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

LABORATORY INVESTIGATION

cardiopulmoitary resuscitation, electromechanical dissociation, cardiopulmonary bypass, epinephrine

Use of Cardiopulmonary Bypass, High-Dose Epinephrine, and Standard-Dose Epinephrine in Resuscitation From Post-Countershock Electromechanical Dissociation From the Department of Emergency Medicine, Wright State University, Dayton, Ohio.

Daniel J DeBehnke, MD Mark G Angelos, MD, FACEP James E Leasure

Receivedfor publication May 22, 1991. Revisions received October 11 and December 12, 1991, and January 29, 1992. Accepted for p~blication February 10, 1992. Presented at the Society for Academic Emergency Medicine Annual Meeting in Washington, DC, May 1991. This study was funded by the Kettering Medical Center Resident Research Grant, Wright State University Department of Emergency Medicine Resident Research Fund, and the Kettering Medical Center Foundation.

SEPTEMBER1992 21:9 ANNALS OF EMERGENCY MEDICINE

Study objective: Todetermine 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< .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 significant!y in the cardiopulmonary bypass with standard-dose epinephrine group when compared with the other groups (cardiopulmonary bypass with standarddose epinephrine, 76 _+45mm Hg; high-dose epinephrine, 24 + 12 mm Hg; standard-dose epinephrine, 3 +14 mm Hg; P< .005). Myocardial blood flow was higher in cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephrine animals compared with standarddose epinephrine animals but did not reach statistical significance. Cardiac output increased during cardiopulmonary bypass with standarddose epinephrine (P= .001) and standard-dose epinephrine (NS)

1051/21

ELECTROMECHANICAL

DISSOCIATION

DeBehnke, Angelos & Leasure

I

compared with basicCPR but decreased after epinephrine administration in the high-dose epinephrine group (NS). Conclusion: Resuscitationfrom electromechanical dissociationwas improved with cardiopulmonary bypassand 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 bypasswith epinephrine after prolonged post-countershock electromechanical dissociation cardiac arrest can re-establish sufficient circulation to effect successful early resuscitation. [DeBehnke DJ, Angelos MG, Leasure JE: Use of cardiopulmonary bypass, high-dos,eepinephrine, and standard-dose epinephrine in resuscitation from post-countershockelectromechanical dissociation. Ann EmergMed September 1992;21:1051-1057.] INTRODUCTION The presenting cardiac r h y t h m is a key prognostic variable in cardiac arrest. Ventricular fibrillation has the highest resuscitation rates, and electromechanical dissociation and asystole have the lowest. 1-4 Cardiac arrest from electromechanical dissociation has been estimated to occur in up to 20% of prehospital cardiac arrests and 77% of inhospital cardiac arrests. Resuscitation from electromechanical dissociation has been uniformly dismal, ranging from 0% to 7%. 5-9 Electromechanical dissociation can be divided into p r i m a r y and secondary forms. P r i m a r y electromechanical dissociation can occur in end-stage h e a r t disease, after an acute ischemic cardiac event, or after prolonged cardiac arrest. P r i m a r y electromechanical dissociation is thought to result from intrinsic myocardial contractile failure. Secondary electromechanical dissociation results from changes that affect the preload of the h e a r t but have minimal effect on the intrinsic contractility of the myocardium. Examples include massive p u l m o n a r y embolism, cardiac tamponade, tension pneumothorax, and hypovolemic shock.St0, n Current American H e a r t Association advanced cardiac life support guidelines for electromechanical dissociation include maintaining adequate ventilation and perfusion using s t a n d a r d CPR and standard-dose epinephrine while searching for and treating secondary causes of electromechanical dissociation. 12 Data from the Brain Resuscitation Clinical Trial-1 Study Group suggest that short-term survival from electromechanical dissociation may be more feasible than previously thought. Survival to 24 hours was achieved in 79% of patients in electromechanical dissociation with a one-year survival rate of 4%. 6 There was also a low incidence of myocardial infarction and m a j o r cardiac pathology noted

