Lit Bits: Oct 28, 2009

From the recent medical literature...

1. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial

Jabre P, et al. Lancet. 2009;374(9686):293-300.

Introduction
Critically ill patients often require emergency orotracheal intubation for airway control. Rapid sequence intubation with administration of a sedative and a paralytic agent is common. Etomidate is the sedative-hypnotic drug that is most often used in rapid sequence intubation, but its use has been challenged because it can cause a reversible adrenal insufficiency by dose-dependent inhibition of 11β-hydroxylase.

Several studies have suggested an association between the use of etomidate and the occurrence of adrenal insufficiency and increased morbidity in critically ill or injured patients, particularly in those with sepsis. Because adrenal insufficiency when a patient is critically ill can increase the risk of death, several investigators have advised against the use of etomidate, even as a single bolus.9 However, no causal link has been established between its use and an increase in morbidity and mortality.

Etomidate's haemodynamic tolerance, even in patients with shock, and the excellent intubation conditions provided have to be weighed against potential adverse effects, including adrenal insufficiency. A possible alternative to etomidate is ketamine, which is not known to inhibit the adrenal axis. The aim of this randomised controlled study was to compare early and 28-day morbidity after a single dose of etomidate or ketamine used for emergency endotracheal intubation of critically ill patients.

Abstract
BACKGROUND: Critically ill patients often require emergency intubation. The use of etomidate as the sedative agent in this context has been challenged because it might cause a reversible adrenal insufficiency, potentially associated with increased in-hospital morbidity. We compared early and 28-day morbidity after a single dose of etomidate or ketamine used for emergency endotracheal intubation of critically ill patients.

METHODS: In this randomised, controlled, single-blind trial, 655 patients who needed sedation for emergency intubation were prospectively enrolled from 12 emergency medical services or emergency departments and 65 intensive care units in France. Patients were randomly assigned by a computerised random-number generator list to receive 0.3 mg/kg of etomidate (n=328) or 2 mg/kg of ketamine (n=327) for intubation. Only the emergency physician enrolling patients was aware of group assignment. The primary endpoint was the maximum score of the sequential organ failure assessment during the first 3 days in the intensive care unit. We excluded from the analysis patients who died before reaching the hospital or those discharged from the intensive care unit before 3 days (modified intention to treat). This trial is registered with ClinicalTrials.gov, number NCT00440102.

FINDINGS: 234 patients were analysed in the etomidate group and 235 in the ketamine group. The mean maximum SOFA score between the two groups did not differ significantly (10.3 [SD 3.7] for etomidate vs 9.6 [3.9] for ketamine; mean difference 0.7 [95% CI 0.0-1.4], p=0.056). Intubation conditions did not differ significantly between the two groups (median intubation difficulty score 1 [IQR 0-3] in both groups; p=0.70). The percentage of patients with adrenal insufficiency was significantly higher in the etomidate group than in the ketamine group (OR 6.7, 3.5-12.7). We recorded no serious adverse events with either study drug.

INTERPRETATION: Our results show that ketamine is a safe and valuable alternative to etomidate for endotracheal intubation in critically ill patients, and should be considered in those with sepsis.

FUNDING: French Ministry of Health.

Discussion
Our study shows that one etomidate bolus is not associated with a significant increase in morbidity or mortality compared with ketamine in patients admitted to the intensive care unit. The maximum SOFA score did not differ significantly between the two drugs in the subgroup of patients having sepsis or trauma. However, for the subgroup of septic patients (n=76), the small number of patients might account for the absence of significant difference. The mortality rate at day 28 in this subgroup did not differ between the treatment groups.

An association between the administration of etomidate and an increased mortality of patients with sepsis has been suggested previously. In a retrospective study of children with meningococcal sepsis or shock, mortality rate was 30% in patients who received etomidate versus 12% in those who did not, but the difference was not significant (OR 3•1 [95% CI 0•3–79•3]). In a post-hoc analysis of the Corticus study undertaken in patients with severe sepsis, the 28-day mortality rate was significantly higher in patients who received etomidate than in those who did not (p=0•03). The investigators, however, did not draw any cause and effect conclusion, presumably because of the lack of randomisation to sedative agents.

By contrast with the substantial increase in mortality reported by Ledingham and Watts, etomidate did not affect outcome in trauma patients in our study. This discrepancy between the two studies is probably related to the duration of etomidate administration: one bolus in our study versus prolonged sedation in Ledingham and Watts' study. Hildreth and co-workers reported increased use of blood products, ventilator days, and days in intensive care in trauma patients randomly assigned to etomidate (n=18) versus midazolam (n=12), but reported no difference in mortality. However, interpretation of this study is difficult because half of the eligible patients were excluded, with 11 of 31 patients having received etomidate.

Although adrenal axis dysfunction arises to some extent after etomidate use for rapid sequence intubation, the effect of such adrenal suppression on patients' outcome remains debated. Studies have reported increased mortality in non-responders to the adrenocorticotropin hormone stimulation test and in patients with adrenal insufficiency. One bolus of etomidate decreases cortisol secretion, which contributed to the increased morbidity and mortality reported in several studies. However, these findings have not been confirmed by other investigators. Clearly, the results of these studies could be biased owing to the presence of multiple confounding factors.

Our study confirms the finding of others that etomidate affects the adrenal axis: according to our criteria, more than four-fifths of etomidate recipients had adrenal insufficiency and were non-responders to the adrenocorticotropin hormone stimulation test. About half of patients given ketamine also had adrenal insufficiency, which emphasises that critical illness per se affects adrenal function. In one study, more than 30% of non-responders had not been exposed to etomidate, and in another, 51% of patients with septic shock who had not received etomidate were non-responders. Indeed, multiple mechanisms could account for adrenal insufficiency in critically ill patients. Adrenal insufficiency is probably associated with increased mortality in critically ill patients, including those with sepsis; however, whether the adrenal axis suppression and mortality are the result of some underlying process, or whether the adrenal axis suppression causes death, has never been established. Among established independent predictors of low cortisol response to adrenocorticotropin hormone stimulation are a low pH or bicarbonate and platelet count, disease severity, and organ failure. Fentanyl or sufentanil infusion can also modify cortisol concentrations. However, these factors should not affect the results of our study since both patient groups received the same type of continuous sedation (fentanyl or sufentanil combined with midazolam).

