pituitrin and Ventricular-Fibrillation

Advanced Life Support guidelines recommend the use of epinephrine during Cardiopulmonary Resuscitation (CPR), as to increase coronary blood flow and perfusion pressure through its alpha-adrenergic peripheral vasoconstriction, allowing minimal rises in coronary perfusion pressure to make defibrillation possible. Contrasting to these alpha-adrenergic effects, epinephrine's beta-stimulation may have deleterious effects through an increase in myocardial oxygen consumption and a reduction of subendocardial perfusion, leading to postresuscitation cardiac dysfunction.. The present paper consists of a systematic review of the literature regarding the use of beta-blockade in cardiac arrest due to ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT).. Studies were identified through MEDLINE electronic databases research and were included those regarding the use of beta-blockade during CPR.. Beta-blockade has been extensively studied in animal models of CPR. These studies not only suggest that beta-blockade could reduce myocardial oxygen requirements and the number of shocks necessary for defibrillation, but also improve postresuscitation myocardial function, diminish arrhythmia recurrences and prolong survival. A few case reports described successful beta-blockade use in patients, along with two prospective human studies, suggesting that it could be safe and effectively used during cardiac arrest in humans.. Even though the existing literature points toward a beneficial effect of beta-blockade in patients presenting with cardiac arrest due to VF/pulseless VT, high quality human trials are still lacking to answer this question definitely.

Topics: Adrenergic beta-Antagonists; Animals; Cardiopulmonary Resuscitation; Coronary Circulation; Epinephrine; Heart Arrest; Humans; Myocardium; Oxygen Consumption; Propanolamines; Propranolol; Tachycardia, Ventricular; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

The best chance of survival with a good neurological outcome after cardiac arrest is afforded by early recognition and high-quality cardiopulmonary resuscitation (CPR), early defibrillation of ventricular fibrillation (VF), and subsequent care in a specialist center. Compression-only CPR should be used by responders who are unable or unwilling to perform mouth-to-mouth ventilations. After the first defibrillator shock, further rhythm checks and defibrillation attempts should be performed after 2 min of CPR. The underlying cause of cardiac arrest can be identified and treated during CPR. Drugs have a limited effect on long-term outcomes after cardiac arrest, although epinephrine improves the success of resuscitation, and amiodarone increases the success of defibrillation for refractory VF. Supraglottic airway devices are an alternative to tracheal intubation, which should be attempted only by skilled rescuers. Care after cardiac arrest includes controlled reoxygenation, therapeutic hypothermia for comatose survivors, percutaneous coronary intervention, circulatory support, and control of blood-glucose levels and seizures. Prognostication in comatose survivors of cardiac arrest needs a careful, multimodal approach using clinical and electrophysiological assessments after at least 72 h.

Topics: Airway Management; Anti-Arrhythmia Agents; Cardiopulmonary Resuscitation; Defibrillators; Epinephrine; Heart Arrest; Humans; Prognosis; Sympathomimetics; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Vasopressin is a 9-amino acid peptide synthesized by magnocellular neurons of the hypothalamus and released from posterior pituitary gland. The primary physiological role of vasopressin is the maintenance of fluid homeostasis. In this review, the classification of vasopressin receptors, namely V1 vascular, V2 renal, V3 pituitary, oxytocin receptors, and purinergic receptors, and the effects of vasopressin on vascular smooth muscles, the heart, and the kidneys are discussed. Mortality rates of vasodilatory (or distributive), for example septic shock, are high. The use of vasopressin is an alternative therapy for vasodilatory shock with better outcome. Vasopressin is effective in resuscitation of adults after ventricular fibrillation or pulseless tachycardia, when epinephrine is not effective.

Topics: Adult; Clinical Trials as Topic; Dilatation, Pathologic; Heart; Heart Arrest; Homeostasis; Humans; Intensive Care Units; Kidney; Muscle, Smooth, Vascular; Receptors, Vasopressin; Resuscitation; Shock; Shock, Septic; Survival Analysis; Tachycardia; Time Factors; Treatment Outcome; Vasoconstrictor Agents; Vasodilation; Vasopressins; Ventricular Fibrillation

To determine the rate of return of spontaneous circulation (ROSC) in animal models performing resuscitation from induced ventricular fibrillation (VF) in severe hypothermia (<30 degrees C).. A medical literature database search from 1966 to present was performed identifying placebo controlled trials using anti-arrhythmic or vasopressor medications to treat ventricular fibrillation in the setting of severe hypothermia.. 7 controlled studies were identified (n=117) testing 6 combinations of resuscitative medications. ROSC rates for treatment versus control groups were as follows: amiodarone (6% vs. 18%, p=0.6, n=34), bretylium (35% vs. 35%, p=1.0, n=40), intermediate- and high-dose epinephrine (adrenaline) (36% vs. 27%, p=1.0, n=22), vasopressin (60% vs. 0%, p<0.0001, n=39), vasopressin and amiodarone (0% vs. 0%, p=NS, n=11), low-dose epinephrine and amiodarone (91% vs. 30%, p=0.0075, n=21). Cumulatively, among all studies administering vasopressors, the rate of ROSC was 62% in treatment groups contrasted to 17% in control groups (p<0.0001, n=77).. In controlled animal models of severe hypothermia, ROSC rates for induced ventricular fibrillation are higher with utilization of vasopressor medications. Current guidelines which recommend withholding these medications in the setting of hypothermic cardiac arrest should be re-evaluated.

Topics: Animals; Anti-Arrhythmia Agents; Disease Models, Animal; Hypothermia; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

This article is a review of the most recent findings in resuscitation techniques in advanced cardiac life support. The article focuses particularly on the period after July 1, 2003, but relevant new findings before this period are also included.. Randomized clinical trial results suggest that the current cardiopulmonary resuscitation and advanced cardiac life support guidelines may need to be modified. Early defibrillation during the electrical phase of cardiac arrest remains the most crucial intervention, but performing cardiopulmonary resuscitation before defibrillation may be more effective, as compared with immediate defibrillation, during the circulatory phase of cardiac arrest. Biphasic waveforms are superior to monophasic damped sine waveforms in achieving defibrillation. Novel cardiopulmonary resuscitation methods that increase negative intrathoracic pressure promote an increase in blood flow return to the heart. These devices have been correlated with improved short-term survival rates during the circulatory phase of cardiac arrest. Vasopressin administration, given alone or in combination with epinephrine, should be considered during the circulatory phase of out-of-hospital cardiac arrest, particularly in patients presenting with asystole as the initial rhythm. Induction of hypothermia during the metabolic phase in cardiac arrest survivors improves 6-month survival rates and neurologic outcomes.. Strategies to improve the low survival outcomes of cardiac arrest victims are available. Clinical trials testing these strategies suggest benefit from certain interventions but are not definitive. These different therapeutic interventions should be performed in a phase-specific-oriented fashion according to the three-phase time-sensitive model of cardiac arrest.

Topics: Amiodarone; Anti-Arrhythmia Agents; Cardiopulmonary Resuscitation; Clinical Trials as Topic; Electric Countershock; Emergency Medical Services; Epinephrine; Heart Arrest; Humans; Hypothermia, Induced; Life Support Care; Practice Guidelines as Topic; Time Factors; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

The current guidelines for cardiopulmonary resuscitation recommend vasopressin as an alternative to epinephrine for the treatment of adult shock-refractory ventricular fibrillation. The objective of this study was to determine the effectiveness of vasopressin in the treatment of cardiac arrest.. We performed a systematic review and meta-analysis of 1519 patients with cardiac arrest from 5 randomized controlled trials that compared vasopressin and epinephrine. Two reviewers conducted a systematic search of electronic databases, complemented by hand searches, to identify randomized trials. Reviewers evaluated the quality of the trials, extracted data, and derived pooled estimates using a random-effects model.. There were no statistically significant differences between the vasopressin and epinephrine groups in failure of return of spontaneous circulation (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.58-1.12), death before hospital admission (RR, 0.72; 95% CI, 0.38-1.39), death within 24 hours (RR, 0.74; 95% CI, 0.38-1.43), death before hospital discharge (RR, 0.96; 95% CI, 0.87-1.05), or combination of number of deaths and neurologically impaired survivors (RR, 1.00; 95% CI, 0.94-1.07). Subgroup analysis based on initial cardiac rhythm showed no statistically significant difference in the rate of death before hospital discharge between the vasopressin and epinephrine groups in any of the 3 subgroups: ventricular fibrillation or ventricular tachycardia (RR, 0.97; 95% CI, 0.79-1.19), pulseless electrical activity (RR, 1.02; 95% CI, 0.95-1.10), or asystole (RR, 0.97; 95% CI, 0.94-1.00).. There is no clear advantage of vasopressin over epinephrine in the treatment of cardiac arrest. Guidelines for Advanced Cardiac Life Support should not recommend vasopressin in resuscitation protocols until more solid human data on its superiority are available.

Topics: Bias; Confidence Intervals; Heart Arrest; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Shock-resistant ventricular fibrillation is defined as ventricular fibrillation persisting after three defibrillation attempts. In approximately 10 to 25% of all cardiac arrests, shock-resistant ventricular fibrillation develops, and 87 to 98% of these patients die.. In the treatment of shock-resistant ventricular fibrillation, defibrillation using biphasic waveforms is considered as an intervention of choice. Intravenous amiodarone is also acceptable, safe, and useful, based on evidence from two randomized clinical trials. Intravenous vasopressin is acceptable and probably safe and useful, but the evidence supporting this recommendation is coming from a small, randomized clinical trial. Procainamide is acceptable but not recommended. In the presence of acute myocardial infarction and recurrent ventricular fibrillation, if all other therapies fail, beta-blockers can be considered. Magnesium, lidocaine, and bretylium are not recommended in the treatment of shock-resistant ventricular fibrillation.. Biphasic defibrillation and intravenous amiodarone are useful in shock-resistant ventricular fibrillation.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Bretylium Compounds; Cardiopulmonary Resuscitation; Electric Countershock; Heart Arrest; Hemodynamics; Humans; Lidocaine; Magnesium; Procainamide; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

The chain of survival concept implies that provision of early access, early advanced care, including early intravenous drugs would improve survival in sudden cardiac arrest. Intravenous adrenaline (epinephrine) has been used as the drug of choice since 1906. What is the evidence for its effectiveness? Is vasopressin a better alternative?. We performed a systematic literature search in order to answer these questions. Evidence from the clinical trials that have been conducted on this subject was reviewed.. Experimental evidence confirms the beneficial effect adrenaline has on coronary perfusion pressure. However, adrenaline has not been shown conclusively to improve survival in clinical trials. Extensive trials have also failed to show any benefit of high-dose adrenaline over standard doses. Vasopressin seems to be more effective than adrenaline in animal studies for treatment of cardiac arrest due to resistant ventricular fibrillation. However, it has yet to be proven to be superior to adrenaline in clinical trials.. More research is needed into this area, especially randomised controlled trials studying the effectiveness of vasopressin. Meanwhile, in order to improve survival from sudden cardiac arrest, continuing effort should be made to achieve early initiation of cardiopulmonary resuscitation, early defibrillation and early advanced care.

