• Users Online: 364
  • Print this page
  • Email this page


 
 
Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 21  |  Issue : 1  |  Page : 24-29

Efficacy of bicarbonate therapy for adults with cardiac arrest: A systematic review and meta-analysis of randomized-controlled trials


Department of Emergency Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

Date of Submission01-Jul-2020
Date of Decision09-Aug-2020
Date of Acceptance04-Sep-2020
Date of Web Publication01-Dec-2020

Correspondence Address:
Dr. Wachira Wongtanasarasin
Department of Emergency Medicine, Faculty of Medicine, Chiang Mai University, 110 Intavarorot Street, Sriphum, Chiang Mai 50200
Thailand
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2452-2473.301917

Rights and Permissions
  Abstract 


OBJECTIVES: Because the benefits of bicarbonate therapy remain unclear, it is not routinely recommended for the cardiopulmonary resuscitation (CPR) given to individuals with cardiac arrest (CA). This study aims to evaluate the clinical benefits of bicarbonate therapy in adults with CA.
METHODS: Without any language restriction, we searched PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL from the inception until April 30, 2020. We performed hand-search to identify the relevant trials included in previous meta-analyses. Included studies were randomized controlled trials (RCTs) comparing bicarbonate and placebo treatment in adults with CA. Two authors independently assessed the trial risk of bias. The primary outcome was the survival to hospital admission. The secondary outcomes included the return of spontaneous circulation, the survival to hospital discharge, and the neurological outcome at discharge. We calculated the odds ratios of those outcomes using the Mantel-Haenszel model and assessed the heterogeneity using the I2 statistic.
RESULTS: Our searches found 649 unduplicated studies. Of these, three RCTs involving 1344 patients were included in the meta-analysis. The trial risk of bias ranged between fair and poor, mainly due to no blindness of outcome assessment and the selective reports of outcomes. Bicarbonate therapy showed no significant improvement in the survival to hospital admission (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.73–1.25). Subgroup analysis in those receiving prolonged CPR showed a similar result (OR 0.88; 95% CI 0.10–8.01). No study reported the predefined secondary outcomes.
CONCLUSION: For both acute and prolonged CPR, bicarbonate therapy might not show benefit to improve the rate of survival to hospital admission in adults with cardiac arrest.

Keywords: Bicarbonate, cardiac arrest, meta-analysis, survival, systematic review


How to cite this article:
Wongtanasarasin W, Srisurapanont K. Efficacy of bicarbonate therapy for adults with cardiac arrest: A systematic review and meta-analysis of randomized-controlled trials. Turk J Emerg Med 2021;21:24-9

How to cite this URL:
Wongtanasarasin W, Srisurapanont K. Efficacy of bicarbonate therapy for adults with cardiac arrest: A systematic review and meta-analysis of randomized-controlled trials. Turk J Emerg Med [serial online] 2021 [cited 2021 Dec 8];21:24-9. Available from: https://www.turkjemergmed.org/text.asp?2021/21/1/24/306273




  Introduction Top


Cardiac arrest (CA) is a common health problem that needs a life-saving intervention of cardiopulmonary resuscitation (CPR). CA also remains one of the most serious health conditions. Each year, CA claims around 3.7 million lives across the world.[1] In the United States, the annual incidence of CA ranged between 180,000 and 450,000 times, which accounts for 7%–18% of all deaths.[2] CPR is a complicated procedure with an effort to restart the cardiac function and restore normal circulation. Standard CPR involves both basic life support and advanced cardiac life support (ACLS).



Bicarbonate therapy for CA remains controversial. According to the latest standard guideline for managing CA,[3] ACLS consists of defibrillation for a shockable cardiac rhythm and medication administration if indicated. Three medications recommended in the latest guideline of CA include adrenaline (epinephrine), amiodarone, and lidocaine.[4] Bicarbonate therapy for CA has been an issue of debate.[5] Two studies showed the positive outcomes with the use of bicarbonate.[6],[7] However, the predominant evidences showed no benefit.[8],[9],[10],[11] Early ACLS guidelines recommended the use of routine bicarbonate administration as part of the algorithm,[12] but recent guidelines, latest in 2018,[4] no longer recommended its use. The debate in the literature is continuing, but at the present moment, bicarbonate administration is only recommended for CA related to hyperkalemia or tricyclic antidepressant overdose (class IIb recommendation, level of evidence C).[13]

Thus, this study aimed to perform an up-to-date systematic review and meta-analysis to determine the efficacy of bicarbonate therapy for adults with CA.


