The December 2011 Digital Edition of Anesthesiology News by McMahon Group

2012

65th PostGraduate Assembly in Anesthesiology meeting issue

Buyer’s Guide Winter/Spring

accompanies this issue

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The Independent Monthly Newspaper for Anesthesiologists AnesthesiologyNews.com • D e c e m b e r 2 0 1 1 • Volume 37 Number 12

Is QT Prolongation A Valid Reason To Abandon Zofran?

lthough the FDA announced it is conducting a safety review of the antinausea drug Zofran (ondansetron, ondansetron hydrochloride and their generics) because of its potential to increase the risk for cardiac arrhythmias, some experts say the drug is still useful in many patients, provided it is appropriately monitored. Zofran, used to prevent nausea and vomiting caused

Opioid Gene Variants Linked To Cancer Survival in Women

ounting laboratory and epidemiologic data have suggested a link between exposure to opioids during cancer surgery and metastasis of, and eventual death from, the disease. Now, a major genetics study has turned up some of the most compelling evidence yet for a connection between opioids and malignancy, even beyond the operating room. The new work, by researchers at the University of North Carolina, in Chapel Hill, found that breast cancer patients with variants of the µ-opioid receptor that make their cells less responsive to the analgesic are as much as fourfold less likely to die of their tumors as those with the most widespread form of the receptor.

see zofran page 58

see genes page 44

INside

Uninformed Consent

Average Study Participant Likely Unaware of Risks

nformed consent is a must for any clinical researcher, a legacy of Boston anesthesiologist Henry Knowles Beecher, MD, an early pioneer in the field of medical ethics. Dr. Beecher’s 1966

paper in the New England Journal of Medicine exposing widespread ethical lapses in clinical research helped lay the foundations for the research protections that most investigators now take for granted. But a new study suggests that even today, a key safeguard against potential abuse— consent forms—is troublingly vulnerable. Informed consent documents are written at a reading level too high for the average research participant, according to an analysis of forms from 15 studies conducted at two tertiary care centers. see consent page 60

08 | Ad Lib

34 | Pain Medicine

Robbing the captain’s pantaloons— crime and the history of anesthesia.

A pair of unusual cases in pain management.

10 | COMMENTARY

55 | CLinical Anesthesiology

Anesthesia and the Feres Doctrine.

Walking speed pegged to successful surgical recovery.

17 | CME Malignant Hyperthermia: Diagnosis, Treatment, and Prevention

30 |

Goal-directed Therapies for Positive Patient Outcomes: Monitoring and Volume Replacement With 6% Hydroxyethyl Starch 130/0.4 in 0.9% Sodium Chloride for Injection

47 | CME—PreAnesthetic Assessment Lesson 295: PreAnesthetic Assessment of the Patient With Systolic Or Diastolic Heart Failure

Newproducts

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The Wireless Videoassisted Intubating Stylet from Disposcope, see pages 38 and 66.

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4 I AnesthesiologyNews.com

December 2011

Discuss these and other articles @ AnesthesiologyNews.com.

Heard Here First: It seems to be that after a while, the OR personnel no longer follow the rules.

December 2011

The five most-viewed articles last month on AnesthesiologyNews.com 1. “Herculean” Study of Airway Complications Finds Room for Improvement 2. Nagging Drug Shortages Defy Easy Fixes 3. Tablet Devices Get Thumbs-up From Anesthesia Residents

See article on page 26.

4. Dutch Researcher Poldermans Ousted In Misconduct Investigation 5. Electronic Distraction: An Unmeasured Variable In Modern Medicine

Robert S. Lagasse, MD, New Haven, CT

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AnesthesiologyNews.com • mcmahonmed.com

An·es·the·si·o·gist n. A practitioner of the medical science of anesthesia (November 2011, page 1). See more common alternative spelling AnesthesiOLogist. AnesthesiOLogy News regrets the error.

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All U.S. anesthesiologists should receive Anesthesiology News free of charge. If you are not receiving the publication, or if you are changing your name or address, please follow these instructions: 1) Contact the American Medical Association (AMA) at (800) 262-3211 or the American Osteopathic Association (AOA) at (800) 621-1773, and notify them of your name, address and professional specialty. You need not be a member of the AMA or AOA to receive the publication. 2) For added assurance of uninterrupted service, you may also mail or fax a copy of your current mailing label, along with your change of name or address to: Circulation Coordinator, Anesthesiology News 545 West 45th Street, 8th Floor New York, New York 10036 Fax: (212) 664-1242 Email: circulation@mcmahonmed.com Please sign and date all requests. If you are not a U.S. anesthesiologist and would like to subscribe, please send a check payable to Anesthesiology News to the Circulation Coordinator. Annual subscription: $70 (outside U.S.A., $90). Single copies: $7 (outside U.S.A., $10). Please allow 8-12 weeks for delivery of the first issue. McMAHON PUBLISHING, Sales, Production and Editorial Offices: 545 W. 45th St., 8th Floor, New York, NY 10036, Tel. (212) 957-5300. Copyright © 2011 McMahon Publishing, New York, NY 10036. All rights reserved. Anesthesiology News (ISSN 0747-4679) is published monthly for $70 per year by McMahon Publishing. Periodicals postage paid at New York, NY, and at additional mailing offices.

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December 2011

IN BRIEF

NIH Study Finds Black Investigators Less Likely To Receive NIH Funding

lack scientists are less likely to receive research funding from the National Institutes of Health (NIH) than their white counterparts, according to a new study (Science 2011;333:1015-1019). The study, commissioned by the agency, revealed that black researchers are 13% less likely to receive NIH investigator-initiated research funding compared with white researchers, whereas Asians were 4% less likely. After

controlling for applicant education and research experience, the investigators found that blacks are still 10% less likely than whites to receive NIH funding. However, proposals that received strong priority scores from the NIH during the review process were equally likely to be funded, regardless of the racial background of the applicants. “I do not think there’s a policy of exclusion at NIH,” said Donna K. Ginther, PhD, director of the Center for

Science, Technology & Economic Policy at the University of Kansas in Lawrence, and lead investigator on the study. “Once a grant receives a competitive score, it’s funded regardless of race. Instead, I think it’s probably a lack of effective training and mentoring [at the institutional level].” Dr. Ginther’s prior research has included analyses of gender differences in scientific careers. She said that “the methods used in those studies apply

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equally well to research on race/ethnicity differences.” The study analyzed 83,188 applications (representing 40,069 unique investigators) for NIH R01 grants, the oldest and most commonly awarded research funding, submitted between 2000 and 2006. According to Dr. Ginther, as part of the application process, applicants “self-identified” their race and ethnicity. The study was limited to PhD investigators at U.S. institutions. Dr. Ginther’s research did not analyze funding applications by NIH departments, so there are no data indicating how the funding trends across individual therapeutic areas, such as pain and pain management. One reason for this is that relatively few black scientists apply for research funding across all NIH departments, an indication that the funding disparity may be the result of failure to develop and groom minority researchers at the academic or institutional level. The NIH has already announced plans to act on the data revealed in the study. In a statement, the agency called the findings “unacceptable.” It has implemented the “Early Career Reviewer” program to encourage junior faculty to participate in peer-review panels, with the ultimate goal of increasing the diversity (in terms of race and age) among panel membership. The NIH also has promised to conduct a formal review of its grant review process to identify bias and implement corrective measures. It has formed two advisory “task forces” to solicit expert opinion and recommend steps to improve diversity within the grant application process. “There are actually a lot of good things about this; one is that the NIH had the courage to do the study,” noted Carmen R. Green, MD, professor of anesthesiology, obstetrics and gynecology, and health management and policy at the University of Michigan, in Ann Arbor, who was not involved in the project. Dr. Green noted, however, that the study did not “look at MDs or the intersection of race and gender,” and “these aspects should probably be explored further. “It is also disappointing in the sense that good people are potentially not getting funding,” she continued. “We live in an increasingly aging and diverse society and need more voices to help everyone learn about the issues our changing population faces.” —Brian P. Dunleavy

December 2011

B. Braun

AnesthesiologyNews.com I 7

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Considerations When Filling Pain Pumps, With Mike Koch, RPh, MBA Mike Koch, RPh, MBA, is vice president of sales and support services for Central Admixture Pharmacy Services, Inc. (CAPS). His 30 years of pharmacy practice include more than 18 years of compounded sterile preparation outsourcing experience. Q: Why should pain pumps be filled in a pharmacy? A: Pain pumps should be filled in a pharmacy because pharmacies have the facilities and equipment, trained employees and proper procedures to ensure aseptic and safe preparation. Most surgery suites and personnel are not validated to conduct aseptic processing of compounded sterile preparations. These validations include process and personnel media fills and evaluation of proper sterile compounding technique. Equipment required includes filling pumps to ensure that a closed system—and thereby asepsis—is maintained.

A: CAPS ensures stability and sterility through the combination of the CAPS stability studies, periodic testing specific to the sterility of the compounding process, container-closure integrity testing, extensive validation of individual and process media fill, comprehensive monitoring of clean rooms and the employee environment and enhanced controls of process and quality.

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8 I AnesthesiologyNews.com

December 2011

A D L IB

Robbing the Captain’s Pantaloons This article is the first in a two-part look at crime and the history of anesthesia

The British War Steamer Meden at Boston—Desperate Encounter with River Thieves

n August 1853, The New York Times ran an article about a curious caper: In late July of that year, brigands had boarded a ship, “the captain was put to sleep with chloroform and his pantaloons robbed of $375.” Remarkably, the article wasn’t describing a single Figure 3. Adelaide Bartlett. episode but a trend. The paper noted that thieves “had been boarding and robbing vessels in this port, Figure 1. Headline from The New York Times, Aug. 1, 1853. [Source: Wikipedia] disguised in masks, and sometimes using chloroform.” The digitization of newspapers has produced easy access to hundreds of stories about chloroform and other anesthetic agents that were used in criminal activities. A search of the Times archives (1851-1980) for “chloroform thieves” produced about 170 results from 1853 to the 1920s (Figures 1 and 2). More recently, Casey Anthony is alleged to have W. Sherrard, His Wife, and Four Children searched the Internet for information about chloroform to use on her young daughter, Caylee. For the Put to Sleep in Roslyn Heights. last two months of his life, Michael Jackson used propofol to help him sleep. Ketamine and its illegal “cousins” are widely abused by celebrities and noncelebrities alike. News outlets in the United States C.H. Mackay’s Next Door Neighbor Revives in and around the world often carry stories in which Time to Give an Alarm, but Burglars Escape. chloroform apparently has been used on victims of rapes, robberies or murders. Anesthetic agents—old Figure 4. A novel inspired by and new—seem to be present outside the operating the story of Adelaide Bartlett. Figure 2. Headline from The New York Times, Sept. 24, 1907. [Source: Amazon] room as often in real life as in movies and novels.

THIEVES CHLOROFORM AN ENTIRE FAMILY; servants not disturbed.

An Original Indication? The problem has been around as long as anesthesia itself. In 1847, James Young Simpson described the ease with which chloroform could be used to produce unconsciousness, and criminals took note. Four years later, the British humor magazine Punch published a cartoon on the subject. Yet in 1850, two articles by John Snow were published that poured cold water on fevered press stories about crime and chloroform. His argument has been echoed by many others since then. Attempted use may be common; successful use is much less so. In 1886, at her trial in London’s Old Bailey, Adelaide Bartlett (Figure 3) was accused of exactly that kind of success. In the early morning hours of Jan. 1, Adelaide summoned the household maid and asked her to send for Alfred Leach, physician to her husband, Edwin. When Dr. Leach arrived, he determined that Edwin was dead and his stomach filled with chloroform. Thomas Edwin Bartlett was a successful London grocer who met the French-born Adelaide Blanche de la Tremoille in 1875, when she was 19 years old; he was 11 years older. The couple soon married, and to complete her education Edwin sent his young bride first to boarding school in England and then finishing school in Belgium. Adelaide finally moved in with her husband in 1878. After living in a series of residences, they settled into furnished rooms in the Pimlico section of London, in August 1885. During those seven years, their relationship was marked by various oddities. After Adelaide had completed her schooling, the couple moved into rooms over one of Edwin’s stores. After the death of Edwin’s

mother, his father moved in with the couple. He disapproved of Adelaide, however, and soon accused her of sleeping with his youngest son, Frederick. Adelaide denied the affair, and Edwin supported her. Adelaide would later claim that she had sex with her husband only once, which resulted in a pregnancy and stillborn child. After another move, the couple met a young Wesleyan minister, George Dyson. Edwin encouraged Dyson’s presence in their home, and after the move to Pimlico, Mr. Dyson began tutoring Adelaide in several subjects, including Latin and mathematics. Of course, rumors developed about the pair’s actual relationship. In his final months, Edwin suffered from several health problems. Poor dental care had left him with decayed teeth and very bad breath. He also was convinced he had syphilis and probably self-administered mercury as a treatment. After a better dentist improved his teeth, Edwin’s physician, Dr. Leach, concluded that his patient suffered from gastritis and diarrhea. Yet Edwin’s mental state in the weeks before his death indicated depression and hysteria. On the morning of his death, Edwin’s body was examined first by Frederick Doggett, the Bartletts’ landlord and a registrar of births and deaths. He found various substances in the bedroom, but no evidence of chloroform. Mr. Doggett refused to certify the death without an inquest. Dr. Leach and Adelaide agreed, and the next day five physicians conferred but could not establish a natural cause of death. They did find chloroform in Edwin’s stomach and intestines, but no signs of vomiting, damage to his trachea or other evidence of its administration.

Adelaide soon admitted that the minister, Mr. Dyson, had obtained chloroform for her, and that she planned to put it on a handkerchief to subdue Edwin if he attempted sex with her. However, she claimed never to have used it in such a manner. By mid-April, Adelaide and Mr. Dyson were both on trial for Edwin’s murder. The prosecution’s attempt to prove murder did not succeed because the confusing evidence in the case indicated the possibility of either an accident or suicide. The verdict of not guilty was followed by wild applause from the spectators, although many still assumed the pair was guilty. A prominent physician, Sir James Paget, is purported to have said that since Adelaide could not be tried again, she “should tell us, in the interests of science, how she did it.” The widow and her presumed paramour quickly disappeared from London; nothing is known of their subsequent lives. Little more than rumors have continued through the years—Adelaide’s wealthy royal father took her back to France; she and Mr. Dyson both ended up in America; Adelaide became a nurse in South Africa, and so on. Numerous books and chapters have been devoted to the case over the years, and it also has been fictionalized. The novel Sweet Adelaide (1980) by British writer Julian Symons (Figure 4) and the Jodie Foster film, My Letter to George (1986) were suggested by the case. —A.J. Wright, MLS Mr. Wright is an historian in the Anesthesiology Department at the University of Alabama School of Medicine, at Birmingham, and a frequent contributor to Anesthesiology News.

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10 I AnesthesiologyNews.com

December 2011

COMMENTA RY

Extubation Case Challenged Long-standing Legal Doctrine

he practice of anesthesiology does not often come before the U.S. Supreme Court, but the case of Air Force Staff Sgt. Dean Witt had the potential to radically remake a feature of tort law that has been in effect for more than 60 years. In October 2003, Sgt. Dean Witt arrived at Travis Air Force Base Medical Center with appendicitis. Three months later, following a routine appendectomy complicated by postextubation laryngospasm, a failed attempt at resuscitation and anoxic brain injury, the family withdrew life support, and Sgt. Witt was dead. Last June, the Supreme Court declined to hear the case Sgt. Witt’s family brought against the hospital. In doing so, the justices tacitly upheld the Feres Doctrine—a decades-old prohibition against allowing the government to be held liable for negligence when military members are injured or killed while on active duty. Established in 1950 with the decision Feres v. United States, the Feres Doctrine was the result of three separate cases brought before the court: the Feres case, in which a soldier was killed by fire in his barracks because of a defective heating plant; the Jefferson case, in which a surgical towel was accidentally left inside a soldier’s abdomen following surgery; and the Griggs case, in which a soldier died at the hands of allegedly remiss Army surgeons. All three cases had in common negligence by military members that resulted in the death or injury of other military members while they were on active duty. All three asked the justices to determine whether these activeduty military members or their families were eligible for reparations from the government under the Federal Tort Claims Act (FTCA) of 1948.

asked whether active-duty military personnel could sue the federal government for harm caused by other representatives of the government. The court said no, and 60 years later, it stands by its initial decision. By declining to hear Witt v. United States, the Supreme Court effectively decided that only Congress can change the meaning of the FTCA to allow active-duty military members to sue the government. Mike Navarre, a former Navy judge advocate and a member of the board of advisors for the National Institute of Military Justice, stated, “If you use Congress as a barometer as to the sentiments of the American people, Congress has had 60 years to deal with the Feres Doctrine … and Congress has not dealt with it.” The Supreme Court reasoned then, as it has ever since, that members of the military have access to remuneration through the Veterans Benefits Act (VBA), and thus have no further claim on the public treasury. Indeed, the Congressional Budget Office has reported that if the Supreme Court were to reverse its decision regarding the Feres Doctrine, and active-duty military members could sue the government for damages, approximately 750 malpractice lawsuits would be filed each year, resulting in payments of $2.7 billion. Shortly after Sgt. Witt died, the Air Force barred the nurse anesthetist responsible for his death from practicing medicine within a military institution, and the state of California revoked her medical license. Sgt. Witt’s family received $350,000 in reparations from the VBA. Given the state of the nation’s economy and our ever-growing debt, Congress appears to be in no hurry to increase the benefits military members killed in the line of duty receive from Plane Crash Spurred Law the VBA, nor do they seem eager to Congress passed the FTCA after a allow them to sue the United States B-25 bomber accidentally crashed into for further monetary gain by revising the fog-shrouded Empire State Build- the FTCA. The Feres Doctrine stands ing in 1945, killing 14 people. The as strongly today as it did when it was law as it ultimately developed allowed first enacted. for retroactive provisions so families of the deceased could sue the U.S. govern—Kristin Adams Forner, MD ment for monetary restitution. The FTCA was enacted to allow Dr. Forner is staff anesthesiologist and medical private parties—civilians—to sue director for the Department of Anesthesiology at for actionable wrongs committed by Wright-Patterson Air Force Base, in Dayton, Ohio. agents of the government. The three You can read more of her writing at cases within Feres v. United States www.docbehindthedrapes.com.

December 2011

AnesthesiologyNews.com I 11

COMMENTA RY

Lessons Learned In the Peace Corps

his summer I went to a reunion in Albuquerque attended by exPeace Corps volunteers who had served in the same country as I had almost 40 years ago. Our project had been in aquaculture and we had dug and stocked fishponds in a land-locked country in Equatorial Africa. Although most of us successfully contracted schistosomiasis and a variety of intestinal parasites, we had more limited success with the fishponds. Our major stumbling block had been the host country government. Whenever we needed cement, shovels, nets and more, we would request them from charitable organizations that would donate the material to the host country for our use so that the developing government would learn how to distribute materials to a project. Our problem then was keeping these materials out of the hands of government officials who were quick to realize that the materials could be used in their own homes or could be sold in the marketplace. The mantra mumbled by everybody in those early days of international development was “planned obsolescence,” meaning that all efforts should be made to build the infrastructure of the host country to take over the local projects rather than have the contractors doing the work indefinitely. Once the infrastructure was fully developed, the outside assistance would eventually become unneeded and consequently obsolete. This “top-down” approach still sounds like a good idea because the long-term investment in infrastructure should have a greater effect than the short-term provision of cement and tools. In our country, the president, his ministers, their assistants and the village chiefs took their cut of the resources and very little ever trickled down to the villagers or local projects where it was needed. Unfortunately, there was a political coup 10 years into our project and we were forced to leave. A colleague who returned some years later told me that the wonderful fish station on which I had spent so much time building a cement drainage system, keeping the ponds manicured and organizing the tool sheds, was now abandoned and had been reclaimed by the forest. Our project had never received enough of

the trickle-down resources to become fully independent or sustainable. Our planned obsolescence, unfortunately, referred not only to the contractors who are gone but also to the projects that are now abandoned. This pattern has repeated itself so often and in so many developing countries that the international development community has changed its strategy. It delivers resources directly to the villages and the local projects where they are needed rather than to the host country’s government. This “bottom-up” approach may not create a host country infrastructure but it is much more successful in getting wells dug, schools built, fish ponds stocked and the like. U.S. Health Care So why am I relating this fish story to a medical readership? As I was listening to my international development colleagues talk about their new bottom-up approach, I realized that we should adopt a similar policy in health care. Typically, what we do in medicine is identify a clinical problem at the bedside. The problem is communicated up to the hospital administration and, in my circumstance as a federal employee, it then gets communicated to regional and national offices. A committee to study the problem is formed; a policy change is formulated and circulated. Often, a local committee is assigned to design and institute some kind of inservice training. The changes will sometimes, although not always, improve the bedside problem. To demonstrate whether the policy change has been effective, we then devote even more resources into doing follow-up studies. We are learning now that this laborintensive process does not always have the desired result. It was recently demonstrated (and reported in a recent issue of Anesthesiology News) that the Surgical Care Improvement Project (SCIP) measures addressing surgical infections, which have been laboriously collected, collated and reported, have not resulted in a decrease in wound infections. One wonders if those resources would have been better spent on bedside problems, such as outdated equipment or nursing shortages. Ideally, this process of studying see Peace Corps page 12

SonoPlex – THE Ultrasound Nerve Block Cannula With SonoPlex, PAJUNK® has developed a new cannula-generation, an innovation, which for the first time facilitates the unerring localization by means of ultrasound technology. The distal end of the cannula shaft has been equipped with a circumferential array of reflectors. The nature of the „Corner Stone“ reflectors renders optimal reflection properties in any position, at steep and at flat puncture angles as well.

Visible cannula tip The distal end has been provided with two pattern-embossed sections, each having a length of 10 mm and separated from each other by a blank zone, which provides for additional orientation. The visibility of the cannula therefore covers a total length of 20 mm, and it is thus distinctively recognizable.

The reﬂection guarantee The embossed indentations at the tip of the cannula are shaped as if the corner of a cube had been impressed into the surface: This renders three surfaces which respectively coincide in 90° angles. The surface is thereby enlarged in such way to permit the - direct or indirect - reﬂection of the ultrasound waves from almost every angle of incidence.

100 % reflection - thanks to „Corner Stone“ reflectors The „Corner Stone“ reflectors reflect ultrasound waves in a spectrum of incidence angles ranging from 60° to -20°. The visibility of the cannula is therefore guaranteed at a flat puncture angle, and at a steep puncture angle as well.

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Regional Anaesthesia • Laparoscopy • Biopsy • Worldwide

12 I AnesthesiologyNews.com

December 2011

C OMM E NT A R Y Peace Corps continued from page 11 problems, changing practices and re-evaluating these changes should never end and, theoretically, it makes the system better. It sounds just as good as the international development theories of top-down development and planned obsolescence. The problem with the top-down theory in international development is that after 50 years of heavy investment, too few schools had been built, too few fishponds had been dug and too few wells had been drilled. The host country infrastructures that were the beneficiaries of most of this largesse and were supposed to keep up this good work in most cases have become as obsolete as the outside contractors. My concern for health care is that after we have spent much of our resources on infrastructure such as committees, commissions, workshops, quality assurance offices, patient safety committees, patient satisfaction questionnaires, and so on, there will not be enough left to deal with the bedside problems, which are usually solved by something as mundane but critically important as equipment or manpower needs. Quality assurance and patient safety offices do some important work, but as their numbers swell, their policies grow and the in-service training that they require have become more burdensome, their efforts are distracting from the essential mission of direct patient care. To support their efforts, they have developed a lexicon of words that get liberally sprinkled throughout any proposals with the thought that this lofty terminology lends credence to what they are doing. Problems get “work-shopped,” changes become “paradigm shifts,” training courses or new strategies become “tools,” evaluating becomes “benchmarking,” problems become “missed opportunities” and people assigned to coordinate these efforts become “champions.” As soon as one of these terms is dragged out, there seems to be a tacit understanding that we are on the right track. In my role as a department chief, I am continuously faced with workforce shortages and outdated equipment. Over the years, we have been trying to address problems at my hospital using the top-down strategy. We hear from those at the bedside that we have a problem and it seems like a reasonable strategy to study the problem, form a committee of interested people, meet, record minutes and then announce that we are addressing the problem. The only problem is that the issue often has not been addressed most of time and resources are spent on data gathering, writing policies and in-service training. Unfortunately, this is a zero-sum proposition and the creation of this infrastructure requires resources and many man-hours of work, which comes at the expense of needed equipment and time not spent on clinical duties. We have lost many of our talented nurses and physicians to the safety office, quality improvement office, informatics division and a variety of other services that document, measure and report deficiencies in the system, which ironically we can’t adequately address because we don’t have the bedside resources. I do not mean to denigrate years of work devoted to quality management and patient safety, which is critically important. We as a profession are now

The quality assurance and patient safety offices do some important work, but as their numbers swell, their policies grow and the in-service training that they require have become more burdensome, their efforts are distracting from the essential mission of direct patient care.

beginning to recognize and address problems, such as the Institute of Medicine’s 100,000 deaths. I just think we have lost our sense of proportion. We seem to be very good at creating the infrastructure (committees, commissions, study groups, etc) but less good at solving the problems. If we spend all of our resources on studying, reporting and formulating strategies to address these problems, we will not have the resources remaining to institute our laboriously crafted solutions. The last part of any organization to go is the infrastructure. We have recently witnessed the slow deterioration and failure of some of the largest U.S. automobile manufacturers. The earliest signs of deterioration were plant closings, which resulted in workers being laid off and fewer cars being manufactured. As the finances got worse, more plants closed and more workers were laid off. By the end, the only thing remaining for these auto giants were their corporate headquarters, replete with water fountains and landscaped gardens. I get the unsettling feeling that we are witnessing early signs of deterioration in the health care industry. Compensation for our workforce is being reduced, we are developing labor shortages, and access for our consumers is a growing problem. We continue, however, to invest heavily in our infrastructure. There are committees and subcommittees of patient safety, patient satisfaction, quality assurance, infection control and the like, which seem to spring up almost monthly. Their purpose is unquestionably important but they have had two adverse effects on our patient-care mission. First, they tap off some of the resources that are sorely needed in the clinical realm and, second, they take some of our clinical workforce away from their clinical duties, usually temporarily, but sometimes permanently. Recently, I sent a surgeon in my department across the country for a two-day meeting on ensuring correct-site surgery. He returned with a

two-hour training module that must be completed by all clinicians in the hospital involving invasive procedures. Operating on the correct site is critically important, but we should question whether this type of reallocation of resources from the bedside to the conference room is a good way to solve the problem and that it makes sense in an industry that is having such financial difficulties. Back to Albuquerque As the sun rose on an unseasonably hot day in Albuquerque, we were clustered under a group of trees that afforded a little shade. I pulled my lawn chair closer to a fellow ex-volunteer who had served in a village neighboring mine in the Central African Republic. After his service, he had stayed in international development and was now working with the United Nations’ Food and Agriculture Organization (FAO). As heat rose, the beer was going down easily and we discussed the relative merits of the amber I was drinking, the lager that he had pulled out of the cooler. Our conversation drifted into a discussion of how his development work was going. He stated that the results were much better since they had abandoned their top-down strategy. He added that they had learned over the years that their limited resources are better used when sent directly to the bare feet on the ground rather than to the wing tips on the 10th floor of the FAO building in Rome. I replied that I hoped my health care industry would learn that they too should direct more of their resources to the rubber soles in the operating rooms and on the wards rather than to the leather soles in the administrative wing of the hospital. He hoisted his beer and said, “Bottoms up.” — Jon C. White, MD Dr. White is professor of surgery at George Washington University, in Washington, D.C.

