Lit Bits: Feb 10, 2010

From the recent medical literature...

1. Nasogastric Aspiration and Lavage in Emergency Department Patients with Hematochezia or Melena Without Hematemesis

Palamidessi N, et al. Acad Emerg Med. 2010;17:126–132.

Objectives: The utility of nasogastric aspiration and lavage in the emergency management of patients with melena or hematochezia without hematemesis is controversial. This evidence-based emergency medicine review evaluates the following question: does nasogastric aspiration and lavage in patients with melena or hematochezia and no hematemesis differentiate an upper from lower source of gastrointestinal (GI) bleeding?

Methods: MEDLINE, EMBASE, the Cochrane Library, and other databases were searched. Studies were selected for inclusion in the review if the authors had performed nasogastric aspiration (with or without lavage) in all patients with hematochezia or melena and performed esophagogastroduodenal endoscopy (EGD) in all patients. Studies were excluded if they enrolled patients with history of esophageal varices or included patients with hematemesis or coffee ground emesis (unless the data for patients without hematemesis or coffee ground emesis could be separated out). The outcome was identifying upper GI hemorrhage (active bleeding or high-risk lesions potentially responsible for hemorrhage) and the rate of complications associated with the nasogastric tube insertion. Quality of the included studies was assessed using standard criteria for diagnostic accuracy studies.

Results: Three retrospective studies met our inclusion and exclusion criteria. The prevalence of an upper GI source for patients with melena or hematochezia without hematemesis was 32% to 74%. According to the included studies, the diagnostic performance of the nasogastric aspiration and lavage for predicting upper GI bleeding is poor. The sensitivity of this test ranged from 42% to 84%, the specificity from 54% to 91%, and negative likelihood ratios from 0.62 to 0.20. Only one study reported the rate complications associated with nasogastric aspiration and lavage (1.6%).

Conclusions: Nasogastric aspiration, with or without lavage, has a low sensitivity and poor negative likelihood ratio, which limits its utility in ruling out an upper GI source of bleeding in patients with melena or hematochezia without hematemesis.

2. Muscle Relaxant Adds No Benefit to Ibuprofen for Cervical Strain

Pain relief did not differ among patients who received ibuprofen, cyclobenzaprine, or both drugs.

Muscle relaxants often are prescribed for neck and back pain, despite the lack of evidence of benefit. Researchers evaluated the effect of cyclobenzaprine in a prospective, randomized, double-blind study in a convenience sample of 61 adult patients (mean age, 34; 58% women) who presented to a level I trauma center emergency department with acute cervical strain (87% caused by motor vehicle collisions). Patients received ibuprofen (800 mg), cyclobenzaprine (5 mg), or both drugs three times daily for up to 7 days, as needed for pain. All patients received an initial dose of 800 mg of ibuprofen in the ED.

Patients rated pain severity on a 100-mm visual analog scale 30 to 60 minutes after taking the morning dose of medication. Pain scores improved significantly over 7 days in all three groups and did not differ among groups. Adverse effects were minimal and included dizziness in four patients who received cyclobenzaprine alone or with ibuprofen and nausea in one patient who received ibuprofen alone.

Comment: A small dose of cyclobenzaprine was used in this study, perhaps to avoid the anticholinergic, antihistaminic, and sedative side effects of this drug, which is closely related chemically to tricyclic antidepressants. No convincing evidence supports the use of cyclobenzaprine in painful musculoskeletal conditions, and the drug's benefit-to-adverse effect profile therefore argues against prescribing it. Most patients with cervical strain will get better. Provide adequate analgesia as needed, and leave the cyclobenzaprine in the pharmacy.

— Kristi L. Koenig, MD, FACEP. Published in Journal Watch Emergency Medicine February 5, 2010. Citation: Khwaja SM et al. Comparison of ibuprofen, cyclobenzaprine or both in patients with acute cervical strain: A randomized controlled trial. CJEM 2010 Jan; 12:39.

3. Aspirin for the Primary Prevention of Stroke and Myocardial Infarction: Ineffective or Wrong Dose?

Dalen JE. Amer J Med. 2010;123:101-102.

The concluding paragraphs:

It is difficult to ignore the results of 7 consecutive randomized clinical trials. There are 2 possible conclusions. One conclusion is that the recommendations of aspirin for primary prevention by the organizations shown in Table 1 are incorrect because aspirin is ineffective. Millions of people throughout the world are taking aspirin for primary prevention. Should they be told to discontinue aspirin?

The other conclusion is that the recommended dose is insufficient; 7 clinical trials have documented that doses of 100 mg or less are ineffective. The US Physicians Health study reported a 44% reduction in myocardial infarction in physicians taking 325 mg every other day (162 mg/d). One might reasonably conclude that the recommended dosage should be increased to 162 mg per day. I will continue to recommend 162 mg per day to my patients.

Full-text (free): http://www.amjmed.com/article/S0002-9343(09)00976-0/fulltext

4. Spine Immobilization for Penetrating Trauma Can Be Harmful

Patients who underwent immobilization were twice as likely to die as those who did not.

Despite a lack of supportive evidence for the practice, prehospital providers often apply spine immobilization to patients who have penetrating trauma to the head, neck, or torso without neurological symptoms or deficit. These authors retrospectively assessed the effect of prehospital spine immobilization on mortality in patients with penetrating trauma using data from the American College of Surgeons National Trauma Data Bank between 2001 and 2004.

Of 45,284 patients (median age, 29), 4.3% received cervical collars, spinal backboards, or both. The overall mortality rate was 8.1%. Multiple logistic regression analysis that controlled for confounders, including Injury Severity Score and Revised Trauma Score, showed that immobilized patients had significantly increased mortality (odds ratio, 2.06); this finding held true in subgroups of patients with gunshot wounds (OR, 2.12), hypotension (OR, 2.42), and gunshot wounds and hypotension (OR, 3.19). Complete data on in-hospital procedures were available for about 31,000 patients. Only 30 patients (0.1%) underwent operative spine stabilizing procedures for incomplete spinal-cord injury. The number needed to treat with spine immobilization to potentially benefit 1 patient was 1032. The number needed to harm with spine immobilization to potentially contribute to 1 death was 66.

