Wilhelm Behringer

Cumulative Epinephrine Dose during Cardiopulmonary Resuscitation and Neurologic Outcome

For more than 90 years, epinephrine has been used in cardiopulmonary resuscitation to improve myocardial and cerebral perfusion [1]. The recommended standard dose of 1 mg of epinephrine administered intravenously [2] was first used more than 30 years ago [3-5]. Numerous attempts have been made to find either an optimal dose for epinephrine [6-8] or new vasopressor agents [9-11] to treat patients with cardiac arrest. The use of epinephrine in cardiopulmonary resuscitation continues to be controversial [12]. Despite its advantages [13-17], epinephrine has deleterious side effects during cardiac arrest and after restoration of spontaneous circulation [18-25]. Both the standard epinephrine dose and the recommendation of unlimited subsequent epinephrine doses administered every 3 to 5 minutes [2] remain matters of debate. In children, administration of more than two epinephrine doses is associated with poor prognosis [26]. Because it is difficult to determine whether outcomes are related to the duration of the resuscitative efforts or to the adverse effects of repeated epinephrine doses, the association between epinephrine dose and outcome in adults has not yet been defined. Although epinephrine can restore spontaneous circulation, favorable neurologic function does not necessarily ensue. In a retrospective cohort study, we investigated the association between cumulative epinephrine dose used in advanced cardiac life support and neurologic outcome in patients with witnessed, normothermic ventricular fibrillation cardiac arrest and unsuccessful initial defibrillation. Methods From 1 August 1991 to 31 December 1995, data were collected on patients admitted to the Department of Emergency Medicine at the University Hospital of Vienna, Austria, after cardiac arrest that occurred before or during hospitalization. Collection was done according to the recommended guidelines for uniform reporting of data on out-of-hospital cardiac arrest [27]. The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration of 1975, as revised in 1983. Patients Included patients had witnessed, nontraumatic, normothermic cardiac arrest of presumed cardiac origin. To exclude the influence of the initial rhythm on outcome [28-30], we focused on patients whose initial rhythm was ventricular fibrillation. Cardiac arrest was defined as the absence of both spontaneous respiration and palpable pulses. Patients were excluded if spontaneous circulation returned within 3 minutes after the initial three countershocks and if they had an additional cardiac arrest within 6 months after the first. We also excluded patients with known unfavorable overall performance or cerebral performance (New York Heart Association class 3 or 4 or a cerebral performance category [CPC] of 3 or 4) before cardiac arrest, a factor that is known to affect outcome [31-33]. Return of spontaneous circulation was defined as any, even transient (nonsustained), return of a palpable arterial pulse [27]. Acute care consisted of basic and advanced cardiac life support performed by the Vienna Ambulance Service or in-hospital emergency medical technicians and physicians according to standard protocol [2]. The interval from the time of collapse (the presumed time of cardiac arrest) to basic or advanced life support was defined as the no-flow duration, and the interval from the beginning of life support until the return of spontaneous circulation or termination of resuscitative efforts was called the low-flow duration. The cumulative epinephrine dose was defined as the overall dose of epinephrine subsequently administered during advanced cardiac life support. One physician was responsible for obtaining data through interviews with the ambulance physicians, paramedics, bystanders, and families and from computerized patient records. Outcome Measures Cerebral function, expressed in terms of CPC, was assessed prospectively on arrival at the emergency department and 6 hours, 12 hours, 24 hours, 2 days, 3 days, 1 week, 1 month, and 6 months after return of spontaneous circulation [27, 34]. The CPC category is based on the Glasgow outcome performance categories [35]. The performance categories are defined as follows: CPC 1, conscious and alert with normal function or only slight disability; CPC 2, conscious and alert with moderate disability; CPC 3, conscious with severe disability; CPC 4, comatose or in a persistent vegetative state; and CPC 5, certifiably brain dead or dead by traditional criteria. The best CPC score achieved within 6 months was used for calculation. A CPC score of 1 or 2 represents favorable functional neurologic recovery because patients with these scores have sufficient cerebral function for independent activities of daily living. A CPC score of 3, 4, or 5 reflects unfavorable functional neurologic recovery. The investigator assessing the CPC score by examining