Abbasciano_et_al-2024-Cochrane_Database_of_Systematic_Reviews

Cochrane
Library
Cochrane Database of Systematic Reviews
Prophylactic corticosteroids for cardiopulmonary bypass in adult

cardiac surgery (Review)
Abbasciano RG, Olivieri GM, Chubsey R, Gatta F, Tyson N, Easwarakumar K, Fudulu DP, Marsico R,
Kofler M, Elshafie G, Lai F, Loubani M, Kendall S, Zakkar M, Murphy GJ
Abbasciano RG, Olivieri GM, Chubsey R, Gatta F, Tyson N, Easwarakumar K, Fudulu DP, Marsico R, Kofler M, Elshafie G, Lai F,
Loubani M, Kendall S, Zakkar M, Murphy GJ.
Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery.
Cochrane Database of Systematic Reviews 2024, Issue 3. Art. No.: CD005566.
DOI: 10.1002/14651858.CD005566.pub4.
www.cochranelibrary.com
Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review)

Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews
TABLE OF CONTENTS
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2
SUMMARY OF FINDINGS.............................................................................................................................................................................. 4
BACKGROUND.............................................................................................................................................................................................. 6
OBJECTIVES.................................................................................................................................................................................................. 7
METHODS..................................................................................................................................................................................................... 7
RESULTS........................................................................................................................................................................................................ 10
Figure 1.................................................................................................................................................................................................. 11
Figure 2.................................................................................................................................................................................................. 13
Figure 3.................................................................................................................................................................................................. 14
Figure 4.................................................................................................................................................................................................. 17
Figure 5.................................................................................................................................................................................................. 18
Figure 6.................................................................................................................................................................................................. 19
DISCUSSION.................................................................................................................................................................................................. 21
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 23
ACKNOWLEDGEMENTS................................................................................................................................................................................ 24
REFERENCES................................................................................................................................................................................................ 25
CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 34
DATA AND ANALYSES.................................................................................................................................................................................... 136
Analysis 1.1. Comparison 1: Primary outcomes, Outcome 1: Mortality, including 'no major complications'.................................. 137
Analysis 1.2. Comparison 1: Primary outcomes, Outcome 2: Cardiac complications, including 'no major complications'............ 138
Analysis 1.3. Comparison 1: Primary outcomes, Outcome 3: Pulmonary complications, including 'no major complications'....... 139
Analysis 2.1. Comparison 2: Secondary outcomes, Outcome 1: Infectious complications.............................................................. 140
Analysis 2.2. Comparison 2: Secondary outcomes, Outcome 2: Gastrointestinal bleeding............................................................. 141
Analysis 2.3. Comparison 2: Secondary outcomes, Outcome 3: Atrial fibrillation............................................................................ 141
Analysis 2.4. Comparison 2: Secondary outcomes, Outcome 4: Re-thoracotomy............................................................................ 142
Analysis 2.5. Comparison 2: Secondary outcomes, Outcome 5: Neurological complication (stroke).............................................. 142
Analysis 2.6. Comparison 2: Secondary outcomes, Outcome 6: Renal failure.................................................................................. 143
Analysis 2.7. Comparison 2: Secondary outcomes, Outcome 7: Inotropic support.......................................................................... 143
Analysis 2.8. Comparison 2: Secondary outcomes, Outcome 8: Postoperative bleeding (mL)........................................................ 144
Analysis 2.9. Comparison 2: Secondary outcomes, Outcome 9: Mechanical ventilation time (minutes)........................................ 144
Analysis 2.10. Comparison 2: Secondary outcomes, Outcome 10: ICU stay (hours)......................................................................... 145
Analysis 2.11. Comparison 2: Secondary outcomes, Outcome 11: Hospital stay (days)................................................................... 146
Analysis 3.1. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 1: Mortality...................................................... 148
Analysis 3.2. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 2: Cardiac complications................................ 149
Analysis 3.3. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 3: Pulmonary complications........................... 150
Analysis 3.4. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 4: Atrial fibrillation.......................................... 151
Analysis 3.5. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 5: Inotropic support........................................ 152
Analysis 3.6. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 6: Mechanical ventilation (minutes)............... 153
Analysis 3.7. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 7: Length of ICU stay (hours)........................... 154
Analysis 3.8. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 8: Length of hospital stay (days)..................... 155
Analysis 4.1. Comparison 4: Subgroup analyses: surgery type, Outcome 1: Mortality..................................................................... 157
Analysis 4.2. Comparison 4: Subgroup analyses: surgery type, Outcome 2: Cardiac complications............................................... 158
Analysis 4.3. Comparison 4: Subgroup analyses: surgery type, Outcome 3: Pulmonary complications......................................... 159
Analysis 4.4. Comparison 4: Subgroup analyses: surgery type, Outcome 4: Atrial fibrillation......................................................... 160
Analysis 4.5. Comparison 4: Subgroup analyses: surgery type, Outcome 5: Inotropic support....................................................... 161
Analysis 4.6. Comparison 4: Subgroup analyses: surgery type, Outcome 6: Mechanical ventilation (minutes).............................. 162
Analysis 4.7. Comparison 4: Subgroup analyses: surgery type, Outcome 7: Length of ICU stay (hours)......................................... 163
Analysis 4.8. Comparison 4: Subgroup analyses: surgery type, Outcome 8: Length of hospital stay (days).................................... 164
Analysis 5.1. Comparison 5: Subgroup analyses: steroid type, Outcome 1: Mortality...................................................................... 167
Analysis 5.2. Comparison 5: Subgroup analyses: steroid type, Outcome 2: Cardiac complications................................................ 169
Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) i

Informed decisions.
Analysis 5.3. Comparison 5: Subgroup analyses: steroid type, Outcome 3: Pulmonary complications.......................................... 170
Analysis 5.4. Comparison 5: Subgroup analyses: steroid type, Outcome 4: Atrial fibrillation.......................................................... 171
Analysis 5.5. Comparison 5: Subgroup analyses: steroid type, Outcome 5: Inotropic support........................................................ 173
Analysis 5.6. Comparison 5: Subgroup analyses: steroid type, Outcome 6: Mechanical ventilation (minutes)............................... 174
Analysis 5.7. Comparison 5: Subgroup analyses: steroid type, Outcome 7: Length of ICU stay (hours).......................................... 175
Analysis 5.8. Comparison 5: Subgroup analyses: steroid type, Outcome 8: Length of hospital stay (days)..................................... 176
Analysis 6.1. Comparison 6: Sensitivity analyses, Outcome 1: Mortality (sensitivity analysis)........................................................ 177
Analysis 6.2. Comparison 6: Sensitivity analyses, Outcome 2: Cardiac complications (sensitivity analysis)................................... 177
Analysis 6.3. Comparison 6: Sensitivity analyses, Outcome 3: Pulmonary complications (sensitivity analysis)............................. 177
ADDITIONAL TABLES.................................................................................................................................................................................... 178
APPENDICES................................................................................................................................................................................................. 189
WHAT'S NEW................................................................................................................................................................................................. 197
HISTORY........................................................................................................................................................................................................ 198
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 198
DECLARATIONS OF INTEREST..................................................................................................................................................................... 199
SOURCES OF SUPPORT............................................................................................................................................................................... 199
DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 200
INDEX TERMS............................................................................................................................................................................................... 200
Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) ii

Informed decisions.
[Intervention Review]
Prophylactic corticosteroids for cardiopulmonary bypass in adult

cardiac surgery
Riccardo Giuseppe Abbasciano1, Guido Maria Olivieri2, Rachel Chubsey3, Francesca Gatta4, Nathan Tyson5, Keertana Easwarakumar3,
Daniel P Fudulu6, Roberto Marsico3, Markus Kofler7, Ghazi Elshafie8, Florence Lai9, Mahmoud Loubani8, Simon Kendall10, Mustafa
Zakkar1, Gavin J Murphy1
1Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. 2Niguarda Hospital, Milan, Italy. 3University Hospitals
of Leicester NHS Trust, Leicester, UK. 4Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, UK.
5Department of Cardiac Surgery, University Hospitals of Leicester, Leicester, UK. 6Department of Cardiac Surgery, University Hospital
Bristol NHS Trust, Bristol, UK. 7Deutsches Herzzentrum Berlin, Berlin, Germany. 8Department of Cardiothoracic Surgery, Hull and East
Yorkshire Hospitals NHS Trust, Hull, UK. 9Leicester Clinical Trials Unit, University of Leicester, Glenfield Hospital, Leicester, UK. 10James
Cook University Hospital, Middlesbrough, UK
Contact: Riccardo Giuseppe Abbasciano, rga8@leicester.ac.uk.
Editorial group: Cochrane Heart Group.

Publication status and date: New search for studies and content updated (conclusions changed), published in Issue 3, 2024.
Citation: Abbasciano RG, Olivieri GM, Chubsey R, Gatta F, Tyson N, Easwarakumar K, Fudulu DP, Marsico R, Kofler M, Elshafie G, Lai F,
Loubani M, Kendall S, Zakkar M, Murphy GJ. Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery. Cochrane
Database of Systematic Reviews 2024, Issue 3. Art. No.: CD005566. DOI: 10.1002/14651858.CD005566.pub4.
ABSTRACT
Background
Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been
suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety
and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18
studies added.
Objectives
Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary
bypass on the:
- co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and
- secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical
ventilation, prolonged postoperative stay, and cost-effectiveness.
Secondary objective: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the
treatment effects via a series of prespecified subgroup analyses.
Search methods
We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult
cardiac surgery. The latest searches were performed on 14 October 2022.
Selection criteria
We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease,
or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There
Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 1

Informed decisions.
were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more
endpoints.
Data collection and analysis

We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications.
Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-
thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation
time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess
the certainty of evidence for each outcome.
Main results
This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data
synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies
was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery.
The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per
1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940
participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with
placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce
the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88,
0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence).
Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with
corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771
participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with
corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants;
low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84,
95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence
is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841
participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings
from the meta-analysis.
Authors' conclusions
A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment
effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary
complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the
level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the
evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data
on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable
cohorts.
PLAIN LANGUAGE SUMMARY
What are the benefits and risks of corticosteroids in adults undergoing heart surgery?
Key messages
- Anti-inflammatory medicines such as corticosteroids make little to no difference to survival after heart surgery, and may have both
important benefits (on the function of the lungs) and adverse, or harmful, effects (in damaging the heart).
- There are not enough large, well-conducted studies to be certain about the effects of corticosteroids, particularly in high-risk groups.
Future studies should explore the role of these medicines in vulnerable people.
What concerns are there when people have heart surgery?
People undergoing heart surgery may develop a strong response to different kinds of stress from the operation. This response –
inflammation – is thought to be responsible for many common complications, and it may be increased by the use of the heart-lung machine,
a device that temporarily takes over the work of the heart and lungs during surgery.
What is the role of corticosteroids in heart surgery?

Informed decisions.
Corticosteroids are well-known, widely-available medicines that are often used as a treatment for excess inflammation. Studies to evaluate
their use after heart surgery show mixed results, as corticosteroids also have important side effects (infection, bleeding, and damage to
the heart) that may offset any potential benefits (quicker recovery and better lung function).
What did we want to find out?
We wanted to find out what are the benefits and harms of corticosteroid treatment on the risks of major complications (death; injury to
the heart and lungs) following heart surgery.
What did we do?
We searched major databases of medical literature for reports of studies that had randomly assigned adults undergoing heart surgery to
receive either corticosteroids or no treatment or placebo (dummy pill). We then analysed their combined results.
What did we find?
We found a total of 72 studies that involved 17,282 people over approximately 50 years. The people included in these studies had an average
age of about 60 years. The most frequent surgery performed in the studies was coronary artery bypass graft, a common operation to restore
blood flow to the heart muscle.
When we pooled the studies together, we showed that, compared with no treatment or placebo, corticosteroids had little or no effect on
the risk of in-hospital death, increased the risk of heart complications, and reduced the risk of lung complications.
If corticosteroids were given to 1000 people undergoing heart surgery:
- between 25 and 36 people would die after the surgery, compared to 33 not given these medicines;
- between 68 and 86 people would suffer a heart attack, compared to 66 not given corticosteroids; and
- between 61 and 77 people would have problems in their lungs, compared to 78 not given corticosteroids.
We also showed that corticosteroids reduced the risk of heart rhythm disturbances (atrial fibrillation) and infections, but increased the risk
of having a second operation for bleeding.
What are the limitations of the evidence?
Most of the studies had important flaws that make us question the certainty of their pooled results. For example, they defined events, such
as having a heart attack, in different ways; they did not adopt adequate measures to ensure that the patients and investigators did not
know certain information that might influence their participation in the study; some studies were very small.
The studies involved different types of people, and much has changed in the practice of heart surgery over the decades. Also, the studies
used different ways of delivering corticosteroids. These factors might make it more difficult to understand if the results from these studies
are the same as would be obtained in the general population.
Also, the results from the two largest studies that we included may influence the overall findings of our review.
How up to date is this evidence?
This review updates our previous review from 2011. The evidence is current to October 2022.

SUMMARY OF FINDINGS
Summary of findings 1. Prophylactic corticosteroids compared with placebo or no corticosteroids in adults undergoing cardiac surgery with
Library
Cochrane
cardiopulmonary bypass
Patients or population: adults diagnosed with coronary artery disease or cardiac valve disease, and candidates for cardiac surgery with cardiopulmonary bypass
Settings: cardiac surgery with cardiopulmonary bypass
Better health.
Informed decisions.
Trusted evidence.
Intervention: prophylactic corticosteroids
Comparison: placebo or no corticosteroids
Outcomes Anticipated absolute effects*(95% CI) Relative effect № of participants Certainty of the
(95% CI) (studies) evidence
Risk with place- Risk with prophy- (GRADE)
bo/no treatment lactic corticos-
teroids
All-cause mortality 33 per 1000 30 per 1000 RR 0.90 14,940 ⨁⨁◯◯

(25 to 36) (0.75 to 1.07) (25 RCTs) Lowa,b
(during the index hospital admission, or within 30 days,
at the longest follow-up available)
Cardiac complications 66 per 1000 77 per 1000 RR 1.16 14,766 ⨁⨁◯◯

(68 to 86) (1.04 to 1.31) (25 RCTs) Lowa,c
(as defined by study authors, including cardiac compro-
mise and fatal and non-fatal myocardial infarction, de-
fined as ECG changes, echocardiological changes, or dis-
proportionate elevation of troponins, during the index
hospital admission)
Pulmonary complications 78 per 1000 69 per 1000 RR 0.88 13,549 ⨁⨁◯◯

(61 to 77) (0.78 to 0.99) (18 RCTs) Lowa,d

(as defined by study authors, including pneumonia, em-
bolism, reduced pulmonary function, prolonged ventila-
tion, and pleural effusion, during the index hospital ad-
mission)
Infectious complications 123 per 1000 103 per 1000 RR 0.84 14,771 ⨁⨁◯◯
(94 to 113) (0.76 to 0.92) (28 RCTs) Lowa,e
(as defined by study authors, including mediastinitis,
wound infections, pneumonia, and need for antibiotic
therapy, during the index hospital admission)
Gastrointestinal (GI) bleeding 10 per 1000 12 per 1000 RR 1.21 12,533 ⨁⨁◯◯
4
(as defined by study authors, including any upper and (9 to 17) (0.87 to 1.67) (6 RCTs) Lowb,f
lower GI bleeding, during the index hospital admission)
Library
Cochrane
Renal failure 34 per 1000 28 per 1000 RR 0.84 12,799 ⨁⨁◯◯
(23 to 35) (0.69 to 1.02) (13 RCTs) Lowa,b
(as defined by study authors, including dialysis, creati-
nine rise, and oliguria, during the index hospital admis-
sion)
Better health.
Informed decisions.
Trusted evidence.
Length of hospital stay The mean length of The mean length of - 1841 ⨁◯◯◯
hospital stay was hospital stay in the (25 RCTs) Very lowg,h,i
(measured in days, during the index hospital admission) 9.5 days intervention groups
was, on average,0.5
days shorter
(0.97 less to 0.04
less)
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
An RR < 1 or an MD < 0 indicates a benefit of corticosteroid treatment.
CI: confidence interval; ECG: electrocardiogram; MD: mean difference; RR: risk ratio; RCT: randomised controlled trial.
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.
aWe downgraded the evidence by one level for study limitations: most studies had no clear information about blinding of outcome assessment, and lack of blinding could have
produced a serious risk of detection bias.
bWe downgraded the evidence by one level for imprecision as this outcome includes a 95% confidence interval that may fail to exclude important benefit or important harm.

cWe downgraded the certainty of the evidence by one level for indirectness due to the direction of effect being heavily determined by a large, high-quality study (Whitlock 2015),
conducted in high-risk patients.
dWe downgraded the certainty of the evidence by one level for indirectness due to the direction of effect being heavily determined by a large, high-quality (Dieleman 2012),
conducted in low-risk patients.
eWe downgraded the certainty of the evidence by one level for inconsistency in categorisation of infectious complications.
fWe downgraded the certainty of the evidence by one level for imprecision due to the low number of events.
gWe downgraded the certainty of the evidence by one level for study limitations (serious risk of selection and detection bias).
hWe downgraded the certainty of the evidence by one level for inconsistency for substantial statistical heterogeneity between the studies.
iWe downgraded the certainty of the evidence by one level for imprecision, in view of the minimal treatment effect, possibly of no clinical importance.
5
Informed decisions.
BACKGROUND occurrence of postoperative atrial fibrillation (odds ratio (OR)

0.60, 95% confidence interval (CI) 0.46 to 0.78) (Dieleman 2011).
Description of the condition The review also failed to identify adverse effects attributable to
corticosteroid use. Since the publication of that review, two large
Cardiovascular diseases (CVDs) are still the leading cause of
trials evaluating corticosteroid administration in cardiac surgery
mortality in the world, causing 17.5 million deaths per year
have been published: the Dexamethasone for Cardiac Surgery
(Veervort 2020). Millions of cardiovascular interventions are
(DECS) trial (Dieleman 2012), and the Steroids In caRdiac Surgery
undertaken every year worldwide. A significant number of these are
(SIRS) trial (Whitlock 2015).
cardiac surgical procedures, including coronary revascularisation
or treatment of valve defects. • Dieleman 2012 randomised 4494 participants to receive either
one single dose of dexamethasone (1 mg/kg intraoperatively)
Most cardiac surgeries are conducted using cardiopulmonary
or placebo. The reduction in the incidence of the primary
bypass (CPB). Cardiopulmonary bypass diverts a patient's blood
outcome (a composite of mortality, myocardial, cerebral, renal,
from circulation and oxygenates it externally to the body. The
and respiratory complications) of 7%, versus 8.5% in the
advantages of this procedure include having a still heart and a
control group, did not reach conventional statistical significance
relatively bloodless field in which to conduct the surgery. However,
(relative risk 0.83, 95% CI 0.67 to 1.01; P = 0.07).
it is well known that CPB also has unwanted, potentially harmful,
adverse effects (Kirklin 1983). Principally, the contact of patient’s • Whitlock 2015 recruited and randomised 7507 participants to
blood with the extracorporeal bypass circuit causes a complex 500 mg of intraoperative methylprednisolone or placebo. There
inflammatory response involving serum protease, platelet, and were no statistically significant differences in mortality 30 days
leukocyte activation that may progress in some cases towards a after surgery (4% in the treatment group versus 5% in the control
systemic inflammatory response syndrome (SIRS). SIRS may in group), or for a composite endpoint of mortality and major
turn be responsible for organ injury that can result in morbidity, morbidity (24% versus 24% in each group). In this trial, there
increased resource use, and mortality (Murphy 2004). was a higher rate of myocardial injury in the intervention group
(relative risk 1.22, 95% CI 1.07 to 1.38).
Description of the intervention
In a systematic review and meta-analysis, Dvirnik 2018 pooled the
By virtue of their anti-inflammatory effect, corticosteroids have results from 56 randomised controlled trials (RCTs), including the
been adopted as an optimal pharmacological strategy to reduce SIRS and DECS trials. Their findings demonstrated evidence of little
the risk of SIRS in the immediate perioperative period. Their effect or no treatment effect of corticosteroids versus placebo/controls on
is obtained through the modulation of several signal transduction mortality (3.0% versus 3.5%, respectively; RR 0.85, 95% CI 0.71 to
pathways, mostly via the nuclear factor kappa-B (NF-kB) regulated 1.01; P = 0.07, I2 = 0%), and an increased risk of myocardial injury
genes. Additional effects are also due to messenger ribonucleic acid in the corticosteroid group (8.0% versus 6.9%; RR 1.17, 95% CI 1.04
(mRNA) degradation (Barnes 2006). to 1.31; P = 0.008, I2 = 0%). The review also identified a reduced
incidence of atrial fibrillation with corticosteroid treatment (25.7%
A wide range of dosages and formulations (both intravenous
versus 28.3%; RR 0.91, 95% CI 0.86 to 0.96; P = 0.0005, I2 = 43%),
and oral) has been adopted over the years in prophylaxis of
although this analysis included the results of multiple small trials.
inflammation for cardiac surgery.
No subgroup analysis based on age was conducted as part of the
How the intervention might work review, despite it being a significant moderator of steroids’ effects
in major trials in a previous study (Dieleman 2012).
Steroids are inexpensive, generic drugs that can attenuate the
systemic inflammatory response by acting on several pathways Current treatment guidelines reflect the uncertainty of the current
involved in the inflammation caused by CPB (Chaney 2002; Hill evidence, and recommend that corticosteroids are not used
1998; Wan 1997a). routinely in adults undergoing cardiac surgery (Sousa-Uva 2017;
Wahba 2019). They also identify uncertainty as to whether
Previous systematic reviews have demonstrated that corticosteroid these drugs might have benefits in specific subgroups (younger
use can reduce the frequencies of prolonged ventilation and atrial patients), based largely on the results of a subgroup analysis of
fibrillation post-surgery, and reduce post-surgery bleeding and the the DECS trial (Dieleman 2016). Outcomes such as new onset
length of stay in the intensive care unit (ICU) (Dieleman 2011; of postoperative atrial fibrillation and infections after cardiac
Whitlock 2008). However, corticosteroids have also been shown to surgery (Zacharias 2005), on which steroids have a recognised
increase the risk of wound infection and gastrointestinal bleeding, treatment effect, may also be influenced by patient characteristics
and they have a higher rate of myocardial injury (Dieleman 2012; such as body mass index (BMI). The type of surgery is also
Whitlock 2015). a potential determinant of the potential benefit from steroid
treatment, as certain complications (such as atrial fibrillation,
Why it is important to do this review whose reduction is frequently given as a reason to use steroids) are
Despite refinement of CPB circuits and surgical techniques, organ more common in certain classes of procedures than others (Gillinov
injury and infection remain common and severe complications 2016). The evolution through the years in surgical techniques and
of cardiac surgery and account for the majority of post-surgery patient characteristics might influence corticosteroids' effects on
deaths. outcomes. A final consideration is whether the type or dose of
corticosteroid may have differing treatment effects (Dvirnik 2018).
The previous Cochrane review did not identify clinical benefits
from prophylactic corticosteroid use in adults undergoing cardiac In this review update, we aimed to build on the strengths of the
surgery with cardiopulmonary bypass, beyond a reduction in the previous version (Dieleman 2011), and to expand the evidence base

Informed decisions.
by incorporating data from new trials. Our prespecified secondary We planned to exclude studies reporting data on mixed cohorts of
aim was to evaluate specific treatment effects of moderators patients, where only a minority of the trial cohort was eligible for
such as age, BMI, and types and doses of the drugs included as this review.
intervention.
Types of interventions
Although several systematic reviews have been conducted on the
We included trials conducted in adults undergoing cardiac
topic, we believe our work expands on the current body of evidence
surgery with cardiopulmonary bypass, comparing prophylactic
by:
corticosteroid administration versus no prophylactic corticosteroid
• updating the searches (our last search was performed in October administration or placebo. We imposed no restrictions based on
2022, which, compared to the recent work by Dvirnik 2018, adds corticosteroid delivery route, dosage, duration, or intensity, nor on
seven years' worth of cardiac surgery trials to the analysis); the length of the study follow-up period. Concomitant medications
and interventions were allowed, as long as participants in the
• adopting Cochrane's current methodology and dissemination
experimental and comparator arm received the same concomitant
strategies, which ensure the rigour of the analysis and make the
medication/intervention, and the only difference between the
review’s results more accessible to and trustworthy for readers;
study arms was the corticosteroid administration.
and
• expanding the subgroup analyses and meta-regressions to Types of outcome measures
include relevant characteristics, such as the surgical operation
performed and the demographics of the trials’ participants. We recorded the number of participants with at least one event for
each of the dichotomous outcomes.
OBJECTIVES
Reporting one or more of the outcomes listed below was not an
Primary objective inclusion criterion for the review. Where a published report did
not appear to report one of these outcomes, we accessed the trial
To estimate the effects of prophylactic corticosteroid use in adults protocol and contacted the trial authors to ascertain whether the
undergoing cardiac surgery with cardiopulmonary bypass on the: outcomes were measured but not reported. Relevant trials that
measured these outcomes but did not report the data at all, or
• co-primary endpoints of mortality, myocardial, and pulmonary not in a usable format, were included in the review as part of the
complications; and narrative. In particular, since a meta-analysis of resource use and
• secondary outcomes including atrial fibrillation, infection, cost data was not feasible for the cost-effectiveness analysis due
organ injury, known complications of steroid therapy, prolonged to estimates not being generalisable, we summarised the collected
mechanical ventilation, prolonged post-operative stay, and evidence in a narrative paragraph.
cost-effectiveness.
Primary outcomes
Secondary objective
As per the original Cochrane review, we considered three primary
To explore the role of characteristics of the study cohort and specific outcomes of interest (recorded as number of affected participants):
features of the intervention in determining the treatment effects via
a series of prespecified subgroup analyses. • all-cause mortality (dichotomous outcome, during the index
hospital admission, or within 30 days, at the longest follow-up
METHODS available);
• cardiac complications (dichotomous outcome, as defined by
Criteria for considering studies for this review study authors, including cardiac compromise and fatal and
Types of studies non-fatal myocardial infarction, defined as electrocardiogram
(ECG) changes, echocardiological changes, disproportionate
Under Cochrane guidance, we updated the preplanned methods elevation of troponins); and
used in the previous version of this review (Dieleman 2010; • pulmonary complications (dichotomous outcome, as defined
Dieleman 2011). We included RCTs with parallel-group design. We by study authors, including pneumonia, embolism, reduced
excluded cross-over studies, as this study design is inappropriate pulmonary function, prolonged ventilation, pleural effusion).
given the review's focus on prophylaxis in the perioperative period
of cardiopulmonary bypass. We excluded cluster-RCTs because of Secondary outcomes
the potential confounding role of centre-specific protocols on the
clinical outcomes. Quasi-randomised trials were not eligible due to • Infectious complications (dichotomous outcome, as defined
the risk of selection bias resulting from their inclusion in the review. by study authors, including mediastinitis, wound infections,
pneumonia, need for antibiotic therapy)
Types of participants • Gastrointestinal (GI) bleeding (dichotomous outcome, as
defined by study authors, including any upper and lower GI
We included adults (18 years or older) who were:
bleeding)
• diagnosed with coronary artery disease (CAD) or cardiac valve • Occurrence of new post-surgery atrial fibrillation (dichotomous
disease (as per study authors' diagnostic criteria); and outcome, as defined by study authors)
• candidates for cardiac surgery with the use of cardiopulmonary • Re-thoracotomy for bleeding (dichotomous outcome)
bypass (according to study authors).

Informed decisions.
• Neurological complications (dichotomous outcome, as defined We also examined any relevant retraction statements and errata
by study authors, including stroke, delirium, and transitory that applied to otherwise included studies.
ischaemic attack)
• Renal failure (dichotomous outcome, according to study We did not perform a separate search for health economic studies,
authors, including dialysis, creatinine rise, and oliguria) but we examined the trial reports retrieved for data related to cost-
effectiveness of the intervention.
• Inotropic support (dichotomous outcome)
• Postoperative bleeding (continuous outcome, mL) Data collection and analysis
• Mechanical ventilation time (continuous outcome, minutes)
Selection of studies
• Length of ICU stay (continuous outcome, hours)
• Length of hospital stay (continuous outcome, days) Teams of two authors (from RGA, DF, RM, GMO, NT, RC, KE, GE,
FG) independently screened batches of titles and abstracts of all
• Patient quality of life (continuous outcome, measured from four
the potential studies we identified as a result of the search and
weeks after discharge up to one year of follow-up, reported with
coded them as 'retrieve' (eligible or potentially eligible/unclear) or
validated tools, e.g. EQ-5D-5L (Herdman 2011), a standardised
'do not retrieve'. If there were any disagreements, a third author
measure of health-related quality of life developed by the
was asked to arbitrate (from ML, SK or GJM). We retrieved the full-
EuroQol Group and administered via a simple questionnaire)
text study publication and teams of two authors (from RGA, DF,
• Cost-effectiveness analysis RM, GMO, NT, RC, KE, GE, FG) independently screened the full texts
and identified studies for inclusion, and identified and recorded
Except for patient quality of life, we recorded the outcomes at the
reasons for exclusion of the ineligible studies. We resolved any
longest available follow-up during the index hospital admission,
disagreement through discussion or, if required, we consulted a
from the day of surgery until discharge.
third author (from ML, SK, or GJM). We identified and excluded
For outcomes that could potentially occur more than once during duplicates and collated multiple reports of the same study so that
the period of interest, only first events were recorded. each study rather than each report is the unit of interest in the
review. We recorded the selection process in sufficient detail to
Search methods for identification of studies complete a PRISMA flow diagram and 'Characteristics of excluded
studies' table (Liberati 2009).
Electronic searches
Data extraction and management
The following electronic databases were searched on 14 October
2022 to identify reports of relevant randomised clinical trials: We extracted data from the full-text article of every included study
using a standardised, piloted, data-extraction form. When authors
• Cochrane Central Register of Controlled Trials (CENTRAL; 2022, stated explicitly "no major complications" occurred in the study,
Issue 10) in the Cochrane Library; we interpreted this as no deaths, and no cardiac or pulmonary
• MEDLINE Ovid (1946 to 13 October 2022); complications for that specific study.
• Embase Ovid (1947 to 13 October 2022);
Two review authors (from RGA, DF, RM, GMO, NT, RC, KE, GE, FG, MK)
• Science Citation Index Expanded (SCI-EXPANDED) and Social
independently extracted study characteristics and outcome data
Science Citation Index (SSCI), Web of Science via Clarivate
from included studies. We extracted the following information.
Analytics (1900 to 14 October 2022); and
• CINAHL (Cumulative Index to Nursing and Allied Health • Methods: study design, total duration of study, number of study
Literature) EBSCO (1937 to 14 October 2022). centres and location, study setting, and date of study.
• Participants: number randomised, number lost to follow-up/
The sensitivity-maximising version of the Cochrane RCT filter was
withdrawn, number analysed, mean age, body mass index
applied to MEDLINE (Lefebvre 2021), and adaptations of it to the
(BMI), gender, severity of condition according to study authors
other databases where appropriate. Search strategies are displayed
(high risk setting), surgery type, inclusion criteria, and exclusion
in Appendix 1. No language restrictions were applied; native
criteria.
speakers were contacted for translation of articles in languages
other than English. • Interventions: intervention, comparison, dose and type of
steroid, concomitant medications, and excluded medications.
We included studies reported as full text, those published as • Outcomes: primary and secondary outcomes specified and
abstract only, and unpublished data. collected, and time points reported where applicable.
• Notes: funding for trial, and notable conflicts of interest of trial
We also conducted a search of ClinicalTrials.gov
authors.
(www.ClinicalTrials.gov) and the World Health Organization (WHO)
International Clinical Trials Registry Platform (ICTRP) Search Portal We resolved disagreements by consensus or by involving a third
(apps.who.int/trialsearch) for ongoing or unpublished trials (up to person (from RGA, ML, SK, or GJM). One review author (RGA)
5 November 2022). transferred data into Review Manager (RevMan; RevMan 2023).
We double-checked that the data were entered correctly by
Searching other resources
comparing the data presented in the systematic review with the
We screened the reference lists from retrieved randomised trials, data-extraction form. A second review author (from FG, RM, GMO)
meta-analyses, and systematic reviews to identify additional trials. spot-checked study characteristics for accuracy against the trial
report.

Informed decisions.
Open-source computer software was used for data extraction from Dealing with missing data
figures (Plot Digitizer).
We analysed the data on an intention-to-treat basis (once
We attempted to contact study authors for any missing data. randomised to an intervention, the participants are analysed in that
intervention and analysis includes all randomised participants) as
Assessment of risk of bias in included studies far as possible (Higgins 2023b). We contacted investigators or study
sponsors in order to verify key study characteristics and obtain
Teams of two authors (from RGA, DF, RM, GMO, NT, RC, KE, GE,
missing numerical outcome data where possible (e.g. when a study
FG) independently assessed risk of bias for batches of the included
was only available in abstract form). Where possible, we used
studies using the criteria outlined in the risk of bias 1 (RoB 1) tool
the RevMan calculator to calculate missing standard deviations
in the Cochrane Handbook for Systematic Reviews of Interventions
using other data from the trial, based on methods outlined in the
(Higgins 2011). We resolved any disagreements by discussion or
Cochrane Handbook (Higgins 2023c).
by involving another author (GJM). We assessed the risk of bias
according to the following domains. Assessment of heterogeneity
• Random sequence generation We followed guidance for assessing heterogeneity described in
• Allocation concealment Chapter 10 of the Cochrane Handbook (Deeks 2023). We examined
clinical (participants' characteristics, nature of the intervention)
• Blinding of participants and personnel
and methodological aspects (trials' design and specifics of how
• Blinding of outcome assessment they were conducted) of the included studies, and reflected
• Incomplete outcome data our observations about these features in the certainty of the
• Selective outcome reporting evidence judgements available in the summary of findings table.
• Other bias (e.g. potential sources of bias introduced by the trial We also visually inspected forest plots to consider the direction
design, or by specific aspects of the surgical techniques and and magnitude of effects and the degree of overlap between
materials used) confidence intervals. We used the I2 statistic to measure statistical
heterogeneity amongst the trials in each analysis, and used the
We assessed each potential source of bias as high, low, or unclear rough guide for interpreting I2 values, as set out in the Cochrane
risk, and provided a quote from the study report where appropriate, Handbook:
together with a justification for our judgement in the risk of bias
table. We summarised the risk of bias judgements across different • 0% to 40%: might not be important;
studies for each of the domains listed and presented these in • 30% to 60%: may represent moderate heterogeneity;
a graph. We also summarised the risk of bias across studies for • 50% to 90%: may represent substantial heterogeneity; and
outcomes reported in the summary of findings table as part of our
GRADE assessment (integrating information about the individual • 75% to 100%: considerable heterogeneity.
ratings and the seriousness of the concerns. If a study was rated a We acknowledge that there is substantial uncertainty in the
low risk of bias across all domains, we rated it at low risk of bias
value of I2 when there are few studies. We therefore also
overall; if it was rated at high risk of bias on any domain, we rated it
considered the P value (level of significance below 0.05) from the
at high risk of bias overall; and if it was rated at unclear risk of bias
Chi2 test to assess heterogeneity. If we identified substantial or
or a mixture of both low and unclear risk but not at high risk, we
considerable heterogeneity, we reported it and explored possible
rated it as unclear overall). When considering treatment effects, we
causes by subgroup analyses (Subgroup analysis and investigation
took into account the risk of bias for the studies that contributed to
of heterogeneity). Our exploration of heterogeneity took into
that outcome.
account current areas of uncertainty identified by international
Where information on risk of bias related to unpublished data or guidelines (Sousa-Uva 2017); specifically, the potential differences
correspondence with a trialist, we noted this in the risk of bias table. in outcomes due to characteristics of the study population (e.g.
age, BMI), the interventions (e.g. steroids, dose), and the trials (e.g.
Measures of treatment effect publication year), by means of a meta-regression analysis.
We analysed dichotomous data as risk ratios with 95% confidence Assessment of reporting biases
intervals and continuous data as mean difference with 95%
confidence intervals. We entered the data presented as a scale with We explored reporting bias for primary outcomes by funnel plot
a consistent direction of effect. When skewed data were reported, inspections, and a formal test of asymmetry (Egger 1997). We
we presented these narratively as medians and interquartile also compared outcomes with those specified in the protocol or
ranges. methods section of the included reports, as per the guidance in the
Cochrane Handbook (Page 2023).
Unit of analysis issues
Data synthesis
Individual adults were the unit of analysis in the review. If studies
reported outcomes at multiple time points, we considered the We undertook meta-analyses only where this was meaningful;
outcome measurements reported at the longest available follow- that is, if the treatments, participants, and the underlying clinical
up. For multi-armed trials in which more than one experimental question were similar enough for pooling to make sense. We
arm was of interest in the review, we created multiple parallel anticipated the direction of effect across studies to vary based
comparisons by splitting the control group equally (Higgins 2023a). on population characteristics, specifics of the intervention itself,
and study setting. We therefore used random-effects models
to pool the evidence. We used the Mantel-Haenszel method
Informed decisions.
for dichotomous variables and the inverse-variance method for We created a summary of findings table using GRADEpro software
continuous outcomes. We followed the guidance from Chapter (Guyatt 2011), for the comparison of corticosteroids with placebo/
10 of the Cochrane Handbook (Deeks 2023). We carried out all no treatment, for the following outcomes:
analyses in RevMan (RevMan 2023). We performed additional
quantitative analysis (such as a meta-regression using a mixed- • all-cause mortality;
effects model) outside of RevMan in R (R 4.0, R foundation for • cardiac complications;
Statistical Computing, Vienna, Austria) (R; Viechtbauer 2010). When • pulmonary complications;
pooling the data in a meta-analysis was unfeasible, we summarised • infectious complications;
the results from the studies in narrative paragraphs.
• gastrointestinal bleeding;
Subgroup analysis and investigation of heterogeneity • renal failure; and
We carried out the following subgroup analyses for our primary • length of hospital stay.
outcomes and for any outcomes with substantial heterogeneity: Outcomes were recorded at the longest available follow-up during
the index hospital admission, from the day of surgery until
• high dose (total administered dose > 1000 mg hydrocortisone
equivalents*) and low dose (total administered dose < 1000 mg discharge.
hydrocortisone equivalents*); We used the five GRADE considerations (study limitations,
• surgery type (CABG, valve surgery, both CABG and valve consistency of effect, imprecision, indirectness, and publication
surgeries); and bias) to assess the certainty of a body of evidence as it
• steroid type (dexamethasone, prednisolone, relates to the studies which contributed data to the meta-
methylprednisolone, hydrocortisone). analyses for the prespecified outcomes. The overall risk of bias
assessment was used for GRADE assessments. We used methods
*The dose equivalent was calculated based on a dose of and recommendations described in Chapter 14 of the Cochrane
hydrocortisone administered to a patient weighing 70 kg. We Handbook for Systematic Reviews of Interventions (Schünemann
performed steroid conversion calculations using online software 2023). We justified all decisions to downgrade the certainty of
(Steroid Conversion Calculator), following the principles described the evidence using footnotes, and we made comments to aid
in pharmacology textbooks (Katzung 2014). readers' understanding of the review where necessary. Working
independently, two review authors (from RGA, DF, RM, GMO, NT,
We used the formal test for subgroup differences in RevMan, and
RC, KE, GE, FG) made judgements about evidence certainty, and
based our interpretation on this test.
we resolved disagreements through discussion or by involving a
We performed a post hoc meta-regression using a mixed-effects third author (from RGA, ML, SK, or GJM). Judgements were justified,
model to explore the role of continuous moderators such as steroid documented, and incorporated into the reporting of results for each
dose, participants’ age, BMI, and publication year on primary outcome.
outcomes and on any outcomes with substantial heterogeneity.
RESULTS
Sensitivity analysis
Description of studies
We performed a sensitivity analysis for the primary outcomes, to
test whether characteristics of the studies that could introduce Results of the search
bias affected the results of our analyses. We considered exclusively Searches of CENTRAL, MEDLINE (PubMed), Embase, CINAHL, and
studies with a low risk of bias for all of the following domains: Web of Science (SCI/SSCI) identified 4561 records (zero records
random sequence generation; allocation concealment; blinding were obtained from searching other sources), of which 3520
of participants, healthcare providers, or outcome assessors; and remained after duplicates were removed. After screening of titles
incomplete outcome data and attrition (we considered > 10% and abstracts and removal of 3347 irrelevant records, we retrieved
missing data across each arm as a cut-off value). 173 potentially relevant reports for detailed assessment. After
assessments of the full-text papers, we excluded 41 as irrelevant
Summary of findings and assessment of the certainty of the and a further 34 with reasons (Excluded studies). We included
evidence a total of 72 studies (95 reports) related to completed studies
We based our conclusions only on findings from the quantitative or (Characteristics of included studies) and three reports for three
narrative synthesis of studies included in this review. ongoing studies (Characteristics of ongoing studies) in the review.
See Figure 1.

Informed decisions.
Figure 1. Study flow diagram
4561 records 0 records

identified through identified through
database searching other sources
3520 records after

duplicates removed
3347 records
3520 records
excluded as
screened
irrelevant
41 full-text reports
excluded as irrelevant
34 studies (34 reports)
excluded with reasons:
• ineligible population
173 full-text
(n = 3)
reports assessed
• ineligible
for eligibility
intervention (n = 3)
• ineligible control
group (n = 3)
• no relevant
outcomes assessed
(n = 25)
72 studies (95
reports) included
in qualitative
synthesis
3 ongoing studies
(3 reports)
72 studies included
in quantitative
synthesis
(meta-analysis)

Informed decisions.
72 studies included
Figure 1. (Continued)
in quantitative
synthesis
(meta-analysis)
Included studies support in 23 studies (32%), postoperative bleeding in five studies

(7%), mechanical ventilation time in 32 studies (44%), ICU length of
We have summarised participant demographics, interventions, and
stay in 30 studies (42%), hospital length of stay in 25 studies (35%),
outcomes in Characteristics of included studies and Table 1. A
quality of life in two studies (3%). (See Table 2.)
summary with the extracted data from each study is provided in
Table 2. Three studies declared support by industry or commercial
companies (Kilger 2003a; Volk 2001; Volk 2003). Nine studies were
Of the included studies, 17/72 were published after 2010, 37/72
multi-arm trials (Bourbon 2004; Chaney 2001; Ferries 1984; Harig
were published in the 2000s, 11/72 in the 1990s, 4/72 in the 1980s,
1999; Kilickan 2008; Oliver 2004; Rubens 2005; Turkoz 2001; Vukovic
and 3/72 in the 1970s. Most of the studies were conducted in Europe
2011).
(44/72) and North America (18/72).
Excluded studies
A total of 17,282 participants were included in these 72 trials.
Sample size in the studies ranged from 13 (Rumalla 2001) to 7507 We excluded forty-one reports as irrelevant after full-text screening.
(Whitlock 2015), with a median number of 52 participants. The The table of excluded studies lists 34 studies that did not meet
median age for people included in the studies was 62.9 years inclusion criteria on closer inspection (Characteristics of excluded
(lowest in Abd El-Hakeem 2003a at 36 years, highest in Yared 2007 studies). The reasons for exclusion in these were as follows: three
at 71 years); and the median BMI was 27.4 (lowest in Maddalli 2019 studies (9%) reported the results of a ineligible population (Launo
at 26, highest in Lomirovotov 2013 at 29.4). 1990; Toledo-Pereyra 1980; Vallejo 1977); three studies (5%) did
not have an eligible control group (Santarpino 2009a; Santarpino
Coronary surgery was the most common setting. Nine studies 2009b; Vogelzang 2007); 25 studies (49%) did not assess relevant
included high-risk surgery patients (Ferries 1984; Kilger 2003a; endpoints (Anic 2004; Biagioli 1981; Boldt 1986; Jansen 1991b;
Kilger 2003b; Taleska Stupica 2020; Vukovic 2011; Weis 2006; Weis Jorens 1993; Karlstad 1993; Kawamura 1995; Kawamura 1999; Kito
2009; Whitlock 2006; Whitlock 2015). The other study populations 1980; Kobayashi 1996; Loubser 1997; Ming 2001; Miranda 1982;
consisted mainly (89%) of low-risk, first-time CABG or valve surgery. Raff 1987; Ranucci 1994; Schmartz 1996; Tabardel 1996; Thompson
Forty-three studies were conducted in cohorts undergoing CABG, 1980; Thompson 1982; Turkoz 2000; Us 2001; Van Overveld 1994;
three in participants undergoing exclusively valve surgery (Abd Wan 1997b; Yaeger 2005; Yasuura 1977); and three studies (9%) did
El-Hakeem 2003a; Abd El-Hakeem 2003b; Mayumi 1997), and 26 not test an eligible intervention (Kirsh 1979; Lee 2005; Levinsky
studies in participants undergoing both CABG and valve surgeries. 1979).
Type and dosage of steroids and postoperative management Ongoing studies
varied across studies. Methylprednisolone was the treatment
administered in 39 trials, dexamethasone in 17, hydrocortisone We identified three ongoing studies (Ongoing studies).
in nine trials (Halonen 2007; Hauer 2012; Kilger 2003a; Kilger
DECS-II will test the effect of a single intravenous (IV) injection
2003b; Mahrose 2019; Sano 2003; Sano 2006; Weis 2006; Weis
of dexamethasone after induction of anaesthesia, but before
2009), prednisolone in two (Bingol 2005; Harig 1999), a combination
initiation of CPB. The trial will be a multicentre study and assessor-
of methylprednisolone and dexamethasone in three (Gomez
blinded, with a pragmatic design with post-randomisation consent.
Polo 2018; Oliver 2004; Prasongsukarn 2005), a combination of
It is expected to recruit 2800 participants.
methylprednisolone and hydrocortisone in one (Al-Shawabkeh
2017), and betamethasone dipropionate in one (Starobin 2007). A NCT00879931 is an ongoing trial in Belgium, testing the impact of
high dose of steroids (> 1000 mg total hydrocortisone equivalents) methylprednisolone against placebo in people undergoing elective
was used in 54 trials, low doses (< 1000 mg hydrocortisone cardiac surgery, in regard to postoperative renal dysfunction and
equivalents) in 18. The median dosage used was 3500 mg of failure in the first 48 hours. Investigators have not specified the
hydrocortisone equivalent (ranging from 100 mg in Halonen 2007 target sample size.
to 25,000 mg in Engelman 1995). The mean was 4689 mg with a
standard deviation of 4600 mg. A placebo was used as comparison NCT00807521 will study the impact of high-dose dexamethasone
in 53 trials, while 19 adopted no treatment in the control group. before surgery against placebo on expression of p38 in adults
undergoing cardiac surgery. The target sample size is 96
Outcomes were reported as following: all-cause mortality participants.
in 47 studies (65%), cardiac complications in 29 studies
(40%), pulmonary complications in 22 studies (31%), infectious Risk of bias in included studies
complications in 35 studies (49%), gastrointestinal bleeding in 11
studies (15%), atrial fibrillation in 30 studies (42%), re-thoracotomy Only four studies scored low risk in all bias assessment domains
in 18 studies (25%), renal failure in 19 studies (26%), inotropic (Dieleman 2012; Mayumi 1997; Prasongsukarn 2005; Whitlock
2015), while the remaining studies were rated as at unclear or high
Informed decisions.
risk for at least one of the criteria, with risk of detection bias due to inadequate blinding of outcome assessment being the most
common in 60/72 (84%) of trials (Figure 2; Figure 3).
Figure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages
across all included studies.
Random sequence generation (selection bias)

Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias): All outcomes
Selective reporting (reporting bias)
Other bias
0% 25% 50% 75% 100%
Low risk of bias Unclear risk of bias High risk of bias

Informed decisions.
Figure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Blinding of participants and personnel (performance bias)
Incomplete outcome data (attrition bias): All outcomes

Blinding of outcome assessment (detection bias)
Random sequence generation (selection bias)
Allocation concealment (selection bias)
Selective reporting (reporting bias)

Other bias
Abbaszadeh 2012 + + + ? + + +
Abd El-Hakeem 2003a + + + ? + + +
Abd El-Hakeem 2003b + + + ? + + +
Al-Shawabkeh 2017 + + + ? + + +
Amr 2009 ? ? ? ? + + +
Andersen 1989 ? ? ? ? ? ? +
Bingol 2005 + ? + − ? ? +
Boscoe 1983 + ? ? ? ? ? +
Bourbon 2004 ? ? ? ? + ? +
Cavarocchi 1986 ? ? − ? + ? +
Celik 2004 ? ? + ? + + +
Chaney 1998 ? ? + ? + + +
Chaney 2001 ? ? + ? + + +
Codd 1977 − ? ? ? + ? +
Coetzer 1996 + ? ? ? ? + +
Demir 2009 ? ? ? ? + + +
Demir 2015 ? ? ? ? + + +
Dieleman 2012 + + + + + + +
El Azab 2002 ? ? ? ? + + +
Enc 2006 ? ? + ? + + +
Engelman 1995 ? ? ? ? + + +

Informed decisions.
Enc 2006 ? ? + ? + + +
Engelman 1995 ? ? ? ? + + +
Ferries 1984 + + + ? + + +
Fillinger 2002 ? ? + ? + + +
Giomarelli 2003 + + + ? + + +
Glumac 2017 + + + ? + + +
Gomez Polo 2018 ? ? + ? + + +
Halonen 2007 + ? + ? + + +
Halvorsen 2003 + + + ? ? + +
Hao 2019 ? ? ? ? ? + +
Harig 1999 ? ? ? ? ? + +
Hauer 2012 + ? + + − + +
Jansen 1991 ? ? ? ? + + +
Kerr 2012 + + + + ? + +
Kilger 2003a ? ? − − + + +
Kilger 2003b ? ? ? ? + ? +
Kilickan 2008 ? ? ? ? ? + +
Liakopoulos 2007 + ? ? ? + + +
Loef 2004 ? ? + ? + + +
Lomirovotov 2013 + + ? ? + + +
Maddalli 2019 + + ? + + + +
Mahrose 2019 + ? ? ? + + +
Mardani 2012 + ? ? ? ? + +
Mayumi 1997 + + + + + + +
McBride 2004 ? ? + ? + + +
Morton 1976 + ? + + + + +
Murphy 2011 + ? + ? + + +
Oliver 2004 ? ? + + + ? +
Prasongsukarn 2005 + + + + + + +
Rao 1977 ? ? − − + + +
Rubens 2005 + + + ? + + +
Rumalla 2001 − ? ? ? + + +
Sano 2003 ? ? ? ? + + +
Sano 2006 ? ? + ? + + +
Schurr 2001 ? ? − − + + +
Sobieski 2008 ? ? + ? + + +

Informed decisions.
Sobieski 2008 ? ? + ? + + +
Starobin 2007 ? ? ? ? + + +
Taleska Stupica 2020 + + + + ? + +
Tassani 1999 ? ? + ? + + +
Toft 1997 ? ? ? ? + + +
Turkoz 2001 ? ? ? ? ? + +
Volk 2001 ? ? + ? ? + +
Volk 2003 ? ? ? ? + + +
Von Spiegel 2001 ? ? + ? + + +
Vukovic 2011 + ? − + + + +
Wan 1999 ? + − ? + + +
Weis 2006 ? + + ? + + +
Weis 2009 + ? + ? + + +
Whitlock 2006 + ? + + + + +
Whitlock 2015 + + + + + + +
Yared 1998 ? ? + ? − ? +
Yared 2007 + ? + ? + + +
Yilmaz 1999 ? ? + ? − + +
Amongst the primary outcomes, blinding of outcome assessment unclear risk. In 8% (6/72), the blinding was inadequate, and we
was the domain with the lowest number of studies at low risk of rated these studies as at high risk.
bias (4/25, 7/25, and 6/18 studies at low risk of bias for mortality,
cardiac, and pulmonary complications, respectively). Although this Blinding of outcome assessment
is probably of limited importance for the outcome of mortality, Seventeen percent (12/72) of the studies had put in place adequate
it could influence the certainty of the findings related to cardiac measures to blind the researchers assessing outcomes, so were
complications and pulmonary complications. rated at low risk of bias. In 78% (56/72) of the studies, those
measures were not adequately described, leading to a rating
Allocation
of unclear risk. In 6% (4/72), there was evidence of inadequate
Random sequence generation blinding of outcome assessment, and we rated these studies as at
high risk.
Adequate random sequence generation was present in 43% (31/72)
of the studies, while 54% (39/72) provided insufficient information Incomplete outcome data
and were therefore rated as unclear. We judged 3% (2/72) of the
studies as at high risk for the choice of randomisation technique. Risk of attrition bias was low (adequate completeness of outcome
data, with reporting of attrition and exclusions and adequate
Allocation concealment rationale for these) for 78% of the studies (56/72), unclear
(insufficient information about the above) in 18% (13/72), and high
Adequate concealment of allocation (sufficient information to
in 4% (3/72), with studies from this last group reporting losses at
determine that intervention allocations could not have been
follow-up of up to 30% of the participants.
foreseen before or during enrolment) was present in 26% (19/72) of
the trials, and 74% (53/72) of the studies had an unclear risk. Selective reporting
Blinding Eighty-eight percent (63/72) of the studies scored a low risk
(adequate reporting of prespecified outcomes) for reporting bias.
Blinding of participants and personnel
We rated 12% (9/72) as at unclear risk because of poor definitions of
We classified 56% (40/72) of studies as blinded for both participants the outcome selection and inadequate information on the process.
and investigators, and rated these at low risk. In 36% of the studies
(26/72), there was insufficient information, leading to a rating of Other potential sources of bias
No other sources of bias were identified.

Informed decisions.
Effects of interventions Primary outcomes

See: Summary of findings 1 Prophylactic corticosteroids All-cause mortality
compared with placebo or no corticosteroids in adults undergoing The use of corticosteroids in adult cardiac surgery with
cardiac surgery with cardiopulmonary bypass cardiopulmonary bypass may have little or no effect on mortality
Below, we present the results for the comparison of prophylactic (RR 0.90, 95% CI 0.75 to 1.07; 25 studies, 14,940 participants;
corticosteroids to placebo or no corticosteroids. See also Summary low-certainty evidence; Analysis 1.1), compared to placebo or no
of findings 1. treatment.
The funnel plots and Egger’s tests for mortality did not demonstrate
important asymmetry (Figure 4).
Figure 4. Funnel plot of mortality. Abbreviations

Log: logarithm; RR: risk ratio; SE: standard error.
0 SE(log[RR])
0.5
1.5
RR
2
0.01 0.1 1 10 100
Cardiac complications (RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-
certainty evidence; Analysis 1.2).
The evidence also suggested that corticosteroids may increase
the risk of cardiac complications by 7.7% (range 6.8% to 8.6%) The funnel plots and Egger’s tests for the cardiac complications did
compared with 6.6% in the group given placebo or no treatment not demonstrate important asymmetry (Figure 5).

Informed decisions.
Figure 5. Funnel plot of cardiac complications. Abbreviations

0 SE(log[RR])
0.5
1.5
RR
2
0.01 0.1 1 10 100
Pulmonary complications to 0.99; 18 studies, 13,549 participants; low-certainty evidence;

Analysis 1.3).
Corticosteroids may slightly reduce the risk of pulmonary
complications by 6.9% (range 6.1% to 7.7%) compared with 7.8% The funnel plots and Egger’s tests for pulmonary complications did
in the group given placebo or no treatment (RR 0.88, 95% CI 0.78 not demonstrate important asymmetry (Figure 6).