Comment: Increasing evidence indicates that limited intervention at the scene allows trauma patients to receive definitive care at a trauma center more rapidly. This study indicates that prehospital spine immobilization is associated with increased mortality in patients with penetrating trauma. Trying to assign cause and effect in a retrospective study is risky, but possibly increased scene time or interference with later care (e.g., intubation, radiography, examination of the patient's back) contribute to worse outcomes. Spine immobilization might be applied more wisely to patients with altered mental status, spine tenderness, or sensorimotor dysfunction.

— John A. Marx, MD, FAAEM. Published in Journal Watch Emergency Medicine January 29, 2010. Citation: Haut ER et al. Spine immobilization in penetrating trauma: More harm than good? J Trauma 2010 Jan; 68:115.

5. Placing Thoracic Central Lines in Coagulopathic Patients: A Sampling of the Lit

A. Low levels of prothrombin time (INR) and platelets do not increase the risk of significant bleeding when placing central venous catheters.

Weigand K, et al. Med Klin (Munich). 2009;104:331-5.

BACKGROUND AND PURPOSE: Central venous catheters are frequently placed in intensive care medicine for multiple indications. The risk of severe bleeding after cannulation is considered to be increased in patients with abnormal coagulation, common in critically ill patients. PATIENTS AND METHODS: This open prospective trial, performed at two medical intensive care units and one hematology intermediate care ward, investigated whether insertion of a central venous catheter in patients with coagulopathy (prothrombin time less than 50% [International Normalized Ratio, INR, 1.5 or greater] and/or platelets less than 50 x 10(9)/l) bears an increased risk of bleeding. RESULTS: In 196 patients with and without severe disorders of hemostasis, no significant difference in decrease of hemoglobin after catheter placement was observed. In addition, no correlation between a significant drop in hemoglobin and increased levels of creatinine or urea was seen. Mechanical complications were similar in frequency compared to previous publications. CONCLUSION: These findings demonstrate that coagulation disorders with altered prothrombin time (INR) or platelets do not increase the risk of significant bleeding when inserting a central venous catheter. Therefore, the prophylactic correction of coagulation by transfusion of blood products or coagulation factors is not necessary before central venous catheter insertion.

B. Central venous catheter placement in patients with disorders of hemostasis.

Mumtaz H, et al. Am J Surg. 2000;180:503-5; discussion 506.

BACKGROUND: Patients requiring central venous access frequently have disorders of hemostasis. The aim of this study was to identify factors predictive of bleeding complications after central venous catheterization in this group of patients. METHODS: A retrospective analysis of all central venous catheters placed over a 2-year period (1997 to 1999) at our institution were performed. The age, sex, clinical diagnosis, most recent platelet count, prothrombin international normalized ratio (INR), activated partial thromboplastin time (aPTT), catheter type, the number of passes to complete the procedure, and bleeding complications were retrieved from the medical records. RESULTS: In a 2-year period, 2,010 central venous catheters were placed in 1,825 patients. Three hundred and thirty placements were in patients with disorders of hemostasis. In 88 of the 330 patients, the underlying coagulopathy was not corrected before catheter placement. In these patients, there were 3 bleeding complications requiring placement of a purse string suture at the catheter entry site. In the remaining 242 patients, there was 1 bleeding complication. Of the variables analyzed, only a low platelet count (below 50 x 10(9)/L) was significantly associated with bleeding complications. CONCLUSION: Central venous access procedures can be safely performed in patients with underlying disorders of hemostasis. Even patients with low platelet counts have infrequent (3 of 88) bleeding complications, and these problems are easily managed.

C. Central venous catheter placement in patients with disorders of hemostasis.

Doerfler ME, et al. Chest. 1996;110:185-8.

OBJECTIVE: To define the incidence of bleeding complications from central venous access procedures performed by a critical care service in patients with disorders of hemostasis. DESIGN: Prospective, consecutive sample, collection of clinical data. SETTING: University teaching hospital. PATIENTS: Seventy-six consecutive patients with disorders of hemostasis who required central venous access for clinical management between October 1992 and October 1993. MEASUREMENTS: Age, sex, clinical diagnosis, most recent platelet count, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were recorded from the medical record of patients with known coagulation or platelet abnormalities. The site of central venous catheter placement, the number of needle passes necessary to complete the procedure, and the occurrence of complications were reported by the critical care attending physician performing or supervising the procedure. RESULTS: One hundred four central venous access procedures were performed on 76 patients with disorders of hemostasis. Seventy-three percent of catheters were placed in patients with platelet counts less than 100,000/mL and 40% of catheters were placed in patients with abnormalities of PT, aPTT, or both. Thirteen percent of patients had abnormalities of both platelets and coagulation profile. There were no serious complications. Bleeding complicated 7 (6.5% of the procedures; 5 patients had bleeding from the skin (from the suture sites in four), and 2 patients developed small periosteal hematomas. All patients with bleeding complications had thrombocytopenia with mean platelet counts of 22,000/mL and a range of 6,000 to 37,000/mL. Most patients with platelet counts in this range did not have clinically evident bleeding. CONCLUSIONS: Central venous access procedures can be done safely in patients with disorders of hemostasis by skilled physicians who frequently perform these procedures. Patients most likely to experience bleeding from these procedures are patients with severe thrombocytopenia. In this series, only a single patient, with a platelet count of 6,000/mL, required therapeutic blood product administration.

D. Invasive line placement in critically ill patients: do hemostatic defects matter?

DeLoughery TG, et al. Transfusion. 1996;36:827-31.

