Saturday, January 15, 2011

Lit Bits: Jan 15, 2011

From the recent medical literature...

1. Deception Not Required For Placebo Effect to Work

Placebos can be effective in medical treatments--even if the patients taking them know that they're not actual medications, researchers from Harvard Medical School's (HMS) Osher Research Center and Beth Israel Deaconess Medical Center (BIDMC) have discovered.

In the study, researchers selected 80 individuals who were suffering from irritable bowel syndrome (IBS) and divided them into two groups. The first received no treatment, while the others were given placebos, told that they were effectively just sugar pills, and were told to take them two times each day for a period of three weeks.

"Not only did we make it absolutely clear that these pills had no active ingredient and were made from inert substances, but we actually had 'placebo' printed on the bottle," HMS Associate Professor of Medicine Ted Kaptchuk said in a statement Wednesday. "We told the patients that they didn't have to even believe in the placebo effect. Just take the pills."

According to an HMS press release, by the end of the trial, nearly twice as many of those who received the placebo treatment reported "adequate symptom relief" (59 percent) when compared to the control group (35 percent). The results showed that those patients taking the placebo showed improvement rates "to a degree roughly equivalent to the effects of the most powerful IBS medications."

The study, which appears in the Public Library of Science journal PLoS ONE, illustrate that fooling patients is not required in order for the placebo effect to work, allowing medical professionals to harness the positive traits of the treatment without compromising their ethics through deception, the researchers report.

"I didn't think it would work," admitted senior author Anthony Lembo, an associate professor of medicine at BIDMC and an IBS authority. "I felt awkward asking patients to literally take a placebo. But to my surprise, it seemed to work for many of them."

"Nevertheless," added Kaptchuk, "these findings suggest that rather than mere positive thinking, there may be significant benefit to the very performance of medical ritual. I'm excited about studying this further. Placebo may work even if patients know it is a placebo."

Kaptchuk TJ, et al. Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome. PLoS ONE 2010;5(12):e15591.


Placebo treatment can have a significant impact on subjective complaints. Furthermore, recent studies have shown measurable physiological changes in response to placebo treatment that could explain how placebos alter symptoms. A critical question is establishing how physicians and other providers can take optimal advantage of placebo effects consistent with their responsibility to foster patient trust and obtain informed consent. Directly harnessing placebo effects in a clinical setting has been problematic because of a widespread belief that beneficial responses to placebo treatment require concealment or deception. This belief creates an ethical conundrum: to be beneficial in clinical practice placebos require deception but this violates the ethical principles of respect for patient autonomy and informed consent. In the clinical setting, prevalent ethical norms emphasize that “the use of a placebo without the patient's knowledge may undermine trust, compromise the patient-physician relationship, and result in medical harm to the patient.” Nevertheless, a recent national survey of internists and rheumatologists in the US found that while only small numbers of US physicians surreptitiously use inert placebo pills and injections, approximately 50% prescribe medications that they consider to have no specific effect on patients' conditions and are used solely as placebos (sometimes called “impure placebos.”) Many other studies confirm this finding. Given this situation, finding effective means of harnessing placebo responses in clinical practice without deception is a high priority….


… In addition to its clinical significance, our study has important ethical implications. As mentioned above, evidence indicates that physicians continue to use placebo treatment without transparent disclosure to patients [5], [6] Our results suggest that the placebo response is not necessarily neutralized when placebos are administered openly. Thus our study points to a potential novel strategy that might allow the ethical use of placebos consistent with evidence-based medicine. Minimally, open-label placebo may have potential as a “wait and watch” strategy before prescriptions drugs are prescribed. Further studies of open placebo are merited not only for IBS but for illnesses primarily diagnosed by subjective symptoms and introspective self-appraisal. In sum, our study suggests that for some disorders it may be appropriate for clinicians to recommend that patients try an inexpensive and safe placebo accompanied by careful monitoring before and after prescribing medication. Clearly replication and further research is essential before such a practice could be implemented.

Full-text (free):

2. The Incremental (Non-)Value of the ABCD2 Score in the ED Evaluation of TIA

Stead LG, et al. Ann Emerg Med. 2011;57:46-51.

Study objective
We study the incremental value of the ABCD2 score in predicting short-term risk of ischemic stroke after thorough emergency department (ED) evaluation of transient ischemic attack.

This was a prospective observational study of consecutive patients presenting to the ED with a transient ischemic attack. Patients underwent a full ED evaluation, including central nervous system and carotid artery imaging, after which ABCD2 scores and risk category were assigned. We evaluated correlations between risk categories and occurrence of subsequent ischemic stroke at 7 and 90 days.

The cohort consisted of 637 patients (47% women; mean age 73 years; SD 13 years). There were 15 strokes within 90 days after the index transient ischemic attack. At 7 days, the rate of stroke according to ABCD2 category in our cohort was 1.1% in the low-risk group, 0.3% in the intermediate-risk group, and 2.7% in the high-risk group. At 90 days, the rate of stroke in our ED cohort was 2.1% in the low-risk group, 2.1% in the intermediate-risk group, and 3.6% in the high-risk group. There was no relationship between ABCD2 score at presentation and subsequent stroke after transient ischemic attack at 7 or 90 days.

The ABCD2 score did not add incremental value beyond an ED evaluation that includes central nervous system and carotid artery imaging in the ability to risk-stratify patients with transient ischemic attack in our cohort. Practice approaches that include brain and carotid artery imaging do not benefit by the incremental addition of the ABCD2 score. In this population of transient ischemic attack patients, selected by emergency physicians for a rapid ED-based outpatient protocol that included early carotid imaging and treatment when appropriate, the rate of stroke was independent of ABCD2 stratification.

