The Effects of Endothelin–1 on Coronary Perfusion Pressure during Cardiopulmonary Resuscitation in a Canine Model

Objective: To study the hemodynamic effects of exogenously administered endothelin–1 (ET–1), a peptide produced by endothelial cells with potent non–adrenergically mediated vasoconstrictor properties.
Methods: A prospective drug intervention study was carried out in a resuscitation research laboratory.
Fifteen mixed–breed dogs were anesthetized and instrumented for hemodynamic monitoring. Asphyxia arrest was produced by clamping the endotracheal tube. Hemodynamic data were collected continuously.
Following loss of aortic fluctuations monitored by thoracic aortic catheter, the animals remained in pulseless electrical activity (PEA) for 10 minutes. After 10 minutes of no–flow PEA, closed–chest CPR was begun and the animals were randomized to one of three treatment groups (epi, 0. 02 mg/kg epinephrine IV every 3 minutes; endo, 100 μg ET–1 IV at 0 minutes; and epi/endo, a combination of the epi and endo treatments).
Results: endo and epi alone produced similar coronary perfusion pressures (CPPs). The epi/endo combination produced significantly improved CPP compared with that of either epi or endo alone. In the epi group, the best mean CPP was 16 ± 14 mm Hg and occurred 7 minutes after drug administration. In the endo group, the best mean CPP was 28 ± 7 mm Hg and occurred 13 minutes after drug administration. In the epi/endo combination group, the best mean CPP was 61 ± 37 mm Hg and occurred 7 minutes after drug administration (p < 0. 05 compared with the epi and endo groups alone).
Conclusion: ET–1 is a potent vasoconstrictor. The combination of epi and endo significantly improved CPP compared with that for either agent alone. ET–1 should be investigated further as a vasoconstrictor in cardiac arrest.     

Association of Drug Therapy with Survival in Cardiac Arrest: Limited Role of Advanced Cardiac Life Support Drugs

OBJECTIVE: To generate hypotheses regarding the association of standard Advanced Cardiac Life Support (ACLS) drugs with human cardiac arrest survival. METHODS: This observational cohort study was conducted over a two-year period in the wards, intensive care units, and EDs of two tertiary care hospitals. Included werc adult patients who suffered cardiac arrest either inside or outside the hospital and who required epinephrine according to standard ACLS guidelines. Six standard ACLS drugs (given while CPR was in progress) were assessed for association with survival from resuscitation to one hour and to hospital discharge by univariate and multivariate logistic regression analyses. RESULTS: In the 529 patients studied, initial cardiac rhythm had no impact on the association between drug administration and survival. The time of drug administration (quartile of ACLS period) was associated with resuscitation for atropine (p < 0.05) and lidocaine (p < 0.01). The odds ratios (95% CIs) for successful resuscitation, after multivariate adjustment for potential confounders, were: a respiratory initiating cause, 3.7 (2.1 -6.4); each 5-minute increase in CPR-ACLS interval, 0.5 (0.4-0.7); each 5-minute duration of ACLS. 0.9 (()1.8- 1.0; atropine, 1.2 (1.0-1.3); bretylium. (0.4 (0.1-1.1); calcium 0.8 (0.2-2.4); lidocaine, 0.9 (0.7-1.1); procainamide. 21.0 (5.2-84.0) d sodium bicarbonate 1.2 (1.0-1.6). All other potential confounding variables entered into the model were not significantly associated with resuscitation. CONCLUSION: Initiating cause of arrest, time to ACLS, and duration of ACLS were important correlates of survival. Other than procainaimide, standard ACLS drugs had relatively little association with survival, but timing of administration may be an important factor. Further research using definitive large randomized controlled trials is warranted to assess the role of drug therapy in improving cardiac arrest survival.     