December 2011

AnesthesiologyNews.com I 15

PR N

New Treatment Options for C. difficile Raise More Questions

n the past six months, new surgical and medical options became available to treat patients with Clostridium difficile. As the options for treating the infection have increased, so too have the questions about who should get what treatments and when. The ambiguity over how best to treat C. difficile became especially clear after fidaxomicin (Dificid, Optimer Pharmaceuticals Inc.) was FDA-approved in May. Clinicians are now trying to determine whether fidaxomicin is as good or better than the two long-time standards, vancomycin and metronidazole. “The answer to that is not clear yet,” said Lawrence Brandt, MD, professor of medicine and surgery at Albert Einstein College of Medicine of Yeshiva University, in New York City. An additional two up-and-coming treatments also have been touted as possible game changers in the C. difficile realm. Fecal transplants (FCTs)— a procedure first reported in the medical literature in 1958—have been garnering attention as a highly successful therapy for C. difficile infection. One report published this fall suggests FCTs could be considered a first-line therapy for severe infection (J Clin Gastroenterol 2011;45:655-657). On the surgical front, surgeons are reporting that performing a diverting ileostomy with colonic lavage for severe, complicated infections could be used to spare patients from subtotal colectomy and may reduce the mortality rate (Ann Surg 2011;254:423-429).

”We believe that the current classification schema understages the severity of illness in many patients.”

1 (NAP) strains were randomly assigned to fidaxomicin (200 mg twice daily) or vancomycin (125 mg four times daily) orally for 10 days. The analysis showed no differences in clinical cure rates but there was a reduced risk for recurrence with fidaxomicin at 13% versus 26.6% (P=0.02) for the intent-to-treat analysis and 11.7% versus 23.2% (P=0.05) for the per-protocol analysis (N Engl J Med 2011;364:422-431). The lower rate of recurrence was seen in patients with non-NAP1 strains, representing a 69% relative reduction in recurrences with fidaxomicin compared with vancomycin in patients with nonNAP1/BI/027 strains. That’s a tantalizing finding but one that needs confirmation in further trials before clinical practice patterns change, experts said. The researchers also found that in patients with the NAP1/BI/027 strain, the rates of recurrence in the fidaxomicin and vancomycin groups were similar: 24.4% (11 of 45 patients) and 23.6% (13 of 55), respectively (P=0.93). Fidaxomicin’s approval could “potentially be an important change” in C. difficile treatment, given the decreased risk for recurrent infection in patients with non-NAP1 strains but that must be balanced against the cost, said Darrell Pardi, MD, associate professor see C. diff page 16

Newproduct

—Brian Zuckerbraun, MD

algorithm remains to be seen. This antibiotic is more active in vitro than vancomycin, by a factor of approximately 8, against clinical isolates of C. difficile, including NAP1/ BI/027 strains, according to the researchers. But the long-term risk for resistance with fidaxomicin is unknown. Moreover, fidaxomicin costs significantly more, suggesting it may be best reserved for patients at highest risk for recurrence. For mild to moderate disease, the guidelines advocate, and experts still support, metronidazole over vancomycin as first-line therapy because of reduced costs, comparable clinical effectiveness and concerns about vancomycin-resistant enterococci; this line of treatment remains unchanged by the approval of fidaxomicin. “I think we’re comfortable saying that patients with mild to moderate infections should start with oral vancomycin and intravenous metronidazole. But after that point, we’re not sure of the best thing to do when medical therapy starts to fail,” said Peter K. Kim, MD, assistant professor of surgery at Albert Einstein. “There is no evidence one way or the Fidaxomicin on the Scene other.” Although patients with C. difficile colitis now In the company-sponsored Phase III trial that led have more treatment possibilities, the developments to fidaxomicin’s approval by the FDA, fidaxomicin have revealed new clinical uncertainties about treat- and vancomycin were compared head to head; 548 ments. Importantly, how fidaxomicin fits into the patients with non–North American pulse-field type

Dynasthetics Vapor-Clean Now recognized by MHAUS, Vapor-Clean filters prepare anesthesia machines for MH-susceptible patients in less than 90 seconds. Instead of lengthy flushing of the machine, simply connect the inspiratory and expiratory Vapor-Clean filters between the anesthesia machine and a new breathing circuit to reduce exposure to less than 5 ppm of volatile agent for a case of up to 12 hours regardless of fresh gas flow. Contact Info: Dynasthetics 3487 W. 2100 S. #300 Salt Lake City, Utah 84119 Phone: (801) 484-3820 Fax: (801) 483-2123 Email: query@dynasthetics.com Web site: www.dynasthetics.com See our ad on page 43.

16 I AnesthesiologyNews.com

December 2011

PRN c. diff

continued from page 15

of medicine at Mayo Clinic, in Rochester, Minn. The price of fidaxomicin is set at $2,800 for a 10-day course, about double that of vancomycin. That price drops more when vancomycin is compounded into a powder, further widening the differential cost. So far, the cost of fidaxomicin has limited insurance company approval and most patients cannot afford to pay for it out of pocket, Dr. Pardi said. That has slowed the adoption of fidaxomicin. “Despite the impressive results from the clinical trial, this drug is not being used all that often yet,” he said. Many hospital formularies are considering certain restrictions on fidaxomicin use, reserving it for patients with multiple recurrences or predicted severe infections. However, these indications were not studied in the trials for fidaxomicin, “so we don’t know for sure if its benefit over vancomycin applies to these patient groups,” Dr. Pardi said. More trials will be needed to tease out the health benefits and cost issues for each antibiotic, Dr. Brandt said. Beyond Antibiotics Adding to the murkiness of clinical decision making for C. difficile infections is the growing list of options besides antibiotic regimens. Treatments such as FCTs and vancomycin enemas also are increasing in popularity. The evidence for FCTs Advertisement

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is growing with results from more than 300 FCTs published worldwide with cure rates close to 90%. In the September edition of the Journal of Clinical Gastroenterology, Dr. Brandt and colleagues argued that endoscopic fecal microbiota transplants should be elevated to first-line treatment of patients with deteriorating and severe infection and its complications at the earliest possible time (2011;45:655-657). The authors noted that FCTs are low-tech, costeffective and require no additional training. The cure rate is “unparalleled, with 90% to 100% of reported patients achieving cure.” Moreover, FCTs are the only treatment that can restore the underlying flora deficiency, “changing the composition of the recipient’s intestinal microbiota in a durable manner.” The investigators concluded that “as the risks of FCT are minimal and the potential gain in critically ill patients is great, we believe the use of FCT in this patient population is rational and clinically well grounded.” For vancomycin enemas, fewer cases have been reported and they are limited to patients with severe, fulminant C. difficile colitis. In a series of 47 consecutive patients treated at an American hospital from January 2007 to October 2009, 37 (79%) survived and 33 (70%) had complete resolution of colitis, Dr. Kim and his associates reported in a poster at the 2010 annual meeting of the Surgical Infection Society. Dr. Kim said that vancomycin enemas are an option for some very ill patients who have failed medical therapy and are being considered for surgery. However, with only limited retrospective data available, a trial is necessary to show where this treatment fits into the spectrum of options for patients with severe infections. “Unfortunately, it’s very hard to develop a trial because these are very, very sick patients, and ethically it’s difficult to justify some of these things in this population,” he said. A group from the University of Pittsburgh recently described another new surgical therapy that might help fill the gap between medical failure and total abdominal colectomy in patients with severe, complicated C. difficile-associated disease (Ann Surg 2011;254:423-429). Brian Zuckerbraun, MD, and colleagues at Pitt perform a diverting loop ileostomy and intraoperatively lavage the colon with warmed polyethylene glycol 3350/electrolyte solution via the ileostomy. After the operation, they do antegrade colonic enemas with 500 mg of vancomycin in 500 mL three times daily for 10 days, also via the ileostomy. The procedure, they hope, will improve on the poor outcomes associated with total abdominal colectomy with end ileostomy. The traditional procedure has reported mortality rates ranging from 35% to 80%. In a study comparing 42 patients who underwent diverting ileostomy with historical controls, investigators reported reduced mortality—19% versus 50% (odds ratio, 0.24; P=0.006). Of the 42 patients, 39 had preservation of the colon (93%) and 35 were treated laparoscopically. “In a critically ill and complex patient population, we can successfully avoid the need for colectomy in severe, complicated [C. difficile-associated disease] by performing a diverting ileostomy with colonic

lavage,” Dr. Zuckerbraun said. He cautioned that the success of any surgical therapy depends on timing. Surgical therapies, including ileostomy and colonic lavage or total abdominal colectomy, should be considered earlier in the course of patients with severe, complicated disease than what has been practiced over the past several decades, he said. At Pitt, Dr. Zuckerbraun’s team set a low threshold for instituting surgical therapy. A surgical consultation is called for any patient requiring vasopressors or intubation or who has a white blood cell count greater than 20,000 or less than 3,000/mm2. The surgeons consider each patient’s case individually, he stressed, but “as soon as they cross that threshold of signs in their illness, we institute surgical therapy.” Future of C. difficile Treatment One of the challenges of treating C. difficile patients is the lack of a prognostic scoring system to help clinicians differentiate early which patients are likely to fail medical therapy. There is no clear stage between moderate and severe disease, according to guidelines. “We believe that the current classification schema understages the severity of illness in many patients and fails to adequately identify patients who are likely to become critically ill,” Dr. Zuckerbraun said. As a result, surgeons often are not called in until patients are very ill and their risk for dying during or after surgery is extremely high. What is required now is that specialists from gastroenterology, surgery and infectious disease meet to discuss the treatment options. Dr. Kim said he would like to see a symposium in 2012 where clinicians and researchers begin to develop a risk stratification strategy, a treatment algorithm and multicenter trials. “There are many questions that we just do not know the answers to,” Dr. Kim said. “When medical therapy fails, what do we try next? Is it fecal transplant, vancomycin enemas, ileostomy with washout? It’s great that there are more options, but we simply do not know [the best course of action].” —Christina Frangou

Anesthesianews

CONTINUING MEDICAL EDUCATION

ANESTHESIOLOGY NEWS • DECEMBER 2011

Malignant Hyperthermia

Diagnosis, Treatment, and Prevention RELEASE DATE: December 1, 2011 EXPIRATION DATE: December 1, 2013 CHAIR Cynthia A. Wong, MD Professor of Anesthesiology Northwestern University Feinberg School of Medicine Chicago, Illinois

FACULTY Bonnie Denholm, MS, BSN, RN, CNOR Perioperative Nursing Specialist Center for Nursing Practice Association of periOperative Registered Nurses, Inc. Denver, Colorado

GOAL The goal of this educational activity is to provide anesthesiologists, perioperative nurses, and other health care professionals with current, clinically useful information on malignant hyperthermia (MH).

LEARNING OBJECTIVES At the completion of this activity, participants should be better prepared to: 1. Discuss the pathophysiology of MH. 2. Describe the characteristic clinical findings that identify an MH crisis. 3. Identify all supplies required to manage an MH crisis. 4. Discuss, in order, the appropriate steps that must be taken to manage an MH crisis. 5. Discuss preventive measures required to provide safe care to patients who are susceptible to MH.

INTENDED AUDIENCE This activity is intended for physicians, perioperative nurses, and other health care professionals responsible for managing MH.

STATEMENT OF NEED Malignant hyperthermia (MH) is a life-threatening pharmacogenetic disorder triggered by the administration of volatile anesthetics, succinylcholine, or both. It manifests in a hypermetabolic crisis that is likely to be fatal if left untreated. Because MH is rare, clinicians may lack awareness of it, may not recognize it, and may not be prepared to treat it. Important steps in the treatment protocol may be omitted, with potentially lethal results, when clinicians rely on unaided memory alone to treat MH. In addition, stocks of dantrolene or other supplies may be inadequate or not readily accessible in the event of an MH crisis, particularly in non-hospital surgical settings. Finally, preoperative and post-episode evaluation of patients often is inadequate. Clinical education is necessary to close these practice gaps.

CONFLICT OF INTEREST STATEMENT It is the policy of AKH Inc. and the AORN to ensure independence, balance, objectivity, scientific rigor, and integrity in all continuing education activities. The faculty and planning committee must disclose any significant relationship with a commercial interest whose product or device may be mentioned in the activity or with the commercial supporter of this activity. Identified conflicts of interest are resolved by AKH Inc. and the AORN prior to accreditation of the activity.

FINANCIAL DISCLOSURES Cynthia A. Wong, MD: Nothing to disclose Bonnie Denholm, MS, BSN, RN, CNOR: Nothing to disclose Oren Traub, MD, PhD (medical writer): Nothing to disclose AKH planners and reviewers: Nothing to disclose

DISCLOSURE OF UNLABELED USE This educational activity may contain discussion of products or procedures that have been studied but are not FDA-approved for MH. Please refer to all official product information for approved indications, contraindications, and warnings.

ESTIMATED TIME OF COMPLETION 60 minutes

METHOD OF PARTICIPATION There are no fees for participating in and receiving credit for this activity. The participant should, in order, read the objectives and monograph and complete the multiple-choice post-test. Participation is available online at CMEZone.com. Enter IP112 in the keyword field to access this activity directly. Or, complete the answer sheet with registration and evaluation on page 22 and mail to: AKH Inc., PO Box 2187, Orange Park, FL 32067-2187; or fax to (904) 683-3803. Statements of participation will be mailed/emailed approximately 6 to 8 weeks after receipt of mailed or faxed submissions. A score of at least 70% is required to complete this program successfully. One retake is allowed. Credit is available through December 1, 2013. For questions regarding this CME/CE activity, please contact AKH Inc. at trish@akhealthcare.com.

DISCLAIMER This course is designed solely to provide the health care professional with information to assist in his or her practice and professional development and is not to be considered a diagnostic tool to replace professional advice or treatment. The course serves as a general guide to the health care professional, and therefore, cannot be considered as giving legal, nursing, medical, or other professional advice in specific cases. AKH Inc., ACE, the AORN, the authors, and the publisher specifically disclaim responsibility for any adverse consequences resulting directly or indirectly from information in the course, for undetected error, or through the reader’s misunderstanding of the content. Copyright © 2011 AKH Inc. and Applied Clinical Education.

SPONSORED BY

ACCREDITATION STATEMENTS Physicians: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of AKH Inc., Advancing Knowledge in Healthcare and Applied Clinical Education (ACE). AKH Inc. is accredited by the ACCME to provide continuing medical education for physicians. AKH Inc. designates this enduring monograph educational activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Perioperative nurses: This continuing nursing education activity was approved by the Association of periOperative Registered Nurses, Inc., an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation. AORN recognized this activity as continuing education for registered nurses. This recognition did not imply that AORN or the ANCC Commission on Accreditation approved or endorsed any product included in the presentation.

Introduction Malignant hyperthermia (MH) is a serious and potentially life-threatening hypermetabolic skeletal muscle disorder induced in response to certain anesthetics in genetically susceptible individuals.1-5 Because the condition is relatively uncommon, most clinicians may not have extensive firsthand experience with its diagnosis and clinical management and thus may not be prepared to act quickly and appropriately in an MH crisis. Indeed, a recent study reported that operating room personnel are not prepared to detect and manage episodes of MH sufficiently.6 These limitations may be magnified in ambulatory surgery settings, which have relatively fewer resources for the management of complex patients.7,8 This activity provides an overview of the pathophysiology, epidemiology, clinical presentation, diagnosis, management, and prevention of MH. It also discusses recent changes in the formulation of the major treatment agent, dantrolene, as well as evolving guidelines for the transfer of affected patients to appropriate treatment facilities.

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ANESTHESIOLOGY NEWS • DECEMBER 2011

Why wait? Access this program and post-test @ CMEZone.com Table 1. Anesthetic Drugs and Malignant Hyperthermia Susceptibility Triggering Agents Unsafe for Use in MH-susceptible Patients Inhaled general anesthetics Desflurane Isoflurane Halothane Sevoflurane Depolarizing muscle relaxants Succinylcholine Nontriggering Agents Safe for Use in MH-susceptible Patients Sedative-hypnotics Diazepam Etomidate Ketamine Methohexital Midazolam Pentobarbital Propofol Thiopental Inhaled nonvolatile general anesthetic Nitrous oxide Local anesthetics (all local anesthetics) Bupivacaine Chloroprocaine Levobupivacaine Lidocaine Mepivacaine Prilocaine Procaine Ropivacaine Opioids (all opioids) Alfentanil Codeine Diamorphine Fentanyl Hydromorphone Meperidine Methadone Morphine Naloxone Oxycodone

Pathophysiology and Epidemiology The level of calcium in the cytoplasm of skeletal muscle cells is the primary determinant of muscular contraction. In the baseline relaxed state, intracellular calcium is sequestered within a specialized organelle, the sarcoplasmic reticulum (SR). Upon stimulation of skeletal muscle at the neuromuscular junction, membrane depolarization leads to activation of dihydropyridine receptors on the skeletal muscle cell membrane, which subsequently activate ryanodine-sensitive calcium channels on the SR.2-4 This results in the release of calcium from the SR into the intracellular cytoplasm, thereby activating actin and myosin and producing skeletal muscle cell contraction. When the neuromuscular stimulus is terminated, the ryanodinesensitive calcium channel closes, and calcium is resequestered into the SR via specialized calcium pumps, resulting in cessation of muscular contraction.2-4 In some individuals, inherited or spontaneous mutation of genes associated with the dihydropyridine receptor, ryanodine-sensitive calcium channel receptor (RYR1) or possibly other proteins lead to excess and/or sustained release of calcium from the SR, resulting in persistent skeletal muscle contraction.2-4 The sustained contraction leads to a hypermetabolic state represented by excess production of lactate, carbon dioxide (CO2), and heat, as well as excess consumption of adenosine triphosphate (ATP) and oxygen. Ultimately, ATP depletion causes the failure of cellular homeostatic mechanisms and the release of potassium, creatine kinase (CK), and myoglobin from skeletal muscle cells into the bloodstream, resulting in hyperkalemia, rhabdomyolysis, arrhythmias, end-organ damage, and death.2-4 Individuals who possess these genetic mutations are designated as “MH-susceptible” or as having “MH susceptibility.” Numerous genetic mutations associated with MH susceptibility, mostly in the RYR1, have been identified.2-5 An episode of MH typically requires underlying MH genetic susceptibility and the presence of a triggering agent, the most common being volatile inhalational anesthetic agents (eg, halothane, sevoflurane, or desflurane), the depolarizing muscle relaxant succinylcholine, and rarely (in humans), stresses such as vigorous exercise and heat (Table 1).2-4 Very little is known about the specific mechanisms by which anesthetics interact with these abnormal receptors to trigger an MH crisis. The estimated prevalence of abnormalities in gene coding for RYR1 may be as great as 1 in 3,000 individuals.5 The incidence of MH episodes is lower (between 1 in 5,000 and 1 in 50,000 to 100,000 anesthetics), due to the variable penetrance of genetic abnormalities and the requirement for a triggering factor.5,9 Further, an MH crisis may develop at first exposure to anesthesia with triggering agents or patients may experience multiple uneventful anesthetics before having an episode.5 Reactions occur more commonly in younger patients and in males, but there is no ethnic or geographic predominance.5,10

Remifentanil Sufentanil Muscle relaxants (all nondepolarizing) Atracurium Cisatracurium Pancuronium Rocuronium Vecuronium Anxiolytics (all benzodiazepines) Diazepam Lorazepam Midazolam Adapted from: http://wp2.mhaus.org/anesthetics.

Clinical Presentation and Consequences Clinical manifestations of MH may vary, and not all of the classic symptoms associated with MH may occur. The most reliable initial clinical sign heralding the development of acute MH is an increase in end-tidal CO2 (ETCO2) that is resistant to increasing the patient’s minute ventilation.2 The increase in exhaled CO2 may heat the CO2 absorbent in the circle system and exhaust the absorbant rapidly.11 Other early signs may include sinus tachycardia and masseter muscle spasm (or tension) and/or generalized muscle rigidity.1-5 Contrary to its nomenclature, hyperthermia often is a later sign of MH and may be absent when the diagnosis is suspected initially.12 Sustained muscle contraction from unregulated calcium release generates more heat than the

body is able to dissipate. The resulting hyperthermia can occur minutes to hours following the initial onset of symptoms.1-5 Severe hyperthermia is associated with development of disseminated intravascular coagulation (DIC), a poor prognostic indicator and often terminal event.13 The severity and timing of other signs of MH can vary and may depend on the degree of muscle mass.1-5,14 They include electrocardiographic (ECG) changes and arrhythmias (eg, peaked T-waves, premature ventricular contractions, ventricular tachycardia, ventricular fibrillation) caused by elevated potassium levels from muscle breakdown. Rhabdomyolysis also can occur, with plasma CK and urine myoglobin levels peaking hours to days after an acute MH episode.14 In muscular patients, plasma CK levels may exceed 100,000 units/L.15 Brownish or tea-colored urine may indicate the presence of myoglobinuria.16 Time of initial symptom onset can vary as well. Most cases occur intraoperatively, within 1 hour of anesthetic induction.1-4,7,14 Following successful treatment, approximately 20% of patients can experience recurrence, usually within the first 24 hours, which may be more common in those with greater muscle mass.14 MH crisis is likely to be fatal if left untreated. Even in nonfatal cases, morbidity can be serious; a North American MH Registry study of reports from 1987 to 2006 showed that nonfatal complications occurred in 35% of patients.12 These complications included cardiac, renal, or hepatic dysfunction; coma or change in consciousness level; pulmonary edema; and DIC. In recent years, the MH-related mortality rate has decreased from an estimated 70% to less than 10% as a result of the availability of an effective treatment and an improved understanding of the clinical manifestation and pathophysiology of the condition.17 One study found that the nationwide mortality rate from MH had fallen further to 6.5% in 2005.17 Although previously controversial, “awake” MH events have been confirmed in individuals found to have mutations in the RYR1 gene.18,19

Diagnosis The signs and symptoms of MH episodes can be variable and nonspecific, making diagnosis difficult.1-5 In addition, risk factors that can predict MH have not been identified. Although specific operative procedures and diseases have been associated with MH, the positive predictive value is extremely low.20 The consequences of difficult diagnosis are magnified by the fact that early detection and treatment of MH are required in order to avoid catastrophic outcomes. Thus, successful diagnosis requires a thorough knowledge of the constellations of possible clinical manifestations and variable time course, in combination with a high degree of clinical suspicion.21 During an acute event, diagnosis of MH is based on clinical signs and symptoms as well as laboratory tests in the appropriate context (ie, recent administration of a triggering agent). The most important indicator of MH is the presence of respiratory acidosis, manifested as increased ETCO2. Muscle rigidity, metabolic acidosis, and hyperthermia may be present.12 In a patient anesthetized with volatile agents, MH should be suspected strongly when there is a significant increase (>55 mm Hg) in ETCO2 that does not respond readily to large increases in minute ventilation. However, increased ETCO2 can be caused by technical factors (eg, malfunction of the circle breathing system, ventilator, monitor), decreased CO2 elimination (eg, hypoventilation, bronchial obstruction, pneumothorax), or increased CO2 production or retention (eg, CO2 insufflation during laparoscopic procedures; reperfusion after prolonged vascular occlusion, thyrotoxicosis, or pheochromocytoma).1-5 During general anesthesia or sedation, the most common cause of sudden or gradual hypercapnia is hypoventilation. Increasing minute ventilation with supplemental ventilation or correcting ventilator settings should correct the ETCO2. Ventilating with a bag mask valve attached to a

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ANESTHESIOLOGY NEWS • DECEMBER 2011

supplemental oxygen source should correct the ETCO2 in the setting of breathing circuit malfunction. A diagnosis of MH can be supported further by venous or arterial blood gas analysis, which demonstrates a mixed metabolic and respiratory acidosis.22 In the very early stages of acute MH, the metabolic component of the acidosis may be mild. The presence of hyperkalemia, indicating significant muscle breakdown, further strengthens the diagnosis.1-5 Masseter muscle tension normally increases after the administration of succinylcholine, but typically lasts only a few seconds; if it persists, it may indicate MH.23 Generalized muscle rigidity in the presence of neuromuscular blockade is considered pathognomonic for MH in the presence of other signs of hypermetabolism. The CK level may or may not be elevated in the initial stages of acute MH and, like potassium, increases greatly due to lysis of muscle cell membranes. Detection of urine myoglobin during the clinical course also supports a diagnosis of MH.1-5 A rapid test for urine myoglobin is the presence of heme on the dipstick with lack of red blood cells on the urinalysis. Tachycardia often occurs during the early course of MH but is relatively nonspecific. Other causes of tachycardia that must be distinguished from MH include inadequate depth of anesthesia and sympathomimetic toxicity, among a multitude of others.2 Timely detection of an MH event is aided by core temperature monitoring. Skin temperature does not reflect MH adequately in a swine model, therefore, core (esophageal, nasopharyngeal, tympanic, pulmonary artery) or near-core (oral, bladder, axillary) temperature monitoring is recommended.24 Experts recommend temperature monitoring for general anesthetics longer than 30 minutes in duration.24 Hyperthermia may be hard to distinguish from causes of perioperative fever, including transient bacteremia, endothelial cell disruption, and drug effects (recreational drug overdose, serotonin syndrome).2 Sepsis may be accompanied by fever, metabolic acidosis, and elevated CK, making it difficult to distinguish from MH. Because of the catastrophic consequences associated with delayed therapy, exploration of the differential diagnosis of a potential MH episode should not delay initiation of therapy if MH cannot be excluded rapidly.

Management Early identification of MH and initiation of treatment is the main factor determining success in rescue from an MH event (Figure 1).7 The Malignant Hyperthermia Association of the United States (MHAUS) provides clinicians with emergency consultation to help guide management of an MH episode via a hotline telephone number: (800) 644-9737 (outside the United States: 001-303-389-1647).

Acute Treatment Once an episode of MH is recognized, anesthetic triggering agents should be discontinued immediately, the patient’s inspired oxygen concentration should be increased to 100%, and ventilation should be increased with high oxygen flows to prevent rebreathing.1-5,25 Surgery should be aborted if the procedure is elective and at a point when it can be stopped. Otherwise, the patient should continue to receive general anesthesia with nontriggering agents (eg, propofol, ketamine, opioids, or benzodiazepines).1-5,25 If the patient’s trachea is not intubated, ETT placement should be performed simultaneously with the remainder of the protocol. Additional personnel should be summoned to assist with drug preparation and administration, as well as other aspects of patient management.1-5,25 Dantrolene, the only known antidote for MH, should be administered immediately. Dantrolene binds to ryanodine receptors (RYR1) and inhibits SR calcium release, thereby reversing skeletal muscle hypermetabolism.1-5 Dantrolene is

• Notify surgeon, get help, get dantrolene

• Dantrolene sodium for injection 2.5 mg/kg, rapid IV • Repeat if necessary

• Discontinue triggering agents

• Treat metabolic acidosis, hyperkalemia: insulin, glucose, bicarbonate, calcium (arrhythmia usually responds to treatment of acidosis, hyperkalemia)

Cool the patient

• Hyperventilate with 100% oxygen

Follow: ETCO2, electrolytes, blood gases, CK, serum myoglobin, core temperature, urine output, coagulation studies

Figure 1. Emergency therapy for malignant hyperthermia. CK, creatine kinase; ETCO2, end-tidal carbon dioxide; IV, intravenous Adapted from reference 25.

administered as a loading bolus of 2.5 mg/kg intravenously via large-bore IV access. If the patient does not respond to the first dose within minutes, subsequent bolus doses of 2.5 mg/kg should be administered until the signs of acute MH have abated.25 Some patients, especially muscular males, may require initial dantrolene doses approaching 10 mg/kg, and some case reports have described necessary doses of approximately 40 mg/kg.26 If a response does not occur after repeated dantrolene administration, alternative diagnoses should be considered. Dantrolene is supplied as a lyophilized powder (20 mg) in a vial that also contains 3 g of mannitol and sodium hydroxide to maintain pH of 9.0 to 10. The powder should be mixed with sterile water. The older formulation of dantrolene did not dissolve readily27; a newer, rapidly mixing formulation that solubilizes much more readily (reconstitution time of 20 seconds) is available currently.28 Dantrolene generally is safe when administered at recommended dosages.29 It has no effect on cardiac or smooth muscle. Side effects include nausea, malaise, light-headedness, muscle weakness, and irritation and thrombosis at the IV site due to the high pH of the drug.30 Limb muscle weakness usually occurs. Respiratory muscle weakness may occur when large doses are used or when administered to patients with an underlying debility. Pulmonary edema has been described.30

Additional Treatment Simultaneous to dantrolene administration, treatment to address the metabolic effects of MH should be initiated.1-5,25 The patient’s temperature should be monitored, and blood should be collected for assessment of electrolytes, acid–base status, CK, and coagulation parameters. Arterial or venous blood gases should be collected as needed until pH and potassium levels trend toward normal values. An indwelling urinary catheter should be used to monitor urine color and volume. Hyperkalemia is treated via standard measures (ie, calcium, bicarbonate, and insulin-glucose); lacking laboratory confirmation, treatment should be initiated based on the presence of abnormal ECG waveforms (ie, peaked T-waves) to prevent the development of life-threatening arrhythmias or cardiac arrest.1-5,18 Persistent metabolic acidosis can be treated with repeated doses of sodium bicarbonate, 1 to 2 mEq/kg.1-5,25 Cooling measures should be instituted to maintain patient temperature at below approximately 38.5ºC (101.3ºF).1-5,25 This can be achieved by uncovering the patient; decreasing ambient temperature; using cooling blankets, ice packs, IV infusion of cooled saline or ice saline lavage via nasogastric tube; or wound irrigation. Care should be taken not to overcool the patient.

