The effects of epinephrine/norepinephrine on end-tidal carbon dioxide concentration, coronary perfusion pressure and pulmonary arterial blood flow during cardiopulmonary resuscitation

End-tidal CO2 concentration correlates with pulmonary blood flow during cardiopulmonary resuscitation and has been claimed to be a useful tool to judge the effectiveness of chest compression. A high concentration of end-tidal CO2 has been related to a better outcome. However, most authors have noticed a decrease in end-tidal CO2 concentration after administration of epinephrine, concomitant with an increase in coronary perfusion pressure and an increased incidence of return of spontaneous circulation. This study was performed to evaluate changes in end-tidal CO2 concentration after injection of vasopressors during cardiopulmonary resuscitation and to investigate the time-course of the response and possible explanations for it. After 1 min of electrically induced cardiac arrest and 5 min of chest compressions, 18 pigs were randomly assigned to receive 0.045 mg kg(-1) epinephrine, 0.045 mg kg(-1) norepinephrine or no drug. After another 4 min of chest compressions the pigs were defibrillated. End-tidal CO2, pulmonary blood flow and coronary perfusion pressure decreased immediately after the induction of cardiac arrest, increased slightly during chest compressions and increased initially to supernormal levels after the return of spontaneous circulation. Injection of epinephrine or norepinephrine during chest compressions decreased end-tidal CO2 51 +/- 2%, (mean +/- S.E.M.), and 43 +/- 1%, respectively, and pulmonary blood flow by 134 +/- 13 and 125 +/- 16%, respectively, within 1 min, simultaneously increasing coronary perfusion pressure from 10 +/- 2 to 45 +/- 5 mm Hg and from 11 +/- 1 to 38 +/- 5 mm Hg, respectively. The coronary perfusion pressure slowly fell, but the effects on end-tidal CO2 and pulmonary blood flow were prolonged. In conclusion, vasopressors increased coronary perfusion pressure and the likelihood of a return of spontaneous circulation, but decreased end-tidal CO2 concentration and induced a critical deterioration in cardiac output and thus oxygen delivery in this model of cardiopulmonary resuscitation.     

Cardiac resuscitation by extracorporeal circulation after failure of conventional CPR

After cardiac arrest, return of cardiac function and effective circulation are contingent on prompt restoration of myocardial blood flow. Because conventional closed-chest CPR has limited hemodynamic efficiency, we investigated venoarterial ECC utilizing peripheral vascular access as an alternative for cardiac resuscitation. Ventricular fibrillation was induced in domestic pigs by alternating current delivered to the endocardium of the right ventricle. Conventional closed-chest CPR was begun after 10 minutes. In each instance, precordial compression and external defibrillation failed to restore a viable rhythm. ECC was begun at 15 minutes at an average flow rate of 183 ml/kg/min. In each of eight animals, sinus rhythm was restored. In six of these eight animals, spontaneous circulation was reestablished after an average interval of 152 minutes. When epinephrine was administered concomitantly with ECC in an additional eight animals so as to maintain mean aortic pressure between 60 and 100 mm Hg, sinus rhythm and spontaneous circulation were reestablished in each pig after an average of only 23 minutes. The effects of ECC in conjunction with epinephrine were then compared with those of conventional precordial compression in conjunction with epinephrine (sham ECC). In contrast to ECC, which successfully resuscitated each of five animals, none of five sham ECC-treated animals was resuscitated by continued precordial compression and maximal doses of epinephrine (p less than 0.01). We conclude that ECC in conjunction with epinephrine emerges as a highly effective experimental intervention for resuscitation when conventional techniques of precordial compression and external defibrillation fail to reverse cardiac arrest.     

