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Researchers Close In on Causes of CRPS Toronto—Researchers tasked with developing a rudimentary understanding of complex regional pain syndrome (CRPS) are dividing their attention ttention in several different directions. Acccor o di ding n ng to experts who spoke at the 2013 Int I ter ernational Congress on Neuropathic Pain, there is evidence for inflammatory, neuropathic and immunologic roots to her the enigmatic syndrome, and furth investigation into these three aspeccts of the condition is necessary forr the development of more effective treatments. “These different contributing fa facctors all influence each other, so we nee eedd atie ient ie ntss nt to address all of them so that paat don’t get onto a downward spiral whe herre

Anesthesia an The Real-Time Interdisciplinary group seeks mechanism of action for inhalation agents

allopius of Padua, the 16th-century anatomist and physician, famously complained, “When soporifics are weak, they are useless, and when strong, they kill.” Western medicine has come a long way in the centuries since, but anesthesiologists are only beginning to understand how the drugs of their trade work at the most fundamental level. “We don’t understand how general aneesthetics work in any detail,” said Roderic Eckenhoff, MD, the Austin Lamont Professoor of Anesthesiology and Critical Care at the Perrelman

see CRPS pag p page 20

see voltage e page 18

Consciousness Raising George Mashour, MD, PhD, hopes the darkness of anesthesia will shed light on the nature of the mind

f you want to commingle the arts with the science of anesthesiology without scaring away the audience for either, telling a zombie tale never hurts. That’s what George A. Mashour, MD, PhD, did when he co-authored a 2008 article in the journal Consciousness and Cognition that could have passed peer review in a Poe anthology. The paper argued that a “philosophical zombie”—an unconscious creature that behaves and responds like a human—is “naturally improbable.” But

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an “inverse zombie”—a creature that appears to be unconscious but in fact is not—is possible. Indeed, such a state fairly describes a patient experiencing awareness during anesthesia. Dr. Mashour’s blending of scifi horror with anesthesiology produced “an absolutely brilliant article,” said Max B. Kelz, MD PhD, professor of anesthesiology at the University of Pennsylvania, in Philadelphia. Dr. Mashour “is see consciousness page 16

COMMENTARY

Go “Team”!—how a single word is changing medicine.

CLINICAL ANESTHESIOLOGY

Even when healthy, obese patients receive a higher ASA surgical status.

CLINICAL ANESTHESIOLOGY

After outbreaks linked to nerve blocks, practice guidelines look to improve patient safety.

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For Afghan boy with rare bladder malformation, a soldier’s efforts lead to life-altering surgery.

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of 2013

The Top 10 Articles of 2013 on AnesthesiologyNews.com, see page 4.

April 11-13, 2014

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Make An Educated Decision Information You Need To Be Informed and Stay Competitive Anesthesia Business Consultants (ABC) believes the more you know, the better the decisions you can make. ABC places the highest value on continuing education. As the health care world continues to evolve, offering new technological advances and business models, along with changing laws and regulations, it’s imperative to keep informed. We provide our clients and associates regular updates on what is happening in the world of anesthesiology through our weekly eAlerts. These Alerts highlight the very latest in developments, changing requirements and opportunities and are a complimentary service. If you are interested in receiving these Alerts just send your name, e-mail address, the name of your practice or company, city and state to info@anesthesiallc.com. ABC is also pleased to offer the Communiqué, our quarterly newsletter, to interested individuals. It is available electronically as well as in print. The Communiqué features articles written by industry leaders focusing on the latest hot topics in group management, compliance and future business models for anesthesiologists, nurse anesthetists, pain management specialists and anesthesia practice administrators. We look forward to providing you with many more years of practice management news through the Communiqué and our weekly Alerts. Please log on to ABC’s web site at www.anesthesiallc.com and click on the “Publications” link to view the electronic version of the Communiqué online or to see copies of our previous Alerts. ABC does not share this list with any third parties nor use it for purposes other than distributing the Alerts, the quarterly Communiqués and the very occasional special announcement. If you have any questions or would like additional information please call 517-787-6440 x 4113, send an email to info@anesthesiallc.com, or visit our website at www.anesthesiallc.com. This communication is for educational informational purposes only and is not intended or offered as legal advice.

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Comment on these and other articles @ AnesthesiologyNews.com.

of 2013

Heard Here First: As we train ourselves in electronic etiquette and the proper way to interact with technology in both our personal p and professional p lives,

January 2014

The 10 most-viewed articles of 2013 on AnesthesiologyNews.com

we must look at society as a whole. Health professionals should be at the forefront of educating the general

dangers of electronic intrusion. These public in the many

1. Study Probes Anesthesia-Erection Link 2. Current Concepts in the Management of the Difficult Airway (Educational Review) 3. Marathon Bombing Put Local Anesthetists to Grim Test

devices are rapidly changing how humans interact with and behave toward each other.

4. Telemere Length Linked to Fibromyalgia Pain 5. CMS Ruling Exposes Organizational Rift Between Anesthesiologists, CRNAs

SEE ARTICLE ON PAGE 8.

6. Perioperative Approach to Patients With Opioid Abuse and Tolerance (Educational Review) 7. Propofol Dosing by Weight May Shortchange Obese Patients

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8. Systemic Strategies for Reducing Blood Loss in Surgery (Educational Review) 9. Seven Red Flags for Outpatient Surgery 10. Registry Sheds Light on Poor Outcomes of Nerve Blocks

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C OMM E NT A R Y

Brave New Word Let’s keep the “MD-led care” in “team” By Robert E. Johnstone, MD

new word is overtaking anesthesiolog y, a tendentious, troublesome, even truculent t-word. Hear it during educational talks, read it in science articles, find it in futurist discussions. The word is “team”—its glow bright, its definition unclear, its appearances often, as friends and foes alike use it to advance their disparate agendas, and put patients at risk. “Team” did not appear in the journal Anesthesiology for 27 years, until a 1947 book review, and then a 1970 article. It took 50 years before it popped up in 10 articles. Now it appears in 10 or so per issue, often multiple times per article. Seventy percent of articles with the word “team” were written in the past decade. Although trendy and prevalent, team remains ambiguous, usually paired

with a helper noun for some meaning and presumptive make-up. Thus in the October issue, find “operating team,” “perioperative team,” “surgical team,” “health care team,” “treating team” and, of course, “our team.” “Team” seems to have snuck past editors, hidden from definition, flattered health care reformers and gained respectability. Now it is running amok. Reformers and wellintended clinicians use this word to appear modern and connected, with whatever meaning they want, but with its ambiguity create disorder and confusion. The authors of a recent article on human factors engineering of operating rooms demonstrate the cachet of “team” when they describe themselves as “a team of collaborators” and previous human factor researchers as “groups.”1 They demonstrate its shiftiness when they divide operating room

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Leaderless anesthesia would be like a football team without a quarterback, a road without street signs, or house construction without a floor plan: a setup for fumbles, wrecks and collapses. occupants into “anesthesia team,” “surgery team,” “nursing team” and “perfusion team”—making readers wonder if their operating rooms are overpopulated, team memberships overlap or they have teams of ones and twos. Drs. Gravenstine, Steinhaus and Volpitto gave birth to anesthesia teams in their 1970 article, “Analysis of Manpower in Anesthesiology.” They wrote: “It is possible to design a system in which one anesthesiologist directs anesthetic procedures in more than one room with the help of an anesthesia team. Members of the team may include nurses and technicians.” Other anesthesiologists have since tried to define the members and duties of this anesthesia team, and over the past decade the American Society of Anesthesiologists (ASA) has crafted a statement on the Anesthesia Care Team (ACT). They all thought these teams should have leaders as well as members. Not surprisingly, nurse anesthetists, putative members of the team and thus empowered to comment, have rejected that notion, preferring some version of separate but equal. Gene Blumenreich, writing in the American Association of Nurse Anesthetists [AANA] Journal,l described the ACT as “offensive to many nurse anesthetists because it requires the ACT to be directed by an anesthesiologist.”2 He declared these teams are “not a standard of care … defining the standard of care is complicated … which brings me to Tiger Woods … (who) does not win every

golf tournament in which he wears a red shirt on the last day of the tournament.” This weirdness is as good as any of the AANA arguments for leaderless anesthesia care teams. Perhaps because this selff servingg assertion makes little sense, the AANA recently issued another statement that renames leaderless anesthesia teams as “patientcentered care” and asserts, “medical direction is solely a reimbursement concept.”3 At least credit these nurses with chutzpah—and raising their real issue—more money at less cost, or anesthesiologist pay without anesthesiologist education. Also credit them with generating a buzzwordfull, meaning-empty, y double-speak explanation. To wit: “The AANA also y valuebelieves that safe, high-quality, driven, patient-centered care is not a value held by one profession or the responsibility of one health care professional, but rather is a process that occurs throughout a patient’s care under the auspices of team-based health care.”3 Apparently this is a team of the nurse anesthetist and patient. That the incomes of nurse anesthetists have increased approximately 15-fold since 1970—much faster than physician anesthesiologists over that time— has helped them understand this nonsense. Fewer Horsemen? All of this raises an important question, however: Does a team need a

