LABORATORY INVESTIGATION bicarbonate, cardiac arrest; cardiac arrest, bicarbonate
The Effect of B i c a r b o n a t e on R e s u s c i t a t i o n From C a r d i a c A r r e s t Study objectives: This study attempted to determine the effect of bicarbonate administration on resuscitation in a porcine model of prolonged cardiac arrest. Design: After instrumentation, 26 swine were subjected to ventricular fibrillation for i5 minutes (16 animals) or 20 minutes (ten animals) with no resuscitative efforts. Interventions: Resuscitation attempts with open-chest cardiac massage and epinephrine were used in all animals after the arrest period. The experimental group was given sodium bicarbonate (3 mEq/kg), and the control group received 3% saline (5 mL/kg) at the initiation of cardiac massage. Measurements: Resuscitation success, hemodynamics, and arterial and mixed venous gases were compared in the bicarbonate and hypertonic saline-treated groups. Results: There was no difference in resuscitation rates between bicarbonate and nonbicarbonate-treated swine. After 15 minutes of ventricular fibrillation, six of eight bicarbonate-treated swine were resuscitated successfully compared with five of eight hypertonic saline-treated animals. None of the five bicarbonate-treated or five hypertonic saline-treated swine that underwent 20 minutes of ventricular fibrillation were resuscitated. The arterial and mixed venous pH values were significantly different in the bicarbonate-treated animals from values in the control group. There was no difference in systolic or diastolic blood pressures or myocardial perfusion pressure between the bicarbonate and hypertonic salinetreated animals. Conclusion: Despite correlation of arterial and venous acidemia, the use of sodium bicarbonate did not improve resuscitation from prolonged cardiac arrest. [Federiuk CS, Sanders AB, Kern KB, Nelson J, Ewy GA: The effect of bicarbonate on resuscitation from cardiac arrest. Ann Emerg Med November 1991;20:1173-1177.]
Carol S Federiuk, MD, PhD* Arthur B Sanders, MD, FACEP* Karl B Kern, MD, FACCt Jay Nelsont Gordon A Ewy, MD, FACCt Tucson, Arizona From the Section of Emergency Medicine, Department of Surgery,* and Section of Cardiology, Department of Internal Medicine,t University of Arizona Health Sciences Center, Tucson, Arizona. Received for publication October 30, 1991. Revision received March 4, 1991. Accepted for publication June 3, 1991. This research was supported by a grant from the Emergency Medicine Foundation and the Emergency Medicine Residents Association. Address for reprints: Carol S Federiuk, MD, PhD, Emergency Medicine, Oregon Health Sciences Center, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201.
INTRODUCTION The i m p o r t a n c e of acid-base balance in resuscitation from cardiac arrest remains unclear. Controversy still exists concerning the efficacy of treatm e n t of acid-base i m b a l a n c e during cardiac arrest and the accuracy of measurement of acid-base status during arrest through the use of arterial blood gases. Early studies of cardiac arrest in a n i m a l m o d e l s suggested that s o d i u m bicarbonate used in addition to epinephrine facilitated resuscitation from ventricular fibrillation and i m p r o v e d survival.I, 2 Concern for the use of bicarbonate was occasioned by the observations that bicarbonate m a y induce h y p e r o s m o l a r i t y and alkalosis in patients3, 4 and m a y result in central nervous s y s t e m acidosis in an a n i m a l m o d e l s O t h e r investigators, however, found no significant h y p e r o s m o l a r i t y or alkalosis w i t h the recomm e n d e d doses of bicarbonate6, 7 and no significant central nervous s y s t e m acidosis during prolonged arrest.8, 9 Despite m u l t i p l e studies that have disputed the findings of d e t r i m e n t a l effects of bicarbonate, evidence for a beneficial effect of bicarbonate in resuscitation from cardiac arrest r e m a i n s limited. In one a n i m a l study, animals that did n o t receive bicarbonate were resuscitated as easily as those
20:11 November 1991
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that did receive bicarbonate. 1° Evaluation of acid-base status and the effects of acid-base therapy during cardiac arrest is p e r f o r m e d rout i n e l y t h r o u g h t h e u s e of a r t e r i a l gases. Investigators have c o n f i r m e d t h e p r e s e n c e of a s i g n i f i c a n t arteriovenous gradient in pH and Pco2.11-13 Some suggest t h a t m i x e d v e n o u s b l o o d gases r e f l e c t c h a n g e s occurring in the s y s t e m i c c a p i l l a r y bed and m a y b e t t e r r e p r e s e n t intracellular metabolic status. 11-t3 The aim of this study is to test the h y p o t h e s i s t h a t b i c a r b o n a t e has no beneficial effect in resuscitation from prolonged cardiac arrest. The effect of a c i d - b a s e s t a t u s on r e s u s c i t a t i o n f r o m c a r d i a c a r r e s t is e v a l u a t e d t h r o u g h use of a r t e r i a l and m i x e d venous blood gases.
TABLE 1. Arterial and m i x e d venous blood gases in the 15-minute fibrillation group Bicarbonate
No Bicarbonate
O
Arterial pH Baseline
1 rain 14 rain 18rain 25 rain
7.48 7.50 7.44 7.51 7,24
± 0.09 --_ 0.10 ± 0.15 ± 0,17 ± 0.05
7.48 7,54 7.48 7.09 7.05
± ± ± ± ±
0.06 0.10 0.13 0.09 0.04
NS NS NS < .01 < .01
7.44 7.43 7,32 7.31 7.18
± ± ± ± ±
0.09 0.08 0.06 0.13 0.03
7.44 7.41 7.30 7.00 7.03
± +_ ± ±
0.05 0.05 0.06 0.08 0.03
NS NS NS < .01 < .01
37.2 33,9 39.4 74.9 62.7
± ± ± ± ±
9.4 7.9 12.0 32.4 8.3
37.1 32.5 36.6 58.6 66.0
± ± ± ± ±
5.2 7.5 10.9 14.2 8.7
NS NS NS NS NS
_+ 9.4 + 9.0 ± 6,6 ± 31.1 ± 6.7
42.3 44.9 52.7 72.7 72.0
_+ ± ± + +
4.1 5.4 6.2 24.9 9.6
NS NS NS < .05 NS
VenouspH Baseline
1 rain 14 rain
18 rain 25 rain Arterial Pco2 (mm Hg) Baseline
1 rain 14 rain 18 rain
25 min
Venous Pco2 (mm Hg)