3. IDSA Issues First Guidelines for Treatment of MRSA

Megan Brooks. January 5, 2011 — The Infectious Diseases Society of America (IDSA) has issued its first clinical practice guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in children and adults.

The guidelines, released today, will be published in the February 1 issue of Clinical Infectious Diseases.

The 13-member MRSA guidelines panel was convened by the IDSA Standards and Practice Guidelines Committee in 2007 to develop evidence-based, consensus guidelines for clinicians managing patients with MRSA infections.

The guidelines have been endorsed by the Pediatric Infectious Diseases Society, the American College of Emergency Physicians, and the American Academy of Pediatrics.

"These guidelines for MRSA have been eagerly anticipated," Paul Auwaerter, MD, MBA, who was not involved in their development, noted in an interview with Medscape Medical News.

"The guidelines synthesize current information in one comprehensive piece, even though they aren't all as evidenced-based as we'd like; a couple are way down in the C-III world," said Dr. Auwaerter, clinical director of the Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.

"A lot of this is only expert opinion," he added, "but that's the best we have right now."

A "Living Document"

"MRSA is a major cause of both healthcare associated and community-associated infections," Catherine Liu, MD, lead author of the guidelines and assistant clinical professor in the Division of Infectious Diseases, University of California–San Francisco, told Medscape Medical News.

"It is the predominant cause of skin infections among patients presenting to the emergency room, and can also cause more serious, invasive infections that account for about 18,000 deaths in the United States per year," she noted.

"MRSA clearly has an enormous clinical and economic impact, and clinicians often struggle with the management of these infections," Dr. Liu added. The guidelines provide a "framework" to help clinicians determine how best to evaluate and treat patients with both uncomplicated and invasive infections caused by MRSA.

"It's designed to be a living document, meaning the recommendations will evolve as new information and antibiotics become available," Dr. Liu emphasized.

The guidelines address the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTIs), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system infections.

Some of the key recommendations, according to Dr. Liu, include the following:

• The management of all MRSA infections should include identification, elimination, and/or debridement of the primary source and other sites of infection when possible (eg, drainage of abscesses, removal of central venous catheters, debridement of osteomyelitis, etc).

• Education on personal hygiene and appropriate wound care is recommended for all patients with SSTIs. Patients should be instructed to keep draining wounds covered with clean, dry bandages; maintain good personal hygiene with regular bathing and cleaning of hands with soap and water or an alcohol-based hand gel, particularly after touching infected skin; and avoid reusing or sharing personal items that have contacted infected skin.

• For most simple abscesses or boils, incision and drainage alone is likely adequate, and antibiotic therapy is not needed. Antibiotic therapy is recommended for abscesses associated with the following conditions: severe or extensive disease or rapid progression in presence of associated cellulitis, signs and symptoms of systemic illness, associated comorbidities or immunosuppression (diabetes, HIV), extremes of age, abscess in area difficult to drain completely (eg, face, hand, genitalia), associated septic phlebitis), and lack of response to incision and drainage alone.

• In patients with MRSA bacteremia, follow-up blood cultures 2 to 4 days after initial positive cultures and as needed thereafter are recommended to document clearance of bacteremia.

• To optimize serum trough concentrations in adult patients, vancomycin should be dosed according to actual body weight (15 - 20 mg/kg/dose every 8 - 12 hours), not to exceed 2 g/dose. Trough monitoring is recommended to achieve target concentrations of 15 to 20 mg/mL in patients with serious MRSA infections and to ensure target concentrations in those who are morbidly obese, have renal dysfunction, or have fluctuating volumes of distribution. The efficacy and safety of targeting higher trough concentrations in children requires further study but should be considered in those with severe sepsis or persistent bacteremia.

• When an alternative to vancomycin is being considered for use, in vitro susceptibility should be confirmed and documented in the medical record.

• For methicillin-sensitive S aureus infections, a beta-lactam antibiotic is the drug of choice in the absence of allergy.

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Each section of the guidelines begins with a specific clinical question, followed by numbered recommendations and a summary of the most relevant evidence in support of the recommendations.

"Certainly, where MRSA gets a lot of concern and treatment is in SSTIs, and here the guidelines give some nice and fairly clear-cut advice" on what to do in what specific situations, Dr. Auwaerter told Medscape Medical News.

"To me, as an infectious disease person, nothing is surprising in the guidelines," he added.

The guidelines also clearly highlight some of the knowledge gaps in certain areas. "Hopefully, this information could provide a map to address some additional key questions regarding MRSA that are out there," Dr. Auwaerter said.

Clin Infect Dis. 2011;52:285-322.

4. Propofol versus propofol/ketamine for brief painful procedures in the emergency department: clinical and bispectral index scale comparison.

Phillips W, et al. J Pain Palliat Care Pharmacother. 2010 Dec;24(4):349-55.

Single-agent techniques may include traditional “pure” sedatives such as propofol, methohexital, midazolam, and etomidate, or primary analgesics such as opiates. Ketamine stands alone as an agent with both significant sedative and analgesic properties. Unfortunately, all these agents have some clinical drawbacks. Propofol may produce significant respiratory depression and hypotension (1, 2). Methohexital may likewise produce apnea and hemodynamic compromise similar to that of propofol (3, 4). Despite its hemodynamic stability, etomidate has been associated with significant adrenal suppression and increased morbidity (5). Midazolam, used alone or in combination with fentanyl, may produce respiratory depression just as with other sedatives (6, 7). Ketamine, as a sole agent, may be associated with hypertension, emesis, dysphasia, emergence phenomena, and increased respiratory secretions (7–9).

