LABORATORY INVESTIGATION cardiopulmonary bypass; CPR; myocardial infarction; ventricular fibrillation
Comparison of Standard External CPR, Open-Chest CPR, and Cardiopulmonary Bypass in a Canine Myocardial Infarct Model Study objectives: After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model. Type of participants: Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight). Design and interventions: All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper ® CPR. A t 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas. Measurements: Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group. Main results: Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P < .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +- 37 m m Hg) and OCCPR (56 + 31 m m Hg) than in SECPR animals (16 +- i6 m m Hg, P < .04). Epinephrine required for resuscitation was significantly less w i t h CPB (0.10 +_ 0.02 mg/kg) than for SECPR (0.28 ++-0.11 mg/kg, P < .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +_ 0.31) and OCCPR (0.39 +_ 0.25) than for SECPR (I.i6 -- 0.31, P < .02). Conclusion: OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB. [DeBehnke D J, Angelos MG, Leasure JE: Comparison of standard external CPR, open-chest CPR, and cardiopuImonary bypass in a canine myocardial infarct model. A n n Emerg Med July 1991;20:754-760.]
Daniel J DeBehnke, MD Mark G Angeles, MD, FACEP James E Leasure Dayton, Ohio From the Department of Emergency Medicine, Wright State University School of Medicine, Dayton, Ohio. Received for publication May 9, 1990. Revision received September 10, 1990. Accepted for publication January 21, 1991. Presented at the Society for Academic Emergency Medicine Annual Meeting in Minneapolis, Minnesota, May 1990; and the Emergency Medicine Research Society/Society for Academic Emergency Medicine Combined International Meeting in Edinburgh, Scotland, October 1990. This research was funded by the Emergency Medicine Foundation/Carl Jelenko Research Award and the Kettering Medical Center Resident Research Fund. Address for reprints: Daniel J DeBehnke, MD, Medical Coqlege of Wisconsin, Department of Emergency Medicine, Box 204, 8700 West Wisconsin Avenue, Milwaukee, Wisconsin 53226.
INTRODUCTION Cardiac arrest and sudden cardiac death are important problems in our society; an estimated 1,000 cardiac arrests occur every day.l Survival to hospital discharge is variable, ranging from 2% to 25% depending on the presenting cardiac rhythm and the emergency medical services system operating within the community, z-4 Based on current survival data, successful short- and long-term resuscitation from cardiac arrest remains low with standard external CPR (SECPR). Open-chest CPR (OCCPR) was the method of choice for resuscitation of
20:7 July 1991
Annals of Emergency Medicine
754/7 c
CPR & CPB DeBehnke, A n g e l o s & Leasure
in-hospital, nontraumatic cardiac arrest until Kouwenhouven et al's research in 1960. 5 0 C C P R is occasionally used today for victims of penetrating chest t r a u m a w h o suffer cardiac arrest. O C C P R has been shown to produce improved perfusion pressures and resuscitation rates compared with SECPR in animal models of cardiac arrest. 6-9 Cardiopulmonary bypass (CPB} has been used extensively for cardiac maintenance during myocardial revascularization and other cardiac surgical procedures. There have been several uncontrolled clinical reports of successful resuscitation from cardiac arrest with closed-chest CPB. 1°-1~ More recently, CPB has been investigated as a resuscitation tool after cardiac arrest in canine models and has been shown to improve perfusion pressures and resuscitation rates compared with SECPR.13~15 Return of spontaneous circulation (ROSC) after cardiac arrest appears to be correlated with the coronary perfusion pressure (CorPP) generated during CPR. 16-18 Techniques used to improve CorPP during CPR should lead to improved resuscitation. Both OCCPR and CPB have been shown to increase CorPP and improve resuscitation from cardiac arrest in canine models. One major criticism of survival studies in the canine model has been the use of healthy animal preparations. No short- or long-term survival studies have compared various CPR techniques in a canine infarct model. We investigated the ability of OCCPR and CPB to improve CorPP and resuscitation rates compared with SECPR in a canine model of acute myocardial infarction followed by ventricular fibrillation (VF) cardiac arrest. Our null hypothesis stated that there is no difference between resuscitation techniques with respect to CorPP generated or resuscitation rates achieved. MATERIALS A N D M E T H O D S This study was approved by the laboratory animal utilization committee at our institution. Twentyeight mongrel dogs of both sexes (weight, 15 to 30 kg) were used. All animals were anesthetized using 20 mg/kg thiopental, intubated, and placed on a ventilator. Respiratory rate was adjusted to maintain a nor80/755
TABLE 1. Modified ACLS protocol for different resuscitation groups VF Time (min)
SECPR Group*
VF Time (min)
CPB and OCCPR Groups*
14
100J x 3
17
100J x 3(15J x 3)
15 16
Epinephrine 200J x 3
18 19
Epinephrine 200J x 3(15J x 3)
17
Epinephrine and lidocaine
20
Epinephrine and lidocaine
18
300J x 3
21
300J x 3(15J x 3)
20
Epinephrine
23
Epinephrine
21 23 24
300J x 3 300J x 3 Epinephrine
24 26 27
300J x 3(20J x 3) 300J x 3(30J x 3) Epinephrine 300J x 3(30J x 3)
26
300J x 3
29
27
Lidocaine
30
Lidocaine
28
300J x 3
31
300J x 3(30J x 3)
29
Epinephrine
32
Epinephrine
31 33
300J x 3 300J x 3
34 36
300J x 3(30J x 3) 300J x 3(30J x 3)
34 36
Epinephrine 300J x 3
37 39
Epinephrine 300J x 3(30J x 3)
37
Lidocaine
40
Lidocaine
38 39
300J x 3 Epinephrine
41 42
300J x 3(30J x 3) Epinephrine
41 44
300J x 3 End
44 47
300J x 3(30J x 3) End
*Epinephrine dose 40 t~g/kg; lidocaine dose 1 mg/kg.
ma] Pco2 and pH based on arterial blood gases (Instrumentation Laboratory Model 1304, Lexington, Massachusetts). Thiopental was administered at doses of 2 to 5 mg/kg interm i t t e n t l y throughout the study to maintain general anesthesia. Cutdowns were performed on the femoral vessels, both external jugular veins, and the left c o m m o n carotid artery. A 5F Millar microtip-catheter pressure transducer (model SPL-350, Millar I n s t r u m e n t s , Inc, Houston, Texas) was placed through the right femoral artery to record left ventricular pressure. A right atrial line was placed through the right femoral vein for drug administration and pressure 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 through the left femoral artery in nonCPB group animals and through the left carotid artery after coil placement in CPB animals to monitor aortic pressures. Animals in the CPB group had two 18F bypass cannulae placed in the external jugular veins and a 12F bypass cannula Annals of Emergency Medicine
placed in the left femoral artery for bypass. The jugular vein bypass cannulae were advanced to the level of the right atrium. Placement of all catheters was confirmed by standard pressure waveforms and fluoroscopy. Pressures were measured and recorded using a physiological monitoring system (model VR 12, Electronics for Medicine, Inc, White Plains, New York). All catheters were flushed with heparinized saline. After catheter placement, baseline h e m o d y n a m i c and ECG measurements were determined. Using the left common carotid artery, a copper coil was placed in the left anterior descending coronary artery using the two-catheter technique of Kordenat et al. 19 Fluoroscopy was used to ensure proper coil placement. With this technique, the coil was consistently placed between the first and second diagonal branches of the left anterior descending coronary artery as previously described. 2o All animals received ECG, aortic, and right atrial pressure monitoring until 1 m m of ST segment elevation occurred or 20:7 July 1991
CPR & CPB DeBehnke, A n g e l u s & L e a s u r e
TABLE 2. Baseline values SECPR Group
CPB Group
OCCPR Group
Blood sugar (mg/dL)
96 ± 13
82 + 19
84 ± 12
Hematocrit (%)
48 +_ 5
38 + 4
44 ± 5
Temperature(C)
37.8 _+ 0.9
38.3 +_ 0,6
37.8 ± 0.7
Heart rate
168 ± 25
177 ± 30
171 ± 23
MAP (mm Hg)*
142 ± 23
139 +_ 26
144 ± 19
LVP (mm Hg)
58 ± 13
59 -+ 16
73 ± 30
CorPP (mm Hg)
121 ± 23
118 ± 22
124 _+ 17
pH
7.31 ± 0.06
7.32 ± 0,08
7.34 ± 0.03
Pao2
89 ± 14
91 ± 38
84 _+ 9
Paco2
44 ± 11
38 ± 9
39 ± 4
Values are given as mean ± SD. *MAP, mean arterial pressure; LVP, mean left venlricular pressure; CorPP, aortic diaslolic pressure minus right atrial diastolic pressure.
TABLE 3. Prearrest values SECPR Group
CPB Group
IV fluids (mL)
250 ± 315
330 ± 204
OCCPR Group 252 ± 91
Heart rate
154 ± 12
174 ± 32
148 ± 33
LVP (mm Hg)*
61 _+ 17
54 _+ 13
51 _+ 19
MAP (mrn Hg)
149 ± 28
147 ± 23
133 ÷ 31
CorPP (mm Hg)
123 ± 26
125 ± 22
106 + 30
pH
7.32 ± 0.07
7.33 + 0.12
7.31 ± 0.06
Pao2
83 + 15
76 ± 13
77 ± 8
Paco2
40 ± 11
42 ± 16
39 ± 5
Values are given as mean ± SD. *LVP, mean left ventricular pressure; MAP, mean arterial pressure; CorPP, aorlic diaslolic pressure minus right alrial diaslelic pressure.