Epinephrine, but not vasopressin, improves survival rates in an adult rabbit model of asphyxia cardiac arrest

Although vasopressin has been reported to be more effective than epinephrine for cardiopulmonary resuscitation in ventricular fibrillation animal models, its efficacy in asphyxia model remains controversy. The purpose of this study was to investigate the effectiveness of vasopressin vs epinephrine on restoration of spontaneous circulation (ROSC) in a rabbit model of asphyxia cardiac arrest. Cardiac arrest was induced by clamping endotracheal tube. After 5 minutes of basic life-support cardiopulmonary resuscitation, animals who had no ROSC were randomly assigned to receive either epinephrine alone (epinephrine group; 200 microg/kg) or vasopressin alone (vasopressin group; 0.8 U/kg). The coronary perfusion pressure (CPP) was calculated as the difference between the minimal diastolic aortic and simultaneously recorded right atrial pressure. Restoration of spontaneous circulation was defined as an unassisted pulse with a systolic arterial pressure of 60 mm Hg or higher for 5 minutes or longer. We induced arrest in 62 rabbits, 15 of whom had ROSC before drug administration and were excluded from analysis. The remaining 47 rabbits were randomized to epinephrine group (n = 24) and vasopressin group (n = 23). Before and after drug administration, CPP in epinephrine group increased significantly (from -4 +/- 4 to 36 +/- 9 mm Hg at peak value, P = .000), whereas CPP in vasopressin group increased only slightly (from 9 +/- 5 to 18 +/- 6 mm Hg at peak value, P = .20). After drug administration, 13 of 24 epinephrine rabbit had ROSC, and only 2 of 23 vasopressin rabbit had ROSC (P < .01). Consequently, we conclude that epinephrine, but not vasopressin, increases survival rates in this adult rabbit asphyxia model.     

Selective Aortic Arch Perfusion Using Serial Infusions of Perflubron Emulsion

Objective : To determine whether selective aortic arch perfusion (SAAP) using serial infusions of oxygenated perflubron emulsion combined with aortic epinephrine (AoE) administration is more effective than conventional therapy in treating cardiac arrest.
Methods : An experimental cardiac arrest model (10 min ventricular fibrillation and 2 min CPR) was used with 12 mixed-breed canines, randomized into 2 groups: control ( n = 6), CPR and IV epinephrine, 0.01 mgkg, at 12 rnin and then every 3 min; or AoE-SAAP ( n = 6), CPR and aortic epinephrine, 0.01 mgkg, at 12 rnin and then every 3 min, and serial SAAP with oxygenated 60% weightholume (w/v) perflubron emulsion as follows: 300 mL over 30 sec at 12 rnin as continuous SAAP without CPR; 150 mL over 20–30 sec at 15 min and 18 rnin as pulsed diastolic SAAP during CPR.
Results : AoE-SAAP resulted in increased coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC) compared with control. CPR-diastolic (release phase) CPP during pulsed diastolic SAAP was similar to or greater in magnitude than the CPP generated during the initial SAAP infusion without CPR. ROSC for control was 0/6 and for AoE-SAAP was 416 (p < 0.05, Fisher's exact test). Time from initiation of CPR to ROSC with a sustained systolic aortic pressure >60 mm Hg was 8.0 ± 1.2 rnin in the 4 resuscitated AoE-SAAP animals.
Conclusion : The combination of AoE with SAAP infusions of oxygenated perflubron emulsion was more effective than conventional resuscitation therapy. Pulsed diastolic SAAP is a promising method for performing SAAP.     

Vasopressin improves vital organ blood flow after prolonged cardiac arrest with postcountershock pulseless electrical activity in pigs

OBJECTIVE: Although a benefit of vasopressin when compared with epinephrine was shown during cardiopulmonary resuscitation (CPR) after a short duration of ventricular fibrillation cardiac arrest, the effect of vasopressin during prolonged cardiac arrest with pulseless electrical activity is currently unknown. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Eighteen domestic pigs. INTERVENTIONS: After 15 mins of cardiac arrest and 3 mins of chest compressions, 18 animals were randomly treated with either 0.8 units/kg vasopressin (n = 9) or 200 microg/kg epinephrine (n = 9). MEASUREMENTS AND MAIN RESULTS: Compared with epinephrine, vasopressin resulted, at both 90 secs and 5 mins after drug administration, in significantly higher (p < .05) median (25th-75th percentiles) left ventricular myocardial blood flow (120 [range, 96-193] vs. 54 [range, 11-92] and 56 [range, 41-80] vs. 21 [range, 11-40] mL/min/100 g, respectively) and total cerebral blood flow (85 [78-102] vs. 24 [18-41] and 50 [44-52] vs. 8 [5-23] mL/min/100 g, respectively). Spontaneous circulation was restored in eight of nine animals in the vasopressin group and in one of nine animals in the epinephrine group (p = .003). CONCLUSIONS: Compared with a maximum dose of epinephrine, vasopressin significantly increased left ventricular myocardial and total cerebral blood flow during CPR and return of spontaneous circulation in a porcine model of prolonged cardiac arrest with postcountershock pulseless electrical activity.     

