Maximum postoperative BP was available for 136 discontinuation subjects and 150 continuation group subjects. Stage 1 HTN was present in 64/150 (42%) patients in the discontinuation group vs 56/136 (41%) in the continuation group; Stage 2 HTN was found in 34/150 (23%) patients in the discontinuation group and in 30/135 (22%) patients in the continuation group (P = 0.934). There were too few patients in either group who received treatment in the PACU for HTN to be considered for analysis. No cases were cancelled preoperatively or admitted to hospital postoperatively, due to uncontrolled perioperative HTN. There were no deaths or any hospital admissions related to adverse events (myocardial infarction or stroke).
We investigated the consequences, if any, of instructing patients scheduled for elective surgery on an ambulatory or same-day surgery basis to discontinue their ACEIs or ARBs preoperatively. These instructions were based primarily on earlier inpatient literature, suggesting that patients continuing to take ACEIs and ARBs before surgery were more likely to experience hypotension after induction of general anesthesia.2–10 More recent literature continues to recommend discontinuation of these medications preoperatively because of reported increased risk of death, use of inotrophic support, postoperative renal dysfunction, and atrial fibrillation in patients undergoing CABG or major vascular procedures.12,13 In addition, the presence of ACEIs might inhibit the effectiveness of other endogenous or exogenous vasoconstrictors needed to treat postinduction hypotension.19 However, few investigators looked for or evaluated unintended effects of discontinuing the medication. Pigott et al.14 studied 40 patients undergoing cardiac surgery and found that, although patients in the group that suspended ACEI therapy experienced less of a reduction in BP after anesthetic induction, they did experience a marked increase in BP postoperatively that necessitated the administration of vasodilators.
This has created a clinical dilemma: is the benefit, after anesthetic induction, of discontinuing treatment offset by the risk of HTN preoperatively or postoperatively? After nearly 2 decades of discussion of the pros and cons of perioperative ACEI and ARB therapy, there is no evidence-based consensus. The uncertainty stems in part from the absence of RCTs designed to examine potential deleterious consequences.
The current study, which is the largest, prospective RCT related to continuation of ACEI/ARB therapy before surgery, conducted on ambulatory and same-day surgery patients, demonstrated that discontinuing ACEIs and ARBs does not put patients at risk for preoperative HTN, increased cancellations, admissions, or significant HTN in the PACU. In addition, patients who continued treatment did not have a more stable preoperative BP than those who discontinued treatment and were no less likely to be hypertensive postoperatively than those who discontinued their medications. The question of whether the effect of drug discontinuation varies by ethnic group cannot be answered with great confidence from these data, because the test of interaction yielded a P value of marginal statistical significance. We can, however, state with some confidence that reported results for the primary outcome are not meaningfully biased by a confounding effect of ethnicity. Further study is needed in African Americans who have already been identified in the medical literature as having more difficult to treat HTN.20–22
A meta-analysis (3 RCTs and 2 observational studies) totaling 434 patients undergoing nonemergency surgery15 suggested that patients receiving immediate preoperative ACEI or ARB medication were more likely (relative risk [RR] 1.5, 95% CI, 1.15–1.96) to develop hypotension requiring a vasopressor at or shortly after induction. The 3 RCTs3,7,14 were limited to CABG and vascular surgery and were small with 20 to 30 patients in each arm. One of the observational studies was conducted in a broader population of patients (including outpatients and same-day surgery patients) but was retrospective, nonrandomized, and did not report on preoperative HTN.6 Insufficient data in this meta-analysis limited further conclusion about the consequences of potential hemodynamic changes on adverse outcomes. Unfortunately, it is trials like these that have formed the basis for publications, recommending the withholding of ACEIs on the day of surgery.20
Because the primary outcome measurement in our study was preoperative BP, patients were not excluded based on the types of surgery or anesthesia and included monitored anesthesia care, regional and general anesthesia. As there are other intraoperative factors that affect BP under various surgical and anesthesia conditions, we did not evaluate the intraoperative hemodynamics. As the study continued, we considered whether discontinuation might be associated with rebound HTN in the immediate postoperative period and therefore added as a secondary outcome, measurement of postoperative BP in the PACU. We did not find the incidence of PACU Stage 1 and Stage 2 HTN to differ between the 2 groups. The lack of rebound HTN in the ACEI/ARB-treated groups might be related to a persistent tissue effect of ACEIs/ARBs,7,21 although we did not measure this. Chronic ACEI/ARB treatment exerts long-lasting beneficial effects on the structural and or functional vascular myocardial alterations that accompany chronic hypertensive disease.7,21 The point might be made that many of our patients were taking multiple additional antihypertensive medications and that this might explain the absence of significant preoperative or postoperative HTN changes in the discontinuation group, or any differences between the 2 groups in the various measurements. However, the relevant information is that there were no differences between the 2 groups in the additional antihypertensive medications taken (Appendix 1, 2).
