Wednesday, May 03, 2006

Lit Bits: May 3, 2006

From the recent medical literature...

1. Cardiocerebral Resuscitation: A Newsmaker Interview With Gordon A. Ewy, MD

Laurie Barclay, MD

April 17, 2006 ­ Editor's Note: Cardiocerebral resuscitation (CCR) ­ employing chest compressions but no ventilations ­ improves survival of out-of-hospital cardiac arrest, according to the results of an observational study published by Michael J. Kellum, MD, and colleagues in the April issue of the American Journal of Medicine. Unlike traditional cardiopulmonary resuscitation (CPR), which was designed both for cardiac and respiratory arrest, CCR is designed only for unexpected, witnessed, cardiac arrest, which is by far more common than respiratory arrest as a cause of sudden collapse in adults.

Animal experiments showed that the most important factor determining survival after CPR is cardiac perfusion pressure, achieved by continuous chest compressions. Ventilations may actually be harmful because they interrupt chest compressions, decrease venous return to the heart, and increase intrathoracic pressure. When paramedics in Wisconsin employed the new CCR protocol, with chest compressions before and after defibrillation but no intubation or ventilations, they achieved a 300% increase in survival compared with use of traditional CPR.

To learn more about the clinical implications of this new protocol, Medscape's Laurie Barclay interviewed study coauthor Gordon A. Ewy, MD, director and pioneer of the CPR Research Group at the University of Arizona Sarver Heart Center in Tucson.


2. Viewpoint: Appendicitis -- How Much Time Do We Have Until Rupture?

Posted 04/11/2006. Albert B. Lowenfels, MD

Bickell NA, Aufses AH, Rojas M, Bodian C. J Am Coll Surg. 2006;202:401-406

The aim of this report was to study the timing between the onset of symptoms of appendicitis and the risk for rupture. The investigators studied the records of 219 patients from a total of 731 with documented appendicitis over a 2-year period in 2 metropolitan hospitals. At the time of surgery, 16% (n = 36) of the patients had sustained appendiceal rupture. The frequency of rupture was low in the first 36 hours after the onset of symptoms (< 2%), but increased to 5% in each of the ensuing 12-hour periods. In a multivariate analysis, total time since the beginning of the attack was the strongest risk factor (relative risk, 6.6). Other significant factors were age 65 (relative risk, 4.2), fever, and tachycardia.
This report quantifies the relationship between the duration of symptoms and risk for appendiceal rupture with well-known complications. Important factors that were associated with delay in diagnosis included the absence of right lower quadrant tenderness (19% of patients) and performance of a computed tomographic (CT) scan (18% of patients). The study results emphasize the benefit to the patient of making a diagnosis within a "golden" period of 36 hours.

3. Oral Ondansetron Appears Beneficial for Emergent Pediatric Gastroenteritis

News Author: Laurie Barclay, MD. April 19, 2006 ­ Orally disintegrating ondansetron may be beneficial for the treatment of pediatric patients with gastroenteritis in the emergency department, according to the results of a randomized study published in the April 20 issue of The New England Journal of Medicine.

"Vomiting limits the success of oral rehydration in children with gastroenteritis," Stephen B. Freedman, MDCM, from the Hospital for Sick Children, University of Toronto. "Thus, a safe and effective method of controlling vomiting is likely to increase the use and success rate of oral rehydration... We conducted a double-blind trial to determine whether a single oral dose of ondansetron, an antiemetic, would improve outcomes in children with gastroenteritis."

At a pediatric emergency department, 215 children ranging in age from 6 months through 10 years who were being treated for gastroenteritis and dehydration were randomized to treatment with orally disintegrating ondansetron tablets or placebo. The primary outcome was the proportion that vomited while receiving oral rehydration, according to a standardized protocol, and secondary outcomes were the number of episodes of vomiting and the proportions of children who were treated with intravenous rehydration or hospitalized.

Compared with the placebo group, children in the ondansetron group were less likely to vomit (14% vs 35%; relative risk [RR], 0.40; 95% confidence interval [CI], 0.26 - 0.61). They also had a lower mean number of vomiting episodes per child (0.18 vs 0.65; P < .001), greater oral intake (239 vs 196 mL; P = .001), and lower rate of treatment by intravenous rehydration (14% vs 31%; RR, 0.46; 95% CI, 0.26 - 0.79).

The mean length of stay in the emergency department was 12% lower in the ondansetron group than in the placebo group (P = .02). However, the rates of hospitalization (4% vs 5%; P = 1.00) and of return visits to the emergency department (19% vs 22%; P = .73) did not differ significantly between groups.