the patients according to a neuropsychiatric protocol was blinded to the resuscitation data. Statistical Analysis Data are given as the median and interquartile range (the difference between the 25th and 75th percentiles) unless otherwise specified. We used the Kruskal-Wallis test and the Mann-Whitney U test to compare continuous variables and used the chi-square test or the Fisher exact test to compare proportions. We calculated Spearman rank correlation coefficients to assess the relation between the cumulative epinephrine dose, the no-flow and low-flow durations, and the sum of these durations. Logistic regression analysis was used to assess the association between neurologic recovery and cumulative epinephrine dose. To control for potential cofounders, we included the following variables in the logistic regression model: age, sex, body mass index, bystander-administered basic life support (yes or no), site of cardiac arrest (in the hospital or outside of the hospital), no-flow duration, and low-flow duration. The logistic regression model was tested for collinearity of the independent variables by using standard procedures. No substantial collinearity between the independent variables was found. Logistic regression coefficients were converted to odds ratios with 95% CIs. All data were computed by using SPS for Windows, release 6.0 (SPS, Inc., Chicago, Illinois). A P value less than 0.05 was considered statistically significant. Results Within the 65-month study period, 698 patients who were having or had had cardiac arrest were admitted to the emergency department. Of these, 178 fulfilled the inclusion criteria and were enrolled. The median age of the 178 patients was 61 years (range, 50 to 71 years), and 148 patients (83%) were male. In 160 patients (90%), cardiac arrest occurred outside of the hospital. The estimated median no-flow duration was 2 minutes (interquartile range, <1 to 10 minutes), and the median low-flow duration was 16 minutes (interquartile range, 7 to 34 minutes). The median no-flow duration can be attributed to the 57 patients (32%) who underwent bystander-administered basic life support and to the 32 patients (18%) whose cardiac arrest was witnessed by emergency medical service personnel. The median no-flow duration in the patients who had bystander-administered basic life support was 1 minute (interquartile range, <1 to 2.5 minutes). This duration can be explained by the fact that in 35 patients, basic life support was initiated immediately after arrest. If arrest is witnessed by emergency medical service personnel, the no-flow duration can be expected to be 0 minutes. In all 32 patients whose cardiac arrest was witnessed by emergency medical service personnel, spontaneous circulation could be restored. Twenty-four of these patients (75%) showed favorable functional neurologic recovery. Of 119 patients whose cardiac arrest was not witnessed by emergency medical service personnel, 39 (33%) had favorable functional neurologic recovery. The median cumulative epinephrine dose administered intravenously during cardiopulmonary resuscitation was 4 mg (interquartile range, 1 to 6 mg). The median epinephrine dose administered every fifth minute was 1.2 mg (interquartile range, 0.6 to 2.1 mg). Patients with and without Return of Spontaneous Circulation In 151 patients (84%), spontaneous circulation was restored. Compared with patients in whom spontaneous circulation was not restored, patients with restoration of spontaneous circulation had a similar no-flow duration (2 minutes [interquartile range, <1 to 9 minutes] and 1 minute [interquartile range, <1 to 10 minutes]; P > 0.2) and a shorter low-flow duration (13 minutes [interquartile range, 5 to 24 minutes] and 80 minutes [interquartile range, 58 to 119 minutes]; P < 0.001) and received a lower cumulative dose of epinephrine (3 mg [interquartile range, 1 to 6 mg] and 8 mg [interquartile range, 4 to 18 mg]; P < 0.001). Restoration of spontaneous circulation was possible with increasing cumulative doses of epinephrine, but good functional neurologic recovery was less likely (Figure 1 and Figure 2). Figure 1. Patients who achieved restoration of spontaneous circulation (striped bars) after administration of epinephrine. Figure 2. Patients who achieved good neurologic outcome after administration of epinephrine (striped bars). Patients with Favorable and Unfavorable Functional Neurologic Recovery after Return of Spontaneous Circulation Of 151 patients with return of spontaneous circulation, neurologic recovery was favorable in 63 (42%). Within a 6-month observation period, 80 patients died (median duration of survival, 4 days [interquartile range, 0.5 to 14 days; range, 0.4 hours to 111 days]). Of the 80 patients who died within the 6-month observation period, 77 had unfavorable functional neurologic recovery (median duration of survival, 4 days [interquartile range, 0.5 to 13 days]). Durations of survival in the 3 patients with favora

