Optimizing drug therapy during cardiopulmonary resuscitation.
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Animals↗
Biomedical subjects
K B Kern
Publications and source records attributed to K B Kern.
Internal mammary artery and saphenous vein graft patency. Effects of aspirin.
As part of two Department of Veterans Affairs Cooperative Trials, we obtained angiographic patency data for internal mammary artery (IMA) and saphenous vein grafts to the left anterior descending (LAD) coronary artery at 1 year after coronary artery bypass surgery. Patients received either aspirin 325 mg q.d., aspirin 325 mg t.i.d., aspirin 325 mg and dipyridamole 75 mg t.i.d., or placebo. Aspirin was initiated either 12 hours before or 6 hours after operation. Patients were stratified preoperatively for extent of disease and randomized to the therapies outlined above. There was no randomization to IMA versus saphenous vein grafts to the LAD. When the patients taking placebo were compared with those taking aspirin, there were no differences in the IMA (100.0% versus 92.1%, p = 0.385) or vein graft (88.8% versus 90.4%, p = 0.675) patency rates. The patency rate, irrespective of treatment, for all IMA grafts was 92.8% (220 of 237) versus 90.1% (345 of 383) for all vein grafts to the LAD (p = 0.309). Thus, both the IMA and vein grafts had excellent patency rates at 1 year. Aspirin did not alter this at 1 year, and there were no differences between IMA and vein graft patency to the LAD.
Aspirin↗
End-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. A prognostic indicator for survival.
The effectiveness of ongoing cardiopulmonary resuscitation efforts is difficult to evaluate. Recent studies suggest that carbon dioxide excretion may be a useful noninvasive indicator of resuscitation from cardiac arrest. A prospective clinical study was done to determine whether end-tidal carbon dioxide monitoring during cardiopulmonary resuscitation could be used as a prognostic indicator of resuscitation and survival. Thirty-five cardiac arrests in 34 patients were monitored with capnometry during cardiopulmonary resuscitation during a 1-year period. Nine patients who were successfully resuscitated had higher average end-tidal carbon dioxide partial pressures during cardiopulmonary resuscitation than 26 patients who could not be resuscitated (15 +/- 4 vs 7 +/- 5 mm Hg). The 3 patients who survived to leave the hospital had a higher average end-tidal carbon dioxide partial pressure than the 32 nonsurvivors (17 +/- 6 vs 8 +/- 5 mm Hg). All 9 patients who were successfully resuscitated had an average end-tidal carbon dioxide partial pressure of 10 mm Hg or greater. No patient with an average end-tidal carbon dioxide partial pressure of less than 10 mm Hg was resuscitated. Data from this prospective clinical trial indicate that findings from end-tidal carbon dioxide monitoring during cardiopulmonary resuscitation are correlated with resuscitation from and survival of cardiac arrest.
Blood Gas Monitoring, Transcutaneous↗
Changes in expired end-tidal carbon dioxide during cardiopulmonary resuscitation in dogs: a prognostic guide for resuscitation efforts.
Expired end-tidal carbon dioxide (PCO2) measurements made during cardiopulmonary resuscitation have correlated with cardiac output and coronary perfusion pressure when wide ranges of blood flow are included. The utility of such measurements for predicting resuscitation outcome during the low flow state associated with closed chest cardiopulmonary resuscitation remains uncertain. Expired end-tidal PCO2 and coronary perfusion pressures were measured in 15 mongrel dogs undergoing 15 min of closed chest cardiopulmonary resuscitation after a 3 min period of untreated ventricular fibrillation. In six successfully resuscitated dogs, the mean expired end-tidal PCO2 was significantly higher than that in nine nonresuscitated dogs only after 14 min of cardiopulmonary resuscitation (6.2 +/- 1.2 versus 3.4 +/- 0.8 mm Hg; p less than 0.05). No differences in expired end-tidal PCO2 values were found at 2, 7 or 12 min of cardiopulmonary resuscitation. A significant decline in end-tidal PCO2 levels during the resuscitation effort was seen in the nonresuscitated group (from 6.3 +/- 0.8 to 3.4 +/- 0.8 mm Hg; p less than 0.05); the successfully resuscitated group had constant PCO2 levels throughout the 15 min of cardiac arrest (from 6.8 +/- 1.1 to 6.2 +/- 1.2 mm Hg). Changes in expired PCO2 levels during cardiopulmonary resuscitation may be a useful noninvasive predictor of successful resuscitation and survival from cardiac arrest.