To prevent vomiting in 1 child, 5 children had to receive ondansetron (95% CI, 3.2 - 10.6). To prevent 1 child from having to be treated by intravenous rehydration, 6 had to receive ondansetron (95% CI, 3.6 - 17.0).

"In children with gastroenteritis and dehydration, a single dose of oral ondansetron reduces vomiting and facilitates oral rehydration and may thus be well suited for use in the emergency department," the authors write. "Our data suggest that it is safe to administer oral ondansetron to children with gastroenteritis, with diarrhea being the most notable side effect."

Study limitations include inability to rule out the possibility that viruses or bacteria may explain the differences in the frequency of diarrhea between groups; use of an invalidated scale for dehydration; and duration of oral rehydration limited to 1 hour.

"We found that treatment with orally disintegrating ondansetron tablets was beneficial in children with vomiting and dehydration due to gastroenteritis," the authors conclude. "The ondansetron tablet is easy to administer, has few side effects, and is safe and effective. Therefore, it may be a useful therapy in the emergency department for children with vomiting and mild-to-moderate dehydration as a result of gastroenteritis."

The National Center for Research, the National Institutes of Health, and GlaxoSmithKline, the maker of ondansetron, supported this project. The authors have disclosed no relevant financial relationships.

N Engl J Med. 2006;354:1698-1704

4. Ximelagatran May Cause Less Bleeding Than Warfarin in Patients With Nonvalvular AFib

News Author: Laurie Barclay, MD. April 28, 2006 ­ Ximelagatran is associated with less bleeding then warfarin for patients with nonvalvular atrial fibrillation, according to the results of a pooled analysis of the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III and V participants reported in the April 24 issue of the Archives of Internal Medicine.

"Ximelagatran is a novel direct thrombin inhibitor that can be administered as a fixed oral dose, without the need for anticoagulant monitoring," write James D. Douketis, MD, from McMaster University in Hamilton, Ontario, and colleagues. "Managing warfarin therapy is problematic because of the need for anticoagulant monitoring, with INR [International Normalized Ratio] testing required every 1 to 4 weeks for dose adjustments. Warfarin also interacts with other drugs, food, genetic polymorphisms, and acute illness, with the potential to cause excessive anticoagulation and bleeding."

This pooled analysis included 7329 patients with nonvalvular atrial fibrillation enrolled in the SPORTIF III and V trials to compare bleeding outcomes in patients who received ximelagatran, 36 mg twice daily, or warfarin sodium (target INR, 2.0 - 3.0). Outcome measures included annual risk of any and major bleeding, case-fatality rate, time course and anatomic sites of major bleeding, and risk factors for major bleeding with ximelagatran and warfarin treatment.

The annual incidence of any bleeding was 31.75% for ximelagatran and 38.82% for warfarin (relative risk reduction, 18.2%; 95% confidence interval [CI], 13.0 - 23.1; P < .001); and incidence of major bleeding was 2.01% vs 2.68% (relative risk reduction, 25.1%; 95% CI, 3.2 - 42.1; P = .03). The case-fatality rate of bleeding was similar with ximelagatran and warfarin (8.16% vs 8.09%; P = .98). After 24 months of treatment, the cumulative incidence of major bleeding was higher with warfarin than with ximelagatran (4.7% vs 3.7%; P = .04). Both treatments were similar in terms of anatomic sites of bleeding.

Risk factors for bleeding with ximelagatran treatment were diabetes mellitus (hazard ratio [HR], 1.81; 95% CI, 1.19 - 2.77; P = .006), previous stroke or transient ischemic attack (HR, 1.78; 95% CI, 1.16 - 2.73; P = .008), age 75 years or older (HR, 1.70; 95% CI, 1.33 - 2.18; P < .001), and aspirin use (HR, 1.68; 95% CI, 1.08 - 2.59; P = .02). In warfarin-treated patients, risk factors for bleeding were previous liver disease (HR, 4.88; 95% CI, 1.55 - 15.39; P = .007); aspirin use (HR, 2.41; 95% CI, 1.69 - 3.43; P < .001); and age 75 years or older (HR, 1.26; 95% CI, 1.03 - 1.52; P = .02).

Study limitations include pooling of the study sample from 2 studies of different design; the inclusion of intracerebral bleeding episodes as major episodes, which might have exaggerated the number of major bleeding episodes if some intracerebral episodes initially were ischemic strokes with subsequent hemorrhagic transformation; and lack of evidence of causality.

