandro’s alleged theft, according to Ms. Brennan’s statement. The administration then launched an internal investigation and audit before referring the case to the Office of the Special Narcotics Prosecutor. The investigations found that D’Alessandro used his position and knowledge of the hospital’s systems to divert 193,376 oxycodone pills on at least 218 dates between January 2009 and April 2014, the statement said. He accessed the hospital medication vault and removed various quantities of oxycodone, initially 100 to 500 pills at a time. On April 2, the day after hospital administrators questioned him, he removed 1,500 pills from the vault. D’Alessandro made false entries to the electronics narcotics inventory system indicating the medication was being sent to the hospital’s research pharmacy, known as the Investigational Drug Service (IDS). But the pills were never shipped to the service, which also fell under D’Alessandro’s control. Additionally, he filled at least seven fraudulent prescriptions written in his wife’s name at a hospital pharmacy. Beth Israel personnel declined to be interviewed for this story. “In light of the ongoing investigation, we are going to decline further comment at this time,” said hospital spokesman Sid Dinsay. But pharmacists knowledgeable about preventing drug diversion said the prosecutor’s statement revealed an apparent breakdown in policies or procedures that should have prevented D’Alessandro from taking drugs from the vault. “That director of pharmacy should never have been processing controlled substances; that should have been a red flag,” said Jim Jorgenson, RPh, CEO

of Visante Inc., a health care consulting organization, in Salt Lake City. “Directors in a hospital the size of Beth Israel shouldn’t be doing anything at all with controlled substances other than checking processes to provide oversight.” Mr. Catizone said he would be interested to know how D’Alessandro explained so much missing product during regularly scheduled inventories. The fact that such a deception can occur underscores that hospitals may be more prone to diversion than is often assumed, he noted. “People may think that within hospital pharmacies, diversion [occurs infrequently] because there are controls in place,” he said. “But if the pharmacists don’t have accountability, it can be just as prevalent as in community pharmacy locations.”

who signed in to the vault immediately after the thefts occurred, he added. However the specifics of the case pan out, Dr. Martin noted, “this is a shocking accusation against a pharmacy director.” Could the D’Alessandro thefts have been foreseen and prevented? In Dr. Adamson’s view, “there are a lot of red flags that are obvious now but are not that obvious when you’re going through it.”

Internal, External Reviews The experts offered several tips to prevent diversion. According to Mr. Jorgenson, one good place to begin is to ensure that your organization is frequently taking a step back to review not only how controlled substances are handled but also how it approaches its entire inventory process. No matter how good systems are, some people will try to get around them, so regular reviews are essential. Sometimes an external review also is helpful. “You become so comfortable with your own systems, just having someone else take a look uncovers opportunities for other things to do,” he said. Mr. Catizone said background checks— both criminal and financial—of all pharmacy employees are essential. Regular inventories also are critical, and ideally they should be kept in real time. For Dr. Martin, workflow considerations need to be part of the selff assessment plan. “You need a division of duties,” he said. For example, the employee ordering medication should not be the one receiving it. Many times in cases of diversion, he noted, an employee will order two shipments of drugs at the same time and divert the second shipment. Pharmacies also need to ensure that stock transferred to another area of the hospital is actually received in that area. Finally, the head pharmacist should stay out Robert Adamson, PharmD, vice president of clin- of the vault except to perform audits, Dr. Martin ical pharmacy services at Barnabas Health, a large stressed, adding that in a smaller or one-pharmacist health care network in New Jersey, said if one of his hospital, the head pharmacist should invite a hospitals had an investigational drug protocol, the pharmacy employee or compliance officer to drug used for that protocol would be stored locally participate in an audit. with the IDS—not in the main hospital vault. “You Automation Can Succeed don’t want to commingle inventory,” he said. Where Humans Fail He added, “I cannot fill a family member’s prescription. I can bring it to the pharmacy but I can’t Barnabas Health uses a Pyxis CII Safe (CareFuprocess it, and I don’t want to.” sion) to track and monitor controlled substances, Emory Martin, PharmD, vice president of phar- and pharmacy staff who use it must register their macy services at Baylor Scott & White Health Sys- fingerprints, Dr. Adamson said. It’s easier than tem in Temple, Texas, said he found it interesting remembering codes, and employees can’t punch that the anonymous tip came after the parent com- in for someone else. He recommended that hospany merger. The exposure to a higher level of pital pharmacies also conduct regular surveillance checks and balances that occurred as a result of the of inventory to protect against diversion, and that merger, he noted, may well have been the tipping reviews be performed by at least two employees. point in uncovering the oxycodone diversion. “In If you find diversion, “the best thing you can posa stand-alone hospital, the pharmacist-in-charge sibly do is quantify the diversion as best you can and [PIC] is generally the last protection against diver- divulge the information to the Drug Enforcement sions,” Dr. Martin explained. Although such solo Administration [DEA],” Mr. Jorgenson said. “If you practice sites have an internal audit arm and an can be as proactive as possible, it can help mitigate internal compliance area, “those [safeguards] are potential sanctions and fines to the hospital imposed generally not sophisticated enough to catch diver- by the DEA.” sion by the PIC.” Indeed, the only employees who —Karen Blum likely would have noticed the thefts would be those

Precedex has a different mechanism of action. The ﬁrst and only alpha2 agonist indicated for sedation.1-3

Precedex exerts sympatholytic effects. Reduces the sympathetic stress response.1 May be used in conjunction with vasopressors.1

Precedex maintains respiratory stability. Maintains consistent respiratory rates and oxygen saturation before, during and after extubation without discontinuing the sedative.4-6 Does not have to be discontinued prior to extubation.1

Patients may be arousable from a sedative state when stimulated. May be able to interact with clinicians and complete cognitive and pulmonary function assessments.1,7,8

Reduces the need for opioids while maintaining patient comfort.1,4,9,10 In a randomized, open-label, multicenter trial of 295 adults undergoing CABG surgery, the mean dose of morphine needed for adequate postoperative analgesia was 4 times less in patients sedated with Precedex than in patients sedated with propofol.4 Only 28% of patients receiving Precedex-based sedation required morphine for postoperative pain compared to 63% of patients receiving propofol-based sedation during assisted ventilation.4

Precedex Indications and Usage Precedex is indicated for: • Sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. Administer Precedex by continuous infusion not to exceed 24 hours. • Sedation of non-intubated patients prior to and/or during surgical and other procedures.

Precedex Important Safety Information • Monitoring: Continuously monitor patients while receiving Precedex. • Bradycardia and Sinus Arrest: Have occurred in young healthy volunteers with high vagal tone or with different routes of administration, e.g., rapid intravenous or bolus administration. • Hypotension and Bradycardia: May necessitate medical intervention. May be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension, and in the elderly. Use with caution in patients with advanced heart block or severe ventricular dysfunction. • Co-administration with Other Vasodilators or Negative Chronotropic Agents: Use with caution due to additive pharmacodynamic effects. • Transient Hypertension: Observed primarily during the loading dose. Consider reduction in loading infusion rate. • Arousability: Patients can become aroused/alert with stimulation; this alone should not be considered as lack of efficacy. • Prolonged exposure to dexmedetomidine beyond 24 hours may be associated with tolerance and tachyphylaxis and a dose-related increase in adverse events. • The most common adverse reactions (incidence > 2%) are hypotension, bradycardia, and dry mouth.

Please see adjacent pages for the Brief Summary of Prescribing Information.

Hospira, Inc., 275 North Field Drive, Lake Forest, IL 60045 P14-0252-5, 10.5x13, Jun., 14

1. Precedex [package insert]. Lake Forest, IL: Hospira, Inc; 2013. 2. Richards G, Schock P, Haefely W. Benzodiazepine receptors: new vistas. Sem Neurosci. 1991;3(3):191-203. 3. Vanlersberghe C, Camu F. Propofol. In: Schuttler J, Schwilden H, eds. Modern Anesthetics: Handbook of Experimental Pharmacology 182. Berlin, Germany: Springer-Verlag; 2008:227-252 4. Herr DL, Sum-Ping STJ, England M. ICU sedation after coronary bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens. J Cardiothorac Vasc Anesth. 2003:17(5):576-584. 5. Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine in surgical patient requiring intensive care. Crit Care. 2000;4(5):302-308. 6. Data on ﬁle. Hospira, Inc. Protocol W99-302 7. Hall JE, Uhrich TD, Barney JA, et al. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg. 2000;90(3): 699-705. 8. Data on ﬁle. Hospira, Inc. Protocol DEX-97-028 9. Martin E, Ramsay G, Mantz J, et al. The role of the a2-andrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med. 2003;18(1):29-41. 10. Candiotti KA, Bergese SD, Bokesch PM, et al. Monitored anesthesia care with dexmedetomidine: a prospective, randomized, double-blind, multicenter trial. Anesth Analg. 2010;110(1):47-56.

BRIEF SUMMARY OF PRESCRIBING INFORMATION PLEASE SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION.

Precedex™ (dexmedetomidine hydrochloride) Injection For intravenous use.

Precedex

™

(dexmedetomidine hydrochloride) in 0.9% Sodium Chloride Injection

Rx Only

6 ADVERSE REACTIONS 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reﬂect the rates observed in practice. Use of Precedex has been associated with the following serious adverse reactions: • Hypotension, bradycardia and sinus arrest [see Warnings and Precautions (5.2)] • Transient hypertension [see Warnings and Precautions (5.3)] Most common treatment-emergent adverse reactions, occurring in greater than 2% of patients in both Intensive Care Unit and procedural sedation studies include hypotension, bradycardia and dry mouth. Intensive Care Unit Sedation Adverse reaction information is derived from the continuous infusion trials of Precedex for sedation in the Intensive Care Unit setting in which 1007 adult patients received Precedex. The mean total dose was 7.4 mcg/kg (range: 0.8 to 84.1), mean dose per hour was 0.5 mcg/kg/hr (range: 0.1 to 6.0) and the mean duration of infusion of 15.9 hours (range: 0.2 to 157.2). The population was between 17 to 88 years of age, 43% ≥65 years of age, 77% male and 93% Caucasian. Treatment-emergent adverse reactions occurring at an incidence of >2% are provided in Table 1. The most frequent adverse reactions were hypotension, bradycardia and dry mouth [see Warnings and Precautions (5.2)]. Table 1: Adverse Reactions with an Incidence >2%—Adult Intensive Care Unit Sedation Population <24 hours*

1 INDICATIONS AND USAGE 1.1 Intensive Care Unit Sedation Precedex™ is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. Precedex should be administered by continuous infusion not to exceed 24 hours. Precedex has been continuously infused in mechanically ventilated patients prior to extubation, during extubation, and post-extubation. It is not necessary to discontinue Precedex prior to extubation.

1.2 Procedural Sedation Precedex is indicated for sedation of non-intubated patients prior to and/or during surgical and other procedures.

CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS 5.1 Drug Administration Precedex should be administered only by persons skilled in the management of patients in the intensive care or operating room setting. Due to the known pharmacological eﬀects of Precedex, patients should be continuously monitored while receiving Precedex.

5.2 Hypotension, Bradycardia, and Sinus Arrest Clinically significant episodes of bradycardia and sinus arrest have been reported with Precedex administration in young, healthy adult volunteers with high vagal tone or with different routes of administration including rapid intravenous or bolus administration. Reports of hypotension and bradycardia have been associated with Precedex infusion. If medical intervention is required, treatment may include decreasing or stopping the infusion of Precedex, increasing the rate of intravenous fluid administration, elevation of the lower extremities, and use of pressor agents. Because Precedex has the potential to augment bradycardia induced by vagal stimuli, clinicians should be prepared to intervene. The intravenous administration of anticholinergic agents (e.g., glycopyrrolate, atropine) should be considered to modify vagal tone. In clinical trials, glycopyrrolate or atropine were effective in the treatment of most episodes of Precedex-induced bradycardia. However, in some patients with significant cardiovascular dysfunction, more advanced resuscitative measures were required. Caution should be exercised when administering Precedex to patients with advanced heart block and/or severe ventricular dysfunction. Because Precedex decreases sympathetic nervous system activity, hypotension and/or bradycardia may be expected to be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension and in elderly patients. In clinical trials where other vasodilators or negative chronotropic agents were co-administered with Precedex an additive pharmacodynamic effect was not observed. Nonetheless, caution should be used when such agents are administered concomitantly with Precedex.

5.3 Transient Hypertension Transient hypertension has been observed primarily during the loading dose in association with the initial peripheral vasoconstrictive eﬀects of Precedex. Treatment of the transient hypertension has generally not been necessary, although reduction of the loading infusion rate may be desirable.

5.4 Arousability Some patients receiving Precedex have been observed to be arousable and alert when stimulated. This alone should not be considered as evidence of lack of eﬃcacy in the absence of other clinical signs and symptoms.

5.5 Withdrawal Intensive Care Unit Sedation With administration up to 7 days, regardless of dose, 12 (5%) Precedex adult subjects experienced at least 1 event related to withdrawal within the ﬁrst 24 hours after discontinuing study drug and 7 (3%) Precedex adult subjects experienced at least 1 event 24 to 48 hours after end of study drug. The most common events were nausea, vomiting, and agitation. In adult subjects, tachycardia and hypertension requiring intervention in the 48 hours following study drug discontinuation occurred at frequencies of <5%. If tachycardia and/or hypertension occurs after discontinuation of Precedex supportive therapy is indicated. Procedural Sedation In adult subjects, withdrawal symptoms were not seen after discontinuation of short term infusions of Precedex (<6 hours).

5.6 Tolerance and Tachyphylaxis Use of dexmedetomidine beyond 24 hours has been associated with tolerance and tachyphylaxis and a dose-related increase in adverse reactions [see Adverse Reactions (6.1)].

5.7 Hepatic Impairment Since Precedex clearance decreases with severity of hepatic impairment, dose reduction should be considered in patients with impaired hepatic function [see Dosage and Administration (2.2) in full prescribing information].

All Precedex Adverse Event

(N = 1007) (%)

Hypotension Hypertension Nausea Bradycardia Atrial Fibrillation Pyrexia Dry Mouth Vomiting Hypovolemia Atelectasis Pleural Eﬀusion Agitation Tachycardia Anemia Hyperthermia Chills Hyperglycemia Hypoxia Post-procedural Hemorrhage Pulmonary Edema Hypocalcemia Acidosis Urine Output Decreased Sinus Tachycardia Ventricular Tachycardia Wheezing Edema Peripheral

25% 12% 9% 5% 4% 4% 4% 3% 3% 3% 2% 2% 2% 2% 2% 2% 2% 2% 2% 1% 1% 1% 1% 1% <1% <1% <1%

Randomized Precedex (N = 798) (%) 24% 13% 9% 5% 5% 4% 3% 3% 3% 3% 2% 2% 2% 2% 2% 2% 2% 2% 2% 1% 1% 1% 1% 1% 1% 1% 0

Placebo

Propofol

(N = 400)

(N = 188)

(%)

12% 19% 9% 3% 3% 4% 1% 5% 2% 3% 1% 3% 4% 2% 3% 3% 2% 2% 3% 1% 0 1% 0 1% 1% 0 1%

13% 4% 11% 0 7% 4% 1% 3% 5% 6% 6% 1% 1% 2% 0 2% 3% 3% 4% 3% 2% 2% 2% 2% 5% 2% 2%

* 26 subjects in the all Precedex group and 10 subjects in the randomized Precedex group had exposure for greater than 24 hours. Adverse reaction information was also derived from the placebo-controlled, continuous infusion trials of Precedex for sedation in the surgical intensive care unit setting in which 387 adult patients received Precedex for less than 24 hours. The most frequently observed treatment-emergent adverse events included hypotension, hypertension, nausea, bradycardia, fever, vomiting, hypoxia, tachycardia and anemia (see Table 2). Table 2: Treatment-Emergent Adverse Events Occurring in >1% Of All Dexmedetomidine-Treated Adult Patients in the Randomized Placebo-Controlled Continuous Infusion <24 Hours ICU Sedation Studies Adverse Event Hypotension Hypertension Nausea Bradycardia Fever Vomiting Atrial Fibrillation Hypoxia Tachycardia Hemorrhage Anemia Dry Mouth Rigors Agitation Hyperpyrexia Pain

Randomized Dexmedetomidine

Placebo

(N = 387) 28% 16% 11% 7% 5% 4% 4% 4% 3% 3% 3% 3% 2% 2% 2% 2%

(N = 379) 13% 18% 9% 3% 4% 6% 3% 4% 5% 4% 2% 1% 3% 3% 3% 2%

Table 2: Treatment-Emergent Adverse Events Occurring in >1% Of All Dexmedetomidine-Treated Adult Patients in the Randomized Placebo-Controlled Continuous Infusion <24 Hours ICU Sedation Studies (continued) Adverse Event Hyperglycemia Acidosis Pleural Eﬀusion Oliguria Thirst

Randomized Dexmedetomidine

Placebo

(N = 387) 2% 2% 2% 2% 2%

(N = 379) 2% 2% 1% <1% <1%

The mean total dose was 1.6 mcg/kg (range: 0.5 to 6.7), mean dose per hour was 1.3 mcg/kg/hr (range: 0.3 to 6.1) and the mean duration of infusion of 1.5 hours (range: 0.1 to 6.2). The population was between 18 to 93 years of age, 30% ≥65 years of age, 52% male and 61% Caucasian. Treatment-emergent adverse reactions occurring at an incidence of >2% are provided in Table 5. The most frequent adverse reactions were hypotension, bradycardia, and dry mouth [see Warnings and Precautions (5.2)]. Pre-speciﬁed criteria for the vital signs to be reported as adverse reactions are footnoted below the table. The decrease in respiratory rate and hypoxia was similar between Precedex and comparator groups in both studies. Table 5: Adverse Reactions With an Incidence > 2%—Procedural Sedation Population

Adverse Event In a controlled clinical trial, Precedex was compared to midazolam for ICU sedation exceeding 24 hours duration in adult patients. Key treatment emergent adverse events occurring in dexmedetomidine or midazolam treated patients in the randomized active comparator continuous infusion long-term intensive care unit sedation study are provided in Table 3. The number (%) of subjects who had a dose-related increase in treatment-emergent adverse events by maintenance adjusted dose rate range in the Precedex group is provided in Table 4.

Hypotension1 Respiratory Depression2 Bradycardia3 Hypertension4 Tachycardia5 Nausea Dry Mouth Hypoxia6 Bradypnea

Table 3: Key Treatment-Emergent Adverse Events Occurring in Dexmedetomidine- or Midazolam-Treated Adult Patients in the Randomized Active Comparator Continuous Infusion Long-Term Intensive Care Unit Sedation Study Adverse Event

Dexmedetomidine

Midazolam

(N = 244)

(N = 122)

56%

28%

27%

42%

19%

28%

42%

Hypotension1 Hypotension Requiring Intervention Bradycardia2 Bradycardia Requiring Intervention Systolic Hypertension3 4

Precedex

Placebo

(N = 318)

(N = 113)

(%)

54% 37% 14% 13% 5% 3% 3% 2% 2%

30% 32% 4% 24% 17% 2% 1% 3% 4%

Hypotension was deﬁned in absolute and relative terms as Systolic blood pressure of <80 mmHg or ≤30% lower than prestudy drug infusion value, or Diastolic blood pressure of <50 mmHg.

Respiratory depression was deﬁned in absolute and relative terms as respiratory rate (RR) <8 beats per minute or > 25% decrease from baseline.

Bradycardia was deﬁned in absolute and relative terms as <40 beats per minute or ≤30% lower than pre-study drug infusion value.

Hypertension was deﬁned in absolute and relative terms as Systolic blood pressure >180 mmHg or ≥30% higher than pre-study drug infusion value or Diastolic blood pressure of >100 mmHg.

Tachycardia was deﬁned in absolute and relative terms as >120 beats per minute or ≥30% greater than pre-study drug infusion value. Hypoxia was deﬁned in absolute and relative terms as SpO2 <90% or 10% decrease from baseline.

25%

44%

10%

12%

15%

11%

15%

19%

30%

Hypokalemia

13%

6.2 Postmarketing Experience

Pyrexia

Agitation

Hyperglycemia

Constipation

The following adverse reactions have been identiﬁed during post approval use of Precedex. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypotension and bradycardia were the most common adverse reactions associated with the use of Precedex during post approval use of the drug.