2 2 / 1 052

clinically and at autopsy in those patients presenting with electromechanical dissociation. This study also found the causes of secondary electromechanical dissociation were r a r e , with no cases of cardiac tamponade, myocardial rupture, p u l m o n a r y embolism, or large myocardial infarction found. However, m a j o r cardiac pathology and secondary causes of electromechanieal dissociation have been reported in other autopsy studies of electromechanical dissociationJ 3-15 The literature on pharmacologic resuscitation from electromechanical dissociation is extensive. Redding et a116 studied methoxamine, calcium, and atropine in a canine asphyxiation model of electromeehanical dissociation and found that methoxamine improved resuscitation. In 1984, Otto and Yakaitis 17 reviewed the literature on epinephrine in electromechanical dissociation and found that epinephrine and methoxamine had similar resuscitation rates in canine models. Turner et al ia compared epinephrine (1 rag) and methoxamine (10 rag) in a clinical study of electromechanical dissociation. Survival to one hour was achieved in 55% of patients in both groups. Survival to hospital discharge was achieved in 3% of patients in the epinephrine group and 0% in the methoxamine group, t8 These d a t a support the use of adrenergic agents for improving coronary perfusion pressure and early resuscitation in electromechanical dissociation cardiac arrest. However, the optimal agent and dosage have not been established. Several studies suggested use of higher than s t a n d a r d doses of epinephrine in ventricular fibrillation cardiac arrest. These studies showed higher regional myocardial blood flow, coronary perfusion pressure, and defibrillation rates when higher doses (0.09-0.20 mg/kg) of epinephrine were used in animal models of cardiac arrestfl 9-22 To date, one animal study has used higher doses of epinephrine for resuscitation from electromechanical dissociation; however, epinephrine was administered by the endotracheal route. 23 Cardiopulmonary bypass has shown improved coronary perfusion pressure and defibrillation rates in ventricular fibrillation cardiac arrest models. 24-27 To date, no study has investigated the use of high-dose epinephrine or cardiopulmouary bypass in resuscitation from electromechanical dissociation. Our p r i m a r y null hypothesis stated that there is no difference in resuscitation rate and early survival between s t a n d a r d dose epinephrine, high-dose epinephrine, and c a r d i o p u l m o n a r y bypass with standard-dose epinephrine in a canine model of post-countershock electromechanical dissociation.

MATERIALS

AND M E T H O D S

Anesthesia and Instrumentation This s t u d y w a s approved by our university laboratory animal use committee. Twenty-five mongrel dogs of either sex (weighing 15 to 35 kg) were anesthetized with 20 mg/kg thiopental, intubated, and placed on a ventilator. Respiratory rate was adjusted to maintain a normal P a c o 2 and p H based on arterial blood

ANNALS OF EMERGENCY MEDICINE

21:9

SEPTEMBER 1992

ELECTROMECHANICAL DISSOCIATION DeBehnke, Angelos & Leasure

gases (Instrumentation Laboratory, Model 1304, Pittsburgh, Pennsylvania). Thiopental was administered in doses of 2 to 5 mg/kg intermittently throughout the study to maintain general anesthesia. Surgical cutdowns were performed on the femoral vessels, both external jugular veins, and the carotid arteries. A pigtail catheter was placed through the right femoral a r t e r y for microsphere injection in nonbypass animals and to r e c o r d left ventricular pressure. A right atrial line was placed through the right femoral vein for drug administration, pressure monitoring, and central t e m p e r a t u r e monitoring. A pacing catheter was placed in the right ventricle through the left femoral vein to fibrillate the heart. An intrathoracic aortic catheter was placed in the left femoral a r t e r y in nonbypass animals and through the right carotid a r t e r y in bypass animals to monitor aortic pressures. A catheter was placed in the left carotid artery just distal to the aortic arch for sampling during blood flow measurements. _Animals in the c a r d i o p u l m o n a r y bypass with standard-dose epinephrine group had 18F and 16F bypass cannulae placed in the external jugular veins and a 12F bypass cannula placed in the left femoral artery. The j u g u l a r vein bypass cannulae were advanced to the level of the right atrium. Placement of all catheters was confirmed by pressure wave forms and fluoroscopy. Pressures were measured and recorded using physiologic monitoring system (Electronics for Medicine, Inc, Model VR-12, White Plains, New York). All catheters were flushed with heparinized saline. Arrest and R e s u s c i t a t i o n After catheter placement, baseline hemodynamics and arterial blood gas measurements were determined. Ventricular fibrillation was induced by delivering a 60-Hz alternating current to the right ventricular endocardinm through the pacing catheter. Ventricular fibrillation was confirmed using ECG and aortic pressure tracings. Ventricular fibrillation continued without ventilatory support for five minutes. At five minutes, a 400-J e x t e r n a l countershock was delivered and repeated as necessary to produce post-countershock electromechanical dissociation. Electromechanical dissociation was defined as a supraventricular or ventricular r h y t h m other than ventricular fibrillation without aortic pressure fluctuations by thoracic aortic line. The ECG and aortic pressure were monitored immediately after countershock to confirm a nonperfusing rhythm. After confirmation of electromechanical dissociation, closed-chest CPR and ventilation with 100% oxygen were performed using a pneumatic chest compression device (Michigan Instruments Thumper®, G r a n d Rapids, Michigan). The T h u m p e r ® delivered 60 compressions p e r minute with a 50% duty cycle and a compression ventilation ratio of 5:1. Compression depth was two inches. After ten minutes of basic CPR, animals were block-randomized to receive one of three resuscitation techniques. Standard-dose epinephrine animals received continued CPR and epinephrine (0.02 mg/kg) through the central line