JANUARY 2014

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COMME N TA R Y Dr. Johnstone is professor of anesthesiology at West Virginia University in Morgantown, and a frequent contributor to Anesthesiology News. You might have caught him at the recent PostGraduate Assembly in Anesthesiology, where he appeared on a panel talking about, what else, “Team-Driven Anesthesiology Practice.”

leader? The ASA statement on the ACT addresses this in terms of a leader who prescribes an anesthetic plan, coordinates perioperative care, assumes overall responsibility and monitors and improves quality. But it does not clearly answer the question. The literature is not much better. Studies of teams and their qualities all seem to assume someone is leading them. John Maxwell stated, “A leader is one who knows the way, goes the way, and shows the way.” John F. Kennedy said, “Leadership and learning are indispensable to each other.” And from Theodore Roosevelt: “The best executive is the one who has sense enough to pick good men to do what he wants done.” Basketball coach Phil Jackson has replaced Teddy Roosevelt as our model for a leader, so current culture may explain the possibility of leaderless teams. Roosevelt, as a military commander, led a Rough Rider cavalry charge in the SpanishAmerican war. He saved the country, and famously said, “Speak softly and carry a big stick; you will go far.” Jackson, who has won 11 National Basketball Association championships coaching two different teams, derides stars, declaring, “The strength of each member is the team.” Roosevelt was elected president, but times have changed. Basketball coaches and players now earn far more than presidents. (In fact, Phil Jackson likely has earned more, in current dollars, than nearly all U.S. presidents combined.) Aldous Huxley in his 1932 novel, “Brave New World,” described a dystopia built on the principles of assembly lines, homogeneity, enforced happiness, repurposed words and omnipresent slogans, such as “everyone belongs to everyone else.” He might recognize leaderless anesthesia teams as fitting into his new world order. Fortunately, Huxley’s dystopia hasn’t arrived and probably never will. It would violate enduring qualities, human needs and common sense. Leaderless anesthesia teams will probably also never arrive, at least at institutions providing tertiary care, cardiac

surgery, neurosurgery or transplants. Someone needs to evaluate patient morbidities, interpret advanced monitoring and coordinate postoperative care. Leaderless anesthesia teams would be out of sync with developing models of care, such as perioperative homes, the coordination of care from preoperative to postoperative phases. Leaderless anesthesia would be like a

football team without a quarterback, a eminently useful. Anyone misusing road without street signs, or house con- “team” can be tweeted, and told they struction without a floor plan: a setup are twerking with the public good. for fumbles, wrecks and collapses. The new t-word is flourishing, used 1. Palmer G 2nd, Abernathy JH 3rd, Swinton G, et al. Realizing improved patient care through humanby many virtuously, promoted by centered operating room design. Anesthesiology. y some selfishly, distorting our think2013;119:1066-1077. ing and potentially damaging patient Blumenreich GA. Standards of care and the care. But there is hope. The ram- 2. ASA medical direction statement. AANA J. paging days of “team” are limited. 2004;72:91-94. New t-words are arriving, even more 3. AANA. Patient-centered care: CRNAs and the in sync with current culture. They interprofessional team. Position statement, June 2012. are “tweet” and “twerk,” and each

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Reference: 1 4th National Audit Project of the Royal College of Anesthetists and the Difﬁcult Airway Society: Major complications of Airway Management in the United Kingdom. Report and ﬁndings: March 2011. Editors: Dr. Tim Cook, Dr. Nick Woodall, and Dr. Chris Frerk.

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C OMM E NT A R Y

Digital Distraction: Signs of Improvement, But More Focus Needed By Peter Papadakos, MD

of addiction with health care workers. One of the tools that has become popular during these educational programs is the University of Rochester Modified CAGE Questions (Table). CAGE is a highly validated survey of alcohol addiction, which has been modified and replaces drinks with personal electronic devices (PEDs). This survey selff validates to the participant his or her own shortcomings with PEDs and is a springboard to starting a dialogue and correction of behavior in the professional environment. Organized medicine has thus started to selff correct and educate its practitioners at all levels of technical staff. But as we train ourselves in electronic etiquette and the proper way to interact with technology in both our personal and professional lives, we must look at society as a whole. Health professionals should be at the forefront of educating the general public in the many dangers of electronic intrusion. These devices are rapidly changing how humans interact with and behave toward each other. The ever-risingg figures of mortality and morbidity

n the November 2011 issue of Anesthesiology News, I wrote an article outlining my observations of the growing addiction of hospital staff to their smartphones. Not long after the piece, “Electronic Distraction: An Unmeasured Variable in Modern Medicine” (page 8) appeared, I received a call from a reporter for The New York Times, which ran its own article about digital distractions—what the paper dubbed “digital doctoring”—on the front page some weeks later. The Times story, and subsequent media coverage, served as a call to action in the fields of professionalism and patient safety. Professional societies in the United States and beyond began to address the issue through their annual meetings, safety committees, guidelines and studies. The issue was widely addressed in the newsletters of many health care groups including the ECRI Institute, the Association of periOperative Registered Nurses (AORN), the American Academy of Orthopaedic Surgeons (AAOS), Canadian and American respiratory therapists and the Congress of Neurological Surgeons. So, where do we stand? The signs are encouraging. Table. University of Rochester Modified Medical centers throughout the country have started CAGE Questions to develop guidelines and recommendations on the use of electronic devices and professional behavior. Have you ever felt you needed to cut down on the use of your PED? Hospitals, medical schools and clinical departments Have people annoyed you by criticizing your use of have addressed the issue thorough grand rounds and staff education. It is being addressed in operat- your PED? ing rooms throughout the United States through the Have you felt guilty about your overuse of your PED recommendations of AORN. ECRI even listed elec- at work? tronic distraction as one of the top 10 technology Do you reach for your PED first thing in the morning? hazards for 2013. We have made strides to at least address this issue PED,, pe p so a eelectronic personal ect o c de device ce ((includes c udes ssmartphone, a tpp o e, tab tablet et aandd mini-computer). co pute p )

Dr. Papadakos is professor of anesthesiology, neurology, neurosurgery and surgery at the University of Rochester Medical Center in New York. He is a member of the editorial board of Anesthesiology News.

by texting while driving—a reporter earlier this year said texting at the wheel now kills 3,000 American teens per year, making it the leading cause of death in this age group—and the tens of thousands of braininjured survivors and the millions of dollars required for their care will, of course, increase costs and burden the already strained rehabilitation system. New mental illnesses identified as an addiction to PEDs and to the Internet are reshaping our understanding of how the human brain functions. And virtual relationships like cyber-bullying, pornography and online gaming are altering our society in ways we have not yet begun to fully comprehend. Medicine also is identifying physical conditions that can cause lifelong disabilities such as injury due to repetitive use of the thumbs and back deformities such as “Game Boy back” from prolonged hours of texting. As health professionals, we already have become leaders in selff correction of this behavior and developing ways of addressing these technology issues. I call on each of us to begin educating both our families and communities. Hospitals and health professionals should educate young people in the schools of the dangers of overuse of this technology. We should pressure our elected officials on the dangers of not only texting and driving, but on distracted pedestrians and their other psychological and physical problems. Through education, we can effect great, positive change in how we interact with these new technologies.