BACKGROUND: Blood components are often given prophylactically before the placement of invasive lines in patients with coagulation defects. Little, however, is known about the epidemiology of defects in these patients. The purpose of this study is to ascertain what proportion of intensive care patients who receive invasive lines have hemostatic defects, what actions are taken by physicians to correct these abnormalities before invasive line insertion, and what the incidence is of bleeding complications after invasive line placement. STUDY DESIGN AND METHODS: Charts were retrospectively reviewed for 490 intensive care patients in whom 938 arterial, pulmonary artery, and central venous lines were placed. RESULTS: At least one defect in hemostasis was documented for 388 patients (41%) before line placement, with 253 (27%) of these patients evidencing severe abnormalities. Seventeen percent of patients had no preprocedure laboratory evaluation. Trauma patients showed the highest numbers of abnormalities in hemostatic testing, but medical patients had more-severe defects. The occurrence of isolated abnormal laboratory values did not predict bleeding, but a score derived from a consideration of multiple defects did. Correction of the abnormalities was attempted in 37 percent of patients with hemostatic defects. Sixteen patients had bleeding complications, but only two had complications that were life-threatening. None of the complications were fatal. CONCLUSION: Invasive lines are used frequently in patients with hemostatic defects, often without any attempt to correct the abnormalities. Nevertheless, rates of hemorrhage are low and appear to be closely related to the level of experience of the physician rather than to defects in hemostasis. These findings suggest that the use of blood components for preprocedure correction of hemostatic defects is not necessary, except in those patients who have the most severe hemostatic abnormalities.

6. Risk of Deep Vein Thrombosis Following a Single Negative Whole-Leg Compression Ultrasound: A Systematic Review and Meta-analysis

Johnson SA, et al. JAMA. 2010;303:438-445.

Context: In patients with suspected lower extremity deep vein thrombosis (DVT), compression ultrasound (CUS) is typically the initial test to confirm or exclude DVT. Patients with an initial negative CUS result often require repeat CUS after 5 to 7 days. Whole-leg CUS may exclude proximal and distal DVT in a single evaluation.

Objective To determine the risk of venous thromboembolism after withholding anticoagulation in patients with suspected lower extremity DVT following a single negative whole-leg CUS result.

Data Sources: MEDLINE, EMBASE, CINAHL, LILACS, Cochrane, and Health Technology Assessments databases were searched for articles published from January 1970 through November 2009. Supplemental searches were performed of Internet resources, reference lists, and by contacting content experts.

Study Selection: Included studies were randomized controlled trials and prospective cohort studies of patients with suspected DVT and a negative whole-leg CUS result who did not receive anticoagulant therapy, and were followed up at least 90 days for venous thromboembolism events.

Data Extraction: Two authors independently reviewed and extracted data regarding a single positive or negative whole-leg CUS result, occurrence of venous thromboembolism during follow-up, and study quality.

Results: Seven studies were included totaling 4731 patients with negative whole-leg CUS examinations who did not receive anticoagulation. Of these, up to 647 patients (13.7%) had active cancer and up to 725 patients (15.3%) recently underwent a major surgery. Most participants were identified from an ambulatory setting. Venous thromboembolism or suspected venous thromboembolism–related death occurred in 34 patients (0.7%), including 11 patients with distal DVT (32.4%); 7 patients with proximal DVT (20.6%); 7 patients with nonfatal pulmonary emboli (20.6%); and 9 patients (26.5%) who died, possibly related to venous thromboembolism. Using a random-effects model with inverse variance weighting, the combined venous thromboembolism event rate at 3 months was 0.57% (95% confidence interval, 0.25%-0.89%).

Conclusion: Withholding anticoagulation following a single negative whole-leg CUS result was associated with a low risk of venous thromboembolism during 3-month follow-up.

7. Red Flags May Help Identify Serious Infection in Children

Laurie Barclay, MD. February 5, 2010 — Rapid breathing, parental concern, and the clinician's instinct are among the red flags warning of serious infection in children in developed countries, according to the results of a systematic review reported online in the February 3 issue of The Lancet.

"Our aim was to identify which clinical features have value in confirming or excluding the possibility of serious infection in children presenting to ambulatory care settings in developed countries," write Ann Van den Bruel, MD, from Katholieke Universiteit in Leuven, Belgium, and colleagues from the European Research Network on Recognising Serious Infection investigators.

The reviewers searched electronic databases (Medline, Embase, DARE, CINAHL) and bibliographies of identified relevant studies. In addition, they asked experts to identify articles evaluating clinical characteristics of serious infection in children.

Inclusion criteria for studies were analysis of diagnostic accuracy or prediction rules, enrollment of otherwise healthy children aged 1 month to 18 years, ambulatory care setting, outcome measure of serious infection, features evaluable in the ambulatory care setting, and sufficient data reported.

Evaluation of study quality was based on Quality Assessment of Diagnostic Accuracy Studies criteria. For each clinical feature, the reviewers calculated likelihood ratios for the presence (positive likelihood ratio) or absence (negative likelihood ratio) of the outcome, as well as pretest and post-test probabilities.

Red flags, or warning signs for serious infection, were defined as clinical characteristics with a positive likelihood ratio of more than 5.0. Rule-out signs were defined as clinical characteristics with a negative likelihood ratio of less than 0.2.

Of 1939 potentially relevant studies identified, 30 studies met selection criteria and were included in the analysis. Red flags identified from several studies were cyanosis (positive likelihood ratio range, 2.66 - 52.20), rapid breathing (1.26 - 9.78), poor peripheral perfusion (2.39 - 38.80), and petechial rash (6.18 - 83.70). Factors identified as strong red flags in 1 primary care study were parental concern (positive likelihood ratio, 14.40; 95% confidence interval [CI], 9.30 - 22.10) and clinician instinct (positive likelihood ratio, 23.50; 95% CI, 16.80 - 32.70).

In settings with a low prevalence of serious infection, a temperature of 40°C or more had value as a red flag. Although no single clinical characteristic had rule-out value, some combinations were helpful in ruling out the possibility of serious infection. For example, if the child is not short of breath and there is no parental concern, pneumonia is very unlikely (negative likelihood ratio, 0.07; 95% CI, 0.01 - 0.46).