MATERIALS A N D M E T H O D S The protocol was approved by the i n s t i t u t i o n a l l a b o r a t o r y a n i m a l research c o m m i t t e e . After an overnight fast, 26 swine (weight, 18 to 32 kg) were a n e s t h e t i z e d w i t h i s o f l u r a n e . The animals were endotracheally intubated and v e n t i l a t e d using a volu m e v e n t i l a t o r w i t h 100% O2 at a rate of 12 to 16 per m i n u t e and a tidal volume of 15 m L / k g to keep end-tidal CO2 at 30 to 40 m m Hg. The external jugular vein was c a n n u l a t e d by c u t d o w n w i t h a n 8F i n t r o d u c e r sheath, and a 7F p u l m o n a r y a r t e r y catheter was a d v a n c e d t h r o u g h t h e introducer into the p u l m o n a r y artery using pressure tracing guidance. High-fidelity micromanometertipped catheters (Millar PC-500, M i l l a r I n s t r u m e n t s Inc, H o u s t o n , Texas) were inserted into the carotid artery and e x t e r n a l jugular v e i n by cutdown and advanced into the chest using pressure-tracing guidance. A m e d i a n s t e r n o t o m y w a s performed, and the h e a r t was exposed. Ventricular f i b r i l l a t i o n was i n d u c e d using rapid ventricular pacing at 700 to 800 beats per minute. Fibrillation was c o n f i r m e d by the ECG p a t t e r n and by the decrease in arterial blood pressure. Ventilation was discontinued, and cardiac arrest was monitored for 15 m i n u t e s (16 animals) or 20 m i n u t e s (ten a n i m a l s ) w i t h no resuscitative efforts. A t the end of v e n t r i c u l a r fibrillation (15 or 20 minutes), v e n t i l a t i o n was restarted, and open-chest cardiac massage was performed at a rate of 80 per minute, keeping the perfusion 24/1174
Baseline 1 rain 14 rain 18 min 25 rain
41.4 42.0 50.3 111.8 78.0
pressure (diastolic aortic pressure min u s r i g h t a t r i a l pressure) a b o v e 30 m m Hg. A t i n i t i a t i o n of open-chest cardiac massage, animals in the contro] g r o u p (group A) r e c e i v e d epinephrine (0.04 mg/kg) and saline 3% (5 mL/kg). Group B received epinephrine (0.04 mg/kg) and s o d i u m bicarbonate (3 mEq/kg, or 3 mL/kg) at ons e t of c a r d i a c m a s s a g e . A f t e r five m i n u t e s of o p e n - c h e s t cardiac massage, defibrillation was a t t e m p t e d up to three times at 30 J in an effort to restore a perfusing r h y t h m . Those animals successfully resuscitated were observed for 30 m i n u t e s after the ret u r n of spontaneous circulation without further treatment. A n i m a l s that had a m e a n arterial pressure of 75% of baseline at 30 m i n u t e s after defibrillation were considered resuscitated. ECG and aortic and right atrial pressure waveforms were m o n i t o r e d c o n t i n u o u s l y and recorded throughout the e x p e r i m e n t on a four-channel Gould recorder (Gould Electronics, Cleveland, Ohio). Arterial and m i x e d v e n o u s b l o o d gases were d r a w n before fibrillation, at one m i n u t e of fibrillation, at one m i n u t e before onset of CPR (14 or 19 minutes), at three m i n u t e s of cardiac massage (18 or 23 minutes), and at one, five, and t e n m i n u t e s after r e s u s c i t a t i o n . Blood gases were collected into heparinized Annals of Emergency Medicine
gas-free s y r i n g e s and s t o r e d on ice u n t i l analysis i m m e d i a t e l y after the experiment. D i f f e r e n c e s in r e s u s c i t a t i o n bet w e e n groups A and B were evaluated by Fisher's exact test w i t h a significance set at P < .05. Differences in arterial and mixed venous blood gases and h e m o d y n a m i c s b e t w e e n groups w e r e a s s e s s e d at i n d i v i d u a l t i m e points by the Student's t test. A repeated measures m u l t i v a r i a t e analysis of v a r i a n c e was used to determ i n e differences in blood gases measurements during the t i m e course of the e x p e r i m e n t w i t h i n groups.
RESULTS The resuscitation rates b e t w e e n bicarbonate- and nonbicarbonatetreated groups of animals undergoing 15 m i n u t e s of ventricular fibrillation did n o t differ s i g n i f i c a n t l y . Six of eight bicarbonate-treated swine were resuscitated successfully compared w i t h five of eight h y p e r t o n i c salinetreated animals. N o n e of the five bic a r b o n a t e - t r e a t e d or five h y p e r t o n i c s a l i n e - t r e a t e d swine t h a t u n d e r w e n t 20 m i n u t e s of ventricular fibrillation were resuscitated. Blood gas values and hemodynamics were studied in the bicarbonate- and n o n b i c a r b o n a t e - t r e a t e d groups of animals. In those animals subjected to 15 m i n u t e s of ventricu20:11 November 1991
BICARBONATE Federiuk et al
TABLE 2. Arterial and m i x e d venous blood gases in the 20-minute fibrillation group Bicarbonate
No Bicarbonate
P
Arterial pH BaseLine 1 rnin 19 min 23 min
7.49 7.53 7.45 7.47
± ± ± ÷
0.05 0.10 0.15 0.18
7.53 7.55 7.44 7.04
_+ ± ± ±
0.03 0.11 0.03 0.11
NS NS NS < .01
7.42 7.42 7.26 7.27
± ± _+ +
0.06 0.05 0.07 0.16
7.47 7.43 7.19 6.96
+_ ± + ±
0.02 0.03 0.22 0.14
NS NS NS < .05
36.2 32.2 39.0 86.2
± + ± +
5.4 8.6 11.9 24.9
35.0 34.6 41.0 57.8
± ± ± +
2.4 6.1 2.4 20.4
NS NS NS NS
44.8 43.4 52.6 116.8
± ± _+ ±
6.2 8.0 11.3 25.4
37.8 44.2 51.8 74.5
± _+ _+ ±
7.1 4.2 9.0 26.9
NS NS NS < .05
Venous pH Baseline 1 rnin 19 rain 23 rnin
Arterial Pco2 (mm Bg) Baseline 1 rain 19 min 23 min
Venous Pco2 (mm Hg) Baseline 1 min 19 min 23 min
TABLE 3. Comparison of h e m o d y n a m i c s during CPR in bicarbonate- and nonbicarbonate-treated groups after 15 m i n u t e s of cardiac arrest
Time Pressure (min) (mm Hg)
BicarbonateTreated Group
No Bicarbonate Treatment
P
16
Systolic Diastolic Myocardial perfusion pressure
113 ± 14 76 ± 17 69 _+ 20
102 ± 50 60 _+ 43 55 + 46
NS NS NS
17
Systolic Diastolic Myocardial perfusion pressure
88 +_ 43 51 _+ 34 44 ± 32
97 + 36 50 _+ 30 41 + 31
NS NS NS
18
Systolic Diastolic Myocardial perfusion pressure
85 + 12 60 + 11 40 ± 7
81 -,- 15 59 ± 13 33 + 6
NS NS NS
19
Systolic Diastolic Myocardial perfusion pressure
81 ± 6 39 ± 6 32 _+ 6
82 + 19 36 ± 14 27 ± 16
NS NS NS
20
Systolic Diastolic Myocardial perfusion pressure
80 ÷ 7 36 ± 4 27 +_ 5
71 _+ 20 34 + 12 26 ÷ 14
NS NS NS
lar fibrillation, the arterial p H was significantly different between groups during CPR at 18 m i n u t e s of arrest (7.51 ± 0.17 in b i c a r b o n a t e treated group vs 7.09 + 0.07 in the control group; P < .01; Table 1). In a n i m a l s t h a t w e r e r e s u s c i t a t e d successfully, a difference in arterial p H persisted at 25 m i n u t e s (five m i n u t e s after defibrillation) (7.24 -+ 0.05 in the bicarbonate-treated group vs 7.05 ± 0.04 in the control group; P < .01; Table 1). A difference was also noted in m i x e d v e n o u s p H at 18 m i n u t e s (7.31 ± 0.13 in b i c a r b o n a t e - t r e a t e d group vs 7.00 _+ 0.08 in the control group; P < .01; Table 1). 20:11 November 1991
There was no significant difference in arterial P c o 2 b e t w e e n groups in animals that sustained 15 m i n u t e s of v e n t r i c u l a r f i b r i l l a t i o n ( T a b l e 1). M i x e d v e n o u s Pco2, h o w e v e r , differed at 18 m i n u t e s during CPR (111.8 ± 31.1 in b i c a r b o n a t e - t r e a t e d anim a l s vs 72.7 ± 24.9 in the control group; P < .05). This difference did not persist at 25 m i n u t e s in resuscitated a n i m a l s (Table 1). Differences in arterial and m i x e d venous p H values at 23 m i n u t e s also were observed b e t w e e n bicarbonateand nonbicarbonate-treated groups in animals that u n d e r w e n t 20 m i n u t e s of ventricular fibrillation before CPR Annals of Emergency Medicine
