RESUSCITATION 162 (2021) 188 197

Available online at www.sciencedirect.com

Resuscitation
journal homepage: www.elsevier.com/locate/resuscitation

Review
Sodium bicarbonate administration during in-hospital
pediatric cardiac arrest: A systematic review and
meta-analysis

Chih-Yao Chang a , Po-Han Wu a, Cheng-Ting Hsiao a,b, Chia-Peng Chang a ,

Yi-Chuan Chen a,c , Kai-Hsiang Wu a,c, *
a
Department of Emergency Medicine, Chang Gung Memorial Hospital, No. 6, W. Sec., Jiapu Rd., Puzih City, Chiayi County 613, Taiwan
b
Department of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 333, Taiwan
c
Department of Nursing, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi, Taiwan

Abstract
Background: Current American Heart Association Pediatric Life Support (PLS) guidelines do not recommend the routine use of sodium bicarbonate
(SB) during cardiac arrest in pediatric patients. However, SB administration during pediatric resuscitation is still common in clinical practice. The
objective of this study was to assess the impact of SB on mortality and neurological outcomes in pediatric patients with in-hospital cardiac arrest.
Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to January 2021. We included studies
of pediatric patients that had two treatment arms (treated with SB or not treated with SB) during in-hospital cardiac arrest (IHCA). Risk of bias was
assessed using the Newcastle-Ottawa Scale and the certainty of evidence was assessed using GRADE system.
Results: We included 7 observational studies with a total of 4877 pediatric in-hospital cardiac arrest patients. Meta-analysis showed that SB
administration during pediatric cardiac resuscitation was associated with a significantly decreased rate of survival to hospital discharge (odds ratio
[OR], 0.40; 95% confidence interval [CI], 0.25 0.63, p value = 0.0003). There were insufficient studies for 24-h survival and neurologic outcomes
analysis. The subgroup analysis showed a significantly decreased rate of survival to hospital discharge in both the “before 2010” subgroup (OR
0.47; 95% CI 0.30 0.73; p value = 0.006) and the “after 2010” subgroup (OR 0.46; 95% CI 0.25 0.87; p value = 0.02). The certainty of evidence
ranged from very low to low.
Conclusions: This meta-analysis of non-randomized studies supported current PLS guideline that routine administration of SB is not recommended in
pediatric cardiac arrest except in special resuscitation situations.
Trial registration: The protocol was registered with PROSPERO on 8 August 2020 (registration number: CRD42020197837).
Keywords: Sodium bicarbonate, In-hospital cardiac arrest, Pediatric, Cardiac resuscitation, Systematic review, Meta-analysis

Abbreviations: CI, confidence interval; IHCA, in-hospital cardiac arrest; LOE, level of evidence; NOS, Newcastle-Ottawa scale; OHCA, out-of-hospital
cardiac arrest; OR, odds ratio; PALS, pediatric advanced life support; PCPC, pediatric cerebral performance category; PLS, Pediatric Life Support;
PRISMA, preferred reporting items for systematic reviews and meta-analysis; ROSC, return of spontaneous circulation; SB, sodium bicarbonate; GRADE,
The Grading of Recommendations Assessment, Development and Evaluation.
* Corresponding author.
E-mail address: eilrahc1219@hotmail.com (K.-H. Wu).
https://doi.org/10.1016/j.resuscitation.2021.02.035
Received 28 November 2020; Received in revised form 23 January 2021; Accepted 12 February 2021
0300-9572/© 2021 Elsevier B.V. All rights reserved.

