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Critical Care Explorations www.ccejournal.org 1
DOI: 10.1097/CCE.0000000000001071
Copyright © 2024 The Authors.
Published by Wolters Kluwer Health,
Inc. on behalf of the Society of
Critical Care Medicine. This is an
open-access article distributed under
the terms of the Creative Commons
Attribution-Non Commercial-No
Derivatives License 4.0 (CCBY-
NC-ND), where it is permissible to
download and share the work pro-
vided it is properly cited. The work
cannot be changed in any way or
used commercially without permis-
sion from the journal.
Dipayan Chaudhuri, MD1
Lori Israelian, MD1
Zbigniew Putowski, MD2
Jay Prakash, MBBS3
Tyler Pitre, MD4
Andrea M. Nei, PharmD5
Joanna L. Spencer-Segal, MD,
PhD6,7
Hayley B. Gershengorn, MD8,9
Djillali Annane, MD10,11
Stephen M. Pastores, MD12,13
Bram Rochwerg, MD1
SYSTEMATIC REVIEW
Adverse Effects Related to Corticosteroid
Use in Sepsis, Acute Respiratory Distress
Syndrome, and Community-Acquired
Pneumonia: A Systematic Review and
Meta-Analysis
OBJECTIVES: We postulate that corticosteroid-related side effects in critically ill
patients are similar across sepsis, acute respiratory distress syndrome (ARDS),
and community-acquired pneumonia (CAP). By pooling data across all trials that
have examined corticosteroids in these three acute conditions, we aim to examine
the side effects of corticosteroid use in critical illness.
DATA SOURCES: We performed a comprehensive search of MEDLIN E, Embase,
Centers for Disease Control and Prevention library of COVID research, CINAHL,
and Cochrane center for trials.
STUDY SELECTION: We included randomized controlled trials (RCTs) that
compared corticosteroids to no corticosteroids or placebo in patients with sepsis,
ARDS, and CAP.
DATA EXTRACTION: We summarized data addressing the most described side
effects of corticosteroid use in critical care: gastrointestinal bleeding, hypergly-
cemia, hypernatremia, superinfections/secondary infections, neuropsychiatric
effects, and neuromuscular weakness.
DATA SYNTHESIS: We included 47 RCTs (n = 13,893 patients). Corticosteroids
probably have no effect on gastrointestinal bleeding (relative risk [RR], 1.08; 95%
CI, 0.87–1.34; absolute risk increase [ARI], 0.3%; moderate certainty) or sec-
ondary infections (RR, 0.97; 95% CI, 0.89–1.05; absolute risk reduction, 0.5%;
moderate certainty) and may have no effect on neuromuscular weakness (RR,
1.22; 95% CI, 1.03–1.45; ARI, 1.4%; low certainty) or neuropsychiatric events
(RR, 1.19; 95% CI, 0.82–1.74; ARI, 0.5%; low certainty). Conversely, they in-
crease the risk of hyperglycemia (RR, 1.21; 95% CI, 1.11–1.31; ARI, 5.4%; high
certainty) and probably increase the risk of hypernatremia (RR, 1.59; 95% CI,
1.29–1.96; ARI, 2.3%; moderate certainty).
CONCLUSIONS: In ARDS, sepsis, and CAP, corticosteroids are associated
with hyperglycemia and probably with hypernatremia but likely have no effect on
gastrointestinal bleeding or secondary infections. More data examining effects
of corticosteroids, particularly on neuropsychiatric outcomes and neuromuscular
weakness, would clarify the safety of this class of drugs in critical illness.
KEYWORDS: complications; corticosteroids; critical illness; systematic review
Corticosteroids are essential for survival of critical illness, and changes
in endogenous corticosteroid signaling involving hypothalamic-
pituitary-adrenal axis activity, cortisol metabolism, and glucocorticoid
sensitivity may contribute to clinical outcomes (1). Recent guidelines have cau-
tiously recommended corticosteroid administration to critically ill patients with
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sepsis, acute respiratory distress syndrome (ARDS),
and community-acquired pneumonia (CAP) (2, 3).