Informed decisions.
Figure 6. Funnel plot of pulmonary complications. Abbreviations

0 SE(log[RR])
0.5
1.5
RR
2
0.01 0.1 1 10 100
Secondary outcomes 1.14 to 1.72; 12 studies, 5683 participants; Analysis 2.4), compared
to those receiving placebo or no treatment.
Infectious complications
The frequency of post-surgery infections may be reduced by Neurological complications
corticosteroids by 10.3% (range 9.4% to 11.3%) compared with Corticosteroids may have little or no effect on neurological
12.3% in the placebo and no treatment groups (RR 0.84, 95% CI complications (RR 0.92, 95% CI 0.73 to 1.15; 17 studies, 13,514
0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence; participants; Analysis 2.5), compared to placebo or no treatment.
Analysis 2.1).
Renal failure
Gastrointestinal bleeding
The evidence suggests that corticosteroids may have little or
Corticosteroids administration may have little or no effect on no effect on renal failure (RR 0.84, 95% CI 0.69 to 1.02; 13
gastrointestinal bleeding, a recognised adverse effect of CPB (RR studies, 12,799 participants; low-certainty evidence; Analysis 2.6),
1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low- compared to placebo or no treatment.
certainty evidence; Analysis 2.2), compared to placebo or no
treatment. Inotropic support
Occurrence of new post-surgery atrial fibrillation Corticosteroids may have little or no effect on the use of inotropic
support (RR 0.93, 95% CI 0.76 to 1.13; 23 studies, 1878 participants;
Compared to placebo or no treatment, corticosteroids may reduce Analysis 2.7), compared to placebo or no treatment.
the frequency of new-onset post-surgery atrial fibrillation by 7.1%
(range 4.3% to 9.9%) (RR 0.75, 95% CI 0.65 to 0.85; 28 studies, Postoperative bleeding
14,468 participants; Analysis 2.3), although this result was affected
Results from the pooled analysis of postoperative bleeding (mLs)
by moderate heterogeneity (I2 = 50%).
were unclear due to considerable heterogeneity (I2 = 92%; Analysis
Re-thoracotomy for bleeding 2.8).
The risk of re-thoracotomy may be increased by 2% (range 0.7% to

3.7%) amongst patients receiving corticosteroids (RR 1.40, 95% CI

Informed decisions.
Mechanical ventilation time Surgery type

The result of the analysis of duration of ventilation (hours) was also There was no evidence of a difference between the different surgery
limited by considerable heterogeneity (I2 = 92%; Analysis 2.9). types for the primary outcomes (test for subgroup differences P >
0.05; Analysis 4.1; Analysis 4.2; Analysis 4.3).
Length of ICU stay
There was evidence of treatment subgroup interaction (test
Similarly, the analysis of length of intensive care unit stay was for subgroup differences P < 0.01) by type of surgery for the
limited by considerable heterogeneity (I2 = 86%; Analysis 2.10). outcome atrial fibrillation. Corticosteroids reduced the rate of atrial
fibrillation amongst CABG patients (RR 0.61, 95% CI 0.52 to 0.72;
Length of hospital stay
I2 = 0%; 16 studies, 1400 participants; Analysis 4.4.1), and cohorts
Although this result is unclear due to the high heterogeneity (I2 where mixed types of surgical procedures were performed (RR
= 81%), the mean length of hospital stay (days) may be slightly 0.86, 95% CI 0.76 to 0.98; I2 = 48%; 11 studies, 13,048 participants;
reduced in the corticosteroid groups (MD -0.50, 95% CI -0.97 to Analysis 4.4.3). Only one study assessed the effects in isolated valve
-0.04; 25 studies, 1841 participants; very low-certainty evidence; surgery and reported little to no evidence of a difference between
this equates to alength of hospital stay in the intervention groups the groups (RR 0.33, 95% CI 0.04 to 2.96; 1 study, 20 participants;
which was on average 0.5 days shorter; Analysis 2.11), compared to Analysis 4.4.2).
the groups receiving placebo or no treatment.
There was evidence of treatment subgroup interaction by type of
Patient quality of life and cost-effectiveness analysis surgery for length of ICU stay (test for subgroup differences P < 0.01)
amongst the three subgroups (CABG: MD -5.41 hours, 95% CI -8.05
Two studies reported data about participants’ quality of life (QoL)
and health economics using two different metrics (EQ-5D and to -2.77; I2 = 85%; 21 studies, 859 participants; Analysis 4.7.1; valve:
SF-36) at two different time points and were not amenable to MD -18.09 hours, 95% CI -23.68 to -12.49; I2 = 25%; 2 studies, 66
pooled analyses; hence, we have narratively summarised the participants; Analysis 4.7.2; mixed: MD -4.45 hours, 95% CI -12.30 to
collected evidence. 3.39; I2 = 71%; 7 studies, 729 participants; Analysis 4.7.3). In-group
heterogeneity, however, remained substantial.
In a sub-study Dieleman and colleagues conducted as part of the
DECS trial (evaluating the effect of 1 mg/kg of dexamethasone; There was no evidence of subgroup treatment interaction for the
Dieleman 2012) at 12-month follow-up, the authors analysed outcomes inotropic support, mechanical ventilation, and length of
health-related QoL at 30 days and 12 months (Dieleman 2017), hospital stay (test for subgroup differences P > 0.05; Analysis 4.5;
and performed a cost analysis of the trial results. After one year, Analysis 4.6; Analysis 4.8, respectively).
QoL was unaltered between the two groups, despite a higher
incidence of respiratory failure in the control cohort, and a higher Steroid type
mean cost per patient (EUR 13,448 (euros)) when compared to There was no evidence of a difference (test for subgroup differences
the dexamethasone group (EUR 12,364). Authors estimated a 97% P > 0.05) between the different steroid types for the primary
probability of high-dose dexamethasone being cost-effective, at a outcomes of mortality, cardiac complications, and pulmonary
willingness-to-pay threshold of EUR 20,000. complications (Analysis 5.1; Analysis 5.2; Analysis 5.3).
Weis and colleagues measured health-related QoL at six months Steroid type also had evidence of subgroup treatment interaction
after discharge from the ICU via the Short Form 36 (SF-36) survey for the secondary outcomes: duration of mechanical ventilation
(Weis 2009). Of 36 participants included in the trial, 28 were (test for subgroup differences P < 0.001; Analysis 5.6) and
included in the six-month follow-up analysis. Domains related to length of hospital stay (test for subgroup differences P < 0.001;
physical function, chronic pain, general health, vitality, and mental Analysis 5.8), but heterogeneity remained high.A combination
health all showed improved scores in participants who received of methylprednisolone plus dexamethasone was also the only
hydrocortisone (a total of 310 mg). intervention that determined a reduction in duration of mechanical
ventilation (-398.70 minutes, 95% CI -520.98 to -276.42; 1 study,
Subgroup analyses 125 participants; Analysis 5.6.4), although the validity of this finding
High dose versus low dose is limited by the fact that is based on the report from a single
small trial. In subgroups assessing dexamethasone (-52.27 minutes,
We performed subgroup analyses for the primary outcomes of 95% CI -98.24 to -6.31; I2 = 80%; 9 studies, 896 participants;
mortality, cardiac complications, and pulmonary complications. Analysis 5.6.1), methylprednisolone (5.44 minutes, 95% CI -69.58
There was no evidence of a difference between the different doses
to 80.47; I2 = 90%; 18 studies, 721 participants; Analysis 5.6.2),
for any outcome (test for subgroup differences P > 0.05; Analysis 3.1;
prednisolone (-172.42 minutes, 95% CI -816.86 to 472.02; I2 =
Analysis 3.2; Analysis 3.3, respectively).
95%; 2 studies, 60 participants; Analysis 5.6.3), and hydrocortisone
There was no evidence of subgroup treatment interaction for (-122.44 minutes, 95% CI -428.40 to 183.52; I2 = 16%; 2 studies,
the outcomes atrial fibrillation, inotropic support, mechanical 171 participants; Analysis 5.6.5), effects on length of mechanical
ventilation time, length of ICU stay, and length of hospital stay (test ventilation were unclear and in-group heterogeneity remained
for subgroup differences P > 0.05; Analysis 3.4; Analysis 3.5; Analysis substantial. Prednisolone (-4.65 days, 95% CI -6.04 to -3.26; 1 study,
3.6; Analysis 3.7; Analysis 3.8, respectively). 40 participants; Analysis 5.8.3) and hydrocortisone (-0.70 days,
95% CI -1.12 to -0.28; 1 study, 176 participants; Analysis 5.8.4)
reduced hospital stay, whereas dexamethasone (-0.03 days, 95%
CI -0.82 to 0.75; I2 = 75%; 5 studies, 598 participants; Analysis
Informed decisions.
5.8.1) and methylprednisolone (-0.46 days, 95% CI -1.09 to 0.17; certainty evidence) and new-onset post-surgery atrial fibrillation.
I2 = 74%; 17 studies, 687 participants; Analysis 5.8.2) did not. However, further analyses suggested prevention of atrial fibrillation
Persistent substantial heterogeneity still prevents us from drawing was effective in trials conducted on CABG patients (while findings
meaningful conclusions from these subgroup analyses. in the mixed and valve groups are limited by heterogeneity and
small sample size, respectively) and in studies where low doses
There was no evidence of subgroup treatment interaction for the of steroids were used. Prophylactic corticosteroids may increase
outcomes atrial fibrillation, inotropic support, and length of ICU slightly the risk of re-thoracotomy for bleeding. There were no
stay (test for subgroup differences P > 0.05; Analysis 5.4; Analysis important treatment effects demonstrated for other secondary
5.5; Analysis 5.7, respectively). outcomes, including renal failure, gastrointestinal bleeding (both
low-certainty evidence), neurological complications, and inotropic
Meta-regression analyses support. Results are unclear for mechanical ventilation time,
Meta-regression analyses indicated that treatment effects were length of ICU stay, and length of hospital stay (very low-certainty
consistent across different age groups and body mass index evidence). One large trial indicated that high-dose dexamethasone
(BMI) levels, with minimal impact on secondary outcomes. In a was extremely likely to be cost-effective, at a willingness-to-pay
moderator analysis (Table 3), dose equivalent of steroid (calculated threshold of EUR 20,000. Another trial found that patients' health-
by conversion to an equal dose of hydrocortisone) was a positive related quality of life improved after treatment.
moderator on the duration of mechanical ventilation (regression
coefficient 0.009, 95% CI 0.003 to 0.022; P = 0.009). BMI (regression There were insufficient numbers of studies to assess whether
coefficient -19.091, 95% CI -31.446 to -6.736; P = 0.003) and dose the type of corticosteroid was an important determinant of
equivalent of steroid (regression coefficient -0.001, 95% CI -0.001 to outcome. For instance, a combination of methylprednisolone
less than 0.001; P = 0.034) were negative moderators for ICU length and dexamethasone was the only intervention that reduced
of stay. Publication year was a positive moderator for postoperative the duration of mechanical ventilation and length of hospital
bleeding (regression coefficient 11.096, 95% CI 2.542 to 19.649; P = stay, but the evidence was based on a single small trial.
0.011). Effects of dexamethasone, methylprednisolone, prednisolone, and
hydrocortisone on outcomes were unclear and inconsistent, with
Sensitivity analyses high heterogeneity amongst the studies.
A sensitivity analysis, conducted exclusively in the studies that were Whilst there was no evidence of an effect in most analyses,
rated at low risk in all bias assessments, demonstrated little or no which were limited by high heterogeneity and by the numbers of
treatment effect on mortality (RR 0.88, 95% CI 0.72 to 1.06; 2 studies, studies included, subgroup and moderator analyses also suggested
11,989 participants; Analysis 6.1), and important uncertainty as that treatment effects were similar in younger and older trial
to the treatment effects on cardiac complications (RR 1.14, 95% participants or those with higher versus lower BMI, with minimal
CI 0.89 to 1.45; 2 studies, 11,989 participants; Analysis 6.2) and moderator effects in secondary outcomes. Publication year was a
pulmonary complications (RR 0.83, 95% CI 0.64 to 1.07; 2 studies, positive moderator for postoperative bleeding. Dose equivalent of
11,989 participants; Analysis 6.3), although the direction of the steroid was a positive moderator on the duration of mechanical
treatment effects was the same as in the primary analyses. ventilation but a negative moderator (along with BMI) for ICU length
of stay.
DISCUSSION
Overall completeness and applicability of evidence
Summary of main results
The trials included in this analysis were conducted across 40
This updated systematic review and meta-analysis of trials different countries in the last four decades. Improvements in
evaluating the risks and benefits of corticosteroids versus placebo/ surgical and perioperative practices are likely to have resulted in
control in adults undergoing cardiac surgery with cardiopulmonary better overall outcomes over this time. Definitions used for some of
bypass demonstrated evidence of little or no treatment effect the outcomes – for example, renal complications – have changed
on mortality, but slight reductions in pulmonary complications considerably over time.
and increased cardiac complications attributable to corticosteroid
administration. We reviewed a total of 72 studies (compared to Heterogeneity in the reported data and in the results of the trials
54 in the previous version of this work), enroling a total of 17,282 might also be due to the specific primary outcomes considered
participants. Nine studies were multi-arm trials. The main setting in the individual studies (biochemical versus clinical), the study
was elective coronary artery bypass grafting, and the median age year and related improvements in surgical and perioperative
of participants was 63 years. Only 6% of 72 trials included in the management, and the evolving definitions of clinical endpoints.
analysis were considered at low risk of bias overall. A sensitivity Nonetheless, the treatment effects of steroid therapy were not
analysis restricted to those trials did not demonstrate evidence of influenced by the publication year of the trial report. Further, the
treatment effects for any of the primary outcomes, although the study findings are also likely to be applicable to modern clinical
direction of the treatment effects on cardiac complications and practice, given that the analyses included two large trials, including
pulmonary complications were the same as those of the primary those at low risk of bias, undertaken since 2012 (Dieleman 2012;
analyses. GRADE assessment of the certainty of the evidence was Whitlock 2015), and a total of 13,299 participants were recruited in
low for the primary outcomes of mortality, cardiac complications, trials conducted after 2010 compared to 3663 in trials conducted
and pulmonary complications (Summary of findings 1). before 2010. However, none of the studies included in the pooled
analyses of the primary outcomes were restricted to participants
Analyses of secondary outcomes suggested prophylactic with valvular or aortic disease; therefore, this review cannot inform
corticosteroids may also reduce infectious complications (low- the reader about the potential specific effect of the steroids in

Informed decisions.
treating these populations. Moreover, only eight (11%) of the A risk reduction for postoperative atrial fibrillation was confirmed
studies were conducted in high-risk cohorts. in this review, as has been demonstrated previously (Dvirnik 2018).
The potential mechanisms are unclear, although some studies have
The indirectness identified in cardiac and pulmonary outcome shown that the inflammatory response might be linked to the
definitions reduced our certainty in the results for these outcomes, incidence of atrial fibrillation (Halonen 2007; Whitlock 2006). In
although indirectness did not manifest as increased heterogeneity mitigation, the effect on atrial fibrillation in this review is based
in the analyses of primary outcomes. Inconsistency of the on the results from small trials, is limited by heterogeneity, and
definitions of these outcomes between studies also reduced characterised by significant publication bias (Egger’s test P = 0.007),
applicability. For example, results related to cardiac complications further limiting interpretation.
are influenced mainly by the outcomes reported in the SIRS
trial (Whitlock 2015), where myocardial injury was measured by Lastly, the analyses related to the use of inotropic support are
elevation of the creatine kinase-myocardial band (CK-MB) enzyme. limited by the use of a dichotomous approach, which is nonetheless
However, from the data reported in SIRS, the rise in CK-MB did the most frequent way to report these outcomes in the trials
not translate into a higher risk of myocardial infarctions when included in the review.
electrocardiographic criteria were adopted. Specifically, the risk of
myocardial infarction documented by Q waves was not different Certainty of the evidence
between steroids and placebo (RR 0.87, 95% CI 0.49 to 1.57).
In the GRADE assessment, concerns about methodological quality/
Moreover, in the DECS trial (Dieleman 2012), where infarctions
risk of bias affected the certainty rating for several outcomes (all-
were reported based on biomarker elevation in association with
cause mortality, cardiac complications, pulmonary complications,
electrocardiographic signs (new Q waves or left bundle branch
infectious complications, renal failure, length of hospital stay).
block), the risk of myocardial infarction was not different between
Risks for inconsistency were judged serious for infectious
the two groups (RR 0.90, 95% CI 0.57 to 1.42); see Table 4.
complications and hospital length of stay, due to the categorisation
Besides the indirectness deriving from the outcome definition, of the outcome and the substantial heterogeneity between studies.
several additional confounding factors that could not be reported
We downgraded the certainty of the evidence for cardiac and
at a trial level might have influenced the severity of myocardial
pulmonary complications to low. In addition to a possible risk
injury after surgery (extent of the operation, duration of the
of detection bias, we identified concerns related to indirectness,
procedure, technical complexity of surgery). Troponin release
as the overall direction of effect was mainly determined by two
has been shown to be extremely variable after cardiac surgery
large trials (Dieleman 2012; Whitlock 2015), conducted with specific
(Devereaux 2022), but its absolute value to determine a meaningful
outcome definitions and cohort characteristics.
clinical impact is different from the threshold considered in non-
surgical settings. Nonetheless, a recent work (Whitlock 2020), We downgraded the evidence for gastrointestinal bleeding by two
by the authors of the two largest trials included in the review levels to low certainty because of imprecision due to the low
(Dieleman 2012; Whitlock 2015), re-analysed the individual patient number of events and for including 95% confidence intervals
data from the two trials with both definitions for myocardial overlapping the line of no effect. Imprecision affected the outcomes
infarction. The results confirmed a potential role of corticosteroids of mortality and renal failure as well, as they included 95%
on myocardial infarction, which might strengthen the confidence in confidence intervals that may fail to exclude important benefit or
the finding produced by this review. important harm. Lastly, we judged the evidence related to length of
stay to be of very low certainty, due to study limitations arising from
The anti-inflammatory role of steroids might have a more
a severe risk of selection and detection bias, inconsistency from the
pronounced, protective effect on the lungs, as these contain a
substantial heterogeneity between studies, and imprecision due to
resident population of immune system cells that, when activated
the minimal treatment effect, possibly of no clinical importance.
(for example, as part of the inflammatory response to cardiac
surgery), could potentially cause acute organ injury (Quatrini 2021). Potential biases in the review process
Another explanation of the reduction in pulmonary complications
from corticosteroids can also be related to the effect of steroids Our search of major databases was overseen by an Information
in reducing infections in the studies included in this review, as Specialist and was as comprehensive as possible. However, some
pneumonia was considered as both an infectious and a pulmonary studies might still have been erroneously missed, particularly those
complication across the trials assessed. added retrospectively to databases. Also, our search did not cover
specific databases for the identification of health economic studies.
The findings from this review are greatly influenced by the presence Hence, there is a possibility (although very remote) that potential
of two large trials (Dieleman 2012; Whitlock 2015), both of high studies that focused on steroids and their cost-effectiveness that
quality. For example, the reduced risk of infectious complications were not mentioned in clinical journals were missed.
in patients treated with corticosteroids was mainly determined by
the weight of the outcomes recorded in the DECS (Dieleman 2012) We adhered to Cochrane's risk of bias 1 (RoB 1) tool to assess risk
and SIRS (Whitlock 2015) trials. This finding might be explained in of bias. However, current Cochrane guidance recommends RoB 2.
agreement with the reduced risk of pulmonary complications (and, The revised tool is thought to result in a better-quality review by
hence, pneumonia), which has been demonstrated in our review, improving the quality and relevance of the risk of bias assessments,
and recently constituted the basis for dexamethasone treatment particularly for cluster-RCTs. We did not include cluster-RCTs in this
of COVID-19 patients supported by the RECOVERY trial (RECOVERY review, so this was less of an issue for this review; however, we will
2020). adopt RoB 2 for the next update of this work.

Informed decisions.
There were instances when contacting the study authors was No previous report on pulmonary complications was available for
not feasible or was unsuccessful, due to the publication year of comparison. To the best of our knowledge, the present work is the
the study. In those cases, we adopted the data and information first meta-analysis to present this finding.
extracted as part of the previous version of this review, with no
changes. This might have introduced bias in the review process The moderator analysis in this systematic review expands on
(as we could not directly verify the information obtained in the the Dvirnik 2018 review by highlighting some possible sources of
previous work). We will undertake further efforts to obtain these heterogeneity that were not previously identified. For example,
data in the next update of this work. we found evidence of a potential relationship between the year in
which the study was conducted and the amount of postoperative
Despite our efforts, we could not confirm whether Abd El-Hakeem bleeding (as improved haemostatic materials and refinements
2003a and Abd El-Hakeem 2003b, Kilger 2003a and Kilger 2003b, in surgical techniques may have been more widely adopted in
Volk 2001 and Volk 2003, and Weis 2006 and Weis 2009 are pairs of recent years). Most importantly, we also found evidence of a
separate studies, or separate publications from the same record. potential relationship between the dose of steroids and mechanical
We included the studies in this review as this was the approach ventilation (a reduction in mechanical ventilation with a higher
adopted by the authors in the previous version of this review, dose of steroids), and the characteristics of the participants (BMI)
although this could potentially be a source of additional bias. and length of postoperative stay in the ICU (people with a higher
BMI had longer lengths of stay). However, due to the exploratory
We decided to report the analyses on continuous outcomes, nature of these analyses, these findings should be interpreted with
despite the high heterogeneity, for transparency and caution.
comprehensiveness. We had also selected length of hospital stay as
an outcome for the summary of findings table in the protocol phase. We did not perform a trial sequential analysis (TSA) on our
Statistical heterogeneity is, unfortunately, known to be frequently primary outcomes, as this was not part of our prespecified
higher and more common in meta-analysis of continuous outcomes protocol. However, in a recent systematic review using TSA, Ng
(Alba 2016). Binary outcomes in our review do not show the same and colleagues showed how a potential effect of corticosteroids on
degree of heterogeneity, despite including the same study cohorts. mortality cannot reliably be excluded based on currently available
We downgraded the certainty of the evidence for length of hospital trials (Ng 2020). Future versions of this review that will include
stay to very low, and we reiterate this here to emphasise that more trials assessing mortality might therefore have a different
interpretation of this result is limited. treatment effect compared to the present one.
Recording the outcome atrial fibrillation as reported by study AUTHORS' CONCLUSIONS

authors could also have contributed to the high heterogeneity seen
in the analysis. Implications for practice
Lastly, our analysis of study publication year as a potential Although some clinical benefits are highlighted in the present meta-
moderator was a post hoc addition to the review, which may analysis (corticosteroids may reduce pulmonary complications and
be regarded as arbitrary and non-transparent. Nonetheless, we infections), these are mitigated by potential concerns in terms
decided to include it as we believed it could be informative to the of cardiac complications (corticosteroids may increase the risk of
reader, given the long range of years covered by this review. myocardial complications). In this analysis, corticosteroids may
result in little to no difference in all-cause mortality, gastrointestinal
Agreements and disagreements with other studies or bleeding, and renal failure. The effect on length of hospital stay
reviews was very unclear. The results from this meta-analysis are possibly
skewed by the two largest trials included (Dieleman 2012; Whitlock
This is an update of a Cochrane review previously published 2015).
in 2011 (Dieleman 2010; Dieleman 2011). Since the publication
of the last review, the two largest trials conducted on this Implications for research
topic were published (Dieleman 2012; Whitlock 2015). These
developments made this update necessary to make the findings The opposing effects on cardiac and pulmonary complications
relevant to contemporary clinical practice. As in the previous point toward distinct mechanisms of corticosteroids on injury
version of the review, the use of perioperative corticosteroids did mechanisms in these organs and provide useful pointers for further
not affect mortality in adults undergoing cardiac surgery. However, research. The magnitude of the innate immune system activation is
in contrast to the findings of the 2011 version, our analysis revealed associated with suppression of the adaptive and humoral immune
an increase in the risk of cardiac complications, and a decrease in responses (which are thought to increase the risk of infection after
the occurrence of pulmonary complications. day four) (Warltier 2002). Attenuating the initial innate response (i.e.
systemic inflammatory response syndrome (SIRS)) might attenuate
In agreement with a recent review (Dvirnik 2018), which assessed this later immunosuppression and subsequent infection and
studies conducted between 1977 and 2015 with a total of therefore pulmonary complications by reducing lower respiratory
16,013 participants, our analysis demonstrated evidence that tract infection. Our own evidence demonstrates a heterogeneous
corticosteroid use has little or no treatment effect on mortality, an association between SIRS and myocardial injury, and there are
increased risk of cardiac complications, and a reduction in atrial questions as to the cause and effect of the inflammatory response
fibrillation, compared to placebo or no treatment. and myocardial injury (Abbasciano 2021). Indeed, inflammation
may be beneficial in terms of the response to myocardial injury in
some patient groups.

Informed decisions.
Future studies that aim to investigate the effects of corticosteroids review process. Cochrane Heart was supported by the National
on vasoplegia should consider including a more detailed report of Institute for Health and Care Research (NIHR) via Cochrane
this outcome (along with recording of fluid administration in the Infrastructure funding. The views expressed are those of the
postoperative period). authors and not necessarily those of the NIHR or the Department of
Health and Social Care.
Another unanswered question is whether there may be subgroups
or organ injury phenotypes that benefit from corticosteroids, The authors are indebted to the team responsible for the previous
although the current moderator analyses did not identify version of this systematic review for their remarkable work.
candidates for further research. In fact, although subgroup
analyses for the heterogeneous outcomes in this systematic review Editorial and peer-reviewer contributions
did not identify age as a significant moderator, corticosteroids
The following people conducted the editorial process for this
reduced the risk of the composite primary endpoint in the
article:
DExamethasone for Cardiac Surgery (DECS) study (RR 0.74, 95% CI
0.58 to 0.95; P = 0.017), in preplanned subgroup analysis in younger • Sign-off Editor (final editorial decision): Michael Brown,
(< 75 years) patients (Dieleman 2012). Cochrane Editorial Board;
Future large trials should focus on defining a specific patient • Managing Editor (selected peer reviewers, provided editorial
profile in which prophylactic steroids might be beneficial without guidance to authors, edited the article): Joanne Duffield,
significant increase in undesirable outcomes. Current research is Cochrane Central Editorial Service;
also examining the impact of steroids on patient-centred, clinically • Editorial Assistant (conducted editorial policy checks, collated
important endpoints (DECS-II). As of January 2023, DECS-II was peer-reviewer comments and supported editorial team): Sara
reported as in the recruitment phase. Hales-Brittain, Cochrane Central Editorial Service;
• Copy Editor (copy editing and production): Faith Armitage,
There are conflicting results on the potential benefits that steroids Cochrane Central Production Service;
might confer, including whether they facilitate a swifter recovery • Peer-reviewers (provided comments and recommended an
(Engelman 2019; Gregory 2021). This ambiguity, together with editorial decision): Rakesh C Arora, Harrington Heart and
further questions about steroids' potential for organ injury (and the Vascular Institute, University Hospitals, Cleveland, Ohio,
cost implications of this), warrant further research. USA (clinical/content review), Brian Duncan (consumer
review), Nuala Livingstone, Cochrane Evidence Production
ACKNOWLEDGEMENTS
and Methods Directorate (methods review), Jo Platt, Central
Cochrane Heart, including Nicole Martin and Charlene Bridges, Editorial Information Specialist (search review), Jan M
supported the authors in the development of this review. The Dieleman, Department of Anaesthesia & Perioperative Medicine,
authors thank Cochrane Heart for the invaluable support and Westmead Hospital, Western Sydney University, Sydney,
precious advice throughout the protocol-writing phase and the Australia (clinical/content review).

Informed decisions.
REFERENCES
References to studies included in this review Bourbon 2004 {published data only}
Abbaszadeh 2012 {published data only} Bourbon A, Vionnet M, Leprince P, Vaissier E, Copeland J,
McDonagh P, et al. The effect of methylprednisolone
Abbaszadeh M, Khan ZH, Mehrani F, Jahanmehr H. Perioperative
treatment on the cardiopulmonary bypass-induced systemic
intravenous corticosteroids reduce incidence of atrial
inflammatory response. European Journal of Cardio-Thoracic
fibrillation following cardiac surgery: a randomized study.
Surgery 2004;26(5):932-8. [PMID: 15519185]
Brazilian Journal of Cardiovascular Surgery 2012 ;27(1):18-23.
[DOI: https://doi.org/10.5935/1678-9741.20120005] Cavarocchi 1986 {published data only}
Abd El-Hakeem 2003a {published data only} Cavarocchi NC, Pluth JR, Schaff HV, Orszulak TA,
Homburger HA, Solis E, et al. Complement activation during
Abd El-Hakeem JJ, Zareh ZE. Effects of dexamethasone on the
cardiopulmonary bypass: comparison of bubble and membrane
incidence of shivering and recovery in patients undergoing
oxygenators. Journal of Thoracic and Cardiovascular Surgery
valve replacement surgery. Egyptian Journal of Anaesthesia
1986;91(2):252-8. [PMID: 3511328]
2003;19:361-70. [EMBASE: 37369829]
Celik 2004 {published data only}
Abd El-Hakeem 2003b {published data only}
Celik JB, Gormus N, Okesli S, Gormus ZI, Solak H.
Abd El-Hakeem EE, Ashry MA, El-Minshawy A, Maghraby EA.
Methylprednisolone prevents inflammatory reaction occurring
Influence of dexamethasone on cytokine balance in
during cardiopulmonary bypass: effects on TNF-alpha, IL-6, IL-8,
patients undergoing valve replacement surgery. Egyptian
IL-10. Perfusion 2004;19(3):185-91. [PMID: 15298427]
Journal of Anaesthesia 2003;3:205-14. [RESEARCHGATE:
www.researchgate.net/publication/288809174_ Influence_ Chaney 1998 {published data only}
of_ dexamethasone_ on_ cytokine_ balance_ in_ patients_
* Chaney MA, Nikolov MP, Blakeman B, Bakhos M, Slogoff S.
undergoing_ valve_ replacement_ surgery]
Pulmonary effects of methylprednisolone in patients
Al-Shawabkeh 2017 {published data only}10.1016/ undergoing coronary artery bypass grafting and early tracheal
j.jsha.2016.03.005 extubation. Anesthesia and Analgesia 1998;87(1):27-33. [PMID:
9661540]
Al-Shawabkeh Z, Al-Nawaesah K, Anzeh RA, Al-Odwan H, Al-
Rawashdeh WA, Altaani H. Use of short-term steroids in the Chaney MA, Nikolov MP, Blakeman BP, Bakhos M, Slogoff S.
prophylaxis of atrial fibrillation after cardiac surgery. Journal Hemodynamic effects of methylprednisolone in patients
of the Saudi Heart Association 2017;29(1):23-9. [DOI: https:// undergoing cardiac operation and early extubation. Annals of
doi.org/10.1016/j.jsha.2016.03.005] Thoracic Surgery 1999;67(4):1006-11. [PMID: 10320243]
Amr 2009 {published data only} Chaney 2001 {published data only}
Amr YM, Elmisekawy E, El-serogy H. Effects of dexamethasone Chaney MA, Durazo-Arvizu RA, Nikolov MP, Blakeman BP,
on pulmonary and renal functions in patients undergoing CABG Bakhos M. Methylprednisolone does not benefit patients
with cardiopulmonary bypass. Seminars in Cardiothoracic undergoing coronary artery bypass grafting and early tracheal
and Vascular Anesthesia 2009;13(4):231-7. [DOI: https:// extubation. Journal of Thoracic and Cardiovascular Surgery
doi.org/10.1177/1089253209351598] 2001;121(3):561-9. [PMID: 11241092]
Andersen 1989 {published data only} Codd 1977 {published data only}
Andersen LW, Baek L, Thomsen BS, Rasmussen JP. Effect Codd JE, Wiens RD, Barner HB, Kaiser GC, Willman VL.
of methylprednisolone on endotoxemia and complement Steroids and myocardial preservation. Journal of Thoracic and
activation during cardiac surgery. Journal of Cardiothoracic Cardiovascular Surgery 1977;74(3):418-22. [PMID: 302373]
Anesthesia 1989;3(5):544-9. [PMID: 2520931]
Coetzer 1996 {published data only}
Bingol 2005 {published data only}
Coetzer M, Coetzee A, Rossouw G. The effect of
Bingol H, Cingoz F, Balkan A, Kilic S, Bolcal C, Demirkilic U, et methylprednisolone, given prior to cardiopulmonary bypass, on
al. The effect of oral prednisolone with chronic obstructive indices of gas exchange. Cardiovascular Journal of South Africa
pulmonary disease undergoing coronary artery bypass surgery. 1996;86:C188-92. [DOI: 10.10520/AJA10159657_484]
Journal of Cardiac Surgery 2005;20:252-6. [DOI: https://
doi.org/10.1111/j.1540-8191.2005.200392.x] Demir 2009 {published data only}
Demir T, Demir H, Tansel T, Kalko Y, Tireli E, Dayioglu E, et
Boscoe 1983 {published data only}
al. Influence of methylprednisolone on levels of neuron-
Boscoe MJ, Yewdall VM, Thompson MA, Cameron JS. specific enolase in cardiac surgery: a corticosteroid derivative
Complement activation during cardiopulmonary bypass: to decrease possible neuronal damage. Journal of Cardiac
quantitative study of effects of methylprednisolone and Surgery 2009;24:397-403. [DOI: https://doi.org/10.1111/
pulsatile flow. British Medical Journal 1983;287(6407):1747-50. j.1540-8191.2009.00842.x]
[PMID: 6416575]

Informed decisions.
Demir 2015 {published data only} Sauër AC, Slooter AJ, Veldhuijzen DS, Van Eijk MM, Van
Demir T, Ergenoglu MU, Demir HB, Tanrikulu N, Sahin M, Dijk D. Intraoperative dexamethasone and delirium
Gok E, et al. Pretreatment with methylprednisolone improves after cardiac surgery: a randomized clinical trial. Critical
myocardial protection during on-pump coronary artery bypass Care 2013;17(2):1-200. [DOI: https://doi.org/10.1213/
surgery. Heart Surgery Forum 2015;18(4):E171-7. [DOI: https:// ane.0000000000000248]
doi.org/10.1532/hsf.1367]
Van Osch D, Dieleman JM, Bunge JJ, Van Dijk D,
Dieleman 2012 {published data only} Doevendans PA, Suyker WJ, et al. Risk factors and prognosis
of postpericardiotomy syndrome in patients undergoing
Bunge JJ, van Osch D, Dieleman JM, Jacob KA, Kluin J,
valve surgery. Journal of Thoracic and Cardiovascular
Van Dijk D, et al. Dexamethasone for the prevention of
Surgery 2017;153(4):878-85. [DOI: https://doi.org/10.1016/
postpericardiotomy syndrome: a DExamethasone for Cardiac
j.jtcvs.2016.10.075]
Surgery substudy. American Heart Journal 2014;168(1):126-31.
[DOI: https://doi.org/10.1016/j.ahj.2014.03.017] Van Osch D, Dieleman JM, Nathoe HM, Boasson MP, Kluin J,
Bunge JJ, et al. Intraoperative high-dose dexamethasone
* Dieleman JM, Nierich AP, Rosseel PM, van der Maaten JM,
in cardiac surgery and the risk of rethoracotomy. Annals
Hofland J, Diephuis JC, et al. Intraoperative high-dose
of Thoracic Surgery 2015;100(6):2237-42. [DOI: https://
dexamethasone for cardiac surgery: a randomized controlled
doi.org/10.1016/j.athoracsur.2015.06.025]
trial. JAMA 2012;308(17):1761-7. [DOI: https://doi.org/10.1001/
jama.2012.14144] El Azab 2002 {published data only}
Dieleman JM, de Wit GA, Nierich AP, Rosseel PM, van El Azab SR, Rosseel PM, de Lange JJ, Groeneveld AB, van Strik R,
der Maaten JM, Hofland J, et al. Long-term outcomes and cost van Wijk EM, et al. Dexamethasone decreases the pro- to anti-
effectiveness of high-dose dexamethasone for cardiac surgery: inflammatory cytokine ratio during cardiac surgery. British
a randomised trial. Anaesthesia 2017;72(6):704-13. [DOI: https:// Journal of Anaesthesia 2002;88(4):496-501. [PMID: 12066724]
doi.org/10.1111/anae.13853]
Enc 2006 {published data only}
Jacob K, Dieleman S, Nathoe H, Van Osch D, De Waal E, Enc Y, Karaca P, Ayoglu U, Camur G, Kurc E, Cicek S. The
Cramer M, et al. Intraoperative dexamethasone on left atrial acute cardioprotective effect of glucocorticoid in myocardial
function and postoperative atrial fibrillation in cardiac ischemia-reperfusion injury occurring during cardiopulmonary
surgical patients. Critical Care 2014;18(1):1-82. [DOI: https:// bypass. Heart and Vessels 2006;21(3):152-6. [PMID: 16715189]
doi.org/10.1186%2Fcc13372]
Engelman 1995 {published data only}
Jacob KA, Leaf DE, Dieleman JM, Van Dijk D, Nierich AP, Engelman RM, Rousou JA, Flack JE 3rd, Deaton DW, Kalfin R,
Rosseel PM, et al. Intraoperative high-dose dexamethasone Das DK. Influence of steroids on complement and cytokine
and severe AKI after cardiac surgery. Journal of the American generation after cardiopulmonary bypass. Annals of Thoracic
Society of Nephrology 2015;26(12):2947-51. [DOI: https:// Surgery 1995;60(3):801-4. [PMID: 7677537]
doi.org/10.1681/asn.2014080840]
Ferries 1984 {published data only}
Kok L, Hillegers MH, Veldhuijzen DS, Cornelisse S, Nierich AP,
Ferries LH, Marx JJ, Ray JF. The effect of methylprednisolone
van der Maaten JM, et al. The effect of dexamethasone on
on complement activation during cardiopulmonary bypass.
symptoms of posttraumatic stress disorder and depression
Journal of Extracorporeal Technology 1984;16:83-8. [DOI:
after cardiac surgery and intensive care admission: longitudinal
https://doi.org/10.1051/ject/1984163083]
follow-up of a randomized controlled trial. Critical Care
Medicine 2016;44(3):512-20. [DOI: https://doi.org/10.1097/ Fillinger 2002 {published data only}
ccm.0000000000001419]
Fillinger MP, Rassias AJ, Guyre PM, Sanders JH, Beach M, Pahl J,
Ottens TH, Dieleman JM, Sauër AM, Peelen LM, Nierich AP, et al. Glucocorticoid effects on the inflammatory and clinical
de Groot WJ, et al. Effects of dexamethasone on cognitive responses to cardiac surgery. Journal of Cardiothoracic and
decline after cardiac surgery: a randomized clinical Vascular Anesthesia 2002;16(2):163-9. [PMID: 11957164]
trial. Anesthesiology 2014;121(3):492-500. [DOI: https://
doi.org/10.1097/aln.0000000000000336] Giomarelli 2003 {published and unpublished data}
Giomarelli P, Scolletta S, Borrelli E, Biagioli B. Myocardial and
Ottens TH, Hendrikse J, Slooter AJ, van Herwerden LA, lung injury after cardiopulmonary bypass: role of interleukin
Dieleman JM, van Dijk D. Low incidence of early postoperative (IL)-10. Annals of Thoracic Surgery 2003;76(1):117-23. [PMID:
cerebral edema after coronary artery bypass grafting. Journal of 12842524]
Cardiothoracic and Vascular Anesthesia 2015;29(3):632-6. [DOI:
https://doi.org/10.1053/j.jvca.2014.12.004] Glumac 2017 {published data only}
Glumac S, Kardum G, Sodic L, Supe-Domic D, Karanovic N.
Ottens TH, Nijsten MW, Hofland J, Dieleman JM, Hoekstra M, Effects of dexamethasone on early cognitive decline after
Van Dijk D, et al. Effect of high-dose dexamethasone on cardiac surgery. European Journal of Anaesthesiology
perioperative lactate levels and glucose control: a randomized 2017;34(11):776-84. [DOI: https://doi.org/10.1097/
controlled trial. Critical Care 2015;19(1):1-3. [DOI: https:// eja.0000000000000647]
doi.org/10.1186/s13054-015-0736-9]

Informed decisions.
Gomez Polo 2018 {published data only} Kerr 2012 {published data only}
Gomez Polo JC, Vilacosta I, Gomez-Alvarez Z, Vivas D, Kerr KM, Auger WR, Marsh JJ, Devendra G, Spragg RG, Kim NH,
Martin-Garcia AG, Fortuny-Frau E, et al. Short term use of et al. Efficacy of methylprednisolone in preventing lung
corticosteroids in the prophylaxis of atrial fibrillation after injury following pulmonary thromboendarterectomy. Chest
cardiac surgery and impact on the levels of acute phase 2012;141(1):27-35. [DOI: https://doi.org/10.1378/chest.10-2639]
proteins in this context. European Heart Journal 2018 ;39
Suppl 1:ehy563-3275. [DOI: https://doi.org/10.1093/eurheartj/ Kilger 2003a {published data only}
ehy563.3275] * Kilger E, Weis F, Briegel J, Frey L, Goetz AE, Reuter D, et
al. Stress doses of hydrocortisone reduce severe systemic
Halonen 2007 {published data only} inflammatory response syndrome and improve early outcome
Halonen J, Halonen P, Jarvinen O, Taskinen P, Auvinen T, in a risk group of patients after cardiac surgery. Critical Care
Tarkka M, et al. Corticosteroids for the prevention of atrial Medicine 2003;31(4):1068-74. [PMID: 12682474]
fibrillation after cardiac surgery: a randomized controlled trial.
JAMA 2007;297(14):1562-7. [PMID: 17426275] Schelling G, Kilger E, Roozendaal B, de Quervain DJ, Briegel J,
Dagge A, et al. Stress doses of hydrocortisone, traumatic
Halvorsen 2003 {published data only} memories, and symptoms of posttraumatic stress disorder in
Halvorsen P, Raeder J, White PF, Almdahl SM, Nordstrand K, patients after cardiac surgery: a randomized study. Biological
Saatvedt K, et al. The effect of dexamethasone on side effects Psychiatry 2004;55(6):627-33. [PMID: 15013832]
after coronary revascularization procedures. Anesthesia and
Kilger 2003b {published data only}
Analgesia 2003;96(6):1578-83. [PMID: 12760978]
Kilger E, Weis F, Briegel J. Einfluss von Hydrocortison
Hao 2019 {published data only} auf die Klinische Entwicklung bei Operationen mit Herz-
Hao X, Han J, Zeng H, Wang H, Li G, Jiang C, et al. Lung-Maschine. Journal für Anästhesie 2003;10:135-6.
The effect of methylprednisolone prophylaxis on [URL: https://scholar.google.com/scholar_lookup?
inflammatory monocyte subsets and suppressive title=Einfluss+von+Hydrocortison+auf+die+Klinische
regulatory T cells of patients undergoing cardiopulmonary +Entwicklung+bei+Operationen+mit+Herz%E2%80%90Lung
bypass. Perfusion 2019;34(5):364-74. [DOI: https:// %E2%80%90Maschine&author=E+Kilger&author=F
doi.org/10.1177/0267659118820777] +Weis&author=J+Briegel&publication_year=2003&hl=en]
Harig 1999 {published data only} Kilickan 2008 {published data only}
* Harig F, Feyrer R, Mahmoud FO, Blum U, von der Emde J. Kilickan L, Yumuk Z, Bayindir O. The effect of combined
Reducing the post-pump syndrome by using heparin-coated preinduction thoracic epidural anaesthesia and glucocorticoid
circuits, steroids, or aprotinin. Thoracic and Cardiovascular administration on perioperative interleukin-10 levels and
Surgeon 1999;47(2):111-8. [PMID: 10363611] hyperglycemia. A randomized controlled trial. Journal of
Cardiovascular Surgery 2008;49(1):87-93. [PMID: 18212693]
Harig F, Hohenstein B, von der Emde J, Weyand M. Modulating
IL-6 and IL-10 levels by pharmacologic strategies and the impact Liakopoulos 2007 {published data only}
of different extracorporeal circulation parameters during Liakopoulos OJ, Schmitto JD, Kazmaier S, Brauer A, Quintel M,
cardiac surgery. Shock 2001;16 Suppl 1:33-8. [PMID: 11770031] Schoendube FA, et al. Cardiopulmonary and systemic effects
of methylprednisolone in patients undergoing cardiac surgery.
Hauer 2012 {published data only} Annals of Thoracic Surgery 2007;84(1):110-8; discussion 118-9.
* Hauer D, Weis F, Campolongo P, Schopp M, Beiras- [PMID: 17588396]
Fernandez A, Strewe C, et al. Glucocorticoid-endocannabinoid
interaction in cardiac surgical patients. Relationship to Loef 2004 {published data only}
early cognitive dysfunction and late depression. Reviews * Loef BG, Henning RH, Epema AH, Rietman GW, van Oeveren W,
in the Neurosciences 2012;23(5-6):681–90. [DOI: https:// Navis GJ, et al. Effect of dexamethasone on perioperative
doi.org/10.1515/revneuro-2012-0058] renal function impairment during cardiac surgery with
cardiopulmonary bypass. British Journal of Anaesthesia
NCT00490828. Influence of hydrocortisone on immunologic 2004;93(6):793-8. [PMID: 15377582]
markers and health care related quality of life in patients
after cardiac surgery [Influence of hydrocortisone on humoral Morariu AM, Loef BG, Aarts LP, Rietman GW, Rakhorst G,
and cellular immunologic markers in high risk patients after van Oeveren W, et al. Dexamethasone: benefit and prejudice for
cardiac surgery]. clinicaltrials.gov/ct2/show/NCT00490828 (first patients undergoing on-pump coronary artery bypass grafting:
received 25 June 2007). [CLINICALTRIALS.GOV: NCT00490828] a study on myocardial, pulmonary, renal, intestinal, and hepatic
injury. Chest 2005;128(4):2677-87. [PMID: 16236942]
Jansen 1991 {published data only}
Jansen NJ, van Oeveren W, van den Broek L, Oudemans- Lomirovotov 2013 {published data only}
van Straaten HM, Stoutenbeek CP, Joen MC, et al. Inhibition Lomivorotov VV, Efremov SM, Kalinichenko AP, Kornilov IA,
by dexamethasone of the reperfusion phenomena Knazkova LG, Chernyavskiy AM, et al. Methylprednisolone use
in cardiopulmonary bypass. Journal of Thoracic and is associated with endothelial cell activation following cardiac
Cardiovascular Surgery 1991;102(4):515-25. [PMID: 1656149]

Informed decisions.
surgery. Heart, Lung and Circulation 2013 ;22(1):25-30. [DOI: Prasongsukarn 2005 {published data only}
https://doi.org/10.1016/j.hlc.2012.08.001] Prasongsukarn K, Abel JG, Jamieson WR, Cheung A, Russell JA,
Walley KR, et al. The effects of steroids on the occurrence of
Maddalli 2019 {published data only}
postoperative atrial fibrillation after coronary artery bypass
Maddali MM, Waje ND, Arora NR, Panchatcharam SM. Effect grafting surgery: a prospective randomized trial. Journal of
of low-dose dexamethasone on extra vascular lung water Thoracic and Cardiovascular Surgery 2005;130(1):93-8. [PMID:
in patients following on-pump elective primary coronary 15999046]
artery bypass graft surgery. Annals of Cardiac Anaesthesia
2019;22(4):372. [DOI: https://doi.org/10.4103/aca.aca_122_18] Rao 1977 {published data only}
Rao G, King J, Ford W, King G. The effects of methylprednisolone
Mahrose 2019 {published data only}
on the complications of coronary artery surgery. Vascular
Mahrose R, Elsayed AM, Elshorbagy MS. Bisoprolol versus Surgery 1977;11(1):1-7. [PMID: 308283]
corticosteroid and bisoprolol combination for prevention of
atrial fibrillation after on-pump coronary artery bypass graft Rubens 2005 {published data only}
surgery. Open Anesthesia Journal 2019;13(1):18-24. [DOI: http:// Rubens FD, Nathan H, Labow R, Williams KS, Wozny D, Karsh J,
dx.doi.org/10.2174/2589645801913010018] et al. Effects of methylprednisolone and a biocompatible
copolymer circuit on blood activation during cardiopulmonary
Mardani 2012 {published data only}
bypass. Annals of Thoracic Surgery 2005;79(2):655-65. [PMID:
Mardani D, Bigdelian H. The effect of dexamethasone 15680854]
prophylaxis on postoperative delirium after cardiac
surgery: a randomized trial. Journal of Research Rumalla 2001 {published data only}
in Medical Sciences 2012 ;17:S113-19. [URL: Rumalla V, Calvano SE, Spotnitz AJ, Krause TJ, Lin E, Lowry SF.
www.researchgate.net/profile/Davoud-Mardani/ The effects of glucocorticoid therapy on inflammatory
publication/227859160_The_effect_of_dexamethasone_prophylaxis_on_postoperative_delirium_after_cardiac_surgery_A_randomized_trial/
responses to coronary artery bypass graft surgery. Archives of
links/546455bc0cf2c0c6aec506ad/The-effect-of- Surgery 2001;136(9):1039-44. [PMID: 11529827]
dexamethasone-prophylaxis-on-postoperative-delirium-after-
cardiac-surgery-A-randomized-trial.pdf] Sano 2003 {published data only}
Sano T, Morita S, Masuda M, Tomita Y, Nishida T, Tatewaki H,
Mayumi 1997 {published data only}
et al. Cardiopulmonary bypass, steroid administration, and
Mayumi H, Zhang QW, Nakashima A, Masuda M, Kohno H, surgical injury synergistically impair memory T cell function and
Kawachi Y, et al. Synergistic immunosuppression caused by antigen presentation. Interactive Cardiovascular and Thoracic
high-dose methylprednisolone and cardiopulmonary bypass. Surgery 2003;2(4):598-602. [PMID: 17670133]
Annals of Thoracic Surgery 1997;63(1):129-37. [PMID: 8993254]
Sano 2006 {published data only}
McBride 2004 {published data only}
Sano T, Morita S, Masuda M, Yasui H. Minor infection encouraged
McBride WT, Allen S, Gormley SM, Young IS, McClean E, by steroid administration during cardiac surgery. Asian
MacGowan SW, et al. Methylprednisolone favourably alters Cardiovascular & Thoracic Annals 2006;14(6):505-10. [PMID:
plasma and urinary cytokine homeostasis and subclinical renal 17130328]
injury at cardiac surgery. Cytokine 2004;27(2-3):81-9. [PMID:
15242697] Schurr 2001 {published data only}
Schurr UP, Zund G, Hoerstrup SP, Grunenfelder J, Maly FE,
Morton 1976 {published data only}
Vogt PR, et al. Preoperative administration of steroids: influence
Morton JR, Hiebert CA, Lutes CA, White RL. Effect of on adhesion molecules and cytokines after cardiopulmonary
methylprednisolone on myocardial preservation during bypass. Annals of Thoracic Surgery 2001;72(4):1316-20. [PMID:
coronary artery surgery. American Journal of Surgery 11603453]
1976;131(4):419-22. [PMID: 773198]
Sobieski 2008 {published data only}
Murphy 2011 {published data only}
Sobieski MA, Graham JD, Pappas PS, Tatooles AJ, Slaughter MS.
Murphy GS, Sherwani SS, Szokol JW, Avram MJ, Greenberg SB, Reducing the effects of the systemic inflammatory response
Patel KM, et al. Small-dose dexamethasone improves to cardiopulmonary bypass: can single dose steroids blunt
quality of recovery scores after elective cardiac surgery: a systemic inflammatory response syndrome? ASAIO Journal
randomized, double-blind, placebo-controlled study. Journal of 2008;54:203-6. [DOI: 10.1097/MAT.0b013e3181640331]
Cardiothoracic and Vascular Anesthesia 2011;25(6):950-60. [DOI:
https://doi.org/10.1053/j.jvca.2011.03.002] Starobin 2007 {published data only}
Starobin D, Rehuven Kramer M, Garty M, Shitirt D. Morbidity
Oliver 2004 {published data only}
associated with systemic corticosteroid preparation for
Oliver WC Jr, Nuttall GA, Orszulak TA, Bamlet WR, Abel MD, coronary artery bypass grafting in patients with chronic
Ereth MH, et al. Hemofiltration but not steroids results in earlier obstructive pulmonary disease: a case control study.
tracheal extubation following cardiopulmonary bypass: a Journal of Cardiothoracic Surgery 2007;2:25. [DOI: https://
prospective, randomized double-blind trial. Anesthesiology doi.org/10.1186/1749-8090-2-25]
2004;101(2):327-39. [PMID: 15277915]

Informed decisions.
Taleska Stupica 2020 {published data only} an old and a new anti-inflammatory strategy
Taleska Stupica G, Sostaric M, Bozhinovska M, Rupert L, compared. Perfusion 2011;26(1):31-7. [DOI: https://
Bosnic Z, Jerin A, et al. Extracorporeal hemadsorption versus doi.org/10.1177/0267659110385607]
glucocorticoids during cardiopulmonary bypass: a prospective,
Wan 1999 {published data only}
randomized, controlled trial. Cardiovascular Therapeutics
2020;2020:15. [DOI: 10.1155/2020/7834173] Wan S, LeClerc JL, Huynh CH, Schmartz D, DeSmet JM, Yim AP,
et al. Does steroid pretreatment increase endotoxin release
Tassani 1999 {published data only} during clinical cardiopulmonary bypass? Journal of Thoracic
Tassani P, Richter JA, Barankay A, Braun SL, Haehnel C, and Cardiovascular Surgery 1999;117(5):1004-8. [PMID:
Spaeth P, et al. Does high-dose methylprednisolone 10220696]
in aprotinin-treated patients attenuate the systemic
Weis 2006 {published data only}
inflammatory response during coronary artery bypass grafting
procedures? Journal of Cardiothoracic and Vascular Anesthesia Weis F, Kilger E, Roozendaal B, de Quervain DJ, Lamm P,
1999;13(2):165-72. [PMID: 10230950] Schmidt M, et al. Stress doses of hydrocortisone reduce chronic
stress symptoms and improve health-related quality of life
Toft 1997 {published data only} in high-risk patients after cardiac surgery: a randomized
Toft P, Christiansen K, Tonnesen E, Nielsen CH, Lillevang S. study. Journal of Thoracic and Cardiovascular Surgery
Effect of methylprednisolone on the oxidative burst activity, 2006;131(2):277-82. [PMID: 16434254]
adhesion molecules and clinical outcome following open heart
Weis 2009 {published data only}
surgery. Scandinavian Cardiovascular Journal 1997;31(5):283-8.
[PMID: 9406295] Weis F, Beiras-Fernandez A, Schelling G, Briegel J, Lang P,
Hauer D, et al. Stress doses of hydrocortisone in high-risk
Turkoz 2001 {published data only} patients undergoing cardiac surgery: effects on interleukin-6
Turkoz A, Cigli A, But K, Sezgin N, Turkoz R, Gulcan O, et al. The to interleukin-10 ratio and early outcome. Critical Care
effects of aprotinin and steroids on generation of cytokines Medicine 2009;37(5):1685-90. [DOI: https://doi.org/10.1097/
during coronary artery surgery. Journal of Cardiothoracic and ccm.0b013e31819fca77]
Vascular Anesthesia 2001;15(5):603-10. [PMID: 11688002]
Whitlock 2006 {published data only}
Volk 2001 {published data only} Whitlock RP, Young E, Noora J, Farrokhyar F, Blackall M,
Volk T, Schmutzler M, Engelhardt L, Docke WD, Volk HD, Teoh KH. Pulse low dose steroids attenuate post-
Konertz W, et al. Influence of aminosteroid and glucocorticoid cardiopulmonary bypass SIRS; SIRS I. Journal of Surgical
treatment on inflammation and immune function Research 2006;132(2):188-94. [PMID: 16566943]
during cardiopulmonary bypass. Critical Care Medicine
Whitlock 2015 {published data only}
2001;29(11):2137-42. [PMID: 11700410]
Garg AX, Chan MT, Cuerden MS, Devereaux PJ, Abbasi SH,
Volk 2003 {published data only} Hildebrand A, et al. Effect of methylprednisolone on acute
Volk T, Schmutzler M, Engelhardt L, Pantke U, Laule M, Stangl K, kidney injury in patients undergoing cardiac surgery with a
et al. Effects of different steroid treatment on reperfusion- cardiopulmonary bypass pump: a randomized controlled trial.
associated production of reactive oxygen species and CMAJ 2019;191(9):E247-56. [DOI: https://doi.org/10.1503/
arrhythmias during coronary surgery. Acta Anaesthesiologica cmaj.181644]
Scandinavica 2003;47(6):667-74. [PMID: 12803583]
McClure G, Belley-Cote E, Tong W, Xie F, Vincent J, Lamy A, et
Von Spiegel 2001 {published data only} al. Steroids in cardiac surgery (SIRS): economics substudy.
Canadian Journal of Cardiology 2017;33(10):S93-4. [DOI: https://
Von Spiegel T, Giannaris S, Wietasch GJ, Schroeder S, Buhre W,
doi.org/10.1016/j.cjca.2017.07.185]
Schorn B, et al. Effects of dexamethasone on intravascular and
extravascular fluid balance in patients undergoing coronary McClure GR, Belley-Cote EP, Harlock J, Lamy A, Stacey M,
bypass surgery with cardiopulmonary bypass. Anesthesiology Devereaux PJ, et al. Steroids in cardiac surgery trial: a
2002;96(4):827-34. [PMID: 11964588] substudy of surgical site infections. Canadian Journal of
Anesthesia 2019;66(2):182-92. [DOI: https://doi.org/10.1007/
* Von Spiegel T, Giannaris S, Wrigge H, Schorn B, Hoeft A.
s12630-018-1253-5]
Effects of dexamethasone on extravascular lung water
and pulmonary haemodynamics in patients undergoing Paparella D, Parolari A, Rotunno C, Vincent J, Myasoedova V,
coronary artery bypass surgery [Einfluss einer präoperativen Guida P, et al. The effects of steroids on coagulation dysfunction
dexamethasongabe auf das extravaskulare lungenwasser induced by cardiopulmonary bypass: a steroids in cardiac
und die pulmonale hämodynamik bei koronarchirurgischen surgery (SIRS) trial substudy. Seminars in Thoracic and
patienten]. Anasthesiologie, Intensivmedizin, Notfallmedizin, Cardiovascular Surgery 2017;29(1):35-44. [DOI: https://
Schmerztherapie 2001;36(9):545-51. [PMID: 11577353] doi.org/10.1053/j.semtcvs.2017.01.007]
Vukovic 2011 {published data only} Royse CF, Saager L, Whitlock R, Ou-Young J, Royse A, Vincent J,
Vukovic PM, Maravic-Stojkovic VR, Peric MS, Jovic MD, et al. Impact of methylprednisolone on postoperative quality
Cirkovic MV, Gradinac SD, et al. Steroids and statins: of recovery and delirium in the steroids in cardiac surgery

