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Significant improvements have been achieved in cardiac arrest resuscitation and postarrest resuscitation care, but mortality remains high. Most of the poor outcomes and deaths of cardiac arrest survivors have been attributed to widespread brain injury. This brain injury, commonly manifested as a comatose state, is a marker of poor outcome and a major basis for unfavorable neurological prognostication. Accurate prognostication is important to avoid pursuing futile treatments when poor outcome is inevitable but also to avoid an inappropriate withdrawal of life-sustaining treatment in patients who may otherwise have a chance of achieving meaningful neurological recovery. Inaccurate neurological prognostication leading to withdrawal of life-sustaining treatment and deaths may significantly bias clinical studies, leading to failure in detecting the true study outcomes. The American Heart Association Emergency Cardiovascular Care Science Subcommittee organized a writing group composed of adult and pediatric experts from neurology, cardiology, emergency medicine, intensive care medicine, and nursing to review existing neurological prognostication studies, the practice of neurological prognostication, and withdrawal of life-sustaining treatment. The writing group determined that the overall quality of existing neurological prognostication studies is low. As a consequence, the degree of confidence in the predictors and the subsequent outcomes is also low. Therefore, the writing group suggests that neurological prognostication parameters need to be approached as index tests based on relevant neurological functions that are directly related to the functional outcome and contribute to the quality of life of cardiac arrest survivors. Suggestions to improve the quality of adult and pediatric neurological prognostication studies are provided.

Successful resuscitation from cardiac arrest results in a post-cardiac arrest syndrome, which can evolve in the days to weeks after return of sustained circulation. The components of post-cardiac arrest syndrome are brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathophysiology. Pediatric post-cardiac arrest care focuses on anticipating, identifying, and treating this complex physiology to improve survival and neurological outcomes. This scientific statement on post-cardiac arrest care is the result of a consensus process that included pediatric and adult emergency medicine, critical care, cardiac critical care, cardiology, neurology, and nursing specialists who analyzed the past 20 years of pediatric cardiac arrest, adult cardiac arrest, and pediatric critical illness peer-reviewed published literature. The statement summarizes the epidemiology, pathophysiology, management, and prognostication after return of sustained circulation after cardiac arrest, and it provides consensus on the current evidence supporting elements of pediatric post-cardiac arrest care.

Background: We have previously shown that hydrogen (H2) inhalation, begun at the start of hyperoxic cardiopulmonary resuscitation, significantly improves brain and cardiac function in a rat model of cardiac arrest. Here, we examine the effectiveness of this therapeutic approach when H2 inhalation is begun on the return of spontaneous circulation (ROSC) under normoxic conditions, either alone or in combination with targeted temperature management (TTM)., Methods and Results: Rats were subjected to 6 minutes of ventricular fibrillation cardiac arrest followed by cardiopulmonary resuscitation. Five minutes after achieving ROSC, post-cardiac arrest rats were randomized into 4 groups: mechanically ventilated with 26% O2 and normothermia (control); mechanically ventilated with 26% O2, 1.3% H2, and normothermia (H2); mechanically ventilated with 26% O2 and TTM (TTM); and mechanically ventilated with 26% O2, 1.3% H2, and TTM (TTM+H2). Animal survival rate at 7 days after ROSC was 38.4% in the control group, 71.4% in the H2 and TTM groups, and 85.7% in the TTM+H2 group. Combined therapy of TTM and H2 inhalation was superior to TTM alone in terms of neurological deficit scores at 24, 48, and 72 hours after ROSC, and motor activity at 7 days after ROSC. Neuronal degeneration and microglial activation in a vulnerable brain region was suppressed by both TTM alone and H2 inhalation alone, with the combined therapy of TTM and H2 inhalation being most effective., Conclusions: H2 inhalation was beneficial when begun after ROSC, even when delivered in the absence of hyperoxia. Combined TTM and H2 inhalation was more effective than TTM alone., (© 2014 American Heart Association, Inc.)

Background: The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope., Methods and Results: Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12 ± 10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40-74) with pacemaker OFF and 25% (95% CI, 13-45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4-81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient., Conclusions: Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.

