Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition (PREOP-ACEI)
BACKGROUND: Intraoperative hypotension is associated with an increased risk of end organ damage and death. The transient preoperative interruption of angiotensin-converting enzyme inhibitor (ACEI) therapy prior to cardiac and vascular surgeries decreases the occurrence of intraoperative hypotension.
OBJECTIVE: We sought to compare the effect of two protocols for preoperative ACEI management on the risk of intraoperative hypotension among patients undergoing noncardiac, nonvascular surgeries.
DESIGN: Prospective, randomized study.
SETTING: Midwestern urban 489-bed academic medical center.
PATIENTS: Patients taking an ACEI for at least six weeks preoperatively were considered for inclusion.
INTERVENTIONS: Randomization of the final preoperative ACEI dose to omission (n = 137) or continuation (n = 138).
MEASUREMENTS: The primary outcome was intraoperative hypotension, which was defined as any systolic blood pressure (SBP) < 80 mm Hg. Postoperative hypotensive (SBP < 90 mm Hg) and hypertensive (SBP > 180 mm Hg) episodes were also recorded. Outcomes were compared using Fisher’s exact test.
RESULTS: Intraoperative hypotension occurred less frequently in the omission group (76 of 137 [55%]) than in the continuation group (95 of 138 [69%]) (RR: 0.81, 95% CI: 0.67 to 0.97, P = .03, NNH 7.5). Postoperative hypotensive events were also less frequent in the ACEI omission group (RR: 0.49, 95% CI: 0.28 to 0.86, P = .02) than in the continuation group. However, postoperative hypertensive events were more frequent in the omission group than in the continuation group (RR: 1.95, 95%: CI: 1.14 to 3.34, P = .01).
CONCLUSION: The transient preoperative interruption of ACEI therapy is associated with a decreased risk of intraoperative hypotension.
REGISTRATION: ClinicalTrials.gov: NCT01669434.
© 2018 Society of Hospital Medicine
Participants
Patients who presented to the preoperative evaluation clinic between May 2015 and November 2016 and who had been taking an ACEI for at least 6 weeks were eligible for inclusion. Patients taking angiotensin receptor blockers were excluded. Enrollment was limited to patients planning NCNV surgery. Patients planning intrathoracic, major vascular, organ transplant, and oncologic surgery were excluded. Patients undergoing outpatient procedures not requiring an overnight stay in the hospital were also excluded. Patients with preoperative clinic systolic blood pressure (SBP) <90 or ≥160 or diastolic blood pressure (DBP) <60 or ≥ 95 were excluded. Patients with moderate to severe or clinically decompensated heart failure (left ventricular ejection fraction < 40% or New York Heart Association class III or IV) and those with end-stage renal disease requiring dialysis were also excluded. Patients presenting more than once during the accrual period were eligible for the initial surgery only. All participating patients provided written informed consent. This project was approved by the University of Nebraska Medical Center Institutional Review Board.
Data Collection
Baseline characteristics were recorded by study personnel at the time of enrollment. We measured serum creatinine level at the preoperative visit and on postoperative day 1. An automated anesthesia information management system was used to measure intraoperative blood pressures every three minutes. Postoperative blood pressures through discharge were measured by hospital staff per usual care. During postoperative hospitalization, we queried patients about preoperative adherence to allocation. The digital abstraction of data from the electronic medical record was supplemented by chart review when necessary.
Outcomes
The primary outcome was intraoperative hypotension defined as any SBP < 80 mm Hg occurring from the administration of the first induction agent through transfer to the postanesthesia care unit (PACU). We also examined hypotension during anesthesia induction, which we defined as the 20-minute period following the administration of the first anesthesia induction agent. Episodes of SBP < 80 were defined as being associated with vasopressor administration when any vasopressor was administered during or within 10 min of the episode.
Secondary analyses included postoperative acute kidney injury (AKI), postoperative hypotensive and hypertensive episodes, cardiac events, and mortality. When comparing postoperative day 1 creatinine levels to preoperative creatinine levels, we used the Acute Kidney Injury Network definition of AKI as an increase in creatinine of 0.3 mg/dl or 50%.15 Postoperative hypotension was defined as any SBP < 90 mm Hg and postoperative hypertension as any SBP > 180 mm Hg occurring after arrival in the PACU. Major adverse cardiac events (MACE) were defined as a composite of acute coronary syndrome, acute heart failure, or new-onset arrhythmia. Discharge from the hospital served as the study endpoint for each patient.
Analysis
Fisher’s exact test was used to compare categorical outcomes between groups. The independent sample t-test or Wilcoxon rank–sum test, as appropriate, was used to compare continuous measures. We selected Fisher’s exact test over χ2-test to produce conservative estimates. Patients were maintained in their allocated group as randomized for analytical purposes regardless of adherence to allocation. We performed all analyses using SAS version 9.4 for Windows (SAS institute, Cary, North Carolina).
