The January 2013 Digital Edition of Anesthesiology News by McMahon Group

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THE INDEPENDENT MONTHLY NEWSPAPER FOR ANESTHESIOLOGISTS AnesthesiologyNews.com • J a n u a r y 2 0 1 3 • Volume 39 Number 1

Preventable Injuries Frequent in Anesthesia

Peds Group Outlines Global Anesthesia Needs

n analysis of more than 9,500 closed claims filed against anesthesiologists found that many patients experience preventable injuries that could be avoided with proper use of equipment. “In about 40% to 50% of the claims we reviewed, the care seemed totally appropriate,” said Karen Domino, MD, MPH, former director of the Closed Claims Project, who presented the findings at the 2012 annual meeting of the American Society of Anesthesiologists. “But

Washington—Presenters at the Society for Pediatric Anesthesia’s first International Assembly for Pediatric Anesthesia asked anesthesiologists to open their minds, and in some cases their wallets, in support of efforts to provide safe anesthesia to children worldwide. Johns Hopkins intensivist Peter Pronovost, MD, PhD, director of the institution’s Armstrong Institute for Patient Safety and Quality, kicked off the meeting, asking the more than 700 attendees from around the world to take ownership of improving pediatric patient safety, starting with writing the words, “I will.”

see closed claims page 12

see global page 20

Canadian Study Reveals High Rate Of Residual Paralysis

INSIDE

Paresis observed in nearly 60% of patients undergoing abdominal procedures

15 | CLINICAL ANESTHESIOLOGY

ore than half of patients undergoing elective open abdominal or laparoscopic surgery experience residual neuromuscular blockade after tracheal extubation, according to an interim analysis of a Canadian multicenter study. “There are currently no prospective, multicenter studies assessing residual paralysis in Canada,” said Andre Galarneau, PhD, medical advisor at

10 | PAIN MEDICINE Saline preinjection expands lesion size for RF. Seven red flags for outpatient surgery.

Merck Canada in Kirkland, Quebec, who led the study. “When we started asking researchers to estimate the incidence of residual paralysis in their centers, everyone was saying between 10% and 15%. But as we found out, it’s actually a lot more than that.” The RECITE study (REsidual Curarization and its Incidence at Tracheal Extubation) prospectively examined the incidence of residual neuromuscular

18 | TECHNOLOGY Multiple monitors may be key to reducing risk for awareness during surgery.

26 | PRN Inside the ISPCOP: A society focused on the surgical issues of the obese patient.

EDUCATIONAL REVIEW Systemic Strategies for Reducing Blood Loss In Surgery see insert at page 14.

see RECITE page 16

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McMahonMedicalBooks.com Hadzic’s Peripheral Nerve Blocks and Anatomy for Ultrasound-Guided Regional Anesthesia Admir Hadzic see page 24

The Top 10 Articles of 2012 on AnesthesiologyNews.com, see page 4.

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ABC is your full data management partner in the Meaningful Use initiative. We manage the data entry, the compliance, and ultimately, your long term success—since we are not paid until you are paid. While the daily operations that are undertaken to ensure your compliance may not be visible to you, rest assured, the F1RSTUse team at ABC is focused on achieving your successful attestation and participation in the EHR Incentive Program.

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JANUARY 2013

Comment on these and other articles @ AnesthesiologyNews.com.

Heard Here First: Lactate increases when the brain is January 2013

The 10 most-viewed articles of 2012 on AnesthesiologyNews.com

activated, so the higher level of lactate in the brain of a child administered sevoflurane is likely the result of

1. Survey Finds “Discouraging” Injection Habits Among Anesthesiologists

more neuronal firing

2. Japanese PONV Researcher Probed in Sweeping Research Fraud Case (Web Exclusive) 3. Hospital Closings Helping Reshape Anesthesia Job Market

during the unconscious state. It’s

4. Current Concepts in the Management of the Difficult Airway (Educational Review)

like having a motor running but

5. Cancelled Surgeries Costing Hospitals Millions

the car is not going anywhere.

6. Ultrasound-Guided Central Vein Cannulation: Current Recommendations and Guidelines (Educational Review) 7. Paravertebral Blocks: The Evolution of a Standard of Care (Educational Review)

SEE ARTICLE ON PAGE 22.

8. Report: Japanese Anesthesiologist Fabricated Data in 172 Studies (Web Exclusive) 9. As Liposuction Deaths Mount, Study Exposes Cracks in Safety 10. Neuromuscular Blockers Linked to Post-op Breathing Problems

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Correction: Figure 2 in Lesson 301 of the PreAnesthetic Assessment (Anesthesiology News, December 2012) contained an erroneous label. All sigma should have been delta.

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IN B R I E F

Unsafe Injections: A Timeline S

ince 2007, the Centers for Disease Control and Prevention has investigated at least 17 major cases of injection-related infection scares, culminating in the 2012 outbreak of fungal meningitis from epidural steroid injections linked to a compounding pharmacy in Framingham, Mass. The death toll from the latest outbreak currently stands at 37, with some 14,000 potential exposures across 23 states. The pharmacy, New England Compounding Center (NECC), is now the subject of a grand

2007

2008

jury investigation and its operators could face criminal charges. The company, which has suspended operations, already has been named in approximately 70 civil suits, according to the Reuters news agency. U.S. Rep. Edward Markey, the Massachusetts Democrat whose district includes Framingham, has said that compounding pharmacies like NECC fall into a “regulatory black hole” that provides little oversight— leading to what he called “the worst public health disaster in recent memory.” In November, Mr. Markey

2009

Pediatric Oncology Clinic

Pain Clinic

Primary Care Clinic

Pathogen: Multiple organisms Infection: Bloodstream infection No patient notification performed

Pathogen: Klebsiella pneumoniae, Enterobacter aerogenes Infection: Bloodstream Infection No patient notification performed

Pathogen: Staphylococcus aureus Infection: Joint infection No patient notification performed Mishandling of multidose vials used for more than one patient (e.g., handling in the immediate patient treatment area and failure to store according to manufacturer instructions)

Contents from single-dose vials used for more than one patient Predrawing saline flush solutions

Dermatology Office Pathogen: N/A*; Infection: N/A* 13,500 patients notified Medical equipment (scalpels, gloves, syringes and suture material) designed and intended to be used on a single patient used on more than one patient.

Contents from single-dose vials used for more than one patient Lack of hand hygiene before procedures Not appropriately cleaning the injection site prior to injection

Syringe reuse (using the same syringe to administer influenza vaccine to more than one patient)

Multiple Gastroenterology Clinics

Incorrect cleaning and disinfection of medical equipment

Outpatient Pain Clinic

Pathogen: Hepatitis C virus Infection: Hepatitis 1,205 patients notified

Pathogen: Staphylococcus aureus Infection: Bloodstream infection, meningitis, epidural/presacral abscess 110 patients notified

Syringe reuse

Syringe reuse†

Endoscopy Center Pathogen: Hepatitis C virus Infection: Hepatitis More than 50,000 patients notified Syringe reuse† Contents from singledose vials used for more than one patient

Pathogen: Hepatitis C virus, Hepatitis B virus Infection: Hepatitis 4,490 patients notified Syringe reuse† Contents from singledose vials used for more than one patient

Contents from singledose vials used for more than one patient Health care providers did not wear facemasks when performing spinal injection procedures

Allergy Clinic Pathogen: Mycobacterium abscessus Infection: Skin and soft tissue infection No patient notification performed Inappropriate selection and dilution of skin disinfectant

Hematology-Oncology Clinic Pathogen: Hepatitis B virus Infection: Hepatitis 2,700 patients notified Medication preparation in a blood processing area

Source: Centers for Disease Control and Prevention

Outpatient Radiology Facility Pathogen: Streptococcus salivarius Infection: Meningitis No patient notification performed Health care providers did not wear facemasks when performing spinal injection procedures Contents from single-dose vials used for more than one patient

Pain Clinic

Cardiology Clinic

OB/GYN Office Pathogen: N/A*; Infection: N/A* 36 patients notified

Inadequate hand hygiene

2010

Contents from single-dose vials and saline bags used for more than one patient

Pathogen: Hepatitis C virus Infection: Hepatitis More than 2,000 patients notified Syringe reuse†

Health Fair Pathogen: N/A*; Infection: N/A* 50 patients notified Same fingerstick device used on more than one patient to obtain blood samples for blood glucose monitoring

introduced a bill—the Verifying Authority and Legality in Drug (VALID) Compounding Act—to strengthen FDA regulatory authority over the companies. —AN Staff * Infection control breach, not infections, prompted patient notification. It is not known if any infections resulted from the unsafe practices. † Double Dipping: Syringe that had been used to inject medication into a patient, reused to enter a medication vial. The syringe is discarded but contents from that vial, which were contaminated through reuse of the syringe, are then used for subsequent patients.

2011 Pediatric Clinic Pathogen: N/A*; Infection: N/A* Unreported Syringe reuse (using the same syringe to administer influenza vaccine to more than one patient)

Urology Clinic Pathogen: N/A*; Infection: N/A* 101 patients notified Single-use needle guides (for prostate biopsy) used for more than one patient

2012 Multiple Health Care Facilities in 23 States Pathogens: Exserohilum rostratum, Aspergillus fumigatus (one case) Approximately 14,000 potentially exposed, 590 confirmed infections, 37 patient deaths Steroids contaminated with fungi

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P A IN M E D I C I NE

New Research Sheds Light on Opioid Resistance

esearchers now have some answers to the lingering question of why opioid analgesics gradually lose their effectiveness. Investigators at the University of Montreal recently identified how neural cells build up resistance to opioids, an effect that causes patients to require stronger doses of the drugs over time. “We show there’s a molecular basis

for creating a drug that produces less tolerance,” said Graciela Pineyro, MD, PhD, lead author of the study and research professor in the Departments of Psychiatry and Pharmacology at the University of Montreal’s Sainte-Justine Hospital. “With this knowledge, we can design better drugs with fewer secondary side effects.” The study was published in The

that exist in every human cell. Receptors receive signals from the chemicals that they come into contact with, which cause various cells to react in different ways. The researchers found the reaction of receptors that sit on the membranes of nerve cells varies when Receptor ‘Recycling’ they come into contact with differDr. Pineyro’s team looked at how ent opioids. Once activated by a drug, drug molecules interact with receptors δ-opioid receptors move inside the cell. They are then either destroyed, or return to the surface and are used again through a process known as “receptor recycling.” Dr. Pineyro said the ultimate goal is to develop new opioids that will encourage this recycling, which works against drug tolerance. Wendy Walwyn, PhD, adjunct associate professor at the UCLA David Geffen School of Medicine, who has been following the work of Dr. Pineyro, explained recycling another way: Imagine that a car (the drug) picks up a passenger (the receptor) at a traffic circle. It can then either drive through the circle and continue on the same road, or go around the circle and return to the same place—and be “recycled,” so to speak. For continuous pain relief, you want the car to cycle around so it can pick up another passenger. If the car continues through the circle and goes on a long road trip, the passenger is taken out of the system and there’s no continuous analgesic effect. “As scientists, we now need to find the drugs that prefer to take the passenger on shorter ‘recycling’ trips,” Dr. Walwyn said. Dr. Pineyro’s study has interesting implications, added Dr. Walwyn: “Some of these ideas have been floating around, but she put them all together so elegantly. Her work will influence the scientific community for years to come.” Dr. Pineyro said it is important to realize there is, as yet, no breakthrough treatment. “We’ll need lots more research to develop a drug that recycles, creates less tolerance, and produces a long-lastingg analgesic response that you can administer in pill form.”

Journal of Neuroscience (2012; 32: 4827-4840), and was funded by the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research.

—Dana Hawkins-Simons Drs. Pineyro and Walwyn had no conflicts of interest to disclose.

JANUARY 2013

AnesthesiologyNews.com I 9

PA IN M E D ICIN E

Pain Primer Identifies Pathways to Optimal Treatment

ccording to interventional pain specialist Andrea Trescot, MD, who authored a new book along with David Kloth, MD, and Francis Riegler, MD, their motivation was the many misconceptions that patients—and often their physicians— have about the efficacy of interventional pain treatments. “We decided to do the book specifically to address the bad public relations that pain management gets,” said Dr. Trescot, who is in private practice in Florida and Alaska. “Pain-Wise : A Patient’s Guide to Pain Management” was published late last year by Hatherleigh Press (2011) in the United Kingdom. The book uses clear and sometimes humorous lay person’s language, with lots of illustrations, to help people living with chronic pain to become advocates for getting timely and appropriate treatment for their individual needs. It also explains that, although pain has many causes that may present similarly, there are different modes of treatment, depending on what the diagnostic tests find.