Drug Abuse Among Residents Uncommon, But Occasionally Fatal

etween 1975 and 2009, 28 anesthesiology residents died as a result of substance use disorder (SUD), according to a study by the American Board of Anesthesiology (ABA) and Mayo Clinic. During the 35-year period, the study found roughly one in every 100 residents had abused drugs or alcohol—most frequently opioids, with 151 total incidents. The rate of SUD fell between 1996 and 2003, but it has risen in recent years, according to the researchers. “Although relatively few anesthesiology

residents develop SUD, the incidence is continuing to increase,” said David Warner, MD, an author of the study and an anesthesiologist at Mayo Clinic in Rochester, Minn., in a statement. “The problem is as serious now as it has been at any time over the period of study, and the consequences can be severe. Residents who develop substance use problems are at high risk for relapse after treatment or, in some cases, die as a result of the disorder.” Taking a retrospective look through the training data of 44,600 residents collected by the ABA, Dr. Warner

and his colleagues found evidence of SUD in 0.86% of trainees. In comparison, the Substance Abuse and Mental Health Services Administration estimates that 8.5% of the general U.S. population had abused or were dependent on drugs or alcohol in 2012. After IV opioids, alcohol was the most commonly abused drug among anesthesiology residents, followed by marijuana, cocaine, and anesthetics or hypnotics. LSD, MDMA and psilocybin mushrooms accounted for fewer than 14% of cases. Men had a higher incidence of SUD than women (92%

vs. 8% of SUD cases, respectively), according to the findings. Although the study did not collect data regarding patient harm, Dr. Warner warned that clinicians under the influence pose risks to themselves and their patients. “It’s incumbent upon us as medical professionals to do what we can to identify and address substance use disorders as quickly as possible,” he said, “to protect both the involved physicians and their patients.” —Ben Guarino

JANUARY 2014

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

Study Links Low Melatonin With Postoperative Delirium

atients in the ICU with postoperative delirium have lower melatonin levels in the hour following surgery than those who do not experience this complication, findings from a small Japanese study suggest. The results also found a negative correlation between melatonin levels and sevoflurane exposure and a positive correlation between fentanyl concentrations and melatonin levels. Alan Chaput, MD, an expert in postoperative delirium who was not involved in the research, applauded the investigators for tackling the causes of what is an often severe postoperative complication in the ICU population. “This is a complication associated with increased morbidity and mortality,” said Dr. Chaput, associate professor at the University of Ottawa, Canada. “However ... based on these findings, the relationship can by no means be said to be causal.” Several previous studies in nonICU patients who develop postoperative delirium also have found alterations in melatonin levels (e.g., Anesthesiology 2009;111:44-49). To examine this correlation in ICU patients, Moritoki Egi, MD, a researcher at the Okayama University Hospital in Okayama, and several colleagues analyzed prospectively collected data from 10 ICU surgical patients who met the Confusion Assessment Method for the ICU (CAMICU) delirium criteria and 23 similar patients without delirium. Both groups had a minimum of two days of ICU stay and had their plasma melatonin levels measured in the early morning on the day of surgery as well as one hour postoperatively and in the early morning on postoperative days (POD) 1 and 2. Delirious patients had average plasma melatonin levels of 0.45 pg/ mL compared with 2.8 pg/mL in the non-delirious group, at one hour postoperatively (P=0.037). There were no significant differences in melatonin levels preoperatively or at POD 1 and 2. Exposure to sevoflurane or fentanyl significantly correlated with melatonin levels, with each 1% increase in cumulative sevoflurane exposure associated with a 0.41 pg/mL decrease in melatonin levels (P<0.01). Conversely, each 1% increase in total fentanyl dose was associated with a 0.008 pg/mL increase in melatonin levels (P<0.01). Maximal end-tidal sevoflurane concentrations also significantly correlated with lower melatonin levels at one hour postoperatively.

Dr. Egi speculated that postoperative decreases in melatonin levels may increase the risk for delirium by triggering sleep disturbances, a known risk factor for delirium. “If this is the case, it would be worth conducting a randomized trial to see how exogenous melatonin affects melatonin levels and whether this will have an impact on delirium,” he said.

Dr. Chaput said, “In my mind, the dependent variable should have been the presence or absence of delirium, with melatonin included as a covariate along with other pre- and intraoperative variables, such as exposure to anticholinergic drugs in the perioperative period, which are known or suspected to be associated with postoperative delirium. As for the reported associations between

increased sevoflurane exposure and lower melatonin levels and increased fentanyl doses and higher melatonin levels, the study is really too small to draw any conclusions.” Dr. Egi presented the findings at the 2012 annual meeting of the American Society of Anesthesiologists (abstract 267). —David Wild

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C LIN I C A L A N ES THES IO LO G Y

Three Perioperative Interventions Do Not Affect Quality of Life San Francisco—The administration of steroids in the perioperative period, tight glucose control during surgery and light anesthesia do not affect patient quality of life measured at 30 days after major noncardiac surgery, a new study shows. Although previous studies have found an association between steroids and improved quality of life (QoL)

after cardiac surgery, results of the DeLiT (Dexamethasone, Light Anaesthesia, and Tight Glucose Control) randomized controlled trial failed to support those results. Also of note, this is the first and only randomized trial to date to study tight versus conventional glucose control in noncardiac surgery patients. “Initially, investigators were under

the impression that tight glucose control is beneficial,” said Basem Abdelmalak, MD, associate professor of anesthesiology and director of anesthesia for bronchoscopic surgery at Cleveland Clinic in Ohio. “Dexamethasone is currently being used for postoperative nausea and vomiting prophylaxis, or to help decrease airway edema in airway surgery.” However, this study

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did not show either intervention to be beneficial. Dr. Abdelmalak presented the results of his team’s study at the 2013 annual meeting of the American Society of Anesthesiologists (ASA; abstract 4168). Previous work indicates that highdose steroids improve QoL after cardiac surgery; it also indicates that intensive glucose control reduces sepsis and improves mortality outcomes in some patient populations, according to the researchers. Anesthesia guided by bispectral index monitoring (BIS; Covidien) reportedly speeds recovery and reduces respiratory complications as well as nausea and vomiting. The investigators thus expected to demonstrate beneficial effects of each tested intervention, Dr. Abdelmalakk said. The study consisted of 326 patients scheduled for noncardiac surgery under general anesthesia. They were randomized to receive 14 mg of IV dexamethasone tapered over three days versus placebo, intensive versus conventional glucose control (blood sugar goal of

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CL IN ICA L A N E STH E SIOL OG Y Table. Impact on Major Morbidity of Perioperative Interventions Intervention

Odds Ratio

Glucose control

0.96

Anesthetic depth

1.00

Steroids

0.96

Odds ratios of major morbidity after adjusting for history of coronary artery disease. Sou ce BJA Source: BJ 2013;111:209-211 0 3; 09

SF-12v2 scores 30 days after surgery (P>0.4 for all). Quality of life was a secondary outcome for DeLiT. The recently published primary results of the study, based on a composite of serious complications, showed no significant effect on perioperative morbidity from any of the three treatments (Table; Br J Anaesth 2013;111:209-221). “Given that none of the interventions influenced the primary outcome, it is perhaps unsurprising that there

80-110 mg/dL vs. 180-200 mg/dL), and light (BIS target 55) versus deep anesthesia (BIS target 35). The researchers assessed QoL using the SF-12v2 Health Survey, a shorter version of the SF-36v2, obtaining scores preoperatively and 30 days after surgery. The researchers evaluated the effect of each intervention on physical and mental components of the survey. After adjusting for minor differences in baseline ASA physical status, type of surgery and history of congestive heart failure and coronary artery disease, the researchers found no difference for any intervention on physical or mental

was also no effect on quality of life. It remains possible, though, that a larger dose of steroid may yet prove effective,” said Daniel I. Sessler, MD, the senior investigator on the study and director of outcomes research at the institution. “There is increasing interest in quality of life as a primary or secondary end point in large perioperative trials, as researchers realize that survival is not the only outcome that is valued by patients and their carers,” said Kate Leslie, professor and head of

Anaesthesia Research at the Royal Melbourne Hospital in Melbourne, Australia, who was not involved in the work. “The investigators tested three perioperative interventions with the potential to improve quality of life after surgery. Although none were shown to improve quality of life, these data provide a suitable basis for further study of different doses of dexamethasone and other anti-inflammatoryy treatments.” —Mandy Armitage, MD