one hour had elapsed since coil placement. A standard precordial lead was used to monitor ST segment elevation, and elevation was confirmed by two observers. After 1-mm ST segment elevation, VF was induced by delivering DC to the right ventricular endocardium through the pacing catheter. VF was confirmed u s i n g ECG and aortic pressure tracings. VF continued without respiratory support for four minutes to simulate the period of noflow VF in cardiac arrest. This period was selected based on prehospital response times reported in clinical cardiac arrest studies. 2>24 During four to 12 minutes of VF, basic CPR consisted of mechanical chest compression' and v e n t i l a t i o n {Thumper ®, Michigan Instruments, Grand Rapids, Michigan). The Thumper ® delivered 60 compressions per minute with a 50% duty cycle and a compression-ventilation ratio of 5:1. Compression depth was 2 in. Oxygen concentration was 100%. After eight minutes of basic CPR (12 minutes total VF time), animals that had been 20:7: July 1991
r a n d o m i z e d before arrest using a block design received one of three resuscitation techniques. SECPR animals received continued SECPR and epinephrine (0.04 mg/kg) through the central line at 12 minutes. Epinephrine was administered two minutes before initial defibrillation a t t e m p t s to increase CorPP, thereby o p t i m i z i n g the chance of successful defibrillation to a perfusing r h y t h m and d e c r e a s i n g t h e chance of postcountershock electromechanical dissociation. 2S-2r Defibrillation was begun at 14 minutes, and a modified advanced cardiac life support (ACLS) protocol was followed until successful resuscitation or an additional 30 minutes of therapy had elapsed (Table 1). CPB animals received 150 units/kg heparin during the one-minute "setup period" from minutes 12 to 13. No CPR was done during this minute. At 13 minutes, CPB was begun at 100 mL/kg/min using an extracorporeal p u m p i n g s y s t e m (Bioconsole 520, Biomedicus Inc, Eden Prairie, Minnesota) with an electromagnetic flow Annals of Emergency Medicine
probe (Bio Probe ®TX20, Biomedicus). At 15 minutes, epinephrine (0.04 mg/ kg) was given through the central line. Animals were defibrillated at 17 minutes. A modified ACLS protocol was followed until successful resuscitation or an additional 30 minutes of therapy had elapsed (Table 1). Once successfully defibrillated, CPB was continued for 30 minutes; then, the animal was weaned off. OCCPR animals underwent a left lateral t h o r a c o t o m y between minutes 12 and 13. Using a one-handed technique, OCCPR was performed at a rate of 60. At 15 minutes, epinephrine (0.04 mg/kg) was given through the central line, and internal defibrillation was performed at 17 minutes. A modified ACLS protocol, including continued OCCPR and internal defibrillation, was followed until successful resuscitation or 30 minu t e s of a d d i t i o n a l t h e r a p y had elapsed (Table 1). ROSC was defined as a spontaneous heart rhythm with a mean arterial pressure of more than 60 m m Hg. After ROSC, all animals received intensive care support for four hours. This included ventilatory support, blood pressure support with titration of norepinephrine to keep mean arte~ ria] pressure at more than 80 m m Hg, temperature control w i t h heating blankets, sodium bicarbonate for acidosis, supplemental oxygen, and IV fluids. Arterial blood gases, ECG, and hemodynamic variables were monitored. O C C P R animals had their chest closed during this time, whereas CPB animals had their bypass cannulae removed. At the end of four hours, 60 mL of a 5% fluorescein solution was injected into the left atrium and allowed to circulate for 60 seconds. The h e a r t was arrested in diastole using a potassium chloride bolus (2 mEq/kg). The heart was excised, washed, weighed, and sliced into 1-cm sections beginning above the level of the coil and extending to the apex. The heart slices then were photographed under UV light to highlight perfused myocardium. Sections were incubated in triphenyl tetrazolium hydrochloride (TTC) and photographed under tungsten lights to identify necrotic myocardium. 2a With a digitizing pad interfaced with an IBM-PC computer, areas of f l u o r e s c e i n and T T C stain were quantified. The individual perform756/81
CPR & CPB DeBehnke, Angelos & Leasure
ing these m e a s u r e m e n t s was blinded to the resuscitation technique. Area of infarct (no TTC stain, no fluorescein stain), i s c h e m i a (TTC stain, no fluorescein), ratios of infarct to ischem i a , a n d p e r c e n t a g e of m y o c a r d i a l i n v o l v e m e n t were determined. I m m e d i a t e and four-hour survival rates were d e t e r m i n e d for each group. Group h e m o d y n a m i c , blood gas, drug dosage, and infarct size data were expressed as m e a n + SD. Data were analyzed between groups using analysis of v a r i a n c e w i t h a T u k e y p o s t - h o c c o m p a r i s o n test and w i t h i n groups using paired t tests w i t h a Bonferroni adjustment. Correlation data was analyzed using Pearson's correlation w i t h B o n f e r r o n i c o r r e c t i o n . Resuscitation rates and survival were compared using an exact probability calculation. P < .05 was considered statistically significant.
RESULTS T w e n t y - e i g h t a n i m a l s w e r e entered into the study w i t h 26 used for s t a t i s t i c a l a n a l y s i s (SECPR, eight; CPB, nine; OCCPR, nine). Two CPB a n i m a l s w e r e e x c l u d e d b e c a u s e of cannula occlusion when nonrigid cannulae were used during the early p i l o t i n g phase. A l l s u b s e q u e n t CPB a n i m a l s u s i n g m o r e rigid c a n n u l a e were included.
Baseline B a s e l i n e v a l u e s w e r e s i m i l a r bet w e e n groups (Table 2). Baseline hem a t o c r i t w a s s t a t i s t i c a l l y l o w e r in the CPB group (P - .001) compared w i t h the SECPR group. These values were not clinically significant.
Infarct and Prearrest The t i m e for 1-mm ST segment ele v a t i o n to o c c u r w a s n o t s i g n i f i cantly different among groups (SECPR, 33.0 ± 22.4 m i n u t e s ; CPB, 39.9 ± 24.9 minutes; OCCPR, 35.1 ± 24.1 minutes). T h r e e SECPR animals, five CPB animals, and four OCCPR animals did not achieve l - r a m ST s e g m e n t e l e v a t i o n d u r i n g the one-hour period after left anterior descending coronary artery coil placement. The t i m e to ST segment elevation was not significantly different b e t w e e n survivors and nonsurvivors (31.3 ± 21.9 vs 38.6 ± 23.9 minutes). P r e a r r e s t v a l u e s for a n e s t h e t i c dose, h e a r t rate, m e a n arterial pressure, m e a n left ventricular pressure,
82/757
TABLE 4. Coronary perfusion pressure during resuscitation
SECPR Group Baseline Basic CPR Technique before epinephrine
121 16 16 15
Technique after epinephrine
_ ± ± +_
CPB Group
23 16 16 13
118 17 75 110
_+ ± ± _+
22 11 37"t
40,§it
OCCPR Group 124 17 56 68
± ± ± _+
17 9 31"t 44~
Values are given as mean -+ SO in mm Hg *P < .04 vs SECPR group. tp ~ 004 vs basic CPR *P 005 vs technique before epinephrine §P < .02 vs SECPR group. d!p _ 05 vs OCCPR group -
TABLE 5. Myocardial infarct size
Ischemic Myocardium
Necrotic Myocardium
Necrotic Myocardium/ Ischemic Myocardium
Group
(%)
(%)
(%)
SECPR CPB 0CCPR
9.9 _+ 2.3 22.4 + 21.3 37.3 _+ 11.8
11.2 _+ 0.52 2.4 _+ 5.6 10.5 _+ 7.2
1.16 _+ 0.31 0.15 ÷ 0.31" 0.39 _+ 0.25t
Values are given as mean ± SD *P .004 vs SECPR group rp - 02 vs SECPR group -
CorPP, and arterial blood gas values were comparable among groups (Table 3). Prearrest h e m a t o c r i t was sign i f i c a n t l y l o w e r in t h e CPB group t h a n in t h e SECPR group (SECPR, 54 ± 4%; CPB, 44 ± 5%; OCCPR, 48 ± 6%; P = .02). Prearrest anest h e t i c dose was s i g n i f i c a n t l y h i g h e r in the CPB group than in the SECPR group (SECPR, 23.6 ± 10.1 mL; CPB, 34.6 ± 8.2 mL; OCCPR, 26.0 -+ 7.1 mL; P = .04). These statistical differences were not considered clinically significant.
Resuscitation All animals had similar CorPP during basic CPR before beginning OCCPR or CPB. CorPP increased significantly once O C C P R or CPB was begun. T h e C o r P P p r o d u c e d d u r i n g O C C P R and CPB was s i g n i f i c a n t l y higher compared w i t h SECPR (Table 4). T h e r e was no significant difference in CorPP b e t w e e n OCCPR and CPB. S u r v i v o r s h a d s i g n i f i c a n t l y h i g h e r C o r P P a f t e r i n s t i t u t i o n of technique compared with nonsurvivors (64 ± 35 vs 23 + 24 m m Hg, P = .0051. A f t e r i n j e c t i o n of e p i n e p h r i n e , CorPP increased significantly in the CPB group but not in the SECPR or O C C P R group. The CorPP produced d u r i n g O C C P R and CPB w i t h epinephrine was significantly higher than CorPP during SECPR With epi-
Annals of Emergency Medicine
nephrine. CorPP produced w i t h CPB and epinephrine was significantly h i g h e r t h a n CorPP d u r i n g O C C P R and epinephrine (Table 4). Survivors had significantly higher CorPP after i n j e c t i o n of e p i n e p h r i n e c o m p a r e d with nonsurvivors ( 9 7 - + 45 vs 22 -+ 39 m m Hg, P < .001). Epinephrine dosage required for res u s c i t a t i o n was s i g n i f i c a n t l y less in t h e CPB group c o m p a r e d w i t h t h e SECPR group (SECPR, 0.28 ± 0.11 m g / k g ; CPB, 0.10 + 0.02 m g / k g ; O C C P R , 0.20 ± 0.12 m g / k g ; P = .002). There was no significant difference in epinephrine dosage between t h e CPB and O C C P R groups. Survivors required less epinephrine than nonsurvivors (0.12 ± 0.07 vs 0.32 -+ 0.04 mg/kg, P < .001). The n u m b e r of c o u n t e r s h o c k s n e e d e d for resuscitation was n o t s i g n i f i c a n t l y different a m o n g groups (SECPR, 8.0 _+ 6.5; CPB, 2.1 ± 1.5; OCCPR, 7.6 _+ 11.2). Survivors required fewer countershocks to achieve ROSC c o m p a r e d w i t h nonsurvivors (2.2 ±: 1.9 vs 12.6 _+ i0.2, P = .001).
