Clinical use of sodium bicarbonate during cardiopulmonary resuscitation—is it used sensibly?

Resuscitation 54 (2002) 47 /55 www.elsevier.com/locate/resuscitation

Clinical use of sodium bicarbonate during cardiopulmonary resuscitation* is it used sensibly? /

Gad Bar-Joseph a,c,*, Norman S. Abramson a, Linda Jansen-McWilliams b, Sheryl F. Kelsey b, Tatiania Mashiach d, Mary T. Craig a, Peter Safar a, Brain Resuscitation Clinical Trial III (BRCT III) Study Group a

Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA 15260, USA b Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA 15260, USA c Pediatric Intensive Care Unit, Rambam Medical Center and the Bruce Rappaport Faculty of Medicine, Technion */Israel Institute of Technology, Haifa 31096, Israel d Quality Assurance Department, Rambam Medical Center and the Bruce Rappaport Faculty of Medicine, Technion */Israel Institute of Technology, Haifa 31096, Israel Received 27 August 2001; received in revised form 21 January 2002; accepted 21 January 2002

Abstract This study retrospectively analyzed the pattern of sodium bicarbonate (SB) use during cardiopulmonary resuscitation (CPR) in the Brain Resuscitation Clinical Trial III (BRCT III). BRCT III was a prospective clinical trial, which compared high-dose to standard-dose epinephrine during CPR. SB use was left optional in the study protocol. Records of 2915 patients were reviewed. Percentage, timing and dosage of SB administration were correlated with demographic and cardiac arrest variables and with times from collapse to Basic Life Support, to Advanced Cardiac Life Support (ACLS) and to the major interventions performed during CPR. SB was administered in 54.5% of the resuscitations. The rate of SB use decreased with increasing patient age */primarily reflecting shorter CPR attempts. Mean time intervals from arrest, from start of ACLS and from first epinephrine to administration of the first SB were 299/16, 199/13, and 10.89/11.1 min, respectively. No correlation was found between the rate of SB use and the pre-ACLS hypoxia times. On the other hand, a direct linear correlation was found between the rate of SB use and the duration of ACLS. We conclude that when SB was used, the time from initiation of ACLS to administration of its first dose was long and severe metabolic acidosis probably already existed at this point. Therefore, if SB is used, earlier administration may be considered. Contrary to physiological rationale, clinical decisions regarding SB use did not seem to take into consideration the duration of preACLS hypoxia times. We suggest that guidelines for SB use during CPR should emphasize the importance of pre-ACLS hypoxia time in contributing to metabolic acidosis and should be more specific in defining the duration of ‘protracted CPR or long resuscitative efforts’, the most frequent indication for SB administration. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Acid /base; Acidosis; Bicarbonate; Sodium bicarbonate; Buffer therapy; Cardiac arrest; Cardiopulmonary resuscitation; Advanced life support

1. Introduction Excessive lactate production always results from tissue hypoxia and anaerobic metabolism. Since severe



Presented in part at the 7th World Congress of Intensive and Critical Care Medicine, Ottawa, Canada, July 1997. * Corresponding author. Tel.: /972-4-8542855/9834948; fax: /9724-8542864 E-mail address: [email protected] (G. BarJoseph).

metabolic acidosis was considered detrimental during cardiopulmonary resuscitation (CPR), buffering with sodium bicarbonate (SB) was intuitively and empirically included in its initial pharmacological armamentarium [1]. SB was subsequently recommended as a first line drug in the first American Heart Association’s (AHA) Standards for Cardiopulmonary Resuscitation and Advanced Cardiac Life Support (ACLS) [2]. Its use was re-evaluated in the 1986 update of the ACLS Guidelines, where it was no longer recommended, but rather ‘could be used at the discretion of the team

0300-9572/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 0 0 - 9 5 7 2 ( 0 2 ) 0 0 0 4 5 - X

