Benton R. Hunter

No benefit to prehospital initiation of therapeutic hypothermia in out-of-hospital cardiac arrest: a systematic review and meta-analysis.

OBJECTIVES The aim of this review was to define the effect of prehospital therapeutic hypothermia (TH) on survival and neurologic recovery in patients who have suffered out-of-hospital cardiac arrest (OHCA). METHODS Included in this review are randomized trials assessing the effect of prehospital TH in adult patients suffering nontraumatic OHCA. Trials assessing the effect of in-hospital TH were excluded. Only studies with a low risk of bias were eligible for meta-analysis. A medical librarian searched PubMed, Ovid, EMBASE, Ovid Global Health, the Cochrane Library, Guidelines.gov, EM Association Websites, CenterWatch, IFPMA Clinical Trial Results Portal, CINAHL, ProQuest, and the Emergency Medical Abstracts Database without language restrictions. Clinicaltrials.gov was searched for unpublished studies. Bibliographies were hand searched and experts in the field were queried about other published or unpublished trials. Using standardized forms, two authors independently extracted data from all included trials. Results from high-quality trials were pooled using a random-effects model. Two authors, using the Cochrane risk of bias tool, assessed risk of bias independently. RESULTS Of 740 citations, six trials met inclusion criteria. Four trials were at a low risk of bias and were included in the meta-analysis (N=715 patients). Pooled analysis of these trials revealed no difference in overall survival (relative risk [RR]=0.98, 95% CI=0.79 to 1.21) or good neurologic outcome (RR=0.96, 95% CI=0.76 to 1.22) between patients randomized to prehospital TH versus standard therapy. Heterogeneity was low for both survival and neurologic outcome (I2=0). CONCLUSIONS Randomized trial data demonstrate no important patient benefit from prehospital initiation of TH. Pending the results of ongoing larger trials, resources dedicated to this intervention may be better spent elsewhere.

Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study

Background: Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome. Methods: This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (PaO2) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a PaO2 >300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between PaO2 and poor neurological outcome. To assess whether there was an association between other supranormal PaO2 levels and poor neurological outcome, we used other PaO2 cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg). Results: Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1–23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11–1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02–1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg. Conclusions: Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge.

Are Plain Radiographs Sufficient to Exclude Cervical Spine Injuries in Low-Risk Adults?

BACKGROUND The routine use of clinical decision rules and three-view plain radiography to clear the cervical spine in blunt trauma patients has been recently called into question. CLINICAL QUESTION In low-risk adult blunt trauma patients, can plain radiographs adequately exclude cervical spine injury when clinical prediction rules cannot? EVIDENCE REVIEW Four observational studies investigating the performance of plain radiographs in detecting cervical spine injury in low-risk adult blunt trauma patients were reviewed. CONCLUSION The consistently poor performance of plain radiographs to rule out cervical spine injury in adult blunt trauma victims is concerning. Large, rigorously performed prospective trials focusing on low- or low/moderate-risk patients will be needed to truly define the utility of plain radiographs of the cervical spine in blunt trauma.

In Patients With Severe Sepsis, Does a Single Dose of Etomidate to Facilitate Intubation Increase Mortality?

Currently, single-dose etomidate has not been shown to cause increased mortality in septic patients requiring intubation; however, sufficiently powered randomized trials are required before definitive conclusions can be drawn.

Receiving Hospital Characteristics Associated With Survival in Patients Transported by Emergency Medical Services After Out-of-hospital Cardiac Arrest.

OBJECTIVE To test whether primary emergency medical services (EMS) transport to hospitals with certain characteristics (24/7 percutaneous coronary intervention [PCI] availability, trauma center status, large [>24 bed] intensive care unit [ICU]) versus hospitals without those characteristics is associated with improved hospital survival after out-of-hospital cardiac arrest (OHCA). METHODS This is an analysis of a prospectively collected EMS database, which archives patients with OHCA treated by a single large metropolitan EMS system. The database contains Utstein data, EMS transport data, and survival to hospital discharge. EMS providers uniformly apply advanced cardiac life support protocols to OHCA patients in the field. Patients with return of spontaneous circulation (ROSC) are transported to one of 10 hospitals in the area. If ROSC is not achieved within 30 minutes, efforts are terminated and the patient is not transported. We used multivariate logistic regression to test if receiving hospital characteristics were independently associated with survival among those transported after ROSC. We excluded patients not transported to a hospital and patients with incomplete outcome data. RESULTS Between January 2011 and December 2014, a total of 1,188 OHCA patients were resuscitated in the field and transported to an area hospital. After patients with missing data were excluded, 1,024 patients were included in the analysis. The mean (±SD) age was 61.1 (±17.0) years, and 57.7% were male. Of transported patients, 76% were taken to 24/7 PCI centers, 46% were taken to trauma centers, and 37% were taken to hospitals with large ICUs. There was considerable overlap in these hospital characteristics. A multivariate logistic regression model including age, sex, shockable rhythm, EMS time to scene, and dispatch complaint of cardiac arrest found that none of the hospital characteristics were independently associated with increased survival to discharge. The odds ratios (95% confidence intervals) for survival were as follows: PCI center, 1.28 (0.80 to 2.04); trauma center, 1.44 (0.73 to 2.85); and large ICU, 1.39 (0.69 to 2.80). CONCLUSIONS After adjusting for patient demographic data, we found no significant independent association between receiving hospital characteristics and survival to discharge among OHCA patients transported after ROSC by a single EMS agency.

