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Sodium bicarbonate improves the chance of resuscitation after 10 minutes of cardiac arrest in dogs
Resuscitation 51 (2001) 309– 315 www.elsevier.com/locate/resuscitation
Sodium bicarbonate improves the chance of resuscitation after 10 minutes of cardiac arrest in dogs Elaine C.M. Leong, Jason C. Bendall, Anita C. Boyd, Rosemarie Einstein * Department of Pharmacology, Uni6ersity of Sydney, Sydney, NSW 2006, Australia Received 19 April 2001; received in revised form 13 June 2001; accepted 13 June 2001
Abstract The likelihood of successful defibrillation and resuscitation decreases as the duration of cardiac arrest increases. Prolonged cardiac arrest is also associated with the development of acidosis. These experiments were designed to determine whether administration of sodium bicarbonate and/or adrenaline in combination with a brief period of cardiopulmonary resuscitation (CPR) prior to defibrillation would improve the outcome of prolonged cardiac arrest in dogs. Ventricular fibrillation (VF) was induced by a.c. shock in anaesthetised dogs. After 10 min of VF, animals received either immediate defibrillation (followed by treatment with bicarbonate or control) or immediate treatment with bicarbonate or saline (followed by defibrillation). Treatment with bicarbonate was associated with increased rates of restoration of spontaneous circulation. This was achieved with fewer shocks and in a shorter time. Coronary perfusion pressure was significantly higher in NaHCO3-treated animals than in control animals. There were smaller decreases in venous pH in NaHCO3-treated animals than in controls. The best outcome in this study was achieved when defibrillation was delayed for approximately 2 min, during which time NaHCO3 and adrenaline were administered with CPR. The results of the present study indicate that in prolonged arrests bicarbonate therapy and a period of perfusion prior to defibrillation may increase survival. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Ventricular fibrillation; Defibrillation; Acidosis; Bicarbonate; Cardiac arrest; Resuscitation
1. Introduction In cardiac arrests that occur out-of-hospital, it is not uncommon for a significant time to elapse between discovery of the cardiac arrest and arrival of paramedics. Approximately two-thirds of these patients present with the potentially reversible rhythm of ventricular fibrillation (VF) [1]. The likelihood of successful defibrillation and resuscitation decreases with duration of VF [2]. Although early defibrillation is associated with a good prognosis following brief arrest, immediate defibrillation in prolonged arrest commonly results in asystole or electromechanical dissociation, both of which are associated with poor outcome [1,3]. The inevitable development of metabolic and respiratory acidosis that has been demonstrated in studies in animals [4] and humans [5] is one of the key physiological differences between brief and prolonged cardiac * Corresponding author. E-mail address: [email protected] (R. Einstein).
arrest and could contribute to different patient outcomes. Acidosis influences a variety of cellular electrophysiological parameters including resting membrane potential, threshold potential and conduction velocities. These effects are likely to contribute to the pro-arrhythmic influence of acidosis [6]. In addition, hypoxia and acidosis produce reversible myocardial depression [1,7], the major cause being a decrease in the sensitivity of contractile proteins to calcium [6]. The systemic response to vasopressors may be decreased in the presence of acidosis [4,8] and this may also affect the outcome of resuscitation. In experiments in animals, Vukmir et al. [4] showed that, after prolonged (15 min) arrest, there was an improved survival rate in animals that were treated with sodium bicarbonate and adrenaline. In these studies, however, sodium bicarbonate and adrenaline were only administered after immediate defibrillation had been unsuccessful. Other workers have suggested that a brief period of myocardial perfusion before countershock improves cardiac resuscitation outcome from cardiac arrest in dogs [9] and humans [10].
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Myocardial damage is associated with the cumulative electrical energy of defibrillation shocks [11,12]. Therefore, any procedure that decreases the number of defibrillation attempts needed to restore circulation would be clinically desirable. The experiments described in this report were designed to determine whether administration of sodium bicarbonate and/or adrenaline in combination with a brief period of cardiopulmonary resuscitation (CPR) prior to delivery of the first counter shock would improve the chance of successful defibrillation after 10 min of cardiac arrest in dogs.
2. Material and methods The experiments were conducted in 24 adult mongrel dogs (16–23 kg). The University of Sydney Animal Care and Ethics Committee approved the procedures. Animals were anaesthetised, intubated and allowed to breathe spontaneously. Anaesthesia induction was with sodium thiopentone (17 mg/kg intravenously (i.v.)) and maintained with halothane (1– 2%) in 100% 02. Electrocardiography was monitored continuously (79D Polygraph; Grass Medical Instruments) via subcutaneous electrodes. Femoral veins and arteries were cannulated bilaterally for drug administration, blood sampling and continuous blood pressure recording (Statham P23AC transducer, 79D Polygraph; Grass Medical Instruments). Central venous pressure was recorded continuously (Statham P23D transducer, 79D Polygraph; Grass Medical Instruments), via a catheter in the right external jugular vein, advanced to the right atrium. The coronary perfusion pressure (CoPP) was calculated as the difference between aortic diastolic pressure and the right atrial pressure. Anaesthesia was discontinued prior to the initiation of cardiac arrest. The animals breathed 100% O2 for 1 min and then room air until the corneal reflex could be elicited. VF was then induced by applying a 110V a.c. shock (50 Hz) to transthoracic subcutaneous chest electrodes for 2 s, repeated if required. Induction of arrest was followed by a non-intervention time of 10 min. Animals were then randomly assigned to receive CPR and drug treatment prior to defibrillation (n = 12) or immediate defibrillation followed by drug treatment (n =12). Closed-chest CPR was performed continuously with a Thumper® Cardio-Pulmonary Resuscitator Model 1005 (Michigan Instruments). The compression pad was placed on the lateral chest wall of the animal and a force (30–40 kg) was applied (approximately 5 cm compression depth) at 60 compressions/min, with a 50% duty cycle and a compression:ventilation (100% oxygen) ratio of 5:1. Ventilation was provided at a maximum airway pressure of 25 mmHg. Restoration of spontaneous circulation (ROSC) was defined as a systolic blood pressure of 60 mmHg, sustained for a
minimum of 10 min. Survival was defined as ROSC for 30 min.
2.1. Immediate treatment Following 10 min of VF, animals were randomly assigned to receive adrenaline (0.1 mg/kg i.v.) in combination with either sodium bicarbonate (2 mmol/kg i.v.) or NaCl (2 ml/kg, 0.9% i.v.) at the commencement of the resuscitation procedure. After drug administration and 2 min of CPR, a 200 J defibrillation shock was delivered (LIFEPAK 10 Monitor Defibrillator; PhysioControl Corporation). If VF was not terminated by defibrillation, lignocaine (2 mg/kg i.v.) was administered and defibrillation repeated (360 J). If ROSC did not occur, a further dose of the treatment (either sodium bicarbonate (1 mmol/kg i.v.) or NaCl (1 ml/kg, 0.9% i.v.)) was administered. Resuscitation continued with Advanced Life Support (ALS) if required. Administration of sodium bicarbonate or sodium chloride was blinded during the resuscitation period.