"Treatment with ximelagatran, 36 mg twice daily, is associated with a lower risk of bleeding than warfarin in patients with nonvalvular atrial fibrillation," the authors write. "Aspirin use and increasing age were associated with an increased risk of bleeding in ximelagatran- and warfarin-treated patients.... These potential benefits of ximelagatran therapy should be weighed against potential risks of treatment, which include elevated serum liver enzyme levels in approximately 6% of patients with atrial fibrillation and, rarely, severe and possibly fatal hepatitis."

AstraZeneca, the maker of ximelagatran, employs one of the authors. The other authors have disclosed no relevant financial relationships.

Arch Intern Med. 2006;166:853-859

5. Distraction Can Help Make Laceration Repair More Tolerable for Children

NEW YORK (Reuters Health) Apr 14 - Using age-appropriate distractors, such as listening to a CD player, may help reduce the anxiety and pain of laceration repair in children presenting to the ER, new research suggests.

Previous reports have suggested beneficial effects using distraction techniques, but until now no controlled studies have evaluated their ability to facilitate completion of painful procedure in the pediatric ER setting.

As reported in the April issue of Pediatrics, Dr. Madhumita Sinha, from Maricopa Medical Center in Phoenix, Arizona, and colleagues assessed the outcomes of 240 children, between 6 and 18 years of age, who were randomized to receive a distractor or no distractor during laceration repair. All of the children received a topical anesthetic and a supplemental local anesthetic was given if deemed necessary.

Children in the intervention group were given a choice of a music, video game, or cartoon video distractors. If the child showed no interest in any of these, a certified child life worker offered to read a book or blow bubbles with them. In children younger than 10 years of age, the average change in Facial Pain Scales scores did not differ significantly between the groups. However, parental perception of pain distress was lower in the distractor group than in the control group.

In older subjects, the distractors seemed to have no effect on pain, but were tied to a reduction in situational anxiety. Distraction techniques "may have a role in improving the quality of management of procedural pain in a pediatric ER setting," the authors note. Because such interventions "require minimal training and effort, integrating these techniques into existing pain management protocols might complement standard pharmacologic therapy in the pediatric ER and even in other outpatient settings."

Pediatrics 2006;117:1163-1167.

6. CT Angiography for the Evaluation of Aneurysmal SAH

Shaun D. Carstairs, MD, et al. Acad Emerg Med Volume 13, Number 5 486-492.

Objectives: Computed tomography (CT) followed by lumbar puncture (LP) is currently the criterion standard for diagnosing subarachnoid hemorrhage (SAH) in the emergency department (ED); however, this is based on studies involving a limited number of patients. The authors sought to assess the ability of CT angiography (CTA), a new diagnostic modality, in conjunction with CT/LP to detect SAH.

Methods: Consecutive patients presenting to the ED with symptoms concerning for SAH were approached. All patients had an intravenous catheter placed and underwent a noncontrast head CT followed by CTA. Patients whose CT did not reveal evidence of SAH or other pathology underwent LP in the ED. CTAs were read within 24 hours by a neuroradiologist blinded to the patient's history.

Results: A total of 131 patients were approached, 116 were enrolled, and 106 completed the study. In six of 116 patients (5.1%), aneurysm was found on CTA with normal CT and positive findings on LP; three had a positive CTA with normal CT and LP findings (one of which had a negative cerebral angiogram), and there was one false-positive CTA. Follow-up of all 131 patients showed no previously undiagnosed intracranial pathology. In this patient population, 4.3% (5/116) were ultimately found to have an SAH and/or aneurysm.

Conclusions: In this pilot study, CTA was found to be useful in the detection of cerebral aneurysms and may be useful in the diagnosis of aneurysmal SAH. A larger multicenter study would be useful to confirm these results.

7. Necessity breeds invention: a study of outpatient management of low velocity gunshot wounds

A Byrne, et al. Emergency Medicine Journal 2006;23:376-378

Background: Since the late 1980s, the emergency department (ED) at the Mater Hospital, Belfast, has implemented a policy of treating conservatively patients who sustain low velocity gunshot wounds to the lower limbs. Wounds are cleaned and minimally debrided under local anaesthetic in the ED. Patients are given oral antibiotics, and reviewed 48 hours later at the ED review clinic.

Objective: To investigate the outcome of outpatient ED management of low velocity gunshot wounds to the lower limbs.

Method: This was a retrospective, observational study from January 2000 to September 2004 inclusive. Notes were retrieved of those patients who had gunshot wound mentioned in the triage text. Patients were included if they presented with a low velocity gunshot wound to the lower limbs. Demographics and treatment regimen were recorded.