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leader’ [3]. This change was based mainly on a newly conceived hypothesis regarding the kinetics of carbon dioxide in very low flow states [3 /6]. This approach was only somewhat modified in the 1992 version of the ACLS Guidelines, according to which SB may be indicated in cases of protracted arrest or long resuscitative efforts or with preexisting metabolic acidosis [7,8]. The 2000 ACLS Guidelines do not offer any new discussion of buffer therapy and their section on SB use is basically a copy of the 1992 version [9]. Although SB is used in ACLS for over four decades and buffer therapy became a highly controversial issue during the past 15 years [4,6,10,11], we could not find any systematic analysis of its clinical use in the literature. Almost all published studies were endeavors to retrospectively evaluate the effect of SB on CPR outcome, and most of them focused on in-hospital arrests [12 /17] rather than on the more frequent outof-hospital arrest [18,19]. The Brain Resuscitation Clinical Trial III (BRCT III) was a large, randomized multicenter clinical trial, comparing, in a double blinded fashion, two epinephrine dosages during CPR [20]. The use of SB was left optional in the study protocol of BRCT III. The purpose of the present study was to retrospectively analyze the pattern of SB use in the large patient population of this clinical trial and to determine whether clinical practices reflected the physiologic rationale behind the use of SB.

2. Methods This study represents a secondary analysis of the BRCT III database regarding SB usage during CPR. Sixteen hospitals in seven countries participated in this randomized clinical trial, coordinated by the International Resuscitation Research Center team at the University of Pittsburgh with the support of the Epidemiology Data Center at the University of Pittsburgh’s Graduate School of Public Health. The Institutional Review Boards of each of the participating hospitals approved the research protocol. Patients were enrolled between January 1, 1990 and November 30, 1992. Included were patients who presented in asystole, pulseless electrical activity or those who had failed to regain spontaneous circulation following three counter shocks for ventricular fibrillation or pulseless ventricular tachycardia. Excluded were patients with known terminal illness, cardiac arrest due to trauma, drug overdose or intracranial disease, age less than 18 years, known pregnancy, or those who had received standard doses of epinephrine prior to consideration for study entry. Patients were randomly assigned to receive up to three sequential intravenous (IV) bolus injections of either

standard (0.5, 1, 1.5 mg) or high dose (5, 10, 15 mg) epinephrine. If restoration of spontaneous circulation (ROSC) was not achieved after the three study epinephrine doses, subsequent epinephrine doses, if needed, were all of 1 mg. All hospital investigators and all clinical personnel on the Steering Committee remained blinded to the identity of the treatment for each patient throughout the study. Resuscitation efforts were conducted according to the 1986 American Heart Association ACLS guidelines [3]. The use of SB was left ‘to the discretion of the team leader’ [3]. Data of each case were recorded by the study site’s investigator and were reviewed by the central reviewers. Time intervals for each case were estimated as accurately as possible by the site’s investigator after interviews with witnesses, ambulance personnel and hospital staff. In general, Utstein style reporting was used [21], although BRCT III was performed before the Utstein guidelines were published. For the analysis of SB usage, the BRCT III database was reviewed and the following variables were extracted and tabulated: Demographics, arrest variables, times from collapse to Basic Life Support (BLS) and to ACLS, CPR time line, outcome variables and the timing and number of SB doses administered. The following time intervals were calculated: Duration of arrest /time from collapse to the initiation of BLS, or of ACLS if no BLS was performed. Time to ACLS /time from collapse to the initiation of ACLS. Duration of CPR /time from BLS, or from ACLS if no BLS was performed, until ROSC or termination of resuscitation efforts. Times to intubation, to starting an IV line, to administration of the first study epinephrine and to the administration of the first SB dose were calculated as intervals from collapse to the application of the respective intervention. 2.1. Statistical analysis Statistical calculations were performed using the Statistical Product for Service Solution (SPSS, Windows version 9, USA). Data are reported as mean9/SD as well as 95% confidence intervals where relevant. x2-test was used to compare frequencies of SB usage between groups and t-test was used to compare continuous data. The relations between age and time intervals and the use of SB were examined with a test for linear trends in proportions. A P value of less than 0.05 was considered statistically significant.

3. Results In the BRCT III 2915 patients were included and their records were reviewed for this analysis. Sixteen study

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Table 1 Demographic and the cardiac arrest variables in relation to SB use Rate of SB use (%) P valueb

n (%)

No SB

1 dose SB

 1 dose SB

All patients

2915a

46.4

38.3

15.3

Sex Males Females

1955 (67.4) 945 (32.6)

44.8 50.2

39.7 34.9

15.5 14.9

B 0.001

Location of cardiac arrest Out of hospital In hospital Other

2533 (87.3) 308 (10.6) 59 (2)

46.6 44.5 55.9

39.3 29.2 33.9

14.1 26.3 10.2

0.5

Cause of cardiac arrest Cardiac Pulmonary Other

2048 (84.3) 263 (10.8) 118 (4.9)