was started. The arterial pH was 7.47 _+ 0.18 in t h e b i c a r b o n a t e - t r e a t e d group versus 7.04 +_ 0.11 in the control group (P K .01; Table 2). Venous p H at 23 m i n u t e s was 7.27 + 0.16 in the bicarbonate-treated group versus 6.96 +- 0.14 in the control group (P < .05; Table 2). Postresuscitation blood gases were not obtained because t h e r e w e r e no s u r v i v o r s in t h e s e groups. A r t e r i a l P c o 2 d i d n o t differ between groups in animals undergoing 20 m i n u t e s of ventricular fibrillation (Table 2). Mixed venous Pco2, however, d e m o n s t r a t e d divergence at 23 m i n u t e s during CPR (116.8 + 25.4 in the bicarbonate-treated group vs 74.5 _+ 26.9 in the control group; P < .05; Table 2). There were no differences between b i c a r b o n a t e - and h y p e r t o n i c salinet r e a t e d a n i m a l s in s y s t o l i c or diastolic blood pressure or in myocard i a l p e r f u s i o n p r e s s u r e ( a o r t i c diastolic minus right atrial diastolic pressure during CPR) in animals undergoing 15 m i n u t e s of ventricular fibrillation (Table 3). Similarly, no diff e r e n c e in h e m o d y n a m i c s b e t w e e n b i c a r b o n a t e - and h y p e r t o n i c salinet r e a t e d a n i m a l s were f o u n d in animals that u n d e r w e n t 20 m i n u t e s of ventricular fibrillation (Table 4). R e t r o s p e c t i v e l y , t h e 11 a n i m a l s w h o were r e s u s c i t a t e d s u c c e s s f u l l y a f t e r 15 m i n u t e s of c a r d i a c a r r e s t were compared w i t h the five animals not resuscitated w i t h regard to blood gases and h e m o d y n a m i c s during CPR (Table 5). T h e r e was no significant difference in arterial p H (7.35 ± 0.23 vs 7.18 ± 0.13) or m i x e d venous p H (7.18 + 0.22 vs 7.10 _+ 0.11) in resuscitated and nonresuscitated animals. Systolic blood pressure was not significantly different in the two groups (86 + 15 vs 75 + 1 2 m m H g ) . However, diastolic blood pressure (45 ± 6 vs 36 ± 6 m m Hg, P < .05) and myocardial perfusion pressure (38 + 7 vs 26 _+ 11 m m Hg, P < .05) was significantly better in the resuscitated animals. DISCUSSION T h e p r o p o s e d effectiveness of sod i u m b i c a r b o n a t e in r e s u s c i t a t i o n f r o m p r o l o n g e d c a r d i a c a r r e s t is based on the hypothesis that neutralization of acidosis m a y p o t e n t i a t e defibrillation1, 2 and improve tissue viab i l i t y and cardiac function. In addition, bicarbonate may improve 1175/25
BICARBONATE F e d e r i u k et al
perfusion by providing fluid and electrolyte replacements. In this study, both control and bicarbonate-treated groups received s i m i l a r o s m o l a r loads in s m a l l volu m e s of fluid (3 to 5 mL/kg). Bicarbonate was n o t shown to improve resuscitation after 15 m i n u t e s of vent r i c u l a r f i b r i l l a t i o n despite the fact that bicarbonate significantly improved arterial and mixed venous acidemia compared w i t h the control group (Table 1). In pilot studies, we noted that large doses of bicarbonate (3 mEq/kg) w e r e n e e d e d to c o r r e c t the a c i d e m i a after 15 to 20 m i n u t e s of v e n t r i c u l a r f i b r i l l a t i o n . R e s u s c i tated animals r e m a i n e d significantly more acidemic at five m i n u t e s after defibrillation in the nonbicarbonatetreated group (Table 1). Our m e t h o d o l o g y was not designed to d i f f e r e n t i a t e t h e m e t a b o l i c a n d respiratory components of t h e acidosis during cardiac arrest. There is c o n c e r n t h a t b i c a r b o n a t e m a y worsen the acidosis of cardiac arrest, particularly, i n t r a c e l l u l a r and intracerebral acidosis, by i n c r e a s i n g carbon dioxide levels.4, 5 In this experiment, we did not measure intracellular or intracerebral acidosis. A n i m a l s t h a t r e c e i v e d bicarbonate, however, n o r m a l i z e d their arterial and m i x e d venous a c i d e m i a despite increases in P c o 2 (Table 1). Our study had a n u m b e r of potential l i m i t a t i o n s t h a t m u s t be t a k e n into account in evaluating the data. A porcine m o d e l of cardiac arrest was used, and caution should be used in e x t r a p o l a t i n g t h e r e s u l t s to h u m a n beings w i t h coronary artery disease. The s a m p l e size was s m a l l and although we found no statistical difference, a type II error is possible. We n o t e t h a t a l t h o u g h there was n o t a s t a t i s t i c a l d i f f e r e n c e in a r t e r i a l p H b e t w e e n t h e r e s u s c i t a t e d a n d nonresuscitated animals, the resuscitated animals had a higher p H (7.35 + 0.23 vs 7.18 -+ 0.13) and the probability of a type II (13) error is .64 for this observation. If we had used a larger n u m ber of animals, group differences m a y have been detected. Arterial and m i x e d v e n o u s b l o o d a c i d e m i a was used to m o n i t o r the acid-base status rather than continuous m o n i t o r i n g of tissue or cellular acidosis. Finally, no difference was detected in perfusion pressures b e t w e e n t h e bicarbonate and nonbicarbonatetreated groups when calculated every 26/1176
TABLE 4. Hemodynamics in the 20-minute fibrillation group Bicarbonate Myocardial perfusion pressure (mm Hg) at baseline
No Bicarbonate
P
46.3 -+ 5.1
52.0 + 8.3
NS
33.8 ± 20.9
32.8 + 5.8
NS
73,4 ± 6.2
78.6 + 3.8
NS
Systolic pressure (mm Hg) at 23 minutes during CPR
91.4 + 13.9
75.4 _+ 16.4
NS
Diastolic pressure (ram Hg) at baseline
51.0 ± 7.0
56.0 ± 6.7
NS
Diastolic pressure (ram Hg) at 23 minutes during CPR
46.0 ± 22.7
39.0 ± 7.2
NS
Myocardial perfusion pressure (mm Hg) at 23 minutes during CPR Systolic pressure (mm Hg) at baseline
TABLE 5. Comparison of resuscitated versus nonresuscitated animals after 15 minutes of cardiac arrest Resuscitated
Nonresuscitated
P
Arterial pH (18 minutes)
7.35 + 0.23
7.18 _+ 0.13
NS
Venous pH (18 minutes)
7.18 ± 0.22
7.10 ± 0.11
NS
Systolic blood pressure (18 minutes) Diastolic blood pressure (18 minutes)
86 ± 15
75 ± 12
NS
45 -,- 6
36 _+ 6
< .05*
Myocardial perfusion pressure (18 minutes)
38 ± 7
26 ± 11
< .05*
*Significant dilferences in myocardial perlusion pressure and diastolic blood pressure between resuscitated and nonresuscilated animals. NS, no diffeF ences in arterial or mixed venous pH or systolic blood pressure.
