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. METHODS: The 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.

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 duration of the resuscitation attempt (42+/-16.4 and 43+/-16.3 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 percent and 73 percent). More patients in the amiodarone group than in the placebo group had hypotension (59 percent vs. 48 percent, P=0.04) or bradycardia (41 percent vs. 25 percent, P=0.004) after receiving the study drug. Recipients of amiodarone were more likely to survive to be admitted to the hospital (44 percent, vs. 34 percent of the placebo group; P=0.03). The benefit of amiodarone was consistent among all subgroups and at all times of drug administration. The adjusted odds ratio for survival to admission to the hospital in the amiodarone group as compared with the placebo group was 1.6 (95 percent confidence interval, 1.1 to 2.4; P=0.02). The trial did not have sufficient statistical power to detect differences in survival to hospital discharge, which differed only slightly between the two groups. CONCLUSIONS: In patients with out-of-hospital cardiac arrest due to refractory ventricular arrhythmias, treatment with amiodarone resulted in a higher rate of survival to hospital admission. Whether this benefit extends to survival to discharge from the hospital merits further investigation.

Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation.

CONTEXT: Use of automated external defibrillators (AEDs) by first arriving emergency medical technicians (EMTs) is advocated to improve the outcome for out-of-hospital ventricular fibrillation (VF). However, adding AEDs to the emergency medical system in Seattle, Wash, did not improve survival. Studies in animals have shown improved outcomes when cardiopulmonary resuscitation (CPR) was administered prior to an initial shock for VF of several minutes' duration. OBJECTIVE: To evaluate the effects of providing 90 seconds of CPR to persons with out-of-hospital VF prior to delivery of a shock by first-arriving EMTs. DESIGN: Observational, prospectively defined, population-based study with 42 months of preintervention analysis (July 1, 1990-December 31, 1993) and 36 months of post-intervention analysis (January 1, 1994-December 31, 1996). SETTING: Seattle fire department-based, 2-tiered emergency medical system. PARTICIPANTS: A total of 639 patients treated for out-of-hospital VF before the intervention and 478 after the intervention. INTERVENTION: Modification of the protocol for use of AEDs, emphasizing approximately 90 seconds of CPR prior to delivery of a shock. MAIN OUTCOME MEASURES: Survival and neurologic status at hospital discharge determined by retrospective chart review as a function of early (<4 minutes) and later (> or =4 minutes) response intervals. RESULTS: Survival improved from 24% (155/639) to 30% (142/478) (P=.04). That benefit was predominantly in patients for whom the initial response interval was 4 minutes or longer (survival, 17% [56/321] before vs 27% [60/220] after; P = .01). In a multivariate logistic model, adjusting for differences in patient and resuscitation factors between the periods, the protocol intervention was estimated to improve survival significantly (odds ratio, 1.42; 95% confidence interval, 1.07-1.90; P = .02). Overall, the proportion of victims who survived with favorable neurologic recovery increased from 17% (106/634) to 23% (109/474) (P = .01). Among survivors, the proportion having favorable neurologic function at hospital discharge increased from 71% (106/150) to 79% (109/138) (P<.11). CONCLUSION: The routine provision of approximately 90 seconds of CPR prior to use of AED was associated with increased survival when response intervals were 4 minutes or longer.

The Western Washington Myocardial Infarction Registry and Emergency Department Tissue Plasminogen Activator Treatment Trial.

This study comprised a registry and an emergency department treatment trial using recombinant tissue plasminogen activator. During 1 year, 1,028 patients with documented acute myocardial infarction (AMI) were evaluated for eligibility for thrombolytic therapy. Of these, 221 patients (22%) were eligible for thrombolytic therapy under currently accepted criteria, 175 (79%) of them were correctly identified by emergency department physicians for thrombolytic therapy, and 160 were enrolled in the trial. Only 3 patients (2%) enrolled by emergency department physicians did not subsequently evolve documented AMI. In all, 807 patients (78%) were ineligible for thrombolytic therapy: 335 (33%) because of greater than or equal to 1 contraindications, 364 (36%) because of nondiagnostic electrocardiograms on presentation, and 105 (10%) because of age greater than 75 years, or greater than 6 hours of chest pain at presentation, or both. Mortality in treated patients at 14 days was 5.6%, and survival at 1 year was 92%. The mean time from hospital arrival to thrombolytic treatment was 55 +/- 27 minutes. Initial management of AMI with recombinant tissue plasminogen activator in the emergency department provided rapid and safe treatment comparable to that reported in trials that started treatment in the coronary care unit. The proportions of eligible patients could be increased from 1 in 5 to 1 in 3, if patients currently excluded only because of age greater than 75 years or because of greater than 6 hours of chest pain were offered treatment.

Early versus late hospital arrival for acute myocardial infarction in the western Washington thrombolytic therapy trials.

In the 3 Western Washington thrombolytic therapy trials, 54.9% of patients with acute myocardial infarction arrived at the hospital within 2 hours of symptom onset. These early arrivers were younger and more likely to be hypotensive and in cardiogenic shock than were patients arriving later. There were decreases in the time from symptom onset to hospital arrival (p = 0.0002) and in the time from hospital arrival to institution of thrombolytic therapy (p less than 0.0001) in the 8 hospitals that participated in both the Western Washington intravenous streptokinase and tissue plasminogen activator trials from 1983 to 1988. For those patients receiving thrombolysis, early arrival was associated with increased survival (p = 0.031) after adjustment by Cox regression analysis for important clinical predictors of long-term survival. These covariates included pulmonary edema, anterior wall acute myocardial infarction, hypotension and absence of chest pain at hospital arrival. Reductions in barriers to timely administration of thrombolytic therapy can be achieved and can result in improved survival.