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Obese Patients More Likely To Receive Acute ASA Status, Even When Relatively Healthy San Diego—Although the American Society of Anesthesiologists’ physical status classification system has proven to be an important predictive tool, its value may be degraded by consistent “upclassification” of obese patients. A recent analysis of more than 300,000 patients found that obese individuals are more likely to be classified as ASA II-IV than their normal-weight counterparts, regardless of their overall health. “One of the things that has haunted ASA classification over the years is the question of interobserver variability,” said Christopher H. Guerry, MD, an anesthesia resident at Virginia Commonwealth University in Richmond. “And it is in the setting of obesity in which we find some of the greatest interobserver variability.” Given that such inconsistencies can degrade the predictive value of surgical outcome models that use ASA physical status as a risk input, Dr. Guerryy and his colleagues examined trends in the classification

system across body mass index (BMI)-basedd categories between 1986 and 2010 in both emergent and nonemergent surgical cases. Researchers stratified 302,829 patients (ages 18-89 years; mean 48) according to BMI, after which they determined the relative risk for up-classification according to ASA physical status. As Dr. Guerryy reported at the 2013 annual meeting of the International Anesthesia Research Society (abstract S-153), 10.9% of patients were classified as ASA I, 47.7% as ASA II, 32.5% as ASA III, 8.4% as ASA IV and 0.6% as ASA V. Over the study period, the percentage of surgical patients who were of normal weight fell from 42% to 29%, whereas the proportion of obese patients rose from 20% to 39%. Compared with normal-weight patients, individuals with higher BMI were more likely to be upclassified on the ASA scale (Table 1). “One of the arguments you can make is that an increasing prevalence of comorbidities is a big part of increasing BMI, which would obviously be part

Table 1. ASA Classification by Weight: All Ages (18-89) ASA I-II

ASA I-III

ASA I-IV

1.05

1.11

Obese I (BMI 30-34 kg/m )

1.14

1.20

1.38

Obese II (BMI 35-39 kg/m )

1.21

1.33

1.69

Obese III (BMI >40 kg/m2)

1.25

1.42

2.15

ASA I-II

ASA I-III

ASA I-IV

Overweight

1.06

0.94

0.79

Obese I (BMI 30-34 kg/m2)

1.28

1.27

0.68

Obese II (BMI 35-39 kg/m2)

1.51

2.00

1.85

1.62

3.22

3.23

Overweight 2

Table 2. ASA Classification by Weight: Ages 18-25

Obese III (BMI >40 kg/m )

of the classical definition of ASA physical status,” Dr. Guerryy said. “So we looked at a subgroup of patients aged 18 to 25, the ones in which a diagnosis of comorbidities would be less likely.” Yet the up-classification association was more pronounced for these younger patients (Table 2). “Although the ASA classification system was not originally designed to be a risk predictor, there has been a lot of interest recently in coming up with complex models for predicting outcomes with it,” Dr. Guerryy said. And as it turns out, the system has been highly predictive. “But obesity adds inconsistency to the classification system, and with obesity rates increasing, we’re introducing a certain amount of uncertainty into these predictive models,” he continued. “So we can spend time debating whether or not it’s legitimate to upclassifyy obese patients, but the most important thing is that as a professional community we need to be consistent. Once consistent, then we can go back and look at the predictive value of the ASA classification system in these patients.” Charles B. Watson, MD, chief of anesthesia and deputy surgeon in chief at Bridgeport Hospital in Bridgeport, Conn., said there are legitimate reasons for counting marked obesity as a factor in assigning an ASA physical status. “The ASA [classification] was designed to predict the difficulty of the anesthetic, not outcome, and many of us believe that very obese patients are more difficult to care for,” Dr. Watson said. “Many arguments for and against the issue of whether obese patients, smokers, infants and others should be ASA I or II have been bandied about over the years. Most of us believe that very heavy patients are more likely to have comorbidities and worse outcomes, although there are published series showing ‘acceptable’ preoperative morbidity in this population.” —Michael Vlessides Dr. Watson is a member of the editorial board of Anesthesiology News.

Report Sees Low Risk for Hematoma From Regional Anesthesia During Joint Surgery

espite concerns about the risk for hematoma during spinal or epidural anesthesia, the rate of complications among patients undergoing joint replacement surgery is extremely low, according to new research released at the 2013 annual Euroanaesthesia meeting (abstract 457). The poster was named one of the best of the meeting. These types of regional anesthesia

have been used for many decades with great success, said Otto Stundner, MD, a research fellow at the Hospital for Special Surgery (HSS) in New York City. “One really should consider the major associated benefits when contemplating the only rare complications.” Anesthesiologists traditionally have been concerned about the risk for hematoma following spinal or epidural anesthesia because inserting a needle

into such a sensitive area could damage blood vessels. This could cause blood to build up at the injection site, damaging nerves and leading to temporary, or if untreated, permanent paralysis. But at HSS, among more than 100,000 knee or hip replacements that included either spinal or spinalepidural anesthesia with an indwelling catheter, eight patients (0.008%), or one in 12,500, showed signs of

collected blood or gas at the injection site. All eight had symptoms of a hematoma—back pain and movement problems—and two required additional treatment, such as removing bone fragments around the damaged site to alleviate some of the pressure. “All eight patients recovered well,” said r who also has an appointDr. Stundner, ment in the Department of Anesthesiology at the Medical University of Salzburg, in Austria. During the study, Dr. Stundner and his team reviewed the medical records from all patients who received spinal or epidural anesthesia during joint see hematoma page 15

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After Outbreaks, Experts Await Block Safety Advisory Boston—In 2012, a rash of deadly fungal infections linked to pain interventions highlighted the devastating outcomes that can occur from improper aseptic techniques in regional anesthesia and analgesia. The outbreak makes timely the upcoming updated practice advisory from the American Society of Regional Anesthesia and Pain Medicine (ASRA): “Infectious Complications Associated With Regional Anesthesia and Pain Medicine.” This updated advisory, first published in 2006 in Regional Anesthesia and Pain Medicine (Reg Anesth Pain Med 2006;31:311-352), will be available soon in the journal. The practice advisory addresses four topics: the importance and implications of aseptic techniques, the use of regional anesthesia in the febrile or infected patient, the use of regional anesthesia in patients with compromised immune systems and infectious risks associated with interventional pain management techniques. “Although infectious complications are exceedingly rare after regional anesthesia and pain management techniques, they remain relevant to the practice of every clinician because of the potentially devastating consequences they may have on our patients,” said James R. Hebl, MD, professor of anesthesiology at Mayo Clinic, in Rochester, Minn., who was involved in the update. The 20-state outbreak of meningitis triggered by contaminated methylprednisolone aceetate from the New England Compounding Centerr, a Massachusetts-based compounding pharmacy, harmed 750 patients and resulted in 64 deaths, according to the Centers for Disease Control and Prevention (Figures 1 and 2). One of the most important measures in preventing infectious complications is adherence to proper aseptic technique. Essential components of aseptic technique during regional anesthesiaa include proper hand hygiene, the use of a surgical face mask during medication preparation and procedural interventions, effective skin antisepsis—which includes both proper selection and use of an appropriate antiseptic—and avoiding the use of single-dose medication vials for multiple patients. Proper hand hygiene involves the use of an alcohol-basedd antiseptic solution, preferably chlorhexidine gluconate (CHG), with an alcohol content between 60% and 90%, Dr. Hebll said. Wear That Mask In 2007, the Centers for Disease Control and Prevention (CDC) echoed the 2006 ASRA practice advisory recommendations that clinicians wear a surgical face mask when “placing a catheter or injecting material into the spinal canal or subdural space.” These recommendations were based on a series of patients who developed streptococcal meningitis after myelography during which physicians used proper antiseptic cleansing and gloves, but no face mask. Subsequent investigations determined that the culprit bacteria had the same genetic profile as the bacterial species collected from the proceduralists’ nasopharynx. Not all anesthesia and pain management specialists

have been following the ASRA and CDC recommendations, Dr. Hebll noted. For example, an outbreak of Klebsiella pneumoniaee and Enterobacter aerogenes bacteremia occurred in 2008, after an interventional pain management specialist in New York City breached several aseptic recommendations. The New York City Department of Health and Mental Hygiene found evidence of improper hand hygiene, no surgical mask use, and the use of single-dose medication vials in multiple patients (Reg Anesth Pain Med 2010;35:496-499). In 2012, another infectious outbreak, this time of Staphylococcus aureus, was reported at an Arizona pain clinic and a Delaware orthopedic clinic following a variety of pain management interventions ((MMWR 2012;61:501-514). In Arizona, medication preparation occurred hours before intended use of the drugs. In Delaware, a surgical mask was not worn during preparation of the agents. In all of the cases, a single-dose vial of contrast dye or bupivacaine had been used for more than one patient, with clinicians citing the national drug shortage crisis as the reason for this practice. In response to the infections, the CDC issued a statement that in times of critical need, the contents of unopened single-dose/single-use vials could be repackaged by a pharmacist for multiple patients using national guidelines for medication use and handling.

Figure 1. Persons with fungal infections linked to steroid injections, by state.

Figure 2. States with health care facilities that received recalled lots of methylprednisolone acetate (PF) from New England Compounding Center on Sept. 26, 2012.

