Predictive indices of successful cardiac resuscitation after prolonged arrest and experimental cardiopulmonary resuscitation

To determine if clinically accessible hemodynamic and blood gas measurements are of value in predicting outcome of countershock after prolonged ventricular fibrillation (VF) and artificial cardiopulmonary support, 14 dogs were studied during 30 minutes of VF using two randomly assigned closed-chest techniques. Seven dogs underwent conventional CPR; the other seven were supported with a pneumatic thoracic vest and abdominal binder, which were inflated synchronously with the airway. Ascending aortic (Ao), right atrial (RA), and instantaneous coronary perfusion pressures (Ao - RA) were measured at five-minute intervals. Ao and RA blood samples were analyzed at 10, 20, 25 and 30 minutes for PO2, PCO2, and pH. After 25 minutes, 1 mg epinephrine was given intravenously, and five minutes later defibrillation was attempted. If unsuccessful, repeated countershocks, conventional pharmacologic therapy, and artificial support were continued. If a perfusing spontaneous cardiac rhythm did not result within an additional 30 minutes, the experiment was terminated. Six animals developed a perfusing cardiac rhythm after one or more countershocks (Group 1); eight failed to develop a perfusing rhythm after repeated countershocks and an additional 30 minutes of resuscitative effort (Group 2). Five Group 1 dogs received vest/binder artificial support. When measured values were averaged over the study period, Group 1 was found to have a significantly greater Ao end-diastolic pressure (AoEDP) and peak diastolic coronary perfusion pressure (CPP) when compared to Group 2 (23 +/- 6 vs 14 +/- 8 mm Hg, P less than .05; and 22 +/- 6 vs 5 +/- 10 mm Hg, P less than .01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanical "cough" cardiopulmonary resuscitation during cardiac arrest in dogs

Hemodynamic findings during ventricular fibrillation (VF) and closed-chest cardiopulmonary resuscitation (CPR) are similar to those described during VF and vigorous coughing. Interventions during CPR that mimic the physiologic events of coughing (high intrathoracic pressure and high intraabdominal pressure) improve perfusion during VF and CPR. An external circulatory assist apparatus was devised to emulate cough physiology, i.e., simultaneous pulsatile increases in intrathoracic pressure (pneumatic vest), intraabdominal pressure (abdominal binder) and airway pressure (high-pressure airway inflation). In this study, vest/binder CPR was compared with conventional CPR during 30 minutes of VF and artificial support in 18 randomized dogs. Defibrillation and long-term (more than 24 hours) survival were chosen as end points. During VF and artificial support, aortic and right atrial (RA) pressures, the instantaneous aortic-RA pressure difference (coronary perfusion pressure) and blood gas levels were measured. After 30 minutes of VF and administration of 1 mg of epinephrine, countershock was attempted. Systolic aortic and RA pressures, mean aortic-RA pressure difference and blood gas levels were not significantly different between dogs that were successfully resuscitated and those that were not. However, peak diastolic coronary perfusion pressure (peak diastolic aortic-RA pressure) for survivors averaged 23 +/- 6 mm Hg, but only 6 +/- 10 mm Hg for nonsurvivors (p less than 0.001). A peak diastolic coronary perfusion pressure 16 mm Hg or greater had a positive and negative predictive value for a successful outcome of 1.00. Only 1 of 9 conventional CPR dogs survived 24 hours; 7 of 9 dogs supported with the vest/binder device were alive and neurologically normal at 24 hours (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)     

Beneficial effect of epinephrine infusion on cerebral and myocardial blood flows during CPR