"The Yale Observation Scale had little value in confirming (positive likelihood ratio range 1.10–6.70) or excluding (negative likelihood ratio range 0.16–0.97) the possibility of serious infection," the study authors write. "The red flags for serious infection that we identified should be used routinely, but serious illness will still be missed without effective use of precautionary measures. We now need to identify the level of risk at which clinical action should be taken."

Limitations of this review are primarily those inherent in the included studies, such as reproducibility and poor interobserver agreement, and the paucity of studies from first-contact care settings.

"The main strength of this systematic review is that it highlights the nature and difficulty of the diagnostic task facing primary care and hospital clinicians responsible for identifying seriously ill children at initial presentation in countries where serious childhood illness is now rare," the study authors conclude. "Most of the red flags already recommended by WHO [World Health Organization] for use in developing countries can be used in the initial assessment of children presenting to ambulatory care settings in developed countries. There should be more emphasis on parental concern in the diagnostic process."

In an accompanying comment, Martin Dawes, MBBS, MD, from McGill University in Montreal, Canada, notes that how to effectively recognize or rule out severe disease in ill children is still unclear and that there is no cohesive national or global research strategy to address this problem.

"We need better-designed diagnostic and prognostic studies in primary care," Dr. Dawes writes. "Such studies require properly documented histories and examination as well as follow-up, but both are well within the scope of an organised practice and if centrally coordinated we could have ten times the evidence within a year or two. This research cannot be done without adequate funding and should be a priority for national and international research foundations."

Health Technology Assessment and National Institute for Health Research National School for Primary Care Research supported this study. The study authors and Dr. Dawes have disclosed no relevant financial relationships.

Lancet. Published online February 3, 2010.

8. Applying the Lean principles of the Toyota Production System to reduce wait times in the emergency department

Ng D, et al. CJEM 2010;12:50-57.

Objective: In recognition of patient wait times, and deteriorating patient and staff satisfaction, we set out to improve these measures in our emergency department (ED) without adding any new funding or beds.

Methods: In 2005 all staff in the ED at Hôtel Dieu Grace Hospital began a transformation, employing Toyota Lean manufacturing principles to improve ED wait times and quality of care. Lean techniques such as value stream mapping, just in time delivery techniques, workplace organization, reduction of systemic wastes, use of the worker as the source of quality improvement and ongoing refinement of our process steps formed the basis of our project.

Results: Our ED has achieved major improvements in depart mental flow without adding any additional ED or inpatient beds. The mean registration to physician time has decreased from 111 minutes to 78 minutes. The number of patients who left without being seen has decreased from 7.1% to 4.3%. The length of stay (LOS) for discharged patients has decreased from a mean of 3.6 to 2.8 hours, with the largest decrease seen in our patients triaged at levels 4 or 5 using the Canadian Emergency Department Triage and Acuity Scale. We noted an improvement in ED patient satisfaction scores following the implementation of Lean principles.

Conclusion: Lean manufacturing principles can improve the flow of patients through the ED, resulting in greater patient satisfaction along with reduced time spent by the patient in the ED.

9. Tachypnea Is a Poor Predictor of Pneumonia in Children

An elevated respiratory rate in children younger than 5 years is less than 50% sensitive for predicting pneumonia.

Shah S et al. Pediatr Infect Dis J 2009 Dec 21.

Background: The World Health Organization (WHO) recommends the use of tachypnea as a proxy to the diagnosis of pneumonia in resource poor settings.

Objective: To assess the relation between tachypnea and radiographic pneumonia among children evaluated in a pediatric emergency department (ED).

Methods: Prospective study of children less than 5 years of age undergoing chest radiography (CXR) for possible pneumonia was conducted in an academic pediatric ED. Tachypnea was defined using 3 different measurements: (1) mean triage respiratory rate (RR) by age group, (2) age-defined tachypnea based on WHO guidelines (less than 2 months [RR 60/min or greater], 2 to 12 months [RR 50 or greater], 1 to 5 years [RR 40 or greater]), and (3) physician-assessed tachypnea based on clinical impression assessed before CXR. The presence of pneumonia on CXR was determined by an attending radiologist.

Results: A total of 1622 patients were studied, of whom, 235 (14.5%) had radiographic pneumonia. Mean triage RR among children with pneumonia (RR = 39/min) did not differ from children without pneumonia (RR = 38/min). About 20% of children with tachypnea as defined by WHO age-specific cut-points had pneumonia, compared with 12% of children without tachypnea (P less than 0.001). About 17% of children who were assessed to be tachypneic by the treating physician had pneumonia, compared with 13% of children without tachypnea (P = 0.07).

Conclusion: Among an ED population of children who have a CXR performed to assess for pneumonia, RR alone, and subjective clinical impression of tachypnea did not discriminate children with and without radiographic pneumonia. However, children with tachypnea as defined by WHO RR thresholds were more likely to have pneumonia than children without tachypnea.

10. Standard Medical Care May Not Relieve Symptoms of Nonspecific Chest Pain

Laurie Barclay, MD. February 8, 2010 — Standard medical care may not relieve symptoms of nonspecific chest pain, according to the results of a prospective, general physician–based cohort study reported in the February 8 issue of the Archives of Internal Medicine.

"Nonspecific chest pain is common in primary care, yet knowledge is sparse about its course and outcome and how they relate to optimum health care usage," write Julia Anna Glombiewski, PhD, from Philipps-University of Marburg, Germany, and colleagues. "We investigated the following observations: (1) many patients who present with nonspecific chest pain in primary care show symptom persistence for 6 months, (2) many patients with nonspecific chest pain showed signs of overinvestigation, and (3) many patients with chronic chest pain were referred to mental health specialists."