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 RESUSCITATION 162 (2021) 188
Background
During cardiac arrest, metabolic acidosis develops because of
hypoxia-induced anaerobic metabolism and decreased metabolic
acid excretion predisposed by inadequate renal perfusion.1 There-
fore, sodium bicarbonate (SB) administration was considered as a
buffer therapy to correct metabolic acidosis.2 However, due to the
potential harm and insufficient evidence of benefit, the American Heart
Association discouraged the use of SB in guidelines.3,4 The 2010
Pediatric Advanced Life Support (PALS) guideline stated that routine
administration of SB was not recommended for cardiac arrest (Class
of Recommendation (COR) III, Level of Evidence (LOE) B), except in
special resuscitation situations, such as hyperkalemia or certain
toxidromes. These recommendations were not revised in the 2015
PALS.4,5 An evidence update was conducted in 2020 Pediatric Life
Support (PLS) guideline and the recommendations of 2010 remain
valid (COR III, LOE B-NR (Nonrandomized)).6 Although recent
guidelines advise against the routine use of SB in pediatric
resuscitation, there is still frequent use of SB during cardiac arrest.7
Consequently, the purpose of this systematic review and meta-
analysis was to evaluate the impact of SB use on mortality
and neurological outcomes in pediatric patients who presented with
in-hospital cardiac arrest (IHCA).
Methods
The systematic review and meta-analysis were conducted according
to the Preferred Reporting Items for Systematic Reviews and
Meta-Analysis (PRISMA) guidelines.8 The protocol was registered
with PROSPERO on 8 August 2020 (registration number:
CRD42020197837).
Search strategy
We performed a systematic search for published data using PubMed,
Embase, and the Cochrane Central Register of Controlled Trials from
their inception to January 04, 2021. The search strategy included the
following keywords: “Pediatrics”, “Child”, “Adolescent”, “Infant”, “Heart
arrest”, “Cardiac resuscitation”, “Cardiopulmonary resuscitation”, “In
hospital cardiac arrest”, “Life support care”, “Resuscitation”, “Sodium
bicarbonate”, and “Bicarbonate”. We did not set a limitation on the
study language or type. We reviewed the bibliographies of the
included trials and related review articles for relevant references.
Study selection
Pre-defined inclusion criteria were as follows: (1) patients less than 18
years of age, (2) in-hospital cardiac arrest, and (3) intravenous SB
administered during cardiac resuscitation. We excluded articles with
adult patients, out-of-hospital cardiac arrest (OHCA) patients, patients
who suffered from respiratory arrest with a pulse, and studies that only
included specific populations, such as patients with congenital heart
disease or inherited metabolic disorders. We also excluded case
series, case reports, and animal studies. We included only published
papers. All included studies had two treatment arms consisting of one
arm with and one arm without SB. Any discrepancies regarding study
selection were resolved by consensus among the authors. In case of
considerable overlap in data between studies, we selected the study
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197 189
that had the largest population and contained data of interest for our
meta-analysis.
Outcomes and subgroup analysis
The primary outcome was the rate of survival to hospital discharge
after IHCA. The secondary outcomes were the 24-h survival rate and
neurological outcomes. Neurological outcomes were assessed
according to the scoring criteria from the Pediatric Cerebral
Performance Category (PCPC) scale.9 This scoring system groups
the neurological status into 6 categories: (1) a normal neurological
state, (2) mild disability, (3) moderate disability, (4) severe disability,
(5) coma or vegetative state, and (6) death. A PCPC score of 1, 2, or 3
at discharge is defined as a good neurological outcome.10,11
As stated previously, the 2010 PALS guidelines advised against
the routine use of sodium bicarbonate in pediatric cardiac resuscita-
tion.4 Therefore, the protocol and the clinical judgment for the use of
this medication during resuscitation may have changed in the last
decade. Since the year factor may have been a major potential
confounding factor, we selected this factor for subgroup analysis at the
beginning of this study. Furthermore, three special resuscitation
situations, including hyperkalemia, metabolic acidosis and tricyclic
antidepressant overdose were considered for the subgroup analyses.
Data extraction and quality assessment
Two investigators (CYC and PHW) examined all selected studies
independently and extracted data in a predetermined form. The
following information was recorded: last name of the first author,
publication year, study design, study inclusion and exclusion criteria,
the period of data collection, country, resuscitation location, patient
number, age, and survival outcomes. The two investigators used the
Newcastle-Ottawa Scale (NOS) to evaluate the methodological
quality of the included observational studies. The NOS scoring
system contains 3 parts: (1) selection (4 items), (2) comparability
(4 items), and (3) outcome (3 items).12 Each item is awarded up to
1 star, except for comparability, which can be awarded up to 2 stars.
Each study was scored up to 9 stars. The authors rated the
methodological quality of each study as follows: (1) high quality if
the NOS score was >6, (2) moderate quality if the NOS score was
between 4 and 6, and (3) low quality if the NOS score was <4. Any
discrepancies were resolved through discussion among the two
investigators (CYC and PHW) and a third experienced reviewer (KHW).
Data synthesis, statistical analysis and confidence in
cumulative evidence
Meta-analysis was used to synthesize the outcomes. The odds ratios
(ORs) and 95% confidence intervals (CIs) were calculated using the
Review Manager software (RevMan, version 5.4, the Cochrane
Collaboration, 2020) with a random-effects model. A p-value < 0.05
was defined as statistically significant. We performed the heteroge-
neity assessment using I2 with low, moderate, and high levels of
heterogeneity designated as 25%, 50%, and 75%, respectively.13 The
prespecified subgroup analysis was planned to evaluate the potential
confounder that caused heterogeneity.
The certainty of evidence for each outcome was assessed using
the Grading of Recommendations Assessment, Development and
Evaluation (GRADE) system.14 Overall risk of bias, inconsistency,
indirectness, imprecision and other consideration such as publication
190 RESUSCITATION 162 (2021) 188 197