From the outset of the book, the authors dissuade patients from expecting a pain physician to banish their pain symptoms quickly and completely, whether they are back problems or pelvic pain, but rather to understand that treatments for such chronic conditions are often chronic themselves. “The goal of interventional pain management procedures should be to reduce and manage pain, with emphasis on the word ‘manage,’” the authors write in the first chapter. “Your [pain] physician may not necessarily be able to cure the problem, but they can help you control the pain and maximize your functional level.” The book includes general guidance on choosing a pain physician and

understanding one’s health insurance options, as well as more specific information on diagnostic testing (noting “there is no test for pain”), medications and their indications, and other options for treatment that are part of comprehensive pain therapy, along with the risks and potential complications. The authors also discuss interventional pain techniques such as

peripheral nerve blocks, facet injections, sacroiliac injections, epidural injections, adhesiolysis, diskography, minimally invasive disk surgery, radiofrequency ablation and cryoneuroablation, regenerative therapy and implantable techniques including spinal cord stimulation, spinal drug delivery systems and peripheral nerve field stimulation. Cancer-related pain

control is given particular emphasis. “Because the well-intentioned oncologist concentrates on the disease and its potential cure, pain management often isn’t fully addressed,” the authors write. “Being informed and knowing what questions to ask improves your chance that these options will be made available.” —Rosemary Frei, MSc

, a pattern begins to emerge. “Amazing” gets tossed around quite a bit these days, and too often it’s used to describe products that deliver far less than advertised. 3M™ Bair Hugger™ therapy was introduced in 1987 as an ingeniously simple way to warm patients. Today, the Bair Hugger product lineup continues to lead the industry with 25 innovative blanket models (including seven underbody designs) and a record of safety, quality and effectiveness that is second to none. Bair Hugger therapy has warmed more than 160 million patients over the past 25 years, improving the quality of care by preventing unintended hypothermia and thus reducing its associated complications – an amazing feat that takes place 50,000 times each day. We invite you to share the warmth. Visit www.bairhugger.com/amazing to learn more or share your experience with Bair Hugger therapy. *US World & News Report.t Best Hospitals 2011-2012. 3M is a trademark of 3M Company, used under license in Canada. BAIR HUGGER and the BAIR HUGGER logo are trademarks of Arizant Healthcare Inc., used under license in Canada. ©2013 Arizant Healthcare Inc. All rights reserved. 603581G 01/13

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P A IN M E D I C I NE

Saline Preinjection Increases Size of RF Lesions Miami Beach—Although monopolar radiofrequency (RF) ablation offers great promise to relieve facet joint pain, technical limitations can impede optimal use and the widespread adoption of the therapy. Researchers traditionally focus on three “T’s” to overcome these limitations: adjusting the time, temperature and tip size of the RF needle to find the ideal approach to the nerve. But what if a simpler strategy—preinjection of just the right amount and concentration of saline—could significantly increase the lesion size and thereby decrease the margin of error inherent in targeting these small nerves? That might work, according to results of a study from pain specialist David Provenzano, MD, of the Institute for Pain Diagnostics and Care at Ohio Valley General Hospital in McKees Rocks, Pa. Dr. Provenzano and his colleagues found that increasing the NaCl concentration of a preinjected fluid significantly increases the lesion size, particularly the horizontal diameter of the RF target. Although the findings come from the laboratory and not the clinic—similar to other research on lesion size published to date—translation to the patients may not be far off. “We’re already injecting lidocaine” for preprocedure analgesia, and most commercial preparations contain saline, said Dr. Provenzano. “Practitioners in radiology and interventional cardiology already utilize saline preinjection to alter the biological environment of the tissue surrounding the RF electrode,” he added. “This is a viable option for our specialty in the future.” Dr. Provenzano presented the findings at the 2012 annual fall meeting of the American Society of Regional Anesthesia and Pain Medicine (abstract 17). “This is an important study,” said Steven P. Cohen, MD, professor of anesthesiology and critical care medicine at the Johns Hopkins School of Medicine, in Baltimore. “The main thing that will have to be addressed is whether hypertonic saline is neurotoxic in this context, and if so, what dose, if any, is safe. We know from other studies that sometimes when performing medial branch blocks, the injectate extravasates into the intervertebral foramen or epidural space. There is the potential that very high concentrations of hypertonic saline can cause nerve damage. Whether this is clinically

relevant or not is something that needs to be determined,” he added. Dr. Provenzano agreed that this concern was among the important caveats of the study. “I want to caution practitioners when considering the preinjection of very high concentrations of saline solutions because of the possible risk for toxicity to nontargeted central and peripheral nervous systems

structures,” he told Anesthesiology News. What’s more, he said, power requirements associated with high concentrations of saline may exceed the capabilities of RF and interventional pain equipment. “Higher concentrations of saline result in an improvement in tissue conductivity—lower impedance—and a higher-power output at the targeted site,” Dr. Provenzano

INDICATIONS ULTIVA is indicated for intravenous administration:

said. “Therefore, it’s not surprising that 23.4% saline preinjection significantly increased lesion size by a mean 154% compared with water [P<0.001].” However, 8% NaCl might strike the right balance in terms of safety and effectiveness, contingent on careful evaluations in future clinical trials. In comparison with the standard 1% lidocaine in 0.7% NaCl, 8%

IMPORTANT RISK INFORMATION

JANUARY 2013

AnesthesiologyNews.com I 11

PA IN M E D ICIN E ‘The main thing that will

NaCl preinjection resulted in a 66% increase in the mean surface area of the lesion. “You still have to be safe with your placement, and make sure if you get a bigger lesion, you are not targeting unwanted tissue,” Dr. Provenzano said. Safety was not relevant in the current study because investigators assessed monopolar RF at 80 C for 90 seconds in 110 samples of chicken tissue with nerves. Seven groups of 10 samples each were preinjected with

have to be addressed is whether hypertonic saline is neurotoxic in this context, and if so, what dose, if any, is safe.’ — Steven P. Cohen, MD

On Off

0.74 mL of NaCl at the following concentrations: 0.7%, 0.9%, 3%, 8%, 13%, 18% and 23.4%. They also assessed lesion-size effects from 1% lidocaine in 0.7% NaCl, water and 5% dextrose in water (D5W). A control group of samples received no fluid preinjection. When compared with no fluid injection, preinjection of D5W, but not water, increased the mean lesion area by 57% (P=0.012), particularly the horizontal diameter, which increased 47% (P<0.001). Water also increased mean

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horizontal diameter by 35% (P<0.012). Both D5W and water significantly increased mean maximal effective radius by 57% (P<0.002), but not the distal lesion radius (an increase of 50%; P<0.020). —Damian McNamara Dr. Provenzano is a consultant for Janssen Pharmaceuticals and Medtronic and receives honoraria from Cadence Pharmaceuticals, although no industry money financed the study. Dr. Cohen is a consultant to Halozyme and NDI.

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P OLI C Y & M A NAGEMENT CLOSED CLAIMS

CONTINUED FROM PAGE 1

in many cases, the patient’s injury is a result of [the anesthesiologist] not following directions or not being vigilant.” Dr. Domino, chair of the ASA’s professional liability committee, and her colleagues found that patients continue to experience preventable injuries from gas delivery equipment, burns from the misuse of forced-air warming units and complications from central venous catheters (CVCs). Many ULTIVA® for Injection

of these injuries could be prevented by following instructions from the manufacturer of the devices, along with ASA recommendations for use of the equipment, Dr. Domino said. Wade Willard, JD, vice president of claims at Preferred Physicians Medical (PPM), a provider of anesthesia malpractice insurance, said reviewing previous mistakes enables doctors to prevent future losses. “It’s like that old saying: You’ve got to learn from your history, or you’re doomed to repeat it.”

(remifentanil hydrochloride) For IV Use Only Rx only Brief Summary: The following is a brief summary only. Before prescribing, see complete ULTIVA prescribing information. CONTRAINDICATIONS Due to the presence of glycine in the formulation, ULTIVA is contraindicated for epidural or intrathecal administration. ULTIVA is also contraindicated in patients with known hypersensitivity to fentanyl analogs. WARNINGS AND PRECAUTIONS Continuous infusions of ULTIVA should be administered only by an infusion device. IV bolus administration of ULTIVA should be used only during the maintenance of general anesthesia. In nonintubated patients, single doses of ULTIVA should be administered over 30 to 60 seconds. Interruption of an infusion of ULTIVA will result in rapid offset of effect. Rapid clearance and lack of drug accumulation result in rapid dissipation of respiratory depressant and analgesic effects upon discontinuation of ULTIVA at recommended doses. Discontinuation of an infusion of ULTIVA should be preceded by the establishment of adequate postoperative analgesia. Injections of ULTIVA should be made into IV tubing at or close to the venous cannula. Upon discontinuation of ULTIVA, the IV tubing should be cleared to prevent the inadvertent administration of ULTIVA at a later point in time. Failure to adequately clear the IV tubing to remove residual ULTIVA has been associated with the appearance of respiratory depression, apnea, and muscle rigidity upon the administration of additional fluids or medications through the same IV tubing. USE OF ULTIVA IS ASSOCIATED WITH APNEA AND RESPIRATORY DEPRESSION. ULTIVA SHOULD BE ADMINISTERED ONLY BY PERSONS SPECIFICALLY TRAINED IN THE USE OF ANESTHETIC DRUGS AND THE MANAGEMENT OF THE RESPIRATORY EFFECTS OF POTENT OPIOIDS, INCLUDING RESPIRATORY AND CARDIAC RESUSCITATION OF PATIENTS IN THE AGE GROUP BEING TREATED. SUCH TRAINING MUST INCLUDE THE ESTABLISHMENT AND MAINTENANCE OF A PATENT AIRWAY AND ASSISTED VENTILATION. ULTIVA SHOULD NOT BE USED IN DIAGNOSTIC OR THERAPEUTIC PROCEDURES OUTSIDE THE MONITORED ANESTHESIA CARE SETTING. PATIENTS RECEIVING MONITORED ANESTHESIA CARE SHOULD BE CONTINUOUSLY MONITORED BY PERSONS NOT INVOLVED IN THE CONDUCT OF THE SURGICAL OR DIAGNOSTIC PROCEDURE. OXYGEN SATURATION SHOULD BE MONITORED ON A CONTINUOUS BASIS. RESUSCITATIVE AND INTUBATION EQUIPMENT, OXYGEN, AND AN OPIOID ANTAGONIST MUST BE READILY AVAILABLE. Respiratory depression in spontaneously breathing patients is generally managed by decreasing the rate of the infusion of ULTIVA by 50% or by temporarily discontinuing the infusion. Skeletal muscle rigidity can be caused by ULTIVA and is related to the dose and speed of administration. ULTIVA may cause chest wall rigidity (inability to ventilate) after single doses of >1 mcg/kg administered over 30 to 60 seconds, or after infusion rates >0.1 mcg/kg/min. Single doses <1 mcg/kg may cause chest wall rigidity when given concurrently with a continuous infusion of ULTIVA. Muscle rigidity induced by ULTIVA should be managed in the context of the patient’s clinical condition. Muscle rigidity occurring during the induction of anesthesia should be treated by the administration of a neuromuscular blocking agent and the concurrent induction medications. Muscle rigidity seen during the use of ULTIVA in spontaneously breathing patients may be treated by stopping or decreasing the rate of administration of ULTIVA. Resolution of muscle rigidity after discontinuing the infusion of ULTIVA occurs within minutes. In the case of life-threatening muscle rigidity, a rapid onset neuromuscular blocker or naloxone may be administered. ULTIVA should not be administered into the same IV tubing with blood due to potential inactivation by nonspecific esterases in blood products. PRECAUTIONS Vital signs and oxygenation must be continually monitored during the administration of ULTIVA. General: Bradycardia has been reported with ULTIVA and is responsive to ephedrine or anticholinergic drugs, such as atropine and glycopyrrolate. Hypotension has been reported with ULTIVA and is responsive to decreases in the administration of ULTIVA or to IV fluids or catecholamine (ephedrine, epinephrine, norepinephrine, etc.) administration. Intraoperative awareness has been reported in patients under 55 years of age when ULTIVA has been administered with propofol infusion rates of ≤ 75 mcg/kg/min. Rapid Offset of Action: WITHIN 5 TO 10 MINUTES AFTER THE DISCONTINUATION OF ULTIVA, NO RESIDUAL ANALGESIC ACTIVITY WILL BE PRESENT. However, respiratory depression may occur in some patients up to 30 minutes after termination of infusion due to residual effects of concomitant anesthetics. Standard monitoring should be maintained in the postoperative period to ensure adequate recovery without stimulation. For patients undergoing surgical procedures where postoperative pain is generally anticipated, other analgesics should be administered prior to the discontinuation of ULTIVA. ULTIVA should not be used as a sole agent for induction of anesthesia because loss of consciousness cannot be assured and because of a high incidence of apnea, muscle rigidity, and tachycardia. Pediatric Use: The efficacy and safety of ULTIVA as an analgesic agent for use in the maintenance of general anesthesia in outpatient and inpatient pediatric surgery have been established in controlled clinical trials in pediatric patients from birth to 12 years. In clinical trials, the clearance rate observed in neonates was highly variable and on average was two times higher than in the young healthy adult population. While a starting infusion rate of 0.4 mcg/ kg/min may be appropriate for some neonates, an increased infusion rate may be necessary to maintain adequate surgical anesthesia, and additional bolus doses may be required. The individual dose for each patient should be carefully titrated (see ULTIVA Prescribing Information [PI], DOSAGE AND ADMINISTRATION, Table 11). ULTIVA has not been studied in pediatric patients for use as a postoperative analgesic or as an analgesic component of monitored anesthesia care. Geriatric Use: Of the total number of subjects in clinical studies of ULTIVA, 486 were in the age range 66 to 90 years. While the effective biological half-life of remifentanil is unchanged, elderly patients have been shown to be twice as sensitive as the younger population to the pharmacodynamic effects of remifentanil. The recommended starting dose of ULTIVA should be decreased by 50% in patients over 65 years of age. Use in Morbidly Obese Patients: As for all potent opioids, caution is required with use in morbidly obese patients because of alterations in cardiovascular and respiratory physiology. Long-term Use in the ICU: No data are available on the longterm (> 16 hours) use of ULTIVA as an analgesic in ICU patients. Carcinogenesis, Mutagenesis, Impairment of Fertility: Animal carcinogenicity studies have not been performed with remifentanil. Remifentanil did not induce gene mutation in prokaryotic cells in vitroo and was not genotoxic in an in vivo rat assay. No clastogenic effect was seen in hamster or mouse studies. In the in vitroo mouse lymphoma assay, mutagenicity was seen only with metabolic activation. Remifentanil has been shown to reduce fertility in male rats when tested after approximately 40 times the maximum recommended human dose (MRHD). The fertility of female rats was not affected at IV doses as high as 1 mg/kg when administered for at least 15 days before mating. Pregnancy Category C: Teratogenic effects were not observed in either rats or rabbits following administration of remifentanil at doses up to 400 times and 125 times the MRHD, respectively. Administration of radiolabeled remifentanil to pregnant rabbits and rats demonstrated significant placental transfer to fetal tissue. There are no adequate and well-controlled studies in pregnant