Vasopressin administered with epinephrine is associated with a return of a pulse in out-of-hospital cardiac arrest

OBJECTIVE: Recent data suggest that using vasopressin in combination with epinephrine (adrenaline) may improve treatment of out-of-hospital cardiac arrest. This study examined local experience with the combination of epinephrine and vasopressin administration. METHODS: Data were obtained from an urban, municipal emergency medical service that does not include vasopressin in its formulary. A physician is dispatched to the scene of all cardiac arrest patients treated by this system. Vasopressin could be administered in addition to epinephrine to subjects with out-of-hospital cardiac arrest by the on-scene physician. Demographic information, drug administration and return of pulses were abstracted from patient care records for a 1-year interval. Multivariate logistic regression was used to assess the relationship between vasopressin use and outcomes. RESULTS: During the study period, data were available for 298 subjects receiving epinephrine-only (n=231, 78%), a combination of 40 IU vasopressin and epinephrine (n=37, 12%) or no vasopressor drugs (n=30, 10%). Among patients receiving vasopressor drugs, pulse was restored for 74 subjects (28%), and 56 subjects (21%) had a pulse on arrival at the hospital. Return of pulses was associated with witnessed collapse, bystander CPR, and an initial ECG rhythm of ventricular fibrillation or tachycardia. Subjects receiving vasopressin and epinephrine were more likely to have a return of pulses during the resuscitation (LR: 2.73; 95% CI: 1.24, 6.03) and at hospital arrival (3.85; 1.71, 8.65) than subjects treated with epinephrine alone. CONCLUSIONS: There is an association between using vasopressin in combination with epinephrine and restoration of circulation after out-of-hospital cardiac arrest.     

The Effects of Graded Doses of Endothelin-1 on Coronary Perfusion Pressure and Vital Organ Blood Flow during Cardiac Arrest

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor and has been shown to improve coronary perfusion pressure (CPP) during arrest. The effects of ET-1 on organ blood flow during arrest have not been extensively studied. OBJECTIVE: To investigate the effects of ET-1 on myocardial and cerebral blood flow during cardiac arrest. METHODS: Sixty immature swine were anesthetized and instrumented. The animals were randomized to receive one of three doses of ET-1 (50, 150, or 300 microg) or placebo with/without standard-dose epinephrine (SDE) during cardiac arrest. After a 10-minute period of no-flow ventricular fibrillation (VF), cardiopulmonary resuscitation (CPR) was performed for 3 minutes, followed by drug administration. Placebo or SDE was given every 3 minutes. Myocardial and cerebral blood flow was measured using a fluorescent microsphere technique. RESULTS: Prearrest and CPR variables were not different between groups. Beginning 4 minutes after giving 300 microg ET-1 with or without SDE, CPP was significantly increased compared with SDE alone. Total myocardial blood flow following ET-1 administration was no different than myocardial blood flow following SDE alone. Cerebral blood flow increased 3.5 minutes after administration of 300 microg ET-1 with SDE and reached significance 9.5 minutes after drug administration when compared with SDE alone [92.5 (48.8-117.9) vs 15.6 (7.7-23) mL/min/100 g]. CONCLUSIONS: Three hundred microg ET-1 with SDE increases CPP and improves cerebral blood flow but does not improve myocardial blood flow during cardiac arrest. The peripheral effects of ET-1 significantly improve CPP and cerebral blood flow, but myocardial blood flow is not increased due to coronary vasoconstriction.     

