Howard A. Werman

The effects of graded doses of epinephrine on regional myocardial blood flow during cardiopulmonary resuscitation in swine

Although epinephrine has been shown to improve myocardial blood flow during cardiopulmonary resuscitation (CPR), the effects of standard as well as larger doses of epinephrine on regional myocardial blood flow have not been examined. In this study we compared the effects of various doses of epinephrine on regional myocardial blood flow after a 10 min arrest in a swine preparation. Fifteen swine weighing greater than 15 kg each were instrumented for regional myocardial blood flow measurements with tracer microspheres. Regional blood flow was measured during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun and regional myocardial blood flow was determined. Animals were then randomly assigned to receive 0.02, 0.2, or 2.0 mg/kg epinephrine by peripheral injection. One minute after drug administration, regional myocardial blood flow measurements were repeated. The adjusted regional myocardial blood flows (ml/min/100 g) for animals given 0.02, 0.2, and 2.0 mg/kg epinephrine, respectively, were as follows: left atrium, 0.9, 67.4, and 58.8; right atrium, 0.3, 46.2, and 38.5; right ventricle, 0.7, 82.3, and 66.9; right interventricular septum, 1.7, 125.5, and 99.1; left interventricular septum, 2.8, 182.8, 109.5; mesointerventricular septum, 16.8, 142.2, and 79.2; left ventricular epicardium, 19.2, 98.5 and 108.7; left ventricular mesocardium, 22.8, 135.0, and 115.8; and left ventricular endocardium, 2.5, 176.1, and 132.9). All comparisons between the groups receiving 0.02 and 0.2 mg/kg epinephrine were statistically significant (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effect of graded doses of epinephrine on regional brain blood flow during CPR in a swine model

Cerebral blood flow (CBF) with conventional closed-chest cardiopulmonary resuscitation (CCPR) has been measured at only 2% to 11% of prearrest values. The purpose of our study was to determine whether the peripheral administration of higher doses of epinephrine than currently recommended during CCPR following a prolonged cardiac arrest improves CBF compared to CCPR using a standard dose of epinephrine. Fifteen swine were randomized to receive CCPR plus 0.02 mg/kg, 0.2 mg/kg, or 2.0 mg/kg epinephrine through a peripheral IV line following a ten-minute cardiopulmonary arrest and three minutes of CCPR. Regional CBF measurements were made by radionuclide microsphere technique during normal sinus rhythm (NSR), CCPR, and following epinephrine administration. The adjusted regional blood flows (in mL/min/100 g) following epinephrine administration for the 0.02-, 0.2-, and 2.0-mg/kg groups were, respectively, left cerebral cortex (3.3, 13.1, 11.8); right cerebral cortex (3.9, 13.8, 12.2); cerebellum (9.2, 32.0, 33.1); midbrain/pons (9.9, 32.1, 32.3); medulla (10.6, 61.5, 54.2); and cervical spinal cord (12.2, 53.8, 35.8). In this swine model, 0.2 mg/kg and 2.0 mg/kg epinephrine significantly increased regional CBF over that seen with standard doses. Because neuronal survival is dependent on flow rates of 10 to 15 mL/min/100 g, this preliminary evidence suggests that these higher doses of epinephrine may help improve neurological outcome in CCPR.

Myocardial oxygen delivery/consumption during cardiopulmonary resuscitation: A comparison of epinephrine and phenylephrine

Our study compared the effect of high-dose epinephrine with the pure alpha-agonist phenylephrine on regional myocardial blood flow (MBF), myocardial oxygen delivery (MDO2), myocardial oxygen consumption (MVO2), and defibrillation rates during CPR. Fifteen swine weighing more than 15 kg were instrumented for measurement of regional MBF using radiolabeled tracer microspheres. Measurements of regional MBF, MDO2, and MVO2 were made during normal sinus rhythm. Ventricular fibrillation was induced and persisted for ten minutes. CPR was begun using a pneumatic compression device. Regional MBF, MDO2, and MVO2 were measured during CPR. Following three minutes of CPR, animals (N = 15) were allocated to one of three groups (n = 5): Group 1, epinephrine 0.2 mg/kg; Group 2, phenylephrine 0.1 mg/kg; or Group 3, phenylephrine 1.0 mg/kg. Measurements of regional MBF, MDO2, and MVO2 were repeated after drug administration. Extraction ratios, defined as MVO2/MDO2, were calculated during normal sinus rhythm, CPR, and after drug administration. Defibrillation was attempted 3 1/2 minutes after drug administration. There was no significant difference in MBF, MDO2, MVO2, and extraction ratio during normal sinus rhythm and CPR for any of the groups. Total MBF following drug administration was 67.2 +/- 49.4 mL/min/100 g for the group receiving epinephrine 0.2 mg/kg; 7.0 +/- 7.1 mL/min/100 g for the group receiving phenylephrine 0.1 mg/kg; and 36.7 +/- 21.1 mL/min/100 g for the group receiving phenylephrine 1.0 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimating the duration of ventricular fibrillation

