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Meta-Analysis
. 2019 Mar 1;3(3):CD006715.
doi: 10.1002/14651858.CD006715.pub3.

Epidural analgesia for adults undergoing cardiac surgery with or without cardiopulmonary bypass

Joanne Guay  1 , Sandra Kopp
Affiliations
Meta-Analysis

Epidural analgesia for adults undergoing cardiac surgery with or without cardiopulmonary bypass

Joanne Guay et al. Cochrane Database Syst Rev. .

Abstract

Background: General anaesthesia combined with epidural analgesia may have a beneficial effect on clinical outcomes. However, use of epidural analgesia for cardiac surgery is controversial due to a theoretical increased risk of epidural haematoma associated with systemic heparinization. This review was published in 2013, and it was updated in 2019.

Objectives: To determine the impact of perioperative epidural analgesia in adults undergoing cardiac surgery, with or without cardiopulmonary bypass, on perioperative mortality and cardiac, pulmonary, or neurological morbidity.

Search methods: We searched CENTRAL, MEDLINE, and Embase in November 2018, and two trial registers up to February 2019, together with references and relevant conference abstracts.

Selection criteria: We included all randomized controlled trials (RCTs) including adults undergoing any type of cardiac surgery under general anaesthesia and comparing epidural analgesia versus another modality of postoperative pain treatment. The primary outcome was mortality.

Data collection and analysis: We used standard methodological procedures as expected by Cochrane.

Main results: We included 69 trials with 4860 participants: 2404 given epidural analgesia and 2456 receiving comparators (systemic analgesia, peripheral nerve block, intrapleural analgesia, or wound infiltration). The mean (or median) age of participants varied between 43.5 years and 74.6 years. Surgeries performed were coronary artery bypass grafting or valvular procedures and surgeries for congenital heart disease. We judged that no trials were at low risk of bias for all domains, and that all trials were at unclear/high risk of bias for blinding of participants and personnel taking care of study participants.Epidural analgesia versus systemic analgesiaTrials show there may be no difference in mortality at 0 to 30 days (risk difference (RD) 0.00, 95% confidence interval (CI) -0.01 to 0.01; 38 trials with 3418 participants; low-quality evidence), and there may be a reduction in myocardial infarction at 0 to 30 days (RD -0.01, 95% CI -0.02 to 0.00; 26 trials with 2713 participants; low-quality evidence). Epidural analgesia may reduce the risk of 0 to 30 days respiratory depression (RD -0.03, 95% CI -0.05 to -0.01; 21 trials with 1736 participants; low-quality evidence). There is probably little or no difference in risk of pneumonia at 0 to 30 days (RD -0.03, 95% CI -0.07 to 0.01; 10 trials with 1107 participants; moderate-quality evidence), and epidural analgesia probably reduces the risk of atrial fibrillation or atrial flutter at 0 to 2 weeks (RD -0.06, 95% CI -0.10 to -0.01; 18 trials with 2431 participants; moderate-quality evidence). There may be no difference in cerebrovascular accidents at 0 to 30 days (RD -0.00, 95% CI -0.01 to 0.01; 18 trials with 2232 participants; very low-quality evidence), and none of the included trials reported any epidural haematoma events at 0 to 30 days (53 trials with 3982 participants; low-quality evidence). Epidural analgesia probably reduces the duration of tracheal intubation by the equivalent of 2.4 hours (standardized mean difference (SMD) -0.78, 95% CI -1.01 to -0.55; 40 trials with 3353 participants; moderate-quality evidence). Epidural analgesia reduces pain at rest and on movement up to 72 hours after surgery. At six to eight hours, researchers noted a reduction in pain, equivalent to a reduction of 1 point on a 0 to 10 pain scale (SMD -1.35, 95% CI -1.98 to -0.72; 10 trials with 502 participants; moderate-quality evidence). Epidural analgesia may increase risk of hypotension (RD 0.21, 95% CI 0.09 to 0.33; 17 trials with 870 participants; low-quality evidence) but may make little or no difference in the need for infusion of inotropics or vasopressors (RD 0.00, 95% CI -0.06 to 0.07; 23 trials with 1821 participants; low-quality evidence).Epidural analgesia versus other comparatorsFewer studies compared epidural analgesia versus peripheral nerve blocks (four studies), intrapleural analgesia (one study), and wound infiltration (one study). Investigators provided no data for pulmonary complications, atrial fibrillation or flutter, or for any of the comparisons. When reported, other outcomes for these comparisons (mortality, myocardial infarction, neurological complications, duration of tracheal intubation, pain, and haemodynamic support) were uncertain due to the small numbers of trials and participants.

Authors' conclusions: Compared with systemic analgesia, epidural analgesia may reduce the risk of myocardial infarction, respiratory depression, and atrial fibrillation/atrial flutter, as well as the duration of tracheal intubation and pain, in adults undergoing cardiac surgery. There may be little or no difference in mortality, pneumonia, and epidural haematoma, and effects on cerebrovascular accident are uncertain. Evidence is insufficient to show the effects of epidural analgesia compared with peripheral nerve blocks, intrapleural analgesia, or wound infiltration.