Comparison of epinephrine and vasopressin in a pediatric porcine model of asphyxial cardiac arrest

OBJECTIVE: This study was designed to compare the effects of vasopressin vs. epinephrine vs. the combination of epinephrine with vasopressin on vital organ blood flow and return of spontaneous circulation in a pediatric porcine model of asphyxial arrest. DESIGN: Prospective, randomized laboratory investigation using an established porcine model for measurement of hemodynamic variables, organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Eighteen piglets weighing 8-11 kg. INTERVENTIONS: Asphyxial cardiac arrest was induced by clamping the endotracheal tube. After 8 mins of cardiac arrest and 8 mins of cardiopulmonary resuscitation, a bolus dose of either 0.8 units/kg vasopressin (n = 6), 200 microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered in a randomized manner. Defibrillation was attempted 6 mins after drug administration. MEASUREMENTS AND MAIN RESULTS: Mean +/- SEM coronary perfusion pressure, before and 2 mins after drug administration, was 13 +/- 2 and 23 +/- 6 mm Hg in the vasopressin group; 14 +/- 2 and 31 +/- 4 mm Hg in the epinephrine group; and 13 +/- 1 and 33 +/- 6 mm Hg in the epinephrine-vasopressin group, respectively (p = NS). At the same time points, mean +/- SEM left ventricular myocardial blood flow was 44 +/- 31 and 44 +/- 25 mL x min-(1) x 100 g(-1) in the vasopressin group; 30 +/- 18 and 233 +/- 61 mL x min(-1) x 100 g(-1) in the epinephrine group; and 36 +/- 10 and 142 +/- 57 mL x min(-1) x 100 g(-1) in the epinephrine-vasopressin group (p < .01 epinephrine vs. vasopressin; p < .02 epinephrine-vasopressin vs. vasopressin). Total cerebral blood flow trended toward higher values after epinephrine-vasopressin (60 +/- 19 mL x min(-1) x 100 g(-1)) than after vasopressin (36 +/- 17 mL x min(-1) x 100 g(-1)) or epinephrine alone (31 +/- 7 mL x min(-1) x 100 g(-1); p = .07, respectively). One of six vasopressin, six of six epinephrine, and four of six epinephrine-vasopressin-treated animals had return of spontaneous circulation (p < .01, vasopressin vs. epinephrine). CONCLUSIONS: Administration of epinephrine, either alone or in combination with vasopressin, significantly improved left ventricular myocardial blood flow during cardiopulmonary resuscitation. Return of spontaneous circulation was significantly more likely in epinephrine-treated pigs than in animals resuscitated with vasopressin alone.     

Intraosseous vasopressin improves coronary perfusion pressure rapidly during cardiopulmonary resuscitation in pigs.

OBJECTIVE: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) may be more effective than optimal doses of epinephrine. The main purpose of this study was to determine whether intraosseous vasopressin achieves serum drug levels comparable with intravenous doses during CPR and, additionally, to evaluate the effects of intraosseous vasopressin during CPR. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Twelve domestic pigs. INTERVENTIONS: After 4 mins of untreated ventricular fibrillation and 3 mins of CPR, 12 pigs were randomized to be treated with intravenous administration of vasopressin (0.8 unit/kg vasopressin; n = 6) or intraosseous vasopressin (0.8 unit/kg vasopressin; n = 6). Defibrillation was performed 5 mins after drug administration to attempt the return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: At both 90 secs and 5 mins after drug administration, intravenous and intraosseous administration of vasopressin resulted in comparable mean (+/-SEM) coronary perfusion pressure (43+/-4 vs. 44+/-3 and 30+/-2 vs. 37+/-2 mm Hg, respectively) and vasopressin plasma concentrations (13,706+/-1,857 vs. 16,166+/-3,114 pg/mL and 10,372+/-883 vs. 8246+/-2211 pg/mL, respectively). All animals in both groups were successfully resuscitated; pigs that received intraosseous vasopressin had a significantly higher (p < .05) mean arterial (92+/-6 vs. 129+/-12 mm Hg) and coronary perfusion pressure (84+/-11 vs. 119+/-11 mm Hg) at 5 mins of return of spontaneous circulation. CONCLUSIONS: Intraosseous vasopressin resulted in comparable vasopressin plasma levels, hemodynamic variables, and return of spontaneous circulation rates as did intravenous vasopressin. Intraosseous vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available.     

