BEST EVIDENCE TOPIC – ADULT CARDIAC
Interactive CardioVascular and Thoracic Surgery 18 (2014) 225–229 doi:10.1093/icvts/ivt486 Advance Access publication 19 November 2013
Is perioperative corticosteroid administration associated with a reduced incidence of postoperative atrial fibrillation in adult cardiac surgery? Alessandro Viviano, Robin Kanagasabay and Mustafa Zakkar* Department of Cardiothoracic Surgery, St. George’s Hospital, London, UK * Corresponding author. Department of Cardiothoracic Surgery, St. George’s Hospital, Blackshaw Road, London SW17 0QT, UK. Tel: +44-208-7251000; fax: +44-208-7250068; e-mail: [email protected] (M. Zakkar). Received 11 June 2013; received in revised form 22 September 2013; accepted 21 October 2013
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Is perioperative corticosteroid administration associated with a reduced incidence of postoperative atrial fibrillation (POAF) in adult cardiac surgery? A total of 70 papers were identified using the search as described below. Of these, eight were identified to provide best evidence to answer the clinical question. These papers consisted of well-designed, double-blinded randomized control trials (RCTs) or meta-analysis of RCTs that presented sufficient data to reach conclusions regarding the issues of interest for this review. Postoperative atrial fibrillation occurrence, outcomes and complications were included in the assessment. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. Literature search showed that the prophylactic use of hydrocortisone (100 mg/day, 4 days) can reduce the incidence of POAF to 30%, compared with 48% in the control group (P = 0.004). One gram of methylprednisolone before surgery followed by 4 mg of dexamethasone every 6 h for 1 day after surgery was also associated with a significant reduction in POAF (21 vs 51%; P = 0.003). Moreover, a single dose of dexamethasone (0.6 mg/kg) can significantly diminish POAF (18.95 vs 32.3%; P = 0.027). The changes in POAF appeared greatest in patients receiving intermediate doses of corticosteroid (50– 210 mg of dexamethasone equivalent), while both lower (up to 8 mg) and higher (236–2850 mg) dosing resulted in blunted effects. Similarly, a moderate dose of hydrocortisone (200–1000 mg/day) is as effective as high (1001–10 000 mg/day) and very high doses (10 000 mg/day). Although the optimal dose, dosing interval and duration of therapy are unclear, meta-analysis suggests that a single dose can be as effective as multiple doses. No statistically significant complications associated with the use of corticosteroids were reported in any of the studies. We conclude that a single prophylactic moderate dose of corticosteroid (50–210 mg of dexamethasone equivalent or 200–1000 mg/day hydrocortisone) can significantly reduce the risk of POAF with no significant increase in morbidity or mortality. Keywords: Atrial fibrillation • Cardiac surgery • Prophylaxis • Steroids
INTRODUCTION
coronary artery bypass graft, and the question is whether perioperative prophylaxis with corticosteroids for AF is appropriate.
A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1].
SEARCH STRATEGY
In [ patients undergoing cardiac surgery] is [ perioperative prophylaxis with corticosteroids] associated with [reduced incidence of postoperative atrial fibrillation]?
Medline from 1950 to April 2013 using the PubMed interface (Steroids’ [Mesh] AND ‘Cardiac Surgical Procedures’ [Mesh]) AND (‘Atrial Fibrillation’ [Mesh]). The search was limited to English language articles and human studies only. This search was repeated in the Cochrane Central Register of Controlled Trials. In addition, the reference lists of each publication were searched.
CLINICAL SCENARIO
SEARCH OUTCOME
A 72-year old male patient with severe triple-vessel coronary artery disease is referred for coronary artery bypass surgery. He has no significant past medical history. He is scheduled for elective
A total of 70 papers were found using the reported search. Of these, eight provided the best evidence to answer the question. These are presented in Table 1.