bias were assessed. Publication bias was evaluated through
visualization of funnel plots. Imprecision was considered if the optimal
information size (OIS) criterion is not met or OIS is met but 95% CI
overlap no effect.15 Furthermore, GRADE includes three criteria for
rating up the certainty of evidence: (1) large magnitude of effect, (2)
dose-response gradient, and (3) plausible confounding.16 Then an
overall rating for each outcome was graded from very low certainty of
evidence to high certainty of evidence and the summary of findings
was tabulated.
Quality assessment and risk of bias
The NOS was used to evaluate the methodological quality and risk of
bias for the included studies, and a summary of the NOS scores is
provided in Table 2. The quality assessment showed 1 moderate-
quality and 6 high-quality observational studies in our systematic
review.
Outcomes and subgroup analysis

The rates of survival to hospital discharge were reported in the 7

Results
Search results and characteristics of included studies
A total of 2205 records were identified through our search strategy.
A total of 1992 articles were reviewed after removing the duplicates,
and 25 full-text articles underwent detailed assessment (Fig. 1). We
excluded 7 articles that did not include data on SB use during
cardiac resuscitation,17 22 3 articles that included patients who had
respiratory arrest with a pulse,23 25 2 articles that only included
patients with preexisting cardiogenic problems,7,26 1 article that only
included patients who had out-of-hospital cardiac arrest,27 and 1
article that only included patients with sustained ROSC for more
than 20 min.28 . Moreover, 4 articles reported using the same
prospective multi-center research protocol,29 32 and out of these 4
articles, the study by López-Herce et al.32 was selected for having
the largest number of patients and data of interest. In addition, 2
articles reported using the National Registry of CPR (NRCPR)
database,10,11 the study by Raymond et al.11 was selected for
having longer data collection period and more number of patients.
Finally, 7 studies were included in our systematic review and meta-
analysis.11,32 37 The final quantitative analysis included 4877
patients. Characteristics of the included studies and a brief overview
of each trial are provided in Table 1.
studies. The meta-analysis showed a significant decrease in the rate
of survival to hospital discharge with the use of SB during cardiac
resuscitation compared to that with no SB treatment (OR 0.40; 95% CI
0.25 0.63; p-value = 0.0003; I2 = 76%) (Fig. 2).
Only the study by Raymond et al. reported the 24-h survival rate
after cardiac arrest and neurological outcomes at the time of
discharge.11 Therefore, the meta-analysis was not performed for
the 24-h survival rate and neurologic outcomes due to insufficient
studies.
The 7 articles were divided into 2 subgroups based on the period of
data collection instead of the year of publication. Five articles were
categorized into the “before 2010” subgroup and one article was
categorized into the “after 2010” subgroup. The study by Mok et al.
was not included in the subgroup analysis because the study period
spanned across 2010.36 The subgroup analysis showed that the rates
of survival to hospital discharge significantly decreased in patients
who were administered SB than in the no SB subgroup in both the
“before 2010” subgroup (OR 0.47; 95% CI 0.30 0.73; p value = 0.006;
I2 = 72%) and the “after 2010” subgroup (OR 0.46; 95% CI 0.25 0.87;
p value = 0.02; I2 not applicable) (Fig. 3).
The subgroup analyses based on the three special resuscitation
situations, including hyperkalemia, metabolic acidosis and tricyclic
antidepressant overdose, were not performed due to a lack of
published studies on the mortality in these situations.

Fig. 1 – Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flowchart of included studies.