m i n u t e d u r i n g CPR (Table 1). It is possible that a significant difference in perfusion pressures w o u l d be present if each pressure wave during CPR was compared between the two groups. Despite these limitations, our data did not d e m o n s t r a t e a beneficial effect of bicarbonate t r e a t m e n t for resuscitation from cardiac arrest. Previous studies have indicated that acidosis during cardiac arrest does n o t b e c o m e severe u n t i l relatively late (15 to 20 minutes) in the arrest. 14,15 To d e t e r m i n e if increasing the d u r a t i o n of v e n t r i c u l a r fibrillation and thereby increasing the severi t y of the a c i d e m i a w o u l d r e s u l t in an i m p r o v e m e n t i n r e s u s c i t a t i o n w i t h b i c a r b o n a t e , a d d i t i o n a l studies were carried out u s i n g a 2 0 - m i n u t e period of ventricular fibrillation. Alt h o u g h b i c a r b o n a t e s i g n i f i c a n t l y increased arterial and m i x e d venous p H values (Table 2), no a n i m a l s in the bicarbonate-treated or hypertonic sal i n e - t r e a t e d groups were able to be resuscitated after 20 m i n u t e s of ventricular fibrillation. This finding suggests that a critical and p o t e n t i a l l y irreversible alteration Annals of Emergency Medicine
in m e t a b o l i s m t h a t occurs b e t w e e n 15 and 20 m i n u t e s p r e v e n t s resuscitation using current methods. This alteration is not affected by the addition of bicarbonate during resuscitat i o n , i n d i c a t i n g t h a t r e v e r s a l of acidemia alone late in arrest does n o t s i g n i f i c a n t l y affect the process. T h e o b s e r v a t i o n in this s t u d y is consistent w i t h other CPR studies indicating t h a t i n a d e q u a t e c i r c u l a t i o n for m o r e than 15 m i n u t e s is poorly correlated with successful resuscitation.16,17 T h e i n a b i l i t y to r e s u s c i t a t e after prolonged arrest could represent depletion of energy stores such as phosp h o c r e a t i n e a n d ATP, w h i c h m a y halt cellular m e t a b o l i s m and lead to a l t e r a t i o n s in m e m b r a n e p e r m e a b i l i t y or o t h e r i r r e v e r s i b l e cell d a m age.18,19 Alternately, irreversible enz y m e inactivation m a y occur secondary to progressive acidosis. W h a t e v e r the m e c h a n i s m , it does n o t appear to be reversed by IV s o d i u m bicarbonate. The use of bicarbonate in the treatm e n t of p a t i e n t s in c a r d i a c a r r e s t m a y be i n d i v i d u a l i z e d . Bicarbonate 20:11 November 1991
BICARBONATE Federiuk et al
appears to be useful for patients with suspected h y p e r k a l e m i a or preexisting acidosis, z0 Other patients may n o t d e v e l o p a s i g n i f i c a n t acidosis until relatively late (15 to 20 minutes) in the arrest. The development of acidosis during cardiac arrest will depend on the cardiac output and perfusion pressures generated with CPR efforts. Our model had no CPR performed for 15 to 20 minutes to maximize the insult. Thus, in clinically evaluating a patient's need for bicarbonate during cardiac arrest, one must take into account downtime, pre-existing metabolic state, and time and efficacy of resuscitation efforts. CONCLUSION This study supports the hypothesis that sodium bicarbonate does not improve resuscitation from prolonged cardiac arrest. Improvement of arterial and venous acidemia by sodium bicarbonate did not correlate with an increase in ability to resuscitate. Prolongation of cardiac arrest from 15 to 20 minutes in this animal model re-
20:11 November 1991
sulted in irreversible arrest. Further investigation is needed to elucidate the mechanism of irreversible cardiac arrest. REFERENCES 1. Reading JS, Pearson JW: Resuscitation from ventricular fibrillation. JAMA 1968;203:93-98. 2. Kirimli B, Harris LC, Safar P: Evaluation of sodium bicarbonate and epinephrine in cardiopulmonary resuscitation. Anesth Anaf 1969~48:649-658. 3. Mattar JA, Well MH, Shubin H, et al: Cardiac arrest in the critically ill. A m J Med 1974;56:162-168. 4. Well MH, Ruiz CE, Michaels 8, et al: Acid-base determinants of survival after cardiopulmonary resuscitation. Crit Care Med 1985;13:888-892. 5. Berenyi KJ, Wolk M, Killip T: Cerebrospinal fluid acidosis: Complicating therapy of experimental cardiopulmonary arrest. Circulation 1975;52:319 324. 6. White BC, Tintinalli JE: Effects of sodium bicarbonate administration during cardiopulmonary resuscitation. JACEP 1977;6:187-190. 7. Marrinez LR, Holland S, Fitzgerald J, et al: pH homeostasis during cardiopulmonary resuscitation in critically ill patients. Resuscitation I979~7:109-117.
tricular fibrillation in dogs. Circulation 1986;74(suppl IV):W-75-IV-79. 11. Grundler W, Weft MH, Rackow EC: Arteriovenons carbon dioxide and pH gradients during cardiac arrest. Circulation 1986;74:1071 1074. 12. Ralston SH, Voorhees WD, Schmitz P, et af: Venous and arterial blood gases during and after cardiopulmonary resuscitation in dogs. A m J Emerg 1984;3:132-136. 13. Well MH, Rackow EC, Trevino R, et al: Differences in acid-base status between venous and arterial blood during cardiopuImonary resuscitation. N Engl J M e d 1986;315:153-156. 14. Bishop RL, Weisfeldt ML: Sodium bicarbonate administration during cardiac arrest. JAMA 1976;235: 506-509. 15. ganders AB, Ewy GA, Taft TV: Resuscitation and arterial blood gas abnormalities during prolonged cardiopulmonary resuscitation. Ann Emerg Med 1984;13: 676-679. 16. BedelI SE, Delbanneo TL, Cook EF, et al: Survival after cardiopulmonary resuscitation in the hospital. N Engl [ Med 1983;309:569-576. 17. Sanders AB, Kern KB, Atlas M, et al: Importance of the duration of inadequate coronary perfusion pressure on resuscitation from cardiac arrest. J A m Coil CardioI 1985;6:113-118.