Topics: Critical Care; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Administration Schedule; Epinephrine; Female; Heart Arrest; Humans; Infusions, Intravenous; Male; Probability; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome; Vasopressins; Ventricular Fibrillation

Topics: Advanced Cardiac Life Support; Anti-Arrhythmia Agents; Humans; Practice Guidelines as Topic; Tachycardia, Ventricular; Takayasu Arteritis; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Advanced Cardiac Life Support; Algorithms; Anti-Arrhythmia Agents; Bicarbonates; Bradycardia; Calcium Channel Blockers; Cardiac Pacing, Artificial; Cardiotonic Agents; Dobutamine; Dopamine; Electric Countershock; Electrocardiography; Epinephrine; Heart Arrest; Humans; Injections, Intravenous; Isoproterenol; Sympathomimetics; Tachycardia; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation; Verapamil

Topics: Amines; Anesthesia; Animals; Arrhythmias, Cardiac; Blood Pressure; Blood Vessels; Catecholamines; Coronary Vessels; Dogs; Electrocardiography; Epinephrine; Halothane; Heart Rate; Humans; Injections, Intravenous; Models, Structural; Regional Blood Flow; Sympathomimetics; Time Factors; Vasoconstrictor Agents; Vasomotor System; Vasopressins; Ventricular Fibrillation

Introduction The American Heart Association (AHA; Dallas, Texas USA) and European Resuscitation Council (Niel, Belgium) cardiac arrest (CA) guidelines recommend the intraosseous (IO) route when intravenous (IV) access cannot be obtained. Vasopressin has been used as an alternative to epinephrine to treat ventricular fibrillation (VF). Hypothesis/Problem Limited data exist on the pharmacokinetics and resuscitative effects of vasopressin administered by the humeral IO (HIO) route for treatment of VF. The purpose of this study was to evaluate the effects of HIO and IV vasopressin, on the occurrence, odds, and time of return of spontaneous circulation (ROSC) and pharmacokinetic measures in a swine model of VF.. Twenty-seven Yorkshire-cross swine (60 to 80 kg) were assigned randomly to three groups: HIO (n=9), IV (n=9), and a control group (n=9). Ventricular fibrillation was induced and untreated for two minutes. Chest compressions began at two minutes post-arrest and vasopressin (40 U) administered at four minutes post-arrest. Serial blood specimens were collected for four minutes, then the swine were resuscitated until ROSC or 29 post-arrest minutes elapsed.. Fisher's Exact test determined ROSC was significantly higher in the HIO 5/7 (71.5%) and IV 8/11 (72.7%) groups compared to the control 0/9 (0.0%; P=.001). Odds ratios of ROSC indicated no significant difference between the treatment groups (P=.68) but significant differences between the HIO and control, and the IV and control groups (P=.03 and .01, respectively). Analysis of Variance (ANOVA) indicated the mean time to ROSC for HIO and IV was 621.20 seconds (SD=204.21 seconds) and 554.50 seconds (SD=213.96 seconds), respectively, with no significant difference between the groups (U=11; P=.22). Multivariate Analysis of Variance (MANOVA) revealed the maximum plasma concentration (Cmax) and time to maximum concentration (Tmax) of vasopressin in the HIO and IV groups was 71753.9 pg/mL (SD=26744.58 pg/mL) and 61853.7 pg/mL (SD=22745.04 pg/mL); 111.42 seconds (SD=51.3 seconds) and 114.55 seconds (SD=55.02 seconds), respectively. Repeated measures ANOVA indicated no significant difference in plasma vasopressin concentrations between the treatment groups over four minutes (P=.48).. The HIO route delivered vasopressin effectively in a swine model of VF. Occurrence, time, and odds of ROSC, as well as pharmacokinetic measurements of HIO vasopressin, were comparable to IV. Burgert JM , Johnson AD , Garcia-Blanco J , Fulton LV , Loughren MJ . The resuscitative and pharmacokinetic effects of humeral intraosseous vasopressin in a swine model of ventricular fibrillation. Prehosp Disaster Med. 2017;32(3):305-310.

Topics: Animals; Cardiopulmonary Resuscitation; Disease Models, Animal; Drug Administration Schedule; Infusions, Intraosseous; Infusions, Intravenous; Male; Swine; Treatment Outcome; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Topics: Cardiopulmonary Resuscitation; Double-Blind Method; Drug Therapy, Combination; Epinephrine; Heart Arrest; Humans; Vasopressins; Ventricular Fibrillation

Vasopressin is an alternative to epinephrine for vasopressor therapy during cardiopulmonary resuscitation, but clinical experience with this treatment has been limited.. We randomly assigned adults who had had an out-of-hospital cardiac arrest to receive two injections of either 40 IU of vasopressin or 1 mg of epinephrine, followed by additional treatment with epinephrine if needed. The primary end point was survival to hospital admission, and the secondary end point was survival to hospital discharge.. A total of 1219 patients underwent randomization; 33 were excluded because of missing study-drug codes. Among the remaining 1186 patients, 589 were assigned to receive vasopressin and 597 to receive epinephrine. The two treatment groups had similar clinical profiles. There were no significant differences in the rates of hospital admission between the vasopressin group and the epinephrine group either among patients with ventricular fibrillation (46.2 percent vs. 43.0 percent, P=0.48) or among those with pulseless electrical activity (33.7 percent vs. 30.5 percent, P=0.65). Among patients with asystole, however, vasopressin use was associated with significantly higher rates of hospital admission (29.0 percent, vs. 20.3 percent in the epinephrine group; P=0.02) and hospital discharge (4.7 percent vs. 1.5 percent, P=0.04). Among 732 patients in whom spontaneous circulation was not restored with the two injections of the study drug, additional treatment with epinephrine resulted in significant improvement in the rates of survival to hospital admission and hospital discharge in the vasopressin group, but not in the epinephrine group (hospital admission rate, 25.7 percent vs. 16.4 percent; P=0.002; hospital discharge rate, 6.2 percent vs. 1.7 percent; P=0.002). Cerebral performance was similar in the two groups.. The effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine may be more effective than epinephrine alone in the treatment of refractory cardiac arrest.

Topics: Aged; Cardiopulmonary Resuscitation; Drug Therapy, Combination; Emergency Medical Services; Epinephrine; Female; Heart Arrest; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Survival Rate; Sympathomimetics; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Studies in animals have suggested that intravenous vasopressin is associated with better vital-organ perfusion and resuscitation rates than is epinephrine in the treatment of cardiac arrest. We did a randomised comparison of vasopressin with epinephrine in patients with ventricular fibrillation in out-of-hospital cardiac arrest.. 40 patients in ventricular fibrillation resistant to electrical defibrillation were prospectively and randomly assigned epinephrine (1 mg intravenously; n = 20) or vasopressin (40 U intravenously; n = 20) as primary drug therapy for cardiac arrest. The endpoints of this double blind study were successful resuscitation (hospital admission), survival for 24 h, survival to hospital discharge and neurological outcome (Glasgow coma scale). Analyses were by intention to treat.. Seven (35%) patients in the epinephrine group and 14 (70%) in the vasopressin group survived to hospital admission (p = 0.06). At 24 h, four (20%) epinephrine-treated patients and 12 (60%) vasopressin-treated patients were alive (p = 0.02). Three (15%) patients in the epinephrine group and eight (40%) in the vasopressin group survived to hospital discharge (p = 0.16). Neurological outcomes were similar (mean Glasgow coma score at hospital discharge 10.7 [SE 3.8] vs 11.7 [1.6], p = 0.78).. In this preliminary study, a significantly larger proportion of patients created with vasopressin than of those treated with epinephrine were resuscitated successfully from out-of-hospital ventricular fibrillation and survived for 24 h. Based upon these findings, larger multicentre studies of vasopressin in the treatment of cardiac arrest are needed.

Topics: Aged; Double-Blind Method; Electric Countershock; Emergency Medical Services; Epinephrine; Female; Heart Arrest; Humans; Male; Middle Aged; Prospective Studies; Resuscitation; Vasopressins; Ventricular Fibrillation

Compare vasopressin, amiodarone, and epinephrine administration by sternal intraosseous (SIO), tibial intraosseous (TIO), and intravenous (IV) routes in a swine model of cardiac arrest.. Prospective, randomized, between subjects, experimental design.. Laboratory.. Male Yorkshire-cross swine (N = 35), seven per group.. Swine were randomized to SIO, TIO, IV, cardiopulmonary resuscitation (CPR) with defibrillation, or CPR-only groups. Ventricular fibrillation (VF) was induced under general anesthesia. Mechanical CPR began 2 minutes postarrest. Vasopressin (40 U) was administered to the SIO, TIO, and IV groups 4 minutes postarrest. Defibrillation was performed and amiodarone (300 mg) was administered 6 minutes postarrest. Defibrillation was repeated, and epinephrine (1 mg) was administered 10 minutes postarrest. Defibrillation was repeated every 2 minutes and epinephrine repeated every 4 minutes until return of spontaneous circulation (ROSC) or 26 postarrest minutes elapsed.. Rate of ROSC, time to ROSC, and odds of ROSC.. There were no significant differences in rate of ROSC between the SIO and TIO (p = 0.22) or IV groups (p = 1.0). Time to ROSC was five times less in the SIO group than the TIO group (p = 0.003) but not compared to IV (p = 0.125). Time to ROSC in the IV group was significantly less than the TIO group (p = 0.04). Odds of ROSC for the SIO group were five times higher compared to the TIO group but same as IV. Odds of ROSC in the IV group were higher than the TIO group.. There was a statistically significant delay in the time to ROSC and a clinically significant difference in odds of ROSC when resuscitative drugs, including lipophilic amiodarone, were administered by the TIO route compared to the SIO and IV routes in a swine model of sudden cardiac arrest. Further investigations are warranted to isolate the mechanism behind these findings.

Topics: Administration, Intravenous; Amiodarone; Animals; Anti-Arrhythmia Agents; Cardiopulmonary Resuscitation; Disease Models, Animal; Electric Countershock; Epinephrine; Heart Arrest; Infusions, Intraosseous; Male; Prospective Studies; Random Allocation; Sternum; Sus scrofa; Swine; Tibia; Time Factors; Treatment Outcome; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Adrenaline (ADR) and vasopressin (VAS) are used as vasopressors during cardiopulmonary resuscitation. Data regarding their effects on blood-brain barrier (BBB) integrity and neuronal damage are lacking. We hypothesised that VAS given during cardiopulmonary resuscitation (CPR) after haemorrhagic circulatory arrest will preserve BBB integrity better than ADR.. Twenty-one anaesthetised sexually immature male piglets (with a weight of 24.3 ± 1.3 kg) were bled 35% via femoral artery to a mean arterial blood pressure of 25 mmHg in the period of 15 min. Afterwards, the piglets were subjected to 8 min of untreated ventricular fibrillation followed by 15 min of open-chest CPR. At 9 min of circulatory arrest, piglets received amiodarone 1.0 mg/kg and hypertonic-hyperoncotic solution 4 ml/kg infusions for 20 min. At the same time, VAS 0.4 U/kg was given intravenously to the VAS group (n = 9) while the ADR group received ADR 20 μg/kg (n = 12). Internal defibrillation was attempted from 11 min of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 h after resuscitation.. The intracranial pressure (ICP) in the post-resuscitation phase was significantly greater in ADR group than in VAS group. VAS group piglets exhibited a significantly smaller BBB disruption compared with ADR group. Cerebral pressure reactivity index showed that cerebral blood flow autoregulation was also better preserved in VAS group.. Resuscitation with ADR as compared with VAS after haemorrhagic circulatory arrest increased the ICP and impaired cerebrovascular autoregulation more profoundly, as well as exerted an increased BBB disruption though no significant difference in neuronal injury was observed.