Top 10 Health Technology Hazards for 2013 he ECRI Institute has released its annual list of the 10 most significant technology-related hazards in health care. Some items— surgical fires and alarm issues, for example—have appeared before. One newcomer, however, has particular relevance for Anesthesiology News: No. 9, digital distractions. To our knowledge, this potential hazard

women. ULTIVA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Administration of remifentanil to rats throughout late gestation and lactation at IV doses up to 400 times the MRHD in terms of mg/m2 of body surface area, had no significant effect on the survival, development, or reproductive performance of the F1 generation. Animal Toxicology: Intrathecal administration of the glycine formulation without remifentanil to dogs caused agitation, pain, hind limb dysfunction, and incoordination. These effects are believed to be caused by the glycine. Glycine is a commonly used excipient in IV products and this finding has no relevance for IV administration of ULTIVA. Labor and Delivery: Respiratory depression and other opioid effects may occur in newborns whose mothers are given ULTIVA shortly before delivery. The safety of ULTIVA during labor or delivery has not been demonstrated. Placental transfer studies in rats and rabbits showed that pups are exposed to remifentanil and its metabolites. In a human clinical trial, the average maternal remifentanil concentrations were approximately twice those seen in the fetus. In some cases, however, fetal concentrations were similar to those in the mother. The umbilical arteriovenous ratio of remifentanil concentrations was approximately 30% suggesting metabolism of remifentanil in the neonate. Nursing Mothers: It is not known whether remifentanil is excreted in human milk. After receiving radioactive-labeled remifentanil, the radioactivity was present in the milk of lactating rats. Because fentanyl analogs are excreted in human milk, caution should be exercised when ULTIVA is administered to a nursing woman. ADVERSE EVENTS In controlled clinical trials in approximately 2770 adult patients, ULTIVA produced adverse events characteristic of μ-opioids, such as respiratory depression, bradycardia, hypotension, and skeletal muscle rigidity. These adverse events dissipated within minutes of discontinuing or decreasing the infusion rate of ULTIVA. Table 1: Adverse Events Reported in ≥ 1% of Adult Patients in General Anesthesia Studies* at the Recommended Doses† of ULTIVA Induction/Maintenance

Postoperative Analgesia

ULTIVA (n=921)

Alfentanil/ Fentanyl (n=466)

ULTIVA (n=281)

Morphine (n=98)

ULTIVA (n=929)

Alfentanil/ Fentanyl (n=466)

Nausea Hypotension Vomiting Muscle rigidity Bradycardia Shivering Fever Dizziness Visual disturbance Headache Respiratory depression Apnea Pruritus Tachycardia Postoperative pain Hypertension Agitation Hypoxia

8 (<1%) 178 (19%) 4 (<1 % ) 98 (11%)‡ 62 (7%) 3 (<1%) 1 (<1%) 0 0 0

0 30 (6%) 1 (<1%) 37 (8%) 24 (5%) 0 0 0 0 0

61 (22%) 0 22 (8%) 7 (2%) 3 (1%) 15 (5%) 2 (<1%) 1 (<1%) 0 1 (<1%)

15 (15%) 0 5 (5%) 0 3 (3%) 9 (9%) 0 0 0 1 (1%)

339 (36%) 16 (2%) 150 (16%) 2 (<1%) 11 (1%) 49 (5%) 44 (5%) 27 (3%) 24 (3%) 21 (2%)

202 (43%) 9 (2%) 91 (20%) 1 (<1%) 6 (1%) 10 (2%) 9 (2%) 9 (2%) 14 (3%) 8 (2%)

1 (<1%) 0 2 (<1%) 6 (<1%) 0 10 (1%) 2 (<1%) 0

0 1 (<1%) 0 7 (2%) 0 7 (2%) 0 0

19 (7%) 9 (3%) 7 (2%) 0 7 (2%) 5 (2%) 3 (1%) 1 (<1%)

4 (4%) 2 (2%) 1 (1%) 0 0 3 (3%) 1 (1%) 0

17 (2%) 2 (<1%) 22 (2%) 10 (1%) 4 (<1%) 12 (1%) 6 (<1%) 10 (1%)

20 (4%) 1 (<1%) 7 (2%) 8 (2%) 5 (1%) 8 (2%) 1 (<1%) 7 (2%)

*Does not include adverse events from cardiac studies or the neonatal study. See ULTIVA PI, Tables 6, 7, and 8 for cardiac information. † See ULTIVA PI, Table 10 for recommended doses. Not all doses of ULTIVA were equipotent to the comparator opioid. Administration of ULTIVA in excess of the recommended dose (i.e., doses >1 and up to 20 mcg/kg) resulted in a higher incidence of some adverse events: muscle rigidity (37%), bradycardia (12%), hypertension (4%), and tachycardia (4%). ‡ Included in the muscle rigidity incidence is chest wall rigidity (5%). The overall muscle rigidity incidence is <1% when remifentanil is administered concurrently or after a hypnotic induction agent. In the elderly population (> 65 years), the incidence of hypotension is higher, whereas the incidence of nausea and vomiting is lower. DRUG ABUSE AND DEPENDENCE ULTIVA is a Schedule II controlled drug substance that can produce drug dependence of the morphine type and has the potential for being abused. OVERDOSAGE As with all potent opioid analgesics, overdosage would be manifested by an extension of the pharmacological actions of ULTIVA. Expected signs and symptoms of overdosage include: apnea, chest-wall rigidity, seizures, hypoxemia, hypotension, and bradycardia. In case of overdosage or suspected overdosage, discontinue administration of ULTIVA, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function. If depressed respiration is associated with muscle rigidity, a neuromuscular blocking agent or a μ-opioid antagonist may be required to facilitate assisted or controlled respiration. Intravenous ﬂuids and vasopressors for the treatment of hypotension and other supportive measures may be employed. Glycopyrrolate or atropine may be useful for the treatment of bradycardia and/or hypotension. Intravenous administration of an opioid antagonist such as naloxone may be employed as a speciﬁc antidote to manage severe respiratory depression or muscle rigidity. Respiratory depression from overdosage with ULTIVA is not expected to last longer than the opioid antagonist, naloxone. Reversal of the opioid effects may lead to acute pain and sympathetic hyperactivity. ULTIVA is a registered trademark of Glaxo Group Limited. US Patent Nos. 5,019,583; and 5,866,591 Manufactured for Bioniche Pharma USA LLC, Lake Forest, IL 60045 Manufactured by Hospira, Inc. Lake Forest IL 60045

Alarm hazards

Medication administration errors using infusion pumps

Unnecessary exposures and radiation burns from diagnostic radiology procedures

Patient/data mismatches in EHRs and other health IT systems

Interoperability failures with medical devices and health IT systems

Air embolism hazards

Inattention to the needs of pediatric patients when using “adult” technologies

Inadequate reprocessing of endoscopic devices and surgical instruments

Caregiver distractions from smartphones and other mobile devices

10. Surgical fires

After Discontinuation

Adverse Event

Version B, 06/08/2011

was first raised in a November 2011 commentary in these pages by Peter Papadakos, MD, a board member of Anesthesiology News.

In the latest analysis, Dr. Domino’s group reviewed a database of 9,536 closed claims dating from the 1970s to 2010, housed at the University of Washington, in Seattle, where she is a professor of anesthesiology. The Closed Claims Project is now receiving support from the Anesthesia Quality Institute. Passing Gas—Badly Claims decreased over time for injuries involving anesthesia gas delivery equipment (abstract 1072), from 4% of claims in the 1970s to 1% in the 20 years between 1990 and 2010. The drop likely resulted from improvements in equipment design, such as alarms to alert physicians that a ventilator has shut off, Dr. Domino said. During that time, the severity of injuries also fell; however, more than one-third of injured patients experienced permanent brain damage or died, demonstrating how dangerous these injuries are when they occur. Mr. Willard, who did not participate in the study, said that given PPM’s own experience the new data were not surprising. The best way to avoid problems with gas delivery equipment, he said, is to perform preoperative checks that ensure the device is functioning properly. “If you do that, you can completely head off possible claims with just a few minutes of checks,” he said.

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AnesthesiologyNews.com I 13

POL ICY & M A N A G E ME N T Too Hot To Handle In another analysis, Dr. Domino and her team looked at burns to patients from warming devices or heated materials, which represented 1% of closed claims and resulted in median payments of $97,980 for new claims (abstract 1079). Most of these injuries occur when doctors do not use the devices properly, she told Anesthesiology News. Rather, they place the forced-air warming hose next to patients without putting it into a specially designed warming blanket, or they use warm IV bags to position patients, leading to burns. “This is just a reminder for people to not do that,” she said.

of which (59%) resulted in permanent brain damage or death (abstract 1075). The most common complication, carotid cannulation/puncture, increased in more recent years. The reason for the trend is unclear, Dr. Domino said. Although current guidelines recommend doctors use ultrasound to guide the placement of CVCs, none of the doctors named in the malpractice claims did so. Another potential explanation for the increase in these injuries,

Mr. Willard said, is that doctors who use ultrasound may pay less attention to their technique. “You don’t want to erase all the things you would normally do if you didn’t have ultrasound in your hand.” When these injuries happen, they are serious. According to the analysis, median payment in CVC claims from 1995 to 2009 was $226,400. The largest was more than $9 million. “When they occur, they can be a fairly significant injury,” Mr. Willard said.

The bottom line, Dr. Domino said, is that when using their equipment, anesthesiologists should follow instructions from the manufacturer as well as the ASA and other bodies that issue guidelines on the proper use of medical equipment. “We need to use the equipment in the proper fashion, in the way the companies that manufactured it have instructed,” she said. —Alison McCook

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hours, if the patient is unconscious or the item is placed on an insensate place on the skin.’ —Mark Bruley “No one should be using heated IV bags or bottles for warming patients,” said Mark Bruley, vice president of accident and forensic investigation at ECRI Institute, a nonprofit organization that investigates patient safety. In 2005, ECRI “strenuously recommended” limiting temperatures of warming devices to avoid such problems. He noted that warming cabinets for blankets should be kept at no more than 130 F, and IV bags should be housed in a solution cabinet at no more than 110 F. Mr. Bruleyy said his group has received pushback from clinicians who say they fear patients will not warm up. But blankets simply eliminate heat loss, they do not raise core temperatures, he explained. “Something that does not feel hazardously hot to a clinician can burn a patient in minutes or hours, if the patient is unconscious or the item is placed on an insensate place on the skin,” Mr. Bruleyy said. “It’s a bit surprising to me that, up to 2010, we continue to see bags and bottles causing burns.” Catheter Complications Finally, Dr. Domino and her colleagues looked at closed claims for injuries involving CVCs, the majority

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Meta-Analysis: IV Analgesic Reduces PONV When Given Early

ntravenous acetaminophen prevents postoperative nausea and vomiting (PONV), but only if given prophylactically, a new metaanalysis has found. The study, by researchers at the University of California, San Francisco School of Medicine, showed that IV acetaminophen—marketed in the United States as Ofirmev by Cadence

Pharmaceuticals and as Perfalgan by Bristol-Myers Squibb abroad—had antiemetic effects as long as patients received the drug before, during or immediately after surgery. It did not appear to help ease nausea or vomiting in patients who had already begun experiencing pain during recovery. The researchers presented their study at the 2012 annual meeting of the American

Society of Anesthesiologists (abstract 1314). Christian Apfel, MD, PhD, and his colleagues analyzed 30 studies, involving 2,364 patients, of whom 1,223 had received IV acetaminophen during the perioperative period. Dr. Apfel’s group found that patients who received IV acetaminophen were about 40% less likely to experience PONV, but those

who got the analgesic at the first sign of pain during recovery had no reduction in risk. “Prophylactically administered IV acetaminophen reduces postoperative nausea and postoperative vomiting,” the researchers wrote. “The effect size measured on a relative risk scale to reduce PONV is comparable with that of antiemetics used for the prevention of PONV.” —Adam Marcus

Lidocaine + Propofol = Less Injection Pain

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dministering lidocaine along with — but not before — propofol during IV sedation reduces the burning sensation associated with the injection, researchers have found. In the retrospective analysis, by a group at the UMDNJ-Robert Wood Johnson University Hospital, in New Brunswick, N.J., 103 patients received IV lidocaine before they received an injection of propofol. Another group (n=82) received a combination of 60 mg of lidocaine and 200 mg of propofol. The researchers found that patients who received the combined injection were about half as likely to report pain as those who received lidocaine prior to propofol (P<0.00001). P Patients given the combination of agents reported lower pain scores than those who received the drugs sequentially—0.8 versus 1.7 on a 10-point scale. “The rationale for mixing lidocaine with propofol is based on the idea that lidocaine may act as a stabilizer of the kinin cascade,”which propofol may activate, the researchers explained. “Another possible mechanism is that mixing the two agents decreases the pH of propofol, resulting in a lower concentration of propofol in its aqueous phase and subsequently less pain.” The researchers presented their findings at the 2012 PostGraduate Assembly in Anesthesiology (abstract P-9023). —Adam Marcus