8. Sanders AB, Otto CW, Kern KB, et al: Acid-base balance in a canine model of cardiac arrest. A n n Emerg Med 1988;17:667-671.
18. Kern KB, Garewal HS, ganders AB, et ah Depletion of myocardial adenosine triphosphate during prolonged untreated ventricular fibrillation: Effect on defibrillation success. Resuscitation 1990;20:2214229.
9. Sessler DI, Gregory GA, Lih L, et ah Bicarbonate administration does not cause a paradoxical brain intracellular acidosis during recovery from hypoxie Iactie acidosis. Anesthesiology 1986;65:A442.
19. Neumar R, Brown CG, Van Ligten P, et al: High energy phosphate metabolism during ventricnlar fibrillation (abstract). Ann Emerg Med 1989;18:472-473.
10. Guerci AD, Chandra N, Johnson E, et al: Failure of sodium bicarbonate to improve resuscitation from yen-
Annals of Emergency Medicine
20. Standards and guidelines for cardiopuImonary resuscitation (CPR} and emergency cardiac care (ECC}. JAMA 1986~255:2841-3044.
1177/27
The Effect of B i c a r b o n a t e on R e s u s c i t a t i o n From C a r d i a c A r r e s t Study objectives: This study attempted to determine the effect of bicarbonate administration on resuscitation in a porcine model of prolonged cardiac arrest. Design: After instrumentation, 26 swine were subjected to ventricular fibrillation for i5 minutes (16 animals) or 20 minutes (ten animals) with no resuscitative efforts. Interventions: Resuscitation attempts with open-chest cardiac massage and epinephrine were used in all animals after the arrest period. The experimental group was given sodium bicarbonate (3 mEq/kg), and the control group received 3% saline (5 mL/kg) at the initiation of cardiac massage. Measurements: Resuscitation success, hemodynamics, and arterial and mixed venous gases were compared in the bicarbonate and hypertonic saline-treated groups. Results: There was no difference in resuscitation rates between bicarbonate and nonbicarbonate-treated swine. After 15 minutes of ventricular fibrillation, six of eight bicarbonate-treated swine were resuscitated successfully compared with five of eight hypertonic saline-treated animals. None of the five bicarbonate-treated or five hypertonic saline-treated swine that underwent 20 minutes of ventricular fibrillation were resuscitated. The arterial and mixed venous pH values were significantly different in the bicarbonate-treated animals from values in the control group. There was no difference in systolic or diastolic blood pressures or myocardial perfusion pressure between the bicarbonate and hypertonic salinetreated animals. Conclusion: Despite correlation of arterial and venous acidemia, the use of sodium bicarbonate did not improve resuscitation from prolonged cardiac arrest. [Federiuk CS, Sanders AB, Kern KB, Nelson J, Ewy GA: The effect of bicarbonate on resuscitation from cardiac arrest. Ann Emerg Med November 1991;20:1173-1177.]
Carol S Federiuk, MD, PhD* Arthur B Sanders, MD, FACEP* Karl B Kern, MD, FACCt Jay Nelsont Gordon A Ewy, MD, FACCt Tucson, Arizona From the Section of Emergency Medicine, Department of Surgery,* and Section of Cardiology, Department of Internal Medicine,t University of Arizona Health Sciences Center, Tucson, Arizona. Received for publication October 30, 1991. Revision received March 4, 1991. Accepted for publication June 3, 1991. This research was supported by a grant from the Emergency Medicine Foundation and the Emergency Medicine Residents Association. Address for reprints: Carol S Federiuk, MD, PhD, Emergency Medicine, Oregon Health Sciences Center, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201.
INTRODUCTION The i m p o r t a n c e of acid-base balance in resuscitation from cardiac arrest remains unclear. Controversy still exists concerning the efficacy of treatm e n t of acid-base i m b a l a n c e during cardiac arrest and the accuracy of measurement of acid-base status during arrest through the use of arterial blood gases. Early studies of cardiac arrest in a n i m a l m o d e l s suggested that s o d i u m bicarbonate used in addition to epinephrine facilitated resuscitation from ventricular fibrillation and i m p r o v e d survival.I, 2 Concern for the use of bicarbonate was occasioned by the observations that bicarbonate m a y induce h y p e r o s m o l a r i t y and alkalosis in patients3, 4 and m a y result in central nervous s y s t e m acidosis in an a n i m a l m o d e l s O t h e r investigators, however, found no significant h y p e r o s m o l a r i t y or alkalosis w i t h the recomm e n d e d doses of bicarbonate6, 7 and no significant central nervous s y s t e m acidosis during prolonged arrest.8, 9 Despite m u l t i p l e studies that have disputed the findings of d e t r i m e n t a l effects of bicarbonate, evidence for a beneficial effect of bicarbonate in resuscitation from cardiac arrest r e m a i n s limited. In one a n i m a l study, animals that did n o t receive bicarbonate were resuscitated as easily as those
20:11 November 1991
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BICARBONATE F e d e r i u k et al
that did receive bicarbonate. 1° Evaluation of acid-base status and the effects of acid-base therapy during cardiac arrest is p e r f o r m e d rout i n e l y t h r o u g h t h e u s e of a r t e r i a l gases. Investigators have c o n f i r m e d t h e p r e s e n c e of a s i g n i f i c a n t arteriovenous gradient in pH and Pco2.11-13 Some suggest t h a t m i x e d v e n o u s b l o o d gases r e f l e c t c h a n g e s occurring in the s y s t e m i c c a p i l l a r y bed and m a y b e t t e r r e p r e s e n t intracellular metabolic status. 11-t3 The aim of this study is to test the h y p o t h e s i s t h a t b i c a r b o n a t e has no beneficial effect in resuscitation from prolonged cardiac arrest. The effect of a c i d - b a s e s t a t u s on r e s u s c i t a t i o n f r o m c a r d i a c a r r e s t is e v a l u a t e d t h r o u g h use of a r t e r i a l and m i x e d venous blood gases.