Topics: Amiodarone; Animals; Blood-Brain Barrier; Capillary Permeability; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Dobutamine; Electric Countershock; Enzyme Activation; Epinephrine; Fluid Therapy; Heart Arrest; Hemodynamics; Hemorrhage; Intracranial Pressure; Male; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Sus scrofa; Swine; Vasopressins; Ventricular Fibrillation

Supplemental digital content is available in the text.. The aim of this experimental study was to compare survival and hemodynamic effects of a low-dose amiodarone and vasopressin compared with vasopressin in hypovolemic cardiac arrest model in piglets.. Eighteen anesthetized male piglets (with a weight of 25.3 [1.8] kg) were bled approximately 30% of the total blood volume via the femoral artery to a mean arterial blood pressure of 35 mm Hg in a 15-minute period. Afterward, the piglets were subjected to 4 minutes of untreated ventricular fibrillation followed by 11 minutes of open-chest cardiopulmonary resuscitation. At 5 minutes, circulatory arrest amiodarone 1 mg/kg was intravenously administered in the amiodarone group (n = 9), while the control group received the same amount of saline (n = 9). At the same time, all piglets received vasopressin 0.4 U/kg intravenously administered and hypertonic-hyperoncotic solution 3-mL/kg infusion for 20 minutes. Internal defibrillation was attempted from 7 minutes of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 hours after resuscitation.. Three-hour survival was greater in the amiodarone group (p = 0.02). After the successful resuscitation, the amiodarone group piglets had significantly lower heart rate as well as greater systolic, diastolic, and mean arterial pressure. Troponin I plasma concentrations were lower and urine output was greater in the amiodarone group.. Combined resuscitation with amiodarone and vasopressin after hemorrhagic circulatory arrest resulted in greater 3-hour survival, better preserved hemodynamic parameters, and smaller myocardial injury compared with resuscitation with vasopressin only.

Topics: Amiodarone; Animals; Antidiuretic Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Heart Arrest; Hemodynamics; Hemorrhage; Injections, Intravenous; Male; Resuscitation; Swine; Treatment Outcome; Vasodilator Agents; Vasopressins; Ventricular Fibrillation

The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified.. To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC).. A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC.. Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p < 0.001). Vasopressin effect remained at 15-20 mmHg after three doses versus zero with adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019).. The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate.

Topics: Animals; Cardiopulmonary Resuscitation; Disease Models, Animal; Double-Blind Method; Drug Evaluation, Preclinical; Epinephrine; Heart Arrest; Prospective Studies; Random Allocation; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Local anesthetic (LA) intoxication with cardiovascular arrest is a potential fatal complication of regional anesthesia. Lipid resuscitation has been recommended for the treatment of LA-induced cardiac arrest. Aim of the study was to compare four different rescue regimens using epinephrine and/or lipid emulsion and vasopressin to treat cardiac arrest caused by bupivacaine intoxication.. Twenty-eight piglets were randomized into four groups (4 × 7), anesthetized with sevoflurane, intubated, and ventilated. Bupivacaine was infused with a syringe driver via central venous catheter at a rate of 1 mg·kg(-1)·min(-1) until circulatory arrest. Bupivacaine infusion and sevoflurane were then stopped, chest compression was started, and the pigs were ventilated with 100% oxygen. After 1 min, epinephrine 10 μg·kg(-1) (group 1), Intralipid(®) 20% 4 ml·kg(-1) (group 2), epinephrine 10 μg·kg(-1) + Intralipid(®) 4 ml·kg(-1) (group 3) or 2 IU vasopressin + Intralipid(®) 4 ml·kg(-1) (group 4) were administered. Secondary epinephrine doses were given after 5 min if required.. Survival was 71%, 29%, 86%, and 57% in groups 1, 2, 3, and 4. Return of spontaneous circulation was regained only by initial administration of epinephrine alone or in combination with Intralipid(®). Piglets receiving the combination therapy survived without further epinephrine support. In contrast, in groups 2 and 4, return of spontaneous circulation was only achieved after secondary epinephrine rescue.. In cardiac arrest caused by bupivacaine intoxication, first-line rescue with epinephrine and epinephrine + Intralipid(®) was more effective with regard to survival than Intralipid(®) alone and vasopressin + Intralipid(®) in this pig model.

Topics: Anesthetics, Local; Animals; Blood Gas Analysis; Blood Pressure; Bupivacaine; Cardiopulmonary Resuscitation; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Electrocardiography; Emulsions; Epinephrine; Female; Heart Arrest; Male; Mass Spectrometry; Phospholipids; Soybean Oil; Survival Analysis; Swine; Tachycardia, Ventricular; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Coronary perfusion pressure (CPP) during resuscitation from cardiac arrest has been shown to correlate with return of spontaneous circulation. Adrenergic blockade of beta-1 and alpha-1 receptors is common in the long-term management of ischemic heart disease and congestive heart failure. We sought to compare the CPP response to vasopressin vs. epinephrine in a swine model of cardiac arrest following pre-arrest adrenergic blockade.. Eight anesthetized and instrumented swine were administered 0.1mg epinephrine and arterial pressure and heart rate response were measured. An infusion of labetalol was then initiated and animals periodically challenged with epinephrine until adrenergic blockade was confirmed. The left anterior descending coronary artery was occluded to produce ventricular fibrillation (VF). After 7min of untreated VF, mechanical chest compressions were initiated. After 1min of compressions, 1mg epinephrine was given while CPP was recorded. When CPP values had returned to pre-epinephrine levels, 40U of bolus vasopressin was given. Differences in CPP (post-vasopressor-pre-vasopressor) were compared within animals for the epinephrine and vasopressin response and with eight, non-adrenergically blocked, historical controls using Bayesian statistics with a non-informative prior.. The CPP response following epinephrine was 15.1mmHg lower in adrenergically blocked animals compared to non-adrenergically blocked animals (95% Highest Posterior Density [HPD] 2.9-27.2mmHg lower). CPP went up 18.4mmHg more following vasopressin when compared to epinephrine (95% HPD 8.2-29.1mmHg). The posterior probability of a higher CPP response from vasopressin (vs. epinephrine) in these animals was 0.999.. Pre-arrest adrenergic blockade blunts the CPP response to epinephrine. Superior augmentation of CPP is attained with vasopressin under these conditions.

Topics: Adrenergic Antagonists; Animals; Blood Pressure; Coronary Circulation; Disease Models, Animal; Epinephrine; Heart Arrest; Heart Rate; Male; Swine; Vasopressins; Ventricular Fibrillation

No single drug improves survival after cardiac arrest, despite success in animal studies. We sought to determine the duration of circulatory arrest after which maximal drug treatment and a rescue shock would fail to achieve return of spontaneous circulation (ROSC).. Retrospective analysis of 271 swine (20-30 kg) resuscitation attempts during ventricular fibrillation. Protocols were divided into five categories: immediate countershock, cardiopulmonary resuscitation (CPR) with standard-dose drugs, CPR alone, CPR and high-dose epinephrine (CPR+HDE) (0.1 mg/kg), and CPR with a drug cocktail (CPR+DC) of propanolol (1 mg), epinephrine (adrenaline) (0.1 mg/kg) and vasopressin (40IU). Time to first CPR, time to first drug administration, time to first shock, and protocol were examined as predictors of ROSC using logistic regression with Hosmer-Lemeshow test of fit. Probability of ROSC was calculated from logistic curves.. ROSC occurred in 119 of the 271 swine (44%). Time to first drug and the CPR+DC group were predictors of ROSC. Time to first CPR, the CPR+DC group, and the CPR+HDE group were also predictors of ROSC. Time to first rescue shock, the CPR+DC group, and the CPR+HDE groups were predictors of ROSC. In the CPR+DC group, 50% ROSC occurred at a first CPR time of 13.4 min, first drug time of 14.1 min and first rescue shock time of 17.5 min.. Pre-shock delivery of CPR+DC increases the likelihood of ROSC, and reaches 50% with a time of drug delivery of 14.1 min. ROSC rates of 50% may be achievable using an optimized resuscitation in experimental CPR.

Topics: Animals; Cardiopulmonary Resuscitation; Coronary Circulation; Drug Combinations; Electric Countershock; Epinephrine; Female; Heart Arrest, Induced; Male; Models, Animal; Propranolol; Recovery of Function; Retrospective Studies; Swine; Time Factors; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Synergistic effects of adrenaline (epinephrine) and vasopressin may be beneficial during cardiopulmonary resuscitation. However, it is unknown whether either adrenaline alone or an alternating administration of adrenaline and vasopressin is better for restoring vital organ perfusion following basic life support (BLS) according to the revised algorithm with a compression-to-ventilation (c/v) ratio of 30:2.. After 4min of ventricular fibrillation, and 6min of BLS with a c/v ratio of 30:2, 16 pigs were randomised to receive either 45microg/kg adrenaline, or alternating 45microg/kg adrenaline and 0.4U/kg vasopressin, respectively.. Coronary perfusion pressure (mean+/-S.D.) 20 and 25min after cardiac arrest was 7+/-4 and 5+/-3mm Hg after adrenaline, and 25+/-2 and 14+/-3mm Hg after adrenaline/vasopressin (p<0.001 and <0.01 versus adrenaline), respectively. Cerebral perfusion pressure was 23+/-7 and 19+/-9mm Hg after adrenaline, and 40+/-10 and 33+/-7mm Hg after adrenaline/vasopressin (p<0.001 and <0.01 versus adrenaline), and cerebral blood flow was 30+/-10 and 27+/-11% of baseline after adrenaline, and 65+/-40 and 50+/-31% of baseline after adrenaline/vasopressin (p<0.05 versus adrenaline), respectively. Return of spontaneous circulation (ROSC) did not differ significantly between the adrenaline group (0/8) and the adrenaline/vasopressin group (3/8).. Adrenaline/vasopressin resulted in higher coronary and cerebral perfusion pressures, and cerebral blood flow, while ROSC was comparable.

Topics: Animals; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Coronary Circulation; Disease Models, Animal; Drug Therapy, Combination; Epinephrine; Female; Heart Arrest; Male; Practice Guidelines as Topic; Random Allocation; Swine; Treatment Outcome; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

An increasing body of evidence from laboratory and clinical studies suggests that vasopressin may represent a promising alternative vasopressor for use during cardiac arrest and resuscitation. Current guidelines for cardiopulmonary resuscitation recommend the use of adrenaline (epinephrine), with vasopressin considered only as a secondary option because of limited clinical data.. The present study was conducted in a prehospital setting and included patients with ventricular fibrillation or pulseless ventricular tachycardia undergoing one of three treatments: group I patients received only adrenaline 1 mg every 3 minutes; group II patients received one intravenous dose of arginine vasopressin (40 IU) after three doses of 1 mg epinephrine; and patients in group III received vasopressin 40 IU as first-line therapy. The cause of cardiac arrest (myocardial infarction or other cause) was established for each patient in hospital.. A total of 109 patients who suffered nontraumatic cardiac arrest were included in the study. The rates of restoration of spontaneous circulation and subsequent hospital admission were higher in vasopressin-treated groups (23/53 [45%] in group I, 19/31 [61%] in group II and 17/27 [63%] in group III). There were also higher 24-hour survival rates among vasopressin-treated patients (P < 0.05), and more vasopressin-treated patients were discharged from hospital (10/51 [20%] in group I, 8/31 [26%] in group II and 7/27 [26%] group III; P = 0.21). Especially in the subgroup of patients with myocardial infarction as the underlying cause of cardiac arrest, the hospital discharge rate was significantly higher in vasopressin-treated patients (P < 0.05). Among patients who were discharged from hospital, we found no significant differences in neurological status between groups.. The greater 24-hour survival rate in vasopressin-treated patients suggests that consideration of combined vasopressin and adrenaline is warranted for the treatment of refractory ventricular fibrillation or pulseless ventricular tachycardia. This is especially the case for those patients with myocardial infarction, for whom vasopressin treatment is also associated with a higher hospital discharge rate.