Hypoglycemia

Respiratory Failure

Renal Failure Acute

Acute Respiratory Distress Syndrome

Generalized Edema

Hypomagnesemia

Tachycardia

Tachycardia Requiring Intervention Diastolic Hypertension3 Hypertension

Hypertension Requiring Intervention†

Table 6: Adverse Reactions Experienced During Post-approval Use of Precedex Body System

Preferred Term

Body as a Whole

Fever, hyperpyrexia, hypovolemia, light anesthesia, pain, rigors

Cardiovascular Disorders, General

Blood pressure ﬂuctuation, heart disorder, hypertension, hypotension, myocardial infarction

Central and Peripheral Nervous System Disorders

Dizziness, headache, neuralgia, neuritis, speech disorder, convulsion

Gastrointestinal System Disorders

Abdominal pain, diarrhea, vomiting, nausea

Heart Rate and Rhythm Disorders

Arrhythmia, ventricular arrhythmia, bradycardia, hypoxia, atrioventricular block, cardiac arrest, extrasystoles, atrial ﬁbrillation, heart block, t wave inversion, tachycardia, supraventricular tachycardia, ventricular tachycardia

Liver and Biliary System Disorders

Increased gamma-glutamyl transpepsidase, hepatic function abnormal, hyperbilirubinemia, alanine transaminase, aspartate aminotransferase

The following adverse events occurred between 2 and 5% for Precedex and Midazolam, respectively: renal failure acute (2.5%, 0.8%), acute respiratory distress syndrome (2.5%, 0.8%), and respiratory failure (4.5%, 3.3%).

Metabolic and Nutritional Disorders

Acidosis, respiratory acidosis, hyperkalemia, increased alkaline phosphatase, thirst, hypoglycemia

Table 4. Number (%) of Adult Subjects Who Had a Dose-Related Increase in Treatment Emergent Adverse Events by Maintenance Adjusted Dose Rate Range in the Precedex Group

Psychiatric Disorders

Agitation, confusion, delirium, hallucination, illusion

Red Blood Cell Disorders

Anemia

Renal Disorders

Blood urea nitrogen increased, oliguria

Respiratory System Disorders

Apnea, bronchospasm, dyspnea, hypercapnia, hypoventilation, hypoxia, pulmonary congestion

Skin and Appendages Disorders

Increased sweating

Vascular Disorders

Hemorrhage

Vision Disorders

Photopsia, abnormal vision

†

Includes any type of hypertension.

Hypotension was deﬁned in absolute terms as Systolic blood pressure of <80 mmHg or Diastolic blood pressure of <50 mmHg or in relative terms as ≤30% lower than pre-study drug infusion value.

Bradycardia was deﬁned in absolute terms as <40 bpm or in relative terms as ≤30% lower than pre-study drug infusion value.

Hypertension was deﬁned in absolute terms as Systolic blood pressure >180 mmHg or Diastolic blood pressure of >100 mmHg or in relative terms as ≥30% higher than pre-study drug infusion value.

Tachycardia was deﬁned in absolute terms as >120 bpm or in relative terms as ≥30% greater than pre-study drug infusion value.

Precedex mcg/kg/hr Adverse Event Constipation Agitation Anxiety Edema Peripheral Atrial Fibrillation Respiratory Failure Acute Respiratory Distress Syndrome

≤0.7*

>0.7 to ≤1.1*

>1.1*

(N = 95)

(N = 78)

(N = 71)

6% 5% 5% 3% 2% 2% 1%

5% 8% 5% 5% 4% 6% 3%

14% 14% 9% 7% 9% 10% 9%

* Average maintenance dose over the entire study drug administration Procedural Sedation Adverse reaction information is derived from the two trials for procedural sedation in which 318 adult patients received Precedex.

Adapted from: EN-3411; Revised 12/2013 Manufactured and Distributed by: Hospira, Inc., Lake Forest, IL 60045 USA Licensed from: Orion Corporation, Espoo, Finland P14-0164-5-10.5x13-Feb.,14 Printed in USA Hospira, Inc., Lake Forest, IL 60045 USA

24 I AnesthesiologyNews.com

SEPTEMBER 2014

POLICY & MANAGEMENT

Fast-Track Process Cuts Time in PACU and Saves Money

sing an approach originally developed x-rayy clear?” The answer determines the next action in the manufacturing sector, the Univer- step. The researchers calculated the time each action sity of Texas MD Anderson Cancer Cen- or decision took, and they assigned a minute value to ter, in Houston, reduced by nearly 21 minutes the each unit on their process map. time patients spent in recovery after placement of a As part of the intervention, patients were shown a port-a-cath. video early in their visit to help them decide whether The alarming rise in cancer care costs prompted to fast-trackk their procedure. physicians at the institution to seek out cost-effective The study authors also solicited feedback from the solutions to reduce the financial burden on patients. entire medical staff and revised their process based “I think it’s a smart thing to always be looking at on this knowledge. They also shortened patients’ what your processes are and to eliminate waste if pos- charts, eliminating unnecessary questions. sible,” said Karen Carlson, MD, assistant professor Dr. Rebello’s group pulled data from their facilof anesthesiology at Emory University Hospital, in ity’s anesthesia information management systems Atlanta, who was not involved with the Texas project. on all port-a-cath cases under monitored anesthesia Time-driven activity-based costing (TDABC) is from Feb. 1, 2010 through Feb. 28, 2013. They coman approach developed by Harvard Business School strategists in the 1980s. Elizabeth Rebello, The investigators used a three-pronged MD, assistant professor in the Department of Anesthesiology strategy: patient and health care provider and Perioperative Medicine, and education; fast-tracking bed space her colleagues at MD Anderson tailored this concept to a study in the postanesthesia care unit that focused on improving one segment of one type of hospital (PACU); and simplifying the visit: recovery time for patients PACU nurse’s charting template. receiving a port-a-cath. The investigators used a three-pronged strategy: patient and health care provider education; fast-trackingg bed space in the pared 1,566 prreintervention cases postanesthesia care unit (PACU); and simplifying with the 287 postinterventhe PACU nurse’s charting template. tion cases, from m Dr. Rebello’s group compared the time patients May 1 to Octt. receiving a port-a-cath spent in the PACU before 1, 2013. and after implementing the fast-trackk system to test The periodd whether their intervention decreased recovery time. between Marcch 1, They identified, mapped and labeled individual steps and May 1, 2013, and decision points in the recovery process. In one was viewed as a step or unit, a nurse admits and assesses a patient transition time. in the recovery room and phones an x-rayy techniThe mean time cian. Another unit is “x-rayy technician takes chest patients spen nt recovx-ray.” y Decision points are questions, such as “Is the ering in th he PACU

preintervention period was 85.9 minutes, falling to 65.2 minutes in the postintervention period. (Patients who stayed in the PACU for longer than 200 minutes were excluded from the study.) Extending the average difference of 20.7 minutes across the total number of postintervention cases, 287, yielded a reduction of 940.9 minutes or 99 hours over six months. Dr. Carlson noted that the study authors might have had more impact if they zeroed in on problem areas. “What I would have looked at is the place where the biggest chunks of time were spent,” she said. However, she added, “65 minutes is still a long time to be in the recovery room after a port-a-cath.” “More than the average time, the fast-trackk process using TDABC methodology has decreased the variability significantly, producing a tighter end result,” Dr. Rebello said. “This has allowed us to utilize our resources, such as PACU nurse time, more efficiently.” Because many patients pat went to chemotherapy after surgery, it’s possible that PACU time was affected by the process flow doownstream, Dr. Carlson said. In other words, patien nts may have been ready to leave the recovery rooom but the chemotherapy department may not haave been prepared to receive them. By keeping a reccord of who went to chemotherapy and who diddn’t, the study authors might have determined whetheer additional appointments were a limiting factor. The fast-track t k approach is not ideal for patients whoo are claustrophobic or have anxiety because these patients may need the extra sedation,, but Dr. Rebello said the process is ssuitable for many of the patients u undergoing port-a-cath placement. “T These patients appreciate being leess sedated in the recovery room an nd are able to go to their next appoointment or have chemotherapy that dayy,” she said. “The important thing is to educatee them early in the process.” —Shannon Firth

Post-Op Surgical Ward Pneumonia Cut by More Than 40%

postoperative pneumonia prevention program for patients in the surgical ward nearly halved the incidence of the condition, California researchers have found. The program, at the VA Palo Alto Health Care System, emphasized ongoing education for nurses, pneumonia prevention, coughing and deepbreathingg exercises with an incentive spirometer, twice-daily oral hygiene with chlorhexidine, walking and sitting up to eat. The study included patients who were not on a mechanical ventilator from 2008 to 2012. During this time, there were 18 cases of postoperative pneumonia among 4,099 at-riskk patients, for a case rate of 0.44%. That marked a 44% decrease from the hospital’s

preintervention rate of 0.78%, according to the researchers. Pneumonia rates in all years were lower than the preintervention rate (0.25%, 0.50%, 0.58%, 0.68% and 0.13% in 2008 to 2012, respectively). “The standardized pneumonia prevention program achieved substantial and sustained reduction in postoperative pneumonia incidence on our surgical ward; its wider adoption could improve postoperative outcomes and reduce overall health care costs,” wrote the authors, who published their findings in JAMA Surgery (2014 Jul 23 [Epub ahead of print]). Although encouraging, these findings should be interpreted with caution, said Catherine Lewis, MD, a specialist in surgical critical care at the University of California, Los Angeles.

“Although the number of ward cases decreased from 13 to three, the number of non–ventilator-associated pneumonia ICU cases increased from four to 17, and therefore, the reported decrease could be due to redistribution in the location of patients,” Dr. Lewis wrote in an invited commentary to the paper. “[Another] concern is that the authors did not evaluate changes in patient care or surgical technique that could have altered the incidence of postoperative pneumonia.” However, despite these concerns, she added, “The authors should be commended for the development and implementation of a quality improvement measure aimed at decreasing the rate of postoperative pneumonia in a Veterans Affairs population.” —Paul Bufano

SEPTEMBER 2014

AnesthesiologyNews.com I 25

POLICY & MANAGEMENT

Pre-Op Routines Reduce Post-Op Risks in Obese Patients

edicated protocols for patients undergoing abdominal surgery can greatly reduce their risk for complications after the procedure, researchers have found. Ensuring that patients are physically fit and knowledgeable about the procedure, combined with steps to minimize the risk for blood clots and other complications, might be key to preventing adverse outcomes and hastening recovery, the researchers said. “This gives us a good opportunity to have patients go through major surgery and still prevent the more frustrating complications of surgery, like developing a clot, or developing pneumonia after an operation,” said David Shaz, MD, a pulmonary intensivist at the James J. Peters VA Medical Center in New York City, where the retrospective chart review was conducted. Dr. Shaz and his colleagues presented their findings at the 2014 annual meeting of the Society of Critical Care Medicine (abstract 603). The study included 105 morbidly obese patients (90 men) who had been referred for laparoscopic sleeve gastrectomy surgery by their primary care physicians. The average age of the patients was 51, and their average body mass index was 45 kg/m2. To qualify for the surgery, patients first had to undergo a fitness and nutrition regimen that lasted between six and 12 months, to ensure that the regimen did not aid significantly with weight loss. The surgeries were performed over a span of about three years, between January 2010 and June 2013. Once accepted for surgery, patients were required to comply with a strict exercise and dietary program, and were thoroughly educated about the procedure and its risks. Psychologists and psychiatrists also worked with the patients. Before surgery, doctors administered heparin and applied compression boots to prevent blood clots. In addition, 95 patients were given heparin on postoperative day 1. Continuous or bilevel positive airway pressure was applied to 30 patients on the first night postsurgery, to assist with sleep apnea. To prevent lung collapse, 70 patients were encouraged to walk more than 100 feet within five hours of undergoing surgery. On average, the patients were discharged 2.44 days after the procedure. No patients experienced blood clots or collapsed lungs, although a few contracted pneumonia or bronchitis. These results suggest that following dedicated

protocols can lead to better patient outcomes, Dr. Shaz said. Patient preparedness is the key factor, he said. The protocols show promise not just for laparoscopic sleeve gastrectomy procedures, but other types of surgery as well, said Megan Anders, MD, assistant professor of anesthesiology at the University of Maryland Medical Center, in Baltimore.

“In the prior literature there are mixed data on the relative rate of complications after bariatric surgery, with some authors noting that an apparent lower rate of [venous thromboembolism] in some studies, for example, may be due to use of stricter protocols in these populations,” Dr. Anders said. “The data from this abstract, although limited in sample size, would support that theory.

“This report does a nice job of demonstrating the importance of diligently measuring the outcomes we believe we are impacting with targeted protocols,” she added. “Being able to demonstrate that their complication rate is low when using this protocol can help maintain enthusiasm among medical professionals.” —Ajai Raj

When MH strikes,

Keep cool in the crisis with administration in

LESS THAN 1 MINUTE

ADVANCING THE STANDARD IN MALIGNANT HYPERTHERMIA (MH) TREATMENT. RYANODEX® (dantrolene sodium) for injectable suspension is changing how MH is treated. • Less time for reconstitution and administration – Less than 1 minute for a loading dose (2.5 mg/kg) of dantrolene sodium in an MH crisis1,2 • Less risk of complications with less fluid – Over 99% less sterile water for injection than other dantrolene sodium IV treatments3-5 • Less effort to stay cool in an MH crisis – 1 vial provides a loading dose for patients up to 100 kg and can be administered by 1 healthcare professional (eg, an anesthesia provider)1,3 To request that RYANODEX® be stocked in your institution or obtain ordering information, visit RYANODEX.com/anesnews or call 855.318.2170. References: 1. Data on file. Eagle Pharmaceuticals, Inc. 2. Managing an MH crisis. Malignant Hyperthermia Association of the United States website. http://www.mhaus.org/healthcareprofessionals/managing-a-crisis. Accessed June 18, 2014. 3. RYANODEX [package insert]. Woodcliff Lake, NJ: Eagle Pharmaceuticals, Inc.; 2014. 4. Dantrium Intravenous [package insert]. Rochester, MI: JHP Pharmaceuticals, LLC; 2008. 5. Revonto [package insert]. Louisville, KY: US WorldMeds, LLC; 2011.

Please see Brief Summary of Prescribing Information on the following page. © 2014 Eagle Pharmaceuticals, Inc. All rights reserved. 50 Tice Blvd, Suite 315 Woodcliff Lake, NJ 07677 (201) 326-5300 RYN14-0027-01 8/2014

INDICATION RYANODEX® (dantrolene sodium) for injectable suspension is indicated for the treatment of malignant hyperthermia in conjunction with appropriate supportive measures, and for the prevention of malignant hyperthermia in patients at high risk. IMPORTANT SAFETY INFORMATION RYANODEX® is not a substitute for appropriate supportive measures in the treatment of malignant hyperthermia (MH), including: • Discontinuing triggering • Instituting cooling when necessary anesthetic agents • Administering diuretics to prevent late kidney injury due to • Increasing oxygen myoglobinuria (the amount • Managing the of mannitol in RYANODEX® is metabolic acidosis insufficient to maintain diuresis)

26 I AnesthesiologyNews.com

SEPTEMBER 2014

POLICY & MANAGEMENT

Methadone Guidelines Focus on Addiction, Primary Care

ew guidelines drafted by the American Pain Society (APS) for the safe administration of methadone for the first time focus particular attention on the potential for abuse and misuse of the drug, highlighting the need for additional awareness and education within the pain management community, after a significant increase in deaths related to its use.

RYANODEX® (dantrolene sodium) for injectable suspension, for intravenous use. Brief Summary of Prescribing Information. See Package Insert For Full Prescribing Information INDICATIONS AND USAGE RYANODEX® is indicated for the: • Treatment of malignant hyperthermia in conjunction with appropriate supportive measures (see Dosage and Administration) • Prevention of malignant hyperthermia in patients at high risk. DOSAGE AND ADMINISTRATION (Selected Information) In addition to RYANODEX treatment, institute the following supportive measures: • Discontinue use of malignant hyperthermia (MH)-triggering anesthetic agents (i.e., volatile anesthetic gases and succinylcholine). • Manage the metabolic acidosis • Institute cooling when necessary • Administer diuretics to prevent late kidney injury due to myoglobinuria (the amount of mannitol in RYANODEX is insufficient to maintain diuresis) Administer RYANODEX by intravenous push at a minimum dose of 1 mg/kg. If the physiologic and metabolic abnormalities of MH continue, administer additional intravenous boluses up to the maximum cumulative dosage of 10 mg/kg. If the physiologic and metabolic abnormalities reappear, repeat RYANODEX dosing by intravenous push starting with 1 mg/kg. Dosage for Prevention of Malignant Hyperthermia The recommended prophylactic dose of RYANODEX is 2.5 mg/kg administered intravenously over a period of at least 1 minute, starting approximately 75 minutes prior to surgery. Avoid agents that trigger MH. If surgery is prolonged, administer additional individualized RYANODEX doses during anesthesia and surgery. Dosage for Pediatric Patients The recommended weight-based dose of RYANODEX for pediatric patients in the treatment and prevention of MH is the same as for adults for these indications (see Dosage and Administration). Reconstitution and Administration Instructions The supplied lyophilized powder must be reconstituted prior to administration: Reconstitute each vial of RYANODEX lyophilized powder by adding 5 mL of sterile water for injection (without a bacteriostatic agent). Do not reconstitute with any other solution (e.g., 5% dextrose injection, 0.9% sodium chloride injection). Shake the vial to ensure an orange-colored uniform suspension. Visually inspect the vial for particulate matter and discoloration prior to administration. Must use the contents of the vial within 6 hours after reconstitution. Store reconstituted suspensions at controlled room temperature (68°F to 77°F or 20°C to 25°C). (For complete Dosage and Administration Section, see full Prescribing Information)

RYANODEX has been associated with dysphasia. Assess patients for difficulty swallowing and choking. Somnolence and Dizziness Somnolence and dizziness can occur following administration of RYANODEX and may persist up to 48-hours post-dose. Patients should not be permitted to ambulate without assistance until they have normal strength and balance. Patients must not operate an automobile or engage in other hazardous activities for 48-hours post-dose. The concomitant use of sedative agents with RYANODEX may increase the risk of somnolence and dizziness. Potential for Tissue Necrosis with Extravasation Care must be taken to prevent extravasation of RYANODEX into the surrounding tissues due to the high pH of the reconstituted RYANODEX suspension and potential for tissue necrosis. ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a study designed to evaluate the safety and tolerability of RYANODEX, healthy volunteers were randomly assigned to receive treatment with RYANODEX or an active comparator at doses ranging from 1 mg/kg to 2.5 mg/kg. • The RYANODEX dose was infused over the course of 1 minute for each of the doses evaluated. • The active comparator was an injectable formulation of dantrolene sodium that differed from RYANODEX in that it contained dantrolene sodium and mannitol at concentrations of 0.33 mg/mL and 50 mg/mL, respectively, when reconstituted according to the product’s prescribing information. The active comparator was infused at a rate that administered 20 mg of dantrolene per minute for each of the doses evaluated. Table 1 displays the most common adverse events in this study. These data are not an adequate basis for comparison of the types or frequencies of adverse event types between RYANODEX and the dantrolene sodium comparator. Adverse events increased in frequency with increasing doses in the trial, but did not differ in frequency between the two treatment groups. RYANODEX-treated subjects were more likely to report immediate adverse events of flushing, dystonia, and dysphagia than those receiving the active comparator. In all dose groups, hand grip strength declined after dosing. In general, the decline in hand grip strength was more pronounced and occurred more rapidly in the RYANODEX-treated subjects in the 1.0, 1.75, 2.0 and 2.25 mg/kg treatment groups. In the 2.5 mg/kg treatment group, the decline in hand grip strength both in amount and duration was similar between the two treatment groups. Table 1: Adverse Events in Healthy Volunteers Number(%) of subjects RYANODEX [N=30]

DANTROLENE SODIUM COMPARATOR [N=31]

Flushing

8 (27)

1 (3)

Somnolence

5 (17)

4 (13)

Dysphonia

4 (13)

1 (3)

Dysphagia

3 (10)

4 (13)

Nausea

3 (10)

Feeling abnormal

3 (10)

Headache

1 (3)

4 (13)

Vomiting

1 (3)

2 (6)

CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Muscle Weakness RYANODEX is associated with skeletal muscle weakness. The administration of RYANODEX in human volunteers has been associated with loss of grip strength and weakness in the legs. Patients should not be permitted to ambulate without assistance until they have normal strength and balance. RYANODEX has been associated with dyspnea, respiratory muscle weakness, and decreased inspiratory capacity. Monitor patients for the adequacy of ventilation.