  Methods Top


This manuscript was prepared based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for systematic reviews.[14] Two authors (WW/KS) independently conducted a comprehensive search on multiple bibliographic databases, including PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL. The searches covered the periods since their inceptions until April 30, 2020. No language restriction was applied. The Medical Subject Headings terms included a combination of search terms with various spelling and endings: “bicarbonate,” “sodium bicarbonate,” “lithium bicarbonate,” “cardiac arrest,” “heart arrest,” “cardiopulmonary arrest,” “cardiopulmonary resuscitation,” “sudden death,” and “sudden collapse”. The references of all relevant meta-analyses were further screened to identify the additional trials. The regulatory website “clinicaltrials.gov” was also searched to identify any unpublished trial. Our review was prospectively registered with PROSPERO (CRD42020151624).

Eligible criteria and study selection

Included studies were randomized controlled trials (RCTs) comparing bicarbonate and placebo therapy in adults (≥18 years) with CA. Each included trial must report at least one of the following outcomes: Survival to hospital admission, the return of spontaneous circulation, survival to hospital discharge, and neurological outcome at discharge. We did not limit the sites of CA, and both out-of-hospital and in-hospital CA were included. Two authors (WW/KS) independently screened the search results to identify potentially eligible trials, and obviously unrelated articles were excluded. Full manuscripts of the potential trials were subsequently retrieved with eligibility independently assessed by two reviewers (WW/KS) against prespecified criteria and evaluated for inclusion [Figure 1]. At each step of selection, disagreements were discussed and resolved or referred to a third reviewer for the conclusion.
Figure 1: Flow diagram

Click here to view


Outcomes of interest

The primary outcome was the rate of survival to hospital admission. The secondary outcomes of interest were the rate of return of spontaneous circulation, the rate of survival to hospital discharge, and neurological outcome at discharge. Good neurological outcome was defined by the cerebral performance category score of 1–2. There is no universal definition of prolonged CPR, according to the Utstein standard reporting guidelines.[15],[16] To determine the beneficial effects of bicarbonate therapy during prolonged CPR, we performed a subgroup analysis of outcomes reported after 15 min of resuscitation referred to the previously published studies.[9],[17]

Assessment of trial risk of bias

Two assessors (WW/KS) independently evaluated the risk of bias of each trial using the modified version of the Cochrane collaboration's tool for assessing the risk of bias.[18],[19] Three categories of the risks of bias were high, unclear, and low. The areas of bias being assessed included random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias (including intention-to-treat analysis). Any discrepancies arisen were resolved by the third-party consensus.

Data synthesis and statistical analysis

Two authors (WW/KS) independently extracted the data on participant demographics, sample sizes, details of the intervention, protocols used, and reported outcomes using a standardized data collection form. We used the Review Manager version 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) to perform the statistical analysis.[20] We intended to calculate odds ratio (OR) with 95% confidence intervals (CIs) using the Mantel-Haenszel model because we presumed that identified studies were homogeneous. The statistical significance was defined as the P < 0.05. We assessed the heterogeneity of data using I2 statistic. We performed the Egger's test for funnel plot asymmetry to determine the publication bias.


  Results Top


Search strategies

From the PRISMA flow diagram [Figure 1], we retrieved 894 citations from the database as mentioned earlier searches and two relevant studies from hand searches. After removing the duplicates, 649 abstracts remained. Of these, 605 articles were excluded by abstract screening, and 41 articles were excluded after full-text assessment. Finally, only three trials were included in the meta-analysis.[8],[9],[21]

Characteristics and risk of bias of the included trials

The meta-analysis consisted of 1344 participants. All included trials were performed in high-income countries, one from South Korea, one from the United States, and the other from Norway [Table 1]. Participants' mean age was above 60 years old. About half of the CA s were witnessed, but the bystander CPR varies among the trials. The included studies were assessed using the Cochrane Risk of Bias Tool for RCTs.[18] Two and one trials had fair and poor risk of bias, respectively [Figure 2].
Table 1: Characteristics of included trials