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 Table 1 – Characteristics of the studies included in the systematic review and meta-analysis.
Study Study design Inclusion criteria Exclusion criteria Data collection Patient Age Outcome
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period number
Mos et al.33 Patients aged <18 years
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Retrospective co- Cardiac arrest occurring as a January 1997 to Total: 91 SB: 46 Mean age: 4.0 years old Survival to hospital discharge
hort study who experienced a cardiac terminal event in children with June 2002 (range: 1 day old to 17.7 — OR 0.68 (95% CI 0.26 1.77)
arrest during admission to a treatment restrictions was years old)
pediatric intensive care unit excluded
Wu et al.34 Observational Patients aged between 7 Patients who only received January 2000 to Total: 252 SB: Mean age: 3.8 years old Survival to hospital discharge
study: data re- days and 18 years who resuscitation drugs or positive December 2006 168 — OR 0.63 (95% CI 0.33 1.18)
trieved retrospec- experienced a in-hospital pressure ventilation without
tively from 2000 to cardiac arrest need of chest compression or
2003 and prospec- defibrillation, premature or term
tively from 2004 to neonates treated in the delivery
2006 room or neonatal ward, and
patients who were subject to
palliative treatment or to a DNR
order were excluded.

RESUSCITATION 162 (2021) 188

Haque et al.35 Retrospective co- Patients aged between 1
hort study month and 14 years who
experienced a in-hospital
cardiac arrest
López-Herce et al.32 Prospective obser- Patients aged between 1
vational study month and 18 years who
experienced a in-hospital
cardiac arrest
Raymond et al.11 Retrospective co- Patients aged <18 years
hort study experienced a in-hospital
cardiac arrest
Neonates (<28 days) and pa- January 2001 to Total: 106 SB: Mean age: 2.1 years old Survival to hospital discharge
tients with DNR order were December 2006 47 (range: 1 month old to — OR 0.09 (95% CI 0.01 0.76)
excluded 14 years old)
N/A December 2007 to Total: 494 SB: Mean age: 3.7 years old Survival to hospital discharge
December 2009 278 (range: 1 month old to — OR 0.30 (95% CI 0.20 0.43)
18 years old)
Cardiac arrest in the delivery June 1, 2000 to Total: 3719 SB: SB group - median age: Survival to hospital discharge
room, newborn nursery, or un- September 14, 2536 0.83 years old No SB — OR 0.60 (95% CI 0.51 0.70)
known location, cardiac arrest 2010 group - median age: 24-h survival — OR 0.72 (95%
in which epinephrine was not 0.42 years old CI 0.62 to 0.84) Survival with

197
given, cardiac arrest with un- good neurologic outcome —
known CPR duration, CPR du- OR 0.59 (95% CI 0.48 0.73)
ration <5 min, CPR duration
>120 min, and cardiac arrest
with no survival to hospital
discharge data were excluded.
Patients with very short dura-
tion of CPR and those patients
with very, very prolonged du-
ration of CPR were excluded as
both of these groups are
‘contaminants’.
Mok et al.36 Retrospective co- Patients aged <18 years Events occurring in the emer- January 2009 to Total: 51 SB: 23 Survivors — median Survival to hospital discharge
hort study who a in-hospital cardiac gency room, non-clinical area December 2014 age: 0.6 years old (IQR — OR 0.03 (95% CI 0.01 0.17)
arrest or neonatal unit were excluded. 0.3 5.5) Non-

(continued on next page)

191
 192
Table 1 (continued)

Study Study design Inclusion criteria Exclusion criteria Data collection Patient Age Outcome
period number
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We also excluded patients who Survivors — median

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had a prior DNR order. age: 2.9 years old (IQR

Sutton et al.37 Prospective cohort Patients aged between 37
study weeks gestation and 18
years who received exter-
nal chest compressions for
at least 1 min and had
invasive arterial blood
pressure monitoring prior to
and during CPR in a ICU
1.0 8.7)
Subjects were excluded if the July 2013 to June Total: 164 SB: Age < 1 year: 98 pa- Survival to hospital discharge
first compression was not cap- 2016 93 tients Age  1 year: 66 — OR 0.46 (95% CI 0.25 0.87)
tured on the waveform data or patients
compression rate was unable to
be determined

Abbreviations: CPR, cardiopulmonary resuscitation; DNR, do-not-resuscitate; ICU, intensive care unit; SB, sodium bicarbonate; IQR, interquartile range.