Proper Antisepsis The ASRA practice advisory recommends CHG, in an alcohol base, as the antiseptic of choice prior to all regional techniques—although chlorhexidine is not FDA-approved prior to lumbar puncture. However, because of its clear clinical benefit, and the lack of clinical testing to suggest that the agent is unsafe, the American Society of Anesthesiologists (ASA) and the Royal College of Anaesthetists in the United Kingdom have published similar recommendations regarding the use of CHG for regional anesthesia. Dr. Hebl highlighted a recent Mayo Clinic investigation, which he helped conduct, in which chlorhexidine antisepsis was used before the administration of 12,465 spinal anesthetics. The authors identified an overall rate of neurologic complications of 0.04%, similar to the rate reported in other large-scale studies not using chlorhexidine for spinal anesthesia (Reg Anesth Pain Medd 2012;37:139-144). “The incidence of neurologic complications possibly associated with spinal anesthesia (0.04%) after CHG skin antisepsis is consistent with previous reports of neurologic complications after spinal anesthesia. These results support the hypothesis that CHG can be used for skin antisepsis before spinal placement without increasing the risk of neurologic complications attributed to the spinal anesthetic,” tthe authors wrote. Terese T. Horlocker, MD, professor of anesthesiology and orthopedic surgery at Mayo Clinic, in Rochester, Minn., pointed out that clinicians are increasingly using perineural catheters as a component of their postn ooperative analgesic regimen after orthopedic surgery. A 2007 investigation evaluated infecttious complications after the placement of 2,,285 perineural catheters and found that local inflam mmation occurred in 4.2%, localized signs of infection occurred in 3.2%, and surgical intervention was needed in 0.9% (Acta Anaesthesiol Scand 20007;51:108-114). Anterior proximal sciatic catheters were associated with a lower risk for local inflammation (1.7%) and infection (0.4%). An increased risk for infection was seen with interscalene catheters (4.3%) and perineural catheters that remained in place for a prolonged period of time. James P. Rathmell, MD, professor of anesthesiology at Massachusetts General Hospital, in Boston, said one of the recent important studies of interventional pain practice is work he coauthored on cervvical spine pain procedures (Anesthesiology 2 2011;114: 918-926). In an analysis of chronic pain treatment claims from the ASA Closed Claims database (from Jan. 1, 2005 to Dec. 31, 2008), procedures performed at the leveel of the cervical spine accounted for 22% of all claiims. The most common injury included direct needle trauma to the spinal cord (31%), followed by spinal cord infarction or stroke related to intraarterial injection (14%). Infectious complications accounted for only 5% of cervical spine claims. —Kate O’Rourke

JANUARY 2014

AnesthesiologyNews.com I 15

CLINICAL ANESTHESI OLOGY HEMATOMA

CONTINUED FROM PAGE 12

replacements between January 2000 and October 2010. Although this type of anesthesia is frequently used during cesarean deliveries, those data only show its effects on a relatively young, healthy population, Dr. Stundner said. In contrast, people undergoing joint replacements are typically elderly with additional comorbidities such as cardiovascular disease, and take anticoagulants or other medications that could interfere with the procedure. Despite the fact that he and his colleagues found a relatively low rate of complications, 25% of anesthesiologists opt for spinal or epidural anes-

Hospital, in New York City, said he uses spinal or combined spinal epidurals for “at least 95%” of the joint replacements he performs, mostly because doing so avoids general anesthesia and all the complications that come with it. The HSS researchers’ estimate of the rate of hematoma was somewhat higher than what has been reported in previous studies of nonobstetric patients, Dr. Choi noted. “But the risk is still low, even with their number. And I think the important thing is to really try to figure out the factors that do increase the risk.” Specifically, Dr. Choi noted there might be some significance in the fact

Study finds one in 12,500 patients experience hematoma after spinal-epidural anesthesia for

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lower extremity surgeries, but some evidence points to gauge of needle as a possible risk factor. thesia during joint replacements, Dr. Stundner told Anesthesiology News. Why they do so is not clear, he said: Perhaps some practitioners do not feel comfortable with spinal injections, or are simply afraid of the potential, albeit rare, complications. Dr. Stundner,r however, said he mostly uses local spinal anesthesia during joint replacement surgery. Inserting a catheter prolongs analgesia and avoids the use of mechanical ventilation, whereas general anesthesia has its own set of potential complications. Spinal or epidural anesthesia “is really ideal for this type of surgery,” he said. “It doesn’t make me nervous at all to use it.” Even so, HSS has a protocol to ensure its clinicians monitor all patients closely to spot signs of hematoma early. This may help explain why all eight patients who developed the complication during the study period recovered well, Dr. Stundner said. “Although complications are very infrequent, one should always think about them whenever these procedures are done,” he added. Jason Choi, MD, a regional anesthesia fellow at St. Luke’s-Roosevelt

that all eight patients who experienced complications received an epidural, which is a significantly larger needle than what is used for a spinal anesthesia. “Their data suggest larger-gauge needles may have a potentially higher risk,” Dr. Choi said. “We need further research that includes a large population at more than one center to isolate the critical factors that may increase that risk.” In the meantime, Emily Lin, MD, MS, also a regional anesthesia fellow at St. Luke’s-Roosevelt Hospital, who used to work with Dr. Stundner and his coauthors, recommended that anesthesiologists follow guidelines established by the American Society of Regional Anesthesia and Pain Medicine (ASRA), the European Society of Anaesthesiology and other groups when determining how to administer spinal or epidural anesthesia to patients receiving anticoagulants. “At the end of the day, you should practice according to these guidelines, making sure that you individualize your decisions based on the patient,” she said. —Alison McCook

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attract and entertain folks question,” he said. “We wake up in the mornat a dinner party who had extremely well-read and able to see never laid eyes on a meding. We open our eyes and From Aladdin’s Lamp to ical textbook. His manconnections between ideas that span this world shows up for us. Areas Under the Curve diverse fields.” uscripts are just as liable The question is how does Dr. Mashour, professor of anesthethat happen? What is the Much of his work uses electroen- to contain references to siology at the University of Michi- cephalograms (EEGs) to parse the Aladdin’s lamp and psymechanism in the human gan, in Ann Arbor, is interested in effects of different anesthetic drugs on chedelic mushrooms as brain that allows us to generate experience? How the hard science behind his field. His the brain. That’s not terribly unusual. they are to P values and George Mashour, MD, PhD is it that the anesthetics most recent study, for instance, found But what sets Dr. Mashour apart from confidence intervals. Dr. Mashour is particuwe use are able to turn that that patients who previously experi- his peers is his desire to have an intelenced intraoperative awareness with lectual, liberal arts conversation about larly interested in understanding con- off in a rapidly reversible way?” Although anesthesia has been recall were five times more likely to do anesthesiolog y—one that would sciousness. “It’s really a fundamental around the better part of two centuries, the scientific study of consciousness is relatively young. Dr. Mashour counts himself among the early adopters. An acceptable scientific definition of “consciousness” remains ephemRisk Evaluation and Mitigation Strategies: an Employer-Driven CME Initiative for Efﬁcacy and Safety eral to him. “Philosophers have been asking this question for millennia,” he said. “Everybody knows what it is. You know what it’s like to see a sunset or Complete Parts 1 and 2 to meet the requirements of the FDA Blueprint for fo hear a symphony. But how do we put this subjective process into objective Prescriber Education fo for Extended-Release and Long-Acting Opioid Analgesics terms? And if I use a term, how can I be sure that I mean the same thing you CO C O OR RE R E C CU UR U RR R RIIIC R CU C U UL LU L UM U M 1 1.2 ..2 25 2 5 C CR R RE E ED DIIIT D TS T S E EA A AC CH C H do? How do I know what you’re calling ‘green’ isn’t something different? PA PAR PA ART RT 2 RT PAR PA ART RT 1 This problem becomes even more difficult when considering a scientific or Navig N aviga a v i gating g ating a t i n g Opioid O p i o i d REMS R E M S Navig N aaviga viggating ating Opioid Opioid REMS REMS quantitative description of a subjective process.” Dr. Mashour received what he called a “classical liberal arts” education, but became interested in the conscious Monograph or Webinar M Monograph or Webinar M mind when he read DNA pioneer Francis Crick’s articles on the subject. He had just started at Georgetown SU S UP U PP P PL P LE L EM E ME M E EN NT N TA TA AR R Y ..5 RY 5 CR RE ED DII T S E EA AC CH H University School of Medicine (he completed his MD and PhD in 2001), PE P ER E RS RSI RS SIIIS ST S TE T EN E NT N T MANA MA MAN AN A NA N NAG AG AGI AG GIIIN NG N G and it “opened my eyes.” He became LOW LO L OW O WB BA BAC AC AC CK K PA AIIN AIN N OP O PIIOIID P DT TH HE H ERA ER E RA RAP RA APY AP PY PY further interested when he began his at Harvard. residency A Virtual Patient Activity A Virtual Patient Activity “For most of the 20th century, consciousness—even in the field of psySU S UP U PP P PL P LE L EM E ME M EN E NT N TA TA AR R Y ..5 RY 5 CR RE ED DII T S E EA AC CH H chology—was not considered a valid topic of interest,” he said. A multidisMY F MY FIRST-C FIIIR RS RST RS ST T-C T --C CH C HO H OIIIC O CE IIS S IIS SM MY Y PA PAT PAT ATIE ATI EN NT N T ciplinary approach to it wasn’t taken until the 1990s. Even today, seriously NO N OT O T WO WO OR RKI RK RKI K KIN ING AB BU US U SIN NG G OP PIIIO OIIDS O DS S? ? anesthesiologists “have a very small Now What? representation in this field.” Jamie Sleigh, MD, an anesthesiologist at the University of Auckland, SU S UP U PP P PL P LE L EM E ME M EN E NTA NT N TA TA ARY RY 2 RY 20 0 CR RE ED DII T TS S in New Zealand, who has followed Dr. Mashour’s work, said the study of consciousness had been frowned Enroll E n nroll roll today todday ay upon for too long. “It was ridiculous to ignore such a fundamental phenomenon,” Dr. Sleigh said. “It is driven by fear that it would expose the limitaRelease Date: May 9, 2013 Expiration Date: May 9, 2014 tions of reductionist science—which is probably true.” TM Each part of this activity has been approved as indicated above for AMA PRA Category 1 Credits Dr. Mashour’s contribution is to For information about the accreditation of this program, please contact Global at (303) 395-1782 or inquire@globaleducationgroup.com examine anesthesia’s role in consciousJointly sponsored by Global Education Group Supported by an ness. “Is that the same brain that’s comand Applied Clinical Education educational grant from ing out of the general anesthetic, or CONTINUED FROM PAGE 1

