Perioperative use of angiotensin blockade

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Perioperative use of angiotensin blockade Dr Fiona Chow on behalf of A/Prof Ian Fraser Epworth HealthCare 1 surgical_operation_with_surgeons_and_nurses_royalty_free_clipart_picture_100616-172691-620048.jpg

Avoid prolonged intraoperative hypotension (vasoplegia) Reduce post-operative AF? Reduces acute kidney injury? Continuing ACEI/A2RA may be associated with mortality in vascular surgery?* Risk of hypertensive episodes Angiotensin blockade may be cardioprotective RAAS activation in surgery can mediate microvascular and ischaemic injury No effect on acute kidney injury? Continuing ACEI/A2RA may be associated with mortality in noncardiac surgery?* PROS OF STOPPING ACEI or A2RA CONS OF STOPPING ACEI or A2RA Epworth HealthCare 2 *observation study level of evidence http://www.clipartkid.com/balance-with-empty-pans-clipart-etc-zkfpyu-clipart/

Patients on angiotensin blockade are higher risk for surgery Diabetic Left ventricular dysfunction Hypertensive Older Proteinuric/albuminuric Epworth HealthCare 3

The problem with knowing whether to stop angiotensin blockade or not: a lack of randomized controlled trials Epworth HealthCare 4

American College of Cardiology Guidelines Epworth HealthCare 5

Pharmacology Epworth HealthCare 6 http://www.anesthesiologynews.com/review-articles/article/02-16/angiotensin-axis-blocking-drugs-in-the-perioperative-period/35357/ses=ogst

Pharmacology Epworth HealthCare 7

Pharmacology Table 1. Half-life and Duration of Antihypertensive Effect of Commonly Used ACEIs and ARBs ACEI t 1/2, h a,b h c,d Duration of Antihypertensive Effect, Captopril 1.7 6-10 Enalapril 11 18-30 Lisinopril 12 18-30 Ramipril 4-18 24-60 ARB Candesartan 6-13 12 Losartan 1-3 11 Telmisartan 21-38 10 Valsartan 6-10 13 a Brown and Vaughan, 1998. b Williams et al, 1988. c Israili, 2000. d Nishimura et al, 2005. t 1/2, half-life; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker Epworth HealthCare 8 http://www.anesthesiologynews.com/review-articles/article/02-16/angiotensin-axis-blocking-drugs-in-the-perioperative-period/35357/ses=ogst

What happens to blood pressure if ACEI and A2RA are continued in surgical patients? Epworth HealthCare 9

Effect of pre-operative discontinuation of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists on intra-operative arterial pressures after induction of general anesthesia. Anesth Essays Res. 2014 Jan-Apr;8(1):32-5 RCT of 60 patients, aged 40-60, ASA Grade II to III, to either continue or with hold treatment on the day of surgery Excluded IHD and valvular heart disease On ACEI/A2RA for at least three months Epworth HealthCare 10

Systolic blood pressure change =ACEI/A2RA withheld =ACEI/A2RA continued Epworth HealthCare 11

Diastolic blood pressure change =ACEI/A2RA withheld =ACEI/A2RA continued Epworth HealthCare 12

Does perioperative ACEI or A2RA use affect perioperative mortality? Epworth HealthCare 13

Perioperative angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers for preventing mortality and morbidity in adults. Zou Z et al Cochrane Database Syst Rev. 2016 Jan 27;(1):CD009210. Identified 7 RCTs, only three (total 419 patients) reported deaths Starting ACEI or A2RA varied from 11 days up to at induction Epworth HealthCare 14

Perioperative angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers for preventing mortality and morbidity in adults All cause mortality favours not being on ACEI/ARB Epworth HealthCare 15

Perioperative angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers for preventing mortality and morbidity in adults ST elevation or new Q waves favours being on ACEI/ARB Epworth HealthCare 16

Does perioperative ACEI or A2RA use affect perioperative outcomes in non-cardiac surgery patients? Epworth HealthCare 17

Angiotensin Converting Enzyme Inhibitors Are Not Associated with Respiratory Complications or Mortality After Noncardiac Surgery Anesthesia and Analgesia 2012;114;552-565 METHODS: We evaluated 79,228 patients (9905 ACEI users [13%] and 66,620 [87%] non-acei users) who had noncardiac surgery at the Cleveland Clinic between 2005 and 2009. Propensity matching successfully paired 9028 ACEI users (91% of 9905 patients) with 9028 controls. Matched intraoperative ACEI users and non-acei users were compared on intraoperative and postoperative respiratory morbidity composites as well as individual complications, 30-day mortality, and a composite of in-hospital morbidity and mortality Epworth HealthCare 18

Epworth HealthCare 19

Does perioperative ACEI or A2RA use affect perioperative outcomes in cardiac surgery patients? Epworth HealthCare 20

Patterns of Use of Perioperative Angiotensin-Converting Enzyme Inhibitors in Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass Effects on In-Hospital Morbidity and Mortality Circulation. 2012;126:261-269 This observational study examined cardiac surgery patients - a group more likely to have CCF, recent coronary ischaemia and valvular heart disease Epworth HealthCare 21

Diagram of patient enrollment through the study. Benjamin Drenger et al. Circulation. 2012;126:261-269 Copyright American Heart Association, Inc. All rights reserved.

Kaplan Meier survival analysis of event-free status by angiotensin-converting enzyme inhibitor (ACEI) therapy. Benjamin Drenger et al. Circulation. 2012;126:261-269 Copyright American Heart Association, Inc. All rights reserved.

Does perioperative use of ACEI and A2RB increase the risk of acute kidney injury? Epworth HealthCare 24

Preoperative renin angiotensin system inhibitors use linked to reduced acute kidney injury: a systematic review and meta-analysis Nephrol. Dial. Transplant. (2015) 30 (6): 978-988. 1 RCT and 23 observational studies Varying diagnoses of AKI Many of the studies withdrew ACEI/A2RA prior to surgery, and did not state when Epworth HealthCare 25

Forest plot of the all included studies comparing risk of postoperative AKI in patients who received preoperative RAS inhibitors and those who did not; square data markers represent RRs; horizontal lines, the 95% CIs with marker size reflecting the statistical weight of the study using random-effects meta-analysis. W isit Cheungpasitporn et al. Nephrol. Dial. Transplant. 2015;30:978-988 The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. Epworth HealthCare 26

Preoperative Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Is Associated with Increased Risk for Acute Kidney Injury after Cardiovascular Surgery CJASN September 2008 3): (5) 1266-1273 Epworth HealthCare 27

Summary ACEI/A2RA treatments are associated with intra operative hypotension The reports that looked at chronic ACEI/A2RA use mostly withheld treatment on the day of surgery, restarting at clinician discretion. This practice is not associated with harm, and would minimise intra operative hypotension Poorer cardiac outcomes only appeared to pertain to patients who had a long standing indication for treatment, and the treatment was stopped and not restarted