RESUSCITATION 162 (2021) 188

Table 2 – Scores using the Newcastle-Ottawa Scale for the quality assessment of the included observational studies.
Study Year Selection Comparability Outcome Score

1) Representativeness 2) Selection 3) Ascertainment 4) Demonstration that 1) Comparability of 1) Assessment 2) Was follow-up 3) Adequacy of

197
of the exposed cohort of the non of exposure outcome of interest cohorts on the of outcome long enough for follow up of
exposed was not present basis of the design outcomes to occur cohorts
cohort at start of study or analysisa
Mos et al. 2006 $ $ $ $ $ $ $ 7
Wu et al. 2009 $ $ $ $ $ $ $ $ 8
Haque 2011 $ $ $ $ $ $ $ 7
et al.
López- 2013 $ $ $ $ $ $ 6
Herce et al.
Raymond 2015 $ $ $ $ $ $ $ 7
et al.
Mok et al. 2016 $ $ $ $ $ $ $ 7
Sutton 2018 $ $ $ $ $ $ $ 7
et al.
a
A maximum of 2 stars can be scored in this category, one star for age and the second star for other controls.
 RESUSCITATION 162 (2021) 188 197 193

Fig. 2 – Forest plot of odds ratio (OR) for rate of survival to hospital discharge.

Fig. 3 – Forest plot of subgroup analysis based on the year factor for survival to hospital discharge.

situations in pediatric patients who presented with in-hospital cardiac

Certainty of evidence
The certainty of evidence for the survival to hospital discharge rate,
subgroup analysis based on the year factor, the 24-h survival rate and
the favorable neurologic outcomes were assessed. The outcomes
started at low certainty of evidence due to its being extracted from
observational studies. We downgraded the survival to hospital
discharge rate for inconsistency and suspected publication bias,
the before 2010 subgroup for inconsistency and the after 2010
subgroup for imprecision. Inconsistency and publication bias
assessment were not applicable to the after 2010 subgroup, the
24-h survival and the good neurologic outcomes due to only one study
being included in each outcome. The overall certainty of evidence for
the outcomes ranged from very low to low. The summary of findings
table is provided in Table 3 and additional information, such as
GRADE evidence profile and funnel plots, is included in Supplemen-
tary material.
Discussion
In this systematic review and meta-analysis, we evaluated the effect of
SB on mortality, neurological outcomes and special resuscitation
arrest. We found that (1) SB use during pediatric cardiac resuscitation
was associated with loministering SB as a buffer therapy during
resuscitation was based on the premise that metabolic acidosis may
cause adverse effects, including decreased myocardial performance,
increased pulmonary vascular resistance, increased risk of develop-
ing arrhythmias, and attenuated vascular pressor responses.39 41
However, SB has several side effects, such as hypernatremia,
metabolic alkalosis, ionized hypocalcemia, hypercapnia, impairment
of tissue oxygenation, intracellular acidosis, hyperosmolarity, and
increased lactate production.2,42,43 Therefore, the disadvantages of
SB therapy may outweigh the advantages.
Although the PLS guidelines recommend against routine SB
administration, the use of SB during pediatric cardiac resuscitation is
still common. In a large retrospective, observational study that
included 7926 pediatric patients in cardiac intensive care units across
the United States of America, Loomba et al. revealed that the use of
SB during cardiac arrest significantly declined from 2004 through the
end of 2015.7 However, the percentage of SB administration was still
as high as 43.7% in 2015. In our meta-analysis, 3168 patients (65.6 %)
had received SB treatment and 93 patients (56.7 %) had undergone
SB therapy in the “after 2010” subgroup. This inconsistency between
clinical practice and consensus guidelines may result from the
lack of strength of evidence. We believe our systematic review and

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 194
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Table 3 – GRADE Summary of Findings table.