Click here to view
Figure 2: Risk of bias summary

Click here to view


Survival to hospital admission of the whole cohort

Based on the homogenous data, the pooled ORs showed no significant improvement on the survival to hospital admission (OR = 0.96, 95% CI = 0.73–1.25, I2 = 0%) [Figure 3]. Moreover, due to limited number of included trials, the Egger's test could not be analyzed.
Figure 3: Forest plot comparing the odd ratios of survival to hospital admission between bicarbonate and placebo therapy in the whole cohort

Click here to view


Survival to hospital admission after prolonged cardiopulmonary resuscitation

We performed a subgroup analysis of two studies reporting the outcome of prolonged CPR. The heterogeneous data showed no significant improvement of survival to hospital admission (OR = 0.88, 95% CI = 0.10–8.01, I2 = 71%) [Figure 4].
Figure 4: Forest plot comparing the odd ratios of survival to hospital admission between bicarbonate and placebo therapy in participants receiving prolonged cardiopulmonary resuscitation

Click here to view



  Discussion Top


Based on the consistent outcomes obtained from three RCTs, bicarbonate therapy for adults with CA cannot improve the survival to hospital admission. The therapy also gives no benefit for those receiving prolonged CPR. The 2019 Utstein-style reporting templates were not applied,[15],[16] which results in no report of other important outcomes after CPR, including the rates of return of spontaneous circulation, survival to hospital discharge, and neurological outcome at discharge. Moreover, qualities of the included studies were slightly low which resulted in inconcludable results.

To our knowledge, this is the first systematic review and meta-analysis of RCTs assessing the benefits of bicarbonate therapy for adults with CA. Bicarbonate therapy was routinely administered during the CPR taken place in the 1980s. However, this practice has been less common due to several reports of no beneficial effects and some unintentional harmful effects.[8],[10],[22],[23],[24],[25] A previous literature review in this topic published in 2016 included a total of 16 studies. However, most of them were retrospective and observational studies. That review concluded that bicarbonate therapy demonstrated little benefit and might harm the patients.[5] The latest ACLS guidelines do not recommend the routine administration of bicarbonates.[4] However, this following guideline still mentions the use of bicarbonates for correcting the metabolic acidosis, which is a reversible cause of CA. Because of the unclear indication of bicarbonate, some researchers tried to propose the availability of using bicarbonate or an appropriate indication for bicarbonate during resuscitation both in animal and human studies.[26],[27],[28],[29],[30]

Bicarbonate therapy for adults with CA receiving prolonged CPR has been controversial. Vukmir et al. found that bicarbonate therapy during prolonged CPR improved the rate of survival to hospital admission (OR = 2.17,P= 0.007).[9] However, after synthesizing these data with those obtained from another study,[21] such benefit could not be found.

Limitations

There were several limitations to this study. First, its sample size was small (n = 1344). Although there have been many retrospective and observational studies in this area, our meta-analysis focused only on the RCTs, which have a superior study design for minimizing the risk of bias especially in the therapeutic study. For this reason, only three trials could match with our inclusion criteria. In addition, two of three studies in the analysis have data collection periods that are very dated (Dybvik: 1987-1994; Vukmir: 1994-1998). The treatment protocols and emergency medical service systems in place at that time are quite contradictory to current guidelines. Second, the included trials did not report many outcomes recommended by the Utstein standard reporting guidelines. Some key outcomes of CPR were not available, including the rates of return of spontaneous circulation, survival to hospital discharge, and neurological outcome at discharge. Finally, the included trials applied different protocols of intervention (study participants, types of CA, and doses and times of administration). Therefore, no specific protocol of intervention can be recommended during bicarbonate administration. Despite these differences, we tried to separate and report as early and late administration which was already discussed.


  Conclusion Top


For both acute and prolonged CPR, bicarbonate therapy might not show benefit to improve the rate of survival to hospital admission in adults with CA. Future trials should be carried out in larger sample sizes and include all outcomes recommended by the Utstein standard reporting guidelines.

Acknowledgment

We gratefully acknowledge Prof. Manit Srisurapanont for his comment on the drafted manuscript.

Author contributions statement

W.W. and K.S. conceived and contributed to the design and implementation of the research. W.W. processed the data, interpreted the results, drafted the manuscript, and designed the figures. K.S. performed the analysis. All authors discussed the results and commented on the manuscript.