2.2. Immediate defibrillation Following 10 min of VF, resuscitation commenced with delivery of a 200 J defibrillation shock. If ROSC did not occur, animals were randomly assigned to receive sodium bicarbonate (2 mmol/kg i.v.) and adrenaline (0.1 mg/kg i.v.) or adrenaline (0.1 mg/kg i.v.) alone. CPR was performed for 60 s followed by a 360 J defibrillation shock. If ROSC was not attained, a further dose of NaHCO3 (1 mmol/kg) was administered to the sodium bicarbonate group. If ROSC had not occurred, resuscitation continued with standard ALS.
2.3. Ad6anced Life Support CPR was performed continuously, except during defibrillation. ALS comprised of adrenaline (0.1 mg/kg) administered every 5 min for the duration of the arrest. Further defibrillation shocks (360 J) were delivered to terminate VF as required. Lignocaine (2 mg/kg) was administered for VF refractory to treatment and/or adrenaline and defibrillation. This dose was repeated once if required. Atropine (0.04 mg/kg) was administered to animals with pulseless, organized rhythms or asystole. Prior to defibrillation all drugs were circulated for approximately 60 s using mechanical CPR. Resuscitation was continued until ROSC occurred or for a total resuscitation period of 30 min. CPR was discontinued when a perfusing rhythm was obtained. Lignocaine (2 mg/min) and adrenaline infusions (as required) were administered following ROSC to treat ventricular arrhythmias and maintain systolic blood pressure \80 mmHg, respectively.
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Blood samples were taken at pre-arrest and at 5 min after initiation of resuscitation and analysed for pH and PCO2 (Radiometer ABL, System 625).
2.4. Statistical analysis All results are expressed as mean9 standard error of the mean. The outcome of resuscitation (ROSC and survival) was compared by Fisher’s exact test. The number of defibrillation attempts and the coronary perfusion pressures were compared with the Mann– Whitney U-test and unpaired Student t-test (twotailed), respectively. Blood gas analysis variables (pH and PCO2) were compared by repeated-measures analysis of variance. Differences were considered to be significant when PB0.05.
3. Results Control values for the immediate treatment and immediate defibrillation groups are shown in Table 1. With the exception of resting heart rates, where the NaHCO3 immediate defibrillation group had a significantly lower rate, there were no statistically significant differences in pre-arrest variables between or within groups. Data from one animal was not included in the results due to technical difficulties during resuscitation. Ventricular fibrillation was successfully induced in all animals with a.c. shocks. All animals remained in VF for the 10 min non-intervention period. Both ROSC and survival rate were higher in NaHCO3-treated animals than in control animals. This difference was significant in the immediate treatment group (PB0.05); however, it just failed to reach statistical significance in the immediate defibrillation group (P= 0.06) (Table 2). Furthermore, for animals that were resuscitated, NaHCO3-treated animals attained ROSC in a shorter time than control animals (Table 2).
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NaHCO3-treated animals also required significantly fewer defibrillation shocks during the resuscitation period than control animals (PB 0.05) (Table 2). For the animals in which ROSC was achieved, the average number of shocks required in bicarbonate-treated animals was 1.8. The immediate defibrillation and immediate treatment control animals that achieved ROSC required four and five shocks respectively. Coronary perfusion pressure (measured 5 min after commencement of resuscitation or, for those animals achieving ROSC, immediately prior to ROSC) was significantly higher in NaHCO3-treated animals than in control animals (PB 0.05) (Table 2). At 5 min after resuscitation was commenced, the venous pH in control animals was significantly less than pre-arrest values (PB0.05) (Table 3). There were smaller decreases in venous pH in NaHCO3-treated animals so that, at 5 min, the pH was not significantly different from pre-arrest values (Table 3). Venous PCO2 of control animals was not significantly different after 5 min of resuscitation compared with pre-arrest values (Table 3). However, in the NaHCO3-treated animals, venous PCO2 increased significantly (PB 0.05) in this period (Table 3). 4. Discussion Sudden cardiac death is most commonly associated with ventricular fibrillation (VF). The majority of these events occur out-of-hospital [13,14] and therefore there is a significant interval while awaiting the arrival of emergency medical services. Current resuscitation guidelines recommend immediate defibrillation as the treatment of choice for ventricular fibrillation [15]. The major determinant of resuscitation success is the time to defibrillation [16], so that prompt defibrillation substantially improves the likelihood of success in animals [2] and survival in humans following out-of-hospital cardiac arrest [17].
Table 1 Pre-arrest values for haemodynamic parameters and blood variables in dogs assigned to receive immediate treatment or immediate defibrillation after 10 min of cardiac arresta Variable
MAP (mmHg) Heart rate (b.p.m.) Arterial pH PaCO2 (mmHg) Sodium (mmol/l) Potassium (mmol/l) Calcium (mmol/l)
Immediate treatment
Immediate defibrillation
Control (n=6)
NaHCO3 (n =6)
Control (n =6)
NaHCO3 (n = 5)
12497 1429 11 7.49 0.0 279 2 1469 1 4.39 0.1 1.19 0.04
12696 163 917 7.5 90.0 32 9 4 143 9 1 4.0 90.1 1.1 9 0.04
122 95 162 96 7.4 9 0.1 35 9 6 146 9 1 4.3 9 0.3 1.1 90.04
114 9 9 137 9 2* 7.3 9 0.0 34 91 143 9 3 4.5 9 0.2 1.1 9 0.07
a Within these groups, animals were randomly assigned to either control or sodium bicarbonate treatment groups. *PB0.05 compared with respective control.
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Table 2 Outcome of resuscitation in dogs after immediate treatment or immediate defibrillationa Variable
ROSC Time to ROSC (min) Survival Defibrillation attempts CoPP (mmHg)
Immediate treatment
Immediate defibrillation
Control (n=6)
NaHCO3 (n =6)
Control (n =6)
NaHCO3 (n =5)
1 14 0 4.59 0.8 99 2
5* 7 91 4* 1.7 90.3* 23 9 6*
1 30 1 5.5 90.5 8 91
4 59 2 4 2.4 90.8* 29 93*
a Within these groups, animals were randomly assigned to either control or sodium bicarbonate treatment groups. * PB0.05 compared with respective control.