Does Endovascular Therapy Benefit Patients With Acute Ischemic Stroke

Study Selection Randomized trials of endovascular therapy (ET) vs. standard care without ET in patients with acute ischemic stroke were included. Two authors independently screened titles and abstracts, and then conducted full text review of those articles that met the inclusion criteria. To be included in the meta-analysis, trials were requited to report data necessary to calculate a risk estimate for all cause mortality, functional outcome, and/or symptomatic intracranial hemorrhage.

Utility of Central Venous Pressure as a Predictor of Fluid Responsiveness.

The search strategy identified 4,767 potential studies. After review, 51 total studieswere selected and the authors were contacted for raw patient data. No formal assessment of study quality was performed. Twenty-two studies were performed in operative or postoperative patients, and the remainder evaluated ICU patients. Patients received mechanical ventilation in most trials. Only 4 studies assessedmixed populations of patients receiving both mechanical ventilation and no ventilation and 1 study assessed exclusively patients with no ventilation. Colloids and starches were used for fluid challenges in the majority of trials, with crystalloids allowed in only 7 studies. Most studies used a bolus of fluid of either 500 mL or 7 to 10 mL/kg, with values ranging from 100 to 1,000 mL. Thermodilution was the most common method for determining fluid responsiveness, typically defined as an increase in stroke volume or cardiac output. Two thirds of studies used stroke volume index or cardiac index in place of stroke volume or cardiac output. Stroke volume index and cardiac index are calculated by dividing a patient’s stroke volume or cardiac output by his or her total body surface area, potentially providing amore accuratemeasure of fluid responsiveness. Twentytwo studies, comprising 1,148 total patient data sets, submitted raw data, which was included in the final analysis.

Effect of Vapocoolant on Pain During Peripheral Intravenous Cannulation

The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Literatura Latino Americana em Ciencias da Saude, Cumulative Index to Nursing and Allied Health Literature, and ISI Web of Science were searched from inception to May 2015 without language restriction. Trial registries were searched, including clinicaltrials.gov, controlled-trials.com, and trialscentral.org. Additionally, the authors hand searched the references of retrieved articles and abstracts of the American Society of Anesthesiologists.

Do Orthostatic Vital Signs Have Utility in the Evaluation of Syncope

BACKGROUND Syncope is a common presentation in the emergency department (ED). The differential diagnosis is long and includes benign conditions as well as acute life threats, such as dysrhythmias or pulmonary embolism. OBJECTIVE The specific goals of this review are twofold: 1) to define the diagnostic utility of orthostatic vital signs (OVS) as a test for orthostatic syncope, and 2) to determine whether OVS help diagnose or exclude life-threatening causes of syncope in ED patients. METHODS Three prospective cohort studies plus 2017 national guidelines for syncope management were identified, reviewed, and critically appraised. RESULTS This literature review found that orthostatic hypotension is common among ED patients with syncope and is often diagnosed as the cause of syncope. CONCLUSIONS OVS measurements do not, in isolation, reliably diagnose or exclude orthostatic syncope, nor do they appear to have value in ruling out life-threatening causes of syncope.

Review: Adjunctive corticosteroids do not reduce mortality or clinical failure in adult inpatients with CAP