Topics: Adult; Aged; Ambulatory Care; Cardiopulmonary Resuscitation; Cohort Studies; Female; Heart Arrest; Humans; Male; Middle Aged; Prospective Studies; Survival Rate; Tachycardia, Ventricular; Treatment Outcome; Vasopressins; Ventricular Fibrillation

Elevated coronary perfusion pressure (CPP) during CPR is associated with return of spontaneous circulation (ROSC). We compared CPP achieved with three methods of chest compression: manual (MAN), mechanical (MECH) and high-impulse mechanical (HI) in a porcine model of prolonged ventricular fibrillation (VF). We hypothesized that HI (very rapid acceleration of the down-stroke) would produce greater CPPs than MAN or MECH, and that HI would also produce a higher rate of ROSC.. Twenty-eight domestic swine (mean 27.8 kg) were randomly assigned to three methods of chest compression. Animals were instrumented under anesthesia, and VF was induced and untreated for 8 min. After 2 min of CPR, epinephrine (adrenaline) (0. 1 mg/kg), vasopressin (40 U) and propranolol (1.0 mg) were administered. CPR continued for three more minutes, after which up to three rescue shocks were delivered. CPP was determined in an automated fashion by measuring the difference between aortic and right atrial pressures 0.1s prior to the down-stroke of each compression (i.e. end-relaxation). ROSC was defined as a systolic pressure greater than 80 mmHg sustained for at least 1 min. We analyzed CPP and ROSC using repeated measures ANOVA and Fisher's exact test.. Over the 5 min of CPR, CPP increased more with HI compression than with MAN compression (p=0.017). ROSC was attained in 4/9 MAN, 6/9 MECH and 10/10 HI (HI versus MAN p=0.01).. Over the course of CPR, HI compression increased CPP more than MAN compression. HI compression produced a significantly higher rate of ROSC than MAN, but not MECH compression.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Antagonists; Animals; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Coronary Circulation; Disease Models, Animal; Epinephrine; Perfusion; Pressure; Propranolol; Random Allocation; Reference Values; Regional Blood Flow; Sus scrofa; Thoracic Wall; Time Factors; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Direct measurement of brain tissue oxygenation (PbtO2) is established during spontaneous circulation, but values of PbtO2 during and after cardiopulmonary resuscitation (CPR) are unknown. The purpose of this study was to investigate: (1) the time-course of PbtO2 in an established model of CPR, and (2) the changes of cerebral venous lactate and S-100B.. In 12 pigs (12-16 weeks, 35-45 kg), ventricular fibrillation (VF) was induced electrically during general anaesthesia. After 4 min of untreated VF, all animals were subjected to CPR (chest compression rate 100/min, FiO2 1.0) with vasopressor therapy after 7, 12, and 17 min (vasopressin 0.4, 0.4, and 0.8 U/kg, respectively). Defibrillation was performed after 22 min of cardiac arrest. After return of spontaneous circulation (ROSC), the pigs were observed for 1h.. After initiation of VF, PbtO2 decreased compared to baseline (mean +/- SEM; 22 +/- 6 versus 2 +/- 1 mmHg after 4 min of VF; P < 0.05). During CPR, PbtO2 increased, and reached maximum values 8 min after start of CPR (25 +/- 7 mmHg; P < 0.05 versus no-flow). No further changes were seen until ROSC. Lactate, and S-100B increased during CPR compared to baseline (16 +/- 2 versus 85 +/- 8 mg/dl, and 0.46 +/- 0.05 versus 2.12 +/- 0.40 microg/l after 13 min of CPR, respectively; P < 0.001); lactate remained elevated, while S-100B returned to baseline after ROSC.. Though PbtO2 returned to pre-arrest values during CPR, PbtO2 and cerebral lactate were lower than during post-arrest reperfusion with 100% oxygen, which reflected the cerebral low-flow state during CPR. The transient increase of S-100B may indicate a disturbance of the blood-brain-barrier.

Topics: Animals; Brain; Brain Chemistry; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Disease Models, Animal; Electric Countershock; Female; Heart Arrest; Lactates; Male; Oxygen; Swine; Vasopressins; Ventricular Fibrillation

Survival after prolonged cardiopulmonary resuscitation (CPR) is often associated with neurological and other sequelae. We describe a patient who survived prolonged cardiac arrest due to ventricular fibrillation neurologically intact but suffered colon ischaemia and necrosis in the post-resuscitation period. Subtotal colectomy was performed. We wonder whether this complication was related to the use of vasopressin.

Topics: Adrenergic Agonists; Adult; Amiodarone; Anti-Arrhythmia Agents; Cardiopulmonary Resuscitation; Colectomy; Colon; Electric Countershock; Epinephrine; Female; Heart Arrest; Humans; Ischemia; Necrosis; Time Factors; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

The efficacy of vasopressor therapy during closed-chest resuscitation is limited and decreases over time. We previously reported that sodium-hydrogen exchanger isoform-1 inhibition during ventricular fibrillation (VF) using cariporide ameliorates ischemic contracture and enhances the efficacy of chest compression. We currently investigated whether cariporide could potentiate pressor responses to epinephrine and vasopressin.. VF was induced and left untreated for 12 min in two series of 16 rats each. Chest compression was then started and the depth adjusted within the initial 2 min to attain an aortic diastolic pressure between 26 and 28 mm Hg. In one series, rats received boluses of epinephrine (150 microg/kg); in the other series, rats received boluses of vasopressin (0.8 U/kg) to maintain the aortic diastolic pressure > 25 mm Hg. Within each series, rats were randomized to receive a 3 mg/kg bolus of cariporide or 0.9% NaCl immediately before starting chest compression. Defibrillation was attempted at 20 min of VF (8 min of chest compression).. Cariporide prompted higher and more sustained coronary perfusion pressures in both the epinephrine group (37 +/- 5 mm Hg vs 29 +/- 7 mm Hg, p < 0.05) and the vasopressin group (36 +/- 5 mm Hg vs 28 +/- 6 mm Hg +/- SD, p < 0.02) even though fewer additional vasopressor doses were required. After resuscitation, cariporide-treated rats had less ventricular ectopic activity, better hemodynamic function, and improved survival scores. In separate experiments, in situ perfusion of the aorta excluded a vascular-mediated effect of cariporide.. Cariporide enhanced the hemodynamic efficacy of vasopressor agents and improved resuscitation outcomes probably as a result of enhanced forward blood flow without effect on the peripheral vasculature.

Topics: Animals; Anti-Arrhythmia Agents; Drug Synergism; Epinephrine; Guanidines; Male; Rats; Rats, Sprague-Dawley; Resuscitation; Sulfones; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Topics: Cardiopulmonary Resuscitation; Epinephrine; Heart Arrest; Humans; Sympathomimetics; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

To evaluate the effects of a bolus dose of vasopressin compared to continuous adrenaline (epinephrine) infusion on vital organ blood flow during cardiopulmonary resuscitation (CPR).. Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. After 2 min of CPR the animals were randomly assigned to receive either vasopressin (0.4 U/kg) or adrenaline (bolus of 20 microg/kg followed by continuous infusion of 10 microg/(kg min)). Defibrillation was attempted after 9 min of CPR.. Vasopressin generated higher cortical cerebral blood flow (P < 0.001) and lower cerebral oxygen extraction (P < 0.001) during CPR compared to continuous adrenaline. Coronary perfusion pressure during CPR was higher in vasopressin-treated pigs (P < 0.001) and successful resuscitation was achieved in 12/12 in the vasopressin group versus 5/12 in the adrenaline group (P = 0.005).. In this experimental model, vasopressin caused a greater increase in cortical cerebral blood flow and lower cerebral oxygen extraction during CPR compared to continuous adrenaline. Furthermore, vasopressin generated higher coronary perfusion pressure and increased the likelihood of restoring spontaneous circulation.

Topics: Animals; Brain; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Electrocardiography; Epinephrine; Hemodynamics; Oxygen Consumption; Swine; Vasopressins; Ventricular Fibrillation

We showed previously that whole body periodic acceleration along the spinal axis (pGz) is a novel method of cardiopulmonary resuscitation (CPR). The ultimate assessment of the value of any CPR technique is the neurological outcome after using such a technique. In this study, we determined the neurological outcome in pigs after prolonged pGz-CPR, with administration of vasopressin immediately prior to defibrillation. Neurological outcome after pGz-CPR was compared to a control group where no intervention occurred for the same time period (C-NoInterv).. Ventricular Fibrillation (VFIB) was induced in 12 animals. After a 3 min non-interventional interval, the animals received either pGz-CPR (n=7), or C-NoInterv (n=5) for 15 min. After 18 min of VFIB, a single dose of vasopressin (0.8 U/kg) was administered along with sodium bicarbonate and bretylium, and defibrillation was attempted. All animals in the pGz-CPR group had return of spontaneous circulation (ROSC) and normal neurological assessment at 24 h. Neurologic outcome remained normal at 48 h. In contrast, none of the animals in the C-NoInterv had ROSC.. Prolonged pGz-CPR, with administration of vasopressin immediately prior to defibrillation results in normal neurological outcomes at 24 h.

Topics: Acceleration; Animals; Cardiac Output; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Electric Countershock; Female; Male; Neurologic Examination; Probability; Random Allocation; Reference Values; Refractory Period, Electrophysiological; Statistics, Nonparametric; Survival Rate; Swine; Treatment Outcome; Vasopressins; Ventricular Fibrillation

Despite the important role of the adrenal gland during cardiac arrest, little is known about changes in the adrenal medullary or cortical blood flow in this setting. This study was designed to assess regional adrenal gland perfusion in the medulla and cortex during cardiopulmonary resuscitation (CPR), and after administration of adrenaline (epinephrine) versus vasopressin versus saline placebo.. After 4 min of untreated ventricular fibrillation, and 3 min of basic life support CPR, 19 animals were randomly assigned to receive either vasopressin (0.4 U/kg; n=7), adrenaline (45 microg/kg; n=6) or saline placebo (n=6), respectively. Haemodynamic variables, adrenal, and renal blood flow were measured after 90 s of CPR, and 90 s and 5 min after drug administration.. All values are given as mean+/-S.E.M. Blood flow in the adrenal medulla was significantly higher 90 s after adrenaline when compared with saline placebo in the right adrenal medulla (210+/-14 vs. 102+/-5 ml/min per 100 mg), and in the left adrenal medulla (218+/-14 vs. 96+/-3 ml/min per 100 mg). Blood flow in the adrenal medulla was significantly higher 90 s and 5 min after vasopressin when compared with adrenaline in the right (326+/-22 mg vs. 210+/-14 ml/min per 100 mg, and 297+/-17 vs. 103+/-5 ml/min per 100 mg), and in the left medulla (333+/-25 vs. 218+/-14 ml/min per 100 mg, and 295+/-14 vs. 111+/-7 ml/min per 100 mg). Ninety seconds and five minutes after vasopressin, and 90 s after adrenaline, adrenal cortex blood flow was significantly higher when compared with saline placebo. After 12 min of cardiac arrest, including 8 min of CPR, seven of seven pigs in the vasopressin group, one of six pigs in the adrenaline group, but none of six placebo were successfully defibrillated.. Both vasopressin and adrenaline produced significantly higher medullary and cortical adrenal gland perfusion during CPR than did a saline placebo; but vasopressin resulted in significantly higher medullary adrenal gland blood flow when compared with adrenaline.