Postresuscitation ROSC was achieved in nine of nine CPB and six of nine O C C P R animals compared w i t h two of eight SECPR a n i m a l s (P < .01). Survival to four hours Was achieved in two of eight SECPR a n i m a l s a n d t h r e e of n i n e CPB and three of nine O C C P R ani-
20:7 Ju}y 1991
CPR & CPB DeBehnke, Angelos & Leasure
reals. One a n i m a l in the O C C P R group had a tear in the inferior vena cava during OCCPR and died during the r e s u s c i t a t i o n period. One CPB animal had a laceration of the right atrium and s u b s e q u e n t pericardial tamponade and died early during the p o s t r e s u s c i t a t i o n period. S u r v i v a l time (time from ROSC to death) was significantly higher in the CPB group compared w i t h SECPR and OCCPR groups (SECPR, 60.0 _+ 111.1 m i n utes; CPB, 195.6 +- 48.5 m i n u t e s ; OCCPR, 115.7 -+ 104.7 minutes; P = .02). There was no significant difference between g r o u p s r e g a r d i n g h e m o dynamic data or arterial blood gas measurements in the postresuscitation period. Due to e x t r a c o r p o r e a l oxygenation, Po 2 was s i g n i f i c a n t l y higher in the CPB group one minute after ROSC compared with the OCCPR group (CPB, 391.7 -+ 127.6 m m Hg; OCCPR, 76.0 + 28.5 m m Hg; P = .0003). Postresuscitation fluid, bicarbonate, and norepinephrine dosage were not significantly different among groups.
Infarct Size All animals achieving ROSC had significant areas of ischemic and necrotic myocardium corresponding to the left anterior descending coronary artery bed. The ratio of necrotic to ischemic m y o c a r d i u m was s i g n i f i cantly lower in the CPB and OCCPR groups. H o w e v e r , t h e p e r c e n t ischemic m y o c a r d i u m t e n d e d to be higher in t h e s e g r o u p s c o m p a r e d with the SECPR group (Table 5). The percent ischemic, percent necrotic, and necrotic-to-ischemic ratio were not significantly different in animals that achieved ST segment elevation compared with those that did not.
DISCUSSION After left anterior descending coronary artery occlusion, OCCPR and CPB showed improved immediate resuscitation from VF cardiac arrest. Our i m m e d i a t e r e s u s c i t a t i o n rates are consistent with previous studies of OCCPR in the canine model.8, 9 The resuscitation technique was begun after four minutes of no-flow VF and nine minutes of basic CPR. Animals in the control group (SECPR) received epinephrine and defibrillation three m i n u t e s earlier than those in the OCCPR and CPB groups. The delay in the other two groups was to al20:7: July 1991
low time to perform a thoracotomy or s t a r t bypass. Our e x p e r i m e n t a l model was therefore slightly biased in favor of the SECPR animals. OCCPR has been previously studied in animal models as an alternative to SECPR. Most animal studies showed improved hemodynamics and survival with OCCPR. Bircher et al showed OCCPR increased arterial p r e s s u r e , s y s t e m i c p e r f u s i o n pressures, and c o m m o n c a r o t i d blood flow to twice that of control compared with SECPR and military antishock trousers (MAST)-augmented CPR. 6 Neither short- nor long-term survival rates were studied. 6 Jackson and coworkers showed increased mean systolic pressure with OCCPR compared w i t h SECPR and SECPR plus epinephrine. Again, survival was not studied. 7 Kern and coworkers studied survival from cardiac arrest using OCCPR as a reperfusion technique. After 15 minutes of SECPR, OCCPR produced ROSC in six of eight animals compared with one of eight SECPR animals. Resuscitation declined to three of eight and none of eight animals when OCCPR was delayed to 20 and 25 minutes after beginning SECPR. 8 A similar study of short- and longterm survival found improved immediate resuscitation (14 of 14 OCCPR vs five of 14 SECPR) and seven-day survival (11 of 14 OCCPR vs four of 14 SECPR) when OCCPR followed three minutes of VF and 12 minutes of ineffective SECPR. 9 These studies support the role of OCCPR in improving perfusion pressures and survival from VF cardiac arrest. In cont r a s t to o u r m y o c a r d i a l i n f a r c t model, these studies used healthy animal preparations with nonischemic hearts before arrest. W e i s e r et al s t u d i e d b l o o d flow during OCCPR in infarcted canine hearts and found that OCCPR produced an average cardiac output of 67% of prearrest values compared with 15% for SECPR. 29 Byrne and coworkers compared OCCPR and SECPR in chronically ischemic dog hearts. They showed an increase in cardiac output and improved myocardial blood flow in dogs treated with OCCPR. 3° Survival from cardiac arrest was not reported in e i t h e r of these studies. CPB has been investigated as a reperfusion tool after cardiac arrest in the canine model. Using a stanAnnals of Emergency Medicine
dardized dog VF cardiac arrest model, m u l t i p l e i n v e s t i g a t i o n s have compared CPB with SECPR and advanced life support. P r e t t o et al d e m o n strated i m p r o v e d r e s u s c i t a t i o n and 72-hour survival after CPB reperfus i o n . 13 S i m i l a r l y , M a r t i n et al showed improved resuscitation rates and survival after a 12-minute VF arrest w i t h o u t CPR. 14 In a prolonged dog CPR model of four minutes VF followed by 30 minutes of CPR and then CPB, Levine et al noted significant i m p r o v e m e n t in i n i t i a l resusc i t a t i o n and 72-hour survival w i t h CPB. ~5 Using the current model, we similarly showed improved resuscitation with CPB in an earlier study. 31 The improved survival and resuscitability w i t h OCCPR and CPB in animal models appear to be due to the higher aortic diastolic and coronary perfusion pressures generated. Kern et al s h o w e d s i g n i f i c a n t l y higher CorPP during OCCPR compared w i t h SECPR w h e n OCCPR was begun 12 minutes after ineffective SECPR. 9 Angelos et al showed significantly higher CorPP with CPB after 20 minutes of VF including ten minutes of CPR ACLS. 3~ In another study, CorPP s i m i l a r to p r e a r r e s t values could be obtained with CPB after 15 to 20 minutes of VF without prior CPR. 33 Previous a n i m a l CPR studies have shown aortic diastolic pressure and CorPP to be the best prognostic i n d i c a t o r s of successful resuscitation from cardiac arrest. ~4,17 Recent clinical data have also supported the prognostic value of CorPP during CPR. 18 In our study, CorPP during OCCPR and CPB was s i g n i f i c a n t l y h i g h e r than during SECPR. CorPP similar to prearrest values could be produced by OCCPR and CPB. There did not appear to be any difference in CorPP produced by OCCPR compared with CPB before a d m i n i s t r a t i o n of epinephrine. However, CorPP increased significantly in the CPB group compared with the OCCPR group after epinephrine injection. Survivors from cardiac arrest, regardless of reperfusion technique, had higher CorPP than nonsurvivors. Our data support the prognostic value of CorPP in canine cardiac arrest b e c a u s e a n i m a l s w i t h h i g h e r CorPP were more likely to survive cardiac arrest. Furthermore, animals with higher CorPP were easier to resuscitate from cardiac arrest, when 758/83
CPR & CPB DeBehnke, Angelos & Leasure
epinephrine dosage and n u m b e r of countershocks were used as indicators of ease of resuscitation. OCCPR and CPB produced higher i m m e d i a t e resuscitation rates from cardiac arrest compared with SECPR but s i m i l a r s u r v i v a l rates at four hours. These data are disappointing but not dissimilar to recent clinical experience. OCCPR and CPB produce the CorPP needed for immediate r e s u s c i t a t i o n of the heart, but this does not ensure long-term cardiac stability. One measure of postresuscitation stability, survival time, was improved in CPB animals comp a r e d w i t h SECPR a n d O C C P R . However, survival to our end point (four hours) was n o t d i f f e r e n t between groups. Due to the small number of animals in each group, there is the possibility of significant type II F-error. Therefore, we may not have been able to detect a difference in four-hour survival when one actually existed. To a c c u r a t e l y assess techniques with respect to long-term survival and neurologic outcome, threeto seven-day survival studies with a larger number of animals would need to be done. Because OCCPR and CPB produce higher perfusion pressures, they m i g h t be e x p e c t e d to salVage ischemic myocardium and thereby prevent ischemic myocardium from becoming necrotic during resuscitation. CPB-resuscitated animals were noted in an e a r l i e r s t u d y to have a decreased n e e r o t i c - t o - i s c h e m i c r a t i o compared with SECPR. ,~ In our study, we used the ratio of necrotic-to-ischemic tissue as a measure of infarct size to normalize for the v a r i a b i l i t y in area of risk. We noted that the ratio of necrotic-to-isc h e m i c m y o c a r d i u m was s i g n i f i cantly less in the CPB and OCCPR groups compared w i t h the SECPR group. However, in the absence of m y o c a r d i a l b l o o d flow m e a s u r e ments to establish postocclusion area of risk and subepicardial c o l l a t e r a l blood flow, it is u n c l e a r w h e t h e r these differences in group infarct size were due to resuscitation techniques or to variation in regional myocardial necrosis in the distribution of the occluded artery. The distribution of the necrosis was consistent with an earlier study that demonstrated necrosis in the distribution of the left anterior descending coronary artery occluded before cardiac arrest. In contrast, the 84/759
