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Should angiotensin converting enzyme inhibitors/angiotensin II receptor antagonists be omitted before cardiac surgery to avoid postoperative vasodilation?

Department of Cardiothoracic Surgery, Harefield Hospital, Hill End Road, Harefield, UB9 6JH, Middlesex, UK

Received 29 December 2007; received in revised form 21 January 2008; accepted 24 January 2008

*Corresponding author. Tel.: +44 1895 828665; fax: +44 1895 828666.

E-mail address: drrajashahzad{at}hotmail.com (S.G. Raja).

	Abstract

Top Abstract 1. Introduction 2. Clinical scenario 3. Three-part question 4. Search strategy 5. Search outcome 6. Discussion 7. Clinical bottom line References

 
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the omission of angiotensin converting inhibitors (ACEI)/angiotensin II receptor antagonists (AIIA) before cardiac surgery leads to avoidance of postoperative vasodilation. Using the reported search 421 papers were identified. Eleven papers including three randomised controlled trials (RCTs) represented the best evidence on the subject. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study comments and weaknesses were tabulated for these. Whereas the three small RCTs on this topic provided conflicting evidence, the remaining seven large cohort and case-control studies confirmed that preoperative ACEI therapy resulted in postoperative low systemic vascular resistance (SVR)/vasoplegia. Only two small RCTs with conflicting conclusions specifically addressed the issue of omitting ACEI/AIIA before cardiac surgery. We conclude that preoperative administration of ACEI/AIIA in patients undergoing cardiac surgery contributes to lowering of SVR/vasoplegia postoperatively thereby making omission of ACEI/AIIA before cardiac surgery a rational strategy to avoid postoperative vasodilation. However, the current available evidence to support this strategy is weak.

Key Words: Angiotensin converting enzyme inhibitors; Angiotensin II receptor blockers; Systemic vascular resistance; Cardiac surgery; Evidence-based medicine

	1. Introduction

Top Abstract 1. Introduction 2. Clinical scenario 3. Three-part question 4. Search strategy 5. Search outcome 6. Discussion 7. Clinical bottom line References

 
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].

	2. Clinical scenario

Top Abstract 1. Introduction 2. Clinical scenario 3. Three-part question 4. Search strategy 5. Search outcome 6. Discussion 7. Clinical bottom line References

 
You are clerking a patient who has been admitted for elective coronary artery bypass grafting (CABG) the next day. The responsible consultant asks you to omit the morning dose of ACE inhibitor for this patient. When you ask him ‘why?’ he replies that patients who get a morning dose of ACE inhibitor before surgery need more vasoconstrictors and inotropes postoperatively. Although you omit the morning dose of ACE inhibitor for this patient, however, you are confused as none of the other consultants in the unit practice this strategy. To resolve this issue you decide to carry out a literature search.

	3. Three-part question

Top Abstract 1. Introduction 2. Clinical scenario 3. Three-part question 4. Search strategy 5. Search outcome 6. Discussion 7. Clinical bottom line References

 
In [patients prior to cardiac surgery] should [angiotensin converting enzyme inhibitors/angiotensin II receptor antagonists] be omitted to avoid [postoperative vasodilation]?

	4. Search strategy

Top Abstract 1. Introduction 2. Clinical scenario 3. Three-part question 4. Search strategy 5. Search outcome 6. Discussion 7. Clinical bottom line References

 
The English language scientific literature was reviewed primarily by searching Medline from 1950 through November 2007 using Ovid interface.

[Angiotensin converting enzyme inhibitors.mp OR exp ACE inhibitors OR Angiotensin II receptor blockers.mp OR exp Angiotensin II type 1 receptor blockers] AND [CABG.mp OR exp Thoracic surgery/OR Coronary art$ bypass.mp OR Cardiopulmonary bypass.mp OR exp Cardiovascular surgical procedures/OR exp Thoracic surgical procedures/OR exp Coronary artery bypass] AND [Vasodilation.mp OR exp vascular resistance.mp OR vasoplegi$.mp].

The ‘related articles’ function was used to broaden the search and all abstracts, studies, and citations scanned were reviewed. The reference lists of articles found through these searches were also reviewed for relevant articles.

	5. Search outcome

Top Abstract 1. Introduction 2. Clinical scenario 3. Three-part question 4. Search strategy 5. Search outcome 6. Discussion 7. Clinical bottom line References

 
A total of 421 papers were found using the search strategy. Eleven papers [2–12] including three RCTs [4, 7, 9] were deemed to represent the best evidence on the topic and are summarised in Table 1.

	6. Discussion

Top Abstract 1. Introduction 2. Clinical scenario 3. Three-part question 4. Search strategy 5. Search outcome 6. Discussion 7. Clinical bottom line References

Devbhandari et al. [3] published the results of a UK national survey to address the issue whether it is beneficial or not to stop ACEI before cardiac surgery. Questionnaires were sent to 167 currently practicing UK cardiac surgeons, out of which 105 (62%) replied back. Analysis of their responses revealed that majority (63%) were of the opinion that the use of ACEI leads to vasodilatation resulting in increased usage of fluids, inotropes and vasoconstrictors. However, there was no agreement on the issue of stopping it prior to surgery. Forty-one (39%) felt it was beneficial to stop the ACEI prior to surgery whereas 40 (38%) of them thought it was harmful to stop it. Twenty-one (20%) were of the opinion that it made no difference. Thirty-nine per cent of respondents practiced stopping the drug prior to planned operation.

