Sandra H. Ralston

Intrapulmonary epinephrine during prolonged cardiopulmonary resuscitation: Improved regional blood flow and resuscitation in dogs

Blood flow to vital organs was measured at five-minute intervals during 20 minutes of cardiopulmonary resuscitation (CPR) and ventricular fibrillation in two groups of anesthetized dogs (n = 15 per group). The relationship between organ blood flow and restoration of circulation after 20 minutes was assessed with no additional treatment in Group I and with intrapulmonary epinephrine in Group II. Cardiac output and organ blood flow did not vary significantly in Group I. In Group II, intrapulmonary epinephrine significantly improved blood flow to the myocardium, the brain, and the adrenals. A mean myocardial blood flow of less than 0.13 mL/min/g resulted in no survival, while a flow of greater than 0.16 mL/min/g resulted in survival. These studies show that a critical level of myocardial blood flow is required to restore ability of the heart to function as a pump after prolonged CPR, and that a drug that increases flow improves resuscitation efforts.

Cardiopulmonary resuscitation with interposed abdominal compression in dogs

This study was conducted to evaluate the hemodynamic effectiveness of a new modification of cardiopulmonary resuscitation (CPR), termed interposed abdominal compression-CPR (IAC-CPR). IAC-CPR utilizes all the steps of standard CPR with the addition of abdominal compressions interposed during the release phase of chest compression. Ventricular fibrillation was induced electrically in 10 anesthetized dogs, and either IAC-CPR or standard CPR was initiated while arterial and venous blood pressures and cardiac output were monitored. The two CPR methods were alternated every 3 minutes over a period of 30 minutes. The addition of interposed abdominal compressions to standard CPR improved arterial pressures and perfusion in 10 of 10 dogs. Brachial arterial blood pressure averaged 87/32 mm Hg during IAC-CPR vs 58/16 mm Hg during standard CPR. Cardiac output (±SE) averaged 24.2 ± 5.7 ml/min/kg during IAC-CPR vs 13.8 ± 2.6 ml/min/kg during standard CPR. IAC-CPR requires no extra mechanical equipment, and, if proven effective in human trials, may improve resuscitation success in the field and in the hospital.

Endotracheal versus intravenous epinephrine during electromechanical dissociation with CPR in dogs.

The dose-response curves of epinephrine given either IV or endotracheally (ET) were compared during resuscitation from electromechanical dissociation (EMD). Ten anesthetized dogs were subjected to a two-minute period of electrically induced ventricular fibrillation (VF) followed by defibrillation without CPR to produce EMD. Mechanical CPR was followed by injection of either ET or IV epinephrine. Successful response was defined as a return of pulsatile blood pressure within two minutes of drug administration. Using log-dose increments of epinephrine, experimental trials were repeated in each animal. The IV and ET median effective doses were 14 and 130 micrograms/kg, respectively. When the trials were successful, the time between drug administration and either arterial blood pressure increases or return of spontaneous circulation did not differ significantly for the ET and IV groups. These results show that the dosage for epinephrine delivered ET must be higher than the IV dosage to achieve the same response during CPR.

Regional blood flow during cardiopulmonary resuscitation with abdominal counterpulsation in dogs

The addition of abdominal counterpulsation to standard cardiopulmonary resuscitation (AC-CPR) during ventricular fibrillation has been shown to improve cardiac output, oxygen uptake, and central arterial blood pressure in dogs. The present study was performed to determine the effect of AC-CPR on regional blood flow. Regional blood flow was measured with radioactively labeled microspheres during sinus rhythm and during alternate periods of AC-CPR and standard CPR (STD-CPR) in nine dogs anesthetized with pentobarbital. Blood pressures and oxygen uptake were measured continuously. As in previous studies, diastolic arterial pressure was higher (30.8%) during AC-CPR than during STD-CPR, as were cardiac output (24.5%) and oxygen uptake (37.5%). Whole brain and myocardial blood flow increased 12.0% and 22.7%, respectively, during AC-CPR. Blood flow to abdominal organs was not changed appreciably in response to abdominal compression, and postmortem examination revealed no gross trauma to the abdominal viscera. The AC-CPR technique is simple and is easily added to present basic life support procedures. In light of the improvements observed in myocardial and cerebral blood flow, AC-CPR could significantly improve the outcome of CPR attempts.