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CL IN ICA L A N E STH E SIOL OG Y

Seven Red Flags for Outpatient Surgery Database study IDs risk factors for poor outcomes Washington—With outpatient surgeries now accounting for more than 60% of all operations performed each year in the United States, the complexity of such cases is on the rise. And although outpatient surgery generally is quite safe, some anesthesiologists have begun to question whether certain patients present more of a risk than others. A national database review of more than 240,000 records by researchers at the University of Michigan has identified seven independent preoperative risk factors that increase the risk for morbidity and mortality after ambulatory surgery. “We know that the prevalence of morbidity and mortality after outpatient surgery is relatively low,” said Michael Mathis, MD, an anesthesiology resident at the Ann Arbor institution. “We also know the risk factors for inpatient admission following outpatient surgery, but we don’t know the specific risk factors for morbidity and mortality after outpatient surgery. So this study set out to test the hypothesis that patient history and intraoperative characteristics do, indeed, predispose patients to major morbidity and mortality after common outpatient surgical procedures.” The researchers used databases from the Centers for Medicare & Medicaid Services and Blue Cross Blue Shield to identify 150 of the most commonly performed outpatient surgeries. These procedure codes were then used as inclusion criteria for an analysis of the outpatient surgeries recorded within the American College of Surgeons National Surgical Quality

Improvement Program Participant Use File (2005-2010). “This yielded a population of more than 244,000 [244,397] patients, which gave us excellent statistical power for the study,” Dr. Mathis explained. The study population was then assessed for a variety of risk factors, including patient demographic data such as age and body mass index (BMI); past medical history data such as neurovascular, cardiovascular and pulmonary pathologies; and surgical characteristics, including a recent or a prolonged procedure. The five most commonly experienced complications included unplanned reintubation, postoperative pneumonia, surgical site infection, intraoperative blood transfusion and the inability to intubate. As Dr. Mathis reported at the 2012 annual meeting of the American Society of Anesthesiologists (abstract 017), 629 of the 244,397 cases analyzed (0.3%) involved major morbidity or mortality, corresponding to an incidence of approximately one per every 389 patients. The seven independent preoperative risk factors identified by the multivariate logistic regression analysis were disseminated cancer, paraplegia/quadriplegia, age 70 years or older, use of steroids, chronic obstructive pulmonary disease and history of transient ischemic attack or stroke (Figure). Dr. Mathis said that although outpatient surgery is safe, “we believe the results of the study can be used to direct outpatient surgical centers in adopting improvements in

preoperative patient screening. In this regard, we believe our model provides much-needed hard data and allows for preoperative screening to be a practice based on evidence rather than solely on clinical intuition and experience.” Stavros G. Memtsoudis, MD, PhD, clinical associate professor of anesthesiology and public health at Weill Cornell Medical College, in New York City, called the new study a good example of research that can be conducted using large databases. But Dr. Memtsoudis stressed that clinicians should exercise caution when interpreting results from such sources. “The incidence of major morbidity and mortality in the study population is very low, thus requiring the use of a cumulative outcome measure comprised of individual complication of arguably very different severity and impact,” he said. “It must be noted that the risk factor with the highest odds for adverse

‘Our model provides muchneeded hard data and allows for preoperative screening to be a practice based on evidence rather than solely on clinical intuition and experience.’ —Michael Mathis, MD outcome is the presence of a diagnosis of cancer,” Dr. Memtsoudis added. “One is therefore left speculating if the adverse event studied here is a consequence of the natural progression of the disease in patients undergoing ambulatory procedures rather than a complication of the intervention itself.”

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History of cancer

4.24 (2.60-6.92)

Paraplegia/quadriplegia

3.53 (1.30-9.56)

Age ≥81

2.43 (1.57-3.77)

History of renal failure/dialysis

2.31 (1.12-4.75)

Current steroid use

1.80 (1.10-2.94)

Chronic obstructive pulmonary disease

1.67 (1.13-2.46)

expires April 1, 2013

History of TIA/CVA

1.50 (1.05-2.14)

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Adjusted odds ratio (95% confidence interval)

Figure. Independent risk factors for major morbidity or mortality after outpatient surgery. CVA, cerebral vascular attack; TIA, transient ischemic attack

—Michael Vlessides

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CONTINUED FROM PAGE 1

blockade (defined by the researchers as a train of four [TOF] ratio lower than 0.9) during routine anesthesia practice. The interim analysis included 141 patients recruited at eight centers between June and December 2011. Neuromuscular function was assessed in each subject using acceleromyography. Although the attending anesthesiologist and nurses in the post-anesthesiaa care unit (PACU) were blinded to the results of acceleromyography monitoring, they were free to provide care to the patients as they saw fit. That flexibility included the dosing of the neuromuscular blocking agent, administration of the reversal agent and the decision to extubate. The use of reversal agents and the effect of neuromuscular blocker reversal on the incidence of residual neuromuscular blockade were assessed both at extubation and on arrival in the PACU. “You need to reach a TOF of 0.9 to be considered to be safely extubated and not have any residual paralysis,” said Dr. Galarneau, who reported the

IT ’S N

Table. Incidence of Residual Neuromuscular Blockade (TOF<0.9) Reversal Agent

No Reversal Agent

P Value

At extubation (n=141)

60% (62/103)

47% (18/38)

0.185

On PACU arrival (n=126)

49% (48/97)

31% (9/29)

0.092

PACU, CU, post post-anesthesia a est es a ca caree uunit; t; TOF, O , train-of-four t a o ouu

findings at the 2012 annual meeting of the Canadian Anesthesiologists’ Society (abstract 1344674). The study population was primarily female (74%), with a median age of 45 years. Patients were undergoing laparoscopic (54%) or open abdominal (46%) surgeries, and rocuronium was used in 99% of cases. Patients received neostigmine for reversal; the median dose was 35 mcg/kg (range, 6-77 mcg/kg). The overall incidence of residual paralysis was 57% at tracheal extubation and 45% on arrival to the PACU (Table). Yet despite the fairly high rate of residual blockade in the study subjects, Dr. Galarneau was not surprised by the findings. “We hypothesized that we would find a rate of about 30%, but

E... M A G OT A

other studies have shown that these rates can be all over the map,” he said. “Nevertheless, the power of this study is that it’s multicentered and there was very little difference in terms of residual neuromuscular blockade rates between centers.” Residual paralysis has proved to be a nettlesome problem for anesthesiologists. Recent data suggest that as many as 40,000 surgery patients in the United States each year experience serious respiratory problems resulting from unresolved neuromuscular blockade (see Anesthesiology News, August 2011, page 1). Better use of conventional reversal agents or other interventions may be warranted in the typical clinical setting. Other potential solutions include improving the timing of reversal and better monitoring of

patients, according to Dr. Galarneau. Colin J.L. McCartney, MBChB, director of anesthesia research at Sunnybrook Health Sciences Centre in Toronto, Ontario, found the study’s incidence of residual neuromuscular block surprisingly high. “However, it is important to realize that these data are not from a randomized trial, nor do we have any information on rocuronium dose or incidence of any patient complications (subjective or objective) related to residual neuromuscular block. In other words, although the measured incidence of residual neuromuscular block was high, did this in fact make any clinical difference?” He added, “Nevertheless, I agree with the investigators that the study underlines the need to monitor neuromuscular block in all patients given muscle relaxants, and further research to determine the clinical impact of residual neuromuscular block.” Merck makes the reversal agent sugammadex, which is sold as Bridion outside the United States. The company hopes to obtain FDA approval for its drug later this year. —Michael Vlessides

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Study: Lower HES Not Linked to Post-Craniotomy Bleeding Hextend or Voluven (P=0.60). Dr. McDonagh noted that the patients in his group’s analysis had received fairly low doses of HES, which are defined as less than 1,600 mL. He also said the number of HES-exposed patients was relatively small. “Given these factors, I would say that although the findings suggest HES use in craniotomy is not likely to be a major

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review of nearly 300 craniotomy patients who received lowdose intraoperative hydroxyethyl starch (HES) has found no increase in risk for hemorrhage with use of the intravascular volume expander. The findings, presented at the 2012 annual meeting of the American Society of Anesthesiologists (abstract 464), are the latest to address the safety of an agent that has been at the center of a series of recent controversies. Most notably, several dozen studies on the topic published by German anesthesiologist Joachim Boldt, MD, were retracted following discoveries of improper research methods, including falsified data (see Anesthesiology News October 2010, page 1). Most of Dr. Boldt’s work concluded HES was safe to administer during a variety of procedures. The removal of Dr. Boldt’s studies from the literature on HES means the agent now needs to be evaluated anew, said Robert A. Peterfreund, MD, PhD, anesthetist in the Department of Anesthesia, Critical Care and Pain Medicine, at Massachusetts General Hospital, in Boston. “I don’t think we can factor Dr. Boldt’s studies into the discussion of HES,” said Dr. Peterfreund, who was not involved in the latest study. “With that in mind, although the current study is provocative and suggests there may not be an increased risk for hemorrhage following craniotomy, I think it leaves many questions unanswered and, overall, I believe we don’t have adequate data to decide either way whether HES is associated with coagulopathy.” David McDonagh, MD, chief of neuroanesthesia at Duke University Medical Center, in Durham, N.C., and his colleagues analyzed data from 3,768 craniotomies performed there between 2005 and 2011. Of those cases, 190 patients had received Hextend and 106 were given Voluven (both Hospira products). The average volume of Hextend administered was 635 (±286) mL and the average volume of Voluven given was 725 (±350) mL. Dr. McDonagh reported that 1.19% of patients (45 of 3,768) suffered hemorrhage and required craniotomies. Of the repeat craniotomy patients, 11.1% (five of 45) had received Hextend during the initial craniotomy and none had been given either of the two products. A statistical analysis did not find an increased risk for post-craniotomyy hemorrhage when patients received either

contributor to post-craniotomyy hemorrhage, until we have more data, I would not conclude that HES is safe for use during craniotomy,” Dr. McDonagh said. Dr. Peterfreundd agreed that the doses of HES used in these patients were low. He added that the effect of HES on clotting function is believed to be dose-dependent. Furthermore, he said, the Duke study

did not control for potentially confounding variables such as patient age, type of lesion targeted during the first surgery and whether the surgery was elective or emergent. Both physicians called for further prospective study of the safety of HES in neurosurgical as well as other patient populations. —David Wild

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Multimodal Monitoring May Minimize Risk For Intraoperative Awareness Strategy combines EEG and physiologic parameters of activity from the main target organ: the brain,” Dr. Kochs told Anesthesiology News. “This combination allows a better separation of different anesthetic levels than standard monitoring parameters or EEG monitors alone.” The ability of AMI to exclude EEG frequencies above 30 Hz may reduce the influence of muscle activity on EEG readings, “avoiding the risk that a patient who is awake under neuromuscular blockade may be classified as unconscious,” the researchers wrote. “The ability to predict the transition between states was less reliable

with both monitors, but the combination of common parameters and their EEG algorithm was better than the BIS number,” said Leslie C. Jameson, MD, associate professor and vice chair of anesthesiology at the University of Colorado School of Medicine, in Denver. In a related study of the same 263 patients (abstract 184), AMI more reliably detected awake and burst suppression EEG levels than BIS monitoring, according to the German team. The prediction probability was significantly higher with AMI, 1.00,

anesthetic dose

burst suppression (BS) anesthetic increase start EEG/AEP

anesthetic decrease

LOC skin incision

ROC

Figure 1. Diagram of the study period. LOC, loss of consciousness; ROC, return of consciousness.

100

AMI

80 60 40 20

100 80

BIS

team of researchers in Germany thinks they may have found a reliable strategy for preventing the rare but potentially devastating patient report of awareness during anesthesia. Traditional approaches such as bispectral index (BIS, Covidien) monitoring have their flaws, and electroencephalography (EEG) alone suffers from artifact sensitivity and interindividual variability. Eberhard F. Kochs, MD, Denis Jordan, PhD, and their colleagues at Klinikum rechts der Isar, Technische Universität München, in Germany, conducted two studies to compare BIS, EEG and the new anesthesia multimodal indicator (AMI) technology. The AMI algorithms integrate EEG findings; physiologic parameters including heart rate, mean arterial pressure and concentrations of inspiratory and expiratory gases; patient data; and drug protocol and concentrations. “Integration of different modalities in one index provides additional information to EEG and leads to reliable detection of different anesthetic states, in particular detection of consciousness,” Dr. Jordan told Anesthesiology News. “The AMI could support the anesthesiologist’s decision making,” said Dr. Jordan, whose group reported its findings at the 2012 annual meeting of the American Society of Anesthesiologists (abstract 190). In a sense, he noted, the AMI algorithms mirror the way a physician collects and integrates information from multiple sources to yield a more complete picture of the anesthetic state. In their multicenter study of 263 patients receiving general anesthesia, the researchers compared the ability of AMI and BIS to detect loss of consciousness (LOC) and return of consciousness (ROC). Multimodal AMI had a significantly higher prediction probability to separate consciousness from unconsciousness (P<0.05) than BIS. AMI was more reliable at detection of LOC/ ROC and ROC, although both methods had similar prediction probabilities for LOC alone. “The AMI combines traditional parameters used to assess the hypnotic component of anesthesia with measures

60 40 20 Awake

Unconscious

Clinical practice

BIS

Figure 2. Indicator value distribution of the AMI (A) and of BIS (B) for the indicated anesthetic levels (central line: median, dots: 5% and 95% percentiles, whiskers: 10% and 90% percentiles, boxes: 50% quartiles). AMI, anesthesia multimodal indicator; BIS, bispectral index

compared with 0.87 with BIS to detect awake and burst suppression levels. “This index is the first EEG analysis in a significant period of time that has systematically evaluated depth of anesthesia monitoring in a multicenter, large randomized trial,” said Dr. Jameson, who was not involved with either trial. “Of significant note was the finding that the study’s new EEG analysis was nearly as effective as the combined parameters plus the study EEG analysis.” That fact, she said, suggests several things: The addition of common parameters had only a small effect on predicting awake or burst suppression with new EEG analysis or the BIS numeric value alone was not a good predictor of awake or burst suppression. “As a clinician, I do not find this surprising,” Dr. Jameson said. “Vital signs and anesthetic concentration alone are poor absolute predictors of anesthetic depth in the individual patient, which leads one empirically to provide very deep hypnosis. Second, a different EEG waveform analysis may be better at predicting the awake to burst suppression threshold than the current BIS analysis.” “The important and exciting concept in both abstracts is that a new analysis of EEG with or without common parameters can better predict depth of anesthesia,” Dr. Jameson said. “The hunt for the best device to measure the response to anesthetic drugs should continue just as it has for other important physiologic measures of well-being, such as noninvasive cardiac output and pulse oximetry. Whether or not the addition of common parameters significantly enhances the monitor will require continued research.” Additional data from prospective, independent studies are needed to confirm the AMI proof of concept and clinical utility, Dr. Kochs said. ”We believe that the basic concept of a multimodal integration including all available data recorded during anesthesia is of high clinical relevance in the near future.” —Damian McNamara Drs. Jordan, Kochs and Jameson reported no relevant financial conflicts.