Inhibition of nitric oxide improves coronary perfusion pressure and return of spontaneous circulation in a porcine cardiopulmonary resuscitation model

OBJECTIVE: During spontaneous circulation, nonspecific inhibition of nitric oxide synthase by N(G)-nitro-L-arginine methyl ester (L-NAME) increases systemic vascular resistance and, therefore, mean arterial pressure. If this effect can be extrapolated to cardiopulmonary resuscitation (CPR), administering L-NAME during CPR may be beneficial by maintaining or even improving coronary perfusion pressure, and hence successful defibrillation. DESIGN: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for hemodynamic variables, blood gases, and defibrillation attempt. SETTING: University medical center experimental laboratory. SUBJECTS: Ten domestic pigs. INTERVENTIONS: After 4 mins of ventricular fibrillation, ten animals were randomly assigned to receive L-NAME (25 mg/kg; n = 5) or saline placebo (n = 5) (given in two doses) after 3 and 13 mins of CPR, respectively. Defibrillation was provided 5 mins after the second dose of active drug or placebo. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem coronary perfusion pressure was significantly (p < .05) higher 90 secs (27 +/- 3 vs. 17 +/- 3 mm Hg), 10 mins (28 +/- 3 vs. 14 +/- 2 mm Hg), and 15 mins (21 +/- 5 vs. 7 +/- 3 mm Hg) after the first L-NAME administration compared with saline placebo. Mean +/- sem coronary perfusion pressure remained significantly higher 90 secs and 5 mins after the second L-NAME vs. saline placebo administration (19 +/- 4 vs. 6 +/- 4 mm Hg, and 17 +/- 3 vs. 4 +/- 4 mm Hg). After 22 mins of cardiac arrest, including 18 mins of CPR, four of five pigs in the L-NAME group were successfully defibrillated, and survived the 60-min postresuscitation phase. In the placebo group, none of five pigs could be defibrillated successfully (p < .05). CONCLUSIONS: Nonspecific blockade of nitric oxide synthase with L-NAME during CPR was associated with an increase in coronary perfusion pressure and resulted in significantly better initial resuscitation when compared with saline placebo.     

Observations of hemodynamics during human cardiopulmonary resuscitation

To evaluate hemodynamics during human CPR, 32 patients with witnessed cardiac arrest were studied during manual and mechanical conventional CPR. In eight patients during manual conventional CPR, peak systolic radial artery, right atrial (RAP), and pulmonary artery pressures were found to be similar (59.8 +/- 4.3, 70.8 +/- 4.7, 71.2 +/- 8.2 mm Hg) and higher than external jugular venous pressure (33.8 +/- 1.9 mm Hg, p less than .0001). The diastolic radial artery to RAP gradient was found to be only 10.7 +/- 2.1 mm Hg. In four patients, maneuvers that avoid chest compression and thus obviate cardiac compression, i.e., rhythmic compression of the abdomen, yielded arterial pressures comparable to those generated by conventional CPR (48 +/- 6.4 vs. 52.8 +/- 3.4 mm Hg, NS). In 13 other patients during mechanical conventional CPR at constant chest compression force, radial artery pressure was higher during the first compression after ventilation as compared with subsequent chest compressions (67.5 +/- 5.0 vs. 61.9 +/- 4.8 mm Hg, p less than .007). These hemodynamic observations are similar to those reported in large dogs during CPR and support the generation of vascular pressures during CPR by an increase in intrathoracic pressure. They also suggest that despite anatomic differences, the similarity of hemodynamics in dogs and humans justifies the use of large dogs as a human model during acute resuscitation studies.     