SEPTEMBER1992

21:9 ANNALSOF EMERGENCYMEDICINE

15 minutes after arrest and at five-minute intervals thereafter until r e t u r n of spontaneous circulation or an additional 30 minutes of t h e r a p y had elapsed. High-dose epinephrine animals received continued CPR and epinephrine (0.2 mg/kg) through the central hne 15 minutes after arrest and at five-minute intervals thereafter until r e t u r n of spontaneous circulation or an additional 30 minutes of t h e r a p y had elapsed. Cardiopulmonary bypass with standard-dose epinephrine animals received 150 ~U/kg heparin 12 minutes after arrest. Fifteen minutes after arrest, cardiopulmonary bypass was begun at 100 mL/kg/min using an extracorporeal pumping system (Biomedicus Inc, Bioconsole 520, Eden P r a i r i e , Minnesota) with an electromagnetic flow probe (Biomedicus Inc, BioProbe TX 20) and CPR was discontinued. At 15 minutes, epinephrine (0.02 mg/kg) was given through the central line and repeated at five-minute intervals until r e t u r n of spontaneous circulation or additional 30 minutes of therapy. Once successfully resuscitated, cardio-pulmonary bypass was continued for 30 minutes and then weaned off. Return of spontaneous circulation was defined in all groups as a spontaneous h e a r t rhythm with a mean arterial pressure of more than 60 mm Hg for one minute without CPR, cardiopulmonary bypass, or vasopressor support. P o s t - A r r e s t I n t e n s i v e Care After successful resuscitation, all animals received standardized intensive care support for two hours. This included ventilatory support to maintain P a c o 2 between 30 to 40 mm Hg, blood pressure support with norepinephrine to keep mean arterial pressure of more than 50 mm Hg, t e m p e r a t u r e control with heating blankets to maintain body t e m p e r a t u r e between 37 and 39 C, sodium bicarbonate for base excess less than - 7 mEq/L, supplemental oxygen to maintain oxygen saturation of more than 90%, and IV fluids. During this time, arterial blood gases, ECG, and hemodynamic variables were monitored. Animals in the c a r d i o p u l m o n a r y bypass group had their bypass cannulae removed during this time. Regional M y o c a r d i a l Blood Flow and Cardiac 0 u t p u t M e a s u r e m e n t Myocardial blood flow was determined at three time points using a colored microsphere technique. Blood flow validation studies were not performed. The colored microsphere technique has shown good correlation with radioactive microsphere techniques (R = .99) in measuring regional myocardial blood flow in the canine model, with flows ranging from 2.0 to 196 mL/min/100 g.Za Flow was measured at the following time points: baseline pre-arrest; 12 minutes of cardiac arrest, which followed seven minutes of basic CPR; 17 minutes of cardiac arrest, which was two minutes after administration of the first epinephrine dose and the beginning of bypass. One of three color-labeled microsphere suspensions containing 1 × 107, 15-~tm same-colored microspheres was injected into the left ventricle of nonbypass animals and the arterial bypass cannula of c a r d i o p u l m o n a r y bypass animals at the predesignated time point while reference blood was

1053/23

ELECTROMECHANICAL DISSOCIATION DeBehnke, Angeles & Leasure

simultaneously collected from the aortic catheter attached to the withdrawal pump (Harvard Apparatus Co, Inc, Model 906, Dover, Massachusetts). The pump withdrew blood at a rate of 10 mL/min, beginning five seconds before the injection and continuing for 90 seconds. Microspheres were injected over a 30-second period. Myocardial tissue samples (2 g) were obtained from the right ventricle, left ventricular endocardium, left ventricular epicardium, left ventricular septum, and apex. Reference blood samples and individual tissue samples were centrifuged, and the sediment was treated with a series of reagents prescribed by the manufacturer (E-Z Trac, West Los Angeles, California) to lyse red blood ceils and digest tissue. The total number of microspheres per reference and tissue sample was determined using an improved Neubaner hemocytometer. S t a t i s t i c a l A n a l y s i s Means + s t a n d a r d deviation were determined for hemodynamic variables, regional myocardial blood flow, and blood gas data at the various time points. Data were analyzed between groups using analysis of variance with a Tukey post-hoc comparison test and within groups using paired t-test with a Bonferroni adjustment. Correlation data were analyzed using Pearson's correlation with Bonferroni correction. Resuscitation rates and survival were compared using Fisher's exact test. Twotailed statistical tests were used. P < .05 was considered statistically significant. RESULTS