so again than were patients who had never had the experience.

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PR N ‘It was ridiculous to ignore such a fundamental phenomenon. It is driven by fear that it would expose the limitations of reductionist science— which is probably true.’

he was senior author describing electrical activity in the brains of dying rats (Proc Natl Acad Sci USA Aug 12, 2013; doi: 10.1073/pnas.1308285110). The researchers found, contrary to commonly accepted belief, that there was a “transient surge” in meaningful neurophysiologic activity in the 30 seconds after a heart attack that exceeded activity during the waking state. A Washington Postt article on the study attracted 1,300 comments and much buzz about whether people who have had

near-death experiences may have experienced heaven, as some have claimed— including a neurosurgeon, Eben Alexander, MD, who wrote about his experience in the book, “Proof of Heaven.” “It’s a topic that transcends science and moves into questions about religion, the afterlife, the existence of God,” Dr. Mashour said. But he hastened to add: “We weren’t making a claim that animals were having a near-death experience.” Instead, the

study showed that after a heart attack, “there are some features associated with conscious processing that seem to come back with a vengeance.” His lab at Michigan is as varied as his writings. It includes biomedical engineers, physicists, neuroscientists and even a philosopher. “I like a multidisciplinary approach,” he said, even if things can get chaotic. “I do like people who are able to take a broad look at the problem.” —John Dillon

—Jamie Sleigh, MD

does that anesthetic have effects that cause persistent cognitive dysfunction?” he said. “Is it a patient factor? Is it the anesthetic? Is it the surgery, stress, inflammation or some combination of these factors? Whether all the pieces are being put back together is a question for the field.” Dr. Mashour’s studies on consciousness provide a bridge between anesthesiology and the outside world because he “links the latest EEG/imaging analysis methods with the clinical and philosophical consequences,” Dr. Sleigh said. “There are not many clinicians, let alone full-time scientists, who could blend seemingly divergent fields as harmoniously as George has,” Dr. Kelz said. “Most amazingly, George’s science isn’t restricted to the lofty towers of academic institutions. Rather, I’m confident that George’s work has already had—and will continue to have—true translational power. His work has adapted and extended previous basic science discoveries—such as the asymmetric directional changes in the EEG that herald the loss and return of consciousness—that may improve patient safety by reducing the incidence of awareness under anesthesia.” Getting Metaphysical Dr. Mashour made a splash in the general news cycle last August with the publication of a study on which

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PRN VOLTAGE

Electrophysiology

“The idea is to identify within these particular types of ion channels, which have raditional anesthetics are highly toxic because they School of Mediccine been impllicated in general anestheare indiscriminate in how they interact with neuronal at the University oof sia, to iddentify binding sites that will membrane proteins, Dr. Covarrubias said. “If we can identify specific Pennsylvania, in allow us to find the best fit for interactions, then we can design more specific anesthetics,” he said. “And we believe these ion channels have those specific interactions.” Philadelphia. “We the ddrug, the way a hand fits in Dr. Covarrubias likens the binding sites in voltage-gated ion channels to gloves, don’t know the a gglove,” Dr. Covarrubias said. and the anesthetics to hands. Only a few of the gloves can provide a perfect fit, by “T To do that, we induce mutamolecular targets producing the desired effects of the anesthetics, without the toxicity. tions in these ion channels that they need to To visualize the binding sites, Dr. Covarrubias uses the polymerase chain reaction to engage to create in specific regions that we induce mutations in genes that encode specific ion channels. These genes are inserted Roderic Eckenhoff, MD guess are the binding sites. their effects.” into frog oocytes, which serve as model cells. Microscopic electrodes record where, and To find out, “Within those regions, how strongly, the anesthetics bind to the channels. Dr. Eckenhofff is leading a multi-institution we have identified specific “Sometimes by making mutations, we make that interaction better, and someteam, along with researchers at Thomas Jeffresidues that are possitimes we make the binding worse,” he said. “So we go back and forth, ferson University, Temple University, Drexxel ble binding sites for anesto make a model of what that channel looks like.” University, Rutgers University and Penn, iin five thetics,” Dr. Covarrubias It’s well known that anesthetics target neurotransmitters, Dr. Covarrubias said. “We believe that that is only part of the connected projects. Each has the dual aim of identifyaadded. That information is story, that general anesthesia not only implicates the cr ucial to creating anestheting the precise binding sites where anesthetiics interact neurotransmitter receptors, but with proteins in the neuronal membrane,, and charics tthat target the binding sites these voltage-gated ion chanacterizing those interactions in detail. In addition a to specificcally, therefore reducing or nels as well.” anesthesiologists, the group includes elecctrophysiol- structural eliminating tthe toxicity of present drugs, ogists, biophysicists, computational physiicists, and and molecular biolsuch as desflurrane and sevoflurane. ogists, who approach the question In addition too identifying the binding of how anesthetics work from differsites, the researchers also a are using nuclear magent angles. netic resonance spectrroscopy to study the inter“If If we can use the parable of the action between the anesthetics an blind man and the elephant, we’re sort and the binding sites in real of each seeing a different bit of this problem,” time. To complement and Dr. Eckenhofff told Anesthesiology News. “But we’re enhance that work, they then able to assemble it back to what’s really happening—what the mechanisms really are.” Inhaled anesthetics produce a variety of effects: analgesia, immobility and amnesia, along with hypnosis and the alteration of blood pressure. Researchers know that the drugs work by regulating the his project requires a wide variety of proMovie 1. Isoflurane flooding. The NaChBac activity of particular proteins in the neuronal memteins, in vast quantities, in order to run the pore domain (blue ribbons) sits in the bilayer brane, but not which proteins are involved or how experiments— a requirement shared by x-ray specific drugs interact with them (Figure). The (headgroups shown as grey spheres) while crystallographers. likeliest candidates are voltage-gated ion channels, isoflurane (red/green molecules) begins in the “It turns out that this technique demands large which control the flow of sodium and potassium aqueous compartment above and below the amounts of pure protein, so crystallographers ions throughout the neuronal membrane, said Manbilayer and partitions first into the bilayer and become good at producing protein,” said Patrick Loll, PhD, a molecular biologist at the Drexel Unithen into the protein structure. Voltage sensing uel Covarrubias, MD, PhD, an electrophysiologist and professor at Thomas Jefferson University’s Farversity College of Medicine, in Philadelphia. “Mandomains, water molecules and lipid alkyl tails ber Institute for Neurosciences, in Philadelphia. ufacturing proteins that are anesthetic targets will are not shown in this movie but are present in be an important part of our work going forward.” the simulation. Dr. Loll and his colleagues use genetic engineerCONTINUED FROM PA AGE 1