It is hypothesized that epinephrine improves the ability to resuscitate the heart through a mechanism thought to be related to the increase in aortic pressure. Our results with epinephrine infusion during CPR are consistent with this hypothesis. Epinephrine selectively increased vascular resistance in noncerebral, noncoronary vascular beds, as indicated by a decrease in microsphere-determined blood flow in these areas. This increased vascular resistance raised aortic pressure during the chest compression phase and the relaxation phase of CPR. Because intracranial and right atrial pressures were only slightly higher with epinephrine, cerebral and myocardial perfusion pressures and blood flows were significantly improved. This beneficial effect (compared to no administration of a vasopressor) was more pronounced as CPR progressed beyond ten minutes. Enhanced cerebral and myocardial perfusion occurred with epinephrine when either the conventional or simultaneous compression and ventilation (SCV) mode of CPR was employed in dogs. Similar selective perfusion was sustained for 50 minutes of SCV-CPR with epinephrine, even when the onset of CPR was delayed five minutes. Regional brain blood flow differed in the delayed-CPR group in that cerebellum, brain stem, and thalamic regions initially had higher blood flows. In an infant animal model of CPR using conventional CPR in piglets, epinephrine also was found to increase cerebral and myocardial blood flows. These results show that administration of epinephrine benefits different age groups of different species with different modes of CPR; that benefits occur even with delayed onset of CPR which is associated with additional anoxia and acidosis; and that epinephrine administration is particularly effective in sustaining cerebral and coronary perfusion during prolonged CPR.     

Postcountershock pulseless rhythms: response to CPR, artificial cardiac pacing, and adrenergic agonists

Clinically, countershock of ventricular fibrillation (VF) may result in asystole or a pulseless rhythm in more than 50% of attempts. We conducted a study to assess the effects of immediate artificial pacing, CPR, and adrenergic drug therapy in the management of postcountershock pulseless rhythms. Thirty-four episodes of VF followed by countershock were studied in eight anesthetized dogs. Transducer-tipped catheters were positioned in the ascending aorta (Ao) and right atrium (RA). A bipolar pacing catheter was advanced to the apex of the right ventricle and a catheter for measurement of coronary sinus blood flow (CSQ) (continuous thermodilution technique) was positioned in the coronary sinus. VF was induced electrically and a countershock at 400 J was given two minutes later; CPR was not performed during VF episodes. Countershock was followed by asystole or a pulseless rhythm in all animals. Immediate endocardial pacing (0.1 to 5 mA) of bradyarrhythmias produced electrical capture but did not result in arterial pressure pulses in any animal. After pacing, CPR was performed for two minutes or until restoration of spontaneous circulation (ROSC). During CPR, the diastolic coronary perfusion gradient (Ao-RA) was 20 +/- 7 mm Hg (mean +/- SD) and CSQ was 14 +/- 7 mL/min/100 g (53% +/- 43% of control). ROSC followed CPR of less than two minutes duration in 24% of VF study episodes. If ROSC did not follow two minutes of CPR, 1 mg epinephrine, or 50 micrograms or 100 micrograms isoproterenol was given IV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of continuous abdominal binding during cardiac arrest and resuscitation

Abdominal binding improves arterial pressure and flow during cardiopulmonary resuscitation (CPR). This study was undertaken to assess the mechanisms of improved hemodynamics during cardiac arrest and CPR with continuous abdominal binding in a canine model (n = 8). Carotid and inferior vena caval (IVC) flow probes and cineangiography were used to observe magnitude and direction of blood flow. CPR with binding significantly increased (p < 0.001) systolic aortic (Ao) (49 ± 11 vs 34± 12mm Hg), right atrial (RA) (49 ± 11 vs 31 ± 10 mm Hg) and IVC pressure (50 ± 7 versus 31 ± 11 mm Hg) and common carotid flow (1.1 ± 0.4 vs 0.7 ± 0.4 ml/min/kg, p < 0.05) compared with CPR without binding. Aortic, RA and IVC diastolic pressures increased similarly. Binding decreased the diastolic Ao-IVC pressure difference by 8 ± 12 mm Hg and decreased net IVC flow (0.5 ± 1.4 vs 1.4 ± 1.2 ml/min/kg, p < 0.05). Binding also decreased coronary perfusion pressure (Ao-RA) in 5 of 8 dogs. Cineangiograms showed tricuspid incompetence and reflux from the right atrium to the inferior vena cava during chest compression and IVC-to-right heart inflow during relaxation, which was confirmed by the flowmeter data. Abdominal binding during CPR decreased the size of the perfused vascular bed by inhibiting subdiaphragmatic flow and increased intrathoracic pressure for a given chest compression force, leading to preferential cephalad flow. However, coronary perfusion pressure was often adversely affected. Further studies should be undertaken before the widespread clinical application of continuous abdominal binding during CPR.     

Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs

The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min . 100 g (41 +/- 15% of control) and an average myocardial blood flow of 18 ml/min . 100 g (15 +/- 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 +/- 1% of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 +/- 2 ml/min . 100 g (73 +/- 25% control) and left ventricular blood flow at 38 +/- 9 ml/min . 100 g (28 +/- 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effects of methoxamine and epinephrine on survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation

This study compares the effects of methoxamine, a pure alpha 1-agonist, and epinephrine on cerebral and myocardial blood flow, central hemodynamics, and survival in a randomized placebo-controlled fashion during prolonged ventricular fibrillation (VF) in a canine model. Twenty-four anesthetized and ventilated adult mongrel dogs were instrumented for regional blood flow determinations using radio-labeled microspheres. The dogs were randomized to receive either 20 mg of methoxamine as a single intravenous bolus or repeated boluses of 0.02 mg/kg of epinephrine, 0.2 mg/kg of epinephrine, or normal saline solution placebo beginning at three minutes following induction of VF and initiation of closed chest cardiac massage (CCCM). Organ blood flow measurements were determined during normal sinus rhythm and after five and 20 minutes of VF. All six dogs receiving methoxamine were successfully resuscitated in contrast to only one in each of the epinephrine-treated groups and none of the dogs receiving placebo (p less than .01). Although epinephrine was associated with significantly higher blood pressures than placebo during cardiopulmonary resuscitation (CPR), blood pressures achieved with methoxamine were significantly higher than those observed in the other three treatment groups (p less than .001). Cerebral blood flow was significantly higher with both methoxamine and high-dose epinephrine (p less than .05). Mean left and right ventricular myocardial flows were highest with methoxamine but this did not achieve statistical significance. In contrast, organ flows measured in the animals receiving the lowest dose of epinephrine were not significantly higher than those associated with placebo. Cardiac output after 20 minutes of CPR was significantly lower with high-dose epinephrine than with methoxamine or placebo (p less than .05). Our results suggest that methoxamine significantly improves regional cerebral blood flow and survival during CPR and although high-dose epinephrine is associated with comparable improvements in regional cerebral blood flow, this treatment is associated with deterioration in central hemodynamics during prolonged VF and does not enhance survival.     

Hemodynamic effects of pneumatic external counterpressure in canine hemorrhagic shock

To assess the effects of external counterpressure in a hypovolemic canine model, mean right atrial pressure (RA), left ventricle end-diastolic pressure (LVEDP), mean aortic pressure (Ao), and cardiac output (CO) (indicator dilution technique or electromagnetic ascending aortic flow) were measured in eight closed-chest mongrel dogs following phlebotomy to an Ao of 50 to 60 mm Hg. Inferior vena cava (IVC) flow was measured electromagnetically with a cannulating probe in four animals. The antishock garment was inflated to pressures of 40, 60, 80, and 100 mm Hg. An extended shock "control" period preceded inflation to minimize the effect of reflex circulatory responses to acute blood loss. IVC flow (2 +/- 1 mL/min/kg) during and immediately following antishock garment inflation was not significantly different from control (3 +/- 1 mL/min/kg) regardless of inflation pressure. Ao, RA, and LVEDP measured 30 seconds and 15 minutes after garment inflation were increased, but CO was not significantly different from control values at each inflation pressure. Garment inflation significantly increased peripheral vascular resistance (PVR) at all inflation pressures, and there was a significant correlation (r = .53; P less than .001) between the change in Ao and PVR. These results indicate that the change in arterial pressure produced by external counterpressure is the result of an increase in PVR and not the result of an autotransfusion and subsequent increased left heart outflow in the canine shock model.     

Selective aortic arch perfusion during cardiac arrest: a new resuscitation technique.