Cardiac, thoracic, and abdominal pump mechanisms in cardiopulmonary resuscitation: Studies in an electrical model of the circulation

To investigate alternative mechanisms generating artificial circulation during cardiopulmonary resuscitation (CPR), an electrical model of the circulation was developed. Heart and blood vessels were modeled as resistive-capacitive networks; pressures in the chest, abdomen, and vascular compartments as voltages; blood flow as electric current; blood inertia as inductance; and the cardiac and venous valves as diodes. External pressurization of thoracic and abdominal vessels, as would occur in CPR, was simulated by application of half-sinusoidal voltage pulses. Three modes of creating artificial circulation were studied: cardiac pump (CP), in which the atria and ventricles of the model were pressurized simultaneously; thoracic pump (TP), in which all intrathoracic elements of the model were pressurized simultaneously; and abdominal pump (AP), in which the abdominal aorta and inferior vena cava of the model were pressurized simultaneously. Flow was greatest with the CP, less with the TP, and least with the AP mechanism. However, the AP could be practically combined with either the CP or TP by interposition of abdominal compressions between chest compressions (IAC-CPR). Our model predicts that this combined method can substantially improve artificial circulation, especially when cardiac compression does not occur and chest compression invokes only the thoracic pump mechanism.

Theoretical advantages of abdominal counterpulsation in CPR as demonstrated in a simple electrical model of the circulation

Recent animal studies and preliminary clinical observations suggest that the addition of interposed abdominal compressions (IAC) to ventilation and chest compression of standard cardiopulmonary resuscitation (CPR) augments blood flow, blood pressures, and immediate survival. To investigate the physical basis for enhanced circulation during IAC-CPR, we developed an electrical model of the circulation. Heart and blood vessels were modeled as resistive-capacitive networks, pressures as voltages, blood flow as electric current, blood inertia as inductance, and the cardiac and venous valves as diodes. External pressurization of the heart and great vessels, as would occur in CPR, was simulated by application by half-sinusoidal voltage pulses between vascular capacitances and ground. Closed-chest CPR was simulated by pressurization of all intrathoracic capacitances. IAC was simulated by similar pressurization of the inferior vena cava and abdominal aorta, 180 degrees out of phase with chest compression. During simulation of CPR, IAC improved cranial and myocardial perfusion at all levels of chest compression pressure by amounts linearly related to peak abdominal pressure, suggesting that the abdomen can function as a second, independent blood pump during CPR. Brain and heart flow were improved further during simulated vasoconstriction in kidneys, abdominal viscera, and extremities. Based on the fundamental properties of the cardiovascular system represented in the model, abdominal counterpulsation provides a rational basis for flow augmentation during CPR.

Fluid loading with whole blood or ringer's lactate solution during cpr in dogs☆

The influence of fluid loading during CPR on oxygen uptake and blood flow was investigated in 18 dogs (12-26 kg). Blood flows were measured with radioactive microspheres at 5 (control CPR), 13 and 20 min after the initiation of ventricular fibrillation and CPR. After 10 min, 9 dogs received a rapid infusion of whole blood (11 ml/kg, i.v.) and 9 dogs received Ringers solution (11 ml/kg, i.v.). Oxygen uptake was not significantly altered by fluid loading with either whole blood or Ringers solution. Fluid loading increased cardiac output 34% over the 5 min control value. However, left ventricular perfusion decreased to 74% and brain flow decreased to 65% of control. At 20 min, cardiac output and brain flow returned to near control values, while left ventricular flow remained low. Changes in organ perfusion can be explained in part by the concurrent changes in blood pressures. Central venous diastolic pressure increased significantly (from 9 to 14 mmHg) after fluid load. However, central arterial diastolic pressure did not rise proportionately (from 32 to 34 mmHg). Hence, the central A-V diastolic pressure difference decreased. Although fluid loading during CPR improved cardiac output, flow to the heart and brain decreased. Further, there was no increase in oxygen consumption, indicating that fluid loading did not improve metabolic status.