From October 1, 2005, to July 31, 2006, approximately 190,000 consecutive patients visited their general physicians at 74 primary care offices in Hessen, Germany. An expert committee identified 807 of these patients as having nonspecific chest pain, with no underlying heart condition. Follow-ups were performed at 6 weeks and 6 months, with a dropout rate of 2.7%.

The primary study endpoints were persistent chest pain at 6-month follow-up and healthcare use at 6 months. Inappropriate healthcare use was defined as at least 2 visits to a cardiologist or at least 3 cardiac diagnostic investigations.

At 6-month follow-up, 55.5% of patients had persistent chest pain, 10.7% of patients had inappropriate healthcare use, and fewer than 2% were referred to mental health specialists. Most patients with persistent nonspecific chest pain were referred to a cardiologist.

"For most patients with nonspecific chest pain, standard medical care does not offer sufficient help for symptom relief," the study authors write. "One-tenth of patients with persistent chest pain underwent additional diagnostic testing of no known clinical benefit. Psychological referrals were rarely given...[which] is surprising because psychological factors are known to contribute to the development of chronic pain, and psychological consultations are covered by the health care system in Germany."

Limitations of this study include the low response rate of general practitioners approached to participate in the study, use of a proposed new cutoff for inappropriate healthcare use, limited generalizability, and use of an informal definition of nonspecific chest pain.

"Patients with psychologically caused non-specific chest pain showed more problematic health care–seeking behavior but were rarely referred to mental health professionals," the study authors conclude. "Patients, general practitioners or both seem to be hesitant to involve psychological interventions.... Future research should investigate the development of effective interventions for non-specific chest pain and their implementation within health care systems."

The German Federal Ministry of Education and Research supported this study. The study authors have disclosed no relevant financial relationships.

Arch Intern Med. 2010;170:251-255.

11. Images in Emergency Medicine

Adult Male with Altered Mental Status and New-Onset Seizures

http://www.annemergmed.com/article/S0196-0644(09)00644-1/fulltext

12. Accuracy of Very Low Pretest Probability Estimates for Pulmonary Embolism Using the Method of Attribute Matching Compared with the Wells Score

Kline JA, et al. Acad Emerg Med. 2010;17:133–141.

Objectives: Attribute matching matches an explicit clinical profile of a patient to a reference database to estimate the numeric value for the pretest probability of an acute disease. The authors tested the accuracy of this method for forecasting a very low probability of venous thromboembolism (VTE) in symptomatic emergency department (ED) patients.

Methods: The authors performed a secondary analysis of five data sets from 15 hospitals in three countries. All patients had data collected at the time of clinical evaluation for suspected pulmonary embolism (PE). The criterion standard to exclude VTE required no evidence of PE or deep venous thrombosis (DVT) within 45 days of enrollment. To estimate pretest probabilities, a computer program selected, from a large reference database of patients previously evaluated for PE, patients who matched 10 predictor variables recorded for each current test patient. The authors compared the outcome frequency of having VTE [VTE(+)] in patients with a pretest probability estimate of less than 2.5% by attribute matching, compared with a value of 0 from the Wells score.

Results: The five data sets included 10,734 patients, and 747 (7.0%, 95% confidence interval [CI] = 6.5% to 7.5%) were VTE(+) within 45 days. The pretest probability estimate for PE was less than 2.5% in 2,975 of 10,734 (27.7%) patients, and within this subset, the observed frequency of VTE(+) was 48 of 2,975 (1.6%, 95% CI = 1.2% to 2.1%). The lowest possible Wells score (0) was observed in 3,412 (31.7%) patients, and within this subset, the observed frequency of VTE(+) was 79 of 3,412 (2.3%, 95% CI = 1.8% to 2.9%) patients.

Conclusions: Attribute matching categorizes over one-quarter of patients tested for PE as having a pretest probability of less than 2.5%, and the observed rate of VTE within 45 days in this subset was less than 2.5%.

13. Kitchen Spoons Don't Work for Meds

The amount of medicine poured varies with the size of the spoon.

Many patients and parents use kitchen spoons to dose liquid medications, but the accuracy of spoon dosing is questionable. These authors conducted a simple study in 195 university students to examine the effect of spoon size on dosing of liquid medication.

Students were asked to pour a 5-mL (teaspoon) dose of cold medicine into a teaspoon, a medium-sized tablespoon, and a larger spoon. The amount of medicine poured varied with the size of the spoon: Participants underdosed by 8.4% (amount poured, 4.58 mL) with the medium-sized tablespoon and overdosed by 11.6% (amount poured, 5.58 mL) with the larger spoon. When asked to judge their dosing accuracy, participants had above average confidence that they had poured the correct dose into the medium and larger spoons.

Comment: Although the dosing errors demonstrated in this study might seem inconsequential for a cold medication, the cumulative effect of 20% variation in the delivery of medications could have considerable clinical impact for drugs with tighter risk-benefit profiles. Clearly, the size of the spoon is important when patients pour their medications. We should encourage parents to use accurate measures (e.g., measuring cap, dropper, or syringe) rather than convenient utensils for liquid-medication dosing.

— F. Bruder Stapleton, MD. Published in Journal Watch Pediatrics and Adolescent Medicine January 27, 2010. Citation: Wansink B and van Ittersum K. Spoons systematically bias dosing of liquid medicine. Ann Intern Med 2010 Jan 5; 152:66.

14. The Etiology and Prognostic Significance of Cardiac Troponin I Elevation in Unselected Emergency Department Patients

Ilva TJ, et al. J Emerg Med. 2010;38:1-5.

Background: Cardiac troponin elevations are associated not only with acute coronary syndromes (ACS) but also with multiple other cardiac and non-cardiac conditions. Study Objectives: To investigate the etiology and clinical significance of cardiac troponin I elevations in an unselected Emergency Department (ED) patient cohort.

Methods: The study population consisted of 991 consecutive troponin-positive patients admitted to the ED of a university hospital with ACS as the presumptive diagnosis. Cardiac troponin I was measured on admission and a follow-up sample was obtained at 6–12 h. Clinical diagnosis was ascertained retrospectively using all the available information including electrocardiogram, clinical data, laboratory tests, and available coronary angiograms.