An attractive option for emergency department (ED) utilization would be the use of a combination technique, using drugs with complementary effects at decreased dosages, with the potential to avoid the unwanted side effects of each agent. The combination of ketamine and propofol (ketofol) has not been directly compared with propofol alone and a retrospective meta-analysis has questioned any advantage of the combination (10, 11).

Bispectral index (BIS) monitoring is a neurophysiological monitoring device that continually analyses a patient's electroencephalogram during anesthesia to assess the level of consciousness. The “depth of anesthesia” is commonly used as a surrogate for “the likelihood of forming experiences or memory,” known as surgical awareness. Current literature on emergency department BIS analysis is largely focused on the pediatric population and there have been no studies using BIS data in evaluating the effectiveness of ketofol in the adult population (12, 13).

Goals of This Investigation
This study evaluated the comparative effectiveness and safety of propofol versus propofol-ketamine (ketofol) combination in the same syringe for procedural sedation in the emergency department. We hypothesized that patients receiving “ketofol” would experience less hypotension and respiratory depression and still achieve an adequate quality of sedation. Primary study end points included systolic blood pressure (SBP), heart rate, respiratory rate, and oxygen saturation as well as sedation characteristics, which included length of sedation, BIS scores, and medication dosing. We considered a decrease in any hemodynamic parameter lower than baseline values as important and enrolled enough patients to provide statistical evidence that “ketofol” attenuated these negative effects.

The ideal procedural sedation drug for emergency department (ED) use would be easily titrated, rapid in onset, brief in duration, and provide sedation and analgesia without respiratory or hemodynamic compromise. Although many agents have been tried, no single drug fits this profile.

The authors evaluated the comparative effectiveness and safety of propofol versus propofol/ketamine combination for procedural sedation using bispectral index monitoring for measuring depth of sedation. A prospective, randomized case series of patients undergoing procedural sedation for fracture manipulation was studied in a Level 1 trauma center emergency department. Patients were randomized to a propofol (P) group with a target dose of 0.5 to 1.5 mg/kg or a propofol/ketamine (P/K) group with a target dose of both ketamine and propofol of 0.75 mg/kg. Procedural success, bispectral index (BIS) score, adverse effects, recovery time, and vital signs were measured.

Twenty-eight patients were enrolled. The P/K group experienced a smaller decline in systolic blood pressure (1.6% versus 12.5%) and BIS score at goal sedation (77 versus 61), a smaller difference between baseline and goal sedation BIS score (18.78 ± 10 versus 34.64 ± 11) and a lower mean propofol dose (92.5 ± 58 versus 177.27 ± 11 mg). No patient in either group experienced respiratory depression or required any intervention.

The combination of propofol and ketamine provides an attractive combination for procedural sedation in the emergency department. Compared to propofol alone, "ketofol" results in less hypotension, better sedation, and enhanced patient comfort and safety.

5. New STD Guidelines

The CDC released last month updated diagnosis and treatment guidelines for STDs. You can find them here:

Included in these updated guidelines is new information regarding 1) the expanded diagnostic evaluation for cervicitis and trichomoniasis; 2) new treatment recommendations for bacterial vaginosis and genital warts; 3) the clinical efficacy of azithromycin for chlamydial infections in pregnancy; 4) the role of Mycoplasma genitalium and trichomoniasis in urethritis/cervicitis and treatment-related implications; 5) lymphogranuloma venereum proctocolitis among men who have sex with men; 6) the criteria for spinal fluid examination to evaluate for neurosyphilis; 7) the emergence of azithromycin-resistant Treponema pallidum; 8) the increasing prevalence of antimicrobial-resistant Neisseria gonorrhoeae; 9) the sexual transmission of hepatitis C; 10) diagnostic evaluation after sexual assault; and 11) STD prevention approaches.

6. More (humour) from the BMJ Holiday Issue

A. Beauty sleep: experimental study on the perceived health and attractiveness of sleep deprived people

Axelsson J, et al. BMJ 2010; 341:c6614

Good clinical judgment is an important skill in medical practice. This is well illustrated in the quote by Joseph Bell, who demonstrated impressive observational and deductive skills. Bell was one of Sir Arthur Conan Doyle’s teachers and served as a model for the fictitious detective Sherlock Holmes. Generally, human judgment involves complex processes, whereby ingrained, often less consciously deliberated responses from perceptual cues are mixed with semantic calculations to affect decision making. Thus all social interactions, including diagnosis in clinical practice, are influenced by reflexive as well as reflective processes in human cognition and communication.

Sleep is an essential homeostatic process with well established effects on an individual’s physiological, cognitive, and behavioural functionality and long term health,8 but with only anecdotal support of a role in social perception, such as that underlying judgments of attractiveness and health. As illustrated by the common expression “beauty sleep,” an individual’s sleep history may play an integral part in the perception and judgments of his or her attractiveness and health. To date, the concept of beauty sleep has lacked scientific support, but the biological importance of sleep may have favoured a sensitivity to perceive sleep related cues in others. It seems warranted to explore such sensitivity, as sleep disorders and disturbed sleep are increasingly common in today’s 24 hour society and often coexist with some of the most common health problems, such as hypertension and inflammatory conditions.