THREE-PART QUESTION
© The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
BEST EVIDENCE TOPIC
Abstract
A. Viviano et al. / Interactive CardioVascular and Thoracic Surgery
226
Table 1: Summary table Author, date, journal and country Study type (level of evidence)
Patient group
Outcomes
Key result
Comments
Yared et al. (2000), Ann Thorac Surg, USA [2]
January 1997–September 1997
Dexamethasone reduces the incidence of POAF
POAF: - Steroid group 18.9%. - Placebo group 32.3% (P = 0.027)
No data regarding the use of β-blockers in the postoperative period
Randomized double-blinded control study (level Ib)
235 adult patients included (216 patients included in the analysis) Different cardiac surgical operations
Dexamethasone treatment does not affect morbidity or mortality
106 patients received dexamethasone, 0.6 mg/kg single dose
Randomized double-blinded control study (level Ib)
88 patients were included (86 patients analysed) Adult patients underwent elective first-time CABG 43 patients received 1 g of methylprednisolone before cardiopulmonary bypass and 4 mg of dexamethasone every 6 h in the first 24 h after surgery
Excluded patients with a history of diabetes
No statistical difference in the ICU or hospital length of stay, or in overall morbidity and mortality (P > 0.999)
Drug/placebo was administered at induction 2000–2001
No data about the high risk or emergency patients
No sternal infection in both groups
110 patients received an equal volume of placebo
Prasongsukarn et al. (2005), J Thorac Cardiovasc Surg, Canada [3]
Outcomes and complications: The steroid group had a lower incidence of early postoperative fever (20.2 vs 36.8%, P = 0.009)
Prophylactic short-term steroid administration in patients undergoing CABG significantly reduced POAF There was no significant difference between the steroid group and the placebo group with regard to the length of hospital stay
POAF: - Steroid group 20.93% (9 of 43) - Placebo group 51.16% (22 of 43) (P = 0.003) Outcomes and complications: No statistically significant difference in the length of hospital stay (P = 0.34) Minor complications occurred in 15 steroid patients (35%) and 6 placebo patients (14%) (P = 0.01)
43 patients received maintenance fluids (placebo)
Major complications occurred in 4 steroid patients (9%) and 2 placebo patients (5%) (P = 0.68)
This was designed as a randomized double-blinded trial; however, after 50% enrolment, the code was broken, and the data showed that the primary outcome was satisfied (AF incidence), so the study was stopped, which can have large implications for the secondary outcomes Patients routinely received β-blockers postoperatively The group had a high number of sternal wound infection, which can bias any analysis of data
One patient in each group developed sternal wound infection and 2 in each group developed sternal wound dehiscence Halonen et al. (2007), JAMA, Finland [4] Multicentre randomized double-blinded control study (level Ia)
2005–2006 241 adult patients included (240 patients analysed) Patients underwent different cardiac operations 120 patients received steroids 120 patients received placebo Each patient was administered either hydrocortisone or placebo as follows: the first dose in the evening of the operative day, then 1 dose every 8 h during the next 3 days)
Intravenous hydrocortisone reduces the incidence of AF after cardiac surgery The administration of hydrocortisone therapy is feasible and well tolerated, and associated with no serious complications
POAF: - Steroids group: 30% (36 of 120) - Placebo group: 48% (58 of 121) (P = 0.01) Outcomes and complications: There were no statistically significant differences between the groups with respect to postoperative complications (P > 0.99)
All patients were administered β-blockers according to the heart rate The group adjusted for potential imbalanced confounders and found that the association between randomization to hydrocortisone and POAF was unchanged The study was underpowered to assess the safety of corticosteroid therapy
Continued
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227
Table 1: (Continued) Author, date, journal and country Study type (level of evidence)
Patient group
Outcomes
Key result
Comments
Marik and Fromm (2009), J Crit Care, USA [5]
1966–2007
Moderate-dosage corticosteroid should be considered for the prevention of AF in high-risk patients undergoing cardiac surgery