STUDY OBJECTIVES: To demonstrate the technique of selective aortic arch perfusion during cardiac arrest and to observe the hemodynamic effects of volume infusion and aortic epinephrine administration. DESIGN: Sequential series, nonrandomized, noncontrolled. TYPE OF PARTICIPANTS: Fourteen mongrel dogs weighing 21 to 36 kg. INTERVENTIONS: Animals had midaortic arch pressure, right atrial pressure, and descending aortic arch balloon occlusion catheters placed. After ten minutes of ventricular fibrillation, balloon inflation and aortic arch infusions were initiated as follows: group 1 (six), 30 mL/kg/min of 0.9% NaCl for two minutes; group 2 (four), 30 mL/kg/min of oxygenated lactated Ringer's with 2 mg/L epinephrine for two minutes, followed by CPR; and group 3 (four), 20 mL/kg/min of oxygenated perfluorochemicals with 4 mg/L epinephrine for one minute, then CPR. MEASUREMENTS AND MAIN RESULTS: Midaortic arch pressure, right atrial pressure, and coronary perfusion pressure each rose significantly in all groups. Midaortic arch pressure and coronary perfusion pressure increases were greater in groups 2 and 3 than in group 1. In groups 1 and 2, right atrial pressure increases at end-selective aortic arch perfusion were excessive as midaortic arch pressure and right atrial pressure increased linearly and similarly after 20 to 30 seconds. In groups 2 and 3, CPR-diastolic midaortic arch pressure and coronary perfusion pressure after selective aortic arch perfusion were good and similar to midaortic arch pressure and coronary perfusion pressure at end-selective aortic arch perfusion. CONCLUSION: Selective aortic arch perfusion is technically feasible, but excessive right atrial pressure increases limit maximal infusion rates and volumes. Selective aortic arch perfusion infusates with epinephrine produce greater midaortic arch pressure and coronary perfusion pressure during infusion than infusate without epinephrine. Controlled studies are needed to determine if selective aortic arch perfusion improves resuscitation outcome.     

Aortic and right atrial systolic pressures during cardiopulmonary resuscitation: a potential indicator of the mechanism of blood flow

The absolute difference between aortic and right atrial systolic pressure (systolic pressure gradient) and the difference between the aortic diastolic and right atrial diastolic pressure (coronary perfusion pressure) were evaluated in a series of 63 adult mongrel dogs undergoing five different methods of cardiopulmonary resuscitation (CPR). Fluid-filled pressure monitoring catheters were placed in the ascending aorta and right atrium in each of the animals after induction of anesthesia with morphine sulfate and 1% halothane and oxygen. The animals were then fibrillated with a transvenous electrode catheter that had been introduced into a ventricle. After a "down time" of 3 minutes during which no CPR was performed, the animals' lungs were ventilated, and one of five methods of CPR was initiated. The systolic pressure gradient and coronary perfusion pressure were measured in all animals 1 minute after CPR was begun, and in all but the group undergoing open-chest cardiac massage after 7 minutes and 17 minutes of CPR. The systolic pressure gradient and coronary perfusion pressure were greatest during open-chest cardiac massage (true cardiac compression), intermediate in external mechanical CPR (Thumper) and standard CPR (greater in small dogs than large dogs), and lowest in CPR performed with a combined thoracic and abdominal vest apparatus (predominantly thoracic pump). The observation that the systolic pressure gradient between intrathoracic chambers is largest in open-chest cardiac massage and smallest in vest CPR suggests that similar measurements recorded during the performance of human cardiac resuscitation may be useful in determining the mechanism of blood flow.     

Comparison of intravenous and intranasal administration of epinephrine during CPR in a canine model.