control group, which did not experience coronary artery occlusion, essentially had no necrosis after cardiac arrest. 2° Additional studies using regional myocardial blood flow measurements to define collateral blood flow and p o s t o c c l u s i o n area at risk are needed to determine any infarct reduction afforded by the various techniques. It may be hypothesized that anim a l s t h a t died e a r l y in the postr e s u s c i t a t i o n period had larger infarcts. However, we found no statistical correlation between postresuscitation survival times and infarct size (percent ischemic R = -0.6924, percent necrotic R = -0.0439, necroticto-ischemic ratio R = 0.3178). H e p a r i n i z a t i o n was used in the CPB group as part of the research protocol. The effects of heparin on blood viscosity, t h r o m b u s f o r m a t i o n and maintenance, infarct size, and resuscitation rates were not specifically studied here but warrant further investigation in similar animal models. Norepinephrine was used in the postresuscitation period for pressor support. Norepinephrine has been shown to increase myocardial oxygen consumption and may increase myocardial infarct size. All animals required a norepinephrine infusion for blood pressure support. We did not specifically study the effect of norepinephrine on infarct size, but it is possible that postresuscitation use of norepinephrine contributed to the ultimate ischemic and necrotic areas. This question requires further investigation. There are few studies of OCCPR in h u m a n beings. Del G u e r c i o et al studied blood flow during open- and closed-chest CPR in h u m a n beings and found i m p r o v e d cardiac index and m e a n c i r c u l a t i o n t i m e during OCCPR. 34 No large, well-controlled clinical study has been done with human beings. Most such reports in the literature of OCCPR have been uncontrolled case series and anecdotal in nature. There are some uncontrolled clinical reports of successful resuscitation w i t h closed-chest CPB techniques. Baird et al reviewed 25 patients with acute myocardial infarction treated with venoarterial bypass using a bubble oxygenator:m Five of 25 patients in cardiogenic shock or cardiac arrest were r e s u s c i t a t e d and s u r v i v e d at Annals of Emergency Medicine
least one m o n t h . M a t t o x et al reported 24 of 39 m o r i b u n d p a t i e n t s initially resuscitated with CPB with 15 long-term survivors.t1 The majority of survivors, 13 of 15, were patients with large pulmonary emboli. Phillips et al reported on 22 patients in cardiac arrest who received femorofemoral CPB; nine survived. 12 Similarly, Reichman et al reported on 38 patients in cardiac arrest refractory to ACLS protocols who were p l a c e d on e m e r g e n c y b y p a s s ; six patients survived. 35 Recent clinical reviews of resusc i t a t i o n from cardiac a r r e s t using SECPR have shown survival rates of 2% to 25%. 2-4 There are m u l t i p l e variables that influence survival (down time, i n i t i a l r h y t h m , emergency medical service system, and so on), b u t u l t i m a t e s u r v i v a l h a s changed little since the introduction of SECPR in 1960. Perhaps a more invasive m e t h o d of reperfusion, one that produces significantly higher CorPP, should be used in selected clinical cardiac arrests. In our study, OCCPR and CPB were comparable resuscitation tools. OCCPR is an easily learned technique requiring m i n i m a l equipment and is currently used in some cases of p e n e t r a t i n g t r a u m a w i t h subsequent cardiac arrest. Once resuscitation has been achieved, surgical cons u l t a t i o n w o u l d be n e c e s s a r y for chest closure. CPB is a less invasive technique but requires more equipment and specially trained perfusionists and may be more difficult to initiate in the emergency department. C a n n u l a t i o n of the femoral artery and v e i n w o u l d h a v e to be done using cutdowns. Once initiated, CPB could be continued in the intensive care period and m a y provide more stable hemodynamic and postr e s u s c i t a t i o n cardiac support. It is premature to advocate one technique over the other. C l i n i c a l feasibility s t u d i e s m u s t be done w i t h these techniques before any recommendations are made. CONCLUSION CPB and OCCPR produced higher CorPP and improved i m m e d i a t e resuscitation compared with SECPR in a. canine infarct model. OCCPR and CPB produced similar CorPP and resuscitation rates when compared with each other; however, CPB produced higher CorPP when used in 20:7 July 1991
CPR & CPB DeBehnke, Angelos & Leasure
conjunction with epinephrine. Clinical survival studies with SECPR have generated an attitude of therapeutic nihilism with respect to prolonged cardiac arrest. OCCPR and CPB are alternative reperfusion techniques that require further evaluation in the clinical arena. The authors extend special thanks to Rhonda Barton, Erik Ramnath, and Scott Russell for their technical assistance; Andrea A r n o l d f o r h e r a s s i s t a n c e w i t h m a n u script preparation; and Biomedicus, Inc, Eden Prairie, Minnesota, for CPB equipment support.
REFERENCES 1. American Heart Association: Standards and guidelines for cardiopulmonary resuscitation (CPR / and e m e r g e n c y c a r d i a c care (ECC}. l A M A 1986;55 fsuppll:2841-3044. 2. Hartgarten KM, Steuven HA, Waite EM, et al: Prehospital experience with defibrillation of coarse ventricular fibrillation: A ten-year review. Ann Emerg Med i990~19:157-162. 3. Eisenberg MS, Horwood BT, C u m m i n s RO, et al: Cardiac arrest and resuscitation: A tale of 29 cities. Ann Emerg Med 1990;19:179-i86. 4. Edgren E, Kelsey S, Sutton K, et al: The presenting ECG pattern in survivors of cardiac arrest and its relation to the subsequeut long-term survival. Acta Anesthesiol Scand 1989;33:265-271. 5. Kouwenhoven WB, Jude JR, Knickerbocker GG: Closed-chest cardiac massage. JAMA 1960;173:94-97. 6. Bircher N, Safar P, Stewart R: A comparison of standard, "MAST"-augmented, and open-chest CPR in dogs. Crit Care Med 1980;8:147-152. 7. Jackson RE, Joyce K, Danosi gP, et al: Blood flow in the cerebral cortex during cardiac resuscitation in dogs. Ann Emerg Med 1984;13:657-659. 8. Kern KB, Sanders AB, Ewy GA: Open-chest cardiac massage after closed-chest compression in a canine model: When to intervene. Resuscitation 1987;15:51-57. 9. Kern KB, Sanders AB, Badylak SF, et al: Long-term
20:7: July 1991
survival with open chest cardiac massage after ineffective dosed-chest compression in a canine preparation. Circulation 1987;75:498-503. 10. Baird R, Rocha A, Miyasishima R, et al: Assisted circulation following myocardial infarction: A review of 25 patients treated before 1971. Can Med Assoc J 1972;107:287-291. 11. Mattox KL, Beall AC: Resuscitation of the moribund patient using portable cardiopulmonary bypass. Ann Thorac Surg 1976;22:436-442. 12. Phillips SJ, Zeff RH, Kongtahvorn C, et al: Percutaneous cardiopulmonary bypass: Application and indication for use. Ann Thorac Surg 1989;47:121-123. 13. Pretto E, gafar P, Saito R, et al: Cardiopulmonary bypass after prolonged cardiac arrest in dogs. Ann Emerg Med 1987;16:611-619. 14. Martin GB, Nowak RM, Carden DL, et al: Cardiopulmonary bypass vs CPR as treatment for prohmged c a n i n e c a r d i o p u l m o n a r y arrest. A n n Emerg Med 1987;I6:628-636. 15. Levine R, Gorayeb M, Safar P, et al: Cardiopulmonary bypass after cardiac arrest and prolonged closed chest CPR in dogs. Ann Emerg Med 1987;16:620 627. 16. Niemann JT, Rosbnrough Jp, Ung S, et al: Coronary perfusion pressure during experimental cardiopulmonary resnscitation. Ann Erner~g Med [982;11:127-131. 17. Sanders AB, Ewy GA, Taft TV: Prognostic and ther apeutic importance of the aortic diastolic pressure in re s u s c i t a t i o n f r o m cardiac arrest. Crit Care Med 1984;12:871 873.
where in the United States. Ann Emerg Med 1985;14: 750-754. 24. Silfvast T: Prehospital resuscitation in Helsinki, Finland. Am J Emerg Med 1990;8:359-364. 25. Rothstein RJ, Niemann IT, Rennie CJ, et al: Use of naloxone during cardiac arrest and CPR: Potential adjunct for post countershock electrical-mechanical dissociation. Ann Emerg Med 1985;14:198-203. 26. Neiman IT, Haynes KS, Garner D, et aI: Post countershock pulseless rhythms: Hernodynamic effects of glucagon in a canine modeh Crit Care Med 1987; 15:554-558. 27. N e i m a n IT, Garner D, Peikon P, et al: Predictive value ;ff the ECG in determining cardiac resuscitation outcome in a canine model of post countershock electromechanical dissociation after prolonged ventricular fibrillation. Ann Emerg Med 1988;17:567-571. 28. Lie JT, Pairolem PC, Holley KE, et al: Macroscopic enzyme-mapping verification of large, homogeneous, experimental myocardial infarcts of predictable size and location in dogs. f Thorac Cardiowisc Surg 1975; 69:599-605. 29. Weiser FM, Adler LN, Kuhn LA: Hemodynamic effects of closed and open chest cardiac resuscitation in normal dogs and those with acute myocardial infarc tion. Am J Cardiol 1962;10:555-561. 30. Byrne D, Pass HI, Neely WA, et al: External versus internal cardiac massage in normal and chronically ischemic dogs. Am Snrg,eon 1980;46:657-662.
18. Paradis NA, Martin GB, Rivers EP, et al: Coronary perfusion pressure and the return of spontaneous circu lation in hmnan cardiopulmonary resuscitation. JAMA 1990;263:1106q113.
31. Angelos M, Gaddis M, Gaddis G, et at: improved survival and reduced myocardial necrosis with cardiopulmonary bypass reperfusion in a canine model of coronary occlusion and cardiac arrest. Ann Emerg Med 1990;19:1122-1128.
19. Kordenat RK, Kezdi P, Stanley EL: A new catheter technique for producing experimental coronary thrombosis and selective coronary visualization. Am Heart J 1972;83:360-364.
32. Angelos M, Reich H, Safar P: Coronary perfusion pressure during external CPR versus cardiopulmonary bypass after prolonged cardiac arrest in dogs (abstract I. Ann Emerg Med 1987;A10 16:1102.
20. Angelos MG, Gaddis M, Gaddis G, et al: Cardiopulmonary bypass in a model of acute myocardial infarction and c a r d i a c a r r e s t . A n n Emerg M e d 1990~ 19:874-880.
33. Reich H, Angelos M, Safar P, et al: Cardiac resus citability with cardiopulmonary byl:mss after increasing ventricular fibrillation times in dogs. Ann Emerg Med 1990;19:887-g90.
21. Roth R, Stewart RD, Rogers K, et al: Out-of-hospital cardiac arrest: Factors associated with survival. Ann Emerg Med 1984;13:237-243. 22. Eisenberg MS, Hallstrom A, Bergner L: Long-term survival after out-of~hospital cardiac arrest. N Engl J Med 1982;306: I340-1343. 23. Thompson BM, Stueven HA, Mateer JR, et aI: Comparison of clinical CPR studies in Milwaukee and else-
Annals of Emergency Medicine
34. Del Guercio LR, Feins NR, Cohn JD, et al: Comparison of blood flow during external and internal cardiac massage in man. Circulation 1965;31,32[suppl I}:I-171 1-180. 35. Reichman RT, Joyo CI, Dembitsky WP, et al: Improved patient survival after cardiac arrest using a card i o p u l m o n a t y support s y s t e m . A n n Thorac Surg 1990;49:101 105.