Etomidate is the sedative-hypnotic drug most often used by emergency physicians for rapid sequence intubation, and is the drug of choice for patients who are haemodynamically unstable. Use of ketamine instead of etomidate might have drawn attention to potential adverse effects of the use of ketamine during the intubation procedure. The most common side-effects of ketamine are psychodysleptic effects, but they could not be observed because, unlike in an operating theatre, patients are not awakened until several hours after intubation. We noted no difference between the sedative drugs tested in our study on the ease of intubation, probably because intubation conditions depend mostly on the muscle relaxant effects of succinylcholine. Accordingly, Sivilotti and Ducharme reported no significant difference in the overall successful intubation in a comparison of three hypnotic drugs.

With regard to the strengths and limitations of our study, we have confirmed the appropriateness of the choice of the maximum SOFA score as the primary endpoint. There is an established relation between the maximum SOFA score and Δ-SOFA score (from maximum to admission) and mortality in patients who are critically ill. Moreover, measurement of the SOFA score has good reliability and accuracy among intensivists. These scores have shown its usefulness in the assessment of in-hospital morbidity in seriously ill patients.

However, our study might not have had sufficient power to show a significant increase in morbidity related to the use of etomidate in patients with sepsis. Our failure to enroll and analyse a larger number of patients with sepsis could have led to a type-II error for this group. A future study should be based on patients with sepsis only, since the controversy regarding the use of etomidate focuses on these patients. We felt that patients admitted with trauma were important to study as well because of suggestions from recent reports that etomidate might be harmful to this group of patients. In conclusion, our results show that ketamine is a safe and valuable alternative to etomidate for intubation in critically ill patients, particularly in septic patients.

2. Lack of association between left bundle-branch block and acute myocardial infarction in symptomatic ED patients

Chang AM, et al. Amer J Emerg Med. 2009;27:916-921.

Objective
Guidelines recommend treating patients with a new or presumed new left bundle-branch block (LBBB) similar to those with an acute ST-segment elevation myocardial infarction. It is often unclear which emergency department (ED) patients with potentially ischemic symptoms actually have an acute myocardial infarction (AMI), even in the setting of LBBB. Our null hypothesis was that in ED patients with potential AMI, the presence of a new or presumed new LBBB would not predict an increased likelihood of AMI.

Methods
This was an observational cohort study. Patients older than 30 years who presented with chest pain or other ischemic equivalent and had an electrocardiogram (ECG) to evaluate potential acute coronary syndrome (ACS) were enrolled. Data collected include demographics, history, ECG, and cardiac markers. Electrocardiograms were classified according to the standardized guidelines, including LBBB not known to be old (new or presumed new LBBB), LBBB known to be old, or no LBBB. The hospital course was followed, and 30-day follow-up was performed on all patients. Our main outcome was AMI.

Results
There were 7937 visits (mean age, 54.3 ± 15 years, 57% female, 68% black): 55 had new or presumed new LBBB, 136 had old LBBB, and 7746 had no LBBB. The rate of AMI was not significantly different between the 3 groups (7.3% vs 5.2% vs 6.1%; P = .75). Revascularization (7.8% vs old 5.2% vs 4.3%; P = .04) and coronary artery disease were more common in patients with new or presumed new LBBB (19.2% vs 11.9% vs 10.1%; P = .0004).

Conclusions
Despite guideline recommendations that patients with potential ACS and new or presumed new LBBB should be treated similar to STEMI, ED patients with a new or presumed new LBBB are not at increased risk of AMI. In fact, the presence of LBBB, whether new or old, did not predict AMI. Caution should be used in applying recommendations derived from patients with definite AMI to ED patients with potential ACS that may or may not be sustaining an AMI.

3. Recent-onset A Fibbers in the ED: Cardiovert?

Stead LG, et al. Rhythm Control With Electrocardioversion for Atrial Fibrillation and Flutter. Ann Emerg Med. 2009;54:745-747.

This review provides little evidence on which emergency physicians can base decisions about patients with acute atrial fibrillation. Because the majority of symptomatic patients encountered in the ED have atrial fibrillation of less than 48 hours’ duration and the risk of stroke and other complications in such patients is low, current practice remains cardioversion (electrical or medical) as soon as possible. In older patients with sustained atrial fibrillation, referral for cardioversion may be warranted for quality of life considerations; however, stroke prevention must be an integral
component of pre- and postcardioversion management to reduce the risk of embolic stroke.

Full-text (free): http://download.journals.elsevierhealth.com/pdfs/journals/0196-0644/PIIS0196064408020866.pdf

4. Arranging Follow-up Appointments for your Discharged Patients

Vinson DR, Patel PB. Facilitating follow-up after emergency care using an appointment assignment system. J Healthcare Quality. 2009; 31:18-24.

Many emergency department patients require urgent follow-up in primary care. The most effective way to help patients obtain their needed after-visit care is to secure the appointment on their behalf prior to their departure from the ED. This study describes the development, implementation, and outcomes of an appointment assignment system that facilitates patient follow-up at two community hospitals in an integrated healthcare system. This patient-centered system resulted in a high rate of compliance and a very low rate of unscheduled ED recidivism. Improving access in this manner will likely strengthen the continuum of care, improve quality, and increase patient satisfaction.

Full-text (free) available from the authors: drvinson@ucdavis.edu

5. Sleep-Deprived Attending Surgeons Have Higher Rates of Procedural Complications

Kathleen Louden. October 19, 2009 (Chicago, Illinois) — Attending surgeons who perform daytime surgical procedures within 6 hours of finishing an overnight shift have a nearly 3-fold higher rate of provider-related complications than when their opportunity for sleep between procedures exceeds 6 hours, a new study finds. The study was published in the October 14 issue of the Journal of the American Medical Association.