Results: At admission, 805 (81.2%) patients were already troponin positive; of these, the troponin elevation was related to myocardial infarction (MI) in 654 (81.2%) patients. Finally, 83.0% of the troponin elevations were due to MI, 7.9% were related to other cardiac causes, and 9.1% to non-cardiac diseases. The leading non-cardiac causes were pulmonary embolism, renal failure, pneumonia, and sepsis. Non-cardiac patients with elevated troponin I at admission showed significantly higher in-hospital mortality (26.7% vs. 13.4%, p = 0.002) compared to cardiac patients.

Conclusion: Elevated troponin levels for reasons other than MI are common in the ED and are a marker of poor in-hospital prognosis.

15. Prehospital ECG Speeds STEMI Patients' Route to Cath Lab

January 27, 2010 (Southfield, Michigan) — Emergency medical services (EMS) evaluating suspected ST-elevation myocardial infarction (STEMI) patients in the field with a prehospital electrocardiogram (ECG) are able to get patients directly to a cath lab much faster than if they had to go through triage in the emergency room (ER), a study in Michigan shows.

A five-year study by Dr Anjani Rao (Providence Hospital, Southfield, MI) and colleagues found that the average door-to-balloon time of patients evaluated by EMS in the field with a 12-lead ECG was about one hour, compared with about 90 minutes for patients presenting to the emergency department without a prehospital ECG (p less than 0.0001). Furthermore, prehospital ECGs reduced the door-to-balloon time, regardless of what time of day the patient came to the hospital. Results of the study by Rao et al are published online January 21, 2010 in Catheterization and Cardiovascular Interventions.

"This study adds to the evidence that prehospital ECGs improve the door-to-balloon time," Dr Deepak Bhatt (Brigham and Women's Hospital, Boston, MA) told heartwire ."The data are now fairly consistent."

The study evaluated data from three hospitals in southeast Michigan from 2003 to 2008. At each center, EMS personnel obtained a 12-lead ECG during initial assessment in the field from patients with symptoms of STEMI and then transmitted that data to the emergency department by cellular link. If the emergency-department physicians determined that the ECG indicated STEMI, they would activate the cath lab immediately. A total of 108 STEMI patients were admitted with prehospital ECG in the study.

For the same period, similar data were collected for all patients who came to the emergency department by EMS or on their own without a prehospital ECG, a total of 241 patients.

The overall average door-to-balloon time for patients with in-hospital ECG only was 90.5 minutes, compared with 60.2 minutes in patients with prehospital ECG, and door-to-balloon time was also significantly lower for the prehospital ECG patients at each of the three hospitals. The median door-to-balloon time was also lower with prehospital ECG (62 vs 82 minutes), and more patients in the prehospital ECG group had door-to-balloon times under 90 minutes, the target set by ACC/AHA guidelines (97.4% vs 61.5%; p less than 0.001). There were no in-hospital deaths in the prehospital ECG group compared with seven (2%) in the control group.

Rao et al note that previous studies show that patients presenting to an emergency room with STEMI during normal working hours are almost twice as likely to have a door-to-balloon time under 90 minutes as patients presenting during off-hours. The southeast Michigan study had similar findings for the in-hospital ECG group, but 98% of the patients with prehospital ECG during off-hours had door-to-balloon times within 90 minutes.

The study did not show a mortality benefit, most likely because of the low total number of deaths, Rao et al observe, but they note that previous trials have shown that delays in reperfusion therapy, such as those encountered during off-hours, increase mortality in STEMI patients. "The use of the prehospital ECG is a way of overcoming the obstacle of delay in cath-lab activation during off-hours."

Bhatt agrees that further studies may show that prehospital ECG saves lives. "There is even some evidence to suggest an associated improvement in hard clinical outcomes, although more data in this regard would be useful."

Bhatt also points out that hospitals relying on prehospital ECG to bypass triage in the emergency department must be carefully managed to ensure there is no loss of diagnostic accuracy when shifting from an in-hospital to prehospital ECG protocol. "There still needs to be careful oversight of these programs to make sure that clinically ambiguous cases get triaged appropriately in the emergency department," he said.

16. Comparison of Antiarrhythmic Drug Therapy and Radiofrequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation: A Randomized Controlled Trial

Wilber DJ, et al. JAMA. 2010;303:333-340.

Context: Antiarrhythmic drugs are commonly used for prevention of recurrent atrial fibrillation (AF) despite inconsistent efficacy and frequent adverse effects. Catheter ablation has been proposed as an alternative treatment for paroxysmal AF.

Objective: To determine the efficacy of catheter ablation compared with antiarrhythmic drug therapy (ADT) in treating symptomatic paroxysmal AF.

Design, Setting, and Participants: A prospective, multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 19 hospitals of 167 patients who did not respond to at least 1 antiarrhythmic drug and who experienced at least 3 AF episodes within 6 months before randomization. Enrollment occurred between October 25, 2004, and October 11, 2007, with the last follow-up on January 19, 2009.

Intervention: Catheter ablation (n = 106) or ADT (n = 61), with assessment for effectiveness in a comparable 9-month follow-up period.

Main Outcome Measures: Time to protocol-defined treatment failure. The proportion of patients who experienced major treatment-related adverse events within 30 days of catheter ablation or ADT was also reported.

Results: At the end of the 9-month effectiveness evaluation period, 66% of patients in the catheter ablation group remained free from protocol-defined treatment failure compared with 16% of patients treated with ADT. The hazard ratio of catheter ablation to ADT was 0.30 (95% confidence interval, 0.19-0.47; P less than .001). Major 30-day treatment-related adverse events occurred in 5 of 57 patients (8.8%) treated with ADT and 5 of 103 patients (4.9%) treated with catheter ablation. Mean quality of life scores improved significantly in patients treated by catheter ablation compared with ADT at 3 months; improvement was maintained during the course of the study.