760/85
Comparison of Standard External CPR, Open-Chest CPR, and Cardiopulmonary Bypass in a Canine Myocardial Infarct Model Study objectives: After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model. Type of participants: Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight). Design and interventions: All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper ® CPR. A t 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas. Measurements: Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group. Main results: Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P < .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +- 37 m m Hg) and OCCPR (56 + 31 m m Hg) than in SECPR animals (16 +- i6 m m Hg, P < .04). Epinephrine required for resuscitation was significantly less w i t h CPB (0.10 +_ 0.02 mg/kg) than for SECPR (0.28 ++-0.11 mg/kg, P < .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +_ 0.31) and OCCPR (0.39 +_ 0.25) than for SECPR (I.i6 -- 0.31, P < .02). Conclusion: OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB. [DeBehnke D J, Angelos MG, Leasure JE: Comparison of standard external CPR, open-chest CPR, and cardiopuImonary bypass in a canine myocardial infarct model. A n n Emerg Med July 1991;20:754-760.]
Daniel J DeBehnke, MD Mark G Angeles, MD, FACEP James E Leasure Dayton, Ohio From the Department of Emergency Medicine, Wright State University School of Medicine, Dayton, Ohio. Received for publication May 9, 1990. Revision received September 10, 1990. Accepted for publication January 21, 1991. Presented at the Society for Academic Emergency Medicine Annual Meeting in Minneapolis, Minnesota, May 1990; and the Emergency Medicine Research Society/Society for Academic Emergency Medicine Combined International Meeting in Edinburgh, Scotland, October 1990. This research was funded by the Emergency Medicine Foundation/Carl Jelenko Research Award and the Kettering Medical Center Resident Research Fund. Address for reprints: Daniel J DeBehnke, MD, Medical Coqlege of Wisconsin, Department of Emergency Medicine, Box 204, 8700 West Wisconsin Avenue, Milwaukee, Wisconsin 53226.
INTRODUCTION Cardiac arrest and sudden cardiac death are important problems in our society; an estimated 1,000 cardiac arrests occur every day.l Survival to hospital discharge is variable, ranging from 2% to 25% depending on the presenting cardiac rhythm and the emergency medical services system operating within the community, z-4 Based on current survival data, successful short- and long-term resuscitation from cardiac arrest remains low with standard external CPR (SECPR). Open-chest CPR (OCCPR) was the method of choice for resuscitation of
20:7 July 1991
Annals of Emergency Medicine
754/7 c
CPR & CPB DeBehnke, A n g e l o s & Leasure
in-hospital, nontraumatic cardiac arrest until Kouwenhouven et al's research in 1960. 5 0 C C P R is occasionally used today for victims of penetrating chest t r a u m a w h o suffer cardiac arrest. O C C P R has been shown to produce improved perfusion pressures and resuscitation rates compared with SECPR in animal models of cardiac arrest. 6-9 Cardiopulmonary bypass (CPB} has been used extensively for cardiac maintenance during myocardial revascularization and other cardiac surgical procedures. There have been several uncontrolled clinical reports of successful resuscitation from cardiac arrest with closed-chest CPB. 1°-1~ More recently, CPB has been investigated as a resuscitation tool after cardiac arrest in canine models and has been shown to improve perfusion pressures and resuscitation rates compared with SECPR.13~15 Return of spontaneous circulation (ROSC) after cardiac arrest appears to be correlated with the coronary perfusion pressure (CorPP) generated during CPR. 16-18 Techniques used to improve CorPP during CPR should lead to improved resuscitation. Both OCCPR and CPB have been shown to increase CorPP and improve resuscitation from cardiac arrest in canine models. One major criticism of survival studies in the canine model has been the use of healthy animal preparations. No short- or long-term survival studies have compared various CPR techniques in a canine infarct model. We investigated the ability of OCCPR and CPB to improve CorPP and resuscitation rates compared with SECPR in a canine model of acute myocardial infarction followed by ventricular fibrillation (VF) cardiac arrest. Our null hypothesis stated that there is no difference between resuscitation techniques with respect to CorPP generated or resuscitation rates achieved. MATERIALS A N D M E T H O D S This study was approved by the laboratory animal utilization committee at our institution. Twentyeight mongrel dogs of both sexes (weight, 15 to 30 kg) were used. All animals were anesthetized using 20 mg/kg thiopental, intubated, and placed on a ventilator. Respiratory rate was adjusted to maintain a nor80/755
TABLE 1. Modified ACLS protocol for different resuscitation groups VF Time (min)
SECPR Group*
VF Time (min)
CPB and OCCPR Groups*
14
100J x 3
17
100J x 3(15J x 3)
15 16
Epinephrine 200J x 3
18 19
Epinephrine 200J x 3(15J x 3)
17
Epinephrine and lidocaine
20
Epinephrine and lidocaine
18
300J x 3
21
300J x 3(15J x 3)
20
Epinephrine
23
Epinephrine
21 23 24
300J x 3 300J x 3 Epinephrine
24 26 27
300J x 3(20J x 3) 300J x 3(30J x 3) Epinephrine 300J x 3(30J x 3)
26
300J x 3
29
27
Lidocaine
30
Lidocaine
28
300J x 3
31
300J x 3(30J x 3)
29
Epinephrine
32
Epinephrine
31 33
300J x 3 300J x 3
34 36
300J x 3(30J x 3) 300J x 3(30J x 3)
34 36
Epinephrine 300J x 3
37 39
Epinephrine 300J x 3(30J x 3)
37
Lidocaine
40
Lidocaine
38 39
300J x 3 Epinephrine
41 42
300J x 3(30J x 3) Epinephrine
41 44
300J x 3 End
44 47
300J x 3(30J x 3) End
*Epinephrine dose 40 t~g/kg; lidocaine dose 1 mg/kg.
ma] Pco2 and pH based on arterial blood gases (Instrumentation Laboratory Model 1304, Lexington, Massachusetts). Thiopental was administered at doses of 2 to 5 mg/kg interm i t t e n t l y throughout the study to maintain general anesthesia. Cutdowns were performed on the femoral vessels, both external jugular veins, and the left c o m m o n carotid artery. A 5F Millar microtip-catheter pressure transducer (model SPL-350, Millar I n s t r u m e n t s , Inc, Houston, Texas) was placed through the right femoral artery to record left ventricular pressure. A right atrial line was placed through the right femoral vein for drug administration and pressure 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 through the left femoral artery in nonCPB group animals and through the left carotid artery after coil placement in CPB animals to monitor aortic pressures. Animals in the CPB group had two 18F bypass cannulae placed in the external jugular veins and a 12F bypass cannula Annals of Emergency Medicine
placed in the left femoral artery for bypass. The jugular vein bypass cannulae were advanced to the level of the right atrium. Placement of all catheters was confirmed by standard pressure waveforms and fluoroscopy. Pressures were measured and recorded using a physiological monitoring system (model VR 12, Electronics for Medicine, Inc, White Plains, New York). All catheters were flushed with heparinized saline. After catheter placement, baseline h e m o d y n a m i c and ECG measurements were determined. Using the left common carotid artery, a copper coil was placed in the left anterior descending coronary artery using the two-catheter technique of Kordenat et al. 19 Fluoroscopy was used to ensure proper coil placement. With this technique, the coil was consistently placed between the first and second diagonal branches of the left anterior descending coronary artery as previously described. 2o All animals received ECG, aortic, and right atrial pressure monitoring until 1 m m of ST segment elevation occurred or 20:7 July 1991
CPR & CPB DeBehnke, A n g e l u s & L e a s u r e
TABLE 2. Baseline values SECPR Group
CPB Group
OCCPR Group
Blood sugar (mg/dL)
96 ± 13
82 + 19
84 ± 12
Hematocrit (%)
48 +_ 5
38 + 4
44 ± 5
Temperature(C)
37.8 _+ 0.9
38.3 +_ 0,6
37.8 ± 0.7
Heart rate
168 ± 25
177 ± 30
171 ± 23
MAP (mm Hg)*
142 ± 23
139 +_ 26
144 ± 19
LVP (mm Hg)
58 ± 13
59 -+ 16
73 ± 30
CorPP (mm Hg)
121 ± 23
118 ± 22
124 _+ 17
pH
7.31 ± 0.06
7.32 ± 0,08
7.34 ± 0.03
Pao2
89 ± 14
91 ± 38
84 _+ 9
Paco2
44 ± 11
38 ± 9
39 ± 4
Values are given as mean ± SD. *MAP, mean arterial pressure; LVP, mean left venlricular pressure; CorPP, aortic diaslolic pressure minus right atrial diastolic pressure.
TABLE 3. Prearrest values SECPR Group
CPB Group
IV fluids (mL)
250 ± 315
330 ± 204
OCCPR Group 252 ± 91
Heart rate
154 ± 12
174 ± 32
148 ± 33
LVP (mm Hg)*
61 _+ 17
54 _+ 13
51 _+ 19
MAP (mrn Hg)
149 ± 28
147 ± 23
133 ÷ 31
CorPP (mm Hg)
123 ± 26
125 ± 22
106 + 30
pH
7.32 ± 0.07
7.33 + 0.12
7.31 ± 0.06
Pao2
83 + 15
76 ± 13
77 ± 8
Paco2
40 ± 11
42 ± 16
39 ± 5
Values are given as mean ± SD. *LVP, mean left ventricular pressure; MAP, mean arterial pressure; CorPP, aorlic diaslolic pressure minus right alrial diaslelic pressure.