Sodium Bicarbonate compared to No Sodium Bicarbonate in Pediatric IHCA patients
Patient or population: Pediatric IHCA patients
Setting: In-hospital cardiac arrest resuscitation
Intervention: Sodium Bicarbonate
Comparison: No Sodium Bicarbonate

Outcomes Anticipated absolute effectsh (95% CI) Relative effect (95% CI) No of participants (studies) Certainty of the evidence Comments

RESUSCITATION 162 (2021) 188

(GRADE)
Without Sodium Bicarbonate With Sodium Bicarbonate
Survival to Hospital Discharge 318 per 1000 157 per 1000 (104 227) OR 0.40 (0.25 0.63) 4877 (7 observational studies)  VERY LOWa,b,c
Subgroup (Before 2010)g 299 per 1000 167 per 1000 (113 237) OR 0.47 (0.30 0.73) 4662 (5 observational studies)  VERY LOWb,d
Subgroup (After 2010)g 577 per 1000 386 per 1000 (255 543) OR 0.46 (0.25 0.87) 164 (1 observational study)  VERY LOWe,f
24-h Survival 365 per 1000 293 per 1000 (263 326) OR 0.72 (0.62 0.84) 3719 (1 observational study)  LOWb,e
Good neurologic Outcomes 155 per 1000 97 per 1000 (81 118) OR 0.59 (0.48 0.73) 3719 (1 observational study)  LOWb,e

GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The
true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the
estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
Explanations:
a
Downgraded for high heterogeneity (Tau = 0.22; Chi2 = 25.23, df = 6 (P = 0.0003); I2 = 76%).