Background: Therapeutic hypothermia is recommended for the treatment of neurological injury after resuscitation from out-of-hospital cardiac arrest. Laboratory studies have suggested that earlier cooling may be associated with improved neurological outcomes. We hypothesized that induction of therapeutic hypothermia by paramedics before hospital arrival would improve outcome., Methods and Results: In a prospective, randomized controlled trial, we assigned adults who had been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of ventricular fibrillation to either prehospital cooling with a rapid infusion of 2 L of ice-cold lactated Ringer's solution or cooling after hospital admission. The primary outcome measure was functional status at hospital discharge, with a favorable outcome defined as discharge either to home or to a rehabilitation facility. A total of 234 patients were randomly assigned to either paramedic cooling (118 patients) or hospital cooling (116 patients). Patients allocated to paramedic cooling received a median of 1900 mL (first quartile 1000 mL, third quartile 2000 mL) of ice-cold fluid. This resulted in a mean decrease in core temperature of 0.8 degrees C (P=0.01). In the paramedic-cooled group, 47.5% patients had a favorable outcome at hospital discharge compared with 52.6% in the hospital-cooled group (risk ratio 0.90, 95% confidence interval 0.70 to 1.17, P=0.43)., Conclusions: In adults who have been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of ventricular fibrillation, paramedic cooling with a rapid infusion of large-volume, ice-cold intravenous fluid decreased core temperature at hospital arrival but was not shown to improve outcome at hospital discharge compared with cooling commenced in the hospital.

Background: Cardiac arrest continues to have poor survival in the United States. Recent studies have questioned current practice in resuscitation. Our emergency medical services system made significant changes to the adult cardiac arrest resuscitation protocol, including minimizing chest compression interruptions, increasing the ratio of compressions to ventilation, deemphasizing or delaying intubation, and advocating chest compressions before initial countershock., Methods and Results: This retrospective observational cohort study reviewed all adult primary ventricular fibrillation and pulseless ventricular tachycardia cardiac arrests 36 months before and 12 months after the protocol change. Primary outcome was survival to discharge; secondary outcomes were return of spontaneous circulation and cerebral performance category. Survival of out-of-hospital arrest of presumed primary cardiac origin improved from 7.5% (82 of 1097) in the historical cohort to 13.9% (47 of 339) in the revised protocol cohort (odds ratio, 1.80; 95% confidence interval, 1.19 to 2.70). Similar increases in return of spontaneous circulation were achieved for the subset of witnessed cardiac arrest patients with initial rhythm of ventricular fibrillation from 37.8% (54 of 143) to 59.6% (34 of 57) (odds ratio, 2.44; 95% confidence interval, 1.24 to 4.80). Survival to hospital discharge also improved from an unadjusted survival rate of 22.4% (32 of 143) to 43.9% (25 of 57) (odds ratio, 2.71; 95% confidence interval, 1.34 to 1.59) with the protocol. Of the 25 survivors, 88% (n=22) had favorable cerebral performance categories on discharge., Conclusions: The changes to our prehospital protocol for adult cardiac arrest that optimized chest compressions and reduced disruptions increased the return of spontaneous circulation and survival to discharge in our patient population. These changes should be further evaluated for improving survival of out-of-hospital cardiac arrest patients.