Topics: Adrenal Glands; Analysis of Variance; Animals; Cardiopulmonary Resuscitation; Disease Models, Animal; Epinephrine; Female; Hemodynamics; Male; Probability; Random Allocation; Reference Values; Regional Blood Flow; Sensitivity and Specificity; Swine; Vasopressins; Ventricular Fibrillation

The objective of this research was to compare the effects of an alpha- and beta-adrenergic agonist, epinephrine, a selective alpha(2)-adrenergic agonist, alpha-methylnorepinephrine (alpha-MNE), and a non-adrenergic vasopressin on post-resuscitation myocardial function and duration of survival. Epinephrine continues to be the primary adrenergic agent for advanced cardiac life support. However, its major inotropic actions and especially its beta-adrenergic and, to a lesser extent, its alpha(1)-actions increase the severity of global ischemia during cardiac arrest and adversely affect post-resuscitation myocardial function and survival. We had previously observed significantly better outcomes with a selective alpha(2)-adrenergic agonist when compared with epinephrine. Non-adrenergic vasopressin also has promise of more favorable actions. The present study was, therefore, undertaken to compare a selective alpha(2)-adrenergic vasopressor drug with vasopressin, epinephrine, and saline placebo. Ventricular fibrillation (VF) was induced in 20 Sprague-Dawley rats. Mechanical ventilation and precordial compression were initiated after 8 min of untreated VF. About 2 min later, alpha-MNE in a dose of 100 microgram/kg, vasopressin in a dose of 0.4 U/kg, epinephrine in a dose of 30 microgram/kg, or saline control was administered. Defibrillation was attempted after 6 min of CPR. Left ventricular pressure, dP/dt(40), -dP/dt, and cardiac index were measured for an interval of 240 min after resuscitation. Except for saline controls, comparable increases in coronary perfusion pressure (CPP) were observed after each drug intervention. All animals were successfully resuscitated. Post-resuscitation myocardial function and survival were significantly better in animals treated with alpha-MNE. Both post-resuscitation myocardial function and survival were most improved after administration of the selective alpha(2)-adrenergic agonist, intermediate after vasopressin and least after epinephrine and saline placebo.

Topics: Analysis of Variance; Animals; Cardiac Output; Cardiopulmonary Resuscitation; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography; Hemodynamics; Male; Nordefrin; Probability; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity; Survival Rate; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

We sought to determine the effects of a combination of vasopressin and epinephrine on neurologic recovery in comparison with epinephrine alone and saline placebo alone in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive, every 5 min, either a combination of vasopressin and epinephrine (vasopressin [IU/kg]/epinephrine [ micro g/kg]: 0.4/45, 0.4/45, and 0.8/45; n = 6), epinephrine alone (45, 45, and 200 micro g/kg; n = 6), or saline placebo alone (n = 5). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve the return of spontaneous circulation. Aortic diastolic pressure was significantly (P < 0.01) increased 90 s after each of 3 vasopressin/epinephrine injections versus epinephrine alone versus saline placebo alone (mean +/- SEM: 69 +/- 3 mm Hg versus 45 +/- 3 mm Hg versus 29 +/- 2 mm Hg, 63 +/- 4 mm Hg versus 27 +/- 3 mm Hg versus 23 +/- 1 mm Hg, and 52 +/- 4 mm Hg versus 21 +/- 3 mm Hg versus 16 +/- 3 mm Hg, respectively). Spontaneous circulation was restored in six of six vasopressin/epinephrine pigs, whereas six of six epinephrine and five of five saline placebo pigs died (P < 0.01). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait and was normal 5 days after the experiment in all vasopressin/epinephrine-treated animals. In conclusion, in this porcine model of prolonged CPR, repeated vasopressin/epinephrine administration, but not epinephrine or saline placebo alone, ensured long-term survival with full neurologic recovery.. We present a study to evaluate the effects of a combination of vasopressin and epinephrine during prolonged cardiopulmonary resuscitation on neurological outcome in pigs. We found that all pigs treated with a combination of vasopressin and epinephrine could be resuscitated and had full neurologic recovery observed over an entire period of 5 days.

Topics: Animals; Blood Gas Analysis; Blood Pressure; Body Weight; Cardiopulmonary Resuscitation; Drug Combinations; Electric Countershock; Electrocardiography; Epinephrine; Heart Arrest; Hemodynamics; Lactic Acid; Nervous System Diseases; Survival; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Both alpha1- and beta-adrenergic agonists increase the severity of global myocardial ischemic injury. We hypothesized that combined beta- and alpha1-adrenergic blockade would improve initial resuscitation and postresuscitation myocardial and neurological functions. We further hypothesized that the resulting alpha2-actions of relatively brief duration would favor improved functions compared with the more prolonged effect of nonadrenergic vasopressin.. Three groups of 5 male domestic pigs weighing 37+/-3 kg were investigated. Ventricular fibrillation was untreated for 7 minutes before the start of precordial compression, mechanical ventilation, and attempted defibrillation. Animals were randomized to receive central venous injections of equipressor doses of (1) epinephrine, (2) epinephrine in which both alpha1- and beta-adrenergic effects were blocked by previous administration of prazosin and propranolol, and (3) vasopressin during CPR. All but 1 animal were successfully resuscitated. After injection of epinephrine, significantly better cardiac output and fractional area change, together with lesser increases in troponin I, were observed after alpha1- and beta-adrenergic blockade. Postresuscitation neurological function was also improved after alpha1- and beta-block in comparison with unblocked epinephrine and after vasopressin.. Equipressor doses of epinephrine, epinephrine after alpha1- and beta-adrenergic blockade, and vasopressin were equally effective in restoring spontaneous circulation after prolonged ventricular fibrillation. However, combined alpha1- and beta-adrenergic blockade, which represented a predominantly selective alpha2-vasopressor effect, resulted in improved postresuscitation cardiac and neurological recovery.

Topics: Adrenergic Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Animals; Blood Pressure; Cardiopulmonary Resuscitation; Disease Models, Animal; Drug Therapy, Combination; Electric Countershock; Epinephrine; Heart Arrest; Heart Massage; Male; Prazosin; Propranolol; Recovery of Function; Respiration, Artificial; Swine; Treatment Outcome; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

There is increasing evidence that the combination of epinephrine (adrenaline) with vasopressin may be superior to either epinephrine or vasopressin alone for treatment of cardiac arrest. However, the optimal combination, and dosage of cardiovascular drugs to minimize side effects, and to improve outcome has yet to be found. We therefore evaluated whether the combination of vasopressin plus epinephrine plus nitroglycerin (EVN), would improve vital organ blood flow during cardiopulmonary resuscitation (CPR) when compared with epinephrine (EPI) alone. After 4 min of ventricular fibrillation (VF) and 4 min of standard CPR, pigs were randomized to the combination of epinephrine (45 microg/kg) plus vasopressin (0.4 U/kg) plus nitroglycerin (7.5 microg/kg; n=12), or epinephrine (40 microg/kg; n=12) alone. Cerebral and myocardial blood flow was measured with radiolabeled microspheres. Defibrillation was attempted after 19 min of VF including 15 min of CPR. Mean+/-SEM coronary perfusion pressures were significantly (P < 0.01) higher 5 min after EVN vs. EPI alone (34+/-3 vs. 24+/-3 mmHg, respectively). At the same time, mean+/-SEM left ventricular, and global cerebral blood flow was also significantly (P < 0.05) higher after EVN vs. EPI alone (0.78+/-0.11 vs. 0.48+/-0.08 ml/min/g; and 0.37+/-0.05 vs. 0.22+/-0.0 3 ml/min/g, respectively). Spontaneous circulation was restored in 11 of 12 animals in the EVN group vs. 6 of 12 swine after EPI alone (P = N.S.). In conclusion, the combination of EVN significantly improved vital organ blood flow during CPR compared with EPI alone. Addition of nitroglycerin to the combination of low dose epinephrine with vasopressin during cardiac arrest may be beneficial.

Topics: Animals; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Coronary Circulation; Drug Therapy, Combination; Epinephrine; Heart Arrest; Nitroglycerin; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

It is well established that epinephrine administered during cardiopulmonary resuscitation results in pulmonary gas exchange disturbances. It is uncertain how vasopressin affects gas exchange after cardiopulmonary resuscitation.. Prospective, randomized experimental study.. Animal research laboratory.. Twenty domestic pigs.. Animals were subjected to ventricular fibrillation and cardiopulmonary resuscitation by using either vasopressin or epinephrine. Hemodynamic and pulmonary gas exchange (multiple inert gas elimination technique) variables were recorded before cardiopulmonary resuscitation and 10, 30, 60, and 120 mins after return of spontaneous circulation when either epinephrine (control) or vasopressin was used.. At 10 mins after return of spontaneous circulation, blood flow to low V /Q lung units was increased in animals treated with epinephrine (17.8 +/- 6 vs. 2.6 +/- 3%, mean +/- sd, p<.01). Resulting carbon dioxide elimination was impaired in animals treated with epinephrine but not in animals treated with vasopressin (PaCO2, 55 +/- 2 vs. 46 +/- 4 torr, p<.05). Thirty minutes after return of spontaneous circulation, blood flow to lung units with a normal VA /Q ratio was reduced in animals treated with epinephrine (79 +/- 1 vs. 84 +/- 12%, p<.05), resulting in a depressed PaO2 (147 +/- 4 vs. 127 +/- 10 torr, p<.05).. Vasopressin compared with epinephrine for cardiopulmonary resuscitation resulted in better gas exchange variables in the early postresuscitation phase.