Conclusion: Among patients with paroxysmal AF who had not responded to at least 1 antiarrhythmic drug, the use of catheter ablation compared with ADT resulted in a longer time to treatment failure during the 9-month follow-up period.

17. New Guidance for In-Hospital Torsades De Pointes

Steve Stiles. February 9, 2010 (Dallas, Texas and Washington, DC) — Many common, useful drugs have the side effect of electrocardiographic QT-interval prolongation, which substantially increases the risk of sudden death from torsades de pointes, a polymorphic VT. A given QT-prolonging drug may more likely cause torsades in hospitalized patients than in the general population, as hospitalized patients "are often elderly people with underlying heart disease who may also have renal or hepatic dysfunction, electrolyte abnormalities, or bradycardia and to whom drugs may be administered rapidly via the intravenous route," observes a new scientific statement from the American Heart Association and American College of Cardiology. Those features, including advanced age, have confirmed or suspected associations with development of the malignant arrhythmia, the document states.

The document, also endorsed by the American Association of Critical-Care Nurses, describes the state of the art of how to identify the arrhythmia and its precursors on the ECG, drugs and patient features that promote it, strategies for prevention and monitoring, and acute management of both QT prolongation and the manifest arrhythmia. Dr Barbara J Drew (University of California, San Francisco) chaired its writing group.

The benefits of using QT-prolonging agents must be weighed against the risk in patients with increased susceptibility to torsades, it states. The susceptibility can include certain genetic mutations that, when such drugs are given, can promote the arrhythmia.

In such cases, continuous monitoring of the corrected QT (QTc) interval is recommended; "prompt action" is needed if the QTc exceeds 500 ms compared with an ECG obtained before drug administration; the QTc must be measured by the same method and/or device each time.

Responses can include drug withdrawal, correction of electrolyte abnormalities, temporary pacing, and "the ready availability of an external defibrillator."

Other ECG features can signal impending torsades, including distortions of the TU wave, visible T-wave alternans, new ventricular ectopic beats, and "couplets and nonsustained polymorphic ventricular tachycardia initiated in the beat after a pause."

Drugs that promote QTc prolongation and torsades, to different degrees, include the antiarrhythmics quinidine, disopyramide, procainamide, sotalol, dofetilide, and ibutilide as well as methadone, thioridazine, and haloperidol, according to the statement.

Still, it notes, "where benefit clearly outweighs risk, QT prolongation should not limit necessary therapy."

Drew BJ, et al. Prevention of torsade de pointes in hospital settings. A scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation 2010; DOI: 10.1161/CIRCULATIONAHA.109.192704.

Full-text (free): http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.109.192704v1

18. Anticholinergics and Ketamine Sedation in Children: A Secondary Analysis of Atropine Versus Glycopyrrolate

Green SM, et al. Acad Emerg Med. 2010;17:157–162.
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Objectives: Adjunctive anticholinergics are commonly administered during emergency department (ED) ketamine sedation in children under the presumption that drying oral secretions should decrease the likelihood of airway and respiratory adverse events. Pharmacologic considerations suggest that glycopyrrolate might exhibit a superior adverse effect profile to atropine. The authors contrasted the adverse events noted with use of each of these anticholinergics in a large multicenter observational database of ketamine sedations.

Methods: This was a secondary analysis of an observational database of 8,282 ED ketamine sedations assembled from 32 prior series. The authors compared the relative incidence of six adverse events (airway and respiratory adverse events, laryngospasm, apnea, emesis, recovery agitation, and clinically important recovery agitation) between children who received coadministered atropine, glycopyrrolate, or no anticholinergic. Multivariable analysis using the specific anticholinergic as a covariate was performed, while controlling for other known predictors.

Results: Atropine was associated with less vomiting (5.3%) than either glycopyrrolate (10.7%) or no anticholinergic (11.4%) in both unadjusted and multivariable analyses. Glycopyrrolate was associated with significantly more airway and respiratory adverse events (6.4%) than either atropine (3.3%) or no anticholinergic (3.0%) and similarly more clinically important recovery agitation (2.1% vs. 1.2 and 1.3%). There were, however, no differences noted in odds of laryngospasm and apnea.

Conclusions: This secondary analysis unexpectedly found that the coadministered anticholinergic atropine exhibited a superior adverse event profile to glycopyrrolate during ketamine sedation. Any such advantage requires confirmation in a separate trial; however, our data cast doubt on the traditional premise that glycopyrrolate might be superior. Further, neither anticholinergic showed efficacy in decreasing airway and respiratory adverse events.

19. A Prospective Case Series of Pediatric Procedural Sedation and Analgesia in the Emergency Department Using Single-syringe Ketamine–Propofol Combination (Ketofol)

Andolfatto G, et al. Acad Emerg Med. 2010;17:194–201.

Objectives: This study evaluated the effectiveness, recovery time, and adverse event profile of intravenous (IV) ketofol (mixed 1:1 ketamine–propofol) for emergency department (ED) procedural sedation and analgesia (PSA) in children.

Methods: Prospective data were collected on all PSA events in a trauma-receiving, community teaching hospital over a 3.5-year period, from which data on all patients under 21 years of age were studied. Patients receiving a single-syringe 1:1 mixture of 10 mg/mL ketamine and 10 mg/mL propofol (ketofol) were analyzed. Patients received ketofol in titrated aliquots at the discretion of the treating physician. Effectiveness, recovery time, caregiver and patient satisfaction, drug doses, physiologic data, and adverse events were recorded.

