Conflict of Interest Declaration
The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: none applicable.
The following Task Force members and other authors declared an intellectual conflict of interest, and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest Committee: Mathias J. Holmberg and Asger Granfeldt are both authors on the Bicarbonate For In-Hospital Cardiac Arrest (BIHCA) trial and did not participate in risk of bias assessments for that trial.
CoSTR Citation
Holmberg MJ, Granfeldt A, Soar J, Wittig J, D’Arrigo S, Zelop C, Nolan J on behalf of the International Liaison Committee on Resuscitation Advanced Life Support Task Force. Buffer Agents During Cardiac Arrest, Consensus on Science with Treatment Recommendations [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force, November 1, 2026.
Background
The continuous evidence evaluation process to produce this Consensus on Science with Treatment Recommendations (CoSTR) followed Morley PT, et al. Methodology and conflict of interest management: 2025 International Liaison Committee on Resuscitation Consensus on Science with Treatment Recommendations. Circulation. 2025;152(suppl 1):S23–S33.
This topic was previously addressed by an ILCOR adolopment of Xu et al1, published in the 2025 CoSTR2. New randomized evidence prompted a systematic review (PROSPERO registration CRD420261424225). All evidence identified was considered by the Advanced Life Support Task Force and is described below. Discussion points and highlights of the evidence-to-decision process are also included. All data were considered when formulating the Treatment Recommendations. Data tables and the evidence-to-decision framework are provided as attachments.
Review Citation
Holmberg MJ, Granfeldt A, Soar J, Wittig J, D’Arrigo S, Zelop C, Nolan J on behalf of the International Liaison Committee on Resuscitation Advanced Life Support Task Force. Buffer Agents For Cardiac Arrest. Not submitted for publication. PROSPERO registration CRD420261424225.
PICOST
The PICOST (Population,
Intervention, Comparator, Outcome, Study Designs and Timeframe)
Population: Adults with cardiac arrest in any setting (in-hospital or out-of-hospital).
Intervention: The administration of buffering agents during cardiopulmonary resuscitation.
Comparators: The use of placebo, no buffering agent, or another buffering agent during cardiopulmonary resuscitation.
Outcomes: Return of spontaneous circulation; survival at hospital admission; survival at hospital discharge, 30 days, or subsequent time points; survival with a favorable neurological outcome at hospital discharge, 30 days, or subsequent time points; health-related quality of life (this outcome was evaluated among survivors rather than among all cases).
Study Designs: Randomized controlled trials (RCTs) will be included. Non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies), unpublished studies (conference abstracts, trial protocols), animal studies, case series, and case reports will be excluded. All relevant publications in any language are included as long as there is an English abstract.
Timeframe: All years.
Registration: PROSPERO Registration CRD420261424225.
Consensus on Science
The systematic review identified 696 unique records from PubMed, Embase, and CENTRAL on June 15, 2026, of which 5 full text articles were assessed for eligibility. We identified 4 randomized clinical trials (RCT) investigating the administration of buffering agents during cardiopulmonary resuscitation.3-6
Three trials enrolled patients with out-of-hospital cardiac arrest (Dybvik 1995, Vukmir 2006, and Ahn 2018) and one trial enrolled patients with in-hospital cardiac arrest (Granfeldt 2026).3-6 All trials compared a buffering agent to 0.9% sodium chloride solution. Dybvik et al used Tribonat (a mixture of sodium bicarbonate, trometamol, and phosphate), while the remaining trials used sodium bicarbonate.
Risk of bias was assessed using version 2 of the Cochrane Risk-of-Bias tool for individually randomized parallel-group trials. Risk of bias was assessed for each outcome within a study but was reported at the study level as the highest risk of bias score across all outcomes. In most studies, the risk of bias was the same across all outcomes.
Out-of-hospital cardiac arrest
For the critical outcome of favorable neurological survival at 6 months, we identified very low certainty evidence (downgraded for risk of bias and imprecision) from one RCT5 enrolling 50 patients with out-of-hospital cardiac arrest, in which no patients in either group survived with a favorable neurological outcome (sodium bicarbonate 0/25 [0.0%] vs control 0/25 [0.0%]; effect estimates not estimable).