However, the adverse eects associated with cortico-
steroid use in critically ill patients has not been well
studied. Previous systematic reviews have examined
corticosteroid-related side eects when administered
for specic indications, however, dierential reporting
across trials and low event rates have resulted in very
low-certainty evidence for most of these adverse out-
comes (4–6).
We postulate that the underlying pathophysiology
leading to corticosteroid-related adverse eects in crit-
ically ill patients is similar across sepsis, ARDS, and
CAP. By pooling data across all trials that have exam-
ined corticosteroid use in these three acute conditions,
we aim to increase precision and certainty of evidence
and better understand the actual harms associated with
this intervention in critically ill patients. e primary
objective of this systematic review and meta-analysis
was to examine patient-important side eects of corti-
costeroid use in patients with sepsis, ARDS, and CAP.
MATERIALS AND METHODS
We registered the protocol for this systematic review on
PROSPERO (No. 42023421151) and used the PRISMA
checklist to report ndings (Supplementary Table 1,
http://links.lww.com/CCX/B327).
Data Sources and Searches
With the help of an experienced medical librarian,
we performed a comprehensive search of relevant
databases (MEDLINE, Embase, Centers for Disease
Control and Prevention library of COVID research,
CINAHL, and Cochrane center for trials). e search
strategy was based on recently published systematic
reviews conducted by authors of this article examin-
ing the eects of corticosteroids in patients with ARDS
(4), sepsis (5), and CAP (6). We updated the searches
for ARDS and CAP to October 2023; the review exam-
ining sepsis was just published in October 2023. We
limited the search to human studies and set no lan-
guage restrictions. We screened reference lists of rel-
evant systematic reviews and contacted experts in the
eld to ensure we were not missing any additional
articles. A copy of the search strategy is included in
the Supplementary Materials (http://links.lww.com/
CCX/B327).
Study Selection
Using (Covidence, Melbourne, Australia) a systematic
review management soware, two reviewers (D.C.,
T.P.) screened citations independently and in dupli-
cate, in two stages: rst, we screened the title and ab-
stract, and then the full text of each abstract selected
as potentially relevant in the rst stage. We captured
reasons for study exclusion at the full-text review stage.
A third author (B.R.) adjudicated disagreements, when
necessary.
Eligibility Criteria
We included randomized controlled trials (RCTs)
that compared corticosteroids to placebo or
usual care in patients with ARDS, sepsis, or CAP.
Previously published reviews and the Supplementary
Materials (http://links.lww.com/CCX/B327) present
more detail on the denition of the study conditions
(4–6). We excluded any nonrandomized, quasi-
randomized, or observational studies. We summa-
rized data addressing the most commonly described
side eects of corticosteroid use in critical care: gastro-
intestinal bleeding, hyperglycemia, hypernatremia,
KEY POINTS
Question: What are the side effects of corti-
costeroid use in critical illness, specifically in
sepsis, acute respiratory distress syndrome, and
community-acquired pneumonia?
Findings: Our meta-analysis shows corticoste-
roids probably have no effect on gastrointestinal
bleeding or secondary infections (both moderate
certainty) and may have no effect on neuromus-
cular weakness or neuropsychiatric events (both
low certainty). Conversely, they increase the risk
of hyperglycemia (high certainty) and probably
increase the risk of hypernatremia (moderate
certainty).
Meaning: While corticosteroids seem to be safe
in critical illness, one must be wary of hypergly-
cemia and hypernatremia and keep in mind that its
effect on weakness and neuropsychiatric events is
unclear.
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Systematic Review
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superinfections/secondary infections, neuropsy-
chiatric eects, and neuromuscular weakness. We
did not have a standardized denition for each of
these outcomes, given variability of reporting, but
rather included them as dened by study authors
(Supplementary Tables 3 and 4 [http://links.lww.
com/CCX/B327] for outcome denitions across
studies). Further, given that none of these trials
were designed for safety, we also collected data on
whether trials systematically screened for predened
complications or whether they were self-reported,
along with the length of follow-up.