In the absence of large RCTs, propensity scoring has been used to analyze large patient databases and focus on the consequences of continuing the ACEI/ARB medications.22,23 Most recently, Turan et al.23 reported the results of propensity matching of 9028 ACEI users who did not take their medication on the day of surgery and controls (patients not taking ACEIs or ARBs) and reported similar intraoperative hemodynamic characteristics at various time points for both groups, similar interventions with vasopressors, and use of crystalloid infusions. They did not extend their measurements into the postoperative period.
We recommend that because of the unresolved nature of the continuing debate medication recommendations be tailored to specific patient populations based on their comorbidities, intended surgery, and concurrent therapies, rather than a 1-size-fits-all approach. Some have suggested the withholding of ACEIs and ARBs for patients who are receiving multiple antihypertensive medications, while, as a safe practice, continuing ACEIs and ARBs on the day of surgery where the only mode of HTN control is renin-angiotensin-system blockade.24 We agree that this is reasonable for many patient scenarios.
Our study involves ambulatory and same-day admission patients undergoing a large variety of relatively low-risk surgical procedures and anesthetics and allows for the study results to be applied more generally to a diverse urban population. The limitations of our study, however, are that our primary and secondary end points are confined to a brief perioperative period. We cannot address whether withholding medications had any significant long-term outcome.
Showing the lack of an effect is always more challenging than demonstrating an effect, especially for infrequent events. In our study, preoperative Stage 2 HTN occurred in 10% of patients who discontinued and 8% of patients who continued ACEI/ARB medications, and therefore, a sample size closer to the original power analysis will be needed to definitively affirm our hypothesis. Although we acknowledge that the study is underpowered with respect to initial projections, the prevalence of preoperative HTN found in both arms of this study was considerably higher than projected based on Wax et al.17 (37% when combining Stage 1 and Stage 2 prevalence as seen in Table 2); also, the CI around observed differences in HTN between discontinuation and continuation groups is so small that it is unlikely to be associated with a clinically meaningful difference between populations. As seen in Table 2, HTN prevalence was almost identical between treatment arms, and a difference of up to 4.8 percentage points for Stage 1 HTN and up to 5.8 percentage points for Stage 2 is not clinically significant. It is unlikely that discontinuation would increase Stage 1 HTN or Stage 2 HTN in any clinically significant way. We have supported our hypothesis that in our population of patients, the prevalence of Stage 1 or Stage 2 HTN would be no different between patients who discontinued versus continued their medications. Finally, the relevance of these findings may be limited without the concurrent study of postinduction hypotension and postoperative outcomes. We are currently conducting a large prospective RCT to evaluate postinduction BPs and perioperative hemodynamic control in ambulatory and same-day patients undergoing general anesthesia, with the intent of providing additional data for development of evidence-based guidelines for the continuation or discontinuation of ACEI/ARB medications perioperatively.
Discontinuing ACEIs and ARBs in patients on the day of surgery did not substantively result in a greater incidence of pre- or postoperative HTN compared with patients who continued these medications, as monotherapy or multidrug therapy on the day of surgery. Our results provide an evidentiary basis for the safety of discontinuing ACEIs and ARBs on the day of surgery without increasing adverse hemodynamic outcomes. Analysis of the intraoperative and postoperative effects of these interventions is ongoing with the intent of providing evidence-based guidelines for safe management of patients taking ACEIs and ARBs scheduled for ambulatory and same-day surgery.
Name: Rebecca S. Twersky, MD, MPH.
Contribution: This author designed and conducted the study, analyzed the data, and prepared the manuscript.
Attestation: Rebecca S. Twersky, MD, MPH, approved the final manuscript. Dr. Rebecca S. Twersky attests to the integrity of the original data and the analysis reported in this manuscript. Dr. Rebecca S. Twersky is the archival author.
Name: Vasudha Goel, MD.
Contribution: This author helped conduct the study and collect and analyze the data.
Attestation: Vasudha Goel, MD, approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.
Name: Preeti Narayan, MD.
Contribution: This author helped with data collection and conduct of the study.
Attestation: Preeti Narayan, MD, approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.
Name: Jeremy Weedon, PhD, MA, BS.
Contribution: This author contributed to study design, power analysis, and conducted the statistical data analysis.
Attestation: Dr. Jeremy Weedon attests to the integrity of the original data and the analysis reported in this manuscript.
This manuscript was handled by: Peter S. A. Glass, MB, ChB.
We gratefully acknowledge the numerous staff, residents, and medical students who participated in the study: Drs. Julia Griffin, Roy Braid, Jacqueline Njiapa, Leon Perel, David Rahmani, Donna Bracken, Monika Jadhav, Dmitry Roizen, Navdeep Nayyar and thank Dr. John Hartung, Dr. Julie Rushbrook, and Dr. Chineze Igboechi for their editorial assistance with the manuscript.
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© 2014 International Anesthesia Research Society
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