To describe the relation between sleep deprivation and perceived health and attractiveness we asked untrained observers to rate the faces of people who had been photographed after a normal night’s sleep and after a night of sleep deprivation. We chose facial photographs as the human face is the primary source of information in social communication. A perceiver’s response to facial cues, signalling the bearer’s emotional state, intentions, and potential mate value, serves to guide actions in social contexts and may ultimately promote survival. We hypothesised that untrained observers would perceive sleep deprived people as more tired, less healthy, and less attractive compared with after a normal night’s sleep.

Objective: To investigate whether sleep deprived people are perceived as less healthy, less attractive, and more tired than after a normal night’s sleep.

Design: Experimental study.

Setting: Sleep laboratory in Stockholm, Sweden.

Participants: 23 healthy, sleep deprived adults (age 18-31) who were photographed and 65 untrained observers (age 18-61) who rated the photographs.

Intervention: Participants were photographed after a normal night’s sleep (eight hours) and after sleep deprivation (31 hours of wakefulness after a night of reduced sleep). The photographs were presented in a randomised order and rated by untrained observers.

Main outcome measure: Difference in observer ratings of perceived health, attractiveness, and tiredness between sleep deprived and well rested participants using a visual analogue scale (100 mm).

Results: Sleep deprived people were rated as less healthy (visual analogue scale scores, mean 63 (SE 2) v 68 (SE 2), P less than 0.001), more tired (53 (SE 3) v 44 (SE 3), P less than 0.001), and less attractive (38 (SE 2) v 40 (SE 2), P less than 0.001) than after a normal night’s sleep. The decrease in rated health was associated with ratings of increased tiredness and decreased attractiveness.

Conclusion: Our findings show that sleep deprived people appear less healthy, less attractive, and more tired compared with when they are well rested. This suggests that humans are sensitive to sleep related facial cues, with potential implications for social and clinical judgments and behaviour. Studies are warranted for understanding how these effects may affect clinical decision making and can add knowledge with direct implications in a medical context.

Full-text (free):

B. Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial

Heinrich H, et al. BMJ 2010; 341:c6731

Objective: To compare the effects of drinking white wine or black tea with Swiss cheese fondue followed by a shot of cherry schnapps on gastric emptying, appetite, and abdominal symptoms.

Design: Randomised controlled crossover study.

Participants: 20 healthy adults (14 men) aged 23-58.

Interventions: Cheese fondue (3260 kJ, 32% fat) labelled with 150 mg sodium 13Carbon-octanoate was consumed with 300 ml of white wine (13%, 40 g alcohol) or black tea in randomised order, followed by 20 ml schnapps (40%, 8 g alcohol) or water in randomised order.

Main outcome measures: Cumulative percentage dose of 13C substrate recovered over four hours (higher values indicate faster gastric emptying) and appetite and dyspeptic symptoms (visual analogue scales).

Results: Gastric emptying was significantly faster when fondue was consumed with tea or water than with wine or schnapps (cumulative percentage dose of 13C recovered 18.1%, 95% confidence interval 15.2% to 20.9% v 7.4%, 4.6% to 10.3%; P less than 0.001). An inverse dose-response relation between alcohol intake and gastric emptying was evident. Appetite was similar with consumption of wine or tea (difference 0.11, −0.12 to 0.34; P=0.35), but reduced if both wine and schnapps were consumed (difference −0.40, −0.01 to −0.79; P less than 0.046). No difference in dyspeptic symptoms was present.

Conclusions: Gastric emptying after a Swiss cheese fondue is noticeably slower and appetite suppressed if consumed with higher doses of alcohol. This effect was not associated with dyspeptic symptoms.

Full-text (free):

More such BMJ articles are listed below, point 21.

7. Variation in Management of Recent-Onset Atrial Fib and Flutter among Academic Hospital EDs

Stiell IG, et al. Ann Emerg Med 2011;57:13-21

Study objective
Although recent-onset atrial fibrillation and flutter are common arrhythmias managed in the emergency department (ED), there is insufficient evidence to help physicians choose between 2 competing treatment strategies, rate control and rhythm control. We seek to evaluate variation in ED management practices for recent-onset atrial fibrillation and flutter patients at multiple Canadian sites and to determine whether hospital site was an independent predictor of attempted cardioversion.

We conducted a cross-sectional survey by health records review on an observational cohort of all eligible adult recent-onset atrial fibrillation and flutter cases, with onset of symptoms less than 48 hours, treated at 8 academic hospital EDs during a 12-month period, and evaluated the variation in practice among sites for important management strategies.

Among the 1,068 study patients, 88.3% had atrial fibrillation and 11.7% had atrial flutter. The proportion of cases managed with rhythm control was 59.4% (interhospital range 42% to 85%) and, among these, electrocardioversion was attempted first for 44.2% (range 7% to 69%). There was variation in most management strategies, including use of rate control drugs 54.9% (range 37% to 65%), choice of procainamide as rhythm control drug 62.1% (range 15% to 89%), referral to cardiology in the ED 30.7% (range 16% to 64%), use of heparin 13.7% (range 1% to 29%), and outpatient cardiology referral 43.0% (range 30% to 65%). Adverse events were relatively uncommon and transient for patients undergoing attempts at pharmacologic (13.0%) or electrocardioversion (12.1%). Overall, 83.3% of patients were discharged home from the ED (range 73% to 90%). After controlling for 12 covariates, multivariate logistic regression found that factors independently associated with attempted cardioversion were age (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.95 to 0.98), history of electrocardioversion (OR 2.73; 95% CI 1.56 to 4.80), associated heart failure (OR 0.29; 95% CI 0.09 to 0.95), and hospital site (ORs ranged from 0.38 to 3.05).

