Michele Olsufka

Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation.

Background Whether antiarrhythmic drugs improve the rate of successful resuscitation after out-of-hospital cardiac arrest has not been determined in randomized clinical trials. Methods We conducted a randomized, double-blind, placebo-controlled study of intravenous amiodarone in patients with out-of-hospital cardiac arrest. Patients who had cardiac arrest with ventricular fibrillation (or pulseless ventricular tachycardia) and who had not been resuscitated after receiving three or more precordial shocks were randomly assigned to receive 300 mg of intravenous amiodarone (246 patients) or placebo (258 patients). Results The treatment groups had similar clinical profiles. There was no significant difference between the amiodarone and placebo groups in the mean (±SD) duration of the resuscitation attempt (42±16 and 43±16 minutes, respectively), the number of shocks delivered (4±3 and 6±5), or the proportion of patients who required additional antiarrhythmic drugs after the administration of the study drug (66...

Pilot Randomized Clinical Trial of Prehospital Induction of Mild Hypothermia in Out-of-Hospital Cardiac Arrest Patients With a Rapid Infusion of 4°C Normal Saline

Background— Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field cooling started immediately after the return of spontaneous circulation may be more beneficial. The aims of the present pilot study were to assess the feasibility, safety, and effectiveness of in-field cooling. Methods and Results— We determined the effect on esophageal temperature, before hospital arrival, of infusing up to 2 L of 4°C normal saline as soon as possible after resuscitation from out-of-hospital cardiac arrest. A total of 125 such patients were randomized to receive standard care with or without intravenous cooling. Of the 63 patients randomized to cooling, 49 (78%) received an infusion of 500 to 2000 mL of 4°C normal saline before hospital arrival. These 63 patients experienced a mean temperature decrease of 1.24±1°C with a hospital arrival temperature of 34.7°C, whereas the 62 patients not randomized to cooling experienced a mean temperature increase of 0.10±0.94°C (P<0.0001) with a hospital arrival temperature of 35.7°C. In-field cooling was not associated with adverse consequences in terms of blood pressure, heart rate, arterial oxygenation, evidence for pulmonary edema on initial chest x-ray, or rearrest. Secondary end points of awakening and discharged alive from hospital trended toward improvement in ventricular fibrillation patients randomized to in-field cooling. Conclusions— These pilot data suggest that infusion of up to 2 L of 4°C normal saline in the field is feasible, safe, and effective in lowering temperature. We propose that the effect of this cooling method on neurological outcome after cardiac arrest be studied in larger numbers of patients, especially those whose initial rhythm is ventricular fibrillation.

Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial.

IMPORTANCE Hospital cooling improves outcome after cardiac arrest, but prehospital cooling immediately after return of spontaneous circulation may result in better outcomes. OBJECTIVE To determine whether prehospital cooling improves outcomes after resuscitation from cardiac arrest in patients with ventricular fibrillation (VF) and without VF. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial that assigned adults with prehospital cardiac arrest to standard care with or without prehospital cooling, accomplished by infusing up to 2 L of 4°C normal saline as soon as possible following return of spontaneous circulation. Adults in King County, Washington, with prehospital cardiac arrest and resuscitated by paramedics were eligible and 1359 patients (583 with VF and 776 without VF) were randomized between December 15, 2007, and December 7, 2012. Patient follow-up was completed by May 1, 2013. Nearly all of the patients resuscitated from VF and admitted to the hospital received hospital cooling regardless of their randomization. MAIN OUTCOMES AND MEASURES The primary outcomes were survival to hospital discharge and neurological status at discharge. RESULTS The intervention decreased mean core temperature by 1.20°C (95% CI, -1.33°C to -1.07°C) in patients with VF and by 1.30°C (95% CI, -1.40°C to -1.20°C) in patients without VF by hospital arrival and reduced the time to achieve a temperature of less than 34°C by about 1 hour compared with the control group. However, survival to hospital discharge was similar among the intervention and control groups among patients with VF (62.7% [95% CI, 57.0%-68.0%] vs 64.3% [95% CI, 58.6%-69.5%], respectively; P = .69) and among patients without VF (19.2% [95% CI, 15.6%-23.4%] vs 16.3% [95% CI, 12.9%-20.4%], respectively; P = .30). The intervention was also not associated with improved neurological status of full recovery or mild impairment at discharge for either patients with VF (57.5% [95% CI, 51.8%-63.1%] of cases had full recovery or mild impairment vs 61.9% [95% CI, 56.2%-67.2%] of controls; P = .69) or those without VF (14.4% [95% CI, 11.3%-18.2%] of cases vs 13.4% [95% CI,10.4%-17.2%] of controls; P = .30). Overall, the intervention group experienced rearrest in the field more than the control group (26% [95% CI, 22%-29%] vs 21% [95% CI, 18%-24%], respectively; P = .008), as well as increased diuretic use and pulmonary edema on first chest x-ray, which resolved within 24 hours after admission. CONCLUSION AND RELEVANCE Although use of prehospital cooling reduced core temperature by hospital arrival and reduced the time to reach a temperature of 34°C, it did not improve survival or neurological status among patients resuscitated from prehospital VF or those without VF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00391469.