Time Course of Serum Neuron-Specific Enolase A Predictor of Neurological Outcome in Patients Resuscitated From Cardiac Arrest

BACKGROUND AND PURPOSE The prediction of neurological outcome in comatose cardiac arrest survivors has enormous ethical and socioeconomic implications. The purpose of the present study was to investigate the prognostic relevance of the time course of serum neuron-specific enolase (NSE) as a biochemical marker of hypoxic brain damage. METHODS Serial analysis of serum NSE levels was performed in 56 patients resuscitated from witnessed, nontraumatic, normothermic, in- or out-of-hospital cardiac arrest. The neurological outcome was evaluated with the use of the cerebral performance category (CPC) within 6 months after restoration of spontaneous circulation (ROSC). The Mann-Whitney U test was used to compare patients with good (CPC 1 to 2) and bad (CPC 3 to 4) neurological outcome. The diagnostic performance at different time points after ROSC was described in terms of areas under receiver operating characteristic curves according to standard methods. RESULTS Patients with a bad neurological outcome (CPC 3 to 4) had significantly higher NSE levels than those with a good neurological outcome at 12 (P=0.004), 24 (P=0.04), 48 (P<0.001), and 72 hours (P<0.001) after ROSC. The maximum NSE level measured within 72 hours after ROSC was also significantly higher in patients with a bad neurological outcome (P<0.001). The NSE value at 72 hours after ROSC was the best predictor of neurological outcome (area under the curve=0.92+/-0.04). In addition, we also found a significant difference in the time course of NSE concentrations during the first 3 days after ROSC. CONCLUSIONS Serum NSE levels are valuable adjunctive parameters for assessing neurological outcome after cardiac arrest.

Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms

AIM Mild therapeutic hypothermia (32-34°C) improves neurological recovery and reduces the risk of death in comatose survivors of cardiac arrest when the initial rhythm is ventricular fibrillation or pulseless ventricular tachycardia. The aim of the presented study was to investigate the effect of mild therapeutic hypothermia (32-34°C for 24h) on neurological outcome and mortality in patients who had been successfully resuscitated from non-ventricular fibrillation cardiac arrest. METHODS In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest with asystole or pulseless electric activity as the first documented rhythm. Data were collected from 1992 to 2009. Main outcome measures were neurological outcome within six month and mortality after six months. RESULTS Three hundred and seventy-four patients were analysed. Hypothermia was induced in 135 patients. Patients who were treated with mild therapeutic hypothermia were more likely to have good neurological outcomes in comparison to patients who were not treated with hypothermia with an odds ratio of 1.84 (95% confidence interval: 1.08-3.13). In addition, the rate of mortality was significantly lower in the hypothermia group (odds ratio: 0.56; 95% confidence interval: 0.34-0.93). CONCLUSION Treatment with mild therapeutic hypothermia at a temperature of 32-34°C for 24h is associated with improved neurological outcome and a reduced risk of death following out-of-hospital cardiac arrest with non-shockable rhythms.

Survival without brain damage after clinical death of 60-120 mins in dogs using suspended animation by profound hypothermia