Informed decisions.
trial: a randomized, double-blind, placebo-controlled Jansen 1991b {published data only}

substudy. Anesthesiology 2017;126(2):223-33. [DOI: https:// Jansen NJ, van Oeveren W, van Vliet M, Stoutenbeek CP,
doi.org/10.1097/aln.0000000000001433] Eysman L, Wildevuur CR. The role of different types
of corticosteroids on the inflammatory mediators in
* Whitlock RP, Devereaux PJ, Teoh KH, Lamy A, Vincent J,
cardiopulmonary bypass. European Journal of Cardio-thoracic
Pogue J, et al. Methylprednisolone in patients undergoing
Surgery 1991;5(4):211-7. [PMID: 1711873]
cardiopulmonary bypass (SIRS): a randomised, double-blind,
placebo-controlled trial. Lancet 2015;386(10000):1243-53. [DOI: Jorens 1993 {published data only}
10.1016/S0140-6736(15)00273-1.]
Jorens PG, De Jongh R, De Backer W, Van Damme J, Van
Yared 1998 {published data only} Overveld F, Bossaert L, et al. Interleukin-8 production in
patients undergoing cardiopulmonary bypass. The influence
* Yared JP, Starr NJ, Hoffmann-Hogg L, Bashour CA, Insler SR,
of pretreatment with methylprednisolone. American Review of
O'Connor M, et al. Dexamethasone decreases the incidence
Respiratory Disease 1993;148(4 Pt 1):890-5. [PMID: 8214944]
of shivering after cardiac surgery: a randomized, double-
blind, placebo-controlled study. Anesthesia and Analgesia Karlstad 1993 {published data only}
1998;87(4):795-9. [PMID: 9768772]
Karlstad MD, Patteson SK, Guszcza JA, Langdon R, Chesney JT.
Yared JP, Starr NJ, Torres FK, Bashour CA, Bourdakos G, Methylprednisolone does not influence endotoxin translocation
Piedmonte M, et al. Effects of single dose, postinduction during cardiopulmonary bypass. Journal of Cardiothoracic and
dexamethasone on recovery after cardiac surgery. Annals of Vascular Anesthesia 1993;7(1):23-7. [PMID: 8431570]
Thoracic Surgery 2000;69(5):1420-4. [PMID: 10881816]
Kawamura 1995 {published data only}
Yared 2007 {published data only} Kawamura T, Inada K, Okada H, Okada K, Wakusawa R.
Yared JP, Bakri MH, Erzurum SC, Moravec CS, Laskowski DM, Van Methylprednisolone inhibits increase of interleukin 8 and 6
Wagoner DR, et al. Effect of dexamethasone on atrial fibrillation during open heart surgery. Canadian Journal of Anaesthesia
after cardiac surgery: prospective, randomized, double-blind, 1995;42(5 pt 1):399-403. [PMID: 7614647]
placebo-controlled trial. Journal of Cardiothoracic and Vascular
Kawamura 1999 {published data only}
Anesthesia 2007;21(1):68-75. [PMID: 17289483]
Kawamura T, Inada K, Nara N, Wakusawa R, Endo S. Influence
Yilmaz 1999 {published data only} of methylprednisolone on cytokine balance during cardiac
Yilmaz M, Ener S, Akalin H, Sagdic K, Serdar OA, Cengiz M. Effect surgery. Critical Care Medicine 1999;27(3):545-8. [PMID:
of low-dose methyl prednisolone on serum cytokine levels 10199534]
following extracorporeal circulation. Perfusion 1999;14(3):201-6.
Kirsh 1979 {published data only}
[PMID: 10411250]
Kirsh MM, Behrendt DM, Jochim KE. Effects of
methylprednisolone in cardioplegic solution during coronary
References to studies excluded from this review bypass grafting. Journal of Thoracic and Cardiovascular Surgery
1979;77(6):896-9. [PMID: 312366]
Anic 2004 {published data only}
Anic D, Gašparovic H, Ivanèan H, Batinic D. Effects Kito 1980 {published data only}
of corticosteroids on inflammatory response Kito Y, Fujita T, Naito Y, Koyanagi H, Obara K, Kosakai Y, et al. The
following cardiopulmonary bypass. Croatian effects of methylprednisolone on myocardial protection during
Medical Journal 2004;45:158-61. [RESEARCHGATE: open heart surgery. Kyobu Geka 1980;33(8):587-91. [PMID:
www.researchgate.net/profile/Drago-Batinic-2/ 7412051]
publication/8600654_Effects_of_corticosteroids_on_inflammatory_response_following_cardiopulmonary_bypass/
links/0deec51df0157890ed000000/Effects-of-corticosteroids- Kobayashi 1996 {published data only}
on-inflammatory-response-following-cardiopulmonary- Kobayashi N. The circulatory and respiratory effects of
bypass.pdf] methylprednisolone associated with catecholamine undergoing
open heart surgery. Tokyo Joshi Ikadaigaku Zasshi 1996;66:1-10.
Biagioli 1981 {published data only}
[PMID: 8515544]
Biagioli B, Rossi C, Giomarelli PP, Pescatori G, Barbini P, Grossi A.
Correlations between membrane and bubble oxygenators Launo 1990 {published data only}
in patients treated with or without methylprednisolone. Launo C, Palermo S, Gobbi GC, Fumagalli C, Federici E,
Haemodynamic and metabolic parameters. Giornale Italiano di Moroni G. Methylprednisolone sodium succinate in the profile
Cardiologia 1981;11(9):1288-300. [PMID: 7327337] of respiratory complications after thoracic surgical intervention.
Minerva Anestesiologica 1990;56(6):219-23. [PMID: 2280848]
Boldt 1986 {published data only}
Boldt J, von Bormann B, Kling D, Jooss D, Moosdorf R, Lee 2005 {published data only}
Hempelmann G. Effect of glucocorticoids on extravascular Lee HS, Lee JM, Kim MS, Kim HY, Hwangbo B, Zo JI. Low-
lung water following extra-corporeal circulation. Anaesthesist dose steroid therapy at an early phase of postoperative acute
1986;35(4):238-44. [PMID: 3487259] respiratory distress syndrome. Annals of Thoracic Surgery
2005;79:405-10. [PMID: 15680804]

Informed decisions.
Levinsky 1979 {published data only} Tabardel 1996 {published data only}
Levinsky L, Schimert G, Lajos TZ, Lee AB Jr, Korenyi-Both A, Taberdel Y, Duchateau J, Schmartz D, Marecaux G, Shahla M,
Vladutiu A, et al. The use of steroids as a potentiator Barvais L, et al. Corticosteroids increase blood interleukin-10
of hypothermic myocardial preservation in man. levels during cardiopulmonary bypass in men. Surgery
Journal of Surgical Research 1979;26(6):629-51. [DOI: 1996;119:76-80. [PMID: 8560390]
10.1016/0022-4804(79)90059-3]
Thompson 1980 {published data only}
Loubser 1997 {published data only} Thompson MA, Broadbent MP. Methylprednisolone prior to
Loubser PG. Effect of methylprednisolone on complement cardiopulmonary bypass. Anaesthesia 1980;35(4):345-53. [PMID:
activation during heparin neutralization. Journal of 7435893]
Cardiovascular Pharmacology 1997;29(1):23-7. [PMID: 9007666]
Thompson 1982 {published data only}
Ming 2001 {published data only} Thompson MA, Broadbent MP, English J. Plasma levels of
Ming W, Yun-Bi L, Bo Y, Shi-Wei X, Ru-Kun C, Han-Liang Z. Effects methylprednisolone following administration during cardiac
of methylprednisolone and aprotinin on phospholipase D surgery. Anaesthesia 1982;37(4):405-7. [PMID: 7081684]
activity of leukocytes in systemic inflammatory response
induced by cardiopulmonary bypass. Acta Pharmacologica Toledo-Pereyra 1980 {published data only}
Sinica 2001;22:913-17. [PMID: 11749774] Toledo-Pereyra LH, Lin CY, Kundler H, Replogle RL. Steroids in
heart surgery: a clinical double-blind and randomized study.
Miranda 1982 {published data only} American Surgeon 1980;46(3):155-60. [PMID: 7377659]
Miranda DR, Stoutenbeek C, Karliczek G, Rating W. Effects of
dexamethason on the early postoperative course after coronary Turkoz 2000 {published data only}
artery bypass surgery. Thoracic & Cardiovascular Surgeon Turkoz A, Cigli A, But K, Sezgin N, Turkoz R, Gulcan O, et
1982;30(1):21-7. [PMID: 6179228] al. The effect of aprotinin and methylprednisolone during
coronary artery surgery induced cytokines. Türk Anesteziyoloji
Raff 1987 {published data only} ve Reanimasyon Cemiyeti Mecmuasi 2000;28:247-54. [PMID:
Raff H, Norton AJ, Flemma RJ, Findling JW. Inhibition of the 11688002]
adrenocorticotropin response to surgery in humans: interaction
between dexamethasone and fentanyl. Journal of Clinical Us 2001 {published data only}
Endocrinology and Metabolism 1987;65(2):295-8. [PMID: Us MH, Ege T, Cakir O, Ozkan S, Duran E, Ozturk OY.
3036903] Effect of methylprednisolone in post-pump syndrome.
Gulhane Tip Dergisi 2001;43(2):197-203. [CENTRAL: https://
Ranucci 1994 {published data only} www.cochranelibrary.com/central/doi/10.1002/central/
Ranucci M, Pavesi M, Conti D, Soro G, Ceocopieri M, Ghanem G, CN-00442345/full]
et al. High-dose steroids during cardiopulmonary bypass:
comparison between two therapeutic approaches. Journal of Vallejo 1977 {published data only}
Cardiothoracic and Vascular Anesthesia 1994;8(3 Suppl 2):134. Vallejo JL, Gemenez-Fernandez R, Mainer JL, Rivera R. Clinical
[DOI: 10.1016/1053-0770(94)90537-1] analysis of the protective effect of methylprednisolone on the
heart in anoxic arrest (random study). Revista Espanola de
Santarpino 2009a {published data only} Cardiologia 1977;30:705-9. [PMID: 609839]
Santarpino G, Caroleo S, Onorati F, Rubino AD, Dardano A,
Gulletta E, et al. Inflammatory response after cardiopulmonary Van Overveld 1994 {published data only}
bypass: a randomized comparison between conventional Van Overveld FJ, De Jongh RF, Jorens PG, Walter P, Bossaert L,
hemofiltration and steroids. Journal of Cardiovascular Surgery De Backer WA. Pretreatment with methylprednisolone in
2009;50(4):555-64. [PMID: 19262457] coronary artery bypass grafting influences the levels of
histamine and tryptase in serum but not in bronchoalveolar
Santarpino 2009b {published data only} lavage fluid. Clinical Science 1994;86(1):49-53. [DOI: 10.1042/
Santarpino G, Caroleo S, Onorati F, Dimastromatteo G, cs0860049]
Abdalla K, Amantea B, et al. Inflammatory response to
cardiopulmonary bypass with enoximone or steroids in patients Vogelzang 2007 {published data only}
undergoing myocardial revascularization: a preliminary report Vogelzang M, Hoekstra M, Drost JT, Janse M, van der Horst IC,
study. International Journal of Clinical Pharmacology and Boonstra PW, et al. The impact of a reduced dose of
Therapeutics 2009;47(2):78-88. [PMID: 19203563] dexamethasone on glucose control after coronary artery bypass
surgery. Cardiovascular Diabetology 2007;17(6):39. [PMID:
Schmartz 1996 {published data only} 18086312]
Schmartz D, Tabardel Y, Duchateau J, Barvais L, Hollander A.
Corticosteroid effects on cytokine production in cardiac Wan 1997b {published data only}
surgery: dose-effect relationship. British Journal of Anaesthesia Wan S, LeClerc JL, Schmartz D, Barvais L, Huynh CH, Deviere J,
1996;76(Suppl 1):53. [ABSTRACT NUMBER: A167] et al. Hepatic release of interleukin-10 during cardiopulmonary
bypass in steroid-pretreated patients. American Heart Journal
1997;133(3):335-9. [PMID: 9060803]

Informed decisions.
Yaeger 2005 {published data only} Deeks 2023

Yeager MP, Rassias AJ, Fillinger MP, DiScipio AW, Gloor KE, Deeks JJ, Higgins JPT, Altman DG, editor(s). Chapter 10:
Gregory JA, et al. Cortisol antiinflammatory effects are maximal Analysing data and undertaking meta-analyses. In: Higgins
at postoperative plasma concentrations. Critical Care Medicine JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch
2005;33:1507-12. [PMID: 16003055] VA, editor(s). Cochrane Handbook for Systematic Reviews of
Interventions Version 6.4 (updated August 2023). Cochrane,
Yasuura 1977 {published data only} 2023. Available from www.training.cochrane.org/handbook.
Yasuura K, Nishitani Y, Tanimoto K, Hashimoto A, Hayashi H.
Administration of steroid during open-heart surgery. Nippon Devereaux 2022
Kyobu Geka Gakkai Zasshi 1977;25(12):1587-91. [PMID: 612691] Devereaux PJ, Lamy A, Chan MT, Allard RV, Lomivorotov VV,
Landoni G, et al. High-sensitivity troponin I after cardiac
surgery and 30-day mortality. New England Journal of Medicine
References to ongoing studies 2022;386(9):827-36. [DOI: 10.1056/NEJMoa2000803]
DECS-II {published data only}
Dieleman 2016
Myles PS, Dieleman JM, Forbes A, Heritier S, Smith JA.
Dieleman JM, Van Dijk D. Corticosteroids for cardiac surgery: a
Dexamethasone for Cardiac Surgery trial (DECS-II): rationale
summary of two large randomised trials. Netherlands Journal of
and a novel, practice preference-randomized consent
Critical Care 2016;24(5):6-10. [CORPUS ID: 53074542]
design. American Heart Journal 2018;204:52-7. [DOI: 10.1016/
j.ahj.2018.06.008] Dieleman 2017
NCT00807521 {published data only} Dieleman JM, de Wit GA, Nierich AP, Rosseel PM, van
der Maaten JM, Hofland J, et al. Long-term outcomes and cost
NCT00807521. Steroid-induced Reduction of Surgical Stress
effectiveness of high-dose dexamethasone for cardiac surgery:
Study (STRESS) [Reduction of the cardiac proapoptotic
a randomised trial. Anaesthesia 2017;72(6):704-13. [PMID:
stress response by dexamethasone in patients undergoing
28317094]
coronary artery bypass grafting]. clinicaltrials.gov/ct2/show/
NCT00807521 (first received 12 December 2008). Dvirnik 2018
NCT00879931 {unpublished data only} Dvirnik N, Belley-Cote EP, Hanif H, Devereaux PJ, Lamy A,
Dieleman JM, et al. Steroids in cardiac surgery: a systematic
NCT00879931. Influence of corticoids on renal function in
review and meta-analysis. British Journal of Anaesthesia
cardiac surgery. clinicaltrials.gov/ct2/show/NCT00879931 (first
2018;120(4):657-67. [PMID: 29576107]
received 13 April 2009).
Egger 1997
Additional references Egger M, Smith GD, Schneider M, Minder C. Bias in
meta-analysis detected by a simple, graphical test. BMJ
Abbasciano 2021 1997;315(7109):629-34. [DOI: 10.1136/bmj.315.7109.629]
Abbasciano RG, Lai FY, Roman MA, Rizzello A, Pathak S, Ramzi J,
et al. Activation of the innate immune response and organ Engelman 2019
injury after cardiac surgery: a systematic review and meta- Engelman DT, Ali WB, Williams JB, Perrault LP, Reddy VS,
analysis of randomised trials and analysis of individual patient Arora RC, et al. Guidelines for perioperative care in
data from randomised and non-randomised studies. British cardiac surgery: enhanced recovery after surgery society
Journal of Anaesthesia 2021;127(3):365-75. [PMID: 34229833] recommendations. JAMA Surgery 2019;154(8):755-66. [PMID:
31054241]
Alba 2016
Alba AC, Alexander PE, Chang J, MacIsaac J, DeFry S, Guyatt GH. Gillinov 2016
High statistical heterogeneity is more frequent in meta- Gillinov AM, Bagiella E, Moskowitz AJ, Raiten JM,
analysis of continuous than binary outcomes. Journal of clinical Groh MA, Bowdish ME, et al. Rate control versus rhythm
epidemiology 2016 Feb 1;70:129-35. [PMID: 26386323] control for atrial fibrillation after cardiac surgery. New
England Journal of Medicine 2016;374(20):1911-21. [DOI:
Barnes 2006 10.1056%2FNEJMoa1602002]
Barnes P. How corticosteroids control inflammation:
Quintiles Prize Lecture 2005. British Journal of Pharmacology Gregory 2021
2006;148(3):245–54. [DOI: 10.1038/sj.bjp.0706736] Gregory AJ, Arora RC, Chatterjee S, Grant MC, Lobdell KW,
Morton V, et al. Selecting elements for a cardiac enhanced
Chaney 2002 recovery protocol. Journal of cardiothoracic and vascular
Chaney MA. Corticosteroids and cardiopulmonary bypass: a anesthesia 2021;35(12):3847-8. [PMID: 34119416]
review of clinical investigations. Chest 2002;121(3):921-31.
[PMID: 11888978] Guyatt 2011
Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P,
Knottnerus A. GRADE guidelines: a new series of articles

Informed decisions.
in the Journal of Clinical Epidemiology. Journal of Clinical Lefebvre 2021

Epidemiology 2011 ;64(4):380-2. [PMID: 21185693] Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C,
Metzendorf M-I, et al. Chapter 4: Searching for and selecting
Herdman 2011
studies. In: Higgins JP, Thomas J, Chandler J, Cumpston
Herdman M, Gudex C, Lloyd A, Janssen MF, Kind P, Parkin D, M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook
et al. Development and preliminary testing of the new five- for Systematic Reviews of Interventions Version 6.2
level version of EQ-5D (EQ-5D-5L). Quality of Life Research (updated February 2021). Cochrane, 2021. Available from
2011 ;20(10):1727-36. [PMID: 21479777] training.cochrane.org/handbook . [PMID: 31643080]
Higgins 2011 Liberati 2009
Higgins JP, Altman DG, Sterne JA, editor(s). Chapter 8: Assessing Moher D, Liberati A, Tetzlaff J, Altman DG, Prisma Group.
risk of bias in included studies. In: Higgins JP, Green S, Preferred reporting items for systematic reviews and meta-
editor(s). Cochrane Handbook for Systematic Reviews of analyses: the PRISMA statement. PLOS Medicine 2009;6(7):264-9.
Interventions Version 5.1.0 (updated March 2011). The Cochrane [DOI: 10.1136/bmj.b2535]
Collaboration, 2011. Available from training.cochrane.org/
handbook/archive/v5.1/. [PMID: 22008217] Murphy 2004
Murphy GJ, Angelini GD. Side effects of cardiopulmonary
Higgins 2023a
bypass: what is the reality? Journal of Cardiac Surgery
Higgins JP, Eldridge S, Li T (editors). Chapter 23: Including 2004;19(6):481-8. [PMID: 15548178]
variants on randomized trials. In: Higgins JP, Thomas J,
Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Ng 2020
Cochrane Handbook for Systematic Reviews of Interventions Ng KT, Van Paassen J, Langan C, Sarode DP, Arbous MS,
version 6.4 (updated August 2023). Cochrane, 2023. Available Alston RP, et al. The efficacy and safety of prophylactic
from www.training.cochrane.org/handbook. corticosteroids for the prevention of adverse outcomes in
patients undergoing heart surgery using cardiopulmonary
Higgins 2023b
bypass: a systematic review and meta-analysis of randomized
Higgins JP, Savović J, Page MJ, Elbers RG, Sterne JAC. Chapter controlled trials. European Journal of Cardio-Thoracic Surgery
8: Assessing risk of bias in a randomized trial. In: Higgins JP, 2020;57(4):620-7. [PMID: 31972000]
Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA,
editor(s). Cochrane Handbook for Systematic Reviews of Page 2023
Interventions Version 6.4 (updated August 2023). Cochrane, Page MJ, Higgins JP, Sterne JAC. Chapter 13: Assessing risk of
2023. Available from www.training.cochrane.org/handbook. bias due to missing results in a synthesis. In: Higgins JP, Thomas
J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s).
Higgins 2023c
Cochrane Handbook for Systematic Reviews of Interventions
Higgins JP, Li T, Deeks JJ, editor(s). Chapter 6: Choosing effect Version 6.4 (updated August 2023). Cochrane, 2023. Available
measures and computing estimates of effect. In: Higgins JP, from www.training.cochrane.org/handbook.
Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA,
editor(s). Cochrane Handbook for Systematic Reviews of Plot Digitizer [Computer program]
Interventions Version 6.4 (updated August 2023). Cochrane, Plot Digitizer. Version 2.6.8. Joseph A. Huwaldt, 27 October
2023. Available from www.training.cochrane.org/handbook. 2015. Available at plotdigitizer.sourceforge.net/History.html.
Hill 1998 Quatrini 2021
Hill GE. Cardiopulmonary bypass-induced inflammation: is Quatrini L, Ugolini S. New insights into the cell-and tissue-
it important? Journal of Cardiothoracic & Vascular Anesthesia specificity of glucocorticoid actions. Cellular & Molecular
1998;12(2 Suppl 1):21-5. [PMID: 9583572] Immunology 2021 ;18(2):269-78. [PMID: 32868909]
Katzung 2014 R [Computer program]
Katzung B, Trevor A. Adrenocorticosteroids and adrenocortical R. Version 4.0. Vienna, Austria: R Foundation for Statistical
antagonists. In: Basic and Clinical Pharmacology. Computing, 2022. Available at cran.r-project.org.
13th edition. New York (NY): McGraw-Hill, 2014:686.
[GOOGLE SCHOLAR URL: scholar.google.com/scholar? RECOVERY 2020
q=Basic+%26+Clinical+Pharmacology,+Thirteenth RECOVERY Collaborative Group. Dexamethasone in hospitalized
+Edition&hl=en&as_sdt=0&as_vis=1&oi=scholart] patients with Covid-19. New England Journal of Medicine
2021;384(8):693-704. [DOI: 10.1056/NEJMoa2021436]
Kirklin 1983
Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenowerh DE, RevMan 2023 [Computer program]
Pacifico AD. Complement and damaging effects of Review Manager (RevMan). Version 6.1.0. The Cochrane
cardiopulmonary bypass. Journal of Thoracic & Cardiovascular Collaboration, 2023. Available at revman.cochrane.org.
Surgery 1983;86(6):845-57. [PMID: 6606084]

Informed decisions.
Schünemann 2023 Warltier 2002

Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Warltier DC, Laffey JG, Boylan JF, Cheng DC. The systemic
Skoetz N, et al. Chapter 14: Completing ‘Summary of findings’ inflammatory response to cardiac surgery: implications
tables and grading the certainty of the evidence. In: Higgins for the anesthesiologist. Journal of the American Society of
JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch Anesthesiologists 2002 ;97(1):215-52. [PMID: 12131125]
VA, editor(s). Cochrane Handbook for Systematic Reviews of
Interventions Version 6.4 (updated August 2023). Cochrane, Whitlock 2008
2023. Available from www.training.cochrane.org/handbook. Whitlock RP, Chan S, Devereaux PJ, Sun J, Rubens FD,
Thorlund K, et al. Clinical benefit of steroids use in patients
Sousa-Uva 2017 undergoing cardiopulmonary bypass: a meta-analysis of
Sousa-Uva M, Head SJ, Milojevic M, Collet JP, Landoni G, randomized trials. European Heart Journal 2008;29:2592-600.
Castella M, et al. 2017 EACTS Guidelines on perioperative [PMID: 18664462]
medication in adult cardiac surgery. European Journal of
Cardio-Thoracic Surgery 2018;53(1):5-33. [PMID: 29029110] Whitlock 2020
Whitlock RP, Dieleman JM, Belley-Cote E, Vincent J, Zhang M,
Steroid Conversion Calculator Devereaux PJ, et al. The effect of steroids in patients undergoing
Steroid Conversion Calculator. mdcalc.com. [URL: cardiopulmonary bypass: an individual patient meta-analysis
www.mdcalc.com/calc/2040/steroid-conversion-calculator] of two randomized trials. Journal of Cardiothoracic and Vascular
Anesthesia 2020 Jan 1;34(1):99-105. [PMID: 31401207]
Veervort 2020
Vervoort D, Meuris B, Meyns B, Verbrugghe P. Global Zacharias 2005
cardiac surgery: access to cardiac surgical care around Zacharias A, Schwann TA, Riordan CJ, Durham SJ, Shah AS,
the world. Journal of Thoracic and Cardiovascular Surgery Habib RH. Obesity and risk of new-onset atrial fibrillation after
2020;159(3):987-96. [PMID: 29029110] cardiac surgery. Circulation 2005 ;112(21):3247-55. [PMID:
16286585]
Viechtbauer 2010
Viechtbauer W. Conducting meta-analyses in R with the metafor
package. Journal of Statistical Software 2010;36(3):1-48. [DOI: References to other published versions of this review
10.18637/jss.v036.i03] Dieleman 2010
Wahba 2019 Dieleman JM, van Paassen J, van Dijk D, Arbous SM,
Kalkman CJ, Vandenbroucke JP, et al. Prophylactic
Wahba A, Milojevic M, Boer C, De Somer FM, Gudbjartsson T,
corticosteroids for cardiopulmonary bypass in adults.
van den Goor J, et al. EACTS/EACTA/EBCP guidelines on
Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No:
cardiopulmonary bypass in adult cardiac surgery. European
CD005566. [DOI: 10.1002/14651858.CD005566.pub2]
Journal of Cardio-Thoracic Surgery 2020 ;57(2):210-51. [PMID:
31576396] Dieleman 2011
Wan 1997a Dieleman JM, van Paassen J, van Dijk D, Arbous MS,
Kalkman CJ, Vandenbroucke JP, et al. Prophylactic
Wan S, LeClerc JL, Vincent JL. Inflammatory response to
corticosteroids for cardiopulmonary bypass in adults.
cardiopulmonary bypass: mechanisms involved and possible
Cochrane Database of Systematic Reviews 2011, Issue 5. Art. No:
therapeutic strategies. Chest 1997;112(3):676-92. [PMID:
CD005566. [DOI: 10.1002/14651858.CD005566.pub3]
9315800]
* Indicates the major publication for the study
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Abbaszadeh 2012
Study characteristics
Methods Study design: prospective, randomised controlled study
Total duration of the study: not stated
Number of study centres and location: single centre; Tehran University of Medical Sciences (Tehran,
Iran)
Date of study: 2012 (study start and end dates not available)

Informed decisions.
Abbaszadeh 2012 (Continued)
Participants Number randomised: 185
Number lost to follow-up/withdrawn: 1
Number analysed: 184
Mean age: 59.9 years
Male gender: 50%
Average BMI: 26.65
Severity of the condition according to study authors: normal risk profile. Elective CABG on CPB
Surgery type: CABG
Inclusion criteria: elective CABG surgery
Exclusion criteria: previous episodes of AF or flutter; uncontrolled diabetes mellitus; systemic bacterial
or mycotic infection; active tuberculosis; Cushing's syndrome; psychotic mental disorder; herpes sim-
plex keratitis or renal insufficiency; history of peptic ulcer or thrombophlebitis
Interventions Intervention: 6 mg of intravenous dexamethasone after anaesthetic induction and then 6 mg of intra-
venous dexamethasone on the morning of postoperative day 1
Comparator: 1 mL of intravenous saline after anaesthetic induction and then 1 mL of intravenous

saline on the morning of postoperative day 1
Outcomes Primary endpoint was the occurrence of AF recorded on continuous ECG during the first 72 hours after
surgery
Secondary endpoints were time to tracheal extubation, time to first oral intake, postoperative bleed-
ing, mortality, and infectious complications
Notes Funding: none identified
Study authors' COI: none identified
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence genera- Low risk Quote: "A block randomization scheme was used with 20 patients allocated to
tion (selection bias) each block".
Comment: Block randomization scheme.
Allocation concealment Low risk Quote: "To maintain the double-blinded study design, the sealed envelope was
(selection bias) opened immediately before surgery, and the study drug was prepared in iden-
tical appearing syringes by a nurse who did not participate in the treatment of
the study patients."
Comment: Sealed envelopes.
Blinding of participants Low risk Quote: "To maintain the double-blinded study design, the sealed envelope was
and personnel (perfor- opened immediately before surgery, and the study drug was prepared in iden-
mance bias) tical appearing syringes by a nurse who did not participate in the treatment of
the study patients."
Comment: Blinding of personnel stated, blinding of participants unstated, but

very likely, as per the measures adopted to blind the study personnel.

Informed decisions.
Abbaszadeh 2012 (Continued)
Blinding of outcome as- Unclear risk No clear description of outcome assessment blinding.
sessment (detection bias)
Incomplete outcome data Low risk Very little missing data, balanced across groups and due to similar causes (one
(attrition bias) patient excluded due to the development of acute abdominal complications
All outcomes after surgery).
Selective reporting (re- Low risk An adequate description of the study protocol is available in the published
porting bias) manuscript and all the study's prespecified outcomes that are of interest have
been reported in a prespecified way.
Other bias Low risk No other potential source of bias identified.
Abd El-Hakeem 2003a

Methods Study design: randomized placebo-controlled, double-blinded trial
Total duration of the study: NR
Number of study centres and location: single centre; Assiut University Hospital, Assiut, Egypt
Date of study: 2003
Number analysed: 46
Mean age: 36
Gender: 55% male
Severity of the condition according to study authors: high risk
Surgery type: valve surgery
Inclusion criteria: adult cardiac surgery patients
Exclusion criteria: none specified
Interventions Intervention: 100 mg dexamethasone, pre-CPB
Comparison: standard management
Outcomes Outcomes were mortality, time to extubation, ICU stay, vasoactive medication, rate of blood transfu-
sions, measured during hospital stay (no distinction between primary and secondary outcomes)
Notes Funding for trial: not stated
Conflicts of interest of trial authors: none stated
Risk of bias

Informed decisions.
Abd El-Hakeem 2003a (Continued)
Random sequence genera- Low risk Quote: "Randomization was by using the sealed envelope method so that
tion (selection bias) there would be equal number of patients in the two groups"
Comment: randomisation by shuffling sealed envelopes
Allocation concealment Low risk Quote: "randomization was by using the sealed envelope method so that there
(selection bias) would be equal number of patients in the two groups".
Comment: sealed envelopes
Blinding of participants Low risk Quote: "randomised double-blind, placebo-controlled study "
and personnel (perfor-
mance bias) Comment: double-blind study
Blinding of outcome as- Unclear risk Comment: probably blinded data collection; unclear whether adjudication of
sessment (detection bias) endpoints or data analyses were blinded
Incomplete outcome data Low risk No missing data

(attrition bias)
All outcomes
Abd El-Hakeem 2003b

Methods Study design: prospective randomised controlled study
Number of study centres and location: single centre; Assiut University Hospital, Assiut, Egypt
Date of study: 2003
Number analysed: 20
Mean age: 35.2 ± 4.2 years
Gender: 55% male
Severity of the condition according to study authors: normal risk profile. Elective valve replacement on
CPB
Surgery type: aortic or mitral valve replacement
Inclusion criteria: elective valve replacement surgery
Exclusion criteria: left ventricular ejection fraction < 50%, ischaemic heart disease, low cardiac output
syndrome, uncontrolled rapid atrial fibrillation, tight mitral stenosis, severe systemic non-cardiac dis-
ease, infection, poorly controlled diabetes mellitus, immunosuppressive therapy

Informed decisions.
Abd El-Hakeem 2003b (Continued)
Interventions Intervention: 100 mg dexamethasone, pre-CPB
Comparison: placebo
Outcomes Primary endpoint was the post-operative serum level of cytokines TNF-a, IL-6, IL-8, and IL-10 up to 24
hours after the completion of surgery
Secondary endpoints were post-operative cardiac index, pulmonary wedge pressure, pulmonary shunt
function up to 24 hours after the completion of surgery; postoperative arrhythmia, inotropic support,
time to tracheal extubation, and length of ICU stay.
Conflicts of interest of trial authors: authors had nothing to disclose with regard to commercial support
Risk of bias
Random sequence genera- Low risk Quote: "Randomisation was done by using the sealed envelope method so
tion (selection bias) that there would be equal number of patients in the two groups".
Comment: shuffling sealed envelopes
Allocation concealment Low risk Quote: "Randomisation was done by using the sealed envelope method so
(selection bias) that there would be equal number of patients in the two groups"
Comment: sealed envelopes
Blinding of participants Low risk Quote: "Randomized double-blind placebo controlled study. This was per-
and personnel (perfor- formed by an anaesthesiologist not involved with the patients perioperative
mance bias) care."
Comment: double-blind placebo-controlled study
Blinding of outcome as- Unclear risk Quote: "Randomized double-blind placebo controlled study. This was per-
sessment (detection bias) formed by an anaesthesiologist not involved with the patients perioperative
care."
Comment: probably blinded data collection; unclear whether adjudication of

endpoints or data analyses were blinded
Incomplete outcome data Low risk Follow-up: ICU stay. 0% loss to follow-up
(attrition bias)
All outcomes
Selective reporting (re- Low risk In sections "Study-design and measurements", "calculation of shunt fraction",
porting bias) "laboratory methods", all endpoints were specified.
Al-Shawabkeh 2017
Total duration of the study: between June 2014 and June 2015
Informed decisions.
Al-Shawabkeh 2017 (Continued)

Number of study centres and location: Queen Alia Heart Institute (Amman, Jordan)
Date of study: 2017
Number analysed: 0
Mean age: 65
Gender: 51% male
Severity of the condition according to study authors: unspecified
Surgery type: CABG, valvular, combined
Inclusion criteria: elective first time CABG or combined with valvular surgery, use of β-adrenergic block-
ade, and normal sinus rhythm
Exclusion criteria: history of heart block; previous episodes of AF or flutter; uncontrolled diabetes melli-
tus; history of peptic ulcer disease; systemic bacterial or mycotic infection; permanent pacemaker; any
documented or suspected supraventricular or ventricular arrhythmias; urgent or emergency surgery; if
the patient underwent cardiac surgery without using cardiopulmonary bypass; and renal insufficiency
(serum creatinine > 20 mg/dL)
Interventions Intervention: 1 g of intravenous methylprednisolone sodium succinate before cardiopulmonary by-

pass, and then 100 mg hydrocortisone every 8 hours for the next 3 days
Comparator: placebo group receiving maintenance fluids (5% dextrose water with potassium chloride
20 milliequivalents per litre (mEq)/L)
Outcomes Primary endpoint was the occurrence of an episode of AF lasting more than 30 minutes or haemo-
dynamic instability due to AF regardless of episode duration during the first 96 hours after cardiac
surgery.
Secondary endpoints were the length of hospital stay and the adverse effects of steroids. Patients were
followed up during the first 2 to 4 weeks after surgery to check for wound infection, and for 6 months
for major postoperative complications.
Risk of bias
Random sequence genera- Low risk Quote: "Randomization was performed on the operation day. The pharmacist
tion (selection bias) selected the next number on the randomization list, labelled the drug contain-
er with the patient’s name, and sent the container to the department where
the patient was treated."
Comment: randomisation list sent to pharmacy.
Allocation concealment Low risk Quote: "Randomization was performed on the operation day. The pharmacist
(selection bias) selected the next number on the randomization list, labelled the drug contain-
er with the patient’s name, and sent the container to the department where
the patient was treated." [...]
Comment: allocation performed centrally by pharmacy.

Informed decisions.
Al-Shawabkeh 2017 (Continued)
Blinding of participants Low risk Blinding of personnel stated, blinding of participants unstated but very likely.
mance bias) Quote: "Both the active drug and the placebo preparations were identical re-
garding color and other characteristics." "The study group remained unknown
to all caring nurses and physicians. The randomization codes were opened af-
ter the end of study."
Blinding of outcome as- Unclear risk Quote: "The randomization codes were opened after the end of study."
Blinding might have been removed before analysis.
Incomplete outcome data Low risk No trial group changes, no withdrawals, no losses to follow-up reported but no
(attrition bias) intention-to-treat analysis. Data from all the participants were included in the
All outcomes final analysis.
Selective reporting (re- Low risk All expected outcomes were reported properly.
porting bias)
Amr 2009
Number of study centres and location: Tanta University, Tanta, Egypt
Mean age: not stated
Gender: 71% male
Severity of the condition according to study authors: normal risk profile
Surgery type: CABG
Inclusion criteria: elective first-time coronary artery bypass graft
Exclusion criteria: left ventricular ejection fraction < 40%, myocardial infarction within the past month,
history of diabetes mellitus, elevated serum creatinine (> 120 micromol/L), impaired hepatic function,
history of respiratory disease or lung surgery, and history of stroke or transient ischaemic attack; ther-
apy with intravenous inotropic agents, vasoactive drugs, diuretics or ACE inhibitors (within 24 hours of
surgery); preoperative use of supplemental oxygen, mechanical ventilation or radio contrast agents
Interventions Intervention: 1 mg/kg of intravenous dexamethasone at the induction of anaesthesia, then 0.5 mg/kg
of intravenous dexamethasone 8 hours after initial dose
Comparator: equivalent volume of intravenous isotonic sodium chloride at the induction of anaesthe-
sia, then equivalent dose of intravenous isotonic sodium chloride 8 hours after initial dose

Informed decisions.
Amr 2009 (Continued)
Outcomes Primary endpoints were the respiratory function (measured by respiratory index, PaO2/FiO2 ratio, A-a
oxygen gradient, and lung compliance) and renal function (measured by creatinine clearance, albumin
to creatinine ratio, and NAG levels) up to 24 hours after the completion of surgery
Secondary endpoints were the presence of postoperative bleeding, myocardial infarction, postopera-
tive respiratory or wound infection, atrial fibrillation, and the length of ICU and total hospitalisation.
Notes Funding for trial: no financial support was received for the research or authorship of the study
Risk of bias
Random sequence genera- Unclear risk No information on randomisation was available

tion (selection bias)
Allocation concealment Unclear risk No information on allocation concealment was available

(selection bias)
Blinding of participants Unclear risk No blinding described

mance bias)
Blinding of outcome as- Unclear risk No description

Incomplete outcome data Low risk No missing data

(attrition bias)
All outcomes
Andersen 1989
Number of study centres and location: single centre; Rigshopitalet (Copenhagen, Denmark)
Number lost to follow-up/withdrawn: 1 passed away
Number analysed: 15
Mean age: 58 years

Informed decisions.
Andersen 1989 (Continued)

Gender: not stated
Severity of the condition according to study authors: not stated
Surgery type: CABG
Inclusion criteria: aortocoronary bypass surgery
Exclusion criteria: preoperative clinical or biochemical evidence of infection, positive blood cultures
Interventions Intervention: 30 mg/kg of intravenous methylprednisolone administered at the induction of anaesthe-

sia
Comparator: no intervention
Outcomes Primary endpoint was serum endotoxin, complement C3c and C3d concentrations at the induction of
anaesthesia, at the start of CPB, during surgery and multiple postoperative time points up to 7 days
Secondary endpoints were the occurrence of significant respiratory or cardiovascular complications

prior to hospital discharge
Risk of bias
Random sequence genera- Unclear risk Quote: "The study included two randomly selected groups of eight patients
tion (selection bias) undergoing aortocoronary bypass grafting"
Comment: randomisation method unclear
Allocation concealment Unclear risk No information on allocation concealment was available.

(selection bias)
Blinding of participants Unclear risk No information regarding blinding available.

mance bias)
Blinding of outcome as- Unclear risk No information regarding blinding available.

Incomplete outcome data Unclear risk No clear information available.

(attrition bias)
All outcomes
Selective reporting (re- Unclear risk No information on selection of outcomes.

porting bias)
Bingol 2005

Informed decisions.
Bingol 2005 (Continued)

Total duration of the study: between January 2000 and January 2003
Number of study centres and location: single centre; Gulhane Military Medical Academy (Ankara,
Turkey)
Date of study: 2005
Number analysed: 40
Mean age: not available
Gender: 77.5% male
Severity of the condition according to study authors: patients at higher risk due to chronic obstructive
pulmonary disease
Surgery type: CABG
Inclusion criteria: patients with chronic obstructive pulmonary disease (clinical signs and symptoms,
FEV1 < 70% and FEV1/FVC < 70%) undergoing first-time coronary artery bypass grafting
Exclusion criteria: history of asthma, a familial history of atopy, left ventricular ejection fraction of less
than 35%, clinical or radiological evidence of pneumonia, pH of < 7.30 on arterial blood gas testing,
history of COPD treatment or diabetes mellitus; concomitant valve surgery, redo surgery or off-pump
surgery
Interventions Intervention: 20 mg of oral prednisolone administered daily from 10 days prior to surgery until the date
of hospital discharge.
Comparison: oral placebo administered daily from 10 days prior to surgery until the date of hospital
discharge.
Outcomes Primary endpoint was the postoperative respiratory function as measured by FEV1 and FEV1/FVC as
measured at the time of withdrawal of prednisolone and three months' postoperatively
Secondary endpoints included the length of ICU and hospital stay, time to extubation, additional surgi-
cal and non-surgical intervention required, pulmonary (including bronchospasm and pleural effusion)
and non-pulmonary complications (wound infection, sternal dehiscence, and rhythm disturbance).
Risk of bias
Random sequence genera- Low risk Quote: "These patients were divided into two groups randomly by using ran-
tion (selection bias) dom numbers on the computer. Each group included 20 patients".
Comment: computer-generated sequence.
Allocation concealment Unclear risk No clear information on allocation concealment.

(selection bias)
Blinding of participants Low risk Quote: "Our study team, the patients and the spirometry technician were blind
and personnel (perfor- to the study"
mance bias)

Informed decisions.
Bingol 2005 (Continued)
Blinding of outcome as- High risk Quote: "the pharmacist and the statistical data analysts were not blind to the
sessment (detection bias) coding of the groups".
Incomplete outcome data Unclear risk Insufficient information.

(attrition bias)
All outcomes
Selective reporting (re- Unclear risk No information on selection of outcomes.

porting bias)
Boscoe 1983
Number of study centres and location: single centre; Guy’s Hospital (London, United Kingdom)
Date of study: 1983
Number analysed: 34
Mean age: 54.2 +/-11.0 years
Gender: 76.5% male
Surgery type: CABG or valve surgery undertaken on cardiopulmonary bypass
Inclusion criteria: coronary artery bypass grafting or valvular surgery undertaken on cardiopulmonary
bypass
Exclusion criteria: not stated
Interventions Intervention: 30 mg/kg of intravenous methylprednisolone administered at the induction of anaesthe-

sia, and an additional 30 mg/kg of intravenous methylprednisolone administered immediately before
commencement of CPB
Comparison: normal general anaesthesia as per practice without the administration of methylpred-
nisolone
Outcomes Primary endpoint was serum complement C3 and C4 concentration at four time points from immedi-
ately after induction of anaesthesia and up to 60 minutes after the institution of bypass.
Secondary endpoint was the measurement of complement activation at the same time points as
above.

Informed decisions.
Boscoe 1983 (Continued)
Risk of bias
Random sequence genera- Low risk Quote: "Thirty four consecutive patients were selected by random number al-
tion (selection bias) location for one of two groups, either control or treatment with intravenous
methylprednisolone"
Allocation concealment Unclear risk Insufficient information on allocation concealment.

(selection bias)
Blinding of participants Unclear risk Insufficient information on blinding.

mance bias)
Blinding of outcome as- Unclear risk Insufficient information.

Incomplete outcome data Unclear risk Insufficient information.

(attrition bias)
All outcomes
Selective reporting (re- Unclear risk Insufficient information.

porting bias)
Bourbon 2004
Methods Study design: prospective randomised controlled trial. Multi-arm trial.
Number of study centres and location: single centre; Pitie-Salpetriere Hospital, Paris, France
Number analysed: 36
Mean age: NR
Gender: NR
Severity of the condition according to study authors: NR
Surgery type: isolated CABG
Inclusion criteria: elective coronary artery bypass grafting
Exclusion criteria: re-do operation, aged less than 50 or over 80 years, weight less than 60 or above 90
kilograms, known renal or hepatic impairment, preoperative infection within 7 days of surgery, preop-
erative use of antibiotics or corticosteroids, and raised white cell count.

Informed decisions.
Bourbon 2004 (Continued)
Interventions Intervention 1: intravenous methylprednisolone administered at 5 mg/kg dose, at commencement of

Intervention 2: intravenous methylprednisolone administered at 10 mg/kg dose, at commencement of

Comparison: no intervention given, routine surgical management only
Outcomes Primary endpoint: serum levels of interleukin-6, TNF-a and oxygen-derived free radicals at 6 time
points, from the induction of anaesthesia, up to 24 hours after protamine administration
Secondary endpoints: duration of endotracheal intubation in hours
Notes Funding for trial: NR
Risk of bias
Random sequence genera- Unclear risk Quote: "Patients were randomised equally to one of the three following
tion (selection bias) groups".
Comment: no detail regarding randomisation technique.
Allocation concealment Unclear risk Quote: "Patients were randomised equally to one of the three following
(selection bias) groups"
Comment: no detail regarding allocation concealment.
Blinding of participants Unclear risk No information regarding blinding available

mance bias)
Blinding of outcome as- Unclear risk No information regarding blinding available

Incomplete outcome data Low risk Follow-up: 24 hours. 0% loss to follow-up

(attrition bias)
All outcomes
Selective reporting (re- Unclear risk No information regarding standardisation of study endpoints available
porting bias)
Cavarocchi 1986
Number of study centres and location: two-centre study; Temple University Hospital, Philadelphia, USA
and Mayo Clinic, Rochester, USA

Informed decisions.
Cavarocchi 1986 (Continued)

Number analysed: 91
Mean age: 61.7 +/- 9.9 years
Gender: 74.7% male
Surgery type: CABG, valvular heart surgery, or combined valve and coronary surgery
Inclusion criteria: coronary artery and valvular cardiac surgery utilising extracorporeal circulation
Exclusion criteria: left ventricular ejection fraction < 40%, history of peptic ulcer disease or recent
steroid use, or a history of severe asthma or chronic obstructive pulmonary disease.
Interventions Intervention: intravenous methylprednisolone administered at a dose of 30 mg/kg twenty minutes

before commencement of cardiopulmonary bypass, extracorporeal circulation achieved with a bub-
ble-type oxygenator.
Comparison: two comparator groups were used. (1) No steroids administered, and extracorporeal by-
pass achieved with a bubble-type oxygenator. (2) No steroids, and extracorporeal bypass achieved with
a silicon membrane oxygenator.
Outcomes Primary endpoint: complement activation as measured by serum C3a and C5a at five time points, from
immediately prior to sternotomy, to the time of skin closure.
Secondary endpoints: white cell sequestration immediately after cardiopulmonary bypass, postopera-
tive cardiac index, requirement for inotropic support postoperatively, and tracheal extubation within
24 hours of surgery.
Risk of bias
Random sequence genera- Unclear risk No information regarding randomisation procedure was available.
Allocation concealment Unclear risk No information regarding allocation concealment was available.
(selection bias)
Blinding of participants High risk Comment: study was designed to evaluate the effect of different types of oxy-
and personnel (perfor- genators, which makes blinding impossible.
mance bias)
Blinding of outcome as- Unclear risk Insufficient information on blinding of outcome assessment.
Incomplete outcome data Low risk Follow-up: 24 hours. 0% loss to follow-up

(attrition bias)
All outcomes

Informed decisions.
Cavarocchi 1986 (Continued)
Selective reporting (re- Unclear risk Insufficient information.

porting bias)
Celik 2004
Methods Study design: prospective randomised placebo-controlled study
Number of study centres and location: single centre; Selcuk University, Meram, Turkey
Number analysed: 60
Mean age: 61.0 +/- 7.5 years
Gender: NR
Surgery type: CABG
Inclusion criteria: patients with coronary artery disease undergoing coronary artery bypass grafting.
Exclusion criteria: left ventricular ejection fraction < 40%, previous pulmonary disease such as ashy,
COPD, lung surgery or a requirement for supplemental oxygen or mechanical ventilatory support, se-
vere systemic non-cardiac disease, insulin dependent diabetes, myocardial infarction within previous 6
weeks, contraindication to corticosteroids or recent infection.
Interventions Intervention: intravenous methylprednisolone 30 mg/kg before and after cardiopulmonary bypass, and
6-hourly for 24 hours postoperatively.
Comparison: intravenous normal saline before and after cardiopulmonary bypass, and 6-hourly for 24
hours postoperatively.
Outcomes Primary endpoint: inflammatory response measured by serum TNFa, interleukin-6, -8 and -10 prior to
the induction of anaesthesia, and at 7 time points up to 24 hours after skin closure.
Secondary endpoints: length of time to tracheal extubation, length of stay in ICU and hospital, inci-
dence of post-operative arrhythmia and myocardial infarction, and postoperative mortality.
Risk of bias

Informed decisions.
Celik 2004 (Continued)
Random sequence genera- Unclear risk No information regarding the exact randomisation method was available.
Allocation concealment Unclear risk No information regarding the concealment of allocation was available.
(selection bias)
Blinding of participants Low risk Quote: "Therefore, all physicians and nursing staff caring for the patients were
and personnel (perfor- blinded to the treatment group."
mance bias)
Blinding of outcome as- Unclear risk Comment: not specified whether data-collection, adjudication of endpoints or
sessment (detection bias) analyses were blinded.
Incomplete outcome data Low risk Follow-up: hospital stay. 0% loss to follow-up
(attrition bias)
All outcomes
Selective reporting (re- Low risk Blood specimen sampling and laboratory handling was specified. Definitions
porting bias) of major clinical complications were specified.
Chaney 1998
Methods Study design: prospective randomised placebo-controlled trial
Number of study centres and location: single centre; Loyola University Medical Centre, Chicago, USA
Number analysed: 30
Gender: 75.0% male
Surgery type: CABG
Inclusion criteria: elective coronary artery bypass grafting and anticipated early extubation (time crite-
ria not stated), including re-do sternotomy and decreased left ventricular function
Exclusion criteria: preoperative steroid administration, previous lung surgery, preoperative require-
ment for respiratory support (supplemental oxygen or mechanical ventilatory support), or preopera-
tive haemodynamic support (including inotropes, vasopressors or intra-aortic balloon pump)
Interventions Intervention: intravenous methylprednisolone 30 mg/kg administered during sternotomy, and 30 mg/
kg administered at the initiation of cardiopulmonary bypass.

Informed decisions.
Chaney 1998 (Continued)

Comparison: intravenous isotonic sodium chloride of the same volume administered during sternoto-
my, and at the initiation of cardiopulmonary bypass.
Outcomes Primary endpoint: serum creatine kinase at three time points up to 12 hours postoperative; respiratory
function measured by lung compliance, oxygen gradient, shunt percentage and dead space percentage
at four time points up to 60 minutes after arrival in intensive care.
Secondary endpoints: postoperative atrial fibrillation or ventricular arrhythmia, cardiovascular compli-

cations, and early tracheal extubation
Notes Funding for trial: Loyola University Medical Centre Research Fund
Risk of bias
Random sequence genera- Unclear risk No detail regarding randomisation technique.

Allocation concealment Unclear risk No detail regarding allocation concealment.

(selection bias)
Blinding of participants Low risk Quote: "An anaesthesia research nurse performed the randomisation and pre-
and personnel (perfor- pared the two syringes of blinded solution that were administered". Quote:
mance bias) "All physicians and nursing staff caring for the patients preoperatively were un-
aware of the treatment group."
Blinding of outcome as- Unclear risk It was not specified whether data collection, adjudication of endpoints or
sessment (detection bias) analyses were blinded.
(attrition bias)
All outcomes
Selective reporting (re- Low risk Blood specimen sampling and laboratory handling was specified. Definitions
porting bias) of major clinical complications were specified.
Chaney 2001
Methods Study design: prospective randomised placebo-controlled trial. Multi-arm trial.
Number of study centres and location: single centre; Loyola University Medical Centre, Chicago, USA
Number analysed: 88

Informed decisions.

Gender: 77.3% male
Surgery type: CABG
Inclusion criteria: elective coronary artery bypass grafting and anticipated early extubation (time crite-
ria not stated), including re-do sternotomy and decreased left ventricular function
Exclusion criteria: preoperative steroid administration, previous lung surgery, preoperative require-
ment for respiratory support (supplemental oxygen or mechanical ventilatory support), or preopera-
tive haemodynamic support (including inotropes, vasopressors or intra-aortic balloon pump)
Interventions Intervention 1: intravenous methylprednisolone 30 mg/kg administered during sternotomy, and 30

mg/kg administered at the initiation of cardiopulmonary bypass.
Intervention 2: intravenous methylprednisolone 15 mg/kg administered during sternotomy, and 15

mg/kg administered at the initiation of cardiopulmonary bypass.
Comparison: intravenous isotonic sodium chloride of the same volume administered during sternoto-
my, and at the initiation of cardiopulmonary bypass.
Outcomes Primary endpoint: serum creatine kinase at three time points up to 12 hours postoperative; cardiovas-
cular function measured by invasive haemodynamic monitoring at four time points up to 60 minutes
after arrival in intensive care.
Secondary endpoints: postoperative atrial fibrillation or ventricular arrhythmia, cardiovascular compli-

cations, and early tracheal extubation, inotrope requirement.
Notes Funding for trial: Loyola University Medical Center Research Fund
Risk of bias
Random sequence genera- Unclear risk No information regarding the exact randomisation method was available
Allocation concealment Unclear risk No information regarding concealment of allocation was available
(selection bias)
Blinding of participants Low risk Quote: "An anaesthesia research nurse performed the randomisation and pre-
and personnel (perfor- pared the two syringes of blinded solution that were administered. All physi-
mance bias) cians and nursing staff caring for the patients perioperatively were unaware of
treatment group".
Blinding of outcome as- Unclear risk Unclear blinding of outcome assessment.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Blood specimen sampling and laboratory handling, postoperative haemody-
porting bias) namic and pulmonary monitoring, and complication definition and monitor-
ing were specified in detail.

Informed decisions.
Codd 1977
Methods Study design: prospective randomised controlled trial
Number of study centres and location: single centre; St Louis University Hospital, Missouri, USA
Date of study: 1977
Mean age: 51.75 years
Gender: 83.3% male
Surgery type: CABG
Inclusion criteria: surgical revascularisation on cardiopulmonary bypass
Exclusion criteria: concomitant surgical procedures, including ventricular aneurysmectomy or valvular

surgery.
Interventions Intervention: intravenous administration of 2 g methylprednisolone 30 minutes prior to the institution

of cardiopulmonary bypass
Comparison: standard cardiopulmonary bypass only; no treatment
Outcomes Primary endpoint: daily serum levels of glutamic oxaloacetic transaminase, lactate dehydrogenase and
creatinine phosphokinase up to day 5 postoperatively.
Secondary endpoints: postoperative left ventricular function, coronary artery graft patency as mea-
sured by angiography, and postoperative rhythm
Risk of bias
Random sequence genera- High risk Quote: "Randomization by hospital number".

Allocation concealment Unclear risk No information regarding concealment of allocation was available.
(selection bias)

Informed decisions.
Codd 1977 (Continued)
Blinding of participants Unclear risk Quote: "randomized placebo-controlled trial". No clear specification of blind-
and personnel (perfor- ing.
mance bias)
Blinding of outcome as- Unclear risk Quote: "randomized placebo-controlled trial". No clear specification of blind-
sessment (detection bias) ing.
Incomplete outcome data Low risk Two participants excluded: study violation. Follow-up: five days. 0% loss to fol-
(attrition bias) low-up
All outcomes
Selective reporting (re- Unclear risk Only surgical technique was specified. Definition of myocardial infarction, tim-
porting bias) ing of electrocardiogram, serum samples and laboratory investigations were
specified.
Coetzer 1996
Methods Study design: prospective randomised controlled trial
Number of study centres and location: single centre; University of Stellenbosch, Tiber, South Africa
Gender: 65.4% male
Surgery type: not stated
Inclusion criteria: patients undergoing cardiac surgery (type not stated) on cardiopulmonary bypass
Exclusion criteria: patients under the age of 18 and those on steroid therapy were excluded
Interventions Intervention: intravenous methylprednisolone 30 mg/kg administered 1 hour before the initiation of
cardiopulmonary bypass.
Outcomes Primary endpoint: respiratory functions, measured by the alveolar-arterial oxygen tension difference,
and the inspired oxygen fraction ratio.
Secondary endpoints: postoperative mortality
Notes Funding for trial: Medical Research Council of South Africa

Informed decisions.
Coetzer 1996 (Continued)

Risk of bias
Random sequence genera- Low risk Quote: "Patients were allocated by random card draw to one of the groups".
Allocation concealment Unclear risk Concealment of allocation was not specified.

(selection bias)
Blinding of participants Unclear risk Quote: "The first author of the study was blinded". Unclear extent of blinding.
mance bias)
Blinding of outcome as- Unclear risk Quote: "The first author of the study was blinded". Unclear extent of blinding.
Incomplete outcome data Unclear risk Follow-up: unclear, at least 30 days with completeness of data.
(attrition bias)
All outcomes
Selective reporting (re- Low risk Clinical outcome measurements and relevant calculations were specified.
porting bias)
Demir 2009
Methods Study design: RCT
Number of study centres and location: single centre; Istanbul University, Istanbul, Turkey
Number analysed: 30
Gender: 66.7% male
Surgery type: CABG
Inclusion criteria: coronary artery bypass grafting utilising cardiopulmonary bypass
Exclusion criteria: history of previous cardiac surgery, the need for concomitant surgery (valve replace-
ment or repair of ventricular aneurysm), the use of anti-inflammatory medications excluding acetyl sal-

Informed decisions.
Demir 2009 (Continued)

icylic acid, contraindication to the administration of corticosteroids, history of insulin-dependent dia-
betes mellitus or active inflammatory disease
Interventions Intervention: intravenous administration of 1 g methylprednisolone prior to cardiopulmonary bypass
Outcomes Primary endpoint: level of inflammatory response measured by serum interleukin-6, -10 and neu-
ron-specific enolase (NSE) at four time points from prior to surgery to 24 hours after cardiopulmonary
bypass.
Secondary endpoints: postoperative recovery including the duration of mechanical ventilation, length
of ICU admission, length of hospital stay, and surgical infections.
Risk of bias
Random sequence genera- Unclear risk No information with regard to randomisation method.
Allocation concealment Unclear risk No information with regard to concealment of allocation was available.
(selection bias)
Blinding of participants Unclear risk No information regarding blinding was present.

mance bias)
Blinding of outcome as- Unclear risk No information regarding blinding was present.
(attrition bias)
All outcomes
Selective reporting (re- Low risk Blood specimen sampling and handling in the laboratory was specified in de-
porting bias) tail.
Demir 2015
Methods Study design: randomised, placebo-controlled trial
Total duration of the study: not specified
Number of study centres and location: single-centre study; Kolan International Hospital, Istanbul,
Turkey
Participants Number randomised: 40 patients scheduled for elective CABG surgery

Informed decisions.
Demir 2015 (Continued)

Number analysed: 40
Mean age: 64
Gender: 12/20 male (steroids) and 13/20 male (control)
Severity of the condition according to study authors: low risk
Surgery type: CABG
Inclusion criteria: adults scheduled for elective CABG surgery
Exclusion criteria: exclusion criteria were emergency surgery, previous heart surgery, other cardiac pro-
cedures in addition to CABG, renal or hepatic dysfunction, immunological or coagulation disorders, in-
fection during the week preceding surgery, preoperative use of antibiotics or corticosteroids, history of
recent peptic ulcer disease, diabetics on insulin therapy, and white blood cell count over 11,000 mm-3.
Interventions Intervention: 1 g intravenous methylprednisolone at the beginning of CPB.
Comparison: similar volumes of intravenous isotonic sodium chloride solution at the beginning of CPB
Outcomes Blood samples were withdrawn prior to surgery (T1) and then 4 hours (T2), 24 hours (T3), and 36 hours
(T4) after CPB to detect plasma levels of interleukin (IL)-6, IL-10, creatine kinase isoenzyme MB (CK-MB),
cardiac troponin-t (cTnT), and blood glucose as well as neutrophil counts.
Surgical infection, inotropic support and length of hospital stay.
Risk of bias
Random sequence genera- Unclear risk No information regarding the exact randomisation method.
Allocation concealment Unclear risk No information regarding the concealment of allocation.