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recommends hand washing, using fullbarrier precautions when inserting At Hopkins, Dr. Pronovost helped central venous catheters, cleaning the implement a five-step checklist and a skin with chlorhexidine, avoiding the culture of safety that reduced the rate femoral site for insertion and removof central-line catheter infections in ing unnecessary catheters—in MichiICUs there from nearly 12% in 1998 gan. He also has been working with the to almost none today. The work was American Hospital Association and conducted largely after the death of the Agency for Healthcare Research an 18-month-old girl at the hospital in and Quality to implement similar pro2001 from a preventable error. grams in 1,100 hospitals in 46 states. Dr. Pronovost since has imple- The average rate of central-line infecmented the checklist protocol—which tions in participating hospitals is now CONTINUED FROM PAGE 1

1%; 65% of the hospitals went one year without any infections, and 25% went twice that long. “When we first started, I didn’t see these infections as my problems and I didn’t really believe I could prevent them, because I take care of sick patients and things happen to sick patients,” Dr. Pronovost said. “What we saw literally across [the] country is that when clinicians said, ‘this is my problem, and I’m able to solve it,’ infections went away.”

Dr. Pronovost asked anesthesiologists to adopt at least one measure in their own settings, such as creating a comprehensive unit-based safety team in their operating room, learning from one defect in their settings, expanding peer-to-peer review or brainstorming a list of potential patient harms. Anesthesia in the Developing World Anesthesia-related mortality has decreased significantly during the past 50 years in the developed world, but not in low- and middle-income countries, according to a panel of experts that discussed provision of safe perioperative care to children worldwide. Problems stem from a lack of resources including water, electricity, oxygen and manpower. In Uganda, for example, 45 anesthesiologists serve the entire country, and anesthesia largely consists of ketamine delivered by a nonphysician workforce, said Isabeau Walker, BSc, MD, consultant pediatric anesthesiologist at Great Ormond Street Hospital, in London. The World Health Organization is one of several groups trying to improve training in developing countries through its Emergency and Essential Surgical Care Program. Experts there are working with more than 34 low-resource countries to establish or improve programs for emergency and surgical care, set standards and research issues surrounding the delivery of these services. Angela Enright, MD, clinical professor of anesthesia at the University of British Columbia, in Canada, discussed the Lifebox Project, a global initiative to donate long–battery life pulse oximeters and provide pulse oximetry education to developing countries. Some 77,000 operating rooms around the world do not have the technology, she said. A $300 donation provides an oximeter and adult, pediatric and neonate probes. New Technologies In a session on new technologies, Daryl Kor, MD, an anesthesiologist at Mayo Clinic, in Rochester, Minn., discussed work at his hospital creating a perioperative “data mart,” a database integrating various sources of information about hospitalized patients, including clinical notes, medication information, lab values and data from anesthesiology information management systems. Studying the combined data, Dr. Kor and his colleagues started developing algorithms to track the incidence of and design

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AnesthesiologyNews.com I 21

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Cutting Complications

nvestigators at Cincinnati Children’s Medical Center have identified risk factors for postoperative respiratory complications in children and decreased the rate of these complications by more than half. In one study, the team collected data on 16,910 children treated in the hospital’s surgical and radiology postanesthesia care units (PACUs) at the hospital’s main and ambulatory campuses, from September 2007 to March 2012. They looked at the following outcomes: apnea or hypopnea (need for bag mask ventilation); laryngospasm (positive pressure ventilation above 20 cm H2O or administration of succinylcholine); bronchospasm (use of albuterol); and oxygen requirement (to maintain SpO2 above 92% for two hours postoperatively). Respiratory complications occurred in 2.2% of all patients. Complications were more likely in patients with American Society of Anesthesiologists physical status scores of at least 3, pre-existing neuromuscular disease or hypotonia, and morbid obesity, and in those who had intraoperative bronchospasm or intraoperative laryngospasm. Younger age (up to 3 years) was not a significant factor for the development of complications. “These can definitely be extrapolated to any institution, whether a community hospital or an academic medical center,” Rajeev Subramanyam, MD, lead author of the study, told Anesthesiology News. In a related quality improvement study, Dr. Subramanyam and his colleagues sought to decrease the rates of postoperative respiratory complications among healthy children undergoing general anesthesia for general surgical, orthopedic and urologic procedures. At the time, the majority of the children

interventions for complications like acute lung injury (ALI), transfusionrelated acute lung injury (TRALI), anemia and septic shock. Using this system, they determined that high tidal volumes and elevated airway pressures were associated with the development of postoperative ALI. Sharing this information led to tidal volumes dropping from greater than 8 cc per kg of ideal body weight to around 6.5; the incidence of ALI declined from 8% to around 4%. The researchers are implementing

were extubated deep and moved to the PACU before emergence from general anesthesia. The researchers implemented four interventions: The day before or on the morning of surgery, the attending anesthesiologist had a formal discussion with the nurse anesthetists or fellow about the awakening plan. They developed an intraoperative electronic record charting variable to remind the nurse anesthetist

or fellow of the plan. They provided feedback to the anesthesia staff on problems and where improvements could be made. And they discussed the project and progress each month at departmental meetings. As a result, the percentage of awake patients on PACU handoff increased from 55% in August 2009 to 75% by January 2010. During 2010, the mean percentage of patients having

postoperative respiratory complications decreased from 2.5% to 1.1%. These interventions easily could be adopted by other hospitals, Dr. Subramanyam said. The researchers presented their study findings at the International Assembly for Pediatric Anesthesia meeting, in Washington, D.C. —K.B.

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OFIRMEV reduces opioid consumption*1 • OFIRMEV 1 g (Q6h) + PCA morphine significantly reduced morphine consumption vs placebo + PCA morphine (–46% over 6 h, P<0.01; –33% over 24 h, P<0.01)1 • The clinical benefit of reduced opioid consumption was not demonstrated

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Discontinue OFIRMEV immediately if symptoms associated with allergy or o hypersensitivity occur. Do not use in patients with acetaminophen allergy. The most common adverse reactions in patients treated with OFIRMEV were nausea, vomiting, headache, and insomnia in adult patients and nausea, vomiting, constipation, pruritus, agitation, and atelectasis in pediatric patients. OFIRMEV is approved for use in patients ≥2 years of age. The antipyretic effects of OFIRMEV may mask fever in patients treated for postsurgical pain. To report SUSPECTED ADVERSE REACTIONS, contact Cadence Pharmaceuticals, Inc. at 1-877-647-2239 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.com. Please see Brief Summary of Prescribing Information on adjacent page or full Prescribing Information at OFIRMEV.com.

OFIRMEV should be administered only as a 15-minute intravenous infusion. *Randomized, double-blind, placebo-controlled, single- and repeated-dose 24-h study (n=101). Patients received OFIRMEV 1 g + PCA morphine or placebo + PCA morphine the morning following total hip or knee replacement surgery. Primary endpoint: pain relief measured on a 5-point verbal scale over 6 h. Morphine rescue was administered as needed. †SPID24=sum of pain intensity differences, based on VAS score, from baseline, at 0 to 24 h.

References: 1. Sinatra RS, Jahr JS, Reynolds LW, Viscusi ER, Groudine SB, Payen-Champenois C. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology. y 2005;102:822-831. 2. Data on file. Cadence Pharmaceuticals, Inc.

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Studies Explore Effects of Anesthesia on Children

hildren exposed to general and related issues of pediatric surgery. anesthetics before their first Researchers presented two of the studbirthday are 4.5 times more ies at the 2012 International Assembly likely to develop learning disabilities for Pediatric Anesthesia (IAPA) meetby age 12 than children not exposed ing in Washington, D.C. The third to anesthesia, according to a study by study appeared in a recent issue of researchers in Singapore. Anesthesiology. That finding comes from a trio of For the Singapore work (abstract recent studies looking at the effects of GA2-44), investigators at the KK anesthesia on the brains of children Women’s and Children’s Hospital

searched the institution’s database for children born in 1998-1999 with no preexisting medical conditions, who were exposed to general anesthesia (GA) with sevoflurane during minor surgical procedures such as herniotomies, circumcision, cystoscopies and pyloromyotomies before their first birthday. They compared the performance of 100 of these children on the

Primary School Leaving Examination (PSLE), a national examination children take in school at age 12, with that of 106 children not exposed to anesthesia. They also interviewed parents about their children’s medical history, school and home environment. “We have kids who are born otherwise healthy who come in for minor procedures, and we like to think they would wind up all right,” Choon Bong, MBChB, FRCA, lead author of the study and consultant anesthetist at the hospital, told Anesthesiology News. But after accounting for variables including race, sex, maternal and paternal education, domestic living arrangements and afterschool activities, the only significant predictor of formally diagnosed learning disability was previous exposure to GA. Fifteen percent of children with early exposure to GA had a learning disability formally diagnosed by a medical or educational professional compared with 3.77% of controls (P<0.001). Of parents whose children were exposed to GA, 27% perceived their children to have learning difficulties such as dyslexia, difficulty with math and problem-solvingg skills, or language problems compared with 4.7% of parents in the control group (P<0.001). Dr. Bongg said the study does not prove a causative link between exposure to GA and subsequent developmental difficulties. But it “has alerted us that if an infant doesn’t really need urgent surgery, it may be prudent to consider waiting.” She said she and her colleagues plan to conduct a larger, prospective study. First Cut Often Not the Last Also at the IAPA meeting, researchers at the University of Vermont College of Medicine (UVM), in Burlington, reported that a large proportion of children who undergo surgery return for more procedures during childhood (abstract GA2-41). The researchers studied medical records from 1,024 children in the Vermont Infant Spinal Registry, a clinical database of every infant undergoing spinal anesthesia at UVM between 1998 and 2003. They then examined full UVM medical records for these patients, noting the initial surgery type, anesthetic technique and duration. Complete medical records were available for 711 patients, of whom 215 (30.2%) had received more than

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PR N one anesthetic before the age of 5 years. Infants who originally came to UVM for inguinal hernia repair had a 28.8% incidence of subsequent surgeries. “Since cognitive delay after exposure to anesthesia and surgery is most strongly associated with multiple exposures, anesthesiologists caring for young children should take note of the nontrivial likelihood that infants may return for another surgery at an early age,” said Robert Williams, MD, associate professor of anesthesia and pediatrics UVM, who helped conduct the study. To minimize children’s exposure to general anesthesia, Dr. Williams said, anesthesiologists should consider alternatives when practical, including regional anesthesia and the use of adjuvants like IV acetaminophen, ketorolac and α-2 medications such as clonidine. The Trouble With Lactate In a third study, researchers at Stony Brook University School of Medicine, in Long Island, N.Y., have found that sevoflurane affects children’s brains differently from propofol. Sevoflurane produced significantly more lactate, which increases during brain activation and in children may be associated with higher risk for anxiety and delirium upon emerging from anesthesia. For the study, published in the November issue of Anesthesiology (117:1062-1071), researchers studied 59 children ages 2 to 7 years scheduled for magnetic resonance imaging under GA. The children were randomized to receive either sevoflurane or propofol. All children received inhalational mask induction with sevoflurane for one to two minutes. Children randomized to receive propofol then were immediately converted to an IV propofol infusion. The duration of anesthesia in each group was about one hour. The researchers mapped the metabolic patterns of the children’s brains during the last 10 minutes of their procedures using proton magnetic resonance spectroscopy. The scans revealed that the parietal cortex of children who received sevoflurane had about twice the amount of lactate and 20% more glucose than did the brains of children receiving propofol. During emergence from anesthesia, recovery room nurses assessed each child for emergence delirium using the Pediatric Anesthesia Emergence Delirium Scale (PAED). The average total PAED score for those receiving sevoflurane was significantly higher than for those receiving propofol (average