POAF: The use of corticosteroids was associated with a significant reduction in the risk of POAF (odds ratio 0.42; 95% CI 0.27–0.68; P = 0.0004)
The corticosteroid regimen significantly differed between all studies
Baker et al. (2007), Heart Rhythm, USA [6] Meta-analysis of RCTs (level I)
Three studies included patients undergoing CABG as well as valve surgery, whereas the remaining four studies included only patients undergoing CABG
A single dose given at induction may be adequate
The meta-analysis is limited by the relatively small size of the included studies
The studies included used different protocols and different types of steroids
When the low- and very high-dose studies were excluded, the treatment effect was highly significant (odds ratio 0.32; 95% CI 0.21– 0.50; P < 0.00001) with insignificant heterogeneity
The total cumulated dose of corticosteroid was classified as low dose (2 decades. Clinical practice in cardiovascular surgery changed significantly over this time, as did the patient demographics
Steroids significantly reduced the postoperative duration of ICU stay (weighted mean difference −0.23 days; 95% CI −0.40 to −0.07). The length of hospital stay was also reduced (weighted mean difference −0.59 days; 95% CI −1.17 to −0.02) Weis et al. (2009), Crit Care Med, Germany [9]
No time span given
Randomized double-blinded control study (level Ib)
Different cardiac operations
36 high-risk patients
Hydrocortisone attenuates AF and stress responses in high-risk patients post-cardiac surgery, which seems to be associated with an improved outcome
POAF: - Steroids group: 26% - Placebo group 59% (P = 0.04) Outcomes: No significant differences noted between the two groups The changes in blood glucose levels were not significant when hydrocortisone is given as a continuous infusion
Small study Excluded patients with a history of diabetes or patients with a body mass index of >30 kg/m2 The definition of high risk included an expected duration of the CPB of longer than 97 min, combined procedures or coronary artery bypass grafting with more than three grafts planned
CABG: coronary artery bypass graft; CPB: cardiopulmonary bypass.
RESULTS Halonen et al. [4] showed in a multicentre randomized control trial (RCT) of 241 patients who received either 100 mg hydrocortisone or matching placebo (one dose in the evening of the operation, then one dose every 8 h during the next 3 days) that the incidence of postoperative atrial fibrillation (POAF) was significantly lower in the hydrocortisone group (30 vs 48%; P = 0.004). In this study, patients receiving hydrocortisone did not have higher rates of wound infections or other major complications. Similarly, Yared et al. [2] randomized 235 patients to receive a single dose of dexamethasone 0.6 mg/kg or placebo at induction, and found that
patients receiving dexamethasone had a lower incidence of POAF during the first 3 days postoperatively (18.9 vs 32.3%; P = 0.027). No statistical differences in the intensive care and hospital length of stay or in overall morbidity and mortality were noted. Prasongsukarn et al. [3] enrolled 88 patients in their RCT (43 patients received 1 g of methylprednisolone before surgery and 4 mg of dexamethasone every 6 h for 1 day after surgery). This study found that POAF occurred in 9 (21%) in the steroid group and 22 (51%) in the placebo group (P = 0.003). Minor postoperative complications occurred in 15 (35%) steroid patients and in 6 (14%) patients receiving placebo (P = 0.01), and no significant differences noted in major complications. It is important to note
A. Viviano et al. / Interactive CardioVascular and Thoracic Surgery
corticosteroid (50–210 mg of dexamethasone equivalent), while both lower (up to 8 mg) and higher (236–2850 mg) dosing resulted in blunted effects.
CLINICAL BOTTOM LINE We conclude that a moderate prophylactic dose of corticosteroid prophylaxis (50–210 mg of dexamethasone equivalent or 200– 1000 mg/day hydrocortisone) can significantly reduce the risk of POAF with no significant increase in morbidity or mortality. Although the optimal dose, dosing interval and duration of therapy are unclear, a single dose given at induction may be adequate. There is, however, need for more specific research to gain a better understanding of the mechanisms involved in modulating POAF and the ideal steroid prophylaxis protocol.
Conflict of interest: none declared.