Animals↗
Changes in right ventricular relaxation during acute anterior myocardial infarction in pigs.
To determine the effect of an anteroseptal myocardial infarction on right ventricular systolic and diastolic function, we studied 12 pigs before and 1 h after left anterior descending coronary artery occlusion. Total arterial occlusion was achieved by the percutaneous, transcatheter placement of a 1 mm Teflon plug into the mid portion of the artery. The resulting infarction involved 28 (SEM 3)% of the left ventricular wall, in the anterior and septal regions. A small rim of the right ventricular free wall adjacent to the septum and the right ventricular apex were also affected. End diastolic pressures in both ventricles rose significantly: left ventricular from 12(1) to 20(2) mm Hg and right ventricular from 8(1) to 10(1) mm Hg. Right ventricular peak systolic pressure increased from 29(2) to 35(2) mm Hg while left ventricular peak systolic pressure did not change. One hour after infarction the half time of isovolumic relaxation of the right ventricle was prolonged from 6.9(0.5) to 8.7(0.4) ms. Ejection fraction in both ventricles was depressed: from 46(1) to 34(2)% in the right ventricle and from 69(3) to 49(3) in the left ventricle. There was no change in either right or left ventricular dP/dt. These data suggest that right ventricular systolic and diastolic dysfunction occurs as the result of an anteroseptal myocardial infarction in pigs.
Acute Disease↗
Plasma catecholamines and resuscitation from prolonged cardiac arrest.
Plasma catecholamine levels rise markedly with cardiac arrest and attempted resuscitation. We examined whether epinephrine (EPI) or norepinephrine (NE) plasma concentrations could predict resuscitation outcome. In nine mongrel dogs, EPI and NE levels were drawn before cardiac arrest and after 8 and 14 min of cardiac arrest and CPR. Intravenous EPI (1 mg) was given 1 min before the last plasma level was drawn. Catecholamines were quantitated by high-performance liquid chromatography with triple-electrode coulometric electrochemical detection. Plasma catecholamines increased significantly with cardiac arrest, EPI levels increased from a control level of 15.9 +/- 3.0 to 396.0 +/- 63.3 pmol/ml after 8 min of cardiac arrest (p less than .05), and NE levels similarly increased from 4.4 +/- 1.7 to 66.5 +/- 12.0 pmol/ml (p less than .01). Neither the absolute catecholamine plasma concentration nor the response to cardiac arrest of the endogenous catecholamine concentrations could predict outcome, but catecholamine responses to exogenous EPI did correlate with outcome. Animals which were subsequently resuscitated had a greater increase in the plasma EPI concentrations after exogenous EPI than animals that were not resuscitated, a 53-fold vs. a 23-fold increase (p less than .05). Successfully resuscitated animals also had increased NE levels after exogenous EPI, while unsuccessfully resuscitated animals had either no change or a decrease (p less than .02). Successfully resuscitated animals had an increase in coronary perfusion pressure (p less than .01) in response to exogenous EPI, in contrast to those that were not resuscitated. This suggests that the exogenous administration of EPI during prolonged CPR is beneficial despite markedly elevated endogenous catecholamine levels.
Animals↗
Continuous transtracheal oxygen delivery during cardiopulmonary resuscitation. An alternative method of ventilation in a canine model.
Adequate oxygenation of apneic subjects can be maintained by constant flow transtracheal oxygen (TTO), but this method alone is associated with hypercapnia. The "bellows" effect of external chest compressions (ECC) might prevent this problem if the airway were kept open by TTO. In dogs, we investigated the utility of TTO delivered at 15 L/min by a percutaneously placed intratracheal catheter, plus ECC (TTO/ECC) as an alternative method of ventilation during CPR. TTO was applied to anesthetized, paralyzed dogs in normal sinus rhythm (NSR) at various rates of ECC and during ventricular fibrillation (VF) at an ECC rate of 80/min. During NSR and VF, hypercapnia did not develop and arterial oxygen saturations were maintained above 90 percent. During NSR, the PaCO2 decreased and the pH increased as the ECC rate increased. For many of the animals, coronary perfusion pressure remained above 20 mm Hg during VF, suggesting that these animals could be resuscitated to NSR. In another phase, after 15 min of VF using TTO/ECC, seven of nine animals were defibrillated. We conclude that ventilatory and hemodynamic support adequate to permit successful resuscitation to NSR is provided by the combination of TTO/ECC to apneic dogs during VF.