The new guidelines, which were published in the April issue of The Journal of Pain (2014;15:338-365), address several key areas, including patient assessment, patient education/counseling and treatment monitoring; in some cases, they also propose the use of alternative medications. The new guidelines call for stratification of patients based on their risk for substance abuse prior to

Vision blurred

1 (3)

Pain in extremity

1 (3)

Muscular Weakness/ Asthenia

1 (3)

Atrioventricular block

1 (3)

Tachycardia

1 (3)

Infusion site pain

1 (3)

Dizziness

1 (3)

methadone treatment, and suggest that the drug be administered at a low starting dose (30-40 mg daily; slow titration as needed) to reduce the incidence of unintended drug accumulation and accidental overdose. Earlier methadone protocols focused primarily on cardiovascular risks, while ignoring the potential for abuse and misuse. According to Roger Chou,

Postmarketing Experience The following adverse reactions have been identified during postapproval use of another formulation of dantrolene sodium for injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Pulmonaryy Edema There have been reports of pulmonary edema developing during the treatment of malignant hyperthermia crises with another dantrolene sodium dosage form. The contributory effect of the diluent volume and mannitol in these cases is not known. Thrombophlebitis p and Tissue Necrosis There have been reports of thrombophlebitis following administration of intravenous dantrolene. Tissue necrosis secondary to extravasation has been reported (see Warnings and Precautions). Hypersensitivity/Anaphylactic yp y p y Reactions There have been reports of urticaria and erythema possibly associated with the administration of dantrolene sodium for injection. Anaphylaxis has been reported. Injection j Site Reactions Injection site reactions including pain, erythema, and swelling, commonly due to extravasation, have been reported. DRUG INTERACTIONS Calcium Channel Blockers Cardiovascular collapse in association with marked hyperkalemia has been reported in patients receiving dantrolene in combination with calcium channel blockers. The concomitant use of RYANODEX and calcium channel blockers is not recommended during the treatment of malignant hyperthermia. Muscle Relaxants The concomitant administration of RYANODEX with muscle relaxants may potentiate the neuromuscular block. Antipsychotics and Antianxiety Agents The concomitant administration of RYANODEX with antipsychotic and antianxiety agents may potentiate their effects on the central nervous system (see Warnings and Precautions). USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy g y Category g yC Adequate and well controlled studies have not been conducted with RYANODEX in pregnant women. However, animal reproduction studies have been conducted with dantrolene sodium. In these studies, dantrolene sodium administered to rats and rabbits produced embryolethality (rabbits) and decreased pup survival (rats) at doses seven times the human oral dose. RYANODEX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Labor and Delivery In one uncontrolled study, 100 mg per day of prophylactic oral dantrolene sodium was administered to term pregnant patients awaiting labor and delivery. Dantrolene readily crossed the placenta, with maternal and fetal whole blood levels approximately equal at delivery; neonatal levels then fell approximately 50% per day for 2 days before declining sharply. No neonatal respiratory and neuromuscular side effects were observed in this study.

Nursing Mothers Dantrolene is present in human milk. In one case report, low dantrolene concentrations (less than 2 micrograms per milliliter) were measured in the breast milk of a lactating woman during repeat intravenous dantrolene administration over 3 days. Because of the potential for serious adverse reactions of respiratory depression and muscle weakness in nursing infants from dantrolene, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use The safety and efficacy of RYANODEX in the treatment and prevention of malignant hyperthermia in pediatric patients is based on clinical experience with other intravenous dantrolene sodium products, which suggests adult weight-based doses are appropriate for pediatric patients. Geriatric Use Clinical studies of RYANODEX did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. OVERDOSAGE Overdosage Symptoms Overdosage symptoms include, but are not limited to, muscular weakness and alterations in the state of consciousness (e.g., lethargy, coma), vomiting, diarrhea, and crystalluria. Management of Overdosage Employ general supportive measures for acute overdosage of RYANODEX. PATIENT COUNSELING INFORMATION Inform patients, their families, or their caregivers of the following: Muscle Weakness Muscle weakness (i.e. decrease in grip strength and weakness of leg muscles, especially walking down stairs) is likely to occur with the use of RYANODEX. Patients should be provided assistance with standing and walking until their strength has returned to normal (see Warnings and Precautions). Difficultyy Swallowingg Caution is indicated at meals on the day of administration because difficulty swallowing and choking have occurred with the use of dantrolene sodium products in general; dysphagia has been reported with the use of RYANODEX (see Warnings and Precautions). Dizziness and Somnolence The use of RYANODEX has been associated with dizziness and somnolence. (see Warnings and Precautions). Drivingg or Operating p g Machineryy Symptoms such as “lightheadedness” may occur. Since some of these symptoms may persist for up to 48 hours, patients must not operate an automobile or engage in other hazardous activity during this time (see Warnings and Precautions). Revised: 7/2014 Marketed by: Eagle Pharmaceuticals, Inc. Woodcliff Lake, NJ 07677

MD, head of the APS Clinical Practice Guideline Program and associate professor of medicine at Oregon Health & Science University, in Portland, “alarming data” on methadone-relatedd deaths prompted the society to change the focus. He cited Centers for Disease Control and Prevention (CDC) statistics that show an increase in deaths associated with methadone, from less than 1,000 in 1999 to nearly 5,000 in 2008. He added that although methadone accounts for “about 10% or less” of all opioids prescribed, the CDC has linked the drug to roughly one-thirdd of all prescription opioid-relatedd deaths. “These trends occurred in the context of markedly increased prescribing of opioids in general for chronic pain, and increased use of methadone as a less expensive alternative to other longactingg opioids,” he said. The new guidelines also focus on methadone as a treatment for patients with opioid addiction. In this context, the authors recommend that routine patient monitoring include echocardiograms and urine drug testing. They also propose buprenorphine as an alternative for these patients. Although the guidelines were written for use by all clinicians who prescribe methadone, Dr. Chou, who served as lead author, admitted that many of the recommendations were aimed at primary care physicians. “A lot of prescribing for chronic pain occurs in primary care settings, where some clinicians may perceive methadone to be interchangeable with other opioids, when that clearly isn’t the case due to its long halff life and potential for QTc prolongation,” he said in an interview. Family practitioner Louis Kuritzky, MD, said that some of his colleagues may not be aware of monitoring protocols for patients receiving methadone for pain. Since not all primary care physicians read The Journal of Pain, he recommended that the authors publish the guidelines in other journals. “The guidelines are a critical step forward, [as they] put clinicians on notice that methadone deserves its own special categorization because of differences in administration and monitoring [compared with] other opioids,” said Dr. Kuritzky, y who is also clinical assistant professor at the University of Florida in Gainesville. He was not involved in the development of the new guidelines. —Brian Dunleavy

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Fluid Overload Heightens Complications and Cost of Care But Is Manageable With Awareness Las Vegas—Not only can fluid overload increase a patient’s risk for death, but it can add several days to the hospital length of stay (LOS) and more than $15,000 to the total health care cost, according to a study presented at the American Society of HealthSystem Pharmacists Summer Meeting (poster 18-T - ). Fluid overload is a serious condition that can affect many organs and systems in a person’s body, including the heart, lungs and kidneys (Hemodial Int 2010;14:348-354). It also is associated with cardiac and renal dysfunction that can lead to a continuous treatment cycle in order to properly manage patient needs (Pediatr Crit Care Medd 2014;15:131-138). Researchers at Smiths Medical, a global provider of medical devices, conducted a study to determine the potential burden of illness of fluid overload and the resulting effect on U.S. health care and pharmacy dispensing. The retrospective cohort study was designed to improve understanding of the potential benefits of conservative fluid management, such as small-volume, maximally concentrated IV solutions delivered via a syringe pump, in contrast to current medication modes of delivery. The study was carried out using information from the Premier Healthcare Solutions (a large group purchasing organization) research database. Subjects consisted of adult patients with a hospitalization that included time in an ICU, central line placement, the administration of an IV loop diuretic and at least two medications from a list of commonly used continuous infusions for at least 50% of ICU days. The database generated 63,974 directly matched patients in each of the fluid overload and comparison cohorts. The fluid overload cohort had an average of 56.7% higher overall hospital costs per visit ($42,368 vs. $27,042), 92.7% higher ICU costs ($10,902 vs. $5,659), and correspondingly longer hospital (11.5 vs. eight days) and ICU LOS (6.2 vs. 3.6 days). These patients also had higher rates of mortality (20% vs. 16.8%) and 30-dayy readmission (21.82% vs. 21.28%) than the comparison group. The researchers also reviewed a subset of common continuous vasopressor medications used in the study, and compared the daily fluid savings from the maximal concentration as opposed to a commonly used standard concentration for patients of average weight and dosage. Fluid savings varied from 460 mL (nitroprusside) to as much as 8,294 mL (epinephrine) per day for the medications reviewed, and patients were required to have at least two of the study medications during their ICU stay. Contributing Factors The results underscore the fact that medication administration can contribute significantly to a patient’s daily fluid intake, according to primary study author Debbi Child, PharmD, BCPS, a clinical resource specialist at Smiths Medical. Dr. Child also pointed to practice patterns that may contribute to fluid overload. “While medication delivery models vary between institutions, it’s common that

continuous medications for U.S. adult ICUs are provided in premixed dilute formulaations,” she said. “Physicians typically order the drug an nd dosaage, but cannot specify the concentration ... that is preddetermined by the pharmacy. While the drug fl fluid voolume is documented in the patient’s chart by nursin ng, this intake is not easily controlled by physicians andd can add to a patient’s daily fluid intake.” When thinking about measurres to prevent fluid overload, it’s important to remeember that fluid is a drug with a therapeutic win ndow, and that dosing rates should be individualized to the goals of therapyy, the clinical scenario and the severityy of illness, noted David Askenazi, MD, direc-tor of the Pediatric and Infant Centerr for Acute Nephrology, Children’ss of Alaabama/University of Alabama at BirrThe retrospective cohort mingham. “It’s generally recognizeed thatt fluid resuscitation improves outtcomes study was designed to early in [patients with] shock,,” said Dr. Askenazi, who was not invvolved improve understanding in the Smiths Medical study. Hoowever, of the potential benefits once the patient moves beyondd that acute phase, caregivers need to keeep in of conservative fluid mind that “how we prescribe fluid can have a direct impact on excesss fluid management, such as accumulation.” One way to keep that small-volume, maximally accumulation in check, he notedd, is to concentrate medications and minimizee concentrated IV solutions IV fluids based on nutrition goals.. It’s also important for phyysicianss delivered via a syringe to “trend the patient’s cumulatiive perrpump, in contrast to cent fluid balance,” Dr. Askenaazi saidd. “This critical vital sign can quaantitatee current medication the degree of fluid overload at on ne timee point, and perhaps more impoortantlyy, modes of delivery. provide insights to where the pattient is heading.” Increasing Awareness The knowledge gained from the current study has helped define the buurden of illness and the patient poppulatioon most at risk (i.e., cardiac) from fluid overloadd, Dr. Child pointed out. Although further research is needded, she noted, the study could yield an immeddiate beenefit—that is, increased awareness of the synddrome. If physicians become more proactive about fluiid overlload as a result, that change “holds promise to deecrease length of stay and costs, and improve patient outcomess.” —Paul Bufano Dr. Child is a full-time employee of Smithss Medicaal, which manufactures the Medfusion syringe pump mp. Her coo-authors are employees of Premier Healthcare Solutionns and reeceived funding from Smiths Medical for this study. Dr. Asskenazi iss on the speaker’s bureau of Baxter/Gambro Renal.

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POLICY & MANAGEMENT

Team Creates Protocol for Handling OR Emergencies Salt Lake City—The worst moments in the operating room, according to surgeon David Earle, MD, are the quiet ones that settle in during intraoperative emergencies, when seconds drag on for minutes and minutes for hours. “Anyone involved in a surgical procedure knows those times, particularly when the patient is bleeding, the

room is quiet, and the team is waiting for the circulator to return with the appropriate supplies and equipment,” said Dr. Earle, director of minimally invasive surgery at Baystate Medical Center, Springfield, Mass. Dr. Earle believes that those moments should not occur. Operating room (OR) teams can prevent them by having a practiced plan of action for

emergencies, similar to those for cardiac arrest and fire, he said. “All hospitals have codes for those emergencies, but almost none have formalized protocols for dealing with high-riskk intraoperative emergencies. “When there is an urgent, unexpected change in the operative plan, even the best teams are strained to perform efficiently, and that’s precisely

when peak performance of the team is essential.” He and his colleagues developed a protocol for intraoperative emergencies. Over several months, the team simulated emergencies in the OR to figure out what is needed during these events. The mock operations were videotaped and assessed by all members of the OR team. After extensive debriefs of the videos, the team created a protocol known as C-STAT. T The keystone of the C-STAT protocol is a rapid technical response team that can be summoned to the OR in an emergency. When an emergency alert is sounded, any OR staff not currently performing a critical patient care duty is expected to stop what they are doing and attend. The primary circulating nurse quickly assigns roles to the first people to arrive. To eliminate confusion about who is responsible for what, every member of the rapid response team carries a card tucked into the back of his or her hospital identification badge. The card outlines the assigned tasks for every person on the C-STAT team. For instance, the first nurse who comes to the OR and assumes the role of C-STAT RN sees the following on the back of his or her card: responsible for ordering blood and setting up additional equipment. As members of the C-STAT team assume their duties, the primary operative team stays focused on the immediate needs of the operative field, said Dr. Earle, who presented details of C-STAT at a panel session on patient safety during the 2014 annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons. The C-STAT protocol takes confusion out of emergencies, said Diane Betti, MSN, RN, CNOR, director of the Daly OR, who helped develop the program. “When there’s an emergency, the first thing that happens is everybody’s attention is diverted away from the operative field just at the critical time when everybody’s attention needs to be on the patient. “Now, there’s an increased ability to focus on the operative field because everyone in the room knows exactly what needs to be done,” Ms. Betti said. Based on the results of their simulation exercises, the Baystate group also developed a conversion pack for cases that require switching from

SEPTEMBER 2014

AnesthesiologyNews.com I 29

CORRESPONDENCE laparoscopic to open surgery. “It’s crazy that a conversion pack didn’t exist before, that we were running around every single time,” Dr. Earle said. “But I don’t think it’s that uncommon.” Emilia Scala, RN, CNOR, service coordinator for Baystate operating rooms, said the C-STAT team typically gets called about once a month. “We had an activation last week. … We were nearing the end of a long operation on a patient with a pancreatic tumor. There was tumor stuck to an artery, and the patient started bleeding. We called for the C-STAT team, and everyone knew exactly what to do,” Ms. Scala said. The C-STAT team has been in existence at Baystate for about seven years. For that period, they have not tracked activations, patient outcomes and staff satisfaction with the program. But even without supporting data, other surgeons say there is a role for programs like C-STAT. T “You don’t need to spend a lot of [research] dollars to understand that a team that’s practiced, rehearsed what they are going to do and are geared up together to address problems are going to be better than the folks caught off guard trying to manage that same situation in an operating room,” said Daniel B. Jones, MD, professor of surgery at Harvard Medical School, Boston. In a crisis, OR team members often have different ideas “of what needs to be done next, where the supplies are, who is doing what,” Dr. Jones said. “But by practicing the drills, orchestrating the team, they are able to respond like Navy Seals in a very coordinated fashion. More likely than not, it would achieve a higher level of care.” Anne Lidor, MD, MPH, associate professor of surgery at Johns Hopkins Hospital, Baltimore, said all hospitals should have programs like C-STAT and practice regularly, “just like we do for trauma and [advanced cardiovascular life support].” But it poses a major challenge to take these programs from concept into reality, she added. “This is something that people should think about and should do. But how to initiate it, how to get people to buy into it—that’s another story. It’s not just surgeons that need to be onboard. It’s everybody in the OR: nurses, techs, OR assistants. You’d have to have a lot of people willing to participate, and you need some sort of impetus to get this done.”

To the Editor: David Wild’s article about new legislation governing sterile compounding (“Does bill have enough muscle to stop another NECC?” Anesthesiology News, April 2014, page 8) leaves out an important fact about Massachusetts, the very center of the New England Compounding Center tragedy. Although Congress passed the federal Drug Quality and Security Act earlier this year to strengthen oversight of the industry,

Massachusetts has yet to implement a new law. A bill has stalled in conference committee, inexplicably, for months. Lawmakers have not, contrary to Dr. Christian Hartman’s statement in the article, handed the state board of pharmacy more regulatory power. Massachusetts also has not sought to license nonresident pharmacies, which every other state except for Pennsylvania has had in place for at least a decade. Since the NECC tragedy, more than 100 pieces of legislation have been

introduced in other states, with many of them passing and now in effect. Legislative and regulatory changes in Massachusetts are important because of the particular history of NECC and the meningitis outbreak. The state should move quickly to enact and implement such changes. David G. Miller, RPh Mr. Miller is Executive VP and CEO of the International Academy of Compounding Pharmacists

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REFERENCES 1. Belena J.M. et al. Journal of Clinical Anesthesia 2011; 23:456-460. | 2. Roiss M. et al. Poster presented at The American Association of Anesthesiologists Annual Meeting 15th -19th, Oct. 2011, Chicago. | 3. Sharma V. et al. BJA 2010; 105(2): 228-232. | 4. Whitacre W. et al. AANA Journal 2014; 82 (2): 101-107. | 5. Abdi W. et al. Acta Anaethesiol Scand. 2010; 54 (2): 141-146. | 6. Bernardini A. et al. Anesthesia 2009; 64: 1289-1294. | 7. Verghese C. et al. Anesthesia and Analgesia 1996; 82: 129-133. | 8. Tretiak S. Anethesiology News 2009. | 9. Viernes D. et al. Anesthesiology News 2010; 9-13. | 10. Verghese C. et al. BJA 2008; 101 (3): 405-410. | 11. Jagannathan N. et al. Pediatric Anesthesia 2012; 22:759-764. | 12. Jagannathan N. et al Anesthesia 2012; 67(2): 139-144. | 13. Ferson D. et al. Anesthesiology 2007; 107:A592.

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CLINICAL ANESTHESIOLOGY ERAS

CONTINUED FROM PAGE 1

surgery and other disciplines. At the 22nd International Congress of the European Association for Endoscopic Surgery (EAES), Nader Francis, MBChB, PhD, and his colleagues presented an up-to-date review of ERAS in colorectal surgery, pinpointing factors that may allow surgeons to enhance and ultimately predict patient outcomes (abstract O074). “There are many features that impact patient outcomes and we don’t necessarily know which are the most relevant to recovery,” said Dr. Francis, consultant colorectal surgeon at Yeovil District Hospital, in Somerset, England. “Our ongoing research is working to uncover the key factors in perioperative care.” Although no standard ERAS protocol yet exists in colorectal surgery, most include formal patient education, eliminating bowel preparation and allowing clear fluids up to three hours before surgery. Intraoperatively, studies show that laparoscopic surgery, goal-directed fluid management, less operative time and reduced blood loss aid patient recovery ((JSLSS 2014;18:265-272). Postoperatively, the use of thoracic epidural analgesia, avoidance of nasogastric tubes, and early feeding, mobilization, discontinuation of IV fluid and removal of urethral catheters are important features as well (Ann ( Surg 2000;232:51-57). Despite the lack of consensus, a growing body of research shows that employing ERAS principles reduces hospital length of stay and complications in colorectal surgery (Ann ( Surgg 2000;232:51-57; Br J Surg 2006;93:800-809; Anesth Analg 2014;118:1052-1061). For instance, in a 2014 study comparing outcomes in a traditional care (99 patients) and ERAS group (142 patients), Julie Thacker, MD, and her colleagues at Duke University Medical Center, Durham, N.C., found that patients following an enhanced recovery protocol had a significantly shorter length of stay (five vs. seven days; P<0.001), fewer urinary tract infections (13% vs. 24%; P=0.03), reductions in duration of ileus and lower readmission rates (9.8% vs. 20.2%; P=0.02). The Duke enhanced recovery protocol was also associated with lower medical costs, about $2,000 per patient or a 10% decrease in the costs of traditional care. “This reduction in cost is a huge bonus for patients and the health system,” said Dr. Thacker, assistant professor in the Department of Surgery. “It could save hundreds of thousands of dollars a year and would require minimal to no extra costs for hospitals to realize.” But, given the abundance of perioperative factors being studied and the complexity of different health systems, ERAS can be difficult to implement. In a 2012 study (Colorectal Dis 14:e727-e734), Dr. Francis and his colleagues retrospectively analyzed outcomes of 385 patients who underwent elective laparoscopic or open colorectal resection at Yeovil District Hospital between 2002 and 2009, and found that 31% of patients stayed more than one week (delayed discharge), and 41% deviated from the ERAS protocol. The authors concluded that failing to comply with ERAS one day

‘[The enhanced recovery protocol] could save hundreds of thousands of dollars a year and would require minimal to no extra costs for hospitals to realize.’