Until now, little was known about the effects of long work shifts and limited sleep opportunity on the performance of attending physicians, said lead author Jeffrey Rothschild, MD, MPH, a surgeon at Brigham and Women's Hospital and an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts.

"Attendings who perform emergency overnight procedures . . . often perform elective procedures the next day," said Dr. Rothschild, who presented the results at a media briefing held to release new research on surgical care.

"Our data suggest that attending physicians, like residents and nurses, may be at increased risk of making errors when sleep-deprived or working extended shifts," he said.

The authors studied the outcomes of 919 "postnighttime" procedures performed by 86 attending surgeons over an 8-year period. The definition of a postnighttime procedure was one performed in the operating room the day after at least 1 operative case between midnight and 6 am. Dr. Rothschild's team compared outcomes of postnighttime procedures with those of 3552 control procedures, which were the same or similar procedures performed by the same 86 surgeons when they had not worked the previous night, within 12 months of the other procedures. Of the 86 surgeons, 32 were general surgeons. Their mean length of experience was 14 years.

Working Late Does Not Increase Next-Day Complications

Dr. Rothschild and colleagues found that the overall rate of complications — intraoperative adverse events likely attributable to the surgeon — did not significantly differ between postnighttime and control procedures. The complication rate was 7.5% in the postnighttime group and 7.8% in the control group. Likewise, the duration of the extended work shift did not have a statistically significant effect on the complication rate.

It was only when the investigators looked at the data by length of sleep opportunity — the time between the end of the last overnight case and the beginning of the first case later that day — that they observed a significant difference in the frequency of complications. When surgeons in the postnighttime group got 6 hours or less of sleep opportunity, there was a 2.7-fold increase in the rate of complications, compared with a longer time between shifts in the same group, Dr. Rothschild said. The difference between that 8.5% complication rate and the 3.1% rate for surgeons whose sleep opportunity was more than 6 hours was significant (P = .03), the authors write.

Actual sleep time was likely to be far shorter than sleep opportunity, owing to the need to change clothes and travel home, Dr. Rothschild noted.

Most of the complications that occurred were preventable, the authors report. The most frequent complications for both groups, according to Dr. Rothschild, were organ injury, bleeding, and infections.

Based on their findings, he said that "a limitless work week for attending physicians is not optimal for patient care."

Self-Regulation Needed

Unlike resident physicians, attending physicians in the United States have no restrictions on the number of hours they can work. Dr. Rothschild did not think that attendings' work hours would become federally regulated. Instead, he recommended strategies that surgeons can take to reduce complications due to fatigue.

"Surgeons can try to avoid scheduling elective surgeries the day after they take emergency call, or at least when risks are high for the elective procedure. And, if possible, they should use back-up personnel to assist when they are fatigued."

A limitation of the study, according to Dr. Rothschild, is that the investigators did not know the surgeons' sleep practices the night before control procedures. "Some physicians could have worked overnight at other hospitals," he explained. Also, the findings might not apply to nonteaching hospitals, he observed.

Although the study included data from only 1 center, it raised the profile of a common problem, said Phil Fontanarosa, MD, MBA, executive deputy editor of JAMA. "More awareness is needed about this problem among attending physicians, because all the focus [of fatigue contributing to medical errors] has been on residents," Dr. Fontanarosa told Medscape General Surgery.

JAMA. 2009;302:1565-1572.

6. Using Nontraditional Risk Factors in Coronary Heart Disease Risk Assessment: U.S. Preventive Services Task Force Says “Don’t Bother”

Ann Intern Med. 2009;151:474-482.

The U.S. Preventive Services Task Force (USPSTF) has issued a recommendation statement on the use of 9 nontraditional risk factors (high-sensitivity C-reactive protein [CRP], ankle–brachial index, leukocyte count, fasting blood glucose level, periodontal disease, carotid intima–media thickness, coronary artery calcification on electron-beam computed tomography, homocysteine level, and lipoprotein[a] level) in assessing coronary heart disease (CHD) risk in asymptomatic persons. It concludes that the current evidence is insufficient to assess the balance of benefits and harms of using these nontraditional risk factors to screen asymptomatic men and women with no history of CHD to prevent CHD events (I statement).

Full-text (free): http://www.annals.org/cgi/content/full/151/7/474

7. Psychosocial Stress: Bad for your Heart

Milani RV, et al. Amer J Med. 2009;122:931-938.

Background
Exercise training reduces mortality in patients with coronary artery disease. Behavioral characteristics, including depression, hostility, and overall psychosocial stress, have been shown to be independent risk factors for recurrent myocardial infarction and death in these patients. Exercise training can reduce these high-risk behaviors, but it remains uncertain as to what extent the health benefits of exercise training can be attributed to improving these behaviors.

Methods
We evaluated the impact of exercise training during cardiac rehabilitation on mortality in 53 patients with coronary artery disease with high levels of psychosocial stress and in 469 patients with coronary artery disease with low levels of psychosocial stress and compared them with 27 control patients with high psychosocial stress who did not undergo formal cardiac rehabilitation and exercise training.

Results
Mortality was approximately 4-fold greater in patients with high psychosocial stress than in those with low psychosocial stress (22% vs 5%; P = .003). Exercise training decreased the prevalence of psychosocial stress from 10% to 4% (P less than .0001) and similarly improved peak oxygen uptake in patients with high and low psychosocial stress. Mortality in patients who improved exercise capacity by greater than 10% (high exercise change) was 60% lower than in patients who had less than 10% improvement in exercise capacity (low exercise change) (P=.009). Mortality was lower in patients with high psychosocial stress with high exercise change compared with patients with high psychosocial stress with low exercise change (0% vs 19%; P=.009). In contrast, there was no significant improvement in mortality in patients with high versus low exercise change with low psychosocial stress (4% vs 8%; P=.14).

Conclusion
Psychosocial stress is an independent risk factor for mortality in patients with coronary artery disease, and exercise training can effectively reduce its prevalence. Exercise training reduces mortality in patients with coronary artery disease, and this effect seems to be mediated in part because of the salutary effects of exercise on psychosocial stress.

