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OBJECTIVE Left ventricular dysfunction after successful cardiopulmonary resuscitation contributes to early death following resuscitation. The stress-induced proinflammatory cytokines, particularly tumor necrosis factor-alpha and interleukin-1beta, are known to depress myocardial function. We hypothesized that tumor necrosis factor-alpha and interleukin-1beta, synthesized and released in response to the stress of global ischemia accompanying cardiac arrest, play a role in development of postresuscitation left ventricular dysfunction. METHODS Hemodynamic variables, tumor necrosis factor-alpha , interleukin-1beta, interleukin-6 (enzyme-linked immunosorbent assay method), and ionized calcium were measured in ten anesthetized swine before and after 7 mins of cardiac arrest and during the early postresuscitation period (60-90 mins). RESULTS Tumor necrosis factor-alpha increased three-fold within 15 mins of restoration of circulation and remained elevated throughout the observation period. A significant negative correlation was observed between tumor necrosis factor-alpha and left ventricular systolic change in pressure over time (r = -.54, p

Objective: In the prehospital setting, countershock terminates ventricular fibrillation (VF) in about 80% of cases. However, countershock is most commonly followed by asystole or pulseless electrical activity (PEA). The consequences of such a countershock outcome have not been well studied. The purpose of this investigation was to compare the outcome of prehospital VF victims shocked into asystole or PEA with that of patients whose first documented rhythm was asystole or PEA (primary asystole or PEA). Design: Observational, retrospective study conducted over 5 yrs (1995-1999). Setting: A municipal hospital with a catchment area of >200,000. Patients: Consecutive adult patients with out-of-hospital non-traumatic cardiopulmonary arrest of cardiac origin. Patients found in VF who developed asystole or PEA after countershocks (group 1) and patients found in asystole or PEA (primary asystole or PEA) (group 2) were included if the reported downtime was

Sepsis is the tenth leading cause of death in the United States. Despite extensive research, mortality rates for sepsis have not substantially improved in the last several decades. We describe an innovative phase II clinical trial design for evaluating the addition of L-carnitine to the treatment of vasopressor-dependent septic shock.The design incorporates a variety of features to increase efficiency, including a normal dynamic linear dose-response model, adaptive randomization, and early stopping for futility or success based on the probability that a future phase III trial using a 28-day mortality outcome would be successful.Trial design and computer simulation of a trial to be conducted in the emergency department and ICU.Proposed to study intravenous L-carnitine.The proposed trial uses an early endpoint, the 48-hour change in Sequential Organ Failure Assessment score, to drive adaptive randomization and dose selection.We use existing data to model the expected relationship between the Sequential Organ Failure Assessment change and the 28-day mortality to determine the trial's operating characteristics using Monte Carlo simulation.The resulting trial efficiently identifies the best dose of L-carnitine and provides clear guidance regarding whether to continue development into phase III.

The standard porcine cardiac arrest model uses electrical induction of ventricular fibrillation. Reported restoration of spontaneous circulation and survival rates in this model are as high as 90% for ventricular fibrillation durations of 7-10 mins, values substantially greater than rates in the clinical population (i.e., 20% to 30%). A high first shock success rate, infrequent refibrillation, and short times for restoration of spontaneous circulation are typical of the model. The purpose of this study was to determine whether ischemic induction of ventricular fibrillation in swine followed by standard advanced cardiac life support would result in short-term outcomes approximating those observed in human victims of out-of-hospital ventricular fibrillation.Randomized comparative trial.Translational research laboratory.Domestic swine (n = 40, mean weight 40 +/- 4 kg, range 34-47 kg) of both genders.Swine were instrumented and randomized to either electrical ventricular fibrillation induction or ischemic ventricular fibrillation, produced by balloon occlusion of the mid-left anterior descending coronary artery (n = 20 per group). Transthoracic impedance was measured and 30 Omega added in series for all animals. The balloon remained inflated during resuscitation efforts in ischemic ventricular fibrillation animals. After 7 mins of ventricular fibrillation, cardiopulmonary resuscitation was initiated and defibrillation was attempted 1 min later. Epinephrine and antiarrhythmics were administered as per guidelines. Resuscitation was terminated if restoration of spontaneous circulation had not occurred after 15 mins of advanced cardiac life support.Although the number of countershocks required to initially terminate ventricular fibrillation was not different (electrical ventricular fibrillation 1.9 +/- 1.6, ischemic ventricular fibrillation 2.4 +/- 2.0), the refibrillation rate was higher in the ischemic ventricular fibrillation group (4.9 +/- 4 vs. 0.8 +/- 1 episodes/animal, p.001), resulting in a greater number of shocks before restoration of spontaneous circulation (total shocks for ischemic ventricular fibrillation 9.4 +/- 5.6 vs. electrical ventricular fibrillation 2.7 +/- 2.2, p.001). Time to restoration of spontaneous circulation was longer in the ischemic ventricular fibrillation group (430 +/- 234 secs vs. 149 +/- 120 secs, p.001). Restoration of spontaneous circulation rates were not different (electrical ventricular fibrillation 90% vs. ischemic ventricular fibrillation 65%). However, survival to 6 hrs was greater in the electrical ventricular fibrillation group (18 of 20, 90%) than in the ischemic ventricular fibrillation group (8 of 20, 40%, p = .002).Resuscitation from ischemic ventricular fibrillation is more difficult than electrical ventricular fibrillation and is characterized by greater time to restoration of spontaneous circulation, frequent refibrillation, greater number of countershocks, higher epinephrine dose during resuscitation efforts, profound cardiac dysfunction, and a short-term survival rate approaching clinical experience. Ischemically induced ventricular fibrillation is a more clinically relevant model for the evaluation of resuscitation interventions.