Animals↗
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.
Animals↗
Open chest massage for resuscitation from cardiac arrest.
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Heart Arrest↗
Myocardial perfusion pressure: a predictor of 24-hour survival during prolonged cardiac arrest in dogs.
Myocardial perfusion pressure, defined as the aortic diastolic pressure minus the right atrial diastolic pressure, correlates with coronary blood flow during cardiopulmonary resuscitation (CPR) and predicts initial resuscitation success. Whether this hemodynamic parameter can predict 24-h survival is not known. We examined the relationship between myocardial perfusion pressure and 24-h survival in 60 dogs that underwent prolonged (20 min) ventricular fibrillation and CPR. Forty-two (70%) animals were initially resuscitated and 20 (33%) survived for 24 h. Myocardial perfusion pressure was significantly greater when measured at 5, 10, 15 and 20 min of ventricular fibrillation in the resuscitated animals than in the non-resuscitated animals (P less than 0.01). Likewise, the myocardial perfusion pressure was also greater in the animals that survived 24 h than in animals that were resuscitated, but died before 24 h (P less than 0.02). Myocardial perfusion pressure measured after 10 min of CPR was 11 +/- 2 mmHg in animals never resuscitated, 20 +/- 3 mmHg in those resuscitated that died before 24 h and 29 +/- 2 mmHg in those that survived 24 h (P less than 0.05). A myocardial perfusion pressure at 10 min of CPR of 20 mmHg or less is an excellent predictor of poor survival (negative predictive value = 96%). Myocardial perfusion pressure is a useful index of CPR effectiveness and therefore may be a useful guide in helping to optimize resuscitation efforts.
Animals↗
Acid-base balance in a canine model of cardiac arrest.
Our study was performed to determine the pattern of arterial, venous, and cerebral spinal fluid (CSF) acidosis in a canine model of cardiac arrest and resuscitation; and the effect of bicarbonate treatment on arterial, venous, and CSF acidosis. Animals were instrumented to sample arterial blood, mixed venous blood, and CSF through a cisternal catheter. Following six minutes of ventricular fibrillation, manual CPR efforts were begun and continued for 30 minutes of cardiac arrest. Arterial, mixed venous, and CS fluids were sampled at baseline, six, 12, 18, 24, 27, and 30 minutes. Ten experimental dogs received sodium bicarbonate (2 mEq/kg) at 20 minutes of cardiac arrest, while ten animals in the control group received no alkali treatment. The experimental group showed a significantly higher arterial (7.79 +/- 0.20 vs 7.46 +/- 0.16 at 30 minutes) and venous pH (7.34 +/- 0.12 vs 7.19 +/- 0.10 at 24 minutes) following bicarbonate administration. This higher pH occurred despite a concomitant increase in arterial (31 +/- 10 vs 19 +/- 9 mm Hg at 27 minutes; 31 +/- 9 vs 10 +/- 8 at 30 minutes) and venous (104 +/- 30 vs 63 +/- 10 mm Hg at 24 minutes) pCO2. CSF analysis showed a gradually worsening acidosis. However, CSF pH (7.12 +/- 0.14 vs 7.16 +/- 0.23 at 30 minutes) and pCO2 were not significantly changed by the administration of bicarbonate.
Acidosis↗
Influence of compression rate on initial success of resuscitation and 24 hour survival after prolonged manual cardiopulmonary resuscitation in dogs.