Although cardiac arrhythmia generally abates when acidosis and hyperkalemia are brought under control, it may persist. In such cases, standard antiarrhythmic agents can be used, but calcium channel blockers are contraindicated because they can worsen the hyperkalemic condition and lead to cardiac collapse.1-5,25 Transfer to an acute care facility should be initiated at any point at which these recommended interventions exceed the capacity of the treatment facility (eg, ambulatory surgical center).7 Patient comfort should be maintained with the administration of sedative–hypnotics.

Ongoing Care Following initial control of the hypermetabolic event, the patient should be transferred to the intensive care unit (or to an acute care facility if not already done) for ongoing monitoring, mechanical ventilation, and treatment.7 Because the anesthesiologist may have the most experience and training with the treatment of MH, his or her ongoing participation in the care of the patient is recommended. CK and renal function (serum creatine) should be monitored, and urine output maintained at 1 to 2 mL/kg per hour until the urine color returns to normal and CK begins to decrease. Peak CK levels occur 14 to 48 hours after the MH crisis. Diuretics and IV bicarbonate may be used to reduce the risk for myoglobin-induced renal failure; consultation with a nephrologist may be helpful.1-5,25 Because recurrence occurs in up to 20% of patients after initial treatment,12 maintenance doses of dantrolene (1 mg/kg every 6 hours) should continue for 24 to 48 hours after the last observed sign of acute MH.1-5,25 If recurrent signs appear despite ongoing treatment, additional dantrolene boluses may be required. Alternatively, a dantrolene infusion (0.25 mg/kg per hour) can be used.25

Post-Recovery Management Following recovery from an acute MH event, patients should be advised to avoid MH-triggering agents and inform future anesthesia providers and emergency response personnel of their susceptibility.1-5,25 A letter from the anesthesia professional who supervised the initial incident should be sent to the patient, and the patient should be instructed to give a copy to all future anesthesia providers. An additional copy should be placed in the patient’s medical record for future reference. A medical alert bracelet, which can be obtained through MHAUS, also may be indicated. Because MH susceptibility is genetic, health care professionals should inform family members of the event to allow them to seek advice from their personal physicians regarding further evaluation or the potential need to avoid triggering agents.

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ANESTHESIOLOGY NEWS • DECEMBER 2011

Why wait? Access this program and post-test @ CMEZone.com All patients with a clinical event suspicious for MH should be referred to a Malignant Hyperthermia Testing Center for further evaluation and consult the MHAUS Web site for additional information. The testing center may recommend testing the patient and family members for MH susceptibility. The gold standard is the caffeine-halothane contracture test, which requires a muscle biopsy.2-5 However, in North America, testing is performed only at a few centers and is expensive. In lieu of contracture testing, some patients with suspected MH susceptibility opt for molecular genetic testing or simply consider themselves (and their family members) MH-susceptible. However, because current genetic testing evaluates only a relatively small percentage of possible mutations, its overall sensitivity is low, and a negative genetic test does not rule out underlying MH susceptibility.

Transfer of Care Considerations MHAUS recently issued recommendations for the transfer of a patient with suspected MH from an ambulatory surgery center (ASC) to an acute care facility (Figure 2).7,8 This

is critical for the patient’s well-being. In general, decisions about the timing and mode of transport should be made by ASC clinicians and take into account the patient’s condition, capabilities of the ASC, capabilities of the transport services, and time needed to arrive at an acute care facility. Because successful treatment for MH requires immediate action, it is preferable that immediate treatment and control of the hypermetabolic event be achieved onsite (eg, ETCO2 declining or normal, heart rate stable or decreasing, no ominous cardiac dysrhythmias, IV dantrolene administration begun, temperature declining, muscular rigidity resolving). However, it will not always be possible for all the indicators of stability to be present before transfer. For the rapidly deteriorating patient, immediate transfer to a sophisticated facility that is prepared to treat MH may be the wisest course of action. The anesthesiologist may have the most experience and training with the treatment of MH and should continue to participate in care of the patient in the ASC, during transport, and/or at the receiving facility. Procedures for transfer

Table 2. Components of MH Treatment Kit/Emergency Cart Drugs

• Dantrolene, 36 vials • Sterile water for injection USP, without bacteriostatic agent, stored in glass vials (not bags) to avoid accidental IV administration - Reconstitute each vial of dantrolene by adding 60 mL, shake until solution is clear - Drug must reach skeletal muscle • Sodium bicarbonate 8.4%, 50 mL × 5 • Furosemide 40 mg × 4 • Dextrose 50%, 50-mL vials × 2 • Calcium chloride 10%, 10 mL × 2 • Regular insulin 100 units/mL × 1, refrigerated • Lidocaine for injection, 100 mg/5 mL or 100 mg/10 mL in preloaded syringes × 3 - Amiodarone also acceptable - Do not give lidocaine or procainamide if wide-QRS complex arrhythmia likely due to hyperkalemia; may result in asystole

General equipment

• Syringes 60 mL × 5 to dilute dantrolene • Mini-Spike® IV additive pins × 2, Multi-Ad fluid transfer sets × 2 to reconstitute dantrolene • IV catheters for venous and arterial access • NG tubes • Toomy irrigation syringes 60 mL × 2 with adapter for NG irrigation • IV pump tubing

Monitoring equipment

• Esophageal or other core temperature probes - Nasopharyngeal, tympanic membrane, rectal, bladder, pulmonary artery catheter • CVP kits • Transducer kits for arterial and central venous cannulation

Nursing supplies

• ≥3,000 mL refrigerated cold saline solution for IV cooling • Large sterile steri-drape • Urine meter × 1 • Irrigation tray with piston syringe, 60 mL, for irrigation • Large clear plastic bags for ice × 4 • Small plastic bags for ice × 4 • Bucket for ice • Test strips for urine analysis

Laboratory testing supplies

• Syringes or kits for blood gas analysis × 6 • Blood specimen tubes × 2 per test - CK, myoglobin, electrolytes, chemistries (LDH, thyroid) - PT/PTT, fibrinogen, D-Dimer - CBC, platelets - Blood gas syringe (lactic acid level) › If no immediate laboratory analysis available, keep samples on ice for later analysis; may prove useful on retrospective review, diagnosis › Include blood cultures to rule out bacteremia • Urine collection container for urine myoglobin level.

CBC, complete blood count; CK, creatine kinase; CVP, central venous pressure; IV, intravenous; LDH, lactate dehydrogenase; NG, nasogastric; PT, prothrombin time; PTT, partial thromboplastin time Adapted from reference 31.

should be formulated ahead of time (eg, admission to the emergency department or direct admission to the ICU); physician-to-physician communication is optimal. The nurse may play an important role by facilitating the transfer and supporting family members.

Reporting All MH events or suspected MH events should be reported to the North American Malignant Hyperthermia Registry (http://www.mhaus.org/malignant-hyperthermiaregistry) which was established to acquire, analyze, and disseminate patient-specific clinical and laboratory information to scientific investigators and physicians caring for MH-susceptible patients. Data also are used in research on the epidemiology, diagnosis, and treatment of MH.

Prevention and Preparedness Any facility that uses MH-triggering agents should be prepared to detect and manage an episode of MH. This includes established protocols for treatment and/or transfer, availability of appropriate drugs and equipment (MH kits, emergency carts), and the presence of personnel who are educated and trained in the detection, treatment, and prevention of MH episodes. MHAUS provides resources for such training, including brochures, posters, and multimedia resources for training and drills (Table 2).31 Prevention of MH episodes also is critical. It is not practical or feasible to screen for MH susceptibility using biopsy or genetic testing in an individual without a personal or family history of MH susceptibility or a previous MH episode, but the preanesthesia evaluation and preoperative nursing assessment should assess for a personal or family history of MH susceptibility.4,5,32 Most patients with underlying MH susceptibility will not be aware of it, however; because MH has variable penetrance, previous uneventful anesthesia does not exclude MH susceptibility. Patients with known or suspected MH should not receive triggering agents but instead should be safely anesthetized using nontriggering agents or local or regional anesthesia.4,5,32 Pretreatment with dantrolene is not recommended. In addition, the anesthesia provider should prepare the anesthesia machine and ensure that the patient will not be exposed to trace anesthetic gases. Measures include flushing the anesthesia machine with high-flow oxygen (at least 10 L per minute) for 20 minutes, and removing or placing tape over the vaporizer canisters to avoid accidental administration.4,5,32 For older machines with copper tubing, the reservoir bag should be attached to the distal end of the ventilator circuit Y-piece with at least 5 ventilator cycles per minute during the 20-minute flushing. Newer anesthesia workstations with plastic components may require more than 60 minutes to purge residual gases.4,5,32,33 Charcoal filters inserted in the breathing circuit have been shown to reduce the residual anesthetic concentration in the breathing circuit quickly.33 Practitioners should consult manufacturer information in regard to the optimal manner for preparing specific equipment. All facilities at which general anesthesia is administered should have adequate stocks of dantrolene in the event that MH occurs. Because of the increasing prevalence of obesity and uncertainty regarding the required dosing (actual body weight vs ideal body weight) for effective relief of MH, MHAUS recommends that at least 36 vials be available at all times.25,31 However, it should be noted that 75 vials (20 mg per vial) would be required in the theoretical instance of an obese patient (150 kg) requiring a dantrolene dose of 10 mg/kg.

Conclusions MH is a serious and potentially life-threatening hypermetabolic condition involving abnormal release of calcium within skeletal muscle cells in response to a

CONTINUING MEDICAL EDUCATION

ANESTHESIOLOGY NEWS • DECEMBER 2011

13. Larach MG, et al. Anesthesiology. 2008;108(4):603-611.

1 Recognize

suspected MH • Discontinue triggering agents, begin treatment

2 Adapt established

• Initiate established emergency MH transfer plan

transfer plan based on real-time assessment • Capabilities of available professionals at receiving health care facility

3 Implement

transfer plan • Notify receiving health care facility

4 Debrief, evaluate transfer plan

• Establish continuous communication among transfer team members, receiving health care facility, MH hotline

• Clinical information, best interests of patient • Transfer team capabilities

• Nursing professionals facilitate communication with family, support system

14. Burkman JM, et al. Anesthesiology. 2007;106(5):901-906. 15. Denborough MA, et al. Br Med J (Clin Res Ed). 1984;288(6434):1878. 16. Huerta-Alardín AL, et al. Crit Care. 2005;9(2):158-169. 17. Rosero EB, et al. Anesthesiology. 2009;110(1):89-94. 18. Groom L, et al. Anesthesiology. 2011;115(5):938-945. 19. Tobin JR, et al. JAMA. 2001;286:168-169. 20. Li G, et al. Ped Anesth. 2011;21:958-963. 21. MHAUS. www.mhaus.org. Accessed October 21, 2011. 22. Glahn KP, et al. Br J Anaesth. 2010;105(4):417-420. 23. van der Spek AF, et al. Anesthesiology. 1987;67:459-465. 24. Sessler D. Anesthesiology. 2008;109(2):318-338. 25. MHAUS. Emergency therapy for MH. http://www.mhaus.org/ malignant-hyperthermia-healthcare-professionals. Accessed October 1, 2011. 26. Blank JW, et al. J Clin Anesth. 1993;5(1):69-72.

Figure 2. MHAUS recommendations for transfer of care in MH. MH, malignant hyperthermia; MHAUS, Malignant Hyperthermia Association of the United States Adapted from references 7 and 8.

triggering agent. It occurs in genetically susceptible individuals. Successful diagnosis requires recognition of the constellation of symptoms in the right clinical context, and avoidance of catastrophic outcomes requires prompt discontinuation of triggering agents, administration of dantrolene, and therapy directed against the metabolic complications of the disorder. Transfer-of-care protocols are critical for patients who experience an MH episode in an ASC. A rapidly mixing formulation of dantrolene became available in 2009. It is easier to prepare than the older formulation and should facilitate the care of patients with an MH episode.

References 1.

Collins CP, Beirne OR. J Oral Maxillofac Surg. 2003;61(11):1340-1305.

McCarthy EJ. AACN Clin Issues. 2004;15(2):231-237.

Litman RS, Rosenberg H. JAMA. 2005;293(23):2918-2924.

27. Mitchell LW, et al. Can J Anaesth. 2003;50(2):127-130. 28. JHP Pharmaceuticals. Dantrium IV Frequently asked questions. http://www.dantrium.com/faq.php. Accessed October 1, 2011. 29. Dantrium (dantrolene sodium for injection) [prescribing information]. Rochester, MN: JHP Pharmaceuticals; 2008.

Hopkins PM. Curr Anaes Crit Care. 2008;19(1):22-33.

30. Brandom BW, et al. Anesth Analg. 2011;112(5):1115-1123.

Rosenberg H, et al. In Pagon RA, et al, eds. GeneReviews [Internet]. Seattle, WA: University of Washington; 1993-2003, updated Jan 19,2010. http://www.ncbi.nlm.nih.gov/books/NBK1146. Accessed October 26, 2011.

31. MHAUS. Stocking the MH cart. http://www.mhaus.org/ malignant-hyperthermia-healthcare-professionals/mhaus-faqshealthcare-professionals/stocking-mh-cart/. Accessed October 1, 2011.

Burden A, et al. Presented at: Annual Meeting of the American Society of Anesthesiologists; October 16-20, 2010; San Diego, CA. Abstract A384.

32. Wappler F. Curr Opin Anaesthesiol. 2010;23(3):417-422. 33. Gunter JB. Anesth Analg. 2008;107(6):1936-1945.

MHAUS. MHAUS transfer of care guidelines. http://medical. mhaus.org. Accessed October 1, 2011.

Resources

MHAUS. Malignant hyperthermia: new transfer guidelines. http:// www.ascassociation.org/MHAUSTransferStory.pdf. Accessed October 1, 2011.

Association of pero-Operative Nurses: http://www.aorn.org/ Education/ConfidenceBasedLearning/MalignantHyperthermia/

Brady JE, et al. Anesth Analg. 2009;109(4):1162-1166.

10. Brady JE, et al. Presented at: Annual Meeting of the American Society of Anesthesiologists; October 17-21, 2009; New Orleans, LA. Abstract A1521. 11. Denborough M. Lancet. 1998;352(9134):1131-1136. 12. Larach MG, et al. Anesth Analg. 2010;110(2):498-507.

American Association of Nurse Anesthetists: http://www.aana. com/uploadedfiles/resources/practice_documents/stds_ officebasedanesth.pdf American Society of Anesthesiologists: http://www.asahq.org/ Knowledge-Base/Diseases-and-Conditions/ASA/MalignantHyperthermia-Syndrome-From-Barnyard-to-Molecular-GeneticsLaboratory.aspx

CME Post-Test 1. Which of the following therapeutic agents is contraindicated in the context of an acute episode of malignant hyperthermia (MH)? a. Amiodarone b. Verapamil c. Furosemide d. Sodium bicarbonate

2. Which of the following is the earliest and most reliable sign of an acute episode of MH? a. Hyperthermia b. Elevation in end-tidal CO2 (ETCO2) c. Increased serum creatine kinase d. Cardiac arrhythmias

3. Which of the following agents represents a potential triggering agent in patients with susceptibility to MH? a. Sevoflurane b. Midazolam c. Fentanyl d. Propofol

4. Which of the following tissues is involved in the pathophysiology of MH? a. Smooth muscle b. Cardiac muscle c. Skeletal muscle d. Endothelial cells

5. Which of the following is most likely a potential complication of an episode of MH? a. Peripheral neuropathy b. Central pontine myelinolysis c. Pericarditis d. Rhabdomyolysis

6. How many vials of dantrolene does the Malignant Hypothermia Association of the United States recommend should be readily available? a. 3 b. 10 c. 16 d. 36

7. Which of the following represents a major advantage of a newer formulation of dantrolene over the previous formulation? a. Easier to reconstitute b. More potent c. Less expensive d. Longer shelf-life

8. MH-triggering agents are contraindicated in which of the following patients? a. Patients with a personal history of an MH episode b. Patients with a history of MH in a first-degree relative c. Patients with a positive halothane-caffeine contracture study d. All of the above

9. Which of the following preventative measures is recommended in an MH-susceptible patient who requires general anesthesia? a. Purging equipment and breathing circuit of volatile anesthetics b. Prophylactic dantrolene administration c. Induction of intraoperative hypothermia d. Prophylactic administration of potassium-binding resins

10. Which of the following is true regarding MH-susceptibility testing? a. All patients anticipating surgery with general anesthesia should undergo susceptibility testing b. The caffeine-halothane contracture test is expensive and available only at certain centers c. Negative genetic testing essentially rules out a diagnosis of MH susceptibility d. All of the above

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ANESTHESIOLOGY NEWS • DECEMBER 2011

Why wait? Access this program and post-test @ CMEZone.com

Answer Sheet and Evaluation Form Malignant Hyperthermia: Diagnosis, Treatment, and Prevention Release Date: December 1, 2011

Expiration Date: December 1, 2013

Participate online at: CMEZone.com Type IP112 in the keyword field (availability may be delayed from print date). Or fax to: (904) 683-3803

Or mail to: AKH Inc. Advancing Knowledge in Healthcare PO Box 2187 Orange Park, FL 32067-2187

Participant Information (please print) First Name:

Last Name:

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Post-Test Answer Section Please circle the correct answer for each question. (A score of at least 70% is required to receive credit.) 1. 2. 3. 4. 5.

a a a a a

b b b b b

c c c c c

d d d d d

6. 7. 8. 9. 10.

a a a a a

b b b b b

c c c c c

d d d d d

Evaluation Questions Strongly Agree

Agree

Disagree

Strongly Disagree

a. Discuss the pathophysiology of MH.

b. Describe the characteristic clinical findings that identify an MH crisis.

c. Identify all supplies required to manage an MH crisis.

d. Discuss, in order, the appropriate steps that must be taken to manage an MH crisis.

e. Discuss preventive measures required to provide safe care to patients who are susceptible to MH.

2. The activity met my educational needs.

3. The faculty were knowledgeable and effective in the presentation of content.

4. The teaching method and educational materials were effective.

5. The learning activities were effective and incorporated active learning methods.

6. The post-test accurately assessed learning.

Please answer the following questions by circling the appropriate rating. 1. After participating in this activity, I am better prepared to:

7. The content was objective, current, scientifically based, and free of commercial bias. ❏ Yes ❏ No (please explain): 8. Based on the information presented in this activity, I will ❏ do nothing, as the content was not convincing. ❏ seek additional information on this topic. ❏ change my practice. ❏ do nothing, as current practice reflects the program’s recommendations. 9. The most important concept learned during this activity that may effect a change in patient care is: 10. What issue(s) related to the therapeutic area discussed in this activity, or other topics, would you like addressed in future continuing education?

11. Additional comments:

IP112

December 2011

Ambu

AnesthesiologyNews.com I 23

The following advertorial is provided as a service to our valued advertisers. It is designed to support the advertisement presented below.

The SmartBlock Pain Pump, From Ambu Q: What are the expected consistency rates of the SmartBlock pain pump? A: The unique design of the Ambu SmartReg allows the SmartBlock pain pump to deliver medication to the patient at a consistent rate of at least 5%. The smart pump relies on an active restriction of pressure, unlike the market standard, which relies on the passive restriction of the pressure created by the reservoir. The flow rates of the SmartBlock pain pump are among the most consistent for any disposable elastomeric pump. Because of the consistency of the pump, clinicians may require less interaction, such as the need for a bolus shot, with patients.

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24 I AnesthesiologyNews.com

December 2011

PRN

Case Study: Anesthetic Implications in the Management Of a Patient With Cowden Syndrome

39-year-old woman presented for reconstructive surgery of her left breast. The patient had a medical history significant for Cowden syndrome, obesity (body mass index, 48.3 kg/m2), polycystic ovary syndrome, thyroid carcinoma, and depression. Past surgeries included a thyroidectomy and multiple procedures on her breasts. She had a Mallampati score of 3, intact craniocervical movement, and adequate mouth opening with history of wide range of intubations.

blockade until the airway has been secured is advisable, especially in patients with dysmorphism in the maxilla and mandible. Thyroid dysfunction is common in patients with Cowden syndrome; thus, thyroid function tests should be obtained before surgery.

Surgery Following intubation, surgery lasted approximately five hours with no complications. The left breast was reconstructed with a latissimus dorsi flap. tAfter proper positioning and IV access were secured, 4 mg of midazolam was administered. Rapid

sequence induction was initiated with propofol (1.2 mg/kg) and succinylcholine (0.7 mg/kg). Video-assisted laryngoscopy was accomplished with a grade II view, and a 7.0-mm standard endotracheal tube (ETT) was placed without difficulty. see Cowden page 27

Pathology Cowden syndrome, or multiple hamartoma syndrome, is a rare autosomal dominant condition from a mutation in the PTEN tumor suppressor gene. Cowden syndrome causes mucocutaneous lesions and neoplasms in the mucosa of the gastrointestinal tract, central nervous system and genitourinary system. Nearly all patients have hamartomas of the skin. Although most features of Cowden syndrome are physical, some patients also experience autism and mental retardation. Anesthetic Concerns The anesthetic management of a patient with Cowden syndrome presents many potential challenges. Mental retardation can affect patient cooperation, and anxiolytics are used during induction. Airway management is of vital importance in these patients, as they often can have macrocephaly, hypoplastic maxilla with a high arched palate, hypoplastic mandible and thyroid tumors. Clinicians also must be careful with papillomatosis at the base of the tongue that warrants an awake fiber-optic intubation. Avoidance of neuromuscular

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CENTURION® CENTRAL LINE BUNDLE SOLUTION – EVERYTHING YOU Figure. Hamartomas characteristic of Cowden syndrome. Source: Marcio A Oliveira et al.

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December 2011

AnesthesiologyNews.com I 25

The following advertorial is provided as a service to our valued advertisers. It is designed to support the advertisement presented below.

Centurion

Centurion CVC Bundle Q: What is a central-line bloodstream infection? A: In the United States, an estimated 248,000 central line–associated bloodstream infections (CLABSIs) occur each year. CLABSIs are associated with high mortality rates (12%-25%) and extended hospital stays, requiring patients to spend an estimated nine to 12 additional days in a hospital. According to the Centers for Disease Control and Prevention (CDC), the cost of treating a single episode of CLABSI can range from $34,500 to $56,000.

Q: Are CLABSIs preventable? A: CLABSIs are preventable; in fact, they are called “never events” precisely because they are avoidable complications of patient care. Recent studies have concluded proper techniques, protocol and bundling can successfully prevent CLABSIs. Bundling is the key. According to every major agency—the CDC, the Joint Commission, the Occupational Safety and Health Administration and the Institute for Healthcare Improvement— following a comprehensive prevention strategy reduces CLABSIs.

Q: What are the basic interventions of the bundle? A: According to the CDC, “Guidelines for the Prevention of Intravascular Catheter-Related Infections, 2011,” a bundle includes: Hand hygiene; maximal barrier precautions at insertion, including cap, mask, gloves and full-body sterile drape; chlorhexidine skin asepsis; optimal catheter site selection; daily review of the necessity of a line with prompt removal of unnecessary lines; and a checklist to support the standardized protocol.

Q: What are the differences between your CVC kit and a Centurion CVC bundle? A: A kit includes items for certain aspects of a procedure such as site preparation, line insertion or site protection. A bundle contains everything needed for the entire procedure, from “prep to dressing.” That’s why Centurion’s CVC bundle saves time, minimizes waste, maximizes savings and ensures procedural excellence.

Q: Why is Centurion’s CVC bundle the ultimate central-line bundle solution? A: Centurion Medical Products is uniquely qualified to help you implement a prevention strategy by constructing a customized CVC bundle to match your team’s needs exactly, with every component needed to maximize efficiency and effectiveness in reducing CLABSIs.

Q: What components are available in a Centurion CVC bundle? A: The components are: • Protective gear—Centurion offers a full line of maximum barrier protective gear for one or more users from gown, gloves and masks to bouffants and caps. • Full-body drapes—Using full-body drapes is key to creating maximal sterile barrier protection. In addition to a large variety of stock drapes, Centurion can customize a drape to suit your specific procedure. • Edwards catheters—Choose from pressure injectable, anti-microbial, multi-lumen Vantex and Multi-Med catheters or IntroFlex and High-Flow advanced venous access introducer catheters. • Prefilled syringes—Exclusively from Centurion, sodium chloride in sterilized, prefilled syringes packaged within your procedure tray. Choose from single, double or triple syringe foil packs to meet your specific needs. • SorbaView shield—The patented SorbaView® SHIELD is a one-step catheter securement system that combines the features and benefits of a SorbaView® dressing with SHIELD Technology that eliminates the need for a secondary securement device. • SorbaView Ultimate IJ dressing system—Particularly suited for multi-lumen and introducer catheters placed on the neck, the SorbaView Ultimate IJ dressing system with tubing anchor stays intact and stable for extended periods. • SnagFree needle holders—Centurion SnagFree® instruments feature a patented hinge design that prevents sutures from catching. • Hospital forms and patient/family education materials—Customized procedural checklists, labels, signs and forms can be built into trays to meet Joint Commission goals for patient safety and ensure proper protocol. • Additional items—Safety components, ChloraPrep applicators, Biopatch, sterile labels, ultrasound gel and probe covers, needle-free valves and saline/heparin/lidocaine solutions.

ARE PREVENTABLE Centurion Medical Products is the only CVC provider that can build you a COMPLETE Bundle.