A selective alpha(2)-adrenergic agonist for cardiac resuscitation

The effects of selective alpha(2)-adrenergic agonist alpha-methylnorepinephrine on the initial success of resuscitation and postresuscitation myocardial function were compared with nonselective alpha- and beta-adrenergic epinephrine in a swine model of cardiac arrest. Epinephrine, the primary pharmacological intervention in the treatment of cardiac arrest, improves immediate outcome. However, epinephrine increases the severity of myocardial dysfunction after cardiac resuscitation. Both inotropic and chronotropic actions provoke disproportionate increases in myocardial oxygen consumption by the ischemic heart, prompting this study, in which we hypothesized that a selective alpha(2)-adrenergic agonist, alpha-methylnorepinephrine (alpha-MNE), would moderate these adverse effects of epinephrine and minimize postresuscitation myocardial dysfunction. After 7 minutes of untreated ventricular fibrillation (VF) in 14 anesthetized male domestic pigs, precordial compression at a fixed rate of 80 compressions/min was begun, along with mechanical ventilation. Either alpha-MNE (100 microg/kg) or epinephrine (20 microg/kg) was administered as a bolus after 2 minutes of precordial compression. After an additional 4 minutes of precordial compression, defibrillation was attempted. Left ventricular systolic and diastolic function was quantitated with the use of transesophageal echo-Doppler imaging. Comparable increases in coronary perfusion pressure to 15 mm Hg were observed after the administration of both drugs. All animals were successfully resuscitated; epinephrine and alpha-MNE were equally quick in restoring spontaneous circulation after 7 minutes of untreated VF. Ejection fraction was reduced by 35% and 14% by epinephrine and alpha-MNE, respectively, after resuscitation. Epinephrine and alpha-MNE increased postresuscitation heart rate by 38% and 15%, respectively. Accordingly, significantly less postresuscitation impairment followed the administration of alpha-MNE. alpha-MNE, a selective alpha-adrenergic agonist, was as effective as epinephrine in restoring spontaneous circulation after 7 minutes of untreated VF in a porcine model for CPR and demonstrated lesser postresuscitation myocardial injury.     

Relative importance of alpha and beta adrenergic receptors during resuscitation.

Successful resuscitation from cardiac arrest in the asphyxiated dog model has been ascribed to the use of artificial ventilation, closed chest cardiac massage, and administration of a vasopressor. Controversy remains over whether the most commonly employed vasopressor, epinephrine, exerts its effects primarily by elevating diastolic pressure and reestablishing coronary flow, or by exciting cardiac pacemaker cells and enhancing myocardial contractility. To observe pure alpha and beta adrenergic receptor influences during resuscitation, three groups (alpha-blocked, beta-blocked, unblocked) of dogs were studied. beta-blocked dogs resuscitated with phenylephrine and unblocked dogs resuscitated with epinephrine experienced 100% successful resumption of spontaneous circulation after 5 min of asphyxia-induced arrest. Only 27% of alpha-blocked animals resuscitated with isoproterenol were successfully revived. The appearance of the ECG during cardiac arrest and resuscitation could in no way be used to predict the outcome of resuscitation attempts. Results suggest that, initially, alpha receptor stimulation with concomitant diastolic pressure elevation is more important to the success of resuscitation than beta receptor stimulation.     

A 2-year prospective cohort study of cardiac resuscitation in a major Canadian hospital

OBJECTIVES: To determine the outcome of cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest and to identify risk factors associated with survival to the time of hospital discharge. DESIGN: A 2-year prospective cohort study. SETTING: Foothills Medical Centre, a 700-bed tertiary, academic and regional referral centre for Calgary and southern Alberta. PATIENTS: Adult inpatients, excluding those who had cardiac arrest in the Emergency Department or operating room. INTERVENTION: Cardiac resuscitation. MAIN OUTCOME MEASURES: Spontaneous return of the pulse with a minimum systolic blood pressure of 80 mm Hg and survival defined as survival to the time of hospital discharge. RESULTS: In 334 patients there were 390 cardiac arrests, of which 200 were primary cardiac arrests and 39 cardiac arrests that occurred while the resuscitation team was in attendance. Of 239 resuscitated patients, 51 (21.3%) survived. Fifteen variables were identified as being associated with survival. This association could be explained, through multivariate analysis, by the effect of the following 3 variables (odds ratio [OR], 95% confidence interval [CI]): initial observed rhythm other than pulseless electrical activity or asystole (OR 17.34, 95% CI 8.2 to 36.8); a patient who was ambulatory and able to provide self-care (OR 3.8, 95% CI 1.9 to 7.5); and a spontaneous return of circulation with resuscitation in less than 20 minutes (OR 12.9, 95% CI 4.8 to 20.7). CONCLUSIONS: Survival to hospital discharge after cardiac arrest remains static. Initial cardiac rhythm and duration of resuscitation before spontaneous return of circulation were the most important risk factors for survival. These factors and the patient's functional status are relevant when discussing cardiac resuscitation with patients or when considering whether to discontinue resuscitation efforts.     