Topics: Animals; Blood Gas Analysis; Cardiopulmonary Resuscitation; Epinephrine; Hemodynamics; Pulmonary Gas Exchange; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

We recently demonstrated that vasopressin alone resulted in a poorer outcome in a pediatric porcine model of asphyxial cardiac arrest when compared with epinephrine alone or with epinephrine plus vasopressin in combination. Accordingly, this study was designed to differentiate whether the inferior effects of vasopressin in pediatrics were caused by the type of cardiac arrest.. Prospective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow.. University hospital laboratory.. Eighteen piglets weighing 8-11 kg.. After 8 mins of ventricular fibrillation and 8 mins of cardiopulmonary resuscitation, either 0.4 units/kg vasopressin (n = 6), 45 microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered. Six minutes after drug administration, a second respective bolus dose of 0.8 units/kg vasopressin, 200 microg/kg epinephrine, or a combination of 200 microg/kg epinephrine with 0.8 units/kg vasopressin was given. Defibrillation was attempted 20 mins after initiating cardiopulmonary resuscitation.. Mean +/- sem left ventricular myocardial blood flow 2 mins after each respective drug administration was 65 +/- 4 and 70 +/- 13 mL x min(-1) x 100 g(-1) in the vasopressin group; 83 +/- 42 and 85 +/- 41 mL x min(-1) x 100 g(-1) in the epinephrine group; and 176 +/- 32 and 187 +/- 29 mL x min(-1) x 100 g(-1) in the epinephrine-vasopressin group (p <.006 after both doses of epinephrine-vasopressin vs. vasopressin and after the first dose of epinephrine-vasopressin vs. epinephrine, respectively). At the same times, mean +/- sem total cerebral blood flow was 73 +/- 3 and 47 +/- 5 mL x min(-1) x 100 g(-1) after vasopressin; 18 +/- 2 and 12 +/- 2 mL x min(-1) x 100 g(-1) after epinephrine; and 79 +/- 21 and 41 +/- 8 mL x min(-1) x 100 g(-1) after epinephrine-vasopressin (p <.025 after both doses of vasopressin and epinephrine-vasopressin vs. epinephrine). Five of six vasopressin-treated, two of six epinephrine-treated, and six of six epinephrine-vasopressin treated animals had return of spontaneous circulation (nonsignificant).. In this pediatric porcine model of ventricular fibrillation, the combination of epinephrine with vasopressin during cardiopulmonary resuscitation resulted in significantly higher levels of left ventricular myocardial blood flow than either vasopressin alone or epinephrine alone. Both vasopressin alone and the combination of epinephrine with vasopressin, but not epinephrine alone, improved total cerebral blood flow during cardiopulmonary resuscitation. In stark contrast to asphyxial cardiac arrest, vasopressin alone or in combination with epinephrine appears to be of benefit after ventricular fibrillation in the pediatric porcine model.

Topics: Animals; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Coronary Circulation; Disease Models, Animal; Epinephrine; Hemodynamics; Prospective Studies; Random Allocation; Swine; Vasopressins; Ventricular Fibrillation

Topics: Animals; Disease Models, Animal; Epinephrine; Heart Arrest; Hemodynamics; Swine; Vasopressins; Ventricular Fibrillation

The use of vasopressin instead of adrenaline/epinephrine during resuscitation improves vital organ perfusion, but the effects on mesenteric perfusion following successful resuscitation are not fully evaluated. The present study was designed to compare the effects of vasopressin and adrenaline/epinephrine, given to rats during resuscitation from ventricular fibrillation, on to mesenteric ischaemia, as determined by intestinal mucosal tonometer pCO(2) during the postresuscitation period.. Male Sprague-Dawley rats (n=28) were allocated randomly to receive vasopressin (0.8 U/kg) or adrenaline/epinephrine (90 microg/kg) after 5 min of ventricular fibrillation. Precordial chest compression was initiated 4 min after the start of ventricular fibrillation, continued for 4 min, and followed by defibrillation. Seven of 14 (vasopressin) and 12 of 14 (adrenaline/epinephrine) rats were successfully defibrillated (P=0.10, Fisher's exact test) and observed for 60 min. Intestinal mucosal tonometer pCO(2) measurements before cardiac arrest and 15, 30, and 60 min following return of spontaneous circulation were 47+/-3, 73+/-8, 63+/-7, and 56+/-6 mmHg in the vasopressin group and 48+/-5, 78+/-7, 67+/-6, and 62+/-6 mmHg in the adrenaline/epinephrine group (P<0.05 at 60 min between vasopressin and adrenaline/epinephrine). Right atrial hemoglobin oxygen saturations at these time points were 73+/-5, 51+/-12, 58+/-11, and 63+/-5% in the vasopressin group and 76+/-7, 44+/-10, 52+/-10 and 54+/-8% in the adrenaline/epinephrine group (P<0.05 at 60 min between vasopressin and adrenaline/epinephrine).. We conclude that in this rat model the administration of vasopressin instead of adrenaline/epinephrine for CPR tends to be associated with lower resuscitation success, but less mesenteric ischaemia during the postresuscitation period in successfully resuscitated rats.

Topics: Adrenergic Agonists; Animals; Blood Gas Analysis; Carbon Dioxide; Epinephrine; Heart Arrest; Ischemia; Male; Manometry; Mesentery; Models, Animal; Rats; Rats, Sprague-Dawley; Resuscitation; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Vasopressin has been investigated as a possible alternative to epinephrine during cardiopulmonary resuscitation (CPR). We tested the hypothesis that vasopressin, in comparison with epinephrine, would improve cerebral blood flow and metabolism during CPR as well as after restoration of spontaneous circulation (ROSC). A total of 22 anaesthetised piglets were subjected to 5 min of ventricular fibrillation followed by 8 min of closed-chest CPR. The piglets were randomly allocated to receive repeated boluses of either 45 microg/kg epinephrine or 0.4 U/kg vasopressin IV. Haemodynamic parameters, cerebral cortical blood flow and cerebral tissue pH and PCO(2) were continuously monitored during CPR and up to 4 h after ROSC. Cerebral oxygen extraction ratio was calculated. Cerebral cortical blood flow increased transiently after each bolus of epinephrine, while only the first bolus of vasopressin resulted in a sustained increase. The peak in cerebral cortical blood flow was reached approximately 30 s later with vasopressin. During the initial 5 min following ROSC, cerebral cortical blood flow was greater in the vasopressin group. In conclusion, there is a difference between epinephrine and vasopressin in the time from injection to maximal clinical response and the duration of their effect, but their overall effects on blood pressures and cerebral perfusion do not differ significantly during CPR. In contrast, vasopressin results in a greater cerebral cortical blood flow during a transient period after ROSC.

Topics: Adrenergic Agonists; Animals; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Epinephrine; Hemodynamics; Oxygen Consumption; Random Allocation; Swine; Time Factors; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Cardiopulmonary resuscitation (CPR) during epidural anesthesia is considered difficult because of diminished coronary perfusion pressure. The efficacy of epinephrine and vasopressin in this setting is unknown. Therefore, we designed this study to assess the effects of epinephrine versus vasopressin on coronary perfusion pressure in a porcine model with and without epidural anesthesia and subsequent cardiac arrest. Thirty minutes before induction of cardiac arrest, 16 pigs received epidural anesthesia with bupivacaine while another 12 pigs received only saline administration epidurally. After 1 min of untreated ventricular fibrillation, followed by 3 min of basic life-support CPR, Epidural Animals and Control Animals randomly received every 5 min either epinephrine (45, 45, and 200 microg/kg) or vasopressin (0.4, 0.4, and 0.8 U/kg). During basic life-support CPR, mean +/- SEM coronary perfusion pressure was significantly lower after epidural bupivacaine than after epidural saline (13 +/- 1 vs 24 +/- 2 mm Hg, P < 0.05). Ninety seconds after the first drug administration, epinephrine increased coronary perfusion pressure significantly less than vasopressin in control animals without epidural block (42 +/- 2 vs 57 +/- 5 mm Hg, P < 0.05), but comparably to vasopressin after epidural block (45 +/- 4 vs 48 +/- 6 mm Hg). Defibrillation was attempted after 18 min of CPR. After return of spontaneous circulation, bradycardia required treatment in animals receiving vasopressin, especially with epidural anesthesia. Systemic acidosis was increased in animals receiving epinephrine than vasopressin, regardless of presence or absence of epidural anesthesia. We conclude that vasopressin may be a more desirable vasopressor for resuscitation during epidural block because the response to a single dose is longer lasting, and acidosis after multiple doses is less severe compared with epinephrine.

Topics: Anesthesia, Epidural; Animals; Blood Gas Analysis; Blood Pressure; Cardiopulmonary Resuscitation; Coronary Circulation; Electrocardiography; Epinephrine; Female; Heart Arrest, Induced; Hemodynamics; Male; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Mean fibrillation frequency may predict defibrillation success during cardiopulmonary resuscitation (CPR). N(alpha)-histogram analysis should be investigated as an alternative. After 4 min of cardiac arrest, and 3 versus 8 min of CPR, 25 pigs received either vasopressin or epinephrine (0.4, 0.4, and 0.8 U/kg vasopressin versus 45, 45, and 200 microg/kg epinephrine) every 5 min with defibrillation at 22 min. Before defibrillation, the N(alpha)-parameter histogramstart/histogramwidth and the mean fibrillation frequency in resuscitated versus non-resuscitated pigs were 2.9+/-0.4 versus 1.7+/-0.5 (P=0.0000005); and 9.5+/-1.7 versus 6.9+/-0.7 (P=0.0003). During the last minute prior to defibrillation, histogramstart/histogramwidth of > or =2.3 versus mean fibrillation frequency > or =8 Hz predicted successful defibrillation with subsequent return of a spontaneous circulation for more than 60 min with sensitivity, specificity, positive predictive value and negative predictive value of 94 versus 82%, 96 versus 89%, 98 versus 93% and 90 versus 74%, respectively. We conclude, that N(alpha)-analysis was superior to mean fibrillation frequency analysis during CPR in predicting defibrillation success, and distinction between vasopressin versus epinephrine effects.

Topics: Algorithms; Analysis of Variance; Animals; Cardiopulmonary Resuscitation; Disease Models, Animal; Electric Countershock; Electrocardiography; Epinephrine; Female; Fourier Analysis; Male; Outcome Assessment, Health Care; Predictive Value of Tests; Sensitivity and Specificity; Spectrum Analysis; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Topics: Emergency Medical Services; Heart Arrest; Hospitalization; Humans; Time Factors; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

We sought to determine the effects of vasopressin and saline placebo in comparison with epinephrine on neurologic recovery and possible cerebral pathology in an established porcine model of prolonged cardiopulmonary resuscitation (CPR).. It is unknown whether increased cerebral blood flow during CPR with vasopressin is beneficial with regard to neurologic recovery or detrimental owing to complications such as cerebral edema after return of spontaneous circulation.. After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive every 5 min either vasopressin (0.4, 0.4 and 0.8 U/kg; n = 6), epinephrine (45, 45 and 200 microg/kg; n = 6) or saline placebo (n = 5). The mean value +/- SEM of aortic diastolic pressure was significantly (p < 0.05) higher 90 s after each of three vasopressin versus epinephrine versus saline placebo injections (60 +/- 3 vs. 45 +/- 3 vs. 29 +/- 2 mm Hg; 49 +/- 5 vs. 27 +/- 3 vs. 23 +/- 1 mm Hg; and 50 +/- 6 vs. 21 +/- 3 vs. 16 +/- 3 mm Hg, respectively). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve return of spontaneous circulation.. All the pigs that received epinephrine and saline placebo died, whereas all pigs on vasopressin survived (p < 0.05). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait in all vasopressin-treated animals; after 96 h, magnetic resonance imaging revealed no cerebral pathology.. During prolonged CPR, repeated vasopressin administration, but not epinephrine or saline placebo, ensured long-term survival with full neurologic recovery and no cerebral pathology in this porcine CPR model.