Pilot Study of Rapid Infusion of 2 L of 4°C Normal Saline for Induction of Mild Hypothermia in Hospitalized, Comatose Survivors of Out-of-Hospital Cardiac Arrest

Background—Recent clinical studies have demonstrated that mild hypothermia (32°C to 34°C) induced by surface cooling improves neurological outcome after resuscitation from out-of-hospital cardiac arrest. Results from animal models suggest that the effectiveness of mild hypothermia could be improved if initiated as soon as possible after return of spontaneous circulation. Infusion of cold, intravenous fluid has been proposed as a safe, effective, and inexpensive technique to induce mild hypothermia after cardiac arrest. Methods and Results—In 17 hospitalized survivors of out-of-hospital cardiac arrest, we determined the effect on temperature and hemodynamics of infusing 2 L of 4°C cold, normal saline during 20 to 30 minutes into a peripheral vein with a high-pressure bag. Data on vital signs, electrolytes, arterial blood gases, and coagulation were collected before and after fluid infusion. Cardiac function was assessed by transthoracic echocardiography before fluid administration and 1 hour after infusion. Passive (fans, leaving patient uncovered) or active (cooling blankets, neuromuscular blockade) cooling measures were used to maintain mild hypothermia for 24 hours. Infusion of 2 L of 4°C cold, normal saline resulted in a mean temperature drop of 1.4°C 30 minutes after the initiation of infusion. Rapid infusion of fluid was not associated with clinically important changes in vital signs, electrolytes, arterial blood gases, or coagulation parameters. The initial mean ejection fraction was 34%, and fluid infusion did not affect ejection fraction or increase central venous pressure, pulmonary pressures, or left atrial filling pressures as assessed by echocardiography. Passive measures were ineffective in maintaining hypothermia compared with active measures. Conclusions—Infusion of 2 L of 4°C cold, normal saline is safe and effective in rapidly lowering body temperature in survivors of out-of-hospital cardiac arrest.

Perishock Pause An Independent Predictor of Survival From Out-of-Hospital Shockable Cardiac Arrest

Background— Perishock pauses are pauses in chest compressions before and after defibrillatory shock. We examined the relationship between perishock pauses and survival to hospital discharge. Methods and Results— We included out-of-hospital cardiac arrest patients in the Resuscitation Outcomes Consortium Epistry–Cardiac Arrest who suffered arrest between December 2005 and June 2007, presented with a shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia), and had cardiopulmonary resuscitation process data for at least 1 shock (n=815). We used multivariable logistic regression to determine the association between survival and perishock pauses. In an analysis adjusted for Utstein predictors of survival, the odds of survival were significantly lower for patients with preshock pause ≥20 seconds (odds ratio, 0.47; 95% confidence interval, 0.27 to 0.82) and perishock pause ≥40 seconds (odds ratio, 0.54; 95% confidence interval, 0.31 to 0.97) compared with patients with preshock pause <10 seconds and perishock pause <20 seconds. Postshock pause was not independently associated with a significant change in the odds of survival. Log-linear modeling depicted a decrease in survival to hospital discharge of 18% and 14% for every 5-second increase in both preshock and perishock pause interval (up to 40 and 50 seconds, respectively), with no significant association noted with changes in the postshock pause interval. Conclusions— In patients with cardiac arrest presenting in a shockable rhythm, longer perishock and preshock pauses were independently associated with a decrease in survival to hospital discharge. The impact of preshock pause on survival suggests that refinement of automatic defibrillator software and paramedic education to minimize preshock pause delays may have a significant impact on survival. # Clinical Perspective {#article-title-32}Background— Perishock pauses are pauses in chest compressions before and after defibrillatory shock. We examined the relationship between perishock pauses and survival to hospital discharge. Methods and Results— We included out-of-hospital cardiac arrest patients in the Resuscitation Outcomes Consortium Epistry–Cardiac Arrest who suffered arrest between December 2005 and June 2007, presented with a shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia), and had cardiopulmonary resuscitation process data for at least 1 shock (n=815). We used multivariable logistic regression to determine the association between survival and perishock pauses. In an analysis adjusted for Utstein predictors of survival, the odds of survival were significantly lower for patients with preshock pause ≥20 seconds (odds ratio, 0.47; 95% confidence interval, 0.27 to 0.82) and perishock pause ≥40 seconds (odds ratio, 0.54; 95% confidence interval, 0.31 to 0.97) compared with patients with preshock pause <10 seconds and perishock pause <20 seconds. Postshock pause was not independently associated with a significant change in the odds of survival. Log-linear modeling depicted a decrease in survival to hospital discharge of 18% and 14% for every 5-second increase in both preshock and perishock pause interval (up to 40 and 50 seconds, respectively), with no significant association noted with changes in the postshock pause interval. Conclusions— In patients with cardiac arrest presenting in a shockable rhythm, longer perishock and preshock pauses were independently associated with a decrease in survival to hospital discharge. The impact of preshock pause on survival suggests that refinement of automatic defibrillator software and paramedic education to minimize preshock pause delays may have a significant impact on survival.

Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrest

Objective To evaluate the feasibility, safety, and efficacy of interventions aimed at improving neurologic outcome after cardiac arrest. MethodsThe authors conducted a double-blind, placebo-controlled, randomized clinical trial with factorial design to see if magnesium, diazepam, or both, when given immediately following resuscitation from out-of-hospital cardiac arrest, would increase the proportion of patients awakening, defined as following commands or having comprehensible speech. If the patient regained a systolic blood pressure of at least 90 mm Hg and had not awakened, paramedics injected IV two syringes stored in a sealed kit. The first always contained either 2 g magnesium sulfate (M) or placebo (P); the second contained either 10 mg diazepam (D) or P. Awakening at any time by 3 months was determined by record review, and independence at 3 months was determined by telephone calls. Over 30 months, 300 patients were randomized in balanced blocks of 4, 75 each to MD, MP, PD, or PP. The study was conducted under waiver of consent. Results Despite the design, the four treatment groups differed on baseline variables collected before randomization. Percent awake by 3 months for each group were: MD, 29.3%; MP, 46.7%; PD, 30.7%; PP, 37.3%. Percent independent at 3 months were: MD, 17.3%; MP, 34.7%; PD, 17.3%; PP, 25.3%. Significant interactions were lacking. After adjusting for baseline imbalances, none of these differences was significant, and no adverse effects were identified. Conclusions Neither magnesium nor diazepam significantly improved neurologic outcome from cardiac arrest.

Public access defibrillation in out-of-hospital cardiac arrest: a community-based study.

Background—The dissemination and use of automated external defibrillators (AEDs) beyond traditional emergency medical services (EMS) into the community has not been fully evaluated. We evaluated the frequency and outcome of non-EMS AED use in a community experience. Methods and Results—The investigation was a cohort study of out-of-hospital cardiac arrest cases due to underlying heart disease treated by public access defibrillation (PAD) between January 1, 1999, and December 31, 2002, in Seattle and surrounding King County, Washington. Public access defibrillation was defined as out-of-hospital cardiac arrest treated with AED application by persons outside traditional emergency medical services. The EMS of Seattle and King County developed a voluntary Community Responder AED Program and registry of PAD AEDs. During the 4 years, 475 AEDs were placed in a variety of settings, and more than 4000 persons were trained in cardiopulmonary resuscitation and AED operation. A total of 50 cases of out-of-hospital cardiac arrest were treated by PAD before EMS arrival, which represented 1.33% (50/3754) of all EMS-treated cardiac arrests. The proportion treated by PAD AED increased each year, from 0.82% in 1999 to 1.12% in 2000, 1.41% in 2001, and 2.05% in 2002 (P = 0.019, test for trend). Half of the 50 persons treated with PAD survived to hospital discharge, with similar survival for nonmedical settings (45% [14/31]) and out-of-hospital medical settings (58% [11/19]). Conclusions—PAD was involved in only a small but increasing proportion of out-of-hospital cardiac arrests.

Underutilization of thrombolytic therapy in eligible women with acute myocardial infarction

New methods for the management of coronary artery disease are almost always evaluated in male patients or in groups of patients who are predominantly male.1 This bias is in part due to the fact that men develop coronary artery disease more frequently and at an earlier age than do women.2 This problem is compounded by the usual practice of excluding elderly patients from therapeutic trials. Most trials of thrombolytic therapy for acute myocardial infarction (AMI) have an upper age limit of 70 or 75 years, as was the case in our own trials.3 Because thrombolytic therapy has been largely evaluated in men, we have been concerned that once this therapy was demonstrated to be effective, it might be preferentially applied. In this analysis, we attempt to specify the role of gender in the eligibility for and use of thrombolytic therapy.