Data Extraction and Quality and Certainty
Assessment
Four reviewers (D.C., L.I., Z.P., J.P.) abstracted data
independently and in duplicate using a structured
data abstraction form. A h reviewer (B.R.) re-
solved any disagreements. We collected study char-
acteristics, patient demographics, intervention,
control details, and denitions of the prespecied
study outcomes.
We assessed risk of bias (ROB) independently
and in duplicate using the (Cochrane Denmark,
Odense, Denmark) ROB 2.0 tool for RCTs. We used
the tool to assess for ROB in the following domains:
randomization process, deviations from intended
interventions, missing outcome data, measurement
of the outcome, and selection of the reported result.
We rated each domain as “low,” “some concerns,” or
“high.” We determined overall ROB for each trial
based on the highest risk attributed to any one do-
main. We assessed certainty of evidence for each
outcome using the Grading of Recommendations,
Assessment, Development, and Evaluation (GRADE)
approach (7). We judged the certainty for each out-
come as high, moderate, low, or very low, based on
considerations of ROB, inconsistency, indirectness,
imprecision, and publication bias.
To make judgments regarding imprecision, we used
a minimally contextualized approach (8). We used a
minimally important absolute dierence of 2% for all
outcomes based on consensus of the authors. Using
updated GRADE guidance, we rated imprecision using
the CI method (9).
In keeping with GRADE methods, we use termi-
nology consistent with the overall certainty of evidence.
is includes stronger language for high-certainty evi-
dence, and less certain language (“probably” or “may”)
for moderate- or low-certainty evidence (7).
Data Analysis
Pairwise Meta-Analyses. To generate forest plots and
conduct pairwise meta-analysis, we used RevMan 5.3
(Cochrane Collaboration, Oxford, United Kingdom)
soware. We used the DerSimonian-Laird random-
eects model with inverse-variance weighting to
generate pooled treatment eects across studies. We
assessed statistical heterogeneity between trials using a
combination of the chi-square test, the I2 statistic, and
visual inspection of the forest plots. We present results
of dichotomous outcomes using relative risk (RR) and
continuous outcomes as mean dierence, both with
95% CIs. We also provide absolute dierences with 95%
CIs. If medians and interquartile ranges (IQRs) were
reported in included trials instead of mean and , we
assumed normality in data distribution and converted
IQR to s using standardized methods (10).
Subgroup Analysis. We planned two a priori sub-
group analyses based on: 1) disease etiology (CAP vs.
ARDS vs. sepsis—hypothesizing that there would be
no dierence between groups) and 2) type of corti-
costeroid used (hypothesizing that there would be no
dierence between groups). We also performed two
post hoc subgroup analyses. First, we examined the
outcome of hyperglycemia based on the denition that
was used. We grouped hyperglycemia into four catego-
ries: glucose greater than 8.3 mmol/L (> 150 mg/dL),
glucose greater than 10 mmol/L (> 180 mg/dL), hyper-
glycemia treated with insulin, and other. Second, we
examined outcomes based on whether trials system-
atically screened for adverse eects or they were self-
reported, hypothesizing that we may see a stronger
signal for harm in the studies that employed system-
atic screening.
For all subgroup analyses, if the p value for the inter-
action term was less than 0.05, we used the ICEMAN
tool (11) to assess for credible subgroup eects.