one hour had elapsed since coil placement. A standard precordial lead was used to monitor ST segment elevation, and elevation was confirmed by two observers. After 1-mm ST segment elevation, VF was induced by delivering DC to the right ventricular endocardium through the pacing catheter. VF was confirmed u s i n g ECG and aortic pressure tracings. VF continued without respiratory support for four minutes to simulate the period of noflow VF in cardiac arrest. This period was selected based on prehospital response times reported in clinical cardiac arrest studies. 2>24 During four to 12 minutes of VF, basic CPR consisted of mechanical chest compression' and v e n t i l a t i o n {Thumper ®, Michigan Instruments, Grand Rapids, Michigan). The Thumper ® delivered 60 compressions per minute with a 50% duty cycle and a compression-ventilation ratio of 5:1. Compression depth was 2 in. Oxygen concentration was 100%. After eight minutes of basic CPR (12 minutes total VF time), animals that had been 20:7: July 1991
r a n d o m i z e d before arrest using a block design received one of three resuscitation techniques. SECPR animals received continued SECPR and epinephrine (0.04 mg/kg) through the central line at 12 minutes. Epinephrine was administered two minutes before initial defibrillation a t t e m p t s to increase CorPP, thereby o p t i m i z i n g the chance of successful defibrillation to a perfusing r h y t h m and d e c r e a s i n g t h e chance of postcountershock electromechanical dissociation. 2S-2r Defibrillation was begun at 14 minutes, and a modified advanced cardiac life support (ACLS) protocol was followed until successful resuscitation or an additional 30 minutes of therapy had elapsed (Table 1). CPB animals received 150 units/kg heparin during the one-minute "setup period" from minutes 12 to 13. No CPR was done during this minute. At 13 minutes, CPB was begun at 100 mL/kg/min using an extracorporeal p u m p i n g s y s t e m (Bioconsole 520, Biomedicus Inc, Eden Prairie, Minnesota) with an electromagnetic flow Annals of Emergency Medicine
probe (Bio Probe ®TX20, Biomedicus). At 15 minutes, epinephrine (0.04 mg/ kg) was given through the central line. Animals were defibrillated at 17 minutes. A modified ACLS protocol was followed until successful resuscitation or an additional 30 minutes of therapy had elapsed (Table 1). Once successfully defibrillated, CPB was continued for 30 minutes; then, the animal was weaned off. OCCPR animals underwent a left lateral t h o r a c o t o m y between minutes 12 and 13. Using a one-handed technique, OCCPR was performed at a rate of 60. At 15 minutes, epinephrine (0.04 mg/kg) was given through the central line, and internal defibrillation was performed at 17 minutes. A modified ACLS protocol, including continued OCCPR and internal defibrillation, was followed until successful resuscitation or 30 minu t e s of a d d i t i o n a l t h e r a p y had elapsed (Table 1). ROSC was defined as a spontaneous heart rhythm with a mean arterial pressure of more than 60 m m Hg. After ROSC, all animals received intensive care support for four hours. This included ventilatory support, blood pressure support with titration of norepinephrine to keep mean arte~ ria] pressure at more than 80 m m Hg, temperature control w i t h heating blankets, sodium bicarbonate for acidosis, supplemental oxygen, and IV fluids. Arterial blood gases, ECG, and hemodynamic variables were monitored. O C C P R animals had their chest closed during this time, whereas CPB animals had their bypass cannulae removed. At the end of four hours, 60 mL of a 5% fluorescein solution was injected into the left atrium and allowed to circulate for 60 seconds. The h e a r t was arrested in diastole using a potassium chloride bolus (2 mEq/kg). The heart was excised, washed, weighed, and sliced into 1-cm sections beginning above the level of the coil and extending to the apex. The heart slices then were photographed under UV light to highlight perfused myocardium. Sections were incubated in triphenyl tetrazolium hydrochloride (TTC) and photographed under tungsten lights to identify necrotic myocardium. 2a With a digitizing pad interfaced with an IBM-PC computer, areas of f l u o r e s c e i n and T T C stain were quantified. The individual perform756/81
CPR & CPB DeBehnke, Angelos & Leasure
ing these m e a s u r e m e n t s was blinded to the resuscitation technique. Area of infarct (no TTC stain, no fluorescein stain), i s c h e m i a (TTC stain, no fluorescein), ratios of infarct to ischem i a , a n d p e r c e n t a g e of m y o c a r d i a l i n v o l v e m e n t were determined. I m m e d i a t e and four-hour survival rates were d e t e r m i n e d for each group. Group h e m o d y n a m i c , blood gas, drug dosage, and infarct size data were expressed as m e a n + SD. Data were analyzed between groups using analysis of v a r i a n c e w i t h a T u k e y p o s t - h o c c o m p a r i s o n test and w i t h i n groups using paired t tests w i t h a Bonferroni adjustment. Correlation data was analyzed using Pearson's correlation w i t h B o n f e r r o n i c o r r e c t i o n . Resuscitation rates and survival were compared using an exact probability calculation. P < .05 was considered statistically significant.
RESULTS T w e n t y - e i g h t a n i m a l s w e r e entered into the study w i t h 26 used for s t a t i s t i c a l a n a l y s i s (SECPR, eight; CPB, nine; OCCPR, nine). Two CPB a n i m a l s w e r e e x c l u d e d b e c a u s e of cannula occlusion when nonrigid cannulae were used during the early p i l o t i n g phase. A l l s u b s e q u e n t CPB a n i m a l s u s i n g m o r e rigid c a n n u l a e were included.
Baseline B a s e l i n e v a l u e s w e r e s i m i l a r bet w e e n groups (Table 2). Baseline hem a t o c r i t w a s s t a t i s t i c a l l y l o w e r in the CPB group (P - .001) compared w i t h the SECPR group. These values were not clinically significant.
Infarct and Prearrest The t i m e for 1-mm ST segment ele v a t i o n to o c c u r w a s n o t s i g n i f i cantly different among groups (SECPR, 33.0 ± 22.4 m i n u t e s ; CPB, 39.9 ± 24.9 minutes; OCCPR, 35.1 ± 24.1 minutes). T h r e e SECPR animals, five CPB animals, and four OCCPR animals did not achieve l - r a m ST s e g m e n t e l e v a t i o n d u r i n g the one-hour period after left anterior descending coronary artery coil placement. The t i m e to ST segment elevation was not significantly different b e t w e e n survivors and nonsurvivors (31.3 ± 21.9 vs 38.6 ± 23.9 minutes). P r e a r r e s t v a l u e s for a n e s t h e t i c dose, h e a r t rate, m e a n arterial pressure, m e a n left ventricular pressure,
82/757
TABLE 4. Coronary perfusion pressure during resuscitation
SECPR Group Baseline Basic CPR Technique before epinephrine
121 16 16 15
Technique after epinephrine
_ ± ± +_
CPB Group
23 16 16 13
118 17 75 110
_+ ± ± _+
22 11 37"t
40,§it
OCCPR Group 124 17 56 68
± ± ± _+
17 9 31"t 44~
Values are given as mean -+ SO in mm Hg *P < .04 vs SECPR group. tp ~ 004 vs basic CPR *P 005 vs technique before epinephrine §P < .02 vs SECPR group. d!p _ 05 vs OCCPR group -
TABLE 5. Myocardial infarct size
Ischemic Myocardium
Necrotic Myocardium
Necrotic Myocardium/ Ischemic Myocardium
Group
(%)
(%)
(%)
SECPR CPB 0CCPR
9.9 _+ 2.3 22.4 + 21.3 37.3 _+ 11.8
11.2 _+ 0.52 2.4 _+ 5.6 10.5 _+ 7.2
1.16 _+ 0.31 0.15 ÷ 0.31" 0.39 _+ 0.25t
Values are given as mean ± SD *P .004 vs SECPR group rp - 02 vs SECPR group -
CorPP, and arterial blood gas values were comparable among groups (Table 3). Prearrest h e m a t o c r i t was sign i f i c a n t l y l o w e r in t h e CPB group t h a n in t h e SECPR group (SECPR, 54 ± 4%; CPB, 44 ± 5%; OCCPR, 48 ± 6%; P = .02). Prearrest anest h e t i c dose was s i g n i f i c a n t l y h i g h e r in the CPB group than in the SECPR group (SECPR, 23.6 ± 10.1 mL; CPB, 34.6 ± 8.2 mL; OCCPR, 26.0 -+ 7.1 mL; P = .04). These statistical differences were not considered clinically significant.
Resuscitation All animals had similar CorPP during basic CPR before beginning OCCPR or CPB. CorPP increased significantly once O C C P R or CPB was begun. T h e C o r P P p r o d u c e d d u r i n g O C C P R and CPB was s i g n i f i c a n t l y higher compared w i t h SECPR (Table 4). T h e r e was no significant difference in CorPP b e t w e e n OCCPR and CPB. S u r v i v o r s h a d s i g n i f i c a n t l y h i g h e r C o r P P a f t e r i n s t i t u t i o n of technique compared with nonsurvivors (64 ± 35 vs 23 + 24 m m Hg, P = .0051. A f t e r i n j e c t i o n of e p i n e p h r i n e , CorPP increased significantly in the CPB group but not in the SECPR or O C C P R group. The CorPP produced d u r i n g O C C P R and CPB w i t h epinephrine was significantly higher than CorPP during SECPR With epi-
Annals of Emergency Medicine
nephrine. CorPP produced w i t h CPB and epinephrine was significantly h i g h e r t h a n CorPP d u r i n g O C C P R and epinephrine (Table 4). Survivors had significantly higher CorPP after i n j e c t i o n of e p i n e p h r i n e c o m p a r e d with nonsurvivors ( 9 7 - + 45 vs 22 -+ 39 m m Hg, P < .001). Epinephrine dosage required for res u s c i t a t i o n was s i g n i f i c a n t l y less in t h e CPB group c o m p a r e d w i t h t h e SECPR group (SECPR, 0.28 ± 0.11 m g / k g ; CPB, 0.10 + 0.02 m g / k g ; O C C P R , 0.20 ± 0.12 m g / k g ; P = .002). There was no significant difference in epinephrine dosage between t h e CPB and O C C P R groups. Survivors required less epinephrine than nonsurvivors (0.12 ± 0.07 vs 0.32 -+ 0.04 mg/kg, P < .001). The n u m b e r of c o u n t e r s h o c k s n e e d e d for resuscitation was n o t s i g n i f i c a n t l y different a m o n g groups (SECPR, 8.0 _+ 6.5; CPB, 2.1 ± 1.5; OCCPR, 7.6 _+ 11.2). Survivors required fewer countershocks to achieve ROSC c o m p a r e d w i t h nonsurvivors (2.2 ±: 1.9 vs 12.6 _+ i0.2, P = .001).