Full-text: http://www.amjmed.com/article/PIIS0002934309004392/fulltext

8. Urinalysis (without culture) is not reliable to detect UTI in febrile ED infants

Reardon JM, et al. Amer J Emerg Med. 2009;27:930-932.

Objective
Urinary tract infections are a common source of serious bacterial infections in febrile infants younger than 2 years. Our objective was to compare urinalysis with urine culture in the emergency department evaluation of febrile infants.

Methods
A febrile infant registry was instituted at a tertiary care hospital treating an average of 55000 patients annually (27% children), from December 2002 to December 2003. Patients were eligible if they were younger than 3 months and had a temperature of at least 38°C or if they were between 3 and 24 months of age and had a temperature of at least 39°C. Data abstracted included age, sex, and temperature. Urinalysis (UA) and urine culture (UCx) results were obtained from electronic hospital archives.

Results
Nine hundred eighty-five patients were entered into the febrile infant registry. Male patients comprised 55%. The mean age of patients was 12.6 months; median was 12 months. Four hundred thirty-five (78% of eligible patients) had both a UA and UCx from the same specimen, and there were 45 (10.3%) positive UCx result. Females accounted for 33 (73%) of 45 positive results. The sensitivity of UA for predicting a positive UCx result was 64% (95% confidence interval [CI], 49%-78%), whereas the specificity was 91% (95% CI, 88%-94%). The positive predictive value was 46% (95% CI, 31%-53%), with a negative predictive value of 96% (95% CI, 93%-97%).

Conclusion
Urinalysis is not reliable for the detection of urinary tract infections in febrile infants when compared with urine cultures.

9. Crowding Delays Treatment and Lengthens Emergency Department Length of Stay, Even Among High-Acuity Patients

McCarthy ML, et al. Ann Emerg Med. 2009;54:492-503.e4.

Study objective
We determine the effect of crowding on emergency department (ED) waiting room, treatment, and boarding times across multiple sites and acuity groups.

Methods
This was a retrospective cohort study that included ED visit and inpatient medicine occupancy data for a 1-year period at 4 EDs. We measured crowding at 30-minute intervals throughout each patient's ED stay. We estimated the effect of crowding on waiting room time, treatment time, and boarding time separately, using discrete-time survival analysis with time-dependent crowding measures (ie, number waiting, number being treated, number boarding, and inpatient medicine occupancy rate), controlling for patient demographic and clinical characteristics.

Results
Crowding substantially delayed patients' waiting room and boarding times but not treatment time. During the day shift, when the number boarding increased from the 50th to the 90th percentile, the adjusted median waiting room time (range 26 to 70 minutes) increased by 6% to 78% (range 33 to 82 minutes), and the adjusted median boarding time (range 250 to 626 minutes) increased by 15% to 47% (range 288 to 921 minutes), depending on the site. Crowding delayed the care of high-acuity level 2 patients at all sites. During crowded periods (ie, 90%), the adjusted median waiting room times of high-acuity level 2 patients were 3% to 35% higher than during normal periods, depending on the site and crowding measure.

Conclusion
Using discrete-time survival analysis, we were able to dynamically measure crowding throughout each patient's ED visit and demonstrate its deleterious effect on the timeliness of emergency care, even for high-acuity patients.

Full-text (free): http://www.annemergmed.com/article/PIIS019606440900239X/fulltext

10. D-dimer Testing in Patients with Suspected Pulmonary Embolism and Impaired Renal Function: Still Useful

Karami-Djurabi R, et al. Amer J Med. 2009;122:1050-1053.

Background
Determination of pretest probability and D-dimer tests are the first diagnostic steps in patients with suspected pulmonary embolism, which can be ruled out when clinical probability is unlikely and D-dimer level is normal. We evaluated the utility of D-dimer testing in patients with impaired renal function.

Methods
D-dimer tests were performed in consecutive patients with suspected pulmonary embolism and an unlikely clinical probability. Creatinine levels were assessed as clinical routine. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. Correlation between D-dimer level and renal function and proportions of patients with normal D-dimer in different categories of estimated glomerular filtration rate (eGFR) were assessed. Different categories of decreasing eGFR were defined as: normal renal function (eGFR over 89 mL/min), mild decrease in eGFR (eGFR 60-89 mL/min), and moderate decrease in eGFR (eGFR 30-59 mL/min).

Results
Creatinine levels were assessed in 351 of 385 patients (91%). D-dimer levels significantly increased in 3 categories of decreasing eGFR (P = .027 and P = .021 for moderate renal impairment compared with mild renal impairment and normal renal function, respectively). Normal D-dimer levels were found in 58% of patients with eGFR above 89 mL/min, in 54% with eGFR 60-89 mL/min, and in 28% with eGFR 30-59 mL/min.

Conclusions
The specificity of D-dimer testing in patients with suspected pulmonary embolism and decreased GFR is significantly decreased. Nonetheless, performing D-dimer tests is still useful because computed tomography scanning can be withheld in a significant proportion of these patients.

11. Pediatric myocarditis: presenting clinical characteristics

Durani Y, et al. Amer J Emerg Med. 2009;27:942-947.

Objective
The objective of the study was to characterize the clinical profiles of pediatric patients with acute myocarditis and dilated cardiomyopathy (DCM) before diagnosis.

Methods
A retrospective cross-sectional study was conducted to identify patients with myocarditis and DCM who presented over a 10-year span at 2 tertiary care pediatric hospitals. Patients were identified based on the International Classification of Diseases, Ninth Revision, diagnostic codes.