197
b
Optimal information size criterion is met, and the 95% confidence interval excludes no effect.
c
The funnel plot showed that the smaller studies were not symmetrically distributed.
d
Downgraded for high heterogeneity (Tau = 0.15; Chi2 = 14.27, df = 4 (P = 0.006); I2 = 72%).
e
The assessment of Inconsistency and publication bias were not applicable since only one study was included.
f
Downgraded for not meeting the optimal information size.
g
The subgroup analysis of survival to hospital discharge is based on the year factor.
h
The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio.
 RESUSCITATION 162 (2021) 188
meta-analysis provides a higher level of evidence to support the
current guidelines.
This meta-analysis revealed SB administration during in-hospital
pediatric cardiac resuscitation was associated with a significantly
decreased survival to hospital discharge rate. Several studies have
reported poor outcomes with SB administration in other resuscitation
situations. In pediatric patients with preexisting cardiac disease, SB
was independently associated with increased mortality in the study
reported by Loomba et al.7 Furthermore, in a multicenter cohort study
including 138 patients, Frank et al. reported a lower hospital survival
rate when SB was administered during pediatric OHCA resuscitation
compared to no SB treatment.27 Two retrospective cohort studies
showed increased mortality with SB use during resuscitation in
patients who presented with either respiratory arrest or cardiac
arrest.23,24 In addition, one randomized controlled trial showed that SB
use in neonatal resuscitation did not improve mortality and
neurological outcomes.44 Thus, our meta-analysis is consistent with
these studies and supports the current PALS guidelines that advise
against routine SB administration during resuscitation, especially for
IHCA patients.
Although our meta-analysis revealed SB was associated with an
increased overall mortality during pediatric resuscitation, several
issues remain unclear. The first issue is that the PLS guidelines state
that “sodium bicarbonate may be administered for treatment of some
toxidromes or special resuscitation situations, such as hyperkalemic
cardiac arrest”.4,5 This recommendation was based on one case
report and one animal study during the 1990s.45,46 To our knowledge,
there are a lack of studies that evaluated the efficiency of SB during
pediatric resuscitation under these special situations. However, there
were several studies that assessed SB use during adult cardiac
resuscitation under these special situations. In a retrospective cohort
study that included 180 adult OHCA patients, Koller et al. revealed that
SB was not associated with mortality in suspected cases of drug
overdose.47 Wang et al. reported that SB was positively associated
with sustained return of spontaneous circulation (ROSC) in adult IHCA
patients with hyperkalemia.48 Ahn et al. showed SB administration
improved acid-base status, but did not improve the rate of ROSC and
neurological outcomes in a small randomized control trial that included
50 adult OHCA patients with severe metabolic acidosis.49 Despite
recent studies, there is still limited evidence regarding the efficacy of
SB use in special resuscitation situations, such as toxidromes,
hyperkalemia, and preexisting metabolic acidosis. More research is
required to determine the efficiency and safety of SB use in these
situations.
The second issue is the relationship between prolonged
cardiopulmonary resuscitation (CPR) and sodium bicarbonate
administration. The 2005 PALS guidelines suggested considering
sodium bicarbonate for prolonged cardiac arrest (Class IIb; LOE 6)
after patients were provided effective ventilation, chest compres-
sions, and administered epinephrine.3 However, this recommenda-
tion was removed from the 2010 PALS guidelines.4 Matos et al.
demonstrated that CPR duration was an independent factor
associated with increased mortality.50 In our meta-analysis, several
included studies also revealed a significant increase in CPR
duration in the non-survival group and SB was administered more
frequently to patients with prolonged cardiac arrest.11,32 37
Therefore, SB administration might be a last-ditch effort to obtain
ROSC rather than a factor that caused a decreased survival rate.
Only Raymond et al. performed multivariable logistic regression to
evaluate the efficiency of SB use, and the rate of survival to hospital
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197 195
discharge still significantly decreased after the factors associated
with mortality were adjusted.11 In our study, subgroup analysis
based on CPR duration was considered as a potential confounding
factor. Nonetheless, this subgroup analysis was not performed in
our study due to a lack of published data on the efficiency of SB
based on CPR duration. Thus, further studies are needed to address
this important issue.
Limitations
This systematic review and meta-analysis contained limitations that
should be addressed. First, only 7 studies were included in our primary
outcome analysis and there were insufficient studies for secondary
outcomes analysis. In addition, there was only one study included in
the “after 2010” subgroup for subgroup analysis. Second, all included
studies were observational studies. The use of SB was not
randomized and all clinical management decisions during resuscita-
tion, such as whether to administer the SB, were made by the
resuscitation team. Therefore, different characteristics between the
SB and no SB groups and unidentified confounders may have existed
in our study. For example, Raymond et al. revealed that SB was
administered more frequently to patients with prolonged CPR,
metabolic or electrolyte disturbance, ventricular fibrillation or pulse-
less ventricular tachycardia during resuscitation, or hypotension
before cardiac arrest.11 Thus, further prospective studies are
necessary to address these confounding factors. Third, several
unidentified confounders were not completely reported in each study
used for our analysis, such as (1) conditions before cardiac arrest,
including hypotension, preexisting metabolic acidosis and hyper-
kalemia, septicemia, and comorbidity; (2) variables in cardiac
resuscitation, including response time, initial cardiac rhythm,
medication used during cardiac arrest, total SB amount, time to first
SB administration, and the use of extracorporeal membrane
oxygenation; and (3) post-ROSC management, such as medication,
including inotropes and vasopressor agents, and management of
target temperature.51,52 Finally, the heterogeneities were high in our
meta-analysis. Factors, including unidentified confounding factors,
limitations of observational research, and inconsistency between
consensus guidelines and clinical practice may have led to
heterogeneity in our study. Nevertheless, the individual studies in
our meta-analysis have a similar trend toward increased mortality
when SB is used during cardiac arrest for in-hospital pediatric patients.
Conclusions
In this systematic review and meta-analysis of observational studies,
SB administration was associated with increased in-hospital mortality
in pediatric IHCA patients. Therefore, current data supports the 2020
PLS guidelines that routine administration of SB is not recommended
in pediatric cardiac arrest, especially in IHCA patients, except in
special resuscitation situations. Further multicenter prospective
studies are required to investigate the efficiency of SB in special
resuscitation situations and to address confounders, such as CPR
duration.
Ethics approval and consent to participate
Not applicable.
196 RESUSCITATION 162 (2021) 188
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Funding
None of the authors received any financial support for the systematic
review and meta-analysis reported here.
CRediT authorship contribution statement
Chih-Yao Chang: Conception and design, Analysis and interpreta-
tion, Drafting of the manuscript for important intellectual content,
Revising the manuscript for important intellectual content, Approval of
the manuscript. Po-Han Wu: Analysis and interpretation, Revising the
manuscript for important intellectual content, Approval of the
manuscript. Cheng-Ting Hsiao: Analysis and interpretation, Revis-
ing the manuscript for important intellectual content, Approval of the
manuscript. Chia-Peng Chang: Analysis and interpretation, Revising
the manuscript for important intellectual content, Approval of the
manuscript. Yi-Chuan Chen: Analysis and interpretation, Revising
the manuscript for important intellectual content, Approval of the
manuscript. Kai-Hsiang Wu: Conception and design, Analysis and
interpretation, Drafting of the manuscript for important intellectual
content, Revising the manuscript for important intellectual content,
Approval of the manuscript.
Acknowledgements
The authors would like to thank all of the participants in this study.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the online
version, at doi:https://doi.org/10.1016/j.resuscitation.2021.02.035.
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