Background: The effect of prearrest left ventricular ejection fraction (LVEF) on outcome after cardiac arrest is unknown., Methods and Results: During a 26-month period, Utstein-style data were prospectively collected on 800 consecutive inpatient adult index cardiac arrests in an observational, single-center study at a tertiary cardiac care hospital. Prearrest echocardiograms were performed on 613 patients (77%) at 11+/-14 days before the cardiac arrest. Outcomes among patients with normal or nearly normal prearrest LVEF (> or = 45%) were compared with those of patients with moderate or severe dysfunction (LVEF < 45%) by chi(2) and logistic regression analyses. Survival to discharge was 19% in patients with normal or nearly normal LVEF compared with 8% in those with moderate or severe dysfunction (adjusted odds ratio, 4.8; 95% confidence interval, 2.3 to 9.9; P<0.001) but did not differ with regard to sustained return of spontaneous circulation (59% versus 56%; P=0.468) or 24-hour survival (39% versus 36%; P=0.550). Postarrest echocardiograms were performed on 84 patients within 72 hours after the index cardiac arrest; the LVEF decreased 25% in those with normal or nearly normal prearrest LVEF (60+/-9% to 45+/-14%; P<0.001) and decreased 26% in those with moderate or severe dysfunction (31+/-7% to 23+/-6%, P<0.001). For all patients, prearrest beta-blocker treatment was associated with higher survival to discharge (33% versus 8%; adjusted odds ratio, 3.9; 95% confidence interval, 1.8 to 8.2; P<0.001)., Conclusions: Moderate and severe prearrest left ventricular systolic dysfunction was associated with substantially lower rates of survival to hospital discharge compared with normal or nearly normal function.

Background: The 2005 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care changed the previous ventilations-to-chest-compression algorithm for bystander cardiopulmonary resuscitation (CPR) from 2 ventilations before each 15 chest compressions (2:15 CPR) to 30 chest compressions before 2 ventilations (30:2 CPR). It was acknowledged in the guidelines that the change was based on a consensus rather than clear evidence. This study was designed to compare 24-hour neurologically normal survival between the initial applications of continuous chest compressions without assisted ventilations with 30:2 CPR in a swine model of witnessed out-of-hospital ventricular fibrillation cardiac arrest., Methods and Results: Sixty-four animals underwent 12 minutes of ventricular fibrillation before defibrillation attempts. They were divided into 4 groups, each with increasing durations (3, 4, 5, and 6 minutes, respectively) of untreated ventricular fibrillation before the initiation of bystander resuscitation consisting of either continuous chest compression or 30:2 CPR. After the various untreated ventricular durations plus bystander resuscitation durations, all animals were given the first defibrillation attempt 12 minutes after the induction of ventricular fibrillation, followed by the 2005 guideline-recommended advanced cardiac life support. Neurologically normal survival at 24 hours after resuscitation was observed in 23 of 33 (70%) of the animals in the continuous chest compression groups but in only 13 of 31 (42%) of the 30:2 CPR groups (P=0.025)., Conclusions: In a realistic model of out-of-hospital ventricular fibrillation cardiac arrest, initial bystander administration of continuous chest compressions without assisted ventilations resulted in significantly better 24-hour postresuscitation neurologically normal survival than did the initial bystander administration of 2005 guideline-recommended 30:2 CPR.

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.

Background: Therapeutic hypothermia can improve survival after cardiopulmonary resuscitation (CPR). Coenzyme Q10 (CoQ10) has shown a protective effect in neurodegenerative disorders. We investigated whether combining mild hypothermia with CoQ10 after out-of-hospital cardiac arrest provides additional benefit., Methods and Results: Forty-nine patients were randomly assigned to either hypothermia plus CoQ10 or hypothermia plus placebo after CPR. Hypothermia with a core temperature of 35 degrees C was instituted for 24 hours. Liquid CoQ10 250 mg followed by 150 mg TID for 5 days or placebo was administered through nasogastric tube. Age, sex, premorbidity, cause of arrest, conditions of CPR, and degree of hypoxia were similar in both groups; no side effects of CoQ10 were identified. Three-month survival in the CoQ10 group was 68% (17 of 25) and 29% (7 of 24) in the placebo group (P=0.0413). Nine CoQ10 patients versus 5 placebo patients survived with a Glasgow Outcome Scale of 4 or 5. Mean serum S100 protein 24 hours after CPR was significantly lower in the CoQ10 group (0.47 versus 3.5 ng/mL)., Conclusions: Combining CoQ10 with mild hypothermia immediately after CPR appears to improve survival and may improve neurological outcome in survivors.

Background: We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome., Methods and Results: Plasma cytokine, endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed Staphylococcus aureus. In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell-derived IL-10 and interferon-gamma were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients' leukocytes and that an immunosuppressive activity was also present in their plasma., Conclusions: Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis.