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Conflict of interest statement

Joanne Guay: none known

Sandra Kopp: none known

Figures

1
1
Study flow diagram for update in 2019.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Meta‐regression. Effect of epidural analgesia on tracheal extubation versus year of publication. The effect was more evident in older trials: P value for the meta‐regression effect size versus year of publication was < 0.0001.
1.1
1.1. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 1 Mortality at 0 to 30 days.
1.2
1.2. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 2 Mortality at 6 months.
1.3
1.3. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 3 Mortality at 1 year.
1.4
1.4. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 4 Myocardial infarction (0 to 30 days).
1.5
1.5. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 5 Respiratory complications: respiratory depression (0 to 30 days).
1.6
1.6. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 6 Respiratory complications: pneumonia (0 to 30 days).
1.7
1.7. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 7 Atrial fibrillation or flutter within 2 weeks.
1.8
1.8. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 8 Neurological complications: cerebrovascular accident (0 to 30 days).
1.9
1.9. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 9 Neurological complications: epidural haematoma (0 to 30 days).
1.10
1.10. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 10 Duration of tracheal intubation.
1.11
1.11. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 11 Duration of tracheal intubation in hours (for studies for which means and standard deviations could be extracted).
1.12
1.12. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 12 Pain at rest at 6 to 8 hours after surgery.
1.13
1.13. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 13 Pain at rest at 6 to 8 hours: data available as means and standard deviations.
1.14
1.14. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 14 Pain on movement/coughing at 6 to 8 hours.
1.15
1.15. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 15 Pain on movement/coughing at 6 to 8 hours: data available as means and standard deviations.
1.16
1.16. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 16 Pain at rest at 24 hours after surgery.
1.17
1.17. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 17 Pain at rest at 24 hours: data available as means and standard deviations.
1.18
1.18. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 18 Pain scores on movement/coughing at 24 hours.
1.19
1.19. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 19 Pain scores on movement/coughing at 24 hours: data available as means and standard deviations.
1.20
1.20. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 20 Pain at rest at 48 hours after surgery.
1.21
1.21. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 21 Pain at rest at 48 hours after surgery: data available as means and standard deviations.
1.22
1.22. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 22 Pain scores on movement/coughing at 48 hours.
1.23
1.23. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 23 Pain scores on movement/coughing at 48 hours: data available as means and standard deviations.
1.24
1.24. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 24 Pain at rest at 72 hours after surgery.
1.25
1.25. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 25 Pain at rest at 72 hours after surgery: data available as means and standard deviations.
1.26
1.26. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 26 Pain scores on movement/coughing at 72 hours.
1.27
1.27. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 27 Pain scores on movement/coughing at 72 hours: data available as means and standard deviations.
1.28
1.28. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 28 Hypotension or vasopressor bolus during surgery.
1.29
1.29. Analysis
Comparison 1 Epidural analgesia compared with systemic analgesia, Outcome 29 Needed vasopressor/inotropic infusion.
2.1
2.1. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 1 Mortality at 0 to 30 days.
2.2
2.2. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 2 Myocardial infarction (0 to 30 days).
2.3
2.3. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 3 Neurological complications: cerebrovascular accident (0 to 30 days).
2.4