NEED TO STOP CLABSIs

Centurion Medical Products 301 Catrell Dr. Howell, MI 48843 800-248-4058 www.centurionmp.com Please visit us at the PGA Booth #233

800-248-4058 | www.cvcbundle.com

26 I AnesthesiologyNews.com

December 2011

PRN

ECG Cables Are Common Source of Contaminants in OR

urrent sterilization protocols may be ineffective in eliminating pathogenic microorganisms from operating room equipment, French researchers have found. Investigators found that 34% of the 50 sets of electrocardiograph (ECG) cables they examined tested positive for a host of bacteria and fungi. The results were presented at the 2011

annual meeting of the American Society of Anesthesiologists (abstract 1111). The findings are consistent with other research suggesting that some nosocomial infections can be traced back to contaminated OR equipment, said Nancy Nussmeier, MD, professor of anesthesiology at the State University of New York Upstate Medical

University, in Syracuse, who was not involved in the study. “There is a growing concern that resistant organisms are emerging in the OR, and these authors should be congratulated for pointing out important—and often overlooked—potential sources of patient infection,” Dr. Nussmeier told Anesthesiology News. “This study supports other literature suggesting the

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need for more rigorous decontamination of reusable equipment that comes into direct contact with patients in every operating room.” In previous research, up to 75% of laryngoscope handles were found to be contaminated with bacteria (e.g., Anesth Analg 2009;109:479-483). However, the full extent of cross-contamination of OR equipment is not known. In the current study, lead investigator Brice Samyn, MD, staff anesthesiologist at Strasbourg University Hospital, and several colleagues preoperatively collected swab samples from ECG cables used during 50 procedures in the OR. The cables were swabbed after ostensibly having been disinfected with a 0.25% quaternary ammonium solution, according to protocol. Each set of swab samples was tested for both bacterial and mycological contaminants. The OR staff was unaware that the ECG cables were being tested for potential contaminants. Seventeen of the 50 sets of cables tested positive for bacteria or fungi (Table). The microorganisms most commonly found were coagulase-negative Staphylococcus aureus, methicillin-sensitive S. aureus, Staphylococcus epidermis, several species of the genus Bacillus, Aspergillus fumigatus and, in some cases, Enterococcus faecalis. Contaminated cables largely originated from ORs where gastrointestinal and gynecologic surgeries had been performed. Co-investigator Pierre Diemunsch, MD, PhD, chief of the Department of Anesthesia at Strasbourg University Table. ECG Cable Contamination Findings by Specialty

Spinal Underbody Model 575

Lithotomy Underbody Model 585

Full Access Underbody

Models 635/637

Samples by OR Specialty, n=50

Negative Samples, n=33 (68%)

Digestive, n=34

Gynecologic, n=12

ENT, n=1

–

Other, n=3

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ECG, electrocardiograph; ENT, ear, nose and throat; OR, operating room

December 2011

AnesthesiologyNews.com I 27

PR N Hospital, said it is not clear whether the pathogens they found are affecting patient safety. “Fortunately, none of our patients has developed infections that can clearly be related to this cross-contamination issue,” Dr. Diemunsch told Anesthesiology News. “However, we also did not look for this etiology.” Dr. Diemunsch suspected one reason for the high contamination rates might be poor adherence to otherwise effective decontamination protocols.

‘There is a growing concern that resistant organisms are emerging in the OR, and these authors should be congratulated for pointing out important—and often overlooked—potential sources of patient infection.’ —Nancy Nussmeier, MD “It seems to be that after a while, the OR personnel no longer follow the rules,” he said. However, he stopped short of attributing the problem of contaminated equipment entirely to poor protocol adherence, adding that cables that had been in use for more than six months tended to be more contaminated than newer cables. He speculated that equipment becomes more porous over time and surfaces therefore become more adherent. Dr. Diemunsch’s group currently is examining rates of cross-contamination in finger pulse oximeter sensors and noninvasive blood pressure cuffs in the OR. —David Wild

Positive Samples, n=17 (34%) 1 methicillin-sensitive Staphylococcus aureus 8 coagulase-negative staphylococci 2 coagulase-negative staphylococci + Bacillus sp. 2 Bacillus sp. 1 Aspergillus fumigatus 2 coagulase-negative staphylococci 1 coagulase-negative staphylococci –

Cowden continued from page 24 An arterial line was placed on the patient’s right radial position. The patient was maintained on desflurane and an infusion of remifentanil (0.1 mcg/kg per minute) for the case. Reversal of neuromuscular blockade was achieved with neostigmine (3 mg) and glycopyrrolate (0.6 mg), and the ETT was removed following extubation criteria. The patient was discharged

with an uneventful postoperative period and returned subsequently for additional planned procedures. Suggested Reading 1. Lloyd KM II, Dennis M. Cowden’s disease. A possible new symptoms complex with multiple involvement. Ann Intern Med. 1963;58:136-142. 2. Shiraishi N, Nakamura T, Saito H, Ogawa S, Suzuki H. Anesthetic management of a patient with Cowden syndrome. Masui. 1995;44(2):282-285. 3. Pilarski R. Cowden syndrome: a critical review of the clinical literature. J Genet Couns. 2009;18(1):13-27.

4. To EW, Tsang WM, Pak MW, Cheng JH, Tse GM, van Hasselt CA. Cowden’s disease with vocal fold involvement. Ear Nose Throat J. 2001;80(10)754-756. 5. Omote K, Kawamata T, Imaizumi H, Namiki A. Case of Cowden’s disease that caused airway obstruction during induction of anesthesia. Anesthesiology. 1999;91(5):1537-1540.

Anoushka Afonso, MD Larry Hausman, MD Department of Anesthesia Mount Sinai School of Medicine New York, New York

28 I AnesthesiologyNews.com

December 2011

PRN

Survey: Multimodal Analgesia Underused Jefferson University, who queried anesthesiologists, nurse anesthetists and other OR-based providers and administrators about the use of multimodal analgesia at their institutions. Fewer than 25% of physicians surveyed said they used more than two nonopioid

espite 2004 recommendations from the American Society of Anesthesiologists, clinicians haven’t fully embraced multimodal analgesia for the management of perioperative pain. That’s according to a recent survey by researchers at Thomas

drugs to control pain perioperatively, the researchers found, while 75% said they administered acetaminophen preoperatively in less than 25% of cases. For the full range of responses, see the Table below. The findings were presented at the 2011 annual meeting of the American Society of Anesthesiologists (abstract 1178). —AN Staff

Table. Behavioral Patterns Among Anesthesia Providers Question

Answer

Anesthesiologist

CRNA

Other

P value

1. Who in your facility makes the decision to use nonopioids/multimodal therapy to treat perioperative pain?

Anesthesiologist/CRNA

82.9%

90%

81%

0.063

Surgeon

17.1%

10%

19%

2. When you use a multimodal agent, how many nonopioid analgesics do you include?

43.9%

35%

47.6%

34.1%

65%

47.6%

22%

4.8%

<25%

41.5%

36.8%

68.2%

25-50%

19.5%

26.3%

4.5%

50-75%

24.4%

10.5%

13.6%

>75%

14.6%

26.3%

13.6%

<25%

12.8%

20%

45.5%

25-50%

30.8%

15%

27.3%

50-75%

30.8%

30%

9.1%

>75%

25.6%

35%

18.2%

<25%

56.1%

68.4%

70%

25-50%

36.6%

21.1%

25%

50-75%

7.3%

10.5%

>75%

<25%

70.7%

65%

85.7%

25-50%

14.6%

30%

4.8%

50-75%

12.2%

4.8%

>75%

2.4%

4.8%

<25%

82.9%

95%

88.2%

25-50%

12.2%

5.9%

50-75%

4.9%

5.9%

>75%

<25%

75%

55%

88.2%

25-50%

10%

25%

5.9%

50-75%

12.5%

10%

>75%

2.5%

10%

5.9%

Reduced opioid use

46.3%

40%

19%

Decreased length of stay

9.8%

15%

19%

Decreased postoperative nausea/vomiting

17.1%

20%

33.3%

Increased patient satisfaction

26.8%

25%

28.6%

3. How often do you administer nonopioids/ multimodal therapy preoperatively?

4. How often do you administer nonopioids/ multimodal therapy postoperatively?

5. How often do surgeons oppose the use of nonsteroidal anti-inflammatory drugs in your patients? 6. How often do you administer nonsteroidal anti-inflammatory drugs preoperatively?

7. How often do you administer gabapentinoids preoperatively?

8. How often do you administer acetaminophen preoperatively?

9. What is the most significant benefit that you achieve from employing a nonopioid/multimodal therapy?

0.043

0.183

0.063

0.349

0.312

0.681

0.227

0.484

CRNA, certified registered nurse anesthetist

290

Total discharges, thousands

300

280 270 260 250 240 230 220 210 200

70 60 50 40 30 20 10

19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00 20 01 20 02 20 03 20 04 20 05 20 06 20 07

f you feel like you’re spending more time on prostate surgery cases, there’s a reason: Diagnosis of prostate cancer has surged in recent years, as has the number of prostatectomy procedures to remove the diseased glands, new research shows. Steven Roth, MD, professor of anesthesia and critical care at the University of Chicago, used diagnostic coding to chart the trends (Figures 1 and 2), which he said likely reflect the growing acceptance of robotic-assisted surgery in prostate cancer cases. “Laparoscopic techniques offer faster recovery at lower cost and anesthesiologists can expect to be performing more of these procedures in the future,” stated Dr. Roth, who presented his findings at the 2011 annual meeting of the American Society of Anesthesiologists (abstract 715).

Total discharges, thousands

Prostate Cases Taking More of the Anesthesia Workday

Figure 1. Total number of discharges for diagnosis of prostate cancer.

Figure 2. Total number of discharges for radical prostatectomy.

(ICD-9-CM all-listed diagnosis code 185, malignant neoplastic prostate)

(ICD-9-CM all-listed procedure code 60.5)

THE SCIENCE BEHIND POSITIVE PATIENT OUTCOMES

Goal-directed Therapies for Positive Patient Outcomes:

Monitoring and Volume Replacement With 6% Hydroxyethyl Starch 130/0.4 in 0.9% Sodium Chloride for Injection Faculty David D. Rose, CRNA, PhD Staff Anesthetist/Volunteer Assistant Clinical Professor Department of Anesthesiology and Pain Medicine UC Davis School of Medicine Sacramento, California

Neal W. Fleming, MD, PhD Professor of Clinical Anesthesia Director, Cardiovascular and Thoracic Anesthesia UC Davis School of Medicine Sacramento, California

Rainer Kentner, MD, PhD Assistant Professor of Anesthesiology Department of Anesthesiology/Trauma Section Washington University School of Medicine St. Louis, Missouri

Introduction Goal-directed strategies for optimal patient assessment and treatment are facilitated when practitioners use minimally invasive technologies, such as arterial pressure contour wave analysis and esophageal Doppler flow measurement, to assess perioperative fluid responsiveness in the hypotensive patient. Additionally, a more balanced approach to volume replacement for patients undergoing surgeries with the potential for large intraoperative fluid shifts and blood loss—one that incorporates colloids for intravascular volume expansion—has been advocated.1 Typically, colloid selection is based on multiple factors including availability, clinical experience, and cost. Albumin, a human-derived protein, is commonly available and has been used as an effective volume expander; however, albumin is more expensive when compared with crystalloid solutions.2 Its use also may be associated with a higher mortality rate in certain patient populations, such as traumatic brain injury, and it has been shown to be no more effective than less expensive colloids (eg, hydroxyethyl starch [HES] solutions).3,4 Use of HES solutions has increased during the last decade and represents an important addition to resuscitation fluid management strategy. HES solutions carry the risk of anaphylactoid or hypersensitivity reactions with the most common adverse reactions including pruritus, elevated serum amylase, and hemodilution. 5 Six percent HES 130/0.4 in 0.9% sodium chloride for injection has been accepted as an alternative to earlier HES solutions Hespan® (6% HES 600/0.75 in 0.9% sodium chloride for injection; B. Braun) and Hextend® (6% HES 670/0.75 in lactated electrolyte for injection; Hospira). Compared with earlier HES solutions, HES 130/0.4 offers a lower mean molecular weight and molar substitution along with a higher C2/C6 ratio, allowing for similar intravascular expansion time with less plasma accumulation. Lower plasma accumulation is associated with less effect on coagulation and renal dysfunction. Lower molecular weight and lower molar substitution decrease the potential for coagulopathic side effects,6 due to reduced influence on factor VIII, von Willebrand factor, and ristocetin cofactor.7

ANESTHESIOLOGY NEWS • DECEMBER 2011

A reduction in coagulopathic side effects is of particular importance for trauma patients as well as patients receiving larger total volumes of colloids. HES 130/0.4 is similar to the other starches in that it is contraindicated in patients receiving dialysis treatment or in patients who have renal failure with oliguria or anuria not related to hypovolemia. In addition, it should not be used in patients with intracranial bleeding.5 HES 130/0.4 also possesses a higher plasma clearance and lower elimination half-life when compared with older HES solutions.8 Even after repetitive doses, HES 130/0.4 accumulates less in plasma and tissues than older starches.7,9 HES 130/0.4 has 0.9% sodium chloride as the diluent solution and as such, it is contraindicated in patients with severe hypernatremia or severe hyperchloremia.5 These enhanced qualities increasingly have led practitioners to use HES 130/0.4 when volume expansion is necessary for a variety of surgical procedures or if immediate fluid responses are required.

Case Study 1: Use of HES 130/0.4 in a ColloidBased, Goal-directed Approach to Volume Management in a Major Orthopedic Procedure A 53-year-old woman with a history of osteoarthritis was scheduled for bilateral total hip replacements. The patient also had a history of myalgia/myositis and depression. Her prescription medications included clonazepam 2 mg, duloxetine 30 mg, and oxaprozin 1,200 mg each daily, as well as hydrocodone 10 mg/acetaminophen 325 mg (1 to 2 tablets every 6 hours) and morphine 60 mg every 8 hours. Additionally, she admitted daily marijuana use. She denied any drug allergies or complications from previous anesthetic use for a cesarean delivery and tubal ligation performed in the 1980s. Her height and weight were 157 cm and 63 kg, respectively, with a body mass index of 26. The patient was brought to the operating room (OR) after receiving IV midazolam 2 mg for preoperative anxiolysis. Standard monitors were applied and general

anesthesia was induced with propofol 2.5 mg/kg. Rocuronium 0.8 mg/kg was administered for muscle relaxation. Maintenance of anesthesia was achieved with sevoflurane 0.8-1.2 minimum alveolar concentration in addition to fentanyl and hydromorphone. A dexmedetomidine bolus (0.5 mcg/kg) and infusion (0.2-0.6 mcg/kg per hour) were used during the procedure as an adjunct to her intraoperative and postoperative pain medication needs. After the placement of an additional large-bore IV, an esophageal Doppler monitoring probe (CardioQ-ODM™, Deltex Medical) was inserted following the manufacturer’s recommended technique in order to guide a goal-directed strategy for fluid optimization. The cardiac output (CO), cardiac index (CI), and stroke volume (SV) were monitored throughout the procedure (Table 1). Then, the patient was placed in the right lateral position for a left total hip replacement. Blood pressure (BP) was kept to within 20% of the patient’s baseline, and fluid optimization was guided using the esophageal Doppler. A fluid strategy was developed using HES 130/0.4 (colloid) and Lactated Ringer’s (LR) solution (crystalloid). Serial venous hematocrit evaluation allowed for red cell mass assessment with a transfusion trigger of 25%. Beginning with a hematocrit of 30%, CO, CI, and SV were evaluated. SV change of greater than 10% was an indication of potential fluid responsiveness. After positioning and equilibration time, the initial CO, CI, and SV were 4.8 L/min, 2.6 L/min/m 2 and 71 mL, respectively. Approximately 60 minutes into the procedure, estimated blood loss (EBL) was 500 mL. CO, CI, and SV were recorded at 4.2 L/min, 2.3 L/min/m2, and 68 mL, respectively; hematocrit was 29%. With 1,000 mL of LR already infused, HES 130/0.4 500 mL was given over the next 30 minutes, which led to an increase in CO to 4.8 L/min, CI to 2.5 L/min/m2, and SV to 78 mL. At the completion of the first hip replacement, EBL was 900 mL, and CO, CI, and SV were noted to be 5 L/min, 2.8 L/min/m2, and 83 mL, respectively. Urine

Table 1. Vitals During Surgery Time SBP (mm Hg) DBP (mm Hg) HR (beats per min) CO (L/min) CI (L/min/m2) SV (mL) UOP (mL/kg/h) EBL (mL) Crystalloid HES 130/0.4 (mL) HCT (%) PRBC (# of units)

8 AM 8:30 9:00 9:30 10:00 10:30 11:00 11:30 12 PM 12:30 1:00 1:30 2:00 98 56 61 4.8 2.6 71

113 64 64 5.0 3.2 89

104 63 52 5.5 3.0 88

96 50 51 4.2 2.3 68

90 50 51 4.8 2.5 78 280

500 1,000

88 51 62 5.0 2.8 83

100 58 61 4.5 2.3 69 340

100 64 58 4.2 2.1 66

900 1,600

101 63 58 4.8 2.4 71 410 1,100

105 62 62 5.1 2.8 84

98 60 62 5.6 2.9 92

1,800 2,000

500/ 500 29

104 66 59 5.5 2.9 90

100 64 63 5.6 2.8 91 480 1,900 2,500

500/ 1,000 25 1

31 2

CI, cardiac index; CO, cardiac output; DBP, diastolic blood pressure; EBL, estimated blood loss; HCT, hematocrit; HES 130/0.4, 6% HES 130/0.4 in 0.9% sodium chloride for injection; HR, heart rate; PRBC, packed red blood cells; SBP, systolic blood pressure; SV, stroke volume; UOP, urinary output

Supported by

Table 2. Labs During Trauma Fluid Resuscitation

pHa

Start

7.09

7.22

7.38

7.32

7.35

paCO2 (mm Hg)

paO2 (mm Hg)

154

500

440

281

110

HCO3

artBE (mmol/L)

-15

-7

-1

HCT (%)

Platelets (000/mcL)

105

PT (sec)

15.1

18.6

18.5

16.4

PTT (sec)

37.7

44.3

46.2

58.1

47.5

44.2

49.0

INR

1.2

1.6

1.4

1.1

1.2

FFP (# of units)

Platelets (# of units)

PRBC (# of units)

HES 130/0.4 (mL)

1,000

5% Human albumin (mL) Crystalloids (mL)

Postop 12 h

Postop 24 h

110

103

15.2

13.9

17.1

38.7

33.0

1.2

1.5

1.3

2 1

2,000 1,500 1,500

2,000 1,000 1,000

1,000

2,000

artBE, arterial base excess; FFP, fresh frozen plasma; HCO3, bicarbonate; HCT, hematocrit; HES 130/0.4, 6% HES 130/0.4 in 0.9% sodium chloride for injection; INR, international normalized ratio; paCO2, arterial pCO2; paO2, arterial pO2; pHa, arterial pH; PRBC, packed red blood cells; PT, prothrombin time; PTT, partial thromboplastin time

output remained stable and was measured at 280 mL at this point of the procedure. Approximately 30 minutes into the second hip replacement, EBL was 1,100 mL. CO, CI, and SV were measured at 4.2 mL/min, 2.1 L/min/m2, and 66 mL, respectively. A venous hematocrit was measured at 25%. Packed red blood cells (PRBC) were ordered and the infusion started. An additional 500 mL of HES 130/0.4 was given during this time, and a total of 3 PRBC units were infused during the second procedure. Urine output was maintained at greater than 0.5 mL/kg per hour throughout the procedure, with a total output of 480 mL. Along with 3 PRBC units, the final fluid totals were: HES 130/0.4, 1,000 mL; LR solution, 2,500 mL; and EBL, 1,900 mL. Final hematocrit after the blood transfusion was 31%, and final Doppler readings were CO, 5.6 mL/min; CI, 2.9 L/min/m2; and SV, 92 mL.

Case Study 2: Use of HES 130/0.4 in the Management of Massive Blood Loss in a Patient With Penetrating Abdominal Injury A 32-year-old woman (estimated height 165 cm, weight 70 kg) with a stab wound to the upper abdomen was brought to the emergency room. No other injuries were noted. Her vitals were initially stable (heart rate [HR], 90 beats per minute; BP, 125/90 mm Hg), with normal lab values (hematocrit, 40%; platelets, 290 000/mcL; prothrombin time, 12.1 seconds; partial thromboplastin time, 22 seconds; international normalized ratio, 0.95; creatinine, 1.2 mg/dL). A FAST (Focused Assessment with Sonography in Trauma) procedure revealed free fluid in her abdomen. She quickly became hypotensive despite a fluid challenge of 2 L of crystalloids. A large-bore cordis line (8.5 French) was placed in the left subclavian vein and a blood transfusion was initiated (emergency release, uncrossmatched). The patient was rushed to the OR for an emergency exploratory laparotomy. Upon arrival in the OR, patient BP was 80/35 mm Hg and HR was 95 beats per minute. One liter of HES 130/0.4 was started to stabilize BP and to bridge the time until more blood

complicated by renal impairment and reduced liver function. The patient was transferred to the floor on postoperative day 21 and discharged at postoperative day 35. This case is presented as a fictitious report. Any similarities to an original case would be coincidental.

Conclusion

2,500 500

1,000

Postop 6h

products became available. The massive transfusion protocol was activated, and anesthesia was induced using etomidate, fentanyl, midazolam, rocuronium, and sevoflurane. Despite surgical efforts to control bleeding, EBL was massive (ie, greater than 6 L per hour), thus requiring the infusion of large amounts of blood products, including crystalloids and colloids. After 3 hours into ongoing fluid resuscitation, the blood bank could not maintain the timely delivery of blood products, which resulted in a significant compromise of hemodynamics (BP, 45/22 mm Hg; HR, 120 beats per minute). At this time, 2.5 L of HES 130/0.4 along with 500 mL of 5% human albumin were administered as the maximum daily dose of HES 130/0.4 had been reached, and crystalloids (2 L of normal saline [NS]) were given until blood products became available. As the bleeding could not be controlled surgically, the liver/abdomen was packed and the patient was ordered to be transferred to the Interventional Radiology Suite. Before the patient left the OR, rebleeding occurred, which led to immediate abdominal re-exploration and re-packing. Under massive fluid resuscitation with PRBC, fresh frozen plasma (FFP), platelets, HES, and crystalloids, the patient became more stable and then was transferred to Interventional Radiology. One bleeding vessel could be identified (right hepatic artery) and was successfully embolized. About 6 hours after admission to the ER, the patient became hemodynamically more stable and was transferred to the intensive care unit (ICU). EBL was approximately 37 L. Intraoperative fluid resuscitation included 53 units of PRBC, 33 units of FFP, 6 units of platelets, 20 units of cryoprecipitate, 3.5 L of HES 130/0.4, 5.5 L of 5% human albumin, and 6 L of crystalloids (NS) [Table 2]. Despite the massive blood loss and fluid resuscitation with blood products and large amounts of crystalloids and colloids, lab values of coagulation showed close to normal values after admission to the ICU. No re-bleeding occurred. The patient returned to the OR for abdominal washout the following day. The abdominal cavity was surgically closed 3 days later and the patient was extubated on postsurgery day 5. The postoperative course was

Clinical application of current concepts in goal-directed therapy have been facilitated by the development of novel, minimally invasive technologies for the assessment of CO, intravascular volume, and preload responsiveness. Esophageal Doppler flow monitoring of the descending thoracic aorta is one of several modalities currently available to the anesthesia practitioner. This method of functional hemodynamic monitoring allows for real-time intravascular volume assessment of fluid challenges in order to estimate if the patient is fluid responsive and functioning on the steep portion of the Frank-Starling curve.10,11 Colloids have been advocated because of their ability to expand and remain in the intravascular space for a prolonged period of time.1 The safety profile of HES 130/0.4, characterized by a similar duration of volume expansion and decreased plasma accumulation, allows for the administration of larger volumes than previously used with older HES solutions with fewer side effects.7 HES 130/0.4 should not be used in patients with fluid overload, for example patients with pulmonary edema and congestive heart failure. Caution should also be observed in patients with severe liver disease or bleeding disorders.5 Since the introduction of HES 130/0.4 to our institution, practitioners have selected it over other available colloid solutions. Because of the different pharmacokinetic properties of HES 130/0.4, our practitioners have reported more confidence both in its safety and efficacy to correct intravascular volume deficits.

References 1. Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. A rational approach to perioperative fluid management. Anesthesiology. 2008; 109(4):723-740. 2. Rizoli SB. Crystalloids and colloids in trauma resuscitation: a brief overview of the current debate. J Trauma. 2003;54(5 suppl):S82-S88. 3. Finfer S, Bellomo R, Boyce N, et al, and the SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350(22):2247-2256. 4. Choi YS, Shim JK, Hong SW, Kim JC, Kwak YL. Comparing the effects of 5% albumin and 6% hydroxyethyl starch 130/0.4 on coagulation and inflammatory response when used as priming solutions for cardiopulmonary bypass. Minerva Anestesiol. 2010;76(8):584-591. 5. Voluven™ prescribing information. www.fda.gov/downloads/ BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/ NewDrugApplicationsNDAs/UCM083138.pdf. Accessed November 9, 2011. 6. Jungheinrich C, Sauermann W, Bepperling F, Vogt NH. Volume efficacy and reduced influence on measures of coagulation using hydroxyethyl starch 130/0.4 (6%) with an optimised in vivo molecular weight in orthopaedic surgery: a randomised, double-blind study. Drugs R D. 2004;5(1):1-9. 7. Neff TA, Doelberg M, Jungheinrich C, Sauerland A, Spahn DR, Stocker R. Repetitive large-dose infusion of the novel hydroxyethyl starch 130/0.4 in patients with severe head injury. Anesth Analg. 2003;96(5):1453-1459. 8. James MF, Latoo MY, Mythen MG, et al. Plasma volume changes associated with two hydroxyethyl starch colloids following acute hypovolaemia in volunteers. Anaesthesia. 2004;59(8):738-742. 9. Waitzinger J, Bepperling F, Pabst G, Opitz J, Muller M, Baron JF. Pharmacokinetics and tolerability of a new hydroxyethyl startch (HES) 130/0.4 specification: [HES (130/0.4)] after single-dose infusion of 6% or 10% solutions in healthy volunteers. Clin Drug Invest. 1998;16(2):151-160. 10. Noblett SE, Snowden CP, Shenton BK, Horgan AF. Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection. Br J Surg. 2006;93(9):1069-1076. 11. Chatti R, de Rudniki S, Marqué S, et al. Comparison of two versions of the Vigileo-FloTrac system (1.03 and 1.07) for stroke volume estimation: a multicentre, blinded comparison with oesophageal Doppler measurements. Br J Anaesth. 2009;102(4):463-469.