United States has also seen varied success. In the United Kingdom, hospitals are encouraged to adopt enhanced recovery for colorectal surgery, and their payment schemes are tied to protocol compliance. “Over the last 10 years, we’ve seen an amazing spread of ERAS,” Dr. Francis said. “The program now exists in every hospital in England.” But looking beyond the United Kingdom to the rest of Europe and the United States, ERAS is not —Julie Thacker, MD taking hold as quickly. “National mandates, transparent audits and government-funded implementation efforts in the U.K. create a very different after surgery was strongly associated with delayed picture than surgeon and anesthesiologist-driven discharge. work in the U.S.,” said Dr. Thacker. “Trying to In a recent analysis, Dr. Francis and his colleagues change a little bit about everything included in tried to determine what factors cause patients to perioperative care in the U.S. is extraordinarily deviate from an enhanced recovery protocol. After challenging.” prospectively collecting data from 178 patients who Part of the difficulty is that each hospital in the had undergone open or laparoscopic colorectal sur- United States has different capabilities and guidegery between January 2006 and December 2009, lines, which means the challenges to implementing the surgeons found that of the 32% of patients an enhanced recovery protocol will vary by hospital, who deviated from the program, the most com- Dr. Thacker noted. mon reasons cited were failure to mobilize after Despite these complex barriers, Dr. Thacker has surgery (80.7%), continued use of IV fluids beyond started to garner support from surgical societies 24 hours (59.7%), failure to resume an oral diet throughout the United States. “The more inter(45.6%) and inadequate pain control (10.5%). est we get at the society and health system level, the The adoption of ERAS across Europe and the easier it will be to improve perioperative care.”

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Surgeons Say ‘No’ to Noncompliant Hernia Patients Las Vegas—Expert hernia surgeons are asking patients to adhere to strict preoperative regimens that include weight loss, smoking cessation and nutritional supplementation before surgery. If patients fail to comply, surgeons say they will not operate or will postpone surgery, contending that the risks for infection or failure are too high. “I make a deal with patients: When we go to the operating room, I will be an A-plus and you will be an A-plus. That’s just non-negotiable. If they want to meet those goals, then we talk about surgery,” said Michael Rosen, MD, a hernia surgeon and professor of surgery at Case Western Reserve University, in Cleveland.

priority to weight loss and smoking cessation. “We have protocols in place, particularly pertaining to smoking and achieving optimal weight loss before proceeding to surgery,” said Brent D. Matthews, MD, AHS president and professor of surgery and chief

‘If we can get the patient optimized, we will wait to get them optimized. That’s one thing people miss— just because you can do a component separation, doesn’t mean you should [do it] right away.’

Science University, Portland. “We don’t use all of them on everybody. We prioritize them.” It is a practice that falls into a longstanding controversy in general surgery: Is a surgeon ethically obligated to operate on a noncompliant patient? Last January, Frederick Greene, MD, the chief medical advisor for General see Hernia page 50

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Dr. Rosen was one of a group of hernia surgeons who spoke at a panel session during the 2014 annual meeting of the Americas Hernia Society (AHS). All six panelists said they have adopted preoperative protocols that require patients to comply with various steps before surgery. When Dr. Rosen meets with a patient for the first time, he limits the conversation to a discussion of the patient’s smoking habits and obesity. “We don’t talk about the operating room. We don’t talk about any of that. Without those two things, you don’t get to go to the next step. We talk about goals. We achieve those goals. It’s simple to me.” He sees the patient again three months later. Then, provided the patient has quit smoking and lost the recommended amount of weight, he will discuss surgical options. Not all surgeons focus on the same processes, although most gave high

of minimally invasive surgery, Washington University School of Medicine, St. Louis. “We have a whole series of protocols for patients,” said Robert Martindale, MD, PhD, professor of surgery and chief of general surgery at Oregon Health &

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PAIN MEDICINE ‘On the Spot’: Agree or Disagree?

The State of Palliative Oncology Care in the U.S. “On the Spot” is an occasional feature in which a panel of experts is asked to agree or disagree with a series of questions. This time we focus on palliative care, which has evolved considerably over the past 20 years. But, according to those who shaped this growth, there is still work to be done.

I would like to extend my thanks to all of the contributors as well as to Betty Ferrell, RN, PhD, professor and research scientist at City of Hope and editor-in-chief of Journal of Hospice & Palliative Nursing, for sharing her perspective from 35 years in oncology and palliative care medicine. Dr. Ferrell is a

fundamental part of the history of the palliative care movement and has been repeatedly recognized as such, most recently by being named as one of the 30 most influential leaders in hospice and palliative care medicine. —Colleen Hutchinson

P ARTICIPANTS Amy Abernethy, MD, PhD Hematologist/oncologist, palliative care physician, and Director, Duke Center for Learning Health Care Duke University Durham, North Carolina

R. Sean Morrison, MD Director, Hertzberg Palliative Care Institute and National Palliative Care Research Center, Mount Sinai Hospital New York, New York

Porter Storey, MD Executive Vice President American Academy of Hospice and Palliative Medicine Denver, Colorado

Kimberly Bower, MD Clinical Medical Director, The Institute for Palliative Medicine, San Diego Hospice San Diego, California

Timothy Quill, MD Gosnell Distinguished Professor of Palliative Care, University of Rochester Medical Center, Immediate Past-President, American Academy of Hospice and Palliative Medicine Rochester, New York

Jamie Von Roenn, MD Professor of Medicine, Northwestern University Senior Director of Education, Science and Professional Development American Society of Clinical Oncology Chicago, Illinois

Thomas Smith, MD Director of Palliative Medicine Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore, Maryland

Susannah Ellsworth, MD Radiation Oncologist Johns Hopkins University Baltimore, Maryland

Gail Austin Cooney, MD President, Hospice Medical Director Certification Board, American Academy of Hospice and Palliative Medicine West Palm Beach, Florida

Although the Institute of Medicine (IOM), in its recent guidelines, and the U.S. health care system in general have evolved appropriately in terms of recognizing the legitimate need for palliative care in oncology over the past couple of decades, and great strides have been made in palliative care development and standardization, barriers exist that make the implementation of current guidelines and recommendations unrealistic.

medical centers, the variation in implementation in both domains is very wide, and the farther outside of these academic centers one ventures, the more uneven the availability and presence of primary or secondary palliative care become.

patient’s health in the context of the patient’s life circumstances and values. This approach is time-intensive and requires an interdisciplinary team. It is effective in ensuring that the patient’s goals and values are driving the medical treatment plan and that everything possible is done to maximize not only the length of a patient’s life but also the quality of the patient’s life. This approach often increases patient satisfaction and leads to better utilization of limited health care resources. Despite these advantages, in a fee-for-service medical model that pays better for procedures than for face time with patients, reimbursement alone is not adequate to support the growth of palliative medicine programs. With each additional palliative care service that is added, the cost of the program to the institution increases. If cost avoidance is not taken into account, then the larger the palliative care program becomes, the more money it appears to lose.

Jamie Von Roenn, MD: Disagree. It is difficult but possible even in the current environment. There is the misperception that integrating palliative care is unrealistic because “it takes too much time.” Some simple strategies that add little time to routine office visits include the use of brief symptom assessment tools and triggers for palliative care/hospice referrals. Furthermore, structured prognosis and goalTimothy Quill, MD: Agree. The two biggest settingg conversations have been documented to take barriers to implementing these guidelines are the less time than many clinicians anticipate. lack of standardization of required training and quality measurement in these domains for all oncologists—both trainees and those already in practice— Kimberly Bower, MD: Agree. Many of the curand the lack of adequate numbers of palliative care rent barriers to the implementation of palliative care Gail Austin Cooney, MD: On the fence. I specialists to help care for the more challenging programs are financial. Palliative medicine is a high- have to say “on the fence” because implementapatients and to help train all oncology practitioners touch field that requires physicians to step back in tion is challenging but not unrealistic. Two of the in primary palliative care. Even among academic order to see all of the factors that are affecting a see Palliative page 34

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greatest barriers to implementing successful palliative care are time and money. Physician time is a limited commodity, and excellent communication takes time. Additionally, palliative care is grounded in the concept of interdisciplinary care, but usually only the physician or physician-level provider is able to bill. The payor systems in the United States compound this problem by focusing on payment for tests and treatments—a curative model of care that does not meet the needs of many patients and families with potentially life-limitingg disease. Amy Abernethy, MD, PhD: Agree. More palliative care is needed in oncology—there is clear consensus from the IOM, health system executives, the American Society of Clinical Oncology (ASCO), guideline statements, oncologists, patients and caregivers. But the impediments are real. For the oncologist, not only is it a problem of needing basic palliative care skills and tools, there is the reality of multiple competing demands: The same person is expected to manage complex biology, a dizzying array of new biomarkers and drugs that expands daily, comorbid illnesses, financial hardship of patients, data and information overload, shifting regulatory expectations, a busy clinical practice and the complex emotional and symptom landscape of advanced cancer care. It is simply hard to fit it all in. Meanwhile, adding more palliative care specialists isn’t very feasible either. Reimbursement challenges make it hard to adequately pay for palliative care; quite simply, this needs to be fixed. But, even if we fix reimbursement, there simply aren’t enough palliative care specialists—nor specialists in training—to be able to fill the expanding gap. We need new models for palliative medicine education and training, for example, mid-career pathways; expansion of the palliative care discipline to diverse kinds of providers such as physician assistants; and tools to support efficiency in palliative care practice, such as health information technology, just to name a few.

It is offered simultaneously with life-prolongingg therapies for individuals living with serious or complex illness. Over the past decade, we have seen dramatic growth in the numbers of palliative care teams such that 66% of all American hospitals and almost 90% of those with more than 300 beds report having palliative care teams. A solid business case exists for the integration of palliative care teams in hospitals and cancer centers, and new successful models of communityy basedd palliative care have been developed but need dissemination. What then are the barriers? First, we need to develop an adequate workforce—all cancer clinicians need to be trained in the fundamentals of palliative care. Educational materials exist—they need to be disseminated. Second, we need to enhance the evidence base. To date, the National Cancer Institute spends less than 0.5% of its annual research budget on palliative care—this needs to change, and funds need to be reallocated. Third, we need to disseminate existing successful models of palliative care—models exist, they need to be implemented. Fourth, we need a public education campaign. A recent national public opinion survey revealed that more than 95% of the American public wanted palliative care for their loved ones when informed about it; however, only 8% knew what it was. Porter Storey, MD: Agree. Oncology and hospital programs are integrating palliative care, but there are few trained professionals to meet the needs of these expanding programs. Astronomical costs of newer chemotherapy agents are draining crucial resources from oncology programs that could have been used for palliative care programs. Radical cuts to hospice reimbursement are denying hospice care to patients with a few months to live. Palliative care teams are scrambling to fill these gaps.

Susannah Ellsworth, MD: Disagree. The evidence base for palliative medicine is expanding rapidly, as is the number of physicians with formal training in palliative medicine. One of the most important barriers to more widespread use of palliative care is a lack of access, with access to care varying depending on geographic area, health care R. Sean Morrison, MD: Disagree. Palliative care business models and referral patterns. However, a is a relatively new interdisciplinary specialty that has growing number of trained palliative care practiemerged in response to the unmet needs of patients tioners will increase access, although this will take with serious illness and their families. Palliative care, time, and an increasing awareness of the value of delivered by teams comprised of doctors, nurses, social palliative care will broaden the referral base and workers, chaplains and child life specialists (when increase the acceptance of palliative care in the appropriate), focuses on relieving suffering and achiev- community. ing the best possible quality of life for patients and their caregivers. It is appropriate at the point of diagnosis of a serious illness. Thomas Smith, MD: Agree. There aren’t Palliative care goes beyond hospice care to offer enough hospice and palliative medicine docs and patients and their families treatments focused on nurse practitioners. But even with five randomized improving quality of life while they are receiving life- controlled trials showing benefit, less than 10% of prolongingg and curative treatments. It involves symp- lung cancer patients get referred to palliative care, tom assessment and treatment; help with decision and usually only for end-off life care in the last two making and establishing goals of care; practical sup- weeks. The barriers are oncologists who never refer; port for patients and their caregivers; mobilization of families who won’t accept that their loved one community support and resources to assure a secure could possibly die from this; patients who won’t and safe living environment; and collaborative and accept that medical science cannot cure everything; seamless models of care (hospital, home and hospice). patients and families who would prefer to avoid the

tough issues, hoping they will go away; and insurance companies that won’t reimburse. Better implementation is possible, probable even, with education.

Dr. Van Roenn: Agree. We can’t do what we don’t know how to do. Physicians want to do what’s best for their patients. Skill in communication promotes greater understanding of patient– family concerns, clarity with regard to goals of care and a richer doctor–patient relationship. Recognizing and treating symptoms effectively, regardless of the goals of care and prognosis, leads to a better patient–family experience. Dr. Bower: Agree. Part of the role of palliative medicine is to change the culture of medicine so that skillful communication with patients is valued as highly as skillful disease management, and so that treatment plans are based on achieving patient goals as opposed to being based on attempting to fix individual organ systems. Didactic teaching alone may have minimal effect on providers’ behavior, but didactic teaching in combination with role modeling by palliative medicine specialists will gradually improve other providers’ palliative care skills. As other providers’ skills in primary palliative medicine improve, palliative medicine subspecialists will be able to focus on treating the most complex patients. Additionally, as providers become more familiar with the positive effects that palliative medicine can have in the management of their patients, they will demand better access to palliative care services. As demand grows, administrators will be more likely to invest resources in the implementation of palliative care services. With advancements in medicine, we are able to extend the lives of sicker and sicker patients. In this context, the need for palliative medicine will only continue to grow. There will never be enough palliative medicine specialists to meet the demand for palliative care services, so part of the mandate of palliative medicine specialists is to train other providers in primaryy level palliative care. Dr. Smith: Education never killed anyone, but it rarely changes practice. Better results change practice. Making oncologists’ lives easier and better changes practice. The first time an oncologist has a good referral—“they really solved his apathy and depression”—or gains some time, then they start referring more. The benefits to the patient and family are a real bonus. Dr. Quill: Agree. The one caveat being that although pain and symptom management may be teachable in large-group formats with a mix of didactic presentation and then practice calculations on representative cases, the teaching of the requisite communication skills is much more see Palliative page 36

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challenging. The latter requires practice in observed small-group learning situations, using role play, interview of standardized patients and observation in real time with actual patients. The rate-limitingg parts are protecting enough time for the clinicians to practice, and developing and supporting oncology and palliative care clinicians with the key associated communication skills. Such training is critical but labor-intensive. On the other hand, we do not let surgeons operate without demonstrating high-level skills under supervision, and the same should be said about having such critical conversations with patients and families facing difficult oncologic decisions. Dr. Cooney: Disagree. Sadly, there’s very little evidence to support changing practice through education. The focus needs to be on changing our systems of care.

inadequately treated physical distress; fragmented care systems; poor communication between doctors, patients and families; and strains on family caregiver and support systems. Indeed, the recently published Institute of Medicine report, “Delivering HighQualityy Cancer Care,” concluded that “cancer care often is not patient-centered, many patients do not receive palliative care to manage their symptoms and side effects from treatment, and decisions about care often are not based on the latest scientific evidence.” It is clear that if we’re going to improve the care of persons living with cancer and their families, we will require a workforce that can provide specialistlevel palliative care to the most complicated patients through palliative care teams and primary palliative care—routine pain and symptom management, goals of care discussions and assistance with community resources—through the primary cancer provider.

Dr. Smith: Agree. I never got any training during hem/onc training. Most of us don’t have specific ways Dr. Abernethy: Agree. Basic palliative care educa- of doing goals-off care discussions, don’t use a symption will help. Why do I say that, when I just said that tom assessment tool and don’t inquire about spiritual the oncologist is too busy anyway? Efficiency comes needs. And we refer too late to hospice or not at all. when things are second nature. I always say that you Less than half of cancer patients died with hospice last need your palliative care skills in your “hip pocket,” so year. After 40 years of hospice showing patients receivthat you can pull them out at a moment’s notice with- ing better care and maybe even living longer—c’mon, out really thinking too hard about it. For example, folks, we can do better. Communication 101: How are you going to structure the conversation to confidently and safely present bad news? Or, do you know the starting dose for mor- Dr. Abernethy: On the fence. Cancer care prophine to manage shortness of breath? Have you prac- viders are just like the rest of us: They have an uneven ticed this enough times that it is second nature and skill base, and this time the patchwork is palliative care you don’t have to think about it? So, yes, education skills. I find that oncologists generally are motivated and interested in making sure that they have the basic can help. Education also provides confidence—confidence to tools—for example, communication skills and pain be ready to acknowledge, intervene and help, as well management—even if every oncologist is not prepared as to know when to call in the specialist palliative care with those tools. They have formed close bonds with doctor. Often, this is what patients and families want their patients, and it is hard to transition care to somemost—a sense of their doctor’s confidence in how to one else just because times are tough and the disease manage the situation and help keep the patient and has progressed. family safe, even in very difficult circumstances. That being said, oncologists that I meet are interested in having input from specialist palliative medicine providers as an “extra set of eyes” when the Cancer care providers currently are situation is complex; in my experience, younger practrained and educated inadequately to titioners who have been trained at a time when palliaprovide primary- and secondary-level tive care has been more commonplace are more willing palliative care across the trajectory of to request palliative care help. The ground is fertile cancer care. for oncologists to provide primary palliative care, and when available, transition patients to specialists for complex cases. There is the opportunity to expand the Dr. Morrison: Agree. In the United States, approx- skill base in basic palliative care skills for the oncoloimately 14 million people have had cancer and more gist so that everyone has the basic tools. This way we than 1.6 million new cases are diagnosed each year. can ensure that there is a consistent knowledge base By 2022, it is projected that there will be 18 million for oncology that extends beyond basic pain managecancer survivors and, by 2030, cancer incidence is ment to include the enlarging basis of primary palliaexpected to rise to 2.3 million new diagnoses per year. tive care knowledge. Although medical advances have transformed cancer into a disease that people can live with for many years, they have not been accompanied by corresponding Dr. Von Roenn: Agree. Despite favorable physiimprovements in quality of life for these patients and cian selff assessments of their knowledge in primary their families. Living with or surviving cancer should and secondary palliative care, multiple examinations of not mean living in pain or experiencing distressing their skills, as reported in the Journal of Clinical Oncolsymptoms. ogy and other journals, have noted a lack of adequate Abundant evidence suggests that the advanced proficiency in initiating and titrating opioids, treatstages of cancer for most are characterized by ing common treatment- and cancer-relatedd symptoms,

timely referral to hospice and accurate communication about prognosis. Furthermore, the majority of oncology training programs do not have required rotations in palliative medicine and the majority of fellows do not receive formal feedback assessing their skill in communicating difficult news or leading family meetings. Dr. Ellsworth: On the fence. Although resources exist to support oncologists who wish to obtain midcareerr training in palliative medicine, this training can be time-consumingg for practitioners who already have many competing scheduling demands. Furthermore, current oncology practice models do not always support practitioners’ efforts to obtain this training or to devote additional clinic time to providing palliative care hand in hand with cancer care. Creative solutions are needed to support oncologists in obtaining additional palliative care training and taking the time to implement it in the clinic setting. Dr. Cooney: Agree. Oncology training programs now include exposure to palliative care concepts, but I do not believe that it is sufficient to enable most oncologists to provide the generalist palliative care interventions that their patients need, including open and honest communication about prognosis and treatment options, setting of appropriate goals and symptom management. Oncologists should not be expected to provide secondary, specialist-level palliative care. Rather, they must recognize when it is needed and ensure that, within their health care system, this care is available to their patients and families. Dr. Quill: Agree. All oncology providers should be trained to provide basic palliative care, which should include basic pain and symptom management, basic discussions about prognosis, the risks and benefits of oncologic treatments and lack of efficacy of CPR [cardiopulmonary resuscitation] in the presence of severe oncologic illness. More complex symptom management and difficult medical decision making should more often be the domain of specialty palliative care. Teaching oncologists about the basic communication skills needed to inform and support cancer patients is much more challenging than basic symptom management because it requires practice in an observed environment over time. Excellent programs such as Oncotalk have been developed, and many recent oncology trainees have been exposed to it, but there remain large numbers of oncology practitioners and trainees who have never been taught basic symptom management or been observed having these discussions with patients and families. Dr. Storey: Agree. The administration of chemotherapy and radiation are complex and these areas demand close attention. Comfort, quality of life and family support can become secondary concerns but are very important to the patient and family. Palliative care providers often enable patients to tolerate lifeextendingg therapies by addressing these concerns. see Palliative page 38

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patients and care for patients through the end of life. Although many oncologists can provide primary-level Dr. Bower: Agree. Cancer provid- palliative care, they deserve the supers vary in their interest and aptitude port of palliative medicine specialists in providing palliative care. Most in managing patients who have a sigproviders received minimal exposure nificant symptom burden, refractory to palliative medicine in their train- pain or a prognosis that is uncertain ing, yet do a significant amount of or poor. Oncologists are busy enough primary-level palliative care as they keeping up with advancements in manage the multitude of symptoms oncology and designing treatment associated with cancer and its treat- plans for complex patients. It is ment, discuss treatment options with unreasonable to expect them to also CONTINUED FROM PAGE 36

have an expertise in the management of the most complex refractory symptoms, and it is imperative that patients’ symptoms are not ignored but instead are managed just as aggressively as their underlying disease. Colleen Hutchinson is a medical communications consultant based in Philadelphia.