Dose-Response Analysis. For each outcome, we per-
formed a dose-response meta-analysis. For the dose-
response analysis, we conducted a random-eects
dose-response meta-analysis using the restricted max-
imum likelihood heterogeneity estimator and methods
proposed by Greenland and Longnecker (12) and Orsini
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et al (13) using a one-stage approach (14). For this dose-
response analysis, we considered the daily dose of cor-
ticosteroids administered during the trial. We used the
following corticosteroid conversions for glucocorticoid
potency: 1 mg of dexamethasone = 26.7 mg of hydrocor-
tisone = 5.3 mg of methylprednisolone/prednisolone =
6.7 mg of prednisone. For all dose-response analyses
with ve or more studies, we assessed for nonlinearity
by using restricted cubic splines with knots at 10%, 50%,
and 90% and a Wald-type test (15). Restricted cubic
splines accommodate nonlinear relationships by split-
ting the independent variable (i.e., dose) at “knots” and
tting separate curves between knots. For analyses in
which we observed statistically signicant associations,
we present results from that model. If no statistically sig-
nicant association was observed, we present only the
goodness-of-t statistic. If both linear and nonlinear
dose-response models for an outcome were statisti-
cally signicant, we presented the more accurate model.
We performed analyses using the “dosresmeta” in R
(Version 4.03; R Foundation for Statistical Computing,
Vienna, Austria).
Trial Sequential Analysis. To help inform our
assessment of imprecision, we performed trial sequen-
tial analysis (TSA). We conducted TSA (16) using the
random-eects model for all included outcomes. For the
TSA, we used a statistical signicance level of 5%, a power
of 80%, and a RR reduction of 15% to represent a clini-
cally important dierence. We performed TSA analyses
using TSA, Version 0.9.5.10 beta (Copenhagen Trial Unit,
Centre for Clinical Intervention Research, Rigshospitalet,
Copenhagen, Denmark; www.ctu.dk/tsa).
RESULTS
e updated search yielded 6505 unique citations
addressing patients with ARDS and 579 citations
addressing patients with CAP. Aer screening, we did
not nd any new eligible trials beyond those included
in the previous reviews (4–6). Overall, we included 47
trials (n = 13,893) (17–61) that reported adverse eects
related to corticosteroid use in critically ill patients
with ARDS, CAP, and sepsis/septic shock, the details
of which are presented in Supplementary Table 2
(http://links.lww.com/CCX/B327).
Of the included studies, 12 were in patients with
ARDS (n = 1739) (17, 18, 29, 40, 51, 56–60), 15 were in
patients with CAP (n = 4415) (19–28, 30–33, 61), and
20 trials included patients with sepsis or septic shock
(n = 7739) (34–39, 41–50, 52–55). All trials included
adult patients except for one that enrolled only chil-
dren with septic shock (46). For type of corticosteroid
molecule, 22 trials used hydrocortisone, 13 used meth-
ylprednisolone, six used dexamethasone, and ve used
prednisone or prednisolone. e dose of corticosteroid
varied, although the majority of trials (31/47) used
400 mg/d of hydrocortisone or less. Most studies used
corticosteroids for 7 days or fewer (87%, n = 40). Of
the 47 studies, 26 systematically screened for adverse
eects (17, 18, 22–24, 26–28, 34–39, 45–47, 50, 51, 55–
60), 16 self-reported (20, 21, 25, 29–33, 40–43, 48, 52,
59, 61), and ve did both depending on outcome (19,
44, 49, 53, 54). Only three trials followed patients for
safety outcomes for longer than 30 days (17, 22, 35).
Supplementary Tables 2 and 3 (http://links.lww.com/
CCX/B327) illustrate how outcomes were dened and
collected across studies.
We judged seven RCTs to be at high ROB for all out-
comes (19, 25, 27, 32, 40, 47, 49). All seven were at ROB
due to concerns regarding randomization, six were at
ROB due to deviations from the intended interventions
and four were at ROB due to missing outcome data.
When examining the specic outcomes of neuropsychi-
atric adverse eects and neuromuscular weakness, we
had concerns regarding measurement of this outcome
and selection of the reported result for all included tri-
als. Supplementary Table 5A–E (http://links.lww.com/
CCX/B327) presents all ROB assessments.