ANESTHESIOLOGY NEWS • DECEMBER 2011

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Are People Still the Weak Link in Drug Safety? Pittsburgh—Human failures rather than technology flaws were the cause of most technology-associated medication errors reported last year at a large Illinois hospital, according to a study presented at the annual meeting of the American College of Clinical Pharmacy (ACCP; abstract 338E). The retrospective analysis of 703 reported medication errors at

Chicago’s Advocate Lutheran General Hospital in 2010, showed that 88% of those associated with technology were human errors and 12% were the result of system malfunctions. The researchers defined technology-related errors as those caused by programming flaws or system breakdowns. All other events were counted as human errors. “We were not surprised to find that

most were human errors and not system errors,” said lead author Jennifer Phillips, PharmD, BCPS, assistant professor of pharmacy practice at Midwestern University Chicago College of Pharmacy. That just meant that a technology worked as programmed, but was used incorrectly or built-in safety nets were bypassed, she said. “It could be a training issue, or maybe

BRIEF SUMMARY CONSULT PACKAGE FOR FULL PRESCRIBING INFORMATION

VOLUVEN® (6% HYDROXYETHYL STARCH 130/0.4 IN 0.9% SODIUM CHLORIDE INJECTION) 1 INDICATIONS AND USAGE Voluven® (6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride injection) is indicated for the treatment and prophylaxis of hypovolemia. It is not a substitute for red blood cells or coagulation factors in plasma. 4 CONTRAINDICATIONS The use of Voluven® is contraindicated in the following conditions: • known hypersensitivity to hydroxyethyl starch [see General Warnings and Precautions (5.1)] • fluid overload (hyperhydration) and especially in cases of pulmonary edema and congestive heart failure • renal failure with oliguria or anuria not related to hypovolemia • patients receiving dialysis treatment • severe hypernatremia or severe hyperchloremia • intracranial bleeding. 5 WARNINGS AND PRECAUTIONS 5.1 General Warnings and Precautions Anaphylactoid reactions (mild influenza-like symptoms, bradycardia, tachycardia, bronchospasm, non-cardiac pulmonary edema) have been reported with solutions containing hydroxyethyl starch. If a hypersensitivity reaction occurs, administration of the drug should be discontinued immediately and the appropriate treatment and supportive measures should be undertaken until symptoms have resolved. [see Adverse Reactions (6)] Fluid status and rate of infusion should be assessed regularly during treatment, especially in patients with cardiac insufficiency or severe kidney dysfunction. In cases of severe dehydration, a crystalloid solution should be given first. Generally, sufficient fluid should be administered in order to avoid dehydration. Caution should be observed before administering Voluven® to patients with severe liver disease or severe bleeding disorders (e.g., severe cases of von Willebrand´s disease). 5.2 Monitoring: Laboratory Tests Clinical evaluation and periodic laboratory determinations are necessary to monitor fluid balance, electrolyte concentrations, kidney function, acid-base balance, and coagulation parameters during prolonged parenteral therapy or whenever the patient’s condition warrants such evaluation. 5.3 Interference with Laboratory Tests Elevated serum amylase levels may be observed temporarily following administration of the product and can interfere with the diagnosis of pancreatitis. At high dosages the dilutional effects may result in decreased levels of coagulation factors and other plasma proteins and a decrease in hematocrit. 6 ADVERSE REACTIONS 6.1 Overall Adverse Reaction Profile From the accumulated clinical development experience, expected adverse reactions after administration of Voluven® occurring in less than 10% of patients are as follows: Immune system disorders (Rare, >0.01% to <0.1%): Products containing hydroxyethyl starch may lead to anaphylactoid reactions (hypersensitivity, mild influenza-like symptoms, bradycardia, tachycardia, bronchospasm, non-cardiac pulmonary edema). In the event of an intolerance reaction, the infusion should be discontinued immediately and the appropriate emergency medical treatment initiated. [see General Warnings and Precautions (5.1)] Skin and subcutaneous tissue disorders (Common, >1 to <10%, dose dependent): Prolonged administration of high dosages of hydroxyethyl starch may cause pruritus (itching) which is an undesirable effect observed with all hydroxyethyl starches. Investigations (Common, >1% to <10%, dose dependent): The concentration of serum amylase can rise during administration of hydroxyethyl starch and can confound the diagnosis of pancreatitis. At high doses the dilutional effects may result in decreased levels of coagulation factors and other plasma proteins and in a decrease of hematocrit. [see Interference with Laboratory Tests (5.3)]

6.2 Adverse Reactions in Clinical Trials Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug may not reflect the rates observed in practice. During clinical development, 471 patients were exposed to Voluven®, and a total of 768 patients received the hydroxyethyl starch 130/0.4 drug substance contained in Voluven® at different concentrations (2%, 4%, 6%, or 10%) and at cumulative doses of several mL up to 66 L1). The mean duration of treatment with hydroxyethyl starch 130/0.4 was 3.9 ± 3.3 days, mean cumulative doses were 3338 ± 3695 mL, and the longest follow-up period was 90 days. In the US trial, 100 patients undergoing elective orthopedic surgery were treated either with Voluven® (N=49) or hetastarch (6% hydroxyethyl starch in 0.9% sodium chloride injection) (N=51) for intraoperative volume replacement. Mean infusion volumes were 1613 ± 778 mL for Voluven® and 1584 ± 958 mL for hetastarch. Adverse reactions observed in at least 1% of patients: In the US trial comparing Voluven® with hetastarch, a possible relationship to Voluven® was reported in five cases in a total of three patients (aPTT elevated, PT prolonged, wound hemorrhage, anemia, pruritus). A possible relationship to hetastarch was reported in five patients (three cases of coagulopathy; two cases of pruritus). The three coagulopathy cases in the hetastarch group were serious and occurred in patients receiving more than the labeled ceiling dose (20 mL/kg), whereas no serious coagulopathy occurred in the Voluven® group. 6.3 Postmarketing Experience The following adverse reactions have been identified during the post-approval use of Voluven® and other types of hydroxyethyl starch solutions. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The safety profile from postmarketing experience of Voluven® is not different from the profile obtained from clinical trials performed using the product. Based on spontaneous reporting of hypersensitivity reactions, urticaria, bronchospasm, or hypotension were the most frequently reported serious adverse drug reactions for patients treated with Voluven®. With the administration of hydroxyethyl starch solutions, disturbances of blood coagulation can occur depending on the dosage2). 10 OVERDOSAGE As with all plasma volume substitutes, overdosage can lead to overloading of the circulatory system (e.g. pulmonary edema). In this case, the infusion should be stopped immediately and if necessary, a diuretic should be administered. [see General Warnings and Precautions (5.1)] 16 HOW SUPPLIED/STORAGE AND HANDLING Voluven® (6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride injection) for intravenous infusion is supplied in the following primary container and carton sizes: Polyolefin bag (freeflex®) with overwrap: 500 mL Carton of 15 x 500 mL NDC 0409-1029-01 Store at 15° to 25°C (59° to 77°F). Do not freeze.

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there are too many alerts and we need to reduce them to prevent alert fatigue,” Dr. Phillips said. The study’s main objective, however, was not to determine a human-versustechnology error ratio, but to see if one type of technology was more prone to errors than others. The researchers found that the answer was yes. Errors associated with computerized physician order entry (CPOE) led all other types with 30% of 303 reported technology-associated errors. The pharmacy information system (PIS) ranked second with 20% of reported errors. Dr. Phillips said one factor in the higher proportion of CPOE errors might be the large number of resident physicians at the 654-bed teaching hospital. An institution that has a smaller resident staff might have fewer CPOErelated medication errors because of a more stable cadre of physicians better trained in technology system use, she said. Digging Deeper A second goal was to determine at which points in the medication use process various types of errors were mostly likely to occur. The results showed that much depended on whether or not errors were associated with technology. If they were, errors were more likely to happen during prescribing (35% of reported

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TE CH N OL OG Y ‘[Tech-related errors] could be a training issue, or maybe there are too many alerts and we need to reduce them to prevent alert fatigue.’ —Jennifer Phillips, PharmD, BCPS technology-related errors vs. 16% of non–technology-related ones). In contrast, the highest proportion of non– technology-related errors occurred during administration (34% of non– technology-related errors vs. 13% of technology-related ones). In addition, the research showed that technology-related errors were more likely than non–technologyrelated errors to be near misses (59% vs. 51%, respectively), and non–technology-related errors were more apt to reach patients than technology-related errors (45% vs. 35%, respectively), although these errors did not result in harm. To Dr. Phillips, these findings made sense because the largest percentage of technology-related errors occurred during prescribing, where the errors were most likely to be caught in downstream safety nets. Conversely, the large proportion of non–technology-related errors occurring in the final stage meant a lower likelihood of detection

before reaching the patient. The number of errors resulting in harm was too small to draw any conclusions, she said. The next phase of the investigation, Dr. Phillips said, will be to look at the top two or three technologyrelated errors and see what can be done to prevent them and also improve performance.

Medication Practices (ISMP), in reviewing the study, noted that “just because you have technology doesn’t mean it’s safer. Certainly, there are unintended consequences of all the new technologies that we have to try to address.” But overall, Dr. Levine added, technology has been “very beneficial” to pharmacy. “Certainly having comISMP’s Take on Results mon databases has been a big plus,” he Stuart Levine, PharmD, informat- said, and so have “clinical decision supics specialist at the Institute for Safe port systems that provide information

to pharmacists as to when they should contact the physician when doses are out of range.” Dr. Levine took issue with the focus on human activity as the source of a high proportion of the medication errors reported in the study. “Rather than human errors, these may be system flaws and deficiencies that lead people down the wrong path,” he said. —Bruce Buckley

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Managing the Difficult Pain Case

Case Study 1:

Spinal Cord Stimulation as Treatment for Neuropathic Pruritus Sanjay S. Sastry, MD Director, Lake Mary Pain Relief Center Lake Mary, Florida Kristina H. Berger, MD Family Practice Physician Oviedo, Florida

Case Description The patient was a 44-year-old white woman who was a homemaker from Florida. She was referred by her neurologist and presented with complaints of daily severe itching discomfort in the plantar aspect of the left foot for approximately 1 year. The symptom was reported as deep within the sole of her foot. The itching was so severe that the patient scratched incessantly at night. When scratching would not relieve the itching, the patient stated she took a kitchen knife or fork and “carved into” her foot for relief. Her primary care provider, dermatologist, allergist, and physiatrist could not determine the etiology of her symptom. She had tried different shoes, various skin creams, and medications including pregabalin and loratadine, all without improvement in her symptom. She reported several surgeries for left ankle fractures secondary to injuries sustained 30 years ago when she was a gymnast.

Diagnosis and Treatment After evaluating the patient, the physician deemed she was within normal limits except for the plantar aspect of the left foot. The top half of the sole of the foot demonstrated open wounds in various stages of healing. The patient stated this was due to her scratching her foot with a kitchen utensil to relieve the itching. Magnetic resonance imaging (MRI) of the left foot and ankle showed no obvious abnormality. Electromyography (EMG) with nerve conduction velocities demonstrated findings consistent with left tarsal tunnel syndrome. The patient subsequently was referred for psychiatric evaluation to rule out psychological disorders. She also was referred to podiatry for further foot care. Three nerve blocks were performed at 2-week intervals toward the posterior tarsal tunnel. This treatment alleviated her itching

for 5 days after each block was done. Peripheral nerve blocks at the foot and ankle levels did not result in prolonged relief of pruritus. Her podiatrist reported that the patient was at high risk for amputation because of chronic infections of the left foot. Her psychiatrist and neurologist said the patient exhibited no psychological impairment, but recommended long-term relief of her symptoms. At this point, the potential benefits of spinal cord stimulation (SCS) were discussed with the patient and she consented to a trial. Treatment was initiated by fluoroscopically guided trial placement of dual percutaneous spinal cord stimulator cylindrical octrode leads in the lumbar epidural space. This procedure was performed in the office under mild sedation with 5 mg of oral diazepam 30 minutes prior to the procedure. Using retrograde technique, after injecting

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Pa in M e d ic ine local anesthesia, access was gained to the L2-3 epidural space. The first octrode lead was placed left paramedian to the L4-5 region from lateral to medial. The second lead was placed through the L3-4 epidural space as well as crossing the primary octrode lead and left paramedian to the spinous process of L4-5 epidural space region. The distal end of the second lead was focused toward stimulating the left L4-5 nerve root (Figure 1). The patient reported paresthesia covering the left foot. The best coverage was with the octrode lead, which was most lateral. The patient subsequently returned after 3 days of the trial period, at which time the trial leads were removed. The patient stated that she had 80% to 90% relief of her pruritus. A month later, she had permanent implant of spinal cord stimulator using dual cylindrical octrode leads in the L4-5 region with retrograde placement (Figure 2). The patient had excellent stimulation, which provided effective relief. At 1-month followup, the patient’s left foot wounds had completely healed. At 1-year follow-up, the patient continued to be symptom-free.

Discussion

Figure 1.

SCS has been used to treat many pain syndromes, but there are very few cases involving treatment for non–pain-related syndromes. This patient had intractable pruritus, which endangered The difficulty lies in creating substantial paresthenot only her left foot, but also her overall health. sia, which is stimulation for pain relief in the soles SCS evidently provided relief from pruritus. The of the feet not easily covered by the usual anterorarity of this syndrome makes it difficult to con- grade thoracolumbar approach. Therefore, a retroduct a large-scale assessment of the effectiveness grade approach creating stimulation close to the of SCS. SCS for lower-extremity pain takes place L4-5 nerve root is indicated for a patient such as usually in the low thoracic, high lumbar region. this one.

Figure 2.

Now, 2.5 years after the procedure, the patient has continuing relief from her symptom. Thus, SCS may be a viable treatment option for patients with continuous intractable neuropathic pruritus, and further studies are warranted.

Case Study 2:

The Addicted Patient in Acute Care Yvonne D’Arcy, MS Pain Management and Palliative Care Nurse Practitioner Suburban Hospital-Johns Hopkins Medicine Bethesda, Maryland

Case Description Cindy C. was a 46-year-old patient admitted to the hospital emergency room with right thigh pain. She rated her pain at 10/10 and reported the pain as constant on the anterior aspect of her thigh. She said she had started having the discomfort 2 days before and it was getting worse. She requested intravenous hydromorphone to relieve her pain. In her history, she revealed no major health problems but had pollen allergy and asthma. Cindy said the pain started a day after she injected heroin into a vein in her thigh. On examination, the area was tender but not red or warm. A Doppler study revealed a significant blood clot in a thigh vessel, for which the patient needed surgery.

In her pain history, Cindy said she not only used heroin, but chewed 6 to 8 tablets of 80 mg extended-release oxycodone and used 30 mg of oxycodone several times per day between her extended-release doses. She said she enjoyed the way oxycodone made her feel, but she did not have pain diagnoses. Her heroin use was reported as infrequent but her legs had depressed circular scars indicating subcutaneous injections called “skin popping”—a route used by addicts when they have damaged their veins beyond repair. After the surgery, Cindy was placed in the postanesthesia care unit. Again, she said her pain was severe and she needed something to manage it. She was put on a hydromorphone patient-controlled analgesia (PCA) pump with a baseline

infusion of 1 mg per hour and a frequent bolus dose. She also was offered extended-release morphine 45 mg twice per day to supplement the intravenous medications. Within 24 hours, Cindy refused the morphine, stating it caused headache and nausea. She requested extended-release oxycodone. The postoperative course was complicated by an infection that required incision and drainage. The postoperative pain relief was provided by PCA for the first 3 days along with low-dose extendedrelease oxycodone, then a conversion was made to oral extended-release oxycodone 80 mg 3 times per day with oxycodone 20 mg every 3 hours as needed. Cindy became oversedated on the drugs see difficult pain page 36

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P A I N M E DI C I NE Difficult Pain continued from page 35 when the dose was increased to 4 times per day, so the dose was decreased to 3 times per day. At best, her pain was rated 5/10, which she deemed acceptable. She also had intravenous hydromorphone available for dressing changes. In addition to the opioids, she received pregabalin 75 mg twice per day, off-label, to help reduce opioid use and address any neuropathic elements of the pain.1 On discharge, the patient was grateful for the help she received with her pain management. She never revealed the source of her prescription medications, and she did not wish to enter an outpatient treatment program. But she realized that her drug injecting was beginning to present serious health problems for her; however, this realization was not enough to motivate her to change her lifestyle.

Discussion This patient presented with several interesting issues. She was an addict but she had also just had a painful surgery. She not only used illicit drugs but she also used prescription drugs for pleasure. Treating an addicted patient such as this one means using opioids in some form. In the acute care setting, a physician’s focus after surgery is on treating the pain and moving the addicted patient to discharge. Trying to withhold pain medication or switch to a nonopioid drug will leave the patient with uncontrolled pain and withdrawal. Using standard techniques, such as PCA, also can present a problem for some prescribers who believe that an IV drug abuser will just escalate medication use once it begins. Dose control and frequent use monitoring will determine how the medication is being used and the

effect it produces. The addicted patient may never reach a pain level below 5/10 but it should be possible to move the pain intensity score 2 points to make a clinically significant pain reduction.2 Also problematic are which drug and the route to use. The patient is an admitted IV drug injector and abuses prescription medications. Her drug source is unknown so drug quality is questionable. Using a PCA will help establish what the patient needs to control pain at a reasonable level. This patient needs to understand that the medication is not being used to further her addiction, but to control her pain. Close monitoring of PCA use along with the extended-release medication can help determine what the real need is for adequate pain control. This particular patient also used oral medication. The trial of moving to another extendedrelease oral medication was not successful, but switching to extended-release oxycodone provided adequate pain relief and allowed the patient to be discharged in a timely fashion. This was not the first choice, but helped improve the level of pain relief and allowed the patient to work toward discharge. Even though not opioid-naive, it is possible for that patient to become oversedated if enough medication is taken. As health care providers in acute care, we need to treat all patients who are admitted to the facility. This means, in some cases, we have to treat patients who are addicted to illicit drugs or who are abusing prescription drugs. We may be seeing more addicted patients because prescription drug abuse is currently increasing. One estimate puts the national rate of sales in the United States at 710 mg of prescription opioids per person.3 Additionally, increased access to these drugs is attributable to “pill mills” or illegitimate pain clinics,

where prescriptions are provided to almost any patient who complains of pain.3 Cindy was an honest patient. She was able to provide a good report of what she was doing with drugs so we could move her toward better pain relief. Patients who continue to report unrelieved pain may be abusing opioids or illicit drugs and their cases may require further investigation. Most case reports of unrelieved pain may be resolved with dose or medication adjustments, but in other cases, addiction may be a factor. Signs of addiction such as track marks, irritated nasal mucosa, or skin popping scars will signal that the patient either is actively using illicit drugs or has a history of illicit drug use. For those health care providers who feel reluctant or unsure of how to best treat these individuals, consulting professionals such as pain management specialists or behavioral health specialists can provide direction and support for treatment decisions.

References 1. Tippana EM, Hamunen K, Kontinen VK, Kalso E. Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety. Anesth Analg. 2007;104(6):1545-1556. 2. Farrar JT, Young JP, Lamoreaux L, Werth JL, Poole R. Clinical importance of changes in chronic pain intensity measured on an 11 point numerical pain rating scale. Pain. 2001;94:149-158. 3. Fiore K. Deaths for OD of RX pain killers triple in 10 years. 2011; Health News from Medpage Today. Available at www. everydayhealth.com/printview.

Additional information American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine Public Policy Statement on the Rights and Responsibilities of Health Care Professionals in the Use of Opioids for the Treatment of Pain (2004). Available at www.ampainsoc.org. D’Arcy Y. How to manage pain in addicted patients. Nursing. 2010;40(8):60-64.

ClipChart Madison, Wis: After the long, northern winters here, more than six in 10 anesthesia providers at the University of Wisconsin have inadequate blood levels of vitamin D, a critical nutrient for healthy bones, researchers have found. he study, of 124 anesthesiT ologists, residents and other anesthesia caregivers, found that 25% had vitamin D levels below 20 ng/dL, 61% had levels below 30 ng/dL and 6% had levels considered deficient—putting them at increased risk for fractures. Madison is at the 43rd parallel north, approximately the same latitude as Boston.

Boston: In Africa, roughly 75% of patients do not have access to a pulse oximeter. In Latin America, the figure is 41%; in southern Asia, 49%. All told, 77,000 operating rooms worldwide do not have the devices—considered one of the most important monitors in the hospital by the World Health Organization. The nonprofit group Lifebox (www.lifebox.org) hopes to change those statistics. ed by Atul Gawande, MD, the Harvard L surgeon and OR checklist advocate, Lifebox has launched a campaign to close what it calls the “pulse oximetry gap.” Working with Acare Technology Co., a Taiwan-based device maker, the group promises to provide the instruments to operating rooms in need for a donation of $250. Lifebox is a collaboration of the Harvard School of Public Health, the Association of Anaesthetists of Great Britain and Ireland and the World Federation of Societies of Anaesthesiologists.

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Former Smokers Report Less Chronic Pain Than Current Smokers Chicago—For smokers with chronic pain, kicking the habit may do more than simply reduce the risk for cancer and other health problems associated with tobacco use—it may also ease their discomfort. A new study presented at the 2011 annual meeting of the American Society of Anesthesiologists (ASA; abstract 462) found that current smokers had

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significantly more intense and impairing pain, as well as more anxiety and depression than people who never smoked; however, former smokers and never-smokers scored the same in these areas. According to Michael Hooten, MD, associate professor of anesthesiology at Mayo Clinic, in Rochester, Minn., the results help confirm a link between

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smoking and pain severity suggested by previous research, including his own. However, the nature of that link is not fully understood, said Dr. Hooten, an expert on smoking and pain who was not involved in the current study. “This is an evolving area of research and, at the moment, we don’t really know exactly how smoking impacts pain severity,” Dr. Hooten told

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Anesthesiology News. “For example, it may be that quitting smoking improves depression, a factor known to affect pain. Less depression might in turn reduce pain.” Lead investigator Jenna Goesling, PhD, a postdoctoral fellow in the Department of Anesthesiology at the University of Michigan Medical School, in Ann Arbor, noted the importance of elucidating the relationships among smoking, pain and mood disorders. “Approximately 23% of the general population are smokers, compared with as many as 40% of chronic pain patients,” Dr. Goesling said. “At our center, about 30% of patients are current smokers and another 30% are former smokers, so this is a very relevant focus of research interest.” Dr. Goesling and her team analyzed data from 321 consecutive chronic pain patients treated at the University of Michigan’s Back & Pain Center, including 88 current smokers, 97 former smokers and 136 never-smokers.

Blocking Morphine’s Itchy Side Effect

tching is one of the most prevalent side effects of opioids like morphine. But until now, researchers have been stumped as to why these effective pain suppressors cause the irritation. New research shows that a particular variant of the µ-opioid receptor (MOR) in the spinal cord, called MOR1D, controls itch. Investigators from Washington University in St. Louis found that blocking MOR1D in the spinal cord of mice halted morphine-induced itching without interfering with the drug’s ability to relieve pain (Cell 2011;147:447-458). “It is exciting to know that MOR1D actually functions as an itch-specific receptor,” said principal investigator Zhou-Feng Chen, PhD, director of Washington University’s Center for the Study of Itch, a new multidisciplinary center aimed at translating basic itch research into novel treatments.

December 2011

AnesthesiologyNews.com I 39

Pa in M e d ic ine

BPI Pain Intensity subscale BPI Pain Interference subscale a

HADS - Depression subscale HADS - Anxiety subscale

Former vs. Never-Smokers (P value)

6.95

6.16

6.28

0.001

7.56

6.59

6.43

0.000

11.64

8.17

8.11

0.000

10.70

7.48

7.84

0.000

BPI, Brief Pain Inventory; HADS, Hospital Anxiety and Depression Scale; NS, not significant a

Current vs. Never-Smokers (P value)

Never-Smokers (n=136)

Former Smokers (n=97)

Current Smokers (n=88)

Table. Pain, Depression and Anxiety Among Current, Former And Never-Smokers

A score of 11 to 21 on the HADS for depression or anxiety indicates need for psychiatric treatment.

Dr. Hooten’s suspicion that improved mood can partly explain why quitting smoking may improve pain symptoms. Giving up cigarettes has “important tangible benefits in [the chronic pain] population” and clinicians should include smoking cessation as an element of care for the growing number of chronic pain patients, he said. “These results are very hopeful in that they demonstrate a significant potential benefit of quitting smoking on the severity and impact of chronic

pain,” Dr. Goesling said. She urged clinicians to address comorbid mood disorders in chronic pain patients who smoke, but also emphasized the importance of using “caution when interpreting these results as our understanding of the relationship between quitting smoking and pain is still preliminary.” The ASA has made smoking cessation a priority. For more on the group’s antismoking initiative, visit www.asahq. org/stopsmoking. —David Wild

The researchers conducted statistical analyses to determine any correlation between smoking status and pain severity, which they measured using the 11-point Brief Pain Inventory. They also examined scores on the Hospital Anxiety and Depression Scale (HADS), which includes two 21-point anxiety and depression subscales. The investigators controlled for the potential confounding effects of depression, age, sex and education. The team found that smokers had significantly higher average scores on all of the measures than never-smokers (Table). In contrast, former smokers and chronic pain patients who had never smoked had nearly identical scores. The analysis also revealed no dose–response relationship between the amount of cigarette consumption and the severity of pain. But controlling for depression reduced the statistical difference in scores between current smokers and never-smokers, supporting More specifically, Dr. Chen explained, opioids such as morphine first activate MOR1D, which subsequently connects to an itch-specific receptor in the spinal cord called gastrin-releasing peptide receptor (GRPR). GRPR specifically transmits itch but does not carry pain information. The researchers also found that another variant of the µ-opioid receptor called MOR1 exclusively mediates morphine’s analgesic effects in the spinal cord but does not prevent itch; when blocking MOR1, the mice no longer received the drug’s pain-killing benefits, but continued to scratch. Based on the results of the current study, Dr. Chen suspects that additional variants of the receptor may be related to nausea, respiratory depression, constipation or other common side effects associated with the use of pain-killing drugs. This discovery raises the hope of generating new treatments to eliminate itch, and potentially other side effects, in patients who rely on opioids to relieve chronic and severe pain, the researchers said. —Victoria Stern

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40 I AnesthesiologyNews.com

December 2011

P A I N M E DI C I NE

Simulated Patient Assessment Powerful Tool In Pain Medicine Education Las Vegas—The Pain Paradox, an hour-long continuing medical education program, has the potential to significantly boost pain clinicians’ comfort and competence with prescribing opioids, according to a study presented at PAINWeek 2011. The program significantly increased

the percentage of clinicians who said they were “comfortable” or “very comfortable” prescribing controlled substances, and clinicians were better able to assess the potential of pain patients to become addicted to opioids, the investigators said. “There is a compelling need to

improve the competencies of clinicians who undertake the management of long-term opioid therapy,” said Russell K. Portenoy, MD, the Gerald J. Friedman Chair in Pain Medicine and Palliative Care at Beth Israel Medical Center, in New York City, who was not involved in the Pain

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Clinicians’ comfort level prescribing controlled substances significantly improved. Paradox program. “This early experience is encouraging and supports the value of additional work using the simulated patient strategy to teach safe opioid prescribing.” The investigators collected data during the Pain Paradox activities held at five medical meetings over two years: PAINWeek 2009 and 2010, American Pain Society 2009 and 2010 and the American Academy of Pain Medicine 2010. Physicians, nurses, pharmacists and psychologists viewed a number of educational posters using an audio guide, and then participated in a simulated assessment with a live patient led by an experienced pain physician. Simulated patient scenarios included an elderly woman who runs out of prescriptions early and a middle-aged woman with an inappropriate result on a urine drug test (UDT). Before and after the assessment, participants responded to multiple-choice questions regarding risk factors associated with addiction, UDT, treatment agreements, legal requirements for prescribing controlled substances and differential diagnoses related to aberrant behaviors. These questions were designed to showcase any gaps in knowledge, such as the subtle but significant differences between addiction, pseudoaddiction, physical dependence and medication intolerance. For example, participants

December 2011

AnesthesiologyNews.com I 41

Pa in M e d ic ine More Education Needed The study, however, also exposed gaps in knowledge that persisted after the program. At baseline, 56% of clinicians considered unexpected UDT results for prescribed medications as definitive evidence of diversion rather than a broad differential that included diversion. When educated on the complexities of UDT, including variable metabolism and the possibility of laboratory error, 32% of participants still interpreted the lack of an opioid in a

UDT as definite diversion. After the simulation, clinicians continued to struggle to differentiate between pseudoaddiction (50%), medication tolerance (60%) and physical dependence (51%), and still showed significant deficiencies about current legal obligations for prescribing controlled substances. “There is a need for future programming, as demonstrated by the fact that we identified some large knowledge gaps,” said James Miller, MD, of

Educational Awareness Solutions in Norwalk, Conn., who helped design the Pain Paradox program and tabulating answers to the pre- and post-program test questions. “We were trying to move [pain clinicians] a little bit outside their comfort zone, to be able to make quick judgments, such as ‘I need to get more information before I make a decision, ask the patient some more questions or get some more testing done.’” —Rosemary Frei, MSc

Focus on Inhaled Anesthesia Podcast Series had to answer several true or false statements such as “It is easy to determine who will become a problematic user of opioids” and “A patient who escalates his dose and returns early for a refill is probably developing an addiction.” Both statements are false. The investigators found that clinicians’ comfort level prescribing controlled substances significantly improved from 67% at baseline to 87% after the activity (P<0.01). Furthermore, 86% of clinicians reported comfort with prescribing controlled substances three months after the program. “The participants were very positive—they found this [program] innovative and unique, and could go back to their practices on Monday and make positive changes, feel more comfortable and give their patients better care,” said Howard Heit, MD, a pain specialist at Georgetown University’s School of Medicine, in Washington, D.C. Dr. Heit was one of the program’s creators along with Douglas Gourlay, MD, MSc, of the Wasser Pain Management Centre, at Mount Sinai Hospital, in Toronto, Canada; John Peppin, MD, of The Pain Treatment Center of the Bluegrass, in Lexington, Ky.; and Paul Arnstein, RN, PhD, of Massachusetts General Hospital, in Boston. The program was funded by unrestricted educational grants from Cephalon, Mallinckrodt and Purdue.