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atients visiting a clinic for an injection to relieve their pain or for chemotherapy probably don’t expect to leave with a new condition like hepatitis, but it is a scenario that thousands of patients have already lived through. Since 2001, at least 49 outbreaks have occurred due to the misuse of injectable medical products, according to the Centers for Disease Control and Prevention (CDC). Despite this, adverse events related to unsafe injection practices and lapses in infection control practices remain underreported, making it difficult to measure their actual occurrence. To raise awareness of the issue, the Joint Commission released a Sentinel Event Alert (bit.ly/1qlnbn4) to educate health care organizations and health care workers about the risks associated with mishandling vials of injectable medical products. The alert describes the factors that contribute to the misuse and recommends strategies for improvement. The problem primarily involves the reuse of single-dose vials, which are only intended to be used once. These vials typically lack preservatives; therefore, using them more than once carries substantial risks for bacterial contamination, growth and infection. According to the CDC, adverse events caused by this misuse have occurred in both inpatient and outpatient settings. In outpatient settings, a high percentage happened in pain management clinics where injections often are administered using preservative-free medications, and in cancer clinics providing chemotherapy or other infusion services to immunocompromised patients.

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PAIN MEDICINE

Small Study Finds Off-Pump Surgery Reduces CABG Pain

iven the proposed association between inflammation and chronic persistent pain, offf pump surgery may hold certain benefits for patients undergoing coronary artery bypass graft (CABG). This hypothesis seems to have been borne out in an unpublished pilot study by a Japanese research team, which concluded that postoperative chest and forearm pain were significantly greater in patients undergoing on-pump surgery than their offf pump counterparts. “About half of patients who undergo cardiac surgery suffer from persistent postoperative pain,” said Kimito Minami, MD, a consultant anesthetist at the National Cerebral and Cardiovascular Center in Osaka, Japan. “Current research suggests there is an association between inflammation and persistent pain. During cardiac surgery, cardiopulmonary bypass induces intense inflammation, so we studied prospectively whether cardiopulmonary bypass affects the severity of postoperative persistent pain.”

forearm pain (on-pump 3.50±2.95 vs. offf pump 1.95±1.79; P=0.208). On postoperative day 7, however, VAS chest pain was significantly greater in on-pump patients (4.95±3.01 vs. 2.68±1.72; P=0.045); there was no significant difference in VAS forearm pain at the same point (3.08±3.58 vs. 2.30±1.93; P=0.208). One month after surgery, both VAS chest pain

scores (4.06±1.92 vs. 1.69±1.96; P=0.028) and VAS forearm pain scores (2.00±1.08 vs. 0.50±0.80; P=0.021) were significantly greater in on-pump patients. “The use of cardiopulmonary bypass could be one reason for the higher VAS scores,” Dr. Minami said. “Quite a few studies have shown that inflammation and postoperative

persistent pain are strongly associated,” he said. “For example, a Danish nationwide cohort study showed that patients who are taking immunosuppressant medication after graft transplantation have more moderate to severe persistent pain than nontransplant patients. “Large-scale studies have failed to see Off-pump page 46

Postoperative chest and forearm pain were significantly greater in patients undergoing on-pump surgery than their offpump counterparts. The researchers enrolled 21 patients into the trial; participants were undergoing elective on-pump (n=10) or offf pump (n=11) CABG surgery. Patients completed a pain questionnaire at one day, seven days and one month after surgery; entries assessed the intensity of the chest and forearm pain using an 11-point visual analog scale (VAS). Study participants all had internal thoracic artery harvesting; six onpump and 10 offf pump patients also had radial artery harvesting. Although the groups were demographically similar, operation, anesthesia and cardiopulmonary bypass times were significantly longer in on-pump patients. On postoperative day 1, there was no significant difference in VAS between groups with respect to chest pain (on-pump 6.00±2.99 vs. offf pump 3.85±2.43; P=0.111) or

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Pain Care Improving in Hospitals, but Slowly and Minimally

ain management in hospitals is improving across the board, but not as much as might be hoped, according to the results of a study pending publication. The study found a statistically significant increase in patient satisfaction with pain care in governmentowned, for-profit and nonprofit hospitals between October 2006 and March 2012, but also found that this increase did not keep pace with other improvements, such as patient satisfaction with overall care. The study examined data collected from more than 1,800 hospitals by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, created by the Centers for Medicare & Medicaid Services (CMS). The survey asks patients 27 questions about their experiences while hospitalized. The 2012 survey results indicated that, on average, hospitals were able to “always” control a patient’s pain 70% of the time, an increase of 2.54% from 2008, when the results were first published. By comparison, the other dimensions measured by the HCAHPS survey, including the quality of communication with doctors and nurses and staff responsiveness, improved by 4.49%. “Essentially, the data show that there’s only a minor uptick in the

amount of patients who had significant improvements of their pain control during their hospitalization,” said Anita Gupta, DO, PharmD, principal investigator of the study and vice chair of the Division of Pain Medicine and Regional Anesthesiology at Drexel University College of Medicine, in Philadelphia. “With the increasing amount of pain physicians who are being trained in the treatment of acute and chronic pain, and in addition, the increasing advocacy related to the treatment of pain and chronic pain, the expectation would be to see more significant improvement with patient satisfaction. “Overall, a majority of patients in the hospital setting are still moderately satisfied with their pain control, but we can certainly do better,” Dr. Gupta added. These results extend a 2009 study by Dr. Gupta and her colleagues published in the Journal of Pain Research (2009;2:157-164), that examined the first round of data from the HCAHPS survey. The relatively modest level of improvement in patient satisfaction with pain care may indicate a need for increased initiatives for advocacy, research and education in the management of both acute and chronic pain, Dr. Guptaa said. “I intend to continue to study the

‘Overall, a majority of patients in the hospital setting are still moderately satisfied with their pain control, but we can certainly do better.’ —Anita Gupta, DO, PharmD

HCAHPS data over the next several years to see if improvements are being made,” she said. “Unless more stakeholders make significant initiatives and commitments in the treatment of pain, there likely will be minimal change in how patients perceive their pain during a hospital stay.” The study represents a good first step in helping anesthesiologists assess the quality of care that they provide, said John Dombrowski, MD, medical director of the Anesthesiologist Assistant Program and clinical assistant professor at Case Western Reserve University’s campus in Washington, D.C. However, he added that the survey data, although valuable, are inherently subjective, and objective measures also should be taken into account when assessing the quality of physicians’ work.

“Some patients will always say that they’re in pain because they want to get a certain feeling. And that’s just the way some patients can be in certain settings,” Dr. Dombrowski said. “We need to look at other measurements, like their blood pressure and their heart rate. If their blood pressure and heart rate are normal, they can’t be in much pain because these would be elevated.” Moreover, Dr. Dombrowski said, although the data provide valuable information to help anesthesiologists to improve their work, the HCAHPS survey also represents an attempt on the part of the government to cut costs. “In the world of government, nothing is about quality,” he said. “That’s the fig leaf they use. Everyone wants quality, including anesthesiologists— we all want to do good work. But for the government, it’s about cost containment or cost cutting. “That’s important right now, because the government is looking in terms of value-added services,” he continued. “If I’m paying you this money, you have to prove to me that you earned it in some way. That being said, we at the ASA [American Society of Anesthesiologists] are trying to find quality measures or tools that we can use, and this is a helpful tool.” —Ajai Raj

IV Acetaminophen a Cost Saver in Pediatric Tonsillectomy

dding IV acetaminophen to IV opioids for pediatric tonsillectomy can reduce costs by nearly $20 per case, a recent study has found. That might seem trivial, but with more than a half million tonsillectomies performed each year in the United States alone, the projected savings approach $9 million annually, according to the researchers, who presented their findings at Pediatric Anesthesiology 2014 (abstract OS2-93). The FDA approved IV acetaminophen (Ofirmev, Cadence) for use in 2010. “We started using it in many of our tonsillectomy patients, but there was a concern that it may not be cost-effective secondary to the associated costs,” said Rajeev Subramanyam, MD, assistant professor of anesthesia and pediatrics at the University of Cincinnati, who led the study. “When we examined the literature, we were surprised to find that there has not been a cost-effectiveness analysis on the use of IV acetaminophen in tonsillectomy patients.” Dr. Subramanyam and his colleagues compared the costs of treatment with IV opioids alone and a combination of IV acetaminophen and opioids. In all,

139 children under the age of 17 years were enrolled in the study. The researchers collected data on use of rescue analgesics and the incidence and treatment of side effects in the postanesthesia care unit (PACU). Cost calculations were based on the hospital’s 2013 purchasing contracts. Roughly 62% of children in the combination group required rescue analgesia, compared with 65.2% for those who received opioids alone. That difference was not statistically significant. The probability of not requiring rescue analgesia but still developing side effects was the same in both groups, at 34.8%. Dr. Subramanyam said there were 3.3% fewer rescue events with the combination treatment. Moreover, the combination strategy was found to cost $56.36, which was $17.12 less than the $73.48 for opioid-only treatment. Although medication costs were greater with the combination strategy, the lower total expenditure reflected less patient time in the PACU. However, the combination regimen was

cost-effective only as long as the need for rescue analgesics was lower for these patients than for those receiving opioids alone. As the probability of requiring rescue analgesics increased, the marginal costeffectiveness of the combination strategy decreased. “Based on sensitivity analysis, the incidence of postoperative pain has to be more than 36% for the IV acetaminophen to be cost-effective,” Dr. Subramanyam said. “Although the up-front costs of IV acetaminophen may be higher than the opioid-alone option, in our decision-analytic model the combination strategy resulted in cost savings nonetheless.” Dr. Subramanyam concluded that the routine use of IV acetaminophen as an adjunct to IV opioids should be considered for tonsillectomy with or without adenoidectomy in children under the age of 17. This strategy, he said, likely will reduce the need for rescue analgesia and, in turn, costs. The study was not funded by Cadence. —Michael Vlessides

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Mistakes Prompt Insourcing of IV Sterile Compounding

etermined to cement access to reliable and safe sources for crucial IV drug admixtures, a growing number of hospitals are bringing production of compounded sterile products (CSPs) in-house and turning their backs on external compounding pharmacies. Such far-reachingg decisions reflect the lingering distrust of outsourced CSPs, according to several administrators from hospitals that have made this move. “People were really pulled up short by the events related to the New England Compounding Center [NECC],” said Eric Kastango, MBA, RPh, FASHP, president and CEO of Clinical IQ and formerly a member of the United States Pharmacopeial (USP) Convention’s Compounding Expert Committee. “Warnings issued by the FDA to other compounding pharmacies have brought to light a lot of the ugly stuff that was going on.” That “ugly stuff ” included a wide range of manufacturing and quality control issues that resulted in a nationwide outbreak of severe meningitis cases caused by tainted steroid injections. To date, about 750 people have developed the infections; 64 have died, according to federal health officials. As a result of this massive breakdown in drug safety, Mr. Kastango noted, “hospitals are looking for strategies to become selff sufficient and vertically integrated, and to decrease reliance on these vendors.” A Wake-Up Call To Gain More Control For some hospitals the decision was, by necessity, sudden. In March 2013, Yale-New w Haven Hospital, in Connecticut, received contaminated magnesium sulfate from a compounding pharmacy. No patients were harmed, but the incident was a wake-up call, according to Lorraine Lee, MHA, BS Pharm, director of pharmacy. “It was much too real because it happened here, we didn’t just read about it,” Ms. Lee said. “Something had to change.” The hospital’s multiphase transition to insourcing—still a work in progress—began with cutting off the pharmacy responsible for the contaminated drugs. Producing enough CSPs internally then required a 260% increase in staff hours and far greater use of existing infrastructure. “The bulk of the CSP deficiencies was counteracted without the acquisition of additional equipment,” Ms. Lee said.

Other adjustments included reevaluatingg the use of previously outsourced CSPs. For example, tightening use restrictions for magnesium sulfate, as recommended by a group of physicians at the hospital, reduced demand for the drug by 30%. Help also came from nursing, which increased its use of closed systems that allow nurses to reconstitute IV drugs in patient care areas safely. Ideally,

the second phase will be to divest all third-partyy CSPs, including total parenteral nutrition (TPN) products. The hospital is considering construction of a new 5,000- to 8,000-square-foot cleanroom at a cost upward of $1 million. Phase 3 would be construction of a centralized compounding service to supply all three of the system’s hospitals. Ms. Lee noted that insourcing

changes the equation for beyond-use dating (BUD). One attraction of outsourcing has been that compounding pharmacies offered extended BUD for the drugs they ship to the hospital, which potentially reduces wasted doses and allows hospitals to stock up on high-volume admixtures. But Ms. Lee became skeptical after her experience see Insourcing page 42

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SEPTEMBER 2014

POLICY & MANAGEMENT INSOURCING

of NECC) for multiple manufacturing violations in fall 2012. The company, which delivered about 68,000 doses to MGH monthly, had been the hospiwith contaminated products. â&#x20AC;&#x153;They tell you they can provide CSPs that have talâ&#x20AC;&#x2122;s primary CSP supplier, according to extended beyond-use dates [without Erasmo A. Mitrano, RPh, MS, MGHâ&#x20AC;&#x2122;s associate chief of pharmacy. â&#x20AC;&#x153;We compromising stability or sterility of the products] and they have the studneeded very quickly to change gears to Mass General Pivots Quickly ies to back that up, but do they really? take care of patients,â&#x20AC;? he said. Thatâ&#x20AC;&#x2122;s a big red flag to me now,â&#x20AC;? she said. Massachusetts General Hospital In the year before the AmeriHospitals that decide to do a higher (MGH), in Boston, decided to fast- dose closing, the hospital produced percentage of sterile compounding in- trackk CSP insourcing after the FDA about 200,000 CSPs. The following house must be ready to commit to the shut down Ameridose (a sister company year, insourced production reached CONTINUED FROM PAGE 41

added time, training and testing necessary to comply with USP standards for BUD, Ms. Lee stressed. â&#x20AC;&#x153;Operationally, itâ&#x20AC;&#x2122;s hard to manage and comes at a high cost, and thatâ&#x20AC;&#x2122;s why hospital pharmacies typically donâ&#x20AC;&#x2122;t put beyond-use dates on the drugs they make,â&#x20AC;? she noted.

Rationale, Reversal, and Recovery Of Neuromuscular Blockade Part 2: Ongoing Challenges and Opportunities Case Study Dennis is a 68-year-old man undergoing open abdominal surgery (colectomy). Current Symptoms Â&#x2021; Dyspnea Vital Signs Â&#x2021; Height: 175 cm Â&#x2021; Weight: 85 kg 6LJQLÂżFDQW 0HGLFDO +LVWRU\ Â&#x2021; Hypertension Â&#x2021; Congestive heart failure Â&#x2021; Obstructive sleep apnea &XUUHQW 0HGLFDWLRQV Â&#x2021; Metoprolol 100 mg PO Â&#x2021; Ramipril 2.5 mg PO Laboratory Results Â&#x2021; Apnea hypopnea index: 26/h Â&#x2021; Left ventricular ejection fraction: 30%-35% Anesthesia is induced with sufentanil, propofol, and 0.6 mg/ kg rocuronium based on total body weight and maintained ZLWK GHVĂ&#x20AC;XUDQH LQ DLU R[\JHQ DQG VXIHQWDQLO 6XUJLFDO FRQGLWLRQV DUH GLIÂżFXOW ZLWK D ODFN RI DEGRPLQDO ZDOO PXVFOH relaxation and poor paralysis. An extra dose of rocuronium is administered for deeper neuromuscular block (NMB), and fewer than 2 train-of-four (TOF) responses are noted.

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320,000â&#x20AC;&#x201D;a 150% increase, according to Nathan Van Allen, PharmD, the pharmacy compounding manager. The hefty increase was made possible through increased staffing (including pharmacy students, overtime and outside agency help) and around-the-clockk operation of compounding facilities. The pharmacy leadership at MGH reached out to other services, particularly nursing and anesthesia, to help fill the vast shortfall. Systems such as MiniBagg Plus (Baxter) allowed drugs to be reconstituted safely by nurses outside of a cleanroom. Anesthesia providers, who had been receiving 13,000 syringes monthly from Ameridose, began drawing up their own syringes in preparation forâ&#x20AC;&#x201D;and duringâ&#x20AC;&#x201D;surgery. â&#x20AC;&#x153;That type of help had an enormous impact and took a lot of weight off our shoulders,â&#x20AC;? Mr. Mitrano said. Making such a titanic transitionâ&#x20AC;&#x201D;either under the gun or more deliberatelyâ&#x20AC;&#x201D;requires tremendous support from hospital administration, Mr. Mitrano stressed. â&#x20AC;&#x153;You must have their total commitment that this is the way the institution wants to go; it canâ&#x20AC;&#x2122;t be a partial effort,â&#x20AC;? he said. To keep up the momentum, the pharmacy is undergoing a build-out of its current facility and has acquired additional IV workstations and robotics, Mr. Mitrano noted. He predicted that automated production eventually will account for 75% of CSP preparation. â&#x20AC;&#x153;Weâ&#x20AC;&#x2122;ll essentially have our own compounding facility within the hospital.â&#x20AC;? Selff sufficiencyy is getting closer, added Dr. Van Allen. The hospital now produces about 90% of its CSPs; for now, it will continue to outsource TPN products. BWH a Fan of â&#x20AC;&#x2DC;Re-Insourcingâ&#x20AC;&#x2122; At Brigham and Womenâ&#x20AC;&#x2122;s Hospital (BWH) in Boston, CSP supply lines were disrupted to a lesser extent than at other facilities during the IV compounding crisis, because the hospital already had begun the process of ramping up internal compounding of IV sterile products, according to Bill Churchill, MS, RPh, chief of pharmacy services. Although quality and safety were major driving forces for â&#x20AC;&#x153;re-insourcingâ&#x20AC;? (the term Mr. Churchill prefers for describing the hospitalâ&#x20AC;&#x2122;s new direction), so were financial implications. The hospital projected, and realized, major savings (estimated at $1.5 million) over the past few years, which it attributes to the strategic shift. â&#x20AC;&#x153;Bringing production inside and having control of our own environment with our own staff was a much better see Insourcing page 46

This activity is jointly sponsored by Global Education Group and Applied Clinical Education. 6XSSRUWHG E\ DQ HGXFDWLRQDO JUDQW IURP 0HUFN