(selection bias)
Blinding of participants Unclear risk No information regarding blinding of participants and personnel.
mance bias)
Blinding of outcome as- Unclear risk No information regarding blinding of outcome assessors.
Incomplete outcome data Low risk No participants were lost at follow-up, data are reported for the entire cohort.
(attrition bias)
All outcomes
Selective reporting (re- Low risk Blood specimen sampling and laboratory handling, postoperative haemody-
porting bias) namic and pulmonary monitoring, and complication definition and monitor-
ing were specified in detail.

Informed decisions.
Dieleman 2012
Methods Study design: multicenter, randomised, double-blind, placebo-controlled study
Total duration of the study: between 13 April 2006 and 23 November 2011
Number of study centres and location: 8 cardiac surgical centres in the Netherlands: University Med-
ical Center, Utrecht; Isala Klinieken, Zwolle; Amphia Ziekenhuis, Breda; University Medical Center,
Groningen; Erasmus Medical Center, Rotterdam; Medisch Spectrum Twente, Enschede; Medical Center,
Leeuwarden; Vrije Universiteit Medical Center, Amsterdam; and Academic Medical Center, University of
Amsterdam, Amsterdam
Date of study: 2012
Mean age: 66.2
Surgery type: any type of elective or urgent cardiac surgical procedure requiring CPB
Inclusion criteria: patients aged 18 years or older who were scheduled for any type of elective or urgent
cardiac surgical procedure requiring CPB
Exclusion criteria: emergent or off-pump procedure and a life expectancy of less than 6 months
Interventions Intervention: dexamethasone (1 mg/kg of body weight, with a 100 mg maximum)
Comparison: placebo
Outcomes The primary study endpoint of major adverse events was a composite of death, myocardial infarction
(MI), stroke, renal failure, or respiratory failure, occurring within 30 days of randomisation.
An exploratory analysis of prospectively defined secondary outcomes included each separate compo-
nent of the primary end point (i.e. death, MI, stroke, renal failure, or respiratory failure, within the first
30 days); postoperative infections; postoperative atrial fibrillation; highest serum glucose concentra-
tion in the ICU; highest body temperature in the ICU; postoperative delirium (defined as the postopera-
tive indication for treatment with neuroleptic drugs); time to weaning from postoperative mechanical
ventilation; and time to discharge from the ICU and from the hospital.
Patient follow-up for secondary outcomes was until 1 year from randomisation by study protocol.
During the study, 3 preplanned interim analyses on the primary study endpoint were performed when
1000, 2000, and 3250 participants, respectively, had been enroled.
Notes Funding for trial: this work was supported by grants 80-82310-98-08607 from the Netherlands Organiza-
tion for Health Research and Development (ZonMw) and 2007B125 from the Dutch Heart Foundation.
Conflicts of interest of trial authors: none
Risk of bias

Informed decisions.
Dieleman 2012 (Continued)
Random sequence genera- Low risk Computer-generated randomisation scheme.

Allocation concealment Low risk Central allocation (pharmacy).

(selection bias)
Blinding of participants Low risk Double-blind RCT.

mance bias)
Blinding of outcome as- Low risk Quote: "An independent, blinded critical event adjudication committee re-
sessment (detection bias) viewed all cases of death, possible MI, and possible stroke. Cases of possible
MI or stroke were either confirmed or revoked according to the study defini-
tions of these events."
Comment: blinding preserved throughout the study.
Incomplete outcome data Low risk 12 participants lost at primary endpoint (0.2%) and 25 (0.5%) lost at secondary
(attrition bias) endpoint.
All outcomes
Selective reporting (re- Low risk Results for stated outcomes reported, protocol published.
porting bias)
El Azab 2002
Methods Study design: randomised controlled trial
Number of study centres and location: single centre; Department of Anaesthesia and Intensive Care,
Amphia Hospital, Breda, the Netherlands
Number analysed: 17
Mean age: 63
Gender: male/total 7/9 (steroids) and 6/8 (control)
Surgery type: CABG
Inclusion criteria: patients undergoing elective CABG surgery with CPB
Exclusion criteria: patients with severely impaired left ventricular function (ejection fraction < 40%),
pulmonary disease, severe systemic non-cardiac disease, renal or liver impairment, insulin-dependent
diabetes, recent myocardial infarction (< 6 weeks), infectious disease before operation, and those re-
ceiving corticosteroid or other immunosuppressive treatment.

Informed decisions.
El Azab 2002 (Continued)
Interventions Intervention: on the morning of the operation, dexamethasone 100 mg
Comparison: on the morning of the operation, placebo
Outcomes Primary outcomes were blood levels of TNF-a, IL-6, IL-8, IL-10 and IL-4 at the following times: before in-
duction of anaesthesia (T0), after induction of anaesthesia and before skin incision (T1), before start-
ing cardiopulmonary bypass (T2), after aortic declamping (T3), at the end of CBP (T4), 2 hours after skin
closure (T5), and 24 hours after skin closure (T6). Samples were collected in tubes containing lithium
heparin (VenoJectâ, Terumo, Europe NV, Leuven, Belgium). The samples were immediately centrifuged
at 1000 g, and the plasma was stored at ±70°C until assays were performed. Enzyme-linked immunosor-
bent assays (ELISA; Immuliteâ, DPC, Los Angeles, USA) were used to measure TNF-a, IL-6, IL-8, IL-10 and
IL-4.
Secondary outcomes were min/max mean arterial pressure, mean heart rate, mean cardiac index,
mean pulmonary artery pressure, mean pulmonary artery pressure, mean respiratory rate, mean tem-
perature, mean time to tracheal extubation, mean length of stay in ICU and need for inotropic support
(number of participants).
Notes Funding for trial: Egyptian Ministry of High Education and Scientific Research
Conflicts of interest of trial authors: no
Risk of bias
Random sequence genera- Unclear risk Insufficient information

Allocation concealment Unclear risk No information regarding the exact randomisation procedure or concealment
(selection bias) of allocation was available.
Blinding of participants Unclear risk Insufficient information

mance bias)
Blinding of outcome as- Unclear risk Insufficient information

Incomplete outcome data Low risk No missing outcome data.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Results for stated outcomes reported.
porting bias)
Enc 2006
Methods Study design: double-blind randomised prospective study

Informed decisions.
Enc 2006 (Continued)

Number of study centres and location: single centre; Thoracic and Cardiovascular Surgery Center, Is-
tanbul, Turkey
Number analysed: 40
Mean age: 60.1 (steroid); 56.6 (control)
Gender: male/total 40/40
Surgery type: CABG
Inclusion criteria: non-diabetic male patients with three-vessel disease undergoing first-time bypass
surgery
Exclusion criteria: NR
Interventions Intervention: 25 mg/kg methylprednisolone
Comparison: saline
Outcomes Primary outcome was myocardial tissue damage measured by cTnI levels (before surgery, at the sec-
ond hour after CPB, and postoperatively at 6 hours, 24 hours, and on day 5).
Secondary outcomes were in-hospital length of stay, rate of infection/wound problems, and postopera-
tive AF.
Notes Funding for trial: none
Risk of bias
Random sequence genera- Unclear risk Insufficient information regarding randomisation technique.
Allocation concealment Unclear risk No information regarding allocation concealment was available.
(selection bias)
Blinding of participants Low risk Double-blind study - however, no further details given.
mance bias)
Blinding of outcome as- Unclear risk Not documented.

Incomplete outcome data Low risk 40 participants randomised and 40 analysed.

(attrition bias)
All outcomes
porting bias)

Informed decisions.
Enc 2006 (Continued)
Engelman 1995
Number of study centres and location: single centre; Division of Cardiac Surgery, Baystate Medical Cen-
ter, Springfield, Massachusetts, USA
Number analysed: 19
Gender: male/total 7/10 (steroid) - 7/9 (control)
Surgery type: CABG
Inclusion criteria: elective coronary revascularisation patients
Interventions Intervention: 1 g of methylprednisolone sodium succinate intravenously before bypass and 4 mg of

dexamethasone every 6 hours for four doses during the first 24 hours of recovery.
Outcomes Primary outcomes: C3a, C5a, IL-1B, IL-8 levels were measured before bypass, immediately after bypass,
and at 24, 48 and 72 hours of recovery.
Secondary outcomes were peak weight gain, maximal creatine kinase-MB, ICU length of stay and hospi-
tal length of stay.
Notes Funding for trial: National Institutes of Health grants HL 22559-14 and HL 34360-07.
Risk of bias
Random sequence genera- Unclear risk Insufficient information.

Allocation concealment Unclear risk No concealment of allocation was described.

(selection bias)

Informed decisions.
Engelman 1995 (Continued)
Blinding of participants Unclear risk Study only documents that blood work was blinded.
mance bias)

Incomplete outcome data Low risk 19 participants randomised and analysed.

(attrition bias)
All outcomes
porting bias)
Ferries 1984
Methods Study design: randomised controlled trial. Multi-arm trial.
Number of study centres and location: single centre
Number analysed: 80
Mean age: 60
Gender: 39% male
Severity of the condition according to study authors: not specified
Surgery type: mixed
Inclusion criteria: adults undergoing cardiac surgery with CPB
Exclusion criteria: refusal to consent, emergency operations, Friday operations
Interventions Intervention: methylprednisolone, 30 mg/kg; membrane and bubble oxygenators.
Comparison: no steroids; membrane and bubble oxygenators.
Outcomes Primary outcomes were complement factors assays (C3a) in the postoperative period.
Authors report on in-hospital mortality.
Notes Same study population as Ferries 1987
Funding for trial: supported in part by the Marshfield Clinic, Marshfield Medical Foundation, and Up-
john Diagnostics

Informed decisions.
Ferries 1984 (Continued)

Conflicts of interest of trial authors: unclear
Risk of bias
Random sequence genera- Low risk Quote: "the randomization was planned so as to create four groups of 20 pa-
tion (selection bias) tients by random number allocation using a standard table of random num-
bers".
Comment: random number generator used.
Allocation concealment Low risk Pharmacists prepped the medication in coded syringes.
(selection bias)
Blinding of participants Low risk Surgeon, perfusionist, and laboratory technician did not know which partici-
and personnel (perfor- pants were in which group.
mance bias)

Incomplete outcome data Low risk 80 participants randomised and analysed.

(attrition bias)
All outcomes
porting bias)
Fillinger 2002
Methods Study design: randomised, prospective, double-blind, placebo-controlled clinical trial with concurrent
comparison groups.
Number of study centres and location: single centre; Departments of Anesthesiology, Surgery, Physiol-
ogy, and Pathology, Dartmouth–Hitchcock Medical Center, Lebanon; and Dartmouth Medical School,
Hanover, NH USA
Number analysed: 30
Gender: male/total - NR
Surgery type: CABG

Informed decisions.
Fillinger 2002 (Continued)

Inclusion criteria: elective CABG surgery as the first case of the day; had no history of immune dysfunc-
tion; had not had prior cardiac surgery; had no history of a bacterial infection within 30 days of surgery;
and were not taking any drugs, including glucocorticoids, known to affect immune function.
Interventions Intervention: 15 mg/kg intravenously 60 minutes before surgical incision followed by 0.3 mg/kg intra-
venously every 6 hours for 4 doses beginning 2 hours after completion of surgery
Comparison: isotonic sodium chloride
Outcomes Primary outcomes were circulating plasma levels of IL-6 and IL-10 at baseline (immediately after place-
ment of a radial arterial catheter and before the induction of anaesthesia), at 60 minutes after the end
of CPB, and on the morning of the 1st and 3rd postoperative days (POD1 and POD3).
Secondary outcomes were postoperative length of hospital stay (days after surgery until time of dis-
charge); duration of postoperative endotracheal intubation (hours); and convalescence endpoints, in-
cluding pain (serial visual analogue scales, analgesic use), nausea and vomiting, and pulmonary func-
tion (vital capacity, peak expiratory flow rates, alveolar-arterial oxygen gradient); cardiovascular mea-
surements (heart rate, mean arterial pressure, cardiac output, central venous pressure, pulmonary
artery systolic and diastolic pressures, and systemic vascular resistance) were determined at baseline
before induction of general anaesthesia (T0), after induction of general anaesthesia (T1), 2 minutes
post-sternotomy (T2), 5 minutes after separation from CPB (T3), 2 minutes after sternal closure (T4),
and on admission to the cardiothoracic ICU (T5).
Risk of bias
Random sequence genera- Unclear risk Quote: "Randomization was performed by the hospital pharmacy with pre-
tion (selection bias) pared syringes of solution administered by the anaesthesiologist intraopera-
tively and by the cardiothoracic intensive care unit nurses"
Comment: the exact manner of randomisation was not described.
Allocation concealment Unclear risk Quote: "Randomization was performed by the hospital pharmacy with pre-
(selection bias) pared syringes of solution administered by the anaesthesiologist intraopera-
tively and by the cardiothoracic intensive care unit nurses"
Comment: unclear whether allocation concealment was adequate.
Blinding of participants Low risk Study participants, investigators, and other physicians and nurses caring for
and personnel (perfor- the participants perioperatively were blinded to the treatment group.
mance bias)
Blinding of outcome as- Unclear risk No description.

Incomplete outcome data Low risk 30 participants randomised and 30 analysed.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Results for outcomes reported.

porting bias)

Informed decisions.
Giomarelli 2003
Methods Study design: prospective, randomised, double-blind, placebo-controlled clinical study
Total duration of the study: 4 months
Number of study centres and location: single centre - Istituto di Chirurgia Toracica e Cardiovascolare,
Università di Siena, Italy
Date of study: 2002
Number analysed: 20
Gender: male/total 7/10 (steroid); 6/10 (control)
Surgery type: CABG
Inclusion criteria: CABG
Exclusion criteria: urgency/emergency surgery; previous heart surgery; valve or combined CABG and
valve surgery; left ventricular ejection less than 0.35; diabetics on insulin therapy; active gastropath-
ic disorder; chronic obstructive pulmonary disease on therapy; preoperative use of steroids and con-
traindications to steroid administration; Cleveland Clinic score of 4 or higher.
Interventions Intervention: 1 g intravenous methylprednisolone (MPS) preoperatively and 125 mg at the end of CPB.
Comparison: isotonic sodium chloride solution.
Outcomes Primary and secondary outcomes were interleukin-6, IL-8, IL-10 and TNF-a levels measured at the fol-
lowing intervals: T1 = 15 minutes after intubation, T2 = 5 minutes after aortic cross-clamp release, T3 =
10 minutes after CPB, T4 = 3 hours after CPB, T5 = 12 hours after CPB, T6 = 24 hours after CPB, and T7 =
4 days after operation.
Secondary outcomes: mean arterial pressure, cardiac index (CI, by thermodilution), systemic vascu-
lar resistance, pulmonary artery pressure, pulmonary vascular resistance, and central venous pressure
were recorded at the same intervals, except T7. Also, alveolar-arterial oxygen gradient (A- aDo2), respi-
ratory index (RI), shunt (Qs/Qt), dead space (Vd/Vt), arterial-venous difference in oxygen (a-vo2D), oxy-
gen extraction ratio (o2ER), and oxygen delivery (Do2) were calculated using standard formulas. Serial
temperature measurements were also obtained. CK and CK-MB were evaluated at following intervals:
T0 = basal value, T4 = 3 hours after CPB, T5 = 12 hours after CPB, T6 = 24 hours after CPB and T7 = 4 days
after operation.
Outcomes retrieved after correspondence with author
Risk of bias

Informed decisions.
Giomarelli 2003 (Continued)
Random sequence genera- Low risk Quote: "Patients were randomized according to a computer-generated se-
tion (selection bias) quence and assigned either to the standard care..."
Allocation concealment Low risk Only an anaesthetic nurse not involved in the study was aware of the alloca-
(selection bias) tion while making up the syringes.
Blinding of participants Low risk An anaesthesia nurse performed the randomisation and prepared the syringes
and personnel (perfor- of blinded solution that were administered by the anaesthesiologist managing
mance bias) the case. All physicians and nursing staff caring for the participants periopera-
tively were unaware of the treatment groups.

Incomplete outcome data Low risk 20 participants randomised and subsequently analysed.
(attrition bias)
All outcomes
Selective reporting (re- Low risk Results for outcomes stated have been reported.
porting bias)
Glumac 2017
Methods Study design: randomised, double-blind, placebo-controlled, parallel-arm trial
Total duration of the study: 10 months, March 2015 to January 2016
Number of study centres and location: single centre; University Hospital of Split, Croatia
Study setting: Clinical Department of Anaesthesiology and Intensive Care
Date of study: 2017
Mean age: 63.7 (steroids) and 64.2 (control)
Surgery type: CABG, heart valve surgery or combined surgery (CABG and valve surgery)
Inclusion criteria: patients aged between 41 and 84 years who were scheduled for elective coronary
artery bypass graft surgery (CABG), heart valve surgery or combined surgery (CABG and valve surgery)
with or without CPB
Exclusion criteria: any cerebrovascular incident in the last 3 years; mental illness; visual, hearing or mo-
tor impairment interfering with cognitive assessment; previous cardiac or carotid surgery; left ventricu-

Informed decisions.
Glumac 2017 (Continued)

lar ejection fraction of less than 35%; adrenal gland disease requiring steroid treatment for longer than
7 days in the past year; alcohol (> 50 g/day or > 500 g/week) or controlled substance abuse; a preoper-
ative Mini Mental State Examination (MMSE) score less than 26 points; a preoperative Beck Depression
Inventory-Second Edition (BDI-II) score more than 19 points; a preoperative CRP level more than 5 mg/
L; a preoperative white blood cell (WBC) count less than 4 or more than10 × 109/L; perioperative stroke
and additional corticosteroid treatment throughout the study period. Stroke was defined as focal brain
injury as detected via standard neurological examination and signs of new ischaemia-induced cerebral
infarction on a computed tomography scan.
Interventions Intervention: single intravenous bolus of 0.1 mg/kg dexamethasone 10 hours before surgery.
Comparison: same volume of placebo (0.9% NaCl) 10 hours before surgery.
Outcomes Primary outcomes specified: incidence of postoperative cognitive dysfunction (POCD) on the 6th day
after surgery
Secondary outcomes specified: incidence of SIRS, CRP levels 12 hours after surgery and on the 1st, 2nd
and 3rd postoperative days, S100b protein levels at 6 and 30 hours following the end of CPB or 3 hours
following the end of beating-heart surgery.
Time points reported: main time point was 6th POD
Notes Funding for trial: Clinical Department of Anaesthesiology and Intensive Care, University Hospital of
Split, Split, Croatia.
Risk of bias
Random sequence genera- Low risk The pharmacy of the University Hospital of Split prepared the trial medication
tion (selection bias) in computer-randomised blocks.
Allocation concealment Low risk Indistinguishable, sequentially numbered vials.

(selection bias)
Blinding of participants Low risk The patients, their treating physicians, the biochemists and the investigators
and personnel (perfor- were blind to the treatment allocation.
mance bias)
Blinding of outcome as- Unclear risk Insufficient description.

Incomplete outcome data Low risk No missing data.

(attrition bias)
All outcomes
Selective reporting (re- Low risk No evidence of selective reporting.

porting bias)
Gomez Polo 2018


Informed decisions.
Gomez Polo 2018 (Continued)
Methods Study design: double-blind randomised controlled trial
Number of study centres and location: three cardiac centres (Hospital Clinic San Carlos, Madrid; Hospi-
́
tal Clinico Universitario, Salamanca; University Hospital Son Espases, Palma de Mallorca)
Mean age: 64
Gender: 73% males
Severity of the condition according to study authors: normal risk profile. Elective cardiac surgery pa-
tients.
Surgery type: mixed
Inclusion criteria: patients without prior history of AF or atrial flutter and scheduled to undergo cardiac
surgery (coronary artery bypass graft surgery, valve replacement or combined surgery).
Exclusion criteria: not specified
Interventions Intervention: methylprednisolone or placebo administered at the time of anaesthetic induction and
dexamethasone or placebo every 8 hours during the 24 hours after surgery. All participants were treat-
ed with oral carvedilol before and after surgery.
Control: standard treatment
Outcomes Patient acute phase protein levels (IL-6) after cardiac surgery and new onset of AF documented during
hospital stay.
Notes Abstract only
Funding for trial: none specified
Conflicts of interest of trial authors: none specified
Risk of bias
Random sequence genera- Unclear risk No description.

Allocation concealment Unclear risk No description.

(selection bias)
Blinding of participants Low risk Double-blind RCT.

mance bias)
Blinding of outcome as- Unclear risk No description.


Informed decisions.
Gomez Polo 2018 (Continued)
Incomplete outcome data Low risk No missing data.

(attrition bias)
All outcomes
Halonen 2007
Methods Study design: double-blind, randomised multicenter trial
Total duration of the study: 10 months, between August 2005 and June 2006
Number of study centres and location: 3 university hospitals (University Hospital of Kuopio, University
Hospital of Oulu, and University Hospital of Tampere) in Finland
Date of study: 2006
Mean age: 64.4 (steroids) and 66.1 (control)
Average BMI: 27.8
Surgery type: on-pump coronary artery bypass graft (CABG) surgery, aortic valve replacement, or com-
bined CABG surgery and aortic valve replacement.
Inclusion criteria: people aged between 30 and 85 years without prior AF or flutter and scheduled to
undergo first on-pump coronary artery bypass graft (CABG) surgery, aortic valve replacement, or com-
bined CABG surgery and aortic valve replacement.
Exclusion criteria: "Previous episodes of AF or flutter, uncontrolled diabetes mellitus, systemic bacteri-
al or mycotic infection, active tuberculosis, Cushing syndrome, psychotic mental disorder, herpes sim-
plex keratitis, or renal insufficiency (serum creatinine concentration > 20 mg/dL [>1768 μmol/L]). We al-
so excluded patients with a history of peptic ulcer or thrombophlebitis."
Interventions Intervention: 100-mg hydrocortisone as follows: the first dose in the evening of the operative day,
then 1 dose every 8 hours during the next 3 days. In addition, all participants received oral metoprolol
(50-150 mg/day) titrated to heart rate.
Comparison: placebo as follows: the first dose in the evening of the operative day, then 1 dose every
8 hours during the next 3 days. In addition, all participants received oral metoprolol (50-150 mg/day)
titrated to heart rate.
Outcomes Occurrence of AF during the first 84 hours after cardiac surgery. Major postoperative complications
(mediastinitis or other complications requiring hospitalisation)

Informed decisions.
Halonen 2007 (Continued)
Notes Funding for trial: Kuopio University EVO Foundation.
Risk of bias
Random sequence genera- Low risk Randomisation lists were produced by a biostatistician (P.H.). The groups were
tion (selection bias) block-randomised with block sizes of 6, separately in each hospital.
Allocation concealment Unclear risk Quote: "Randomization lists were produced by a biostatistician. The groups
(selection bias) were block-randomized with block sizes of 6, separately in each hospital"
Comment: no further details on allocation concealment.
Blinding of participants Low risk The study group remained unknown to all caring nurses and physicians. Par-
and personnel (perfor- ticipants were also blinded to allocation. It was not necessary to break the
mance bias) code for any of the participants, so blinding was ensured.
Blinding of outcome as- Unclear risk There is no documentation regarding when investigators were made aware of
sessment (detection bias) participant randomisation; these investigators then called the participants for
follow-up.
Incomplete outcome data Low risk One participant died but none lost to follow-up.
(attrition bias)
All outcomes

porting bias)
Halvorsen 2003
Methods Study design: prospective, randomised, double-blinded, placebo-controlled study
Number of study centres and location: not stated; Norway
Study setting: Department of Anesthesiology
Number lost to follow-up/withdrawn: 6 (abdominal complications, anaphylaxis, study violation)
Mean age: 63 (steroids) and 64 (control)

Informed decisions.
Halvorsen 2003 (Continued)

Surgery type: CABG
Inclusion criteria: patients scheduled for elective CABG surgery
Exclusion criteria: patients receiving chronic corticosteroid medication and those with a history of AF
(or other cardiac arrhythmias)
Interventions Intervention: dexamethasone (8 mg IV) after initiating maintenance of anaesthesia and on the morning
of the first postoperative day
Comparison: saline after initiating maintenance of anaesthesia and on the morning of the first postop-
erative day
Outcomes Primary outcomes were incidences of postoperative nausea and vomiting (PONV) requiring a therapeu-
tic intervention and new onset AF during the first 72 hours after surgery.
Secondary outcomes were severity of pain and the opioid analgesic requirement.
Notes Funding for trial: institutional sources only
Conflicts of interest of trial authors: no clear conflict of interest
Risk of bias
Random sequence genera- Low risk A block randomisation scheme was used with 20 participants allocated to each
tion (selection bias) block.
Allocation concealment Low risk Quote: "The sealed envelope was opened immediately before surgery..."
(selection bias)
Blinding of participants Low risk To maintain the double-blinded study design, the sealed envelope was opened
and personnel (perfor- immediately before surgery, and the study drug was prepared in identical-ap-
mance bias) pearing syringes by a nurse who did not participate in the treatment of the
study participants.
Blinding of outcome as- Unclear risk No documentation of how and when randomisation outcome was disclosed
sessment (detection bias) and who collected the outcome data.
Incomplete outcome data Unclear risk Six participants were excluded from analysis for the following reasons: (1) an
(attrition bias) anaphylactoid reaction to protamine (n = 1); (2) development of acute abdom-
All outcomes inal complications after surgery (n = 2); (3) a perforated ventricular ulcus (n =
1); and (4) protocol violations related to the use of non-approved antiemetic
drugs (n = 2).
Selective reporting (re- Low risk No clear evidence of selective reporting.

porting bias)
Hao 2019

Informed decisions.
Hao 2019 (Continued)

Number of study centres and location: single centre - Beijing Anzhen Hospital, Capital Medical Universi-
ty
Number analysed: 36
Mean age: 53.3 ± 14.41
Gender: 58.3% male
Surgery type: valvular surgery (MVR 14, AVR 4, MVR+AVR 18)
Inclusion criteria: patients undergoing valvular surgery
Exclusion criteria: underlying infection, tumour, pregnancy, autoimmune disorders
Interventions Intervention: methylprednisolone 500 mg in CPB prime
Control: no steroids administration
Outcomes Primary outcome: changes of phenotypically and functionally different subpopulations of T-reg cells
and monocytes in the peripheral blood in the early postoperative period
Notes Funding for trial: National Natural Science Foundation of China (No. 81071587 to Hui Zeng, No.
81270327 to Xiaotong Hou and No. 81470528 to Xiaotong Hou
Risk of bias
Random sequence genera- Unclear risk No documentation of randomisation process

Allocation concealment Unclear risk No clear documentation of allocation concealment

(selection bias)
Blinding of participants Unclear risk No documentation so could not be assessed.

mance bias)
Blinding of outcome as- Unclear risk No documentation so could not be assessed.

Incomplete outcome data Unclear risk No documentation so could not be assessed.

(attrition bias)
All outcomes

porting bias)

Informed decisions.
Harig 1999
Number of study centres and location: single centre - Center for Cardiac Surgery, Friedrich-Alexander
University Erlanqen-Numberq. Erlangen, Germany
Number analysed: 20
Mean age: 62
Gender: 35% male
Surgery type: elective coronary artery bypass grafting
Inclusion criteria: informed consent
Exclusion criteria: renal or hepatic insufficiency and a known anaphylaxis to aprotinin
Interventions Intervention: prednisolone 250 mg pre- and postoperatively
Outcomes Outcomes were mortality, time to extubation, ICU stay, re-thoracotomy, biomarkers measured during
hospital stay
Notes Funding for trial: none reported
Conflicts of interest of trial authors: no clear COI identified
Risk of bias
Random sequence genera- Unclear risk No description of randomisation process.

Allocation concealment Unclear risk Quote: "Cohorts of 10 patients were randomized independently"
(selection bias)
Comment: concealment of allocation was unclear.
Blinding of participants Unclear risk No documentation so could not be assessed.

mance bias)

Incomplete outcome data Unclear risk No documentation so could not be assessed.

(attrition bias)
Informed decisions.
Harig 1999 (Continued)

All outcomes

porting bias)
Hauer 2012
Methods Study design: randomised, double-blinded, controlled trial
Number of study centres and location: single centre
Number lost to follow-up/withdrawn: 3 died perioperatively in the ICU and 40 were lost to follow-up (n
= 11) or because they could not be contacted after discharge from the hospital (n = 29)
Number analysed: 97 (32 had received placebo and 36 had received hydrocortisone)
Mean age: 69
Gender: 82% male
Severity of the condition according to study authors: standard risk
Surgery type: mixed (CABG) and valve surgery
Inclusion criteria: adults undergoing CABG and valve surgery
Exclusion criteria: combined surgical procedures, emergency surgery, pregnancy, plasma interleukin-6
(IL-6) levels higher than 10 pg/mL preoperatively, hepatic dysfunction (bilirubin > 3 mg/dL), renal dys-
function (plasma creatinine > 2 mg/dL), a positive serological test result for HIV or hepatitis, manifest
insulin-dependent diabetes mellitus, use of steroidal or nonsteroidal antiphlogistics (except low-dose
aspirin) during the last 7 days before surgery, an extracardial septic focus, chronic or acute inflammato-
ry disease, and an inability to give informed consent. In addition, patients with previous intensive care
unit (ICU) treatment (with the exception of brief stays in coronary care units) and those who required
glucocorticoids for medical reasons (e.g. asthma or rheumatism).
Interventions Intervention: "Hydrocortisone was administered by using a loading dose (100 mg over 10 min, intra-
venous [IV]) before induction of anesthesia, followed by a continuous infusion of 10 mg/h for 24 h (POD
1), which was reduced to 5 mg/h on POD 2, and then tapered to 3 × 20 mg IV on POD 3, and 3 × 10 mg IV
on POD 4."
Comparison: placebo (administration not specified)
Outcomes Primary outcome: occurrence of delirium and the incidence and intensity of depression at 6 months af-
ter cardiac surgery in relation to EC plasma concentrations and the use of hydrocortisone.
Notes Discrepancy for male/female proportion in control group.
Funding for trial: Else Kröner-Fresenius Foundation (non-profit)
Conflicts of interest of trial authors: none identified

Informed decisions.
Hauer 2012 (Continued)
Risk of bias
Random sequence genera- Low risk Quote: "Randomization to hydrocortisone or placebo treatment was per-
tion (selection bias) formed in blocks of four by using a computer-generated randomization list"
Comment: adequate, computer-generated randomisation list
Allocation concealment Unclear risk No clear documentation of allocation concealment, although likely present
(selection bias) (based on the general quality of the trial and on the measures adopted to re-
duce other sources of bias)
Blinding of participants Low risk Quote: "Patients, investigator staff, persons performing the assessments, and
and personnel (perfor- data analysts remained blinded to the identity of the treatment from the time
mance bias) of randomization until database lock when data entry was finished."
Blinding of outcome as- Low risk Quote: "Patients, investigator staff, persons performing the assessments, and
sessment (detection bias) data analysts remained blinded to the identity of the treatment from the time
of randomization until database lock when data entry was finished."
Incomplete outcome data High risk 13% of the participants randomised excluded from the analysis, 30% lost at 6-
(attrition bias) month follow-up.
All outcomes
Selective reporting (re- Low risk Quote: "The study was approved by the Institutional Review Board of the Lud-
porting bias) wig-Maximilians University of Munich (protocol number 149/00, Amendment)
and the relevant government and regulatory agencies. Data protection met
the standard set by German law."
Comment: protocol registered and approved with the Institutional University

Board and on Clinicaltrials.gov (NCT00490828).
Jansen 1991
Methods Study design: randomised, placebo-controlled, double-blinded trial
Number of study centres and location: single centre - Department of Cardia-Pulmonary Surgery, Re-
search Division, University Hospital, Groningen, and the Department of Intensive Treatment, Depart-
ment of Hematology and Department of Cardia-Pulmonary Surgery, Onze Lieve Vrouwe Gasthuis, Ams-
terdam, Groningen and Amsterdam, the Netherlands.
Number analysed: 25
Mean age: 62

Informed decisions.
Jansen 1991 (Continued)

Gender: not specified
Surgery type: CABG
Inclusion criteria: patients undergoing elective CABG
Exclusion criteria: insulin-dependent diabetes mellitus, preoperative use of corticosteroids, chronic ob-
structive lung disease, CPB time longer than 180 minutes, use of an intra-aortic balloon pump, and re-
operation
Interventions Intervention: 1 mg/kg dexamethasone
Outcomes Outcomes were mortality, ICU stay, infections, biomarkers measured during hospital stay (no distinc-
tion between primary and secondary outcomes)
Notes 3 excluded, study violation
Funding for trial: none specified
Conflicts of interest of trial authors: none specified
Risk of bias
Random sequence genera- Unclear risk No information on randomisation procedure

Allocation concealment Unclear risk No information on allocation procedure

(selection bias)
Blinding of participants Unclear risk Insufficient information

mance bias)

Incomplete outcome data Low risk One participant in the placebo group excluded for incomplete data.
(attrition bias)
All outcomes

porting bias)
Kerr 2012
Methods Study design: randomised, double-blind, placebo-controlled, parallel study
Total duration of the study: between April 2000 and October 2004

Informed decisions.
Kerr 2012 (Continued)

Number of study centres and location: single centre; University of California
Date of study: 2012
Number analysed: 98
Mean age: 49
Gender: 45.9% male
Severity of condition according to study authors: high risk setting
Surgery type: pulmonary thromboendarterectomy (PTE)
Inclusion criteria: 18 years, scheduled for pulmonary thromboendarterectomy
Exclusion criteria: systemic (oral or IV) corticosteroids, immunosuppressive drugs, investigational drug
within the previous 30 days, history of previous sternotomy, pre-existing neurologic disease, diabetes,
current pregnancy or lactation, current use of epoprostenol, or an additional planned cardiothoracic
procedure (e.g. coronary artery bypass grafting, valve replacement) to be performed at the time of the
pulmonary thromboendarterectomy.
Interventions Intervention: 30 mg/kg methylprednisolone (Pfizer Pharmacia Upjohn) IV push bolus delivered in the
CPB prime solution, 500 mg methylprednisolone (62.5 mg/mL) IV over 15 minutes upon rewarming
while on CPB following PTE, and 250 mg methylprednisolone diluted in 50 mL 0.9% normal saline IV
over 15 minutes at 36 hours following the start of surgery.
Comparison: 0.9% Sodium chloride at the same time points
Excluded concomitant medications: corticosteroids, immunosuppressive drugs, investigational drug,

epoprostenol
Outcomes Primary outcomes: incidence and/or severity of lung injury following thromboendarterectomy (in-hos-
pital)
Secondary outcomes: mortality; ventilator-free, ICU-free, and hospital-free days; lung injury scores;
and biologic end points (selected cytokine levels in both plasma and BAL fluid)
Time points reported - after induction of anaesthesia and prior to incision (T1), 60 minutes after the fi-
nal circulatory arrest was completed (T2), 2 hours after discontinuation of CPB (T3), and 24 hours (T4)
and 48 hours (T5) following the start of surgery. BAL was performed immediately before surgery (day 1)
and approximately 24 hours later (day 2).
Notes Funding for trial: study was supported by the National Institutes of Health [Grants from the National
Center for Research Resources for the University of California, San Diego, General Clinical Research
Center]
Conflict of interest: Dr Spragg served as a consultant to Nycomed GmbH.
Risk of bias
Random sequence genera- Low risk Computer-based randomisation was performed by the investigational phar-
tion (selection bias) macist.

Informed decisions.
Kerr 2012 (Continued)
Allocation concealment Low risk All study medications were prepared by the investigational pharmacist, who
(selection bias) otherwise was not involved in patient care, and were concealed in foil to main-
tain blinding.
Blinding of participants Low risk The investigators and site personnel (with the exception of the investigational
and personnel (perfor- pharmacist) were blinded to the assigned treatment group.
mance bias)
Blinding of outcome as- Low risk Each participant was evaluated daily on days 1 to 3 by two independent blind-
sessment (detection bias) ed investigators for the presence of lung injury using criteria used in a previous
study.
Incomplete outcome data Unclear risk Three participants were withdrawn from the study after enrolment: two be-
(attrition bias) cause of a change in the surgery schedule and one because of the inadvertent
All outcomes administration of corticosteroids into the CPB prime.

porting bias)
Kilger 2003a
Methods Study design: randomised, non-blinded, controlled trial
Total duration of the study: from 1999 to 2000
Number of study centres and location: single centre; Department of Cardiac Surgery (GN), Ludwig-Max-
imilians University, Munich, Germany
Date of study: 2003
Number analysed: 91
Mean age: 69
Surgery type: mixed
Inclusion criteria: 1) coronary artery bypass grafting (CABG) with four or more grafts; or 2) valve surgery
combined with CABG; or 3) a preoperative cardiac ejection fraction of less than 40%
Exclusion criteria: emergency surgery, pregnancy, interleukin (IL)-6 levels higher than 10 pg/mL preop-
eratively, hepatic dysfunction (bilirubin > 3 mg/dL), renal dysfunction (plasma creatinine > 2 mg/dL),
positive serologic test for human immunodeficiency virus, manifest insulin-dependent diabetes melli-
tus, use of steroidal or nonsteroidal antiphlogistics (except low-dose aspirin) during the last 7 days be-
fore surgery, an extracardial septic focus, chronic or acute inflammatory disease, and inability to give
informed consent

Informed decisions.
Kilger 2003a (Continued)
Interventions Intervention: hydrocortisone, 1 x 100 mg before induction, followed by 240 mg/day, 120 mg/day, 60
mg/day, 30 mg/day (n = 48)
Comparison: standard management (n = 43)
Outcomes Outcomes were mortality, time to extubation, ICU stay, hospital stay, number of blood transfusions, in-
flammatory biomarker measured during hospital stay (authors do not distinguish between primary and
secondary outcomes)
Notes Funding for trial: Eli-Lilly International Foundation, Bad Homburg, Germany
Conflicts of interest of trial authors: not stated
Risk of bias
Random sequence genera- Unclear risk Quote: "patients were allocated randomly to two groups"
Comment: randomisation technique was not described.
Allocation concealment Unclear risk Quote: "patients were allocated randomly to two groups"
(selection bias)
Comment: allocation procedure was not described.
Blinding of participants High risk Quote: "one limitation of this study is that it was performed only in a random-
and personnel (perfor- ized
mance bias) controlled, but not in a double-blind manner."
Blinding of outcome as- High risk Quote: "one limitation of this study is that it was performed only in a random-
sessment (detection bias) ized
controlled, but not in a double-blind manner."
Incomplete outcome data Low risk Follow-up: six months. 0% loss to follow-up.
(attrition bias)
All outcomes
Selective reporting (re- Low risk Both primary and secondary endpoints were specified.
porting bias)
Kilger 2003b
Methods Study design: randomised, non-blinded, controlled trial
Number of study centres and location: single centre; Department of Cardiac Surgery (GN), Ludwig-Max-
imilians University, Munich, Germany
Date of study: 2003
Participants Number randomised: not stated
Number lost to follow-up/withdrawn: not stated

Informed decisions.
Kilger 2003b (Continued)

Number analysed: 80
Mean age: not specified
Severity of the condition according to study authors: not specified
Surgery type: not specified
Inclusion criteria: not specified
Exclusion criteria: not specified
mg/day, 30 mg/day
Outcomes Outcomes were mortality, time to extubation, ICU stay, hospital stay, number of blood transfusions, in-
flammatory biomarker measured during hospital stay (authors do not distinguish between primary and
secondary outcomes)
Notes Funding for trial: not available
Conflicts of interest of trial authors: not available
Risk of bias
Random sequence genera- Unclear risk No information on randomisation procedure.

Allocation concealment Unclear risk No information on concealment of allocation procedure.

(selection bias)
Blinding of participants Unclear risk Quote: "die patienten erhielten randomisiert vor narkoseeinleitung"
mance bias) Comment: patients were randomised at anaesthesia induction, unclear de-
scription of blinding manners.
Blinding of outcome as- Unclear risk Quote: "die patienten erhielten randomisiert vor narkoseeinleitung"
Comment: patients were randomised at anaesthesia induction, unclear de-
scription of blinding manners.
Incomplete outcome data Low risk Follow-up: hospital stay. 0% loss to follow-up.
(attrition bias)
All outcomes
Selective reporting (re- Unclear risk There were no details regarding study endpoints.
porting bias)

Informed decisions.
Kilickan 2008
Total duration of study: NR
Number of study centres and locations: single centre; Department of Anaesthesiology and Intensive
Care, Instanbul Bilim University School of Medicine, Instanbul, Turkey
Number analysed: 60
Mean age: 62
Gender: 75% male
Severity of the condition according to study authors: high-risk setting
Surgery type: CABG
Inclusion criteria: elective CABG with CPB
Exclusion criteria: ejection fraction (EF) < 0.40, diabetes, active gastropathic disorder, preopera-
tive steroid use, contraindication to steroid use, contraindication to epidural (anticoagulation), sys-
temic/local infection, treatment with cyclo-oxygenase inhibitors, ticlopidine, drugs inhibiting thrombo-
cyte function 7 days before procedure. Excluded medications: preoperative corticosteroid use, preop-
erative antiplatelet use, ticlopidine.
Interventions Intervention:
• Group S - corticosteroid 6-methylprednisolone 15 mg/kg IV 60 minutes before induction;

• Group TEA + S - steroid and thoracic epidural analgesia;
• Group TEA - thoracic epidural analgesia only
Comparison - standard care
Outcomes Primary outcomes: effect of pre-induction TEA and/or steroids on perioperative inflammation and hy-
perglycaemia. Time points reported - bloods taken 1 hour before surgery, 1 hour post CPB, in ICU, and
24 hours post surgery
Notes Funding for trial: none stated
Risk of bias
Random sequence genera- Unclear risk No documentation so cannot be assessed.

Allocation concealment Unclear risk Insufficient documentation so cannot be assessed.

(selection bias)

Informed decisions.
Kilickan 2008 (Continued)
Blinding of participants Unclear risk No clear documentation so cannot be assessed.

mance bias)
Blinding of outcome as- Unclear risk No clear documentation so cannot be assessed.

Incomplete outcome data Unclear risk No documentation so cannot be assessed.

(attrition bias)
All outcomes

porting bias)
Liakopoulos 2007
Total duration of the study: November 2003 to July 2004
Number of study centres and location: 1 centre; Department of Thoracic and Cardiovascular Surgery,
Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany
Date of study: 2007
Number lost to follow-up/withdrawn: 2 (control)
Number analysed: 78, 40 methylprednisolone, 38 control
Mean age: 66
Gender: 75% male
Average BMI: 26.9
Surgery type: coronary artery bypass graft
Inclusion criteria: CABG with CPB
Exclusion criteria: emergency or concomitant cardiac procedures, neoplasia, LVEF < 0.30, renal/hepatic
dysfunction, autoimmune disease, anti-inflammatory treatment
Interventions Intervention: 15 mg/kg methylprednisolone pre-CPB, single dose
Comparison: placebo
Outcomes Outcomes: mortality, pulmonary complications, re-intubation, time to extubation, ICU stay, hospi-
tal stay, renal failure, infections, biomarker, haemodynamic data, inotrope requirement, Ventricular
Stroke Work Index, troponin T, serum glucose, cytokine concentrations, wound complications, mea-
sured during hospital stay.

Informed decisions.
Liakopoulos 2007 (Continued)
Risk of bias
Random sequence genera- Low risk Quote: "following a computer-generated sequence, patients were randomly
tion (selection bias) assigned to receive either a single intravenous bolus of 15 mg/kg methylpred-
nisolone (Urbason, Sanofi-Aventis, Frankfurt, Germany; MP group) or placebo
(NaCl 0.9%; PLA group) 30 minutes before CPB was instituted."
Allocation concealment Unclear risk Quote: "Following a computer-generated sequence, patients were randomly
(selection bias) assigned to receive either a ..."
Comment: no information given on concealment procedure after randomisa-

tion.
Blinding of participants Unclear risk No information given on blinding of personnel or participants.

mance bias)
Blinding of outcome as- Unclear risk No information given about when disclosure of allocation occurred.
Incomplete outcome data Low risk Quote: "Two patients in the PLA group were excluded from the study after re-
(attrition bias) ceiving aprotinin treatment for postoperative bleeding in the ICU."
All outcomes
Selective reporting (re- Low risk All endpoints included in analysis were defined a priori.
porting bias)
Loef 2004
Number of study centres and location: 1 centre, University Hospital Groningen, Groningen, the Nether-
lands
Number analysed: 20; 10 steroids, 10 control
Mean age: 64

Informed decisions.
Loef 2004 (Continued)

Gender: 85% male
Average BMI: 26.1
Inclusion criteria: CABG patients with normal cardiac, cerebral, and hepatic function
Exclusion criteria: diabetes, recent myocardial infarction, hypertension, unstable angina, or recent use
of radiocontrast media
Interventions Intervention: 2x dexamethasone dosing - 1 mg/kg prior to anaesthetic induction, 0.5 mg/kg 8 hours lat-
er.
Comparison: placebo
Outcomes Outcomes: mortality, time to extubation, ICU stay, vasoactive medication, number of blood transfu-
sions, biomarkers, myocardial infarction, atrial fibrillation, inotropic usage, bleeding, renal function
(measured during hospital stay). Authors do not differentiate between primary and secondary out-
comes.
Risk of bias
Random sequence genera- Unclear risk Unspecified randomisation method.

Allocation concealment Unclear risk No information on concealment of allocation was provided

(selection bias)
Blinding of participants Low risk Quote: "Patients (n=20) were randomized in a double-blind fashion to receive
and personnel (perfor- either dexamethasone or a placebo".
mance bias)
Comment: double-blind.
Blinding of outcome as- Unclear risk No information given about when disclosure of allocation occurred.
Incomplete outcome data Low risk No loss to follow-up. No exclusions.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Adequate selection and reporting of outcomes.
porting bias)
Lomirovotov 2013

Informed decisions.
Lomirovotov 2013 (Continued)
Methods Study design: double-blinded, placebo-controlled, randomised study
Total duration of the study: 2009 (1 year)
Number of study centres and location: single centre, Research Institute of Circulation Pathology,
Novosibirsk, Russia
Date of study: 2013
Mean age: 58
Gender: 84% male
Average BMI: 29.4
Inclusion criteria: adults undergoing CABG
Exclusion criteria: age > 70 years, left ventricular ejection fraction < 40%, diabetes mellitus, chronic ob-
structive pulmonary disease, and chronic renal disease.
Interventions Intervention: 20 mg/kg methylprednisolone, single dose
Comparison: placebo
Outcomes Primary outcome: endothelin-1
Secondary outcomes: E-Selectin, interleukin-6, interleukin-10, partial pressure of oxygen and fraction
of inspired oxygen coefficient, microalbuminuria, hospital mortality, ventilation time after surgery, in-
otropic support, atrial fibrillation (during the first 24 hours), infectious complications, (ICU) and hospi-
tal stay durations, and ICU readmission.
Risk of bias
Random sequence genera- Low risk Quote: "Randomisation was performed using opaque sealed envelopes".
Comment: clear comment on random component in the sequence generation
process.
Allocation concealment Low risk Quote: "Randomisation was performed using opaque sealed envelopes… the
(selection bias) solution for injections was prepared in a non-transparent syringe by an inde-
pendent pharmacist".
Comment: clear comment on concealment of allocations prior to assignment.

Informed decisions.
Lomirovotov 2013 (Continued)
Blinding of participants Unclear risk No clear information given on blinding of personnel or participants.
mance bias)
Blinding of outcome as- Unclear risk No comment on measures taken to blind data assessment.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Quote: "a total of 44 patients comprising 22 in the study group and 22 in the
porting bias) placebo group were included for the final statistical analyses… the primary
endpoint was endothelin-1, and secondary endpoints were interleukin-6, in-
terleukin-10, partial pressure of oxygen and fraction of inspired oxygen coeffi-
cient and microalbuminuria".
Comment: an adequate description of the study protocol is available in the

published manuscript and all the study's prespecified outcomes that are of in-
terest have been reported in a prespecified way.
Maddalli 2019
Number of study centres and location: single centre, Department of Cardiac Anesthesia, National Heart
Center, Royal Hospital, Muscat, Oman
Mean age: 61
Gender: not stated
Average BMI: 26
Inclusion criteria: elective CABG on pump
Exclusion criteria: weight < 40kg, valvular abnormalities, arrhythmias, emergency or combined coro-
nary bypass surgery, preoperative inotropes, IABP, preoperative steroid therapy, poorly controlled dia-
betes mellitus, pulmonary disease, renal impairment, ejection fraction < 30%
Interventions Intervention: 0.1 mg/kg dexamethasone twice before the institution of cardiopulmonary bypass

Informed decisions.
Maddalli 2019 (Continued)

Comparison: saline placebo
Outcomes Primary outcomes: extravascular lung water index, haemodynamic parameters, vasoactive-inotropic
scores, haematocrit values (1st postoperative day).
Secondary outcomes: baseline and 1st postoperative day serum osmolality
Risk of bias
Random sequence genera- Low risk Quote: "20 patients were allocated by computer-generated block randomiza-
tion (selection bias) tion numbers using the block sizes of 2, 4, 6 to either the steroid group (n=10)
or the nonsteroid group (n=10)".

process.
Allocation concealment Low risk Quote: "20 patients were allocated by computer-generated block randomiza-
(selection bias) tion numbers using the block sizes of 2, 4, 6 to either the steroid group (n=10)
or the nonsteroid group (n=10)".
Comment: clear comment on concealment of allocations prior to assignment.
Blinding of participants Unclear risk Quote: "One anaesthesiologist who was blinded to the randomization con-
and personnel (perfor- ducted the anaesthesia for the patient and a second anaesthesiologist also
mance bias) blinded to the drug administered collected all the data."
Comment: shows measures taken to blind care providers involved in the study.
However, measures taken to blind personnel not commented on.
Blinding of outcome as- Low risk Quote: "… a second anaesthesiologist also blinded to the drug administered
sessment (detection bias) collected all the data."
Comment: personnel collecting data were blinded to the drug administered to

each participant.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Quote: "20 patients were randomized to receive either dexamethasone
porting bias) (steroid group, n=10) or placebo (non-steroid group, n=10) twice before the in-
stitution of cardiopulmonary bypass. EVLWI (Extravascular lung water index)
and other volumetric parameters were obtained... Haemodynamic parame-
ters, vasoactive-inotropic scores, haematocrit values were recorded at the pre-
determined time intervals. Baseline and 1st post-operative day serum osmo-
lality values were also obtained."
Comment: adequate selection and reporting of outcomes.

Informed decisions.
Mahrose 2019
Number of study centres and location: single centre, Department of Anesthesiology, Faculty of Medi-
cine, Ain Shams University, Cairo, Egypt
Mean age: range of age was between 40 and 79 years
Gender: 71% male
Inclusion criteria: elective on-pump CABG operations without concomitant procedures
Exclusion criteria: arrhythmias, thyroid disease, renal or hepatic disease, peripheral arterial atheroscle-
rosis, thrombophlebitis, uncontrolled diabetes mellitus, systemic bacterial or fungal infection, active
tuberculosis, Cushing’s disease, peptic ulcer, psychotic mental disorder, herpes simplex keratitis, and
chronic obstructive lung disease
Interventions Intervention: hydrocortisone 100 mg was intravenously given on the evening of the operation and then
100 mg every eight hours throughout the following 2 days
Outcomes Outcomes: incidence of postoperative atrial fibrillation, death, myocardial infarction, chest infection
and C-reactive protein, duration of hospital stay, postoperative infective status. Outcomes were mea-
sured during hospital stay. There was no distinction between primary and secondary outcomes.
Risk of bias
Random sequence genera- Low risk Quote: "176 patients were included in the study. Patients were arbitrarily allot-
tion (selection bias) ted by computer-generated random variety list into 2 study groups of 88 pa-
tients each."

process.
Allocation concealment Unclear risk Quote: "176 patients were included in the study. Patients were arbitrarily allot-
(selection bias) ted by computer-generated random variety list into 2 study groups of 88 pa-
tients each."
Comment: unclear allocation concealment technique

Informed decisions.
Mahrose 2019 (Continued)
Blinding of participants Unclear risk No comment on blinding of personnel or participants.

mance bias)
Blinding of outcome as- Unclear risk No comment on blinding during outcome assessment.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Quote: "the following data was collected: gender, preoperative diseases, car-
porting bias) diopulmonary bypass time, intraoperative cross clamp time, Left internal
mammary artery usage, incidence of post-operative atrial fibrillation, death,
myocardial infarction, chest infection and CRP amount in plasma."
Comment: n adequate description of the study protocol is available in the

Mardani 2012
Total duration of the study: from January of 2009 to February 2011
Number of study centres and location: single centre; Chamran Heart Center, Isfahan University of Med-
ical Sciences, Isfahan, Iran
Date of study: 2012
Number analysed: 93; 43 corticosteroids and 50 comparison
Mean age: 62
Gender: 85% male
Severity of the condition according to study authors: normal risk profile
Surgery type: CABG
Inclusion criteria: elective CABG on CPB patients only
Exclusion criteria: inability to read and write, prolonged intubation, longer duration of CPB (more than
3 hours), older than 80 years of age, ejection fraction (EF) lower than 20%, haemodynamic instability,
history of delirium and emergency operation.
Interventions Intervention: dexamethasone or placebo administered at the time of anaesthetic induction and every 8
hours for the first 3 postoperative days
Comparison: placebo

Informed decisions.
Mardani 2012 (Continued)
Outcomes Outcomes: postoperative delirium and clinical complications (measured during hospital stay). No dis-
tinction between primary and secondary outcomes.
Risk of bias
Random sequence genera- Low risk Block randomisation.

Allocation concealment Unclear risk Unspecified.

(selection bias)
Blinding of participants Unclear risk Unspecified.

mance bias)
Blinding of outcome as- Unclear risk Unspecified.

Incomplete outcome data Unclear risk 17 participants withdrawn (15.4%) because of death (9), prolonged intubation
(attrition bias) (5) or refused to complete survey (3). All known exclusion criteria.
All outcomes No information about patients withdrawn amongst intervention/placebo
group (specified only 5 withdrawn from placebo group and 12 in steroid
group).
porting bias) manuscript and all of the study's prespecified outcomes that are of interest
have been reported in a prespecified way.
Mayumi 1997
Total duration of the study: between December 1993 and July 1994
Number of study centres and location: single centre; Division of Cardiovascular Surgery, Research Insti-
tute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan
Date of study: 1997
Number lost to follow-up/withdrawn: 3 participants who underwent intra-aortic balloon pumping (n =

1) or allogeneic blood transfusion (n = 2)
Number analysed: 24; 12 intervention and 12 comparison
Mean age: 53

Informed decisions.
Mayumi 1997 (Continued)

Gender: 63% male
Surgery type: valve surgery
Inclusion criteria: elective valve replacement surgery
Exclusion criteria: cardiac cachexia due to end-stage valvular disease
Interventions Intervention: 2 x 20 mg/kg methylprednisolone, before and after bypass
Comparison: placebo
Outcomes Outcomes were mortality, time to extubation, infection, rate of transfusion, biomarker, measured dur-
ing hospital stay. No distinction between primary and secondary outcomes.
Risk of bias
Random sequence genera- Low risk Quote: "A chief anaesthesiologist, who was not directly involved in the present
tion (selection bias) study, was responsible for opening an envelope indicating the drug, and also
for preparing the drug in a covered syringe".
Comment: shows blinded randomisation of the sequence generation process.
Allocation concealment Low risk Quote: "a chief anaesthesiologist, who was not directly involved in the present
(selection bias) study, was responsible for opening an envelope indicating the drug"
Comment: this quote indicates a sealed envelope method used for randomisa-
tion and allocation concealment.
Blinding of participants Low risk Double-blind trial.

mance bias)
Blinding of outcome as- Low risk Quote: "The patient names, but not the drug names, included in the two
sessment (detection bias) groups were told by the anaesthesiologist to the senior author at the end of
study. After the statistical analysis was completed, the used drug for each
group and the used dose of the steroid in each patient were disclosed to the
senior author."
Comment: outcome assessors completely blinded to knowledge of allocated

interventions.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Quote: "24 patients undergoing valve replacement were studied… 12 of these
porting bias) patients received bolus methylprednisolone and the remaining 12 patients
received a placebo intravenously before and after bypass. Blood cell count,
CRP, Lymphocyte surface markers, phytohaemagglutinin response, inter-
leukin-2 production and natural killer cell activity were examined on admis-
sion through day 7."

Informed decisions.
Mayumi 1997 (Continued)

McBride 2004
Number of study centres and location: single centre; Department of Anaesthetics and Intensive Care
Medicine, The Queen's University of Belfast, Belfast, Northern Ireland, Ireland
Mean age: 61
Gender: 94% male
Surgery type: CABG
Inclusion criteria: elective CABG
Exclusion criteria: unstable angina, previous steroid therapy, myocardial infarction within the previous
three months, diabetes, heart or liver failure, and patients with documented renal dysfunction (plasma
creatinine greater than 125 μmol l−1).
Interventions Intervention: 30 mg/kg methylprednisolone, before induction
Comparison: placebo
Outcomes Outcomes were mortality, cardiac complications, time to extubation, hospital stay, vasoactive medica-
tion, re-thoracotomy, biomarkers measured during hospital stay. No distinction between primary and
secondary outcomes.
Risk of bias
Random sequence genera- Unclear risk Unclear randomisation technique.


Informed decisions.
McBride 2004 (Continued)
Allocation concealment Unclear risk Unclear technique for allocation concealment.

(selection bias)
Blinding of participants Low risk Quote: "The study was double blind with respect to the patient and the labora-
and personnel (perfor- tory investigators."
mance bias)
Comment: no indication as to how blinding of participants was ensured. How-
ever, clear statement that participants and lab investigators were blinded.
Blinding of outcome as- Unclear risk Quote: "The study was double blind with respect to the patient and the labora-
sessment (detection bias) tory investigators."
Comment: no comment on how blinding was ensured - therefore we cannot

tell whether blinding could have been broken or if there was at any point in-
complete blinding.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Quote: "Patients undergoing coronary artery bypass grafting with cardiopul-
porting bias) monary bypass were randomised to receive methylprednisolone (n=18) or
placebo (n=17) before induction of anaesthesia. Plasma and urinary pro and
anti-inflammatory cytokine balance was determined along with subclinical
proximal tubular injury and dysfunction, measured by urinary N-acetyl-Be-
ta-D-glucosaminidase/creatinine and alpha-1 microglobulin/creatinin ratios
respectively".