2.4. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 4 Neurological complications: epidural haematoma (0 to 30 days).
2.5
2.5. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 5 Duration of tracheal intubation (hours).
2.6
2.6. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 6 Pain scores at rest at 6 to 8 hours.
2.7
2.7. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 7 Pain scores on movement/coughing at 6 to 8 hours.
2.8
2.8. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 8 Pain at rest at 24 hours.
2.9
2.9. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 9 Pain on movement/coughing at 24 hours.
2.10
2.10. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 10 Pain at rest at 48 hours.
2.11
2.11. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 11 Pain at rest on movement/coughing at 48 hours.
2.12
2.12. Analysis
Comparison 2 Epidural analgesia compared with peripheral nerve blocks, Outcome 12 Hypotension or need for vasopressor.
3.1
3.1. Analysis
Comparison 3 Epidural analgesia compared with intrapleural analgesia, Outcome 1 Myocardial infarction (0 to 30 days).
3.2
3.2. Analysis
Comparison 3 Epidural analgesia compared with intrapleural analgesia, Outcome 2 Neurological complications: epidural haematoma (0 to 30 days).
3.3
3.3. Analysis
Comparison 3 Epidural analgesia compared with intrapleural analgesia, Outcome 3 Duration of tracheal intubation (hours).
3.4
3.4. Analysis
Comparison 3 Epidural analgesia compared with intrapleural analgesia, Outcome 4 Pain scores at rest at 6 hours.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Kundu 2007 {published data only (unpublished sought but not used)}
    1. Kundu RK, Beg AK, Hossain S, Haque N, Mahafuddoza, Chowdury A. Comparative study of haemodynamic status and arrhythmia between combined epidural with general anaesthesia and general anaesthesia alone in off‐pump coronary artery bypass (OPCAB) surgery. Journal of Bangladesh College of Physicians and Surgeons 2008;26:116‐20.
Kunstyr 2001 {published data only (unpublished sought but not used)}
    1. Kunstýř J, Stříteský M, Krištof J, Škrovina B, Kotulák T. Postoperative analgesia in cardiac surgery [Pooperační analgezie v kardiochirurgii]. Anesteziologie a Neodkladna Pece 2001;12(4):191‐4.
Lenkutis 2009 {published data only (unpublished sought but not used)}
    1. Lenkutis T, Benetis R, Sirvinskas E, Raliene L, Judickaite L. Effects of epidural anesthesia on intrathoracic blood volume and extravascular lung water during on‐pump cardiac surgery. Perfusion 2009;24(4):243‐8. [DOI: 10.1177/0267659109348724; PUBMED: 19808745] - DOI - PubMed
Liem 1992 {published data only (unpublished sought but not used)}
    1. Liem TH, Booij LH, Gielen MJ, Hasenbos MA, Egmond J. Coronary artery bypass grafting using two different anesthetic techniques: part 3 ‐ adrenergic responses. Journal of Cardiothoracic and Vascular Anesthesia 1992;6(2):162‐7. [PUBMED: 1533167] - PubMed
    1. Liem TH, Booij LH, Hasenbos MA, Gielen MJ. Coronary artery bypass grafting using two different anesthetic techniques: part 1 ‐ hemodynamic results. Journal of Cardiothoracic & Vascular Anesthesia 1992;6(2):148‐55. [PUBMED: 1533165] - PubMed
    1. Liem TH, Hasenbos MA, Booij LH, Gielen MJ. Coronary artery bypass grafting using two different anesthetic techniques: part 2 ‐ postoperative outcome. Journal of Cardiothoracic and Vascular Anesthesia 1992;6(2):156‐61. [PUBMED: 1533166] - PubMed
Loick 1999 {published data only (unpublished sought but not used)}
    1. Loick HM, Mollhoff T, Erren M, Berendes E, Rolf N, Aken H. Thoracic epidural anesthesia lowers catecholamine and YNF alpha release after CABG in humans. Anesthesia and Analgesia. Orlando, FL; March 7‐11, 1998: International Anesthesia Research Society; 72nd Clinical and Scientific Congress: Cardiovascular Anesthesia, 1998; Vol. 86, issue 2S:81S. [DOI: 10.1097/00000539-199802001-00081] - DOI
    1. Loick HM, Schmidt C, Aken H, Junker R, Erren M, Berendes E, et al. High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting. Anesthesia and Analgesia 1999;88(4):701‐9. [PUBMED: 10195508] - PubMed
Lundstrom 2005 {published data only (unpublished sought but not used)}
    1. Lundstrom LH, Nygard E, Hviid LB, Pedersen FM, Ravn J, Aldershvile J, et al. The effects of thoracic epidural analgesia on the occurence of late postoperative hypoxemia in patients undergoing elective coronary bypass surgery: a randomized controlled trial. Chest 2005;128(3):1564‐70. [PUBMED: 16162759] - PubMed