SEPTEMBER 2014

AnesthesiologyNews.com I 43

PRN

Pralidoxime for Organophosphate Poisoning Is Ineffective

eripatetic practitioners take note: New research suggests that treatment guidelines for organophosphate poisoning may be off the mark. Although uncommon in the United States, organophosphate poisoning (OP) is a serious public health problem in developing countries where pesticides are widely available. Now, a study performed at the Sheri Kashmir Institute of Medical Sciences (SKIMS) in Kashmir, India, has found that the dose of pralidoxime recommended by the World Health Organization does not help patients with OP, and merely adds to the cost of treatment, said study leader Tariq Wani, MD, an anesthesiologist at Nationwide Children’s Hospital, Columbus, Ohio, who practices at SKIMS one month each year. As many as 3 million people worldwide are exposed to organophosphates annually, resulting in an estimated 250,000 deaths. “Anyone can go to the shop to get pesticides, and they store them openly in their homes,” Dr. Wani said. “Some of the poisonings are

accidental, but some are intentional.” Organophosphates attack the central nervous system of the victim. They inhibit the enzyme acetylcholinesterase (AChE), causing acetylcholine accumulation, which results in muscle overstimulation. “Depending on the severity of poisoning, patients present with increased salivation, pupil constriction, anxiety, headaches, convulsion, generalized weakness and coma,” Dr. Wani said. “The type of patients we see are severe—they are convulsing and drowning in their own secretions; they cannot breathe properly; and their blood pressure and heart rate are very low.” Pralidoxime binds to organophosphates, theoretically releasing AChE from the poison. It has been recommended as an add-on therapy to atropine for OP since 1993, based primarily on animal studies. “If you look at the studies from 1993 to 2003, most of those studies say that pralidoxime was helpful. But some of the studies showed that the use of pralidoxime was

of no benefit or [was] associated with increased mortality,” Dr. Wani said. To clarify the drug’s effectiveness, he and his colleagues compared pralidoxime with placebo in a randomized, double-blind trial of 100 patients with OP who presented at SKIMS. All patients received atropine, and then half were randomized to receive pralidoxime and the other half received a placebo. “We found that giving pralidoxime did not make any difference,” Dr. Wani said. “It didn’t increase mortality, but it didn’t help either.” Although increased mortality may not be an issue with pralidoxime treatment, Dr. Wani said the cost of care—roughly $300 for a five-day infusion for a 60-kgg (132-lb) patient— can be overwhelming for the victims, who tend to be poor and reside in rural areas of developing countries. “Decreasing the cost for the patient makes a big difference for the families and for the outcome.” The study results prompted a policy

change at SKIMS, and the institute has stopped using pralidoxime to treat patients with OP. “We have to be very cautious in suggesting treatments because in our hospital, families must pay,” said Khalid Sofi, MD, assistant professor of anesthesiology at SKIMS. The severity of the poisoning and high mortality make it difficult to perform large-scale studies that could have a greater effect on WHO recommendations. Meanwhile, the study shed light on a possible prognostic indicator for patients with OP: serum sodium levels. As part of the intake procedure for poisoning victims, blood gas evaluation of electrolytes was performed on admission. “We found that those patients who came [in] with higher serum sodium levels on admission, the majority of them died,” Dr. Wani said. “The higher the serum sodium, the worse the outcome. This may be a new prognostic factor for these patients.” —Keely Savoie

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SEPTEMBER 2014

PRN

States Have Wide Differences in Rate of Narcotic Use

ouisiana and New York state have the highest amount of narcotics use in workers’ compensation cases among the 25 states included in a recent study. The research, conducted by the Workers Compensation Research Institute (WCRI) in Cambridge, Mass., found nearly a fourfold variation between the high- and low-use states. “This is part of an ongoing series starting in 2011,” said Dongchun Wang, an economist at WCRI and an author of the latest published study, “Interstate Variations in Use of Narcotics, Second Edition.” “Several years ago when we did the first studdy, we were surprised at the substantial variation amon ng the states studied. In this year’s report, Louisianaa and New York continue to be the top two states, where the average worker received more than 3,600 mg of morphine-equivalent narcotics.”

more workers taking narcotics for pain control with physicians continuing opioid medications for a longer period. This raises questions about screening patients for psychological and addiction concerns, she said. “Even if you decide to put patients on long-term opioid treatment, you probably want to follow medical treatment guidelines for long-term opioid management to use random drug testing, frequent psychological h l i l reevaluations l i

‘These results should provide additional information for providers, and more importantly, state regulators, to see what their state’s pattern is like [so they can] take steps as needed to bring down opioid usage if needed.’ —Kathryn L. Mueller, MD, MPH

To put this in perspective, Mr. Wangg noted that the average amounts given in New York and Louisiana were equivalent to a worker taking a 5-mgg tablet of hydrocodone every four hours continuously for an entire month (or a 120-mg morphine-equivalent daily dose for an entire month). Missouri and Iowa were the states lowest in terms of narcotics use, with an average morphine equivalent per claim of around 1,000 mg. “Two things stand out,” said Dr. Wang. “Although there are large differences across regions, physicians within a state may have prescribing patterns that are similar to their peers. It appears that these variations are related to local practice patterns.” She also noted that high-use states tend to have

and other interventions to avoid addiction,” she said. “After all, the most important thing is to help injured workers recover and function well following an injury, so they can return to work quickly.” Kathryn L. Mueller, MD, MPH, FACOEM, professor in the School of Medicine and School of Public Health at the University of Colorado, in Denver, noted that the period during which this study took place was one of greatly increasing prescribing of opioids throughout medicine. Even in this context, the use in some areas was staggering. “In some ways, it isn’t surprising to see these differences,” she said. “Within some states there was more pressure on the provider, as regulators and hospital staffs expected providers to prescribe narcotics for

relief of almost any level of pain. Depending on the level of enforcement and the importance put on it by providers, you are going to see some differences.” Dr. Mueller, who is president of the American College of Occupational and Environmental Medicine, also pointed out that the average dose was very high over multiple months in a group of nonsurgical patients with nonspecific back pain. This is a cohort for which current clinical guidelines discourage the use off opioids i id entirely. Even when appropriate, en the guideelines also suggest courses of no longer than seven too 14 days. The findings aree what she called a “radical depparture” from establlished prottocols. ““There is no clinically valid reasoon to havee this much disparity in n the amoount of morphineequivvalent meedications we are givingg to clientts,” she said. “These results should pprovide additional informattion for providers, and more importan ntly, state regulators, to see what theeir state’s pattern is like [so they can]] take steps as needed to bring down oppioid usagee if needed.” The sttudy was based on approximately 264,000 workeers’ compeensation claims and 1.5 million prescriptioons from the 25 states. The claims represent injuriees occurrin ng from Oct. 1, 2007 to Sept. 30, 2010. Prescription P ns included in the study were filled up too March 31, 31 2012. On average, the study contained data for roughly 24 months per individual included. In addition to New York and Louisiana, the study included workers’ compensation claims data from Arkansas, California, Connecticut, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Maryland, Massachusetts, Michigan, Missouri, New Jersey, North Carolina, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia and Wisconsin. Copies of the study are available for purchase from the WCRI at http://www.wcrinet.org/result/ use_narcotics2_result.html. —Kurt Ullman

FDA Approves Ryanodex for Malignant Hyperthermia

he FDA has approved Ryanodex (Eagle Pharmaceuticals) for the treatment and prevention of malignant hyperthermia (MH), marking the first new drug for the lifethreateningg complication of anesthesia in more than 30 years. The drug was also approved for prevention in patients determined to be at high risk.

The drug, an injectable suspension of dantrolene sodium, is available in 250 mg single-use vials containing the active ingredient in a lyophilized powder. “When a patient experiences malignant hyperthermia during surgery, it is a life-threateningg emergency requiring immediate treatment, including

the administration of the antidote drug dantrolene sodium,” said Henry Rosenberg, MD, president of the Malignant Hyperthermia Association of the United States, in a statement. “The ability for health care professionals in hospitals and surgery centers to more quickly prepare and administer this new formulation of the antidote

dantrolene sodium is expected to bring the crisis under control more rapidly, and prevent severe complications from MH.” For more information, visit ryanodex.com. —AN Staff

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SEPTEMBER 2014

COMMENTARY

When Prosecution Replaces Prescription BBy Lynn Webster, MD

hances are that most of us know someone with disabling chronic pain. Spottting these people is not very easy. If sshe is in pain, for instance, you can bbet she won’t share it with anyone. The stigma associated with chronic T pain i often f produces d a sense of shame and, therefore, desire for concealment. Imagine this same scenario but on a national scale, with the only difference being that instead of some people withholding problems, society is withholding the solutions. Such is the plight of Americans who suffer from some type of chronic, persistent pain—a group of people that the Institute of Medicine estimates to number more than 100 million. Many of these people find relief with nonopioid treatment, but there are countless others whose pain is so severe that opioid therapy is the only option that provides enough relief for them to live functional lives. Because of this, it is critical for opioids to remain an available option to those who suffer agonizing pain. It also means that we must take the necessary steps to ensure that these medications are not abused or inappropriately prescribed. Today, in the U.S., prescription drug abuse and opioid-relatedd deaths are a full-fledgedd epidemic. Drug overdoses have tripled since 1990, and prescription drugs are a driving factor. More than 12 million people reported using prescription painkillers (i.e., opioids) without consent of a prescribing physician in 2010, and opioid-relatedd ER visits have skyrocketed. To combat these tragic realities, the federal government has moved aggressively to regulate, restrict and

OFF-PUMP...

monitor the use of painkillers. Even so, the prescription drug abuse and overdose epidemic persists. Now, in the face of increasing pressure to do more, we’ve turned to a new tactic: the prosecution of doctors who treat patients using painkillers. Quite recently, a pain physician in Des Moines, Iowa, was accused of involuntary manslaughter and nine counts of criminal wrongdoing. The physician, Daniel Baldi, DO, thankfully, was cleared of any wrongdoing by the judge and jury. Far from proving the prosecution’s assertion that reckless prescribing led inevitably to the deaths, testimony revealed that the decedents died from a variety of causes, including deteriorating medical conditions, the use of medications not prescribed by Dr. Baldi and the abuse of illicit substances. Tragically, Dr. Baldi is professionally scarred and financially ruined, and the legal system offers no recourse for this gross prosecutorial overreach. When a physician stands trial for criminal charges for essentially practicing medicine, patients pay the ultimate price, through inevitable abandonment by the medical establishment. Fearing reprisals, practitioners reduce their willingness to prescribe strong medications, even when they are critical to recovery and administered in a safe manner. In short, patients are denied the care that they need. Oftentimes, these patients resort to a hopeless and dehumanizing search for medical professionals who are willing to help them. They find themselves set adrift in a health care system that does not reimburse appropriately for safer alternatives and evidence-based therapies. In desperation, patients turn to clinicians whose medical training lacks even the most basic instruction on managing pain. Former colleagues and I also have dealt personally with the tragedy of patients who died, not as a

CONTINUED FROM PAGE 39

show the advantage of offf pump cardiac surgery on mortality and morbidity,” he said. “But according to our research, reducing mild persistent pain could be an advantage of offf pump surgery.” Daniel T. Bainbridge, MD, lauded the researchers for tackling an important topic, but refrained from drawing firm conclusions with so few participants. “I’m actually surprised the investigators found much difference at all, since they had only 21 patients. You also have to be careful of potential confounding factors because of the small numbers as well as selection bias for patients who underwent offf or on-pump surgery. So the decreased pain may be due to reduced inflammation, but it also might be due to the surgical approach or even the patients. And with 21 people in the study, it’s fairly difficult to tease out.” Compounding the issue is the fact that few studies on CABG patients have used pain as a primary end point. “This makes it difficult to corroborate the current findings with other studies,” said Dr. Bainbridge, associate professor of anesthesia at The University of Western Ontario in London, Ontario, Canada. “Most of these studies have been done by surgeons who are interested in issues like stroke, [myocardial infarction], transfusion. And one of the problems we run into as anesthesiologists is that if the only difference between offf pump and on-pump surgery is pain at one month, they’d never switch for that reason. When a surgeon thinks of outcomes after CABG, pain is at the bottom of the outcome list.” Dr. Minami reported his findings at the 2013 annual meeting of the American Society of Anesthesiologists (abstract A2152). —Michael Vlessides

result of treatment but in spite of it, at a pain clinic in Salt Lake City. We all felt great torment throughout our practice when forced to choose between treating patients in excruciating pain and becoming a target for prosecution, especially in treatment plans involving opioids. That dilemma is only worsened when one realizes how close the link is between chronic pain and suicide. The scientific literature tells us that patients with chronic pain are two to three times more likely to take their own lives. Opioid medications are not the only therapy, nor are they always the best therapy for patients in varying degrees of pain. They clearly bring risk and should be reserved for a subset of the patient population who truly need them. Then—and only then—should opioids be prescribed by clinicians with the training and competence to assess and monitor patients in accordance with accepted medical guidelines. Moreover, each and every patient with chronic pain should have access to a minimum level of insurance benefits, and for some patients with certain pain conditions, that may include opioids. Over the long term, while we work toward finding better, nonopioid therapies, we need to change our attitudes about chronic pain in America. More people than we realize live with chronic pain every day. When I practiced medicine, I heard the cry for help from patients too often, many of whom just wanted someone to believe that their pain was real. Hopefully, society soon will start to believe that we need a better way before the chronic pain and drug overdose epidemic claims one more life. Dr. Webster is the immediate past president of the American Academy of Pain Medicine.

INSOURCING CONTINUED FROM PAGE 42

way for us to go,” Mr. Churchilll said. The hospital also hired a microbiologist to work in the pharmacy department to coordinate all IV compounding quality assessment, including end-product testing, staff testing and facility testing. “Only after they pass muster with my microbiologist do they move into circulation for patients,” Mr. Churchill explained. BWH also invested in upgrading onsite cleanroom facilities. Once a new negative-pressure cleanroom is completed, the existing main cleanroom will be upgraded and renovated to further increase capacity. BWH also has purchased four IV compounding robots, with a fifth one dedicated to oncology.

Centralized Compounding? The pharmacy now produces about 70% of the CSPs used at the hospital—up from about 40% two years ago. Going forward, Partners HealthCare, the umbrella system for both BWH and MGH, is contemplating the feasibility of a centralized compounding facility to supply all 13 of its hospitals. In the interim, the steps taken have been challenging and progress gradual. “It’s an ongoing process where you take things in bite sizes that you feel comfortable with,” Mr. Churchill said. “To make the change, operationalize that change, go back and re-evaluate it, then continue to evolve your process with the next change until you finally get it where you want it, takes time and patience. The process simply cannot be rushed.” —Steve Frandzel

SEPTEMBER 2014

AnesthesiologyNews.com I 47

CLINICAL ANESTHESIOLOGY

Vasoconstrictor May Treat Anesthesia-Induced Hypotension

pilot study has concluded that 0.5 mg of the blood pressure drug metaraminol has a variable effect on cardiac output and oxygen delivery in patients who develop hypotension during induction of anesthesia. The researchers said they planned to test the drug at different doses as a treatment for hypotension in surgical patients. In the study, Scottish researchers set out to test how effective metaraminol would be as a treatment. This commonly used blood pressure medication directly stimulates vascular α-receptors and indirectly stimulates noradrenaline. To find out if the drug could improve cardiac index and oxygen delivery index in a group of hypovolemic, vasodilated patients, the investigators conducted a prospective observational trial of 11 patients undergoing major colorectal surgery with or without synchronous liver resection. “This is a group purposefully dehydrated to reduce blood loss. They were vasodilated because the anesthetist involved establishes an epidural pre-induction of anesthesia,” said Alex Puxty, MBChB, an anesthesiologist at Glasgow Royal Infirmary, who presented the study at the 2014 annual meeting of the Society of Critical Care Medicine (abstract 291). Clinicians measured each patient’s hemodynamics on a beat-to-beat basis and stopped collecting data when a patient moved to the operating theater. The anesthetist was blinded to the invasive blood pressure during anesthesia induction, but had access to noninvasive blood pressure monitoring. Patients were given 0.5 mg of metaraminol at the discretion of the anesthetist, and changes in cardiac index and oxygen delivery index were measured at the highest mean arterial pressure. During the study, physicians used 18 doses of metaraminol in 11 patients during 14 hypotensive events. Hypotension was defined as a mean arterial pressure less than 70 mm Hg. The median absolute rise in arterial pressure was 41 mm Hg (interquartile range [IQR], 31-60). Whereas systemic vascular resistance index rose for all patients, cardiac index and oxygen delivery index increased on 12 occasions and decreased on two occasions. The median rise in cardiac index was 0.53 L/min/m2 (IQR, 0.3-0.84). The median decline in cardiac index was –0.13 L/min/m2 (IQR, –0.19 to 0.07). The median increase in oxygen delivery

index was 92 mL/min/m2 (IQR, 93-232.8), and the median decrease in oxygen delivery index was –25 mL/ min/m2 (IQR, –36.9 to 13.3). “We will be doing further studies to look at a longer period of the operation and also to measure other perfusion variables and strategies of giving metaraminol,” Dr. Puxtyy said. Matthew A. Levin, MD, assistant

professor in the Division of Cardiothoracic Anesthesia, Icahn School of Medicine at Mount Sinai, in New York City, said metaraminol is not commonly used to counter hypotension in anesthetized patients in the United States. “Since the primary mechanism [of action] of metaraminol is systemic vasoconstriction, it is not surprising that it only had a small and variable effect on

cardiac output,” Dr. Levin said. “Without a better characterization of the baseline cardiac function of these patients presenting for elective surgery, it is hard to say that the changes in cardiac index and oxygen delivery index observed are clinically significant.” —Kate O’Rourke

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Using SCOR Data To Address PONV

any pediatric anesthesiologists fall short when it comes to preventing nausea and vomiting in their patients, according to a recent analysis of data from the Society for Ambulatory Anesthesia (SAMBA). The findings come from SAMBA’s Clinical Outcomes Registry (SCOR), which is allowing ambulatory surgery

centers (ASCs) to assess complications in subsets of patients. “Everybody thinks, ‘Oh, my patients are fine,’ but when you have a report to look at and you can see how you’re doing, you learn from it,” said Lucinda Everett, MD, associate professor of anesthesia at Harvard Medical School, in Boston, who runs the database. The database has been tracking

ambulatory surgery cases since 2010 and currently includes more than 100,000 cases. These records include demographic details as well as data reflecting comorbidities, operative and postoperative times, and outcomes. Dr. Everett recently completed an analysis of SCOR data that showed many pediatric anesthesiologists are not offering high-risk patients more

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than one antiemetic as per the recommended guidelines. Dr. Everett pulled 273 strabismus cases from eight centers and 695 tonsillectomies from 14 centers for patients under age 18 years. Both types of surgeries have a slightly higher rate of postoperative nausea and vomiting (PONV) as well as antiemetic rescue after discharge than other pediatric surgeries. High-risk patients should receive at least two medications to prevent PONV, but that was not happening, according to Dr. Everett. Although nearly eight of 10 patients undergoing surgery for strabismus received two prophylactic antiemetics, only four of 10 tonsillectomy patients received the requisite dose. Dr. Everett also found that 4% of patients with strabismus and 3% of tonsillectomy patients did not receive any antiemetic. Another 17% of strabismus patients and 24% of tonsillectomy patients received only one antiemetic. “There’s still a 15% to 20% range where there’s room for improvement,” she said. Only four of the strabismus patients and 4% of the tonsillectomy patients required antiemetic rescue in the recovery room. Nearly one-third of the strabismus patients and almost half of the tonsillectomy patients required pain medications after the procedure. Among the 192 patients with strabismus reached by phone after discharge, the incidence of PONV was 7%. Of the 71% of tonsillectomy patients who were reached, 11% reported PONV. Kelly Ryan, MD, assistant professor in the Department of Anesthesiology and Perioperative Medicine at Oregon Health & Science University, in Portland, said the study did not specify how many antiemetics the children who experienced PONV received. “These children could have received two antiemetics already and still been nauseated or vomiting.” Dr. Everett confirmed that some patients who took two antiemetics did experience PONV, but these reactions were more common in patients who did not receive multimodal therapy, she said. The absence of more specific population data also concerned Dr. Ryan. “Maybe every patient who did have PONV was a teenage girl,” she said. Hormonal issues after onset of the menstrual cycle is thought to be associated with PONV in teenage girls, Dr. Everett said. This variable would be less of a concern with strabismus patients, who were younger.