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42 I AnesthesiologyNews.com

December 2011

C LI N I C A L A N ESTHESI O LO G Y

Results for Glucose Control in Cardiac ICU Not All Sweet

wo different critical care teams are reporting mixed results meeting infection prevention goals set forth by the Surgical Care Improvement Project (SCIP). For investigators at the University of Chicago, the problematic goal was SCIP INF-4, which specifies keeping blood glucose levels in cardiac surgery patients to less than 200 mg/dL

at 6 a.m. on the first and second days after surgery. Clinicians at the university’s medical center routinely failed to hit the goal, they reported at the 2011 annual meeting of the American Society of Anesthesiologists (ASA; abstract 1372). However, missing the goal had no demonstrable effect on infection rates or hospital length of stay (LOS). In the second study (abstract 1706),

by researchers at Maimonides Medical Center, in New York City, compliance with some of the SCIP modules increased significantly over the study period. And they documented shorter hospital LOS, as well as a trend toward decreased mortality. But the team was unable to show a significant reduction in rates of infection as a result of the SCIP compliance efforts.

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The University of Chicago Experience In the University of Chicago study, the investigators conducted an eightmonth retrospective review of patients who had undergone cardiac surgery. The researchers examined patient charts and ICD-9 codes to determine the type of surgery the patients had and the presence of diabetes, congestive heart failure, hypertension and ischemic heart disease. They also measured ICU duration, hospital LOS and infection rates. Of the 188 patients who had undergone cardiac surgery during the study period, 165 passed the blood glucose control measure and 23 did not. Although patients who did not meet the required level had a significantly higher incidence of diabetes (52% vs. 29%; P<0.03), those who passed and those who failed had similar outcomes with regard to ICU duration (median, 60.43 vs. 72.6 hours; P=0.928), hospital LOS (median, 171.83 vs. 211.25 hours; P=0.328) and infection rates (15.15% vs. 13.04%; P=1.00), the investigators reported. “In our small population, we found no real difference between the two groups,” said Avery Tung, MD, professor and quality chief for anesthesia in the University of Chicago’s Department of Anesthesia and Critical Care, who led the study. “Looking at our outcomes, it’s not apparent what the risk factors are for infection. In this case, it may not be just glucose.” Whatever the explanation may be for the disconnection between SCIP and noncompliance, the implications are clear, Dr. Tung said. “Our data clearly suggest that complying with SCIP INF-4 may not improve outcomes, and it also raises the possibility that the benefits of glucose control in cardiac surgery patients may be overstated.” Study co-author Katherine D. Mieure, PharmD, a clinical pharmacy resident specializing in cardiothoracic surgery, noted that although there is evidence to support the requirements for people with diabetes, the breadth of the SCIP glucose control module may be problematic. “One study in patients with diabetes showed an association between blood glucose over 200 mg/dL and deep tissue infections, but we are obligated to follow these measures for all patients, not only those with diabetes,” she said. “The [ideal blood glucose goal] may differ depending on pre-op

December 2011

AnesthesiologyNews.com I 43

CL I N I CA L A N E S TH E SIOL OG Y

risk, including whether patients have diabetes.” In other words, she said, patients who don’t have diabetes may have more leeway, and higher blood glucose levels may not present as much risk for them as for their diabetic counterparts. Dr. Mieure stressed that variables affecting blood glucose need to be considered in this clinical setting. “A protocol would help as would finding a systematic way to affect patient outcomes, but as all pharmacists and physicians know, the variables for blood glucose control are many. There may

not be just one stan- the 200 mg/dL postsurgical blood gludard that will work.” cose target set forth by SCIP INF-4— was not significantly different (22.3% At Maimonides, of patients in 2006 vs. 15.6% in 2009; A Bit More Success P=0.17). Possible contributing facThe team at Maimonides tors included higher body mass index Medical Center tracked out- of patients in 2009 vs. 2006 (30.75 vs. comes related to several SCIP 29.12 kg/m2; P=0.024) and inadequate infection prevention measures, efforts to optimize serum glucose preincluding prophylactic adminis- operatively, the investigators suggested. tration of antibiotics, perioperative glucose control and intraoperative use of insulin. Mortality and hospi- ‘Looking at our outcomes, tal LOS also were assessed. it’s not apparent what The study was based on a review of 460 cardiac surgeries performed the risk factors are for at the hospital in 2006 (n=227) and 2009 (n=233; the SCIP national infection. In this case, it campaign began in 2005). Overall, 179 patients had diabetes and 284 may not be just glucose.’ were using insulin. The intraoperative use of insu—Avery Tung, MD lin was significantly higher in 2009 than in 2006 (66.7% vs. 57.3%; As far as other SCIP quality control P=0.043), indicating a growing awareness of the SCIP INF-4 qual- measures, the study showed that comity measure, the team reported. How- pliance with antibiotic prophylaxis was ever, despite increased use of insulin, significantly increased in 2009 comcompliance with intraoperative blood pared with 2006 (93.2% vs. 88.75%, glucose goals—a precursor to meeting respectively; P<0.001).

Altogether, the infection control measures had some impact: Patients in 2009 had a significantly shorter hospital LOS (7.71 vs. 8.4 days; P<0.001) and slightly lower mortality (3.16% vs. 5.6%; P<0.1) than 2006 patients, the team reported. However, rates of sternal wound infection did not differ significantly between the two groups (0.63% in 2009 vs. 1.53% in 2006; P<0.2). More Questions Than Answers? For Dr. Tung, these types of studies may raise more questions than answers, especially in the assessment of the impact of blood glucose on postoperative infection. “It comes down to the risk-and-gain argument,” he said. “What are you risking by tighter control, and what do you have to gain by meeting these requirements? And is there any way we can predict risks associated with not meeting the requirements? A larger study might help us get a better grip on that. But right now, the answers are not clear.” —Terri D’Arrigo

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44 I AnesthesiologyNews.com

December 2011

C LI N I C A L A N ESTHESI O LO G Y Table. The Double-A Genotype Was Strongly Associated With Cancer Deaths

Genes continued from page 1 The findings, presented at the 2011 annual meeting of the American Society of Anesthesiologists (ASA; abstract JS05), came as “pretty much of a surprise” to the investigators, said study leader Andrey Bortsov, MD, PhD, assistant professor of anesthesiology at UNC. “We think this is a very strong association.” Dr. Bortsov and colleagues analyzed the genetic makeup of 2,039 women diagnosed with breast cancer, who had participated in the Carolina Breast Cancer Study—a longitudinal, population analysis of the disease that began in 1993. Opioid Genetics The researchers wanted to see if variations in the G allele of the µ-opioid receptor gene, OPRM1 A118G, affected a woman’s risk for death from breast cancer. In particular, because the 118G form of the allele ratchets down the receptor’s responsiveness to opioids, the UNC team hypothesized that women with one or more of these variants would be more likely to survive their cancer.

The results of the study supported that hypothesis. According to Dr. Bortsov’s group, women who had at least one variant copy of the allele were half as likely to die of breast cancer by 2006 as those with the typical form. Women with two copies of the 118G variant were four times as likely to survive the disease (Table). Samuel McLean, MD, said OPRM1 is the best understood opioid gene. “We know that if you have a G allele, you respond less well” to the drugs. “If you have cancer, you will need more opioids over time if you have a G allele. If it takes more opioids, that’s bad for you for controlling your pain, but it may be good because of the other effect,” he said. Most Americans of European and African ancestry have an A allele of the OPRM1 gene, Dr. McLean noted. The G allele is less common, appearing in about 30% of European Americans, but only about 7% of African Americans. That difference might help explain why black women are significantly more likely to die of breast cancer than women from other racial and ethnic groups with the malignancy, the researchers suggested.

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Number of Participants

Breast Cancer Deaths

% of Breast Cancer Deaths P Value

A/A

1,682

296

17.6

A/G

323

8.7

G/G

4.6

A/A

1,332

290

21.8

A/G

233

G/G

A118G Genotype All cases

0.0001

Invasive cases 0.0006

‘We’re a long way from having any evidence that opioids patients take for cancer pain are harming them. There is animal data that’s provocative, but obviously we can’t take humans and not give them opioids if they have cancer. That’s the last thing we want to do.’ —Samuel McLean, MD Dr. McLean cautioned that although opioids appear to play an important role in the growth and spread of cancer, how they do so remains unclear. Indeed, it’s not even known if the opioids that patients take for cancer pain have an effect on cancer cells beyond that of the endogenous opioids that the body already produces. “We’re a long way from having any evidence that opioids patients take for cancer pain are harming them,” Dr. McLean said. “There is animal data that’s provocative, but obviously we can’t take humans and not give them opioids if they have cancer. That’s the last thing we want to do.”

Jonathan Moss, MD, PhD, professor of anesthesia and critical care at the University of Chicago, said the North Carolina work “confirms a growing body of in vitro and animal data from several laboratories, including our own, suggesting a role of the µ-opioid receptor in cancer progression.” However, Dr. Moss said, too many questions remain to consider altering clinical practice. “We don’t want to scare patients,” Dr. Moss said. “Our paper and theirs did not address giving opioids and may relate to endogenous opioids. While I may personally believe there could be effects which would change practice, there are no randomized, double-blind studies on Mouse Data Bolster Link this. There are no direct, prospective, New cellular evidence backs the randomized controlled [trial] data UNC findings. In an unrelated study suggesting that opioids influence canalso presented at the ASA meeting cer progression in humans, but several (abstract JS08), researchers from the studies contribute to the debate.” University of Chicago showed that Jeffrey L. Apfelbaum, MD, profescancer cells modified to overexpress sor of anesthesia at the University of the µ-opioid receptor are far more Chicago, who was not involved in likely to grow and spread than those the studies, agreed. “They need some with normal levels of the protein. prospective studies to clearly delinUsing a line of human lung can- eate what major practice changes cer cells that they transplanted into might need to take place,” said nude mice, the researchers found that Dr. Apfelbaum, a member of the editooverexpression of the opioid receptor rial board of Anesthesiology News. “But caused the growth rate of the tumors they’re working on that.” to rise 2.5-fold. Metastasis of the tumors spiked by a factor of 20. —Adam Marcus

December 2011

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CL I N I CA L A N E S TH E SIOL OG Y

Heart Health Strongly Linked to Outcomes After Neurosurgery

atients with heart failure are nearly five times more likely to die after neurosurgery than patients without the condition, according to new research from the University of Virginia in Charlottesville. The investigators reviewed the records of all neurosurgical patients at UVA between 1994 and 2008. Patients were divided into those with congestive heart failure (CHF; n=906) and those without the condition (n=20,968), which affects roughly 20% of the population. The investigators took data from the first neurosurgery in patients who had multiple surgeries during the study period. They also performed statistical analyses to evaluate the impact of CHF and other comorbidities on mortality after neurosurgery, hospital length of stay (LOS) and hospitalization costs. Approximately 4% of patients who underwent neurosurgery had CHF. Patients with CHF had a mortality rate of 14.7%, compared with 3.2% in patients without the illness (P<0.001). CHF was found to be an independent factor in determining mortality. CHF also was shown to increase hospital LOS by 8.2 days and the adjusted cost of hospitalization by $20,096 per patient. “It’s kind of obvious that folks who are sicker will do worse,” said study co-author Narayana Varhabhatla, MD, an anesthesiology resident at UVA, whose group reported its findings at the 2011 annual meeting of the American Society of Anesthesiologists (abstract 1021). “But the significant increase in mortality was the most surprising finding. It’s important to optimize patients with CHF before any surgery. What’s special about neurosurgery needs to be teased out.” “Like any good study, this raised more questions,” said study senior author Zhiyi Zuo, MD, PhD, professor of anesthesiology at UVA. These include whether physicians can improve heart function—through the use of diuretics, digoxin and cardiac rehabilitation—to reduce mortality and LOS. The authors said they hope to study these associations in a larger database of patients. The current study is a follow-up to work showing that patients with chronic pulmonary disease undergoing neurosurgery had statistically

significant increases in hospital LOS and costs. Those results were published earlier this year in the Journal of Neurosurgery (2011;115:375-379). George Williams II, MD, assistant professor of anesthesiology and neurosurgery at the University of Texas Medical School at Houston, said he would have liked more information about the severity of patients’

heart failure, as CHF is a broad term encompassing illness of varying degrees. “Without knowing the types of heart failure and types of neurosurgery that these patients had, it’s hard to tell what to conclude from this,” he said. “But it is very interesting, and perhaps we can draw something useful from this study.”

One mechanism that could explain the higher mortality is that patients with CHF have less perfusion to the end organs, he said. It could be that they need better perfusion to heal well. “Heart failure patients would do worse secondary to reduced perfusion, fluid retention and a diminished tolerance to surgical stress,” Dr. Williams added. —Karen Blum

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Anesthesia Oral Board Review: Knocking Out the Boards

Jessica A. Lovich-Sapola Cambridge University Press, October 30, 2009 This book is specially designed for the American Board of Anesthesiology Oral Examination. The evidence-based approach is presented in a concise outline-oriented format. More than 100 topics have already been board review–tested by residents who have passed the oral board exam.

Anesthesiology Oral Board Flash Cards

Jeff Gadsden; Dean Jones McGraw-Hill, August 25, 2011 The cards are designed to impart best patient care for a specific disease/ condition or surgical procedure. Great for studying alone or with a partner, these cards teach residents how to think through an unexpected operating scenario.

ORDeR ONlINe For pricing, a more complete review and easy ordering with a credit card, go to McMahonMedicalBooks.com. We can supply any medical book in print, so if you don’t find the book you want, email your request with billing information to RMcMahon@McMahonMed.com. If you are an author and would like your medical book featured in this book section, contact Ray McMahon, Publisher, at RMcMahon@McMahonMed.com.

Atlas of Airway Management: Techniques and Tools

Steven Orebaugh Lippincott Williams & Wilkins, October 10, 2011 Clinical applications in airway management are dependent on both the anatomy of the individual and the individual’s comorbidities, with different tools available for different patient presentations. New sections have been created on pediatric applications, bronchoscopy, special airway considerations in the emergency room and the ICU, and postintubation care issues.

Atlas of Image-Guided Intervention in Regional Anesthesia and Pain Medicine

James Rathmell Lippincott Williams & Wilkins, November 7, 2011 This atlas is a practical guide for practitioners who perform interventional procedures with radiographic guidance to alleviate acute or chronic pain. The author provides an overview of each technique, with detailed illustrations of the relevant anatomy, technical aspects of each treatment, and a description of potential complications. The author also discusses medical evidence on the technique’s applicability.

Diagnosis, Management, and Treatment of Discogenic Pain: Volume 3: A Volume in the Interventional and Neuromodulatory Techniques for Pain Management Series Leonardo Kapural; Philip Kim Elsevier/Saunders, September 29, 2011 This book presents state-of-the-art guidance on the full range of discogenic pain relief techniques performed today. The authors offer expert advice on a variety of procedures to manage and treat discogenic pain.

Intrathecal Drug Delivery for Pain and Spasticity: Volume 2: A Volume in the Interventional and Neuromodulatory Techniques for Pain Management Series Asokumar Buvanendran; Sudhir Diwan Elsevier/Saunders, September 29, 2011 This book presents state-of-the-art guidance on the full range of intrathecal drug delivery techniques performed today. The authors offer expert advice on a variety of procedures to treat chronic non-malignant pain, cancer pain, and spasticity.

Spinal Injections & Peripheral Nerve Blocks: Volume 4: A Volume in the Interventional and Neuromodulatory Techniques for Pain Management Series Marc Huntoon; Honorio Benzon; Samer Nauroze Elsevier/Saunders, September 29, 2011 This book presents state-of-the-art guidance on when and why these procedures should be performed, the mechanisms of action on pain and current guidelines for practice. The authors offer expert advice and scientific evidence supporting the use of spinal injections and sympathetic nerve blocks.

Understanding Pain Anatomical Chart

Lippincott Williams & Wilkins Lippincott Williams & Wilkins, November 8, 2006 This visual and textual overview of pain provides an easy-to-understand tool for patient interaction with health professionals. A pain scale and a sample human figure are provided so patients can give their health professionals information about the level and location of pain. AN1211

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Lesson 295: PreAnesthetic Assessment of the Patient With Systolic or Diastolic Heart Failure WRITTEN BY:

CALL FOR WRITERS

Megan Lanigan, MD,a and Richa Dhawan, MDb a Resident, Department of Anesthesia and Critical Care, University of Chicago Medical Center, Chicago, Illinois b Assistant professor, Department of Anesthesia and Critical Care, University of Chicago Medical Center, Chicago, Illinois

If you would like to write a CME lesson for Anesthesiology News, please send an email to Elizabeth A.M. Frost, MD, at ElzFrost@aol.com.

REVIEWED BY: Mark Chaney, MD Professor, Department of Anesthesia and Critical Care, University of Chicago Medical Center, Chicago, Illinois

DATE REVIEWED: November 2011 DISCLOSURES The authors and the reviewer have no relationships with pharmaceutical companies or manufacturers of products to disclose. This educational activity may contain discussion of published and/or investigational uses of agents for the treatment of disease. The FDA has not approved some uses of these agents. Please refer to the official prescribing information for each product for approved indications, contraindications, and warnings.

NEEDS STATEMENT Diagnosing congestive heart failure (CHF) may be difficult in the elderly or obese patient. Complications during anesthesia can lead to increased morbidity and mortality. Recognizing this common condition has been identified by committee as required knowledge for anesthesiologists.

TARGET AUDIENCE Anesthesiologists

LEARNING OBJECTIVES At the end of this activity, the participant should be able to: 1. List the diagnostic criteria for CHF with preserved ejection fraction (EF). 2. Differentiate the diagnostic criteria between CHF with, and without, preserved EF. 3. Define the American College of Cardiology/American Heart Association and New York Heart Association classifications for CHF. 4. Identify differences in ventricular structural abnormalities in CHF with and without preserved EF. 5. Quote the prevalence and demographics of CHF. 6. Outline the pathophysiology leading to CHF. 7. Discuss the treatment options for patients with CHF. 8. Evaluate the patient with acute decompensated heart failure. 9. Explain the anesthetic implications for CHF. 10. Establish hemodynamic goals for patients with CHF.

CASE HISTORY A 55-year-old woman presented for ventral hernia repair. Her medical history included several hospitalizations during the past 5 years for shortness of breath and chest pain. The most recent occurrence was 9 months previously, at which time changes were made to her medications. A recent cardiac catheterization revealed nonobstructive coronary artery disease; stress echocardiography revealed an EF of 68%. The patient had a history of long-standing hypertension—poorly controlled as a result of sporadic compliance with medication regimens. Physical examination findings were unremarkable. Her medications included lisinopril, metoprolol, and aspirin. Her blood pressure was 165/85 mm Hg, and heart rate was 70 beats per minute.

eart failure (HF) is a complex syndrome that can be defined hemodynamically as an inability to provide adequate cardiac output to support the metabolic demands of the body, or to do so only at elevated filling pressures. Clinically, it is characterized by signs and symptoms of dyspnea on exertion, fatigue, orthopnea, edema, and rales. Congestive heart failure (CHF) typically has been subdivided into systolic heart failure (SHF) and diastolic heart failure (DHF). The ejection fraction (EF) is normal or near normal in almost 50% of patients diagnosed with HF.1 Numerous underlying alterations in cardiovascular physiology lead to HF, including myocardial ischemia, congenital anomalies, valvular disease, and pericardial disease; all result in a constellation of similar clinical signs and symptoms. HF continues to be a major health problem in the United States with nearly 5 million people affected.2 As the management of HF improves, the

PREANESTHETIC ASSESSMENT Dr. Elizabeth A.M. Frost, who is the editor of this continuing medical education series, is clinical professor of anesthesiology at the Mount Sinai School of Medicine in New York City. She is the author of Clinical Anesthesia in Neurosurgery (Butterworth-Heinemann, Boston) and numerous articles. Dr. Frost is past president of the Anesthesia History Association and former editor of the journal of the New York State Society of Anesthesiologists, Sphere. She is also editor of the book series based on this CME program, Preanesthetic Assessment, Volumes 1 through 3 (Birkhäuser, Boston) and 4 through 6 (McMahon Publishing, New York City).

A COURSE OF STUDY FOR AMA/PRA CATEGORY 1 CREDIT Read this article, reflect on the information presented, then go online (www.mssm.procampus.net) and complete the lesson posttest and course evaluation before December 31, 2012. (CME credit is not valid past this date.) You must achieve a score of 80% or better to earn CME credit. TIME TO COMPLETE ACTIVITY: 2 hours RELEASE DATE: December 2011 TERMINATION DATE: December 31, 2012 ACCREDITATION STATEMENT The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT The Mount Sinai School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credits.™ Physicians should only claim credit commensurate with the extent of their participation in the activity. It is the policy of Mount Sinai School of Medicine to ensure objectivity, balance, independence, and scientific rigor in all CMEsponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled or unapproved drugs or devices.

CONTINUING MEDICAL EDUCATION

This lesson is available online at www.mssm.procampus.net

number of individuals living with the disease increases. As a result, more patients admitted for surgery have HF.

Prevalence and Demographics The prevalence of HF has been increasing both within the United States and worldwide. In the United States, about 500,000 new cases are diagnosed annually. Approximately 1 in every 5 people aged 40 in the United States will develop HF in his or her lifetime, with the prevalence increasing with increasing age. Approximately 6% to 10% of people older than 65 years have HF. The prevalence of DHF is estimated to be 15%, 33%, and 50% at ages less than 50 years, 50 to 70 years, and more than 70 years, respectively.1,3,4 Patients with DHF are more likely to be older, women, and hypertensive, and less likely to have had previous myocardial infarction or coronary artery disease (CAD) than patients with SHF.2

Clinical Manifestations The symptoms are similar between SHF and DHF. Typically, patients have poor exercise tolerance, dyspnea on exertion, fatigue, orthopnea, paroxysmal nocturnal dyspnea, or chest pain. Accompanying signs indicating fluid overload include peripheral edema, an S3 or S4 heart sound on auscultation, pulmonary crackles, and jugular venous distention.2 Some patients predominantly experience dyspnea and intolerance to activity, whereas others may have signs of fluid overload exclusively, without dyspnea.5 Patients with DHF typically have exercise intolerance secondary to an elevation in left atrial and pulmonary venous pressures that occur with worsening left ventricular (LV) relaxation. Under normal circumstances, exercise results in an increased heart rate that reduces diastolic filling time and may result in pulmonary edema and worsened cardiac output in patients with impaired ventricular relaxation.6

Classifications of Heart Failure The American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the assessment of chronic HF classifies patients based on 4 stages of symptoms (Table 1). The New York Heart Association (NYHA) categorizes HF based on levels of physical exertion required to illicit symptoms (Table 2).4,7 In addition to various methods for classifying chronic HF, it has been divided classically into 2 distinct phenotypes: HF with reduced ejection fraction (HFrEF) or SHF

and HF with preserved ejection fraction (HFpEF) or DHF (Table 3). HFrEF or SHF is a pathologic state in which abnormal cardiac function results in an inability of the heart to pump adequate blood at a rate required to meet the metabolic demands of the body. The principal derangement in SHF is impaired contractile function leading to a decreased EF. HFpEF or DHF is a pathologic state in which impaired relaxation or resistance to LV filling results in congestion, or in filling of the ventricular chamber only at elevated pressures to maintain sufficient stroke volume.5 DHF affects approximately 50% of patients with chronic HF. Whether SHF and DHF are 2 distinct forms of HF, or instead are extremes in a spectrum of overlapping phenotypes remains controversial. Those who support the spectrum hypothesis claim that HF is a complex multifactorial disease, and similar to other complex diseases, it has a broad linear distribution with varying phenotypes at opposite ends of a bell-shaped spectrum. The distribution of EFs in HF falls along a bell-shaped curve, and under this hypothesis, DHF and SHF fall at opposite ends of the spectrum. It is for this reason, proponents argue, that the 2 forms of HF have different characteristics and clinical responses to therapy. They note that systolic dysfunction is not unique to HFrEF, as aspects of systolic dysfunction can be found in HFpEF.8 Proponents of the theory that SHF and DHF are 2 separate phenotypes within a spectrum of HF argue that the distribution of EFs seen in HF actually is bimodal, not unimodal. They also point out that the ventricular and cellular remodeling patterns seen in SHF and DHF are distinct from one another, that SHF and DHF tend to develop in different patient populations, and that the progression and pathogenesis of the disease are distinct.2

Pathophysiology The syndrome of HF can progress from a number of chronic cardiovascular conditions, including hypertension, ischemic myocardial disease, myocarditis, valvular disease, disorders of the pericardium, and other cardiomyopathies ultimately leading to the expression of similar signs and symptoms in the spectrum of HF. The underlying pathogenesis of HF is widespread. Hypertension and advancing age are the greatest risk factors for the development of DHF. By contrast, CAD causes about two-thirds of SHF cases; other nonischemic causes include myocarditis, thyroid disease, alcohol use, and other behaviors inflicted on the myocardium.2,4

Table 1. ACC/AHA Classification of Chronic Heart Failure Stage

Description

A: High-risk for HF

HTN, DM, CAD, family history of CHF

B: Asymptomatic HF

Valve disease, previous MI, LV dysfunction

C: Symptomatic HF

Dyspnea, fatigue, exercise intolerance

D: Refractory end-stage HF

Marked symptoms of HF despite optimal medical management

ACC, American College of Cardiology; AHA, American Heart Association; CAD, coronary artery disease; CHF, congestive heart failure; DM, diabetes mellitus; HF, heart failure; HTN, hypertension; LV, left ventricle; MI, myocardial infarction

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Table 2. New York Heart Association Classification System Stage

Description

Asymptomatic with normal physical activity

Symptomatic with moderate exertion

III

Symptomatic with minimal exertion

Symptomatic at rest

Adequate peripheral circulation in HF is maintained by compensatory mechanisms that include hypertrophy, stimulation of the reninâ&#x20AC;&#x201C;angiotensinâ&#x20AC;&#x201C;aldosterone system, and retention of salt and water. Myocardial remodeling and conversion from compensated hypertrophy to HF involve complex molecular and cellular changes, including myocyte growth and death, as well as changes in the extracellular matrix. These alterations result in changes to myocardial structure and function that impair systolic function, diastolic function, or both. Stimuli for these changes include mechanical strain on myocytes, neurohormones (eg, norepinephrine and angiotensin), inflammatory cytokines, and other growth factors.9 Increased LV mass is seen in most forms of HF; however, the patterns of ventricular remodeling differ between SHF and DHF. The ventricular chamber often is dilated in HFrEF, but less so in HFpEF.2 In HFpEF, the ventricular cavity size often remains the same or decreases, and end-diastolic and end-systolic volumes remain normal or decrease. In HFpEF, there is an increase in wall thickness, mass, and the ratio of mass-to-chamber volume.5 In HFrEF, the cardiomyocyte is narrow and elongated with reduced myofibrillar density. By contrast, in HFpEF the myocyte diameter and resting tension are both increased. There also are differences in the balance between matrix metalloproteinases (enzymes that play a role in cell proliferation and apoptosis) and their inhibitors in HFrEF and HFpEF.2 In animal models of HFrEF, fibrillar collagen is degraded. This differs from the pressure-overloaded hypertrophy seen in HFpEF, a result of increased collagen and collagen crosslinks.5 The resulting hemodynamic profile may be similar between SHF and DHF. In SHF, a reduced EF leads to decreased cardiac output, increased LV end-diastolic volumes, and a passive increase in left atrial and pulmonary venous pressures. In DHF, there also is an increase in left atrial and pulmonary venous pressures resulting from the increase in LV diastolic pressure. Thus, both forms may lead to pulmonary congestion, and chronically can lead to increased pulmonary vascular resistance.5 Normal diastolic function involves a process of active myocardial relaxation, which occurs early in diastole. It results in a rapid decline in pressure causing a suction effect that helps LV filling, as well as passive distention of the LV that occurs in late diastole. During this later phase of diastole, atrial contraction contributes approximately 20% to 30% of the total LV filling volume at low pressures. In diastolic dysfunction, loss of normal LV relaxation and distensibility from either structural or functional abnormalities results in impaired ventricular filling and