Conflicts of interest

None declared.

Funding

None declared.

Ethical Consent

Not applicable



 
  References Top

1.
Kudenchuk PJ, Sandroni C, Drinhaus HR, Böttiger BW, Cariou A, Sunde K, et al. Breakthrough in cardiac arrest: Reports from the 4th Paris International Conference. Ann Intensive Care 2015;5:22.  Back to cited text no. 1
    
2.
Stecker EC, Reinier K, Marijon E, Narayanan K, Teodorescu C, Uy-Evanado A, et al. Public health burden of sudden cardiac death in the United States. Circ Arrhythm Electrophysiol 2014;7:212-7.  Back to cited text no. 2
    
3.
Duff PJ, Panchal AR, Hazinski MF. Highlights of the 2018 Focused Updates to the American Heart Association Guidelines for CPR and ECC: Advanced Cardiovascular Life Support and Pediatric Advanced Life Support. American Heart Association. Available from: https://eccguidelines.heart.org/wp-content/uploads/2018/10/2018-Focused-Updates_Highlights.pdf. Published 2018. [Last Accessed on 2020 Apr 30].  Back to cited text no. 3
    
4.
Panchal AR, Berg KM, Kudenchuk PJ, Del Rios M, Hirsch KG, Link MS, et al. American heart association focused update on advanced cardiovascular life support use of antiarrhythmic drugs during and immediately after cardiac arrest: An update to the American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2018;138:e740-9.  Back to cited text no. 4
    
5.
Velissaris D, Karamouzos V, Pierrakos C, Koniari I, Apostolopoulou C, Karanikolas M. Use of sodium bicarbonate in cardiac arrest: Current guidelines and literature review. J Clin Med Res 2016;8:277-83.  Back to cited text no. 5
    
6.
Bar-Joseph G, Abramson NS, Kelsey SF, Mashiach T, Craig MT, Safar P, et al. Improved resuscitation outcome in emergency medical systems with increased usage of sodium bicarbonate during cardiopulmonary resuscitation. Acta Anaesthesiol Scand 2005;49:6-15.  Back to cited text no. 6
    
7.
Douglas Weaver W, Fahrenbruch CE, Johnson DD, Hallstrom AP, Cobb LA, Copass MK. Effect of epinephrine and lidocaine therapy on outcome after cardiac arrest due to ventricular fibrillation. Circulation 1990;82:2027-34. Available form: https://www2.scopus.com/inward/record.uri?eid=2-s2.0-0025689894&partnerID=40&md5=85a0851162edc29e443c8971caee5c01. [Last Accessed on 2019 Sep 19].  Back to cited text no. 7
    
8.
Dybvik T, Strand T, Steen PA. Buffer therapy during out-of-hospital cardiopulmonary resuscitation. See comment. Resuscitation 1995;29:89-95. Available from: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-00582924/full. [Last Accessed on 2019 Sep 19].  Back to cited text no. 8
    
9.
Vukmir RB, Katz L, Sodium Bicarbonate Study Group. Sodium bicarbonate improves outcome in prolonged prehospital cardiac arrest. Am J Emerg Med 2006;24:156-61.  Back to cited text no. 9
    
10.
Aufderheide TP, Martin DR, Olson DW, Aprahamian C, Woo JW, Hendley GE, et al. Prehospital bicarbonate use in cardiac arrest: A 3-year experience. Am J Emerg Med 1992;10:4-7.  Back to cited text no. 10
    
11.
van Walraven C, Stiell IG, Wells GA, Hébert PC, Vandemheen K. Do advanced cardiac life support drugs increase resuscitation rates from in-hospital cardiac arrest? The OTAC study group. Ann Emerg Med 1998;32:544-53.  Back to cited text no. 11
    
12.
Batenhorst RL, Clifton GD, Booth DC, Hendrickson NM, Ryberg ML. Evaluation of 516 cardiopulmonary resuscitation attempts. Am J Hosp Pharm 1985;42:2478-83.  Back to cited text no. 12
    
13.
Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al. Part 12: Cardiac arrest in special situations: 2010 American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2010;122:S829-61.  Back to cited text no. 13
    
14.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009;6:e1000097.  Back to cited text no. 14
    