Morton 1976
Number of study centres and location: single centre; Department of Surgery, Maine Medical Center.
Portland, Maine
Gender: not stated

Informed decisions.
Morton 1976 (Continued)

Surgery type: CABG
Exclusion criteria: associated valve replacement or ventricular aneurysmectomy
Interventions Intervention: 30 mg/kg or 2000 mg methylprednisolone, before induction
Comparison: placebo
Outcomes Outcomes were mortality, cardiac complications, pulmonary complications measured during hospital
stay. No distinction between primary and secondary outcomes.
Risk of bias
Random sequence genera- Low risk Quote: "The drug and placebo were supplied, packaged and randomly coded
tion (selection bias) by the Upjohn company. The code was not revealed until the study was com-
pleted and all the data had been collected and interpreted."
Comment: clear randomisation of allocation to groups.
Allocation concealment Unclear risk Insufficient information

(selection bias)
Blinding of participants Low risk Quote: "The drug and placebo were supplied, packaged and randomly coded
and personnel (perfor- by the Upjohn company. The code was not revealed until the study was com-
mance bias) pleted and all the data had been collected and interpreted."
Comment: blinding adequate.
Blinding of outcome as- Low risk Quote: "The code was not revealed until the study was completed and all the
sessment (detection bias) data had been collected and interpreted."
Comment: outcome assessors completely blinded to knowledge of allocated

interventions.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Quote: "…undertaken a … study of the effect of a single large dose of corti-
porting bias) costeroids on intraoperative myocardial preservation during coronary artery
surgery… serum creatine phosphokinase, lactic dehydrogenase and serum
glutamic oxalacetic transaminase were measured on the first three days post-
operatively.
Comment: study protocol is available and all the study's prespecified out-
comes that are of interest have been reported in a prespecified way.

Informed decisions.
Murphy 2011
Methods Study design: double-blind randomised controlled trial
Number of study centres and location: two cardiac surgery centres (NorthShore University HealthSys-
tem and Northwestern University Feinberg School of Medicine, Chicago, IL)
Number analysed: 104 ; 60 corticosteroids and 49 comparison
Mean age: 63
Gender: 70% male
Surgery type: CABG or heart valve surgery
Inclusion criteria: elective coronary artery bypass graft (CABG) surgery with CPB or single valvular re-
pair/replacement surgery and anticipated early tracheal extubation.
Exclusion criteria: combined (CABG/valve) procedures, ejection fraction 30%, preoperative use of in-
otropic agents or an intra-aortic balloon pump, preoperative use of steroids or anti-emetic agents,
acute or chronic renal failure, pulmonary disease necessitating oxygen therapy or any patient assessed
as potentially requiring prolonged postoperative mechanical lung ventilation, poorly controlled di-
abetes, poor English comprehension or psychiatric/central nervous system disturbances precluding
completion of the QoR-40 questionnaire.
Interventions Intervention: dexamethasone (8 mg) administered at the time of anaesthetic induction (approximately
45 minutes before surgical incision). A second dose of 8 mg of dexamethasone was administered on the
initiation of CPB.
Comparison: placebo
Outcomes Primary endpoint: postoperative QoR-40 score (POD 1-2).

Secondary endpoints: postoperative (in-hospital) nausea, vomiting, fatigue, febrile responses, shiver-
ing, pulmonary gas exchange and analgesic requirements.
Risk of bias

Allocation concealment Unclear risk Not sufficiently described.

(selection bias)

Informed decisions.
Murphy 2011 (Continued)
Blinding of participants Low risk Double-blinded RCT.

mance bias)

Incomplete outcome data Low risk 13 participants withdrawn (11.1%) because did not received study drug in time
(attrition bias) (8, 7 in steroid group and 1 in placebo group) or refused to complete survey (5,
All outcomes 3 in steroid group and 2 in placebo group). Both known exclusion criteria.
Oliver 2004
Methods Study design: randomised, placebo-controlled, double-blinded trial. Multi-arm trial.
Total duration of the study: unspecified
Number of study centres and location: single centre, Mayo Medical School, Rochester, Minnesota
Number lost to follow-up/withdrawn: 3 exclusions; study violation (lateral thoracotomy, retrosternal

mass, surgery cancelled)
Number analysed: 189; (62 steroids, 63 placebo, 64 haemofiltration), 125 included in meta-analysis
Mean age: 63
Gender: 71% male
Surgery type: mixed (valve surgery and CABG)
Inclusion criteria: scheduled to undergo elective primary coronary artery bypass grafting or valvular re-
placement or repair requiring cardiopulmonary bypass.
Exclusion criteria: presence of congenital heart disease, left ventricular ejection fraction ≤ 0.35, end-
stage pulmonary disease, previous difficult intubation, pulmonary hypertension, neurologic deficits or
disease, serum creatinine ≥ 2.0 mg/dL, recent or long-term steroid usage, insulin-dependent diabetes
mellitus, and age ≥ 85 years.
Interventions Intervention: 1000 mg methylprednisolone, before induction, 4 x 4 mg dexamethasone 6 hourly.
Comparison: placebo.
Outcomes Outcomes were mortality, cardiac complications, pulmonary complications, time to extubation, ICU
stay, neurological complications, transfusion Y/N, re-thoracotomy measured during hospital admis-
sion. No distinction between primary and secondary outcomes.

Informed decisions.
Oliver 2004 (Continued)
Notes Funding for trial: none declared
Risk of bias
Random sequence genera- Unclear risk Quote: "Patients were randomized in a double blinded manner to one of
tion (selection bias) (three) groups."
Comment: no comment on how randomisation was achieved
Allocation concealment Unclear risk Unclear risk of allocation concealment due to insufficient information.
(selection bias)
Blinding of participants Low risk Quote: "Patients were randomized in a double blinded manner to one of
and personnel (perfor- (three) groups… all remaining operating room and intensive care unit person-
mance bias) nel were blinded to group identity".
Comment: although there is no indication as to how blinding was ensured, pa-

per clearly states that participants and personnel were blinded.
Blinding of outcome as- Low risk Quote: "all remaining operating room and intensive care unit personnel were
sessment (detection bias) blinded to group identity"
Comment: personnel collecting data were blinded to allocation.

(attrition bias)
All outcomes
Selective reporting (re- Unclear risk Study protocol with primary and secondary objectives not clearly stated in
porting bias) "background" or "method" sections of paper.
Prasongsukarn 2005
Total duration of the study: from 1 August 2000 to 28 February 2001
Number of study centres and location: single centre, St Paul’s Hospital, University of British Columbia,
Vancouver, British Columbia, Canada.
Date of study: 2005
Number lost to follow-up/withdrawn: 2 patients excluded; off pump
Number analysed: 86
Mean age: 64
Gender: 77% male

Informed decisions.
Prasongsukarn 2005 (Continued)

Surgery type: CABG
Inclusion criteria: informed consent, age greater than 18 years, elective first-time CABG, β-adrenergic
blockade, and normal sinus rhythm
Exclusion criteria: "history of heart block; a permanent pacemaker; any documented or suspected
supraventricular or ventricular arrhythmias, including isolated atrial or ventricular premature depo-
larization noted on preoperative surface electrocardiography; requirement for additional procedures,
such as valvular operation or left ventricular aneurysmectomy; refusal to participate in this study; use
of a radial artery for grafting; steroid dependency; steroid allergy; and participation in another investi-
gational protocol."
Interventions Intervention: 1000 mg methylprednisolone, before induction, 4 x 4 mg dexamethasone 6 hourly
Comparison: placebo group receiving maintenance fluids (5% dextrose water with potassium chloride
20 milliequivalent (mEq)/L)
Outcomes Mortality, renal failure, neurological complications, atrial fibrillation, gastrointestinal complications,
infections, biomarkers measured during hospital admission.
Risk of bias
Random sequence genera- Low risk Quote: "Patients were randomily assigned in a double blind fashion either to
tion (selection bias) a placebo group… or to a steroid group… All vials of the steroid and placebo
medications were prepared and randomized by the hospital pharmacy. The
steroid and placebo silutions were visually indistinguishable."
Comment: clear statement on method of randomisation of allocations.
Allocation concealment Low risk Quote: "All vials of the steroid and placebo medication were prepared and ran-
(selection bias) domized by the hospital pharmacy. The steroid and placebo solution were vi-
sually indistinguishable".
Blinding of participants Low risk Quote: "…surgical staff, principal investigators and patiens were blinded to the
and personnel (perfor- assigned therapy. Clinical data were collected and recorded in the database by
mance bias) independent blinded investigators."
Comment: clear statement on blinding of both participants and study person-

nel.
Blinding of outcome as- Low risk Quote: "surgical staff, principal investigators…were blinded to the assigned
sessment (detection bias) therapy. Clinical data were collected and recorded in the database by inde-
pendent blinded investigators".
Comment: measures taken to ensure unbiased data analysis.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Study protocol available in paper. Quote: "The primary end point was the
porting bias) overall occurrence of postoperative atrial fibrillation… In a supplementary
component of the study, we measured the cytokine concentrations and com-

Informed decisions.
Prasongsukarn 2005 (Continued)

pared the measurements between groups. Concentrations of TNF-alpha, IL-6,
IL-8 and IL-10 were measured with enzyme-linked immunosorbent assay at 4
and 24 hours after surgery."

Rao 1977
Number of study centres and location: single centre, Department of Thoracic and Cardiovascular
Surgery and Clinical Engineering, University of Pittsburgh, Pennsylvania, USA
Study setting: tertiary cardiac surgery centre
Number analysed: 150 elective CABG patients
Mean age: unspecified
Gender: unspecified
Surgery type: CABG
Inclusion criteria: unspecified
Exclusion criteria: unspecified
Interventions Intervention: 1000 mg methylprednisolone before CPB
Outcomes Mortality, cardiac complications, pulmonary complications, neurological complications, infections

measured during hospital stay. No distinction between primary and secondary outcomes.
Risk of bias
Random sequence genera- Unclear risk No randomisation procedure was described.


Informed decisions.
Rao 1977 (Continued)
Allocation concealment Unclear risk No concealment of allocation or blinding was described.

(selection bias)
Blinding of participants High risk Unspecified. Insufficient information. The study was classified as a "prospec-
and personnel (perfor- tive randomized study". This indicates an unblinded study.
mance bias)
Blinding of outcome as- High risk Unspecified. Insufficient information. The study was classified as a "prospec-
sessment (detection bias) tive randomized study". This indicates an unblinded study.
Incomplete outcome data Low risk Complete report. Follow-up: hospital stay. 0% loss to follow-up.
(attrition bias)
All outcomes
Selective reporting (re- Low risk No evidence of selective reporting; all described outcomes were reported.
porting bias)
Rubens 2005
Methods Study design: randomised, placebo-controlled, double-blinded trial. Multi-arm trial.
Number of study centres and location: single centre; Ottawa Heart Institute, University of Ottawa, Ot-
tawa, Ontario, Canada
Number lost to follow-up/withdrawn: 3 excluded before surgery started at surgeon's request.
Number analysed: 68 elective CABG. Factorial design study. 68 participants were split into 4 groups (n
= 17 each). The groups were 1. Control, 2. Steroids, 3. Cardiopulmonary bypass (CPB) with surface mod-
ifying additive (SMA), and 4. SMA, CPB and Steroids together. For the purposes of this review, groups 1
and 3, and 2 and 4 have been merged.
Mean age: 56
Gender: 87% male
Surgery type: CABG
Inclusion criteria: scheduled for coronary artery bypass grafting on CPB
Exclusion criteria: patients on steroids or Coumadin and those undergoing emergency, reoperative
surgery or other cardiac procedures in addition to CABG. Patients were also excluded if there was ev-
idence of preoperative coagulopathy, bleeding diathesis, thrombocytopenia (< 140,000 μL), severe
chronic obstructive pulmonary disease (COPD) (FEV1 < 1.5L), history of recent peptic ulcer disease (< 6
months), chronic renal failure (creatinine > 120 μmol/L), or steroid dependency.
Interventions Intervention: 1000 mg methylprednisolone, before CPB
Informed decisions.
Rubens 2005 (Continued)

Comparison: no intervention
Outcomes Mortality, cardiac complications, ICU stay, hospital stay, atrial fibrillation, rate of infections, and bio-
markers measured during hospital stay. No distinction between primary and secondary outcomes.
Risk of bias
Random sequence genera- Low risk Quote: "The perfusionist performed the treatment assignment immediately
tion (selection bias) preoperatively by opening a sealed, numbered envelope. Randomization was
in blocks of four, generated using SAS version 8.2"
Comment: clear method of randomisation using computer generation.
Allocation concealment Low risk Quote: "Syringes containing the methylprednisolone or the placebo were pre-
(selection bias) pared in the hospital pharmacy and labelled with a code"
Comment: low risk of allocation concealment.
Blinding of participants Low risk Quote: "All members of the surgical and anaesthetics teams were blinded to
and personnel (perfor- the use of methylprednisolone."
mance bias)
Comment: participants and investigators enroling participants could not fore-
see assignment due to these measures.
Blinding of outcome as- Unclear risk Quote: "The cannulas and tubing used in all of the cardiopulmonary bypass
sessment (detection bias) circuits were identical in appearance, so that all members of the surgical and
anaesthesia teams, except the perfusionist, were blinded to the circuit assign-
ment… All members of the surgical and anaesthetics teams were blinded to
the use of methylprednisolone. Syringes containing the methylprednisolone
or the placebo were prepared in the hospital pharmacy and labelled with a
code".
Comment: adequate blinding of care providers; blinding of outcome assessors

unspecified.

(attrition bias)
All outcomes
Selective reporting (re- Low risk Quote: "In a factorial design, patients undergoing CABG were randomised in-
porting bias) to four groups… Leukocyte and complement activation, cytokine release and
bradykinin generation were measured. Clinical outcomes (blood loss, trans-
fusion, arterial pressure response and post-operative cardiac and pulmonary
functions) were also examined."
Comment: adequate selection and reporting of outcomes.
Informed decisions.
Rumalla 2001
Total duration of the study: 6-month period
Number of study centres and location: single centre: Robert Wood Johnson Medical School New
Brunswick, NJ, USA
Study setting: tertiary cardiac surgery centre
Number analysed: 13 elective CABG
Mean age: 62
Gender: unspecified
Surgery type: coronary artery bypass graft surgery
Inclusion criteria: coronary artery bypass graft surgery patients
Exclusion criteria: known immunodeficiency conditions and those undergoing short- or long-term
steroid therapy were excluded from study
Interventions Intervention: 1000 mg methylprednisolone, at induction
Comparison: placebo
Outcomes Mortality, neurological complications, infections, re-thoracotomy, biomarkers measured during hos-
pital stay. Blood samples were drawn before induction, 20 minutes after sternotomy and bypass, im-
mediately postoperatively, and on postoperative day 1. No distinction between primary and secondary
outcomes.
Notes Funding for trial: GM-34695 from the US Public Health Service, Bethesda, MD
Risk of bias
Random sequence genera- High risk Randomly assigned by the investigator (unspecified).
Allocation concealment Unclear risk Not specified.

(selection bias)
Blinding of participants Unclear risk Unspecified.

mance bias)

Informed decisions.
Rumalla 2001 (Continued)
Selective reporting (re- Low risk No evidence of selective reporting. All expected outcomes were reported prop-
porting bias) erly.
Sano 2003
Number of study centres and location: single centre; Department of Cardiovascular Surgery, Graduate
school of Medical Sciences, Kyushu University, Fukuoka, Japan
Date of study: 2003
Participants Number randomised: unspecified
Number lost to follow-up/withdrawn: unspecified
Number analysed: 28 elective CABG (10 steroids, 10 placebo, 10 off pump), 20 included in meta-analysis
Mean age: 63
Gender: 55% male
Surgery type: CABG
Interventions Intervention: 2 x 50 mg/kg hydrocortisone, before and after CPB
Comparison: placebo
Outcomes Mortality, pulmonary complications, blood transfusion Y/N, biomarkers, "no major complications"
measured during hospital stay. Blood samples were taken from participants just before the induction
of anaesthesia (Pre), at the end of surgery (Post), and on days 1, 3 and 7 post-operation (POD1, POD3
and POD7).
Risk of bias
Random sequence genera- Unclear risk Randomisation procedure was not specified.
Informed decisions.
Sano 2003 (Continued)
Allocation concealment Unclear risk Concealment of allocation was not described.

(selection bias)
Blinding of participants Unclear risk Unspecified. Not described, plausible for participants.
mance bias)
Blinding of outcome as- Unclear risk Unspecified. No clear details given.

porting bias) erly.
Sano 2006
Number of study centres and location: single centre, Department of Cardiovascular Surgery Graduate
School of Medical Sciences The Kyushu University Fukuoka, Japan
Participants Number randomised: 31 (steroids) versus 29 (placebo)
Mean age: 62
Gender: 51% male
Surgery type: CABG
Interventions Intervention: 50 mg/kg hydrocortisone, before and after CPB
Comparison: placebo
Outcomes Outcomes were pulmonary complications, time to extubation, ICU stay, renal failure, atrial fibrillation,
infections, "no major complications", measured during hospital stay. No distinction between primary
and secondary outcomes.
Informed decisions.
Sano 2006 (Continued)

Risk of bias
Random sequence genera- Unclear risk Quote: "Were prospectively randomized into two groups by our operation-reg-
tion (selection bias) istry staff who were not involved in this study".
Comment: randomisation by staff member (unclear method).
Allocation concealment Unclear risk Quote: "Were prospectively randomized into two groups by our operation-reg-
(selection bias) istry staff who were not involved in this study".
Comment: unclear concealment of allocation.
Blinding of participants Low risk Double-blind study.

mance bias)

Incomplete outcome data Low risk Complete report.

(attrition bias)
All outcomes

porting bias)
Schurr 2001
Total duration of the study: between August 1999 and November 2000
Number of study centres and location: single centre, Clinic for Cardiovascular Surgery, University Hos-
pital Zurich, Zurich, Switzerland
Date of study: 2001
Participants Number randomised: group A (n = 24) received intravenous methylprednisolone (10 mg/kg) 4 hours
preoperatively, and group B (n = 26) served as controls.
Mean age: 64 (intervention) and 60.8 (control)
Gender: males/total 21/24 (intervention) and males/total 22/26 (control)
Surgery type: CABG
Informed decisions.
Schurr 2001 (Continued)

Inclusion criteria: elective isolated CABG patients.
Exclusion criteria: patients with insulin-dependent diabetes mellitus, peptic ulcer history, malignant
tumours, immunologic deficiencies, renal or hepatic insufficiency, and chronic pulmonary obstructive
disease.
Interventions Intervention: 10 mg/kg methylprednisolone, 4 hours before surgery
Outcomes Time to extubation, ICU stay, hospital stay, atrial fibrillation, vasoactive medication, re-thoracotomy,
biomarker, "no major complications", measured during hospital stay. Preoperative blood samples (10
mL) were taken before the administration of 10 mg/kg body weight methylprednisolone, delivered 4
hours before induction of anaesthesia. Postoperatively, blood samples were collected after 24 hours,
48 hours, and on the sixth postoperative day.
Risk of bias
Random sequence genera- Unclear risk Authors state that participants were randomised but process not described.
Allocation concealment Unclear risk Not specified.

(selection bias)
Blinding of participants High risk Study was unblinded.

mance bias)
Blinding of outcome as- High risk Study was unblinded.

porting bias) erly.
Sobieski 2008
Methods Study design: randomised placebo-controlled double-blinded trial
Number of study centres and location: single centre, Division of Cardiac Surgery, Advocate Christ Med-
ical Center, Oak Lawn, Illinois
Informed decisions.
Sobieski 2008 (Continued)

Date of study: 2008
Participants Number randomised: unspecified
Number analysed: 28 elective CABG patients
Mean age: 63
Gender: 82% male
Surgery type: CABG
Inclusion criteria: patients undergoing elective coronary artery revascularisation, less than 80 years
old, no clinically significant end-organ dysfunction, no acute myocardial infarction, and no intra-aortic
balloon pump (IABP).
Exclusion criteria: people actively receiving corticosteroids, anti-inflammatory (Aspirin, Dipyridamole,

Ibuprofen) or anticoagulation therapies (Coumadin, Lovenox) for other medical conditions were ex-
cluded from the study.
Interventions Intervention: 100 mg dexamethasone pre-CPB
Comparison: placebo.
Outcomes Mortality, time to extubation, ICU stay, hospital stay, renal failure, neurological complications, atrial
fibrillation, re-thoracotomy measured during hospital stay. No distinction between primary and sec-
ondary outcomes.
Risk of bias
Random sequence genera- Unclear risk Quote: "On the day of surgery, patient enrolled in the study were randomized
tion (selection bias) by the pharmacy."
Comment: unclear method.
Allocation concealment Unclear risk Insufficient information.

(selection bias)
Blinding of participants Low risk Anaesthetist had syringes with names only.
mance bias)

porting bias) erly.
Informed decisions.
Sobieski 2008 (Continued)
Starobin 2007
Methods Study design: randomised placebo-controlled trial
Total duration of the study: between 1 February 2004 and 31 January 2005
Number of study centres and location: single centre, Pulmonary Institute, Rabin Medical Center, Beilin-
son Campus, Petach Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Study setting: tertiary centre
Date of study: 2007
Mean age: 67
Gender: 56% male
Surgery type: CABG
Inclusion criteria: elective CABG, both smokers and non-smokers
Exclusion criteria: people who had an upper respiratory tract infection or an exacerbation of COPD,
people who were receiving mandatory oral (more than 5 mg) or parenteral corticosteroid treatment for
one month before the study, people who required emergency CABG and those with asthma
Interventions Intervention: 5 mg betamethasone slow release, 2 mg betamethasone rapid-release 2 to 3 weeks prior

to surgery
Comparison: placebo
Outcomes Primary endpoints of the study were postoperative pulmonary complications (atelectasis, pneumonia,
pneumothorax, bronchospasm, retained secretion, sustained pleural effusion and respiratory failure)
and non-pulmonary complications (arrhythmias, renal failure, heart failure, infections, bleeding, re-
peated surgery).
Secondary endpoints were length of stay (LOS) in the intensive care unit (ICU), ICU stay less than 24
hours, ICU stay more than 48 hours, duration of mechanical ventilation and chest tube use, LOS in hos-
pital, and intensity of rehabilitation (time to sitting and walking).
Participants were followed for 2 weeks after discharge by either a clinic visit or a phone call.
Risk of bias
Informed decisions.
Starobin 2007 (Continued)
Random sequence genera- Unclear risk No information on randomisation procedure or concealment of allocation.
Allocation concealment Unclear risk No information on concealment of allocation.

(selection bias)
Blinding of participants Unclear risk Not described, plausible for participants.

mance bias)
Blinding of outcome as- Unclear risk Not documented. No clear details given.
Incomplete outcome data Low risk 90 participants randomised and 90 analysed. No trial group changes, no with-
(attrition bias) drawals, no losses to follow-up reported but no intention-to-treat analysis. Da-
All outcomes ta from all the participants were included in the final analysis.
Selective reporting (re- Low risk Results for outcomes presented. All expected outcomes were reported proper-
porting bias) ly.
Taleska Stupica 2020

Methods Study design: prospective, randomised, blinded, interventional, controlled clinical trial
Total duration of the study: 23 months, starting in 2016.
Number of study centres and location: single centre; Clinical Department of Cardiovascular Surgery at
the University Medical Centre in Ljubljana
Date of study: 2020 (exact study start and end dates not available)
Participants Number randomised:76
Mean age: 69
Gender: 45% male
Surgery type: mixed
Inclusion criteria: people > 18 years old who were admitted for elective complex cardiac surgery with
an expected CPB duration of > 90 minutes.
Exclusion criteria: included refusal to participate in the study; age < 18 years; pregnant women; emer-
gency procedures; heart transplantation; implantation of the left ventricular assist device, right ventric-
ular assist device, or total artificial heart; treatment with chemo/immunosuppressive therapy; treat-
ment with anti-leukocyte drugs or TNF-α blockers; immunocompromised patients; leucopenia; clinical
and/or laboratory signs of infection; serum creatinine > 2 mg/dL (176 μmol/L); bilirubin > 2 mg/dL (34.2
μmol/L); history of stroke; malnourished patients; body mass index < 18 kg/m2.
Informed decisions.
Taleska Stupica 2020 (Continued)

Excluded medications: chemo/immunosuppressive therapy; treatment with anti-leukocyte drugs or
TNF-α blockers
Interventions Intervention: methylprednisolone (1 g of methylprednisolone added in the CPB priming solution)
Outcomes Primary outcome measures were for evolution of cytokine levels (TNF-α, IL-1β, IL-6, IL-8, and IL-10) and
complement C5a, as well as expression of CD64 and CD163 markers on monocytes, granulocytes, and
lymphocytes.
Secondary outcome measures were for changes in serum hs-CRP and procalcitonin levels, leukocyte
count, albumin, fibrinogen, and haemodynamic measurements (i.e. cardiac index, systemic vascular
resistance index, central venous oxygen saturation, and mean arterial pressure). Other prespecified
outcome measures included duration of postoperative mechanical ventilation, length of ICU stay, use
of inotropic/vasoactive drugs, use of fluid/blood products and insulin, length of in-hospital stay, and
30-day mortality.
Time points reported: before induction, after CPB, on admission to cardiovascular intensive treatment
unit (CVITU), 24 hours after surgery, 48 hours after surgery, 5th POD
Risk of bias
Random sequence genera- Low risk Randomisation was carried out by one of the members of the study team a
tion (selection bias) day before surgery and achieved by using identical sealed envelopes, where-
by each participant selected an envelope that assigned him/her to one of three
treatment groups. Randomisation allocation numbers were generated by the
Research Randomizer.
Allocation concealment Low risk Sealed envelopes.

(selection bias)
Blinding of participants Low risk Participants, ICU and ward personnel, and laboratory staff who participated in
and personnel (perfor- the trial were “blinded” for assigned treatment throughout the duration of the
mance bias) study. Exception from being blinded was for personnel in the operating the-
atre, who, on the other hand, were not included in data collection and analy-
sis.
Blinding of outcome as- Low risk No one who was aware of the randomisation was involved with data collec-
sessment (detection bias) tion.
Incomplete outcome data Unclear risk 76 randomised and 60 analysed - reasons for loss recorded.
(attrition bias)
All outcomes
Selective reporting (re- Low risk Results for outcomes stated have been reported.
porting bias)
Informed decisions.
Tassani 1999
Methods Study design: randomised, double-blinded study
Number of study centres and location: single centre; Institute of Anesthesiology, Department of Car-
diac Surgery, and Institute of Laboratory Analysis, German Heart Center Munich at the Technical Uni-
versity, München, Germany
Number analysed: 52
Mean age: not reported
Gender: not reported
Surgery type: elective CABG
Inclusion criteria: New York Heart Association groups II and III, American Society of Anesthesiologists
physical status groups III and IV, Higgins score of 1.4 ± 0.15, scheduled for elective CABG were investi-
gated. Only those scheduled for the first operation of the day were included.
Exclusion criteria: older than 75 years, body weight greater than 30% greater or less than ideal body
weight, left ventricular ejection fraction of 40% or less, haemodynamic instability or emergency opera-
tions, additional valvular diseases, complete bundle-branch block, third degree atrioventricular block;
renal (creatinine level > 1.2 mg/dL) or hepatic failure, and haematocrit less than 30%.
Interventions Intervention: 1 g of methylprednisolone was administered 30 minutes before cardiopulmonary bypass.

High-dose aprotinin was administered to all participants.
Comparison: placebo. High-dose aprotinin was administered to all participants.
Outcomes Primary end point: arterial partial pressure of oxygen (PO2) after CPB
Secondary end points: CPB time, aortic cross clamp time, concentration of interleukin-6, concentra-
tion of interleukin-8, concentration of interleukin-10, concentration of interleukin-1ra, intrapulmonary
shunt fraction, dynamic lung compliance, oxygen delivery index, oxygen extraction rate, mean arterial
pressure, heart rate, central venous pressure, cardiac index, systemic vascular resistance, pulmonary
vascular resistance, blood glucose concentration, postoperative blood loss and transfusion, urine out-
put, time to chest drain removal, time to extubation, time to discharge.
Outcomes were measured during hospital stay
Notes Funding for trial: not documented
Conflicts of interest of trial authors: not documented
Risk of bias
Random sequence genera- Unclear risk Unspecified method of randomisation.

Informed decisions.
Tassani 1999 (Continued)
Allocation concealment Unclear risk Quote: "The study drug or placebo was prepared in the morning at the hospital
(selection bias) pharmacy."
Blinding of participants Low risk Double-blinded trial.

mance bias)
Blinding of outcome as- Unclear risk Double-blinded trial, unspecified blinding of outcome assessors.
Incomplete outcome data Low risk No withdrawals.

(attrition bias)
All outcomes

porting bias)
Toft 1997
Total duration of the study: not documented
Number of study centres and location: not documented
Number analysed: 16
Mean age: 64
Gender: 88% male
Surgery type: mixed
Inclusion criteria: cardiovascular-stable patients, scheduled for open heart surgery and in whom no
surgical problems were expected.
Exclusion criteria: people with endocrine disorders were excluded.
Interventions Intervention: methylprednisolone (30 mg/kg intravenously) at the induction of anaesthesia
Outcomes Primary end point: granulocyte activation, measured as the oxidative burst activity.
Secondary end point: aortic cross clamp time, operative duration, CPB time, ICU length of stay, blood
glucose, blood pressure, temperature.
Informed decisions.
Toft 1997 (Continued)

Outcomes were measured during hospital stay. No distinction between primary and secondary out-
comes.
Risk of bias
Random sequence genera- Unclear risk Unspecified method for randomisation.

Allocation concealment Unclear risk No concealment of allocation was described.

(selection bias)
Blinding of participants Unclear risk Unspecified blinding of participants and personnel.

mance bias)
Blinding of outcome as- Unclear risk Unspecified (unlikely).


(attrition bias)
All outcomes

porting bias)
Turkoz 2001
Methods Study design: randomised, placebo-controlled trial. Multi-arm trial.
Number of study centres and location: single centre; Departments of Anesthesiology, Biochemistry,
and Cardiovascular Surgery, İnönü University Hospital, Malatya, Turkey
Date of study: 2001
Number analysed: 30
Mean age: 61
Gender: 85% male
Surgery type: CABG

Informed decisions.
Turkoz 2001 (Continued)

Exclusion criteria: people undergoing a re-operation, had a myocardial infarction within 1 month, suf-
fering from an uncontrolled systemic disease (diabetes mellitus, hypertension, or renal failure), or re-
ceiving long-term glucocorticoids were excluded.
Interventions Intervention: methylprednisolone-treated patients received methylprednisolone (30 mg/kg intra-

venously) before CPB
Outcomes Primary end point: haemodynamic changes and alveolar-arterial partial pressure of oxygen (PO2) dif-
ference (AaDO2) until the first postoperative day
Secondary end points: plasma levels of pro-inflammatory cytokines (tumour necrosis factor [TNF]-a, in-
terleukin [IL]-1beta, IL-6, and IL-8). Haemodynamic measurements (mean arterial pressure [MAP], mean
pulmonary arterial pressure [MPAP], pulmonary capillary wedge pressure [PCWP], and thermodilution
cardiac index [CI]). Operative outcomes (CPB time, cross clamp time and blood transfusion).
Risk of bias
Random sequence genera- Unclear risk Randomisation procedure and concealment of allocation was not described.
Allocation concealment Unclear risk Concealment of allocation was not described.

(selection bias)
Blinding of participants Unclear risk Unspecified blinding of participants and personnel.

mance bias)

Incomplete outcome data Unclear risk Two participants were excluded because retrograde coronary sinus cannula-
(attrition bias) tion could not be performed.
All outcomes

porting bias)
Volk 2001
Informed decisions.
Volk 2001 (Continued)

Number of study centres and location: single centre; Department of Anesthesiology and Intensive Ther-
apy University Hospital Charité, Campus Mitte, Humboldt-University, Berlin, Germany
Number analysed: 38; 13 steroids, 13 placebo, 13 tirilazad mesylate
Mean age: 63
Gender: 88% male
Average BMI: 28.3
Inclusion criteria: three-vessel disease older than 18 years with stable angina pectoris, left ventricle
ejection fraction (LVEF) >0.4, left ventricular end diastolic pressure < 17 mm Hg, absence of pre-existing
pulmonary diseases (determined by clinical examination, chest radiography, lung function tests, and
blood gas analyses), absence of insulin-dependent diabetes mellitus, and clinically relevant renal, he-
patic, or cerebrovascular disease
Exclusion criteria: preoperative signs of infection (WCC > 12,000/microL), temperature (> 38 degrees),
CRP > 5mg/dL, chronic inflammatory diseases, or those treated with either cyclo-oxygenase inhibitors,
steroids, or lazaroids within 7 days before the operation were excluded. Patients admitted for emer-
gency surgical intervention were also excluded.
Interventions Intervention: 15 mg/kg methylprednisolone, one and a half hours before CPB
Comparator: placebo
Outcomes Primary end point: effects on circulating pro-inflammatory markers including interleukin (IL)-6, IL-8,
monocyte chemoattractant protein 1, and C-reactive protein.
Secondary end points: pro- and anti-inflammatory markers, monocyte count. Operative outcomes (by-
pass time, operative time), length of ICU stay, length of hospital stay, in-hospital mortality.
Notes Funding for trial: grant from Pharmacia and Upjohn GmbH + University Hospital Charite.
Conflicts of interest of trial authors: not documented
Risk of bias
Random sequence genera- Unclear risk Randomisation procedures were not specified.
Allocation concealment Unclear risk Concealment of allocation techniques were not specified.
(selection bias)
Blinding of participants Low risk Double-blinded study.

mance bias)

Informed decisions.
Incomplete outcome data Unclear risk One participant withdrawn.

(attrition bias)
All outcomes

porting bias)
Volk 2003
Number of study centres and location: not documented
Number analysed: 36
Mean age: 63
Gender: 88% male
Average BMI: 28
Inclusion criteria: aged older than 18 years with three-vessels disease and with stable angina pectoris,
left ventricular ejection fraction (LVEF) >0.4, left ventricular end-diastolic pressure < 17 mmHg, absence
of pre-existing pulmonary diseases (determined by clinical examination, chest radiography, lung func-
tion tests and blood gas analyses), absence of insulin-dependent diabetes mellitus and clinically rele-
vant renal, hepatic or cerebrovascular disease.
Exclusion criteria: pre-operative signs of infection (WCC >12,000/microL), temperature (> 38 degrees),
CRP > 5 mg/dL, chronic inflammatory diseases, or those treated with either cyclo-oxygenase inhibitors,
steroids, or lazaroids within 7 days before the operation were excluded. Patients admitted for emer-
gency surgical intervention were also excluded.
Interventions Intervention: methylprednisolone 15 mg/kg body weight within 1.5 hours before extracorporeal circu-
lation
Comparison: placebo NaCl 0.9%; within 1.5 hours before extracorporeal circulation
Outcomes Primary end point: oxidized and reduced glutathione, protein oxidation, lipid peroxidation. Periopera-
tive arrhythmias.
Secondary end points: haemodynamic measurements (cardiac output, heart rate, peripheral vascular
resistance, left ventricular stroke work index and MAP).
Notes Funding for trial: grant from Pharmacia and Upjohn GmbH + University Hospital Charite
Informed decisions.

Conflicts of interest of trial authors: none declared
Risk of bias
Random sequence genera- Unclear risk Quote: "Patients were randomized to receive..."
Comment: no randomisation procedure technique was described.
Allocation concealment Unclear risk No concealment of allocation technique was described.

(selection bias)
Blinding of participants Unclear risk Insufficient information on blinding.

mance bias)
Blinding of outcome as- Unclear risk Insufficient information on blinding.

Incomplete outcome data Low risk No withdrawals reported.

(attrition bias)
All outcomes

porting bias)
Von Spiegel 2001

Number of study centres and location: single centre; Department of Anesthesiology and Intensive Care
Medicine, University of Bonn, Bonn, Germany
Number analysed: 20
Mean age: 65
Gender: 75% male
Inclusion criteria: patients undergoing elective coronary artery bypass grafting
Informed decisions.
Von Spiegel 2001 (Continued)

Exclusion criteria: people older than 75 years or with restricted left ventricular function (ejection frac-
tion < 50%), unstable angina, left main coronary artery stenosis, valvular disease, kidney or liver dys-
function, diabetes mellitus, or peripheral arterial occlusive disease were excluded. People with a
known allergic diathesis or previously treated with corticosteroids and those being treated with aspirin
or nonsteroidal anti-inflammatory drugs were also excluded.
Interventions Intervention: 1 mg/kg dexamethasone, drawn up in a syringe to 10 mL with normal saline after induc-
tion of anaesthesia
Comparison: placebo - 10 mL of normal saline after induction of anaesthesia
Outcomes Primary end point: haemodynamic stability by reducing capillary leakage, as indicated by both ex-
travascular lung water and total fluid balances.
Secondary end points: haemodynamic variables (heart rate, mean arterial pressure, mean pulmonary
artery pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, stroke
volume index, pulmonary vascular resistance index, systemic vascular resistance index). Administra-
tion of vasoactive substances, infusion of crystalloids, colloids, and erythrocytes, administration of
furosemide. Total blood volume, intrathoracic blood volume, changes in extra-vascular fluid volume
Outcomes were measured during hospital stay.
Risk of bias
Random sequence genera- Unclear risk Quote: "individuals were randomized into two groups under controlled, dou-
tion (selection bias) ble-blind conditions".
Comment: insufficient details
Allocation concealment Unclear risk Quote: "individuals were randomized into two groups under controlled, dou-
(selection bias) ble-blind conditions".
Comment: insufficient details on allocation concealment.
Blinding of participants Low risk Quote: "individuals were randomized into two groups under controlled, dou-
and personnel (perfor- ble-blind conditions".
mance bias)
Blinding of outcome as- Unclear risk Unspecified blinding of outcome assessors.


(attrition bias)
All outcomes

porting bias)
Informed decisions.
Vukovic 2011
Methods Study design: randomised, controlled, single-centre, single-blinded trial. Multi-arm trial.
Total duration of the study: February 2009 to May 2009
Number of study centres and location: Cardiovascular Institute, School of Medicine, University of Bel-
grade, Serbia
Date of study: 2009
Number analysed: 86
Mean age: 61
Gender: 84%
Surgery type: elective on pump CABG.
Inclusion criteria: undergoing elective CABG. All participants were found to have significantly impaired
left ventricular function (EF ≤ 30%)
Exclusion criteria: people with acute myocardial infarction (< 4 weeks), acute and chronic infections,
autoimmune disease or preceding anti-inflammatory therapy, severe renal dysfunction demanding
preoperative dialysis, hepatic dysfunction and previous or concomitant cardiac surgical procedures
were excluded.
Interventions Intervention: methylprednisolone group (MP), a single intravenous bolus of methylprednisolone (10
mg/kg) administered after induction of anaesthesia.
An additional group had treatment with atorvastatin (20 mg/day) during the 3 weeks before surgery,
not included in the review.
Outcomes Primary endpoint: impact on myocardial function
Secondary endpoints: heart rate, mean arterial pressure, central venous pressure, mean pulmonary ar-
terial pressure, pulmonary capillary wedge pressure, cardiac output, cardiac index, systemic vascular
resistance index, pulmonary vascular resistance index, left ventricular stroke work index and inotrop-
ic medication administration. Measurements of pH and glucose and lactate concentrations. Troponin
I and cytokine levels (IL-6), C-reactive protein and white blood cell count. Postoperative length of ICU
stay, postoperative arrhythmia, CPB time and cross-clamp time.
Risk of bias
Random sequence genera- Low risk Quote: "Randomization was achieved by the use of computer-generated ran-
tion (selection bias) dom numbers"
Informed decisions.
Vukovic 2011 (Continued)
Allocation concealment Unclear risk Inadequate description of allocation concealment.

(selection bias)
Blinding of participants High risk Quote: "Patients were blinded to the drug assignment group. Caregivers were
and personnel (perfor- aware of the drug used, but were not involved in data collection and interpre-
mance bias) tation."
Blinding of outcome as- Low risk Quote: "Caregivers were aware of the drug used, but were not involved in data
sessment (detection bias) collection and interpretation."
Comment: outcome assessors were blinded.

(attrition bias)
All outcomes

porting bias)
Wan 1999
Number of study centres and location: not stated
Number analysed: 20
Mean age: 65
Gender: 70% male
Surgery type: mixed
Inclusion criteria: people undergoing CPB for coronary artery bypass grafting (CABG) or valvular opera-
tions
Exclusion criteria: people undergoing a potentially short duration of CPB such as for CABG of fewer
than 3 grafts, those undergoing a redo or an emergency procedure, those who had infectious disease
before the operation, and those who had used steroids in the preoperative period were not included.
Interventions Intervention: 30 mg/kg dose of methylprednisolone during induction of anaesthesia.
Comparison: placebo
Outcomes Primary outcomes: endotoxin levels.
Informed decisions.
Wan 1999 (Continued)

Secondary outcomes: postoperative serum creatine kinase MB and lactate values, postoperative blood
losses, duration of mechanical ventilation, length of ICU stay.
Outcomes were measured during hospital stay. No distinction between primary and secondary out-
comes.
Notes 77 eligible patients were excluded from the final study because they didn't meet the inclusion criteria.
Funding for trial: none declared
Risk of bias
Random sequence genera- Unclear risk Quote: "the type of treatment was determined by opening a sealed envelope
tion (selection bias) prepared in advance".
Comment: unclear randomisation process.
Allocation concealment Low risk Quote: "the type of treatment was determined by opening a sealed envelope
(selection bias) prepared in advance".
Comment: sealed envelope.
Blinding of participants High risk Quote: "the type of treatment was determined by opening a sealed envelope
and personnel (perfor- prepared in advance".
mance bias)
Comment: staff aware of the treatment
Blinding of outcome as- Unclear risk Quote: "The type of treatment was determined by opening a sealed envelope
sessment (detection bias) prepared in advance. The ICU staff was blinded as to the pre-treatment of
steroids. Laboratory technicians were not aware of the clinical data".
Comment: unclear extent of the outcome assessment blinding.

(attrition bias)
All outcomes

porting bias)
Weis 2006
Total duration of the study: 12 months (Sept 2002 to Sept 2003)
Number of study centres and location: single centre; Departments of Anesthesiology and Cardiac
Surgery and the Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-Maximil-
ians-University, Munich, Germany
Informed decisions.
Weis 2006 (Continued)

Date of study: 2006
Number analysed: 28
Mean age: 69
Gender: 68%
Surgery type: CABG, Valve procedures, both
Inclusion criteria: preoperative left ventricular ejection fraction of less than 35% or an expected dura-
tion of CPB of greater than 97 minutes.
Exclusion criteria: pregnancy, emergency operation, hepatic dysfunction (bilirubin > 3 mg/dL), renal
dysfunction (plasma creatinine (> 2 mg/dL), a positive serologic test result for HIV, manifest insulin-de-
pendent diabetes mellitus, an extracardial septic focus, chronic or acute inflammatory disease, and in-
ability to provide informed consent. In addition, patients who required glucocorticoids other than hy-
drocortisone were excluded.
Interventions Intervention: hydrocortisone administration started with a loading dose (100 mg over 10 minutes ad-
ministered intravenously) before induction of anaesthesia, followed by a continuous infusion of 10 mg/
hour for 24 hours (postoperative day [POD] 1), which was reduced to 5 mg/hour on POD 2 and then ta-
pered to 3 20 mg administered intravenously on POD 3 and 3 10 mg administered intravenously on POD
4.
Comparison: placebo
Outcomes Primary end point: duration of administration and the maximal doses of the stress hormones epineph-
rine (as an inotropic agent) and norepinephrine.
Secondary end points: long-term incidence of chronic stress symptoms and health-related quality of
life after cardiac surgery. Length of mechanical ventilation, peak plasma concentration of lactic acid
measured during ICU therapy, serum levels of the pro-inflammatory cytokine interleukin 6 (IL-6), the
Simplified Acute Physiology Score during the first 24 hours in the ICU, the Therapeutic Intervention
Scoring System (TISS) score daily during the stay in the ICU and length of stay in the ICU.
Notes 8 participants lost to follow-up
Funding for trial: none declared
Risk of bias
Random sequence genera- Unclear risk Quote: "... in identical vials in a double-blind fashion. The vials were prepared
tion (selection bias) by a study nurse who was not involved in the care of patients participating in
the trial"
Comment: randomisation procedure not specified.
Allocation concealment Low risk Quote: "... in identical vials in a double-blind fashion. The vials were prepared
(selection bias) by a study nurse who was not involved in the care of patients participating in
the trial"
Informed decisions.

Comment: identical vials, prepared by personnel not involved in the trial.
Blinding of participants Low risk Quote: "The patients were randomly assigned to one of 2 treatment groups
and personnel (perfor- with the use of a computer-generated randomization list. The vials were pre-
mance bias) pared by a study nurse who was not involved in the care of patients participat-
ing in the trial."
Comment: double-blinded study.


(attrition bias)
All outcomes

porting bias)
Weis 2009
Number of study centres and location: single centre; departments of Anesthesiology and Cardiac
Surgery, University of Munich, Klinikum Grosshadern, Munich, Germany.
Mean age: 68
Gender: 50% male
Surgery type: mixed
Inclusion criteria: left ventricular ejection fraction lower than 39% or an expected duration of the CPB
of longer than 97 minutes (combined procedures or coronary artery bypass grafting with more than
three grafts planned)
Exclusion criteria: age < 18 years, pregnancy, preoperative IL-6 levels >10 pg/mL, hepatic insufficiency
(bilirubin > 3 mg/dL), renal insufficiency (creatinine > 2 mg/dL), a positive serologic test for HIV, man-
ifest insulin-dependent diabetes mellitus, adipositas permagna (body mass index > 30 kg/m2), use of
steroidal or nonsteroidal antiphlogistics during the last 7 days (except 100 mg acetylsalicylic acid per
day), an extracardial septic focus, or chronic or acute inflammatory diseases.
mg/day, 30 mg/day
Informed decisions.

Comparison: placebo
Outcomes Outcomes were mortality, pulmonary complications, intubation time, ICU stay, hospital stay, renal fail-
ure, atrial fibrillation, infections, number of blood transfusions, biomarkers measured during hospital
stay. No distinction between primary and secondary outcomes.
Risk of bias
Random sequence genera- Low risk Quote: "patients were randomly allocated to two groups by block randomiza-
tion (selection bias) tion".
Comment: block randomisation.
Allocation concealment Unclear risk Quote: "patients were randomly allocated to two groups by block randomiza-
(selection bias) tion".
Comment: insufficient information.
Blinding of participants Low risk Double-blind study.

mance bias)


(attrition bias)
All outcomes

porting bias)
Whitlock 2006
Total duration of the study: 1 April 2004 to 28 February 2005
Number of study centres and location: single centre; Department of Surgery, Division of Cardiovascular
Surgery, McMaster University, Hamilton, Canada
Date of study: 2006
Informed decisions.
Whitlock 2006 (Continued)

Mean age: 67
Gender: 73% male
Average BMI: 29.2
Surgery type: CABG, single valve and complex
Inclusion criteria: provision of informed consent, age greater than 18 years, and a cardiac surgical pro-
cedure requiring CPB
Exclusion criteria: use of systemic steroids, history of bacterial or fungal infection in the previous 30
days, or steroid intolerance.
Interventions Intervention: 250 mg IV methylprednisolone on anaesthetic induction and again on institution of CPB
Comparison: identical placebo solution
Outcomes Primary endpoint: IL-6 concentration at 4 and 8 hours after surgery.
Secondary endpoints: inflammatory-related haemodynamic indices, inotrope/pressor dose and dura-

tion, temperature, fluid balance, duration of mechanical ventilation, steroid-related wound complica-
tions infections, gastrointestinal haemorrhage/perforation, postoperative insulin use/blood sugars, in-
hospital new onset atrial fibrillation > 5 minutes, chest tube output, transfusion requirements, length
of hospital stay.
Risk of bias
Random sequence genera- Low risk Quote: "Block randomization via a computer-generated sequence was per-
tion (selection bias) formed on the day of surgery by the local hospital pharmacy"
Comment: adequate randomisation
Allocation concealment Unclear risk Quote: "Block randomization via a computer-generated sequence was per-
(selection bias) formed on the day of surgery by the local hospital pharmacy"
Comment: no information about concealment after randomisation
Blinding of participants Low risk Quote: "all patients, clinicians, and statisticians were blinded until the comple-
and personnel (perfor- tion of data analyses by group"
mance bias)
Blinding of outcome as- Low risk Quote: "all patients, clinicians, and statisticians were blinded until the comple-
sessment (detection bias) tion of data analyses by group"
Incomplete outcome data Low risk Quote: "Sixty patients were successfully randomized into the two study groups
(attrition bias) with no withdrawals. A single patient was unblinded at the request of the fami-
All outcomes ly after a poor surgical outcome (paraplegia)."
Selective reporting (re- Low risk Quote: "Potential adverse effects of steroids from the available literature were
porting bias) defined a priori."
Informed decisions.
Whitlock 2015
Methods Study design: double-bind, randomised controlled trial
Total duration of the study: 21 January 2007 to 19 December 2013
Number of study centres and location: 80 cardiac surgery centres in 18 countries
Date of study: 2015
Number lost to follow-up/withdrawn: 0 (300 did not receive allocated intervention and 8 lost at fol-
low-up. Data were not collected for the first 490 patients in the pilot study)
Mean age: 67
Gender: 60% male
Average BMI: 26.7
Severity of the condition according to study authors: EuroSCORE of at least 6
Surgery type: CABG, valve, combined
Inclusion criteria: people aged 18 years or older were eligible if they had a European System for Cardiac
Operative Risk Evaluation (EuroSCORE) of at least 6 (from 5 July 2011, in China and India, study accept-
ed inclusion of patients with a EuroSCORE of at least 4 if the patient was undergoing valvular surgery
because research showed that patients from China and India with these lower EuroSCOREs had higher
than expected mortality rates).
Exclusion criteria: people taking or expected to receive systemic steroids in the immediate postopera-
tive period, had a history of bacterial or fungal infection in the preceding 30 days, had an allergy or in-
tolerance to steroids, were expected to receive aprotinin, or had previously participated in SIRS.
Interventions Intervention: methylprednisolone (250 mg at anaesthetic induction and 250 mg at initiation of car-
diopulmonary bypass)
Comparison: placebo
Outcomes Primary endpoint: mortality at 30 days after randomisation and a composite of death, myocardial in-
jury, stroke, renal failure (stage 3 acute kidney injury, 2012 Kidney Disease Improving Global Outcomes
[KDIGO] guidelines), or respiratory failure (uninterrupted postoperative mechanical ventilation for
more than 48 hours) at 30 days after randomisation.
Secondary endpoints: 30-day secondary outcomes included individual components of the primary
composite outcome, myocardial injury or mortality, new atrial fibrillation, chest drain output during
the first 24 hours after surgery, the number of participants with transfusions during the first 24 hours
after surgery, the duration of mechanical ventilation, duration of intensive care unit stay, and length
of hospital stay. Safety outcomes included infection, stroke, wound complications (superficial or deep
surgical site infection, or sterile wound dehiscence), gastrointestinal haemorrhage, gastrointestinal
perforation within 30 days, delirium on postoperative day 3, and postoperative insulin use and peak
blood glucose during the first 24 hours after surgery. Mortality at 6 months was also included.
Notes Funding for trial: SIRS was funded by the Canadian Institutes of Health Research and the Canadian Net-
work and Centre for Trials Internationally
Informed decisions.
Whitlock 2015 (Continued)
Risk of bias

Allocation concealment Low risk Central allocation (pharmacy).

(selection bias)
Blinding of participants Low risk The study is defined as double-blinded and placebo-controlled.
mance bias)
Blinding of outcome as- Low risk Quote: "Patients, health-care providers, data collectors, and outcome adjudi-
sessment (detection bias) cators were masked to treatment allocation."
Incomplete outcome data Low risk Data were not collected for the first 490 participants in the pilot study. With-
(attrition bias) drawal of 300 participants after randomisation. Only 0.1% lost at follow-up.
All outcomes
porting bias)
Yared 1998
Total duration of the study: 15 January 1997 and 25 September 1997
Number of study centres and location: single centre; Departments of Cardiothoracic Anesthesia, Nurs-
ing, Biostatistics, and Thoracic & Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland,
Ohio
Date of study: 1998
Number lost to follow-up/withdrawn: 31; 20 exclusions (no study medication (10), bleeding (3), apro-
tinin (1), additive steroids (6))
Mean age: 63
Gender: 82% male
Surgery type: CABG or valve surgery
Inclusion criteria: 20 years or older undergoing elective coronary and/or valvular surgery
Informed decisions.
Yared 1998 (Continued)

Exclusion criteria: people with a history of hypersensitivity to dexamethasone or poorly controlled dia-
betes mellitus, or who were receiving therapy with corticosteroids were excluded.
Interventions Intervention: dexamethasone 0.6 mg/kg after induction of anaesthesia but before skin incision
Comparison: placebo (saline) after induction of anaesthesia but before skin incision
Outcomes Primary endpoint: incidence of shivering measured during hospital stay
Secondary endpoints: duration of anaesthesia, CPB, cross-clamp time, as well as lowest temperature
(bladder) on CPB and temperature of blood (PA) on admission to the ICU, duration of CPB, aortic cross-
clamp time, temperature gradient on ICU admission, oxygen consumption (MVO2) CO2 production (MV-
CO2).
Risk of bias
Random sequence genera- Unclear risk Comment: unspecified randomisation method

Allocation concealment Unclear risk Comment: concealment of allocation was not specified
(selection bias)
Blinding of participants Low risk Quote: "double-blind, placebo-controlled study was undertaken"
mance bias) Comment: study is defined as double-blinded and placebo controlled
Blinding of outcome as- Unclear risk Quote: "time elapsed from ICU admission to tracheal extubation, ICU and hos-
sessment (detection bias) pital length of stay, and mortality, as well as the incidence of major neurologic,
renal, cardiac, infectious, and pulmonary morbidities were obtained from the
Cardiothoracic Anesthesia Database"
Comment: outcome assessment blinding unclear
Incomplete outcome data High risk Quote: "A total of 20 patients were excluded from analysis"
(attrition bias)
All outcomes Comment: 12 participants in the steroid group were excluded compared to 8 in
the placebo group; unclear if this was prespecified
Selective reporting (re- Unclear risk Quote: "a post hoc analysis of data obtained during the study of the effects of
porting bias) dexamethasone on shivering"
Comment: unclear process of outcome selection and reporting
Yared 2007
Total duration of the study: October 2000 and July 2001
Informed decisions.