43.3 56.7 52.5

40.5 33.1 33.1

16.2 10.3 14.4

B 0.001

Treatment group Standard dose Epi High dose Epi

1452 (50) 1448 (50)

45.9 47.2

39.2 37.1

14.9 15.7

No. of study Epi doses 1 2 3

297 (10.3) 343 (11.9) 2254 (77.9)

72.4 62.1 40.8

23.9 30.6 41.1

3.7 7.3 18.1

Additional non-study Epi

1640

36.4

42

21.6

0.46

B 0.001

Epi, epinephrine. a The numbers not always sum up to n 2915 due to missing data. b P values relate to comparisons (by x2) of the rates of ‘no SB’ and ‘yes SB’ in the respective patients’ groups.

sites participated in the study, and SB usage rate by these sites varied widely, ranging between 3.9 and 98.3% of CPR attempts. Table 1 summarizes the main demographic and the arrest variables in relation to SB use. SB was administered in 53.6% of the resuscitations. The pattern of SB use was similar in the Standard and High Dose Epinephrine groups. More patients with ‘cardiac’ origin of arrest received SB compared to patients with ‘pulmonary’ cause of arrest (56.7 vs. 43.4%, respectively) (P B/0.01 by x2). Cardiac arrests of 87.3% occurred out-of-hospital, 10.6% occurred in-hospital (including emergency department) and 2% occurred in ‘other’ locations, mainly in the presence of teams capable of providing ACLS (such as mobile ICU’s) (Table 2). Although the duration of unattended cardiac arrest and time intervals to ACLS, to establishing an IV line and to administration of the first epinephrine dose were approximately 3 times longer for out-of-hospital compared to in-hospital arrests, SB was used in similar proportions of CPR attempts (53.4 vs. 55.5% respectively, P /NS by x2) (Table 2). However, time intervals to administration of SB were approximately half as long for in-hospital CPR attempts, and a significantly higher proportion of patients undergoing in-hospital CPR received more

than one dose of SB compared to patients undergoing out-of-hospital CPR (P B/0.001 by x2). There was a significant inverse relationship between patients’ age and the SB usage rate (Fig. 1, lower panel): the younger the patient the higher the likelihood of SB administration (P B/0.001 by x2 and P B/0.02 by linear trends in proportions). Also, an inverse relationship was found between the patients’ age and CPR duration (Fig. 1, middle panel): 71.4% of patients younger than 65 compared to only 64.9% of patients older than 66 Table 2 Cardiac arrest and CPR time intervals and SB usage according to location of cardiac arrest

n (% of all patients) Mean time intervals (min) Arrest time Time to ACLS Time from arrest to IV Time from arrest to 1st Epi Time from arrest to 1st SB Time from ACLS to 1st SB Time from 1st Epi to 1st SB

Out of hospital

In hospital

2533 (87.3)

308 (10.6)

7.2 (6.9 /7.6) 11.4 (11 /11.8) 18.1 (17.6 /18.7) 20.4 (19.9 /20.9) 31.3 (30.4 /32.2) 20.3 (19.5 /21.0) 11.4 (10.7 /12.1)

2.3 (1.7 /3.0) 2.5 (1.9 /3.1) 6.4 (4.8 /8.0) 7.2 (6.5 /8.0) 13.2 (11.8 /14.6) 11 (9.7 /12.3) 6.7 (5.5 /8.0)

Data presented as mean (95% CI). ACLS, advanced cardiac life support; IV, intravenous line; Epi, Study epinephrine; SB, sodium bicarbonate.

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Fig. 1. Patients age and SB usage during CPR. Lower panel: Patients’ age and SB usage rates (presented as percentage of patients who received no SB, 1 dose of SB and /1 dose of SB). Middle panel: Patients’ age and the duration of CPR (presented as percentage of patients who underwent CPR for B/20 min, for 21 /40 min and for / 40 min). Upper panel: Patients’ age and the timing of SB administration following the first epinephrine (Epi) dose (presented as percentage of patients who received the first SB dose 1 /5, 6 /10, 11 /15, 16 /20 and over 20 min after the first epinephrine dose). *P B/0.001 by x2, # P B/0.02 by linear trends in proportions.