Background: No proven neuroprotective treatment exists for ischemic brain injury after cardiac arrest. Mild-to-moderate induced hypothermia (MIH) is effective in animal models., Methods and Results: A safety and feasibility trial was designed to evaluate mild-to-moderate induced hypothermia by use of external cooling blankets after cardiac arrest. Inclusion criteria were return of spontaneous circulation within 60 minutes of advanced cardiac life support, hypothermia initiated within 90 minutes, persistent coma, and lack of acute myocardial infarction or unstable dysrhythmia. Hypothermia to 33 degrees C was maintained for 24 hours followed by passive rewarming. Nine patients were prospectively enrolled. Mean time from advanced cardiac life support to return of spontaneous circulation was 11 minutes (range 3 to 30); advanced cardiac life support to initiation of hypothermia was 78 minutes (range 40 to 109); achieving 33 degrees C took 301 minutes (range 90 to 690). Three patients completely recovered, and 1 had partial neurological recovery. One patient developed unstable cardiac dysrhythmia. No other unexpected complications occurred., Conclusions: Mild-to-moderate induced hypothermia after cardiac arrest is feasible and safe. However, external cooling is slow and imprecise. Efforts to speed the start of cooling and to improve the cooling process are needed.

Background: The results of early conventional tests do not correlate with cerebral outcome after cardiac arrest. We investigated the serum levels of astroglial protein S-100 as an early marker of brain damage and outcome after cardiac arrest., Methods and Results: In 66 patients undergoing cardiopulmonary resuscitation after nontraumatic cardiac arrest, blood samples for the evaluation of S-100 were drawn immediately after and 15, 30, 45, and 60 minutes; 2, 8, 24, 48, and 72 hours; and 7 days after initiation of cardiopulmonary resuscitation. Moreover, the serum levels of neuron-specific enolase were determined between 2 hours and 7 days. If patients survived for >48 hours, brain damage was assessed by a combination of neurological, cranial CT, and electrophysiological examinations. Overall, 343 blood samples were taken for the determination of S-100. Maximum S-100 levels within 2 hours after cardiac arrest were significantly higher in patients with documented brain damage (survivors and nonsurvivors, 3.70+/-0.77 microg/L) than in patients without brain damage (0.90+/-0.29 microg/L). Significant differences between these 2 groups were observed from 30 minutes until 7 days after cardiac arrest. In addition, the positive predictive value of the S-100 test at 24 hours for fatal outcome within 14 days was 87%, and the negative predictive value was 100% (P<0.001). With regard to neuron-specific enolase, significant differences between patients with documented brain damage and those with no brain damage were found at 24, 48, and 72 hours and 7 days., Conclusions: Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and short-term outcome after cardiac arrest in humans.

Background: Patients with syncope of unknown etiology after negative noninvasive and electrophysiological testing may suffer from recurrent disability. Syncopal episodes are often too infrequent and unpredictable for detection by conventional ambulatory monitoring techniques., Methods and Results: A long-term subcutaneous monitoring device was implanted in patients with negative ambulatory monitoring, tilt table and electrophysiological testing to establish cardiac rhythm during spontaneous syncope. Sixteen patients aged 57 +/- 19 years with a mean of 8.4 +/- 4.4 previous episodes of syncope underwent device implantation. Fifteen patients (94%) had recurrent syncope 4.4 +/- 4.2 months after implantation. The remaining patient has not had recurrent syncope and continues to be followed. A diagnosis was obtained in every patient who had recurrent episode. Syncope was secondary to sinus arrest in 5, atrioventricular block in 2, ventricular tachycardia in 1, supraventricular tachycardia in 1, and nonarrhythmic in 6. Successful therapy was implemented in all 15 patients, without recurrence of syncope during 13.0 +/- 8.4 months of follow-up., Conclusions: Unexplained syncope in patients with negative investigations has a broad spectrum of etiologies, the most common of which is bradycardia. An implantable long-term monitoring device is useful for establishing a diagnosis when symptoms are recurrent but too infrequent for conventional monitoring techniques.