7.0 vs. 3.9; P=0.037) indicating more agitation and delirium associated with emergence from sevoflurane. Recovery time was shorter for those receiving propofol versus sevoflurane (average 42 vs. 53 minutes; P=0.02). The researchers noted a positive relationship between the magnitude of the PAED score and lactate, suggesting that elevated lactate might predict emergence delirium. Helene Benveniste, MD, PhD, senior author of the paper and vice

chair for research at Stony Brook’s Department of Anesthesiology, said her group is trying to tease apart the relationship between lactate and delirium. “Lactate increases when the brain is activated, so the higher level of lactate in the brain of a child administered sevoflurane is likely the result of more neuronal firing during the unconscious state,” Dr. Benveniste said. “It’s like having a motor running but the car is not going anywhere. It

could also mean that lactate is not being cleared from the brain, and the buildup may increase the chance of children becoming anxious or delirious.” The results are too preliminary to suggest changes in practice, said Dr. Benveniste, who plans to continue studying metabolic changes in other areas of the brain and from different anesthetics. —Karen Blum

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hypothermia, malignant hyperther- or developmental/behavioral disormia, neonatal hyperoxia and sepsis, he ders, said Mike Roizen, MD, chair of the SmartTots (Strategies for Mitia ventilator-induced lung injury alert said. that evaluates patients getting general gating Anesthesia-Related neuroToxBaby Steps for SmartTots anesthesia with an endotracheal tube. icity in Tots) executive board and The second day of the meeting chair of the Cleveland Clinic WellIf patients meet certain criteria suggesting potentially injurious ventilator looked at continuing concerns of ness Institute, in Ohio. SmartTots is a parameters, the system will alert pro- anesthetic drug safety in the develop- partnership of the International Anesthesia Research Society (IARS) and viders through an on-screen display or ing brain. a page. Studies from the past year indi- the Food and Drug Administration In pediatric patients, Dr. Kor’s cate that children exposed to anes- to fund research assessing the safety group is using the data mart to thetics before the age of 3 years are at of anesthetic drugs in infants and look for potential interventions for increased risk for learning disabilities children. CONTINUED FROM PAGE 21

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Early exposure to anesthetics and sedatives has been found to cause loss of nerve cells, abnormal behavior, and memory and learning difficulties in rodents and monkeys, Dr. Roizen said, but there is still insufficient data to translate that to what happens in children. “More research is needed to determine the specific deficit anesthesia impairs in brain function in humans, if it does so, and how it can be prevented and/or treated,” said Dr. Roizen, a member of the Anesthesiology News editorial board. The FDA has funded three ongoing research projects related to SmartTots, which is trying to raise the $40 million that the organization says it needs over the next 20 years for research in this area from industry, foundations and individual donors. The organization so far has raised about $300,000 and funded two studies in 2012. The IARS awarded $750,000 in 2012 to fund a related study. The SmartTots board will donate $1 for every $2 donated by individuals. Anita Lambert, a spokeswoman for IARS, said the group is optimistic about its chances of raising the money. “We expect that as we build awareness of the cause and the need for research, funding will begin to increase substantially over the years. Raising funds for SmartTots is in its infancy but the main obstacle has been building awareness about the need for this important research. As we raise more funds, more research is funded.” For now, Dr. Roizen said, anesthesiologists should try to limit the duration and number of exposures to anesthesia, and delay elective surgery until the child is at least 3 years old. Peter Davis, MD, professor of anesthesiology and pediatrics at the University of Pittsburgh School of Medicine, moderated a panel that reviewed some of the scientific studies in animals and children. He agreed with Dr. Roizen that any changes in anesthesiology practice should be driven by evidence-based medicine. “It’s our ethical obligation to administer anesthesia to children undergoing procedures and also to understand the problems,” said Dr. Davis, a member of the editorial board of Anesthesiology News. “The reality is there’s nothing new, but there is information to suggest this still needs to be further explored.” —Karen Blum

JANUARY 2013

AnesthesiologyNews.com I 25

CL A SSIF IE D S DUKE CME: TRANSFORMING KNOWLEDGE

Duke University School of Medicine & The Department of Anesthesiology PRESENTS

AGENDA

WEDNESDAY, MARCH 6, 2013 Morning Session

SUNDAY, MARCH 3, 2013

6:15 am Breakfast / Meet with Exhibitors

Afternoon Session

7:00 am All Downhill From Here: The Life of a Ski Team Doctor - Olson 8:00 am Massive Hemorrhage in Obstetrics - Muir

Registration / Meet with Exhibitors

7th Annual Winter Anesthesia & Critical Care Review March 3-8, 2013 Canyons Resort Park City, Utah Sponsored by the Duke University School of Medicine.

4:00 pm Billing and Documentation for Regional Anesthesia and Ultrasound - Auyong 5:00 pm LVAD’s in Non Cardiac Surgery - Shaw

9:00 am Adjourn Morning Session Afternoon Session 3:30 pm Afternoon Snacks / Meet with Exhibitors

6:00 pm Adjourn

4:00 pm Non Rational Factors in Medical Decision Making - Tung 5:00 pm Are Starches Good for You? Pro/Con Debate - Shaw, Brudney

MONDAY, MARCH 4, 2013

6:00 pm Adjourn

Morning Session 6:15 am Registration / Breakfast / Meet with Exhibitors

THURSDAY, MARCH 7, 2013

7:00 am Vascular Access - Ultrasound Every Time? - Grant

Morning Session

8:00 am Cerebral Aneurysm Anesthesia Update - Borel

6:15 am Breakfast / Meet with Exhibitors

9:00 am Adjourn Morning Session

7:00 am Anesthesia for Awake Craniotomy - Borel

Afternoon Session

8:00 am Mechanical Ventilation - Tung

3:30 pm Afternoon Snacks / Meet with Exhibitors

9:00 am Adjourn Morning Session

4:00 pm Best Practice in Major Joint Replacement Anesthesia: Shoulder and Ankle - Benonis

Afternoon Session

4:40 pm Best Practice in Major Joint Replacement Anesthesia: Hip and Knee - Auyong

3:30 pm Afternoon Snacks / Meet with Exhibitors

5:20 pm Panel Discussion: Anesthesia and Orthopedics Benonis, Auyoug, Grant 6:10 pm Ultrasound Workshop - Benonis, Auyong, Grant, Brudney

4:00 pm Out There Anesthesia: Anesthesia in the Interventional Radiology Suite - Borel 4:30 pm Pre-Op Management and the Role of a Pre-Op Screening Unit Olson 5:00 pm Tomorrow’s Anesthesia: Federal Regulations and Their Impact Benonis

7:40 pm Adjourn

5:30 pm Panel Discussion - Borel, Olson, Benonis

TUESDAY, MARCH 5, 2013

6:00 pm Adjourn

Morning Session 6:15 am Breakfast / Meet with Exhibitors

FRIDAY, MARCH 8, 2013

7:00 am Sepsis Update - Brudney

Morning Session

8:00 am The Obese Parturient - Muir

6:15 am Breakfast / Meet with Exhibitors

9:00 am Adjourn Morning Session

7:00 am Perioperative Cardiac Protective Strategies - Shaw

Afternoon Session

8:00 am The Impaired Anesthesia Provider - Grant

3:30 pm Afternoon Snacks / Meet with Exhibitors

9:00 am Adjourn Meeting

4:00 pm Anesthesia and the Elderly - Tung 4:45 pm How to Save That Airway - Muir 5:30 pm Panel Discussion: Complex Case Management - Tung, Muir

AN-1212-003.pdf

6:00 pm Airway Management Workshop Muir, Brudney, Benonis, Auyong 7:30 pm Adjourn

We’re in a Clinical or Basic Science Faculty Position, Research Anesthesiologist The Department of Anesthesiology at Penn State Hershey College of Medicine is seeking an experienced, Anesthesiology Board Certified, Clinical or Basic Science Research Faculty member to join a growing Anesthesiology Research Department. The applicant will be a clinical anesthesiologist, preferably at the Associate or Full Professor level, who has demonstrable ongoing research productivity. The candidate will receive suitable seed funding, commensurate academic time as well as the necessary facilities to pursue research interests. The successful candidate will be assigned a named Professorial Endowment for the first three years as a Faculty member in the Department. Interested applicants should submit their CV and cover letter outlining their research interests to: Dr. Berend Mets, MB, ChB, PhD, FRCA, FFA (SA) Eric A. Walker Professor and Chair, Department of Anesthesiology Penn State Milton S. Hershey Medical Center/ Penn State College of Medicine P.O. Box 850, M.C. H187 500 University Drive Hershey, PA 17033-0850 bmets@hmc.psu.edu

to fill your

position For classified advertising:

Applicants can visit: www.pennstatehershey.org/anesthesia to learn more about the Department. Penn State is committed to affirmative action, equal opportunity, and the diversity of its workforce.

position

AN-0113-001

contact Alina Dasgupta 212-957-5300 x338 adasgupta@mcmahonmed.com

26 I AnesthesiologyNews.com

JANUARY 2013

PRN

ISPCOP Seeks To Improve Surgical Care In the Era of Global Obesity

nce almost the exclusive preserve of North America, obesity has become so commonplace around the world that a new term— globesity—is used to describe it. The recent rebirth of the International Society for the Perioperative Care of the Obese Patient (ISPCOP) hopes to help operating room clinicians of all stripes deal with the special challenges presented by these individuals by promoting education and research into their clinical management and treatment. “When it comes to surgery on obese and morbidly obese patients, there’s a lot of expertise around the world, but until now people were not working together; our efforts were a little disparate,” said Jan Paul Mulier, MD, bariatric anesthesiologist at St. Jan’s Hospital in Bruges, Belgium, and the society’s vice president of research. Yet although the expertise may be there, the evidence is not. So there is a real need to do more research in this area, he said. Formed in 2004, ISPCOP fell dormant for a number of years. In the meantime, the European Society for the Perioperative Care of the Obese Patient (ESPCOP) was created, promising its full support to form an international group. It wasn’t long before an international group of anesthesiologists came together at the 2010 Annual Meeting of the American Society of Anesthesiologists (ASA) to discuss the relaunch of ISPCOP. The overwhelming opinion of those in attendance was that the society was needed more than ever, especially in light of the global obesity Advertisement

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epidemic. An interim board of 11 members was chosen, and ISPCOP has the infusion of new blood it needed to begin anew. “We are not only focusing on bariatric surgery, because only a small percentage of anesthesiologists really deal with this type of surgery,” Dr. Mulier told Anesthesiology News. “We also want to be relevant to the anesthesiologist who works with the obese patients for other surgeries, too.” One year later, ISPCOP held a halff dayy meeting at the 2011 ASA Annual Meeting, during which members elected a slate of permanent officers and board of directors, and discussed current standards of care and further areas of research. A scientific exhibit at the meeting also helped the society spread the word about the anesthetic management of obese patients and recruit new members as well. These members sing a common refrain, Dr. Mulier said: There is a noticeable lack of resources and research available for perioperative medical professionals who treat obese and morbidly obese individuals. “Even at the ASA, there are only a few sessions dealing with the problems of morbidly obese patients,” he explained. With that in mind, ISPCOP is pushing relevant anesthesiology societies to afford more of a presence to the issues of obese patients at future meetings. At the 2012 World Congress of Anaesthesiologists, held in March in Buenos Aires, Argentina, ISPCOP dedicated an entire day to treatment of the obese patient. The First Annual ISPCOP Symposium, Current Controversies in Obesity Anesthesia, was held in October during the ASA’s 2012 annual meeting. The society also hosted an educational exhibit during the meeting. The society is another good resource for anesthesiologists interested in caring for obese patients. It offers links to papers discussing such topics as regional anesthesia and obesity, positioning the morbidly obese patient for surgery, and the effects of obesity on anesthetic agents. The site also has book reviews, recommended reading information, listings of upcoming conferences, a discussion board, and information on upcoming meetings and symposia. The society also connects through its Facebook page. “The other thing we do is promote research, because this kind of evidence-based knowledge is missing when it comes to care of obese patients,” said Dr. Mulier.r “We need to do larger-basedd studies to figure out if some of our approaches are right or wrong. And that’s where we need a network of people also on to get involved, including those in the academic realm.” ISPCOP plans to organize expert physicians into panels or groups to provide evidence-based or expert opinion–based recommendations. Subgroups eventually will focus on cardiac, pulmonary and regional anesthesia, or airway issues in obese patients. Confronting Concerns Over Treating the Morbidly Obese ISPCOP is open to any medical professional or trainee who cares for obese patients. An annual

‘Most anesthesiologists will tell you that they know how to handle morbidly obese patients. But when you ask, you find out that most anesthesiologists don’t like to take care of big people; they get quite worried.’ — Roman Schumann, MD membership is $50 for “active” physician members, $50 for nurses and other para-physician members, and $25 for fellows, residents and students. Downloadable membership forms are available on the website (www.ispcop.org). Roman Schumann, MD, associate professor of anesthesiology at Tufts University, in Boston, said that although most anesthesiologists work regularly with morbidly obese patients, many are still uncomfortable with the challenges these patients present. “Most anesthesiologists will tell you that they know how to handle morbidly obese patients. But when you ask, you find out that most anesthesiologists don’t like to take care of big people; they get quite worried.” The source of this duress, Dr. Schumann explained, is what he perceives to be an educational gap. “I think what’s needed is the recognition not just of the obese patient population, but of the fact that this population has its own physiologic dynamics that affect perioperative care. And if there isn’t education on this physiology, then anesthesiologists will be less informed and more worried about taking care of these patients.” “Obese patients don’t just come to the hospital for weight loss surgery,” added ISPCOP president Ashish Sinha, MD, vice chair of anesthesiology and perioperative medicine at Drexel University College of Medicine, in Philadelphia. “These people have trauma, they get pregnant, their gallbladders need to be removed. So the question is how can you take all the expertise that’s in the bariatric operating room and spread that information? That’s the driver for all of this.” —Michael Vlessides

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PRINTER-FRIENDLY VERSION AVAILABLE AT ANESTHESIOLOGYNEWS.COM

“Can’t You Do Something To Stop This Bleeding?” Systemic Strategies For Reducing Blood Loss in Surgery PRANAY KANAKE, MD Fellow in Cardiothoracic Anesthesia University of Rochester School of Medicine and Dentistry Rochester, New York

MICHAEL P. EATON, MD Denham S. Ward Professor and Chair Department of Anesthesiology Executive Director, Perioperative Services University of Rochester School of Medicine and Dentistry Rochester, New York Drs. Kanake and Eaton report no relevant financial conflicts of interest.

urgical procedures account for

the transfusion of nearly 15 million units of red blood cells and 1.5

million platelet (PLT) transfusions per year in the United States.1 Although the risk for transmission of viral diseases with transfusion decreased with the advent of improved screening of blood for pathogens, other adverse effects remain. These include transfusion reactions, immunomodulation, acute lung injury, fluid overload, and, in some cases, mortality.2-4 In the current environment of health care, in which cost containment has become of utmost importance, any intervention that will reduce perioperative bleeding and transfusion should be welcome. This review examines the pharmacologic therapies commonly employed to decrease surgical bleeding and transfusions.