We demonstrated a high degree of variation in management approaches for recent-onset atrial fibrillation and flutter patients treated in academic hospital EDs. Individual hospital site, age, previous cardioversion, and associated heart failure were independent predictors for the use of rhythm control.

Full-text (free):

Related abstract: Managing Emergency Department Patients with Recent-onset Atrial Fibrillation.

Speaking of A Fib…

8. Top Ten Things to Know about the 2011 Focused Update on the Management of Patients with Atrial Fibrillation

1. This guideline updates the 2006 Guideline.

2. New evidence is presented in this guideline to help clinicians with the management of persons with atrial fibrillation.

3. Strict control of heart rate provides no advantage over more lenient control of heart rate.

4. Combination antiplatelet therapy may be considered instead of anticoagulation with warfarin in persons not deemed suitable for warfarin therapy.

5. Recommendations regarding the use of dronedarone are presented in this guideline.

6. Discovering the potential cause of atrial fibrillation and treating it is recommended before initiating antiarrhythmic therapy.

7. Updated recommendations for catheter ablation are presented and are upgraded from the 2006 Atrial Fibrillation guideline.

8. A decision tree is included to guide maintenance of sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation.

9. Future directions for the use of catheter ablation are presented as a new section in this update.

10. Emerging and investigational antithrombotic drugs such as dabigitran were reviewed by this writing group, and will be addressed in the future.

Wann LS, et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2010: published online before print December 20, 2010, 10.1161/CIR.0b013e3181fa3cf4

9. Prehospital Intubation Might Worsen Outcomes in Adults with Cardiac Arrest

Prehospital intubation decreased survival to discharge in patients with ventricular fibrillation/ventricular tachycardia.

A recent study showed possible adverse outcomes in adult cardiac arrest patients who were intubated in the field (JW Emerg Med Nov 19 2010). To assess the effect of prehospital intubation on survival in adult patients with nontraumatic cardiac arrest, researchers reviewed a database of patients with out-of-hospital cardiac arrest who were transported to a single hospital in Michigan between 1995 and 2006.

Of 1414 adult patients with nontraumatic arrest (613 with ventricular fibrillation (VF)/ventricular tachycardia (VT) and 742 with other rhythms), 86% underwent prehospital intubation. Overall, survival to hospital discharge did not differ significantly between intubated and nonintubated patients (6.5% vs. 10.0%). However, among patients with VF/VT, intubation significantly decreased the likelihood of survival to discharge (11.6% vs. 20.8%; adjusted odds ratio, 0.52, after controlling for witnessed cardiac arrest).

Comment: The idea that adults with nontraumatic cardiac arrest could be harmed by field intubation seems counterintuitive, but is it? Recent Advanced Cardiac Life Support guidelines emphasize the proven outcome-value of high-quality chest compressions. The bottom line is that intubation, per se, is not of proven benefit in patients with cardiac arrest, and that oxygenation, not intubation, is the key. Improperly performed intubation can be more harmful than no intubation, and future research should compare intubation to placement of extraglottic airway devices, simple bag-mask ventilation, and no ventilation.

— Kristi L. Koenig, MD, FACEP. Published in Journal Watch EM January 14, 2011. Citation: Egly J et al. Assessing the impact of prehospital intubation on survival in out-of-hospital cardiac arrest. Prehosp Emerg Care 2011 Jan; 15:44.

10. Relationship between Cocaine Use and Coronary Artery Disease in Patients With Symptoms Consistent With an Acute Coronary Syndrome

Chang AM, et al. Acad Emerg Med. 2011;18:1-9

Objectives:  Observational studies of patients with cocaine-associated myocardial infarction have suggested more coronary disease than expected on the basis of patient age. The study objective was to determine whether cocaine use is associated with coronary disease in low- to intermediate-risk emergency department (ED) patients with potential acute coronary syndrome (ACS).

Methods:  The authors conducted a cross-sectional study of low- to intermediate-risk patients under 60 years of age who received coronary computerized tomographic angiography (CTA) for evaluation of coronary artery disease (CAD) in the ED. Patients were classified into three groups with respect to CAD: maximal stenosis less than 25%, 25% to 49%, and 50% or greater. Prespecified multivariate modeling (generalized estimating equations) was used to assess relationship between cocaine and CAD.

Results:  Of 912 enrolled patients, 157 (17%) used cocaine. A total of 231 patients had CAD ≥ 25%; 111 had CAD ≥ 50%. In univariate analysis, cocaine use was not associated with a lesion 25% or greater (12% vs. 14%; relative risk [RR] = 0.89, 95% confidence interval [CI] = 0.5 to 1.4) or 50% or greater (12% vs. 11%; RR = 1.15, 95% CI = 0.6 to 2.3). In multivariate modeling adjusting for age, race, sex, cardiac risk factors, and Thrombosis in Myocardial Infarction (TIMI) score, cocaine use was not associated with the presence of any coronary lesion (adjusted RR = 0.95, 95% CI = 0.69 to 1.31) or coronary lesions 50% or greater (adjusted RR = 0.78, 95% CI = 0.45 to 1.38). There was also no relationship between repetitive cocaine use and coronary calcifications or between recent cocaine use and CAD.

Conclusions:  In symptomatic ED patients at low to intermediate risk of an ACS, cocaine use was not associated with an increased likelihood of coronary disease after adjustment for age, race, sex, and other risk factors for coronary disease.

11. General Anesthesia: A Reversible Coma, Not Sleep

Megan Brooks. December 29, 2010 — Despite what anesthesiologists may tell surgery patients, the brain under general anesthesia is not "asleep," it is placed in a reversible drug-induced coma, according to 3 neuroscientists who reviewed and synthesized the latest research in general anesthesia, sleep, and coma.