STUDY OBJECTIVES: Epinephrine improves coronary perfusion pressure during CPR. However, administration of epinephrine during CPR may be delayed or omitted if IV or endotracheal access is not established. Therefore, the objective of this study was to determine if intranasal administration of epinephrine during CPR would provide an alternate route of drug administration that is readily accessible and requires no special technical skills. DESIGN AND SETTING: Randomized blinded study performed in a controlled laboratory environment. TYPE OF PARTICIPANTS: Twenty mongrel dogs weighing 19.5 +/- 4.6 kg. INTERVENTIONS: All dogs received either IV epinephrine 0.015 mg/kg or intranasal epinephrine 14 mg per nostril. Phentolamine (5 mg per nostril) was administered intranasally one minute before nasal administration of epinephrine to improve absorption. Each dog underwent three minutes of ventricular fibrillation followed by seven minutes of CPR with a pneumatic chest compression device. Epinephrine was administered at two minutes into CPR. MEASUREMENTS AND MAIN RESULTS: Seven dogs were excluded because of inadequate baseline coronary perfusion pressure or compression device displacement, leaving a total of 13 dogs for analysis (six IV epinephrine, seven intranasal epinephrine). Baseline coronary perfusion pressure (mean +/- SD) was similar for IV epinephrine and intranasal epinephrine (16.9 +/- 7.1 mm Hg versus 18.2 +/- 13.8 mm Hg, respectively, P = .84). For IV and intranasal epinephrine, coronary perfusion pressure increased to 21.4 +/- 9.2 mm Hg and 24.4 +/- 18.7 mm Hg one minute after epinephrine, respectively (P = .73). Five minutes after epinephrine coronary perfusion pressure was 18.2 +/- 8.7 mm Hg and 24.3 +/- 13.9 mm Hg for IV epinephrine and intranasal epinephrine, respectively (P = .38). The rate of successful resuscitation was similar for both groups, five of seven dogs for intranasal epinephrine and four of six dogs for IV epinephrine (P = .66). CONCLUSION: Intranasal epinephrine has similar effects on coronary perfusion pressure and resuscitation compared with standard-dose IV epinephrine. Therefore, the nasal route for administration of epinephrine appears to be an acceptable alternate method of drug delivery during CPR and compares favorably with standard IV therapy in the canine model. Because of the obvious benefits to human patients, these observations suggest further investigation.     

Dose-related response of centrally administered epinephrine on the change in aortic diastolic pressure during closed-chest massage in dogs

The current recommendation of the American Heart Association is to give 0.5 to 1.0 mg (7.5 to 15 micrograms/kg in a 70-kg man) of epinephrine intravenously every five minutes during cardiac arrest. The optimal dose of epinephrine to augment the aortic diastolic pressure (ADP) is not known. The effect of various doses of central bolus epinephrine on the ADP during closed-chest massage was studied. A group of 25 large dogs was divided equally into five groups: control and 15, 45, 75, and 150 micrograms/kg. After three minutes of cardiac arrest, closed-chest massage was initiated, and the study drug was given two minutes later. The ADP and right atrial pressures were monitored for 15 minutes. Changes in ADP peaked at two minutes after injection in all groups receiving epinephrine, and the drop in ADP over time noted in the control group was prevented by increasing doses of epinephrine. Among the groups receiving epinephrine, however, there was no difference in the absolute ADP and diastolic coronary perfusion pressure.     

Methods for Calculating Coronary Perfusion Pressure During CPR

Coronary perfusion pressure (CPP) is a major indicator of the effectiveness of cardiopulmonary resuscitation in human and animal research studies, however, methods for calculating CPP differ among research groups. Here we compare the 6 published methods for calculating CPP using the same data set of aortic (Ao) and right atrial (RA) blood pressures. CPP was computed using each of the 6 calculation methods in an anesthetized pig model, instrumented with catheters with Cobe pressure transducers. Aortic and right atrial pressures were recorded continuously during electrically induced ventricular fibrillation and standard AHA CPR. CPP calculated from the same raw data set by the 6 calculation methods ranged from −1 (signifying retrograde blood flow) to 26 mmHg (mean ± SD of 15 ± 11 mmHg). The CPP achieved by standard closed chest CPR is typically reported as 10–20 mmHg. Within a single study the CPP values may be comparable; however, the CPP values for different studies may not be a reliable indicator of the efficacy of a given CPR method. Electronically derived true mean coronary perfusion pressure is arguably the gold standard method for representing coronary perfusion pressure.     

Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs

BACKGROUND: It is unknown whether repeated dosages of vasopressin or epinephrine given early or late during basic life support cardiopulmonary resuscitation (CPR) may be able to increase coronary perfusion pressure above a threshold between 20 and 30 mm Hg that renders defibrillation successful. METHODS AND RESULTS: After 4 minutes of cardiac arrest, followed by 3 minutes of basic life support CPR, 12 animals were randomly assigned to receive, every 5 minutes, either vasopressin (early vasopressin: 0.4, 0.4, and 0.8 U/kg, respectively; n=6) or epinephrine (early epinephrine: 45, 45, and 200 microg/kg, respectively; n=6). Another 12 animals were randomly allocated after 4 minutes of cardiac arrest, followed by 8 minutes of basic life support CPR, to receive, every 5 minutes, either vasopressin (late vasopressin: 0.4 and 0.8 U/kg, respectively; n=6), or epinephrine (late epinephrine: 45 and 200 microg/kg, respectively; n=6). Defibrillation was attempted after 22 minutes of cardiac arrest. Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after early vasopressin compared with early epinephrine (50+/-4 versus 34+/-3 mm Hg, P<0.02; 42+/-5 versus 15+/-3 mm Hg, P<0.0008; and 37+/-5 versus 11+/-3 mm Hg, P<0. 002, respectively). Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after late vasopressin compared with late epinephrine (40+/-3 versus 22+/-4 mm Hg, P<0.004, and 32+/-4 versus 15+/-4 mm Hg, P<0.01, respectively). All vasopressin animals survived 60 minutes, whereas no epinephrine pig had return of spontaneous circulation (P<0.05). CONCLUSIONS: Repeated administration of vasopressin but only the first epinephrine dose given early and late during basic life support CPR maintained coronary perfusion pressure above the threshold that is needed for successful defibrillation.     

Organ blood flow and somatosensory-evoked potentials during and after cardiopulmonary resuscitation with epinephrine or phenylephrine

Pure alpha-adrenergic agonists, such as phenylephrine, and mixed alpha- and beta-adrenergic agonists, such as epinephrine, raise perfusion pressure for heart and brain during cardiopulmonary resuscitation (CPR). However, with the high doses used during CPR, these drugs may directly affect vascular smooth muscle and metabolism in brain and heart. We determined whether at equivalent perfusion pressure, continuous infusion of phenylephrine (20 micrograms/kg/min) or epinephrine (4 micrograms/kg/min) leads to equal organ blood flow, cerebral O2 uptake, and cerebral electrophysiologic function. During 20 minutes of CPR initiated immediately upon ventricular fibrillation in anesthetized dogs, left ventricular blood flow was similar with epinephrine (45 +/- 9 ml/min/100 g) or phenylephrine (47 +/- 8 ml/min/100 g) infusion. The ratio of subendocardial to subepicardial blood flow fell equivalently during CPR with either epinephrine (1.23 +/- 0.06 to 0.70 +/- 0.05) or phenylephrine (1.32 +/- 0.07 to 0.77 +/- 0.05) administration. At similar levels of cerebral perfusion pressure (44 +/- 3 mm Hg), similar levels of cerebral blood flow were measured in both groups (27 +/- 3 ml/min/100 g). Cerebral O2 uptake was maintained at prearrest levels in both groups. Somatosensory-evoked potential amplitude was modestly reduced during CPR, but it promptly recovered after defibrillation. During CPR and at 2 hours after resuscitation, there were no differences between drug groups in the level of regional cerebral or coronary blood flow, cerebral O2 uptake, or evoked potentials. Therefore, with minimal delay in the onset of CPR and with equipotent pressor doses of phenylephrine and epinephrine, we found no evidence that one agent provides superior coronary or cerebral blood flow or that epinephrine by virtue of its beta-adrenergic properties adversely stimulates cerebral metabolism at a critical time that would impair brain electrophysiologic function. Moreover, epinephrine did not preferentially impair subendocardial blood flow as might be expected if it enhanced the strength of fibrillatory contractions.     

The effect of norepinephrine versus epinephrine on myocardial hemodynamics during CPR

Alpha-adrenergic agonists improve myocardial blood flow during CPR by increasing aortic diastolic pressure. Adrenergic agonists with beta-2 properties may enhance peripheral vasodilation and may prove less beneficial during CPR. The purpose of this study was to compare epinephrine (E), an alpha-1,2; beta-1,2 agonist, versus norepinephrine, an alpha-1,2; beta-1 agonist, on myocardial hemodynamics during CPR. Twenty swine were instrumented for pressure, arterial and coronary sinus oxygen content (CAO2 and CCSO2, respectively), and myocardial blood flow measurements using tracer microspheres. CAO2, CCSO2, myocardial blood flow, myocardial oxygen delivery (MDO2) and myocardial oxygen consumption (MVO2), extraction ratio, and aortic diastolic pressure were determined during normal sinus rhythm and during CPR following a ten-minute arrest. After three minutes of CPR, the animals were allocated to receive either norepinephrine 0.08 mg/kg (n = 5), norepinephrine 0.12 mg/kg (n = 5), norepinephrine 0.16 mg/kg (n = 5), or epinephrine 0.20 mg/kg (n = 5). One minute after drug administration, all hemodynamic parameters were again determined. Three and one half minutes after drug administration defibrillation was attempted. A Newman-Keuls multiple comparison procedure was used to compare differences following drug administration. During CPR, aortic diastolic pressure averaged less than 13 mm Hg, and myocardial blood flow averaged less than 6 mL/min/100 g. All doses of norepinephrine and epinephrine improved all hemodynamic parameters over those seen during CPR. The two highest doses of norepinephrine significantly improved extraction ratio compared with norepinephrine 0.08 mg/kg (P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)     