Lyons 1998 {published data only (unpublished sought but not used)}
    1. Lyons FM, Riedel BJ, Haw M, Royston D. Myocardial protection during coronary artery bypass graft surgery with thoracic epidural analgesia. British Journal of Anaesthesia. 1980; Vol. 80, issue Suppl 1:55‐56.
Mehta 1998 {published data only (unpublished sought but not used)}
    1. Mehta Y, Swaminathan M, Mishra Y, Trehan N. A comparative evaluation of intrapleural pain relief after minimally invasive direct coronary artery bypass surgery. Journal of Cardiothoracic and Vascular Anesthesia 1998;12(2):162‐5. [PUBMED: 9583546 ; PUBMED: 9583546] - PubMed
Mehta 2008 {published and unpublished data}
    1. Mehta Y. Information on our trial. Email to: J Guay, 2 April 2018.
    1. Mehta Y, Arora D, Sharma KK, Mishra Y, Wasir H, Trehan N. Comparison of continuous thoracic epidural and paravertebral block for postoperative analgesia after robotic‐assisted coronary artery bypass surgery. Annals of Cardiac Anaesthesia 2008;11(2):91‐6. [DOI: 10.4103/0971-9784.41576; PUBMED: 18603748] - DOI - PubMed
Mehta 2010 {published data only (unpublished sought but not used)}
    1. Mehta Y, Vats M, Sharma M, Arora R, Trehan N. Thoracic epidural analgesia for off‐pump coronary artery bypass surgery in patients with chronic obstructive pulmonary disease. Annals of Cardiac Anaesthesia 2010;13(3):224‐30. [PUBMED: 20826963] - PubMed
Mishra 2004 {published data only (unpublished sought but not used)}
    1. Mishra S Chauhan S, Kiran U, Bhan A, Eisai AK. Does addition of epidural analgesia enhance "Fast tracking" in routine CABG patients?. Indian Journal of Thoracic and Cardiovascular Surgery. 2004; Vol. 20, issue Jan‐Mar:6, Abstract 14.
Moore 1995 {published data only (unpublished sought but not used)}
    1. Moore CM, Cross MH, Desborough JP, Burrin JM, Macdonald IA, Hall GM. Hormonal effects of thoracic extradural analgesia for cardiac surgery. British Journal of Anesthesia 1995;75(4):387‐93. [PUBMED: 7488474] - PubMed
Nagaraja 2018 {published data only}
    1. Nagaraja PS, Ragavendran S, Singh NG, Asai O, Bhavya G, Manjunath N, et al. Comparison of continuous thoracic epidural analgesia with bilateral erector spinae plane block for perioperative pain management in cardiac surgery. Annals of Cardiac Anaesthesia 2018;21(3):323‐7. [CENTRAL: 01629440; DOI: 10.4103/aca.ACA_16_18; EMBASE: 623313977; MEDLINE: ] - DOI - PMC - PubMed
Neskovic 2013 {published and unpublished data}
    1. Neskovic V. Information on our trial. Email to: J Guay, 20 March 2018.
    1. Neskovic V. Information on our trial. Email to: J Guay, 24 March 2018.
    1. Neskovic V, Milojevic P, Unic‐Stojanovic D, Slavkovic Z. Blood transfusion in cardiac surgery ‐ does the choice of anesthesia or type of surgery matter?. Vojnosanitetski Pregled 2013;70(5):439‐44. [DOI: 10.2298/VSP1305439N; PUBMED: 23789281] - DOI - PubMed
Nygard 2004 {published data only (unpublished sought but not used)}
    1. Nygård E, Sørensen LH, Hviid LB, Pedersen FM, Ravn J, Thomassen L, et al. Effects of amiodarone and thoracic epidural analgesia on atrial fibrillation after coronary artery bypass grafting. Journal of Cardiothoracic Vascular Anesthesia 2004;18(6):709‐14. [DOI: 10.1053/j.jvca.2004.08.006; PUBMED: 15650978] - DOI - PubMed
Obersztyn 2018 {published data only}
    1. Obersztyn M, Trejnowska E, Nadziakiewicz P, Knapik P. Evaluation of thoracic epidural analgesia in patients undergoing coronary artery bypass surgery ‐ a prospective randomized trial. Kardiochirurgia I Torakochirurgia Polska 2018;15(2):72‐8. [DOI: 10.5114/kitp.2018.76471; MEDLINE: ] - DOI - PMC - PubMed
Onan 2011 {published data only (unpublished sought but not used)}
    1. Onan IS, Onan B, Korkmaz AA, Oklu L, Kilickan L, Gonca S, et al. Effects of thoracic epidural anesthesia on flow and endothelium of internal thoracic artery in coronary artery bypass graft surgery. Journal of Cardiothoracic and Vascular Anesthesia 2011;25(6):1063‐70. [DOI: 10.1053/j.jvca.2011.06.004; PUBMED: 21835638] - DOI - PubMed
Onan 2013 {published data only (unpublished sought but not used)}
    1. Onan B, Onan IS, Kilickan L, Sanisoglu I. Effects of epidural anesthesia on acute and chronic pain after coronary artery bypass grafting. Journal of Cardiac Surgery 2013;28(3):248‐53. [DOI: 10.1111/jocs.12086; PUBMED: 23461638] - DOI - PubMed
Palomero 2008 {published and unpublished data}