15.
Nolan JP, Berg RA, Andersen LW, Bhanji F, Chan PS, Donnino MW, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the Utstein resuscitation registry template for in-hospital cardiac arrest: A consensus report from a task force of the international liaison committee on resuscitation (American heart association, European resuscitation council, Australian and New Zealand council on resuscitation, heart and stroke foundation of Canada, inter American heart foundation, resuscitation council of southern Africa, resuscitation council of Asia). Circulation 2019;140:e746-57.  Back to cited text no. 15
    
16.
Perkins GD, Jacobs IG, Nadkarni VM, Berg RA, Bhanji F, Biarent D, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: Update of the utstein resuscitation registry templates for out-of-hospital cardiac arrest: A statement for healthcare professionals from a task force of the international liaison committee . Circulation 2015;132:1286-300.  Back to cited text no. 16
    
17.
Vukmir RB, Bircher N, Safar P. Sodium bicarbonate in cardiac arrest: A reappraisal. Am J Emerg Med 1996;14:192-206.  Back to cited text no. 17
    
18.
Higgins JP, Thomas JA, Chandler J, Cumpston M, Li T, Page M, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 6.0. Glasgow, UK: Cochrane; 2019. Available from: www.training.cochrane.org/handbook. [Last Accessed on 2020 Apr 30].  Back to cited text no. 18
    
19.
Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:1-9.  Back to cited text no. 19
    
20.
Review Manager (RevMan) [Computer program]; 2014.  Back to cited text no. 20
    
21.
Ahn S, Kim YJ, Sohn CH, Seo DW, Lim KS, Donnino MW, et al. Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: A double-blind, randomized, placebo-controlled pilot study. J Thorac Dis 2018;10:2295-302.  Back to cited text no. 21
    
22.
Levy RD, Rhoden WE, Shearer K, Varley E, Brooks NH. An audit of drug usage for in-hospital cardiopulmonary resuscitation. Eur Heart J 1992;13:1665-8.  Back to cited text no. 22
    
23.
Stiell IG, Wells GA, Hebert PC, Laupacis A, Weitzman BN. Association of drug therapy with survival in cardiac arrest: Limited role of advanced cardiac life support drugs. Acad Emerg Med 1995;2:264-73.  Back to cited text no. 23
    
24.
Weng YM, Wu SH, Li WC, Kuo CW, Chen SY, Chen JC. The effects of sodium bicarbonate during prolonged cardiopulmonary resuscitation. Am J Emerg Med 2013;31:562-5.  Back to cited text no. 24
    
25.
Roberts D, Landolfo K, Light RB, Dobson K. Early predictors of mortality for hospitalized patients suffering cardiopulmonary arrest. Chest 1990;97:413-9.  Back to cited text no. 25
    
26.
Leong EC, Bendall JC, Boyd AC, Einstein R. Sodium bicarbonate improves the chance of resuscitation after 10 minutes of cardiac arrest in dogs. Resuscitation 2001;51:309-15.  Back to cited text no. 26
    
27.
Bar-Joseph G, Abramson NS, Jansen-McWilliams L, Kelsey SF, Mashiach T, Craig MT, et al. Clinical use of sodium bicarbonate during cardiopulmonary resuscitation–is it used sensibly? Resuscitation 2002;54:47-55.  Back to cited text no. 27
    
28.
Kim J, Kim K, Park J, Jo YH, Lee JH, Hwang JE, et al. Sodium bicarbonate administration during ongoing resuscitation is associated with increased return of spontaneous circulation. Am J Emerg Med 2016;34:225-9.  Back to cited text no. 28
    
29.
Adeva-Andany MM, Fernández-Fernández C, Mouriño-Bayolo D, Castro-Quintela E, Domínguez-Montero A. Sodium bicarbonate therapy in patients with metabolic acidosis. Sci World J 2014;2014:627673.  Back to cited text no. 29
    
30.
Weaver WD, Fahrenbruch CE, Johnson DD, Hallstrom AP, Cobb LA, Copass MK. Effect of epinephrine and lidocaine therapy on outcome after cardiac arrest due to ventricular fibrillation. Circulation 1990;82:2027-34.  Back to cited text no. 30
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed3487    
    Printed12    
    Emailed0    
    PDF Downloaded136    
    Comments [Add]    

Recommend this journal