Question In patients with community-acquired pneumonia (CAP), what are the benefits and harms of adjunctive treatment with corticosteroids? Review scope Included studies compared low-dose oral or IV corticosteroid adjunctive therapy (1 mg/kg/d methylprednisolone or equivalent) with placebo in patients 16 years of age with CAP. Studies with treatment combinations that did not allow assessment of an independent corticosteroid were excluded. Primary outcome was mortality at 30 days; other outcomes included early treatment failure (72 h), later treatment failure (>72 h), nosocomial infections, CAP-related rehospitalization, time to clinical stability, length of hospital stay, length of IV antibiotic treatment, transfer to the intensive care unit from the ward, empyema/complicated parapneumonic effusion, and adverse events. Review methods MEDLINE, EMBASE/Excerpta Medica, and Cochrane Central Register of Controlled Trials (all to Jul 2017), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform Search Portal, reference lists, and proceedings of relevant conferences (2015 and 2016) were searched for randomized controlled trials (RCTs). Investigators of eligible trials were contacted for individual patient data (IPD). 6 RCTs (n =1509, median age 70 y, 59% men), ranging in size from 46 to 785 patients, met the eligibility criteria and provided IPD. IV methylprednisolone was assessed in 2 RCTs, and oral prednisone, IV prednisolone, IV dexamethasone, and IV hydrocortisone were each assessed in 1 RCT; treatments were administered for 4 to 9 days. Main results IPD meta-analysis showed that corticosteroids reduced time to clinical stability (mean difference [MD] 1.0 d, 95% CI 0.4 to 1.6), length of hospital stay (MD 1.2 d, CI 0.6 to 1.8), and length of IV antibiotic treatment (MD 0.62 d, CI 0.2 to 1.1); other main efficacy results are in the Table. Corticosteroids increased risk for CAP-related readmissions and nosocomial infections (Table), and hyperglycemia (odds ratio 2.15, CI 1.6 to 2.9). Conclusion In hospitalized patients with community-acquired pneumonia, adjunctive treatment with corticosteroids improves initial clinical response and reduces length of hospital stay but does not affect mortality or clinical failure and increases readmission rate. Individual patient data meta-analysis of adjunctive corticosteroids vs placebo in community-acquired pneumonia (CAP)* Outcomes Number of trials (n) Event rates RRR (95% CI) NNT Corticosteroids Placebo Mortality (30 d) 6 (1506) 5.0% 5.9% 24% (20 to 52) Not significant Early treatment failure (72 h) 4 (1411) 5.7% 6.4% 15% (31 to 45) Not significant Late treatment failure (>72 h) 4 (1411) 9.5% 9.3% 3% (35 to 31) Not significant Transfer to ICU after admission to the ward 6 (1359) 5.6% 6.3% 25% (20 to 53) Not significant Empyema/complicated parapneumonic effusion 6 (1506) 1.6% 1.9% 10% (93 to 59) Not significant RRI (CI) NNH (CI) Nosocomial infection (30 d) 6 (1506) 4.4% 3.3% 30% (22 to 115) Not significant CAP-related rehospitalization (>30 d from discharge) 5 (1386) 5.0% 2.7% 81% (3 to 212) 46 (18 to 1270) *ICU = intensive care unit; other abbreviations defined in Glossary. RRR, RRI, NNH, and CI calculated from placebo event rates and odds ratios in article. Commentary Corticosteroids are routinely used to treat myriad conditions, including some for which the clinical benefit is marginal or unproven (1, 2). Recently, the question of their utility as adjunct treatment for inpatients with CAP has been raised. The meta-analyses by Stern and colleagues and Briel and colleagues used different methods and different data sets to address this question, resulting in different conclusions. The Cochrane review by Stern and colleagues, which included 13 RCTs of adults, found that steroids reduced mortality but not when the meta-analysis was limited to trials with low risk for bias (RFB) for allocation concealment. This held true even for severe pneumonia, where the treatment effect appeared larger. Briel and colleagues performed an IPD meta-analysis of placebo-controlled trials. The authors were unable to obtain data for 3 small trials, which happened to have unclear RFB for allocation concealment. This resulted in a meta-analysis limited to trials at low RFB for both blinding and allocation concealment, except for 1 trial (n =45) with unclear RFB for allocation concealment. The analysis found no difference in mortality. Although the reviews came to different conclusions regarding the effect of corticosteroids on survival, both found evidence of reduced morbidity during the initial hospitalization and reduced hospital length of stay with steroids. Briel and colleagues also found a reduction in time to clinical stability and shorter duration of IV antibiotics, whereas the Cochrane review reported reductions in intubation, shock, early treatment failure, and pneumonia complications. Unsurprisingly, steroids increased hyperglycemia, although the clinical significance of this is unclear. The analysis by Briel and colleagues found a 2.2% increase in CAP-related rehospitalization, an outcome not reported in the Cochrane review. Neither review found other measurable harms. Despite the amount of data in these reviews, several important questions remain unanswered. There is insufficient evidence to conclude benefit or harm in children, immunocompromised patients, or patients with viral or fungal pneumonia. It is uncertain whether positive findings are driven by patients with COPD, who are known to benefit from systemic steroids during acute exacerbations (3). This seems unlikely given that Briel and colleagues reported that only 16% of their combined population had COPD and they found no modification of effect based on COPD status. Lastly, assuming a net benefit exists, the optimal drug, dose, and duration of corticosteroids are unknown, although Briel and colleagues found no difference in effect based on treatment duration. A trial to differentiate effect sizes between multiple dosing regimens and durations of commonly used corticosteroids would probably require enrollment of tens of thousands of patients. Current evidence supports the use of steroids in patients admitted with CAP to improve early morbidity. There is the suggestion of a mortality benefit in patients with severe pneumonia, but this is based on small trials at high or unclear RFB. Interestingly, steroids are almost universally prescribed for patients with COPD exacerbations, despite a smaller body of evidence that shows similar clinical benefits and no increased survival (3). 3 large trials registered on ClinicalTrials.gov are expected to enroll a total of 2300 patients and to be completed or scheduled for completion by October 2018 (NCT01283009, NCT01743755, NCT02517489). These RCTs will more than double the amount of available data and will help determine whether steroids actually save lives and add precision to the estimates of effects on early morbidity, side effects, and readmissions. While awaiting the results of these trials, the evidence favors the use of steroids for inpatients with CAP but with no convincing evidence to guide choice of drug, dose, or duration.