SEPTEMBER 2014

AnesthesiologyNews.com I 49

PRN As with past SCOR analyses, Dr. Everett observed much variability in physician behavior not only within centers, but also among providers in a single center. Reducing this variability, physicians could improve patient outcomes, she added. Francis Wolf, MD, assistant professor of anesthesiology at Emory University School of Medicine, in Atlanta, said many anesthesiologists do not know how they are performing in terms of complications before, during and after surgery. Nor do they have a sense of their performance goals. Data often are not tracked, and sometimes data that are tracked are not reported back to physicians. Although SCOR is still viewed as a work in progress, researchers are already reaping benefits from using the registry. “There are many questions where we can’t do randomized clinical trials because of the cost or the ethical barriers, and that is where data from registries like SCOR can help,” said Douglas Merrill, MD, professor of anesthesiology at the Geisel School of Medicine at Dartmouth, in Hanover, N.H., and director of the Center for Perioperative

Services at Dartmouth-Hitchcock Medical Center, in Lebanon, N.H. Because the volume of patients in SCOR is not yet large enough to show clinical or statistical significance in some studies, some academics might question its value. What SCOR can do is provide opportunities for centers to virtually network and compare their outcomes, Dr. Merrill said. “I can benchmark care outcomes within my center against those of centers across the country that are doing the same kinds of cases or anesthetics,” he said. In addition to her research on pediatric PONV, Dr. Everett worked with Richard Dutton, MD, executive director of the Anesthesia Quality Institute (AQI), to compare SCOR with the AQI’s National Anesthesia Clinical Outcomes Registry. They found that the two data sets are similar in age distribution, types of cases and surgical status. Three of the top four most common case types were the same: colonoscopy and biopsy; lens and cataract procedures; and other procedures on muscles and tendons. As SCOR grows, it is becoming more representative, Dr. Everett said.

“AQI right now provides a bigger picture but not as focused a picture,” she added. Physicians also can use SCOR data to correct inefficiencies, which saves patients and centers time as well as money. Karen Carlson, MD, assistant professor of anesthesiology at Emory, has been contributing to the SCOR database since 2011. Initially, the hospital’s endoscopy center was underperforming in measures of PONV prophylaxis and temperature. However, instituting a bonus based on physician behavior appears to have improved the center’s performance. Dr. Carlson and her colleagues showed in a poster presented at the annual SAMBA conference (abstract 14) that by incentivizing physicians, Emory’s surgical center reached its target for two measures: PONV prophylaxis and temperature. The center fell just below target on a secondary benchmark for antibiotic administration. From September 2011 to September 2012, the center’s baseline assessment period, 63% of patients received PONV prophylaxis. The following year, delivery of PONV medication shot

to 98%. Temperature—the percentage of patients whose temperature was 36 C including those who were given warming blankets—after recovery also improved, although less dramatically. Meeting these criteria accounted for 60% of the anesthetists’ annual bonuses—or close to 5% of their total income. “They would get 50% if they hit threshold and 100% if they hit target,” Dr. Carlson said. Emory also implemented a criteriabased, rather than a time-based, discharge system. This change reduced time in recovery by 10 minutes, from 46 to 36 minutes. Dr. Carlson and her colleagues also addressed complaints of a high same-dayy cancellation rate and broad variability among anesthesiologists regarding which patients were appropriate for surgery. Dr. Carlson drafted selection criteria to clarify which patients could be seen at Emory’s endoscopy center and which would be better served in a hospital. Ultimately, the group reached consensus and then shared the guidelines with the center’s administrative staff. —Shannon Firth

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50 I AnesthesiologyNews.com

SEPTEMBER 2014

POLICY & MANAGEMENT HERNIA

CONTINUED FROM PAGE 31

Surgery News, a sister publication of Anesthesiology News, suggested in a commentary that surgeons “take a hard line, especially for elective operations” with patients who refuse to quit smoking. Several readers, however, criticized the approach. One called this argument “deeply repugnant.” But others agreed, saying surgeons must consider many factors before taking a patient to the operating room: notably, the risk for postoperative complications or the need for reoperations. Preoperative Optimization Hernia surgeons contend that, particularly for abdominal wall reconstructions, the risks associated with doing surgery outweigh the benefits in patients who continue to smoke or fail to lose excess weight. “If we can get the patient optimized, we will wait to get them optimized. That’s one thing people miss— just because you can do a component separation, doesn’t mean you should [do it] right away,” said Parag Bhanot, MD, associate professor of surgery at Georgetown University School of Medicine, in Washington, D.C. In a telephone interview, William W. Hope, MD, assistant professor of surgery, University of North Carolina-Chapel Hill, Wilmington, said surgeons are asking patients to take a bigger role in their health care “because these hernias are so difficult to treat. “The complication rate is high. If patients are not going to take part in their health care, if they aren’t going to do something to help, then a lot of times these hernias are not fixable or not fixable in a good way. We can withhold surgery or postpone surgery,” said Dr. Hope, who was not one of the panelists at the AHS session. Dr. Martindale said as many as 30% to 40% of patients who undergo abdominal wall reconstruction experience complications, putting these procedures in the same high-riskk group as major gastrointestinal procedures like pancreatic surgery and esophageal surgery. With rates so high, surgeons need to identify areas where they can reduce complications, said Dr. Martindale. He argued that there are numerous opportunities to reduce risk for complications in the preoperative period. “There is certainly lots of data now that we can prevent some [complications] with preoperative planning.” (see Table.) The panelists at the AHS meeting said they considered smoking cessation one of the most critical steps that patients should take before undergoing hernia repair. Multiple studies demonstrated that preoperative smoking cessation makes a difference in surgical outcomes. One of the best-known studies to look at this issue, published in 2003 in the Annals of Surgery, showed smokers have a much higher wound infection rate than never-smokers, at 12% versus 2%. Notably, smokers who quit four weeks before surgery reduced their wound infection rate to a level similar to neversmokers ((Ann Surg 2003;238:1-5). “Smoking is simply non-negotiable,” said Dr. Rosen. “I think the biggest mistake all of us make as surgeons is thinking, ‘I’m just a better technical surgeon at every level,’ but the truth is you’re not. It’s going to catch up to you. For me, I stack the deck in my favor. Smoking

‘I think the biggest mistake all of us make as surgeons is thinking, “I’m just a better technical surgeon at every level,” but the truth is you’re not. It’s going to catch up to you. For me, I stack the deck in my favor. Smoking cessation is part of that.’ —Michael Rosen, MD

who are nutritionally depleted should undergo a “nutritional tune-up” before surgery, he said. Randomized studies have shown that metabolic modulation reduces infectious and noninfectious complications, and shortens hospital length of stay. This trend is particularly pronounced in patients undergoing major open gastrointestinal surgery ((Ann Surg 2012;255:1060-1068). Dr. Martindale suggested that patients have a target for perioperative blood glucose between 140 and 180 mcg/dL and preoperative hemoglobin A1c lower than 8% “or even 7.5% if you want to push it.” Elective procedures in patients with higher levels should be rescheduled for a later date when their glucose is under control, he said. Another recommendation from the panel dealt with carbohydrate loading. Dr. Martindale suggested giving patients an isotonic glucose solution the night before surgery and again two to three hours presurgery. When patients are kept NPO after midnight, their bodies will burn through their carbohydrate reserves, Dr. Martindale said. The stress of surgery bumps their insulin, inhibiting lipolysis and causing the body to burn more lean body tissue to supply gluconeogenic substrate to those tissues requiring carbohydrates. Carbohydrate-loadingg strategies have been embraced in colorectal surgery and form part of the Enhanced Recovery After Surgery protocol (World J Surg 2013;37:259-284). Guidelines from the European Society for Clinical Nutrition and Metabolism stipulate that carb loading is an accepted form Nutritional Risk Screening of metabolic preparation. He recommended screening patients with the “In this country now, there are various soluNutritional Risk Screening (NRS 2002), a tool pop- tions being marketed that you can purular in Europe but not in the United States. Patients chase. I use a commercially available athletic drink that has been diluted to isotonic levels,” Dr. Martindale said. Preoperative Optimization ... Dr. Martindale also recommended testing vita• Smoking cessation min D levels and placing patients with levels below • Lose excess weight 30 ng/mL on a vitamin D protocol. Dr. Martindale – attain a specific body mass index score and his colleagues published a detailed review of • Undergo a methicillin-resistant Staphylococcus strategies for effective preoperative nutrition optiaureus s protocol mization in 2013 and 2014. The manuscripts are • Screen for nutritional risk available in the journal Nutrition in Clinical Prac• Undergo ‘nutritional tune-up’ tice (2014:29:10-21) and Surgical Clinics of North • Attain perioperative blood glucose target America 2013. • Attain preoperative hemoglobin target

cessation is part of that.” At Oregon Health & Science University, Dr. Martindale requires patients to undergo a complete methicillin-resistant Staphylococcus aureus protocol and get their body mass index (BMI) below 50 kg/m2 before surgery. He plans to lower the BMI cutoff to 45 in the near future. “We need to have patients lose weight,” he said. “Now, some patients do and some don’t.” In a presentation outlining the research on preoperative optimization of patients, Dr. Martindale said the only hard data demonstrating a surgical benefit from preoperative weight loss is in the bariatric surgery literature. Countless studies show that patients with an elevated BMI face a substantially increased risk for complications after surgery compared with other patients. This is particularly true for complex abdominal wall reconstructions. Thus, surgeons believe that patients who lose weight before these major operations have a greater likelihood of achieving a better outcome. The cross-sectional ratio of fat-to-lean body mass is also a very good predictor of surgical outcomes, specifically for pancreatic, colorectal, lymphoma and esophageal operations, said Dr. Martindale, an expert in surgical and nutritional patient care. His own unpublished research indicates the ratio of fatto-lean body mass is predictive in abdominal wall reconstruction, as well.

• Give isotonic glucose solution • Assess vitamin D level

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REPORT Clinical and Cost Considerations For Managing Postsurgical Pain: Elastomeric Pumps and Continuous Catheters, or a Single-Dose Non-Opioid Local Analgesic Faculty Susan E. Downey, MD, FACS

John Pilcher, MD, FACS, FASMBS

Clinical Associate Professor of Surgery (Plastic) Department of Surgery University of Southern California Keck School of Medicine Los Angeles, California

Medical Director, Bariatric Surgery TexSan Heart Hospital San Antonio, Texas

Jacob Hutchins, MD

Andrew Rogalski, PharmD, BCPS

Director, Regional and Acute Pain Program Department of Anesthesiology University of Minnesota Medical Center

Clinical Pharmacy Specialist Program Director, Pharmacy Practice (PGY1) Residency University Medical Center of Princeton at Plainsboro Plainsboro, New Jersey

Minneapolis, Minnesota

ostsurgical pain is a common phenomenon and can have a significant effect on patient outcomes and health care costs. For example, in 2003, Apfelbaum and colleagues1 conducted a survey of 250 adults who recently had undergone surgical procedures, and reported that 80% of patients experienced acute pain after surgery; 86% reported moderate, severe, or extreme pain. Furthermore, 23% of patients who received pain

medications experienced adverse effects (AEs). More recently, Gan and colleagues2 conducted a survey of a random sample of 300 adults who had undergone surgery within the previous 5 years. Approximately 86% experienced pain after surgery and of these, 75% had moderate or extreme pain during the immediate postsurgical period (Figure 1).1,2 After being discharged from the hospital, 74% reported a continuation of these pain levels.

Supported by

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as respiratory depression, also were noted.8 In 2012, the Joint Commission issued a Sentinel Event Alert regarding the use of opioids in the inpatient setting. This alert described several populations that were at particularly high risk for experiencing AEs in response to opioids, including the elderly, patients with morbid obesity, and those with sleep apnea.9-11 One strategy to obviate the effect of opioid-related AEs is to employ a multimodal analgesic approach.12 Multimodal analgesia, the use of different classes of analgesics that act on different pathways and receptors, has gained increased acceptance and use over the past decade as a potential strategy for managing postsurgical pain while simultaneously reducing the incidence of AEs related to any single analgesic agent.13-15 Several studies have reported that a multimodal approach that reduces opioid use may result in improved outcomes, increased patient satisfaction, and lower cost of care.6,14,16 These benefits have led both the American Society of Anesthesiologists and the Joint Commission to endorse the use of multimodal analgesia in postsurgical patients.4,9

Undermanaged postsurgical pain has broad implications for clinical care.3-5 Indeed, various studies have demonstrated that undermanaged pain after surgery is associated with longer hospital lengths of stay, a higher rate of complications (including cardiovascular, pulmonary, renal, and psychological sequelae), increased risk for developing chronic pain syndromes, and decreased patient satisfaction.3,5 Because health care utilization organizations are tracking pain-related end points as measures of quality of care in surgical patients (eg, within the Hospital Consumer Assessment of Healthcare Providers and Systems survey), these suboptimal outcomes may have a direct effect on hospital reimbursements.6 Opioids are the current mainstay of postsurgical pain management but have idiosyncratic or dose-limiting side effects that can be serious.7,8 The study by Gan and colleagues showed that 88% of postsurgical patients received analgesic medication after surgery and that opioids were the most commonly administered.2 However, 80% of those patients reported AEs. Although the most common AEs were not severe (eg, drowsiness and constipation), serious AEs, such

100

Gan et al. Apfelbaum et al.

86 82

Patients, %

60 45

40 25

13 8

Any Pain

Slight

Moderate

Severe

Extreme

Figure 1. Percentage of patients reporting various postsurgical pain levels in 2 different studies. Based on references 1 and 2.

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Elastomeric Pumps and Continuous Catheters er strategy that uses local anesthetics or other agents in an effort to augment pain control while simultaneously avoiding the AEs associated with opioids.17-19 However, the duration of action of traditional local anesthetics, such as bupivacaine HCl, does not match the time course of postsurgical pain.1,20 In order to offer longer-lasting pain relief compared with that offered by traditional local anesthetics infiltrated into tissue that may or may not be associated with a nerve block, elastomeric pumps and catheters for continuous infusions of local anesthetics were introduced in the 1990s and are increasingly used in the inpatient postsurgical setting.21-23 The utility of these strategies is promoted by the fact that these analgesic routes can be continued even when the patient is discharged from the hospital. Continuation of these advanced analgesic strategies after hospital discharge more closely mirrors the prolonged time course of postsurgical pain.

However, the use of an indwelling catheter for continuous delivery of local anesthetics has several defined disadvantages (Table). 21,24-32 Indwelling catheter use carries a risk for catheter-related complications, such as dislodgment, migration, infection, or bleeding. 24-26 Additionally, continuous delivery using a pump and catheter incurs financial costs associated with the equipment and the resources needed to safely manage these systems both inside and outside the hospital setting.27

Concerns Raised by the FDA and ISMP Both the Institute for Safe Medication Practices (ISMP) and the FDA have raised concerns about the safety of elastomeric pumps in clinical practice.28,29 In May 2009, the ISMP published a report noting an association between the ON-Q速 system and cartilage destruction, especially in cases in which local anesthetic is infused into a joint rather than the surrounding tissue.28 Similarly, the FDA recommended that elastomeric infusion devices not be used for continuous intra-articular infusion in patients after orthopedic surgery due to the risk for chondrolysis.29

Table. Drawbacks, Limitations, and Safety Issues Associated With Use of Elastomeric Pumps and Indwelling Catheters for Postoperative Analgesia Elastomeric pumps Variable infusion rates and concentrations Administration of additional medications instead of analgesic alone Extended use and refilling may result in infection Premature emptying of the bulb Not suitable for outpatient use for individuals with suboptimal health literacy or who live alone Costs associated with the equipment and the resources needed to safely manage these systems

Indwelling catheters Catheter dislodgment Catheter migration Infection and/or bleeding Potential for cartilage destruction, especially in cases in which local anesthetic is infused into a joint rather than the surrounding tissue Based on references 21 and 24-32.

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Easypump ((n=300) Infusor LV5 (n=130)

Expected Flow Rate, %

-30

-60

Sept.

Nov.

Jan.

Mar.

May

200 300 Number of Elastomeric Pumps p

400

-90

100

Figure 2. Elastomeric pumps are associated with a significant incidence of out-of-target flow rates. The gray area represents the theoretical normal range (±15%) of the set flow rate (5 mL/h). Based on Remerand F, et al. Elastomeric pump reliability in postoperative regional anesthesia: a survey of 430 consecutive devices. Anesth Analg. 2008;107(6):2079-2084. Reprinted with permission.

In July 2009, the ISMP followed up with a report calling for safer practices with the use of ON-Q elastomeric pumps.28 In this report, the ISMP noted several other issues regarding the use of these pumps, including variable infusion rates and concentrations, administration of medication including the vasoconstrictor epinephrine instead of analgesic alone, and extended use and refilling that may result in infection.28 The ISMP warned that elastomeric pump devices are filled outside of the pharmacy, typically in the operating room (OR), which raises concerns regarding accurate filling, labeling, and documentation of the administered medication.28

Clinical Experience In a review of experience at a major regional level 1 trauma center, Birrer and colleagues experienced firsthand many of the issues outlined in the ISMP alert.21 The investigators reported that the hospital’s pharmacy and therapeutics committee did not review the use of the ON-Q system because the pumps used a medication already on the formulary

(bupivacaine). Therefore, there was a lack of training or education in use of the device, leading to a lack of involvement from the pharmacy team and increased human error by the OR staff. As a result, there were several serious incidents. In one incident, a physician inserted 2 pumps with 4 lumens into a patient with traumatic brain injury and rib fractures. In another incident, the pump’s infusion rate was unpredictable, leading to the clearing of the pump’s bulb in 36 hours, despite the fact that it was expected to last 72 hours.21 In a small pilot study evaluating the use of the Homepump Eclipse for the management of acute and chronic pain, 30 investigators reported several safety incidents when using the pumps, including premature emptying of the bulb and variations in drug delivery times. They also highlighted the importance of patient selection when choosing an elastomeric pump, noting that patients with suboptimal health literacy or those who live alone are not good candidates for this strategy. 30 Capdevila and colleagues studied the use of continuous

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peripheral nerve block to manage pain in 1,416 patients after orthopedic surgery. 24 They reported that this strategy was associated with a significant risk for AEs, most of which were related to the catheter and its associated devices (eg, kinked catheter, inadvertent withdrawal of the catheter, and undesired stoppage of the pump). Bacterial colonization of the catheters also was a common occurrence.24 Grant and colleagues also reviewed their experience with 32 elastomeric pumps.31 After excluding data from 1 pump due to a leak, the investigators reported a pattern of over infusion in 7 of the pumps in the first hour after refilling. Furthermore, they reported that pump infusion flow-rate accuracy was variable over time.31 In a study of 430 pumps, Remerand and colleagues found a variety of issues with both the pumps and the catheters (Figure 2).33 For example, 20.5% of pumps did not deflate correctly, and 2 catheters were obstructed. Spontaneous deflation occurred in 40 cases at 6 to 43 hours after connection. These dysfunctions were associated with a decrease in analgesic efficacy during the first postsurgical night, leading to many catheters being removed by the anesthesiologist after 11 to 72 hours.33

EXPAREL—A Long-Acting Single-Dose Formulation of Bupivacaine The bupivacaine in EXPAREL® (bupivacaine liposome injectable suspension) is encapsulated within multivesicular liposomes (DepoFoam® ) that slowly break down and release the agent over a longer period of time than with a conventional bupivacaine formulation, thereby producing longer-lasting analgesia without the need for a continuous catheter.34,35 Due to the DepoFoam carrier matrix, there is only minimal uptake of bupivacaine into the lymphatics and systemic circulation after injection, reducing systemic exposure and toxicity.34 In several studies, administration of EXPAREL led to prolonged concentrations of bupivacaine through 72 hours with plasma levels detectable up to 96 hours, which more closely matches the time course of postsurgical pain.20,36 EXPAREL has demonstrated safety and efficacy in 2 pivotal Phase III trials of patients undergoing bunionectomy or hemorrhoidectomy.37,38 In both cases, EXPAREL was delivered via wound infiltration at the conclusion of the surgical procedure. Results showed that patient satisfaction and pain scores were significantly better for EXPAREL than for placebo at the primary end point (72 hours for hemorrhoidectomy, 24 hours for bunionectomy), and the opioid requirements were reduced when compared with placebo.37,38 In another study, pooled safety data were generated from an analysis of 10 randomized, double-blind studies including 823 patients who received EXPAREL at the surgical site.39 The most common AEs in the EXPAREL arms were nausea, constipation, and vomiting.39 Serious AEs were reported in 2.7% of patients receiving EXPAREL, and in 5.4% and 1.1% of patients who received bupivacaine HCl and placebo, respectively. Additionally, 6.4% of patients experienced a cardiac