Postresuscitation ROSC was achieved in nine of nine CPB and six of nine O C C P R animals compared w i t h two of eight SECPR a n i m a l s (P < .01). Survival to four hours Was achieved in two of eight SECPR a n i m a l s a n d t h r e e of n i n e CPB and three of nine O C C P R ani-
20:7 Ju}y 1991
CPR & CPB DeBehnke, Angelos & Leasure
reals. One a n i m a l in the O C C P R group had a tear in the inferior vena cava during OCCPR and died during the r e s u s c i t a t i o n period. One CPB animal had a laceration of the right atrium and s u b s e q u e n t pericardial tamponade and died early during the p o s t r e s u s c i t a t i o n period. S u r v i v a l time (time from ROSC to death) was significantly higher in the CPB group compared w i t h SECPR and OCCPR groups (SECPR, 60.0 _+ 111.1 m i n utes; CPB, 195.6 +- 48.5 m i n u t e s ; OCCPR, 115.7 -+ 104.7 minutes; P = .02). There was no significant difference between g r o u p s r e g a r d i n g h e m o dynamic data or arterial blood gas measurements in the postresuscitation period. Due to e x t r a c o r p o r e a l oxygenation, Po 2 was s i g n i f i c a n t l y higher in the CPB group one minute after ROSC compared with the OCCPR group (CPB, 391.7 -+ 127.6 m m Hg; OCCPR, 76.0 + 28.5 m m Hg; P = .0003). Postresuscitation fluid, bicarbonate, and norepinephrine dosage were not significantly different among groups.
Infarct Size All animals achieving ROSC had significant areas of ischemic and necrotic myocardium corresponding to the left anterior descending coronary artery bed. The ratio of necrotic to ischemic m y o c a r d i u m was s i g n i f i cantly lower in the CPB and OCCPR groups. H o w e v e r , t h e p e r c e n t ischemic m y o c a r d i u m t e n d e d to be higher in t h e s e g r o u p s c o m p a r e d with the SECPR group (Table 5). The percent ischemic, percent necrotic, and necrotic-to-ischemic ratio were not significantly different in animals that achieved ST segment elevation compared with those that did not.
DISCUSSION After left anterior descending coronary artery occlusion, OCCPR and CPB showed improved immediate resuscitation from VF cardiac arrest. Our i m m e d i a t e r e s u s c i t a t i o n rates are consistent with previous studies of OCCPR in the canine model.8, 9 The resuscitation technique was begun after four minutes of no-flow VF and nine minutes of basic CPR. Animals in the control group (SECPR) received epinephrine and defibrillation three m i n u t e s earlier than those in the OCCPR and CPB groups. The delay in the other two groups was to al20:7: July 1991
low time to perform a thoracotomy or s t a r t bypass. Our e x p e r i m e n t a l model was therefore slightly biased in favor of the SECPR animals. OCCPR has been previously studied in animal models as an alternative to SECPR. Most animal studies showed improved hemodynamics and survival with OCCPR. Bircher et al showed OCCPR increased arterial p r e s s u r e , s y s t e m i c p e r f u s i o n pressures, and c o m m o n c a r o t i d blood flow to twice that of control compared with SECPR and military antishock trousers (MAST)-augmented CPR. 6 Neither short- nor long-term survival rates were studied. 6 Jackson and coworkers showed increased mean systolic pressure with OCCPR compared w i t h SECPR and SECPR plus epinephrine. Again, survival was not studied. 7 Kern and coworkers studied survival from cardiac arrest using OCCPR as a reperfusion technique. After 15 minutes of SECPR, OCCPR produced ROSC in six of eight animals compared with one of eight SECPR animals. Resuscitation declined to three of eight and none of eight animals when OCCPR was delayed to 20 and 25 minutes after beginning SECPR. 8 A similar study of short- and longterm survival found improved immediate resuscitation (14 of 14 OCCPR vs five of 14 SECPR) and seven-day survival (11 of 14 OCCPR vs four of 14 SECPR) when OCCPR followed three minutes of VF and 12 minutes of ineffective SECPR. 9 These studies support the role of OCCPR in improving perfusion pressures and survival from VF cardiac arrest. In cont r a s t to o u r m y o c a r d i a l i n f a r c t model, these studies used healthy animal preparations with nonischemic hearts before arrest. W e i s e r et al s t u d i e d b l o o d flow during OCCPR in infarcted canine hearts and found that OCCPR produced an average cardiac output of 67% of prearrest values compared with 15% for SECPR. 29 Byrne and coworkers compared OCCPR and SECPR in chronically ischemic dog hearts. They showed an increase in cardiac output and improved myocardial blood flow in dogs treated with OCCPR. 3° Survival from cardiac arrest was not reported in e i t h e r of these studies. CPB has been investigated as a reperfusion tool after cardiac arrest in the canine model. Using a stanAnnals of Emergency Medicine
dardized dog VF cardiac arrest model, m u l t i p l e i n v e s t i g a t i o n s have compared CPB with SECPR and advanced life support. P r e t t o et al d e m o n strated i m p r o v e d r e s u s c i t a t i o n and 72-hour survival after CPB reperfus i o n . 13 S i m i l a r l y , M a r t i n et al showed improved resuscitation rates and survival after a 12-minute VF arrest w i t h o u t CPR. 14 In a prolonged dog CPR model of four minutes VF followed by 30 minutes of CPR and then CPB, Levine et al noted significant i m p r o v e m e n t in i n i t i a l resusc i t a t i o n and 72-hour survival w i t h CPB. ~5 Using the current model, we similarly showed improved resuscitation with CPB in an earlier study. 31 The improved survival and resuscitability w i t h OCCPR and CPB in animal models appear to be due to the higher aortic diastolic and coronary perfusion pressures generated. Kern et al s h o w e d s i g n i f i c a n t l y higher CorPP during OCCPR compared w i t h SECPR w h e n OCCPR was begun 12 minutes after ineffective SECPR. 9 Angelos et al showed significantly higher CorPP with CPB after 20 minutes of VF including ten minutes of CPR ACLS. 3~ In another study, CorPP s i m i l a r to p r e a r r e s t values could be obtained with CPB after 15 to 20 minutes of VF without prior CPR. 33 Previous a n i m a l CPR studies have shown aortic diastolic pressure and CorPP to be the best prognostic i n d i c a t o r s of successful resuscitation from cardiac arrest. ~4,17 Recent clinical data have also supported the prognostic value of CorPP during CPR. 18 In our study, CorPP during OCCPR and CPB was s i g n i f i c a n t l y h i g h e r than during SECPR. CorPP similar to prearrest values could be produced by OCCPR and CPB. There did not appear to be any difference in CorPP produced by OCCPR compared with CPB before a d m i n i s t r a t i o n of epinephrine. However, CorPP increased significantly in the CPB group compared with the OCCPR group after epinephrine injection. Survivors from cardiac arrest, regardless of reperfusion technique, had higher CorPP than nonsurvivors. Our data support the prognostic value of CorPP in canine cardiac arrest b e c a u s e a n i m a l s w i t h h i g h e r CorPP were more likely to survive cardiac arrest. Furthermore, animals with higher CorPP were easier to resuscitate from cardiac arrest, when 758/83
CPR & CPB DeBehnke, Angelos & Leasure
epinephrine dosage and n u m b e r of countershocks were used as indicators of ease of resuscitation. OCCPR and CPB produced higher i m m e d i a t e resuscitation rates from cardiac arrest compared with SECPR but s i m i l a r s u r v i v a l rates at four hours. These data are disappointing but not dissimilar to recent clinical experience. OCCPR and CPB produce the CorPP needed for immediate r e s u s c i t a t i o n of the heart, but this does not ensure long-term cardiac stability. One measure of postresuscitation stability, survival time, was improved in CPB animals comp a r e d w i t h SECPR a n d O C C P R . However, survival to our end point (four hours) was n o t d i f f e r e n t between groups. Due to the small number of animals in each group, there is the possibility of significant type II F-error. Therefore, we may not have been able to detect a difference in four-hour survival when one actually existed. To a c c u r a t e l y assess techniques with respect to long-term survival and neurologic outcome, threeto seven-day survival studies with a larger number of animals would need to be done. Because OCCPR and CPB produce higher perfusion pressures, they m i g h t be e x p e c t e d to salVage ischemic myocardium and thereby prevent ischemic myocardium from becoming necrotic during resuscitation. CPB-resuscitated animals were noted in an e a r l i e r s t u d y to have a decreased n e e r o t i c - t o - i s c h e m i c r a t i o compared with SECPR. ,~ In our study, we used the ratio of necrotic-to-ischemic tissue as a measure of infarct size to normalize for the v a r i a b i l i t y in area of risk. We noted that the ratio of necrotic-to-isc h e m i c m y o c a r d i u m was s i g n i f i cantly less in the CPB and OCCPR groups compared w i t h the SECPR group. However, in the absence of m y o c a r d i a l b l o o d flow m e a s u r e ments to establish postocclusion area of risk and subepicardial c o l l a t e r a l blood flow, it is u n c l e a r w h e t h e r these differences in group infarct size were due to resuscitation techniques or to variation in regional myocardial necrosis in the distribution of the occluded artery. The distribution of the necrosis was consistent with an earlier study that demonstrated necrosis in the distribution of the left anterior descending coronary artery occluded before cardiac arrest. In contrast, the 84/759