Vukmir et al. [4] demonstrated significantly higher ROSC and survival benefit with immediate defibrillation followed by bicarbonate administration in prolonged (15 min) arrest, although bicarbonate treatment did not influence the outcome following brief (5 min) arrest. The results of the present study with 10 min non-intervention confirm those of Vukmir et al. [4] and demonstrate increases in ROSC and survival in animals treated with bicarbonate. The same trend was seen in immediate defibrillation group treated with bicarbonate; however, the failure to reach statistical significance could have been associated with the small group size. Treatment of animals with sodium bicarbonate and adrenaline prior to defibrillation was associated with significant increases in ROSC and survival when compared with adrenaline alone. Niemann et al. [9] previously demonstrated a survival benefit in dogs treated with adrenaline prior to defibrillation following 7.5 min of VF; thus, differences in ROSC and survival in this study are likely to be attributable to sodium bicarbonate treatment. There is biochemical, histological and clinical evidence that the cumulative energy delivered to the myocardium during defibrillation attempts is associated with myocardial damage [11,12,18], which decreases the likelihood of successful resuscitation. Furthermore, repeated defibrillation attempts may decrease activity of pacemakers by increasing parasympathetic tone [19], thereby further reducing the likelihood of attaining ROSC. Although Vukmir et al. [4] did not demonstrate any differences in the number of defibrillation attempts between bicarbonate-treated and control animals, this study demonstrates that significantly fewer counter shocks were required during resuscitation in bicarbonate-treated animals compared with the control animals. As ROSC was attained more frequently in bicarbonatetreated animals, fewer shocks would be expected during the resuscitation period. However, where ROSC was achieved, the number of shocks required was less than 50% of the number required in the corresponding con-
trol animals. This indicates that VF either persisted or recurred more frequently during the resuscitation period in control animals. During cardiac arrest, the absence of adequate cardiac output leads to tissue hypoxia, cellular anaerobic metabolism and the depletion of high-energy phosphates [20]. Ultimately, oxidative phosphorylation fails resulting in accumulation of H+ ions that inhibit anaerobic glycolysis and reduce production of ATP [21]. Furthermore, lactate is produced during anaerobic glycolysis, exacerbating acidosis. Failure of ventilation results in the accumulation of CO2, thereby worsening cellular acidosis. Acidosis decreases cardiac contractility [7,1], may decrease CoPP [22] and attenuate the effect of vasopressors [4,8], may cause arrhythmias [6] and is associated with neurological damage [23]. The use of bicarbonate in cardiac arrest has been criticised because of potential adverse effects including systemic alkalosis, paradoxical intracellular acidosis, hypercapnia (due to CO2 production) and hypernatraemia [24]. It was not meaningful to assess the venous pH immediately following 10 min VF (i.e. commencement of resuscitation) due to the absence of tissue blood flow that occurs during VF. The pH measured at 5 min was considered to be reflective of the cumulative metabolic changes during 10 min of VF and during the first 5 min of resuscitation. Acidosis, still present in this model of cardiac arrest 5 min after resuscitation, was reversed by treatment with sodium bicarbonate, so that the venous pH at this time was decreased significantly from pre-arrest values only in control groups. Furthermore, the dose of bicarbonate used (3 mmol/kg) was sufficient to restore pH without causing alkalosis or a significant increase in pH from the pre-arrest values. Although there was no means of determining whether intracellular acidosis occurred, PCO2 increased significantly in bicarbonate-treated animals. These changes in PCO2 have been shown to be transient following the return of ROSC [4]. In vitro studies reporting intracellular acidosis have been used to argue against bicarbonate therapy. However, their validity has been
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Table 3 Venous blood pH and PCO2 5 min after initiation of resuscitation in dogs after 10 min of cardiac arresta Variable
pH PCO2
Time
Pre-arrest 5 min Pre-arrest 5 min
Immediate treatment
Immediate defibrillation
Control (n= 6)
NaHCO3 (n =6)
Control (n =6)
NaHCO3 (n =5)
7.28 9 0.02 6.909 0.07* 55 93 56 913
7.26 9 0.02 7.15 9 0.09 60 93 82 97*
7.24 9 0.02 7.03 9 0.03* 59 9 4 57 9 6
7.22 90.03 7.17 90.05 56 9 5 79 98*
a
Animals received either immediate treatment or immediate defibrillation. Within these groups, animals were randomly assigned to either control or sodium bicarbonate treatment groups. * PB0.05 compared with pre-arrest values.
questioned and they may not be able to be extrapolated to the in vivo setting [25]. In any event, the occurrence of intracellular acidosis (if present) may be an acceptable adverse effect, considering that bicarbonate therapy was associated with significant increases in ROSC and survival. In out-of-hospital arrest in humans, Warner et al. [1] found that the ability to restore a pulse in the field was a major prognostic indicator for survival. Therefore, therapies that increase the likelihood of attaining ROSC are also likely to be useful. The coronary perfusion pressure of bicarbonatetreated animals (\20 mmHg) was significantly higher than that in control animals. Wenzel et al. [8] demonstrated that only the first dose of adrenaline was effective at improving CoPP in a pig model of cardiac arrest; therefore, as the duration of arrest increases, the effectiveness of adrenaline as a vasopressor decreases. Furthermore, the effectiveness of adrenaline as a vasopressor has been shown to decrease in the presence of acidosis [4,8]. The higher CoPP in bicarbonate-treated animals may be due to the increased effectiveness of adrenaline in the less acidotic conditions. One of the best predictors of ROSC during CPR, in both animals and humans, has been shown to be a CoPP of between 20 and 30 mmHg [8]. Thus, the higher rate of ROSC in bicarbonate-treated animals was likely to be due, at least in part, to the improved CoPP. Not only is the effectiveness of adrenaline decreased following the first dose, but Lerman and Engelstein [26] showed that as the duration of VF increased, the defibrillation threshold also increased and, therefore, successful defibrillation was correspondingly less likely to be achieved. Thus, when circulation is not readily restored, the prognosis is poor. In the current study, it appeared that ROSC was attained earlier in the bicarbonate-treated animals than in controls. The best outcome in this study was achieved when defibrillation was delayed for approximately 2 min, during which time NaHCO3 and adrenaline were administered with CPR, despite the fact that this increased the time in VF to approximately 12 min. Cobb et al [10] indicated that, after arrest lasting longer than
4 min, a brief period of CPR prior to defibrillation improved the outcome. Sodium bicarbonate reversed the acidosis associated with cardiac arrest and increased CoPP with out any obvious adverse effects that impacted on outcome. Prolonged cardiac arrest that occurs out-of-hospital presents unique challenges. Significant acidosis is likely to be present by the time paramedics arrive and the opportunity for immediate defibrillation to restore a perfusing rhythm has usually passed. Current guidelines advocate consideration of potentially reversible causes, followed by a standard approach of cluster shocks, adrenaline and CPR [15], regardless of the period of arrest. There has been only one randomised controlled clinical trial investigating buffer therapy in the setting of out-of-hospital cardiac arrest [27]. While this study found no beneficial effect of buffer therapy, there are good reasons why further investigations of immediate treatment with sodium bicarbonate (and adrenaline) prior to defibrillation in prolonged (] 10 min) cardiac arrest in humans are needed [28]. Neurological outcome was not determined in the present study so that the likely impact of this regime on brain resuscitation remains to be determined. It is likely, however, that obtaining ROSC in the field is the first and critical step in obtaining a favourable resuscitation outcome. The results of the present study indicate that in prolonged arrests bicarbonate therapy and a period of perfusion prior to defibrillation may increase survival in this group of patients in whom the prognosis is very poor.
Acknowledgements This study was supported in part by a grant donated by the Laerdal Foundation for Acute Medicine, Stavangar, Norway. Michigan Instruments (Grand Rapids, MI, USA) generously supplied Thumper® and Acute Care Systems (Sydney, Australia) supplied LIFEPAK-10®. The authors gratefully acknowledge the expert technical assistance of Desmond Richardason, Tina Stasinopoulos and Donald Davidson, and the
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extensive out-of-hospital insight provided by Stephen Irons (EMT-P).