Results: In total, 90 patients sustained low energy injuries to the lower limb, with 70.5% of wounds involving the skin and soft tissue only. Most patients (n = 67) were treated as outpatients, which included 80% of unilateral injuries and 46.6% of bilateral injuries presented. There were 56 patients reviewed at clinic. Three patients developed minor complications

Conclusion: Irrigation and minimal debridement in the outpatient setting is an acceptable method of treatment for low energy gunshot wounds to the lower limbs, without orthopaedic or vascular involvement.

8. Effect of population ageing on emergency department speed and efficiency: a historical perspective from a district general hospital in the UK

G George, et al. Emergency Medicine Journal 2006;23:379-383

Objective: To examine changes in the rate of seeing patients between 1990 and 2004 and to see whether performance might be related to patient age, using data held on the patient administration system.

Method: Data collected in 1990 were compared with those collected in 2004. Age related data were examined for the following parameters: the number of patients arriving by ambulance; the time taken to process the attendance; the number of investigations; the number of emergency admissions; and the length of inpatient stay.

Results: Emergency department (ED) performance has fallen markedly since 1990. Between 1990 and 2004, there was a 54% increase in total patients with a disproportionate 198% increase in patients aged more than 70 years, including a 671% increase in those aged more than 90 years. The time taken to manage patients increased with age. In 2004, there was a marked rise in investigation rates, and the probability of having investigations increased with age. In 2004, older patients (aged more than 70 years) were 4.9 times more likely to require admission to hospital than younger patients (aged 30 years or less). Their average length of stay was 6.9 times longer. Younger patients were 3.3 times more numerous than older patients but older patients occupied 9.8 times more emergency bed days.

Conclusions: Pressure on emergency care is associated with a disproportionate increase in the number of elderly patients and with an increased tendency to investigate them. Population ageing is of central importance in planning health services.

9. Alzheimer's Disease Among the 2004 Top Causes of Death in US

WASHINGTON (Reuters) Apr 20 - Americans are living longer, healthier lives -- and among the top 10 causes of death -- only Alzheimer's disease is increasing, the U.S. federal government reported on Wednesday.

Alzheimer's disease moved to seventh place from eighth place among the leading causes of death in 2004, passing influenza and pneumonia, the National Center for Health Statistics reported. "The life expectancy of Americans in 2004 -- 77.9 years -- is the highest it has ever been," the NCHS said in a statement.

"The life expectancy for women in the United States is 80.4 years; the life expectancy for U.S. men is 75.2 years. The life expectancy gender gap is narrowing -- the 5.2 year difference in 2004 was the smallest difference since 1946," according to the report.
This change is related to the 7.3% drop in mortality from influenza and pneumonia, compared with the 1.4% increase in mortality from Alzheimer's disease.

The NCHS, part of the U.S. Centers for Disease Control and Prevention, reported that 2.39 million Americans died in 2004.

The U.S. death rate fell to a record low of 801 deaths per 100,000 people, down from nearly 833 deaths per 100,000 in 2003. Overall, 50,000 fewer people died between 2003 and 2004, the biggest 1-year drop in decades.

The 10 leading causes of death in 2004 were:

1. Heart disease -- 654,000 deaths
2. Cancer -- 550,000 deaths
3. Stroke -- 150,000 deaths
4. Chronic lower respiratory diseases -- 123,000
5. Accidents -- 108,000
6. Diabetes -- 72,800
7. Alzheimer's disease -- 65,829
8. Influenza and pneumonia -- 61,472
9. Kidney disease -- 42,762
10. Septicemia -- 33,464.

10. Coffee May Not Increase Risk for Heart Disease

News Author: Laurie Barclay, MD. April 25, 2006 ­ Coffee does not increase the risk for coronary heart disease (CHD) in men or women, according to the results of a large, prospective cohort study reported in the April 24 Rapid Access issue of Circulation.

"We found that coffee consumption was not associated with an increased risk of CHD," lead author Esther Lopez-Garcia, DrPH, from the Universidad Autonoma de Madrid in Spain, said in a news release. "This lack of effect is good news, because coffee is one of the most widely consumed beverages in the world.... The length of follow up is important because it allowed us to examine the long-term effects of coffee consumption."

The study cohort consisted of 44 005 men and 84 488 women without history of cardiovascular disease or cancer. The investigators first evaluated coffee consumption in 1986 for men and in 1980 for women and then repeatedly every 2 to 4 years. During follow-up through 2000, there were 2173 incident cases of CHD in men, including 1449 nonfatal myocardial infarctions and 724 fatal cases of CHD; and 2254 cases in women, including 1561 nonfatal myocardial infarctions and 693 fatal cases of CHD.