Supplementary Table 6 (http://links.lww.com/
CCX/B327) shows the overall eect estimates and
GRADE certainty assessments. We found that corti-
costeroids probably have no eect on gastrointestinal
bleeding (7053 patients in 32 trials; RR, 1.08; 95% CI,
0.87–1.34; absolute risk increase [ARI], 0.3%; 95% CI,
0.5% fewer to 1.4% more; moderate certainty; Fig. 1)
or secondary infections (11,777 patients in 39 trials;
RR, 0.97; 95% CI, 0.89–1.05; absolute risk reduction,
0.5%; 95% CI, 1.9% fewer to 0.9% more; moderate cer-
tainty; Fig. 2). We found that corticosteroids increase
hyperglycemia (11,536 patients in 32 trials; RR, 1.21;
95% CI, 1.11–1.32; ARI, 5.4%; 95% CI, 2.8–7.9% in-
crease; high certainty; Fig. 3) and probably increase
hypernatremia (5599 patients in seven trials; RR, 1.59;
95% CI, 1.29–1.96; ARI, 2.3%; 95% CI, 1.1–3.8% in-
crease; moderate certainty; Supplementary Fig. 1,
http://links.lww.com/CCX/B327).
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Supplementary Table 3 (http://links.lww.com/
CCX/B327) shows that studies dened neuromus-
cular weakness as any combination of muscle weak-
ness or myopathy or neuropathy, and that of the ten
studies that reported neuropsychiatric outcomes, most
specied delirium and/or psychosis-related side events.
Corticosteroids may have no eect on neuromuscular
weakness (6361 patients in eight trials; RR, 1.22; 95%
CI, 1.03–1.45; ARI, 1.4%; 95% CI, 0.2% more to 2.8%
more; low certainty; Fig. 4) or neuropsychiatric events
(3781 patients in nine trials; RR, 1.19; 95% CI, 0.82–
1.74; ARI, 0.5%; 95% CI, 0.5% fewer to 1.9% more; low
certainty; Supplementary Fig. 2, http://links.lww.com/
CCX/B327). TSA showed that optimal information size
was only reached for hyperglycemia and secondary in-
fection but was not reached for other outcomes, and
Figure 1. Effect of corticosteroids on gastrointestinal bleeding. Studies are grouped by underlying condition. ARDS = acute respiratory
distress syndrome, df = degrees of freedom, M-H = Mantel-Haenszel.
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these ndings were incorporated into GRADE assess-
ments (Supplementary Materials, http://links.lww.com/
CCX/B327).
Other than the outcome of hyperglycemia, we rated
down all outcomes for indirectness as adverse eects
were not reported in a standardized fashion across trials,
Figure 2. Effect of corticosteroids on superinfections. Studies are grouped by underlying condition. ARDS = acute respiratory distress
syndrome, df = degrees of freedom, M-H = Mantel-Haenszel.
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and the severity and, therefore, the patient-importance
of the complication varied. For the outcome of hyper-
glycemia, we opted not to downgrade for indirectness
as regardless of how hyperglycemia was dened, the
eect remained the same in both magnitude and cer-
tainty (Supplementary Fig. 3, http://links.lww.com/
CCX/B327). We downgraded the outcome of neuro-
muscular weakness for imprecision as serious harm
could not be excluded and neuropsychiatric eects for
the same due to very small total event numbers (< 200
overall) increasing the risk of random error.
Subgroup analysis based on corticosteroid type
or on whether adverse events were systematically
screened did not demonstrate any credible subgroup
eects (Supplementary Figs. 4–6 and 11–16, http://
links.lww.com/CCX/B327). However, subgroup anal-
ysis based on disease type showed patients with
ARDS who received corticosteroids had a lower risk
Figure 3. Effect of corticosteroids on hyperglycemia. Studies are grouped by underlying condition. ARDS = acute respiratory distress
syndrome, df = degrees of freedom, M-H = Mantel-Haenszel.
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of secondary infections (p = 0.008; moderate credi-
bility; Fig. 2) compared with other indications that
demonstrated no eect on secondary infections. e
source of secondary infection that was reduced in
ARDS patients was ventilator- or hospital-acquired
pneumonia (Supplementary Fig. 7, http://links.lww.
com/CCX/B327), compared with other sources such
as bloodstream infections, central line-associated
infections, or urinary tract infections (Supplementary
Figs. 8–10, http://links.lww.com/CCX/B327).