Precountershock cardiopulmonary resuscitation improves ventricular fibrillation median frequency and myocardial readiness for successful defibrillation from prolonged ventricular fibrillation: a randomized,controlled swine study

STUDY OBJECTIVE: After prolonged ventricular fibrillation (VF), precountershock cardiopulmonary resuscitation (CPR) will improve myocardial "readiness" for defibrillation compared with immediate defibrillation. METHODS: After 10 minutes of untreated VF, 32 swine (27+/-1 kg) were randomly assigned to receive immediate countershocks (DEFIB), CPR for 3 minutes followed by countershocks (CPR), or CPR for 3 minutes plus intravenous epinephrine followed by countershocks (CPR+EPI). VF waveform was evaluated by fast Fourier transformation. RESULTS: VF amplitude and median frequency by fast Fourier transformation decreased during the untreated VF interval in all groups, and the median frequency subsequently increased during each minute of precountershock CPR. Although the VF median frequency in the 3 groups did not differ after 10 minutes of untreated VF (8.9+/-0.8 Hz versus 8.4+/-0.5 Hz versus 7.3+/-0.5 Hz, respectively), immediately before the first shock the VF median frequency was much lower in the DEFIB group than in either the CPR or CPR+EPI groups (8.9+/-0.8 Hz versus 13.1+/-0.8 Hz versus 13.8+/-0.9 Hz, respectively; P <.01). None of the 10 animals in the DEFIB group attained return of spontaneous circulation after the first set of shocks versus 5 of 10 animals in the CPR group and 6 of 12 animals in the CPR+EPI group (DEFIB versus each CPR group; P <.05). Cardiac output 1 hour after resuscitation was substantially worse in the DEFIB group than in the CPR or CPR+EPI groups (74+/-7 mL/kg per minute versus 119+/-7 mL/kg per minute versus 104+/-15 mL/kg per minute; P <.05). CONCLUSION: Precountershock CPR can result in substantial physiologic benefits compared with immediate defibrillation in the setting of prolonged VF. Moreover, these benefits can be attained with or without the addition of intravenous epinephrine.     

Beta-adrenergic blockade reduces myocardial injury during experimental cardiopulmonary resuscitation

Objectives. We attempted to determine the effects of beta-adrenergie blockade during cardiopulmonary resuscitation (CPR) on defibrillation rates and postresuscitation left ventricular function.Background. The results of previous studies suggest that propranolol administration can both reduce myocardial oxygen requirements and increase coronary perfusion pressure during CPR.Methods. Left ventricular pressure and segment length were measured before and after 5 min of CPR in 22 dogs either given epinephrine (0.015 mg/kg body weight at the onset and after 4 min) or pretreated with propranolol (2 mg/kg) and given epinephrine during CPR.Results. Despite identical epinephrine doses, coronary perfusion pressure during CPR was higher in the epinephrine plus propranolol group (p < 0.05), and defibrillation was successful in 9 of 11 dogs given both epinephrine and propranolol versus 6 of 11 dogs given epinephrine alone (p = NS). Peak and developed left ventricular pressures, left ventricular end-diastolic pressure and the peak rate of left ventricular pressure development (+dP/dt) did not differ between study groups when measured either 5 or 15 min after successful defibrillation. However, when survivors in the epinephrine group were given propranolol after CPR to eliminate compensatory sympathetic stimulation, left ventricular developed pressure and peak +dP/dt were lower (p < 0.05) despite trends toward higher left ventricular end-diastolic pressures and normalized end-diastolic segment lengths compared with dogs given propranolol before CPR.Conclusions. These findings suggest that beta-adrenergic blockade reduces myocardial injury during CPR without decreasing the likelihood of successful defibrillation or compromising spontaneous postresuscitation left ventricular function.     