Twenty-five animals were entered into the study, with 24 used for statistical analysis (cardiopulmonary bypass with standard-dose epinephrine, eight; high-dose epinephrine, Table 1-. Baseline values*

Cardiopulmonary BypassWith High-Dose Standard-Dose Standard-Dose Epinephrine Epinephrine EpinephrineGroup Group Group Blood sugar (mg/dL) Hematocrit (%) Temperature (C) Heart rate Mean arterial pressure (ram Hg) Mean left ventricular pressure (mm Hg) Coronary perfusion pressure (ram HgF pH Pae2 (mm Hg) Pace2 (mm Hg) Fluid (ml_/kg) 5% Thiopental (rnL/kg)

128 _+43 44_+ 7 38.5 _+1.1 186 _+19

83 _+14 41 + 5 37,7 _+0.9 175 _+23

111 +43 40 _+5 37.2 _+0.5 164_+18

174_+ 10

170 _+13

152_+22

101 _+20

90 _+18

92_+19

151 __+7 7.36_+0.04 90-+9 35+3 13+6 1.13_+0.14

142-+21 7.39+0.04 98+7 33-+3 11 +4 1.14_+0.29

*Mean + standard deviation. Aortic diastolic pressure- right atrial diastolic pressure.

24/1054

128_+23 7.36__+0,07 106_+14 34_+5 13_+7 0.95_+0.14

eight; standard-dose epinephrine, eight). One animal was resuscitated with mechanical CPR alone before epinephrine and was excluded. Baseline values were similar between groups (Table 1). A r r e s t and R e s u s c i t a t i o n All animalsdeveloped electromechanical dissociation after one or two external countershocks. The energy required to place animals into electromechanical dissociation was similar between groups (cardiopulmonary bypass with standard-dose epinephrine, 15.5 + 3.1 J/kg; high-dose epinephrine, 19.1 + 4.1 J/kg; standard-dose epinephrine, 20.6 + 9.0 J/kg; P > .2). During CPR, there was a trend toward increased coronary perfusion pressure in the standard-dose epinephrine group, but this was not statistically significant. After administration of highdose epinephrine or beginning cardiopulmonary bypass, coronary perfusion pressure increased significantly when compared with basic CPR. Coronary perfusion pressure was significantly higher two minutes after beginning cardiopulmonary bypass compared with both epinephrine groups at the same time (Table 2). Animals resuscitated from electromechanical dissociation had a significantly higher coronary perfusion pressure two minutes after intervention (cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, or standard-dose epinephrine) than nonresuscitated animals (54 +42 mm Hg versus 6 + 16 mm Hg, P = .004). In accordance with protocol, animals in the high-dose epinephrine group received significantly more epinephrine than animals in the other groups (high-dose epinephrine, 0.64 + 0.21 mg/kg). There was no significant difference in the amount of epinephrine received in the cardiopulmonary bypass with standard-dose epinephrine and standard-dose epinephrine groups (cardiopulmonary bypass with standarddose epinephrine, 0.10 + 0.12 mg/kg; standard-dose epinephrine, 0.18 + 0.13 mg/kg). A f t e r R e s u s c i t a t i o n 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 Table 2. Coronary perfusion pressure during resuscitation*

Cardiopulmonary BypassWith High-Dose Standard-Dose Standard-Dose Epinephrine Epinephrine EpinephrineGroup Group Group Baseline CPR Two minutes after technique

151 +7 3 +_8t 76_+45"*~

142+21 7 _+8t 24_+12~

128_+23 15 -+49t 3+14'

Mean +standard deviation in mm Hg. *P<-.005 when comparedwith high-dose epinephrine and standard-dose epinephrine groups. tp_< .001 when comparedwith baseline. *P< .003when comparedwith baseline, ~P_<.006when comparedwith CPR,