ObjectivesThis study explored the limits of good outcome of brain and organism achievable after cardiac arrest (no blood flow) of 60–120 mins, with preservation (suspended animation) induced immediately after the start of exsanguination cardiac arrest. DesignProspective experimental comparison of three arrest times, without randomization. SettingUniversity research laboratory. SubjectsTwenty-seven custom-bred hunting dogs (17–25 kg). InterventionsDogs were exsanguinated over 5 mins to cardiac arrest no-flow of 60 mins, 90 mins, or 120 mins. At 2 mins of cardiac arrest, the dogs received, via a balloon-tipped catheter, an aortic flush of isotonic saline at 2°C (at a rate of 1 L/min), until tympanic temperature reached 20°C (for 60 mins of cardiac arrest), 15°C (for 60 mins of cardiac arrest), or 10°C (for 60, 90, or 120 mins of cardiac arrest). Resuscitation was by closed-chest cardiopulmonary bypass, postcardiac arrest mild hypothermia (tympanic temperature 34°C) to 12 hrs, controlled ventilation to 20 hrs, and intensive care to 72 hrs. Measurements and Main ResultsWe assessed overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, death), neurologic deficit scores (NDS 0–10%, normal; 100%, brain death), regional and total brain histologic damage scores at 72 hrs (total HDS >0–40, mild; 40–100, moderate; >100, severe damage), and morphologic damage of extracerebral organs. For 60 mins of cardiac arrest (n = 14), tympanic temperature 20°C (n = 6) was achieved after flush of 3 mins and resulted in two dogs with OPC 1 and four dogs with OPC 2: median NDS, 13% (range 0–27%); and median total HDS, 28 (range, 4–36). Tympanic temperature of 15°C (n = 5) was achieved after flush of 7 mins and resulted in all five dogs with OPC 1, NDS 0% (0–3%), and HDS 8 (0–48). Tympanic temperature 10°C (n = 3) was achieved after flush of 11 mins and resulted in all three dogs with OPC 1, NDS 0%, and HDS 16 (2–18). For 90 mins of cardiac arrest (n = 6), tympanic temperature 10°C was achieved after flush of 15 mins and resulted in all six dogs with OPC 1, NDS 0%, and HDS 8 (0–37). For 120 mins of cardiac arrest (n = 7), three dogs had to be excluded. In the four dogs within protocol, tympanic temperature 10°C was achieved after flush of 15 mins. This resulted in one dog with OPC 1, NDS 0%, and total HDS 14; one with OPC 1, NDS 6%, and total HDS 20; one with OPC 2, NDS 13%, and total HDS 10; and one with OPC 3, NDS 39%, and total HDS 22. ConclusionsIn a systematic series of studies in dogs, the rapid induction of profound cerebral hypothermia (tympanic temperature 10°C) by aortic flush of cold saline immediately after the start of exsanguination cardiac arrest—which rarely can be resuscitated effectively with current methods—can achieve survival without functional or histologic brain damage, after cardiac arrest no-flow of 60 or 90 mins and possibly 120 mins. The use of additional preservation strategies should be pursued in the 120-min arrest model.

Relationship between time to target temperature and outcome in patients treated with therapeutic hypothermia after cardiac arrest

IntroductionOur purpose was to study whether the time to target temperature correlates with neurologic outcome in patients after cardiac arrest with restoration of spontaneous circulation treated with therapeutic mild hypothermia in an academic emergency department.MethodsTemperature data between April 1995 and June 2008 were collected from 588 patients and analyzed in a retrospective cohort study by observers blinded to outcome. The time needed to achieve an esophageal temperature of less than 34°C was recorded. Survival and neurological outcomes were determined within six months after cardiac arrest.ResultsThe median time from restoration of spontaneous circulation to reaching a temperature of less than 34°C was 209 minutes (interquartile range [IQR]: 130-302) in patients with favorable neurological outcomes compared to 158 min (IQR: 101-230) (P < 0.01) in patients with unfavorable neurological outcomes. The adjusted odds ratio for a favorable neurological outcome with a longer time to target temperature was 1.86 (95% CI 1.03 to 3.38, P = 0.04).ConclusionsIn comatose cardiac arrest patients treated with therapeutic hypothermia after return of spontaneous circulation, a faster decline in body temperature to the 34°C target appears to predict an unfavorable neurologic outcome.

Successful resuscitation of a verapamil-intoxicated patient with percutaneous cardiopulmonary bypass

OBJECTIVE To describe our experience with the use of percutaneous cardiopulmonary bypass as a therapy for cardiac arrest in an adult patient intoxicated with verapamil. DESIGN Case report. SETTING Emergency department of a university hospital. PATIENT A patient with cardiac arrest after severe verapamil intoxication. INTERVENTIONS Percutaneous cardiopulmonary bypass and theophylline therapy. CASE REPORT A 41-yr-old white male had taken 4800-6400 mg of verapamil in a suicide attempt. On arrival of the ambulance physician, the patient was conscious with weak palpable pulses and was transported to a nearby hospital. The patient developed a pulseless electrical activity, and cardiopulmonary resuscitation was started. Despite all advanced life support efforts, the patient remained in cardiac arrest. Therefore, he was transferred under ongoing cardiopulmonary resuscitation to our department, where percutaneous cardiopulmonary bypass was initiated immediately (2.5 hrs after cardiac arrest). The first verapamil serum concentration obtained at admittance to our institution was 630 ng/mL. After several ineffective intravenous epinephrine applications, the administration of 0.48 g of theophylline as an intravenous bolus 6 hrs and 18 mins after cardiac arrest led to the return of spontaneous circulation. The patient remained stable and was transferred to an intensive care unit the same day. He woke up on the 12th day and was extubated on the 18th day. After transfer to a neuropsychiatric rehabilitation hospital, he recovered totally. CONCLUSION In patients with cardiac arrest attributable to massive verapamil overdose, percutaneous extracorporeal cardiopulmonary bypass can provide adequate tissue perfusion and sufficient cerebral oxygen supply until the drug level is reduced and restoration of spontaneous circulation can be achieved.