REFERENCES [1] Dunning J, Prendergast B, Kway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003; 2:405–9. [2] Yared JP, Starr NJ, Torres FK, Bashour CA, Bourdakos G, Piedmonte M et al. Effects of single dose, postinduction dexamethasone on recovery after cardiac surgery. Ann Thorac Surg 2000;69:1420–4. [3] Prasongsukarn K, Abel JG, Jamieson WR, Cheung A, Russell JA, Walley KR et al. The effects of steroids on the occurrence of postoperative atrial fibrillation after coronary artery bypass grafting surgery: a prospective randomized trial. J Thorac Cardiovasc Surg 2005;130:93–8. [4] Halonen J, Halonen P, Järvinen O, Taskinen P, Auvinen T, Tarkka M et al. Corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial. JAMA 2007;297:1562–7. [5] Marik PE, Fromm R. The efficacy and dosage effect of corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a systematic review. J Crit Care 2009;24:458–63. [6] Baker WL, White CM, Kluger J, Denowitz A, Konecny CP, Coleman CI. Effect of perioperative corticosteroid use on the incidence of postcardiothoracic surgery atrial fibrillation and length of stay. Heart Rhythm 2007;4:461–8. [7] Ho KM, Tan JA. Benefits and risks of corticosteroid prophylaxis in adult cardiac surgery: a dose-response meta-analysis. Circulation 2009;119: 1853–66. [8] Whitlock RP, Chan S, Devereaux PJ, Sun J, Rubens FD, Thorlund K et al. Clinical benefit of steroid use in patients undergoing cardiopulmonary bypass: a meta-analysis of randomized trials. Eur Heart J 2008;29:2592–600. [9] Weis F, Beiras-Fernandez A, Schelling G, Briegel J, Lang P, Hauer D et al. Stress doses of hydrocortisone in high-risk patients undergoing cardiac surgery: effects on interleukin-6 to interleukin-10 ratio and early outcome. Crit Care Med 2009;37:1685–90.
BEST EVIDENCE TOPIC
that in this study after 50% enrolment, the code was broken, and the data showed that the primary outcome was satisfied (AF incidence) so the study was stopped, which can have large implications for the secondary outcomes. The role of steroid prophylaxis in high-risk cardiac patients was addressed by Weis et al. [9] in an RCT of 36 high risk who were randomized to hydrocortisone (loading dose of 100 mg before induction and followed by a continuous infusion of 10 mg/h for the first day reduced to 5 mg/h on the second day and then tapered to 3 × 20 mg on Day 3 and 3 × 10 mg on Day 4) or placebo and showed that patients in the hydrocortisone group had a lower incidence of POAF (26 vs 59%; P = 0.04) and shorter length of stay in the intensive care unit (ICU; 2 [2 of 3] vs 6 [4 of 8] days; P = 0.001). Ho and Tan [7] analysed 50 RCTs including 3323 patients and demonstrated that corticosteroid prophylaxis reduced the risk of POAF (25.1 vs 35.1%; number needed to treat, 10; relative risk 0.74; 95% confidence interval [95% CI] 0.63–0.86; P < 0.01) and length of stay in the ICU (weighted mean difference −0.37 days; 95% CI −0.21 to −0.52; P < 0.01) and hospital (weighted mean difference −0.66 days; 95% CI −0.77 to −1.25; P = 0.03) compared with placebo. Furthermore, the use of corticosteroid was not associated with an increased risk of all-cause infection (relative risk 0.93; 95% CI 0.61–1.41; P = 0.73). The authors noted that no additional benefits were found beyond a total dose of 1000 mg hydrocortisone. Similar outcomes were demonstrated by Whitlock et al. [8] in a meta-analysis of 44 trials including 3205 patients that showed that steroids can reduce POAF (relative risk 0.71; 95% CI 0.59–0.87; P = 0.001), postoperative bleeding (weighted mean difference −99.6 ml, 95% CI −149.8 to −49.3) and duration of ICU stay (weighted mean difference −0.23 days; 95% CI −0.40 to −0.07). Marik and Fromm [5] in a meta-analysis of seven studies that included 1046 patients found that the use of corticosteroids was associated with a significant reduction in the risk of POAF (odds ratio 0.42; 95% CI 0.27–0.68; P = 0.0004). The group reported significant heterogeneity between studies in terms of the corticosteroid regimen used with the total cumulative dose varying from 160 to 21 000 mg of hydrocortisone equivalents. When the low-dose (