ANNALS OF EMERGENCYMEDICINE 21:9 SEPTEMBER1992

ELECTROMECHANICAL DISSOCIATION DeBehnke, Angelos & Leasure

epinephrine animals (P < .04). There was no significant difference in time to return of spontaneous circulation between groups (cardiopulmonary bypass with standarddose epinephrine, 25.2 __%8.2 minutes; high-dose epinephrine, 21.6 + 0.9 minutes; standard-dose epinephrine, 20.9 + 5.3 minutes). 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 (P = .5). There was a trend toward increased heart rate in the high-dose epinephrine group when compared with the other groups in the first ten minutes after resuscitation. However, this did not reach statistical significance. There was no difference between groups in hemodynamic data or arterial blood gas measurements in the post-resuscitation period. Post-resuscitation fluid, bicarbonate, lidocaine, and norepinephrine dosages were not significantly different between groups. R e g i o n a l M y o c a r d i a l Blood F l o w and C a r d i a c Output M e a s u r e m e n t s Baseline and CPR myocardial blood flows were not different between groups. After institution of cardiopulmonary bypass or the administration of epinephrine, there was a trend toward improved myocardial blood flow in all groups when compared with CPR. There was a trend toward improved myocardial blood flowin the cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephrine groups compared with the standard-dose epinephrine group (Table 3). Cardiac output at baseline and during CPR were similar between groups. The cardiopuhnonary bypass with standardTable 3. Regional myocardial blood flow during resuscitation

Tissue

Group

Rightventricle

SOE* HDE* CLSB+SBE*

Left ventricular endocardium " SDE HDE CPB+SDE Left ventricular epicardium SDE HDE CPB+SDE Left ventricular septum SDE HDE CPB+SDE Apex SDE HDE CPB+SDE

Baseline 48,4 _+38,1 74.5_+94.5 92,7_+59.8

CPR

Two Minutes After Technique

14.8 _+38.3 8.2_+13.1 4.0_+3.3

149.5_+164.2 14.0_+35.0 99.8_+87.5 2.2_+1.8 146.5-+181.6 3.8-+4.0

34.0 _+70.5 63.4_+92.8 89.1 _+93.6§ 54.6_+141.2 60.7_+111.6 70.6_+93.9

155.4_+214.4 13.5_+30.4 37.5-+87.2 125.8-+145.8 10.3-+15.6 83.3_+123.8 76.7_+38.2 5 . 6 - + 7 . 1 192.2-+233.511 90.0_+91.2 195.0-+254.7 155.0-+147.0 135.2_+230.7 164.2_+254.5 97.7_+55.1

16.6-+44.7 42.3_+109.9 10.3-+13.8 81.1-+125.7 2.7_+2.0 122.6_+163.5 23.5_+52 46.2_+90.0 9.3_+11.3 84.9_+130.9 4 . 0 _ + 3 . 0 118.0_+161

Valuesare expressedas mean + SD in mL/min/lO0 g tissue. •Standard-doseepinephrine. tHigh-doseepinephrine ~Cardiopulmonarybypassand standard-dose epinephrine. ~P=.07 when comparedwith CPR. Hp=.08when comparedwith OPR.

SEPTEMBER1992 21:9 ANNALS OF EMERGENCY MEDICINE

dose epinephrine animals had significantly highcr cardiac output during cardiopulmonary bypass compared with the standard-dose epinephrine and high-dose epinephrine animals. During cardiopulmonary bypass, cardiac output approached baseline values. Animals in the high-dose epinephrine group tended to have lower cardiac output after administration of high-dose epinephrine (Table 4). DISCUSSION

From our study, cardiopulmouary bypass with standarddose epinephrine appears to significantly improve return of spontaneous circulation compared with high-dose epinephrine and standard-dose epinephrine in this electromechanical dissociation model of cardiac arrest. This improvement in return of spontaneous circulation is secondary to the coronary perfusion pressure produced during cardiopulmonary bypass, which was significantly higher than the coronary perfnsion pressure in the epinephrine groups. However, the two-hour survival rate was similar between groups. This discrepancy between return of spontaneous circulation and two-hour survival rates may be in part because cardiopulmonary bypass is able to resuscitate immediately some animals that would not have been resuscitated with standarddose epinephrine or high-dose epinephrine. In this study, cardiopulmonary bypass was continued for only 30 minutes after return of spontaneous circulation. A longer support period with cardiopuhnonary bypass after return of spontaneous circulation may have ameliorated the myocardial dysfunction and subsequent cardiac deaths noted in three of the eight cardiopulmonary bypass with standard-dose epinephrine animals. High-dose epinephrine significantly improved coronary perfusion pressure when compared with baseline. When comparing resuscitation rates, high-dose epinephrine was not significantly different compared with standard-dose epinephrine. There was a trend toward improved coronary perfusion pressure and myocardial blood flow compared with the standard-dose epinephrine group, but this did not reach statistical significance. One explanation for the lack of Table 4, Cardiac output during resuscitation*