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Vessel injury

Tissue factor

Intrinsic Pathway

Extrinsic Pathway

Surface contact pre-kallikrein HMWK

XIIa

VIIa/VII Calcium, Phospholipid

XIa

IXa

TF-VIIa complex

XII

VIIIa

Common Pathway

Xa Calcium Phospholipid Va

Prothrombin

Calcium

Thrombin

Fibrinogen

Fibrin XIIIa

XIII

Stable crosslinked fibrin

Figure 1. A simplified view of coagulation cascade. HMWK, high-molecular-weight kininogen

Perioperative bleeding often is exacerbated by abnormalities that develop as a result of surgical trauma, component transfusion, and the activation of inflammatory and fibrinolytic cascades (Figures 1 and 2). Surgical patients often are treated for chronic conditions with anticoagulant medications that further complicate perioperative management.5-7 Because abnormal bleeding frequently results from derangement of the coagulation system and pharmacologic interventions typically focus on major aspects of this system, it is important to have a basic knowledge of hemostasis. Clinicians also must understand that, although hypercoagulability may be the major

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hemostatic problem that anesthesiologists address in the operating room, patients become hypercoagulable after surgery as a result of surgical stress, and thrombosis is more likely to produce a catastrophic complication such as myocardial infarction or pulmonary embolism. Thus, therapies that decrease bleeding preoperatively should have a relatively short duration of action to avoid exacerbating a prothrombotic state.

Pharmacologic Interventions Pharmacologic interventions to reduce bleeding and transfusion have been studied most often in cardiac and orthopedic surgeries and aim to either prevent or

Thrombin

FDP

Fibrinogen

Platelets

Fibrin

α-2 Antiplasmin TAFI Plasminogen

PAI-1 EACA, TA

Plasmin

t-PA

Activation Inhibition

Figure 2. The fibrinolytic system.7-9 EACA, ε-aminocaproic acid; FDP, fibrinogen degradation product; TA, tranexamic acid; TAFI, thrombin activatable fibrinolysis inhibitor; t-PA, tissue plasminogen activator

reverse defects associated with coagulopathy (Table).8 Most prospective studies have focused on the effectiveness of individual drugs given prophylactically, although some, like recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk) are given primarily as rescue treatment when bleeding is excessive. Pharmacotherapy for decreasing bleeding and transfusion may be loosely categorized as antifibrinolytic and procoagulant. Surgeons also use topical agents intraoperatively; however, topical therapy to decrease surgical bleeding is outside the scope of this review.

ANTIFIBRINOLYTICS Antifibrinolytics are the most common class of drugs used to improve hemostasis. These agents may be classified into 2 groups—lysine analogs and serine protease inhibitors.

LYSINE ANALOGS Epsilon aminocaproic acid (EACA; Amicar, Pfizer) and tranexamic acid (TA; Cyklokapron, Pfizer) are synthetic lysine analogs that inhibit fibrinolysis. EACA and

TA competitively bind to lysine-binding sites of plasminogen and plasmin. Blockade of these sites prevents activation of the proenzyme plasminogen to the active fibrinolytic enzyme plasmin. EACA binds to plasmin to a lesser degree at a higher dose, and inhibits plasmin from digesting fibrinogen and fibrin.9 TA is 10 times more potent than EACA and approximately 100 times more expensive in the United States,10 although both drugs are available in generic forms. TA also may improve hemostasis by preventing plasmin-induced PLT activation.11 EACA is approved by the FDA to enhance hemostasis when fibrinolysis contributes to bleeding. TA is approved for the short-term treatment or prevention of dental bleeding in hemophiliacs. Lysine analogs are water-soluble molecules that distribute readily into extravascular water spaces.11 EACA is largely excreted intact by the kidneys, and approximately 35% undergoes hepatic metabolism to the metabolite adipic acid. Renal clearance of the compound approximates endogenous creatinine clearance. The terminal elimination half-life of EACA is 1 to 2 hours.11 The pharmacokinetics of TA are similar to those of EACA.5,12-16

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Topical Agents

Procoagulant Drugs

Antifibrinolytics

Table. Current Pharmacological Agents Used for Hemostasis During Surgery Plasminogen inhibitors

EACA TA

Serine protease inhibitors

Aprotinin Nafamostat Ecallantide

Desmopressin Recombinant factor VIIa Prothrombin complex concentrate Fibrin sealant Collagen Thrombin Gelatin sponges EACA, TA, Aprotinin

EACA, ε-aminocaproic acid; TA, tranexamic acid

Dosage protocols for lysine analogs for bleeding prophylaxis have not been standardized. Dosing schemes vary widely, particularly for patients undergoing cardiac and orthopedic surgeries, and are not based on pharmacologic principles. Doses for EACA in cardiac surgery may involve the administration of a loading dose of between 75 and 150 mg/kg before cardiopulmonary bypass (CPB), followed by continuous infusion of 10 to 25 mg/kg per hour. Butterworth et al studied the pharmacokinetics of EACA in cardiac surgery with CPB and found that a loading dose of 75 mg/kg followed by maintenance infusion of 25 mg/kg per hour should produce adequate blood levels of the drug throughout surgery.11 In clinical trials of patients undergoing cardiac surgery, loading doses of TA have ranged from 10 to 30 mg/kg followed by infusion of 1 to 16 mg/kg per hour.12-19 Pharmacokinetic data suggest that the maintenance dose (mg/kg/h) should be close to or the same as the loading dose (in mg/kg) to obtain stable levels during CPB. The plasma level of TA required to inhibit fibrinolysis is unclear. Although many study protocols have used 100 mcg/mL as the minimal plasma concentration required for complete inhibition of fibrinolysis, more recent data suggest that much lower levels—17.5 mcg/mL in adults—are effective, and indicate that a lower dose should be effective. This finding is important given the association between high doses of TA and seizures.20

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Efficacy Numerous studies evaluating the effects of EACA and TA have been published across a variety of patient populations. A recent review found nearly 100 such studies of TA alone.21 Although most clinical research on TA and EACA has been conducted in patients undergoing cardiac and orthopedic surgeries, the drugs also have been evaluated in craniofacial, gynecologic, hepatic, urologic, and vascular surgeries. TA and EACA repeatedly have been found to be effective in reducing bleeding and transfusion in adult and pediatric cardiac surgeries. A 2011 Cochrane review included more than 250 studies of TA and EACA, as well as aprotinin (Trasylol, Bayer), including 34 trials of TA and 11 of EACA in cardiac surgery.22 Despite large variability in dosing, both drugs had clinically significant efficacy in reducing transfusion by about 30%. Trials of TA and EACA in orthopedic surgery have focused primarily on spine surgery and total knee and hip arthroplasty.23 In total joint arthroplasty, TA reduced the risk for transfusion by 53%, and EACA by 36%. Again, disparities in dosing protocols may explain the apparent difference in efficacy more than actual differences in the medication. A 2008 meta-analysis of the use of antifibrinolytic agents in spine surgery found a reduction of about 50% in the risk for transfusion among patients who received TA or EACA,24 although a recent randomized placebo-controlled study in adults undergoing spine surgery found no difference in transfusion associated with use of TA. Two other recent studies did find TA25 and EACA26 to be effective in pediatric spine surgery for scoliosis. Efficacy almost certainly depends on the complexity of the surgery, and the baseline risk for bleeding and transfusion. Dosing regimens that can be predicted to produce subtherapeutic plasma levels also may play a role. Two recent studies have shown marked decreases (66%-75%) in the incidence of transfusion in children undergoing surgery for craniosynostosis.27,28 Another recent study,29 which included open and minimally invasive craniosynostosis repair, did not find TA to be effective; in this trial, all patients were transfused. Multiple studies have shown a decrease in transfusion requirements in liver transplant surgery in patients treated with EACA and TA. Concerns remain about thrombotic complications, particularly thrombosis of the freshly anastomosed hepatic artery. However, the data do not support any increased risk.30 TA also has been studied in trauma patients. 31 CRASH-2 (Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage) is a large (>20,000 patients) placebo-controlled trial of the effects of TA on mortality, vascular occlusive events, and transfusions in trauma patients. The results show that the early administration of the drug to these patients reduces their risk for death from hemorrhage with no increase in vascular occlusive events. Use of TA also

was associated with a significant reduction in all-cause mortality, likely due to the decrease in bleeding and transfusion and transfusion-associated complications. Fewer data are available for other operations; TA and EACA appear to be effective in cesarean delivery, gynecologic surgery, radical prostatectomy, and tonsillectomy.32-35 Adverse Effects EACA and TA have not been studied in large, multicenter randomized controlled trials (RCTs) powered to evaluate safety. However, in small studies the drugs appear generally not to promote severe adverse effects.36 Both EACA and TA can cause hypotension when given as rapid IV bolus. EACA can cause rhabdomyolysis, myonecrosis, anion gap acidosis, upper urinary tract thrombosis, and hyperkalemia.14,36 Lysine analogs have not been associated with an increase in incidence of renal dysfunction or of mortality in cardiac surgery.37 Thromboembolic complications, such as reduced early graft patency, stroke, deep vein thrombosis, pulmonary embolus, and myocardial infarction, are theoretically possible. But focused reviews and meta-analyses have not found such association.37 Large retrospective studies have consistently reported an increased risk for seizures with higher doses of TA compared with other antifibrinolytics and placebo.38-40

SERINE PROTEASE INHIBITORS Aprotinin Serine proteases are ubiquitous enzymes responsible for coordinating a wide variety of physiologic functions. The nonspecific serine protease inhibitor (serpin) aprotinin was in widespread use in cardiac surgery between FDA approval in 1993 and removal from the market in 2007. It also saw use in other surgical applications such as liver transplantation and orthopedic surgery. Although it was withdrawn from the United States market following a large Canadian trial showing an increase in mortality relative to lysine analog antifibrinolytics,41 the drug remains controversial. Both Canadian and European regulatory agencies recently withdrew their prohibition against the marketing of aprotinin. Aprotinin inhibits several serine proteases, including trypsin, plasmin, plasma kallikrein, and tissue kallikrein. It also inhibits the contact phase activation of coagulation that initiates coagulation and fibrinolysis, and has minor inhibitory effects on the intrinsic pathway coagulation factors. Aprotinin also exerts an indirect preservative effect on PLT function during CPB.36 Aprotinin was extensively studied in cardiac surgery patients and found to significantly decrease blood loss and transfusion in adults and children. Comparison studies with the lysine analogs typically demonstrated superiority of aprotinin, particularly in high-risk patients. Multiple RCTs of aprotinin also demonstrated safety, but beginning in 2006, 3 retrospective studies

found an increase in serious adverse events associated with the drug, resulting in an FDA advisory. When the Canadian prospective RCT showed an increase in mortality in patients treated with aprotinin, the FDA decided to remove the drug from the market. Nafamostat Nafamostat mesilate is a synthetic serpin used in Japan since 1981.42 It is not approved in the United States. Nafamostat inhibits thrombin, factors Xa and XIIa, kallikrein, plasmin, and complement factors (C1r, C1s). Nafamostat also preserves PLT function and attenuates systemic inflammatory response. The drug has been investigated as an anticoagulant in extracorporeal circuits and as a hemostatic agent in cardiac surgery. Several studies conducted in Japan reported a significant reduction in postoperative blood loss in cardiac surgery.43 Large RCTs are needed to define its role in the perioperative period. Ecallantide Ecallantide (Kalbitor, Dyax) is a recombinant human peptide derived from tissue factor pathway inhibitor. The drug is FDA-approved for the treatment of hereditary angioedema. Ecallantide inhibits plasma kallikrein with high affinity, and plasmin with lesser effect. Early clinical data demonstrated that ecallantide decreases blood loss and need for transfusion in patients undergoing cardiac surgery.44 However, a recent trial comparing ecallantide with TA in high-risk cardiac surgery patients showed TA to be superior in decreasing blood loss and transfusion, with higher 30-day mortality in the patients receiving ecallantide.45

PROCOAGULANT DRUGS Desmopressin Desmopressin acetate (DDAVP, Sanofi-Aventis) is a synthetic vasopressin analog that stimulates the release of factor VIII and von Willebrand factor from the endothelium into the plasma, where they enhance PLT aggregation.15 DDAVP is FDA-approved for treatment of hemophilia A and type I von Willebrandâ&#x20AC;&#x2122;s disease. The drug is contraindicated in type IIb von Willebrandâ&#x20AC;&#x2122;s as it will cause thrombocytopenia. The recommended dose of DDAVP is 0.3 mcg/kg, and it should be administered slowly to avoid inducing hypotension. DDAVP also has been used in patients with uremia, cirrhosis, or aspirin-associated bleeding.46,47 The effectiveness of DDAVP for the prevention or treatment of perioperative bleeding in patients without known PLT disorders is not well established. DDAVP has not been consistently shown to reduce perioperative blood loss, and is associated with thrombosis and myocardial infarction in unselected cardiac surgery patients.48 Selected patients with demonstrated PLT defects may be responsive to DDAVP.49 Evidence does not support its prophylactic use in hemostatically normal patients undergoing elective noncardiac surgical procedures.