Effects of endothelin-1 on resuscitation rate during cardiac arrest

OBJECTIVES: Endothelin-1 (ET-1) is a potent peripheral and coronary artery vasoconstrictor and has been shown to improve coronary perfusion pressure (CPP) during cardiac arrest. The effect of ET-1 on return of spontaneous circulation (ROSC) following cardiac arrest has not been studied. Our hypothesis was that ET-1 does not improve ROSC from cardiac arrest when compared to placebo. METHODS: A total of 11 immature swine were used in this laboratory study. Animals were randomized to receive 300 microg ET-1 and standard dose epinephrine (SDE) or placebo and SDE during arrest. After a 10-min period of no-flow ventricular fibrillation (VF), CPR was performed for 3 min followed by ET-1/SDE or placebo/SDE administration. Following drug administration, standard ACLS was followed with SDE given every 3 min. Aortic pressure was monitored during resuscitation. ROSC was defined as any perfusing rhythm with a systolic pressure greater than 60 mmHg for 60 s. Animals received post-ROSC care as needed for 2 h post-ROSC. CPP and ROSC were analyzed using repeated measures ANOVA and Fischer's exact test respectively. P<0.05 was considered significant. RESULTS: Pre-arrest variables and CPP prior to ET-1 administration were not different between groups. Following ET-1 administration, CPP was significantly increased at all time points in ET-1/SDE versus placebo/SDE animals. ROSC was achieved in 1/5 (20%) ET-1/SDE versus 1/6 (16.7%) placebo/SDE animals (P>0.05). The resuscitated ET-1/SDE animal survived 6.5 min compared to 120 min for the resuscitated placebo/SDE animal. CONCLUSIONS: In our study, ET-1 administration during cardiac arrest increases CPP but does not improve ROSC.     

Effect of the Addition of Vasopressin or Vasopressin Plus Nitroglycerin to Epinephrine on Arterial Blood Pressure during Cardiopulmonary Resuscitation in Humans

Background: Infusion of a vasopressor during cardiopulmonary resuscitation (CPR) in humans increases end decompression (diastolic) arterial blood pressure, and consequently increases vital organ perfusion pressure and survival. Several vasoactive drugs have been tested alone or in combination, but their hemodynamic effects have not been investigated clinically in humans. Study Objective: We tested the hypothesis that epinephrine (1 mg) co-administered with vasopressin (40 IU) ± nitroglycerin (300 μg) results in higher diastolic blood pressure than epinephrine alone. Study Design: A prospective, randomized, double-blinded controlled trial in the prehospital setting. The study included 48 patients with witnessed cardiac arrest. Patients received either epinephrine alone (E alone) or epinephrine plus vasopressin (E+V) or epinephrine plus vasopressin plus nitroglycerin (E+V+N). A femoral arterial catheter was inserted for arterial pressure measurement. Outcome Measures: The primary end point was diastolic blood pressure during CPR, 15 min after the first drug administration (T = 15 min). Results: After exclusions, a total of 44 patients were enrolled. Diastolic blood pressures (mm Hg) at T = 15 min were not statistically different between groups (median [interquartile range]: 20 [10], 15 [6], and 15 [13] for E alone, E+V, and E+V+N, respectively. The rate of return of spontaneous circulation was 63% (n = 10) in the epinephrine group, 43% (n = 6) in the epinephrine plus vasopressin group, and 36% (n = 5) in the triple therapy group (NS). Conclusions: Addition of vasopressin or vasopressin plus nitroglycerin to epinephrine did not increase perfusion blood pressure compared to epinephrine alone in humans in cardiac arrest, suggesting the absence of benefit in using these drug combination(s).     

延迟使用升压素与肾上腺素在窒息家兔心肺复苏中的疗效比较

目的 观察心肺复苏时延迟使用升压素或肾上腺素对自主循环恢复率的影响，比较两者对窒息性心跳停搏家兔心肺复苏的疗效。方法 62只家兔均在呼气末夹闭气管8min，造成窒息性心脏停搏模型后，开始人工胸外心脏按压及机械通气，期间不用任何药物，复苏5min内恢复自主循环的家兔定义为常规心肺复苏成功，对5min内复苏不成功者，再随机分为两组，分别给予升压素（0．8IU／kg）或肾上腺素（0．2mg／kg）静脉注射，并继续常规心肺复苏：结果 常规心肺复苏的自主循环恢复率为24．19％（15／62），加用升压素和肾上腺素后总的自主循环恢复率提高到48．39％（30／62）。其中升压素组23只家兔中2只复苏成功（8．70％），肾上腺素组24只家兔中13只复苏成功（54．16％），肾上腺素组复苏成功率明显高于升压素组（P=0．001）。结论 对窒息性心脏停搏的家兔心肺复苏时应用升压素或肾上腺素可提高自主循环恢复率。肾上腺素在提高窒息家兔冠脉灌注压及复苏成功率方面明显优于升压素。     