Results
A total of 693 charts were reviewed. Sixty-two patients were enrolled in the study. Twenty-four (39%) patients had a final diagnosis of myocarditis, and 38 (61%) had DCM. Of the 62 patients initially evaluated, 10 were diagnosed with myocarditis or DCM immediately, leaving 52 patients who required subsequent evaluation before a diagnosis was determined. Study patients had a mean age of 3.5 years, 47% were male, and 53% were female. Common primary complaints were shortness of breath, vomiting, poor feeding, upper respiratory infection (URI), and fever. Common examination findings were tachypnea, hepatomegaly, respiratory distress, fever, and abnormal lung examination result. Sixty-three percent had cardiomegaly on chest x-ray, and all had an abnormal electrocardiogram results.

Conclusions
These data suggest children with acute myocarditis and DCM most commonly present with difficulty breathing. Myocarditis and DCM may mimic other respiratory or viral illnesses, but hepatomegaly or the finding of cardiomegaly and an abnormal electrocardiogram result may help distinguish these diagnoses from other more common pediatric illnesses.

12. The Association between Transfer of ED Boarders to Inpatient Hallways and Mortality: A 4-Year Experience

Viccellio A, et al. Ann Emerg Med. 2009;54:487-491.

We posted this pre-publication abstract in our May Lit Bits, abstract #20. Since this article was published this month, the full-text is now available online for free: http://www.annemergmed.com/article/S0196-0644(09)00238-8/fulltext

13. New Analyses From ECASS 3 Support Use of tPA Up to 4.5 Hours After Stroke

Susan Jeffrey. October 20, 2009 (UPDATED October 21, 2009) — Secondary analyses of data from the third European Cooperative Acute Stroke Study (ECASS 3) trial appear to support the use of recombinant tissue plasminogen activator (rt-PA, alteplase) to treat stroke up to 4.5 hours after symptom onset in patients without exclusions for treatment, but who miss the approved time window of 0 to 3 hours.

"Almost all our additional outcome analyses strongly support the positive primary and secondary trial results of ECASS 3," the investigators, with lead author Werner Hacke, MD, PhD, professor and chairman of the Department of Neurology at Ruprecht-Karls-Universität, Germany, conclude.

Although not significant in every analysis, all additional efficacy endpoints showed "at least a clear pattern in favor of alteplase," the authors note, in particular confirming that treatment was effective in patients regardless of stroke severity.

However, Dr. Hacke told Medscape Neurology that in his view, the most critical point to make about ECASS 3, now supported by these subanalyses, is not that the time window for tPA can safely be extended to 4.5 hours.

"It is that the concept of thrombolytic therapy in acute ischemic stroke is supported now by a very straightforward, conservative, randomized clinical trial, a trial that is more than double the size of the National Institute of Neurological Disorders and Stroke trial that was positive for the 3-hour time window," he said.

Along with a collection of pooled and meta-analyses and data from a large European registry, he said, their results bolster the concept, still questioned by some, that thrombolysis as a valid therapy for stroke. "We have 2 independent randomized clinical trials that are positive with the primary outcome in favor of rtPA, so there is no reason any more to not accept this as a scientific fact," Dr. Hacke stressed.

This new report from ECASS 3 was published online October 21 and will appear in the December issue of Lancet Neurology. ECASS 3 was supported by Boehringer Ingelheim.

14. Images in EM

Traumatic Eye Swelling
http://www.annemergmed.com/article/S0196-0644(09)00365-5/fulltext

Psychotic Woman With Painful Abdominal Distension
http://www.annemergmed.com/article/S0196-0644(09)00373-4/fulltext

15. Facemasks and Hand Hygiene to Prevent Influenza Transmission in Households: A Cluster Randomized Trial

Cowling BJ, et al. Ann Intern Med. 2009;151:437-446

Few data are available on the effectiveness of nonpharmaceutical interventions for preventing influenza virus transmission. In this cluster randomized trial of 259 people with confirmed influenza virus infection and 794 household contacts, hand washing and facemasks seemed to prevent influenza virus transmission when healthy people started these measures within 36 hours of symptom onset in an infected family member. Although adherence to the interventions varied, these findings suggest that nonpharmaceutical interventions may help to mitigate pandemic and interpandemic influenza.

Abstract: http://www.annals.org/cgi/content/abstract/151/7/437

16. Validation of a Prediction Rule for the Identification of Children with Intra-abdominal Injuries After Blunt Torso Trauma

Holmes JF, et al. Ann Emerg Med. 2009;54:528-533.

Study objective
We validate the accuracy of a previously derived clinical prediction rule for the identification of children with intra-abdominal injuries after blunt torso trauma.

Methods
We conducted a prospective observational study of children with blunt torso trauma who were evaluated for intra-abdominal injury with abdominal computed tomography (CT), diagnostic laparoscopy, or laparotomy at a Level I trauma center during a 3-year period to validate a previously derived prediction rule. The emergency physician providing care documented history and physical examination findings on a standardized data collection form before knowledge of the results of diagnostic imaging. The clinical prediction rule being evaluated included 6 “high-risk” variables, the presence of any of which indicated that the child was not at low risk for intra-abdominal injury: low age-adjusted systolic blood pressure, abdominal tenderness, femur fracture, increased liver enzyme levels (serum aspartate aminotransferase concentration over 200 U/L or serum alanine aminotransferase concentration over 125 U/L), microscopic hematuria (urinalysis over 5 RBCs/high powered field), or an initial hematocrit level less than 30%.

Results
One thousand three hundred twenty-four children with blunt torso trauma were enrolled, and 1,119 (85%) patients had the variables in the decision rule documented by the emergency physician and therefore made up the study sample. The prediction rule had the following test characteristics: sensitivity=149 of 157, 94.9% (95% confidence interval [CI] 90.2% to 97.7%) and specificity=357 of 962, 37.1% (95% CI 34.0 to 40.3%). Three hundred sixty-five patients tested negative for the rule; thus, strict application would have resulted in a 33% reduction in abdominal CT scanning. Of the 8 patients with intra-abdominal injury not identified by the prediction rule, 1 underwent a laparotomy. This patient had a serosal tear and a mesenteric hematoma at laparotomy, neither of which required specific surgical intervention.