Their review, 3 years in the making, appears in the December 30 issue of The New England Journal of Medicine.

"Anesthesiologists use the term 'sleep' so as not to scare patients with the word 'coma,' " Emery N. Brown, MD, PhD, from the Department of Anesthesia, Critical Care, and Pain Medicine at Massachusetts General Hospital and Harvard Medical School, Boston, pointed out in correspondence with Medscape Medical News. In reality, however, general anesthesia is a type of coma.

Dr. Brown's coauthors on the review are Ralph Lydic, PhD, from the University of Michigan, Ann Arbor, whose expertise is sleep medicine, and Nicholas D. Schiff, MD, from Weill Cornell Medical College in New York City, who specializes in recovery from coma.

"This review was prompted by a recognition that common brain circuit mechanisms may underlie aspects of general anesthesia and recovery from coma and that thinking through the links across these phenomena and their distinction from the natural processes of sleep would reveal important insights," Dr. Schiff told Medscape Medical News.

The realization that general anesthesia and coma have more in common with each other than differences "is very exciting," Dr. Schiff said, "because it gives us new ways to understand each of these states.

"Measuring brain circuit mechanisms may lead to greater diagnostic accuracy and targeted therapeutic strategies for predicting and supporting the recovery process from coma after severe brain injuries," he added. Monitoring brain function under general anesthesia may also help in developing new sleep aids.

Nothing Mysterious About the Anesthetized Brain

The scientists note in their article that there is substantial overlap between the electroencephalograms of patients in coma and of patients during general anesthesia. "The [electroencephalogram] of the states of coma recovery can resemble those of the awake, general anesthesia, or sleep state, depending on how extensive the brain injury is and where the patient is in terms of recovery," Dr. Brown noted.

The team also notes that anesthetic drugs induce unconsciousness or alter arousal through actions at multiple sites in the cerebral cortex, brainstem, and thalamus.

Contrary to what is commonly stated, how these drugs create the state of general anesthesia "is not mysterious," Dr. Brown explained, and "there are multiple mechanisms even for a single drug."

General anesthesia, the scientists say, is functionally equivalent to brainstem death, and perhaps explains why some patients do not fully recover consciousness for several hours after general anesthesia, as well as why postoperative cognitive dysfunction could persist in elderly patients for several months afterward.

"One thing which is evident regarding recovery from general anesthesia is that it tracks the return of function in the brainstem from bottom (respiration) to top (eye-movements and arousal centers)," Dr. Brown noted.

Dr. Brown, Dr. Lydic, and Dr. Schiff hope their article will facilitate more informed discussions among anesthesiology, sleep, and coma researchers and lead to new approaches to creating the state of general anesthesia, sedation, and sleep, as well as new approaches to facilitating coma recovery.

They hope it will also lead to better education of the public about general anesthesia.

This research was supported by the National Institutes of Health, the James S. McDonnell Foundation, Massachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine, and University of Michigan Department of Anesthesiology.

N Engl J Med. 2010;363:2638-2650.

12. Cardiovascular safety of NSAIDs: network meta-analysis

Trelle S, et al. BMJ 2011; 342:c7086

Objective: To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs.

Design: Network meta-analysis.

Data sources: Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data.

Study selection: All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility.

Data extraction: The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data.

Data synthesis: 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death.

Conclusions: Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.


13. Patients Underestimate CT Scan Radiation, Risks

Frederik Joelving. NEW YORK (Reuters Health) Jan 05 - Will getting two or three CT scans of the abdomen expose a person to the same amount of radiation as people who lived near the atomic blast that ravaged Hiroshima in 1945 but survived?

Will they increase a person's lifetime cancer risk?

If you answered yes to both questions, you're spot on. You're also better informed than many patients at inner-city emergency departments, according to a new survey from Cooper University Hospital in Camden, New Jersey.

Researchers there asked more than 1,100 patients who came in with stomach pain to rate statements similar to the questions above. Half said they had very little faith in the comparison between Hiroshima survivors and patients who had CT scans, rating their agreement at 13 on a scale from 0 to a perfect 100.

The majority of patients also tended to disagree that the scans would increase their cancer risk. And three-quarters underestimated the x-ray radiation from a CT scan compared with traditional chest x-rays, which are at least 100 times weaker.

"The point of the paper was not to create mass hysteria," said Dr. Brigitte Baumann, an emergency physician at Cooper, whose findings appeared online December 14th in the Annals of Emergency Medicine.

"The concern is patients who keep coming back to their physicians and get a lot of scans," she told Reuters Health. Some patients - like the ones who come in with chest pain coughing up blood - obviously need a CT scan, she said, but in general "the whole topic is just a big shade of gray."

Remainder of the article:

Ann Emerg Med abstract:

See also: CT Use in ED Has Increased 6-Fold, Used Frequently in Children

14. Three Markers Predict Significant Bleeding From Stable Pelvic Fracture

By Rob Goodier. NEW YORK (Reuters) Dec 24 - Stable pelvic fractures rarely cause bleeding that requires an intervention, but when they do, doctors may have three clues, according to new study findings.

The researchers say three things independently predict significant bleeding in this situation: a hematocrit of 30% or lower at the time of hospital admission (OR: 43.93; p less than 0.001), a pelvic hematoma on a CT scan (OR: 39.37; p less than 0.001), and systolic blood pressure of 90mm Hg or lower (OR: 18.352; p=0.01).

