To evaluate the feasibility, safety, and efficacy of interventions aimed at improving neurologic outcome after cardiac arrest.
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.
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.
Neither magnesium nor diazepam significantly improved neurologic outcome from cardiac arrest.
Recent reports from 2 European cities and an earlier observation from Seattle, Wash, suggest that the number of patients treated for out-of-hospital ventricular fibrillation (VF) has declined.
To ...analyze the incidence of cardiac arrest and to examine relationships among incidence, sex, race, age, and first identified cardiac rhythm in Seattle.
Population-based study of all cardiac arrest cases with presumed cardiac etiology who received advanced life support from Seattle Fire Department emergency medical services during specified periods between 1979 and 2000. United States Census data for Seattle in 1980, 1990, and 2000 were used to determine incidence rates for treated cardiac arrest with adjustments for age and sex.
Changes in incidence of cardiac arrest and initial recorded cardiac rhythm.
The adjusted annual incidence of cardiac arrest with VF as the first identified rhythm decreased by about 56% from 1980 to 2000 (from 0.85 to 0.38 per 1000; relative risk RR, 0.44; 95% confidence interval CI, 0.37-0.53). Similar reductions occurred in blacks (54%; RR, 0.45; 95% CI, 0.26-0.79) and whites (53%; RR, 0.47; 95% CI, 0.38-0.58) and was most evident in men (57%; RR, 0.43; 95% CI, 0.35-0.53), in whom the baseline incidence was relatively high. When all treated arrests with presumed cardiac etiology were considered, that incidence decreased by 43% (RR, 0.58; 95% CI, 0.49-0.67) in men but negligibly in women, for whom a relatively low incidence of VF also declined but was offset by more cases with asystole or pulseless electrical activity.
We observed a major decline in the incidence of out-of-hospital VF and in all cases of treated cardiac arrest presumably due to heart disease in Seattle. These changes likely reflect the national decline in coronary heart disease mortality.
Recent clinical studies have demonstrated that mild hypothermia (32 degrees C to 34 degrees 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.
In 17 hospitalized survivors of out-of-hospital cardiac arrest, we determined the effect on temperature and hemodynamics of infusing 2 L of 4 degrees 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 degrees C cold, normal saline resulted in a mean temperature drop of 1.4 degrees 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.
Infusion of 2 L of 4 degrees C cold, normal saline is safe and effective in rapidly lowering body temperature in survivors of out-of-hospital cardiac arrest.
Whether antiarrhythmic drugs improve the rate of successful resuscitation after out-of-hospital cardiac arrest has not been determined in randomized clinical trials.
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).
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.
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.
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.
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.
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).
Seattle fire department-based, 2-tiered emergency medical system.
A total of 639 patients treated for out-of-hospital VF before the intervention and 478 after the intervention.
Modification of the protocol for use of AEDs, emphasizing approximately 90 seconds of CPR prior to delivery of a shock.
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.
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).
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 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.
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).
PAD was involved in only a small but increasing proportion of out-of-hospital cardiac arrests.
It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting--enzyme inhibitor, ...enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure.
Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months.
There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent an increase of 8 percent to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P less than 0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group; vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P less than 0.001).
The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril.
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.
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