References [1] Warner LL, Hoffman JR, Baraff LJ. Prognostic significane of field response in out-of-hospital ventricular fibrillation. Chest 1985;87:22 – 8. [2] Yakaitis RW, Ewy GA, Otto CW, Taren DL, Moon TE. Influence of time and therapy on ventricular fibrillation in dogs. Crit Care Med 1980;8:157 –63. [3] Hargarten KN, Stueven HA, Waite EM, Olson DW, Mateer JR, Aufderheide TP, Darrin JC. Prehospital experience with defibrillation of course ventricular fibrillation — a ten year review. Ann Emerg Med 1999;19:157 –62. [4] Vukmir RB, Bircher NG, Radovsky A, Safar P. Sodium bicarbonate may improve outcome in dogs with prolonged cardiac arrest. Crit Care Med 1995;23:515 – 22. [5] Levy MM. An evidence-based evaluation of the use of sodium bicarbonate during cardiopulmonary resuscitation. Crit Care Clin 1988;14:457 – 83. [6] Orchard CH, Cingolani HE. Acidosis and arrhythmias in cardiac muscle. Cardiovasc Res 1994;28:1312 – 9. [7] Teplinsky K, O’Toole M, Olman M, Walley KR, Wood LDH. Effect of lactic acidosis on canine haemodynamics and left ventricular function. Am J Physiol 1990;258:1193 – 9. [8] Wenzel V, Linder KH, Krismer AC, Miller EA, Voelckel WG, Lingnau W. Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs. Circulation 1999;99:1379 –84. [9] Niemann JT, Cairns CB, Sharma J, Lewis R. Treatment of prolonged ventricular fibrillation — immediate countershock versus high dose epinephrine and CPR preceding countershock. Circulation 1992;85:281 –7. [10] Cobb LA, Fahrenbruch CE, Walsh TR, Copass MK, Olsufka M, Breskin M, Hallstrom AP. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. J Am Med Assoc 1999;281:1182 – 8. [11] Gaba DM, Talner NS. Myocardial damage following thransthoracic direct current countershock in newborn piglets. Paediatr Cardiol 1982;2:281 –8. [12] Kerber RE, Carter J, Klein S, Grayzel J, Kennedy J. Open chest defibrillation during cardiac surgery: energy and current requirment. Am J Cardiol 1980;46:393 –6. [13] Herlitz J, Ekstrom L, Wennerblom B, Axelsson A, Bang A, Holmberg S. Effect of bystander initiated cardiopulmonary resuscitation on ventricular fibrillation and survival after witnessed
cardiac arrest outside hospital. Br Heart J 1994;72:408 –12. [14] Martens P, Vandekerckhove Y, The Belgian CPCR Study Group. Optimal defibrillation stategy and follow-up of out-ofhospital cardiac arrest. Resuscitation 1996;31:25 – 32. [15] de Latorre F, Nolan J, Robertson C, Chamberlain D, Baskett P. European resuscitation guidelines 2000 for adult advanced life support. Resuscitation 2001;48:211 – 21. [16] Haynes BE, Mendoza A, McNeil M, Schroeder J, Smiley DR. A statewide early defibrillation initiative including lay persons and outcome reporting. J Am Med Assoc 1999;266:545 – 7. [17] Kellerman AL, Hackman BB, Somes G, Kreth TK, Nail L, Dobyns P. Impact of first-responder defibrillation in an urban emergency medical services system. J Am Med Assoc 1994;270:1708 – 1713. [18] Brown CG, Griffith RF, Ligten PV, Hoekstra J, Nejman G, Mitchell L, Dzwonczyk R. Median frequency — a new parameter for prediciting defibrillation success rate. Ann Emerg Med 1991;20:787 – 9. [19] Strohmenger H, Lindner KH, Prengel AW, Pfenninger EG, Bothner U, Lurie KG. Effects of epinephrine and vasopressin on median fibrillation frequency and defibrillation success in a porcine model of cardiopulmonary resuscitation. Resuscitation 1996;31:65 – 73. [20] Kern KB, Garewal HS, Sanders AB, Janas W, Nelson J, Sloan D, Tacker WA, Ewy GA. Depletion of myocardial adenosine triphosphate during prolonged untreated ventricular fibrillation: effect on defibrillation success. Resuscitation 1990;20:221 –9. [21] Halperin ML, Cheema-Dhadli S, Halperin FA, Kamel KS. Rationale for the use of sodium bicarbonate in a patient with lactic acidosis due to a poor cardiac output. Nephron 1994;66:258 – 61. [22] Narins RG, Cohen JJ. Bicarbonate therapy for organic acidosis: the case for its continued use. Ann Intern Med 1987;106:615 –8. [23] Abramson NS, Safar P, Detre KM, Kelsey SF, Monroe J, Reinmuth O, Snyder JV. Neurological recovery after cardiac arrest: effect of duration of ischaemia. Crit Care Med 1985;13:930 – 1. [24] Gazmuri RJ. Buffer treatment for cardiac resuscitation: putting the cart before the horse. Crit Care Med 1999;27:875 – 6. [25] Levraut J, Labib Y, Chave S, Payan P, Raucoules-Aime M, Grimaud D. Effect of sodium bicarbonate on intracellular pH under different buffering conditions. Kidney Int 1996;49:1262 –7. [26] Lerman BB, Engelstein EE. Increased defibrillation threshold due to ventricular fibrillation duration. J Electrocardiol 1995;28:21 – 4. [27] Dybvik T, Strand T, Steen PA. Buffer therapy during out-ofhospital cardiopulmonary resuscitation. Resuscitation 1995;29:89 – 95. [28] Koster RW. Correction of acidosis during cardio-pulmonary resuscitation. Resuscitation 1995;29:87 – 8.