    1. Palomero MA. Information on our trial. Email to: J Guay, 3 April 2018.
    1. Palomero Rodriguez MA. Information on our trial. Email to: J Guay, 21 March 2018.
    1. Palomero Rodriguez MA, Suarez Gonzalo L, Villar Alvarez F, Varela Crespo C, Moreno Gomez Limon I, Criado Jimenez A. Thoracic epidural anesthesia decreases C‐reactive protein levels in patients undergoing elective coronary artery bypass graft surgery with cardiopulmonary bypass. Minerva Anestesiologica 2008;74(11):619‐26. [PUBMED: 18971890] - PubMed
Petrovski 2006 {published data only}
    1. Petrovski V, Slavevski D, Stoicovski E, Belostotskii V, Hristov N, Mitrev Z. The advantages of combined epidural and general anesthesia vs. conventional general anesthesia in off pump coronary artery bypass surgery. Anesthesia and Analgesia. May 1, 2006: Society of Cardiovascular Anesthesiologists 28th AnnualMeeting and Workshops, 2006:SCA68.
Priestley 2002 {published data only (unpublished sought but not used)}
    1. Priestley MC, Cope L, Halliwell R, Gibson P, Chard RB, Skinner M, et al. Thoracic epidural anesthesia for cardiac surgery: the effects on tracheal intubation time and length of hospital stay. Anesthesia and Analgesia 2002;94(2):275–82. [PUBMED: 11812684] - PubMed
Rein 1989 {published data only (unpublished sought but not used)}
    1. Rein KA, Stenseth R, Myhre HO, Levang OW, Krogstad A. The influence of thoracic epidural analgesia on transcapillary fluid balance in subcutaneous tissue. A study in patients undergoing aortocoronary bypass surgery. Acta Anaesthesiologica Scandinavica 1989;33(1):79‐83. [PUBMED: 2644753] - PubMed
Royse 2003 {published and unpublished data}
    1. Royse C. Information on our trial. Email to: J Guay, 16 March 2018.
    1. Royse C, Remedios C, Royse A. High thoracic epidural analgesia reduces the risk of long‐term depression in patients undergoing coronary artery bypass surgery. Annals of Thoracic and Cardiovascular Surgery 2007;13(1):32‐5. [PUBMED: 17392668 ] - PubMed
    1. Royse C, Royse A, Soeding P, Blake D, Pang J. Prospective randomized trial of high thoracic epidural analgesia for coronary artery bypass surgery. Annals of Thoracic Surgery 2003;75(1):93‐100. [PUBMED: 12537199] - PubMed
Scott 2001 {published data only (unpublished sought but not used)}
    1. Scott NB, Turfrey DJ, Ray DAA, Nzewi O, Sutcliffe NP, Lal AB, et al. A prospective randomized study of the potential benefits of thoracic epidural anesthesia and analgesia in patients undergoing coronary artery bypass grafting. Anesthesia and Analgesia 2001;93(3):528‐35. [PUBMED: 11524314] - PubMed
    1. Turfrey D, Ray D. The effect of thoracic epidural analgesia on postoperative complications after cardiac surgery ‐ a prospective study. British Journal of Anaesthesia. 1998; Vol. 80, issue Suppl 2:17.
Sen 2017 {published data only (unpublished sought but not used)}
    1. Sen AC, Rajan S, Balachandran R, Kumar L, Nair SG. Comparison of perioperative thoracic epidural fentanyl with bupivacaine and intravenous fentanyl for analgesia in patients undergoing coronary artery bypass grafting surgery. Anesthesia, Essays and Researches 2017;11(1):105‐9. [DOI: 10.4103/0259-1162.186613; PUBMED: 28298766] - DOI - PMC - PubMed
Sharma 2010 {published data only (unpublished sought but not used)}
    1. Sharma M, Mehta Y, Sawhney R, Vats M, Trehan N. Thoracic epidural analgesia in obese patients with body mass index of more than 30 kg/m² for off pump coronary artery bypass surgery. Annals Cardiac Anaesthesia 2010;13(1):28‐33. [DOI: 10.4103/0971-9784.58831; PUBMED: 20075532 ] - DOI - PubMed
Stenseth 1994 {published data only (unpublished sought but not used)}
    1. Stenseth R. Information on our trial. Email to: J Guay, 28 May 2018.
    1. Stenseth R, Berg EM, Bjella L, Christensen O, Levang OW, Gisvold SE. Effects of thoracic epidural analgesia on coronary hemodynamics and myocardial metabolism in coronary artery bypass surgery. Journal of Cardlothoracic and Vascular Anesthesta 1995;9(5):503‐9. [PUBMED: 8547549] - PubMed
    1. Stenseth R, Bjella L, Berg EM, Christensen O, Levang OW, Gisvold SE. Thoracic epidural analgesia in aortocoronary bypass surgery. I: haemodynamic effects. Acta Anaesthesiologica Scandinavica 1994;38(8):826‐33. [PUBMED: 7887106] - PubMed
    1. Stenseth R, Bjella L, Berg EM, Christensen O, Levang OW, Gisvold SE. Thoracic epidural analgesia in aortocoronary bypass surgery. II: effects on the endocrine metabolic response. Acta Anaesthesiologica Scandinavica 1994;38(8):834‐9. [PUBMED: 7887107 ] - PubMed