TABLE 1. Arterial and m i x e d venous blood gases in the 15-minute fibrillation group Bicarbonate
No Bicarbonate
O
Arterial pH Baseline
1 rain 14 rain 18rain 25 rain
7.48 7.50 7.44 7.51 7,24
± 0.09 --_ 0.10 ± 0.15 ± 0,17 ± 0.05
7.48 7,54 7.48 7.09 7.05
± ± ± ± ±
0.06 0.10 0.13 0.09 0.04
NS NS NS < .01 < .01
7.44 7.43 7,32 7.31 7.18
± ± ± ± ±
0.09 0.08 0.06 0.13 0.03
7.44 7.41 7.30 7.00 7.03
± +_ ± ±
0.05 0.05 0.06 0.08 0.03
NS NS NS < .01 < .01
37.2 33,9 39.4 74.9 62.7
± ± ± ± ±
9.4 7.9 12.0 32.4 8.3
37.1 32.5 36.6 58.6 66.0
± ± ± ± ±
5.2 7.5 10.9 14.2 8.7
NS NS NS NS NS
_+ 9.4 + 9.0 ± 6,6 ± 31.1 ± 6.7
42.3 44.9 52.7 72.7 72.0
_+ ± ± + +
4.1 5.4 6.2 24.9 9.6
NS NS NS < .05 NS
VenouspH Baseline
1 rain 14 rain
18 rain 25 rain Arterial Pco2 (mm Hg) Baseline
1 rain 14 rain 18 rain
25 min
Venous Pco2 (mm Hg)
MATERIALS A N D M E T H O D S The protocol was approved by the i n s t i t u t i o n a l l a b o r a t o r y a n i m a l research c o m m i t t e e . After an overnight fast, 26 swine (weight, 18 to 32 kg) were a n e s t h e t i z e d w i t h i s o f l u r a n e . The animals were endotracheally intubated and v e n t i l a t e d using a volu m e v e n t i l a t o r w i t h 100% O2 at a rate of 12 to 16 per m i n u t e and a tidal volume of 15 m L / k g to keep end-tidal CO2 at 30 to 40 m m Hg. The external jugular vein was c a n n u l a t e d by c u t d o w n w i t h a n 8F i n t r o d u c e r sheath, and a 7F p u l m o n a r y a r t e r y catheter was a d v a n c e d t h r o u g h t h e introducer into the p u l m o n a r y artery using pressure tracing guidance. High-fidelity micromanometertipped catheters (Millar PC-500, M i l l a r I n s t r u m e n t s Inc, H o u s t o n , Texas) were inserted into the carotid artery and e x t e r n a l jugular v e i n by cutdown and advanced into the chest using pressure-tracing guidance. A m e d i a n s t e r n o t o m y w a s performed, and the h e a r t was exposed. Ventricular f i b r i l l a t i o n was i n d u c e d using rapid ventricular pacing at 700 to 800 beats per minute. Fibrillation was c o n f i r m e d by the ECG p a t t e r n and by the decrease in arterial blood pressure. Ventilation was discontinued, and cardiac arrest was monitored for 15 m i n u t e s (16 animals) or 20 m i n u t e s (ten a n i m a l s ) w i t h no resuscitative efforts. A t the end of v e n t r i c u l a r fibrillation (15 or 20 minutes), v e n t i l a t i o n was restarted, and open-chest cardiac massage was performed at a rate of 80 per minute, keeping the perfusion 24/1174
Baseline 1 rain 14 rain 18 min 25 rain
41.4 42.0 50.3 111.8 78.0
pressure (diastolic aortic pressure min u s r i g h t a t r i a l pressure) a b o v e 30 m m Hg. A t i n i t i a t i o n of open-chest cardiac massage, animals in the contro] g r o u p (group A) r e c e i v e d epinephrine (0.04 mg/kg) and saline 3% (5 mL/kg). Group B received epinephrine (0.04 mg/kg) and s o d i u m bicarbonate (3 mEq/kg, or 3 mL/kg) at ons e t of c a r d i a c m a s s a g e . A f t e r five m i n u t e s of o p e n - c h e s t cardiac massage, defibrillation was a t t e m p t e d up to three times at 30 J in an effort to restore a perfusing r h y t h m . Those animals successfully resuscitated were observed for 30 m i n u t e s after the ret u r n of spontaneous circulation without further treatment. A n i m a l s that had a m e a n arterial pressure of 75% of baseline at 30 m i n u t e s after defibrillation were considered resuscitated. ECG and aortic and right atrial pressure waveforms were m o n i t o r e d c o n t i n u o u s l y and recorded throughout the e x p e r i m e n t on a four-channel Gould recorder (Gould Electronics, Cleveland, Ohio). Arterial and m i x e d v e n o u s b l o o d gases were d r a w n before fibrillation, at one m i n u t e of fibrillation, at one m i n u t e before onset of CPR (14 or 19 minutes), at three m i n u t e s of cardiac massage (18 or 23 minutes), and at one, five, and t e n m i n u t e s after r e s u s c i t a t i o n . Blood gases were collected into heparinized Annals of Emergency Medicine
gas-free s y r i n g e s and s t o r e d on ice u n t i l analysis i m m e d i a t e l y after the experiment. D i f f e r e n c e s in r e s u s c i t a t i o n bet w e e n groups A and B were evaluated by Fisher's exact test w i t h a significance set at P < .05. Differences in arterial and mixed venous blood gases and h e m o d y n a m i c s b e t w e e n groups w e r e a s s e s s e d at i n d i v i d u a l t i m e points by the Student's t test. A repeated measures m u l t i v a r i a t e analysis of v a r i a n c e was used to determ i n e differences in blood gases measurements during the t i m e course of the e x p e r i m e n t w i t h i n groups.
RESULTS The resuscitation rates b e t w e e n bicarbonate- and nonbicarbonatetreated groups of animals undergoing 15 m i n u t e s of ventricular fibrillation did n o t differ s i g n i f i c a n t l y . Six of eight bicarbonate-treated swine were resuscitated successfully compared w i t h five of eight h y p e r t o n i c salinetreated animals. N o n e of the five bic a r b o n a t e - t r e a t e d or five h y p e r t o n i c s a l i n e - t r e a t e d swine t h a t u n d e r w e n t 20 m i n u t e s of ventricular fibrillation were resuscitated. Blood gas values and hemodynamics were studied in the bicarbonate- and n o n b i c a r b o n a t e - t r e a t e d groups of animals. In those animals subjected to 15 m i n u t e s of ventricu20:11 November 1991
BICARBONATE Federiuk et al
TABLE 2. Arterial and m i x e d venous blood gases in the 20-minute fibrillation group Bicarbonate
No Bicarbonate
P
Arterial pH BaseLine 1 rnin 19 min 23 min
7.49 7.53 7.45 7.47
± ± ± ÷
0.05 0.10 0.15 0.18
7.53 7.55 7.44 7.04
_+ ± ± ±
0.03 0.11 0.03 0.11
NS NS NS < .01
7.42 7.42 7.26 7.27
± ± _+ +
0.06 0.05 0.07 0.16
7.47 7.43 7.19 6.96
+_ ± + ±
0.02 0.03 0.22 0.14
NS NS NS < .05
36.2 32.2 39.0 86.2
± + ± +
5.4 8.6 11.9 24.9
35.0 34.6 41.0 57.8
± ± ± +
2.4 6.1 2.4 20.4
NS NS NS NS
44.8 43.4 52.6 116.8
± ± _+ ±
6.2 8.0 11.3 25.4
37.8 44.2 51.8 74.5
± _+ _+ ±
7.1 4.2 9.0 26.9
NS NS NS < .05
Venous pH Baseline 1 rnin 19 rain 23 rnin
Arterial Pco2 (mm Bg) Baseline 1 rain 19 min 23 min
Venous Pco2 (mm Hg) Baseline 1 min 19 min 23 min
TABLE 3. Comparison of h e m o d y n a m i c s during CPR in bicarbonate- and nonbicarbonate-treated groups after 15 m i n u t e s of cardiac arrest
Time Pressure (min) (mm Hg)
BicarbonateTreated Group
No Bicarbonate Treatment
P
16
Systolic Diastolic Myocardial perfusion pressure
113 ± 14 76 ± 17 69 _+ 20