As the duration of time between the onset of ventricular fibrillation and the application of defibrillation (downtime) increases, the rate of successful resuscitation decreases. Results of recent animal studies suggest that the rate of successful resuscitation may be increased after a prolonged cardiorespiratory arrest when pharmacologic therapy is instituted before defibrillation. An accurate estimation of downtime could be critical in selecting the most appropriate therapeutic intervention. The purpose of our study was to determine whether changes in the frequency or amplitude of the ventricular fibrillation ECG signal during cardiac arrest could be used to estimate downtime. We characterized the dynamics of both total power and frequency distribution of the power in the ECG during ventricular fibrillation in 11 swine to determine whether enough information existed in either parameter to estimate downtime. The median frequency of the power spectrum was used to track power distribution. Both parameters followed a dynamic, repeatable pattern. However, median frequency showed less intersubject variability than did total power. A mathematical model of median frequency was developed and used with data obtained from ten additional swine to estimate downtime. The model estimated downtime to within 1.3 minutes of actual downtime between one and ten minutes of ventricular fibrillation. Our study has identified a new, potentially useful parameter for studying various management strategies in ventricular fibrillation as a function of downtime.

The median frequency of the ECG during ventricular fibrillation: its use in an algorithm for estimating the duration of cardiac arrest

The dynamics of the frequency distribution in the power spectrum of the ECG recorded form 11 swine during ventricular fibrillation (VF) are characterized to determine whether enough information exists in this domain to estimate downtime (DT). The median frequency (FM) of the power spectrum is used to track the frequency distribution. The FM follows a dynamic repeatable course during the first 10 min of VF. Intersubject variability is small. The FM data of the 11 subjects are modeled with a set of first-order polynomial equations, and the algorithm is tested with data from an additional ten subjects. The algorithm predicts VF duration with an average error of -0.86 min; 71.5% of the predictions fell within the 95% confidence limits of the model. A signal processing tool is identified which may be useful in the prehospital treatment of VF.<<ETX>>

Adrenergic agonists during cardiopulmonary resuscitation

A number of studies have suggested that following a prolonged cardiopulmonary arrest, large doses of alpha-adrenergic agonists that possess post-synaptic alpha-2 agonist properties, i.e. epinephrine and norepinephrine, may be required to enhance myocardial and cerebral hemodynamics. While initial human studies using large doses of epinephrine have shown improved hemodynamics over standard therapy, hospital discharge rates and neurological outcome have been discouraging. This probably reflects the fact that the administration of epinephrine was employed late in the resuscitation effort. Future studies using larger doses of epinephrine as the initial pharmacologic intervention during cardiopulmonary resuscitation (CPR) will help to determine whether there is any therapeutic benefit. In addition, a number of questions still remain unanswered in delineating the specific alpha and beta adrenergic agonist components which will maximally enhance hemodynamics and resuscitation rates during CPR. This will help determine whether norepinephrine or a yet unsynthesized adrenergic agonist may be more beneficial for use during cardiac arrest.

The effect of epinephrine versus methoxamine on regional myocardial blood flow and defibrillation rates following a prolonged cardiorespiratory arrest in a swine model

Recent studies in swine have shown that larger doses of epinephrine than those currently employed for cardiopulmonary resuscitation (CPR) significantly improve regional myocardial blood flow following prolonged cardiac arrest. The dose-response effect of a pure alpha-adrenergic agonist, methoxamine, on regional myocardial blood flow has not been investigated in this setting. This study compared the effect of high-dose epinephrine with graded doses of methoxamine on regional myocardial blood flow, oxygen delivery/utilization, and defibrillation rates during CPR. Twenty swine were instrumented for regional myocardial blood flow measurements using radiolabeled tracer microspheres. Measurements of regional myocardial blood flow, oxygen delivery, and oxygen consumption were made during normal sinus rhythm. Ventricular fibrillation was then induced. Following 10 minutes of ventricular fibrillation, CPR was initiated with a pneumatic compressor. Regional myocardial blood flow, oxygen delivery, and oxygen consumption were then measured during CPR. Following 3 minutes of CPR, the swine were allocated to one of four treatment groups (five per group): group I, epinephrine 0.2 mg/kg; group II, methoxamine 0.1 mg/kg; group III, methoxamine 1.0 mg/kg; and group IV, methoxamine 10.0 mg/kg. One minute after drug administration, regional myocardial blood flow, oxygen delivery, and oxygen consumption measurements again were made. Three and one half minutes after drug administration, defibrillation was attempted. Regional myocardial blood flow following drug administration was compared using an analysis of covariance. Epinephrine (0.2 mg/kg) significantly improved myocardial blood flow (P less than .002) for all tissues examined compared with all doses of methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Emergency scene endotracheal intubation before and after the introduction of a rapid sequence induction protocol.