Extensive atherosclerotic coronary artery disease is by far the most common pathological finding in patients with sudden cardiac death, and acute myocardial ischemia is often a contributing factor. Clinical trials using beta-blockers in postinfarction patients and bypass coronary artery surgery in patients with stable coronary artery disease have demonstrated a reduction in both sudden and total cardiac mortality after intervention. Information concerning the presence and extent of coronary artery disease, global and regional ventricular function, the presence or absence of ventricular aneurysms, and whether or not ischemia is inducible influences therapeutic management. Myocardial revascularization should be considered a primary therapy in patients with critical coronary artery stenosis, significant regions of myocardium at risk, and no inducible ventricular arrhythmias at electrophysiological testing. In patients with inducible polymorphic ventricular tachycardia or ventricular fibrillation, postoperative testing is essential, since only 50% will be suppressed by coronary artery surgery alone. In patients with inducible sustained monomorphic ventricular tachycardia and scars due to prior myocardial infarction, surgical revascularization alone will usually not be sufficient to prevent postoperative induction of the same arrhythmia. There are no data to support percutaneous transluminal coronary angioplasty as the sole therapy for post-sudden death patients who have inducible ventricular tachycardia or ventricular fibrillation on electrophysiological testing.

Invasive electrophysiological testing has contributed importantly to the objective evaluation and management of patients at high risk for sudden cardiac death. The clinical application of the technique is based on the hypothesis that the reproducible induction of ventricular arrhythmias by programmed cardiac stimulation constitutes a marker of risk for spontaneous ventricular arrhythmias and sudden death as well as an objective end point to guide the selection of antiarrhythmic therapy. The value of electrophysiological testing is well established in patients with ischemic heart disease and a history of sustained ventricular tachycardia or fibrillation and in some subsets of patients with unexplained syncope. More recently, the technique has been used by some investigators to identify individuals at high risk for sudden death among patients with recent myocardial infarction and those with left ventricular dysfunction and recurrent nonsustained ventricular tachycardia. The predictive value of the technique in patients with nonischemic heart disease is unknown. In addition to its use as an objective end point in the selection of antiarrhythmic drug therapy, invasive electrophysiological testing has advanced our knowledge of the mechanisms of life-threatening ventricular arrhythmias and contributed importantly to the development of new therapies, such as implantable arrhythmia control devices and catheter ablation techniques.

Background: QTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance., Methods and Results: In the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventricular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazett's formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction less than 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks., Conclusions: These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death.

We investigated the effects of carbon dioxide-producing and carbon dioxide-consuming buffers on intramyocardial pH and on cardiac resuscitability. In 29 pigs, intramyocardial pH was continuously measured with a glass electrode advanced into the midmyocardium of the posterior left ventricle through a diaphragmatic window. Ventricular fibrillation (VF) was electrically induced by alternating current applied to the epicardium of the left ventricle. After 3 minutes of VF, precordial compression was begun and continued for an interval of 8 minutes. Sodium bicarbonate (a carbon dioxide-generating buffer), Carbicarb (a carbon dioxide-consuming buffer), and hypertonic sodium chloride (control solution) were infused into the right atrium during cardiac resuscitation. Defibrillation was attempted by transthoracic direct-current shock after 11 minutes of VF. Intramyocardial pH progressively decreased from an average value of 7.26 before VF to 6.87 before infusion of buffers. Systemic circulation and great cardiac vein pH significantly increased after administration of the two buffer agents. However, intramyocardial pH continued to decline to an average of 6.62 after 11 minutes of VF, and this decline was not altered by either buffer solution or by the saline control. As in previous studies, resuscitability was closely related to coronary perfusion pressure at the time of direct-current countershock but not to pH. Accordingly, the rationale of reversing acidosis by the administration of these buffer agents is not supported. Even more important, neither carbon dioxide-consuming nor carbon dioxide-producing buffers altered myocardial acidosis or improved myocardial resuscitability under controlled experimental conditions of cardiac arrest.