Survival from prehospital cardiac arrest is critically dependent upon response time

STUDY OBJECTIVE: This study correlated the delay in initiation of bystander cardiopulmonary resuscitation (ByCPR), basic (BLS) or advanced cardiac (ACLS) life support, and transport time (TT) to survival from prehospital cardiac arrest. This was a secondary endpoint in a study primarily evaluating the effect of bicarbonate on survival. DESIGN: Prospective multicenter trial. SETTING: Patients treated by urban, suburban, and rural emergency medical services (EMS) services. PATIENTS: Eight hundred and seventy-four prehospital cardiac arrest patients. INTERVENTIONS: This group underwent conventional ACLS intervention followed by empiric early administration of sodium bicarbonate noting resuscitation times. Survival was measured as the presence of vital signs on emergency department (ED) arrival. Data analysis utilized Student's t-test and logistic regression (p<0.05). RESULTS: Survival was improved with decreased time to BLS (5.52 min versus 6.81 min, p=0.047) and ACLS (7.29 min versus 9.49 min, p=0.002) intervention, as well as difference in time to return of spontaneous circulation (ROSC). The upper limit time interval after which no patient survived was 30 min for ACLS time, and 90 min for transport time. There was no overall difference in survival except at longer arrest times when considering the primary study intervention bicarbonate administration. CONCLUSION: Delay to the initiation of BLS and ACLS intervention influenced outcome from prehospital cardiac arrest negatively. There were no survivors after prolonged delay in initiation of ACLS of 30 min or greater or total resuscitation and transport time of 90 min. This result was not influenced by giving bicarbonate, the primary study intervention, except at longer arrest times.     

Comparison of epinephrine with vasopressin on bone marrow blood flow in an animal model of hypovolemic shock and subsequent cardiac arrest

OBJECTIVE: The intraosseous route is an emergency alternative for the administration of drugs and fluids if vascular access cannot be established. However, in hemorrhagic shock or after vasopressors are given during resuscitation, bone marrow blood flow may be decreased, thus impairing absorption of intraosseously administered drugs. In this study, we evaluated the effects of vasopressin vs. high-dose epinephrine in hemorrhagic shock and cardiac arrest on bone marrow blood flow. DESIGN: Prospective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow. SETTING: University hospital laboratory. SUBJECTS: Fourteen pigs weighing 30 +/- 3 kg. INTERVENTIONS: Radiolabeled microspheres were injected to measure bone marrow blood flow during a prearrest control period and during hypovolemic shock produced by rapid hemorrhage of 35% of the estimated blood volume. In the second part of the study, ventricular fibrillation was induced; after 4 mins of untreated cardiac arrest and 4 mins of standard cardiopulmonary resuscitation, a bolus dose of either 200 microg/kg epinephrine (n = 6) or 0.8 units/kg vasopressin (n = 6) was administered. Defibrillation was attempted 2.5 mins after drug administration, and blood flow was assessed again at 5 and 30 mins after successful resuscitation. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem bone marrow blood flow decreased significantly during induction of hemorrhagic shock from 14.4 +/- 4.1 to 3.7 +/- 1.8 mL.100 g-1.min-1 in the vasopressin group and from 18.2 +/- 4.0 to 5.2 +/- 1.0 mL.100 g-1.min-1 in the epinephrine group (p =.025 in both groups). Five minutes after return of spontaneous circulation, mean +/- sem bone marrow blood flow was 3.4 +/- 1.1 mL.100 g-1.min-1 after vasopressin and 0.1 +/- 0.03 mL.100 g-1.min-1 after epinephrine (p =.004 for vasopressin vs. epinephrine). At the same time, bone vascular resistance was significantly (p =.004) higher in the epinephrine group when compared with vasopressin (1455 +/- 392 vs. 43 +/- 19 mm Hg. mL-1.100 g.min, respectively). CONCLUSIONS: Bone blood flow responds actively to both the physiologic stress response of hemorrhagic shock and vasopressors given during resuscitation after hypovolemic cardiac arrest. In this regard, bone marrow blood flow after successful resuscitation was nearly absent after high-dose epinephrine but was maintained after high-dose vasopressin. These findings emphasize the need for pressurized intraosseous infusion techniques, because bone marrow blood flow may not be predictable during hemorrhagic shock and drug therapy.     

Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular fibrillation and cardiopulmonary resuscitation

OBJECTIVE: 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. DESIGN: Prospective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow. SETTING: University hospital laboratory. SUBJECTS: Eighteen piglets weighing 8-11 kg. INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.     

A comparison of alpha-methylnorepinephrine,vasopressin and epinephrine for cardiac resuscitation

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.     

窒息家兔心肺复苏疗效与血浆内皮素变化的关系

目的探讨窒息家兔心肺复苏(cardiopulmonaryresuscitation,CPR)疗效与血浆内皮素(endothelin,ET)变化的关系。方法对62只家兔均在呼气末夹闭气管8min,造成窒息性心脏停搏模型后,开始人工胸外心脏按压及机械通气,期间不用任何药物,复苏5min内恢复自主循环(restorationof spontaneouscirculation,ROSC)的家兔定义为常规CPR成功;对5min内未能ROSC者再随机分为两组,分别给予肾上腺素(0.2mg kg)和加压素(0.8U kg)静脉注射,并继续行常规CPR。分别在窒息前和CPR15、60、120min采血测血浆ET浓度。结果常规CPR的家兔ROSC率为24.16%(1562),加用肾上腺素和加压素后总的ROSC率提高到48.39%(3062)。对常规CPR失败的家兔而言,肾上腺素疗效明显优于加压素(ROSC率分别为54.16%和8.70%,P=0.001)。但复苏成功组和复苏失败组家兔血浆ET的比较,差异无显著性。结论对窒息性心脏停搏的家兔CPR时应用肾上腺素或加压素可提高ROSC率,但肾上腺素疗效明显优于加压素。窒息家兔CPR疗效与血浆内皮素变化无明显相关关系。     

加压素与肾上腺素在小鼠心肺复苏中的疗效比较

目的 比较加压素与肾上腺素在小鼠心肺复苏中的疗效.方法 30只雄性昆明小鼠经食道快速起搏心窒诱发室颤、建立心搏骤停模型,起搏开始后4 min将小鼠随机分成3组(n=10/组):对照组(Sal-gro)、加压素组(Vas-gro)、肾上腺素组(Epi-gro),分别经动脉注射药物(生理盐水、加压素0.4 U/kg和肾上腺素0.04mg/kg)1次,开始胸外心脏按压及机械通气,观察自主循环恢复情况,10min无效则放弃复苏.自主循环恢复的小鼠连续监测心电和血压60 min,观察血压、心率、呼吸恢复情况及生存时间.结果 加压素与肾上腺素组小鼠的自主循环恢复率均显著高于对照组(9/10,10/10和3/10,P＜0.05,P＜0.01).加压素与肾上腺素组组间比较差异无统计学意义(P＞0.05).肾上腺素组小鼠在自主循环恢复后全部出现自主呼吸,而加压素组小鼠只有4只出现自主呼吸(P＜0.05).肾上腺素组小鼠的生存时间明显长于加压素组和对照组小鼠(P＜0.05,P＜0.05).结论 加压素和肾上腺素均可显著提高心搏骤停小鼠的自主循环恢复率,但0.04 mg/kg的肾上腺素对自主循环恢复后小鼠呼吸功能及生存时间的影响明显优于0.4 U/k的加压素,其机制尚不清楚,还有待进一步研究.     

Clinical use of sodium bicarbonate during cardiopulmonary resuscitation--is it used sensibly?