Number of study centres and location: single centre; Department of Cardiothoracic Anesthesiology,
Cleveland Clinic Foundation, Cleveland, OH, USA
Date of study: 2007
Number lost to follow-up/withdrawn: 7 (change in surgical plan (5), aprotinin (1), additives steroids (1)
Mean age: 71
Gender: 65% male
Surgery type: elective, combined coronary and valvular heart surgery
Inclusion criteria: age 20 years or older scheduled for elective, combined coronary and valvular heart
surgery
Exclusion criteria: a history of AF or if they were receiving amiodarone or corticosteroid therapy, re-
ceived aprotinin
Interventions Intervention: 0.6 mg/kg dexamethasone immediately after induction
Comparison: placebo immediately after induction
Outcomes Primary endpoint: incidence of postoperative AF, concentration of perioperative cytokines (IL-6, 8, and
10, TNF-alpha) and acute-phase markers (CRP, C-4)
Secondary endpoints: perioperative haemodynamics (heart rates and cardiac index) and fluid balance,
intubation time, ICU and postoperative hospital LOS, major morbidity (pulmonary, renal, cardiac, neu-
rological complications, infection), body temperature and mortality measured during hospital stay
Risk of bias
Random sequence genera- Low risk Quote: "A computer-generated random table was used"
Comment: adequate randomisation.
Allocation concealment Unclear risk Quote: "A computer-generated random table was used"
(selection bias)
Comment: no description of concealment after randomisation
Blinding of participants Low risk Quote: "a prospective, randomized, double-blind, placebo-controlled study"
mance bias) Comment: double-blind study.
Blinding of outcome as- Unclear risk Quote: "a prospective, randomized, double-blind, placebo-controlled study"
Comment: there is no information available with regard to the timing of disclo-
sure of allocation.
Informed decisions.
Incomplete outcome data Low risk Patients receiving additional steroids were excluded from the trial. Follow-up:
(attrition bias) hospital stay. 0% loss to follow-up.
All outcomes
porting bias)
Yilmaz 1999
Number lost to follow-up/withdrawn: 5 patients excluded: (2 for glucose dysregulation, 3 for transfu-
sion need)
Mean age: 52
Gender: 80% male
Inclusion criteria: isolated coronary artery disease and scheduled to undergo elective CABG
Exclusion criteria: concurrent corticosteroids, salicylates, dipyridamole or anticoagulants were exclud-

ed from the study. Other exclusion criteria were concurrent chronic obstructive pulmonary disease,
chronic renal failure, insulin-dependent diabetes, congestive cardiac failure, peptic ulcer history, prior
cardiac operations, recent (30 days) myocardial infarction and steroid dependency.
Interventions Intervention: 1 mg/kg methylprednisolone in pump prime solution
Comparison: placebo
Outcomes Primary endpoint: circulating levels of serum cytokines (creatine kinase-myocardial band (CK-MB), IL-6
and IL-8 levels)
Secondary endpoints: operative and postoperative variables (cross-clamp time, CPB time, cardiac in-
dex, postoperative inotropic requirement, body temperature, mechanical ventilation time, intensive
care unit and postoperative hospital stay and other morbidity) were recorded. Postoperative transtho-
racic echocardiographic evaluation of left ventricular global and segmental function (5th to 7th postop-
erative day). White blood cell concentrations
Informed decisions.
Yilmaz 1999 (Continued)
Risk of bias
Random sequence genera- Unclear risk Quote: "Twenty patients were randomly divided in two groups"
Comment: no information on randomisation procedure.
Allocation concealment Unclear risk Quote: "Twenty patients were randomly divided in two groups"
(selection bias)
Comment: no information on concealment
Blinding of participants Low risk Study was classified as "a prospective, randomized, double-blind, place-
and personnel (perfor- bo-controlled study"
mance bias)
Comment: double-blind.
Blinding of outcome as- Unclear risk Study was classified as "a prospective, randomized, double-blind, place-
sessment (detection bias) bo-controlled study"
Comment: no information available with regard to the timing of disclosure of

allocation.
Incomplete outcome data High risk Follow-up: hospital stay. 25% loss to follow-up. Five participants excluded (2x
(attrition bias) glucose dysregulation, 3x transfusion need).
All outcomes
porting bias)
AaDO2: alveolar-arterial PO2 difference

ACE: angiotensin-converting enzyme
AF: atrial fibrillation
AVR: aortic valve replacement
BAL: bronchoalveolar lavage
BDI-II: Beck Depression Inventory 2nd Edition
C3: complement factor 3
C3a: complement factor 3a
C4: complement factor 4
CABG: coronary artery bypass grafting
CI: cardiac index
CK-MB: creatine kinase-myocardial band
COI: conflict of interest
COPD: chronic obstructive pulmonary disease
CPB: cardiopulmonary bypass
CRP: C-reactive protein
cTnI: cardiac troponin I
ECG: electrocardiogram
FEV1: forced expiratory volume
FVC: forced vital capacity
IABP: intra-aortic balloon pump
ICU: intensive care unit
IL: interleukin
IV: intravenous
LVEF: left ventricle ejection fraction
MAP: mean arterial pressure
MI: myocardial infarction
Informed decisions.
MMSE: Mini Mental State Examination

MPAP: mean pulmonary arterial pressure
MVO2: oxygen consumption
MVR: mitral valve replacement
NAG: N-acetyl-β-d-glucosaminidase
NR: not reported
PaO2/FiO2: arterial oxygen partial pressure to fractional inspired oxygen ratio
PCWP: pulmonary capillary wedge pressure
POD: postoperative day
QoR: quality of recovery
RCT: randomised controlled trial
SIRS: systemic inflammatory response syndrome
TNF-a: tumour necrosis factor alpha
T-reg: regulatory T cells
WBC: white blood cell
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Anic 2004 No clinical endpoints measured
Biagioli 1981 No clinical endpoints measured
Boldt 1986 No clinical endpoints measured
Jansen 1991b No clinical endpoints measured
Jorens 1993 No clinical endpoints measured
Karlstad 1993 No clinical endpoints measured
Kawamura 1995 No clinical endpoints measured
Kawamura 1999 No clinical endpoints measured
Kirsh 1979 Ineligible intervention (steroids in cardioplegic solution only)
Kito 1980 No clinical endpoints measured
Kobayashi 1996 No clinical endpoints measured
Launo 1990 Ineligible population (no cardiac surgical patients)
Lee 2005 Ineligible intervention (administration only postoperatively, not prophylactic)
Levinsky 1979 Ineligible intervention (steroids in cardioplegic solution only)
Loubser 1997 No clinical endpoints measured
Ming 2001 No clinical endpoints measured
Miranda 1982 No clinical endpoints measured
Raff 1987 No clinical endpoints measured
Ranucci 1994 No clinical endpoints measured
Informed decisions.
Study Reason for exclusion
Santarpino 2009a Ineligible comparison (no untreated control group)
Santarpino 2009b Ineligible comparison (no untreated control group)
Schmartz 1996 No clinical endpoints measured
Tabardel 1996 No clinical endpoints measured
Thompson 1980 No clinical endpoints measured
Thompson 1982 No clinical endpoints measured
Toledo-Pereyra 1980 Ineligible population (study in children)
Turkoz 2000 No clinical endpoints measured
Us 2001 No clinical endpoints measured
Vallejo 1977 Ineligible population (study in children)
Van Overveld 1994 No clinical endpoints measured
Vogelzang 2007 Ineligible comparison (no untreated control group)
Wan 1997b No clinical endpoints measured
Yaeger 2005 No clinical endpoints measured
Yasuura 1977 No clinical endpoints measured
Characteristics of ongoing studies [ordered by study ID]
DECS-II
Study name Dexamethasone for Cardiac Surgery-II Trial (DECS-II)
Methods Study design: randomised, double-blinded, controlled trial
Total duration of the study: N/A
Number of study centres and location: multiple centres
Participants Number randomised: target of 2800 participants
Number lost to follow-up/withdrawn: N/A
Number analysed: N/A
Mean age: N/A
Gender: N/A
Severity of the condition according to study authors: N/A
Surgery type: elective or semi-elective on-pump cardiac surgery identified as being at an increased
risk of major complications
Informed decisions.
DECS-II (Continued)
Inclusion criteria: males and females, age 18 to 75 years, undergoing elective cardiac surgery with
cardiopulmonary bypass, EuroScore-II estimated risk of 1.5% or higher
Exclusion criteria: poor language (English or Dutch) comprehension, type I diabetes, endocarditis
or other evidence of sepsis, preoperative steroid therapy
Interventions Intervention: dexamethasone administered as a single IV injection after induction of anaesthesia,

but before initiation of CPB. Prepare as a 20 mg/mL dexamethasone solution, made up with 0.9%
saline to 10 mL.
Comparison: no steroids
Outcomes Days at home up to 30 days after surgery, respiratory failure, infection, myocardial infarction,
stroke, peak blood glucose, length of stay, quick SOFA score
Starting date 1 September 2018
Contact information p.myles@alfred.org.au
NCT00807521
Study name Reduction of the cardiac proapoptotic stress response by dexamethasone in patients undergoing
coronary artery bypass grafting
Methods Study design: randomised, placebo-controlled, single-blinded trial
Number of study centres and location: unclear
Participants Number randomised: 96 (target)
Number analysed: not stated
Gender: not stated
Surgery type: cardiac surgery
Inclusion criteria: patients undergoing coronary artery bypass surgery (CABG), aged 18 to 75 years,
informed consent
Exclusion criteria: re-operations and emergency operations, patients with anaemia (Hb < 5.0),
emergency operation, patients receiving blood transfusions < 3 months before operation, in-
sulin-dependent diabetes mellitus, hepatic or renal failure, pregnancy, use of steroids
Interventions Intervention: single high-dose bolus of dexamethasone before surgery
Comparison: placebo
Informed decisions.
NCT00807521 (Continued)
Outcomes Expression of p38 in cultured cells and cardiac tissue (time frame of one week)
Starting date December 2008, recruiting
Contact information Dr. Christa Boer, VU Medical Center, Amsterdam, the Netherlands. C.Boer@vumc.nl
NCT00879931
Study name Influence of corticoids on renal function in cardiac surgery
Methods Study design: randomised, placebo-controlled, double-blind trial
Participants Number randomised: estimated enrolment of 80 participants
Number analysed: not stated
Gender: not stated
Surgery type: not stated
Inclusion criteria: aged between 20 and 80 years, patients scheduled for elective cardiac surgery,
preoperative creatinine levels of < 2 mg/dL, no corticoid treatment
Exclusion criteria: non-elective surgery, patients with renal dysfunction: creatinine > 2 mg/dL, pa-
tients treated with corticoids
Interventions Intervention: methylprednisolone
Comparison: placebo
Outcomes Renal dysfunction and renal failure postoperatively within 48 hours after cardiac surgery
Starting date September 2010
Contact information Stefaan.Bouchez@Ugent.be
CABG: coronary artery bypass grafting

CPB: cardiopulmonary bypass
EuroScore-II: European System for Cardiac Operative Risk Evaluation, 2nd version
HB: haemoglobin
Informed decisions.
IV: intravenous
N/A: not applicable
SOFA: Sequential Organ Failure Assessment
DATA AND ANALYSES
Comparison 1. Primary outcomes
Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants
1.1 Mortality, including 'no major compli- 25 14940 Risk Ratio (M-H, Random, 0.90 [0.75, 1.07]
cations' 95% CI)
1.2 Cardiac complications, including 'no 25 14766 Risk Ratio (M-H, Random, 1.16 [1.04, 1.31]
major complications' 95% CI)
1.3 Pulmonary complications, including 18 13549 Risk Ratio (M-H, Random, 0.88 [0.78, 0.99]
'no major complications' 95% CI)
Informed decisions.
Analysis 1.1. Comparison 1: Primary outcomes, Outcome 1: Mortality, including 'no major complications'
Corticosteroids Placebo or no treatment Risk Ratio Risk Ratio Risk of Bias
Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI A B C D E F G
Halonen 2007 1 120 0 121 0.3% 3.02 [0.12 , 73.52] + ? + ? + + +

Abbaszadeh 2012 0 92 1 92 0.3% 0.33 [0.01 , 8.08] + + + ? + + +
Codd 1977 1 75 0 75 0.3% 3.00 [0.12 , 72.49] − ? ? ? + ? +
Chaney 2001 0 59 1 29 0.3% 0.17 [0.01 , 3.97] ? ? + ? + + +
Liakopoulos 2007 1 40 0 38 0.3% 2.85 [0.12 , 67.97] + ? ? ? + + +
Yared 2007 1 37 0 34 0.3% 2.76 [0.12 , 65.62] + ? + ? + + +
Rubens 2005 0 34 1 34 0.3% 0.33 [0.01 , 7.91] + + + ? + + +
Whitlock 2006 1 30 0 30 0.3% 3.00 [0.13 , 70.83] + ? + + + + +
Andersen 1989 1 8 0 8 0.3% 3.00 [0.14 , 64.26] ? ? ? ? ? ? +
Bingol 2005 0 20 2 20 0.4% 0.20 [0.01 , 3.92] + ? + − ? ? +
Boscoe 1983 3 17 0 17 0.4% 7.00 [0.39 , 125.99] + ? ? ? ? ? +
Halvorsen 2003 1 147 1 147 0.4% 1.00 [0.06 , 15.84] + + + ? ? + +
Celik 2004 1 30 2 30 0.6% 0.50 [0.05 , 5.22] ? ? + ? + + +
Chaney 1998 1 30 2 30 0.6% 0.50 [0.05 , 5.22] ? ? + ? + + +
Lomirovotov 2013 2 22 1 22 0.6% 2.00 [0.20 , 20.49] + + ? ? + + +
Gomez Polo 2018 1 52 3 52 0.6% 0.33 [0.04 , 3.10] ? ? + ? + + +
Al-Shawabkeh 2017 2 170 2 170 0.8% 1.00 [0.14 , 7.02] + + + ? + + +
Yared 1998 2 106 3 110 1.0% 0.69 [0.12 , 4.06] ? ? + ? − ? +
Glumac 2017 3 85 2 84 1.0% 1.48 [0.25 , 8.65] + + + ? + + +
Rao 1977 2 75 3 75 1.0% 0.67 [0.11 , 3.88] ? ? − − + + +
Kerr 2012 2 51 3 47 1.0% 0.61 [0.11 , 3.52] + + + + ? + +
Coetzer 1996 7 165 5 130 2.5% 1.10 [0.36 , 3.40] + ? ? ? ? + +
Kilger 2003a 7 43 6 48 3.1% 1.30 [0.47 , 3.57] ? ? − − + + +
Dieleman 2012 31 2235 34 2247 13.4% 0.92 [0.57 , 1.49] + + + + + + +
Whitlock 2015 154 3755 177 3752 70.0% 0.87 [0.70 , 1.07] + + + + + + +
Total (95% CI) 7498 7442 100.0% 0.90 [0.75 , 1.07]

Total events: 225 249
Heterogeneity: Tau² = 0.00; Chi² = 11.15, df = 24 (P = 0.99); I² = 0% 0.01 0.1 1 10 100
Test for overall effect: Z = 1.21 (P = 0.23) Favours corticosteroids Favours no corticosteroids
Test for subgroup differences: Not applicable
Risk of bias legend

(A) Random sequence generation (selection bias)
(B) Allocation concealment (selection bias)
(C) Blinding of participants and personnel (performance bias)
(D) Blinding of outcome assessment (detection bias)
(E) Incomplete outcome data (attrition bias)
(F) Selective reporting (reporting bias)
(G) Other bias
Informed decisions.
Analysis 1.2. Comparison 1: Primary outcomes, Outcome 2:

Cardiac complications, including 'no major complications'
Yared 1998 0 106 1 110 0.1% 0.35 [0.01 , 8.40] ? ? + ? − ? +

Mardani 2012 1 43 0 50 0.1% 3.48 [0.15 , 83.21] + ? ? ? ? + +
Chaney 2001 0 59 1 29 0.1% 0.17 [0.01 , 3.97] ? ? + ? + + +
Yared 2007 1 37 0 34 0.1% 2.76 [0.12 , 65.62] + ? + ? + + +
Taleska Stupica 2020 0 20 1 20 0.1% 0.33 [0.01 , 7.72] + + + + ? + +
McBride 2004 1 18 0 17 0.1% 2.84 [0.12 , 65.34] ? ? + ? + + +
Andersen 1989 1 8 0 8 0.1% 3.00 [0.14 , 64.26] ? ? ? ? ? ? +
Rubens 2005 0 34 3 34 0.2% 0.14 [0.01 , 2.66] + + + ? + + +
Halonen 2007 1 120 1 121 0.2% 1.01 [0.06 , 15.94] + ? + ? + + +
Chaney 1998 1 30 1 30 0.2% 1.00 [0.07 , 15.26] ? ? + ? + + +
Celik 2004 1 30 2 30 0.2% 0.50 [0.05 , 5.22] ? ? + ? + + +
Vukovic 2011 2 29 1 28 0.2% 1.93 [0.19 , 20.12] + ? − + + + +
Halvorsen 2003 3 147 1 147 0.3% 3.00 [0.32 , 28.51] + + + ? ? + +
Mahrose 2019 1 88 3 88 0.3% 0.33 [0.04 , 3.14] + ? ? ? + + +
Whitlock 2006 1 30 3 30 0.3% 0.33 [0.04 , 3.03] + ? + + + + +
Oliver 2004 5 62 1 63 0.3% 5.08 [0.61 , 42.25] ? ? + + + ? +
Murphy 2011 2 60 2 49 0.4% 0.82 [0.12 , 5.59] + ? + ? + + +
Amr 2009 2 50 2 50 0.4% 1.00 [0.15 , 6.82] ? ? ? ? + + +
Abd El-Hakeem 2003a 2 170 3 170 0.4% 0.67 [0.11 , 3.94] + + + ? + + +
Rao 1977 2 75 5 75 0.5% 0.40 [0.08 , 2.00] ? ? − − + + +
Abbaszadeh 2012 4 92 6 92 0.9% 0.67 [0.19 , 2.28] + + + ? + + +
Codd 1977 6 75 5 75 1.0% 1.20 [0.38 , 3.76] − ? ? ? + ? +
Morton 1976 5 22 5 22 1.1% 1.00 [0.34 , 2.97] + ? + + + + +
Dieleman 2012 35 2235 39 2247 6.5% 0.90 [0.57 , 1.42] + + + + + + +
Whitlock 2015 486 3755 399 3752 85.8% 1.22 [1.07 , 1.38] + + + + + + +
Total (95% CI) 7395 7371 100.0% 1.16 [1.04 , 1.31]

Risk of bias legend

(G) Other bias
Informed decisions.
Analysis 1.3. Comparison 1: Primary outcomes, Outcome 3:

Pulmonary complications, including 'no major complications'
Murphy 2011 0 60 1 49 0.1% 0.27 [0.01 , 6.56] + ? + ? + + +

Toft 1997 0 8 1 8 0.1% 0.33 [0.02 , 7.14] ? ? ? ? + + +
Halvorsen 2003 2 147 0 147 0.2% 5.00 [0.24 , 103.26] + + + ? ? + +
Abbaszadeh 2012 2 92 1 92 0.2% 2.00 [0.18 , 21.67] + + + ? + + +
Liakopoulos 2007 2 40 1 38 0.3% 1.90 [0.18 , 20.10] + ? ? ? + + +
Yared 2007 1 37 2 34 0.3% 0.46 [0.04 , 4.84] + ? + ? + + +
Whitlock 2006 2 30 1 30 0.3% 2.00 [0.19 , 20.90] + ? + + + + +
Schurr 2001 1 24 2 26 0.3% 0.54 [0.05 , 5.60] ? ? − − + + +
Bingol 2005 1 20 4 20 0.3% 0.25 [0.03 , 2.05] + ? + − ? ? +
Rao 1977 1 75 7 75 0.3% 0.14 [0.02 , 1.13] ? ? − − + + +
Mardani 2012 2 43 2 50 0.4% 1.16 [0.17 , 7.91] + ? ? ? ? + +
Weis 2009 2 19 2 17 0.4% 0.89 [0.14 , 5.68] + ? + ? + + +
Morton 1976 3 48 3 48 0.6% 1.00 [0.21 , 4.71] + ? + + + + +
Oliver 2004 7 62 4 63 1.0% 1.78 [0.55 , 5.77] ? ? + + + ? +
Starobin 2007 6 30 6 30 1.4% 1.00 [0.36 , 2.75] ? ? ? ? + + +
Kerr 2012 21 51 21 47 6.7% 0.92 [0.58 , 1.46] + + + + ? + +
Dieleman 2012 67 2235 97 2247 15.0% 0.69 [0.51 , 0.94] + + + + + + +
Whitlock 2015 343 3755 375 3752 72.2% 0.91 [0.80 , 1.05] + + + + + + +
Total (95% CI) 6776 6773 100.0% 0.88 [0.78 , 0.99]

Risk of bias legend

(G) Other bias
Comparison 2. Secondary outcomes
pants
2.1 Infectious complications 28 14771 Risk Ratio (M-H, Random, 95% CI) 0.84 [0.76, 0.92]
2.2 Gastrointestinal bleed- 6 12533 Risk Ratio (M-H, Random, 95% CI) 1.21 [0.87, 1.67]
ing
2.3 Atrial fibrillation 28 14468 Risk Ratio (M-H, Random, 95% CI) 0.75 [0.65, 0.85]
2.4 Re-thoracotomy 12 5683 Risk Ratio (M-H, Random, 95% CI) 1.40 [1.14, 1.72]
2.5 Neurological complica- 17 13514 Risk Ratio (M-H, Random, 95% CI) 0.92 [0.73, 1.15]
tion (stroke)
2.6 Renal failure 13 12799 Risk Ratio (M-H, Random, 95% CI) 0.84 [0.69, 1.02]
2.7 Inotropic support 23 1878 Risk Ratio (M-H, Random, 95% CI) 0.93 [0.76, 1.13]
2.8 Postoperative bleeding 5 643 Mean Difference (IV, Random, 95% -61.94 [-142.99,
(mL) CI) 19.11]
Informed decisions.
pants
2.9 Mechanical ventilation 32 1973 Mean Difference (IV, Random, 95% -56.86 [-102.90,
time (minutes) CI) -10.82]
2.10 ICU stay (hours) 30 1656 Mean Difference (IV, Random, 95% -6.26 [-8.77, -3.75]
CI)
2.11 Hospital stay (days) 25 1841 Mean Difference (IV, Random, 95% -0.50 [-0.97, -0.04]
CI)
Analysis 2.1. Comparison 2: Secondary outcomes, Outcome 1: Infectious complications

Abbaszadeh 2012 5 92 3 92 0.4% 1.67 [0.41 , 6.77] + + + ? + + +

Al-Shawabkeh 2017 3 170 2 170 0.3% 1.50 [0.25 , 8.86] + + + ? + + +
Amr 2009 4 50 3 50 0.4% 1.33 [0.31 , 5.65] ? ? ? ? + + +
Bingol 2005 0 20 2 20 0.1% 0.20 [0.01 , 3.92] + ? + − ? ? +
Dieleman 2012 212 2235 333 2247 31.4% 0.64 [0.54 , 0.75] + + + + + + +
Gomez Polo 2018 2 52 1 52 0.1% 2.00 [0.19 , 21.38] ? ? + ? + + +
Halonen 2007 17 120 17 121 2.1% 1.01 [0.54 , 1.88] + ? + ? + + +
Halvorsen 2003 3 147 2 147 0.3% 1.50 [0.25 , 8.85] + + + ? ? + +
Jansen 1991 2 12 2 10 0.3% 0.83 [0.14 , 4.90] ? ? ? ? + + +
Kerr 2012 9 51 11 47 1.3% 0.75 [0.34 , 1.66] + + + + ? + +
Liakopoulos 2007 2 40 1 38 0.1% 1.90 [0.18 , 20.10] + ? ? ? + + +
Lomirovotov 2013 2 22 1 22 0.2% 2.00 [0.20 , 20.49] + + ? ? + + +
Mahrose 2019 8 88 4 88 0.6% 2.00 [0.62 , 6.40] + ? ? ? + + +
Mardani 2012 3 43 2 50 0.3% 1.74 [0.31 , 9.96] + ? ? ? ? + +
Murphy 2011 0 60 1 49 0.1% 0.27 [0.01 , 6.56] + ? + ? + + +
Prasongsukarn 2005 3 43 2 43 0.3% 1.50 [0.26 , 8.53] + + + + + + +
Rao 1977 0 75 1 75 0.1% 0.33 [0.01 , 8.05] ? ? − − + + +
Rubens 2005 1 34 3 34 0.2% 0.33 [0.04 , 3.05] + + + ? + + +
Schurr 2001 2 24 2 26 0.2% 1.08 [0.17 , 7.10] ? ? − − + + +
Starobin 2007 7 30 10 30 1.2% 0.70 [0.31 , 1.59] ? ? ? ? + + +
Taleska Stupica 2020 2 20 4 20 0.3% 0.50 [0.10 , 2.43] + + + + ? + +
Toft 1997 0 8 1 8 0.1% 0.33 [0.02 , 7.14] ? ? ? ? + + +
Vukovic 2011 2 29 2 28 0.2% 0.97 [0.15 , 6.39] + ? − + + + +
Weis 2009 3 19 3 17 0.4% 0.89 [0.21 , 3.85] + ? + ? + + +
Whitlock 2006 2 30 1 30 0.1% 2.00 [0.19 , 20.90] + ? + + + + +
Whitlock 2015 465 3755 493 3752 58.7% 0.94 [0.84 , 1.06] + + + + + + +
Yared 1998 1 106 2 110 0.1% 0.52 [0.05 , 5.64] ? ? + ? − ? +
Yilmaz 1999 0 10 1 10 0.1% 0.33 [0.02 , 7.32] ? ? + ? − + +
Total (95% CI) 7385 7386 100.0% 0.84 [0.76 , 0.92]

Risk of bias legend

(G) Other bias
Informed decisions.
Analysis 2.2. Comparison 2: Secondary outcomes, Outcome 2: Gastrointestinal bleeding

Al-Shawabkeh 2017 7 170 6 170 9.3% 1.17 [0.40 , 3.40] + + + ? + + +

Chaney 1998 0 30 1 30 1.1% 0.33 [0.01 , 7.87] ? ? + ? + + +
Dieleman 2012 13 2235 11 2247 16.7% 1.19 [0.53 , 2.65] + + + + + + +
Prasongsukarn 2005 1 43 0 43 1.1% 3.00 [0.13 , 71.65] + + + + + + +
Whitlock 2006 2 28 0 30 1.2% 5.34 [0.27 , 106.70] + ? + + + + +
Whitlock 2015 55 3755 46 3752 70.7% 1.19 [0.81 , 1.76] + + + + + + +
Total (95% CI) 6261 6272 100.0% 1.21 [0.87 , 1.67]

Total events: 78 64
Risk of bias legend

(G) Other bias
Analysis 2.3. Comparison 2: Secondary outcomes, Outcome 3: Atrial fibrillation
Corticosteroids Placebo or no treatment Risk Ratio Risk Ratio

Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI
Abbaszadeh 2012 40 92 67 92 9.6% 0.60 [0.46 , 0.78]

Abd El-Hakeem 2003b 1 10 3 10 0.4% 0.33 [0.04 , 2.69]
Al-Shawabkeh 2017 36 170 65 170 7.5% 0.55 [0.39 , 0.78]
Amr 2009 7 50 8 50 1.8% 0.88 [0.34 , 2.23]
Bingol 2005 1 20 3 20 0.4% 0.33 [0.04 , 2.94]
Celik 2004 6 30 7 30 1.7% 0.86 [0.33 , 2.25]
Chaney 1998 8 30 9 30 2.3% 0.89 [0.40 , 1.99]
Dieleman 2012 739 2235 790 2247 14.7% 0.94 [0.87 , 1.02]
Enc 2006 2 20 3 20 0.6% 0.67 [0.12 , 3.57]
Giomarelli 2003 0 10 2 10 0.2% 0.20 [0.01 , 3.70]
Gomez Polo 2018 9 52 14 52 2.6% 0.64 [0.31 , 1.35]
Halonen 2007 44 120 62 121 8.9% 0.72 [0.53 , 0.96]
Halvorsen 2003 1 147 1 147 0.2% 1.00 [0.06 , 15.84]
Lomirovotov 2013 5 22 2 22 0.7% 2.50 [0.54 , 11.54]
Mahrose 2019 26 88 42 88 6.7% 0.62 [0.42 , 0.91]
Mardani 2012 5 43 11 50 1.7% 0.53 [0.20 , 1.40]
Murphy 2011 11 60 10 49 2.5% 0.90 [0.42 , 1.94]
Prasongsukarn 2005 9 43 22 43 3.3% 0.41 [0.21 , 0.78]
Rubens 2005 4 34 13 34 1.5% 0.31 [0.11 , 0.85]
Schurr 2001 12 24 17 26 5.0% 0.76 [0.47 , 1.25]
Sobieski 2008 2 13 4 15 0.7% 0.58 [0.13 , 2.65]
Starobin 2007 11 30 8 30 2.6% 1.38 [0.64 , 2.93]
Taleska Stupica 2020 4 20 3 20 0.9% 1.33 [0.34 , 5.21]
Vukovic 2011 3 29 11 28 1.2% 0.26 [0.08 , 0.85]
Weis 2009 5 19 10 17 2.1% 0.45 [0.19 , 1.05]
Whitlock 2006 7 28 10 30 2.3% 0.75 [0.33 , 1.70]
Whitlock 2015 821 3755 846 3752 14.6% 0.97 [0.89 , 1.06]
Yared 2007 15 37 10 34 3.3% 1.38 [0.72 , 2.64]
Total (95% CI) 7231 7237 100.0% 0.75 [0.65 , 0.85]

Test for overall effect: Z = 4.31 (P < 0.0001) Favours corticosteroids Favours no corticosteroids
Informed decisions.
Analysis 2.4. Comparison 2: Secondary outcomes, Outcome 4: Re-thoracotomy

Amr 2009 4 50 3 50 2.1% 1.33 [0.31 , 5.65]

Dieleman 2012 177 2235 128 2247 88.9% 1.39 [1.12 , 1.73]
Halonen 2007 5 120 3 121 2.2% 1.68 [0.41 , 6.88]
Halvorsen 2003 1 147 1 147 0.6% 1.00 [0.06 , 15.84]
Mardani 2012 2 43 1 50 0.8% 2.33 [0.22 , 24.77]
McBride 2004 2 18 0 17 0.5% 4.74 [0.24 , 92.07]
Oliver 2004 0 62 4 63 0.5% 0.11 [0.01 , 2.05]
Rao 1977 4 75 3 75 2.0% 1.33 [0.31 , 5.75]
Rumalla 2001 1 6 0 7 0.5% 3.43 [0.16 , 71.36]
Schurr 2001 1 24 0 26 0.4% 3.24 [0.14 , 75.91]
Starobin 2007 1 30 2 30 0.8% 0.50 [0.05 , 5.22]
Taleska Stupica 2020 3 20 1 20 0.9% 3.00 [0.34 , 26.45]
Total (95% CI) 2830 2853 100.0% 1.40 [1.14 , 1.72]

Analysis 2.5. Comparison 2: Secondary outcomes, Outcome 5: Neurological complication (stroke)

Chaney 1998 3 30 1 29 1.1% 2.90 [0.32 , 26.30]

Chaney 2001 1 59 2 29 0.9% 0.25 [0.02 , 2.60]
Dieleman 2012 29 2235 32 2247 21.1% 0.91 [0.55 , 1.50]
Enc 2006 1 20 1 20 0.7% 1.00 [0.07 , 14.90]
Glumac 2017 2 80 1 81 0.9% 2.02 [0.19 , 21.89]
Halonen 2007 1 120 1 121 0.7% 1.01 [0.06 , 15.94]
Kerr 2012 15 51 11 47 11.7% 1.26 [0.64 , 2.45]
Mardani 2012 4 43 8 50 4.1% 0.58 [0.19 , 1.80]
Oliver 2004 1 62 0 63 0.5% 3.05 [0.13 , 73.41]
Rao 1977 0 75 6 75 0.6% 0.08 [0.00 , 1.34]
Rumalla 2001 0 6 1 7 0.6% 0.38 [0.02 , 7.93]
Schurr 2001 1 24 1 26 0.7% 1.08 [0.07 , 16.38]
Starobin 2007 1 30 0 30 0.5% 3.00 [0.13 , 70.83]
Whitlock 2006 1 30 1 30 0.7% 1.00 [0.07 , 15.26]
Whitlock 2015 71 3755 79 3752 52.3% 0.90 [0.65 , 1.23]
Yared 1998 3 106 3 110 2.1% 1.04 [0.21 , 5.03]
Yared 2007 0 37 2 34 0.6% 0.18 [0.01 , 3.71]
Total (95% CI) 6763 6751 100.0% 0.92 [0.73 , 1.15]

Informed decisions.
Analysis 2.6. Comparison 2: Secondary outcomes, Outcome 6: Renal failure

Demir 2009 0 15 1 15 0.4% 0.33 [0.01 , 7.58] ? ? ? ? + + +

Dieleman 2012 28 2235 40 2247 16.4% 0.70 [0.44 , 1.14] + + + + + + +
Enc 2006 2 20 0 20 0.4% 5.00 [0.26 , 98.00] ? ? + ? + + +
Liakopoulos 2007 5 40 3 38 2.0% 1.58 [0.41 , 6.17] + ? ? ? + + +
Mardani 2012 2 43 3 50 1.2% 0.78 [0.14 , 4.43] + ? ? ? ? + +
Prasongsukarn 2005 1 43 1 43 0.5% 1.00 [0.06 , 15.48] + + + + + + +
Starobin 2007 1 30 0 30 0.4% 3.00 [0.13 , 70.83] ? ? ? ? + + +
Taleska Stupica 2020 0 20 1 20 0.4% 0.33 [0.01 , 7.72] + + + + ? + +
Weis 2009 1 17 3 19 0.8% 0.37 [0.04 , 3.25] + ? + ? + + +
Whitlock 2006 2 30 0 30 0.4% 5.00 [0.25 , 99.95] + ? + + + + +
Whitlock 2015 139 3755 160 3752 75.9% 0.87 [0.69 , 1.08] + + + + + + +
Yared 1998 0 106 3 110 0.4% 0.15 [0.01 , 2.84] ? ? + ? − ? +
Yared 2007 1 37 2 34 0.7% 0.46 [0.04 , 4.84] + ? + ? + + +
Total (95% CI) 6391 6408 100.0% 0.84 [0.69 , 1.02]

Risk of bias legend

(G) Other bias
Analysis 2.7. Comparison 2: Secondary outcomes, Outcome 7: Inotropic support

Abd El-Hakeem 2003a 8 23 14 23 5.9% 0.57 [0.30 , 1.09]

Abd El-Hakeem 2003b 3 10 6 10 2.8% 0.50 [0.17 , 1.46]
Cavarocchi 1986 9 31 5 30 3.3% 1.74 [0.66 , 4.60]
Celik 2004 1 30 2 30 0.7% 0.50 [0.05 , 5.22]
Chaney 1998 24 30 15 30 9.6% 1.60 [1.07 , 2.39]
Chaney 2001 43 59 20 29 11.7% 1.06 [0.79 , 1.41]
Codd 1977 11 75 11 75 4.7% 1.00 [0.46 , 2.16]
El Azab 2002 2 9 3 8 1.6% 0.59 [0.13 , 2.70]
Giomarelli 2003 1 10 1 10 0.6% 1.00 [0.07 , 13.87]
Glumac 2017 37 80 41 81 11.1% 0.91 [0.66 , 1.26]
Halvorsen 2003 2 147 2 147 1.0% 1.00 [0.14 , 7.00]
Loef 2004 7 10 2 10 2.0% 3.50 [0.95 , 12.90]
Lomirovotov 2013 4 22 1 22 0.8% 4.00 [0.48 , 33.00]
Mahrose 2019 39 88 40 88 10.9% 0.97 [0.70 , 1.35]
Mardani 2012 2 43 3 50 1.2% 0.78 [0.14 , 4.43]
McBride 2004 9 18 6 17 4.5% 1.42 [0.64 , 3.13]
Murphy 2011 13 60 9 49 4.7% 1.18 [0.55 , 2.53]
Schurr 2001 3 24 6 26 2.1% 0.54 [0.15 , 1.93]
Von Spiegel 2001 6 10 9 10 7.2% 0.67 [0.39 , 1.15]
Vukovic 2011 5 29 18 29 4.1% 0.28 [0.12 , 0.65]
Whitlock 2006 0 30 8 30 0.5% 0.06 [0.00 , 0.98]
Yared 1998 24 106 29 110 8.3% 0.86 [0.54 , 1.37]
Yilmaz 1999 1 10 2 10 0.8% 0.50 [0.05 , 4.67]
Total (95% CI) 954 924 100.0% 0.93 [0.76 , 1.13]

Informed decisions.
Analysis 2.8. Comparison 2: Secondary outcomes, Outcome 8: Postoperative bleeding (mL)

Corticosteroids Placebo or no treatment Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Abbaszadeh 2012 415 154 92 421 160 92 22.6% -6.00 [-51.38 , 39.38]
Halvorsen 2003 703 247 147 744 279 147 21.5% -41.00 [-101.24 , 19.24]
Mardani 2012 807 506 43 748 496 50 9.6% 59.00 [-145.39 , 263.39]
Tassani 1999 313 28 26 478 49 26 24.0% -165.00 [-186.69 , -143.31]
Turkoz 2001 600 55 10 680 58 10 22.3% -80.00 [-129.54 , -30.46]
Total (95% CI) 318 325 100.0% -61.94 [-142.99 , 19.11]

Heterogeneity: Tau² = 7013.54; Chi² = 52.83, df = 4 (P < 0.00001); I² = 92%
Test for overall effect: Z = 1.50 (P = 0.13) -200 -100 0 100 200
Test for subgroup differences: Not applicable Favours corticosteroids Favours no corticosteroids
Analysis 2.9. Comparison 2: Secondary outcomes, Outcome 9: Mechanical ventilation time (minutes)
Abd El-Hakeem 2003a 407.13 24.1 23 443.9 45.1 23 5.4% -36.77 [-57.67 , -15.87]
Abd El-Hakeem 2003b 480 95 10 516 113 10 4.5% -36.00 [-127.50 , 55.50]
Bingol 2005 404 102 20 894 222 20 4.2% -490.00 [-597.07 , -382.93]
Bourbon 2004 696 276 12 762 5.5 12 3.3% -66.00 [-222.19 , 90.19]
Celik 2004 642 54 30 514 36 30 5.3% 128.00 [104.78 , 151.22]
Chaney 1998 796 294 30 604 315 30 3.4% 192.00 [37.81 , 346.19]
Demir 2009 572 298 15 496 263 15 2.7% 76.00 [-125.14 , 277.14]
Demir 2015 520.2 180 20 481.2 228.6 20 3.8% 39.00 [-88.52 , 166.52]
El Azab 2002 660 120 9 780 180 9 3.6% -120.00 [-261.34 , 21.34]
Engelman 1995 786 135 10 630 60 10 4.5% 156.00 [64.44 , 247.56]
Fillinger 2002 594 85.2 15 936 510 15 2.0% -342.00 [-603.67 , -80.33]
Giomarelli 2003 750 162 10 708 180 10 3.4% 42.00 [-108.09 , 192.09]
Glumac 2017 1164 750 80 1278 738 81 2.3% -114.00 [-343.87 , 115.87]
Halvorsen 2003 148 69 147 149 67 147 5.4% -1.00 [-16.55 , 14.55]
Hao 2019 1257.6 653.4 18 1073.4 526.8 18 1.1% 184.20 [-203.54 , 571.94]
Harig 1999 648 234 10 780 354 10 2.0% -132.00 [-395.01 , 131.01]
Hauer 2012 1026 720 56 1260 1020 55 1.4% -234.00 [-562.98 , 94.98]
Kilickan 2008 375 180 30 348 219 30 4.3% 27.00 [-74.44 , 128.44]
Liakopoulos 2007 840 528 40 684 414 38 2.5% 156.00 [-54.00 , 366.00]
Loef 2004 1131.6 214 10 900.6 188 10 3.0% 231.00 [54.45 , 407.55]
Mardani 2012 550.8 144 43 633.6 231.6 50 4.7% -82.80 [-160.09 , -5.51]
Mayumi 1997 2044 921 12 1872 662 12 0.5% 172.00 [-469.74 , 813.74]
Oliver 2004 519.3 292.8 62 918 404.9 63 3.9% -398.70 [-522.43 , -274.97]
Sano 2006 1320 720 31 1224 1164 29 0.7% 96.00 [-397.67 , 589.67]
Schurr 2001 510 204 24 480 174 26 4.2% 30.00 [-75.52 , 135.52]
Sobieski 2008 185 164 14 541 246 14 3.4% -356.00 [-510.87 , -201.13]
Taleska Stupica 2020 570 660 20 870 705 20 1.0% -300.00 [-723.24 , 123.24]
Tassani 1999 486 42 26 552 48 26 5.3% -66.00 [-90.52 , -41.48]
Vukovic 2011 714 216 29 1026 282 28 3.8% -312.00 [-442.73 , -181.27]
Wan 1999 840 420 10 1080 600 10 0.9% -240.00 [-693.93 , 213.93]
Yared 1998 696 714 106 786 828 110 2.6% -90.00 [-295.95 , 115.95]
Yilmaz 1999 804 663 10 702 213.3 10 0.9% 102.00 [-329.67 , 533.67]
Total (95% CI) 982 991 100.0% -56.86 [-102.90 , -10.82]

Informed decisions.
Analysis 2.10. Comparison 2: Secondary outcomes, Outcome 10: ICU stay (hours)
Abd El-Hakeem 2003a 52.66 1.81 23 66.26 23.09 23 3.6% -13.60 [-23.07 , -4.13]
Abd El-Hakeem 2003b 47.3 5.7 10 67.2 5.7 10 5.7% -19.90 [-24.90 , -14.90]
Amr 2009 64.8 19.2 50 67.2 16.8 50 4.7% -2.40 [-9.47 , 4.67]
Bingol 2005 33.6 16.3 20 105 78 20 0.5% -71.40 [-106.32 , -36.48]
Celik 2004 36.2 4.1 30 42.1 3.7 30 7.1% -5.90 [-7.88 , -3.92]
Demir 2009 55.9 14.64 15 83 75.6 15 0.4% -27.10 [-66.07 , 11.87]
Demir 2015 52.8 9.84 20 58.8 16.32 20 4.1% -6.00 [-14.35 , 2.35]
El Azab 2002 24 8 9 52 32 9 1.1% -28.00 [-49.55 , -6.45]
Engelman 1995 28.8 2.4 10 50.4 7.2 10 5.9% -21.60 [-26.30 , -16.90]
Fillinger 2002 27 11.6 15 36 28.7 15 1.9% -9.00 [-24.67 , 6.67]
Giomarelli 2003 32.1 3.7 10 35.2 4.4 10 6.5% -3.10 [-6.66 , 0.46]
Glumac 2017 51.5 35 80 60.8 33.4 81 3.2% -9.30 [-19.87 , 1.27]
Hao 2019 28 17.06 18 26.61 16.43 18 3.1% 1.39 [-9.55 , 12.33]
Harig 1999 18.1 0.5 10 19.9 0.9 10 7.4% -1.80 [-2.44 , -1.16]
Hauer 2012 38.3 31.7 56 68.4 49.9 55 1.9% -30.10 [-45.68 , -14.52]
Jansen 1991 91.2 27 12 72 27 13 1.2% 19.20 [-1.98 , 40.38]
Liakopoulos 2007 50.4 62.4 40 50 43.2 38 1.0% 0.40 [-23.32 , 24.12]
Loef 2004 29 10 10 26 7 10 4.4% 3.00 [-4.57 , 10.57]
Mardani 2012 68.64 31.2 43 88.32 31.92 50 2.5% -19.68 [-32.53 , -6.83]
Oliver 2004 25.2 14 62 23.9 8.7 63 6.2% 1.30 [-2.79 , 5.39]
Rubens 2005 36 29 34 36 24 34 2.6% 0.00 [-12.65 , 12.65]
Sano 2006 43.2 24 31 34 21.6 29 2.9% 9.20 [-2.34 , 20.74]
Schurr 2001 24 19 24 24 22 26 2.9% 0.00 [-11.37 , 11.37]
Sobieski 2008 23.7 2.6 14 24.6 12.3 14 4.9% -0.90 [-7.49 , 5.69]
Tassani 1999 27.2 2.1 26 28 2.2 26 7.3% -0.80 [-1.97 , 0.37]
Volk 2001 36 29 12 75 158 13 0.1% -39.00 [-126.44 , 48.44]
Volk 2003 36 7.2 12 74 43.2 12 0.9% -38.00 [-62.78 , -13.22]
Wan 1999 29 9 10 32 23 10 2.0% -3.00 [-18.31 , 12.31]
Yared 1998 36.8 28 106 47.9 113.6 110 1.1% -11.10 [-32.99 , 10.79]
Yilmaz 1999 33.71 17.3 10 34.2 7.8 10 2.8% -0.49 [-12.25 , 11.27]
Total (95% CI) 822 834 100.0% -6.26 [-8.77 , -3.75]

Test for overall effect: Z = 4.88 (P < 0.00001) -100 -50 0 50 100
Informed decisions.
Analysis 2.11. Comparison 2: Secondary outcomes, Outcome 11: Hospital stay (days)
Corticosteroids Placebo or no treatment Mean Difference Mean Difference Risk of Bias
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI A B C D E F G
Al-Shawabkeh 2017 6.02 2.25 170 5.95 1.95 170 6.2% 0.07 [-0.38 , 0.52] + + + ? + + +
Amr 2009 15 1 50 14 2 50 5.9% 1.00 [0.38 , 1.62] ? ? ? ? + + +
Bingol 2005 8.3 1.17 20 12.95 2.95 20 4.1% -4.65 [-6.04 , -3.26] + ? + − ? ? +
Celik 2004 10.2 2.2 30 12.4 2.3 30 4.7% -2.20 [-3.34 , -1.06] ? ? + ? + + +
Chaney 1998 6.9 4.1 29 8.3 6.1 28 2.0% -1.40 [-4.11 , 1.31] ? ? + ? + + +
Demir 2009 8.53 2.19 15 12.6 6.76 15 1.3% -4.07 [-7.67 , -0.47] ? ? ? ? + + +
Demir 2015 8.25 1.83 20 9.35 2.39 20 4.3% -1.10 [-2.42 , 0.22] ? ? ? ? + + +
Enc 2006 5.2 0.6 20 6.3 0.7 20 6.2% -1.10 [-1.50 , -0.70] ? ? + ? + + +
Engelman 1995 6.5 1.1 10 5.2 0.4 10 5.6% 1.30 [0.57 , 2.03] ? ? ? ? + + +
Fillinger 2002 4.6 1.5 15 6.1 1.7 15 4.7% -1.50 [-2.65 , -0.35] ? ? + ? + + +
Giomarelli 2003 6 1 10 6 1 10 5.3% 0.00 [-0.88 , 0.88] + + + ? + + +
Glumac 2017 11.2 4 80 11.3 3 81 4.8% -0.10 [-1.19 , 0.99] + + + ? + + +
Hao 2019 21.63 7.68 18 20.44 8.07 18 0.7% 1.19 [-3.96 , 6.34] ? ? ? ? ? + +
Kilickan 2008 7.75 1.69 30 8 1.26 30 5.6% -0.25 [-1.00 , 0.50] ? ? ? ? ? + +
Liakopoulos 2007 13.1 5.2 40 12.3 2.3 38 3.4% 0.80 [-0.97 , 2.57] + ? ? ? + + +
Mahrose 2019 6.5 1.2 88 7.2 1.6 88 6.2% -0.70 [-1.12 , -0.28] + ? ? ? + + +
Mardani 2012 12.93 1.03 43 13.64 1.75 50 5.9% -0.71 [-1.28 , -0.14] + ? ? ? ? + +
McBride 2004 8.06 2.9 18 7.76 3.5 17 2.7% 0.30 [-1.84 , 2.44] ? ? + ? + + +
Rubens 2005 5.4 1.9 17 6.5 2.8 17 3.7% -1.10 [-2.71 , 0.51] + + + ? + + +
Schurr 2001 11 2 24 11 1.6 26 5.0% 0.00 [-1.01 , 1.01] ? ? − − + + +
Sobieski 2008 4.8 1.5 13 5 1.3 15 4.9% -0.20 [-1.25 , 0.85] ? ? + ? + + +
Tassani 1999 13.3 4.6 26 10.5 6.1 26 1.8% 2.80 [-0.14 , 5.74] ? ? + ? + + +
Volk 2001 14.6 16.1 12 8.7 6.8 13 0.2% 5.90 [-3.93 , 15.73] ? ? + ? ? + +
Yared 1998 7 5.2 106 7.3 5.3 110 4.1% -0.30 [-1.70 , 1.10] ? ? + ? − ? +
Yilmaz 1999 6.6 0.9 10 9.2 8.7 10 0.7% -2.60 [-8.02 , 2.82] ? ? + ? − + +
Total (95% CI) 914 927 100.0% -0.50 [-0.97 , -0.04]

Risk of bias legend

(G) Other bias
Comparison 3. Subgroup analyses: corticosteroid dosage
Outcome or sub- No. of studies No. of partici- Statistical method Effect size
group title pants
3.1 Mortality 25 14940 Risk Ratio (M-H, Random, 95% CI) 0.90 [0.75, 1.07]
3.1.1 Low dose 8 1069 Risk Ratio (M-H, Random, 95% CI) 1.33 [0.65, 2.70]
3.1.2 High dose 17 13871 Risk Ratio (M-H, Random, 95% CI) 0.87 [0.73, 1.05]
3.2 Cardiac complica- 25 14766 Risk Ratio (M-H, Random, 95% CI) 1.16 [1.04, 1.31]
tions
3.3 Pulmonary compli- 18 13549 Risk Ratio (M-H, Random, 95% CI) 0.88 [0.78, 0.99]
cations
Informed decisions.
group title pants
3.6 Mechanical venti- 32 1973 Mean Difference (IV, Random, 95% CI) -59.95 [-106.51, -13.39]
lation (minutes)
3.6.1 Low dose 6 650 Mean Difference (IV, Random, 95% CI) -147.32 [-386.74,
92.11]
3.6.2 High dose 26 1323 Mean Difference (IV, Random, 95% CI) -39.33 [-94.96, 16.30]
3.7 Length of ICU stay 30 1656 Mean Difference (IV, Random, 95% CI) -6.25 [-8.74, -3.76]
(hours)
3.7.1 Low dose 4 332 Mean Difference (IV, Random, 95% CI) -22.18 [-41.90, -2.45]
3.7.2 High dose 26 1324 Mean Difference (IV, Random, 95% CI) -5.46 [-7.95, -2.98]
3.8 Length of hospital 25 1841 Mean Difference (IV, Random, 95% CI) -0.51 [-0.97, -0.04]
stay (days)
3.8.1 Low dose 4 397 Mean Difference (IV, Random, 95% CI) -1.82 [-3.80, 0.16]
3.8.2 High dose 21 1444 Mean Difference (IV, Random, 95% CI) -0.30 [-0.77, 0.18]
Informed decisions.
Analysis 3.1. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 1: Mortality

3.1.1 Low dose

Abbaszadeh 2012 0 92 1 92 0.3% 0.33 [0.01 , 8.08]
Andersen 1989 1 8 0 8 0.3% 3.00 [0.14 , 64.26]
Bingol 2005 0 20 2 20 0.4% 0.20 [0.01 , 3.92]
Boscoe 1983 3 17 0 17 0.4% 7.00 [0.39 , 125.99]
Glumac 2017 3 85 2 84 1.0% 1.48 [0.25 , 8.65]
Halonen 2007 1 120 0 121 0.3% 3.02 [0.12 , 73.52]
Halvorsen 2003 1 147 1 147 0.4% 1.00 [0.06 , 15.84]
Kilger 2003a 7 43 6 48 3.1% 1.30 [0.47 , 3.57]
Subtotal (95% CI) 532 537 6.1% 1.33 [0.65 , 2.70]
Total events: 16 12
Heterogeneity: Tau² = 0.00; Chi² = 4.13, df = 7 (P = 0.76); I² = 0%
Test for overall effect: Z = 0.77 (P = 0.44)
3.1.2 High dose

Al-Shawabkeh 2017 2 170 2 170 0.8% 1.00 [0.14 , 7.02]
Celik 2004 1 30 2 30 0.6% 0.50 [0.05 , 5.22]
Chaney 1998 1 30 2 30 0.6% 0.50 [0.05 , 5.22]
Chaney 2001 0 59 1 29 0.3% 0.17 [0.01 , 3.97]
Codd 1977 1 75 0 75 0.3% 3.00 [0.12 , 72.49]
Coetzer 1996 7 165 5 130 2.5% 1.10 [0.36 , 3.40]
Dieleman 2012 31 2235 34 2247 13.4% 0.92 [0.57 , 1.49]
Gomez Polo 2018 1 52 3 52 0.6% 0.33 [0.04 , 3.10]
Kerr 2012 2 51 3 47 1.0% 0.61 [0.11 , 3.52]
Liakopoulos 2007 1 40 0 38 0.3% 2.85 [0.12 , 67.97]
Lomirovotov 2013 2 22 1 22 0.6% 2.00 [0.20 , 20.49]
Rao 1977 2 75 3 75 1.0% 0.67 [0.11 , 3.88]
Rubens 2005 0 34 1 34 0.3% 0.33 [0.01 , 7.91]
Whitlock 2006 1 30 0 30 0.3% 3.00 [0.13 , 70.83]
Whitlock 2015 154 3755 177 3752 70.0% 0.87 [0.70 , 1.07]
Yared 1998 2 106 3 110 1.0% 0.69 [0.12 , 4.06]
Yared 2007 1 37 0 34 0.3% 2.76 [0.12 , 65.62]
Subtotal (95% CI) 6966 6905 93.9% 0.87 [0.73 , 1.05]
Total (95% CI) 7498 7442 100.0% 0.90 [0.75 , 1.07]

Test for subgroup differences: Chi² = 1.23, df = 1 (P = 0.27), I² = 18.7%
Informed decisions.
Analysis 3.2. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 2: Cardiac complications

3.2.1 Low dose

Abbaszadeh 2012 4 92 6 92 0.9% 0.67 [0.19 , 2.28]
Andersen 1989 1 8 0 8 0.1% 3.00 [0.14 , 64.26]
Halonen 2007 1 120 1 121 0.2% 1.01 [0.06 , 15.94]
Halvorsen 2003 3 147 1 147 0.3% 3.00 [0.32 , 28.51]
Mahrose 2019 1 88 3 88 0.3% 0.33 [0.04 , 3.14]
Murphy 2011 2 60 2 49 0.4% 0.82 [0.12 , 5.59]
Subtotal (95% CI) 515 505 2.1% 0.88 [0.39 , 1.95]
Total events: 12 13
3.2.2 High dose

Al-Shawabkeh 2017 2 170 3 170 0.4% 0.67 [0.11 , 3.94]
Amr 2009 2 50 2 50 0.4% 1.00 [0.15 , 6.82]
Celik 2004 1 30 2 30 0.2% 0.50 [0.05 , 5.22]
Chaney 1998 1 30 1 30 0.2% 1.00 [0.07 , 15.26]
Chaney 2001 0 59 1 29 0.1% 0.17 [0.01 , 3.97]
Codd 1977 6 75 5 75 1.0% 1.20 [0.38 , 3.76]
Dieleman 2012 35 2235 39 2247 6.5% 0.90 [0.57 , 1.42]
Mardani 2012 1 43 0 50 0.1% 3.48 [0.15 , 83.21]
McBride 2004 1 18 0 17 0.1% 2.84 [0.12 , 65.34]
Morton 1976 5 22 5 22 1.1% 1.00 [0.34 , 2.97]
Oliver 2004 5 62 1 63 0.3% 5.08 [0.61 , 42.25]
Rao 1977 2 75 5 75 0.5% 0.40 [0.08 , 2.00]
Rubens 2005 0 34 3 34 0.2% 0.14 [0.01 , 2.66]
Taleska Stupica 2020 0 20 1 20 0.1% 0.33 [0.01 , 7.72]
Vukovic 2011 2 29 1 28 0.2% 1.93 [0.19 , 20.12]
Whitlock 2006 1 30 3 30 0.3% 0.33 [0.04 , 3.03]
Whitlock 2015 486 3755 399 3752 85.8% 1.22 [1.07 , 1.38]
Yared 1998 0 106 1 110 0.1% 0.35 [0.01 , 8.40]
Yared 2007 1 37 0 34 0.1% 2.76 [0.12 , 65.62]
Subtotal (95% CI) 6880 6866 97.9% 1.17 [1.04 , 1.32]
Total (95% CI) 7395 7371 100.0% 1.16 [1.04 , 1.31]

Test for subgroup differences: Chi² = 0.49, df = 1 (P = 0.48), I² = 0%
Informed decisions.
Analysis 3.3. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 3: Pulmonary complications

3.3.1 Low dose

Abbaszadeh 2012 2 92 1 92 0.2% 2.00 [0.18 , 21.67]
Bingol 2005 1 20 4 20 0.3% 0.25 [0.03 , 2.05]
Halvorsen 2003 2 147 0 147 0.2% 5.00 [0.24 , 103.26]
Murphy 2011 0 60 1 49 0.1% 0.27 [0.01 , 6.56]
Starobin 2007 6 30 6 30 1.4% 1.00 [0.36 , 2.75]
Weis 2006 2 19 2 17 0.4% 0.89 [0.14 , 5.68]
Subtotal (95% CI) 368 355 2.6% 0.91 [0.44 , 1.89]
Total events: 13 14
3.3.2 High dose

Dieleman 2012 67 2235 97 2247 15.0% 0.69 [0.51 , 0.94]
Kerr 2012 21 51 21 47 6.7% 0.92 [0.58 , 1.46]
Liakopoulos 2007 2 40 1 38 0.3% 1.90 [0.18 , 20.10]
Mardani 2012 2 43 2 50 0.4% 1.16 [0.17 , 7.91]
Morton 1976 3 48 3 48 0.6% 1.00 [0.21 , 4.71]
Oliver 2004 7 62 4 63 1.0% 1.78 [0.55 , 5.77]
Rao 1977 1 75 7 75 0.3% 0.14 [0.02 , 1.13]
Schurr 2001 1 24 2 26 0.3% 0.54 [0.05 , 5.60]
Toft 1997 0 8 1 8 0.1% 0.33 [0.02 , 7.14]
Whitlock 2006 2 30 1 30 0.3% 2.00 [0.19 , 20.90]
Whitlock 2015 343 3755 375 3752 72.2% 0.91 [0.80 , 1.05]
Yared 1998 1 37 2 34 0.3% 0.46 [0.04 , 4.84]
Subtotal (95% CI) 6408 6418 97.4% 0.88 [0.78 , 0.99]
Total (95% CI) 6776 6773 100.0% 0.88 [0.78 , 0.99]

Informed decisions.
Analysis 3.4. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 4: Atrial fibrillation

3.4.1 Low dose

Abbaszadeh 2012 40 92 67 92 9.6% 0.60 [0.46 , 0.78]
Bingol 2005 1 20 3 20 0.4% 0.33 [0.04 , 2.94]
Halonen 2007 44 120 62 121 8.9% 0.72 [0.53 , 0.96]
Halvorsen 2003 1 147 1 147 0.2% 1.00 [0.06 , 15.84]
Mahrose 2019 26 88 42 88 6.7% 0.62 [0.42 , 0.91]
Murphy 2011 11 60 10 49 2.6% 0.90 [0.42 , 1.94]
Starobin 2007 11 30 8 30 2.6% 1.38 [0.64 , 2.93]
Weis 2006 5 19 10 17 2.2% 0.45 [0.19 , 1.05]
Subtotal (95% CI) 576 564 33.2% 0.66 [0.56 , 0.78]
Test for overall effect: Z = 4.92 (P < 0.00001)
3.4.2 High dose

Abd El-Hakeem 2003b 1 10 3 10 0.4% 0.33 [0.04 , 2.69]
Al-Shawabkeh 2017 36 170 65 170 7.6% 0.55 [0.39 , 0.78]
Amr 2009 7 50 8 50 1.8% 0.88 [0.34 , 2.23]
Celik 2004 6 30 7 30 1.7% 0.86 [0.33 , 2.25]
Chaney 1998 8 30 9 30 2.4% 0.89 [0.40 , 1.99]
Dieleman 2012 739 2235 790 2247 14.5% 0.94 [0.87 , 1.02]
Enc 2006 2 20 3 20 0.6% 0.67 [0.12 , 3.57]
Giomarelli 2003 0 10 2 10 0.2% 0.20 [0.01 , 3.70]
Gomez Polo 2018 9 52 14 52 2.7% 0.64 [0.31 , 1.35]
Lomirovotov 2013 5 22 2 22 0.7% 2.50 [0.54 , 11.54]
Mardani 2012 5 43 11 50 1.7% 0.53 [0.20 , 1.40]
Prasongsukarn 2005 9 43 22 43 3.4% 0.41 [0.21 , 0.78]
Rubens 2005 4 34 13 34 1.6% 0.31 [0.11 , 0.85]
Schurr 2001 12 24 17 26 5.1% 0.76 [0.47 , 1.25]
Sobieski 2008 2 13 0 15 0.2% 5.71 [0.30 , 109.22]
Taleska Stupica 2020 4 20 3 20 0.9% 1.33 [0.34 , 5.21]
Vukovic 2011 3 29 11 28 1.2% 0.26 [0.08 , 0.85]
Whitlock 2006 7 28 10 30 2.3% 0.75 [0.33 , 1.70]
Whitlock 2015 821 3755 846 3752 14.4% 0.97 [0.89 , 1.06]
Yared 2007 15 37 10 34 3.4% 1.38 [0.72 , 2.64]
Subtotal (95% CI) 6655 6673 66.8% 0.80 [0.69 , 0.93]
Total (95% CI) 7231 7237 100.0% 0.75 [0.65 , 0.86]