102 ± 50 60 _+ 43 55 + 46
NS NS NS
17
Systolic Diastolic Myocardial perfusion pressure
88 +_ 43 51 _+ 34 44 ± 32
97 + 36 50 _+ 30 41 + 31
NS NS NS
18
Systolic Diastolic Myocardial perfusion pressure
85 + 12 60 + 11 40 ± 7
81 -,- 15 59 ± 13 33 + 6
NS NS NS
19
Systolic Diastolic Myocardial perfusion pressure
81 ± 6 39 ± 6 32 _+ 6
82 + 19 36 ± 14 27 ± 16
NS NS NS
20
Systolic Diastolic Myocardial perfusion pressure
80 ÷ 7 36 ± 4 27 +_ 5
71 _+ 20 34 + 12 26 ÷ 14
NS NS NS
lar fibrillation, the arterial p H was significantly different between groups during CPR at 18 m i n u t e s of arrest (7.51 ± 0.17 in b i c a r b o n a t e treated group vs 7.09 + 0.07 in the control group; P < .01; Table 1). In a n i m a l s t h a t w e r e r e s u s c i t a t e d successfully, a difference in arterial p H persisted at 25 m i n u t e s (five m i n u t e s after defibrillation) (7.24 -+ 0.05 in the bicarbonate-treated group vs 7.05 ± 0.04 in the control group; P < .01; Table 1). A difference was also noted in m i x e d v e n o u s p H at 18 m i n u t e s (7.31 ± 0.13 in b i c a r b o n a t e - t r e a t e d group vs 7.00 _+ 0.08 in the control group; P < .01; Table 1). 20:11 November 1991
There was no significant difference in arterial P c o 2 b e t w e e n groups in animals that sustained 15 m i n u t e s of v e n t r i c u l a r f i b r i l l a t i o n ( T a b l e 1). M i x e d v e n o u s Pco2, h o w e v e r , differed at 18 m i n u t e s during CPR (111.8 ± 31.1 in b i c a r b o n a t e - t r e a t e d anim a l s vs 72.7 ± 24.9 in the control group; P < .05). This difference did not persist at 25 m i n u t e s in resuscitated a n i m a l s (Table 1). Differences in arterial and m i x e d venous p H values at 23 m i n u t e s also were observed b e t w e e n bicarbonateand nonbicarbonate-treated groups in animals that u n d e r w e n t 20 m i n u t e s of ventricular fibrillation before CPR Annals of Emergency Medicine
was started. The arterial pH was 7.47 _+ 0.18 in t h e b i c a r b o n a t e - t r e a t e d group versus 7.04 +_ 0.11 in the control group (P K .01; Table 2). Venous p H at 23 m i n u t e s was 7.27 + 0.16 in the bicarbonate-treated group versus 6.96 +- 0.14 in the control group (P < .05; Table 2). Postresuscitation blood gases were not obtained because t h e r e w e r e no s u r v i v o r s in t h e s e groups. A r t e r i a l P c o 2 d i d n o t differ between groups in animals undergoing 20 m i n u t e s of ventricular fibrillation (Table 2). Mixed venous Pco2, however, d e m o n s t r a t e d divergence at 23 m i n u t e s during CPR (116.8 + 25.4 in the bicarbonate-treated group vs 74.5 _+ 26.9 in the control group; P < .05; Table 2). There were no differences between b i c a r b o n a t e - and h y p e r t o n i c salinet r e a t e d a n i m a l s in s y s t o l i c or diastolic blood pressure or in myocard i a l p e r f u s i o n p r e s s u r e ( a o r t i c diastolic minus right atrial diastolic pressure during CPR) in animals undergoing 15 m i n u t e s of ventricular fibrillation (Table 3). Similarly, no diff e r e n c e in h e m o d y n a m i c s b e t w e e n b i c a r b o n a t e - and h y p e r t o n i c salinet r e a t e d a n i m a l s were f o u n d in animals that u n d e r w e n t 20 m i n u t e s of ventricular fibrillation (Table 4). R e t r o s p e c t i v e l y , t h e 11 a n i m a l s w h o were r e s u s c i t a t e d s u c c e s s f u l l y a f t e r 15 m i n u t e s of c a r d i a c a r r e s t were compared w i t h the five animals not resuscitated w i t h regard to blood gases and h e m o d y n a m i c s during CPR (Table 5). T h e r e was no significant difference in arterial p H (7.35 ± 0.23 vs 7.18 ± 0.13) or m i x e d venous p H (7.18 + 0.22 vs 7.10 _+ 0.11) in resuscitated and nonresuscitated animals. Systolic blood pressure was not significantly different in the two groups (86 + 15 vs 75 + 1 2 m m H g ) . However, diastolic blood pressure (45 ± 6 vs 36 ± 6 m m Hg, P < .05) and myocardial perfusion pressure (38 + 7 vs 26 _+ 11 m m Hg, P < .05) was significantly better in the resuscitated animals. DISCUSSION T h e p r o p o s e d effectiveness of sod i u m b i c a r b o n a t e in r e s u s c i t a t i o n f r o m p r o l o n g e d c a r d i a c a r r e s t is based on the hypothesis that neutralization of acidosis m a y p o t e n t i a t e defibrillation1, 2 and improve tissue viab i l i t y and cardiac function. In addition, bicarbonate may improve 1175/25
BICARBONATE F e d e r i u k et al
perfusion by providing fluid and electrolyte replacements. In this study, both control and bicarbonate-treated groups received s i m i l a r o s m o l a r loads in s m a l l volu m e s of fluid (3 to 5 mL/kg). Bicarbonate was n o t shown to improve resuscitation after 15 m i n u t e s of vent r i c u l a r f i b r i l l a t i o n despite the fact that bicarbonate significantly improved arterial and mixed venous acidemia compared w i t h the control group (Table 1). In pilot studies, we noted that large doses of bicarbonate (3 mEq/kg) w e r e n e e d e d to c o r r e c t the a c i d e m i a after 15 to 20 m i n u t e s of v e n t r i c u l a r f i b r i l l a t i o n . R e s u s c i tated animals r e m a i n e d significantly more acidemic at five m i n u t e s after defibrillation in the nonbicarbonatetreated group (Table 1). Our m e t h o d o l o g y was not designed to d i f f e r e n t i a t e t h e m e t a b o l i c a n d respiratory components of t h e acidosis during cardiac arrest. There is c o n c e r n t h a t b i c a r b o n a t e m a y worsen the acidosis of cardiac arrest, particularly, i n t r a c e l l u l a r and intracerebral acidosis, by i n c r e a s i n g carbon dioxide levels.4, 5 In this experiment, we did not measure intracellular or intracerebral acidosis. A n i m a l s t h a t r e c e i v e d bicarbonate, however, n o r m a l i z e d their arterial and m i x e d venous a c i d e m i a despite increases in P c o 2 (Table 1). Our study had a n u m b e r of potential l i m i t a t i o n s t h a t m u s t be t a k e n into account in evaluating the data. A porcine m o d e l of cardiac arrest was used, and caution should be used in e x t r a p o l a t i n g t h e r e s u l t s to h u m a n beings w i t h coronary artery disease. The s a m p l e size was s m a l l and although we found no statistical difference, a type II error is possible. We n o t e t h a t a l t h o u g h there was n o t a s t a t i s t i c a l d i f f e r e n c e in a r t e r i a l p H b e t w e e n t h e r e s u s c i t a t e d a n d nonresuscitated animals, the resuscitated animals had a higher p H (7.35 + 0.23 vs 7.18 -+ 0.13) and the probability of a type II (13) error is .64 for this observation. If we had used a larger n u m ber of animals, group differences m a y have been detected. Arterial and m i x e d v e n o u s b l o o d a c i d e m i a was used to m o n i t o r the acid-base status rather than continuous m o n i t o r i n g of tissue or cellular acidosis. Finally, no difference was detected in perfusion pressures b e t w e e n t h e bicarbonate and nonbicarbonatetreated groups when calculated every 26/1176