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.     

Hemodynamic effects of vasodilators on pulmonary hypertension in decompensated chronic obstructive pulmonary disease

Vasodilators have been reported to improve the hemodynamic status of some patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD). We investigated the effects of sodium nitroprusside (50 micrograms/min) and hydralazine (25 mg) on pulmonary hemodynamics in 12 patients during acute exacerbation of COPD. Apart from its known systemic effects, nitroprusside decreased significantly mean pulmonary artery pressure (MPAP) from 36 +/- 10 to 31 +/- 12 mm Hg (p less than .04), decreased slightly pulmonary vascular resistance, and did not change cardiac index. Except for a slight but significant increase in MPAP from 35 +/- 5 to 38 +/- 5 mm Hg (p less than .002), hydralazine produced no significant hemodynamic changes. These results suggest that vasodilator therapy with sodium nitroprusside and hydralazine for pulmonary hypertension secondary to acute COPD is probably not helpful.     

Myocardial protection by erythropoietin during resuscitation from ventricular fibrillation

Human recombinant erythropoietin (rhEPO) can protect the myocardium during ischemia and reperfusion. We investigated whether rhEPO could ameliorate previously identified functional myocardial abnormalities that develop during resuscitation from cardiac arrest, using a rat model of ventricular fibrillation (VF) and closed-chest resuscitation. VF was electrically induced and maintained, untreated, for 10 minutes. Chest compression and ventilation were then started and electrical defibrillation was attempted 8 minutes later. Rats were randomized to receive rhEPO (5000 U/kg) in the right atrium at baseline, 15 minutes before induction of VF (rhEPOBL -15-min), or at 10 minutes of VF, immediately before the start of chest compression (rhEPOVF 10-min), or to receive 0.9% NaCl solution instead (control). rhEPO given at the time of resuscitation (rhEPOVF 10-min group) -- but not at baseline -- prompted more effective chest compression, yielding higher coronary perfusion pressures for a given compression depth (1.95 +/- 0.27 mm Hg/mm; P < 0.05 in comparison with rhEPOBL -15-min [1.63 +/- 0.23 mm Hg/mm] and control [1.62 +/- 0.26 mm Hg/mm], by Dunnett's multicomparison method). Post-resuscitation, rats in the rhEPOVF 10-min group displayed higher mean aortic pressure associated with numerically higher cardiac index, stroke work index, and systemic vascular resistance index. rhEPO may rapidly induce myocardial protection during resuscitation from cardiac arrest.     

Excellent coronary perfusion pressure during cardiopulmonary resuscitation is not good enough to ensure long-term survival with good neurologic outcome: a porcine case report

PURPOSE: To report a case of cerebral ischemia confirmed by magnetic resonance imaging after successful cardiopulmonary resuscitation (CPR) complicated by acute respiratory injury. MATERIALS AND METHODS: After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, a female pig weighing 38 kg received every 5 min vasopressin (0.4, 0.4 and 0.8 U/kg). After 22 min of cardiac arrest, including 18 min of CPR, one defibrillation attempt employing 100 J resulted in return of spontaneous circulation. Neurological evaluation was performed 24 and 96 h after successful CPR. Magnetic resonance imaging was carried out 4 days after CPR using a clinical 1.5 T scanner. The magnetic resonance imaging protocol consisted of fast spinecho T2-weighted, as well as spinecho T1-weighted imaging of the brain. RESULTS: CPR with vasopressin resulted in excellent coronary perfusion pressure ranging between 35 and 60 mm Hg throughout CPR. Eight minutes after initiation of chest compressions, bleeding out of the tracheal tube occurred. This was later confirmed as originating from bilateral bloody pulmonary infiltrations, resulting in acute respiratory injury in the post-resuscitation phase. Ninety-six hours after successful CPR, magnetic resonance imaging revealed bilateral diffuse cerebral vasogenic edema. CONCLUSION: Although excellent coronary perfusion pressure renders a return of spontaneous circulation more likely, complications such as acute respiratory injury in the post-resuscitation phase have to be managed carefully in order to ensure good neurological recovery from cardiac arrest.     