After adjustment for age, smoking, and other CHD risk factors, the relative risks (RRs) of CHD for men across categories of cumulative coffee consumption were 1.0 for less than 1 cup/month; 1.04 (95% confidence interval [CI], 0.91 - 1.17) for 1 cup/month to 4 cups/week; 1.02 (95% CI, 0.91 - 1.155 for 7 cups/week; 1.07 (95% CI, 0.88 - 1.31) for 2 to 3 cups/day; 0.97 (95% CI, 0.86 - 1.11) for 4 to 5 cups/day, and 0.72 (95% CI, 0.49 - 1.07) for more than 6 cups/day (P for trend = .41). For women, the corresponding RRs were 1.0, 0.97 (95% CI, 0.83 - 1.14), 1.02 (95% CI, 0.90 - 1.17), 0.84 (95% CI, 0.74 - 0.97), 0.99 (95% CI, 0.83 - 1.17), and 0.87 (95% CI, 0.68 - 1.11; P for trend = .08).

Stratification by smoking status, alcohol consumption, history of type 2 diabetes mellitus, and body mass index did not alter the findings nor did examining the most recent coffee consumption. RRs for quintiles of caffeine intake ranged from 0.97 (95% CI, 0.84 - 1.10) in the second quintile to 0.97 (85% CI, 0.84 - 1.11) in the highest quintile (P for trend = 0.82) in men and from 1.02 (0.90 - 1.16) to 0.97 (0.85 - 1.11; P for trend = 0.37) in women.

"We believe this study clearly shows there is no association between filtered coffee consumption and CHD," Dr. Lopez-Garcia says. "However, because of the modest consumption of non-filtered coffee among participants, this study does not exclude a relationship between high non-filtered consumption and increased CHD risk."

Frequent or heavy coffee consumption was strongly associated with smoking cigarettes, drinking alcohol, and using aspirin and with lower frequency of tea drinking, exercise, and use of multivitamin and vitamin E supplements. Risk for CHD was not significantly different in women who frequently drank decaffeinated coffee and in those who did not. Total cholesterol, low-density and high-density lipoprotein cholesterol levels in men and women coffee drinkers did not differ in those who drank caffeinated or decaffeinated coffee. CHD risk associated with drinking coffee did not differ in people with or without type 2 diabetes.

"We can't exclude the association between coffee consumption and the risk of CHD in small groups of people," says coauthor Rob van Dam, PhD, from Harvard University School of Public Health in Boston, Mass. "For example, a recent study suggested coffee could be detrimental in people with certain genotypes, although that finding requires confirmation."

The National Institutes of Health funded this study. Two authors have disclosed that they are supported by Ministerio de Educacion y Cultura de EspaƱa, Fondo Social Europeo, and/or the American Heart Association. The authors have disclosed no financial relationships.

Circulation. Posted online April 24, 2006.

11. ACS Patients Do Better at Hospitals That Follow Treatment Guidelines

NEW YORK (Reuters Health) Apr 25 - There is a strong link between hospital adherence to treatment guidelines for acute coronary syndromes (ACS) and outcome, according to a new study, which shows that greater adherence to the guidelines is associated with decreased in-hospital mortality in ACS patients.

"Our work supports the central hypothesis of hospital quality improvement; namely, better adherence with evidence-based care practices will result in better outcomes for patients who are treated," write Dr. Eric Peterson and colleagues from Duke University Medical Center in Durham, North Carolina in the April 26th issue of the Journal of the American Medical Association.

The study is based on an analysis of 64,775 ACS patients at 350 academic and nonacademic US medical centers. Overall, the nine treatments recommended by the American College of Cardiology and American Heart Association for non-ST-segment elevation ACS were followed 74% of the time.

"This shows that the care being delivered is not ideal, as in up to one in four cases, patients are not receiving medicines that are proven to save lives," Dr. Peterson noted in a statement from Duke. The data also show that there is wide variance among hospitals -- "some are near perfect in the use of certain drugs while others are in the 50% to 60% range of adherence," he noted.

Specifically, the research team found that hospitals with the highest levels of adherence to the nine different ACS treatment guidelines had an in-hospital death rate of 4.15%, compared with a rate of 6.31% for hospitals with the lowest levels of adherence.

Additionally, after risk adjustment, every 10% improvement in ACS treatment guideline adherence led to a 10% decline in in-hospital mortality. Adherence to proven guidelines "may serve as a marker for the overall culture of the hospital and its commitment to providing the best possible care," Dr. Peterson said.