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Table 3. Comparison of Systolic and Diastolic Heart Failure

Major Criteria

SHF

DHF

Paroxysmal nocturnal dyspnea

Demographics

Younger, male, CAD/history of MI

Older, female, hypertensive

Neck vein distension

Pathophysiology

Impaired contractile function, decreased EF

Impaired myocardial relaxation, normal EF

Rales

Chamber/cellular remodeling

Ventricular chamber dilation, elongated/ narrow myocytes, reduced myofibrillar density, degradation of fibrillar collagen

Normal or decreased ventricular chamber size, increased ventricular wall thickness, increased ratio of mass-to-chamber volume, increased myocyte diameter, increased collagen and collagen crosslinks

Radiographic cardiomegaly

Treatment

β-blockers, ACEIs/ARBs, diuretics, CRT

β-blockers, ACEIs/ARBs, aldosterone antagonists (lack of significant evidence for survival benefit), dihydropyridine CCB Note: sensitive to preload reduction; caution with nitrates, diuretics, ACEIs

ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; CAD, coronary artery disease; CCB, calcium channel blocker; CRT, cardiac resynchronization therapy; DHF, diastolic heart failure; EF, ejection fraction; MI, myocardial infarction; SHF, systolic heart failure

Acute pulmonary edema S3 gallop Increased central venous pressure (>16 cm H2O at right atrium) Hepatojugular reflux Weight loss >4.5 kg in 5 days in response to treatment Minor Criteria Ankle edema, bilaterally Nocturnal cough

elevated filling pressures. LV filling shifts from predominantly occurring in early diastole to more later-phase diastole due to an inability of the ventricle to actively relax. Atrial contraction in turn contributes more to diastolic filling under these conditions.10

Diagnosis The signs and symptoms of HF often are nonspecific and include dyspnea, exercise intolerance, weakness, and fatigue; these also can be present in other disease states—including non-cardiac–mediated diseases such as thyroid abnormalities, pulmonary disease, obesity, and anemia. There is no officially established set of diagnostic criteria for HF; however, there are a number of commonly used systems including the Framingham criteria, Boston criteria, and Duke criteria. In the commonly used Framingham criteria, the diagnosis of HF requires the simultaneous presence of 2 major criteria, or 1 major and 2 minor criteria (Figure 1).11 It is difficult to distinguish between SHF and DHF based on clinical signs and symptoms. An elevated level of brain natriuretic peptide is a reliable means of diagnosing HF, but does not help distinguish between SHF and DHF. A brain natriuretic peptide level greater than 100 pg/mL has been shown to be 95% sensitive for the diagnosis of HF, but only 14% specific for detecting systolic failure.12 Nonspecific tests—such as chest x-ray that reveals cardiomegaly and electrocardiography (ECG) that reveals signs of LV hypertrophy or ischemia—can be used as diagnostic aids. Overall, the diagnosis of SHF involves assessing various clinical signs and symptoms from the patient’s medical history, in addition to echocardiographic evidence of decreased EF. The diagnosis of DHF is more controversial and can include a number of diagnostic methods. In the European Society of Cardiology guidelines, 3 conditions must be met concurrently for a diagnosis of DHF (Figure 2).13 There are a number of methods for evaluating impaired relaxation, the third parameter. Cardiac catheterization is the gold standard because it directly measures ventricular diastolic pressure, particularly the rate of decline in

LV pressure in early diastole, and end-diastolic pressure. The procedure involves the use of fluid-filled catheters or micromanometer catheters. Doppler ECG is less invasive, however, and is now the primary way to noninvasively assess diastolic function.12 Blood inflow velocity in the transmitral valve is evaluated by Doppler ECG. Peak velocities of blood flow during early diastolic filling (E-wave) and atrial contraction (A-wave) are measured and the ratio calculated. Under normal conditions, E-wave velocity is greater than A-wave velocity because atrial contraction contributes little to diastolic filling. The E-to-A ratio is approximately 1.5. In early diastolic dysfunction due to a slower relaxation time secondary to ventricular stiffness, atrial contraction contributes more to filling; the relationship reverses and the E-to-A wave ratio is less than 1—which is typical of grade I diastolic dysfunction. In grade II diastolic dysfunction due to increasing left atrial pressures, early diastolic velocities are elevated. This causes an increase in the E-wave, and the E-to-A ratio increases again to “normal” or pseudonormal levels. With further worsening of diastolic dysfunction, LV diastolic pressure rises considerably. Atrial contraction contributes less to ventricular filling because of high enddiastolic pressures; thus, the E-to-A wave ratio rises significantly due to the drop in A- wave pressure. The ratio often goes above 2, which is seen in grades III and IV diastolic dysfunction. E-to-A wave ratios are affected by mitral valve anatomy, blood volumes, and abnormal cardiac rhythms including atrial fibrillation. Therefore, in these settings the ratios are of limited use for diagnosing diastolic abnormalities.12 In clinical practice, a diagnosis of DHF is usually one of exclusion in symptomatic patients who have documented preserved EF.

Evaluating Acute Decompensated Heart Failure In patients with a history of HF, acute decompensation can commonly present as respiratory failure. It is important for the anesthesiologist to recognize the signs and

Dyspnea on ordinary exertion Hepatomegaly Pleural effusion Decrease in vital capacity by one-third from maximum recorded Tachycardia (heart rate >120 bpm)

Figure 1. In the commonly used Framingham criteria, the diagnosis of heart failure requires the simultaneous presence of 2 major criteria, or 1 major and 2 minor criteria.

The presence of signs and symptoms of CHF (eg, see Figure 1) The presence of normal or mildly abnormal LV systolic function Documented impairment of relaxation, filling, or diastolic compliance

Figure 2. In the European Society of Cardiology guidelines for diagnosing DHF, 3 conditions must be met simultaneously. CHF, congestive heart failure, DHF, diastolic heart failure; LV, left ventricular

symptoms of this hemodynamic state because it presents a significant risk to the patient for complications. Elective surgery should be avoided until the condition is stabilized. Acute decompensated HF typically results from SHF or DHF with a number of different stimulating factors. The clinical presentation commonly includes significant dyspnea because of a rapid accumulation of fluid in interstitial lung spaces that typically results from acutely elevated cardiac filling pressures. Patients characteristically present with cough, dyspnea, fatigue, and occasionally chest pain.

CONTINUING MEDICAL EDUCATION

This lesson is available online at www.mssm.procampus.net

Tachypnea, tachycardia, and either hypertension or hypotension may develop. Classical physical findings include crackles or wheezing on auscultation (indicating significant pulmonary edema), S3 or S4 heart sound on cardiac examination, and elevated jugular venous pressures (indicating elevated right-sided filling pressures).13 The patient should be evaluated for precipitating factors. Common causes include myocardial infarction or ischemia, severe hypertension, atrial fibrillation or other arrhythmias, and acute valvular abnormalities such as mitral or aortic regurgitation. The diagnosis of acute decompensated HF is based on a typical clinical presentation. Supporting tests to confirm the diagnosis include ECG for signs of ischemia, chest radiography for signs of pulmonary edema, brain natriuretic peptide levels that can be significantly elevated, and echocardiography to assess valvular abnormalities and overall cardiac function.

optimal medical management, found that the LVAD group had better 1- and 2-year survival rates than patients in the medical management alone group.3 The goals in treating patients with DHF include relief of symptoms, elimination of exacerbations, and reduced mortality; however, the mainstay drugs used in treating SHF—including ACEIs, ARBs, β-blockers, and aldosterone antagonists—have not been shown to be as effective against DHF in multiple studies. According to the ACC/ AHA guidelines, the management of DHF should include treatment of hypertension, maintenance of sinus rhythm, prevention of tachycardia and ischemia, and reduction of venous pressure.6

Treatment Based on a number of randomized controlled trials, drug therapy has been the primary treatment for SHF. Surgical therapy makes use of several devices as well as transplantation. Diuretics are a key component of drug therapy for symptomatic relief of water retention in patients with SHF. The dose is titrated by monitoring weight and electrolyte status with the goal of maintaining euvolemia. Diuretics, however, have not been shown to prolong survival. By inhibiting the renin–angiotensin–aldosterone system (which often is abnormally activated in the progression of HF), angiotensin-converting enzyme inhibitors (ACEIs) have significantly benefited patients, including fewer symptoms of HF and hospital admissions, and prolonged survival. Angiotensin receptor blockers (ARBs) are an alternative therapy in patients with ACEI intolerance. Multiple randomized trials of various ARBs found beneficial effects, including decreased hospitalizations. Spironolactone, an aldosterone receptor antagonist, has been found to increase survival in patients with HF, in addition to ACEIs. A key component of drug therapy for HF is the use of β-blockers to decrease chronic sympathetic activation.3 Cardiac transplantation remains the definitive treatment for HF, although there is an overall lack of available transplant organs in the United States. A number of alternative surgical treatment options exist, however, including coronary revascularization for ischemic causes of HF, valve replacements, and LV reconstruction for pathologic remodeling. Cardiac resynchronization therapy, which involves the use of biventricular pacing in a synchronized mode, has been used in patients in whom EF is less than 35% and QRS duration is greater than 0.12 seconds (ie, patients with abnormal conduction and possible ventricular contraction dyssynchrony). Cardiac resynchronization therapy in combination with optimal medical management has been shown to improve functional class, exercise capacity, and EF, and reduce mortality in patients with SHF. Increasingly, LV-assist devices (LVADs) are used because many patients develop refractory HF despite medical management. The REMATCH (Randomized Evaluation of Mechanical Assistance in the Treatment of Congestive Heart Failure) trial, in which patients were randomized to receive optimal medical management, or LVAD plus

Blood pressure control reduces LV end-diastolic pressure, improves relaxation of the ventricle leading to improved early filling, decreases ischemia, and reduces LV hypertrophy, thus inhibiting further diastolic dysfunction. ACEIs have been shown to increase exercise capacity and possibly reduce the risk for hospitalization of patients with DHF; however, ACEIs have not been shown to improve overall prognosis in a number of studies evaluating these drugs for treatment of hypertension in HFpEF. Despite a lack of data on overall decrease in mortality, ACEIs, ARBs, and aldosterone antagonists are the recommended drugs for treating hypertension in diastolic failure. Maintenance of sinus rhythm or avoidance of tachycardia improves relaxation and increases diastolic filling time. If conversion to sinus rhythm is not possible, rate control is important. Calcium channel blockers or β-blockers are recommended. Specifically, dihydropyridine calcium channel blockers have been shown to be beneficial in the treatment of diastolic dysfunction, in contrast to SHF.6 Patients with DHF who have a small, stiff left ventricle are particularly sensitive to decreases in preload; this can result in a significant fall in cardiac output. Therefore, these patients may not tolerate diuretics, venodilators such as nitrates, ACEIs, or calcium channel blockers.

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Implications and Goals for Anesthesia CHF has important implications for surgery and anesthesia. A number of studies have demonstrated significant risks for morbidity and mortality after noncardiac surgery in patients with HF. A study by Hammill et al14 looked at 159,327 patients with HF undergoing noncardiac surgery and found an 8.0% incidence of operative mortality—more than double the incidence among patients with CAD and more than triple the incidence in the control group. After controlling for comorbidities, there was a 63% higher incidence of operative mortality among patients with HF compared with controls; the rate for all causes of 30-day readmission also was significantly higher. Perioperatively, a number of hemodynamic changes can occur that affect both systolic and diastolic functions. A thorough preoperative evaluation of the patient’s HF symptoms and exercise tolerance should be obtained. Patients with HF are particularly sensitive to changes in volume status, as well as increases in afterload. Given that there are many different underlying causes of HF, anesthetic and hemodynamic management of these patients may vary depending on the primary pathology. Valvular pathology leading to HF should be treated based on the specific valve affected and the appropriate hemodynamic goals associated with those lesions. In patients with ischemic cardiomyopathies, anesthetic management to optimize myocardial oxygen supply and demand is essential. For the surgical patient with DHF, several hemodynamic changes during the perioperative period exert adverse effects on diastolic filling, including tachycardia, abnormal cardiac rhythm, or myocardial ischemia. Tachycardia decreases the late phase of diastole and reduces cardiac filling, LV end-diastolic volumes, and cardiac output. Atrial fibrillation is not tolerated because optimal cardiac function relies on atrial contraction for LV filling and stroke volume. Acute, severe elevations in systemic blood pressure worsen LV wall stress and can impair myocardial relaxation. Additionally, patients with DHF can be extremely sensitive to decreases in preload, and venodilators should be used with caution. Volume status should be closely monitored, and hypovolemia or volume overload should be avoided. In addition to the negative effects of ischemia on the myocardium, ischemia itself can cause reversible impairment in myocyte relaxation, which further worsens diastolic function. Myocardial ischemia is one of the main mechanisms of LV diastolic dysfunction postoperatively. Factors including pain, shivering, tachycardia, hypertension, and hypoxia increase myocardial oxygen demand and cause ischemia.15 Volatile agents as well as opioids and muscle relaxants do not appear to worsen diastolic dysfunction alone. No studies have demonstrated improved outcomes with certain anesthetic techniques over others, including regional or general anesthesia; however, the anesthesiologist must keep in mind that hemodynamic effects can vary depending on the anesthetic method.

Management of the Case Presented After the patient completed a physical examination and provided her medical history, it was determined that her episodes of HF had been medically optimized. The echocardiogram indicated preserved EF and abnormal relaxation of the left ventricle. Thus, the patient met criteria for diastolic heart dysfunction with episodes of DHF.

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Because this was a laparoscopic repair, general endotracheal anesthesia was chosen. Lidocaine, fentanyl, midazolam, propofol, and vecuronium were administered for induction. Large fluctuations in blood pressure and heart rate were avoided on direct laryngoscopy by administration of 75 mcg of fentanyl before intubation. Routine monitors were used and fluid management was directed at maintaining euvolemia. Small doses of labetalol were administered during emergence and extubation to control heart rate and blood pressure. IV morphine in 5-mg doses was given postoperatively for pain management.

Yuzefpolskaya M, Weinberg C, Kukin M. Advances in systolic heart failure. F1000 Med Rep. 2010;2:31.

Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult; executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to revise the 1995 guidelines for the evaluation and management of heart failure). J Am Coll Cardiol. 2001;38(7):2101-2113.

Oka T, Komuro I. Molecular mechanisms underlying the transition of cardiac hypertrophy to heart failure. Circ J. 2008;72(suppl A):A13-A16.

10. Aurigemma GP, Gaasch WH. Clinical practice: diastolic heart failure. N Engl J Med. 2004;351(11):1097-1105. 11. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971;285(26):1441-1446.

Chatterjee K, Massie B. Systolic and diastolic heart failure: differences and similarities. J Card Fail. 2007;13(7):569-576.

12. Gutierrez C, Blanchard DG. Diastolic heart failure: challenges of diagnosis and treatment. Am Fam Physician. 2004;69(11):2609-2616.

Kazik A, Wilczek K, Poloński L. Management of diastolic heart failure. Cardiol J. 2010;17(6):558-565.

13. Ware LB, Matthay MA. Clinical practice: acute pulmonary edema. N Engl J Med. 2005;353(26):2788-2796.

References 1.

Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure; part I: diagnosis, prognosis, and measurements of diastolic function. Circulation. 2002;105(11):1387-1393.

Criteria Committee of the New York Heart Association. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston, MA: Little, Brown & Co; 1994:253-256.

14. Hammill BG, Curtis LH, Bennett-Guerrero E, et al. Impact of heart failure on patients undergoing major noncardiac surgery. Anesthesiology. 2008;108(4):559-567.

Borlaug BA, Redfield MM. Diastolic and systolic heart failure are distinct phenotypes within the heart failure spectrum. Circulation. 2011;123(18):2006-2014.

De Keulenaer GW, Brutsaert DL. Systolic and diastolic heart failure are overlapping phenotypes within the heart failure spectrum. Circulation. 2011;123(18):1996-2005.

15. Pirracchio R, Cholley B, De Hert S, Solal AC, Mebazaa A. Diastolic heart failure in anaesthesia and critical care. Br J Anaesth. 2007;98(6):707-721.

Visit www.mssm.procampus.net today for instant online processing of your CME post-test and evaluation form. There is a registration fee of $15 for this non–industry-supported activity. For assistance with technical problems, including questions about navigating the Web site, call toll-free customer service at (888) 345-6788 or send an email to Customer.Support@ProCEO.com.

For inquiries about course content only, send an email to ram.roth@mssm.edu. Ram Roth, MD, is director of PreAnesthetic Assessment Online and assistant professor of anesthesiology at The Mount Sinai School of Medicine, New York, NY.

Post-Test 1.

The American College of Cardiology/American Heart Association guidelines for assessing chronic heart failure: a. classify patients according to severity of symptoms b. classify patients based on the stage of symptoms c. include 5 levels of severity d. are the same as the New York Heart Association classification system

The European Society of Cardiology recommends the use of all of the following criteria to diagnose DHF, except: a. presence of symptoms of congestive heart failure (CHF) b. normal LV systolic function c. hypertension d. documented impairment of LV compliance

The principle derangement in diastolic heart failure (DHF) is: a. impaired contractility b. reduced ejection fraction c. impaired ventricular relaxation and compliance d. preserved left ventricular (LV) diastolic pressure

The management of patients with DHF should include: a. treatment of hypertension b. cardiac resynchronization therapy c. aggressive diuresis d. inotropic agents

Which of the following is not a ventricular compensatory mechanism to offset stress on cardiac performance? a. Hypertrophy b. Salt and water retention c. Stimulation of the renin–angiotensin–aldosterone system d. Regional wall motion abnormalities

The incidence of operative mortality for patients with CHF undergoing noncardiac surgery has been reported to be: a. 1% b. 3% c. 8% d. 15%

Risk factors for the development of DHF include: a. hypertension and advancing age b. high-fat diet c. coronary artery disease d. end-stage renal disease

Using the Framingham criteria, a diagnosis of heart failure requires: a. 4 major criteria b. 2 major, or 1 major and 2 minor criteria c. echocardiographic evaluation d. correlation with another system for an accurate diagnosis

Hemodynamic goals during the perioperative period include the following, except: a. maintaining normal sinus rhythm b. avoiding tachycardia c. avoiding hypertension d. avoiding volatile anesthetics because of possible worse outcome

10. In DHF, angiotensin-converting enzyme inhibitors have been shown to: a. improve exercise capacity b. increase the risk for hospitalization c. improve overall prognosis d. lower overall mortality

52 I AnesthesiologyNews.com

December 2011

C LI N I C A L A N ESTHESI O LO G Y

For US-Guided Interscalene Blocks, Close Is Good Enough Las Vegas—Horseshoes, hand grenades, nuclear warfare—and now, it seems, interscalene blocks: four things for which being near the target is basically as good as being smack on it. Needle placement and the distribution of local anesthetics do not seem to affect the characteristics of ultrasoundguided interscalene block after shoulder arthroscopy, according to the results of

a new study by investigators at the University of Pittsburgh Medical Center. Neither variable was associated with significant differences in block setup times, incision pain in the postanesthesia care unit or the duration of analgesia, the researchers reported at the 2011 annual spring meeting of the American Society of Regional Anesthesia and Pain Medicine (abstract 107).

“There can be some variation in terms of what anesthesiologists recommend for interscalene block,” said Steven L. Orebaugh, MD, associate professor of anesthesiology and critical care medicine at Pittsburgh, and leader of the study. “Some [clinicians] have put their needle next to each visible fascicle and injected local anesthetic around them. Others pop into the space near any

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of the fascicles and inject there, wait to see if it surrounds the fascicle, and then adjust the needle position accordingly. Finally, some clinicians simply get a twitch to make sure their needle is in the groove, and inject everything into it.” Dr. Orebaugh and his colleagues sought to determine what happens to the local anesthetic if the needle is inserted in a conventional manner and anesthetic is injected after a twitch is observed. “Where does the local anesthetic go?” he asked. “And does it make a difference in terms of block setup, duration or the success of the block depending on those distribution characteristics?” To help answer these questions, the researchers enrolled 32 patients undergoing shoulder arthroscopy into the trial, all of who received ultrasoundguided anesthesia and nerve stimulation (Table 1). After the brachial plexus was imaged in the interscalene groove, a 5-cm, 22-gauge stimulating needle was inserted and advanced toward visible nerve fascicles. Once any brachial plexus motor stimulation occurred, a solution of 20 mL of 0.75% ropivacaine was injected. The Pittsburgh researchers used a three-point scale for both motor and Table 1. Patient Demographics Age, y

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December 2011

CL I N I CA L A N E S TH E SIOL OG Y 5-6 (n=12)

3-4 (n=10)

1-2 (n=10)

Table 2. Block Characteristics

Duration of Block, h

anesthetic is flowing into the groove, with visible spread adjacent to the Distribution Score nerves, is going to provide an adequate Setup Time interscalene block,” he said. “You don’t necessarily need to go around each visEarly (5 min) 0 0 3 ible fascicle and deliver local anesthetic Intermediate (10 min) 4 6 5 to each one.” Late (20 min) 6 4 4 Jeffrey Gadsden, MD, assistant proMean duration, h 17.4 18.7 17 fessor of clinical anesthesiology at Incision pain in PACU 0 0 1 Columbia University College of PhyPACU, postanesthesia care unit sicians and Surgeons in New York City, sensory blockade to evaluate the degree said the study had important implicaof anesthesia after five, 10 and 20 min- tions for patient safety. utes had elapsed. After surgery, an anesthesiologist blinded to the procedures evaluated ultrasound video and used a six-point quantitative score to rate the degree of distribution around visible nerves. “We found that in about one-third of the blocks, the local anesthetic was completely around and in between the nerve fascicles,” Dr. Orebaugh told Anesthesiology News. “In the other two-thirds, the local anesthetic didn’t completely surround the nerve. In other words, it did not appear to have moved around the nerves to involve the entire medial side as well.” The researchers also reported that when evaluated according to the nature of injectate distribution, no differences were found between patients with early (<5 minutes), intermediate (5-10 minutes) or late block setup time (20 minutes). Similarly, no significant relationship was found between the duration of analgesia and injectate distribution; the typical block lasted 17.6 hours (±4.8 hours; Table 2). “There was a small tendency for those with complete surrounding of the nerves to have a faster setup, but it did not reach statistical significance,” Dr. Orebaugh added. The researchers are planning to enroll more patients into the trial to tease out this finding. The findings indicate that interscalene blocks for shoulder arthroscopy will have a high degree of success regardless of the approach, Dr. Orebaugh said. “For the average shoulder procedure, I think that putting the needle in the groove and making certain that local

“With ultrasound guidance, many of us try to achieve circumferential spread around one or more trunks during interscalene block, often requiring multiple needle passes and increasing the risk for mechanical nerve injury,” Dr. Gadsden said. “These investigators have demonstrated what we long suspected during the era of nerve stimulation: As long as your needle tip is close to the brachial plexus at the interscalene groove, injection of a sufficient volume will ensure a good

30 25 20 15 10 5 0

AnesthesiologyNews.com I 53

Distribution Score

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block, regardless of where the injectate spreads.” It remains to be seen, he added, if this relationship holds true with smaller volumes. “Is unilateral spread around a trunk sufficient if only 5 or 10 mL are used, or do we indeed need to strive for circumferential spread in these cases?” Dr. Gadsden asked. “Since many centers are reducing their local anesthetic volumes substantially, this would be an interesting follow-up study.” —Michael Vlessides

54 I AnesthesiologyNews.com

December 2011

C LI N I C A L A N ESTHESI O LO G Y

Laryngeal Mask Safety in Major Surgery Points to Wider Use

aryngeal masks may be as safe as endotracheal tubes (ETs) for use in surgical procedures lasting more than three hours, a recent study has found. The randomized, prospective trial, presented at the 2011 annual meeting of the American Society of Anesthesiologists (ASA; abstract 1059), comprised 100 patients undergoing

radical retropubic prostatectomy. During procedures averaging nearly four hours, there were no cases of aspiration associated with laryngeal mask airways and fewer cases of intraoperative coughing, compared with the ET group. The study was funded by an unrestricted grant from LMA Deutschland GmbH. “The use of LMAs appears to be

safe and a valuable alternative to ETs for this kind of major surgery in a selected group of patients,” primary investigator Daniel Reuter, MD, PhD, told Anesthesiology News. Dr. Reuter is vice chair of anesthesiology at the University Medical Center HamburgEppendorf, in Germany. Older laryngeal masks are justifiably contraindicated in longer

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procedures because of the risk for aspiration. Newer models that allow for gastric access and can drain gastric contents are likely associated with a lower risk for aspiration—or so hypothesized Dr. Reuter and his colleagues. To test their theory, the researchers randomly assigned the patients to receive airway management with either an LMA (LMA Supreme; LMA North America, Inc.) or endotracheal intubation. Both groups (50 patients each) were similar for premedication, use of spinal anesthesia and respirator settings. The mean age of the patients was 66 years and mean body mass index was 26.9 kg/m2; average ASA physical status was II. The mean length of procedure was 230 minutes (±40 minutes). Dr. Reuter said no patient in either group experienced aspiration; however, four patients in the LMA group and six in the ET group experienced postoperative nausea and vomiting. Seven patients in the ET group experienced intraoperative coughing or choking, compared with none in the LMA group (P<0.01). Although the degree of impairment in lung function was similar between groups immediately after surgery, spirometry testing at 24 hours revealed greater impairment in the ET group (P<0.05). Dr. Reuter said that the only research to examine the safety of LMAs in surgical procedures lasting more than three hours was retrospective and observational, and the results were not conclusive (e.g., Anaesthesia 2009;64:1289-1294). “The fact that ours is the first prospective study looking at this subject strengthens the importance of our results,” Dr. Reuter said. However, Richard Galgon, MD, MS, assistant professor of anesthesiology at the University of Wisconsin School of Medicine and Public Health, in Madison, who was not involved in the trial, said methodological weaknesses limit the ability to draw conclusions from the study. “The most striking design limitation is the size of the study,” Dr. Galgon said. “The aspiration rate in adults is generally about four in 10,000, so it is not surprising that the researchers did not observe any aspirations in either group.” —David Wild

December 2011

AnesthesiologyNews.com I 55

CLINICAL ANESTHESI OLOGY

Walking Speed Good Marker For Surgical Recovery San Francisco—An elderly person’s walking speed can predict how well he or she will fare after an operation, according to a report at the 2011 annual clinical congress of the American College of Surgeons. Researchers from the University of Colorado, in Denver, reported that a simple walking test performed before surgery is a powerful tool for determining the extent to which seniors will recover after heart or colorectal procedures. “Our study showed that this timed up-and-go test is a very sharp predictor of complications and mortality,” said Daniel Wu, MD, study co-author and chief surgical resident at the Denver Veterans Affairs Medical Center, in a press release. “It’s a cheap and simple test that may eventually lead to a change in preoperative care. You really only need a stop watch to perform this test, and the implications are huge.” The findings come from a study of 195 patients aged 65 years and older who were scheduled for heart or colorectal surgery. Before surgery, the researchers gave the patients a short, timed walking test. Patients were asked to stand up from a chair, walk 10 feet, turn around, return to the chair and sit down. After completing the test, the patients were classified as fast (10 seconds or fewer), intermediate (between 11 and 14 seconds) or slow (15 seconds or more). Results showed that slower walking speed was associated with increased risk for complications, longer length of stay and higher rates of discharge to a medical institution after both cardiac and colorectal procedures. Among the 65 colorectal patients, the patients classified as slow spent more than twice as many days in the hospital as fast patients (14.4±12.4 vs. 6.3±4.1 days; P=0.009), and they were 10 times more likely to be discharged to an institution than home (59% vs. 5%; P=0.007). These patients also had significantly higher rates of complications (56% vs. 20%; P=0.0424). Similar differences were shown in patients undergoing heart procedures. Walking speed is a good marker of physical frailty, the investigators said. A walking speed test may distinguish physiologically weak patients in a way that preoperative assessments of heart,

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lung or kidney function might not. The simple walking test is a useful tool that surgeons now can add to their preoperative evaluations of geriatric patients, said Emily Finlayson, MD, assistant professor of surgery, University of California, San Francisco. “It’s something that can be done fairly easily in the clinic. It just takes a minute, and this one simple measure really has a powerful ability to tell us whether patients are going to have complications, whether they are going to have prolonged hospital stays and where they are going to be going after surgery,” she said. Many of the other tests for frailty are cumbersome, she said. This one is not, and the results, although preliminary, are compelling.