Portuguese Abstract and Keywords A probabilidade de desfibrilhac¸ a˜ o e reanimac¸ a˜ o eficazes diminui com o aumento de durac¸ a˜ o da paragem cardı´aca. A paragem cardı´aca prolongada tambe´ m esta´ associada ao desenvolvimento de acidose. Estas experieˆ ncias foram projectadas para determinar se a administrac¸ a˜ o de bicarbonato de so´ dio e/ou adrenalina em combinac¸ a˜ o com um breve perı´odo de reanimac¸ a˜ o cardiopulmonar (CPR) antes da desfibrilhac¸ a˜ o melhorava o progno´ stico da paragem cardı´aca prolongada em ca˜ es. A fibrilhac¸ a˜ o ventricular (VF) era induzida por choque com corrente alterna em ca˜ es anestesiados. Apo´ s 10 min de FV, os animais recebiam ou desfibrilhac¸ a˜ o imediata (seguida de tratamento com bicarbonato ou controle) ou tratamento imediato com bicarbonato ou soro fisiolo´ gico (seguido de desfibrilhac¸ a˜ o). O tratamento com bicarbonato correlacionou-se com aumento da taxa de recuperac¸ a˜ o de circulac¸ a˜ o espontaˆ nea, o que foi conseguido com menos choques e num perı´odo de tempo mais curto. A pressa˜ o de perfusa˜ o corona´ ria era significativamente mais alta em animais tratados com bicarbonato que nos animais de controle. Houve menor descida dos valores de pH venoso nos animais tratados com bicarbonato que nos controle. O melhor progno´ stico neste estudo
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foi conseguido quando a desfibrilhac¸ a˜ o foi atrasada cerca de 2 min, tempo durante o qual, se fez SBV e foram administrados bicarbonato e adrenalina. Os resultados deste estudo indicam que nas paragens prolongadas o tratamento com bicarbonato e um perı´odo de perfusa˜ o antes da desfibrilhac¸ a˜ o podem aumentar a sobrevida. Pala6ras cha6e: Fibrilhac¸ a˜ o ventricular; Desfibrilhac¸ a˜ o; Acidose; Bicarbonato; Paragem cardı´aca; Reanimac¸ a˜ o
Sodium bicarbonate improves the chance of resuscitation after 10 minutes of cardiac arrest in dogs Elaine C.M. Leong, Jason C. Bendall, Anita C. Boyd, Rosemarie Einstein * Department of Pharmacology, Uni6ersity of Sydney, Sydney, NSW 2006, Australia Received 19 April 2001; received in revised form 13 June 2001; accepted 13 June 2001
Abstract The likelihood of successful defibrillation and resuscitation decreases as the duration of cardiac arrest increases. Prolonged cardiac arrest is also associated with the development of acidosis. These experiments were designed to determine whether administration of sodium bicarbonate and/or adrenaline in combination with a brief period of cardiopulmonary resuscitation (CPR) prior to defibrillation would improve the outcome of prolonged cardiac arrest in dogs. Ventricular fibrillation (VF) was induced by a.c. shock in anaesthetised dogs. After 10 min of VF, animals received either immediate defibrillation (followed by treatment with bicarbonate or control) or immediate treatment with bicarbonate or saline (followed by defibrillation). Treatment with bicarbonate was associated with increased rates of restoration of spontaneous circulation. This was achieved with fewer shocks and in a shorter time. Coronary perfusion pressure was significantly higher in NaHCO3-treated animals than in control animals. There were smaller decreases in venous pH in NaHCO3-treated animals than in controls. The best outcome in this study was achieved when defibrillation was delayed for approximately 2 min, during which time NaHCO3 and adrenaline were administered with CPR. The results of the present study indicate that in prolonged arrests bicarbonate therapy and a period of perfusion prior to defibrillation may increase survival. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Ventricular fibrillation; Defibrillation; Acidosis; Bicarbonate; Cardiac arrest; Resuscitation
1. Introduction In cardiac arrests that occur out-of-hospital, it is not uncommon for a significant time to elapse between discovery of the cardiac arrest and arrival of paramedics. Approximately two-thirds of these patients present with the potentially reversible rhythm of ventricular fibrillation (VF) [1]. The likelihood of successful defibrillation and resuscitation decreases with duration of VF [2]. Although early defibrillation is associated with a good prognosis following brief arrest, immediate defibrillation in prolonged arrest commonly results in asystole or electromechanical dissociation, both of which are associated with poor outcome [1,3]. The inevitable development of metabolic and respiratory acidosis that has been demonstrated in studies in animals [4] and humans [5] is one of the key physiological differences between brief and prolonged cardiac * Corresponding author. E-mail address: [email protected] (R. Einstein).
arrest and could contribute to different patient outcomes. Acidosis influences a variety of cellular electrophysiological parameters including resting membrane potential, threshold potential and conduction velocities. These effects are likely to contribute to the pro-arrhythmic influence of acidosis [6]. In addition, hypoxia and acidosis produce reversible myocardial depression [1,7], the major cause being a decrease in the sensitivity of contractile proteins to calcium [6]. The systemic response to vasopressors may be decreased in the presence of acidosis [4,8] and this may also affect the outcome of resuscitation. In experiments in animals, Vukmir et al. [4] showed that, after prolonged (15 min) arrest, there was an improved survival rate in animals that were treated with sodium bicarbonate and adrenaline. In these studies, however, sodium bicarbonate and adrenaline were only administered after immediate defibrillation had been unsuccessful. Other workers have suggested that a brief period of myocardial perfusion before countershock improves cardiac resuscitation outcome from cardiac arrest in dogs [9] and humans [10].
0300-9572/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 0 0 - 9 5 7 2 ( 0 1 ) 0 0 4 2 1 - X
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Myocardial damage is associated with the cumulative electrical energy of defibrillation shocks [11,12]. Therefore, any procedure that decreases the number of defibrillation attempts needed to restore circulation would be clinically desirable. The experiments described in this report were designed to determine whether administration of sodium bicarbonate and/or adrenaline in combination with a brief period of cardiopulmonary resuscitation (CPR) prior to delivery of the first counter shock would improve the chance of successful defibrillation after 10 min of cardiac arrest in dogs.
2. Material and methods The experiments were conducted in 24 adult mongrel dogs (16–23 kg). The University of Sydney Animal Care and Ethics Committee approved the procedures. Animals were anaesthetised, intubated and allowed to breathe spontaneously. Anaesthesia induction was with sodium thiopentone (17 mg/kg intravenously (i.v.)) and maintained with halothane (1– 2%) in 100% 02. Electrocardiography was monitored continuously (79D Polygraph; Grass Medical Instruments) via subcutaneous electrodes. Femoral veins and arteries were cannulated bilaterally for drug administration, blood sampling and continuous blood pressure recording (Statham P23AC transducer, 79D Polygraph; Grass Medical Instruments). Central venous pressure was recorded continuously (Statham P23D transducer, 79D Polygraph; Grass Medical Instruments), via a catheter in the right external jugular vein, advanced to the right atrium. The coronary perfusion pressure (CoPP) was calculated as the difference between aortic diastolic pressure and the right atrial pressure. Anaesthesia was discontinued prior to the initiation of cardiac arrest. The animals breathed 100% O2 for 1 min and then room air until the corneal reflex could be elicited. VF was then induced by applying a 110V a.c. shock (50 Hz) to transthoracic subcutaneous chest electrodes for 2 s, repeated if required. Induction of arrest was followed by a non-intervention time of 10 min. Animals were then randomly assigned to receive CPR and drug treatment prior to defibrillation (n = 12) or immediate defibrillation followed by drug treatment (n =12). Closed-chest CPR was performed continuously with a Thumper® Cardio-Pulmonary Resuscitator Model 1005 (Michigan Instruments). The compression pad was placed on the lateral chest wall of the animal and a force (30–40 kg) was applied (approximately 5 cm compression depth) at 60 compressions/min, with a 50% duty cycle and a compression:ventilation (100% oxygen) ratio of 5:1. Ventilation was provided at a maximum airway pressure of 25 mmHg. Restoration of spontaneous circulation (ROSC) was defined as a systolic blood pressure of 60 mmHg, sustained for a
minimum of 10 min. Survival was defined as ROSC for 30 min.
2.1. Immediate treatment Following 10 min of VF, animals were randomly assigned to receive adrenaline (0.1 mg/kg i.v.) in combination with either sodium bicarbonate (2 mmol/kg i.v.) or NaCl (2 ml/kg, 0.9% i.v.) at the commencement of the resuscitation procedure. After drug administration and 2 min of CPR, a 200 J defibrillation shock was delivered (LIFEPAK 10 Monitor Defibrillator; PhysioControl Corporation). If VF was not terminated by defibrillation, lignocaine (2 mg/kg i.v.) was administered and defibrillation repeated (360 J). If ROSC did not occur, a further dose of the treatment (either sodium bicarbonate (1 mmol/kg i.v.) or NaCl (1 ml/kg, 0.9% i.v.)) was administered. Resuscitation continued with Advanced Life Support (ALS) if required. Administration of sodium bicarbonate or sodium chloride was blinded during the resuscitation period.