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Recombinant Factor VIIa Concentrate rFVIIa is FDA-approved for the management of bleeding related to hemophilia in patients with factor inhibitors. rFVIIa enhances the natural coagulation pathway through the formation of tissue factor–factor VIIa complex at the site of endothelial damage. It binds to the phospholipid membranes of activated PLTs, where it activates factor X independent of the tissue factor pathway. The result is a massive rise in thrombin generation at the surface of the PLTs.50 Because of its short half-life (2.7 hours), rFVIIa must be given as boluses that may be repeated every 2 hours (until bleeding stops) or as a continuous infusion. Recommended doses range from 15 to 90 mcg/kg. Increasing doses are associated with improved effectiveness, but are likely to carry a higher risk for thrombosis, which, along with its high cost, are the major caveats for use of this compound. The off-label use of rFVIIa may be effective in certain settings, such as in cases of intracranial hemorrhage, life-threatening bleeding, or as rescue therapy when excessive bleeding does not respond to routine hemostatic therapy.51 rFVIIa does not produce clots on its own. As a result, the drug should be administered only after patients have been transfused with adequate products to replenish clotting factors, including PLTs and fibrinogen. Although the literature is replete with case reports and small retrospective series showing apparently successful treatment of life-threatening bleeding, large, prospective studies demonstrating the safety and effectiveness of rFVIIa are lacking. Moreover, considerable evidence indicates that off-label use of the drug can cause catastrophic thrombotic complications. The application of rFVIIa for serious hemorrhage should be restricted to situations in which the risk for continued bleeding unresponsive to transfusion therapy clearly outweighs the risk for serious thrombotic complications. Prothrombin Complex Concentrates Prothrombin complex concentrates (PCCs) are pooled factor concentrates of human origin and contain the vitamin K–dependent clotting factors II, VII, IX, and X. Although originally developed and approved for treatment of hemophilia B (factor IX deficiency), PCCs most often are used to reverse the effects of warfarin anticoagulation. Two 4-factor PCCs are approved for use in the United States: Bebulin VH (Baxter) and Profilnine (Grifols). Compared with fresh frozen plasma, these drugs have smaller infusion volumes to reverse warfarin-induced coagulopathy, are more effective, and do not require cross matching. Although PCCs have been used to treat coagulopathic bleeding with some evidence of success, there is insufficient evidence of their safety and effectiveness in conditions other than bleeding resulting from warfarin anticoagulation or known factor deficiencies. Thrombosis and high cost also are major considerations for the use of PCCs.52,53

I N D E P E N D E N T LY D E V E L O P E D B Y M C M A H O N P U B L I S H I N G

Conclusions Anesthesiologists often are asked by their surgical colleagues to administer medication to treat excessive bleeding. Although some agents may decrease blood loss in appropriate cases, it is important to understand the risks and limitations of each drug before it is given to a patient. It also is important to remind the surgeon to first rule out surgical bleeding; no drug is a substitute for surgical hemostasis. The majority of these drugs are used perioperatively outside their FDA indications, and may have unknown safety issues. The search for ideal pharmacologic agents to reduce perioperative bleeding continues, and to date no single universal pharmacologic agent is available to solve the problem of excess perioperative bleeding and transfusion. Although PCCs and rFVIIa may be useful in certain settings, the best data exist for the lysine analog antifibrinolytics. Large safety trials and dose-finding studies for EACA and TA are warranted. TA has emerged as a potential lifesaving drug for trauma patients, and the CRASH-3 study may show similar results for patients with traumatic brain injury.

References 1.

Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP. Transfusion medicine. First of two parts—blood transfusion. N Engl J Med. 1999;340(6):438-447.

Kuduvalli M, Oo AY, Newall N, et al. Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery. Eur J Cardiothorac Surg. 2005; 27(4):592-598.

Taylor RW, Manganaro L, O’Brien J, Trottier SJ, Parkar N, Veremakis C. Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient. Crit Care Med. 2002;30(10):2249-2254.

Reeves BC, Murphy GJ. Increased mortality, morbidity, and cost associated with red blood transfusion after cardiac surgery. Curr Opin Cardiol. 2008;23(6):607-612.

Hoffman R, Benz EJ, Shattil SS, et al, eds. Hematology: Basic Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2008.

Kumar V, Abbas AK, Fausto N, Aster J. Robbins and Cotran Pathologic Basis of Disease, Professional Edition. 8th ed. St. Louis, MO: W. B. Saunders; 2010.

Candler WL. The human fibrinolytic system. Crit Rev Oncol Hematol. 1996;24(1):27-45.

Levy JH, Dutton RP, Hemphill JC 3rd, et al. Multidisciplinary approach to the challenge of hemostasis. Anesth Analg. 2010; 110(2):354-364.

Levy JH. Perioperative methods to reduce perioperative bleeding. Transfusion. 2008;48(1 suppl):31s-38s.

10.

Porte RJ, Leebeek FW. Pharmacological strategies to decrease transfusion requirement in patients undergoing surgery. Drugs. 2002;62(15):2193-2211.

11.

Butterworth J, James RL, Lin Y, Prielipp RC, Hudspeth AS. Pharmacokinetics of epsilon-aminocaproic acid in patients undergoing coronary artery bypass surgery. Anesthesiology. 1999;90(6):1624-1635.

12.

Pilbrant A, Schannong M, Vessman J. Pharmacokinetics and bioavailability of tranexamic acid. Eur J Clin Pharmacol. 1981;20(1): 65-72.

13.

Soslau G, Horrow J, Brodsky I. Effect of tranexamic acid on platelet ADP during extracorporeal circulation. Am J Hematol. 1991; 38(2):113-119.

14.

Verstraete M. Clinical application of inhibitors of fibrinolysis. Drugs. 1985;29(3):236-261.

15.

Franck M, Sladen RN. Drugs to prevent and reverse anticoagulation. Anesthesiol Clin North Am. 1999;17(4):799-811.

33.

Celebi N, Celebioglu B, Selcuk M, Canbay O, Karagoz AH, Aypar U. The role of antifibrinolytic agents in gynecologic cancer surgery. Saudi Med J. 2006;27(5):637-641.

34.

Crescenti A, Borghi G, Bignami E, et al. Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind, randomised, placebo controlled trial. BMJ. 2011;343:d5701.

35.

Chan CC, Chan YY, Tanweer F. Systematic review and meta-analysis of the use of tranexamic acid in tonsillectomy. Eur Arch Otorhinolaryngol. 2012 Sep 21. [Epub ahead of print]

16.

Kang Y, Lewis JH, Navalgund A, et al. Epsilon-aminocaproic acid for treatment of fibrinolysis during liver transplantation. Anesthesiology. 1987;66(6):766-773.

17.

Miller RA, May MW, Hendry WF, Whitfield HN, Wickham JE. The prevention of secondary haemorrhage after prostatectomy: the value of antifibrinolytic therapy. Br J Urol. 1980;52(1):26-28.

18.

Zufferey P, Merquiol F, Laporte S. Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery? Anesthesiology. 2006;105(5)1034-1046.

36.

Eaton MP. Antifibrinolytic therapy in surgery for congenital heart disease. Anesth Analg. 2008;106(4):1087–1100.

37.

Fiechtner BK, Nuttall GA, Johnson ME, et al. Plasma tranexamic acid concentrations during cardiopulmonary bypass. Anesth Analg. 2001;92(5):1131-1136.

Manjunath G, Fozailoff A, Mitcheson D, Sarnak MJ. Epsilon-aminocaproic acid and renal complications: case report and review of the literature. Clin Nephrol. 2002;58(1):63-67.

38.

Keyl C, Uhl R, Beyersdorf F, Stampf S, Lehane C, Wiesenack C, Trenk D. High-dose tranexamic acid is related to increased risk of generalized seizures after aortic valve replacement. Eur J Cardiothorac Surg. 2011;39(5):114-121.

39.

Martin K, Knorr J, Breuer T, et al Seizures after open heart surgery: comparison of ε-aminocaproic acid and tranexamic acid. J Cardiothorac Vasc Anesth. 2011;25(1):20-25.

19.

20.

21.

22.

Koster A, Börgermann J, Zittermann A, Lueth JU, Gillis-Januszewski T, Schirmer U. Moderate dosage of tranexamic acid during cardiac surgery with cardiopulmonary bypass and convulsive seizures: incidence and clinical outcome. Br J Anaesth. 2012 Sep 17. [Epub ahead of print] Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ. 2012;344:e3054. Henry DA, Carless PA, Moxey AJ, et al. Antifibrinolytic use for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011;19(1):CD001886.

23.

Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res. 2009;123(5):687-696.

24.

Gill JB, Chin Y, Levin A, Feng D. The use of antifibrinolytic agents in spine surgery. A meta-analysis. J Bone Joint Surg Am. 2008;90(11):2399-2407.

25.

Yagi M, Hasegawa J, Nagoshi N, et al. Does the intraoperative tranexamic acid decrease operative blood loss during posterior spinal fusion for treatment of adolescent idiopathic scoliosis? Spine. 2012;37(12):E1336-E1342.

26.

Berenholtz SM, Pham JC, Garrett-Mayer E, et al. Effect of epsilon aminocaproic acid on red-cell transfusion requirements in major spinal surgery. Spine. 2009;34(19):2096-2103.

27.

Dadure C, Sauter M, Bringuier S, et al. Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: a randomized double-blind study. Anesthesiology. 2011;114(4):856-861.

28.

Goobie SM, Meier PM, Pereira LM, et al. Efficacy of tranexamic acid in pediatric craniosynostosis surgery: a double-blind, placebo-controlled trial. Anesthesiology. 2011;114(4):862-871.

29.

Maugans TA, Martin D, Taylor J, Salisbury S, Istaphanous G. Comparative analysis of tranexamic acid use in minimally invasive versus open craniosynostosis procedures. J Craniofac Surg. 2011;22(5):1772-1778.

30.

31.

32.

Molenaar IQ, Warnaar N, Groen H, Tenvergert EM, Slooff MJ, Porte RJ. Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta-analysis. Am J Transplant. 2007;7(1):185-194. The CRASH-2 Collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomized controlled trial. Lancet. 2011;377(9771):1096-1101. Xu J, Gao W, Ju Y. Tranexamic acid for the prevention of postpartum hemorrhage after cesarean section: a double-blind randomization trial. Arch Gynecol Obstet. 2012 Oct 13. [Epub ahead of print]

40. Murkins JM, Falter F, Granton J, et al. High dose tranexamic acid is associated with nonischemic clinical seizures in cardiac surgical patients. Anesth Analg. 2011;110(2):350-353. 41.

Fergusson DA, Hébert PC, Mazer CD, et al. A comparison of aprotinin and lysine analogs in high-risk cardiac surgery. N Engl J Med. 2008;358(22):2319-2331.

42.

Fujii S, Hitomi Y. New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. Biochim Biophys Acta. 1981;661(2):342-345.

43.

Murase M, Usui A, Tomita Y, Maeda M, Koyama T, Abe T. Nafamostat mesilate reduces blood loss during open heart surgery. Circulation. 1993;88(5 pt 2):432-436.

44. Data on file. DX-88/3, 2008; DX-88/16, 2009, Cubist Clinical Study. Dyax Corp. Burlington, MA. 45.

Bokesch PM, Szabo G, Wojdyga R, et al. A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial). J Thorac Cardiovasc Surg. 2012;143(5):1022-1029.

46.

Mannucci PM. Treatment of von Willebrand’s disease. N Engl J Med. 2004;351(7):683-694.

47.

Mannucci PM. Hemostatic drugs. N Engl J Med. 1998;339(4): 245-253.

48.

Levi M, Cromheecke ME, de Jonge E, et al. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet. 1999; 354(9194):1940-1947.

49.

Despotis GJ, Levine V, Saleem R, Spitznagel E, Joist JH. Use of point-of-care test in identification of patients who can benefit from desmopressin during cardiac surgery: a randomized controlled trial. Lancet. 1999;354(9173):106-110.

50.

Hedner U, Erhardtsen E. Potential role for rFVIIa in transfusion medicine. Transfusion. 2002;42(1):114-124.

51.

Mayer SA, Brun NC, Begtrup K, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358(20):2127-2137.

52.

Ohga S, Nomura A, Takada H, Suga N, Hara T. Successful selfinfusion of activated prothrombin complex concentrate for prophylaxis in a child with a factor VIII inhibitor. Am J Hematol.

53.

Bruce D, Nokes TJ. Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital. Crit Care. 2008;12(4):R105.

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