Stenseth 1996 {published data only (unpublished sought but not used)}
    1. Stenseth R. Information on our trial. Email to: J Guay, 28 May 2018.
    1. Stenseth R, Bjella L, Berg EM, Christensen O, Levang OW, Gisvold SE. Effects of thoracic epidural analgesia on pulmonary function after coronary artery bypass surgery. European Journal of Cardiothoracic Surgery 1996;10(10):859‐65. [PUBMED: 8911839] - PubMed
Stritesky 2006 {published data only}
    1. Stritesky M, Rubes D, Semrad M, Lips M. A comparison of haemodynamic changes using thoracic epidural anesthesia versus standard balanced anaesthesia during on‐pump coronary artery bypass grafting. Anesteziologie a Intenzivni Medicina 2006;17:138‐44.
Svircevic 2011 {published data only (unpublished sought but not used)}
    1. Svircevic V, Nierich AP, Moons KG, Diephuis JC, Ennema JJ, Brandon Bravo Bruinsma GJ, et al. Thoracic epidural anesthesia for cardiac surgery: a randomized trial. Anesthesiology 2011;114(2):262‐70. [DOI: 10.1097/ALN.0b013e318201d2de; PUBMED: 21239976 ] - DOI - PubMed
Tenenbein 2008 {published and unpublished data}
    1. Kowalski S. Information on our trial. Email to: J Guay, 27 March 2018.
    1. Tenenbein PK, Debrouwere R, Maguire D, Duke PC, Muirhead B, Enns J, et al. Thoracic epidural analgesia improves pulmonary function in patients undergoing cardiac surgery. Canadian Journal of Anaesthesia 2008;55(6):344‐50. [DOI: 10.1007/BF03021489; PUBMED: 18566197] - DOI - PubMed
Tenling 1999 {published data only (unpublished sought but not used)}
    1. Tenling A, Joachimsson P‐O, Tyden H, Hedenstierna G. Thoracic epidural analgesia as an adjunct to general anaesthesia for cardiac surgery. Effects on pulmonary mechanics. Acta Anaesthesiologica Scandinavica 2000;44(9):1071‐6. [PUBMED: 11028725] - PubMed
    1. Tenling A, Joachimsson PO, Tydén H, Wegenius G, Hedenstierna G. Thoracic epidural anesthesia as an adjunct to general anesthesia for cardiac surgery: effects on ventilation‐perfusion relationships. Journal of Cardiothoracic and Vascular Anesthesia 1999;13(3):258‐64. [PUBMED: 10392674] - PubMed
Usui 1990 {published data only (unpublished sought but not used)}
    1. Usui K, Yasuda A, Tadokoro M, Kon‐nai T, Shoji Y, Yoshida S. Epidural morphine as a sedative after open heart surgery: in cases of coronary artery bypass graft. Kyobu Geka ‐ Japanese Journal of Thoracic Surgery 1990;43(1):19‐23. [PUBMED: 2304293] - PubMed
Volk 2003 {published data only}
    1. Volk T, Dopfmer UR, Schmutzler M, Rimpau S, Schnitzler H, Konertz W, et al. Stress induced IL‐10 does not seem to be essential for early monocyte deactivation following cardiac surgery. Cytokine 2003;24(6):237‐43. [DOI: 10.1016/S1043-4666(03)00090-5; PUBMED: 14609565] - DOI - PubMed
Yang 1996 {published data only (unpublished sought but not used)}
    1. Yang C, Deng S. Effects of epidural block combined with general anesthesia on stress response during cardiopulmonary bypass. Chinese Journal of Anesthesiology 1996;16:492.
Yilmaz 2007 {published data only (unpublished sought but not used)}
    1. Yilmaz C, Çoruh T, Yapıcı N, Yılmaz Ö, Maçika H, Aykaç Z. The effects of preemptive analgesia with thoracic epidural on respiratory function tests, pain scores and hemodynamics in coronary artery bypass graft surgery. Anestezi Dergisi 2007;15:20‐7.
Yung 1997 {published data only (unpublished sought but not used)}
    1. Yung MC, Chang Y, Lai ST, Tsou MY, Chan KH. Improved postoperative pain relief via preemptive analgesia in relation to heart rate variability for coronary artery bypass grafting: a preliminary report. Zhonghua Yi Xue Za Zhi 1997;60(1):28‐35. [PUBMED: 9316325] - PubMed
Zawar 2015 {published data only (unpublished sought but not used)}
    1. Zawar BP, Mehta Y, Juneja R, Arora D, Raizada A, Trehan N. Nonanalgesic benefits of combined thoracic epidural analgesia with general anesthesia in high risk elderly off pump coronary artery bypass patients. Annals of Cardiac Anaesthesia 2015;18(3):385‐91. [DOI: 10.4103/0971-9784.159810; PUBMED: 26139745] - DOI - PMC - PubMed
Zhou 2010 {published data only (unpublished sought but not used)}
    1. Zhou X, Hong C. Clinical study of postoperative thoracic epidural block in cardiac thoracic surgery [胸部硬膜外阻滞在心脏开胸手术术后镇痛的临床研究.]. Sichan Medical Journal 2010;31(3):344‐6. [10.16252/j .cnki .issn1004‐0501‐2010.03.021]