Erythropoietin improves the postresuscitation myocardial dysfunction and survival in the asphyxia-induced cardiac arrest model

To investigate the effect of erythropoietin for the management of postresuscitation myocardial dysfunction following asphyxia-induced cardiac arrest. Male adult Wistar rats were used for the prospective controlled animal study. Asphyxia-induced cardiac arrest was performed by turning-off the ventilator and clamping the endotracheal tube. Cardiopulmonary resuscitation with an intravenous injection of 0.01 mg/kg epinephrine and mechanical ventilation were started after 6.5 minutes of asphyxia. The resuscitated animals received either erythropoietin (5000 U/kg) or equivalent volume of 0.9% saline as placebo intravenously 3 minutes after return of spontaneous circulation. The erythropoietin treatment produced better left ventricular dP/dt40 and -dP/dt in the invasive hemodynamic measurements, and left ventricular fraction shortening by echocardiography. Administration of erythropoietin also improved three days survival among those successfully resuscitated. The molecular effects of erythropoietin were shown by activation of its down streaming Akt and ERK 42/44 signaling pathways. EPO has the potential to improve postresuscitation myocardial dysfunction and short term survival in rats after asphyxia-induced cardiac arrest.     

Two-stage resuscitation of the cat brain after prolonged cardiac arrest

Following prolonged cardiac arrest, reperfusion of the brain is endangered by the low blood perfusion pressure during the early resuscitation phase. In order to avoid low perfusion brain injury, a two-stage resuscitation protocol was applied to cats submitted to 30 min potassium chloride induced cardiac arrest: first, the heart was resuscitated, followed — after stabilisation of blood pressure — by recirculation of the brain. During cardiac resuscitation the brain was disconnected from the general circulation by inflating a pneumatic cuff around the neck. The results were compared with the outcome of conventional one-stage resuscitation following 15 min cardiac arrest. Cardiac resuscitation was successful in 5 out of 8 animals with 15 min and in 6 out of 13 animals with 30 min cardiac arrest. In successfully resuscitated animals of both groups, brain energy metabolism recovered to normal within 3 h although two-stage resuscitation increased brain ischemia time to 37–61 min. Twostage resuscitation, in consequence, is a promising approach for revival of the brain after prolonged cardiac arrest.     

Comparison of epinephrine and norepinephrine in the treatment of asphyxial or fibrillatory cardiac arrest in a porcine model

Many animal experiments have shown that alpha-receptor stimulation is a prerequisite for the improvement of myocardial perfusion during CPR. As there are no recent reports on the effectiveness of norepinephrine in the treatment of cardiac arrest, we investigated the effectiveness of epinephrine and norepinephrine after asphyxial or ventricular fibrillation cardiac arrest using a porcine model. After 3 min of asphyxial cardiac arrest, seven animals each received either 45 micrograms/kg epinephrine, 45 micrograms/kg norepinephrine, or placebo (controls). All drugs were given blind. All seven animals given epinephrine could be resuscitated after 174 +/- 53 sec, whereas six of seven given norepinephrine could be resuscitated after 473 +/- 116 sec. None of the seven given the placebo could be resuscitated. After 4 min of ventricular fibrillation cardiac arrest, none of the seven animals that received defibrillating countershocks at 4 min without either mechanical measures or drug therapy, and none of the seven that received CPR and countershocks but no drugs, could be resuscitated. In the group that received CPR plus 45 micrograms/kg epinephrine, defibrillation and restoration of spontaneous circulation were achieved in six of seven animals in 667 +/- 216 sec. In the group that received CPR plus 45 micrograms/kg norepinephrine, defibrillation and restoration of spontaneous circulation were achieved in all seven animals in the significantly shorter time of 86 +/- 18 sec. In this porcine model, norepinephrine appeared superior to the same dose of epinephrine in the treatment of ventricular fibrillation, with respect to resuscitation time.     