Protein Production

Figure. Fenestrations as the hydrophobic access pathway. (A and B) Two views of a representative isoflurane molecule traveling from bulk solution into (A) and back out of (B) the cavity via two adjacent fenestrations. Cavity and fenestrations are shown as gray surfaces for clarity.

ing methods to induce yeast and insect cells to produce the proteins. Once the cells have manufactured the molecules, researchers deploy a combination of affinity chromatography methods and fast protein liquid chromatography instruments to extract them from the cells. “These instruments utilize high pressure to perform the chromatography experiment in a few minutes, so we can isolate these relatively fragile molecules quickly, before they deteriorate,” Dr. Loll said. Once the proteins are extracted, they are analyzed using mass spectroscopy, both initially to confirm their identities, and in experiments to assess their interactions with anesthetics. “Our long-term goal is to gain a mechanistic, molecular view of how anesthetics interact with proteins, and how this interaction gives rise to the physiological changes that we know as anesthesia,” Dr. Loll said. “That’s pretty ambitious, but we have a tremendous team working on this problem, so I’m optimistic that we’ll make great progress.”

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Computational Physics

he interactions between anesthetics and these binding sites occur so quickly, and on such an infinitesimal scale, that even the most precise techniques of physical visualization are unable to render them fully. That’s where computer simulations come in. Each molecule involved in the drug interactions is modeled using data derived from experimental crystallography, a method known as molecular dynamics simulation (Movies 1 and 2). “We’ve got a bunch of atoms basically in a box, and they’re interacting via forces we’ve determined by quantum chemistry,” said Grace Brannigan, PhD, a computational biophysicist at Rutgers University’s Camden, N.J. campus. “And we basically watch a movie of how they interact, which allows us to see how the system evolves over time.” Dr. Brannigan and her colleagues are looking at a group of neurotransmitter receptors in the neuronal membrane called cys-loop receptors. Some cys-loop receptors inhibit neuronal activity, whereas others excite this activity. Anesthetics work by negating these effects—activating cys-loop receptors that cause inhibition, and deactivating those that cause excitation.

By modeling these interactions, researchers are able to generate testable hypotheses about where anesthetics bind with cys-loop receptors, and which effects this binding produces. These hypotheses inform the physical experiments in the project, which in turn enable them to refine the computer models, in a mutually beneficial feedback loop.

of brain activity, Dr. Eckenhofff said. Finally, they are using shallow-angle x-ray scattering and neutron spectroscopy to confirm the electrophysiologic observations and the test hypotheses derived from the computer simulations. The project, Interaction of Inhaled Anesthetics with Macromolecules, is the continuation of a collaboration that began 15 years ago. The researchers recently received $8.6 million in renewed funding for the next five

Part 1: Framing the Issues Case Study Harold is a 74-year-old man undergoing a video-assisted right upper lobectomy for stage I non-small cell lung cancer. Current Symptoms • Dyspnea • Coughing with hemoptysis • Chest pain Vital Signs • Height: 177.8 cm (70”) • Weight: 65 kg (143 lb)

Current Medications • Metoprolol succinate ER 50 mg/d • Tiotropium bromide inhalation powder

also are creating computer simulations to model the activity of these systems over time spans as long as a microsecond—“an eon” in terms

—Ajai Raj

Rationale, Reversal, and Recovery of Neuromuscular Blockade

Signi¿cant Medical History • Hypertension • Chronic obstructive pulmonary disease (moderate)

Movie 2. Representative isoflurane trajectory through fenestration to cavity site. Bottom view of NaChBac structure (grey ribbons) surrounded by lipid molecules (stick representations). Isoflurane (blue, space-filling representation) enters from the lipid phase into the cavity through a fenestration.

years from the National Institutes of Health. “We’re trying to get to the very basic level,” Dr. Eckenhofff said. “If you don’t know what the binding site looks like, and what atoms are needed to bind, it’s hard to do anything besides empirically alter the drug. For us to intelligently alter it—to predictably alter it—we really need to understand, at the atomic level, what’s going on.”

Laboratory Results • 2-cm lesion in right upper lobe revealed on chest computed tomography (CT) scan; malignancy con¿rmed with needle biopsy • No abnormal bronchopulmonary or mediastinal lymph nodes; brain CT, isotopic bone scan, abdominal ultrasonography negative for distant metastases • Forced expiratory volume in the ¿rst second: 43.6% of predicted value (1.44 L) • Carbon monoxide diffusing capacity: 71.7% of predicted values (20.19 mL/min/mmHg) • Cardiac ultrasonography: normal pulmonary artery pressure (22 mm Hg) At induction, Harold receives propofol 1.5 mg/kg and rocuronium 0.6 mg/kg. During the procedure, movement of the diaphragm interferes with surgery. This activity is jointly sponsored by Global Education Group and Applied Clinical Education. Supported by an educational grant from Merck.

Applied Clinical Education is pleased to introduce a new interactive 3-part CME series featuring challenging cases in neuromuscular blockade. Each activity will present a clinical scenario that you face in your daily practice. After reading the introduction to the case, consider the challenge questions, and then visit www.CMEZone.com/nmb1 to ¿nd out how your answers stack up against those of our multidisciplinary faculty panel. Access the activities on your desktop, laptop, or tablet to explore the issues surrounding safe, effective, neuromuscular blockade and reversal via a unique multimedia learning experience and earn 1.0 AMA PRA Category 1 Credit.™ Participate in the coming months as well to complete the whole series and earn a total of 3.0 AMA PRA Category 1 Credits.™ This activity’s distinguished faculty Jon Gould, MD Glenn S. Murphy, MD Chief, Division of General Surgery Alonzo P. Walker Chair in Surgery Associate Professor of Surgery Medical College of Wisconsin Senior Medical Director of Clinical Affairs Froedtert Hospital Milwaukee, Wisconsin

Clinical Professor, Anesthesiology University of Chicago Pritzker School of Medicine Director Cardiac Anesthesia and Clinical Research NorthShore University HealthSystem Evanston, Illinois

Challenge Questions 1. What would you do next? 2. What potential postoperative risks does this patient face?

Access this activity at www.cmezone.com/nmb1

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P A IN M E D I C I NE CRPS

CONTINUED FROM PAGE 1

each factor worsens another,” Anne Louise Oaklander, MD, PhD, associate neurologist at Massachusetts General Hospital and associate professor at Harvard Medical School, both in Boston, said in an interview after the panel discussion. Not a Perfect Fit Ralf Baron, MD, vice chair of the Department of Neurology and head

of the Division of Neurological Pain Research and Therapy at the University Hospital Schleswig-Holstein in Kiel, Germany, told attendees that until recently, CRPS was understood to be clearly a neuropathic pain disorder. However, CRPS does not fit with the 2008 redefinition of neuropathic pain, defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system” (Neurolog y 2008;70:1630-1635).

“CRPS is neuropathic in that there are characteristic neuropathic sensory abnormalities, but it also shows signs of central sensitization, inflammation, and autonomic and motor abnormalities,” Dr. Baron said. One way of grouping CRPS patients is by looking at their distinct somatosensory dysfunctions, Dr. Baron said. Individuals with deficits in temperature detection but no allodynia, and with loss of small nerve fibers, innervation and nerve

SCA/STS Critical Care Symposium March 28, 2014 Sheraton New Orleans • New Orleans, LA

36th Annual Meeting & Workshops March 29–April 2, 2014 Sheraton New Orleans • New Orleans, LA

SAVE THE DATE! 17th Annual Comprehensive Review and Update of Perioperative Echo May 5–9, 2014 Loews Atlanta Hotel • Atlanta, GA

Society of Cardiovascular Anesthesiologists 8735 W. Higgins Road • Suite 300 • Chicago, IL 60631 Phone: 855.658.2828 • Fax: 847.375.6323 • E-mail: info@scahq.org Please keep an eye on www.scahq.org for up-to-date information on these events.

degeneration, can be classified as having a neuropathic disorder. A second cluster of patients can be seen as having central sensitization, with normal temperature sensitivity but severe mechanical and thermal hyperalgesia. A third patient cluster may have inflammatory CRPS, with deep hyperalgesia and heat hyperalgesia but no hyperalgesia to prick testing, Dr. Baron explained. An Autoimmune Disease? Another way of understanding CRPS, proposed by Andreas Goebel, MD, PhD, senior lecturer and honorary consultant at the University of Liverpool and Walton Centre National Health Service Foundation Trust in Liverpool, United Kingdom, is that a subset of CRPS patients have an autoimmune disorder–related condition. “It is possible that a regional immune response is triggered following stress, inflammation and trauma,” he said.