‘You really only need a stop watch to perform this test, and the implications are huge.’ —Daniel Wu, MD “With this, we can have really informed discussions with our patients about what the expected outcomes are after their operations and also help with planning afterward. For instance, if you are somebody who is going to require acute rehabilitation after surgery, you can start organizing that even before surgery.” Study co-author Thomas Robinson, MD, associate professor of surgery at Colorado, said he hopes this approach could lead to a more individualized way of deciding who should undergo surgery. “We are designing tests to get away from chronologic age, and instead are now focusing on physiologic age,” Dr. Robinson said. “Ultimately, what we are trying to do is establish very simple tools that the average surgeon can use to determine who is going to fare poorly after an operation.” The research is a proof-of-concept study, and more work is needed to develop an accurate tool for assessing geriatric patients, he added. The investigators are currently organizing a multi-institution trial to confirm the results. —Christina Frangou

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56 I AnesthesiologyNews.com

December 2011

C LI N I C A L A N ESTHESI O LO G Y

“Med Marijuana” Fizzles in PONV Trial Side effects of injected THC halt study early, but expert sees reason for optimism Chicago—Intravenous tetrahydrocannabinol (THC), the active ingredient in marijuana, does not prevent postoperative nausea and vomiting in high-risk patients undergoing elective surgery under general anesthesia, researchers have found. To the contrary, patients in the study group experienced

more sedation, confusion and anxiety than did controls, which led to the trial being stopped after 40 patients participated. “Despite advances in medical research, we still see a lot of postoperative nausea and vomiting,” said Maren Kleine-Brueggeney, MD, senior fellow

at the University of Washington, in Seattle, who led the research. “Oral THC has been shown to prevent nausea and vomiting in cancer patients who receive chemotherapy, and anecdotal evidence suggests that oral THC may prevent PONV. So we decided to perform our double-blind, randomized

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controlled trial with intravenous THC.” The investigators planned on enrolling 320 patients into the study; only 40 (39 women) participated before the trial was stopped. After accounting for smoking status and history of PONV, the patients were randomly assigned to receive either placebo or one dose of THC (0.125 mg/kg) IV 15 minutes before the end of surgery. The incidence of postoperative nausea was similar for the study and control groups (Table). Moreover, no differences were found with respect to vomiting in the first two hours (26% of patients receiving THC vs. 26% receiving placebo), between two and six hours after surgery (0% for THC vs. 5% for placebo; P=0.35) or between six and 24 hours after surgery (13% for THC vs. 6% for placebo; P=0.44). Retching in the first two hours after surgery proved to be significantly more common in patients who received THC than in those who received placebo (53% vs. 21%; P=0.04). The time to extubation after surgery was longer for patients given THC than for controls (20±16 vs. 12±6 minutes; P=0.04). Patients in the THC group also had higher scores for confusion (P<0.01), anxiety (P=0.03), change of perception (P<0.01) and sedation (P<0.01) at admission to the postoperative care unit (PACU). These scores became equal at all time points between 30 minutes and 24 hours after admission to the PACU. Patients who received THC also consumed significantly less fentanyl in the first two hours after surgery than those in the placebo group (P=0.03). One patient given THC experienced Table. Incidence of Nausea

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THC, tetrahydrocannabinol; VAS, visual analog scale a Data missing for one patient.

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AnesthesiologyNews.com I 57

CL I N I CA L A N E S TH E SIOL OG Y extensive mood swings during the first 24 hours after surgery. No significant cardiovascular or respiratory side effects were observed, according to the researchers, who presented their findings at the 2011 annual meeting of the American Society of Anesthesiologists (abstract 834). Despite the disappointing results, Dr. Kleine-Brueggeney said she is not ready to give up on the possibility that THC may prove to be an effective postoperative antiemetic. “We were really positive about the effects of THC prior to the study because of the knowledge we had from chemotherapy patients, but it really seems to be different in this patient population. “So perhaps in a different setting with a different dosage or a different form of administration it might work, but there is certainly not enough evidence to recommend THC for the prevention of PONV.” Daniel I. Sessler, MD, chair of the Department of Outcomes Research at Cleveland Clinic, in Ohio, said the study was stopped too soon. “PONV studies need hundreds of patients,” Dr. Sessler told Anesthesiology News. “The reported results are perfectly consistent with the 25% relative risk reduction provided by ondansetron, dexamethasone and droperidol. The investigators can’t rule out the expected effect. This is not a negative trial; it’s underpowered.” In a related study (abstract 815), Dr. Kleine-Brueggeney’s group and colleagues from the University of Miami Miller School of Medicine found evidence of a genetic effect on the metabolism of THC. “There is some evidence that certain polymorphisms of the cytochrome P450 enzyme might have an effect on the pharmacodynamics and pharmacokinetics of THC,” she said. “So we studied healthy volunteers [n=40] to

evaluate the effects of those polymorphisms on the metabolism of THC.” The healthy, nonsmoking participants were screened for CYP2C9 polymorphisms on chromosomal location 10q24; interim data are available for 16 patients to date. The researchers found that a person’s CYP2C9*3 status significantly affected how much of the COOH-THC metabolite they produced—leading them to conclude that there is a slow metabolizer phenotype for CYP2C9*3.

In other words, genetic variation determines the pharmacokinetics of THC and may impact vital signs and psychotropic side effects, thereby influencing clinical anesthesiology and potentially explaining the varied results noted in the Seattle group’s study. “We observed very different effects between individual patients,” Dr. Kleine-Brueggeney added. “We had some patients who had had PONV previously, received THC and did not experience PONV

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1 ASA Standards for Basic Anesthetic Monitoring, Committee of Origin: Standards and Practice Parameters (Approved by the ASA House of Del egates on October 21, 1986, and last amended on October 20, 2010 with an effective date of July 1, 2011) - Viewed 3-21-11 at ww.asahq.org/.../Standards%20 Guidelines%20Stmts/Basic%20Anesthetic%20Monitor ing%202011.ashx 2 Stoelting R and Overdyk F. Anesthesia Patient Safety Foundation, Conclusions and Recommendations from June 08, 2011 Conference on Electronic Monitoring Strategies to Detect Drug-Induced Postoperative Respiratory Depression. Accessed August 25, 2011 at http://www.apsf.org/announcements. php?id=7. 3 Standards for Basic Anesthetic Monitoring. American Society of Anesthesiologists. Accessed 6/20/11 at http://www.asahq.org/For-Healthcare-Professionals/~/media/For%20Members/documents/Standards%20Guidelines%20Stmts/Basic%20Anesthetic%20Monitoring%202005.ashx

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December 2011

C LI N I C A L A N ESTHESI O LO G Y Zofran continued from page 1 by surgery, cancer chemotherapy and radiation therapy, is a serotonin type 3-receptor (5-HT3) antagonist. The FDA previously noted cardiovascular safety concerns indicating Zofran could prolong the QT interval of the electrocardiogram, which can lead to the potentially fatal heart rhythm known as torsades de pointes. In September, the agency announced it had reviewed all available information and added a new warning that Zofran should not be used in patients with congenital long QT syndrome because these patients are at particular risk for developing torsades de pointes. (Previous versions of the labels for ondansetron included a warning about QT interval prolongation.) The FDA also added recommendations for electrocardiogram monitoring in patients with electrolyte abnormalities, congestive heart failure and brady-arrhythmias, or in patients taking other medications that can lead to QT prolongation. Furthermore, the FDA is requiring drug manufacturer GlaxoSmithKline to conduct a study to determine the extent to which Zofran may cause QT interval prolongation. The FDA action is a déjà vu moment for the anesthesia community, coming a decade after the agency in 2001 pushed for a black-box warning on another anti-emetic, droperidol. Many anesthesiologists felt then that the label change, which effectively removed droperidol from the armamentarium of drugs for postoperative nausea and vomiting, was an over-reaction. How Much Concern Warranted? Despite all the concern, some clinicians said there’s no reason to be nervous, in part because the relationship between 5-HT3 antagonists and QT prolongation has been well known for years. Last December, the FDA issued a warning about the use of the injection form of Anzemet (dolasetron mesylate) in pediatric and adult cancer patients with underlying heart conditions or heart rate abnormalities. The previous October, the agency changed the label for Kytril (granisetron hydrochloride) to state that the drug should be used with caution in patients with preexisting arrhythmias or cardiac conduction disorders. The anesthesiology literature also has documented QT prolongation as a potential side effect of onsansetron therapy. In fact, two studies published in the journal Anesthesiology helped prompt the FDA review of Zoftran. The first study, by Charbit et al at Beaujon University Hospital in Paris, showed that onsansetron and droperidol increased the QT interval by 17 to 20 milliseconds in patients with postoperative nausea and vomiting (2008;109:206-212). The second study, also by Charbit et al, showed that the drug combination increased QT prolongation in healthy volunteers by an average of 28 milliseconds (2005;102:1094-1100). “As anesthesiologists we see QTc prolongations in the range of 20 to 30 milliseconds with virtually

every anesthetic we provide,” said Christian C. Apfel, MD, PhD, associate professor of anesthesia, epidemiology and biostatistics at the University of California, San Francisco, an an expert in postoperative nausea and vomiting. “And since anesthesia-related complications in otherwise healthy individuals are exceptionally rare—on the order of 1 in every 300,000 cases—it is hard for us to imagine that the use of ondansetron or droperidol, both which have a much smaller effect on the QTc interval, as Dr. [Paul] White et al. have demonstrated for droperidol in a well-designed randomized controlled trial, can lead to any meaningful cardiac outcomes.” However, Dr. Apfel added, the challenge for clinicians is that even young and healthy-looking individuals may have mutations on the HERG receptor, a potassium receptor in the cardiac rhythmogenic circuitry, and thus be at considerably higher risk for severe arrhythmias or cardiac arrest than the average population.

the magnitude of the QT interval increase,” he noted. “An increase of 30 is worrisome; an increase of 60 is bad; but for a 10-millisecond increase, it may not be a big deal. “Should [the FDA warning] be taken seriously? Yes, but I don’t think we should throw [ondansetron] away since we don’t know the magnitude of the problem. About 20% of drugs we use regularly have similar risks.”

Strength of Data Questioned Cynthia Sanoski, PharmD, chair of the Department of Pharmacy Practice at the Jefferson School of Pharmacy at Thomas Jefferson University, in Philadelphia, said the data on QT prolongation from Zofran “is not the strongest evidence in the world. But if you use it in the wrong type of patient—someone with heart issues or on other drugs causing QT prolongation—it could result in a life-threatening emergency.” Physicians had been “giving out Zofran like water,” she added, but the FDA warning gives a reason to pause and take steps like checking patients’ magnesium and potassium levels before administering the medicine. Ali McBride, PharmD, clinical pharmacy specialist at Barnes-Jewish Hospital in St. Louis, said clinicians may be liable if they don’t take steps to monitor patients on 5-HT3 drugs for QT prolongation. “The problem is that nobody has determined, with any degree of scientific rationale, just how much monitor‘Should [the FDA warning] be taken ing is required; how often it should be performed; and whom,” he said. “I can tell you that there is a lot of seriously? Yes, but I don’t think we by concern and confusion on this issue among hematology/oncology pharmacists, and I’m not sure we know should throw [ondansetron] away where to turn for answers.” Dr. McBride also echoed Dr. Kalus’ point that since we don’t know the magnitude there could be considerable financial fallout if cliniof the problem. About 20% of drugs cians switch from ondansetron to a branded drug such as Aloxi that reportedly does not cause heart-rhythm we use regularly have similar risks.’ abnormalities. Such a switch “could be a pharmacy budget buster, especially on the inpatient side,” he said. —James Kalus, PharmD Could the switching strategy ultimately be a cost saver, by reducing Zofran-induced rehospitalizations “This may be the tip of the iceberg we are seeing and lawsuits? “That argument could be made,” Dr. Mc and why alternatives like palonosetron [Aloxi, Eisai], Bride said. “But there is still a large ‘silo’ mentality in which does not possess the class-specific QTc prolon- health systems. Those drug budgets are often viewed gation effect, may be safer,” he said. “And this might in a vacuum. If there is a big uptick in drug spending, be even more relevant for chemotherapy where eyebrows will definitely be raised, and not everyone will have the patience to wait for downstream savings higher doses are used.” The fact that multiple 5-HT3 agents have been to accrue.” implicated has caused some experts, like Dr. Apfel, Risk Not Limited 5-HT3 Drugs who has consulted for Eisai, to suggest QT prolongation is a class effect; others still claim it is agent-speOther types of drugs also can cause QT prolongacific. (Earlier this year, a medical officer at the FDA tion, Dr. Sanoski said, including Celexa (citalopram chimed in by stating in a clinical review that QT pro- hydrobromide). In August, the FDA announced that longation and other electrocardiographic changes are Celexas no longer should be given at daily doses of indeed “class effects” of 5-HT3 antagonists.) more than 40 mg because of the side effect. But with James Kalus, PharmD, senior manager for patient antidepressants, she pointed out, there are so many care services in the Department of Pharmacy Services options that a different drug can easily be selected. at Henry Ford Hospital in Detroit, said he and oth- With nausea and vomiting, in contrast, “there are not ers continue to use Zofran, although they monitor a lot of great alternatives to the 5-HT3 receptor antagfor heart arrhythmias in specific patient populations, onists such as Zofran. In most cases you are probably such as those with low potassium and magnesium still going give the drug and document accordingly. I or those who take other medications that cause QT don’t see this as being any different from other drugs prolongation. in this class of medications that have gotten the same Many antiemetics have similar risks, Dr. Kalus said, warnings with regard to QT prolongation.” and some of the newer ones could be considerably more expensive. “At this point, I don’t have a sense of —Karen Blum

December 2011

AnesthesiologyNews.com I 59

POL I CY & M A N A G E ME N T

ASCs Need Safety Protocols for Better Patient Transitions

mbulatory surgery centers should implement protocols to transfer elderly patients between care settings before and after surgery, according to a report in the October issue of the Journal of the Association of Peri-Operative Nurses (2011;94:348-361). The number of surgical procedures performed annually in ambulatory surgery centers (ASCs) has risen dramatically over the past decade, surpassing the number of operations done in traditional hospitals. At the same time, the patient population has become increasingly complex. ASCs now treat a greater number of older adults than in the past, and these patients are more likely to have multiple care providers, comorbidities and a higher risk for complications related to transition of care, the authors of the report wrote.

‘The most important thing an ambulatory surgical center can do is to appropriately select a patient who should

safety issues, especially in the preoperative period; these included gaps in communication between providers and between providers and patients, poor coordination of paperwork, lack of timing of instructions and an absence of standards of care (Ergonomics 2006;49:470-485). At least one other study came to similar conclusions (Cogn Tech Work 2007;9:219-231).

The authors also described several real-life cases in which poor transitions compromised patient safety and increased the cost of care. In one case, a 68-year-old man had to be transferred to a hospital as an inpatient after experiencing airway compromise during his orthopedic surgery at an ASC. The center’s staff received only partial records that did not mention his

obstructive sleep apnea. In another situation, a 68-year-old woman returned to her assisted-living facility after a radius repair, along with a filled prescription for narcotic analgesics. The nursing staff members were unable to allow her to take the medications or administer them without an order from her primary care provider. see ASC page 62

New Anesthesia Complication: Deep Joint Infections

Bair Hugger® linked to implant infections

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or other facility.’ —Keith Metz, MD Despite the changing patient population, ASCs have been overlooked in health care organizations’ push to improve safety when moving patients from one health care setting to another. Transition protocols so far have focused on hospitals, but ASCs could incorporate some of these best practices, which outline safety measures for transition between hospitals, according to the report. “The ambulatory setting serves an increasingly complex patient population and provides the majority of elective surgeries, and adapting some of the transition tools that have been tested in other settings will benefit health care providers and patients in the ambulatory setting,” the authors wrote. The report detailed the few studies that looked at best practices for transitions of care for ASC settings. In one study, researchers identified many gaps in transition processes as critical

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“The risks of developing deep joint infections were signiﬁcantly greater for patients…treated with forced-air versus conductive fabric warming [3.1% vs 0.8%].”

site. In contrast, conductive fabric warming did not release sufficient excess heat to establish these convection currents.”

“Disruption [by Bair Hugger®] in the ventilation of the surgical site was associated with signiﬁcantly higher risks of joint sepsis...”

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“Excess heat from forcedair warming resulted in [hot air convection currents] that transported ﬂoor-level air upwards and into the surgical

McGovern P.D., Reed M.R., et al, Forced-air warming and ultra-clean ventilation do not mix. J Bone Joint Surg Br. 2011 Nov;93(11): 1537-44.

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P OLI C Y & M A NAGEMENT

Researchers told attendees at the 2011 annual meeting of the American Society of Anesthesiologists (abstract 710) that the consent forms they examined were written at a grade-11 reading level, a full three levels higher than the grade-8 standard recommended by institutional review boards (IRBs). The findings come as no surprise to William Tremaine, MD, director of the Office of Human Research

Protection at Mayo Clinic, in Rochester, Minn., who was not involved in the study. “Everyone knows research consent forms are too long and complicated,” Dr. Tremaine told Anesthesiology News. “These results underscore the importance of using consent forms as only one part of the informed consent process for research.” Dr. Tremaine said that team members obtaining consent for studies must go beyond what is written. “Potential participants need to have an

opportunity to ask questo the primary investitions, including quesgator Madhav Swamitions about the meaning of nathan, MD. However, words and phrases in the forms that are used rarely written consent documents. undergo scrutiny, he said. They need to get answers Dr. Swaminathan, associate in lay language they can professor of anesthesiology understand so that they are and director of perioperafully informed about the tive echocardiography in details of the study.” the Division of CardiothoTemplates for consent Henry Knowles racic Anesthesiology and forms have been tested Beecher, MD Critical Care Medicine at for readability, according Duke University School of Medicine, in Durham, N.C., along with his team, including high school student Param Sidhu, analyzed a random sample of IRB-approved consent forms. The investigators used five validated, standardized readability tests to analyze the consent forms that represented 15 studies—some of which were ongoing at the time and the remainder completed at Duke or the University of California, Los Angeles. Included in the analysis were four observational-noninterventional studies, five observational-interventional studies, three evaluation studies and three randomized controlled trials (RCTs). Dr. Swaminathan’s team found that the average reading level of the consent forms was grade 11, with the observational-noninterventional studies rated at the highest reading level (grade 11.7; Figure). RCTs and evaluation studies were written at a mean reading level of grade 10.7. Although the RCT consent forms were more readable, they also included the most sentences and words, as well as the most complex words. 14.0

13.0

 Flesch–Kincaid Grade Level  ARI (Automated Readability Index)  Coleman–Liau Index  Gunning Fog Score  SMOG Index  Mean

12.0

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Consent continued from page 1

11.0

10.0

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Figure. Grade reading level by study type.

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POL I CY & M A N A G E ME N T Dr. Swaminathan said the findings have implications for the smooth conduct of research. By ensuring that subjects have a firm understanding of the risks and benefits of involvement at the outset of their participation, the execution of the study can improve. “Subjects who do not fully understand a consent form,” he said, “may initially consent to participate, but withdraw after realizing they are receiving an intervention or procedure they did not understand or agree with at the outset of the study.”

The National Institutes of Health and the Department of Health and Human Services’ Office of Human Research Protection are soliciting comments to help improve the readability and usefulness of consent forms. Readers can submit comments to the Department of Health and Human Services at www.regulations.gov; enter docket identification number HHS-OPHS-2011-0005. —David Wild

Contact the editor of Anesthesiology News amarcus@mcmahonmed.com

‘Everyone knows research consent forms are too long and complicated.’ —William Tremaine, MD Although the grade-11 reading level is too complex for the average reader, it may be acceptable for research conducted in more educated populations, such as participants living in urban areas with more educational institutions, according to Dr. Swaminathan. In fact, he said, “that we manage to keep complex research worded at an 11th-grade level is itself an achievement.” Adhering to a grade-8 reading level, however, is necessary for subjects with lower socioeconomic status and less education, Dr. Swaminathan said. “It may be prudent for IRBs and investigators to consider tailoring the reading level to the population served.”

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December 2011

P OLI C Y & M A NAGEMENT Asc continued from page 59 “Postsurgical transitions can be complicated for the older adult with multiple caregivers,” the authors concluded. “Poor communications between the primary caregiver, the ASC staff members and the specialist resulted in pain and suffering for the patient and increased the cost of care.” The authors advised ASCs and their staff to consider using “transition tools” that have been tested in other settings.

The article identified several validated forms and checklists that can be employed at each stage of the transition process. The recommended tools come from groups such as the Centers for Medicare & Medicaid Services, the Society of Hospital Medicine, The Hartford Institute for Geriatric Nursing, The Institute for Healthcare Improvement, The Care Transitions Program, Boston University and the International Anesthesia Research Society.

The authors recommended individual ASCs develop protocols for moving patients to the center, within it and from it to the patient’s home, assistedliving facility or other institutional setting. The authors suggested implementing electronic health records that cover patients through all phases of care, “especially during care transitions, to enhance communication and patient care and reduce error-related costs.” The article highlighted an important issue for ASCs but did not provide

e-Newsletters and e-Alerts Get the latest news from the best-read anesthesiology publication in the country delivered directly to your computer or mobile device for free!

solid evidence that transitions presented problems at these centers, said Keith Metz, MD, an anesthesiologist and medical director of Great Lakes Surgical Center, in Southfield, Mich. “It’s an overview of potential concerns.” Most ASCs do have clear protocols for transitioning patients, he added. “It’s an important issue that all ambulatory surgical centers face. It’s something that we talk about a great deal at our institution, where we do about 7,000 cases a year, including elderly patients.” The real key to safe transitions is a careful selection process when evaluating patients for surgery, Dr. Metz said. “The most important thing an ambulatory surgical center can do is to appropriately select a patient who should be treated at one and not at a tertiary care or other facility.” Dr. Metz questioned whether an electronic health record could play a role because privacy regulations restrict access to electronic medical records and make it impossible for one care center to access another’s computer system. However, he recommended incorporating a detailed discharge plan and thorough physician-to-physician communication throughout the care process involving ASCs. —Christina Frangou

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C A R E E R O P P O R TU NITIES

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December 2011

C OR R E S P O NDENCE To the Editor: n the April 2007 issue of Anesthesiology News, we reported a simple technique for performing an interscalene block, based on a loss-of-resistance (LOR) approach directly analogous to that in widespread use for epidural injections and catheters. Since that time, we have refined this technique. In addition, we have performed several other blocks successfully using the LOR approach. We wish to report these developments here.

Refinements to the Interscalene Technique The most important change in the technique is a shorter needle. Instead of the 2 1/8-inch Braun catheter assembly (no longer in production), we have substituted a 1.5-inch, 22-gauge needle with a short B-bevel. The needle is placed with the bevel parallel to the skin, so that the mouth of the bevel comes into contact with the brachial plexus sheath all at once. This approach makes the resistance, and LOR, markedly easier to feel. We also have found that the advantages of a continuous technique are offset by the tendency of the catheter to kink, especially intraoperatively, when it is not easily reached under the drapes. These considerations, plus the long duration of a bupivacaine/epinephrine block, prompted us to change to a single-shot method. It should be noted that the change to a shorter needle was caused by a case of pneumothorax referable to the longer catheter assembly. With regard to other blocks, they are discussed below in order of number performed. Advertisement

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Figure. Schematic of a loss-of-resistance (LOR) block using a B-bevel needle. The bevel faces the skin. Advancing the 20 degree tip at a 30 degree approach yields a 10 degree angle of incidence at the nerve sheath. This is nearly flush to the sheath, and produces a pronounced sensation of LOR.

Caudal Epidural Block (n>800) To identify the sacral hiatus, with the patient prone, lay the index finger of the left hand in the midline of the upper sacrum, flat and pointing caudad. Slide the finger to the right (caudad) until a gentle downward (ventral) inflection of the spine is felt. The distal phalanx of the finger comes to lie inside a shallow cup, which marks the sacral hiatus. The skin is prepped and a local wheal is placed slightly above the midpoint of the hiatus. A full-thickness nick in the skin is made using a 1.5-inch, 18-gauge long-bevel needle. A twoinch, 21-gauge long-bevel needle attached to a 3 cc syringe of saline is introduced through this opening at a 30-degree angle, with the bevel facing downward. The tough sacrococcygeal ligament will be encountered within a half to one inch, depending on the thickness of the adipose pad. Advance the needle using firm pressure until a “give” is felt. At this point, test the resistance by pushing the plunger of the syringe. If injection is easy, the tip of the needle will be in the caudal epidural space. If not, the needle should be advanced further until LOR is found. (In this block alone, a long-bevel needle is used because pushing a short-bevel needle through the tough sacrococcygeal ligament requires an uncomfortable amount of force.) The two-inch needle is long enough for all but the most obese patients. Dosing for epidural steroid injections is about 18 cc of total volume. For operative cases (e.g., hemorrhoidectomy), 12 cc of a more concentrated solution, such as lidocaine/bupivacaine, works well. Ilioinguinal Nerve Block (n>150) Several conventional landmarks can be used. The point 2 cm rostral and 2 cm medial to the anterior superior iliac spine is commonly employed. Prep and locally anesthetize the skin. Make a full-thickness skin nick using an 18-gauge, long-bevel needle. Introduce a two-inch, 22-gauge short-bevel needle attached to a 3 cc syringe of saline at a 30-degree angle, with the bevel facing downward. A tough membrane will be present at a depth of about one inch (in a thin patient); this is the aponeurosis of the external oblique muscle. Advance the needle slowly until the membrane “gives”—whereupon

injection should be easy. Depending on the strength of the solution, 20 to 60 cc may be injected. In obese patients, a longer needle (3.5–inch, short-bevel, 22 or 20 gauge spinal) may be necessary. Popliteal (Sciatic) Block (n=10) Standard landmarks for the popliteal fossa may be used. Perform the injection between the medial and lateral heads of the biceps femoris muscle, slightly above the equator of the space. Prep the skin and place a local anesthetic wheal. Make a full-thickness nick with an 18-gauge, long-bevel needle. Place a 22-gauge, 1.5-inch needle attached to a 3 cc syringe of saline into the opening at a 30-degree angle to the skin, aimed rostrally (for convenience). A thin membrane will be present at a depth of about 0.5 cm. Gentle pressure advances the needle easily through this membrane. Injection is easy, and 20 cc of local anesthetic may be administered with good effect. (Our attempts at continuous techniques here were not fully satisfactory because of leaking around the catheter, resulting from the thin surrounding tissue.) Femoral Nerve Block (n=6) Use the standard landmark immediately lateral to the femoral arterial pulse. In a thin patient, use a twoinch, 22–gauge, short-bevel needle. For a large patient, a longer needle, such as a 3.5-inch, 22-gauge Quincke spinal, may be necessary. In this procedure, the first resistance encountered is the fascia lata. This should not create ambiguity, because no LOR is found upon piercing this membrane. The second membrane encountered is the sheath of the femoral neurovascular bundle. Use a 3 cc syringe of saline to identify the LOR, followed by the injection of at least 40 cc of local anesthetic. (As an alternative, an 18-gauge, B-bevel introducer for a 22-gauge continuous block catheter may be used. With the bevel of the introducer pointing downward, an excellent LOR is felt.) All of the above blocks were performed by the author from 2006 to 2010, in the setting of a freestanding pain clinic located in Fall River, Mass. The author would like to acknowledge the encouragement of Henry Crowley, DO, in the development and application of these techniques. —Edward Koh, MD, PhD Worcester Surgical Center Worcester, Mass.

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