A dose-response analysis showed a nonlinear dose-
response relationship for the outcome of hypergly-
cemia, although the model becomes less certain at
doses above 400 mg/d of hydrocortisone. e model
suggests increasing harm with higher doses of hydro-
cortisone. ere are no dose-response relationships for
any of the other outcomes (Supplementary Materials,
http://links.lww.com/CCX/B327).
DISCUSSION
e overall ndings of this systematic review and
meta-analysis show that corticosteroid use in ARDS,
CAP, and sepsis is associated with hyperglycemia and
probably with hypernatremia. However, corticosteroid
administration for these conditions probably does not
increase rates of gastrointestinal bleeding or secondary
infections and may not increase neuromuscular weak-
ness and short-term neuropsychiatric sequelae (de-
lirium or psychosis). In addition, other than increasing
corticosteroid doses being associated with an increased
risk of hyperglycemia and patients with ARDS who re-
ceive corticosteroids having a lower rate of secondary
infections (primarily pneumonia), there were no cred-
ible subgroup ndings related to disease/syndrome,
corticosteroid type, or dose.
ere remains a degree of uncertainty regarding the
eect of corticosteroids on neuropsychiatric adverse
eects and neuromuscular weakness, especially in the
long term (> 30 d). Case reports and case series have
indicated an association between corticosteroid use
and weakness (62), although more recent data examin-
ing this association has demonstrated mixed ndings
(17, 18, 50), perhaps in part due to better data collec-
tion and study design or changes in clinical practice
(lower steroid dosing, improvement in mechanical
Figure 4. Effect of corticosteroids on neuromuscular weakness. Studies are grouped by underlying condition. ARDS = acute respiratory
distress syndrome, df = degrees of freedom, M-H = Mantel-Haenszel.
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ventilation). While this review showed that corticoste-
roids may have no eect on neuromuscular weakness,
the lack of consistent denitions of neuromuscular
weakness and long-term follow-up across studies lim-
ited the certainty of conclusions. is is an area requir-
ing high quality RCT data with a focus on long-term
outcomes and careful consideration of the role of po-
tential other factors such as early mobilization and hy-
perglycemia. Similarly, associations have been made
between corticosteroids and delirium (63)—a correla-
tion not observed in larger, well-designed studies (64).
While this review did not indicate an association, the
rates of delirium that were reported across studies were
much lower than expected, with only 2–3% of patients
having neuropsychiatric adverse eects, compared
with the 20–80% rates of delirium typically reported
in ICU studies (65), suggesting likely underreporting.
In addition to variation in the denitions of neuropsy-
chiatric eects across studies and serious imprecision,
this precluded any denitive conclusions. Further, cor-
ticosteroids may have dierential eects on short- and
long-term neuropsychiatric outcomes. In particular,
many prior studies suggest a protective role of corti-
costeroid treatment against post traumatic stress dis-
order in long-term critical illness survivors (66, 67),
which could not be tested here. Moving forward, spe-
cic short- and long-term neuropsychiatric endpoints
should be prespecied and collected systematically to
address the remaining uncertainties regarding cortico-
steroid eects on these outcomes (68).
While we found little subgroup eect modication,
there was one moderately credible subgroup eect
associating corticosteroid use with lower rates of sec-
ondary infections in patients with ARDS, specically
secondary pneumonias. is subgroup eect could
represent a faster resolution of the underlying ARDS in
corticosteroid-treated patients, decreasing the chance
of a secondary pneumonia. However, the lack of a clear
temporal relationship between corticosteroid use and
secondary infections means this correlation must be
interpreted with caution and causality cannot be im-
plied. Importantly, despite the known immunosup-
pressive eects of systemic corticosteroids, there was
no indication of increased secondary infections with
corticosteroid treatment in the current analysis.