For the critical outcome of favorable neurological survival at 1 month, we identified very low certainty evidence (downgraded for risk of bias and imprecision) from one RCT5 enrolling 50 patients with out-of-hospital cardiac arrest, which showed no benefit from the administration of sodium bicarbonate when compared with control (intervention 0/25 [0.0%] vs control 1/25 [4.0%]; RR, 0.33 [95% CI, 0.01 to 7.80]; 27 fewer survivors with favorable neurological outcome per 1000 patients [95% CI, 40 fewer to 272 more]).
For the critical outcome of survival to hospital discharge, we identified very low certainty evidence (downgraded for risk of bias, indirectness, and imprecision) from one RCT3 enrolling 502 patients with out-of-hospital cardiac arrest, which showed no benefit from the administration of Tribonat when compared with control (intervention 24/245 [9.8%] vs control 35/257 [13.6%]; RR, 0.72 [95% CI, 0.44 to 1.17]; 38 fewer survivors per 1000 patients [95% CI, 76 fewer to 23 more]).
For the important outcome of short-term survival (combining survival to hospital admission, intensive care unit admission, or emergency department arrival), we identified very low certainty evidence (downgraded for risk of bias, indirectness, and imprecision) from three RCTs3-5 enrolling 1344 patients with out-of-hospital cardiac arrest, which showed no benefit from the administration of buffering agents when compared with control (intervention 146/690 [21.2%] vs control 148/654 [22.6%]; RR, 0.97 [95% CI, 0.80 to 1.18]; 7 fewer survivors per 1000 patients [95% CI, 45 fewer to 41 more]).
For the important outcome of return of spontaneous circulation, we identified very low certainty evidence (downgraded for risk of bias and imprecision) from one RCT5 enrolling 50 patients with out-of-hospital cardiac arrest, which showed no benefit from the administration of sodium bicarbonate when compared with control (intervention 1/25 [4.0%] vs control 4/25 [16.0%]; RR, 0.25 [95% CI, 0.03 to 2.08]; 120 fewer survivors with return of spontaneous circulation per 1000 patients [95% CI, 155 fewer to 173 more]).
In-hospital cardiac arrest
For the critical outcome of favorable neurological survival at 90 days, we identified moderate certainty evidence (downgraded for imprecision) from one RCT6 enrolling 779 patients with in-hospital cardiac arrest, which showed no benefit from the administration of sodium bicarbonate when compared with control (intervention 32/371 [8.6%] vs control 28/407 [6.9%]; RR, 1.17 [95% CI, 0.73 to 1.90]; 12 more survivors with favorable neurological outcome per 1000 patients [95% CI, 19 fewer to 62 more]).
For the critical outcome of favorable neurological survival at 30 days, we identified low certainty evidence (downgraded for imprecision) from one RCT6 enrolling 779 patients with in-hospital cardiac arrest, which showed no benefit from the administration of sodium bicarbonate when compared with control (intervention 30/371 [8.1%] vs control 22/407 [5.4%]; RR, 1.39 [95% CI, 0.82 to 2.34]; 21 more survivors with favorable neurological outcome per 1000 patients [95% CI, 10 fewer to 72 more]).
For the critical outcome of survival to 90 days, we identified moderate certainty evidence (downgraded for imprecision) from one RCT6 enrolling 779 patients with in-hospital cardiac arrest, which showed no benefit from the administration of sodium bicarbonate when compared with control (intervention 39/372 [10.5%] vs control 33/407 [8.1%]; RR, 1.22 [95% CI, 0.79 to 1.88]; 18 more survivors per 1000 patients [95% CI, 17 fewer to 71 more]).
For the critical outcome of survival to 30 days, we identified moderate certainty evidence (downgraded for imprecision) from one RCT6 enrolling 779 patients with in-hospital cardiac arrest, which showed no benefit from the administration of sodium bicarbonate when compared with control (intervention 45/372 [12.1%] vs control 37/407 [9.1%]; RR, 1.25 [95% CI, 0.84 to 1.88]; 23 more survivors per 1000 patients [95% CI, 15 fewer to 80 more]).