Informed decisions.
Analysis 3.5. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 5: Inotropic support

3.5.1 Low dose

Glumac 2017 37 80 41 81 11.1% 0.91 [0.66 , 1.26]
Halvorsen 2003 2 147 2 147 1.0% 1.00 [0.14 , 7.00]
Mahrose 2019 39 88 40 88 10.9% 0.97 [0.70 , 1.35]
Murphy 2011 13 60 9 49 4.7% 1.18 [0.55 , 2.53]
Yilmaz 1999 1 10 2 10 0.8% 0.50 [0.05 , 4.67]
Subtotal (95% CI) 385 375 28.5% 0.96 [0.77 , 1.19]
Total events: 92 94
3.5.2 High dose

Abd El-Hakeem 2003a 8 23 14 23 5.9% 0.57 [0.30 , 1.09]
Abd El-Hakeem 2003b 3 10 6 10 2.8% 0.50 [0.17 , 1.46]
Cavarocchi 1986 9 31 5 30 3.3% 1.74 [0.66 , 4.60]
Celik 2004 1 30 2 30 0.7% 0.50 [0.05 , 5.22]
Chaney 1998 24 30 15 30 9.6% 1.60 [1.07 , 2.39]
Chaney 2001 43 59 20 29 11.7% 1.06 [0.79 , 1.41]
Codd 1977 11 75 11 75 4.7% 1.00 [0.46 , 2.16]
El Azab 2002 2 9 3 8 1.6% 0.59 [0.13 , 2.70]
Giomarelli 2003 1 10 1 10 0.6% 1.00 [0.07 , 13.87]
Loef 2004 7 10 2 10 2.0% 3.50 [0.95 , 12.90]
Lomirovotov 2013 4 22 1 22 0.8% 4.00 [0.48 , 33.00]
Mardani 2012 2 43 3 50 1.2% 0.78 [0.14 , 4.43]
McBride 2004 9 18 6 17 4.5% 1.42 [0.64 , 3.13]
Schurr 2001 3 24 6 26 2.1% 0.54 [0.15 , 1.93]
Von Spiegel 2001 6 10 9 10 7.2% 0.67 [0.39 , 1.15]
Vukovic 2011 5 29 18 29 4.1% 0.28 [0.12 , 0.65]
Whitlock 2006 0 30 8 30 0.5% 0.06 [0.00 , 0.98]
Yared 1998 24 106 29 110 8.3% 0.86 [0.54 , 1.37]
Subtotal (95% CI) 569 549 71.5% 0.89 [0.67 , 1.19]
Total (95% CI) 954 924 100.0% 0.93 [0.76 , 1.13]

Informed decisions.
Analysis 3.6. Comparison 3: Subgroup analyses: corticosteroid

dosage, Outcome 6: Mechanical ventilation (minutes)
Study or Subgroup Mean [Minutes] SD [Minutes] Total Mean [Minutes] SD [Minutes] Total Weight IV, Random, 95% CI [Minutes] IV, Random, 95% CI [Minutes]
3.6.1 Low dose

Bingol 2005 404 102 20 894 222 20 4.3% -490.00 [-597.07 , -382.93]
Bourbon 2004 696 276 12 762 330 12 2.2% -66.00 [-309.41 , 177.41]
Glumac 2017 1164 750 80 1278 738 81 2.4% -114.00 [-343.87 , 115.87]
Halvorsen 2003 148 69 147 149 67 147 5.5% -1.00 [-16.55 , 14.55]
Hauer 2012 1026 720 56 1260 1020 55 1.5% -234.00 [-562.98 , 94.98]
Yilmaz 1999 804 663 10 702 213.3 10 1.0% 102.00 [-329.67 , 533.67]
Subtotal (95% CI) 325 325 16.8% -147.32 [-386.74 , 92.11]
3.6.2 High dose

Abd El-Hakeem 2003a 407.13 24.1 23 443.9 45.1 23 5.5% -36.77 [-57.67 , -15.87]
Abd El-Hakeem 2003b 480 95 10 516 113 10 4.6% -36.00 [-127.50 , 55.50]
Celik 2004 642 54 30 514 36 30 5.5% 128.00 [104.78 , 151.22]
Chaney 1998 796 294 30 604 615 30 2.2% 192.00 [-51.92 , 435.92]
Demir 2009 572 298 15 496 263 15 2.7% 76.00 [-125.14 , 277.14]
Demir 2015 520.2 180 20 481.2 228.6 20 3.9% 39.00 [-88.52 , 166.52]
El Azab 2002 660 120 9 780 180 9 3.7% -120.00 [-261.34 , 21.34]
Engelman 1995 786 135 10 630 60 10 4.6% 156.00 [64.44 , 247.56]
Fillinger 2002 594 85.2 15 936 510 15 2.0% -342.00 [-603.67 , -80.33]
Giomarelli 2003 750 162 10 708 180 10 3.5% 42.00 [-108.09 , 192.09]
Hao 2019 1257.6 653.4 18 1073.4 526.8 18 1.1% 184.20 [-203.54 , 571.94]
Harig 1999 648 234 10 780 354 10 2.0% -132.00 [-395.01 , 131.01]
Kilickan 2008 375 180 30 348 219 30 4.4% 27.00 [-74.44 , 128.44]
Liakopoulos 2007 840 528 40 684 414 38 2.6% 156.00 [-54.00 , 366.00]
Loef 2004 1131.6 214 10 900.6 188 10 3.1% 231.00 [54.45 , 407.55]
Mardani 2012 550.8 144 43 633.6 231.6 50 4.8% -82.80 [-160.09 , -5.51]
Mayumi 1997 2044 921 12 1872 662 12 0.5% 172.00 [-469.74 , 813.74]
Oliver 2004 519.3 282.8 62 918 404.9 63 4.0% -398.70 [-520.98 , -276.42]
Sano 2006 1320 720 31 1224 1164 29 0.8% 96.00 [-397.67 , 589.67]
Schurr 2001 510 204 24 480 174 26 4.3% 30.00 [-75.52 , 135.52]
Sobieski 2008 185 164 14 541 246 14 3.4% -356.00 [-510.87 , -201.13]
Taleska Stupica 2020 570 660 20 870 705 20 1.0% -300.00 [-723.24 , 123.24]
Tassani 1999 486 42 26 552 48 26 5.5% -66.00 [-90.52 , -41.48]
Vukovic 2011 714 216 29 1026 282 28 3.9% -312.00 [-442.73 , -181.27]
Wan 1999 840 420 10 1080 600 10 0.9% -240.00 [-693.93 , 213.93]
Yared 1998 696 714 106 786 828 110 2.7% -90.00 [-295.95 , 115.95]
Subtotal (95% CI) 657 666 83.2% -39.33 [-94.96 , 16.30]
Total (95% CI) 982 991 100.0% -59.95 [-106.51 , -13.39]

Test for subgroup differences: Chi² = 0.74, df = 1 (P = 0.39), I² = 0% Favours corticosteroids Favours no corticosteroids
Informed decisions.
Analysis 3.7. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 7: Length of ICU stay (hours)
Study or Subgroup Mean [Hours] SD [Hours] Total Mean [Hours] SD [Hours] Total Weight IV, Random, 95% CI [Hours] IV, Random, 95% CI [Hours]
3.7.1 Low dose

Bingol 2005 33.6 16.3 20 105 78 20 0.5% -71.40 [-106.32 , -36.48]
Glumac 2017 51.5 35 80 60.8 33.4 81 3.2% -9.30 [-19.87 , 1.27]
Hauer 2012 38.3 31.7 56 68.4 49.9 55 1.9% -30.10 [-45.68 , -14.52]
Yilmaz 1999 33.71 17.3 10 34.2 7.8 10 2.8% -0.49 [-12.25 , 11.27]
Subtotal (95% CI) 166 166 8.4% -22.18 [-41.90 , -2.45]
3.7.2 High dose

Abd El-Hakeem 2003a 52.66 1.81 23 66.26 23.09 23 3.6% -13.60 [-23.07 , -4.13]
Abd El-Hakeem 2003b 47.3 5.7 10 67.2 5.7 10 5.8% -19.90 [-24.90 , -14.90]
Amr 2009 64.8 19.8 50 67.2 16.8 50 4.6% -2.40 [-9.60 , 4.80]
Celik 2004 36.2 4.1 30 42.1 2.7 30 7.2% -5.90 [-7.66 , -4.14]
Demir 2009 55.9 14.64 15 83 75.6 15 0.4% -27.10 [-66.07 , 11.87]
Demir 2015 52.8 9.84 20 58.8 16.32 20 4.1% -6.00 [-14.35 , 2.35]
El Azab 2002 24 8 9 52 32 9 1.1% -28.00 [-49.55 , -6.45]
Engelman 1995 28.8 2.4 10 50.4 7.2 10 5.9% -21.60 [-26.30 , -16.90]
Fillinger 2002 27 11.6 15 36 28.7 15 1.9% -9.00 [-24.67 , 6.67]
Giomarelli 2003 32.1 3.7 10 35.2 4.4 10 6.5% -3.10 [-6.66 , 0.46]
Hao 2019 28 17.06 18 26.61 16.43 18 3.1% 1.39 [-9.55 , 12.33]
Harig 1999 18 0.5 10 19.9 0.9 10 7.5% -1.90 [-2.54 , -1.26]
Jansen 1991 91.2 27 12 72 27 13 1.2% 19.20 [-1.98 , 40.38]
Liakopoulos 2007 50.4 62.4 40 50 43.2 38 1.0% 0.40 [-23.32 , 24.12]
Loef 2004 29 10 10 26 7 10 4.4% 3.00 [-4.57 , 10.57]
Mardani 2012 68.64 31.2 43 88.32 31.92 50 2.5% -19.68 [-32.53 , -6.83]
Oliver 2004 25.2 14 62 23.9 8.7 63 6.2% 1.30 [-2.79 , 5.39]
Rubens 2005 36 29 34 36 24 34 2.6% 0.00 [-12.65 , 12.65]
Sano 2006 43.2 24 31 34 21.6 29 2.9% 9.20 [-2.34 , 20.74]
Schurr 2001 24 19 24 24 22 26 2.9% 0.00 [-11.37 , 11.37]
Sobieski 2008 23.7 2.6 14 24.6 12.3 14 4.9% -0.90 [-7.49 , 5.69]
Tassani 1999 27.2 2.1 26 28 2.2 26 7.4% -0.80 [-1.97 , 0.37]
Volk 2001 36 29 12 75 158 13 0.1% -39.00 [-126.44 , 48.44]
Volk 2003 36 7.2 12 74 43.2 12 0.9% -38.00 [-62.78 , -13.22]
Wan 1999 29 9 10 32 23 10 2.0% -3.00 [-18.31 , 12.31]
Yared 1998 36.8 28 106 47.9 113.6 110 1.1% -11.10 [-32.99 , 10.79]
Subtotal (95% CI) 656 668 91.6% -5.46 [-7.95 , -2.98]
Total (95% CI) 822 834 100.0% -6.25 [-8.74 , -3.76]

Test for subgroup differences: Chi² = 2.72, df = 1 (P = 0.10), I² = 63.2% Favours corticosteroids Favours no corticosteroids
Informed decisions.
Analysis 3.8. Comparison 3: Subgroup analyses: corticosteroid dosage, Outcome 8: Length of hospital stay (days)
Study or Subgroup Mean [Days] SD [Days] Total Mean [Days] SD [Days] Total Weight IV, Random, 95% CI [Days] IV, Random, 95% CI [Days]
3.8.1 Low dose

Bingol 2005 8.3 1.17 20 12.95 2.95 20 4.1% -4.65 [-6.04 , -3.26]
Glumac 2017 11.2 4 80 11.3 3 81 4.8% -0.10 [-1.19 , 0.99]
Mahrose 2019 6.5 1.2 88 7.2 1.6 88 6.2% -0.70 [-1.12 , -0.28]
Yilmaz 1999 6.6 0.9 10 9.2 8.7 10 0.7% -2.60 [-8.02 , 2.82]
Subtotal (95% CI) 198 199 15.7% -1.82 [-3.80 , 0.16]
3.8.2 High dose

Al-Shawabkeh 2017 6.02 2.25 170 5.95 1.95 170 6.1% 0.07 [-0.38 , 0.52]
Amr 2009 15 1 50 14 2 50 5.8% 1.00 [0.38 , 1.62]
Celik 2004 10.2 2.2 30 12.4 2.3 30 4.7% -2.20 [-3.34 , -1.06]
Chaney 1998 6.9 4.1 29 8.3 5.1 28 2.4% -1.40 [-3.81 , 1.01]
Demir 2009 8.53 2.19 15 12.6 6.76 15 1.3% -4.07 [-7.67 , -0.47]
Demir 2015 8.25 1.83 20 9.35 2.39 20 4.3% -1.10 [-2.42 , 0.22]
Enc 2006 5.2 0.6 20 6.3 0.7 20 6.2% -1.10 [-1.50 , -0.70]
Engelman 1995 6.5 1.1 10 5.2 0.4 10 5.6% 1.30 [0.57 , 2.03]
Fillinger 2002 4.6 1.5 15 6.1 1.7 15 4.7% -1.50 [-2.65 , -0.35]
Giomarelli 2003 6 1 10 6 1 10 5.3% 0.00 [-0.88 , 0.88]
Hao 2019 21.63 7.68 18 20.44 8.07 18 0.7% 1.19 [-3.96 , 6.34]
Kilickan 2008 7.75 1.69 30 8 1.26 30 5.6% -0.25 [-1.00 , 0.50]
Liakopoulos 2007 13.1 5.2 40 12.3 2.3 38 3.3% 0.80 [-0.97 , 2.57]
Mardani 2012 12.93 1.03 43 13.64 1.75 50 5.9% -0.71 [-1.28 , -0.14]
McBride 2004 8.06 2.9 18 7.76 3.5 17 2.7% 0.30 [-1.84 , 2.44]
Rubens 2005 5.4 1.9 17 6.5 2.8 17 3.6% -1.10 [-2.71 , 0.51]
Schurr 2001 11 2 24 11 1.6 26 5.0% 0.00 [-1.01 , 1.01]
Sobieski 2008 4.8 1.5 13 5 1.3 15 4.9% -0.20 [-1.25 , 0.85]
Tassani 1999 13.3 4.6 26 10.5 6.1 26 1.8% 2.80 [-0.14 , 5.74]
Volk 2001 14.6 16.1 12 8.7 6.8 13 0.2% 5.90 [-3.93 , 15.73]
Yared 1998 7 5.2 106 7.3 5.3 110 4.1% -0.30 [-1.70 , 1.10]
Subtotal (95% CI) 716 728 84.3% -0.30 [-0.77 , 0.18]
Total (95% CI) 914 927 100.0% -0.51 [-0.97 , -0.04]

Comparison 4. Subgroup analyses: surgery type
group title pants
4.1.1 CABG 13 1323 Risk Ratio (M-H, Random, 95% CI) 0.91 [0.50, 1.68]
4.1.2 Mixed 12 13617 Risk Ratio (M-H, Random, 95% CI) 0.90 [0.74, 1.08]
4.2 Cardiac compli- 25 14766 Risk Ratio (M-H, Random, 95% CI) 1.16 [1.04, 1.31]
cations
4.3 Pulmonary com- 18 13549 Risk Ratio (M-H, Random, 95% CI) 0.88 [0.78, 0.99]
plications
Informed decisions.
group title pants
4.4.2 Valve 1 20 Risk Ratio (M-H, Random, 95% CI) 0.33 [0.04, 2.69]
4.5.2 Valve 2 66 Risk Ratio (M-H, Random, 95% CI) 0.55 [0.32, 0.96]
4.6 Mechanical venti- 32 1993 Mean Difference (IV, Random, 95% CI) -58.06 [-104.54, -11.58]
lation (minutes)
4.6.1 CABG 21 1114 Mean Difference (IV, Random, 95% CI) -40.55 [-98.61, 17.50]
4.6.2 Valve 3 90 Mean Difference (IV, Random, 95% CI) -36.52 [-56.88, -16.16]
4.6.3 Mixed 8 789 Mean Difference (IV, Random, 95% CI) -149.22 [-305.08, 6.64]
4.7 Length of ICU stay 30 1654 Mean Difference (IV, Random, 95% CI) -6.25 [-8.74, -3.77]
(hours)
4.7.1 CABG 21 859 Mean Difference (IV, Random, 95% CI) -5.41 [-8.05, -2.77]
4.7.2 Valve 2 66 Mean Difference (IV, Random, 95% CI) -18.09 [-23.68, -12.49]
4.7.3 Mixed 7 729 Mean Difference (IV, Random, 95% CI) -4.45 [-12.30, 3.39]
4.8 Length of hospi- 25 1841 Mean Difference (IV, Random, 95% CI) -0.51 [-0.97, -0.04]
tal stay (days)
4.8.1 CABG 21 1088 Mean Difference (IV, Random, 95% CI) -0.60 [-1.15, -0.06]
4.8.2 Mixed 4 753 Mean Difference (IV, Random, 95% CI) 0.02 [-0.37, 0.42]
Informed decisions.
Analysis 4.1. Comparison 4: Subgroup analyses: surgery type, Outcome 1: Mortality

4.1.1 CABG
Abbaszadeh 2012 0 92 1 92 0.3% 0.33 [0.01 , 8.08]
Andersen 1989 1 8 0 8 0.3% 3.00 [0.14 , 64.26]
Bingol 2005 0 20 2 20 0.4% 0.20 [0.01 , 3.92]
Celik 2004 1 30 2 30 0.6% 0.50 [0.05 , 5.22]
Chaney 1998 1 30 2 30 0.6% 0.50 [0.05 , 5.22]
Chaney 2001 0 59 1 29 0.3% 0.17 [0.01 , 3.97]
Codd 1977 1 75 0 75 0.3% 3.00 [0.12 , 72.49]
Halvorsen 2003 1 147 1 147 0.4% 1.00 [0.06 , 15.84]
Kilger 2003a 7 43 6 48 3.1% 1.30 [0.47 , 3.57]
Liakopoulos 2007 1 40 0 38 0.3% 2.85 [0.12 , 67.97]
Lomirovotov 2013 2 22 1 22 0.6% 2.00 [0.20 , 20.49]
Rao 1977 2 75 3 75 1.0% 0.67 [0.11 , 3.88]
Rubens 2005 0 34 1 34 0.3% 0.33 [0.01 , 7.91]
Subtotal (95% CI) 675 648 8.4% 0.91 [0.50 , 1.68]
Total events: 17 20
4.1.2 Mixed
Al-Shawabkeh 2017 2 170 2 170 0.8% 1.00 [0.14 , 7.02]
Boscoe 1983 3 17 0 17 0.4% 7.00 [0.39 , 125.99]
Coetzer 1996 7 165 5 130 2.5% 1.10 [0.36 , 3.40]
Dieleman 2012 31 2235 34 2247 13.4% 0.92 [0.57 , 1.49]
Glumac 2017 3 85 2 84 1.0% 1.48 [0.25 , 8.65]
Gomez Polo 2018 1 52 3 52 0.6% 0.33 [0.04 , 3.10]
Halonen 2007 1 120 0 121 0.3% 3.02 [0.12 , 73.52]
Kerr 2012 2 51 3 47 1.0% 0.61 [0.11 , 3.52]
Whitlock 2006 1 30 0 30 0.3% 3.00 [0.13 , 70.83]
Whitlock 2015 154 3755 177 3752 70.0% 0.87 [0.70 , 1.07]
Yared 1998 2 106 3 110 1.0% 0.69 [0.12 , 4.06]
Yared 2007 1 37 0 34 0.3% 2.76 [0.12 , 65.62]
Subtotal (95% CI) 6823 6794 91.6% 0.90 [0.74 , 1.08]
Total (95% CI) 7498 7442 100.0% 0.90 [0.75 , 1.07]

Informed decisions.
Analysis 4.2. Comparison 4: Subgroup analyses: surgery type, Outcome 2: Cardiac complications

4.2.1 CABG
Abbaszadeh 2012 4 92 6 92 0.9% 0.67 [0.19 , 2.28]
Amr 2009 2 50 2 50 0.4% 1.00 [0.15 , 6.82]
Andersen 1989 1 8 0 8 0.1% 3.00 [0.14 , 64.26]
Celik 2004 1 30 2 30 0.2% 0.50 [0.05 , 5.22]
Chaney 1998 1 30 1 30 0.2% 1.00 [0.07 , 15.26]
Chaney 2001 0 59 1 29 0.1% 0.17 [0.01 , 3.97]
Codd 1977 6 75 5 75 1.0% 1.20 [0.38 , 3.76]
Halvorsen 2003 3 147 1 147 0.3% 3.00 [0.32 , 28.51]
Mahrose 2019 1 88 3 88 0.3% 0.33 [0.04 , 3.14]
Mardani 2012 1 43 0 50 0.1% 3.48 [0.15 , 83.21]
McBride 2004 1 18 0 17 0.1% 2.84 [0.12 , 65.34]
Morton 1976 5 22 5 22 1.1% 1.00 [0.34 , 2.97]
Rao 1977 2 75 5 75 0.5% 0.40 [0.08 , 2.00]
Rubens 2005 0 34 3 34 0.2% 0.14 [0.01 , 2.66]
Vukovic 2011 2 29 1 28 0.2% 1.93 [0.19 , 20.12]
Subtotal (95% CI) 800 775 5.8% 0.88 [0.55 , 1.42]
Total events: 30 35
4.2.2 Mixed
Al-Shawabkeh 2017 2 170 3 170 0.4% 0.67 [0.11 , 3.94]
Dieleman 2012 35 2235 39 2247 6.5% 0.90 [0.57 , 1.42]
Halonen 2007 1 120 1 121 0.2% 1.01 [0.06 , 15.94]
Murphy 2011 2 60 2 49 0.4% 0.82 [0.12 , 5.59]
Oliver 2004 5 62 1 63 0.3% 5.08 [0.61 , 42.25]
Taleska Stupica 2020 0 20 1 20 0.1% 0.33 [0.01 , 7.72]
Whitlock 2006 1 30 3 30 0.3% 0.33 [0.04 , 3.03]
Whitlock 2015 486 3755 399 3752 85.8% 1.22 [1.07 , 1.38]
Yared 1998 0 106 1 110 0.1% 0.35 [0.01 , 8.40]
Yared 2007 1 37 0 34 0.1% 2.76 [0.12 , 65.62]
Subtotal (95% CI) 6595 6596 94.2% 1.18 [1.05 , 1.33]
Total (95% CI) 7395 7371 100.0% 1.16 [1.04 , 1.31]

Informed decisions.
Analysis 4.3. Comparison 4: Subgroup analyses: surgery type, Outcome 3: Pulmonary complications

4.3.1 CABG
Abbaszadeh 2012 2 92 1 92 0.2% 2.00 [0.18 , 21.67]
Bingol 2005 1 20 4 20 0.3% 0.25 [0.03 , 2.05]
Halvorsen 2003 2 147 0 147 0.2% 5.00 [0.24 , 103.26]
Liakopoulos 2007 2 40 1 38 0.3% 1.90 [0.18 , 20.10]
Mardani 2012 2 43 2 50 0.4% 1.16 [0.17 , 7.91]
Morton 1976 3 48 3 48 0.6% 1.00 [0.21 , 4.71]
Rao 1977 1 75 7 75 0.3% 0.14 [0.02 , 1.13]
Schurr 2001 1 24 2 26 0.3% 0.54 [0.05 , 5.60]
Subtotal (95% CI) 489 496 2.5% 0.79 [0.37 , 1.66]
Total events: 14 20
4.3.2 Mixed
Dieleman 2012 67 2235 97 2247 15.0% 0.69 [0.51 , 0.94]
Kerr 2012 21 51 21 47 6.7% 0.92 [0.58 , 1.46]
Murphy 2011 0 60 1 49 0.1% 0.27 [0.01 , 6.56]
Oliver 2004 7 62 4 63 1.0% 1.78 [0.55 , 5.77]
Starobin 2007 6 30 6 30 1.4% 1.00 [0.36 , 2.75]
Toft 1997 0 8 1 8 0.1% 0.33 [0.02 , 7.14]
Weis 2006 2 19 2 17 0.4% 0.89 [0.14 , 5.68]
Whitlock 2006 2 30 1 30 0.3% 2.00 [0.19 , 20.90]
Whitlock 2015 343 3755 375 3752 72.2% 0.91 [0.80 , 1.05]
Yared 1998 1 37 2 34 0.3% 0.46 [0.04 , 4.84]
Subtotal (95% CI) 6287 6277 97.5% 0.88 [0.78 , 0.99]
Total (95% CI) 6776 6773 100.0% 0.88 [0.78 , 0.99]

Informed decisions.
Analysis 4.4. Comparison 4: Subgroup analyses: surgery type, Outcome 4: Atrial fibrillation

4.4.1 CABG
Abbaszadeh 2012 40 92 67 92 9.6% 0.60 [0.46 , 0.78]
Amr 2009 7 50 8 50 1.8% 0.88 [0.34 , 2.23]
Bingol 2005 1 20 3 20 0.4% 0.33 [0.04 , 2.94]
Celik 2004 6 30 7 30 1.7% 0.86 [0.33 , 2.25]
Chaney 1998 8 30 9 30 2.3% 0.89 [0.40 , 1.99]
Enc 2006 2 20 3 20 0.6% 0.67 [0.12 , 3.57]
Giomarelli 2003 0 10 2 10 0.2% 0.20 [0.01 , 3.70]
Halvorsen 2003 1 147 1 147 0.2% 1.00 [0.06 , 15.84]
Lomirovotov 2013 5 22 2 22 0.7% 2.50 [0.54 , 11.54]
Mahrose 2019 26 88 42 88 6.7% 0.62 [0.42 , 0.91]
Mardani 2012 5 43 11 50 1.7% 0.53 [0.20 , 1.40]
Prasongsukarn 2005 9 43 22 43 3.3% 0.41 [0.21 , 0.78]
Rubens 2005 4 34 13 34 1.5% 0.31 [0.11 , 0.85]
Schurr 2001 12 24 17 26 5.0% 0.76 [0.47 , 1.25]
Sobieski 2008 2 13 4 15 0.7% 0.58 [0.13 , 2.65]
Vukovic 2011 3 29 11 28 1.2% 0.26 [0.08 , 0.85]
Subtotal (95% CI) 695 705 37.6% 0.61 [0.52 , 0.72]
4.4.2 Valve
Abd El-Hakeem 2003b 1 10 3 10 0.4% 0.33 [0.04 , 2.69]
Subtotal (95% CI) 10 10 0.4% 0.33 [0.04 , 2.69]
Total events: 1 3
Heterogeneity: Not applicable
4.4.3 Mixed
Al-Shawabkeh 2017 36 170 65 170 7.5% 0.55 [0.39 , 0.78]
Dieleman 2012 739 2235 790 2247 14.7% 0.94 [0.87 , 1.02]
Gomez Polo 2018 9 52 14 52 2.6% 0.64 [0.31 , 1.35]
Halonen 2007 44 120 62 121 8.9% 0.72 [0.53 , 0.96]
Murphy 2011 11 60 10 49 2.5% 0.90 [0.42 , 1.94]
Starobin 2007 11 30 8 30 2.6% 1.38 [0.64 , 2.93]
Taleska Stupica 2020 4 20 3 20 0.9% 1.33 [0.34 , 5.21]
Weis 2009 5 19 10 17 2.1% 0.45 [0.19 , 1.05]
Whitlock 2006 7 28 10 30 2.3% 0.75 [0.33 , 1.70]
Whitlock 2015 821 3755 846 3752 14.6% 0.97 [0.89 , 1.06]
Yared 2007 15 37 10 34 3.3% 1.38 [0.72 , 2.64]
Subtotal (95% CI) 6526 6522 62.0% 0.86 [0.76 , 0.98]
Total (95% CI) 7231 7237 100.0% 0.75 [0.65 , 0.85]

Informed decisions.
Analysis 4.5. Comparison 4: Subgroup analyses: surgery type, Outcome 5: Inotropic support

4.5.1 CABG
Celik 2004 1 30 2 30 0.7% 0.50 [0.05 , 5.22]
Chaney 1998 24 30 15 30 9.6% 1.60 [1.07 , 2.39]
Chaney 2001 43 59 20 29 11.7% 1.06 [0.79 , 1.41]
Codd 1977 11 75 11 75 4.7% 1.00 [0.46 , 2.16]
El Azab 2002 2 9 3 8 1.6% 0.59 [0.13 , 2.70]
Giomarelli 2003 1 10 1 10 0.6% 1.00 [0.07 , 13.87]
Halvorsen 2003 2 147 2 147 1.0% 1.00 [0.14 , 7.00]
Loef 2004 7 10 2 10 2.0% 3.50 [0.95 , 12.90]
Lomirovotov 2013 4 22 1 22 0.8% 4.00 [0.48 , 33.00]
Mahrose 2019 39 88 40 88 10.9% 0.97 [0.70 , 1.35]
Mardani 2012 2 43 3 50 1.2% 0.78 [0.14 , 4.43]
McBride 2004 9 18 6 17 4.5% 1.42 [0.64 , 3.13]
Schurr 2001 3 24 6 26 2.1% 0.54 [0.15 , 1.93]
Von Spiegel 2001 6 10 9 10 7.2% 0.67 [0.39 , 1.15]
Vukovic 2011 5 29 18 29 4.1% 0.28 [0.12 , 0.65]
Yilmaz 1999 1 10 2 10 0.8% 0.50 [0.05 , 4.67]
Subtotal (95% CI) 614 591 63.3% 0.97 [0.75 , 1.27]
4.5.2 Valve
Abd El-Hakeem 2003a 8 23 14 23 5.9% 0.57 [0.30 , 1.09]
Abd El-Hakeem 2003b 3 10 6 10 2.8% 0.50 [0.17 , 1.46]
Subtotal (95% CI) 33 33 8.7% 0.55 [0.32 , 0.96]
Total events: 11 20
4.5.3 Mixed
Cavarocchi 1986 9 31 5 30 3.3% 1.74 [0.66 , 4.60]
Glumac 2017 37 80 41 81 11.1% 0.91 [0.66 , 1.26]
Murphy 2011 13 60 9 49 4.7% 1.18 [0.55 , 2.53]
Whitlock 2006 0 30 8 30 0.5% 0.06 [0.00 , 0.98]
Yared 1998 24 106 29 110 8.3% 0.86 [0.54 , 1.37]
Subtotal (95% CI) 307 300 28.0% 0.96 [0.68 , 1.37]
Total events: 83 92
Total (95% CI) 954 924 100.0% 0.93 [0.76 , 1.13]

Informed decisions.
Analysis 4.6. Comparison 4: Subgroup analyses: surgery type, Outcome 6: Mechanical ventilation (minutes)
4.6.1 CABG
Bingol 2005 404 102 20 894 222 20 4.3% -490.00 [-597.07 , -382.93]
Bourbon 2004 696 276 12 762 330 12 2.2% -66.00 [-309.41 , 177.41]
Celik 2004 642 54 30 514 36 30 5.5% 128.00 [104.78 , 151.22]
Chaney 1998 796 294 30 604 615 30 2.2% 192.00 [-51.92 , 435.92]
Demir 2009 572 298 15 496 263 15 2.7% 76.00 [-125.14 , 277.14]
Demir 2015 520.2 180 20 481.2 228.6 20 3.9% 39.00 [-88.52 , 166.52]
El Azab 2002 660 120 9 780 180 9 3.7% -120.00 [-261.34 , 21.34]
Engelman 1995 786 135 10 630 60 10 4.6% 156.00 [64.44 , 247.56]
Fillinger 2002 594 85.2 15 936 510 15 2.0% -342.00 [-603.67 , -80.33]
Giomarelli 2003 750 162 10 708 180 10 3.5% 42.00 [-108.09 , 192.09]
Halvorsen 2003 148 69 147 149 67 147 5.5% -1.00 [-16.55 , 14.55]
Harig 1999 648 234 10 780 354 10 2.0% -132.00 [-395.01 , 131.01]
Kilickan 2008 375 180 30 348 219 30 4.4% 27.00 [-74.44 , 128.44]
Liakopoulos 2007 840 528 40 684 414 38 2.6% 156.00 [-54.00 , 366.00]
Loef 2004 1131.6 214 10 900.6 188 10 3.1% 231.00 [54.45 , 407.55]
Mardani 2012 550.8 144 43 633.6 231.6 50 4.8% -82.80 [-160.09 , -5.51]
Schurr 2001 510 204 24 480 174 26 4.3% 30.00 [-75.52 , 135.52]
Sobieski 2008 185 164 14 541 246 14 3.4% -356.00 [-510.87 , -201.13]
Tassani 1999 486 42 26 552 48 26 5.5% -66.00 [-90.52 , -41.48]
Vukovic 2011 714 216 29 1026 282 28 3.9% -312.00 [-442.73 , -181.27]
Yilmaz 1999 804 663 10 702 213.3 10 1.0% 102.00 [-329.67 , 533.67]
Subtotal (95% CI) 554 560 75.1% -40.55 [-98.61 , 17.50]
4.6.2 Valve
Abd El-Hakeem 2003a 407.13 24.1 23 443.9 45.1 23 5.5% -36.77 [-57.67 , -15.87]
Abd El-Hakeem 2003b 480 95 10 516 113 10 4.6% -36.00 [-127.50 , 55.50]
Mayumi 1997 2044 921 12 1872 662 12 0.5% 172.00 [-469.74 , 813.74]
Subtotal (95% CI) 45 45 10.5% -36.52 [-56.88 , -16.16]
4.6.3 Mixed
Glumac 2017 1164 750 80 1278 738 81 2.4% -114.00 [-343.87 , 115.87]
Hao 2019 1257.6 653.4 18 1073.4 526.8 18 1.1% 184.20 [-203.54 , 571.94]
Hauer 2012 1026 720 56 1260 1020 55 1.5% -234.00 [-562.98 , 94.98]
Oliver 2004 519.3 282.8 62 918 404.9 63 4.0% -398.70 [-520.98 , -276.42]
Sano 2006 1320 720 31 1224 1164 29 0.8% 96.00 [-397.67 , 589.67]
Taleska Stupica 2020 570 660 20 870 705 20 1.0% -300.00 [-723.24 , 123.24]
Wan 1999 840 660 20 870 705 20 1.0% -30.00 [-453.24 , 393.24]
Yared 1998 696 714 106 786 828 110 2.7% -90.00 [-295.95 , 115.95]
Subtotal (95% CI) 393 396 14.4% -149.22 [-305.08 , 6.64]
Total (95% CI) 992 1001 100.0% -58.06 [-104.54 , -11.58]

Informed decisions.
Analysis 4.7. Comparison 4: Subgroup analyses: surgery type, Outcome 7: Length of ICU stay (hours)
4.7.1 CABG
Amr 2009 64.8 19.2 50 67.2 16.8 50 4.7% -2.40 [-9.47 , 4.67]
Bingol 2005 33.6 16.3 20 105 78 20 0.5% -71.40 [-106.32 , -36.48]
Celik 2004 36.2 4.1 30 42.1 2.7 30 7.2% -5.90 [-7.66 , -4.14]
Demir 2009 55.9 14.64 15 83 75.6 15 0.4% -27.10 [-66.07 , 11.87]
Demir 2015 52.8 9.87 20 58.8 16.32 20 4.1% -6.00 [-14.36 , 2.36]
El Azab 2002 24 8 9 52 32 9 1.1% -28.00 [-49.55 , -6.45]
Engelman 1995 28.8 2.4 10 50.4 7.2 10 5.9% -21.60 [-26.30 , -16.90]
Fillinger 2002 27 11.6 15 36 28.7 15 1.9% -9.00 [-24.67 , 6.67]
Giomarelli 2003 32.1 3.7 10 35.2 4.4 10 6.5% -3.10 [-6.66 , 0.46]
Harig 1999 18 0.5 10 19.9 0.9 10 7.5% -1.90 [-2.54 , -1.26]
Jansen 1991 91.2 27 12 72 27 13 1.2% 19.20 [-1.98 , 40.38]
Liakopoulos 2007 50.4 62.4 40 50 43.2 38 1.0% 0.40 [-23.32 , 24.12]
Loef 2004 29 10 10 26 7 10 4.4% 3.00 [-4.57 , 10.57]
Mardani 2012 68.64 31.2 43 88.32 31.92 50 2.5% -19.68 [-32.53 , -6.83]
Rubens 2005 36 29 34 36 24 34 2.6% 0.00 [-12.65 , 12.65]
Schurr 2001 24 19 24 24 22 24 2.8% 0.00 [-11.63 , 11.63]
Sobieski 2008 23.7 2.6 14 24.6 12.3 14 4.9% -0.90 [-7.49 , 5.69]
Tassani 1999 27.2 2.1 26 28 2.2 26 7.4% -0.80 [-1.97 , 0.37]
Volk 2001 36 29 12 75 158 13 0.1% -39.00 [-126.44 , 48.44]
Volk 2003 36 7.2 12 74 43.2 12 0.9% -38.00 [-62.78 , -13.22]
Yilmaz 1999 33.71 17.3 10 34.2 7.8 10 2.8% -0.49 [-12.25 , 11.27]
Subtotal (95% CI) 426 433 70.3% -5.41 [-8.05 , -2.77]
4.7.2 Valve
Abd El-Hakeem 2003a 52.66 1.81 23 66.26 23.09 23 3.6% -13.60 [-23.07 , -4.13]
Abd El-Hakeem 2003b 47.3 5.7 10 67.2 5.7 10 5.8% -19.90 [-24.90 , -14.90]
Subtotal (95% CI) 33 33 9.4% -18.09 [-23.68 , -12.49]
4.7.3 Mixed
Glumac 2017 51.5 35 80 60.8 33.4 81 3.2% -9.30 [-19.87 , 1.27]
Hao 2019 28 17.06 18 26.61 16.43 18 3.1% 1.39 [-9.55 , 12.33]
Hauer 2012 38.3 31.7 56 68.4 49.9 55 1.9% -30.10 [-45.68 , -14.52]
Oliver 2004 25.2 14 62 23.9 8.7 63 6.2% 1.30 [-2.79 , 5.39]
Sano 2006 43.2 24 31 34 21.6 29 2.9% 9.20 [-2.34 , 20.74]
Wan 1999 29 9 10 32 23 10 2.0% -3.00 [-18.31 , 12.31]
Yared 1998 36.8 28 106 47.9 113.6 110 1.1% -11.10 [-32.99 , 10.79]
Subtotal (95% CI) 363 366 20.3% -4.45 [-12.30 , 3.39]
Total (95% CI) 822 832 100.0% -6.25 [-8.74 , -3.77]

Informed decisions.
Analysis 4.8. Comparison 4: Subgroup analyses: surgery type, Outcome 8: Length of hospital stay (days)
4.8.1 CABG
Amr 2009 15 1 50 14 2 50 5.8% 1.00 [0.38 , 1.62]
Bingol 2005 8.3 1.17 20 12.95 2.95 20 4.1% -4.65 [-6.04 , -3.26]
Celik 2004 10.2 2.2 30 12.4 2.3 30 4.7% -2.20 [-3.34 , -1.06]
Chaney 1998 6.9 4.1 29 8.3 5.1 28 2.4% -1.40 [-3.81 , 1.01]
Demir 2009 8.53 2.19 15 12.6 6.76 15 1.3% -4.07 [-7.67 , -0.47]
Demir 2015 8.25 1.83 20 9.35 2.39 20 4.3% -1.10 [-2.42 , 0.22]
Enc 2006 5.2 0.6 20 6.3 0.7 20 6.2% -1.10 [-1.50 , -0.70]
Engelman 1995 6.5 1.1 10 5.2 0.4 10 5.6% 1.30 [0.57 , 2.03]
Fillinger 2002 4.6 1.5 15 6.1 1.7 15 4.7% -1.50 [-2.65 , -0.35]
Giomarelli 2003 6 1 10 6 1 10 5.3% 0.00 [-0.88 , 0.88]
Kilickan 2008 7.75 1.69 30 8 1.26 30 5.6% -0.25 [-1.00 , 0.50]
Liakopoulos 2007 13.1 5.2 40 12.3 2.3 38 3.3% 0.80 [-0.97 , 2.57]
Mahrose 2019 6.5 1.2 88 7.2 1.6 88 6.2% -0.70 [-1.12 , -0.28]
Mardani 2012 12.93 1.03 43 13.64 1.75 50 5.9% -0.71 [-1.28 , -0.14]
McBride 2004 8.06 2.9 18 7.76 3.5 17 2.7% 0.30 [-1.84 , 2.44]
Rubens 2005 5.4 1.9 17 6.5 2.8 17 3.6% -1.10 [-2.71 , 0.51]
Schurr 2001 11 2 24 11 1.6 26 5.0% 0.00 [-1.01 , 1.01]
Sobieski 2008 4.8 1.5 13 5 1.3 15 4.9% -0.20 [-1.25 , 0.85]
Tassani 1999 13.3 4.6 26 10.5 6.1 26 1.8% 2.80 [-0.14 , 5.74]
Volk 2001 14.6 16.1 12 8.7 6.8 13 0.2% 5.90 [-3.93 , 15.73]
Yilmaz 1999 6.6 0.9 10 9.2 8.7 10 0.7% -2.60 [-8.02 , 2.82]
Subtotal (95% CI) 540 548 84.3% -0.60 [-1.15 , -0.06]
4.8.2 Mixed
Al-Shawabkeh 2017 6.02 2.25 170 5.95 1.95 170 6.1% 0.07 [-0.38 , 0.52]
Glumac 2017 11.2 4 80 11.3 3 81 4.8% -0.10 [-1.19 , 0.99]
Hao 2019 21.63 7.68 18 20.44 8.07 18 0.7% 1.19 [-3.96 , 6.34]
Yared 1998 7 5.2 106 7.3 5.3 110 4.1% -0.30 [-1.70 , 1.10]
Subtotal (95% CI) 374 379 15.7% 0.02 [-0.37 , 0.42]
Total (95% CI) 914 927 100.0% -0.51 [-0.97 , -0.04]

Comparison 5. Subgroup analyses: steroid type
pants
5.1.1 Dexamethasone 6 5416 Risk Ratio (M-H, Random, 95% CI) 0.93 [0.60, 1.44]
5.1.2 Methylprednisolone 14 8708 Risk Ratio (M-H, Random, 95% CI) 0.88 [0.72, 1.08]
5.1.3 Prednisolone 1 40 Risk Ratio (M-H, Random, 95% CI) 0.20 [0.01, 3.92]
and dexamethasone
5.1.5 Hydrocortisone 2 332 Risk Ratio (M-H, Random, 95% CI) 1.41 [0.54, 3.68]
and hydrocortisone
5.2 Cardiac complications 25 14766 Risk Ratio (M-H, Random, 95% CI) 1.16 [1.04, 1.31]
Informed decisions.
pants
and dexamethasone
and hydrocortisone
5.3 Pulmonary complica- 18 13549 Risk Ratio (M-H, Random, 95% CI) 0.88 [0.78, 0.99]
tions
and dexamethasone
5.3.6 Betamethasone dipro- 1 60 Risk Ratio (M-H, Random, 95% CI) 1.00 [0.36, 2.75]
pionate
and dexamethasone
5.4.6 Betamethasone dipro- 1 60 Risk Ratio (M-H, Random, 95% CI) 1.38 [0.64, 2.93]
pionate
and hydrocortisone
Informed decisions.
pants
5.6 Mechanical ventilation 32 1973 Mean Difference (IV, Random, 95% -54.08 [-100.36, -7.81]
(minutes) CI)
5.6.1 Dexamethasone 9 896 Mean Difference (IV, Random, 95% -52.27 [-98.24, -6.31]
CI)
5.6.2 Methylprednisolone 18 721 Mean Difference (IV, Random, 95% 5.44 [-69.58, 80.47]
CI)
5.6.3 Prednisolone 2 60 Mean Difference (IV, Random, 95% -172.42 [-816.86,

CI) 472.02]
5.6.4 Methylprednisolone 1 125 Mean Difference (IV, Random, 95% -398.70 [-520.98,
and dexamethasone CI) -276.42]
5.6.5 Hydrocortisone 2 171 Mean Difference (IV, Random, 95% -122.44 [-428.40,
CI) 183.52]
5.7 Length of ICU stay 25 1300 Mean Difference (IV, Random, 95% -3.58 [-7.79, 0.63]
(hours) CI)
5.7.1 Dexamethasone 10 727 Mean Difference (IV, Random, 95% 0.61 [-12.55, 13.77]
CI)
5.7.2 Methylprednisolone 15 573 Mean Difference (IV, Random, 95% -5.96 [-9.96, -1.96]
CI)
5.8 Length of hospital stay 25 1841 Mean Difference (IV, Random, 95% -0.51 [-0.97, -0.04]
(days) CI)
5.8.1 Dexamethasone 5 598 Mean Difference (IV, Random, 95% -0.03 [-0.82, 0.75]
CI)
5.8.2 Methylprednisolone 17 687 Mean Difference (IV, Random, 95% -0.46 [-1.09, 0.17]
CI)
5.8.3 Prednisolone 1 40 Mean Difference (IV, Random, 95% -4.65 [-6.04, -3.26]
CI)
5.8.4 Hydrocortisone 1 176 Mean Difference (IV, Random, 95% -0.70 [-1.12, -0.28]
CI)
5.8.5 Methylprednisolone 1 340 Mean Difference (IV, Random, 95% 0.07 [-0.38, 0.52]
and hydrocortisone CI)
Informed decisions.
Analysis 5.1. Comparison 5: Subgroup analyses: steroid type, Outcome 1: Mortality

5.1.1 Dexamethasone
Abbaszadeh 2012 0 92 1 92 0.3% 0.33 [0.01 , 8.08]
Dieleman 2012 31 2235 34 2247 13.4% 0.92 [0.57 , 1.49]
Glumac 2017 3 85 2 84 1.0% 1.48 [0.25 , 8.65]
Halvorsen 2003 1 147 1 147 0.4% 1.00 [0.06 , 15.84]
Yared 1998 2 106 3 110 1.0% 0.69 [0.12 , 4.06]
Yared 2007 1 37 0 34 0.3% 2.76 [0.12 , 65.62]
Subtotal (95% CI) 2702 2714 16.4% 0.93 [0.60 , 1.44]
Total events: 38 41
5.1.2 Methylprednisolone
Andersen 1989 1 8 0 8 0.3% 3.00 [0.14 , 64.26]
Boscoe 1983 3 17 0 17 0.4% 7.00 [0.39 , 125.99]
Celik 2004 1 30 2 30 0.6% 0.50 [0.05 , 5.22]
Chaney 1998 1 30 2 30 0.6% 0.50 [0.05 , 5.22]
Chaney 2001 0 59 1 29 0.3% 0.17 [0.01 , 3.97]
Codd 1977 1 75 0 75 0.3% 3.00 [0.12 , 72.49]
Coetzer 1996 7 165 5 130 2.5% 1.10 [0.36 , 3.40]
Kerr 2012 2 51 3 47 1.0% 0.61 [0.11 , 3.52]
Liakopoulos 2007 1 40 0 38 0.3% 2.85 [0.12 , 67.97]
Lomirovotov 2013 2 22 1 22 0.6% 2.00 [0.20 , 20.49]
Rao 1977 2 75 3 75 1.0% 0.67 [0.11 , 3.88]
Rubens 2005 0 34 1 34 0.3% 0.33 [0.01 , 7.91]
Whitlock 2006 1 30 0 30 0.3% 3.00 [0.13 , 70.83]
Whitlock 2015 154 3755 177 3752 70.0% 0.87 [0.70 , 1.07]
Subtotal (95% CI) 4391 4317 78.4% 0.88 [0.72 , 1.08]
5.1.3 Prednisolone
Bingol 2005 0 20 2 20 0.4% 0.20 [0.01 , 3.92]
Subtotal (95% CI) 20 20 0.4% 0.20 [0.01 , 3.92]
Total events: 0 2
5.1.4 Methylprednisolone and dexamethasone

Gomez Polo 2018 1 52 3 52 0.6% 0.33 [0.04 , 3.10]
Subtotal (95% CI) 52 52 0.6% 0.33 [0.04 , 3.10]
Total events: 1 3
5.1.5 Hydrocortisone
Halonen 2007 1 120 0 121 0.3% 3.02 [0.12 , 73.52]
Kilger 2003a 7 43 6 48 3.1% 1.30 [0.47 , 3.57]
Subtotal (95% CI) 163 169 3.4% 1.41 [0.54 , 3.68]
Total events: 8 6
5.1.6 Methylprednisolone and hydrocortisone

Al-Shawabkeh 2017 2 170 2 170 0.8% 1.00 [0.14 , 7.02]
Subtotal (95% CI) 170 170 0.8% 1.00 [0.14 , 7.02]
Total events: 2 2
Informed decisions.
Analysis 5.1. (Continued)

Total (95% CI) 7498 7442 100.0% 0.90 [0.75 , 1.07]

Informed decisions.
Analysis 5.2. Comparison 5: Subgroup analyses: steroid type, Outcome 2: Cardiac complications

5.2.1 Dexamethasone
Abbaszadeh 2012 4 92 6 92 0.9% 0.67 [0.19 , 2.28]
Amr 2009 2 50 2 50 0.4% 1.00 [0.15 , 6.82]
Dieleman 2012 35 2235 39 2247 6.5% 0.90 [0.57 , 1.42]
Halvorsen 2003 3 147 1 147 0.3% 3.00 [0.32 , 28.51]
Mardani 2012 1 43 0 50 0.1% 3.48 [0.15 , 83.21]
Murphy 2011 2 60 2 49 0.4% 0.82 [0.12 , 5.59]
Yared 1998 0 106 1 110 0.1% 0.35 [0.01 , 8.40]
Yared 2007 1 37 0 34 0.1% 2.76 [0.12 , 65.62]
Subtotal (95% CI) 2770 2779 8.7% 0.93 [0.63 , 1.37]
Total events: 48 51
Andersen 1989 1 8 0 8 0.1% 3.00 [0.14 , 64.26]
Celik 2004 1 30 2 30 0.2% 0.50 [0.05 , 5.22]
Chaney 1998 1 30 1 30 0.2% 1.00 [0.07 , 15.26]
Chaney 2001 0 59 1 29 0.1% 0.17 [0.01 , 3.97]
Codd 1977 6 75 5 75 1.0% 1.20 [0.38 , 3.76]
McBride 2004 1 18 0 17 0.1% 2.84 [0.12 , 65.34]
Morton 1976 5 22 5 22 1.1% 1.00 [0.34 , 2.97]
Rao 1977 2 75 5 75 0.5% 0.40 [0.08 , 2.00]
Rubens 2005 0 34 3 34 0.2% 0.14 [0.01 , 2.66]
Taleska Stupica 2020 0 20 1 20 0.1% 0.33 [0.01 , 7.72]
Vukovic 2011 2 29 1 28 0.2% 1.93 [0.19 , 20.12]
Whitlock 2006 1 30 3 30 0.3% 0.33 [0.04 , 3.03]
Whitlock 2015 486 3755 399 3752 85.8% 1.22 [1.07 , 1.38]
Subtotal (95% CI) 4185 4150 90.1% 1.19 [1.06 , 1.35]

Oliver 2004 5 62 1 63 0.3% 5.08 [0.61 , 42.25]
Subtotal (95% CI) 62 63 0.3% 5.08 [0.61 , 42.25]
Total events: 5 1
Halonen 2007 1 120 1 121 0.2% 1.01 [0.06 , 15.94]
Mahrose 2019 1 88 3 88 0.3% 0.33 [0.04 , 3.14]
Subtotal (95% CI) 208 209 0.4% 0.52 [0.09 , 2.95]
Total events: 2 4

Al-Shawabkeh 2017 2 170 3 170 0.4% 0.67 [0.11 , 3.94]
Subtotal (95% CI) 170 170 0.4% 0.67 [0.11 , 3.94]
Total events: 2 3
Total (95% CI) 7395 7371 100.0% 1.16 [1.04 , 1.31]

Informed decisions.
Analysis 5.3. Comparison 5: Subgroup analyses: steroid type, Outcome 3: Pulmonary complications

5.3.1 Dexamethasone
Abbaszadeh 2012 2 92 1 92 0.2% 2.00 [0.18 , 21.67]
Dieleman 2012 67 2235 97 2247 15.0% 0.69 [0.51 , 0.94]
Halvorsen 2003 2 147 0 147 0.2% 5.00 [0.24 , 103.26]
Mardani 2012 2 43 2 50 0.4% 1.16 [0.17 , 7.91]
Murphy 2011 0 60 1 49 0.1% 0.27 [0.01 , 6.56]
Yared 1998 1 37 2 34 0.3% 0.46 [0.04 , 4.84]
Subtotal (95% CI) 2614 2619 16.2% 0.72 [0.53 , 0.96]
Kerr 2012 21 51 21 47 6.7% 0.92 [0.58 , 1.46]
Liakopoulos 2007 2 40 1 38 0.3% 1.90 [0.18 , 20.10]
Morton 1976 3 48 3 48 0.6% 1.00 [0.21 , 4.71]
Rao 1977 1 75 7 75 0.3% 0.14 [0.02 , 1.13]
Schurr 2001 1 24 2 26 0.3% 0.54 [0.05 , 5.60]
Toft 1997 0 8 1 8 0.1% 0.33 [0.02 , 7.14]
Whitlock 2006 2 30 1 30 0.3% 2.00 [0.19 , 20.90]
Whitlock 2015 343 3755 375 3752 72.2% 0.91 [0.80 , 1.05]
Subtotal (95% CI) 4031 4024 80.7% 0.91 [0.80 , 1.04]
5.3.3 Prednisolone
Bingol 2005 1 20 4 20 0.3% 0.25 [0.03 , 2.05]
Subtotal (95% CI) 20 20 0.3% 0.25 [0.03 , 2.05]
Total events: 1 4

Oliver 2004 7 62 4 63 1.0% 1.78 [0.55 , 5.77]
Subtotal (95% CI) 62 63 1.0% 1.78 [0.55 , 5.77]
Total events: 7 4
Weis 2006 2 19 2 17 0.4% 0.89 [0.14 , 5.68]
Subtotal (95% CI) 19 17 0.4% 0.89 [0.14 , 5.68]
Total events: 2 2
5.3.6 Betamethasone dipropionate

Starobin 2007 6 30 6 30 1.4% 1.00 [0.36 , 2.75]
Subtotal (95% CI) 30 30 1.4% 1.00 [0.36 , 2.75]
Total events: 6 6
Total (95% CI) 6776 6773 100.0% 0.88 [0.78 , 0.99]

Informed decisions.
Analysis 5.4. Comparison 5: Subgroup analyses: steroid type, Outcome 4: Atrial fibrillation

5.4.1 Dexamethasone
Abbaszadeh 2012 40 92 67 92 9.6% 0.60 [0.46 , 0.78]
Abd El-Hakeem 2003b 1 10 3 10 0.4% 0.33 [0.04 , 2.69]
Amr 2009 7 50 8 50 1.8% 0.88 [0.34 , 2.23]
Dieleman 2012 739 2235 790 2247 14.7% 0.94 [0.87 , 1.02]
Halvorsen 2003 1 147 1 147 0.2% 1.00 [0.06 , 15.84]
Mardani 2012 5 43 11 50 1.7% 0.53 [0.20 , 1.40]
Murphy 2011 11 60 10 49 2.5% 0.90 [0.42 , 1.94]
Sobieski 2008 2 13 4 15 0.7% 0.58 [0.13 , 2.65]
Yared 1998 15 37 10 34 3.3% 1.38 [0.72 , 2.64]
Subtotal (95% CI) 2687 2694 34.9% 0.81 [0.63 , 1.04]
Celik 2004 6 30 7 30 1.7% 0.86 [0.33 , 2.25]
Chaney 1998 8 30 9 30 2.3% 0.89 [0.40 , 1.99]
Enc 2006 2 20 3 20 0.6% 0.67 [0.12 , 3.57]
Giomarelli 2003 0 10 2 10 0.2% 0.20 [0.01 , 3.70]
Lomirovotov 2013 5 22 2 22 0.7% 2.50 [0.54 , 11.54]
Rubens 2005 4 34 13 34 1.5% 0.31 [0.11 , 0.85]
Schurr 2001 12 24 17 26 5.0% 0.76 [0.47 , 1.25]
Taleska Stupica 2020 4 20 3 20 0.9% 1.33 [0.34 , 5.21]
Vukovic 2011 3 29 11 28 1.2% 0.26 [0.08 , 0.85]
Whitlock 2006 7 28 10 30 2.3% 0.75 [0.33 , 1.70]
Whitlock 2015 821 3755 846 3752 14.6% 0.97 [0.89 , 1.06]
Subtotal (95% CI) 4002 4002 31.1% 0.80 [0.61 , 1.05]
5.4.3 Prednisolone
Bingol 2005 1 20 3 20 0.4% 0.33 [0.04 , 2.94]
Subtotal (95% CI) 20 20 0.4% 0.33 [0.04 , 2.94]
Total events: 1 3

Gomez Polo 2018 9 52 14 52 2.6% 0.64 [0.31 , 1.35]
Prasongsukarn 2005 9 43 22 43 3.3% 0.41 [0.21 , 0.78]
Subtotal (95% CI) 95 95 5.9% 0.50 [0.30 , 0.81]
Total events: 18 36
Halonen 2007 44 120 62 121 8.9% 0.72 [0.53 , 0.96]
Mahrose 2019 26 88 42 88 6.7% 0.62 [0.42 , 0.91]
Weis 2006 5 19 10 17 2.1% 0.45 [0.19 , 1.05]
Subtotal (95% CI) 227 226 17.6% 0.66 [0.53 , 0.83]
5.4.6 Betamethasone dipropionate

Starobin 2007 11 30 8 30 2.6% 1.38 [0.64 , 2.93]
Subtotal (95% CI) 30 30 2.6% 1.38 [0.64 , 2.93]
Total events: 11 8
Informed decisions.
Analysis 5.4. (Continued)