control group, which did not experience coronary artery occlusion, essentially had no necrosis after cardiac arrest. 2° Additional studies using regional myocardial blood flow measurements to define collateral blood flow and p o s t o c c l u s i o n area at risk are needed to determine any infarct reduction afforded by the various techniques. It may be hypothesized that anim a l s t h a t died e a r l y in the postr e s u s c i t a t i o n period had larger infarcts. However, we found no statistical correlation between postresuscitation survival times and infarct size (percent ischemic R = -0.6924, percent necrotic R = -0.0439, necroticto-ischemic ratio R = 0.3178). H e p a r i n i z a t i o n was used in the CPB group as part of the research protocol. The effects of heparin on blood viscosity, t h r o m b u s f o r m a t i o n and maintenance, infarct size, and resuscitation rates were not specifically studied here but warrant further investigation in similar animal models. Norepinephrine was used in the postresuscitation period for pressor support. Norepinephrine has been shown to increase myocardial oxygen consumption and may increase myocardial infarct size. All animals required a norepinephrine infusion for blood pressure support. We did not specifically study the effect of norepinephrine on infarct size, but it is possible that postresuscitation use of norepinephrine contributed to the ultimate ischemic and necrotic areas. This question requires further investigation. There are few studies of OCCPR in h u m a n beings. Del G u e r c i o et al studied blood flow during open- and closed-chest CPR in h u m a n beings and found i m p r o v e d cardiac index and m e a n c i r c u l a t i o n t i m e during OCCPR. 34 No large, well-controlled clinical study has been done with human beings. Most such reports in the literature of OCCPR have been uncontrolled case series and anecdotal in nature. There are some uncontrolled clinical reports of successful resuscitation w i t h closed-chest CPB techniques. Baird et al reviewed 25 patients with acute myocardial infarction treated with venoarterial bypass using a bubble oxygenator:m Five of 25 patients in cardiogenic shock or cardiac arrest were r e s u s c i t a t e d and s u r v i v e d at Annals of Emergency Medicine
least one m o n t h . M a t t o x et al reported 24 of 39 m o r i b u n d p a t i e n t s initially resuscitated with CPB with 15 long-term survivors.t1 The majority of survivors, 13 of 15, were patients with large pulmonary emboli. Phillips et al reported on 22 patients in cardiac arrest who received femorofemoral CPB; nine survived. 12 Similarly, Reichman et al reported on 38 patients in cardiac arrest refractory to ACLS protocols who were p l a c e d on e m e r g e n c y b y p a s s ; six patients survived. 35 Recent clinical reviews of resusc i t a t i o n from cardiac a r r e s t using SECPR have shown survival rates of 2% to 25%. 2-4 There are m u l t i p l e variables that influence survival (down time, i n i t i a l r h y t h m , emergency medical service system, and so on), b u t u l t i m a t e s u r v i v a l h a s changed little since the introduction of SECPR in 1960. Perhaps a more invasive m e t h o d of reperfusion, one that produces significantly higher CorPP, should be used in selected clinical cardiac arrests. In our study, OCCPR and CPB were comparable resuscitation tools. OCCPR is an easily learned technique requiring m i n i m a l equipment and is currently used in some cases of p e n e t r a t i n g t r a u m a w i t h subsequent cardiac arrest. Once resuscitation has been achieved, surgical cons u l t a t i o n w o u l d be n e c e s s a r y for chest closure. CPB is a less invasive technique but requires more equipment and specially trained perfusionists and may be more difficult to initiate in the emergency department. C a n n u l a t i o n of the femoral artery and v e i n w o u l d h a v e to be done using cutdowns. Once initiated, CPB could be continued in the intensive care period and m a y provide more stable hemodynamic and postr e s u s c i t a t i o n cardiac support. It is premature to advocate one technique over the other. C l i n i c a l feasibility s t u d i e s m u s t be done w i t h these techniques before any recommendations are made. CONCLUSION CPB and OCCPR produced higher CorPP and improved i m m e d i a t e resuscitation compared with SECPR in a. canine infarct model. OCCPR and CPB produced similar CorPP and resuscitation rates when compared with each other; however, CPB produced higher CorPP when used in 20:7 July 1991
CPR & CPB DeBehnke, Angelos & Leasure
conjunction with epinephrine. Clinical survival studies with SECPR have generated an attitude of therapeutic nihilism with respect to prolonged cardiac arrest. OCCPR and CPB are alternative reperfusion techniques that require further evaluation in the clinical arena. The authors extend special thanks to Rhonda Barton, Erik Ramnath, and Scott Russell for their technical assistance; Andrea A r n o l d f o r h e r a s s i s t a n c e w i t h m a n u script preparation; and Biomedicus, Inc, Eden Prairie, Minnesota, for CPB equipment support.
REFERENCES 1. American Heart Association: Standards and guidelines for cardiopulmonary resuscitation (CPR / and e m e r g e n c y c a r d i a c care (ECC}. l A M A 1986;55 fsuppll:2841-3044. 2. Hartgarten KM, Steuven HA, Waite EM, et al: Prehospital experience with defibrillation of coarse ventricular fibrillation: A ten-year review. Ann Emerg Med i990~19:157-162. 3. Eisenberg MS, Horwood BT, C u m m i n s RO, et al: Cardiac arrest and resuscitation: A tale of 29 cities. Ann Emerg Med 1990;19:179-i86. 4. Edgren E, Kelsey S, Sutton K, et al: The presenting ECG pattern in survivors of cardiac arrest and its relation to the subsequeut long-term survival. Acta Anesthesiol Scand 1989;33:265-271. 5. Kouwenhoven WB, Jude JR, Knickerbocker GG: Closed-chest cardiac massage. JAMA 1960;173:94-97. 6. Bircher N, Safar P, Stewart R: A comparison of standard, "MAST"-augmented, and open-chest CPR in dogs. Crit Care Med 1980;8:147-152. 7. Jackson RE, Joyce K, Danosi gP, et al: Blood flow in the cerebral cortex during cardiac resuscitation in dogs. Ann Emerg Med 1984;13:657-659. 8. Kern KB, Sanders AB, Ewy GA: Open-chest cardiac massage after closed-chest compression in a canine model: When to intervene. Resuscitation 1987;15:51-57. 9. Kern KB, Sanders AB, Badylak SF, et al: Long-term
20:7: July 1991
survival with open chest cardiac massage after ineffective dosed-chest compression in a canine preparation. Circulation 1987;75:498-503. 10. Baird R, Rocha A, Miyasishima R, et al: Assisted circulation following myocardial infarction: A review of 25 patients treated before 1971. Can Med Assoc J 1972;107:287-291. 11. Mattox KL, Beall AC: Resuscitation of the moribund patient using portable cardiopulmonary bypass. Ann Thorac Surg 1976;22:436-442. 12. Phillips SJ, Zeff RH, Kongtahvorn C, et al: Percutaneous cardiopulmonary bypass: Application and indication for use. Ann Thorac Surg 1989;47:121-123. 13. Pretto E, gafar P, Saito R, et al: Cardiopulmonary bypass after prolonged cardiac arrest in dogs. Ann Emerg Med 1987;16:611-619. 14. Martin GB, Nowak RM, Carden DL, et al: Cardiopulmonary bypass vs CPR as treatment for prohmged c a n i n e c a r d i o p u l m o n a r y arrest. A n n Emerg Med 1987;I6:628-636. 15. Levine R, Gorayeb M, Safar P, et al: Cardiopulmonary bypass after cardiac arrest and prolonged closed chest CPR in dogs. Ann Emerg Med 1987;16:620 627. 16. Niemann JT, Rosbnrough Jp, Ung S, et al: Coronary perfusion pressure during experimental cardiopulmonary resnscitation. Ann Erner~g Med [982;11:127-131. 17. Sanders AB, Ewy GA, Taft TV: Prognostic and ther apeutic importance of the aortic diastolic pressure in re s u s c i t a t i o n f r o m cardiac arrest. Crit Care Med 1984;12:871 873.
where in the United States. Ann Emerg Med 1985;14: 750-754. 24. Silfvast T: Prehospital resuscitation in Helsinki, Finland. Am J Emerg Med 1990;8:359-364. 25. Rothstein RJ, Niemann IT, Rennie CJ, et al: Use of naloxone during cardiac arrest and CPR: Potential adjunct for post countershock electrical-mechanical dissociation. Ann Emerg Med 1985;14:198-203. 26. Neiman IT, Haynes KS, Garner D, et aI: Post countershock pulseless rhythms: Hernodynamic effects of glucagon in a canine modeh Crit Care Med 1987; 15:554-558. 27. N e i m a n IT, Garner D, Peikon P, et al: Predictive value ;ff the ECG in determining cardiac resuscitation outcome in a canine model of post countershock electromechanical dissociation after prolonged ventricular fibrillation. Ann Emerg Med 1988;17:567-571. 28. Lie JT, Pairolem PC, Holley KE, et al: Macroscopic enzyme-mapping verification of large, homogeneous, experimental myocardial infarcts of predictable size and location in dogs. f Thorac Cardiowisc Surg 1975; 69:599-605. 29. Weiser FM, Adler LN, Kuhn LA: Hemodynamic effects of closed and open chest cardiac resuscitation in normal dogs and those with acute myocardial infarc tion. Am J Cardiol 1962;10:555-561. 30. Byrne D, Pass HI, Neely WA, et al: External versus internal cardiac massage in normal and chronically ischemic dogs. Am Snrg,eon 1980;46:657-662.
18. Paradis NA, Martin GB, Rivers EP, et al: Coronary perfusion pressure and the return of spontaneous circu lation in hmnan cardiopulmonary resuscitation. JAMA 1990;263:1106q113.
31. Angelos M, Gaddis M, Gaddis G, et at: improved survival and reduced myocardial necrosis with cardiopulmonary bypass reperfusion in a canine model of coronary occlusion and cardiac arrest. Ann Emerg Med 1990;19:1122-1128.
19. Kordenat RK, Kezdi P, Stanley EL: A new catheter technique for producing experimental coronary thrombosis and selective coronary visualization. Am Heart J 1972;83:360-364.
32. Angelos M, Reich H, Safar P: Coronary perfusion pressure during external CPR versus cardiopulmonary bypass after prolonged cardiac arrest in dogs (abstract I. Ann Emerg Med 1987;A10 16:1102.
20. Angelos MG, Gaddis M, Gaddis G, et al: Cardiopulmonary bypass in a model of acute myocardial infarction and c a r d i a c a r r e s t . A n n Emerg M e d 1990~ 19:874-880.
33. Reich H, Angelos M, Safar P, et al: Cardiac resus citability with cardiopulmonary byl:mss after increasing ventricular fibrillation times in dogs. Ann Emerg Med 1990;19:887-g90.
21. Roth R, Stewart RD, Rogers K, et al: Out-of-hospital cardiac arrest: Factors associated with survival. Ann Emerg Med 1984;13:237-243. 22. Eisenberg MS, Hallstrom A, Bergner L: Long-term survival after out-of~hospital cardiac arrest. N Engl J Med 1982;306: I340-1343. 23. Thompson BM, Stueven HA, Mateer JR, et aI: Comparison of clinical CPR studies in Milwaukee and else-
Annals of Emergency Medicine
34. Del Guercio LR, Feins NR, Cohn JD, et al: Comparison of blood flow during external and internal cardiac massage in man. Circulation 1965;31,32[suppl I}:I-171 1-180. 35. Reichman RT, Joyo CI, Dembitsky WP, et al: Improved patient survival after cardiac arrest using a card i o p u l m o n a t y support s y s t e m . A n n Thorac Surg 1990;49:101 105.
760/85