One hundred forty-four patients with coronary heart disease previously resuscitated from out-of-hospital ventricular fibrillation underwent 24-hour ambulatory ECG monitoring 5 months (median) after cardiac arrest. Patients were then followed for an average of 31.7 months. Fifty-one patients died, 32 from subsequent unexpected cardiac arrest. One hundred twenty-nine patients (90%) had uniform ventricular ectopy. Two-thirds had complex ventricular ectopy (Bigeminy/trigeminy, repetitive forms or frequent multiforms). Complex ectopy, present in 20% or more of the 30-minute recording intervals, occurred in 18 of the patients (56%) who developed subsequent cardiac arrest, compared with 26 of 92 (28%) who survived (P less than 0.005, specificity 72%, relative risk 2.3). Other forms of ventricular ectopy, e.g., uniform, multiform and repetitive beats, were more sensitive but less specific predictors of death or recurrent ventricular fibrillation. Complex ventricular ectopy was associated with certain clinical histories: it occurred in 95% of patients with a history of congestive heart failure and in 79% with remote myocardial infarction, compared with 59% and 56% without these histories (p less than 0.001 and p less than 0.01). As expected, mortality was also greater in patients who had these clinical characteristics. Complex ectopy was related to mortality regardless of the clinical history.

Serial treadmill exercise testing (mean 5.5 tests/patient) was used to evaluate the prognosis of 200 males (mean age 53 years) without clinical heart failure or unstable angina pectoris 3 weeks after acute myocardial infarction (MI). Exercise-induced ischemic ST-segment depression greater than or equal to 0.2 mV 3 weeks after MI was significantly more prevalent in patients with subsequent cardiac arrest (100%) or coronary artery bypass graft surgery (64%) than in patients without subsequent events within 2 years of infarction (35%) (p less than 0.05). Exercise-induced ventricular arrhythmia on multiple tests 5-52 weeks after MI was more prevalent in patients with recurrent myocardial infarction (90%) than in patients without subsequent events (47%) (p less than 0.001). By contrast, exercise-induced ventricular arrhythmia on a single test at 3 weeks was a less powerful predictor of subsequent cardiac events. Exercise-induced ischemia 3 weeks after MI predicted early fatal events, while ventricular arrhythmia on serial testing predicted later nonfatal events.

Electromechanical dissociation (EMD) is the most frequent cause of unsuccessful cardiac resuscitation in critically ill patients. In a clinical study of cardiac arrest, including 54 episodes in 50 fully monitored patients, 14 episodes of ventricular fibrillation were observed and seven were reversed. In the remaining 40 instances, 36 cases of EMD were initially observed. Four patients had asystole. None of the patients with EMD or asystole were successfully resuscitated. For objective study of EMD and its treatment, we developed an experimental model in which ventricular fibrillation was induced in mechanically ventilated dogs. EMD was predictably observed when, after an interval of 120 seconds, ventricular fibrillation was reversed with an external countershock. Neither metabolic acidosis nor metabolic alkalosis modified the incidence of EMD. A few dogs were pretreated with glucose-insulin-potassium or pharmacologic doses of methylprednisolone, but this did not clearly reduce the incidence of EMD. However, the onset of EMD was delayed when the body temperature of the animal was spontaneously reduced.