Interactive CardioVascular and Thoracic Surgery 18 (2014) 225–229 doi:10.1093/icvts/ivt486 Advance Access publication 19 November 2013
Is perioperative corticosteroid administration associated with a reduced incidence of postoperative atrial fibrillation in adult cardiac surgery? Alessandro Viviano, Robin Kanagasabay and Mustafa Zakkar* Department of Cardiothoracic Surgery, St. George’s Hospital, London, UK * Corresponding author. Department of Cardiothoracic Surgery, St. George’s Hospital, Blackshaw Road, London SW17 0QT, UK. Tel: +44-208-7251000; fax: +44-208-7250068; e-mail: [email protected] (M. Zakkar). Received 11 June 2013; received in revised form 22 September 2013; accepted 21 October 2013
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Is perioperative corticosteroid administration associated with a reduced incidence of postoperative atrial fibrillation (POAF) in adult cardiac surgery? A total of 70 papers were identified using the search as described below. Of these, eight were identified to provide best evidence to answer the clinical question. These papers consisted of well-designed, double-blinded randomized control trials (RCTs) or meta-analysis of RCTs that presented sufficient data to reach conclusions regarding the issues of interest for this review. Postoperative atrial fibrillation occurrence, outcomes and complications were included in the assessment. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. Literature search showed that the prophylactic use of hydrocortisone (100 mg/day, 4 days) can reduce the incidence of POAF to 30%, compared with 48% in the control group (P = 0.004). One gram of methylprednisolone before surgery followed by 4 mg of dexamethasone every 6 h for 1 day after surgery was also associated with a significant reduction in POAF (21 vs 51%; P = 0.003). Moreover, a single dose of dexamethasone (0.6 mg/kg) can significantly diminish POAF (18.95 vs 32.3%; P = 0.027). The changes in POAF appeared greatest in patients receiving intermediate doses of corticosteroid (50– 210 mg of dexamethasone equivalent), while both lower (up to 8 mg) and higher (236–2850 mg) dosing resulted in blunted effects. Similarly, a moderate dose of hydrocortisone (200–1000 mg/day) is as effective as high (1001–10 000 mg/day) and very high doses (10 000 mg/day). Although the optimal dose, dosing interval and duration of therapy are unclear, meta-analysis suggests that a single dose can be as effective as multiple doses. No statistically significant complications associated with the use of corticosteroids were reported in any of the studies. We conclude that a single prophylactic moderate dose of corticosteroid (50–210 mg of dexamethasone equivalent or 200–1000 mg/day hydrocortisone) can significantly reduce the risk of POAF with no significant increase in morbidity or mortality. Keywords: Atrial fibrillation • Cardiac surgery • Prophylaxis • Steroids
INTRODUCTION
coronary artery bypass graft, and the question is whether perioperative prophylaxis with corticosteroids for AF is appropriate.
A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1].
SEARCH STRATEGY
In [ patients undergoing cardiac surgery] is [ perioperative prophylaxis with corticosteroids] associated with [reduced incidence of postoperative atrial fibrillation]?
Medline from 1950 to April 2013 using the PubMed interface (Steroids’ [Mesh] AND ‘Cardiac Surgical Procedures’ [Mesh]) AND (‘Atrial Fibrillation’ [Mesh]). The search was limited to English language articles and human studies only. This search was repeated in the Cochrane Central Register of Controlled Trials. In addition, the reference lists of each publication were searched.
CLINICAL SCENARIO
SEARCH OUTCOME
A 72-year old male patient with severe triple-vessel coronary artery disease is referred for coronary artery bypass surgery. He has no significant past medical history. He is scheduled for elective
A total of 70 papers were found using the reported search. Of these, eight provided the best evidence to answer the question. These are presented in Table 1.