Suspended Animation for Delayed Resuscitation from Prolonged Cardiac arrest that is Unresuscitable by Standard Cardiopulmonary-Cerebral Resuscitation

Standard cardiopulmonary-cerebral resuscitation fails to achieve restoration of spontaneous circulation in ∼50% of normovolemic sudden cardiac arrests outside hospitals and in essentially all victims of penetrating truncal trauma who exsanguinate rapidly to cardiac arrest. Among cardiopulmonary-cerebral resuscitation innovations since the 1960s, automatic external defibrillation, mild hypothermia, emergency (portable) cardiopulmonary bypass, and suspended animation have potentials for clinical breakthrough effects. Suspended animation has been suggested for presently unresuscitable conditions and consists of the rapid induction of preservation (using hypothermia with or without drugs) of viability of the brain, heart, and organism (within 5 mins of normothermic cardiac arrest no-flow), which increases the time available for transport and resuscitative surgery, followed by delayed resuscitation. Since 1988, we have developed and used novel dog models of exsanguination cardiac arrest to explore suspended animation potentials with hypothermic and pharmacologic strategies using aortic cold flush and emergency portable cardiopulmonary bypass. Outcome evaluation was at 72 or 96 hrs after cardiac arrest. Cardiopulmonary bypass cannot be initiated rapidly. A single aortic flush of cold saline (4°C) at the start of cardiac arrest rapidly induced (depending on flush volume) mild-to-deep cerebral hypothermia (35° to 10°C), without cardiopulmonary bypass, and preserved viability during a cardiac arrest no-flow period of up to 120 mins. In contrast, except for one antioxidant (Tempol), explorations of 14 different drugs added to the aortic flush at room temperature (24°C) have thus far had disappointing outcome results. Profound hypothermia (10°C) during 60-min cardiac arrest induced and reversed with cardiopulmonary bypass achieved survival without functional or histologic brain damage. Further plans for the systematic development of suspended animation include the following: a) aortic flush, combining hypothermia with mechanism-specific drugs and novel fluids; b) extension of suspended animation by ultraprofound hypothermic preservation (0° to 5°C) with cardiopulmonary bypass; c) development of the most effective suspended animation protocol for clinical trials in trauma patients with cardiac arrest; and d) modification of suspended animation protocols for possible use in normovolemic ventricular fibrillation cardiac arrest, in which attempts to achieve restoration of spontaneous circulation by standard external cardiopulmonary resuscitation-advanced life support have failed.

Rapid Hypothermic Aortic Flush Can Achieve Survival without Brain Damage after 30 Minutes Cardiac Arrest in Dogs

BackgroundNeither exsanguination to pulselessness nor cardiac arrest of 30 min duration can be reversed with complete neurologic recovery using conventional resuscitation methods. Techniques that might buy time for transport, surgical hemostasis, and initiation of cardiopulmonary bypass or other resuscitation methods would be valuable. We hypothesized that an aortic flush with high-volume cold normal saline solution at the start of exsanguination cardiac arrest could rapidly preserve cerebral viability during 30 min of complete global ischemia and achieve good outcome. MethodsSixteen dogs weighing 20–25 kg were exsanguinated to pulselessness over 5 min, and circulatory arrest was maintained for another 30 min. They were then resuscitated using closed-chest cardiopulmonary bypass and had assisted circulation for 2 h, mild hypothermia (34°C) for 12 h, controlled ventilation for 20 h, and intensive care to outcome evaluation at 72 h. Two minutes after the onset of circulatory arrest, the dogs received a flush of normal saline solution at 4°C into the aorta (cephalad) via a balloon catheter. Group I (n = 6) received a flush of 25 ml/kg saline with the balloon in the thoracic aorta; group II (n = 7) received a flush of 100 ml/kg saline with the balloon in the abdominal aorta. ResultsThe aortic flush decreased mean tympanic membrane temperature (Tty) in group I from 37.6 ± 0.1 to 33.3 ± 1.6°C and in group II from 37.5 ± 0.1 to 28.3 ± 2.4°C (P = 0.001). In group I, four dogs achieved overall performance category (OPC) 4 (coma), and 2 dogs achieved OPC 5 (brain death). In group II, 4 dogs achieved OPC 1 (normal), and 3 dogs achieved OPC 2 (moderate disability). Median (interquartile range [IQR]) neurologic deficit scores (NDS 0–10% = normal; NDS 100% = brain death) were 69% (56–99%) in group I versus 4% (0–15%) in group II (P = 0.003). Median total brain histologic damage scores (HDS 0 = no damage; >100 = extensive damage; 1,064 = maximal damage) were 144 (74–168) in group I versus 18 (3–36) in group II (P = 0.004); in three dogs from group II, the brain was histologically normal (HDS 0–5). ConclusionsA single high-volume flush of cold saline (4°C) into the abdominal aorta given 2 min after the onset of cardiac arrest rapidly induces moderate-to-deep cerebral hypothermia and can result in survival without functional or histologic brain damage, even after 30 min of no blood flow.