Conclusion
A clinical prediction rule consisting of 6 variables, easily available to clinicians in the ED, identifies most but not all children with intra-abdominal injury. Application of the prediction rule to this sample would have reduced the number of unnecessary abdominal CT scans performed but would have failed to identify 1 child undergoing (a nontherapeutic) laparotomy. Thus, further refinement of this prediction rule in a large, multicenter cohort is necessary before widespread implementation.

Full-text (free): http://www.annemergmed.com/article/S0196-0644(09)00398-9/fulltext

17. Rapid Viral Testing Promising in Pediatric Emergencies

NEW YORK (Reuters Health) Oct 19 - In children with acute febrile respiratory illness, rapid viral testing techniques may save time and reduce demands on emergency department staff, according to a review published this month in the Cochrane Database of Systematic Reviews.

Nevertheless, lead investigator Dr. Quynh Doan said in a statement that "the existing evidence is not strong enough to prove that these tests help to reduce pressure on health systems, but it certainly does look promising."

Moreover, she told Reuters Health, "Rapid viral testing in a well defined context can provide physicians with very valuable information and potentially impact on management decision." However, "emphasis must be put on 'well defined context.'"

"We must remember," she added, "that only positive rapid viral testing adds any information, as these tests can only detect a specific virus -- commonly influenza -- and the absence of this virus in the sample is in no way indicative of what is causing the illness."

Dr. Doan of the British Columbia Children's Hospital in Vancouver, Canada, and colleagues studied data from 4 trials involving 759 children who underwent rapid testing and 829 who acted as controls.

Three of the studies employed influenza testing and the remaining study used a virus panel test encompassing influenza, parainfluenza, respiratory syncytial virus and adenovirus.

The team found that overall, viral testing reduced the use of chest X-rays (relative risk, 0.77) and that there was a trend toward less antibiotic usage (relative risk, 0.89) and fewer blood and urine investigations.

Dr. Doan also pointed out that "since the rate of positive rapid viral testing varied widely between 20 and 60% of tested subjects -- depending on which studies we look at -- perhaps we should be selective in the population to be tested in order to maximize its usefulness."

"In addition," she concluded, "it is important to note that all these studies were conducted before the H1N1 era. How rapid viral testing can contribute to managing the emergency department volume surges associated with the H1N1 pandemic can only be speculated."

Cochrane Database Syst Rev 2009.

18. The Out-of-Hospital Validation of the Canadian C-Spine Rule by Paramedics

Vaillancourt C, et al. Ann Emerg Med. 2009;54:663-671.e1

Study objective
We designed the Canadian C-Spine Rule for the clinical clearance of the cervical spine, without need for diagnostic imaging, in alert and stable trauma patients. Emergency physicians previously validated the Canadian C-Spine Rule in 8,283 patients. This study prospectively evaluates the performance characteristics, reliability, and clinical sensibility of the Canadian C-Spine Rule when used by paramedics in the out-of-hospital setting.

Methods
We conducted this prospective cohort study in 7 Canadian regions and involved alert (Glasgow Coma Scale score 15) and stable adult trauma patients at risk for neck injury. Advanced and basic care paramedics interpreted the Canadian C-Spine Rule status for all patients, who then underwent immobilization and assessment in the emergency department to determine the outcome, clinically important cervical spine injury.

Results
The 1,949 patients enrolled had these characteristics: median age 39.0 years (interquartile range 26 to 52 years), female patients 50.8%, motor vehicle crash 62.5%, fall 19.9%, admitted to the hospital 10.8%, clinically important cervical spine injury 0.6%, unimportant injury 0.3%, and internal fixation 0.3%. The paramedics classified patients for 12 important injuries with sensitivity 100% (95% confidence interval [CI] 74% to 100%) and specificity 37.7% (95% CI 36% to 40%). The κ value for paramedic interpretation of the Canadian C-Spine Rule (n=155) was 0.93 (95% CI 0.87 to 0.99). Paramedics conservatively misinterpreted the rule in 320 (16.4%) patients and were comfortable applying the rule in 1,594 (81.7%). Seven hundred thirty-one (37.7%) out-of-hospital immobilizations could have been avoided with the Canadian C-Spine Rule.

Conclusion
This study found that paramedics can apply the Canadian C-Spine Rule reliably, without missing any important cervical spine injuries. The adoption of the Canadian C-Spine Rule by paramedics could significantly reduce the number of out-of-hospital cervical spine immobilizations.

Full-text (free): http://www.annemergmed.com/article/PIIS0196064409002418/fulltext

19. Serious Bacterial Infections Uncommon in Infants Who Have Experienced an Apparent Life-Threatening Event

Mittal MK, et al. Ann Emerg Med. 2009;54:523-527.

Study objective
We determine the incidence of serious bacterial infection in infants presenting to the emergency department (ED) with an apparent life-threatening event.

Methods
This was a prospective cohort study of infants younger than 12 months who were treated at an urban children's hospital ED during 1 year and who met standard criteria for an apparent life-threatening event. Sociodemographic data, presenting features, diagnostic testing, hospital course, and final diagnosis were collected. Follow-up information was obtained 4 weeks after the visit.

Results
Of the 198 infants enrolled, 44 (22.2%) had evaluation for serious bacterial infection: urine culture 36 (18%), blood culture 38 (19%) and cerebrospinal fluid culture 18 (9%). No infant (0/198; 95% confidence interval 0% to 1.8%) was found to have bacteremia, urinary tract infection, or bacterial meningitis, which was confirmed at the 4-week interview (99% ascertainment). Two infants were found to have enteroviral meningitis.

Conclusion
The incidence of serious bacterial infection in this cohort was extremely low. Infants presenting with an apparent life-threatening event need not be subjected to a full serious bacterial infection evaluation routinely.

20. Do Not Pardon the (CPR) Interruption

Interruptions in Cardiopulmonary Resuscitation From Paramedic Endotracheal Intubation

Wang HE, et al. Ann Emerg Med. 2009;54:645-652.e1

Emergency cardiac care guidelines emphasize treatment of cardiopulmonary arrest with continuous uninterrupted cardiopulmonary resuscitation (CPR) chest compressions. Paramedics in the United States perform endotracheal intubation on nearly all victims of out-of-hospital cardiopulmonary arrest. We quantified the frequency and duration of CPR chest compression interruptions associated with paramedic endotracheal intubation efforts during out-of-hospital cardiopulmonary arrest.