Bertrand et al. [4] in a small RCT recruiting 37 patients, randomized to Group I: AIIA discontinued on the day before surgery (n=18); Group II: AIIA given 1 h before anaesthesia (n=19), showed that more severe hypotensive episodes (P<0.01), requiring vasoconstrictor treatment, occur after induction of general anaesthesia in patients chronically treated with AIIA and receiving this drug on the morning before operation, in comparison with those in whom AIIA were discontinued on the day before operation.

Mekontso-Dessap et al. [5] in a 2:1 case-control study, comparing 36 patients undergoing CABG who developed vasoplegia with 72 control patients without vasoplegia, and Carrel et al. [6] in a large prospective cohort study of 800 consecutive CABG patients, in which 115 patients developed a mild vasoplegia, and 60 patients suffered from severe vasoplegia, showed by logistic regression analysis that preoperative use of ACEI was an independent predictor for postoperative low SVR.

Piggot et al. [7] in their RCT, randomizing 40 patients with good left ventricular function to omit or continue ACEI before surgery, showed that there was no difference in hypotension on induction of anaesthesia or in the use of vasoconstrictors after CPB. Similar findings were reported by Webb et al. [9] in their double-blind RCT randomising 96 CABG patients to receive 20 mg quinapril or placebo administered for six weeks preoperatively, with the final day of treatment being the morning of surgery.

On the other hand, Boeken et al. [8] in their study of 240 patients undergoing CABG or valve surgery, divided into three matched groups (group A: pre- and postoperative ACEI; group B: ACEI only pre-, not postoperatively; group C: no ACEI), reported that there were significant differences in the intra- and postoperative need for catecholamines in groups A and B compared to C (intraop. A: 35%, B: 35%, C: 15%; postop. A: 21.2%, B: 16.2%, C: 10%) (P<0.05). In the ACEI groups (A and B) there were nine patients with a postoperative low SVR, only two cases in group C.

Deakin et al. [10] in their case-control study of 62 CABG patients also showed that preoperative ACEI therapy decreased SVR during the rewarming phase of CPB (P=0.006) and increased post-bypass vasoactive drug requirements (P<0.01).

Licker et al. [11] in their case-control study of 41 patients failed to show alteration in haemodynamic stability during cardiac surgery in patients on ACEI therapy. However, the pressor and constrictor effects of norepinephrine infusion were attenuated markedly in the ACEI group.

Tuman et al. [12] in their case-control study of 4301 patients showed that more patients on ACEI therapy exhibited low values of SVR (P=0.0002) and required at least two vasoconstrictor infusions (phenylephrine, norepinephrine, or dopamine) (P=0.0001) postoperatively.

	7. Clinical bottom line

Top Abstract 1. Introduction 2. Clinical scenario 3. Three-part question 4. Search strategy 5. Search outcome 6. Discussion 7. Clinical bottom line References

 
We conclude that preoperative administration of ACEI/AIIA in patients undergoing cardiac surgery contributes to lowering of SVR/vasoplegia postoperatively thereby making omission of ACEI/AIIA before cardiac surgery a rational strategy to avoid postoperative vasodilation. However, the current available evidence to support this strategy is weak.

	References

Top Abstract 1. Introduction 2. Clinical scenario 3. Three-part question 4. Search strategy 5. Search outcome 6. Discussion 7. Clinical bottom line References

 

1. Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact CardioVasc Thorac Surg 2003;2:405–409.[Abstract/Free Full Text]
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3. Devbhandari MP, Balasubramanian SK, Codispoti M, Nzewi OC, Prasad SU. Preoperative angiotensin-converting enzyme inhibition can cause severe post CPB vasodilation – current UK opinion. Asian Cardiovasc Thorac Ann 2004;12:346–349.[Abstract/Free Full Text]
4. Bertrand M, Godet G, Meersschaert K, Brun L, Salcedo E, Coriat P. Should the angiotensin II antagonists be discontinued before surgery? Anesth Analg 2001;92:26–30.[Abstract/Free Full Text]
5. Mekontso-Dessap A, Houël R, Soustelle C, Kirsch M, Thébert D, Loisance DY. Risk factors for post-cardiopulmonary bypass vasoplegia in patients with preserved left ventricular function. Ann Thorac Surg 2001;71:1428–1432.[Abstract/Free Full Text]
6. Carrel T, Englberger L, Mohacsi P, Neidhart P, Schmidli J. Low systemic vascular resistance after cardiopulmonary bypass: incidence, etiology, and clinical importance. J Card Surg 2000;15:347–353.[Medline]
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8. Boeken U, Feindt P, Mohan E, Zimmermann N, Micek M, Kalweit G, Gams E. Post-perfusion syndrome and disturbed microcirculation after cardiac surgery: the role of angiotensin-converting-enzyme inhibitors. Thorac Cardiovasc Surg 1999;47:347–351.[Medline]
9. Webb CM, Underwood R, Anagnostopoulos C, Bennett JG, Pepper J, Lincoln C, Collins P. The effect of angiotensin converting enzyme inhibition on myocardial function and blood pressure after coronary artery bypass surgery – a randomised study. Eur J Cardiothorac Surg 1998;13:42–48.[Abstract/Free Full Text]
10. Deakin CD, Dalrymple-Hay MJ, Jones P, Monro JL. Effects of angiotensin converting enzyme inhibition on systemic vascular resistance and vasoconstrictor requirements during hypothermic cardiopulmonary bypass. Eur J Cardiothorac Surg 1998;13:546–550.[CrossRef][Medline]
11. Licker M, Neidhart P, Lustenberger S, Valloton MB, Kalonji T, Fathi M, Morel DR. Long-term angiotensin-converting enzyme inhibitor treatment attenuates adrenergic responsiveness without altering hemodynamic control in patients undergoing cardiac surgery. Anesthesiology 1996;84:789–800.[CrossRef][Medline]
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