The effectiveness of bystander CPR in an animal model

Several clinical studies have yielded conflicting results in examining the effectiveness of bystander CPR (BCPR). The purpose of this pilot study was to determine the effectiveness of BCPR in an animal model of cardiac arrest and resuscitation. Ten swine were instrumented for hemodynamic and regional blood flow measurements with tracer microspheres. After two minutes of ventricular fibrillation (VF), the animals received eight minutes of either BCPR (five) or no-bystander CPR (NBCPR; five). Defibrillation was then attempted in both groups. If unsuccessful, CPR was begun and epinephrine 0.02 mg/kg was administered. Defibrillation was attempted again three and one-half minutes after epinephrine administration. Regional myocardial and cerebral blood flows were measured 30 seconds and five and one-half minutes after initiation of BCPR and one minute after epinephrine administration. In the BCPR group, myocardial blood flow was initially 29.0 +/- 33.2 and decreased to 15.0 +/- 21.5 mL/min/100 g during the last two and one-half minutes of BCPR. Cortical cerebral blood flow was initially 2.0 +/- 2.8 and fell to 0.6 +/- 0.8 mL/min/100 g during the last two and one-half minutes of BCPR. There were no statistical differences in myocardial blood flow and cerebral blood flow between the initial or late stages of BCPR (P greater than .14). There were no statistical differences in myocardial blood flow and cerebral blood flow between BCPR and NBCPR groups after epinephrine administration (P greater than .09).(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of cardiopulmonary bypass, high-dose epinephrine, and standard-dose epinephrine in resuscitation from post-countershock electromechanical dissociation.

STUDY OBJECTIVE: To determine the effects of cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, and standard-dose epinephrine on perfusion pressures, myocardial blood flow, and resuscitation from post-countershock electromechanical dissociation. DESIGN: Prospective, controlled laboratory investigation using a canine cardiac arrest model randomized to receive one of three resuscitation therapies. INTERVENTIONS: After the production of post-countershock electromechanical dissociation, 25 animals received ten minutes of basic CPR and were randomized to receive cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, or standard-dose epinephrine. MEASUREMENTS AND MAIN RESULTS: Myocardial blood flow was measured using a colored microsphere technique at baseline, during basic CPR, and after intervention. Immediate and two-hour resuscitation rates were determined for each group. Return of spontaneous circulation was achieved in eight of eight cardiopulmonary bypass with standard-dose epinephrine compared with four of eight high-dose epinephrine and three of eight standard-dose epinephrine animals (P less than .04). One animal was resuscitated with CPR alone and was excluded. Survival to two hours was achieved in five of eight cardiopulmonary bypass with standard-dose epinephrine, four of eight high-dose epinephrine, and three of eight standard-dose epinephrine animals (NS). Coronary perfusion pressure increased significantly in the cardiopulmonary bypass with standard-dose epinephrine group when compared with the other groups (cardiopulmonary bypass with standard-dose epinephrine, 76 +/- 45 mm Hg; high-dose epinephrine, 24 +/- 12 mm Hg; standard-dose epinephrine, 3 +/- 14 mm Hg; P less than .005). Myocardial blood flow was higher in cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephrine animals compared with standard-dose epinephrine animals but did not reach statistical significance. Cardiac output increased during cardiopulmonary bypass with standard-dose epinephrine (P = .001) and standard-dose epinephrine (NS) compared with basic CPR but decreased after epinephrine administration in the high-dose epinephrine group (NS). CONCLUSION: Resuscitation from electromechanical dissociation was improved with cardiopulmonary bypass and epinephrine compared with high-dose epinephrine or standard-dose epinephrine alone. However, there was no difference in survival between groups. Cardiopulmonary bypass with standard-dose epinephrine resulted in higher cardiac output, coronary perfusion pressure, and a trend toward higher myocardial blood flow. A short period of cardiopulmonary bypass with epinephrine after prolonged post-countershock electromechanical dissociation cardiac arrest can re-establish sufficient circulation to effect successful early resuscitation.