Out of 391 patients in the study, hip fractures caused significant bleeding in only 5%, and these three risk factors were the only independent indicators found, according to the researchers at the Massachusetts General Hospital who carried out the study.

Significant bleeding occurred in all of the patients who displayed all three of the independent risk factors, and none of those without any.

"If none of the three risk factors is present, the patient can be safely treated in a regular hospital bed or discharged," the researchers wrote in a paper published online December 20 in Archives of Surgery. "If one or two of the risk factors exist, the patient should be monitored in an intensive care environment, and a low threshold for intervention should be maintained. If all of the risk factors exist, the patient should undergo emergent angiography or preperitoneal pelvic packing according to the circumstances."

The research team examined medical records of 465 patients with stable pelvic fractures-all those who were admitted to the level 1 academic trauma center at Massachusetts General Hospital from 2002 to 2007. They excluded 74, most of whom did not have a pelvic CT scan. Then they divided the remaining 391 into three groups: 280 (72%) who did not have significant bleeding, 90 (23%) who had significant bleeding that was not caused by a hip fracture, and 21 (5%) who had significant bleeding caused by a hip fracture.

"A stable pelvic fracture is often dismissed as a source of significant bleeding, possibly resulting in delays of care," the researchers wrote. "For those few patients with stable pelvic fractures and a high likelihood of significant bleeding, early intervention or close monitoring is essential."

Arch Surg 2010.

15. (Tons of Cool) Images in Emergency Medicine

Acute Abdomen in Infant

Elderly Male with Cheek Swelling

Right Axillary Mass

A Woman with Headache

Elderly Male With Cheek Swelling

Wound Butulism

Flail Chest

The Jaw-Thrust Maneuver

Meckel’s Diverticulum

A Smooth Patch on the Tongue

Air in the Middle of the Abdomen

16. Are Non-STEMI Patients with Discordant Cardiac Biomarkers Undertreated?

Patients with non–ST-segment-elevation myocardial infarction who are troponin positive and creatine kinase MB negative undergo fewer treatments and tests than patients who are positive for both markers.

Kontos MC et al. Am Heart J 2010 Nov; 160:819.

BACKGROUND: Despite the 2000 and 2007 redefinition of myocardial infarction (MI), patients who are troponin (Tn) positive ([+]) but MB negative ([-]) may not be considered to have MI, particularly in the absence of known coronary disease (prior MI or revascularization; coronary artery disease [CAD]). How this affects treatment and outcomes has not been well described.

METHODS: Direct arrival patients with non-ST elevation MI (NSTEMI) enrolled in the American College of Cardiology NCDR ACTION-GWTG Registry were included. Patients missing marker data who were Tn (-) and had CAD were excluded. Troponin (+) patients were categorized as MB (+) (n = 11,563) or MB (-) (n = 4,501). Treatments and in-hospital outcomes were compared between the 2 groups using logistic regression.

RESULTS: Of the 16,064 NSTEMI patients, 28% were MB (-). The MB (-) patients were older (median age 68 vs 65 years) and had more comorbidities (hypertension 71% vs 66%, diabetes 31% vs 27%, heart failure 22% vs 19%; all Ps less than .01). After adjusting for baseline characteristics, MB (-) patients were significantly less likely to receive clopidogrel, antithrombins, glycoprotein IIb/IIIa antagonists, or angiography (all Ps less than .001). In-hospital mortality was lower in MB (-) patients (3.8% vs 4.9%, P less than .01), which remained significant after adjusting for baseline variables (odds ratio 0, 69, 95% CI 0.6-0.9, P = .002).

CONCLUSIONS: Patients without known CAD who have NSTEMI and are MB (-) have a higher risk profile but are less likely to receive guideline-recommended acute pharmacologic treatment than those who are MB (+). Given the relatively high mortality in this group, increased emphasis on improving quality of care in Tn (+)/MB (-) patients is warranted.

17. Prostacyclin Effective in Severe Frostbite

Gene Emery. BOSTON (Reuters Health) Jan 12 - The combination of aspirin and prostacyclin can dramatically reduce the risk of amputation in cases of severe frostbite, three doctors in Chamonix, France, report in a letter in the January 13th New England Journal of Medicine.

The physicians, led by Emmanuel Cauchy of Hopitaux du Pays du Mont-Blanc, initially treated 47 patients -- all with stage 3 or 4 frostbite -- by rapidly rewarming the frostbitten area and giving 250 mg of aspirin and 400 mg of buflomedil intravenously.

(Buflomedil is a vasoactive drug that is supposed to help with microcirculation; thus the logic of giving it to try to improve circulation in frostbitten fingers or toes. It is not approved in the U.S.)

The researchers then randomized the patients to three different protocols, each lasting eight days. Fifteen patients stayed on the aspirin/buflomedil regimen, 16 got aspirin plus the prostacyclin iloprost at a dose of 0.5 to 2 ng/kg/min for six hours per day, and the remaining 16 received aspirin, prostacyclin and a one-time 100 mg dose of recombinant tissue-type plasminogen activator (rt-PA).

None of the patients receiving just the aspirin-prostacyclin combination required amputation, compared to 9 of the 15 kept on buflomedil and 3 of the 16 treated with prostacyclin and rt-PA.

"On the basis of these results, we recommend that in the treatment of severe frostbite (stage 3 or above), after rapid rewarming, a combination of aspirin and prostacyclin should be used," they concluded in their letter in the Journal.

"The addition of rt-PA should be considered on a case-by-case basis, depending on the severity of injury (at least stage 4 frostbite), the presence of trauma (especially head trauma), any medical contraindications, and the amount of time passed since rewarming," they said.

