Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial

Abstract

Importance: Perioperative hypotension is associated with an increase in postoperative morbidity and mortality, but the appropriate management strategy remains uncertain.

Objective: To evaluate whether an individualized blood pressure management strategy tailored to individual patient physiology could reduce postoperative organ dysfunction.

Design, setting, and participants: The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study was a multicenter, randomized, parallel-group clinical trial conducted in 9 French university and nonuniversity hospitals. Adult patients (n = 298) at increased risk of postoperative complications with a preoperative acute kidney injury risk index of class III or higher (indicating moderate to high risk of postoperative kidney injury) undergoing major surgery lasting 2 hours or longer under general anesthesia were enrolled from December 4, 2012, through August 28, 2016 (last follow-up, September 28, 2016).

Interventions: Individualized management strategy aimed at achieving a systolic blood pressure (SBP) within 10% of the reference value (ie, patient's resting SBP) or standard management strategy of treating SBP less than 80 mm Hg or lower than 40% from the reference value during and for 4 hours following surgery.

Main outcomes and measures: The primary outcome was a composite of systemic inflammatory response syndrome and dysfunction of at least 1 organ system of the renal, respiratory, cardiovascular, coagulation, and neurologic systems by day 7 after surgery. Secondary outcomes included the individual components of the primary outcome, durations of ICU and hospital stay, adverse events, and all-cause mortality at 30 days after surgery.

Results: Among 298 patients who were randomized, 292 patients completed the trial (mean [SD] age, 70 [7] years; 44 [15.1%] women) and were included in the modified intention-to-treat analysis. The primary outcome event occurred in 56 of 147 patients (38.1%) assigned to the individualized treatment strategy vs 75 of 145 patients (51.7%) assigned to the standard treatment strategy (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = .02; absolute risk difference, -14%, 95% CI, -25% to -2%). Sixty-eight patients (46.3%) in the individualized treatment group and 92 (63.4%) in the standard treatment group had postoperative organ dysfunction by day 30 (adjusted hazard ratio, 0.66; 95% CI, 0.52 to 0.84; P = .001). There were no significant between-group differences in severe adverse events or 30-day mortality.

Conclusions and relevance: Among patients predominantly undergoing abdominal surgery who were at increased postoperative risk, management targeting an individualized systolic blood pressure, compared with standard management, reduced the risk of postoperative organ dysfunction.

Trial registration: clinicaltrials.gov Identifier: NCT01536470.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Futier reported receiving consulting fees from Edwards Lifesciences and Dräger; lecture fees from Dräger, GE Healthcare, Fresenius Kabi, and Fisher and Paykel Healthcare; and travel reimbursement from Fisher and Paykel Healthcare. Dr Leone reported receiving personal fees from LFB and Augettant and nonfinancial support from MSD. Dr Julia reported being an inventor on a patent owned by Aguettant. Dr Bazin reported receiving honoraria for expertise from General Electric, Ambu, and MSD and a grant from General Electric. No other disclosures were reported.

Figures

Figure 1.. Flow of Participants Through the Study

aTwo patients (1 per group) had care adherent to the assigned systolic blood pressure target but nonadherent to the vasopressor; they were included in the analysis of the group to which they were assigned. bTwo patients did not undergo surgery (surgery cancelled) and did not receive the study intervention.

Figure 2.. Systolic Arterial Blood Pressure in the Individualized and Standard Treatment Groups Over the Intervention Period

Systolic arterial blood pressures were higher in the individualized treatment group (P < .001 by random-effect model for the between-group comparison across the entire study intervention). The horizontal line in the center of each box indicates the median; bottom and top borders of the box, 25th and 75th percentiles, respectively; whiskers, 1.5 times the interquartile range (IQR); and circles, extreme outliers. The intervention period lasted from anesthesia induction to 4 hours after completion of surgery. The median (IQR) duration of surgery was 260 (170-365) minutes in the individualized treatment group and 280 (200-375) minutes in the standard treatment group. The median (IQR) duration of the intervention period was 423 (342-550) minutes in the individualized treatment group and 465 (390-600) minutes in the standard treatment group.

Figure 3.. Kaplan-Meier Estimates of the Probability of Postoperative Organ Dysfunction by Day 30 After Surgery

Organ dysfunction was assessed for renal (risk, injury, failure, loss, and end-stage kidney injury [RIFLE] stage of risk or higher), respiratory (need for invasive or noninvasive ventilation), cardiovascular (acute cardiac failure or myocardial ischemia or infarction), neurologic (stroke or altered consciousness), and coagulation (Sequential Organ Failure Assessment subscore ≥2 points in the coagulation component) systems. Data for patients who did not develop organ dysfunction were censored at 30 days after surgery. The adjusted hazard ratio (HR) for postoperative organ dysfunction in the individualized treatment group, as compared with the standard treatment group, was 0.66 (95% CI, 0.52-0.84; P = .001). The median follow-up duration was 30 days (interquartile range, 30-30 days) in the 2 treatment groups.