2.2. Immediate defibrillation Following 10 min of VF, resuscitation commenced with delivery of a 200 J defibrillation shock. If ROSC did not occur, animals were randomly assigned to receive sodium bicarbonate (2 mmol/kg i.v.) and adrenaline (0.1 mg/kg i.v.) or adrenaline (0.1 mg/kg i.v.) alone. CPR was performed for 60 s followed by a 360 J defibrillation shock. If ROSC was not attained, a further dose of NaHCO3 (1 mmol/kg) was administered to the sodium bicarbonate group. If ROSC had not occurred, resuscitation continued with standard ALS.
2.3. Ad6anced Life Support CPR was performed continuously, except during defibrillation. ALS comprised of adrenaline (0.1 mg/kg) administered every 5 min for the duration of the arrest. Further defibrillation shocks (360 J) were delivered to terminate VF as required. Lignocaine (2 mg/kg) was administered for VF refractory to treatment and/or adrenaline and defibrillation. This dose was repeated once if required. Atropine (0.04 mg/kg) was administered to animals with pulseless, organized rhythms or asystole. Prior to defibrillation all drugs were circulated for approximately 60 s using mechanical CPR. Resuscitation was continued until ROSC occurred or for a total resuscitation period of 30 min. CPR was discontinued when a perfusing rhythm was obtained. Lignocaine (2 mg/min) and adrenaline infusions (as required) were administered following ROSC to treat ventricular arrhythmias and maintain systolic blood pressure \80 mmHg, respectively.
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Blood samples were taken at pre-arrest and at 5 min after initiation of resuscitation and analysed for pH and PCO2 (Radiometer ABL, System 625).
2.4. Statistical analysis All results are expressed as mean9 standard error of the mean. The outcome of resuscitation (ROSC and survival) was compared by Fisher’s exact test. The number of defibrillation attempts and the coronary perfusion pressures were compared with the Mann– Whitney U-test and unpaired Student t-test (twotailed), respectively. Blood gas analysis variables (pH and PCO2) were compared by repeated-measures analysis of variance. Differences were considered to be significant when PB0.05.
3. Results Control values for the immediate treatment and immediate defibrillation groups are shown in Table 1. With the exception of resting heart rates, where the NaHCO3 immediate defibrillation group had a significantly lower rate, there were no statistically significant differences in pre-arrest variables between or within groups. Data from one animal was not included in the results due to technical difficulties during resuscitation. Ventricular fibrillation was successfully induced in all animals with a.c. shocks. All animals remained in VF for the 10 min non-intervention period. Both ROSC and survival rate were higher in NaHCO3-treated animals than in control animals. This difference was significant in the immediate treatment group (PB0.05); however, it just failed to reach statistical significance in the immediate defibrillation group (P= 0.06) (Table 2). Furthermore, for animals that were resuscitated, NaHCO3-treated animals attained ROSC in a shorter time than control animals (Table 2).
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NaHCO3-treated animals also required significantly fewer defibrillation shocks during the resuscitation period than control animals (PB 0.05) (Table 2). For the animals in which ROSC was achieved, the average number of shocks required in bicarbonate-treated animals was 1.8. The immediate defibrillation and immediate treatment control animals that achieved ROSC required four and five shocks respectively. Coronary perfusion pressure (measured 5 min after commencement of resuscitation or, for those animals achieving ROSC, immediately prior to ROSC) was significantly higher in NaHCO3-treated animals than in control animals (PB 0.05) (Table 2). At 5 min after resuscitation was commenced, the venous pH in control animals was significantly less than pre-arrest values (PB0.05) (Table 3). There were smaller decreases in venous pH in NaHCO3-treated animals so that, at 5 min, the pH was not significantly different from pre-arrest values (Table 3). Venous PCO2 of control animals was not significantly different after 5 min of resuscitation compared with pre-arrest values (Table 3). However, in the NaHCO3-treated animals, venous PCO2 increased significantly (PB 0.05) in this period (Table 3). 4. Discussion Sudden cardiac death is most commonly associated with ventricular fibrillation (VF). The majority of these events occur out-of-hospital [13,14] and therefore there is a significant interval while awaiting the arrival of emergency medical services. Current resuscitation guidelines recommend immediate defibrillation as the treatment of choice for ventricular fibrillation [15]. The major determinant of resuscitation success is the time to defibrillation [16], so that prompt defibrillation substantially improves the likelihood of success in animals [2] and survival in humans following out-of-hospital cardiac arrest [17].
Table 1 Pre-arrest values for haemodynamic parameters and blood variables in dogs assigned to receive immediate treatment or immediate defibrillation after 10 min of cardiac arresta Variable
MAP (mmHg) Heart rate (b.p.m.) Arterial pH PaCO2 (mmHg) Sodium (mmol/l) Potassium (mmol/l) Calcium (mmol/l)
Immediate treatment
Immediate defibrillation
Control (n=6)
NaHCO3 (n =6)
Control (n =6)
NaHCO3 (n = 5)
12497 1429 11 7.49 0.0 279 2 1469 1 4.39 0.1 1.19 0.04
12696 163 917 7.5 90.0 32 9 4 143 9 1 4.0 90.1 1.1 9 0.04
122 95 162 96 7.4 9 0.1 35 9 6 146 9 1 4.3 9 0.3 1.1 90.04
114 9 9 137 9 2* 7.3 9 0.0 34 91 143 9 3 4.5 9 0.2 1.1 9 0.07
a Within these groups, animals were randomly assigned to either control or sodium bicarbonate treatment groups. *PB0.05 compared with respective control.
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Table 2 Outcome of resuscitation in dogs after immediate treatment or immediate defibrillationa Variable
ROSC Time to ROSC (min) Survival Defibrillation attempts CoPP (mmHg)
Immediate treatment
Immediate defibrillation
Control (n=6)
NaHCO3 (n =6)
Control (n =6)
NaHCO3 (n =5)
1 14 0 4.59 0.8 99 2
5* 7 91 4* 1.7 90.3* 23 9 6*
1 30 1 5.5 90.5 8 91
4 59 2 4 2.4 90.8* 29 93*
a Within these groups, animals were randomly assigned to either control or sodium bicarbonate treatment groups. * PB0.05 compared with respective control.