Methods
We studied adult out-of-hospital cardiopulmonary arrest treated by an urban and a rural emergency medical services agency from the Resuscitation Outcomes Consortium during November 2006 to June 2007. Cardiac monitors with compression sensors continuously recorded rescuer CPR chest compressions. A digital audio channel recorded all resuscitation events. We identified CPR interruptions related to endotracheal intubation efforts, including airway suctioning, laryngoscopy, endotracheal tube placement, confirmation and adjustment, securing the tube in place, bag-valve-mask ventilation between intubation attempts, and alternate airway insertion. We identified the number and duration of CPR interruptions associated with endotracheal intubation efforts.

Results
We included 100 of 182 out-of-hospital cardiopulmonary arrests in the analysis. The median number of endotracheal intubation–associated CPR interruption was 2 (interquartile range [IQR] 1 to 3; range 1 to 9). The median duration of the first endotracheal intubation–associated CPR interruption was 46.5 seconds (IQR 23.5 to 73 seconds; range 7 to 221 seconds); almost one third exceeded 1 minute. The median total duration of all endotracheal intubation–associated CPR interruptions was 109.5 seconds (IQR 54 to 198 seconds; range 13 to 446 seconds); one fourth exceeded 3 minutes. Endotracheal intubation–associated CPR pauses composed approximately 22.8% (IQR 12.6-36.5%; range 1.0% to 93.4%) of all CPR interruptions.

Conclusion
In this series, paramedic out-of-hospital endotracheal intubation efforts were associated with multiple and prolonged CPR interruptions.

Full-text (free): http://www.annemergmed.com/article/PIIS0196064409005344/fulltext

21. Abstracts from ACEP’s 2009 Scientific Assembly

A. ED Doctors Rarely Adjust Antibiotic Doses for Obese Patients

By Marilynn Larkin. NEW YORK (Reuters Health) Oct 07 - Emergency department physicians rarely adjust antimicrobial medication doses for obese patients, according to research reported Tuesday at the American College of Emergency Physicians annual meeting in Boston.

"We have a one-size-fits-all dose in our minds for most antibiotics, and we tend to give that dose regardless of size and other factors that should affect dosing, like age, renal function, and body mass index," study co-researcher Dr. Michael Mullins told Reuters Health.

Dr. Mullins and his colleagues, from Washington University School of Medicine, St. Louis, analyzed the rate at which their center's emergency physicians adhered to dose adjustment guidelines for selected antibiotics established by the university's antibiotic utilization review (AUR) committee.

They reviewed data for all emergency department patients treated over a 3-month period who weighed more than 100 kg, had a body mass index greater than 40 kg/m2, and were given cefazolin, cefepime, or ciprofloxacin.

Slightly more than a thousand patients met the study criteria. Overall, they were treated with 503 doses of cefepime, 293 doses of cefazolin, and 306 doses of ciprofloxacin. Thirty received more than one antibiotic.

Based on AUR guidelines, the initial dose for these patients should be 2 g IV for cefazolin or cefepime and 800 mg IV or 750 mg PO for ciprofloxacin.

These guidelines were followed for only 48 doses of cefepime (9.5%), 12 doses of cefazolin (4.1%), and 4 doses of ciprofloxacin (1.3%).

"Obesity is an epidemic in North America in particular, and unfortunately, we're seeing more people in the obese and severely obese range than we used to," Dr. Mullins observed. "I think this problem is under-recognized by emergency physicians and other specialists."

"If you give too low a dose," he cautioned, "you'll have treatment failure even if you pick the right antibiotic--and increase the likelihood that some of the bacteria you're trying to kill will form a mutation and become less sensitive to the drug."

B. Vast Increase in ED Visits for Head Injuries Seen After Natasha Richardson's Death

Fran Lowry. October 8, 2009 (Boston, Massachusetts) — Widespread media coverage of Natasha Richardson's death from a head injury on March 18, 2009 prompted a huge increase in emergency department (ED) visits, investigators reported here at the American College of Emergency Physicians 2009 Scientific Assembly.

The actress appeared well after she hit her head in a fall while skiing at Mont Tremblant, Quebec. She initially refused medical help, saying she felt fine, but died shortly afterward.

"We see this all the time in emergency rooms," Brian Walsh, MD, from Morristown Memorial Hospital in New Jersey, told Medscape Emergency Medicine. "Coverage about a certain disease, for instance meningitis deaths in young people, can cause a big bump in visits. We thought that the publicity surrounding her tragic death would do the same thing, and we wanted to quantify that."

Dr. Walsh and his colleagues compared the daily visits for head injury for the 10 days before and after March 18 in the EDs of 19 urban, suburban, and rural hospitals in New Jersey and New York. They classified patients as having head injury based on ICD9 codes.

They found that visits to the ED for head injury increased 73% (95% confidence interval, 53% - 94%; P less than .0001) for the 10 days after March 18 compared with the 10 days before. However, by March 31, the number of ED visits for head trauma was back to the pre–March 18 level.

According to Christina Campo-Ford, PA, from Morristown Memorial Hospital, who coauthored the study with Dr. Walsh, the media can cause quite a scare. "Good Morning America ran a spot a day after Natasha Richardson died about a little girl who was hit in the head with a softball and she was fine but then she went downhill. You can't show that on Good Morning America and not expect parents to bring their children in."

Pediatricians were telling concerned parents to bring their children who fell and hit their heads to the ED "just to be safe," she said. However, although the number of people who came to the ED for head trauma increased, the number of serious head injuries did not, nor did the percentage of computed tomography (CT) scans that were performed.

"We educated patients about the pros and cons of CTs and the radiation exposure risks and so on, and we did not do CTs unnecessarily," said Ms. Campo-Ford. "However, some patients insisted on having a CT, so we couldn't refuse them."