The team also found that hospitals with high adherence to ACS treatment guidelines were also more likely to use "newer" recommended therapies such as glycoprotein IIb/IIIb inhibitors, clopidogrel and lipid-lowering drugs. "Again, keeping up with the latest is another indicator of a hospital's overall culture of providing the best possible care," Dr. Peterson said.

JAMA 2006;295:1912-1920.


2005 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) of Pediatric and Neonatal Patients: Pediatric Advanced Life Support

PEDIATRICS Vol. 117 No. 5 May 2006, pp. e1005-e1028 (doi:10.1542/peds.2006-0219)

Full text, see:

13. Stress Testing: It Is Safe to Wait

David Magid, MD, MPHa, S. Adam Hill, MDb. Ann Emerg Med. 2006;47:436-437.

Patients who present to the emergency department (ED) with chest pain suggestive of a possible acute coronary syndrome pose a diagnostic and disposition challenge. The patient medical history, physical examination, and laboratory and ECG results have limited diagnostic sensitivity for acute coronary syndrome. As a result, a small but significant number of acute coronary syndrome patients are discharged from the ED, some of whom die or experience other adverse outcomes.

In an effort to reduce the rate of inadvertent discharge of acute coronary syndrome patients, many emergency physicians have a low threshold for admitting patients who present to the ED with chest pain. In some studies, fewer than 30% of patients admitted to the hospital with possible acute coronary syndrome receive a final hospital discharge diagnosis of acute myocardial infarction or unstable angina. Such liberal admission policies consume significant resources, contribute to hospital crowding, and drive up the cost of health care. Some estimates place the cost of this practice at upwards of $3 billion annually.

Several approaches have been proposed as alternatives to this traditional approach of ED evaluation and hospital admission for patients with chest pain. These include accelerated inpatient, observation unit, or ED rule-out acute myocardial infarction protocols that include serial ECGs and cardiac biomarkers. A common theme of these approaches is to use risk stratification to identify low-risk patients who can be further evaluated in a more cost-effective manner than a typical hospital admission. Patients whose initial hospital-based evaluation is negative for acute coronary syndrome typically undergo stress testing before discharge.

However, at some hospitals stress testing is not available on all days of the week or times of the day. As a result, patients may have to stay in the hospital overnight just to receive a stress test the next morning. To address this issue, some have suggested that for appropriately selected low-risk patients, it may be safe and more efficient to discharge them from the ED and obtain a stress test as an outpatient.

14. Aspirin May Reduce the Risk for Aminoglycoside-Related Hearing Loss

Yael Waknine. April 26, 2006 ­ Concurrent administration of aspirin therapy significantly reduces the risk for gentamycin-induced hearing loss, according to the results of a prospective, randomized, double-blind, placebo-controlled Chinese trial reported in a letter to the editor in the April 27 issue of the New England Journal of Medicine.

"The incidence of aminoglycoside-induced hearing loss averages 8% but the numbers may be higher in developing countries where aminoglycosides are frequently the only affordable antibiotics and are sold over the counter," lead author Su-Hua Cha, MD, associate laboratory director of the Kresge Hearing Research Institute's biochemistry laboratory at the University of Michigan (U-M) Medical School in Ann Arbor, says in a news release.

For the study, investigators randomized 195 adult patients at the Xijing Hospital and Airforce Chengdu Hospital scheduled for 5 to 7 days of intravenous gentamycin therapy to receive 2 weeks of supplementation with 1 g of aspirin 3 times daily (n = 89) or to placebo (n = 106). Results at 5 to 7 weeks posttherapy showed that aspirin therapy significantly reduced the risk for ototoxicity, defined as a unilateral or bilateral shift from baseline of 15 dB or more at both 6 and 7 kHz (3% vs 13%; P = .013; relative risk, 0.26 [95% confidence interval, 0.08 - 0.86]). The efficacy of gentamycin was similar in both groups.

Potential drawbacks to use of aspirin in this setting include the off-label nature of the indication and the risk for gastric bleeding. In the study, gastrointestinal symptoms were more commonly reported among aspirin-treated patients and gastric bleeding led to discontinuation of treatment in 3 patients.

Nevertheless, aspirin is commonly available and inexpensive. "We would like to see the word get around to the medical community in the world that you can take some precautions to minimize the risk to your patients," senior author Jochen Shacht, PhD, professor of biological chemistry in otolaryngology at the U-M Medical School and director of the Kresge Hearing Research Institute, says in a news release.

Dr. Schacht notes that although gentamycin is not commonly used in the United States and its use has been declining in other industrialized countries, it is unlikely to be replaced in the near future due to the specificity of its applications and its widespread and inexpensive availability in poorer countries.