We studied the long-term effects of membrane-active antiarrhythmic agents on chronic ventricular arrhythmias in patients who have survived prehospital cardiac arrest. Among 16 patients treated with a dose-adjusted, plasma level-monitored antiarrhythmic regimen, eight have survived for longer than 12 months and eight have had recurrent cardiac arrests (RCAs). Monthly Holter monitor tapes (HM) recorded during the 4 months before the eight RCAs were compared with monthly HM tapes matched for time of entry and duration of follow-up in the eight patients who did not have RCAs. Transient or persistent complex ventricular ectopic depolarizations (VEDs) have been recorded on 47 of the 63 monthly HM tapes (75%). The difference between VEDs in the RCA patients (mean 153 VEDs/hr, median 19 VEDs/hr) and VEDs in the patients who have not had RCA (mean 122 VEDs/hr, median 8 VEDs/hr) was not significant (p less than 0.2); nor was there a predictable relationship between therapeutic plasma levels of antiarrhythmic agents and the frequency and complexity of chronic asymptomatic VEDs (therapeutic levels--mean 104 VEDs/hr, median 6 VEDs/hr; subtherapeutic levels--mean 184 VEDs/hr, median 21 VEDs/hr). Differences were not significant (p greater than 0.1). In contrast, all eight RCA patients had unstable plasma levels (21 of 31 determinations subtherapeutic) while six of the eight patients who have not had RCA had consistently therapeutic levels (p less than 0.01). Thus, adequate plasma levels of antiarrhythmic agents may protect against RCA, despite failure to suppress VEDs predictably. The apparent dissociation between predictable suppression of chronic VEDs and protection against RCA suggests that clinical effectiveness of these agents may not be best measured by their effect on chronic VEDs.

Cerebral neurons can tolerate at least 20 min of normothermic ischemic anoxia. Cerebral recovery from more than 5 min of cardiac arrest is hampered by complex secondary derangements of multiple organ systems after reperfusion. There is increasing support of our hypothesis that this "postresuscitation syndrome" includes the following: secondary cerebral perfusion failure, cerebral reoxygenation injury (cell-necrotizing cascades), and cerebral "intoxication" from derangements of extracerebral organs. To be optimal for the brain, CPR with optimal perfusion pressure must be started as promptly as possible. Significant though inconsistent mitigation of permanent brain damage after prolonged complete global brain ischemia has been achieved in animal outcome preparations with the use of the following treatments initiated at the start of reperfusion: brain-oriented extracerebral life support by protocol, intra-arterial hemodilution, hypertension, and artificial circulation, barbiturates, calcium-entry blockers, free-radical scavengers, and multifaceted treatments. We currently recommend treatment 1 for patient care and treatment 2 for clinical feasibility trials. Treatment 3, thiopental loading (starting 10 to 50 min after restoration of spontaneous circulation), was tested in a randomized clinical trial and was not shown to confer a statistically significant benefit. A calcium-entry blocker is under clinical investigation. Many other novel treatments appear promising but further animal studies are required. The complex multifactorial pathogenesis of postcardiac arrest encephalopathy requires systematic multicenter development of etiology-specific combination therapies.

Electrophysiologic studies were performed in 172 consecutive patients for evaluation of documented sustained ventricular tachyarrhythmias. One hundred thirteen patients presented with sustained ventricular tachycardia that was hemodynamically stable, and 59 patients presented with cardiac arrest. Seventy-one patients without previously documented or suspected ventricular arrhythmias were also studied to determine the specificity of our electrophysiologic study protocol. The stimulation protocol included single, double, and triple right ventricular extrastimuli and rapid ventricular pacing at multiple cycle lengths performed at one or more right ventricular sites. Stimulation was performed at one or more left ventricular sites in patients with documented spontaneous arrhythmias when right ventricular programmed stimulation failed to induce sustained ventricular tachycardia. Ventricular tachyarrhythmias were induced in 110 (97%) of the patients who presented with sustained ventricular tachycardia, in 48 (81%) of the patients who presented with cardiac arrest, and in 28 (40%) of the patients without documented spontaneous arrhythmias. Right ventricular triple extrastimuli induced tachycardia in 22% of patients who presented with sustained ventricular tachycardia vs 46% of those who presented with cardiac arrest (p less than .001). Left ventricular stimulation was required for tachycardia induction in 3% of patients with stable tachycardia vs 19% of those with cardiac arrest (p less than .01). Triple extrastimuli induced 57% of tachycardias in the 28 patients without spontaneous arrhythmias, and virtually all of these tachycardias were polymorphic and nonsustained. The cycle lengths of tachycardias induced in each group by double and triple extrastimuli were similar, but the tachycardias induced in patients with cardiac arrest were significantly faster than those induced in the ventricular tachycardia group (mean cycle length 218 vs 291 msec, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)