TABLE 4. Hemodynamics in the 20-minute fibrillation group Bicarbonate Myocardial perfusion pressure (mm Hg) at baseline
No Bicarbonate
P
46.3 -+ 5.1
52.0 + 8.3
NS
33.8 ± 20.9
32.8 + 5.8
NS
73,4 ± 6.2
78.6 + 3.8
NS
Systolic pressure (mm Hg) at 23 minutes during CPR
91.4 + 13.9
75.4 _+ 16.4
NS
Diastolic pressure (ram Hg) at baseline
51.0 ± 7.0
56.0 ± 6.7
NS
Diastolic pressure (ram Hg) at 23 minutes during CPR
46.0 ± 22.7
39.0 ± 7.2
NS
Myocardial perfusion pressure (mm Hg) at 23 minutes during CPR Systolic pressure (mm Hg) at baseline
TABLE 5. Comparison of resuscitated versus nonresuscitated animals after 15 minutes of cardiac arrest Resuscitated
Nonresuscitated
P
Arterial pH (18 minutes)
7.35 + 0.23
7.18 _+ 0.13
NS
Venous pH (18 minutes)
7.18 ± 0.22
7.10 ± 0.11
NS
Systolic blood pressure (18 minutes) Diastolic blood pressure (18 minutes)
86 ± 15
75 ± 12
NS
45 -,- 6
36 _+ 6
< .05*
Myocardial perfusion pressure (18 minutes)
38 ± 7
26 ± 11
< .05*
*Significant dilferences in myocardial perlusion pressure and diastolic blood pressure between resuscitated and nonresuscilated animals. NS, no diffeF ences in arterial or mixed venous pH or systolic blood pressure.
m i n u t e d u r i n g CPR (Table 1). It is possible that a significant difference in perfusion pressures w o u l d be present if each pressure wave during CPR was compared between the two groups. Despite these limitations, our data did not d e m o n s t r a t e a beneficial effect of bicarbonate t r e a t m e n t for resuscitation from cardiac arrest. Previous studies have indicated that acidosis during cardiac arrest does n o t b e c o m e severe u n t i l relatively late (15 to 20 minutes) in the arrest. 14,15 To d e t e r m i n e if increasing the d u r a t i o n of v e n t r i c u l a r fibrillation and thereby increasing the severi t y of the a c i d e m i a w o u l d r e s u l t in an i m p r o v e m e n t i n r e s u s c i t a t i o n w i t h b i c a r b o n a t e , a d d i t i o n a l studies were carried out u s i n g a 2 0 - m i n u t e period of ventricular fibrillation. Alt h o u g h b i c a r b o n a t e s i g n i f i c a n t l y increased arterial and m i x e d venous p H values (Table 2), no a n i m a l s in the bicarbonate-treated or hypertonic sal i n e - t r e a t e d groups were able to be resuscitated after 20 m i n u t e s of ventricular fibrillation. This finding suggests that a critical and p o t e n t i a l l y irreversible alteration Annals of Emergency Medicine
in m e t a b o l i s m t h a t occurs b e t w e e n 15 and 20 m i n u t e s p r e v e n t s resuscitation using current methods. This alteration is not affected by the addition of bicarbonate during resuscitat i o n , i n d i c a t i n g t h a t r e v e r s a l of acidemia alone late in arrest does n o t s i g n i f i c a n t l y affect the process. T h e o b s e r v a t i o n in this s t u d y is consistent w i t h other CPR studies indicating t h a t i n a d e q u a t e c i r c u l a t i o n for m o r e than 15 m i n u t e s is poorly correlated with successful resuscitation.16,17 T h e i n a b i l i t y to r e s u s c i t a t e after prolonged arrest could represent depletion of energy stores such as phosp h o c r e a t i n e a n d ATP, w h i c h m a y halt cellular m e t a b o l i s m and lead to a l t e r a t i o n s in m e m b r a n e p e r m e a b i l i t y or o t h e r i r r e v e r s i b l e cell d a m age.18,19 Alternately, irreversible enz y m e inactivation m a y occur secondary to progressive acidosis. W h a t e v e r the m e c h a n i s m , it does n o t appear to be reversed by IV s o d i u m bicarbonate. The use of bicarbonate in the treatm e n t of p a t i e n t s in c a r d i a c a r r e s t m a y be i n d i v i d u a l i z e d . Bicarbonate 20:11 November 1991
BICARBONATE Federiuk et al
appears to be useful for patients with suspected h y p e r k a l e m i a or preexisting acidosis, z0 Other patients may n o t d e v e l o p a s i g n i f i c a n t acidosis until relatively late (15 to 20 minutes) in the arrest. The development of acidosis during cardiac arrest will depend on the cardiac output and perfusion pressures generated with CPR efforts. Our model had no CPR performed for 15 to 20 minutes to maximize the insult. Thus, in clinically evaluating a patient's need for bicarbonate during cardiac arrest, one must take into account downtime, pre-existing metabolic state, and time and efficacy of resuscitation efforts. CONCLUSION This study supports the hypothesis that sodium bicarbonate does not improve resuscitation from prolonged cardiac arrest. Improvement of arterial and venous acidemia by sodium bicarbonate did not correlate with an increase in ability to resuscitate. Prolongation of cardiac arrest from 15 to 20 minutes in this animal model re-
20:11 November 1991
sulted in irreversible arrest. Further investigation is needed to elucidate the mechanism of irreversible cardiac arrest. REFERENCES 1. Reading JS, Pearson JW: Resuscitation from ventricular fibrillation. JAMA 1968;203:93-98. 2. Kirimli B, Harris LC, Safar P: Evaluation of sodium bicarbonate and epinephrine in cardiopulmonary resuscitation. Anesth Anaf 1969~48:649-658. 3. Mattar JA, Well MH, Shubin H, et al: Cardiac arrest in the critically ill. A m J Med 1974;56:162-168. 4. Well MH, Ruiz CE, Michaels 8, et al: Acid-base determinants of survival after cardiopulmonary resuscitation. Crit Care Med 1985;13:888-892. 5. Berenyi KJ, Wolk M, Killip T: Cerebrospinal fluid acidosis: Complicating therapy of experimental cardiopulmonary arrest. Circulation 1975;52:319 324. 6. White BC, Tintinalli JE: Effects of sodium bicarbonate administration during cardiopulmonary resuscitation. JACEP 1977;6:187-190. 7. Marrinez LR, Holland S, Fitzgerald J, et al: pH homeostasis during cardiopulmonary resuscitation in critically ill patients. Resuscitation I979~7:109-117.
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Annals of Emergency Medicine
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