INTRODUCTION A change in airway management protocol provided the opportunity to evaluate scene airway management by air medical crew before and after the introduction of a rapid sequence induction protocol. METHODS A retrospective chart review and a descriptive study of scene trauma patients whose airway was established primarily by an air medical crew during two study periods: April 1994 through March 1995 (group 1, before rapid sequence induction) and April 1995 through March 1996 (group 2, after rapid sequence induction). Data collected included demographics, type of airway, Glasgow Coma Scale score, scene time, and outcome. The setting included a four helicopter air medical transport program using nurse/paramedic crews with a service area of 25,000 square miles in central, southeastern, and northeastern Ohio. RESULTS Group 1 patients (n = 148) averaged 31.6 years of age and were primarily male (79.7%) with blunt injuries (92.6%) with an average Glasgow Coma Scale score of 7.7. Group 2 (n = 95) was similar, averaging 31.1 years of age, primarily male (77.9%) with blunt injuries (94.7%) and a Glasgow Coma Scale score of 8.6. Groups 1 and 2 differed in oral endotracheal intubation rate (19/118 versus 36/95 [p = 0.03]) and in scene time (15.7 minutes versus 20.1 minutes [p = 0.0012]). The groups did not differ in rate of successful intubation or the rate of subsequent cricothyrotomy. CONCLUSION Rapid sequence induction added significantly to ground time without significantly increasing intubation success rate or decreasing cricothyrotomy rate. Its use at the scene of injury may not be appropriate.

Methoxamine versus epinephrine on regional cerebral blood flow during cardiopulmonary resuscitation.

The improvement in cerebral blood flow (CBF) during CPR after epinephrine administration has been attributed to epinephrines alpha-adrenergic properties. Methoxamine, a pure alpha-1 agonist, has only been shown to be comparable to epinephrine in restoring circulation after cardiac arrest in a canine model. This study compares the effectiveness of equipotent doses of epinephrine and methoxamine in improving CBF during CPR after a prolonged cardiac arrest in a swine model.Twenty-five swine, weighing 15.9 to 28.2 kg, underwent instrumentation for regional CBF using tracer microspheres. CBF was determined during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun with a pneumatic compressor. CBF measurements were again made during CPR. After 3 min of CPR, the swine were randomized to receive 0.02 or 0.2 mg/kg epinephrine, 0.1,1.0, or 10.0 mg/kg methoxamine. Five swine were allocated to each group. CBF measurements were determined after drug administration and compared using a Bonferroni multiple comparison procedure. A p-value less than .05 was considered statistically significant.This study demonstrated that, after a 10-min cardiac arrest, CBF was extremely low, averaging less than 7 ml/min 100 g during external CPR. There were no clinically significant improvements in regional CBF after 0.02 mg/kg of epinephrine, or the two lowest doses of methoxamine. The addition of 10 mg/kg of methoxamine clinically improved blood flow only to the most caudal CNS structures, including the pons, medulla, and cervical spinal cord. On the other hand, with 0.2 mg/kg of epinephrine, regional CBF averaged approximately 12 to 13 ml/min-100 g to the cerebral cortex, and surpassed 29 ml/min 100 g to more caudal CNS structures. All blood flow comparisons between the epinephrine and methoxamine-treated animals were statistically significant (p = .0001). This study suggests that epinephrine in larger doses than currently recommended significantly improves regional CBF compared to equipotent doses of methoxamine during CPR.

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 (CAO 2 and CCSO 2 , respectively), and myocardial blood flow measurements using tracer microspheres. CAO 2 , CCSO 2 , myocardial blood flow, myocardial oxygen delivery (MDO 2 ) and myocardial oxygen consumption (MVO 2 ), 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). Epinephrine 0.20 mg/kg, norepinephrine 0.12 mg/kg, and 0.16 mg/kg significantly improved aortic diastolic pressure ( P = .007) and coronary perfusion pressure ( P = .012) compared with norepinephrine 0.08 mg/kg. With the two largest doses of norepinephrine, myocardial blood flow averaged 94 to 101 mL/min/100 g; average myocardial blood flow with epinephrine 0.20 mg/kg was 69 mL/min/100 g, and myocardial blood flow with norepinephrine 0.08 mg/kg was 35 mL/min/100 g. All the animals were defibrillated successfully with norepinephrine 0.12 and 0.16 mg/kg, 80% with epinephrine, and 40% with norepinephrine 0.08 mg/kg. Although equipressor doses of epinephrine 0.20 mg/kg and norepinephrine 0.16 mg/kg produced statistically similar hemodynamics, a trend toward improved myocardial blood flow and successful defibrillation rates was noted with norepinephrine 0.16 mg/kg. This trend also was noted with norepinephrine 0.12 mg/kg. Thus, alpha-adrenergic agonists such as norepinephrine, which lack beta-2 agonist properties, may be hemodynamically more beneficial during CPR than alpha-adrenergic agonists such as epinephrine with beta-2 activity.