References to studies excluded from this review

Amat‐Santos 2012 {published data only}
    1. Amat‐Santos IJ, Dumont E, Villeneuve J, Doyle D, Rheault M, Lavigne D, et al. Effect of thoracic epidural analgesia on clinical outcomes following transapical transcatheter aortic valve implantation. Heart (British Cardiac Society) 2012;98(21):1583‐90. [DOI: 10.1136/heartjnl-2012-302185; PUBMED: 22791654] - DOI - PubMed
Anderson 2005 {published data only}
    1. Anderson RE, Ehrenberg J, Barr G, Brismar K, Owall A, Alserius T, et al. Effects of thoracic epidural analgesia on glucose homeostasis after cardiac surgery in patients with and without diabetes mellitus. European Journal of Anaesthesiology 2005;22(7):524‐9. [PUBMED: 16045142] - PubMed
Casalino 2006 {published data only}
    1. Casalino S, Mangia F, Stelian E, Novelli E, Diena M, Tesler UF. High thoracic epidural anesthesia in cardiac surgery: risk factors for arterial hypotension. Texas Heart Institute Journal 2006;33(2):148‐53. [PUBMED: 16878616] - PMC - PubMed
Chae 1998 {published data only}
    1. Chae BK, Lee HW, Sun K, Choi YH, Kim HM. The effect of combined epidural and light general anesthesia on stress hormones in open heart surgery patients. Surgery Today 1998;28(7):727‐31. [PUBMED: 9697266] - PubMed
Chakravarthy 2005 {published data only}
    1. Chakravarthy M, Thimmangowda P, Krishnamurthy J, Nadiminti S, Jawali V. Thoracic epidural anesthesia in cardiac surgical patients: a prospective audit of 2113 cases. Journal of Cardiothoracic and Vascular Anesthesia 2005;19(1):44‐8. [PUBMED: 15747268] - PubMed
Crescenzi 2009 {published data only}
    1. Crescenzi G, Landoni G, Monaco F, Bignami E, Luca M, Frau G, et al. Epidural anesthesia in elderly patients undergoing coronary artery bypass graft surgery. Journal of Cardiothoracic and Vascular Anesthesia 2009;23(6):807‐12. [PUBMED: 19376734] - PubMed
Djaiani 2000 {published data only}
    1. Djaiani G. Thoracic epidural anesthesia as an adjunct to general anesthesia for cardiac surgery: effects on ventilation‐perfusion relationships. Journal of Cardiothoracic and Vascular Anesthesia 2000;14(3):359‐60. [DOI: 10.1053/cr.2000.5816; PUBMED: 10890498] - DOI - PubMed
El‐Morsy 2012a {published data only}
    1. El‐Morsy GZ, El‐Deeb A, El‐Desouky T, Elsharkawy AA, Elgamal MA. Can thoracic paravertebral block replace thoracic epidural block in pediatric cardiac surgery? A randomized blinded study. Annals of Cardiac Anaesthesia 2012;15(4):259‐63. [DOI: 10.4103/0971-9784.101848; PUBMED: 23041682] - DOI - PubMed
Jideus 2001 {published data only}
    1. Jideus L, Joachimsson PE, Stridsberg M, Ericson M, Tyden H, Nilsson L, et al. Thoracic epidural anesthesia does not influence the occurrence of postoperative sustained atrial fibrillation. Annals of Thoracic Surgery 2001;72(1):65‐71. [PUBMED: 11465233] - PubMed
Joachimsson 1989 {published data only}
    1. Joachimsson PO, Nystrom SO, Tyden H. Early extubation after coronary artery surgery in efficiently rewarmed patients: a postoperative comparison of opioid anesthesia versus inhalational anesthesia and thoracic epidural analgesia. Journal of Cardiothoracic Anesthesia 1989;3(4):444‐54. [PUBMED: 2520917] - PubMed
Kaunienė 2016 {published data only (unpublished sought but not used)}
    1. Kaunienė A, Urbonaitė A, Lenkutis T, Širvinskas E, Švagždienė M. Effects of combined anesthesia on kidney function after coronary artery bypass graft surgery with cardiopulmonary bypass [Kombinuotos anestezijos poveikis inkstu funkcijaipo vainkinu arteriju suntavimo, naudojant dirtinekraujo apytaka]. Biomedicine 2016;26(4):31‐4. [DOI: 10.5200/sm-hs.2016.054] - DOI
Kessler 2002 {published data only}
    1. Kessler P, Neidhart G, Lischke V, Bremerich DH, Aybek T, Dogan S, et al. Coronary bypass operation with complete median sternotomy in awake patients with high thoracic peridural anesthesia [Koronare bypassoperation mit kompletter medianer sternotomie am wachen patienten in hoher thorakaler periduralanasthesie]. Der Anaesthesist 2002;51(7):533‐8. [PUBMED: 12243038] - PubMed
Kessler 2005 {published data only}
    1. Kessler P, Aybek T, Neidhart G, Dogan S, Lischke V, Bremerich DH, et al. Comparison of three anesthetic techniques for off‐pump coronary artery bypass grafting: general anesthesia, combined general and high thoracic epidural anesthesia, or high thoracic epidural anesthesia alone. Journal of Cardiothoracic and Vascular Anesthesia 2005;19(1):32‐9. [PUBMED: 15747266] - PubMed
Kunstyr 2008 {published data only}
    1. Kunstyr J, Klein A, Lindner J, Rubes D, Blaha J, Jansa P, et al. Use of high‐thoracic epidural analgesia in pulmonary endarterectomy: a randomized feasibility study. Heart Surgery Forum 2008;11(4):E202‐8. [DOI: 10.1532/HSF98.2008i036; PUBMED: 18782697] - DOI - PubMed
Kurtoglu 2009 {published data only}
    1. Kurtoglu M, Ates S, Bakkaloglu B, Besbas S, Duvan I, Akdas H, et al. Epidural anesthesia versus general anesthesia in patients undergoing minimally invasive direct coronary artery bypass surgery. Anadolu Kardiyoloji Dergisi 2009;9(1):54‐8. [PUBMED: 19196575] - PubMed
Lagunilla 2006 {published data only (unpublished sought but not used)}
    1. Lagunilla J, Garcia‐Bengochea JB, Fernandez AL, Alvarez J, Rubio J, Rodriguez J, et al. High thoracic epidural blockade increases myocardial oxygen availability in coronary surgery patients. Acta Anaesthesiologica Scandinavica 2006;50(7):780‐6. [PUBMED: 16879458] - PubMed