THREE-PART QUESTION
© The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
BEST EVIDENCE TOPIC
Abstract
A. Viviano et al. / Interactive CardioVascular and Thoracic Surgery
226
Table 1: Summary table Author, date, journal and country Study type (level of evidence)
Patient group
Outcomes
Key result
Comments
Yared et al. (2000), Ann Thorac Surg, USA [2]
January 1997–September 1997
Dexamethasone reduces the incidence of POAF
POAF: - Steroid group 18.9%. - Placebo group 32.3% (P = 0.027)
No data regarding the use of β-blockers in the postoperative period
Randomized double-blinded control study (level Ib)
235 adult patients included (216 patients included in the analysis) Different cardiac surgical operations
Dexamethasone treatment does not affect morbidity or mortality
106 patients received dexamethasone, 0.6 mg/kg single dose
Randomized double-blinded control study (level Ib)
88 patients were included (86 patients analysed) Adult patients underwent elective first-time CABG 43 patients received 1 g of methylprednisolone before cardiopulmonary bypass and 4 mg of dexamethasone every 6 h in the first 24 h after surgery
Excluded patients with a history of diabetes
No statistical difference in the ICU or hospital length of stay, or in overall morbidity and mortality (P > 0.999)
Drug/placebo was administered at induction 2000–2001
No data about the high risk or emergency patients
No sternal infection in both groups
110 patients received an equal volume of placebo
Prasongsukarn et al. (2005), J Thorac Cardiovasc Surg, Canada [3]
Outcomes and complications: The steroid group had a lower incidence of early postoperative fever (20.2 vs 36.8%, P = 0.009)
Prophylactic short-term steroid administration in patients undergoing CABG significantly reduced POAF There was no significant difference between the steroid group and the placebo group with regard to the length of hospital stay
POAF: - Steroid group 20.93% (9 of 43) - Placebo group 51.16% (22 of 43) (P = 0.003) Outcomes and complications: No statistically significant difference in the length of hospital stay (P = 0.34) Minor complications occurred in 15 steroid patients (35%) and 6 placebo patients (14%) (P = 0.01)
43 patients received maintenance fluids (placebo)
Major complications occurred in 4 steroid patients (9%) and 2 placebo patients (5%) (P = 0.68)
This was designed as a randomized double-blinded trial; however, after 50% enrolment, the code was broken, and the data showed that the primary outcome was satisfied (AF incidence), so the study was stopped, which can have large implications for the secondary outcomes Patients routinely received β-blockers postoperatively The group had a high number of sternal wound infection, which can bias any analysis of data
One patient in each group developed sternal wound infection and 2 in each group developed sternal wound dehiscence Halonen et al. (2007), JAMA, Finland [4] Multicentre randomized double-blinded control study (level Ia)
2005–2006 241 adult patients included (240 patients analysed) Patients underwent different cardiac operations 120 patients received steroids 120 patients received placebo Each patient was administered either hydrocortisone or placebo as follows: the first dose in the evening of the operative day, then 1 dose every 8 h during the next 3 days)
Intravenous hydrocortisone reduces the incidence of AF after cardiac surgery The administration of hydrocortisone therapy is feasible and well tolerated, and associated with no serious complications
POAF: - Steroids group: 30% (36 of 120) - Placebo group: 48% (58 of 121) (P = 0.01) Outcomes and complications: There were no statistically significant differences between the groups with respect to postoperative complications (P > 0.99)
All patients were administered β-blockers according to the heart rate The group adjusted for potential imbalanced confounders and found that the association between randomization to hydrocortisone and POAF was unchanged The study was underpowered to assess the safety of corticosteroid therapy
Continued
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227
Table 1: (Continued) Author, date, journal and country Study type (level of evidence)
Patient group
Outcomes
Key result
Comments
Marik and Fromm (2009), J Crit Care, USA [5]
1966–2007
Moderate-dosage corticosteroid should be considered for the prevention of AF in high-risk patients undergoing cardiac surgery