underwent CPR for longer than 30 min (P B/0.001 by x2). Interestingly, no correlation was found between the patients’ age and the timing of SB administration following the first epinephrine dose (Fig. 1, upper panel). Thus, although younger patients underwent longer CPR attempts and received more SB, they did not receive it earlier compared to older patients. 3.1. Arrest and cardiopulmonary resuscitation time variables and the use of sodium bicarbonate Mean9/SD [median] time intervals from collapse, from start of ACLS and from the administration of the first epinephrine dose to the administration of the first dose of SB, for both out-of-hospital and in-hospital

Fig. 2. The rate of SB use by time intervals from collapse to BLS (Arrest time) (lower panel) and to ACLS (middle panel) and by duration of resuscitation efforts (CPR time) (upper panel). With arrest time and time to ACLS longer than 12 min, even fewer patients received SB compared to those with shorter arrest times (*P B/0.001 by x2). #P B/0.02 by linear trends in proportions.

cardiac arrests, were 299/16.4 [27] 199/13 [17] and 10.89/11.1 [8] min, respectively. The rate of SB use was independent of the time intervals from collapse to BLS or to ACLS (Fig. 2, lower and middle panels). On the other hand, a direct linear correlation was found between the rate of SB use and the duration of CPR (Fig. 2, upper panel): with increasing CPR duration, more SB was used (P B/ 0.001 by x2 and P B/0.02 by linear trends in proportions). The rate of patients receiving more than one dose of SB increased sharply with CPR times longer than 20 min (P B/0.01 by x2 compared to CPR time B/20 min). Similarly, the rate of SB use increased in parallel to the number of epinephrine doses administered during

G. Bar-Joseph et al. / Resuscitation 54 (2002) 47 /55

CPR */reflecting another ‘marker’ of the duration of CPR efforts (Table 1). Out of 2915 patients 853 included in the study (29.3%) achieved ROSC. The same correlations between SB usage rates and times to BLS and to ACLS and CPR duration were found to be statistically significant for the general patient population, for patients who have achieved ROSC and for those who have failed resuscitation attempts (Table 3).

4. Discussion The objective of our analysis was to examine the pattern and timing of SB administration during CPR. Regardless of whether SB therapy during CPR is beneficial or not, we wanted to examine whether it was administered in agreement with the clinical logic behind its ‘instructions for use’. How the rather vaguely defined major indication for SB in CPR, namely ‘long resuscitative efforts’, was actually executed in the field? Our analysis of the large BRCT III database, which included ten American and six European study centers, is more representative of the ‘worldwide’ practice than any of the previously published studies, which were of relatively small scale and involved only a single hospital or emergency medical system. Our study provides, for the first time, data on the actual timing of SB administration along the timeline of CPR in both out-of and in-hospital resuscitation attempts.

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Although this study analyzed the database of BRCT III, which recruited patients from 1990 through 1992, and SB was used according to the then valid ACLS Guidelines [3], we believe that our findings are relevant to current SB usage practices as well. Obviously, neither the recommendations regarding SB use nor the ‘atmosphere’ surrounding the discussion of buffer therapy have basically changed in the 1992 and 2000 versions of the ACLS Guidelines [7,9]. The overall rate of SB usage among the BRCT III patient population was 54.5%, and similar usage rates were found in out-of-hospital and in in-hospital CPR’s. SB usage rates, as reported in the literature, vary widely and seem to decrease in recent years. Almost 85% of patients undergoing CPR in a tertiary-care American hospital in the early 80s received SB, which was the most frequently administered medication [22]. Aufderheide et al. found a 79.9% bicarbonate usage rate among initially resuscitated patients in a single emergency medical service during 1982 /1984 [19]. In contrast, only 40% of patients undergoing CPR in an academic hospital in Canada during 1993/1995 received SB [17]. Levy et al. audited SB usage for CPR in a single district hospital in England, and found that it decreased progressively from 1986 to no use at all by 1991 [16]. The BRCT III study was performed in this same time period. SB usage rate by the various study centers ranged widely, varying between 3.9 and 98.3% of CPR attempts [23]. The 1986 AHA Guidelines, which marked the major shift in the attitude towards SB therapy in CPR, and

Table 3 SB usage according to cardiac arrest and CPR time intervals for patients who achieved return of spontaneous circulation and for those who have not Patients achieving ROSC (Total n 853)

Patients not achieving ROSC (Total n 2062)

SB usage rate (% of n )