The association between blood lactate concentration on admission, duration of cardiac arrest, and functional neurological recovery in patients resuscitated from ventricular fibrillation

ObjectiveTo assess the association between arterial lactate concentration on admission and the duration of human ventricular fibrillation cardiac arrest, and to what degree the arterial lactate concentration on admission is an early predictor of functional neurological recovery in human cardiac arrest survivors.DesignCohort study. Arterial lactate concentrations and out-of-hospital data concerning cardiac arrest and cardiopulmonary resuscitation were collected retrospectively according to a standardized protocol. Functional neurological recovery was assessed prospectively at regular intervals for 6 months.SettingEmergency department of an urban tertiary care hospital.PatientsA total of 167 primary survivors of witnessed out-of-hospital ventricular fibrillation cardiac arrest.MeasurementsThe association between arterial lactate concentration on admission, the duration of cardiac arrest, and functional neurological recovery was assessed. Further, we assessed whether admission concentrations of arterial lactate and duration of cardiac arrest can predict unfavorable functional neurological recovery. Functional neurological recovery was measured in cerebral performance categories (CPC). No or minimal functional impairment (CPC 1 and 2) was defined as favorable outcome; the remaining categories (CPC 3, 4 and 5) were defined as unfavorable functional neurological recovery.ResultsIn 167 patients, a weak association between total duration of cardiac arrest and admission levels of lactate (r=0.49, P<0.001) could be shown. With increasing admission concentrations of arterial lactate functional neurological recovery was more likely to be unfavorable (OR 1.15 per mmol/1 increase, 95 % CI 1.04–1.27). Nevertheless, only at very high levels of lactate (16.3 mmol/1) could unfavorable neurological recovery be detected with 100 % specificity, yielding a very low sensitivity of 16 %.ConclusionsThe arterial admission lactate concentration after out-of-hospital ventricular fibrillation cardiac arrest is a weak measure of the duration of ischemia. High admission lactate levels are associated with severe neurological impairment. However, this parameter has poor prognostic value for individual estimation of the severity of subsequent functional neurological impairment.

Accuracy and Impact of Presumed Cause in Patients With Cardiac Arrest

BACKGROUND International guidelines recommend differentiation between cardiac and noncardiac causes of cardiac arrest. The aim of this study was to find the rate of agreement between primarily postulated and definitive causes of cardiac arrest. METHODS AND RESULTS We retrospectively analyzed the primarily presumed cause of cardiac arrest as determined by the emergency room physician on admission in all patients admitted to the emergency department of one urban tertiary care hospital. This was compared with the definitive cause as established by clinical evidence or autopsy. Within 4 years, the initially presumed cause was unclear in 24 (4%) of 593 patients. In the remaining 569 patients, the presumed cause was correct in 509 (89%) and wrong in 60 (11%) cases. Cardiac origin was presumed in 421 (71%) and the definitive cause in 408 (69%) cases. Noncardiac origin was presumed in 148 (25%) and the definitive cause in 185 (31%) patients. Presumed cardiac cause was sensitive (96%) but less specific (77%). Noncardiac causes such as pulmonary embolism, cerebral disorders, or exsanguination were those most frequently overlooked. Asystole occurred significantly more often in patients in whom presumed cause remained undetermined or differed from the definitive cause. CONCLUSIONS Cause of cardiac arrest is not as easily recognized as anticipated, especially when the initial rhythm is different from ventricular fibrillation. This might affect comparability of study results, therapeutic strategies, prognosis, and outcome. Patients in whom the presumed cause was confirmed as being correct had significantly better survival and neurological outcome.