While aspirin shows promise for reducing the risk for aminoglycoside-induced ototoxicity, the authors conclude that further studies are needed to develop a prophylactic drug with fewer adverse effects and/or new and safer antibiotics.

N Engl J Med. 2006;354:1856-1857.

15. Promethazine Products Contraindicated in Children Under 2 Years

Yael Waknine. April 26, 2006 ­ The US Food and Drug Administration (FDA) is warning healthcare professionals, parents, and caregivers against the use of promethazine HCl in children younger than 2 years due to the risk for fatal respiratory depression, according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program.

The FDA has received postmarketing reports of serious adverse events, including 7 deaths and 22 cases of respiratory depression, that were associated with use of promethazine in children younger than 2 years. As a result, all promethazine-containing syrups, tablets, suppositories, and injectables are contraindicated in this population.

Because these adverse events were not directly related to individualized weight-based dosing, promethazine should be administered with caution and at the lowest effective dose for pediatric patients aged 2 years and older. Concurrent administration of other drugs with the potential for respiratory depression should also be avoided.

Promethazine-containing products are marketed in the United States as brand name (Phenergan, made by Wyeth Pharmaceuticals, Inc) and generic formulations. They are indicated for use in treating hypersensitivity reactions and as an antiemetic and/or sedative in various settings. The FDA notes that antiemetics are not recommended for the treatment of uncomplicated vomiting in pediatric patients; use of these agents should be limited to prolonged vomiting of known etiology.

Because the drug's extrapyramidal effects may be confused with central nervous system signs of undiagnosed primary disease, promethazine should not be used in pediatric patients with signs and symptoms suggestive of Reye's syndrome or other hepatic diseases.

Healthcare professionals are encouraged to report promethazine-related adverse events to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

16. Age Effect on Efficacy and Side Effects of Two Sedation and Analgesia Protocols on Patients Going through Cardioversion: A Randomized Clinical Trial

Mine Parlak, MD, et al. Acad Emerg Med Volume 13, Number 5 493-499.

Background: Cardioversion (CV), a painful procedure, requires sedation and analgesia. Although several sedation agents currently are in use for CV, data on age-specific efficacy and side effects of midazolam and propofol have been limited.

Objectives: To compare the efficacy and side effects of midazolam and propofol in patients of two different age groups, younger than 65 years and 65 years and over, who were going through CV.

Methods: Seventy consented patients with CV indications caused by atrial fibrillation were included in this clinical trial. The participants were placed into four groups by using a stratified randomization method: patients aged younger than 65 years who were receiving midazolam (n = 12) or propofol (n = 11) and patients 65 years and over who were receiving midazolam (n = 25) or propofol (n = 22). Medications were administered by slow intermittent bolus injections. During CV, time to reach Ramsay Sedation Scale level 5 (RSS-5; induction time); time to reach RSS-2 (recovery time); and side effects including desaturation, apnea, and changes in hemodynamic parameters were recorded by a person blinded to the patient treatment allocation.

Results: Mean induction time was similar in all four groups. Mean recovery time (min ± SD) was shorter in both propofol groups when compared with both midazolam groups: 18.8 (± 4.06) and 40.33 (± 20.8) in the group younger than 65 years and 18.2 (± 5.12) and 54.2 (± 20.85) in the group 65 years or older, respectively (p < 0.001). Older participants in each medication group needed less medication than younger patients. There were no hemodynamic differences between the groups. Desaturation was higher in both midazolam groups as compared with individuals in the age-matched propofol groups (both p < 0.05). Patient reactions were less in propofol groups with similar joules during CV procedures than were those in the midazolam groups.

Conclusions: Propofol appears to be a better choice for CV sedation in elders because of its short recovery time, fewer side effects, and its more comfortable sedative effect.

17. Does End-tidal Carbon Dioxide Monitoring Detect Respiratory Events Prior to Current Sedation Monitoring Practices?

John H. Burton, MD, et al. Acad Emerg Med Volume 13, Number 5 500-504.

Objectives: The value of ventilation monitoring with end-tidal carbon dioxide (ETCO2) to anticipate acute respiratory events during emergency department (ED) procedural sedation and analgesia (PSA) is unclear. The authors sought to determine if ETCO2 monitoring would reveal findings indicating an acute respiratory event earlier than indicated by current monitoring practices.