POAF: The use of corticosteroids was associated with a significant reduction in the risk of POAF (odds ratio 0.42; 95% CI 0.27–0.68; P = 0.0004)
The corticosteroid regimen significantly differed between all studies
Baker et al. (2007), Heart Rhythm, USA [6] Meta-analysis of RCTs (level I)
Three studies included patients undergoing CABG as well as valve surgery, whereas the remaining four studies included only patients undergoing CABG
A single dose given at induction may be adequate
The meta-analysis is limited by the relatively small size of the included studies
The studies included used different protocols and different types of steroids
When the low- and very high-dose studies were excluded, the treatment effect was highly significant (odds ratio 0.32; 95% CI 0.21– 0.50; P < 0.00001) with insignificant heterogeneity
The total cumulated dose of corticosteroid was classified as low dose (2 decades. Clinical practice in cardiovascular surgery changed significantly over this time, as did the patient demographics
Steroids significantly reduced the postoperative duration of ICU stay (weighted mean difference −0.23 days; 95% CI −0.40 to −0.07). The length of hospital stay was also reduced (weighted mean difference −0.59 days; 95% CI −1.17 to −0.02) Weis et al. (2009), Crit Care Med, Germany [9]
No time span given
Randomized double-blinded control study (level Ib)
Different cardiac operations
36 high-risk patients
Hydrocortisone attenuates AF and stress responses in high-risk patients post-cardiac surgery, which seems to be associated with an improved outcome
POAF: - Steroids group: 26% - Placebo group 59% (P = 0.04) Outcomes: No significant differences noted between the two groups The changes in blood glucose levels were not significant when hydrocortisone is given as a continuous infusion
Small study Excluded patients with a history of diabetes or patients with a body mass index of >30 kg/m2 The definition of high risk included an expected duration of the CPB of longer than 97 min, combined procedures or coronary artery bypass grafting with more than three grafts planned
CABG: coronary artery bypass graft; CPB: cardiopulmonary bypass.
RESULTS Halonen et al. [4] showed in a multicentre randomized control trial (RCT) of 241 patients who received either 100 mg hydrocortisone or matching placebo (one dose in the evening of the operation, then one dose every 8 h during the next 3 days) that the incidence of postoperative atrial fibrillation (POAF) was significantly lower in the hydrocortisone group (30 vs 48%; P = 0.004). In this study, patients receiving hydrocortisone did not have higher rates of wound infections or other major complications. Similarly, Yared et al. [2] randomized 235 patients to receive a single dose of dexamethasone 0.6 mg/kg or placebo at induction, and found that
patients receiving dexamethasone had a lower incidence of POAF during the first 3 days postoperatively (18.9 vs 32.3%; P = 0.027). No statistical differences in the intensive care and hospital length of stay or in overall morbidity and mortality were noted. Prasongsukarn et al. [3] enrolled 88 patients in their RCT (43 patients received 1 g of methylprednisolone before surgery and 4 mg of dexamethasone every 6 h for 1 day after surgery). This study found that POAF occurred in 9 (21%) in the steroid group and 22 (51%) in the placebo group (P = 0.003). Minor postoperative complications occurred in 15 (35%) steroid patients and in 6 (14%) patients receiving placebo (P = 0.01), and no significant differences noted in major complications. It is important to note
A. Viviano et al. / Interactive CardioVascular and Thoracic Surgery
corticosteroid (50–210 mg of dexamethasone equivalent), while both lower (up to 8 mg) and higher (236–2850 mg) dosing resulted in blunted effects.
CLINICAL BOTTOM LINE We conclude that a moderate prophylactic dose of corticosteroid prophylaxis (50–210 mg of dexamethasone equivalent or 200– 1000 mg/day hydrocortisone) can significantly reduce the risk of POAF with no significant increase in morbidity or mortality. Although the optimal dose, dosing interval and duration of therapy are unclear, a single dose given at induction may be adequate. There is, however, need for more specific research to gain a better understanding of the mechanisms involved in modulating POAF and the ideal steroid prophylaxis protocol.
Conflict of interest: none declared.