‘All of the investigations which we have done, both in the lab and clinically, have been leaning more and more toward confirming there is an autoimmune aspect to CRPS.’ —Andreas Goebel, MD, PhD Dr. Goebel said some of the 15% of CRPS patients with refractory symptoms lasting longer than six to 12 months may fall into this group (Pain 2009;142:218-224). He noted that several studies support the autoimmune paradigm, with results showing that a subset of CRPS patients have elevated levels of serum antibodies to several bacterial pathogens. “Furthermore, there is evidence for CRPS serum immunoglobulin binding to peripheral nerves,” he said (Neurology 2004;9:1734-1736). Indeed, several small case series, including his own, have demonstrated the efficacy of intravenous immunoglobulin G (IgG) in subsets of patients with long-standing, refractory CRPS, Dr. Goebel said (Pain Med 2002;3:119-127). A randomized controlled trial of 12 patients with long-standingg CRPS who received the

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AnesthesiologyNews.com I 21

PA IN ME D ICIN E agent found that 25% reported pain relief of at least 50% relative to baseline and 17% had improvements in pain of between 30% and 50% ((Ann Intern Med 2010;152:152-158). Although IgG has anti-inflammatory effects in addition to being an immunomodulator, Dr. Goebel said IgG’s efficacy is likely not explained by its anti-inflammatoryy effect. “All of the investigations which we have done, both in the lab and clinically, have been leaning more and more toward confirming there is an autoimmune aspect to CRPS,” Dr. Goebel concluded. “However, since we do not know which structures the autoimmune response is targeting, our current evidence remains somewhat indirect.” According to Dr. Goebel, if some patients in fact have CRPS of autoimmune origin, “a range of potential therapies, such as therapeutic plasma exchange and B-cell modulating therapies, can be at our disposal. These have

‘CRPS is neuropathic in that there are characteristic

of the trial (Pain Pract t 2013; May 22: doi: 10.1111/papr.12078). The researcher still believes there could be neuropathic sensory abnormalities, but it also a role for infliximab and other biologshows signs of central sensitization, inflammation, ics in the treatment of CRPS. “Although the sponsor stopped the and autonomic and motor abnormalities.’ study early, preliminary data showed enormous reductions in TNF-α levels —Ralf Baron, MD in blister fluid with infliximab treatment, but these did not correlate with all been tried and tested in other auto- an “ultralocal” inflammatory response. clinical changes,” he said. immune disorders, and we can have “There are inflammatory mediators Summarizing the challenge of access to an armamentarium that we that are increased in the blister fluid understanding and treating a complex did not have before,” he said. of an involved extremity in CRPS,” syndrome, Dr. Baron suggested CRPS Dr. Huygen said. should no longer be seen monolithiAn ‘Ultralocal’ His own research has documented cally as a neuropathic disorder. Inflammatory Response? increased levels of interleukin-6 and “As long as we do not have a clearer Frank Huygen, MD, PhD, professor tumor necrosis factor (TNF)-α in pathophysiological picture of CRPS of anesthesiology at Erasmus Medical some patients (Eur J Pain 2008; patients, and because of the obvious Center in Rotterdam, the Netherlands, 12:716-721). heterogeneity of the signs, symptoms argued the inflammatory component In a small, placebo-controlled, ran- and mechanisms of the syndrome,” he of CRPS could be the most clinically domized trial, Dr. Huygen and his said, “it would be wise to look at the meaningful element of the syndrome colleagues showed that the anti-TNF condition separately from other classiin some patients. However, rather than drug infliximab (Remicade, Janssen) cal neuropathic pain syndromes.” looking for systemic inflammation, he exacerbated symptoms in some CRPS believes researchers need to consider patients, leading to discontinuation —David Wild

CL A SSIF IE D S

The UNMC Department of Anesthesiology seeks applications for positions in a Critical Care Anesthesiology fellowship. The 12-month ACGME-approved fellowship will prepare anesthesiologists for successful clinical practice, board certification and leadership in critical care medicine. UNMC is a 624-bed Level 1 trauma center and a nationally recognized Center of Excellence in solid organ transplantation and hematologic malignancies. UNMC provides fellows with outstanding opportunities to develop expertise in all facets of critical care, including surgical, trauma/burn, cardiac surgical, cardiovascular medicine, general medicine, neurosurgical/neuroscience, extra-corporeal circulatory support and critical care ultrasonography/echocardiography. Applicants seeking a position starting July 2014 or July 2015 should contact the Program Coordinator and visit www.unmc.edu/anesthesia to download an application.

COLORADO REVIEW OF ANESTHESIA FOR SURGICENTERS AND HOSPITALS CRASH 2014 Vail, Colorado 23 February – 28 February 2014 New This Year: Concurrent Intensive Cardio-Thoracic Review

Program Director: Daniel W. Johnson MD (dan.johnson@unmc.edu) Dept. of Anesthesiology, 984455 Nebraska Medical Center, Omaha, NE 68198-4455 Program Coordinator: Mary Bernhagen (mbernhagen@unmc.edu) 402-559-7370

Lectures: OB, Peds, Ambulatory, and much, much more…. Workshops: Airway Management, Ultrasound Guided Regional Anesthesia; 3D Echo Models demonstration. Panels: Cardio-Thoracic; Neuro-Anesthesia; Practice Management, Governmental Affairs and Quality. Special Guest Speakers: Dr Meena Desai and Dr Javier Campos PALS/ACLS/BLS! Detailed information available at http://cucrash.com Don’t forget the Opening Reception and Epic Mix Races

The most CME, the most number and variety of workshops in the #1 ski resort in North America. CRASH FUTURE DATES: 2015 – Sunday, 1 March to Friday 6 March 2016 – Sunday, 28 February to Friday, 4 March

22 I AnesthesiologyNews.com

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AD LIB

Lifesaving Mission for Ailing Afghan Boy Child with rare bladder malformation receives corrective surgery on Long Island after befriending U.S. soldier

ilal Sharif was born in an Afghan refugee camp in Pakistan. For seven years, he had survived with a congenital anomaly called bladder exstrophy in which part of the urinary bladder is present outside of the body. The organ sat below his navel, an open abdominal wound that left him prone to infection, constantly wet and in pain. Nearly two years ago, Bilal crossed paths with Maj. Glenn Battschinger, a member of the Army Reserves 353 Civil Affairs Command. Maj. Battschinger eventually managed to arrange “humanitarian paroles” for Bilal and his father, who came to

From the operating room at Steven and Alexanstay with host parents in Lackawanna County, Pa., late last year in preparation for surgery to repair the dra Cohen Children’s Medical Center of New York malformation. Such operations are not available in in New Hyde Park, pediatric anesthesiologist SanAfghanistan. joy Joshi, MD (below), helped support the humanitarian mission. Dr. Joshi, a 16-year veteran with North Shore-LIJ Health System’s Department of Pediatric Anesthesia, was a member of the medical team, led by surgeon Moneer Hanna, MD, that performed the life-changingg procedure on Nov. 19. “It is all about communication and teamwork,” Dr. Joshi said. “This was a reconstructive procedure [that took] approximately five hours and Bilal was anemic to start. This procedure requires a lot of fluids, and knowing someone who is anemic would run the risk for loower oxygen-carrying capacity and further hemodilution from IV fluids administered during the case. [The patient] can aalso have low blood ppressure from being aanemic.” Bilal received one uunit of blood and “several hundred milliliters” of balanced salt solution during the proceduure, Dr. Joshi said. “He maaintained a good urine ouutput during the case an nd stayed very relaxed.” Complicating his C anaalgesia care, Dr. Joshi saidd, “Bilal’s spine was nevver studied and he had a n new onset of broadbasee gait that contraindicateed placing an epidural cath heter for post-op pain management.” Bilal received a fentanyl drip during and after surggery for pain control. To create an optimal environment for the surgical sutures to heal, the child was m iintubated for 24 hours after the procedure. “These are very challenging cases,” Dr. Joshi added. “I am glad that I could contribute to this lifechangingg surgery and care for this child.” —Donna Clementoni All images copyright ©2014 Leslie Granda-Hill

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