Vukmir et al. [4] demonstrated significantly higher ROSC and survival benefit with immediate defibrillation followed by bicarbonate administration in prolonged (15 min) arrest, although bicarbonate treatment did not influence the outcome following brief (5 min) arrest. The results of the present study with 10 min non-intervention confirm those of Vukmir et al. [4] and demonstrate increases in ROSC and survival in animals treated with bicarbonate. The same trend was seen in immediate defibrillation group treated with bicarbonate; however, the failure to reach statistical significance could have been associated with the small group size. Treatment of animals with sodium bicarbonate and adrenaline prior to defibrillation was associated with significant increases in ROSC and survival when compared with adrenaline alone. Niemann et al. [9] previously demonstrated a survival benefit in dogs treated with adrenaline prior to defibrillation following 7.5 min of VF; thus, differences in ROSC and survival in this study are likely to be attributable to sodium bicarbonate treatment. There is biochemical, histological and clinical evidence that the cumulative energy delivered to the myocardium during defibrillation attempts is associated with myocardial damage [11,12,18], which decreases the likelihood of successful resuscitation. Furthermore, repeated defibrillation attempts may decrease activity of pacemakers by increasing parasympathetic tone [19], thereby further reducing the likelihood of attaining ROSC. Although Vukmir et al. [4] did not demonstrate any differences in the number of defibrillation attempts between bicarbonate-treated and control animals, this study demonstrates that significantly fewer counter shocks were required during resuscitation in bicarbonate-treated animals compared with the control animals. As ROSC was attained more frequently in bicarbonatetreated animals, fewer shocks would be expected during the resuscitation period. However, where ROSC was achieved, the number of shocks required was less than 50% of the number required in the corresponding con-
trol animals. This indicates that VF either persisted or recurred more frequently during the resuscitation period in control animals. During cardiac arrest, the absence of adequate cardiac output leads to tissue hypoxia, cellular anaerobic metabolism and the depletion of high-energy phosphates [20]. Ultimately, oxidative phosphorylation fails resulting in accumulation of H+ ions that inhibit anaerobic glycolysis and reduce production of ATP [21]. Furthermore, lactate is produced during anaerobic glycolysis, exacerbating acidosis. Failure of ventilation results in the accumulation of CO2, thereby worsening cellular acidosis. Acidosis decreases cardiac contractility [7,1], may decrease CoPP [22] and attenuate the effect of vasopressors [4,8], may cause arrhythmias [6] and is associated with neurological damage [23]. The use of bicarbonate in cardiac arrest has been criticised because of potential adverse effects including systemic alkalosis, paradoxical intracellular acidosis, hypercapnia (due to CO2 production) and hypernatraemia [24]. It was not meaningful to assess the venous pH immediately following 10 min VF (i.e. commencement of resuscitation) due to the absence of tissue blood flow that occurs during VF. The pH measured at 5 min was considered to be reflective of the cumulative metabolic changes during 10 min of VF and during the first 5 min of resuscitation. Acidosis, still present in this model of cardiac arrest 5 min after resuscitation, was reversed by treatment with sodium bicarbonate, so that the venous pH at this time was decreased significantly from pre-arrest values only in control groups. Furthermore, the dose of bicarbonate used (3 mmol/kg) was sufficient to restore pH without causing alkalosis or a significant increase in pH from the pre-arrest values. Although there was no means of determining whether intracellular acidosis occurred, PCO2 increased significantly in bicarbonate-treated animals. These changes in PCO2 have been shown to be transient following the return of ROSC [4]. In vitro studies reporting intracellular acidosis have been used to argue against bicarbonate therapy. However, their validity has been
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Table 3 Venous blood pH and PCO2 5 min after initiation of resuscitation in dogs after 10 min of cardiac arresta Variable
pH PCO2
Time
Pre-arrest 5 min Pre-arrest 5 min
Immediate treatment
Immediate defibrillation
Control (n= 6)
NaHCO3 (n =6)
Control (n =6)
NaHCO3 (n =5)
7.28 9 0.02 6.909 0.07* 55 93 56 913
7.26 9 0.02 7.15 9 0.09 60 93 82 97*
7.24 9 0.02 7.03 9 0.03* 59 9 4 57 9 6
7.22 90.03 7.17 90.05 56 9 5 79 98*
a
Animals received either immediate treatment or immediate defibrillation. Within these groups, animals were randomly assigned to either control or sodium bicarbonate treatment groups. * PB0.05 compared with pre-arrest values.
questioned and they may not be able to be extrapolated to the in vivo setting [25]. In any event, the occurrence of intracellular acidosis (if present) may be an acceptable adverse effect, considering that bicarbonate therapy was associated with significant increases in ROSC and survival. In out-of-hospital arrest in humans, Warner et al. [1] found that the ability to restore a pulse in the field was a major prognostic indicator for survival. Therefore, therapies that increase the likelihood of attaining ROSC are also likely to be useful. The coronary perfusion pressure of bicarbonatetreated animals (\20 mmHg) was significantly higher than that in control animals. Wenzel et al. [8] demonstrated that only the first dose of adrenaline was effective at improving CoPP in a pig model of cardiac arrest; therefore, as the duration of arrest increases, the effectiveness of adrenaline as a vasopressor decreases. Furthermore, the effectiveness of adrenaline as a vasopressor has been shown to decrease in the presence of acidosis [4,8]. The higher CoPP in bicarbonate-treated animals may be due to the increased effectiveness of adrenaline in the less acidotic conditions. One of the best predictors of ROSC during CPR, in both animals and humans, has been shown to be a CoPP of between 20 and 30 mmHg [8]. Thus, the higher rate of ROSC in bicarbonate-treated animals was likely to be due, at least in part, to the improved CoPP. Not only is the effectiveness of adrenaline decreased following the first dose, but Lerman and Engelstein [26] showed that as the duration of VF increased, the defibrillation threshold also increased and, therefore, successful defibrillation was correspondingly less likely to be achieved. Thus, when circulation is not readily restored, the prognosis is poor. In the current study, it appeared that ROSC was attained earlier in the bicarbonate-treated animals than in controls. The best outcome in this study was achieved when defibrillation was delayed for approximately 2 min, during which time NaHCO3 and adrenaline were administered with CPR, despite the fact that this increased the time in VF to approximately 12 min. Cobb et al [10] indicated that, after arrest lasting longer than
4 min, a brief period of CPR prior to defibrillation improved the outcome. Sodium bicarbonate reversed the acidosis associated with cardiac arrest and increased CoPP with out any obvious adverse effects that impacted on outcome. Prolonged cardiac arrest that occurs out-of-hospital presents unique challenges. Significant acidosis is likely to be present by the time paramedics arrive and the opportunity for immediate defibrillation to restore a perfusing rhythm has usually passed. Current guidelines advocate consideration of potentially reversible causes, followed by a standard approach of cluster shocks, adrenaline and CPR [15], regardless of the period of arrest. There has been only one randomised controlled clinical trial investigating buffer therapy in the setting of out-of-hospital cardiac arrest [27]. While this study found no beneficial effect of buffer therapy, there are good reasons why further investigations of immediate treatment with sodium bicarbonate (and adrenaline) prior to defibrillation in prolonged (] 10 min) cardiac arrest in humans are needed [28]. Neurological outcome was not determined in the present study so that the likely impact of this regime on brain resuscitation remains to be determined. It is likely, however, that obtaining ROSC in the field is the first and critical step in obtaining a favourable resuscitation outcome. The results of the present study indicate that in prolonged arrests bicarbonate therapy and a period of perfusion prior to defibrillation may increase survival in this group of patients in whom the prognosis is very poor.
Acknowledgements This study was supported in part by a grant donated by the Laerdal Foundation for Acute Medicine, Stavangar, Norway. Michigan Instruments (Grand Rapids, MI, USA) generously supplied Thumper® and Acute Care Systems (Sydney, Australia) supplied LIFEPAK-10®. The authors gratefully acknowledge the expert technical assistance of Desmond Richardason, Tina Stasinopoulos and Donald Davidson, and the
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extensive out-of-hospital insight provided by Stephen Irons (EMT-P).