Venous and arterial blood gases during and after cardiopulmonary resuscitation in dogs

This study was undertaken to characterize blood gas, pH, and lactate changes during and after cardiopulmonary resuscitation (CPR) in arterial and venous samples. Blood samples were withdrawn from the brachial artery, aortic arch, pulmonary artery, coronary sinus, and either the right or left cardiac ventricle of 24 anesthetized dogs. Ventricular fibrillation (VF) was induced electrically, and mechanical CPR was begun. Blood samples were withdrawn before CPR, at 2, 5, 7, and 9 minutes during CPR, and at 1, 3, 10, 30, and 60 minutes after defibrillation. Control arterial and venous samples indicated mild metabolic acidosis. During CPR, there was a significant arteriovenous difference in pH, PCO2, and PO2. With ventilation onset, arterial pH increased 0.25 units, PCO2 decreased 22 mm Hg, and PO2 increased 200 mm Hg. Venous blood gases exhibited gradual changes during the CPR period. With the re-establishment of circulation and spontaneous respirations, both the arterial and venous pH levels decreased to nearly 7.1, and PCO2 approached 40 mm Hg. Lactate increased to 32 mg/dl during 9 minutes of CPR and did not significantly differ after defibrillation. Blood gases and pH returned to control values within an hour. This study suggests that arterial blood gases are sensitive to rapid changes occurring in the pulmonary capillary bed, while venous blood gases reflect changes occurring in the systemic capillary bed.

Effects of naloxone on the adrenomedullary response during and after cardiopulmonary resuscitation in dogs

To determine the effects of naloxone, an opiate antagonist, on the adrenomedullary response to cardiac arrest, plasma epinephrine and norepinephrine levels were measured before, during, and after cardiac arrest in dogs. Ventricular fibrillation was induced in 12 dogs anesthetized with pentobarital sodium (30 mg/kg) and standard American Heart Association cardiopulmonary resuscitation (CPR) was begun using a mechanical device. At 6.5 minutes of CPR, naloxone (10 mg/kg) or 0.9% saline (10 ml) was given intravenously. At 12 minutes of CPR, the cardiac ventricles were electrically defibrillated. Plasma epinephrine and norepinephrine levels were measured before ventricular fibrillation; at 2.5, 4.5, 9.5, and 11.5, minutes of CPR; and at 5, 10, 15, and 20 minutes after resuscitation. Epinephrine and norepinephrine increased from prearrest levels of 3.66 +/- 0.67 (+/- SE) and 24.02 +/- 3.67 ng/ml to 66.67 +/- 9.65 and 74.00 +/- 9.91 ng/ml, respectively, at 4.5 minutes of CPR. After resuscitation, norepinephrine levels remained slightly elevated, while epinephrine fell to prearrest levels. Naloxone did not cause a significant change in either epinephrine or norepinephrine from 6.5 minutes of CPR (time of treatment) through 20 minutes postresuscitation. In addition, naloxone had no effect on either the end-diastolic pressure difference during CPR or resuscitation outcome. We conclude that cardiac arrest causes significant increases in plasma epinephrine and norepinephrine levels, which remain elevated for the duration of the arrest, and that naloxone has no effect on these levels.

Alpha agonist drug usage during CPR

As a result of many investigations, the role of adrenergic drugs in cardiopulmonary resuscitation (CPR) has been identified, but the choice of drug and drug dosage are yet to be defined. It has been suggested that the successful return of circulation following cardiac arrest is linked with the ability to achieve a diastolic arterial pressure of 30 to 40 mm Hg. Since the turn of this century, the addition of epinephrine to resuscitation procedures has been shown to increase greatly diastolic arterial pressures and resuscitation success. The key to epinephrines action lies in its alpha agonist properties (which promote peripheral vasoconstriction, leading ultimately to increased coronary perfusion) rather than its direct beta effects (which increase the workload of the fibrillating myocardium). Indeed, pure alpha agonist drugs work as effectively as epinephrine in restoring the circulation, and beta agonists are totally ineffective when used during the arrest period. The hypothesis that pure alpha agonists may be superior to epinephrine during CPR is the subject of current investigations. To date, drug dosage has been largely empirical. During CPR other factors play a role in drug effectiveness, including the injection site, rate of blood flow, and current metabolic status. Because the early use of effective alpha agonists can improve survival, the search for the best drug, via the best route and at the best dosage deserves additional investigation.