The influence of chest compression rate on initial resuscitation success and 24 hr survival after prolonged manual cardiopulmonary resuscitation (CPR) was investigated in 26 morphine-anesthetized dogs (17 to 30 kg). After placement of aortic and right atrial micromanometers and induction of ventricular fibrillation, manual CPR was commenced immediately and continued for 30 min. One group of 13 dogs underwent manual CPR at a compression rate of 60/min, and the other group at a rate of 120/min. The compression durations in the two groups were not significantly different (51.7 +/- 1.8% at 60/min vs 51.6 +/- 1.9% at 120/min). No drugs other than sodium bicarbonate were administered during CPR. A maximum of three attempts was permitted to defibrillate the heart. Successfully defibrillated animals were followed for 24 hr, during which time no treatment, other than naloxone, was given to reverse the effects of morphine. Arterial blood pH, PCO2, and PO2 were not significantly different in the two groups throughout the CPR period. When compared with the compression rate of 60/min, the compression rate of 120/min produced more successfully defibrillated animals (12/13 at 120/min vs 2/13 at 60/min, p less than .002) and more 24 hr survivors (8/13 at 120/min vs 2/13 at 60/min, p less than .03). All 24 hr survivors were conscious and able to sit, stand, and drink normally. One 24 hr survivor in each group had difficulty walking. Improved survival with the high-rate compression technique was consistent with the significantly higher mean aortic (systolic and diastolic) and coronary perfusion pressures attained with high-rate compressions (all p less than .002). Although the clinical applicability of these findings has yet to be demonstrated, they provide empirical support for the recent decision to increase the chest compression rate for manual CPR recommended by the American Heart Association, and indicate that the hemodynamic and survival benefits of faster compression rates in this experimental preparation were not dependent on covariant alterations in compression duration.
Animals↗
Cardiac catheterization for patients with postinfarction angina.
A retrospective review was conducted to determine the incidence of cardiac catheterization for postinfarction angina, the associated coronary anatomy, and the subsequent clinical course. Over one year, 30 of 178 myocardial infarctions were complicated by postinfarction angina resulting in cardiac catheterization. This was 18% of cardiac catheterizations for evaluation of coronary artery disease. Among the 30 patients, 3 had left main disease, 3 had triple-vessel disease, 11 had double-vessel disease, 11 had single-vessel disease, and 2 had no significant disease. Nine patients had proximal left anterior descending disease without left main disease. In contrast to previous autopsy or surgical series, the extent of coronary artery involvement was less severe and followed a distribution similar to that found in uncomplicated myocardial infarctions. Nevertheless, 17 of the 30 patients underwent revascularization with angioplasty or bypass surgery compared with 41 of 137 without postinfarction angina (p = 0.01). Clinical characteristics of the patients with postinfarction angina did not predict who would ultimately require revascularization. Cardiac catheterization is necessary for management of patients with postinfarction angina, because a majority of them will require revascularization.
Angina Pectoris↗
Open-chest cardiac massage after closed-chest compression in a canine model: when to intervene.
Open-chest cardiac massage appears beneficial in improving hemodynamics during resuscitation efforts and in improving resuscitation success. The time between cardiac arrest and the initiation of open-chest cardiac massage is crucial. It would appear that if initiation of open chest cardiac massage is delayed for more than 20 min from the onset of cardiac arrest, little or no successful outcome can be expected. Further techniques for assessing the adequacy of closed-chest compression CPR are needed. Such techniques would allow early identification of ineffective resuscitation efforts and provide the opportunity for early change to other, presumably more effective, techniques.
Animals↗
Comparison of mechanical techniques of cardiopulmonary resuscitation: survival and neurologic outcome in dogs.
Three currently available mechanical devices for cardiopulmonary resuscitation (CPR) were compared using a canine cardiac arrest model. Twenty-four-hour survival without neurologic deficit was the goal. A group of 30 large mongrel dogs was divided equally among Thumper CPR, simultaneous compression and ventilation (SCV) CPR, and vest CPR. Ventricular fibrillation was induced electrically, and after 3 minutes of no intervention, one of the three types of mechanical CPR was performed for 17 minutes. SCV CPR and vest CPR produced significantly greater aortic and right atrial systolic pressures than Thumper CPR (P less than .03). The SCV CPR technique also produced significantly higher aortic diastolic pressure and right atrial diastolic pressure than either of the other methods (P less than .03). However, coronary perfusion pressure was not different among the three mechanical methods. No differences in immediate resuscitation, 24-hour survival, or neurologic deficit scores at 24 hours were found. Neither SCV nor the vest techniques of CPR appear better for survival or neurologic outcome than standard cardiopulmonary resuscitation performed with the Thumper.