References [1] Warner LL, Hoffman JR, Baraff LJ. Prognostic significane of field response in out-of-hospital ventricular fibrillation. Chest 1985;87:22 – 8. [2] Yakaitis RW, Ewy GA, Otto CW, Taren DL, Moon TE. Influence of time and therapy on ventricular fibrillation in dogs. Crit Care Med 1980;8:157 –63. [3] Hargarten KN, Stueven HA, Waite EM, Olson DW, Mateer JR, Aufderheide TP, Darrin JC. Prehospital experience with defibrillation of course ventricular fibrillation — a ten year review. Ann Emerg Med 1999;19:157 –62. [4] Vukmir RB, Bircher NG, Radovsky A, Safar P. Sodium bicarbonate may improve outcome in dogs with prolonged cardiac arrest. Crit Care Med 1995;23:515 – 22. [5] Levy MM. An evidence-based evaluation of the use of sodium bicarbonate during cardiopulmonary resuscitation. Crit Care Clin 1988;14:457 – 83. [6] Orchard CH, Cingolani HE. Acidosis and arrhythmias in cardiac muscle. Cardiovasc Res 1994;28:1312 – 9. [7] Teplinsky K, O’Toole M, Olman M, Walley KR, Wood LDH. Effect of lactic acidosis on canine haemodynamics and left ventricular function. Am J Physiol 1990;258:1193 – 9. [8] Wenzel V, Linder KH, Krismer AC, Miller EA, Voelckel WG, Lingnau W. Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs. Circulation 1999;99:1379 –84. [9] Niemann JT, Cairns CB, Sharma J, Lewis R. Treatment of prolonged ventricular fibrillation — immediate countershock versus high dose epinephrine and CPR preceding countershock. Circulation 1992;85:281 –7. [10] Cobb LA, Fahrenbruch CE, Walsh TR, Copass MK, Olsufka M, Breskin M, Hallstrom AP. Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation. J Am Med Assoc 1999;281:1182 – 8. [11] Gaba DM, Talner NS. Myocardial damage following thransthoracic direct current countershock in newborn piglets. Paediatr Cardiol 1982;2:281 –8. [12] Kerber RE, Carter J, Klein S, Grayzel J, Kennedy J. Open chest defibrillation during cardiac surgery: energy and current requirment. Am J Cardiol 1980;46:393 –6. [13] Herlitz J, Ekstrom L, Wennerblom B, Axelsson A, Bang A, Holmberg S. Effect of bystander initiated cardiopulmonary resuscitation on ventricular fibrillation and survival after witnessed
cardiac arrest outside hospital. Br Heart J 1994;72:408 –12. [14] Martens P, Vandekerckhove Y, The Belgian CPCR Study Group. Optimal defibrillation stategy and follow-up of out-ofhospital cardiac arrest. Resuscitation 1996;31:25 – 32. [15] de Latorre F, Nolan J, Robertson C, Chamberlain D, Baskett P. European resuscitation guidelines 2000 for adult advanced life support. Resuscitation 2001;48:211 – 21. [16] Haynes BE, Mendoza A, McNeil M, Schroeder J, Smiley DR. A statewide early defibrillation initiative including lay persons and outcome reporting. J Am Med Assoc 1999;266:545 – 7. [17] Kellerman AL, Hackman BB, Somes G, Kreth TK, Nail L, Dobyns P. Impact of first-responder defibrillation in an urban emergency medical services system. J Am Med Assoc 1994;270:1708 – 1713. [18] Brown CG, Griffith RF, Ligten PV, Hoekstra J, Nejman G, Mitchell L, Dzwonczyk R. Median frequency — a new parameter for prediciting defibrillation success rate. Ann Emerg Med 1991;20:787 – 9. [19] Strohmenger H, Lindner KH, Prengel AW, Pfenninger EG, Bothner U, Lurie KG. Effects of epinephrine and vasopressin on median fibrillation frequency and defibrillation success in a porcine model of cardiopulmonary resuscitation. Resuscitation 1996;31:65 – 73. [20] Kern KB, Garewal HS, Sanders AB, Janas W, Nelson J, Sloan D, Tacker WA, Ewy GA. Depletion of myocardial adenosine triphosphate during prolonged untreated ventricular fibrillation: effect on defibrillation success. Resuscitation 1990;20:221 –9. [21] Halperin ML, Cheema-Dhadli S, Halperin FA, Kamel KS. Rationale for the use of sodium bicarbonate in a patient with lactic acidosis due to a poor cardiac output. Nephron 1994;66:258 – 61. [22] Narins RG, Cohen JJ. Bicarbonate therapy for organic acidosis: the case for its continued use. Ann Intern Med 1987;106:615 –8. [23] Abramson NS, Safar P, Detre KM, Kelsey SF, Monroe J, Reinmuth O, Snyder JV. Neurological recovery after cardiac arrest: effect of duration of ischaemia. Crit Care Med 1985;13:930 – 1. [24] Gazmuri RJ. Buffer treatment for cardiac resuscitation: putting the cart before the horse. Crit Care Med 1999;27:875 – 6. [25] Levraut J, Labib Y, Chave S, Payan P, Raucoules-Aime M, Grimaud D. Effect of sodium bicarbonate on intracellular pH under different buffering conditions. Kidney Int 1996;49:1262 –7. [26] Lerman BB, Engelstein EE. Increased defibrillation threshold due to ventricular fibrillation duration. J Electrocardiol 1995;28:21 – 4. [27] Dybvik T, Strand T, Steen PA. Buffer therapy during out-ofhospital cardiopulmonary resuscitation. Resuscitation 1995;29:89 – 95. [28] Koster RW. Correction of acidosis during cardio-pulmonary resuscitation. Resuscitation 1995;29:87 – 8.
Portuguese Abstract and Keywords A probabilidade de desfibrilhac¸ a˜ o e reanimac¸ a˜ o eficazes diminui com o aumento de durac¸ a˜ o da paragem cardı´aca. A paragem cardı´aca prolongada tambe´ m esta´ associada ao desenvolvimento de acidose. Estas experieˆ ncias foram projectadas para determinar se a administrac¸ a˜ o de bicarbonato de so´ dio e/ou adrenalina em combinac¸ a˜ o com um breve perı´odo de reanimac¸ a˜ o cardiopulmonar (CPR) antes da desfibrilhac¸ a˜ o melhorava o progno´ stico da paragem cardı´aca prolongada em ca˜ es. A fibrilhac¸ a˜ o ventricular (VF) era induzida por choque com corrente alterna em ca˜ es anestesiados. Apo´ s 10 min de FV, os animais recebiam ou desfibrilhac¸ a˜ o imediata (seguida de tratamento com bicarbonato ou controle) ou tratamento imediato com bicarbonato ou soro fisiolo´ gico (seguido de desfibrilhac¸ a˜ o). O tratamento com bicarbonato correlacionou-se com aumento da taxa de recuperac¸ a˜ o de circulac¸ a˜ o espontaˆ nea, o que foi conseguido com menos choques e num perı´odo de tempo mais curto. A pressa˜ o de perfusa˜ o corona´ ria era significativamente mais alta em animais tratados com bicarbonato que nos animais de controle. Houve menor descida dos valores de pH venoso nos animais tratados com bicarbonato que nos controle. O melhor progno´ stico neste estudo
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foi conseguido quando a desfibrilhac¸ a˜ o foi atrasada cerca de 2 min, tempo durante o qual, se fez SBV e foram administrados bicarbonato e adrenalina. Os resultados deste estudo indicam que nas paragens prolongadas o tratamento com bicarbonato e um perı´odo de perfusa˜ o antes da desfibrilhac¸ a˜ o podem aumentar a sobrevida. Pala6ras cha6e: Fibrilhac¸ a˜ o ventricular; Desfibrilhac¸ a˜ o; Acidose; Bicarbonato; Paragem cardı´aca; Reanimac¸ a˜ o