Cardiopulmonary BypassWith High-Dese Standard-Dose Standard-Dose Epinephrine Epinephrine EpinephrineGroup Group Group Baseline 4,509 _+1,103 CPR 589_+349 Two minutes after technique 3,313_+1,217"*

4,991 _+2,393 3,650_+1,940 1,070_+1,230' 668_+729~ 537_+613~ 840_+ 1,602~

Mean ±standard deviation in mL/min. *P_< .004when comparedwith high-dose epinephrine and standard-doseepinephrine groups. tp< .009when comparedwith baseline. *P_<.001 when comparedwith CPR. ~P_<.003when comparedwith baseline.

1055/25

ELECTROMECHANICAL DISSOCIATION DeBehnke, Angelos & Leasure

ii

difference between the high-dose epinephrine and standarddose epinephrine groups may be due to the higher coronary perfusion pressure in the standard-dose epinephrine group during CPR. By chance, coronary perfusion pressure during CPR tended to be higher in the standard-dose epinephrine group. This represents a potential bias in favor of the standard-dose epinephrine group and may have improved subsequent coronary perfusion pressure, myocardial blood flow, and resuscitation. Such a bias would make it much more difficult to show statistical differences between groups. Despite the improvement in myocardial blood flow after the administration of high-dose epinephrine, cardiac output actually decreased when compared with the cardiac output during CPR. These data are similar to previously reported data. Roberts et al29 studied high-dose epinephrine (0.2 mg/kg), standard-dose epinephrine (0.02 mg/kg), methoxamine (20 mg), and placebo in a prolonged canine ventricular fibrillation model and found that cardiac output decreased in the high-dose epinephrine group compared with placebo and methoxamine. Chase et al 3° studied standard-dose epinephrine (0.02 mg/kg) and high-dose epinephrine (0.2 mg/kg) in a porcine model of ventricular fibrillation cardiac arrest and found significantly improved myocardial blood flow despite decreased cardiac output after high-dose epinephrine administration. This most likely reflects the result of decreased cardiac output and decreased pulmonary blood flow after high-dose epinephrine administration. Because an electromechanical dissociation model was used in this study, any external eountershocks after the first electromechanical dissociation-producing countershock would be used only if the animal refibrillated. With the initiation of therapy and the improvement of coronary perfusion pressure, there was a trend for animals to refibrillate, thereby requiring additional countershocks. In examining all animals, there was a correlation trend between coronary perfusion pressure and J/kg (R = .47, P = .09). In the cardiopulmonary bypass with standard-dose epinephrine group there Was a stronger correlation between J/kg required and coronary perfusion pressure (R = .87, P = .015). It appears that improving the coronary perfusion pressure in electromechanical dissociation increases the chance of converting the rhythm to ventricular fibrillation, potentially a more easily resuscitated rhythm. The etiology and therapeutic implications of this "conversion" from electromechanical dissociation to ventricular fibrillation deserve further investigation. T h e r e has been speculation regarding possible detrimental myocardial effects of high-dose epinephrine administered during cardiac arrest. In a canine ventricular fibrillation model, Ditchey and Lindenfeld 31 found improved myocardial blood flow after a 1-mg bolus of epinephrine and an epinephrine infusion of 0.2 rag/rain. Despite this improvemeut in myocardial blood flow, myocardial lactate levels increased significantly and myocardial adenosine triphosphate concentration decreased, suggesting a decrease in the