AE consisting of either tachycardia or bradycardia; however, the cardiac events were mild or moderate in severity, and none required therapeutic intervention.39 Studies of EXPAREL suggest that it does not adversely affect wound healing. For example, in a review of all 10 Phase II and III studies of the efficacy and tolerability of EXPAREL when administered into the surgical site, investigators found that EXPAREL did not adversely affect wound or bone healing for up to 2 years in some patients. There were also no reported instances of chondrolysis, although the number needed to detect this is quite large.40 Additionally, the investigators reported that infections occurred in 5% of patients administered bupivacaine HCL, 3% of patients administered EXPAREL, and 2% of patients administered placebo.40 These are all critical factors to consider when choosing the optimal postsurgical analgesic regimen. Based on these and other studies, the FDA approved the use of EXPAREL in October 2011 for single-dose infiltration into the surgical site to produce postsurgical analgesia.41 EXPAREL is supplied in a ready-to-use aqueous suspension.42 The volume can be expanded with up to 280 mL preservative-free normal sterile saline as necessary to accommodate administration into a larger surgical site, allowing for a single maximum dose containing 20 mL of EXPAREL without the need for a catheter or pump.43

A Review of the Recent Literature Several studies in 2013 and 2014 reported more recent experience with EXPAREL since its approval for clinical use. For example, Hollander and colleagues compared the efficacy of EXPAREL (diluted with 40 mL normal saline and injected subfascially before closure of the fascia) versus subfascial continuous local anesthesia (SFCLA; subfascial tunneled catheters and a ropivacaine pump) and patient-controlled analgesia (PCA; morphine) in 195 patients undergoing laparoendoscopic single-site donor nephrectomy.32 Patients managed with PCA required more supplemental narcotics than those on EXPAREL (63.3 vs 29.4 mg; P<0.01) or SFCLA (vs 32.9 mg; P<0.01), but narcotic use was similar between patients treated with EXPAREL and those receiving SFCLA. Pain control (as demonstrated by maximal pain score according to the visual analog scale [VAS]) was comparable between patients receiving EXPAREL and SFCLA (6.3 vs 6.2). Operating time was longer for SFCLA compared with EXPAREL (219.8 vs 199.3 minutes; P<0.01) and PCA (vs 202 minutes; P<0.01). Based on these data, the investigators concluded that EXPAREL was as effective as SFCLA for perioperative analgesia and also was associated with decreased costs and operative time, likely due to its comparative ease of administration.32 Emerson and colleagues compared continuous femoral nerve block (FNB) to wound infiltration with EXPAREL as part of a multimodal pain program in 72 patients undergoing total knee replacement.44 On average, patients receiving EXPAREL required significantly lower amounts of opioid medication during their inpatient stay than those treated with an FNB (hydrocodone equivalent doses: 82.2 vs 176.6 mg; P<0.001), and

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requested fewer narcotic doses (7.5 vs 14.3; Figure 3).44 There was a trend (P=0.09) toward lower inpatient VAS pain scores with EXPAREL compared with FNB (1.8 vs 2.3; P=0.09). In the EXPAREL group, investigators found no incidence of quadriceps weakness, a common drawback to administering traditional local anesthetics via continuous FNB. The investigators concluded that wound infiltration with EXPAREL yielded equivalent postsurgical analgesia compared with a continuous FNB and with significantly less narcotic medication. As a result, they suggested that use of EXPAREL would replace the traditional opioid-reliant model of postsurgical analgesia.44 In another study, Richard and colleagues compared EXPAREL to the ON-Q system in controlling pain at the extraction and stapler insertion sites in patients undergoing

laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB).45 Patients in the EXPAREL group used significantly less narcotics (hydrocodone/acetaminophen) in the immediate postsurgical period than patients in the ON-Q group (<10 vs 30 mg; P= 0.001).45 Additionally, in a single-institution, single-surgeon, retrospective study of 108 patients undergoing robotic-assisted laparoscopic urologic surgeries, Walker and colleagues compared the efficacy of 0.5% ropivacaine delivered via an ON-Q pump (through 2 catheters placed under the fascia at the wound sites at the end of the surgery) versus wound infiltration with EXPAREL (injected subcutaneously into the incision sites and circumferentially along the trocars above and below the fascia down to the peritoneum).46 The investigators

200

186.0 Mean Time to First Opioid Use, min

Average Narcotics Used, mg

176.6

150

100

82.2 P<0.001

100

63.9 P=0.0043 50

EXPAREL

FNB

Figure 3. Patients receiving EXPAREL required significantly lower amounts of opioid medication during their inpatient stay than those treated with an FNB (hydrocodone equivalent doses: 82.2 vs 176.6 mg; P<0.001). FNB, femoral nerve block Based on reference 44.

150

EXPAREL

ON-Q

Figure 4. Comparison of the efficacy of wound infiltration with EXPAREL versus 0.5% ropivacaine delivered via the ON-Q system following robotic-assisted laparoscopic urologic surgery. Based on reference 46.

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reported that the mean morphine equivalent dose was less in the EXPAREL group than in the ON-Q group (23.8 vs 65.9; P<0.0001). Furthermore, the mean time to first opioid use was delayed in favor of EXPAREL (186.0 vs 63.9 minutes; P=0.0043; Figure 4).46 Of particular note, 5 patients in the EXPAREL group and 1 in the ON-Q group did not require any supplemental opioids. Based on these data, the investigators concluded that the use of EXPAREL was an effective strategy for postsurgical analgesia in patients undergoing minimally invasive surgery and was associated with a significant reduction in narcotic use.46

Conclusion Postsurgical pain is common and is associated with worse patient outcomes and higher health care costs. Although the use of local anesthetics as part of a multimodal analgesic approach can reduce opioid use and its associated AEs, the use of elastomeric pumps and continuous catheters needed to

match the protracted time course of postsurgical pain is associated with a variety of potential complications for the patient and can be generally inconvenient and costly to clinicians and institutions. Furthermore, some patients may not be sufficiently health care literate to manage these devices on their own after being discharged, and the devices may require valuable time in the office to be removed if the patient prefers not to do so. The duration of action of EXPAREL more closely matches the time course of postsurgical pain through a single administration. Multiple trials, both clinical and â&#x20AC;&#x153;real world,â&#x20AC;? have demonstrated that wound infiltration with EXPAREL is effective at reducing pain for up to 72 hours after surgery while simultaneously reducing opioid requirements. Furthermore, EXPAREL administered via wound infiltration obviates the need for elastomeric pumps and continuous catheters and their associated complications and limitations. As a result, EXPAREL is well suited for use as a part of the multimodal analgesic approach across a wide range of patients and procedures.

Case Study 1 A 66-year-old woman presented for open total abdominal hysterectomy, bilateral salpingooophorectomy, periaortic lymphadectomy, and omentectomy for ovarian cancer. Jacob Hutchins, MD

he patient had a history of an abnormal right ovary with elevated CA-125. She had no other past medical history and this was her first surgery. She declined to have an indwelling catheter to manage postsurgical pain because neither she nor her husband felt comfortable removing it at home. The decision was made to provide postsurgical analgesia with bilateral classic transversus abdominal plane (TAP) infiltration with EXPAREL. Before surgery, in the preoperative block area, the patient received bilateral ultrasound-guided TAP infiltration. She received 30 mL total volume per side (10 mL EXPAREL and 20 mL normal saline). She was then taken to the OR where she was induced with 100 mg propofol, 100 mcg fentanyl, 100 mg lidocaine, and 50 mg rocuronium. She received a total of 400 mcg of fentanyl intraoperatively and 1 mg hydromorphone for a procedure that lasted 264 minutes. Final pathology showed stage IIc adenocarcinoma of the right fallopian tube. The patientâ&#x20AC;&#x2122;s postoperative pain was well controlled, with her maximal pain score in the postanesthesia care unit (PACU) at 3 out of 10 on the NRS. While in the PACU, she received 50 mcg fentanyl and 1 mg hydromorphone IV. During her first 24 hours postoperatively, her maximal pain score was 3 out of 10 and she received 0.1 mg IV hydromorphone, 5 mg oxycodone, 30 mg IV ketorolac, and 325 mg oral acetaminophen.

During the first postoperative 24 to 48 hours, her maximal pain score was 4 out of 10 and she used only 15 mg ketorolac IV and 1,200 mg ibuprofen. She denied nausea or vomiting during the entire postoperative period. She was discharged home with oral opioids and enoxaparin injections 40.15 hours after surgery. When contacted on postoperative day (POD) 2, she reported continued good pain control without the need for additional opioids and was satisfied with the method of pain management.

Commentary Continuous TAP instillation with a pump and catheter provides incisional pain coverage and can be continued once discharged, but may be contraindicated or not desired in certain patients. By using TAP infiltration with EXPAREL instead of a continuous catheter and pump, a similar duration of analgesia can be provided and all postoperative anticoagulation needs can be met. Additionally, those with limited mental ability or assistance can still receive up to 72 hours of incisional pain relief. This technique also eliminates the potential for accidental catheter removal. With the change to EXPAREL, we have been able to provide postoperative incisional pain control to a more diverse population of total abdominal hysterectomy patients.

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Case Study 2 A 44-year-old man undergoing a skin graft following multiple surgeries. Susan E. Downey, MD, FACS

he patient was previously healthy and had developed chest pain. His medical history was notable for hypertension but he was not on medication. Stress test confirmed an ascending aortic aneurysm. He underwent elective ascending aortic replacement with a femoral artery cut down and repair. Later that same day he began to complain of severe calf pain and was found to have a compartment syndrome in his left calf. He was taken back emergently to the OR and underwent fasciotomies of the calf. A week later, he developed shortness of breath and was found to have a pericardial effusion. This required another return to the OR and subxiphoid drainage. Two weeks later, a plastic surgery consultation was obtained for a skin graft for the fasciotomy wounds on his calf. The nursing staff and the rest of his medical team were concerned about his postoperative pain management because he had been on narcotics in the ICU for several weeks. Due to his many complications and surgical procedures in such a short period of time, the patient was having pain control issues. The Palliative Care Department had been consulted and was following him with the diagnosis of â&#x20AC;&#x153;intractable pain.â&#x20AC;? He was maintained on a hydromorphone PCA 0.9 mg per hour continuous drip with 0.3 mg every 10 minutes as needed and a 3-mg per hour lockout. The patient was taken to the OR and a split-thickness skin graft was harvested from his upper thigh using a dermatome.

The dermatome was set at 18/100,000 of an inch. EXPAREL 20 mL with 40 mL saline (total volume 60 mL) was injected into the donor site. The donor site was dressed with xeroform and a bulky dressing. The skin graft was secured to the recipient site with staples and Adaptic gauze. No local anesthetic was injected into the recipient site. Immediately after the skin graft procedure, the PCA was stopped and the patient was switched to hydromorphone IV push 0.5 mg every 3 hours as needed for pain. Oxycodone/ acetaminophen was administered for breakthrough pain. He was discharged home 2 days after the skin graft procedure on oral oxycodone/acetaminophen alone.

Commentary When harvesting skin grafts, the donor site can be as painful as a second-degree burn. It can take days or even weeks for the pain to subside, and an injection of marcaine or lidocaine only lasts a few hours. A pain pump cannot be used because the harvesting of the skin graft does not leave a cavity for a catheter. The patient was informed that EXPAREL would be used in the donor site before surgery to minimize his postoperative pain. After surgery, the patient was found to be resting comfortably and reported no pain in the donor site.

Case Studies 3 and 4 53- and 46-year-old women undergoing Roux-en-Y gastric bypass. John Pilcher, MD, FACS, FASMBS

The 53-Year-Old Woman: Using an ON-Q Pump and Catheter

he patient suffered from many years of weight gain despite regular diet and exercise. Her medical problems included hypertension, hyperlipidemia, asthma, chronic low back pain, and knee pain. She had previously undergone laparoscopic cholecystectomy and total abdominal hysterectomy. She also had a history of atrial fibrillation and spontaneous deep vein thrombosis 4 years before her initial encounter with the bariatric surgical team. She took ibuprofen regularly for moderate knee and back pain, but was not taking any narcotic pain medication before surgery. Her height was 163 cm and her weight was 113 kg, with a body mass index (BMI) of 43 kg/m2. Medications before surgery included lisinopril,

metoprolol, spironolactone, atorvastatin, and cetirizine. The bariatric surgical team recommended RYGB to treat the patientâ&#x20AC;&#x2122;s progressive metabolic obesity disease. The surgery was performed laparoscopically, without any unusual events. The gastrojejunal anastomosis was accomplished using a size 25 circular stapler, which was introduced into the abdomen by removing the left flank trocar and dilating the site to accommodate the device. At the end of the procedure, the fascia and muscle at the site that had been dilated were closed using a single vicryl suture. The other trocars (all nonbladed) were simply removed and no fascial closure was deemed necessary. No drains were deemed necessary.

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Bupivacaine 0.5% plus epinephrine was infiltrated preemptively at each trocar site after the abdomen was prepped and draped, and an additional 20 mL was infiltrated at the end of the procedure into the left flank fascia where the suture closure was accomplished. An ON-Q catheter was threaded into the preperitoneal plane on the left flank, lateral to the site of the suture closure. The 48-hour elastomeric ON-Q pump was charged with a 120-mL volume of bupivacaine 0.25%, which infused gradually through the catheter during the 2-day hospital stay. The patient received the standard postoperative pain and nausea regimen, which included 2 mg PCA morphine in 10-minute intervals with 30/4-hour lockout; 15 to 30 mL of hydrocodone/acetaminophen elixir (7.5/500 mg per 15 mL) orally every 4 hours as needed for pain; 4 doses of 30 mg IV ketorolac every 8 hours beginning at 4 hours postsurgery; 4 doses of 4 mg IV ondansetron every 6 hours (standing), then 8 mg IV every 6 hours as needed for nausea; and 10 mg of IV metoclopramide every 6 hours as needed for nausea, if ondansetron was not effective.

The postoperative stay was unremarkable, and the patient was discharged home on POD 2. During her hospital stay she received 26 mg morphine via PCA, 120 mL hydrocodone/acetaminophen elixir; ketorolac as scheduled; ondansetron as scheduled followed by 2 additional doses of ondansetron as needed; 20 mg of metoclopramide (2 doses as needed as backup for ondansetron); and bupivacaine via ON-Q catheter, with catheter removal just before discharge. At time of discharge, the patient received a standard prescription for additional hydrocodone/acetaminophen elixir. At her first follow-up visit, the patient reported that she took the as-needed prescription “very regularly” for the first few days at home, obtained the permitted refill (each fill = 1 pint), then used “about one-fourth” of the second pint. Approximately 1 week post-discharge the patient experienced very severe constipation, requiring 2 enemas and self-disimpaction. In long-term follow-up, the patient had experienced substantial weight loss and health improvement. There was no longterm pain, nausea, or constipation sequelae.

The 46-Year-Old Woman: Using EXPAREL

he patient presented to the bariatric clinic for consideration of bariatric surgical intervention. Her height was 170 cm and her weight was 129 kg, with a BMI of 45 kg/m2. Her medical history included gastroesophageal reflux disease, hypertension, obstructive sleep apnea, and depression. She also had longstanding chronic back and knee pain, for which she took approximately 15 mg hydrocodone per day as-needed. Other medications included lisinopril, duloxetine, and zolpidem. She had previously undergone right total knee replacement, and lumbar laminectomy. RYGB was selected in this case as well. The operation was accomplished laparoscopically according to routine. In the same manner as the previous case, the gastrojejunal anastomosis was accomplished using a size 25 circular stapler with dilation of the skin and muscle at the left flank trocar site. The fascia at this location was closed using a single vicryl suture, and suture closure of the other trocar sites was deemed unnecessary. No drain was deemed necessary. A 20 mL dose of EXPAREL was combined with 100 mL sterile normal saline. Approximately 60 mL was infiltrated preemptively at the skin level and the fascia level at each trocar placement site at the beginning of the case. When the procedure was complete, 30 mL was infiltrated into the left flank fascia at the site of suture closure, and 30 mL was

infiltrated into the left TAP lateral to this fascial site. Following surgery, this patient received an updated postoperative pain and nausea regimen, which included 2 to 4 mg morphine every 2 hours as needed for pain (not PCA); 15 to 30 mL of hydrocodone/acetaminophen elixir (7.5/500 mg per 15 mL) orally every 4 hours as needed for pain; 4 doses 30 mg of IV ketorolac every 8 hours beginning at 4 hours postoperatively; 4 doses of 4 mg IV ondansetron every 6 hours (standing) followed by 8 mg IV every 6 hours as needed for nausea; and 10 mg of IV metoclopramide every 6 hours for nausea, if ondansetron was not effective. The postoperative stay was unremarkable, and the patient was discharged home on POD 1. During her hospital stay she received 8 mg morphine; 75 mL hydrocodone/acetaminophen elixir; ketorolac as scheduled; ondansetron as scheduled, no as-needed doses required; and metoclopramide was available but not required. At time of discharge, the patient received a standard prescription for additional hydrocodone/acetaminophen elixir. At her first follow-up visit she reported that she took the as-needed medication only twice, and was pleasantly surprised at how little pain she experienced. In long-term follow-up, the patient had experienced substantial weight loss and health improvement. There was no long-term pain, nausea, or constipation sequelae.

Commentary Although these are 2 different patients, they underwent similar procedures. However, when EXPAREL was

administered, less narcotics were used, resulting in fewer postsurgical side effects.

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A Pharmacist’s Clinical Perspective Andrew Rogalski, PharmD, BCPS ur institution began using EXPAREL in 2012, and it is now used in general, orthopedic, and gynecologic procedures by multiple practitioners. We have seen a number of advantages throughout the institution since making it a part of our multimodal pain control strategy. In discussions with providers, caregivers, and patients there has been a nearly universal description of reduction in requirements for rescue narcotics in the postoperative period, with consistent results into POD 3. Our nurses have even reported narcotic-free PACU discharges for several same-day procedures. Operationally, we had been using considerable numbers of elastomeric infusers and CADD infusers for regional anesthesia and nerve blocks. Many of our surgeons have abandoned these modalities and adopted EXPAREL for its superior simplicity with excellent results. When accounting for costs, we found that the acquisition costs for the infusion devices and standard anesthetics were

initially slightly less than EXPAREL, but when the cost of the catheters, tubing, and preparation time were tabulated, the costs were essentially equivalent. For example, preparation of infusers required a minimum of 12 hours of pharmacy technician resources each week, which have now virtually been eliminated. We have elected to provide EXPAREL at room temperature in a centrally located automated dispensing cabinet (Pyxis) within the OR core. Because of frequency of use, we have encountered no issues with the limited beyond-use dating when removed from refrigeration. Speculative concerns for look-alike issues with propofol have not been observed in our practice; however, as a precaution, our circulating nurses retrieve the EXPAREL and our anesthesiologists have no role in its administration. Our organization has seen many successes with the adoption of EXPAREL as part of our multimodal approach to pain management. When drug, device, and operational costs are considered in totality, we have found it to be at least cost-neutral to other regional anesthetic modalities.

Important Safety Information EXPAREL is contraindicated in obstetrical paracervical block anesthesia. EXPAREL has not been studied for use in patients younger than 18 years of age. Non–bupivacaine-based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after delay of 20 minutes or more. Other formulations of bupivacaine should not be administered within 96 hours following administration of EXPAREL. Monitoring of cardiovascular and neurological status, as well as vital signs should be performed during and after injection of EXPAREL as with other local anesthetic products. Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations. In clinical trials, the most common adverse reactions (incidence ≥10%) following EXPAREL administration were nausea, constipation, and vomiting. Please see full Prescribing Information for EXPAREL.

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Disclosures: Dr. Downey reported that she has acted as a consultant for Allergan, Inc. and Ethicon, Inc. Dr. Hutchins reported that he has received research grants, honoraria, and has served as a consultant for Pacira Pharmaceuticals, Inc. He also reported that he has served on the speakers’ bureaus for I-Flow, LLC and Pacira Pharmaceuticals, Inc. Dr. Pilcher reported that he has served as a consultant for Ethicon, Inc., Intuitive Surgical, Inc., and Pacira Pharmaceuticals, Inc. Dr. Rogalski reported that he has received honoraria from the American Society of Health-Systems Pharmacists and Pacira Pharmaceuticals, Inc. Disclaimer: This monograph is designed to be a summary of information. While it is detailed, it is not an exhaustive clinical review. McMahon Publishing, Pacira Pharmaceuticals, Inc., and the authors neither affirm nor deny the accuracy of the information contained herein. No liability will be assumed for the use of this monograph, and the absence of typographical errors is not guaranteed. Readers are strongly urged to consult any relevant primary literature. Copyright © 2014, McMahon Publishing, 545 West 45th Street, New York, NY 10036. Printed in the USA. All rights reserved, including the right of reproduction, in whole or in part, in any form.

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