For the critical outcome of health-related quality of life at 90 days, we identified low certainty evidence (downgraded for risk of bias and imprecision) from one RCT6 enrolling 779 patients with in-hospital cardiac arrest, which showed no difference in quality of life from the administration of sodium bicarbonate when compared with control among 71 survivors (mean difference 13 points higher on the EQ-5D-5L index based on Danish population data, with index values multiplied by 100 [95% CI, 0 to 26 higher]).
For the critical outcome of health-related quality of life at 30 days, we identified very low certainty evidence (downgraded for risk of bias and imprecision) from one RCT6 enrolling 779 patients with in-hospital cardiac arrest, which showed no difference in quality of life from the administration of sodium bicarbonate when compared with control among 80 survivors (mean difference 5 points higher on the EQ-5D-5L index based on Danish population data, with index values multiplied by 100 [95% CI, 10 lower to 21 higher]).
For the important outcome of return of spontaneous circulation, we identified moderate certainty evidence (downgraded for imprecision) from one RCT6 enrolling 779 patients with in-hospital cardiac arrest, which showed no benefit from the administration of sodium bicarbonate when compared with control (intervention 146/372 [39.2%] vs control 150/407 [36.9%]; RR, 1.05 [95% CI, 0.88 to 1.24]; 18 more survivors with return of spontaneous circulation per 1000 patients [95% CI, 44 fewer to 88 more]).
Subgroup analysis by cardiac arrest setting
Prespecified subgroup analyses comparing out-of-hospital and in-hospital cardiac arrest found no clear evidence of a subgroup difference for favorable neurological survival at 1 month (P value for subgroup difference = 1.00)5,6, survival to hospital discharge or 30 days (P value for subgroup difference = 0.06)3,6, or return of spontaneous circulation (P value for subgroup difference = 0.18)5,6.
Treatment Recommendation
New treatment recommendation (2027)
We suggest against the routine administration of buffering agents for the treatment of out-of-hospital cardiac arrest (weak recommendation, very low certainty of evidence).
We suggest against the routine administration of buffering agents for the treatment of in-hospital cardiac arrest (weak recommendation, low certainty of evidence).
Prior treatment recommendation (2025)
We suggest against the administration of buffering agents such as sodium bicarbonate in the treatment of out-of-hospital cardiac arrest, unless a special circumstance for its use is present (weak recommendation, low certainty of evidence).
We suggest against the administration of buffering agents such as sodium bicarbonate in the treatment of in-hospital cardiac arrest, unless a special circumstance for its use is present (weak recommendation, very low certainty of evidence).
Prior treatment recommendation (2010)
Routine administration of sodium bicarbonate for treatment of in-hospital cardiac arrest and out-of-hospital cardiac arrest is not recommended.
Justification and Evidence to Decision Framework Highlights
In making these recommendations, the ALS Task Force considered the following:
- This CoSTR does not address buffering agents in special circumstances, such as hyperkalemia (PICO ALS 456) or sodium channel blocker or tricyclic antidepressant poisoning (PICO ALS 429).
- The topic was prioritized following publication of a large trial of sodium bicarbonate during in-hospital cardiac arrest6 and because buffering agents remain in frequent use despite guidelines recommending against routine administration7.
- Only randomized trial evidence was considered, since comparative data were available from several trials in both out-of-hospital and in-hospital settings. Observational studies of this topic are at risk of confounding, particularly resuscitation time bias, as buffering agents are often administered late in resuscitation.8
- Data from out-of-hospital and in-hospital cardiac arrest trials were not pooled as the trials differed in aspects other than the setting. Compared to the out-of-hospital trials, a substantially higher proportion of patients in the in-hospital trial had a non-shockable rhythm. Two of the out-of-hospital trials enrolled patients before 19993,4, when resuscitation and post-arrest care differed from current practice, one trial used Tribonat rather than sodium bicarbonate3, and one trial enrolled 50 patients with a median time to drug of 31 minutes5, compared with 8 minutes in the in-hospital trial6.