Ms. Campo-Ford believes that Ms. Richardson's death will continue to influence ED visits for head injury.

Media attention can definitely highlight issues, Debra Houry, MD, from Emory University in Atlanta, Georgia, told Medscape Emergency Medicine. "As emergency physicians, we need to make sure that we talk about injury prevention a well, such as helmet use, as this decreases the morbidity and mortality with a head injury."

Media reporting, which used headlines such as "Stand Up and Die" when reporting Ms. Richardson's death, fuels panic reactions on the part of the public, and encourages them to go to the ED even when such visits are not necessary. "The media called it "stand up and die," so why would you not come in if you hit your head," Ms. Campo-Ford noted.

Such reporting only compounds the already serious problem of ED overcrowding, said Dr. Walsh.
Physicians should educate their patients about head trauma and what symptoms to look for. But even when they do, some patients will insist on coming into the ED and having a CT scan anyway, Dr. Alexander M. Rosenau, DO, FACEP, from Lehigh Valley Hospital in Allentown, Pennsylvania, told Medscape Emergency Medicine. Dr. Rosenau is chair of the Emergency Medicine Foundation.

He pointed out how difficult it is to persuade patients that they don't need to come to the hospital after every head injury as a result of the publicity about Ms. Richardson. "A mother brought her daughter to the ED, insisting on a CT scan because the girl had fallen off her horse about 2 days prior and had hit her head. After taking a careful history and exam, we tried to reassure the mother that a CT was not necessary, but she was not convinced."

American College of Emergency Physicians 2009 Scientific Assembly. Abstract 156. Presented October 5, 2009.

C. Shorter Wait Times in the ED Mean More Patients Stay to See a Doctor

Marilynn Larkin. NEW YORK (Reuters Health) Oct 06 - Modest decreases in emergency department (ED) waiting times can have a big impact on whether a patient stays to see a doctor or leaves without being seen, investigators said Monday at the annual meeting of the American College of Emergency Physicians in Boston.

The research is based on an analysis of all visits to the George Washington Hospital ED from 2006-2008. Dr. Mehdi Sattarian and colleagues compared wait times for walk-in patients who left without being seen, either before or after nursing triage, to waiting times (from arrival to hospital bed) for people who arrived at the hospital at the same hour and stayed to see a doctor. They also recorded the total number of patients in the ED treatment area and lobby at the hour's end, and illness severity, Dr. Sattarian said at the Boston meeting.

During the study period, 187,663 patients came to the ED, 128,430 of whom were walk-ins. (The rest came by ambulance.) Of those, 5.2% left without being seen.

Further analysis revealed the proportion of walk-in patients who left without being seen fell from 5.5% in July-December 2006 to 3.5% in July-December 2008. During the same period, mean waiting times for walk-ins decreased from 61.4 to 52.6 minutes.

The drop in the number of patients who left without being seen occurred even while the total number of patients coming to the ED in a given hour increased (from 6.9 patients in 2006 to 7.5 patients in 2008), along with the number of patients left in the ED at the end of that hour (36.5 in 2006, 39.5 in 2008).

"We saw highly significant relationships between the number of people who left without being seen and both waiting times and the total number of patients in the emergency department," Dr. Sattarian told meeting attendees. In email to Reuters Health, he attributed improvements in "front-end processes" -- for example, streamlining registration and triage -- to the decreased waiting times and concomitant increase in the number of people who stayed to see a doctor.

Improving "back-end" processes -- what happens from the time a patient is seen by a doctor to the time they're either admitted or discharged -- could have "an even greater effect" on the number of people who stay to be seen by reducing the overall number of people in the ED, Dr. Sattarian observed.

Those strategies would include decreasing the amount of time it takes for seriously ill people to be moved to a hospital bed, and "improving laboratory and radiology turnaround times," he concluded.

D. Oxygen Therapy Relieves Headache Pain in the ED, Cuts Length of Stay, Drug Use

Marilyn Larkin. NEW YORK (Reuters Health) Oct 05 - Giving high-flow oxygen therapy for 15 minutes to emergency department patients with headaches provides rapid relief and reduces hospital stays, use of CT scans, and headache pharmacotherapy, according to a pilot study.

Dr. Boris Veysman of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School reported the results on Monday at the annual meeting of the American College of Emergency Physicians in Boston.

"Very often, when a patient comes to the emergency department with one complaint being headache, they're uncomfortable and symptomatic and they have to wait for a workup before anyone can determine the cause. A diagnosis may not even be made in the emergency department," Dr. Veysman told Reuters Health. "So we approached it from a different perspective and asked, 'What if therapy were the first thing you did (for a headache) before attempting to find a cause?' And so we tried giving oxygen therapy, because it's so widespread and safe."

In the placebo-controlled study, 17 patients were randomized to 100% oxygen at 15 L/min for 15 minutes; 14 received high flow air for 15 minutes; and 17 received no intervention prior to standard treatment. Headache intensity was assessed using a 10-point visual analog scale.

Median times to relief were significantly shorter for patients treated with oxygen (40 minutes) compared with those treated with high flow air (110 minutes) or nothing (120 minutes). Median length of stay was also significantly shorter for patients treated with oxygen (57.5 minutes) than for those treated with air (210 minutes) or nothing (180 minutes).

In addition, CT scans were ordered less frequently: for four of 17 patients (24%) who received oxygen; 11 of 14 (79%) who received air; and eight of 17 (47%) who got nothing.

Medication was given to 29% of those who received oxygen, 86% of those who received air, and 82% of those who received no treatment.

Headache intensity was significantly reduced at both 15 minutes and 30 minutes after initiation of treatment, with patients treated with oxygen realizing the greatest reductions.

"It was a small study, and our results are preliminary," Dr. Veysman stressed. "But the medical community is starting to recognize that it's important to treat discomfort even when you don't know what's causing it, as long as you feel confident the treatment won't make the patient worse. In this case, we found more relief with oxygen than with placebo, although the fact that the headache goes away doesn't necessarily mean the patient can go home."