Effect of the 30 degree lateral recumbent position on pulmonary artery and pulmonary artery wedge pressures in critically ill adult cardiac surgery patients.

BACKGROUND: Despite demonstrated benefits of lateral positioning, critically ill patients may require prolonged supine positioning to obtain reproducible hemodynamic measurements. OBJECTIVES: TO determine the effect of 30 degree right and left lateral positions on pulmonary artery and pulmonary artery wedge pressures after cardiac surgery in critically ill adult patients. METHODS: An experimental repeated-measures design was used to study 35 patients with stable hemodynamics after cardiac surgery. Subjects were randomly assigned to 1 of 2 position sequences. Pulmonary artery and pulmonary artery wedge pressures were measured in each position. RESULTS: Measurements obtained from patients in the 30 degree left lateral position differed significantly (all Ps < .05) from measurements obtained from patients in the supine position for pulmonary artery systolic, end-diastolic, and mean pressures. Pulmonary artery wedge pressures did not differ significantly; however, data were available from only 17 subjects. The largest mean difference in pressures between the 2 positions was 2.0 +/- 2.1 mm Hg for pulmonary artery systolic pressures, whereas maximum differences for end-diastolic and pulmonary artery wedge pressures were 1.4 +/- 2.7 mm Hg and 1.6 +/- 2.4 mm Hg, respectively. Clinically significant position-related changes in pressure occurred in 12 (2.1%) of 581 pressure pairs. Clinically significant changes occurred in end-diastolic pressure in 2 subjects and in pulmonary artery wedge pressure in 1 subject. CONCLUSiONS: In patients with stable hemodynamics during the first 12 to 24 hours after cardiac surgery, measurements of pulmonary artery and pulmonary artery wedge pressures obtained in the 30 degree lateral and supine positions are clinically interchangeable.     

Selective aortic arch perfusion with hemoglobin-based oxygen carrier-201 for resuscitation from exsanguinating cardiac arrest in swine.

OBJECTIVE: The prospects for resuscitation after blunt traumatic cardiac arrest are dismal. Selective aortic arch perfusion (SAAP) with a hemoglobin-based oxygen carrier (HBOC-201) offers a potentially effective therapy. This study evaluated the acute cardiovascular and metabolic effects of SAAP with HBOC-201 in an exsanguination model of cardiac arrest. DESIGN: Randomized, controlled, laboratory investigation. SETTING: University research laboratory. SUBJECTS: Domestic swine, 25-39 kg. INTERVENTIONS: Partial resection of four liver lobes rapidly led to profound hemorrhagic shock and subsequent cardiac arrest at 10-13 mins. At 15 mins, swine were randomized to receive either SAAP with oxygenated lactated Ringer's (LR) solution (n = 6) or SAAP with oxygenated HBOC-201 (n = 6) at a rate of 10 mL x kg(-1) x min(-1) until return of spontaneous circulation with a mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved. Epinephrine (0.005 mg/kg) was given via intra-aortic route every 30 secs as needed to promote return of spontaneous circulation beginning at 18 mins after onset of liver injury (3 mins after beginning SAAP). MEASUREMENTS AND MAIN RESULTS: Mean aortic pressure, cardiac output, total blood loss, and time of arrest were similar for both groups before SAAP therapy. In the SAAP-HBOC group, return of spontaneous circulation with a sustained mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved in six of six swine at 1.9 +/- 0.3 mins of SAAP, and none of these swine required epinephrine. In the SAAP-LR group, no swine (from a total of six) achieved return of spontaneous circulation before intra-aortic epinephrine administration, and only two of six swine had brief return of spontaneous circulation with an mean aortic pressure of 60 mm Hg (8.0 kPa) after intra-aortic epinephrine that was sustained for <10 mins. One-hour survival was five of six in the SAAP-HBOC group and none of six in the SAAP-LR group (p <.05, Fisher's exact test). CONCLUSION: SAAP with oxygenated HBOC-201 rapidly restored viable cardiovascular function after exsanguinating cardiac arrest in this swine model of liver injury with profound hemorrhagic shock.     