This study retrospectively analyzed the pattern of sodium bicarbonate (SB) use during cardiopulmonary resuscitation (CPR) in the Brain Resuscitation Clinical Trial III (BRCT III). BRCT III was a prospective clinical trial, which compared high-dose to standard-dose epinephrine during CPR. SB use was left optional in the study protocol. Records of 2915 patients were reviewed. Percentage, timing and dosage of SB administration were correlated with demographic and cardiac arrest variables and with times from collapse to Basic Life Support, to Advanced Cardiac Life Support (ACLS) and to the major interventions performed during CPR. SB was administered in 54.5% of the resuscitations. The rate of SB use decreased with increasing patient age-primarily reflecting shorter CPR attempts. Mean time intervals from arrest, from start of ACLS and from first epinephrine to administration of the first SB were 29+/-16, 19+/-13, and 10.8+/-11.1 min, respectively. No correlation was found between the rate of SB use and the pre-ACLS hypoxia times. On the other hand, a direct linear correlation was found between the rate of SB use and the duration of ACLS. We conclude that when SB was used, the time from initiation of ACLS to administration of its first dose was long and severe metabolic acidosis probably already existed at this point. Therefore, if SB is used, earlier administration may be considered. Contrary to physiological rationale, clinical decisions regarding SB use did not seem to take into consideration the duration of pre-ACLS hypoxia times. We suggest that guidelines for SB use during CPR should emphasize the importance of pre-ACLS hypoxia time in contributing to metabolic acidosis and should be more specific in defining the duration of "protracted CPR or long resuscitative efforts", the most frequent indication for SB administration.     

Synergistic effects of vasopressin plus epinephrine during cardiopulmonary resuscitation

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.     

A Comparison of Multimedia and Standard Advanced Cardiac Life Support Learning

Abstract. Objectives : To compare student performance after Multimedia ACLS Learning System (MM) education compared with that after standard (ST) ACLS education. Methods : Final-year medical students were divided into 2 groups based on convenience scheduling and given ACLS instruction either in a standard format or with the MM course. The sizes of the small groups and the times in small-group instruction were identical. All students were evaluated with the same 50-item multiple-choice written examination, a structured evaluation immediately after the management of a mock cardiac arrest, and a second structured evaluation of the same mock arrest (videotaped) by an instructor blinded to the education method. Students were assigned a mark from 1 to 5 in each of 4 domains: assessment, immediate priorities, continual assessment, and leadership. Results : 75 students took the MM and 38 took the ST course. The mean ± SD mark for the multiple-choice test was 89.3 ± 4.9% (MM) vs 89.3 ± 4.8% (ST); the on-site mock arrest evaluation mark (20 maximum) was 14.1 ± 2.5 (MM) vs 14.1 ± 2.0 (ST); and the blinded mock arrest evaluation was 13.1 ± 2.9 (MM) vs 14.4 ± 2.9 (ST) (p = 0.024). 1/75 (MM) vs 0/38 (ST) did not successfully complete the on-site mock arrest evaluation. More students in the MM group (46% vs 25%) required multiple attempts to successfully complete the mock arrest evaluation (p < 0.02). Conclusion : In medical students with no previous ACLS training, structured access to the multimedia ACLS Learning System provides immediate educational outcomes similar to those of a standard ACLS course. Multimedia computer-interactive learning should be enhanced with a short period of hands-on practice.     

Does prearrest adrenergic integrity affect pressor response? A comparison of epinephrine and vasopressin in a spontaneous ventricular fibrillation swine model

Objectives

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.

Methods

Eight anesthetized and instrumented swine were administered 0.1 mg 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 7 min of untreated VF, mechanical chest compressions were initiated. After 1 min of compressions, 1 mg epinephrine was given while CPP was recorded. When CPP values had returned to pre-epinephrine levels, 40 U 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.

Results

The CPP response following epinephrine was 15.1 mmHg lower in adrenergically blocked animals compared to non-adrenergically blocked animals (95% Highest Posterior Density [HPD] 2.9-27.2 mmHg lower). CPP went up 18.4 mmHg more following vasopressin when compared to epinephrine (95% HPD 8.2-29.1 mmHg). The posterior probability of a higher CPP response from vasopressin (vs. epinephrine) in these animals was 0.999.

Conclusions

Pre-arrest adrenergic blockade blunts the CPP response to epinephrine. Superior augmentation of CPP is attained with vasopressin under these conditions.