- The certainty of evidence for out-of-hospital cardiac arrest is lower than in the previous CoSTR, which was based on an adolopment of a systematic review by Xu et al.1,2 The main reasons for these differences are that we assessed imprecision using the confidence interval on the relative scale (very serious for intervals of < 0.50 or > 2.00, serious for intervals of > 0.50 but < 0.90 or > 1.11 but < 2.00, or in relation to the optimal information size for intervals within 0.90 to 1.11) rather than the absolute risk difference, following the approach of a previous ILCOR review9, we downgraded for risk of bias, and we did not combine return of spontaneous circulation with survival to admission, nor favorable neurological outcome at 1 month with all-cause survival to hospital discharge.
- Health-related quality of life was assessed only among survivors in the in-hospital cardiac arrest trial. These findings were considered less certain than those for survival and neurological outcome due to the small number of survivors available for EQ-5D-5L assessment, which limited the precision of the estimates.6
- In the in-hospital cardiac arrest trial, alkalosis (pH > 7.45, 52/147 [35%] vs 31/153 [20%]) and hypernatremia (sodium > 145 mmol/L, 62/147 [42%] vs 44/153 [29%]) were more common with sodium bicarbonate than with placebo.
- We placed a higher value on not allocating resources to an ineffective intervention, which may divert rescuer time from more beneficial interventions.
Knowledge Gaps
- The effect of buffering agents other than sodium bicarbonate during cardiac arrest remains uncertain.
- The optimal dose of buffering agents during cardiac arrest remains unknown.
- The optimal timing of buffering agent administration during cardiac arrest remains unknown.
Evidence to Decision (EtD) Tables
ALS 3205 Evidence to Decision Table EtD IHCA Buffering Agents_12 October2026
ALS 3205 Evidence to Decision Table EtD OHCA Buffering Agents_12October2026
References
1. Xu T, Wu C, Shen Q, Xu H, Huang H. The effect of sodium bicarbonate on OHCA patients: A systematic review and meta-analysis of RCT and propensity score studies. Am J Emerg Med. 2023;73:40-46. doi: 10.1016/j.ajem.2023.08.020
2. Drennan IR, Berg KM, Böttiger BW, Woon Chia Y, Couper K, Crowley C, D'Arrigo S, Deakin CD, Fernando SM, Garg R, et al. Advanced Life Support: 2025 International Liaison Committee on Resuscitation Consensus on Science With Treatment Recommendations. Circulation. 2025;152:S72-S115. doi: 10.1161/CIR.0000000000001360
3. Dybvik T, Strand T, Steen PA. Buffer therapy during out-of-hospital cardiopulmonary resuscitation. Resuscitation. 1995;29:89-95. doi: 10.1016/0300-9572(95)00850-s
4. Vukmir RB, Katz L, Group SBS. Sodium bicarbonate improves outcome in prolonged prehospital cardiac arrest. Am J Emerg Med. 2006;24:156-161. doi: 10.1016/j.ajem.2005.08.016
5. Ahn S, Kim YJ, Sohn CH, Seo DW, Lim KS, Donnino MW, Kim WY. Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study. J Thorac Dis. 2018;10:2295-2302. doi: 10.21037/jtd.2018.03.124
6. Granfeldt A, Kirkegaard BL, Vallentin MF, Holmberg MJ, Stankovic N, Lind PC, Kjærgaard AG, Houe N, Vested M, Isbye DL, et al. Sodium Bicarbonate for In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2026. doi: 10.1001/jama.2026.10628
7. Moskowitz A, Ross CE, Andersen LW, Grossestreuer AV, Berg KM, Donnino MW, Investigators AHAsGWTGR. Trends Over Time in Drug Administration During Adult In-Hospital Cardiac Arrest. Crit Care Med. 2019;47:194-200. doi: 10.1097/CCM.0000000000003506
8. Andersen LW, Grossestreuer AV, Donnino MW. "Resuscitation time bias"-A unique challenge for observational cardiac arrest research. Resuscitation. 2018;125:79-82. doi: 10.1016/j.resuscitation.2018.02.006
9. Granfeldt A, Holmberg MJ, Nolan JP, Soar J, Andersen LW, Force ILCoRIALST. Temperature control after adult cardiac arrest: An updated systematic review and meta-analysis. Resuscitation. 2023;191:109928. doi: 10.1016/j.resuscitation.2023.109928