REFERENCES [1] Dunning J, Prendergast B, Kway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003; 2:405–9. [2] Yared JP, Starr NJ, Torres FK, Bashour CA, Bourdakos G, Piedmonte M et al. Effects of single dose, postinduction dexamethasone on recovery after cardiac surgery. Ann Thorac Surg 2000;69:1420–4. [3] Prasongsukarn K, Abel JG, Jamieson WR, Cheung A, Russell JA, Walley KR et al. The effects of steroids on the occurrence of postoperative atrial fibrillation after coronary artery bypass grafting surgery: a prospective randomized trial. J Thorac Cardiovasc Surg 2005;130:93–8. [4] Halonen J, Halonen P, Järvinen O, Taskinen P, Auvinen T, Tarkka M et al. Corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial. JAMA 2007;297:1562–7. [5] Marik PE, Fromm R. The efficacy and dosage effect of corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a systematic review. J Crit Care 2009;24:458–63. [6] Baker WL, White CM, Kluger J, Denowitz A, Konecny CP, Coleman CI. Effect of perioperative corticosteroid use on the incidence of postcardiothoracic surgery atrial fibrillation and length of stay. Heart Rhythm 2007;4:461–8. [7] Ho KM, Tan JA. Benefits and risks of corticosteroid prophylaxis in adult cardiac surgery: a dose-response meta-analysis. Circulation 2009;119: 1853–66. [8] Whitlock RP, Chan S, Devereaux PJ, Sun J, Rubens FD, Thorlund K et al. Clinical benefit of steroid use in patients undergoing cardiopulmonary bypass: a meta-analysis of randomized trials. Eur Heart J 2008;29:2592–600. [9] Weis F, Beiras-Fernandez A, Schelling G, Briegel J, Lang P, Hauer D et al. Stress doses of hydrocortisone in high-risk patients undergoing cardiac surgery: effects on interleukin-6 to interleukin-10 ratio and early outcome. Crit Care Med 2009;37:1685–90.
BEST EVIDENCE TOPIC
that in this study after 50% enrolment, the code was broken, and the data showed that the primary outcome was satisfied (AF incidence) so the study was stopped, which can have large implications for the secondary outcomes. The role of steroid prophylaxis in high-risk cardiac patients was addressed by Weis et al. [9] in an RCT of 36 high risk who were randomized to hydrocortisone (loading dose of 100 mg before induction and followed by a continuous infusion of 10 mg/h for the first day reduced to 5 mg/h on the second day and then tapered to 3 × 20 mg on Day 3 and 3 × 10 mg on Day 4) or placebo and showed that patients in the hydrocortisone group had a lower incidence of POAF (26 vs 59%; P = 0.04) and shorter length of stay in the intensive care unit (ICU; 2 [2 of 3] vs 6 [4 of 8] days; P = 0.001). Ho and Tan [7] analysed 50 RCTs including 3323 patients and demonstrated that corticosteroid prophylaxis reduced the risk of POAF (25.1 vs 35.1%; number needed to treat, 10; relative risk 0.74; 95% confidence interval [95% CI] 0.63–0.86; P < 0.01) and length of stay in the ICU (weighted mean difference −0.37 days; 95% CI −0.21 to −0.52; P < 0.01) and hospital (weighted mean difference −0.66 days; 95% CI −0.77 to −1.25; P = 0.03) compared with placebo. Furthermore, the use of corticosteroid was not associated with an increased risk of all-cause infection (relative risk 0.93; 95% CI 0.61–1.41; P = 0.73). The authors noted that no additional benefits were found beyond a total dose of 1000 mg hydrocortisone. Similar outcomes were demonstrated by Whitlock et al. [8] in a meta-analysis of 44 trials including 3205 patients that showed that steroids can reduce POAF (relative risk 0.71; 95% CI 0.59–0.87; P = 0.001), postoperative bleeding (weighted mean difference −99.6 ml, 95% CI −149.8 to −49.3) and duration of ICU stay (weighted mean difference −0.23 days; 95% CI −0.40 to −0.07). Marik and Fromm [5] in a meta-analysis of seven studies that included 1046 patients found that the use of corticosteroids was associated with a significant reduction in the risk of POAF (odds ratio 0.42; 95% CI 0.27–0.68; P = 0.0004). The group reported significant heterogeneity between studies in terms of the corticosteroid regimen used with the total cumulative dose varying from 160 to 21 000 mg of hydrocortisone equivalents. When the low-dose (