SB usage rate (% of n )

na

No SB

1 dose SB

 1 dose SB

Arrest time 1 /4 min 5 /8 min 9 /12 min  12 min

477 150 94 64

51.8 60.7 54.3 73.4

36.7 29.3 36.2 20.3

11.5 10.0 9.6 6.3

786 395 280 280

Time to ACLS 1 /4 min 5 /8 min 9 /12 min  12 min

289 188 160 148

53.6 59.6 50.6 59.5

36.3 27.7 38.1 32.4

10.0 12.8 11.3 8.1

CPR time 1 /5 min 6 /10 min 11 /15 min 16 /20 min  20 min

43 94 120 130 461

74.4 67.0 61.7 62.3 48.6

25.6 29.8 32.5 35.4 35.4

0.0 3.2 5.8 2.3 16.1

55.9

33.8

10.3

All patients

na

No SB

1 dose SB

 1 dose SB

41.7 38.0 43.2 49.6

37.7 47.3 35.7 40.0

20.6 14.7 21.1 10.4

406 405 401 529

43.8 37.3 39.9 47.1

34.0 43.5 40.4 41.4

22.2 19.3 19.7 11.5

1 8 17 71 1944

100.0 87.5 70.6 46.5 41.9

0.0 12.5 23.5 42.3 40.3

0.0 0.0 5.9 11.3 17.8

42.5

40.1

17.4

ROSC, return of spontaneous circulation; ACLS, advanced cardiac life support; SB, sodium bicarbonate. a n does not sum up to total n due to missing data.

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which were valid at the time of the BRCT III, recommended that SB ‘should be used, if at all, only after more proved interventions such as defibrillation, cardiac compression. . .intubation and pharmacologic therapies such as epinephrine and antiarrhythmics have been employed’ [3]. It was estimated that these interventions are usually accomplished during the first 10 min of the routine cardiac arrest sequence [3]. The 1992 and 2000 ACLS Guidelines remain rather vague regarding the timing of SB administration, stating that ‘after prolonged arrest or long resuscitative efforts, bicarbonate possibly benefits the patient’ [7,9]. According to our analysis, in the out-of-hospital arrests a mean of 9 min have elapsed from initiation of ACLS to administration of the first epinephrine. Thus, the above mentioned time estimate was accurate. However, SB was administered over 11 min after the administration of the first epinephrine dose, 20 min after the initiation of ACLS and more than 30 min after collapse. The long time intervals to administration of SB should be related to the development rate of metabolic acidosis in the setting of cardiac arrest and CPR: in experimental animals, serum base deficit increases by 1.1 /1.5 mEq/l for every minute of circulatory arrest [24 /26]. Arterial lactate increases by almost 0.3 mmol/l for every minute of cardiac arrest and CPR when epinephrine is used [24,27], and by almost 0.6 mmol/l when epinephrine is not used [27]. The time from collapse to administration of the first epinephrine dose */considered the earliest point beyond which buffer may be administered */was 17 /21 min in the BRCT III [20] and in other large clinical trials [28,29]. Obviously, at this time point profound metabolic acidosis already exists, and we cannot see any ‘physiologic’ sense in delaying SB administration by another 11 min. In all probability, if SB is to be effective in promoting return of spontaneous circulation, it should be administered earlier in the course of CPR. We found that younger patients received SB more frequently during CPR. This could have been related to CPR duration, i.e. the younger the patient the longer the resuscitative effort and more SB would be administered. Another possible explanation could have been an earlier */and therefore a more frequent */use of SB in younger patients, reflecting a desire to give these patients ‘a better chance’. We therefore analyzed the relationships of age, duration of CPR and the timing of SB administration (Fig. 1). We found a striking inverse relationship between patients’ age and CPR duration in ‘failed’ CPR’s but could not find any correlation between patients’ age and the timing of SB administration. Thus, younger patients received more SB probably as a consequence of longer CPR efforts. A rather disturbing finding of our analysis was that pre-BLS or ACLS intervals did not influence the decision to use SB and when to administer it. This