Total events: 11 8

Al-Shawabkeh 2017 36 170 65 170 7.5% 0.55 [0.39 , 0.78]
Subtotal (95% CI) 170 170 7.5% 0.55 [0.39 , 0.78]
Total events: 36 65
Total (95% CI) 7231 7237 100.0% 0.75 [0.65 , 0.85]

Informed decisions.
Analysis 5.5. Comparison 5: Subgroup analyses: steroid type, Outcome 5: Inotropic support

5.5.1 Dexamethasone
Abd El-Hakeem 2003a 8 23 14 23 5.9% 0.57 [0.30 , 1.09]
Abd El-Hakeem 2003a 3 10 6 10 2.8% 0.50 [0.17 , 1.46]
El Azab 2002 2 9 3 8 1.6% 0.59 [0.13 , 2.70]
Glumac 2017 37 80 41 81 11.1% 0.91 [0.66 , 1.26]
Halvorsen 2003 2 147 2 147 1.0% 1.00 [0.14 , 7.00]
Loef 2004 7 10 2 10 2.0% 3.50 [0.95 , 12.90]
Mardani 2012 2 43 3 50 1.2% 0.78 [0.14 , 4.43]
Murphy 2011 13 60 9 49 4.7% 1.18 [0.55 , 2.53]
Von Spiegel 2001 6 10 9 10 7.2% 0.67 [0.39 , 1.15]
Yared 1998 24 106 29 110 8.3% 0.86 [0.54 , 1.37]
Subtotal (95% CI) 498 498 45.8% 0.84 [0.69 , 1.03]
Cavarocchi 1986 9 31 5 30 3.3% 1.74 [0.66 , 4.60]
Celik 2004 1 30 2 30 0.7% 0.50 [0.05 , 5.22]
Chaney 1998 24 30 15 30 9.6% 1.60 [1.07 , 2.39]
Chaney 2001 43 59 20 29 11.7% 1.06 [0.79 , 1.41]
Codd 1977 11 75 11 75 4.7% 1.00 [0.46 , 2.16]
Giomarelli 2003 1 10 1 10 0.6% 1.00 [0.07 , 13.87]
Lomirovotov 2013 4 22 1 22 0.8% 4.00 [0.48 , 33.00]
McBride 2004 9 18 6 17 4.5% 1.42 [0.64 , 3.13]
Schurr 2001 3 24 6 26 2.1% 0.54 [0.15 , 1.93]
Vukovic 2011 5 29 18 29 4.1% 0.28 [0.12 , 0.65]
Whitlock 2006 0 30 8 30 0.5% 0.06 [0.00 , 0.98]
Yilmaz 1999 1 10 2 10 0.8% 0.50 [0.05 , 4.67]
Subtotal (95% CI) 368 338 43.3% 0.96 [0.64 , 1.43]
Mahrose 2019 39 88 40 88 10.9% 0.97 [0.70 , 1.35]
Subtotal (95% CI) 88 88 10.9% 0.97 [0.70 , 1.35]
Total events: 39 40
Total (95% CI) 954 924 100.0% 0.93 [0.76 , 1.13]

Informed decisions.
Analysis 5.6. Comparison 5: Subgroup analyses: steroid type, Outcome 6: Mechanical ventilation (minutes)
5.6.1 Dexamethasone
Abd El-Hakeem 2003a 407.13 24.1 23 443.9 45.1 23 5.4% -36.77 [-57.67 , -15.87]
Abd El-Hakeem 2003b 480 95 10 516 113 10 4.5% -36.00 [-127.50 , 55.50]
El Azab 2002 660 120 9 780 180 9 3.6% -120.00 [-261.34 , 21.34]
Glumac 2017 1164 750 80 1278 738 81 2.3% -114.00 [-343.87 , 115.87]
Halvorsen 2003 148 69 147 149 67 147 5.5% -1.00 [-16.55 , 14.55]
Loef 2004 1131.6 214 10 900.6 188 10 3.1% 231.00 [54.45 , 407.55]
Mardani 2012 550.8 144 43 633.6 231.6 50 4.8% -82.80 [-160.09 , -5.51]
Sobieski 2008 185 164 14 541 246 14 3.4% -356.00 [-510.87 , -201.13]
Yared 1998 696 714 106 786 828 110 2.6% -90.00 [-295.95 , 115.95]
Subtotal (95% CI) 442 454 35.2% -52.27 [-98.24 , -6.31]
Bourbon 2004 696 276 12 762 5.5 12 3.4% -66.00 [-222.19 , 90.19]
Celik 2004 642 54 30 514 36 30 5.4% 128.00 [104.78 , 151.22]
Chaney 1998 796 294 30 604 615 30 2.2% 192.00 [-51.92 , 435.92]
Demir 2009 572 298 15 496 263 15 2.7% 76.00 [-125.14 , 277.14]
Demir 2015 520.2 180 20 481.2 228.6 20 3.9% 39.00 [-88.52 , 166.52]
Engelman 1995 786 135 10 630 60 10 4.5% 156.00 [64.44 , 247.56]
Fillinger 2002 594 85.2 15 936 510 15 2.0% -342.00 [-603.67 , -80.33]
Giomarelli 2003 750 162 10 708 180 10 3.5% 42.00 [-108.09 , 192.09]
Hao 2019 1257.6 653.4 18 1073.4 526.8 18 1.1% 184.20 [-203.54 , 571.94]
Kilickan 2008 375 180 30 348 219 30 4.3% 27.00 [-74.44 , 128.44]
Liakopoulos 2007 840 528 40 684 414 38 2.6% 156.00 [-54.00 , 366.00]
Mayumi 1997 2044 921 12 1872 662 12 0.5% 172.00 [-469.74 , 813.74]
Schurr 2001 510 204 24 480 174 26 4.3% 30.00 [-75.52 , 135.52]
Taleska Stupica 2020 570 660 20 870 705 20 1.0% -300.00 [-723.24 , 123.24]
Tassani 1999 486 42 26 552 48 26 5.4% -66.00 [-90.52 , -41.48]
Vukovic 2011 714 216 29 1026 282 28 3.8% -312.00 [-442.73 , -181.27]
Wan 1999 840 420 10 1080 600 10 0.9% -240.00 [-693.93 , 213.93]
Yilmaz 1999 804 663 10 702 213 10 1.0% 102.00 [-329.61 , 533.61]
Subtotal (95% CI) 361 360 52.4% 5.44 [-69.58 , 80.47]
5.6.3 Prednisolone
Bingol 2005 404 102 20 894 222 20 4.2% -490.00 [-597.07 , -382.93]
Harig 1999 948 234 10 780 354 10 2.0% 168.00 [-95.01 , 431.01]
Subtotal (95% CI) 30 30 6.2% -172.42 [-816.86 , 472.02]

Oliver 2004 519.3 282.8 62 918 404.9 63 4.0% -398.70 [-520.98 , -276.42]
Subtotal (95% CI) 62 63 4.0% -398.70 [-520.98 , -276.42]
Hauer 2012 1026 720 56 1260 1020 55 1.5% -234.00 [-562.98 , 94.98]
Sano 2003 1320 720 31 1224 1164 29 0.8% 96.00 [-397.67 , 589.67]
Subtotal (95% CI) 87 84 2.2% -122.44 [-428.40 , 183.52]
Total (95% CI) 982 991 100.0% -54.08 [-100.36 , -7.81]

Test for subgroup differences: Chi² = 32.42, df = 4 (P < 0.00001), I² = 87.7% Favours corticosteroids Favours no corticosteroids
Informed decisions.
Analysis 5.7. Comparison 5: Subgroup analyses: steroid type, Outcome 7: Length of ICU stay (hours)
5.7.1 Dexamethasone
Abd El-Hakeem 2003a 52.66 1.81 23 66.26 23.09 23 4.7% -13.60 [-23.07 , -4.13]
Abd El-Hakeem 2003b 47.3 5.7 10 67.2 5.7 10 5.7% -19.90 [-24.90 , -14.90]
Amr 2009 64.8 19.2 50 67.2 16.8 50 5.3% -2.40 [-9.47 , 4.67]
El Azab 2002 24 8 9 52 32 9 2.4% -28.00 [-49.55 , -6.45]
Glumac 2017 51.5 35 80 60.8 33.4 81 4.5% -9.30 [-19.87 , 1.27]
Jansen 1991 91.2 27 12 72 27 13 2.4% 19.20 [-1.98 , 40.38]
Loef 2004 29 10 10 26 7 10 5.2% 3.00 [-4.57 , 10.57]
Mardani 2012 68.64 31.2 43 0 31.92 50 3.9% 68.64 [55.79 , 81.49]
Sobieski 2008 23.7 2.6 14 24.6 12.3 14 5.4% -0.90 [-7.49 , 5.69]
Yared 1998 36.8 28 106 47.9 113.6 110 2.3% -11.10 [-32.99 , 10.79]
Subtotal (95% CI) 357 370 41.9% 0.61 [-12.55 , 13.77]
Celik 2004 36.2 4.1 30 42.1 2.7 30 6.2% -5.90 [-7.66 , -4.14]
Demir 2009 55.9 14.64 15 83 75.6 15 1.0% -27.10 [-66.07 , 11.87]
Demir 2015 52.8 9.84 20 58.8 16.32 20 5.0% -6.00 [-14.35 , 2.35]
Engelman 1995 28.8 2.4 10 50.4 7.2 10 5.8% -21.60 [-26.30 , -16.90]
Fillinger 2002 27 11.6 15 36 28.7 15 3.3% -9.00 [-24.67 , 6.67]
Giomarelli 2003 32.1 3.7 10 35.2 4.4 10 6.0% -3.10 [-6.66 , 0.46]
Hao 2019 28 17.06 18 26.61 16.43 18 4.4% 1.39 [-9.55 , 12.33]
Liakopoulos 2007 50.4 62.4 40 50 43.2 38 2.1% 0.40 [-23.32 , 24.12]
Rubens 2005 36 29 34 36 24 34 4.0% 0.00 [-12.65 , 12.65]
Schurr 2001 24 19 24 24 22 26 4.3% 0.00 [-11.37 , 11.37]
Tassani 1999 27.2 2.1 26 28 2.2 26 6.2% -0.80 [-1.97 , 0.37]
Volk 2001 36 29 12 75 158 13 0.2% -39.00 [-126.44 , 48.44]
Volk 2003 36 7.2 12 74 43.2 12 2.0% -38.00 [-62.78 , -13.22]
Wan 1999 29 9 10 32 23 10 3.4% -3.00 [-18.31 , 12.31]
Yilmaz 1999 33.71 17.3 10 34.2 7.8 10 4.2% -0.49 [-12.25 , 11.27]
Subtotal (95% CI) 286 287 58.1% -5.96 [-9.96 , -1.96]
Total (95% CI) 643 657 100.0% -3.58 [-7.79 , 0.63]

Informed decisions.
Analysis 5.8. Comparison 5: Subgroup analyses: steroid type, Outcome 8: Length of hospital stay (days)
5.8.1 Dexamethasone
Amr 2009 15 1 50 14 2 50 5.8% 1.00 [0.38 , 1.62]
Glumac 2017 11.2 4 80 11.3 3 81 4.8% -0.10 [-1.19 , 0.99]
Mardani 2012 12.93 1.03 43 13.64 1.75 50 5.9% -0.71 [-1.28 , -0.14]
Sobieski 2008 4.8 1.5 13 5 1.3 15 4.9% -0.20 [-1.25 , 0.85]
Yared 1998 7 5.2 106 7.3 5.3 110 4.1% -0.30 [-1.70 , 1.10]
Subtotal (95% CI) 292 306 25.5% -0.03 [-0.82 , 0.75]
Celik 2004 10.2 2.2 30 12.4 2.3 30 4.7% -2.20 [-3.34 , -1.06]
Chaney 1998 6.9 4.1 29 8.3 5.1 28 2.4% -1.40 [-3.81 , 1.01]
Demir 2009 8.53 2.19 15 12.6 6.76 15 1.3% -4.07 [-7.67 , -0.47]
Demir 2015 8.25 1.83 20 9.35 2.39 20 4.3% -1.10 [-2.42 , 0.22]
Enc 2006 5.2 0.6 20 6.3 0.7 20 6.2% -1.10 [-1.50 , -0.70]
Engelman 1995 6.5 1.1 10 5.2 0.4 10 5.6% 1.30 [0.57 , 2.03]
Fillinger 2002 4.6 1.5 15 6.1 1.7 15 4.7% -1.50 [-2.65 , -0.35]
Giomarelli 2003 6 1 10 6 1 10 5.3% 0.00 [-0.88 , 0.88]
Hao 2019 21.63 7.68 18 20.44 8.07 18 0.7% 1.19 [-3.96 , 6.34]
Kilickan 2008 7.75 1.69 30 8 1.26 30 5.6% -0.25 [-1.00 , 0.50]
Liakopoulos 2007 13.1 5.2 40 12.3 2.3 38 3.3% 0.80 [-0.97 , 2.57]
McBride 2004 8.06 2.9 18 7.76 3.5 17 2.7% 0.30 [-1.84 , 2.44]
Rubens 2005 5.4 1.9 17 6.5 2.8 17 3.6% -1.10 [-2.71 , 0.51]
Schurr 2001 11 2 24 11 1.6 26 5.0% 0.00 [-1.01 , 1.01]
Tassani 1999 13.3 4.6 26 10.5 6.1 26 1.8% 2.80 [-0.14 , 5.74]
Volk 2001 14.6 16.1 12 8.7 6.8 13 0.2% 5.90 [-3.93 , 15.73]
Yilmaz 1999 6.6 0.9 10 9.2 8.7 10 0.7% -2.60 [-8.02 , 2.82]
Subtotal (95% CI) 344 343 58.0% -0.46 [-1.09 , 0.17]
5.8.3 Prednisolone
Bingol 2005 8.3 1.17 20 12.95 2.95 20 4.1% -4.65 [-6.04 , -3.26]
Subtotal (95% CI) 20 20 4.1% -4.65 [-6.04 , -3.26]
Mahrose 2019 6.5 1.2 88 7.2 1.6 88 6.2% -0.70 [-1.12 , -0.28]
Subtotal (95% CI) 88 88 6.2% -0.70 [-1.12 , -0.28]

Al-Shawabkeh 2017 6.02 2.25 170 5.95 1.95 170 6.1% 0.07 [-0.38 , 0.52]
Subtotal (95% CI) 170 170 6.1% 0.07 [-0.38 , 0.52]
Total (95% CI) 914 927 100.0% -0.51 [-0.97 , -0.04]

Test for subgroup differences: Chi² = 42.65, df = 4 (P < 0.00001), I² = 90.6% Favours corticosteroids Favours no corticosteroids
Comparison 6. Sensitivity analyses
pants
6.1 Mortality (sensitivity analysis) 2 11989 Risk Ratio (M-H, Random, 0.88 [0.72, 1.06]
95% CI)
6.2 Cardiac complications (sensitivity 2 11989 Risk Ratio (M-H, Random, 1.14 [0.89, 1.45]
analysis) 95% CI)
6.3 Pulmonary complications (sensitivi- 2 11989 Risk Ratio (M-H, Random, 0.83 [0.64, 1.07]
ty analysis) 95% CI)
Informed decisions.
Analysis 6.1. Comparison 6: Sensitivity analyses, Outcome 1: Mortality (sensitivity analysis)

Dieleman 2012 31 2235 34 2247 16.0% 0.92 [0.57 , 1.49] + + + + + + +

Whitlock 2015 154 3755 177 3752 84.0% 0.87 [0.70 , 1.07] + + + + + + +
Total (95% CI) 5990 5999 100.0% 0.88 [0.72 , 1.06]

Risk of bias legend

(G) Other bias
Analysis 6.2. Comparison 6: Sensitivity analyses, Outcome 2: Cardiac complications (sensitivity analysis)
Dieleman 2012 35 2235 39 2247 22.5% 0.90 [0.57 , 1.42] + + + + + + +

Whitlock 2015 486 3755 399 3752 77.5% 1.22 [1.07 , 1.38] + + + + + + +
Total (95% CI) 5990 5999 100.0% 1.14 [0.89 , 1.45]

Risk of bias legend

(G) Other bias
Analysis 6.3. Comparison 6: Sensitivity analyses, Outcome 3: Pulmonary complications (sensitivity analysis)

Dieleman 2012 67 2235 97 2247 37.2% 0.69 [0.51 , 0.94]

Whitlock 2015 343 3755 375 3752 62.8% 0.91 [0.80 , 1.05]
Total (95% CI) 5990 5999 100.0% 0.83 [0.64 , 1.07]

ADDITIONAL TABLES
Table 1. Included studies: additional characteristics of trials, participants, and interventions
Study Country Mean age Male par- Diabetic BMI Surgery Steroid type Dose equiva- High dose
Library
Cochrane
ticipants type lent* (hydro-
cortisone) of
steroid
Abbaszadeh 2012 Iran 60 51% - 26.65 CABG Dexamethasone 320 mg No
Better health.
Informed decisions.
Trusted evidence.
Abd El-Hakeem Egypt 36 55% - - Valve Dexamethasone 2667 mg Yes
2003a
Abd El-Hakeem Egypt - - - - Valve Dexamethasone 2667 mg Yes

2003b
Al-Shawabkeh 2017 Jordan 65 51% 31.80% - Mixed Methylprednisolone + Hydro- 7700 mg Yes
cortisone
Amr 2009 Egypt 68 71% - - CABG Dexamethasone 2800 mg Yes
Andersen 1989 Denmark - - - - CABG Methylprednisolone 700 mg No
Bingol 2005 Turkey 64 78% - - CABG Prednisolone 120 mg No
Boscoe 1983 United King- 53 76% - - Mixed Methylprednisolone 10,500 mg No

dom
Bourbon 2004 France 61 - 14% - CABG Methylprednisolone 5250 mg No
Cavarocchi 1986 USA 63 72% 13% - Mixed Methylprednisolone 10,500 mg Yes
Celik 2004 Turkey 61 - - - CABG Methylprednisolone 10,500 mg Yes

Chaney 1998 USA 67 75% - - CABG Methylprednisolone 10,500 mg Yes
Chaney 2001 USA 65 77% - - CABG Methylprednisolone 21,000 mg Yes

10,500 mg
Codd 1977 USA CABG Methylprednisolone 21,000 mg Yes

10,500 mg
Coetzer 1996 South Africa - 83% - - Mixed Methylprednisolone 10,500 mg Yes

178
Table 1. Included studies: additional characteristics of trials, participants, and interventions (Continued)
Demir 2009 Turkey CABG Methylprednisolone 5000 mg Yes
Library
Cochrane
Demir 2015 Turkey - - - - CABG Methylprednisolone 5000 mg Yes
Dieleman 2012 Netherlands 62 67% 27% - Mixed Dexamethasone 1867 mg Yes
El Azab 2002 Netherlands 64 63% 33% - CABG Dexamethasone 2666mg Yes
Better health.
Informed decisions.
Trusted evidence.
Enc 2006 Turkey 66 73% 19% - CABG Methylprednisolone 8750 mg Yes
Engelman 1995 USA 63 76% 12% - CABG Methylprednisolone 25,000 mg Yes
Ferries 1984 USA 58 100% 0% - Mixed Methylprednisolone 10,500 mg Yes
Fillinger 2002 USA 64 - - - CABG Methylprednisolone 5670 mg Yes
Giomarelli 2003 Italy 60 39% - - CABG Methylprednisolone 8125 mg Yes
Glumac 2017 Croatia 65 - - - Mixed Dexamethasone 187 mg No
Gomez Polo 2018 Spain 64 43% 15% - Mixed Methylprednisolone and Dex- 2820 mg Yes
amethasone
Halonen 2007 Finland 64 79% 30% - Mixed Hydrocortisone 100 mg No
Halvorsen 2003 Norway 64 73% - - CABG Dexamethasone 213 mg No
Hao 2019 China 65 77% 25% 27.8 Mixed Methylprednisolone 2500 mg Yes
Harig 1999 Germany 64 80% 4% - CABG Prednisolone 1000 mg Yes

Hauer 2012 Germany 53 42% - - Mixed Hydrocortisone 560 mg No
Jansen 1991 Netherlands 62 35% - - CABG Dexamethasone 1867 mg Yes
Kerr 2012 USA 69 82% 24% - Mixed Methylprednisolone 4800 mg Yes
Kilger 2003a Germany 62 - - - CABG Hydrocortisone 550 mg No
Kilger 2003b Germany 51 60% - - CABG Hydrocortisone 550 mg No
Kilickan 2008 Turkey 69 - - - CABG Methylprednisolone 5250 mg Yes

179
Liakopoulos 2007 Germany - - - - CABG Methylprednisolone 5250 mg Yes
Library
Cochrane
Loef 2004 Netherlands 62 75% - - CABG Dexamethasone 1750 mg Yes
Lomirovotov 2013 Russia 66 71% 31% 26.9 CABG Methylprednisolone 7000 mg Yes
Maddalli 2019 Oman 64 85% 0% 26.1 CABG Dexamethasone 373 mg No
Better health.
Informed decisions.
Trusted evidence.
Mahrose 2019 Egypt 58 84% - 29.4 CABG Hydrocortisone 700 mg No
Mardani 2012 Iran 61 - - 26 CABG Dexamethasone 2133 mg Yes
Mayumi 1997 Japan - 71% 22% - Valve Methylprednisolone 7000 mg Yes
McBride 2004 Northern Ire- 62 86% 9% - CABG Methylprednisolone 10,500 mg Yes

land
Morton 1976 USA 53 63% 8% - CABG Methylprednisolone 150 mg Yes
Murphy 2011 USA 61 97% 0% - Mixed Dexamethasone 427 mg No
Oliver 2004 USA - - - - Mixed Methylprednisolone and Dex- 5427 mg Yes

amethasone
Prasongsukarn Canada 63 71% 12% - CABG Methylprednisolone and Dex- 5427 mg Yes
2005 amethasone
Rao 1977 USA 63 85% 0% - CABG Methylprednisolone 5000 mg Yes
Rubens 2005 Canada 64 77% - - CABG Methylprednisolone 5000 mg Yes

Rumalla 2001 Canada - - - CABG Methylprednisolone 5000 mg Yes
Sano 2003 Japan 56 87% 21% - Mixed Hydrocortisone 3500 mg Yes
Sano 2006 Japan 62 - 38% - Mixed Hydrocortisone 3500 mg Yes
Schurr 2001 Switzerland 63 55% - - CABG Methylprednisolone 3500 mg Yes
Sobieski 2008 USA 62 51% - - CABG Dexamethasone 2667 mg Yes
Starobin 2007 Israel 62 86% - - Mixed Betamethasone dipropionate 187 mg No

180
Taleska Stupica Slovenia 63 82% 18% - Mixed Methylprednisolone 5000 mg Yes

2020
Library
Cochrane
Tassani 1999 Germany 67 56% - - CABG Methylprednisolone 5000 mg Yes
Toft 1997 Denmark 69 45% - - Mixed Methylprednisolone 10,500 mg Yes
Turkoz 2001 Turkey - - - - CABG Methylprednisolone 10,500 mg Yes
Better health.
Informed decisions.
Trusted evidence.
Volk 2001 Germany 64 88% - - CABG Methylprednisolone 5250 mg Yes
Volk 2003 Germany 61 85% - - CABG Methylprednisolone 5250 mg Yes
Von Spiegel 2001 Germany 63 88% 24% 28.3 CABG Dexamethasone 1867 mg Yes
Vukovic 2011 Serbia 63 88% - 28 CABG Methylprednisolone 3500 mg Yes
Wan 1999 Hong Kong 65 75% - - Mixed Methylprednisolone 10,500 mg Yes

and Belgium
Weis 2006 Germany, 61 84% 33% - Mixed Hydrocortisone 310 mg No

California,
Switzerland
Weis 2009 Germany 65 70% - - Mixed Hydrocortisone 550mg No
Whitlock 2006 Canada 69 68% - - Mixed Methylprednisolone 2500 mg Yes
Whitlock 2015 Canada, Italy, 68 50% - - Mixed Methylprednisolone 2500 mg Yes

USA, India,
Colombia,
China, Brazil,

Australia,
Greece, Iran
Yared 1998 USA 67 73% 33% 29.2 Mixed Dexamethasone 1120 mg Yes
Yared 2007 USA 67 60% 26% 26.7 Mixed Dexamethasone 1120 mg Yes
Yilmaz 1999 Turkey 63 82% - - CABG Methylprednisolone 350 mg No

181
*The dose equivalent was calculated based on a dose of hydrocortisone administered to a person weighing 70 kg. Low dose: ≤ 1000 mg hydrocortisone equivalent; high dose:
> 1000 mg hydrocortisone equivalent.
Abbreviations
BMI: body mass index; CABG: coronary artery bypass grafting
Library
Cochrane
Table 2. Summary of reported outcomes (selected from the summary of findings table) in each study included in the review
All-cause Cardiac com- Pulmonary Infectious GI bleeding Renal failure Hospital LOS
mortality plications complica- complica-
Better health.
Informed decisions.
Trusted evidence.
tions tions
Abbaszadeh 2012 x x x x - - -
Abd El-Hakeem 2003a - - - - - - -
Abd El-Hakeem 2003b - - - - - - -
Al-Shawabkeh 2017 x x - x x - x
Amr 2009 - x - x x - x
Andersen 1989 x x - - - - -
Bingol 2005 x - x x - - x
Boscoe 1983 x - - - - - -
Bourbon 2004 - - - - - - -
Cavarocchi 1986 - - - - - - -
Celik 2004 x x - - - - x

Chaney 1998 x x - - x - x
Chaney 2001 x x - - - - -
Codd 1977 x x - - - - -
Coetzer 1996 x - - - - - -
Demir 2009 - - - - - x x
182
Table 2. Summary of reported outcomes (selected from the summary of findings table) in each study included in the review (Continued)
Demir 2015 x - - x - - x
Library
Cochrane
Dieleman 2012 x x x x x x -
El Azab 2002 x - - - - - -
Enc 2006 - - - - - x x
Better health.
Informed decisions.
Trusted evidence.
Engelman 1995 - - - - - - x
Ferries 1984 x - - - - - -
Fillinger 2002 - - - - - - x
Giomarelli 2003 - - - - - - x
Glumac 2017 x - - - - - x
Gomez Polo 2018 x - - x - - -
Halonen 2007 x x - x - - -
Halvorsen 2003 x x x x - - -
Hao 2019 - - - - - - x
Harig 1999 x - - - - - -
Hauer 2012 - - - - - - -
Jansen 1991 - - - x - - -

Kerr 2012 x - x x - - -
Kilger 2003a x - - - - - -
Kilger 2003b - - - - - - -
Kilickan 2008 - - - - - - x
Liakopoulos 2007 x - x x - x x
183
Loef 2004 x - - - - - -
Library
Cochrane
Lomirovotov 2013 x - - x - - -
Maddalli 2019 - - - x - - -
Mahrose 2019 x x x x - - x
Better health.
Informed decisions.
Trusted evidence.
Mardani 2012 - x x x - x x
Mayumi 1997 x x x x x x -
McBride 2004 x x - - - - x
Morton 1976 - x x - - - -
Murphy 2011 - x x x - x -
Oliver 2004 - x x - - - -
Prasongsukarn 2005 x - - x x x -
Rao 1977 x x x x - - -
Rubens 2005 x x - x - - x
Rumalla 2001 x - - x - - -
Sano 2003 x - - - - - -
Sano 2006 - - - - - - -

Schurr 2001 x - x x - - x
Sobieski 2008 x - - x - x x
Starobin 2007 - - x x - x -
Taleska Stupica 2020 x x - x - x -
Tassani 1999 x x x - x x x
184
Toft 1997 - - x x - x -
Library
Cochrane
Turkoz 2001 x x x x x x -
Volk 2001 x - - - - - x
Volk 2003 x x - - - - -
Better health.
Informed decisions.
Trusted evidence.
Von Spiegel 2001 - - - - - - -
Vukovic 2011 x x - x - - -
Wan 1999 x - - - - - -
Weis 2006 x - - - - - -
Weis 2009 x - x x x x -
Whitlock 2006 x x x x x x -
Whitlock 2015 x x x x x x -
Yared 1998 x x - x - x x
Yared 2007 x x x x - x -
Yilmaz 1999 - - - x - - x
Abbreviations
GI: gastrointestinal; LOS: length of stay

185
Informed decisions.
Table 3. Moderator analysis with meta-regression for primary outcomes and any outcomes with substantial
heterogeneity
Outcome Results
Regression coefficient (95% CI) Test of moderator
Mortality
Publication year -0.01 (-0.04 to 0.02) P = 0.46
Age 0.01 (-0.02 to - 0.03) P = 0.71
BMI 0.45 (-0.28 to 1.18) P = 0.23
Dose equivalent of steroid < -0.001 (< -0.001 to < 0.001) P = 0.86
Cardiac complications
Publication year 0.01 (-0.01 to 0.03) P = 0.42
Age 0.01 (-0.003 to 0.03) P = 0.11
BMI -0.50 (-1.37 to 0.38) P = 0.27
Dose equivalent of steroid < 0.001 (< -0.001 to < 0.001) P = 0.48
Pulmonary complications
Age 0.01 (-0.01 to 0.03) P = 0.38
BMI 0.34 (-0.64 to 1.33) P = 0.49
Atrial fibrillation
Age 0.01 (-0.004 to 0.02) P = 0.16
BMI 0.30 (-0.35 to 0.95) P = 0.37
Inotropic support
Age 0.01 (-0.02 to 0.03) P = 0.65
BMI -0.85 (-3.37 to 1.67) P = 0.51
Informed decisions.
Table 3. Moderator analysis with meta-regression for primary outcomes and any outcomes with substantial
heterogeneity (Continued)
Postoperative bleeding (mL)
Publication year 11.10 (2.54 to 19.65) P = 0.01
Age -3.16 (-41.13 to 34.81) P = 0.87
Dose equivalent of steroid -0.01 (-0.03 to 0.01) P = 0.42
Duration of mechanical ventilation (minutes)
Age -2.45 (-11.91 to 7.01) P = 0.61
Dose equivalent of steroid 0.01 (0.003 to 0.02) P = 0.01
ICU length of stay (hours)
Age -0.02 (-0.47 to 0.44) P = 0.95
BMI -19.09 (-31.45 to -6.74) P = 0.003
Dose equivalent of steroid -0.001 (-0.001 to < 0.001) P = 0.03
Hospital length of stay (days)
Age 0.01 (-0.03 to 0.04) P = 0.78
Low dose: ≤ 1000 mg hydrocortisone equivalent; high dose: > 1000 mg hydrocortisone equivalent.
Abbreviations
BMI: body mass index; CI: confidence interval; ICU: intensive care unit; OR: odds ratio
Table 4. Definitions adopted for cardiac complications

Study ID Cardiac complications definitions
Abbaszadeh 2012 Postoperative MI
Amr 2009 Perioperative MI
Andersen 1989 Perioperative MI
Al-Shawabkeh 2017 Perioperative MI
Celik 2004 MI
Chaney 1998 MI
Informed decisions.
Table 4. Definitions adopted for cardiac complications (Continued)
Chaney 2001 MI
Codd 1977 MI
Dieleman 2012 MI at 30 days: “presence of new Q waves or a new left bundle branch block on the electrocardio-
gram, combined with a biomarker (creatine kinase–MB or troponin) elevation of more than 5 times
the upper reference limit. Data from routine cardiac biomarker surveillance were used to detect
possible perioperative MI. The specific type of biomarker used was dictated by the local protocol in
each center, rather than by the study protocol. Postdischarge MI was defined according to the cri-
teria of the Universal Definition of Myocardial Infarction”.
Halonen 2007 Perioperative myocardial infarction was defined as the development of new Q waves.
Halvorsen 2003 Postoperative myocardial infarction
Mahrose 2019 Postoperative myocardial infarction
Mardani 2012 Cardiac complications (acute myocardial infarction, cardiac arrest, atrioventricular block, atrial fib-
rillation and low cardiac output state)
Morton 1976 Electrocardiographic evidence of either transmural or subendocardial infarction in conjunction

with significant enzyme elevation.
Murphy 2011 Cardiac complications: myocardial infarction defined by new Q waves on electrocardiogram, ev-
idence of congestive heart failure on physical examination or chest radiograph, and need for in-
otropic medications for more than 48 hours or an intra-aortic balloon pump.
Oliver 2004 Myocardial infarction, cardiac arrest, complete heart block, haemodynamically unstable arrhyth-
mias
Rao 1977 MI
Rubens 2005 Electrocardiographic criteria for Q wave MI
Taleska Stupica 2020 Postoperative MI
Vukovic 2011 Perioperative myocardial infarction
Whitlock 2006 MI
Whitlock 2015 Early myocardial injury after cardiac surgery (i.e. within 72 hours of surgery), particularly after non-
coronary-artery bypass-graft surgery. Thresholds were established for CK-MB measured by mass
assay and by activity assay, as well as separately for patients who had isolated coronary artery by-
pass and for those having other cardiac surgeries.
Yared 1998 Cardiac index below 1.8 despite inotropic drugs or MI requiring ventricular assist device
Yared 2007 "Postoperative myocardial infarction, cardiac index below 2.0 L/min/m2, need for mechanical as-
sist device"
Abbreviations
CK-MB: creatine kinase myocardial band; MI: myocardial infarction
Informed decisions.
APPENDICES
Appendix 1. Search strategies

CENTRAL
#1 MeSH descriptor: [Steroids] this term only
#2 MeSH descriptor: [Anti-Inflammatory Agents] this term only
#3 steroid* or steriod*
#4 dexamethaso*
#5 predniso*
#6 methylprednisolo*
#7 glucocortico*
#8 hydrocortiso*
#9 corticosteroid*
#10 corticoid*
#11 anti-inflammator*
#12 anti next inflammator*
#13 antiinflammator*
#14 antiflogistic
#15 antiphlogistic
#16 MeSH descriptor: [Adrenal Cortex Hormones] explode all trees
#17 adrenal next cortex next hormone*
#18 (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17)
#19 MeSH descriptor: [Extracorporeal Circulation] explode all trees
#20 cardiopulmonary next bypass
#21 extracorporeal next circulation
#22 MeSH descriptor: [Heart-Lung Machine] this term only
#23 heart next lung next machine
#24 cpb
#25 MeSH descriptor: [Cardiac Surgical Procedures] explode all trees
#26 (coronary near/6 bypass)
#27 heart near/6 bypass
#28 cardiac near/6 bypass
#29 cardiac next surgery
#30 heart near/2 surgery
#31 open next heart
#32 MeSH descriptor: [Cardiopulmonary Bypass] this term only
Informed decisions.
#33 aortocoronary next bypass*
#34 heart-lung next bypass*
#35 MeSH descriptor: [Heart Bypass, Left] this term only
#36 MeSH descriptor: [Cardiomyoplasty] this term only
#37 MeSH descriptor: [Heart Arrest, Induced] explode all trees
#38 MeSH descriptor: [Heart Valve Prosthesis Implantation] this term only
#39 MeSH descriptor: [Myocardial Revascularization] this term only
#40 MeSH descriptor: [Coronary Artery Bypass] this term only
#41 MeSH descriptor: [Pericardial Window Techniques] this term only
#42 MeSH descriptor: [Cardiomyoplasty] this term only
#43 induc* near/3 (heart or circulatory or cardiac) next arrest
#44 MeSH descriptor: [Heart Bypass, Right] explode all trees
#45 fontan next procedure*
#46 heart next valve near/2 implant*
#47 myocard* next revasculari?ation*
#48 coronary next atherectom*
#49 pericardial next window
#50 MeSH descriptor: [Thoracic Surgery] this term only
#51 (dor or suma) near/10 (reconstruct* or operat* or technique*)
#52 coronary near/2 surgery
#53 thoracic next surgery
#54 cardiomyoplast*
#55 cavopulmonary next anastomos?s
#56 cavopulmonary next shunt*
#57 cardioplegia*
#58 cardiopulmonary next bypass*
#59 cabg
#60 ecc
#61 #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29
#62 #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 or #39
#63 #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or #48 or #49
#64 #50 or #51 or #52 or #53 or #54 or #55 or #56 or #57 or #58 or #59 or #60
#65 #61 or #62 or #63 or #64
#66 #18 and #65
Informed decisions.
MEDLINE Ovid
1. Extracorporeal Circulation/
2. extracorporeal circulation.tw.
3. Cardiopulmonary Bypass/
4. cardiopulmonary bypass*.tw.
5. cardiac bypass*.tw.
6. aortocoronary bypass*.tw.
7. (coronary adj2 bypass*).tw.
8. heart bypass*.tw.
9. heart-lung bypass*.tw.
10. Heart Bypass, Left/
11. Heart-Lung Machine/
12. heart lung machine*.tw.
13. Cardiac Surgical Procedures/
14. Cardiomyoplasty/
15. Heart Arrest, Induced/
16. Heart Valve Prosthesis Implantation/
17. Myocardial Revascularization/
18. Coronary Artery Bypass/
19. Pericardial Window Techniques/
20. Cardiomyoplasty/
21. (induced adj3 heart arrest).tw.
22. (induced adj3 circulatory arrest).tw.
23. (induced adj3 cardiac arrest).tw.
24. exp Heart Bypass, Right/
25. fontan procedure*.tw.
26. (heart valve adj2 implant*).tw.
27. myocard* revasculari?ation*.tw.
28. coronary atherectom*.tw.
29. pericardial window.tw.
30. Thoracic Surgery/
31. ((dor or suma) and (reconstruct* or operat* or technique*)).tw.
32. cardiac surgery.tw.
33. (heart adj2 surgery).tw.
34. (coronary adj2 surgery).tw.
Informed decisions.
35. thoracic surgery.tw.
36. cardiomyoplast*.tw.
37. cavopulmonary anastomos?s.tw.
38. cavopulmonary shunt*.tw.
39. cardioplegia*.tw.
41. open heart.tw.
42. cpb.tw.
43. cabg.tw.
44. ecc.tw.
45. or/1-44
46. Anti-Inflammatory Agents/
47. anti-inflammator*.tw.
48. anti inflammator*.tw.
49. antiinflammator*.tw.
50. antiflogistic.tw.
51. antiphlogistic.tw.
52. glucocortico*.tw.
53. Steroids/
54. steroid*.tw.
55. steriod*.tw.
56. Dexamethaso*.tw.
57. Methylprednisolo*.tw.
58. Predniso*.tw.
59. hydrocortiso*.tw.
60. Adrenal Cortex Hormones/
61. corticosteroid*.tw.
62. corticoid*.tw.
63. adrenal cortex hormone*.tw.
64. or/46-63
65. 45 and 64
66. randomized controlled trial.pt.
67. controlled clinical trial.pt.
68. randomized.ab.
69. placebo.ab.
Informed decisions.
70. drug therapy.fs.
71. randomly.ab.
72. trial.ab.
73. groups.ab.
74. 66 or 67 or 68 or 69 or 70 or 71 or 72 or 73
75. exp animals/ not humans.sh.
76. 74 not 75
77. 65 and 76
Embase Ovid
1. exp extracorporeal circulation/
2. extracorporeal circulation.tw.
3. cardiopulmonary bypass/
4. cardiopulmonary bypass*.tw.
5. cardiac bypass*.tw.
6. (coronary adj2 bypass*).tw.
7. aortocoronary bypass*.tw.
8. heart bypass*.tw.
9. heart-lung bypass*.tw.
10. exp heart lung machine/
11. heart lung machine*.tw.
12. exp heart valve surgery/
13. exp heart surgery/
14. thorax surgery/
15. heart arrest/
16. heart muscle revascularization/
17. (induc* adj3 heart arrest).tw.
18. (induc* adj3 circulatory arrest).tw.
19. (induc* adj3 cardiac arrest).tw.
20. fontan procedure*.tw.
21. (heart valve adj2 implant*).tw.
22. myocard* revasculari?ation*.tw.
23. coronary atherectom*.tw.
24. pericardial window.tw.
25. ((dor or suma) and (reconstruct* or operat* or technique*)).tw.
26. cardiac surgery.tw.
Informed decisions.
27. (coronary adj2 surgery).tw.
28. thoracic surgery.tw.
29. (heart adj2 surgery).tw.
31. cavopulmonary anastomos?s.tw.
32. cavopulmonary shunt*.tw.
33. cardioplegia*.tw.
34. open heart.tw.
35. cpb.tw.
36. cabg.tw.
37. ecc.tw.
38. or/1-37
39. antiinflammatory agent/
40. anti-inflammator*.tw.
41. anti inflammator*.tw.
42. antiinflammator*.tw.
43. antiinflammation.tw.
44. antiflogistic.tw.
45. antiphlogistic.tw.
46. glucocortico*.tw.
47. exp corticosteroid/
48. steroid/
49. steroid*.tw.
50. steriod*.tw.
51. Dexamethaso*.tw.
52. Methylprednisolo*.tw.
53. Predniso*.tw.
54. hydrocortiso*.tw.
55. corticosteroid*.tw.
56. corticoid*.tw.
57. adrenal cortex hormone*.tw.
58. or/39-57
59. 38 and 58
60. random$.tw.
61. factorial$.tw.
Informed decisions.
62. crossover$.tw.
63. cross over$.tw.
64. cross-over$.tw.
65. placebo$.tw.
66. (doubl$ adj blind$).tw.
67. (singl$ adj blind$).tw.
68. assign$.tw.
69. allocat$.tw.
70. volunteer$.tw.
71. crossover procedure/
72. double blind procedure/
73. randomized controlled trial/
74. single blind procedure/
75. 60 or 61 or 62 or 63 or 64 or 65 or 66 or 67 or 68 or 69 or 70 or 71 or 72 or 73 or 74
76. (animal/ or nonhuman/) not human/
77. 75 not 76
78. 59 and 77
79. limit 78 to embase
Science Citation Index Expanded (SCI-EXPANDED) and Social Science Citation Index
#21 #20 AND #19
#20 TS=(random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross-over*)
#19 #18 AND #6
#18 #17 OR #16 OR #15 OR #14 OR #13 OR #12 OR #11 OR #10 OR #9 OR #8 OR #7
#17 TS=((dor or suma) NEAR/2 (reconstruct* or operat* or technique*))
#16 TS=("heart valve" NEAR/2 implant*)
#15 TS=((induced) NEAR/3 (circulatory or cardiac) NEAR/2 (arrest))

#14 TS=(("heart muscle" or myocard*) NEAR/2 (revasculari?ation))
#13 TS=("heart arrest" or fontan* or "pericardial window" or "coronary atherectom*")

#12 TS=("open heart" or cpb or cabg)
#11 TS=(cardiomyoplast* or "cavopulmonary anastomos?s" or "cavopulmonary shunt*" or cardioplegia*)
#10 TS=((cardiac or coronary or heart or thoracic) NEAR/2 (surgery))
#9 TS=("heart lung machine*")
#8 TS=((cardiopulmonary or cardiac or coronary or aortocoronary or heart*) NEAR/2 (bypass*))
#7 TS=("extracorporeal circulation" or ecc)
#6 #5 OR #4 OR #3 OR #2 OR #1
#5 TS=(Dexamethaso* or Methylprednisolo* or Predniso*)
Informed decisions.
#4 TS=(glucocortico* or hydrocortiso*)
#3 TS=(anti-inflammator* or "anti inflammator*" or antiinflammator* or antiflogistic or antiphlogistic)
#2 TS=(corticosteroid* or corticoid* or "adrenal cortex hormone*")
#1 TS=(steroid* or steriod*)
CINAHL
S50 S31 AND S49
S49 S32 or S33 or S34 or S35 or S36 or S37 or S38 or S39 or S40 or S41 or S42 or S43 or S44 or S45 or S46 or S47 or S48
S48 TX cross-over*
S47 TX crossover*
S46 TX volunteer*
S45 (MH "Crossover Design")
S44 TX allocat*
S43 TX control*
S42 TX assign*
S41 TX placebo*
S40 (MH "Placebos")
S39 TX random*
S38 TX (doubl* N1 mask*)
S37 TX (singl* N1 mask*)
S36 TX (doubl* N1 blind*)
S35 TX (singl* N1 blind*)
S34 TX (clinic* N1 trial?)
S33 PT clinical trial
S32 (MH "Clinical Trials+")
S31 S10 AND S30
S30 S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR
S28 OR S29
S29 AB (cardiomyoplast* or "cavopulmonary anastomos?s" or "cavopulmonary shunt*" or cardioplegia* or "open heart" or cpb or cabg)
S28 TI (cardiomyoplast* or "cavopulmonary anastomos?s" or "cavopulmonary shunt*" or cardioplegia* or "open heart" or cpb or cabg)
S27 AB ((cardiac or coronary or thoracic or heart) N2 (surgery))
S26 TI ((cardiac or coronary or thoracic or heart) N2 (surgery))
S25 AB ((dor or suma) N4 (reconstruct* or operat* or technique*))
S24 TI ((dor or suma) N4 (reconstruct* or operat* or technique*))
S23 AB ("heart lung machine*" or "fontan procedure*" or "myocard* revasculari?ation*" or "coronary atherectom*" or "pericardial
window")
Informed decisions.
S22 TI ("heart lung machine*" or "fontan procedure*" or "myocard* revasculari?ation*" or "coronary atherectom*" or "pericardial
window")
S21 AB ((induc*) N3 ("heart arrest" or "circulatory arrest" or "cardiac arrest"))
S20 TI ((induc*) N3 ("heart arrest" or "circulatory arrest" or "cardiac arrest"))
S19 (MH "Heart Arrest")
S18 (MH "Thoracic Surgery")
S17 (MH "Heart Surgery+")
S16 (MH "Heart, Mechanical")
S15 AB ((cardiopulmonary or cardiac or coronary or aortocoronary or heart or heart-lung) N2 (bypass*))
S14 TI ((cardiopulmonary or cardiac or coronary or aortocoronary or heart or heart-lung) N2 (bypass*))
S13 (MH "Cardiopulmonary Bypass")
S12 TI ("extracorporeal circulation" or ecc) or AB ("extracorporeal circulation" or ecc)
S11 (MH "Extracorporeal Circulation+")
S10 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9
S9 AB (Dexamethaso* or Methylprednisolo* or Predniso* or hydrocortiso*)
S8 TI (Dexamethaso* or Methylprednisolo* or Predniso* or hydrocortiso*)
S7 (MH "Adrenal Cortex Hormones+")
S6 AB (steroid* or steriod* or glucocortico* or corticosteroid*or corticoid* or "adrenal cortex hormone*")
S5 TI (steroid* or steriod* or glucocortico* or corticosteroid*or corticoid* or "adrenal cortex hormone*")
S4 (MH "Steroids+")
S3 AB (anti-inflammator* or "anti inflammator*" or antiinflammator* or antiinflammation or antiflogistic or antiphlogistic)
S2 TI (anti-inflammator* or "anti inflammator*" or antiinflammator* or antiinflammation or antiflogistic or antiphlogistic)
S1 (MH "Antiinflammatory Agents+")
Trials Registers (ClinicalTrials.gov and International Clinical Trials Registry Platform)

(cardiac OR heart)
(steroid OR corticosteroids)
(cardiopulmonary bypass OR CPB)
(surgery OR surgical OR procedure)
WHAT'S NEW
Date Event Description
20 March 2024 New search has been performed The review was expanded with the addition of 18 studies, for a
total of 72 included studies. Searches were run initially in July
2020 and updated in October 2022.
Informed decisions.
Date Event Description
20 March 2024 New citation required and conclusions The findings point towards little to no treatment effect on mor-
have changed tality, with opposing effects on cardiac and pulmonary complica-
tions. The certainty of these findings is still low.
HISTORY
Protocol first published: Issue 1, 2006
Review first published: Issue 5, 2011
CONTRIBUTIONS OF AUTHORS
RGA: was involved in the conception and design of the review, formulated the research question, coordinated the review, selected studies
for inclusion; collected data and arbitrated in case of disagreements, managed data entry, analysed the data, interpreted the data, assessed
risk of bias, assessed the certainty of the body of evidence and arbitrated in the case of disagreements, updated the protocol and the wrote
review manuscript.
GO: selected studies for inclusion, collected the data, spot-checked the data entry into RevMan, assessed risk of bias and the certainty of
the evidence, and reviewed and approved the protocol and the final manuscript.
RC: selected studies for inclusion, collected the data, assessed risk of bias and the certainty of the evidence, and reviewed and approved
the protocol and the final manuscript.
FG: selected studies for inclusion, collected the data, spot-checked the data entry into RevMan, assessed risk of bias and the certainty of
the evidence, and reviewed and approved the protocol and the final manuscript.
NT: selected studies for inclusion, collected the data, assessed risk of bias and the certainty of the evidence, and reviewed and approved
KE: selected studies for inclusion, collected the data, assessed risk of bias and the certainty of the evidence, and reviewed and approved
DF: selected studies for inclusion, collected the data, assessed risk of bias and the certainty of the evidence, and reviewed and approved
RM: selected studies for inclusion, collected the data, spot-checked the data entry into RevMan, assessed risk of bias and assessed the
certainty of the evidence, and reviewed and approved the protocol and the final manuscript.
MK: collected the data, and reviewed and approved the protocol and the final manuscript.
GE: selected studies for inclusion, collected the data, assessed risk of bias and the certainty of the evidence, and reviewed and approved
FL: helped in designing the study, provided methodological expert opinion, and reviewed and approved the protocol and the final
manuscript.
ML: helped in designing the study, provided methodological expert opinion, arbitrated in study selection, data collection and assessments
of the certainty of the evidence, and reviewed and approved the protocol and the final manuscript.
SK: helped in designing the study, provided methodological expert opinion, arbitrated in study selection, data collection and assessments
of the certainty of the evidence, and reviewed and approved the protocol and the final manuscript.
MZ: helped in designing the study, provided methodological expert opinion, and reviewed and approved the protocol and the final
manuscript.
GJM: is the guarantor for the review, was involved in the conception and design of the review, supervised the study, formulated the research
question, performed previous work that was the foundation of the current review, coordinated the review, arbitrated in study selection,
data collection and assessments of risk of bias and the certainty of the body of evidence, interpreted the data, and reviewed and approved
Informed decisions.
DECLARATIONS OF INTEREST
RGA: has declared that he has no conflict of interest. RGA was a content editor for Cochrane Heart but had no role in the editorial process
for this review. Although working as a health professional as a Clinical Research Fellow in Cardiothoracic Surgery and as a cardiac surgeon
for Imperial College Healthcare NHS Trust, he does not benefit from the positions expressed in this review.
GO: has declared that he has no conflict of interest. Despite working as a cardiothoracic surgeon at ASST G.O.M. Niguarda Hospital, he does
not benefit from the positions expressed in this review.
RC: has declared that she has no conflict of interest. Despite working as a cardiothoracic surgeon with a National Training Number (NTN),
she does not benefit from the positions expressed in this review.
FG: has declared that she has no conflict of interest. Despite working as a cardiothoracic surgeon NTN, she does not benefit from the
positions expressed in this review.
NT: has declared that he has no conflict of interest. He currently holds an NTN in Cardiothoracic Surgery, and is a Higher Speciality Trainee
at Health Education East Midlands. Despite working as a Cardiothoracic Surgery Registrar at Glenfield Hospital, he does not benefit from
the positions expressed in this review.
KE: has declared that she has no conflict of interest. Despite working as a health professional, she does not benefit from the positions
expressed in this review.
DF: has declared that he has no conflict of interest. Daniel Fudulu has published several papers on the use of prophylactic corticosteroids
in paediatric heart surgery whilst employed at the University of Bristol. Despite working as a Clinical Lecturer in cardiac surgery at Bristol
Royal Infirmary, he does not benefit from the positions expressed in this review.
RM: has declared that he has no conflict of interest. Despite working as a health professional, he does not benefit from the positions
MK: has declared that he has no conflict of interest. Despite working as a consultant of cardiothoracic and vascular surgery at the Deutsches
Herzzentrum der Charité in Berlin, he does not benefit from the positions expressed in this review.
GE: has declared that he has no conflict of interest. Despite working as a health professional, he does not benefit from the positions
FL: has declared that she has no conflict of interest.
ML: declares that he has received personal payments for expert testimony, consulting fees, honoraria for lectures/presentations from
Baxter, 3M, Nordic and Medtronic, unrelated to the current work. Despite working as a health professional, he does not benefit from the
positions expressed in this review.
SK: has declared that he has no conflict of interest. Despite working as a consultant cardiothoracic surgeon at South Tees Hospital, he does
not benefit from the positions expressed in this review.
MZ: has declared that he has no conflict of interest. Despite working as a health professional, he does not benefit from the positions
GJM: undertakes unpaid work as a grant committee member for the British Heart Foundation. He also receives a grant for the British Heart
Foundation that is paid to the University of Leicester and his salary was part funded by this grant until 2022. GJM also declares a grant from
NIHR (health technology assessment grant, programme development grants), which is paid to his institution, though he can direct these
resources to fund research in line with the grant specifications. Despite working as a cardiac surgeon, University Hospitals, Leicester, he
does not benefit from the positions expressed in this review.
SOURCES OF SUPPORT
Internal sources
• British Heart Foundation, UK
British Heart Foundation funding (CH/12/1/29419 and AA18/3/34220) to GJM
External sources
• National Institute for Health and Care Research (NIHR), UK
Informed decisions.
This project was supported by the NIHR via Cochrane Infrastructure funding to the Heart Group to March 2023. The views and opinions
expressed herein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the
Department of Health and Social Care.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW
Differences between protocol and original review

We planned to report data on quality of life and cost-effectiveness. However, we were unable to include these in the previous version of
the review due to a lack of available data.
We decided to perform a sensitivity analysis according to the publication date, given that the included studies were published over a period
of four decades.
Differences between this review update and the previous version

The title of the review was changed to 'Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery', to clarify the
surgical speciality examined in the review.
Although we had planned to exclude studies where a mixed cohort of patients would have made it infeasible to extract data relevant to
our review, we did not encounter such studies in our screening.
We revised our definition of one primary outcome (all-cause mortality during the index hospital admission, or within 30 days, at the longest
follow-up available) to reflect the longer follow-up available for mortality in the two main trials included in the review (Dieleman 2012;
Whitlock 2015). The other studies did not provide multiple time points for mortality.
The search strategy in the review was updated from the original review following the suggestions of the Cochrane Information Specialist.
We opted to measure postoperative bleeding instead of postoperative blood transfusion, as the absolute quantity of bleeding is not
affected by the changes in transfusion thresholds that have been introduced in cardiac surgery in the past decades.
We had planned to use the standardised mean difference for outcomes such as quality of life, where different scales were used in the trial
reports. However, the lack of studies reporting on these outcomes prevented us from using a meta-analytical approach to summarise the
studies; instead, we presented the results in a narrative paragraph. Although we were unable to assess health economics data in the first
version of the review due to lack of data (Dieleman 2011), we have assessed the available evidence in this update.
We adopted risk ratios as our effect measure, instead of odds ratios, to improve the general readability of the results, and used mean
difference (MD) instead of standardised mean difference (SMD) as all studies assessed outcomes using similar measures.
We expanded the subgroup analyses and conducted meta-regressions on the primary outcomes to provide a more thorough exploration
of potential differences deriving from the intervention or the population characteristics.
We did not explore through sensitivity analysis the impact of including studies with missing data in the overall assessment of results, as
the sample size of those studies was unlikely to introduce serious bias.
INDEX TERMS
Medical Subject Headings (MeSH)

Adrenal Cortex Hormones [adverse effects]; *Atrial Fibrillation; *Cardiac Surgical Procedures [adverse effects]; Cardiopulmonary
Bypass [adverse effects]; Gastrointestinal Hemorrhage [drug therapy]; Inflammation; Quality of Life; Randomized Controlled Trials as
Topic; *Renal Insufficiency
MeSH check words

Adult; Humans; Middle Aged

Abbasciano_et_al-2024-Cochrane_Database_of_Systematic_Reviews

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Abbasciano_et_al-2024-Cochrane_Database_of_Systematic_Reviews

Uploaded by

Copyright:

Available Formats

Cochrane

Prophylactic corticosteroids for cardiopulmonary bypass in adult

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review)

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) i

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) ii

Prophylactic corticosteroids for cardiopulmonary bypass in adult

Contact: Riccardo Giuseppe Abbasciano, rga8@leicester.ac.uk.

Editorial group: Cochrane Heart Group.

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 1

Data collection and analysis

PLAIN LANGUAGE SUMMARY

What concerns are there when people have heart surgery?

What is the role of corticosteroids in heart surgery?

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 2

What did we want to find out?

What did we do?

What did we find?

If corticosteroids were given to 1000 people undergoing heart surgery:

What are the limitations of the evidence?

How up to date is this evidence?

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 3

Settings: cardiac surgery with cardiopulmonary bypass

Comparison: placebo or no corticosteroids

All-cause mortality 33 per 1000 30 per 1000 RR 0.90 14,940 ⨁⨁◯◯

Cardiac complications 66 per 1000 77 per 1000 RR 1.16 14,766 ⨁⨁◯◯

Pulmonary complications 78 per 1000 69 per 1000 RR 0.88 13,549 ⨁⨁◯◯

Cochrane Database of Systematic Reviews

An RR < 1 or an MD < 0 indicates a benefit of corticosteroid treatment.

GRADE Working Group grades of evidence

Cochrane Database of Systematic Reviews

BACKGROUND occurrence of postoperative atrial fibrillation (odds ratio (OR)

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 6

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 7

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 8

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 10

Figure 1. Study flow diagram

4561 records 0 records

3520 records after

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 11

Included studies support in 23 studies (32%), postoperative bleeding in five studies

Random sequence generation (selection bias)

0% 25% 50% 75% 100%

Low risk of bias Unclear risk of bias High risk of bias

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 13

Blinding of participants and personnel (performance bias)

Incomplete outcome data (attrition bias): All outcomes

Selective reporting (reporting bias)

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 14

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 15

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 16

Effects of interventions Primary outcomes

Figure 4. Funnel plot of mortality. Abbreviations

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 17

Figure 5. Funnel plot of cardiac complications. Abbreviations

Pulmonary complications to 0.99; 18 studies, 13,549 participants; low-certainty evidence;

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 18

Figure 6. Funnel plot of pulmonary complications. Abbreviations

The risk of re-thoracotomy may be increased by 2% (range 0.7% to

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 19

Mechanical ventilation time Surgery type

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 21

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 22

Recording the outcome atrial fibrillation as reported by study AUTHORS' CONCLUSIONS

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery (Review) 23