Methods: The study included a prospective convenience sample of ED patients undergoing PSA. Clinicians performed ED PSA procedures with generally accepted patient monitoring, including oxygen saturation (SpO2), and clinical ventilation assessment. A study investigator recorded ETCO2 levels and respiratory events during each PSA procedure, with clinical providers blinded to ETCO2 levels. Acute respiratory events were defined as SpO2 92%, increases in the amount of supplemental oxygen provided, use of bag-valve mask or oral/nasal airway for ventilatory assistance, repositioning or airway alignment maneuvers, and use of physical or verbal means to stimulate patients with depressed ventilation or apnea, and reversal agent administration.

Results: Enrollment was stopped after independent review of 20 acute respiratory events in 60 patient sedation encounters (33%). Abnormal ETCO2 findings were documented in 36 patients (60%). Seventeen patients (85%) with acute respiratory events demonstrated ETCO2 findings indicative of hypoventilation or apnea during PSA. Abnormal ETCO2 findings were documented before changes in SpO2 or clinically observed hypoventilation in 14 patients (70%) with acute respiratory events.

Conclusions: Abnormal ETCO2 findings were observed with many acute respiratory events. A majority of patients with acute respiratory events had ETCO2 abnormalities that occurred before oxygen desaturation or observed hypoventilation.

18. Withholding Resuscitation: A New Approach to Prehospital End-of-Life Decisions

Sylvia Feder, MA, MICP; et al. Ann Intern Med. 2 May 2006 Volume 144 Issue 9 Pages 634-640.

This study tested the use of new guidelines that allowed emergency medical services (EMS) personnel to withhold resuscitation if a patient had a terminal condition and if the patient, family, or caregivers asked them not to resuscitate. The EMS units that implemented the guidelines withheld more resuscitations as a result of verbal requests than EMS units that did not implement the guidelines.

Background: Emergency medical services (EMS) personnel often are not permitted to honor requests to withhold resuscitation at the end of life, particularly if there is no written do-not-resuscitate (DNR) order.

Objective: To determine whether EMS personnel from agencies implementing new guidelines would be more likely to withhold resuscitation from persons having out-of-hospital cardiac arrests than would personnel from agencies that did not implement the guidelines.

Design: Observational study in which 16 of 35 local EMS agencies volunteered to implement new guidelines for withholding resuscitation.

Setting: King County, Washington.

Patients: 2770 patients with EMS-attended cardiac arrest.

Intervention: New guidelines adopted by participating agencies permitted EMS personnel to withhold resuscitation if the patient had a terminal condition and if the patient, family, or caregivers indicated, in writing or verbally, that no resuscitation was desired.

Measurements: Proportion of resuscitations withheld in agencies that implemented new guidelines compared with those that did not.

Results: Emergency medical services personnel from agencies implementing new guidelines withheld resuscitation in 11.8% of patients (99 of 841 patients) having cardiac arrests, compared with an average of 5.3% (range, 4.2% to 5.9%) of patients (103 of 1929 patients) in 3 historical and contemporary control groups. Honoring verbal requests alone accounted for 53% of withheld resuscitations in the intervention group (52 of 99 patients) compared with an average of 8% (range, 7% to 9%) in the control groups (8 of 103 patients).

Limitations: The study was not a randomized, controlled trial; individual agencies chose whether to implement the guidelines.

Conclusions: Implementation of new guidelines was associated with an increase in the number of resuscitations withheld by EMS personnel. This increase was primarily due to honoring verbal requests.

19. Patients' Global Ratings of Care Don't Reflect Technical Quality of Care

NEW YORK (Reuters Health) May 01 - Patients' global ratings of their healthcare are not associated with the technical quality of care they receive, according to a new survey. Therefore, "assessments of quality of care should include both patient evaluations and independent assessments of technical quality," conclude researchers in the May 1st issue of the Annals of Internal Medicine.

Patient ratings of care are often used by health plans, payers, providers, and consumers to assess the quality of care received, note the authors. However, the extent to which these assessments of care are related to the technical quality of care received is unclear.

To investigate, a team led by Dr. John T. Chang, from the David Geffen School of Medicine at the University of California, Los Angeles asked 236 independently living frail elderly adults to rate the care they received in two managed care groups over a 12-month period. Dr. Chang's group also reviewed patient medical records to gauge adherence to standard of care for common conditions.

The team found that overall ratings of care were high and correlated strongly and directly with the physician's interpersonal communication skills. "Better communication was associated with higher global ratings of health care," Dr. Chang and colleagues report.

However, higher patient global ratings of health care were not significantly associated with technical quality of care received.

This hints that "technical quality of care and reports about interpersonal quality of care seem to be separate domains, and patients' global ratings of health relate only to the former," Dr. Chang and colleagues conclude.

Ann Intern Med 2006;144:665-672.