suggests that rescue teams either did not inquire about the duration of the arrest prior to their arrival at the scene, or that they disregarded this information when considering SB administration. Again, these findings seem to contrast with both physiological rationale and the intent of the Guidelines which recommend (with reservations) SB after ‘prolonged arrest’ [3,7,9]. Similarly, Aufderheide found that there were no differences in response times in resuscitation attempts of patients who received SB and in those who did not [19]. We could not find in the literature any further information regarding the association between downtimes and the use of SB. On the other hand, we found a direct correlation between SB usage rate and ACLS time. This suggests that rescue teams ‘started the clock’ as they initiated ACLS, and their decision to administer SB was then guided by both physiology and by AHA Guidelines. They seemed to set their clock, however, to a wrong zero time. Not surprisingly, the time intervals to initiation of ACLS and to completion of the initial resuscitation steps, including times to intubation, to starting an IV line and to administration of epinephrine, were three to four times shorter in in-hospital arrests compared to out-of-hospital arrests. Despite these much shorter hypoxia times, the rates of SB usage were identical in these two settings. In the in-hospital resuscitations, SB was administered 13.2 min from arrest and 11 min from initiation of ACLS, compared to 31.3 and 20.3 min, respectively, in out-of-hospital resuscitations. This seems to be another indicator that decisions regarding SB administration were often not based on firm clinical considerations. Cline et al. [30] also found that SB administration was the most common ‘pharmacologic’ deviation from AHA ACLS Guidelines. In the current study we did not intend to analyze the effects of SB administration on CPR outcome. We have shown a direct correlation between SB usage rates and the duration of CPR, and this creates a correlation between SB usage rates and CPR outcome. All published clinical analyses of SB therapy in CPR were retrospective and SB administration was not controlled [13 /15,17 /19,31]. Their results were inconclusive since patients who had undergone longer resuscitative efforts, obviously encountered longer ischemia times and had therefore worse outcome, also received more SB. According to the nature of this kind of retrospective analysis, SB usage becomes basically an epiphenomenon of the duration of CPR and its effect on outcome should be interpreted accordingly [10,13,15,17]. In summary, contrary to physiological rationale, clinical decisions regarding the use of SB during CPR did not seem to take into consideration the duration of pre-ACLS hypoxia times. When used, the time to administration of the first SB dose is very long and

G. Bar-Joseph et al. / Resuscitation 54 (2002) 47 /55

severe metabolic acidosis probably exists much earlier. We propose that ACLS algorithms and ACLS training should emphasize the importance of obtaining information about insult times and the incorporation of this information into the decision on SB administration. For out-of-hospital cardiac arrests, with long time intervals to administration of the first epinephrine, a further delay in the administration of SB may be unwarranted. Further research is required to clarify the role of SB */and possibly of other buffers */in the pharmacologic armamentarium of CPR. In light of the still very poor outcome of ‘modern’ CPR, the results of such inquiry may be rewarding.

Acknowledgements Supported, in part, by NIH (NINDS) Grant # NS 15295.

Appendix A: Brain Resuscitation Clinical Trial III Investigators Steering Committee: Norman S. Abramson, MD (Principal Investigator), Mary T. Craig, RN, BSN (Study Coordinator), Katherine M. Detre, MD, Dr PH (Co-Principal Investigator), Sheryl F. Kelsey, PhD, Oscar Reinmuth, MD, Peter Safar, MD (Co-Principal Investigator), Kim Sutton-Tyrrell, RN, Dr PH, Samuel A. Tisherman, MD, E. Murat Tuzcu, MD.Investigators: Paul Pepe, MD, Brian Zachariah, MD and Vicki Ginger, RN, MSN (Baylor College of Medicine, Houston, TX); Gad Bar-Joseph, MD (Rambam Medical Center, Haifa, Israel); Robert Woolard, MD and Donna Cimini, RN, BS (Rhode Island Hospital, Providence, RI); Bogdan Kaminski, MD, PhD, Wojtek Figiel, MD and Marek Graczynski, MD (Warsaw Medical Academy, Warsaw, Poland); Jay S. Steingrub, MD and Laura Luicci, RN (Baystate Medical Center, Springfield, MA); Kurt R. Duffens, MD (Tualatin Valley Fire and Rescue, Aloha, OR); Keith Bradley, MD (Norwalk Hospital, Norwalk, CT); Michael Jastremski, MD, Leo Rotello, MD and Anne Milewski, RN (Health Sciences Center at Syracuse, Syracuse, NY); Richard T. Davis1, MD, Gary Septon, MD and Katherine Davis, RN, MSN (Lutheran Health Care Network, Tempe, AZ); Darell E. Heiselman, DO and Robin Vidovich, RN (Akron General Medical Center, Akron, OH); Keith T. Ghezzi, MD and Sandra Sanford, RN (The George Washington University Medical Center, Washington, DC); Ulf Hedstrand, MD, PhD and Hans Stjernstrom, MD, PhD (University of Uppsala, Uppsala, Sweden); 1

Died during BRCT III.