Animals↗
Neurologic benefits from the use of early cardiopulmonary resuscitation.
The efficacy of bystander CPR in resuscitation from cardiac arrest when defibrillation is available within five to six minutes has been questioned. Epidemiologic studies from different cities have shown conflicting results. We conducted a study to determine the effect of early CPR versus no CPR on resuscitability, 24-hour survival, and neurologic deficit in an animal model of cardiac arrest. Twenty-two mongrel dogs were subjected to five minutes of electrically induced ventricular fibrillation. In 11 dogs, closed-chest massage and ventilation with room air was begun immediately and was continued for five minutes. The other 11 dogs received no CPR. At five minutes defibrillation was attempted and advanced cardiac life support (ACLS) protocols were followed until the animal was resuscitated or died. No statistical difference in resuscitability or 24-hour survival between the two groups was demonstrated. Eight of 11 "early CPR" animals were resuscitated and survived 24 hours; six of 11 "no CPR" dogs were resuscitated, and five lived for 24 hours. A significant difference was demonstrated by the Student t test in neurologic deficit and ease of resuscitation. "Early CPR" dogs had no neurologic deficit, while "no CPR" dogs had a 41% deficit (P less than .01). "Early CPR" dogs were resuscitated in significantly less time once ACLS was started (29 versus 317 seconds), and required less electrical energy (100 versus 560 J), fewer countershocks (1.3 versus 4.0), and less epinephrine (0.1 versus 1.7 mg) than did "no CPR" animals. In this animal model of cardiac arrest, early CPR was shown to be beneficial to neurologic function and ease of resuscitation, even when ACLS was provided within five minutes.
Animals↗
Long-term survival with open-chest cardiac massage after ineffective closed-chest compression in a canine preparation.
The ultimate goal of cardiopulmonary resuscitation (CPR) is long-term, neurologically intact survival. This study examined whether open-chest cardiac massage could improve 7 day survival and neurologic function when instituted after the failure of standard closed-chest compression CPR. Twenty-nine mongrel dogs were anesthetized and then instrumented with catheters to monitor right atrial and ascending aortic pressures. Ventricular fibrillation was induced and after 3 min standard CPR was begun. Standard CPR was performed with a Thumper programmed for 2 inch chest compressions at 60/min with a 50% duty cycle. External defibrillation was attempted twice after 15 min of ventricular fibrillation. Unsuccessfully defibrillated animals were randomly assigned to either an additional 2 min of continued closed-chest compressions, or 2 min of open-chest cardiac massage. All animals underwent a period of advanced cardiac life support and were followed until they were resuscitated or died. Follow-up care, including scoring of neurologic deficit, was performed for 7 days. In dogs receiving open-chest cardiac massage there was significantly more immediate resuscitation success (14/14 vs 5/14; p less than .005), 24 hr survival (12/14 vs 4/14; p less than .005), and 7 day survival (11/14 vs 4/14; p less than .02) than in those receiving continued closed-chest compression. Open-chest cardiac massage significantly improved long-term outcome when instituted after 15 min of ineffective closed-chest compression.
Animals↗
Digoxin-diltiazem interaction: a pharmacokinetic evaluation.
The pharmacokinetics of digoxin were studied before and after a 2 week course of diltiazem, 30 mg four times daily, in 7 healthy volunteers. Each subject received an IV dose of digoxin before starting diltiazem and again on day 15 of the study. Diltiazem was continued until all sera and urine were collected. During the control and diltiazem phases, respectively, the terminal elimination rate constants were 0.0231 +/- 0.007 h-1 and 0.0254 +/- 0.007 h-1, the volumes of distribution were 10.5 +/- 3.95 l/kg and 10.2 +/- 3.26 l/kg, and the total body clearances were 3.72 +/- 0.78 ml X min-1 X kg-1 and 4.09 +/- 0.94 ml X min-1 X kg-1. None of these pharmacokinetic parameters of digoxin were significantly different before or during diltiazem administration. Overall, there does not appear to be an interaction between digoxin and diltiazem.
Adult↗