Topics: Animals; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Cerebrovascular Disorders; Disease Models, Animal; Electric Countershock; Epinephrine; Magnetic Resonance Imaging; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

This study evaluated ventricular fibrillation mean frequency and amplitude to predict defibrillation success in a porcine cardiopulmonary resuscitation (CPR) model using repeated administration of vasopressin or epinephrine. After 4 min of cardiac arrest and 3 min of CPR, 10 pigs were randomly assigned to receive either vasopressin (early vasopressin: 0.4, 0.4, and 0.8 units/kg, respectively, n = 5) or epinephrine (early epinephrine: 45, 45, and 200 microg/kg, respectively, n = 5). Another 11 animals were randomly allocated after 4 min of cardiac arrest and 8 min of CPR to receive every 5 min either vasopressin (late vasopressin: 0.4 and 0. 8 units/kg, respectively, n = 5) or epinephrine (late epinephrine: 45 and 200 microg/kg, n = 6). Ventricular fibrillation mean frequency and amplitude on defibrillation were significantly higher in the vasopressin groups than in the epinephrine groups, respectively. In vasopressin versus epinephrine animals, mean frequency immediately before defibrillation was 9.6 +/- 1.5 Hz vs 7. 0 +/- 0.7 Hz (P < 0.001), mean amplitude was 0.65 +/- 0.26 mV vs 0. 21 +/- 0.14 mV (P < 0.001, and coronary perfusion pressure was 27 +/- 9 mm Hg vs 8 +/- 4 mm Hg (P < 0.00001), respectively. In contrast to no epinephrine animals, all vasopressin animals were successfully defibrillated and survived 1 h (P < 0.05). Mean fibrillation frequency and amplitude predicted successful defibrillation and may serve as noninvasive markers to monitor continuing CPR efforts. Furthermore, vasopressin was superior to epinephrine in maintaining these variables above a threshold necessary for successful defibrillation.

Topics: Animals; Cardiopulmonary Resuscitation; Coronary Circulation; Drug Administration Schedule; Electrocardiography; Epinephrine; Random Allocation; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) has been shown to be more effective than optimal doses of epinephrine. This study evaluated the effect of endobronchial vasopressin during CPR.. After 4 min of untreated ventricular fibrillation and 3 min of CPR, 21 pigs were randomized to be treated with 0.8 U/kg intravenous vasopressin (n = 7), 0.8 U/kg endobronchial vasopressin (n = 9), or an endobronchial placebo of normal saline (n = 5). Defibrillation was performed 5 min after drug administration to attempt return of spontaneous circulation.. All animals in the intravenous and endobronchial vasopressin group were resuscitated successfully, but only two of five animals in the placebo group were. At 2 and 5 min after drug administration, coronary perfusion pressure in the intravenous and endobronchial vasopressin group was significantly higher than in the placebo group (50 +/- 10, 34 +/- 5 vs. 16 +/- 6 mmHg, respectively; and 35 +/- 10, 39 +/- 10 vs. 19 +/- 5 mmHg, respectively; P < 0.05).. Endobronchial vasopressin is absorbed during CPR, coronary perfusion pressure is increased significantly within a short period, and the chance of successful resuscitation is increased in this porcine model of CPR. Endobronchial vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.

Topics: Animals; Arginine Vasopressin; Bronchi; Cardiopulmonary Resuscitation; Drug Administration Routes; Hemodynamics; Injections, Intravenous; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Both epinephrine (Epi) and vasopressin (VP) increase coronary perfusion pressure (CPP) when administered during cardiac arrest. Given their different mechanisms of action we tested the hypothesis that during cardiopulmonary resuscitation (CPR) a combination of VP plus Epi would be superior to either agent alone. Epi(40 microg/kg), VP(0.3 U/kg) and the combination of both agents were assessed in a porcine model of ventricular fibrillation (VF). Maximum CPP (diastolic aortic-right atrial pressures) during CPR was similar among the groups but the time course of action was different in each group: with Epi + VP the increase in CPP was significantly more rapid than with VP alone whereas the CPP remained significantly higher for a longer periods of time with VP or VP + Epi versus Epi alone. Left ventricular blood flow (ml/min per g) determined during CPR two min after drug administration was similar between groups: Epi 1.06 +/- 0.16; VP 0.82 +/- 0.26; Epi + VP 0.83 +/- 0.14 (P = N.S.). Post drug administration. 2 min, cerebral blood flow (ml/min per g) in the VP group (0.76 +/- 0.15) was more than two times higher compared with Epi alone (Epi:0.30 +/- 0.08, P < 0.01 versus VP) and Epi plus VP (Epi + VP:0.23 +/- 0.03, P < 0.01 versus VP). We conclude that combination of VP + Epi during cardiac arrest results in a more rapid rise in CPP when compared with VP alone and a more sustained elevation in CPP than observed with Epi alone. Thus, the synergistic effects of these two potent vasopressor agents may be of benefit during CPR.

Topics: Adrenergic Agonists; Animals; Aorta; Atrial Function, Right; Blood Pressure; Cardiac Output; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Drug Combinations; Drug Synergism; Epinephrine; Female; Heart Arrest; Heart Atria; Random Allocation; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation; Ventricular Function, Left

Successful outcomes after cardiopulmonary resuscitation remain disappointingly infrequent, in animal studies, administration of exogenous vasopressin during closed- and open-chest cardiopulmonary resuscitation has recently been shown to be more effective than optimal doses of epinephrine in improving vital organ blood flow.. To describe the clinical effects and outcomes of administering vasopressin to patients in cardiac arrest refractory to current medical therapies.. Case reports.. University hospital.. 8 adults with in-hospital cardiac arrest.. After intravenous epinephrine (administered according to American Heart Association guidelines) and defibrillation efforts had failed, patients in cardiac arrest who were having cardiopulmonary resuscitation received 40 U of vasopressin intravenously and then defibrillation.. Return of spontaneous circulation and hospital discharge rates.. After administration of vasopressin, spontaneous circulation was promptly restored in all patients. Three patients were discharged from the hospital with intact neurologic function; the other five lived for between 30 minutes and 82 hours.. In the presence of ventricular fibrillation with severe hypoxia and acidosis, vasopressin seems to be more potent and effective than adrenergic vasopressors for restoring spontaneous cardiovascular function. These results do not justify the widespread use of vasopressin for refractory cardiac arrest. However, on the basis of these cases, further studies comparing vasopressin with epinephrine are warranted in an effort to improve the currently dismal prognosis of patients after cardiac arrest.

Topics: Adult; Aged; Cardiopulmonary Resuscitation; Combined Modality Therapy; Female; Heart Arrest; Humans; Male; Middle Aged; Vasopressins; Ventricular Fibrillation

Administration of vasopressin during cardiopulmonary resuscitation (CPR) improves vital organ blood flow compared with epinephrine, but the effect of vasopressin on cerebral oxygenation and cerebral venous hypercarbia during CPR has not previously been studied.. Fourteen pigs were allocated to receive either epinephrine (0.2 mg/kg) or vasopressin (0.4 U/kg) after 4 minutes of ventricular fibrillation and 3 minutes of CPR. Cerebral blood flow was determined by radiolabeled microspheres, and arterial and cerebral venous blood gases were measured.. Cerebral blood flow, measured before and 90 seconds and 5 minutes after drug administration, was 9 (3; 12), 25 (19; 27), and 18 (10; 23) mL/min per 100 g (median and 25th and 75th percentiles, respectively) in the epinephrine group and 12 (5; 16), 51 (48; 70), and 53 (45; 63) mL/min per 100 g in the vasopressin group (P<.05 at 90 seconds, P<.01 at 5 minutes between groups). Five minutes after drug administration, cerebral venous Pco2 was 63 (59; 68) mm Hg in the epinephrine group and 47 (43; 55) mm Hg in the vasopressin group (P<.01); at the same time cerebral venous pH was 7.18 (7.17; 7.20) and 7.26 (7.22; 7.36) (P<.01) in the epinephrine and vasopressin groups, respectively. Cerebral oxygen extraction ratio, calculated before and 90 seconds and 5 minutes after drug administration, was 0.42 (0.32; 0.57), 0.47 (0.41; 0.57), and 0.56 (0.56; 0.64) in the epinephrine group and 0.43 (0.38; 0.45), 0.38 (0.25; 0.44), and 0.35 (0.33; 0.49) in the vasopressin group (P<.05 at 90 seconds and 5 minutes).. Compared with epinephrine, vasopressin not only increases cerebral blood flow but also improves cerebral oxygenation and decreases cerebral venous hypercarbia when administered during CPR in pigs.

Topics: Acid-Base Equilibrium; Adrenergic Agonists; Animals; Brain; Carbon Dioxide; Cardiopulmonary Resuscitation; Cerebral Veins; Cerebral Ventricles; Cerebrovascular Circulation; Cranial Sinuses; Epinephrine; Hydrogen-Ion Concentration; Hypercapnia; Oxygen; Oxygen Consumption; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

This study was designed to assess whether median frequency of ventricular fibrillation (VF) correlates with myocardial blood flow and defibrillation success during cardiopulmonary resuscitation (CPR) after epinephrine or vasopressin administration.. After 4 min of VF and 3 min of CPR, 14 pigs received 0.045 mg/kg epinephrine or 0.4 U/kg vasopressin. Using radio-labeled microspheres, median myocardial blood flow during CPR before, and 90 s and 5 min after drug administration (DA) was 15.5 (12.6, 23.1; 25th percentile, 75th percentile), 26.4 (18.5, 29.1), 16.9 (14.9, 19.1) mL min-1 100 g-1, respectively, in the epinephrine, and 16.9 (15.4, 18.9), 48.1 (36.9, 68.9) (P < 0.05 vs. before DA), 52.3 (38.5, 65.0) mL min-1 100 g-1, respectively, in the vasopressin group. Using spectral analysis of VF, median frequency of VF was 11.0 (10.7, 11.8), 11.3 (9.6, 13.1), 10.2, (8.8, 11.4) Hz, respectively, in the epinephrine, and 10.1 (10.0, 10.5), 11.7 (11.1, 14.2) (P < 0.05 vs. before DA), 13.2 (11.5, 13.9) Hz, respectively, in the vasopressin group at the same points in time. Median frequency correlates significantly with myocardial blood flow in the epinephrine (n = 21); rs = 0.772; P < 0.001) and in the vasopressin group (n = 21; rs = 0.905; P < 0.001). Median fibrillation frequency before the first defibrillation was 13.0 (12.2, 13.2) Hz in resuscitated (n = 8) and 9.2 (8.3, 10.2) Hz (n = 6) in non-resuscitated animals (P < 0.01).. We conclude that median frequency of VF reflects myocardial blood flow and the chance of successful defibrillation during closed-chest CPR after vasopressor treatment in a porcine model of VF.