Active surface cooling protocol to induce mild therapeutic hypothermia after out-of-hospital cardiac arrest: a retrospective before-and-after comparison in a single hospital.

Objective: To evaluate whether implementation of a therapeutic hypothermia protocol on arrival in a community hospital improved survival and neurologic outcomes in patients initially found to have ventricular fibrillation, pulseless electrical activity, or asystole, and then successfully resuscitated from out-of-hospital cardiac arrest. Design: A retrospective study of patients who presented after implementation of a therapeutic hypothermia protocol compared with those who presented before the protocol was implemented. Setting: Harborview Medical Center, Seattle, WA. Patients: A total of 491 consecutive adults with out-of-hospital, nontraumatic cardiac arrest who presented between January 1, 2000 and December 31, 2004. Interventions: An active cooling therapeutic hypothermia protocol, using ice packs, cooling blankets, or cooling pads to achieve a temperature of 32°C to 34°C was initiated on November 18, 2002 for unconscious patients resuscitated from cardiac arrest. Measurements and Main Results: Demographics and outcomes were obtained from medical records and an emergency medical database. The primary outcomes were survival and favorable neurologic outcome at discharge associated with the therapeutic hypothermia protocol. An adjusted analysis was performed, using a multivariate regression. During the therapeutic hypothermia period, 204 patients were brought to the emergency department; of these 204 patients, 132 (65%) ultimately achieved temperatures of <34°C. Of the 72 patients who did not achieve goal temperatures: 40 (20%) died in the emergency department or shortly after being admitted to the hospital, 15 (7%) regained consciousness, four (2%) had contraindications, 13 (6%) had temperature increase or did not have documented use of the therapeutic hypothermia protocol. In the prior period, none of the 287 patients received active cooling. Patients admitted in the therapeutic hypothermia period had a mean esophageal temperature of 34.1°C during the first 12 hrs compared with 35.2°C in the pretherapeutic hypothermia period (p < .01). Survival to hospital discharge improved in the therapeutic hypothermia period in patients with an initial rhythm of ventricular fibrillation (odds ratio, 1.88, 95% confidence interval, 1.03–3.45), however not in patients with nonventricular fibrillation (odds ratio, 1.17, 95% confidence interval, 0.66–2.05). In adjusted analysis, ventricular fibrillation patients during the therapeutic hypothermia period trended toward improved survival (odds ratio, 1.71, 95% confidence interval, 0.85–3.46) and had favorable neurologic outcome (odds ratio, 2.62, 95% confidence interval, 1.1–6.27) compared with the earlier period. This benefit was not observed in patients whose initial rhythm was pulseless electrical activity or asystole. Conclusions: The therapeutic hypothermia period was associated with a significant improvement in neurologic outcomes in patients whose initial rhythm was ventricular fibrillation, but not in patients with other rhythms.

Transthoracic Incremental Monophasic Versus Biphasic Defibrillation by Emergency Responders (TIMBER) A Randomized Comparison of Monophasic With Biphasic Waveform Ascending Energy Defibrillation for the Resuscitation of Out-of-Hospital Cardiac Arrest due to Ventricular Fibrillation

Background— Although biphasic, as compared with monophasic, waveform defibrillation for cardiac arrest is increasing in use and popularity, whether it is truly a more lifesaving waveform is unproven. Methods and Results— Consecutive adults with nontraumatic out-of-hospital ventricular fibrillation cardiac arrest were randomly allocated to defibrillation according to the waveform from automated external defibrillators administered by prehospital medical providers. The primary event of interest was admission alive to the hospital. Secondary events included return of rhythm and circulation, survival, and neurological outcome. Providers were blinded to automated defibrillator waveform. Of 168 randomized patients, 80 (48%) and 68 (40%) consistently received only monophasic or biphasic waveform shocks, respectively, throughout resuscitation. The prevalence of ventricular fibrillation, asystole, or organized rhythms at 5, 10, or 20 seconds after each shock did not differ significantly between treatment groups. The proportion of patients admitted alive to the hospital was relatively high: 73% in monophasic and 76% in biphasic treatment groups (P=0.58). Several favorable trends were consistently associated with receipt of biphasic waveform shock, none of which reached statistical significance. Notably, 27 of 80 monophasic shock recipients (34%), compared with 28 of 68 biphasic shock recipients (41%), survived (P=0.35). Neurological outcome was similar in both treatment groups (P=0.4). Earlier administration of shock did not significantly alter the performance of one waveform relative to the other, nor did shock waveform predict any clinical outcome after multivariate adjustment. Conclusions— No statistically significant differences in outcome could be ascribed to use of one waveform over another when out-of-hospital ventricular fibrillation was treated.