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William H. Spivey, MD1, John Schoffstall, MD and Janice Mazur, RN (Medical College of Pennsylvania, Philadelphia, PA); Erga L. Cerchiari, MD (Ospedale Niguarda */Ca’ Granda, Milano, Italy); Hendrik W. Gervais, MD (Johannes Gutenberg University, Mainz, Germany); Per Vaagenes, MD, PhD (Akershus Central Hospital, Oslo, Norway).

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[19] Aufderheide T.P., Martin D.R., Olson D.W., et al. Prehospital bicarbonate use in cardiac arrest: a 3-year experience. Am J Emerg Med 1992;10:4 /7. [20] BRCT III Study Group, Abramson N.S., Safar P., Sutton-Tyrrell K., Craig M.T.. A randomized clinical trial of escalating doses of high dose epinephrine during cardiac resuscitation. Crit Care Med 1995;23:A178. [21] Cummins R.O., Chamberlain D.A., Abramson N.S., et al. Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein style. Ann Emerg Med 1991;20:861 /74. [22] Batenhorst R.L., Clifton G.D., Booth D.C., Hendrickson N.M., Ryberg M.L.. Evaluation of 516 cardiopulmonary resuscitation attempts. Am J Hosp Pharm 1985;42:2478 /83. [23] Brain Resuscitation Clinical Trial III Study Group, Bar-Joseph G., Abramson A., Jansen-McWilliams L., Sutton-Tyrrell K., Craig M.T., Safar P.. Differences in the pattern of sodium bicarbonate use during cardiopulmonary resuscitation among study sites in a large clinical trial and its possible effect on outcome. Crit Care Med 1997;25(Suppl 1):A51. [24] Bar-Joseph G., Weinberger T., Castel T., et al. Comparison of sodium bicarbonate, Carbicarb and THAM during cardiopulmonary resuscitation in dogs. Crit Care Med 1998;26:1397 /408.

[25] Angelos M.G., DeBehnke D.J.. Epinephrine-mediated changes in carbon dioxide tension during reperfusion of ventricular fibrillation in a canine model. Crit Care Med 1995;23:925 /30. [26] Capparelli E.V., Chow M.S.S., Kluger J., Fieldman A.. Differences in systemic and myocardial acid /base status during cardiopulmonary resuscitation. Crit Care Med 1989;17:442 /6. [27] Carden D.L., Martin G.B., Nowak R.M., Foreback C.C., Tomlanovich M.C.. Lactic acidosis during closed-chest CPR in dogs. Ann Emerg Med 1987;16:1317 /20. [28] Brown C.G., Martin D.R., Pepe P.E., et al. A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. N Engl J Med 1992;327:1051 /5. [29] Gueugniaud P.Y., Mols P., Goldstein P., et al. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. N Engl J Med 1998;339:1561 /95. [30] Cline D.M., Welch K.J., Cline L.S., Brown C.K.. Physician compliance with advanced cardiac life support guidelines. Ann Emerg Med 1995;25:52 /7. [31] Bishop R.L., Weisfeldt M.L.. Sodium bicarbonate administration during cardiac arrest: effect on arterial pH, pCO2 and osmolarity. J Am Med Assoc 1976;235:506 /9.