The lesion in stage 3 frostbite extends just past the proximal phalanx. In stage 4 it extends proximal to the metacarpal or metatarsal joint.

N Engl J Med. 2010;364;189-190. Abstract:

18. FDA Limits Acetaminophen in Prescription Analgesics

Robert Lowes. January 13, 2011 — The US Food and Drug Administration (FDA) today announced that it is asking drug makers to limit the amount of acetaminophen in prescription combination pain relievers to no more than 325 mg per tablet or capsule to reduce overdoses and the severe liver injury that can follow.

The decision, to be phased in over 3 years, affects dozens of prescription analgesics that contain both acetaminophen and another ingredient, typically opioids such as codeine, oxycodone, and hydrocodone. Some of these combination products now have as much as 750 mg of acetaminophen per dose.

The new dose restriction does not apply to numerous over-the-counter (OTC) pain relievers and cold, sinus, and cough medicines that contain acetaminophen. Normally, the maximum level allowed for these products is 500 mg, although a few extended-action pain relievers that are taken less frequently can go up to 650 mg.

The FDA also is requiring manufacturers to update the labels of all prescription products containing acetaminophen with a boxed warning on the risk of severe liver injury if too much of the ingredient is taken or consumed with alcohol.

Agency officials stress that patients prescribed analgesics with acetaminophen at doses above 325 mg can safely continue to take them under a physician’s supervision. The key to safety, they say, is not exceeding the maximum daily dose of 4000 mg, whether it comes in the form of prescription medications, OTC medications, or both.

"When taken as directed, acetaminophen is a very safe product, and our goal is to make it safer," said Sandra Kweder, MD, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research, at a press conference today.

Accidental overdoses are all too common because patients may be taking a cough medicine containing the ingredient, for example, as well as a prescription analgesic for back pain without knowing the latter also includes acetaminophen. That mistake can easily happen, said Dr. Kweder, because labels for prescription analgesics do not make it crystal clear that acetaminophen is an ingredient. They often use an abbreviation for the medication — APAP — that consumers may not understand.

Overdoses from prescription combination analgesics account for nearly half of all cases of acetaminophen-related liver failure, which often leads to liver transplantation or death, according to the FDA.

More information:

19. Succinylcholine and Rocuronium are Equals for First-attempt Intubation Success in the ED

Patanwala AE, et al. Acad Emerg Med 2011;18:10-14.

Objectives:  The objective was to determine the effect of paralytic type and dose on first-attempt rapid sequence intubation (RSI) success in the emergency department (ED).

Methods:  This was a retrospective evaluation of information collected prospectively in a quality improvement database between July 1, 2007, and October 31, 2008. Information regarding all intubations performed in a tertiary care ED was recorded in this database. All RSI performed using succinylcholine or rocuronium were included. Logistic regression was used to analyze the effect of paralytic type and dosing, as well as age, sex, body mass index, physician experience, device type, and presence of difficult airway predictors on first attempt RSI success.

Results:  A total of 327 RSI were included in the final analyses. All patients received etomidate as the induction sedative and were successfully intubated. Of these, 113 and 214 intubations were performed using succinylcholine and rocuronium, respectively. The rate of first-attempt intubation success was similar between the succinylcholine and rocuronium groups (72.6% vs. 72.9%, p = 0.95). Median doses used for succinylcholine and rocuronium were 1.65 mg/kg (interquartile range [IQR] = 1.26–1.95 mg/kg) and 1.19 mg/kg (IQR = 1–1.45 mg/kg), respectively. In the univariate logistic regression analyses, variables predictive of first-attempt intubation success were laryngeal view (more success if Grade 1 or 2 compared to Grade 3 or 4 of the Cormack-Lehane classification, odds ratio [OR] = 55.18, 95% confidence interval [CI] = 18.87 to 161.39), intubation device (less success if direct laryngoscopy, OR = 0.57, 95% CI = 0.34 to 0.96), and presence of a difficult airway predictor (OR = 0.55, 95% CI = 0.31 to 0.99). In the multivariate analysis, the only variable predictive of first-attempt intubation success was laryngeal view.

Conclusions:  Succinylcholine and rocuronium are equivalent with regard to first-attempt intubation success in the ED when dosed according to the ranges used in this study.

20. Monitoring Shows High Rate of Subclinical Seizures After Cerebral Hemorrhage

Pauline Anderson. December 28, 2010 (San Antonio, Texas) — Emerging epilepsy research highlights the importance of having a high level of suspicion when treating patients who have sustained a major cerebral insult, whether through cerebral hemorrhage or trauma.

One new study found that at least one quarter of patients in intensive care with a cerebral hemorrhage who underwent evaluation with continuous electroencephalography (cEEG) were diagnosed with subclinical seizures, mostly status epilepticus.

A second study showed that children with an acute brain injury had more than double the rate of early posttraumatic seizures (EPTS) of adults with similar injuries.

Both studies were reported here at the American Epilepsy Society 64th Annual Meeting.

The remainder of the article:

21. More BMJ Humour

A. Phantom vibration syndrome among medical staff: a cross sectional survey

Rothberg MB, et al. BMJ 2010; 341:c6914

Full-text (free):

B. The barrier method as a new tool to assist in career selection: covert observational study

McCain RS, et al. BMJ 2010; 341:c6968

Full-text (free):

C. Urine output on an intensive care unit: case-control study

Solomon AW, et al. BMJ 2010; 341:c6761

Full-text (free):

22. Journal Watch’s Emergency Medicine Top Stories of 2010: Editors' Choice