Cariporide minimizes adverse myocardial effects of epinephrine during resuscitation from ventricular fibrillation

OBJECTIVE: Epinephrine given during closed-chest resuscitation increases blood flow across the coronary and cerebral circuits. However, epinephrine worsens reperfusion arrhythmias and intensifies postresuscitation myocardial dysfunction. We investigated whether cariporide-a selective sodium-hydrogen exchanger isoform-1 inhibitor-could ameliorate such adverse effects without diminishing its vasopressor actions. DESIGN: Randomized animal study. SETTING: University-based animal laboratory. SUBJECTS: Twenty-four anesthetized male domestic pigs (29-43 kg). INTERVENTIONS: Ventricular fibrillation was electrically induced and left untreated for 8 mins. Pigs were randomized to receive after 2 mins of chest compression a 3 mg/kg bolus of cariporide (n = 8), a 0.02 mg/kg bolus of epinephrine (n = 8), or a combination of cariporide and epinephrine (n = 8). Additional doses of epinephrine were given if the coronary perfusion pressure decreased below 15 mm Hg. Successfully resuscitated pigs were observed for 72 hrs. MEASUREMENTS AND MAIN RESULTS: The averaged coronary perfusion pressure was higher in the epinephrine (34 +/- 11 mm Hg, p = .001) and cariporide/epinephrine (35 +/- 10 mm Hg, p < .001) groups compared with the cariporide group (15 +/- 6 mm Hg). All pigs in the epinephrine and cariporide/epinephrine groups but only six in the cariporide group were successfully resuscitated and survived 72 hrs. During the immediate postresuscitation period, four of eight pigs in the epinephrine group had episodes of recurrent ventricular fibrillation or pulseless ventricular tachycardia requiring additional electrical shocks (7.0 +/- 6.4) but none in the cariporide and cariporide/epinephrine groups (chi-square, p = .008). Myocardial dysfunction occurred early after return of spontaneous circulation but only in the epinephrine group. CONCLUSIONS: The combined administration of cariporide and epinephrine prompted adequate pressor effects during chest compression and facilitated reestablishment of cardiac activity without episodes of recurrent ventricular fibrillation or transient myocardial dysfunction as with epinephrine alone.     

Adenosine during cardiac arrest and cardiopulmonary resuscitation: a placebo-controlled, randomized trial.

BACKGROUND AND HYPOTHESIS TESTED: The effects of adenosine (100 micrograms/kg/min; n = 7) were examined during rodent cardiopulmonary resuscitation (CPR). Change in coronary artery perfusion pressure, end-tidal PCO2, and arterial acid-base status of anesthetized, male, Sprague-Dawley rats were compared with CPR controls (0.9% sodium chloride; n = 7) and with sham controls (n = 9). Sustained ventricular fibrillation was induced and precordial chest compression was followed by defibrillation. RESULTS: After 6 mins of cardiac arrest, six (86%) of seven adenosine-treated animals were resuscitated after adenosine infusion and four (57%) of seven control animals were resuscitated after sodium chloride infusion. During chest compression, coronary artery perfusion pressure was 7 +/- 2 mm Hg after adenosine, but was 22 +/- 3 mm Hg in the controls (p less than .01). Parallel decreases were observed in mean aortic pressure. Arterial and end-tidal PCO2 significantly (p less than .01) decreased after adenosine. These changes contrasted with a second control group of nine identically prepared animals which, in the absence of ventricular fibrillation and subsequent chest compression, demonstrated no changes in hemodynamic, respiratory, or blood gas variables. CONCLUSIONS: Adenosine decreased coronary artery perfusion pressure. However, despite marked reductions in coronary artery perfusion pressure, survival was not compromised after adenosine infusion in this rodent model of CPR.