Results: Ketofol PSA was performed in 219 patients with a median age of 13 years (range = 1 to 20 years; interquartile range [IQR] = 8 to 16 years) for primarily orthopedic procedures. The median dose of medication administered was 0.8 mg/kg each of ketamine and propofol (range = 0.2 to 3.0 mg/kg; IQR = 0.7 to 1.0 mg/kg). Sedation was effective in all patients. Three patients (1.4%; 95% confidence interval [CI] = 0.0% to 3.0%) had airway events requiring intervention, of which one (0.4%; 95% CI = 0.0% to 1.2%) required positive pressure ventilation. Two patients (0.9%; 95% CI = 0.0% to 2.2%) had unpleasant emergence requiring treatment. All other adverse events were minor. Median recovery time was 14 minutes (range = 3 to 41 minutes; IQR = 11 to 18 minutes). Median staff satisfaction was 10 on a 1-to-10 scale.

Conclusions: Pediatric PSA using ketofol is highly effective. Recovery times were short; adverse events were few; and patients, caregivers, and staff were highly satisfied.

20. Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data

van de Beek D, et al. The Lancet Neurology. 2010; Early Online Publication, 4 February

Background
Dexamethasone improves outcome for some patients with bacterial meningitis, but not others. We aimed to identify which patients are most likely to benefit from dexamethasone treatment.

Methods
We did a meta-analysis of individual patient data from the randomised, double-blind, placebo-controlled trials of dexamethasone for bacterial meningitis in patients of all ages for which raw data were available. The pre-determined outcome measures were death at the time of first follow-up, death or severe neurological sequelae at 1 month follow-up, death or any neurological sequelae at first follow-up, and death or severe bilateral hearing loss at first follow-up. Combined odds ratios (ORs) and tests for heterogeneity were calculated using conventional Mantel-Haenszel statistics. We also did exploratory analysis of hearing loss among survivors and other exploratory subgroup analyses by use of logistic regression.

Findings
Data from 2029 patients from five trials were included in the analysis (833 [41•0%] aged less than 15 years). HIV infection was confirmed or likely in 580 (28•6%) patients and bacterial meningitis was confirmed in 1639 (80•8%). Dexamethasone was not associated with a significant reduction in death (270 of 1019 [26•5%] on dexamethasone vs 275 of 1010 [27•2%] on placebo; OR 0•97, 95% CI 0•79—1•19), death or severe neurological sequelae or bilateral severe deafness (42•3% vs 44•3%; 0•92, 0•76—1•11), death or any neurological sequelae or any hearing loss (54•2% vs 57•4%; 0•89, 0•74—1•07), or death or severe bilateral hearing loss (36•4% vs 38•9%; 0•89, 0•73—1•69). However, dexamethasone seemed to reduce hearing loss among survivors (24•1% vs 29•5%; 0•77, 0•60—0•99, p=0•04). Dexamethasone had no effect in any of the prespecified subgroups, including specific causative organisms, pre-dexamethasone antibiotic treatment, HIV status, or age. Pooling of the mortality data with those of all other published trials did not significantly change the results.

Interpretation
Adjunctive dexamethasone in the treatment of acute bacterial meningitis does not seem to significantly reduce death or neurological disability. There were no significant treatment effects in any of the prespecified subgroups. The benefit of adjunctive dexamethasone for all or any subgroup of patients with bacterial meningitis thus remains unproven.

21. Is there Anybody in There?

By Greg Miller. ScienceNOW Daily News. 3 February 2010

When a brain injury leaves a person unresponsive and unable to communicate, doctors and nurses must provide care without input from their patient, and families agonize over whether their loved one might still have--or someday recover--a flicker of consciousness. A new study provides hope that technology might open a line of communication with some such patients. Researchers report that a man with a severe brain injury can, by controlling his thoughts, influence scans of his brain activity and thereby answer simple questions.

The work builds on a 2006 Science paper by Adrian Owen, a neuroscientist at the Medical Research Council Cognition and Brain Sciences Unit in Cambridge, U.K., and colleagues. Using functional magnetic resonance imaging (fMRI), they tested a young woman diagnosed as being in a vegetative state following a car accident. Although she was unresponsive and apparently unaware of her surroundings, she exhibited distinct patterns of brain activity when asked to imagine herself playing tennis or walking through the rooms of her house. As in healthy volunteers, imagining tennis activated motor planning regions in the woman's brain, whereas picturing her house activated a brain region involved in recognizing familiar scenes.

In the new study, published today in the New England Journal of Medicine, Owen and several colleagues used similar methods to examine 53 additional people who were in a vegetative state or in the slightly less severe minimally conscious state, in which patients show occasional flashes of responsiveness. In four of these patients, the researchers found distinct patterns of brain activity during the tennis versus house imagination task, hinting at some level of awareness that could not be detected by observing their behavior, says co-author Steven Laureys, a neurologist at the University of Liège in Belgium.

In one patient, a 22-year-old man who'd been in a vegetative state for 5 years, the researchers took an additional step, asking him to answer six questions by imagining tennis to indicate "yes" or picturing his house to indicate "no." The questions all involved basic autobiographical details, such as the name of his father or whether he had any brothers or sisters. In a group of 16 healthy volunteers, this method worked 100% of the time, the researchers report. The vegetative state patient answered the first five questions correctly. The final question elicited virtually no activity in the brain regions of interest, and the researchers speculate that the man may have fallen asleep or simply decided not to answer.

"This is a major step forward," says Nicholas Schiff, a neurologist at Weill Cornell Medical College in New York City. The paper is important because it shows that the Science report was not an isolated case and that technology can be used to establish communication with some patients who show no outward signs of consciousness, Schiff says.

Laureys cautions, however, that the fMRI method is not ready for widespread use in hospitals. He and collaborators are now trying to adapt the imagination task to work with electroencephalography, a relatively low-tech alternative to fMRI that's less expensive and easier to operate. "Our mission now is to translate this to clinical reality," Laureys says.

If such methods do become more widely available, they are sure to raise a host of sticky clinical and ethical questions, says James Bernat, a neurologist at Dartmouth Medical School in Hanover, New Hampshire. For example, doctors would want to involve patients in decisions about their care. But, Bernat asks, would a system that allows only yes or no answers make a physician "confident that all the nuances have been dealt with ... that they're dealing with a rational wish of the person that has been thoughtfully considered?"