Liang 2012 {published data only}
    1. Liang Y, Chu H, Zhen H, Wang S, Gu M. A prospective randomized study of intraoperative thoracic epidural analgesia in off‐pump coronary artery bypass surgery. Journal of Anesthesia 2012;26(3):393‐9. [DOI: 10.1007/s00540-012-1325-6; PUBMED: 22274169] - DOI - PubMed
Liem 1998 {published data only}
    1. Liem TH, Williams JP, Hensens AG, Singh SK. Minimally invasive direct coronary artery bypass procedure using a high thoracic epidural plus general anesthetic technique. Journal of Cardiothoracic and Vascular Anesthesia 1998;12(6):668‐72. [PUBMED: 9854665] - PubMed
Martinez 2012 {published data only}
    1. Martinez A, Oslaida M, Jimenez Paneque R, Cordero Escobar I, Cruz Bouza R, Cabrera Pratts A. Neuroaxial anesthesia methods combined with general anesthesia for beating heart surgery. British Journal of Anaesthesia. 2012; Vol. 108 (S2):ii215‐ii277. [DOI: 10.1093/bja/aer485] - DOI
Novikov 2011 {published data only}
    1. Novikov OV, Guleshov VA, Morozov UA, Komarov RN, Iavorovskij AG. Metabolic disorders as a result of intestine ischemia and its defensive factors due to aorta prosthetics and cross‐clamping of descending aorta before celiac trunk [Метаболические нарушения как результат повреждения кишечника и фаторы его защиты при операциях протезироьания аорты с уровнем пережатия выше чревного ствола]. Anesteziologiia i Reanimatologiia 2011;56(6):4‐7. [PUBMED: 22379904]
Olivier 2005 {published data only}
    1. Olivier JF, Le N, Choinière JL, Prieto I, Basile F, Hemmerling T. Comparison of three different epidural solutions in off‐pump cardiac surgery: pilot study. British Journal of Anaesthesia 2005;95(5):685‐91. [PUBMED: 16183682] - PubMed
Orsolya 2015 {published data only}
    1. Orsolya M, Attila‐Zoltan M, Gherman V, Zaharie F, Bolboaca S, Chira C, et al. The effect of anaesthetic management on neutrophil gelatinase associated lipocalin (NGAL) levels after robotic surgical oncology. Journal of B.U.ON. 2015;20(1):317‐24. [PUBMED: 25778333] - PubMed
Ortega 2011 {published data only}
    1. Ortega RH, Alfonso OG, Menéndez PA, Font IM, Rodríguez JM, Martínez JM, et al. Postoperative analgesic efficacy of epidural morphine in myocardial bypass surgery [Efficacia analgesica postoperatoria de la morfina epidural en la cirurgia de revascularizacion miocardica]. Corsalud 2011;3(1):15‐25.
Ovezov 2011 {published data only}
    1. Obezov АМ, Кim SU, Danilin АМ, Prokoshev РV, Charenco DV. Combined inhalation and epidural anaesthesia, during aortocoronary bypass surgery on beating heart [Сочетанная ингаляционно‐эпидуральная анстезия при прямой реваскляризции миокарда на работающем сердце]. Anesteziologiia i Reanimatologiia 2011;54(6):8‐12. [PUBMED: 22379905] - PubMed
Rao 2016 {published data only}
    1. Rao TR, Dal A, Dronumraju A, Kumar KK, J Ibrahim J. Coronary artery bypass surgery in "awake" patient: a prospective study. International Journal of Scientific Study 2016;3(10):18‐22. [DOI: 10.17354/ijss/2016/04] - DOI
Salman 2012 {published data only}
    1. Salman N, Serter FT, Uçar HI, Günaydin S, Yorgancioğlu AC. Comparison between intravenous and thoracic epidural analgesia in single coronary artery bypass graft surgery. Turkish Journal of Medical Sciences 2012;42(4):581‐9. [DOI: 10.3906/sag-1107-9] - DOI
Salvi 2004 {published data only}
    1. Salvi L, Sisillo E, Brambillasca C, Juliano G, Salis S, Marino MR. High thoracic epidural anesthesia for off‐pump coronary artery bypass surgery. Journal of Cardiothoracic and Vascular Anesthesia 2004;18(3):256‐62. [PUBMED: 15232802] - PubMed
Schmidt 2005 {published data only}
    1. Schmidt C, Hinder F, Aken H, Theilmeier G, Bruch C, Wirtz SP, et al. The effect of high thoracic epidural anesthesia on systolic and diastolic left ventricular function in patients with coronary artery disease. Anesthesia and Analgesia 2005;100(6):1561‐9. [DOI: 10.1213/01.ANE.0000154963.29271.36; PUBMED: 15920175] - DOI - PubMed
Stenger 2013 {published data only}
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References to ongoing studies

CTRI/2012/04/002608 {published data only}
    1. Prakash B. Non‐analgesic benefits of combined thoracic epidural analgesia in elderly off‐pump coronary artery bypass grafting patients. World Health Organization Clinical Trials Registry Platform. date first received 27 April 2012. [CTRI/2012/04/002608]
CTRI/2018/05/013902 {published data only}
    1. Sen C. A study of central and mixed venous oxygen saturation with outcomes in open heart surgery patients between two groups: conventional general anaesthesia and combined with perioperative thoracic epidural or intravenous analgesia. World Health Organization Clinical Trials Registry Platform. date first received 15 May 2018. [CTRI/2018/05/013902]
NCT03719248 {published data only}
    1. Elgebaly AS. Thoracic epidural reduces risks of increased left ventricular mass index during coronary artery bypass graft surgery. World Health Organization Clinical Trials Registry Platform. Accessed 25 October 2018. [NCT03719248]

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References to other published versions of this review

Svircevic 2007
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