26/1056

myocardial oxygen supply/demand ratio after epinephrine administration. This change in myocardial oxygen supply/ demand ratio may be detrimental to resuscitation. Roberts et a129 found no improvementin resuscitation comparing high-dose epinephrine and placebo while achieving 100% resuscitation using methoxamine. They speculated that highdose epinephrine did not improve resuscitation because of its increase in myocardial oxygen consumption. There also is some speculation that the potential arrhythmias after successful resuscitation using high-dose epinephrine may preclude its use in clinical cardiac arrest. A clinical study by Callaham et a132 showed no adverse effects after high-dose epinephrine administration in 33 resuscitated adult cardiac arrest patients when compared with 35 resuscitated patients who received standard-dose epinephrine. Goetting and Paradis 33 studied high-dose epinephrine in pediatric cardiac arrest and found sinus tachycardia and mild-to-moderate hypertension in the first 15 to 20 minutes of after resuscitation but no life-threatening tachyarrhythmias or severe hypertension requiring treatment. Our study did not show any increase in post-resuscitation ventricular tachycardia, ventricular fibrillation, or hypertension in those animals resuscitated with high-dose epinephrine. Despite a trend toward sinus tachycardia in the high-dose epinephrine group in the first ten minutes after resuscitation, animals in the high-dose epinephrine group remained as hemodynamically stable as animals resuscitated by cardiopulmonary bypass with standard-dose epinephrine or standard-dose epinephrine alone. There were several limitations to our study. Electromechanical dissociation is an electrical and contractile representation of a broad spectrum of physiologic and pathologic states. A post-countershock model was chosen for our study. The mechanism of electromechanical dissociation in this model is not known but may represent the loss of myocardial highenergy phosphate stores. However, there are other models for electromechanical dissociation (eg, asphyxiation, systemic shock). It is unclear whether our results can be extrapolated to those models or to the various clinical scenarios of electromechanical dissociation. Further studies with different electromechanical dissociation models must be performed before any generahzations can be made. Furthermore, the lack of statistical significance between two-hour group survival rates and myocardial blood flow values may be due in part to lack of power in our study (type II error). Using a two-tailed A of .05, the power to show a 50% difference for two-hour group survival was calculated at .52. 34

CONCLUSION Cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephrine produce improved coronary perfusion pressure during resuscitation from electromechanical dissociation. All animals in the cardiopulmonary bypass with standard-dose epinephrine group were resuscitated.

ANNALS OF EMERGENCY MED[CINE 2/:9

SEPTEMBER1992

ELECTROMECHANICAL D I S S O C I A T I O N

DeBehnke, Angelos & Leasure

Cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephidne showed a trend toward improved myocardial blood flow when compared with standard-dose epinephrine. Cardiopulmonary bypass with standard-dose epinephrine can re-establish sufficient coronary perfusion pressure, cardiac output, and myocardial blood flow for successful resuscitation in this model of prolonged post-countershock electromechanical dissociation cardiac arrest. Highdose epinephrine tended to be better than standard-dose epinephrine, but requires further evaluation. Ultimately, there was no difference in two-hour survival between the three treatment groups.

19. Brown C6, Taylor RB, Werrnan HA, et ah Myocardial oxygen delivery/consumption during cardiopulmenary resuscitation: A comparison of epinephrine and phenylephrine. Ann Emerg Mad 1988;17:302-308.

REFERENCES 1. Stueven HA, Waite EM, Troiano P, et al: Prehospital cardiac arrest- A critical analysisef factors affecting survival. Resuscitation 1989;17:251-259.

24. Martin GB, Newak RM, Carden DL, et el: Cardiopulrnenary bypass vs CPR as treatment for prolonged canine cardiepulmonary arrest. Ann Emerg Med 1987;16:628-636.

2.Stueven HA: Prehospital CPR: A review, in perspective. Resuscitation 1989;17(Suppl):S71-S77.

25. Levine R, Gorayeb M, Safar P, eta[: Cardiopulmonary bypass after cardiac arrest and prolonged closed-chest CPR in dogs. Ann Emerg Mad 1987;16:620-627.

3. Ritter G, Wolfe RA, Goldstein S, et el: The effect of bystander CPR on survival ef outof-hospital cardiac arrest victirns. Am Heart J1985;110:932-937.

26. Pretto E, Safar P, Saito R, et al: Cardiopulmenary bypass after prolonged cardiac arrest in dogs. Ann Emerg Med 1987;16:611-619.

4. Eisenberg MS, Burgher L, Hearne T: Out-of-hospital cardiac arrest: A review of major studiesand a proposed uniform reporting system. Am J Public Health 1980;70:236-240.

27. DeBehnke DJ, Angeles MG, Leasure JE: Comparison of standard external CPR, open-chest CPR and cardiopulmonary bypass in a canine myocardial infarct model. Ann Emerg Med 1991;20:754-760.