Topics: Adrenergic Agonists; Animals; Blood Pressure; Carbon Dioxide; Cardiopulmonary Resuscitation; Coronary Circulation; Disease Models, Animal; Electrocardiography; Epinephrine; Heart Arrest; Microspheres; Oxygen; Potassium; Signal Processing, Computer-Assisted; Sodium; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

To assess the effects of graded doses of vasopressin vs. saline on median fibrillation frequency and defibrillation success in a porcine model of cardiopulmonary resuscitation.. Prospective, randomized, controlled trial.. Animal laboratory in a university medical center.. Twenty-eight domestic pigs (body weight between 26 and 31 kg), aged 12 to 14 wks.. After 4 mins of ventricular fibrillation and 3 mins of closed-chest cardiopulmonary resuscitation, the animals were allocated to receive either 0.2 U/kg of vasopressin (n = 7), 0.4 U/kg of vasopressin (n = 7), 0.8 U/kg of vasopressin (n = 7), or 10 mL of saline (n = 7, control group). Using radiolabeled microspheres, myocardial blood flow rates during cardiopulmonary resuscitation-before drug administration and 90 secs and 5 mins after drug administration-were as follows in the four groups (mean +/- SEM): 18.8 +/- 0.9, 17.2 +/- 1.1, and 14.6 +/- 1.4 mL/min/100 g in the control group; 17.8 +/- 2.2, 49.6 +/- 6.3 (p < .01 vs. control group), and 29.4 +/- 3.1 mL/min/100 g (p < .05 vs. control group) in the group receiving 0.2 U/kg of vasopressin; 17.1 +/- 1.0, 52.4 +/- 7.5 (p < .01 vs. control group), and 52.2 +/- 5.8 mL/min/100 g (p < .001 vs. control group) in the group receiving 0.4 U/kg of vasopressin; and 18.1 +/- 1.6, 94.9 +/- 9.2 (p < .001 vs. control group), and 57.2 +/- 6.3 mL/min/100 g (p < .001 vs. control group) in the group receiving 0.8 U/kg of vasopressin. Using spectral analysis, median frequencies of ventricular fibrillation-before drug administration and 90 secs and 5 mins after drug administration-were as follows in the four groups: 9.6 +/- 0.4, 8.5 +/- 0.8, and 7.2 +/- 1.0 Hz in the control group; 9.7 +/- 0.5, 12.9 +/- 0.8 (p < .01 vs. control group), and 12.7 +/- 0.8 Hz (p < .001 vs. control group) in the group receiving 0.2 U/kg of vasopressin; 10.3 +/- 0.2, 12.7 +/- 0.9 (p < .01 vs. control group), and 12.8 +/- 0.7 Hz (p < .001 vs. control group) in the group receiving 0.4 U/kg of vasopressin; and 10.0 +/- 0.9, 14.1 +/- 0.9 (p < .001 vs. control group), and 12.5 +/- 0.9 Hz (p < .001 vs. control group) in the group receiving 0.8 U/kg of vasopressin at the same points in time. Median frequency before the first defibrillation attempt was 12.3 +/- 0.4 Hz in the resuscitated animals (n = 19) and 8.2 +/- 1.2 Hz in the nonresuscitated animals (n = 9) (p < .001).. This study contributes to the characterization of the effect of increasing global myocardial blood flow on median fibrillation frequency after administration of graded doses of vasopressin in a porcine model of ventricular fibrillation. Interventions such as vasopressor treatment that increase fibrillation frequency improve the chance of successful defibrillation.

Topics: Animals; Cardiopulmonary Resuscitation; Coronary Circulation; Disease Models, Animal; Dose-Response Relationship, Drug; Microspheres; Prospective Studies; Random Allocation; Spectroscopy, Fourier Transform Infrared; Swine; Vasopressins; Ventricular Fibrillation

This study was designed to assess the interference by closed-chest cardiopulmonary resuscitation (CPR) on the ventricular fibrillation (VF) ECG signal in a porcine model of cardiac arrest and to elucidate which variable of VF spectral analysis reflects best myocardial blood flow and resuscitation success during CPR. Fourteen domestic pigs were allocated to receive either 0.4 U/kg vasopressin (n = 7) or 10 ml saline (n = 7) after 4 min of VF and 3 min of CPR. Using radiolabeled microspheres, myocardial blood flow was determined during CPR before, and 90 s and 5 min after, drug administration. Using spectral analysis of VF, the median frequency, dominant frequency, edge frequency and amplitude of VF were determined simultaneously and before the first defibrillation attempt. Using filters in order to specify frequency ranges, stepwise elimination of mechanical artifacts resulting from CPR revealed that at a frequency bandpass of 4.3-35 Hz, median fibrillation frequency has a sensitivity, specificity, positive and negative predictive value of 100% to differentiate between resuscitated and non-resuscitated animals. The best correlation between myocardial blood flow and fibrillation frequency was found at a median frequency range of 4.3-35 Hz. We conclude that spectral analysis of VF can provide reliable information relating to successful resuscitation. In this model after elimination of oscillations due to mechanical CPR, median fibrillation frequency best reflects the probability of resuscitation success.

Topics: Analysis of Variance; Animals; Cardiopulmonary Resuscitation; Coronary Circulation; Electrocardiography; Fourier Analysis; Heart Arrest; Hemodynamics; Microspheres; Resuscitation; Swine; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

We investigated the formation of a "nonthyroidal illness" (NTI) in pigs undergoing ventricular fibrillation (VF) and resuscitation. Seven minutes after VF twenty-one pigs received either Epinephrine (E: 45 micrograms/kg B.W.; n = 7), Norepinephrine (NE: 45 micrograms/kg B.W.; n = 7), or Vasopressin (VP: 0.8 U/kg B.W.; n = 7). We determined the serum concentrations (sc) of total T4 (TT4), FT4, total T3 (TT3) and rT3 120 min before, during (t0), and 5, 15, 60 and 120 min after VF. At the end of the observation period we figured out the in-vitro T3-generation (kM, Vmax), the in-vitro rT3-generation, the in-vitro rT3-decomposition (kM, Vmax) and the content of cytosolic sulfhydryls (total sulfhydryls, non-protein bound sulfhydryls) in liver and kidney specimen. Animals not undergoing VF served as controls (C) for parameters measured in the intracellular compartment. TT4- and TT3-sc decreased to 3.3 +/- 0.6 micrograms/dl (p < 0.05, vs. t0) and 15.2 +/- 4.1 ng/dl (p < 0.05, vs t0), resp. FT4-sc remained stable for five minutes (2.63 +/- 0.41 ng/dl) before declining to 1.8 +/- 0.39 ng/dl (p < 0.05, vs. t0). The rT3-sc raised finally to 46.9 +/- 7.3 ng/dl (p < 0.05, vs t0). Iodothyronine sc did not exhibit differences between E-, NE- and VP-treatment. Neither in-vitro T3-generation, nor in-vitro rT3-generation, nor in-vitro rT3-decomposition nor intracellular sulfhydryl content were affected by the events of VF and resuscitation as compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Epinephrine; Iodide Peroxidase; Kidney; Kinetics; Microsomes, Liver; Norepinephrine; Resuscitation; Sulfhydryl Compounds; Swine; Thyroxine; Triiodothyronine; Vasopressins; Ventricular Fibrillation

This study was designed to compare the effects of epinephrine with those of vasopressin on vital organ blood flow during closed-chest cardiopulmonary resuscitation (CPR) in a pig model of ventricular fibrillation.. Vasopressin was compared with epinephrine by randomly allocating 28 pigs to receive either 0.2 mg/kg epinephrine (n = 7), 0.2 U/kg vasopressin (low dose) (n = 7), 0.4 U/kg vasopressin (medium dose) (n = 7), or 0.8 U/kg vasopressin (high dose) (n = 7) after 4 minutes of ventricular fibrillation and 3 minutes of closed-chest CPR. Left ventricular myocardial blood flow, determined by use of radiolabeled microspheres during CPR, before and then 90 seconds and 5 minutes after drug administration was 17 +/- 2, 43 +/- 5, and 22 +/- 3 mL.min-1.100 g-1 (mean +/- SEM) in the epinephrine group; 18 +/- 2, 50 +/- 6, and 29 +/- 3 mL.min-1.100 g-1 in the low-dose vasopressin group; 17 +/- 3, 52 +/- 8, and 52 +/- 6 mL.min-1.100 g-1 in the medium-dose vasopressin group; and 18 +/- 2, 95 +/- 9, and 57 +/- 6 mL.min-1.100 g-1 in the high-dose vasopressin group (P < .001 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin, and P < .01 at 5 minutes between epinephrine and medium-dose vasopressin). At the same times, calculated coronary systolic perfusion pressures were 12 +/- 2, 36 +/- 5, and 18 +/- 2 mm Hg in the epinephrine group; 10 +/- 1, 39 +/- 6, and 26 +/- 5 mm Hg in the low-dose vasopressin group; 11 +/- 2, 49 +/- 6, and 38 +/- 5 mm Hg in the medium-dose vasopressin group; and 10 +/- 2, 70 +/- 5, and 47 +/- 6 mm Hg in the high-dose vasopressin group (P < .01 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin); and calculated coronary diastolic perfusion pressures were 15 +/- 2, 24 +/- 2, and 19 +/- 2 mm Hg in the epinephrine group; 13 +/- 1, 25 +/- 2, and 20 +/- 1 mm Hg in the low-dose vasopressin group; 13 +/- 2, 25 +/- 2, and 21 +/- 2 mm Hg in the medium-dose vasopressin group; and 13 +/- 2, 35 +/- 3, and 24 +/- 2 mm Hg in the high-dose vasopressin group (P < .05 at 90 seconds between epinephrine and high-dose vasopressin). Total cerebral blood flow was significantly higher after high-dose vasopressin than after epinephrine (P < .05 at 90 seconds and P < .01 at 5 minutes between groups). Five animals in the epinephrine, 5 in the low-dose vasopressin, 7 in the medium-dose vasopressin, and 6 in the high-dose vasopressin groups were successfully resuscitated and survived the 1-hour observation period.. We conclude that administration of vasopressin leads to a significantly higher coronary perfusion pressure and myocardial blood flow than epinephrine during closed-chest CPR in a pig model of ventricular fibrillation.

Topics: Animals; Cardiopulmonary Resuscitation; Disease Models, Animal; Epinephrine; Hemodynamics; Regional Blood Flow; Swine; Vascular Resistance; Vasopressins; Ventricular Fibrillation

Topics: Arrhythmias, Cardiac; Humans; Syndrome; Vasopressins; Ventricular Fibrillation

Topics: Anesthesia, Dental; Anesthesia, Local; Epinephrine; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Norepinephrine; Procaine; Seizures; Unconsciousness; Vasoconstrictor Agents; Vasopressins; Ventricular Fibrillation

Topics: Aconitum; Amides; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Asphyxia; Barium; Calcium Chloride; Cardiac Complexes, Premature; Chlorides; Depression, Chemical; Electrocardiography; Guinea Pigs; Heart Rate; Magnesium; Male; Potassium Chloride; Quinidine; Rats; Strophanthins; Tachycardia; Vasopressins; Ventricular Fibrillation

Topics: Anti-Arrhythmia Agents; Arginine Vasopressin; Arrhythmias, Cardiac; Blood Pressure; Chloroform; Dogs; Electrocardiography; Epinephrine; Peptides; Pharmacology; Quinidine; Research; Toxicology; Vasopressins; Ventricular Fibrillation

Topics: Angiotensins; Arginine Vasopressin; Arrhythmias, Cardiac; Chlorobutanol; Dogs; Oxytocin; Peptides; Pharmacology; Rabbits; Research; Vasopressins; Ventricular Fibrillation