is is a large meta-analysis (over 13,000 patients)
comprehensively examining side eects related to
corticosteroid use in critical illness. Strengths of this
review include the comprehensive search, preregis-
tration of the protocol, meta-regression to evaluate
the impact of corticosteroid dose, assessment of ROB
using Cochrane 2.0, TSA, and assessment of certainty
of evidence using the GRADE approach. is review
also has limitations, primarily related to clinical heter-
ogeneity. First, the outcomes we examined were not al-
ways collected in a standardized fashion, especially in
the case of neuromuscular weakness and neuropsychi-
atric outcomes. We have attempted to address this by
downgrading the certainty of almost all outcomes for
indirectness. Furthermore, when using the GRADE
methodology to rate outcomes, we rated importance of
outcomes through consensus of the coauthor group as
opposed to incorporating input from patients or care-
givers. Additionally, we were limited by adverse eects
commonly reported in clinical trials and thus were
unable to assess all complications of corticosteroid
use such as impairment of wound healing. With only
three trials reporting safety outcomes for longer than
30 days, evidence addressing long-term adverse eects
of corticosteroid use during critical illness was also
insucient as was sucient data specically exam-
ining adverse eects in children. We note that large
well-designed observational studies can be comple-
mentary to RCTs for outcomes with very low-certainty
evidence. While not a part of this review as we a priori
decided to only include RCTs, this may prove to be a
fruitful focus of future work, particularly for outcomes
such as neuromuscular weakness and neuropsychiatric
side eects. Finally, this review focused on the most
common critical illnesses where corticosteroids are
indicated and only examined moderate doses and du-
ration of corticosteroid administration. We were un-
able to comment on the adverse events associated with
the usage of high- or pulse-dose steroids in conditions
such as diuse alveolar hemorrhage, acute transplant
rejection, oncologic therapy-associated toxicities, or
autoimmune crisis.
CONCLUSIONS
Corticosteroid use in ARDS, sepsis, and CAP is asso-
ciated with hyperglycemia, probably with hypernatre-
mia but likely has no eect on gastrointestinal bleeding
or secondary infections. Further research examining
long-term eects of corticosteroid use, particularly
on neuropsychiatric outcomes and neuromuscular
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weakness, would help further clarify the safety of this
class of drugs in critical illness.
1 Department of Medicine, McMaster University, Hamilton,
ON, Canada.
2 Centre for Intensive Care and Perioperative Medicine,
Jagiellonian University Medical College, Krakow, Poland.
3 Department of Critical Care Medicine, Rajendra Institute of
Medical Sciences, Ranchi, Jharkhand, India.
4 Department of Medicine, University of Toronto, Toronto, ON,
Canada.
5 Department of Pharmacy, Mayo Clinic Hospital, Rochester,
MN.
6 Department of Internal Medicine, Division of Metabolism,
Endocrinology, and Diabetes, University of Michigan, Ann
Arbor, MI.
7 Michigan Neuroscience Institute, University of Michigan,
Ann Arbor, MI.
8 Division of Pulmonary, Critical Care, and Sleep Medicine,
University of Miami Miller School of Medicine, Miami, FL.
9 Division of Critical Care Medicine, Albert Einstein College
of Medicine, Bronx, NY.
10 Department of Intensive Care, Hôpital Raymond Poincaré,
FHU SEPSIS, AP-HP, Garches, France.
11 Paris Saclay University, UVSQ, IN SERM, Lab of Inflammation
& Infection 2I (U1173), Montigny-le-Bretonneux, France.
12 Critical Care Center, Department of Anesthesiology and
Critical Care Medicine, Memorial Sloan Kettering Cancer
Center, New York, NY.
13 Weill Cornell Medical College, New York, NY.
Supplemental digital content is available for this article. Direct
URL citations appear in the printed text and are provided in the
HTML and PDF versions of this article on the journal’s website
(http://journals.lww.com/ccejournal).
Dr. Rochwerg is supported by a McMaster Department of
Medicine Mid-Career Research Award. The remaining authors
have disclosed that they do not have any potential conflicts of
interest.
For information regarding this article, E-mail: dipayan.chaud-
huri@medportal.ca
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