5.Vincent JL, Thijs L, Wail MH, et al: Clinical and experimental studies on alectremechanical dissociation. Circulation 1981;64:18-27. 6. Edgren E, Kelsey S, Sutton K, et ah The presenting ECG pattern in survivors of cardiac arrestand its relation to the subsequent long-term su rvival. Acta Anaesthesiol Scand 1989;33:265-271. 7. Sutton-Tyrrel[ K, Abramsen NS, Safar P, et al: Predictors of eleotromechanical dissociation during cardiac arrest. Ann Emerg Meal 1988;17:572-575. 8. Stueven H, Troiano P, Thompson B, et al: Bystander/first responder CPR: Ten years experience in a paramedic system. Ann Emerg Mad1986;15:707-710. 9.Vanags B, Thakur RK, Stueven HA, et ah Interventions in the therapy of dectromechanical dissociation. Resuscitation 1989;17:163-171. 19.Charlap S, Kahlam S, Lichstein E, et ah Electremechanical dissociation: Diagnosis, pathophysiology, and management. Am HeartJ 1989;118:355-360. 11.Ewy GA: Defining electremechanical dissociation. Ann Emerg Mad 1984;13:830-832. 12.American Heart Association, 1985 National Conference: Standards and guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC). JAMA 1986;55(Suppl):2841-3044. 13.Fazzard HA: Electromechanical dissociation and its possible role in sudden cardiac death.J Am Coil Cardiol 1985;5:31B-34B. 14.Pirolo JS, Hutchins GM, Moore 6W: Electromechanical dissociation: Pathologic explanations in 50 patients. Hum Patho11985;16:485-487. 15.Bellotto F, Valente S, Buja OF, et el: Unexpected sudden death during acute myocardial infarction: Role of primary electromechanical dissociation. IntJ Cardiol 1989;24:77-81. 16.Redding JS, Haynes RR, Thernas JD: Drug therapy in resuscitation from eleetromechanical dissociation. Crit Care Med 1983;11:681-684. 17.Otto CW, Yakaitis RW: The role of epinephrine in CPR: A reappraisal. Ann Emerg Mad1984;13:840-843. 18.Turner LM, Parsons M, Luetkemeyer RC, et al: A comparison of epinephrine and rnethoxaminefor resuscitation from electrernechanical dissociation in human beings. AnnEmergMad 1988;17:443-449.

SEPTEMBER 1992 21:9

ANNALS 0FEMERGENCYMEDrC[NE

20. Brown CO, Katz SE, Werrnan HA, et ah The effect of epinephrine versus methoxamine on regional myocardial blood flew and defibrillation rates fallowing a prolonged cardiorespiratery arrest in a swine model. Am J Emerg Med 1987;5:362-369. 21. Brown CO, Werrnan HA, Davis EA, et ah The effects ef graded doses of epinephrine on regional myocardial blood flow during cardiopulmonary resuscitation in swine. Circulation 1987;75:491-497. 22. Lindner KH, Ahnefeld FW, Bowdler IM: Comparison of different doses of epinephrine on myocardial perfusion and resuscitation success during cardiopulmonary resuscitation in a pig model. Am J Emerg Med1991;9:27-31. 23. Ralston SH, Tacker WA, Showen L, et ah Endetracheal versus intravenous epinephrine during electromechaniaal dissociation with CPR in dogs. Ann EmergMed 1985;14:1044-1048.

28. Hale SL, Alker KJ, Kloner RA: Evaluation of nonradioactive, colored rnicrospheres for measurement of regional myocardial blood flow in dogs. Circulation 1988;78:428-434. 29. Roberts D, Landolfo K, Dobson K, et ah The effects of methoxamine and epinephrine an survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation. Chest 1990;98:999-1005. 30. Chase PB, Kern KB, Sanders AB, et al: The effect of high- and tow-dose epinephrine on myocardial perfusion, cardiac output, and end-tidal carbon dioxide during prolonged CPR (abstract). Ann Emerg Med 1990;19:466. 31. Ditchey RV, Lindenfeld J: Failure of epinephrine to improve the balance between myocardial oxygen supply and demand during closed-chest resuscitation in dogs. Circulation 1988;78:382-389. 32. Callaham M, Barton C, Kayser S: Potential adverse effects of high-dose epinephrine therapy in patients resuscitated from cardiac arrest. JAMA 1991;265:1117-1122. 33. Ooetting MG, Paradis NA: High-dose epinephrine improves outcome from pediatric cardiac arrest. Ann Emerg Med 1991;20:22-26. 34. Fleiss J L: Statistical Methods for Rates and Proportions, ed 2. New York, John Wiley, 1981, p 42. The authors extend special thanks to Andrea Arnold for laboratory assistance and manuscript preparation, Erik Ramnath for laboratory assistance, and Laura Grube for manuscript preparation. Cardiopulmonary bypass equipment support was provided by Medtronic Biomedicus ®, Eden Prairie, Minnesota. Address for reprints: Daniel J DeBehnke, MD Department of Emergency Medicine Medical College of Wisconsin Box 204 8700 West Wisconsin Avenue Milwaukee, Wisconsin 53226

1057/27