Portuguese Abstract and Keywords Este estudo analiza de forma retrospectiva o padra˜o da utilizac¸a˜o do bicarbonato de so´dio (BS) durante a Reanimac¸a˜o cardiopulmonar (RCP) no Estudo Brain Resuscitation Clinical Trial III (BRCT III). BRCT III foi um estudo clı´nico retrospectivo que comparou altas doses de epinefrina com as doses standard durante a RCP. A utilizac¸a˜o do BS foi deixada como opcional no protocolo do estudo. Foram revistos os registos de 2915 pacientes. A percentagem, o momento da administrac¸a˜o e a dose de BS administrados foram correlacionados com varia´veis demogra´ficas e da paragem cardı´aca e com tempos do colapso ate´ inı´cio de suporte ba´sico de vida, Suporte Avanc¸ado de Vida (SAV) e de intervenc¸o˜es major realizadas durante a RCP. O BS foi administrado em 54.5% das reanimac¸o˜es. A taxa de utilizac¸a˜o de BS diminuiu com o aumento da idade dos doentes - reflectindo prima´riamente tentativas de RCP mais curtas. Os intervalos de tempo me´dio entre paragem, inı´cio de SAV, administrac¸a˜o da primeira epinefrina ate´ a` administrac¸a˜o do primeiro BS foram respectivamente de 299/16, 199/13, e 10.89/11.1 min. Na˜o se encontrou qualquer correlac¸a˜o entre a taxa de utilizac¸a˜o de BS e o tempo de hipo´xia antes do SAV. Por outro lado identificou-se uma correlac¸a˜o linear directa entre a taxa de utilizac¸a˜o de BS e a durac¸a˜o de SAV. Concluı´mos que quando foi utilizado o BS, o tempo desde o inı´cio de SAV ate´ a` administrac¸a˜o da primeira dose foi longo e nesta altura ja´ existira´ provavelmente acidose metabo´lica grave. Portanto, quando se decide utilizar BS, deve-se fazeˆ-lo precocemente. Ao contra´rio do que seria lo´gico as deciso˜es clı´nicas relativas a´ utilizac¸a˜o do BS na˜o pareciam ter em considerac¸a˜o a durac¸a˜o de hipo´xia pre´-SAV. Sugerimos que as recomendac¸o˜es para a utilizac¸a˜o de BS durante a RCP devem acentuar a importaˆncia do tempo de hipo´xia pre-SAV na sua contribuic¸a˜o para a acidose metabo´lica e devem ser mais especı´ficos na defenic¸a˜o da durac¸a˜o de ‘‘ Esforc¸o de reanimac¸a˜o longo ou RCP prolongada’’, a indicac¸a˜o mais frequente para a administrac¸a˜o de BS. Palavras chave : Acido-base; Acidose; Bicarbonato de Sodio; Terapeˆutica tampa˜o; Paragem cardı´aca; Reanimac¸a˜o Cardiopulmonar; SAV

Spanish Abstract and Keywords Este estudio analizo´ retrospectivamente el patro´n de uso de bicarbonato (SB) durante la resucitacio´n cardiopulmonar (RCP) en el ensayo clı´nico de resucitacio´n cerebral III (BRCT III). El BRCT III fue un estudio clı´nico prospectivo, que comparaba adrenalina a altas dosis con dosis esta´ndar durante la RCP. En este protocolo de estudio, se dejo opcional el uso de SB. Se revisaron los registros de 2915 pacientes. Se correlacionaron porcentaje, tiempo, y dosis de SB administrado con variables demogra´ficas y del paro cardı´aco y con tiempos de colapso a soporte vital ba´sico, a soporte vital avanzado (ACLS) y a las intervenciones mayores realizadas durante la RCP. Se administro´ SB en el 54,5% de las resucitaciones. La tasa de uso de SB decrecio´ con la edad del pacientereflejando primariamente intentos de resucitacio´n mas cortos. Los promedios de intervalos de tiempo desde el paro, desde el inicio de ACLS y desde la primera epinefrina hasta la primera administracio´n de SB fueron 299/16, 199/13, y 109/11.1 min. Respectivamente. No se encontro´ correlacio´n entre la tasa de uso de SB y los tiempos de hipoxia pre-ACLS. Por otro lado, se encontro´ correlacio´n lineal directa entre la tasa de uso de SB y la duracio´n del ACLS. Concluimos que cuando se uso´ SB, el tiempo desde el inicio de ACLS hasta la primera dosis fue largo y probablemente ya existı´a acidosis metabo´lica en este punto. Por ello, si se usa SB, puede considerarse su uso tempranamente. Contrario a las razones fisiolo´gicas, las decisiones clı´nicas respecto al uso de SB no parecen haber considerado la duracio´n de la hipoxia pre-ACLS. Sugerimos que las guı´as para el uso de SB durante RCP deberı´an

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enfatizar la importancia de el tiempo de hipoxia pre-ACLS que contribuye a la acidosis metabo´lica y deberı´an ser mas especı´ficas en la definicio´n de la duracio´n de ‘RCP prolongada o largos esfuerzos de resucitacion’, la mas frecuente indicacio´n de administracio´n de SB. Palabras clave : Acido-base; Acidosis; Bicarbonato; Bicarbonato de sodio; Terapia buffer; Paro cardı´aco; Reanimacio´n cardiopulmonar; Soporte vital avanzado.