Proactive Versus Reactive Intraoperative Blood Pressure Management: Insights from the PRETREAT Randomized Clinical Trial

Highlight

• Intraoperative hypotension is linked to adverse postoperative outcomes, but its optimal management strategy remains unclear.
• The PRETREAT trial compared proactive blood pressure management, based on individual risk stratification, versus standard care during noncardiac surgery.
• No significant improvement in functional disability at 6 months or in secondary outcomes was found with proactive management.
• The study suggests that tailored mean arterial pressure targets may not translate into better long-term functional recovery.

Study Background

Intraoperative hypotension (IOH), characterized by a decrease in blood pressure during surgery, is a common event associated with increased risk of postoperative complications including organ injury and mortality. Maintaining adequate blood pressure is therefore a critical aspect of anesthesia management. While avoiding excessively low pressure is standard practice, the ideal blood pressure target remains debated, particularly regarding whether targeting higher blood pressure thresholds based on patient risk improves long-term outcomes. Previous observational studies have linked IOH to adverse events; however, evidence from randomized trials on whether proactive management strategies that stratify blood pressure targets by hypotension risk actually improve functional outcomes is limited. The PRETREAT trial sought to fill this important knowledge gap by evaluating functional disability and other patient-centered outcomes after noncardiac surgery.

Study Design

This randomized clinical trial was conducted at two tertiary hospitals in the Netherlands between June 17, 2021, and February 7, 2024, with follow-up until October 24, 2024. Adult patients undergoing elective noncardiac surgery were enrolled and randomized 1:1 to two management strategies:

– Proactive intraoperative blood pressure management: Mean arterial pressure (MAP) targets set according to preoperative risk of IOH — ≥70 mm Hg for low risk, ≥80 mm Hg for intermediate risk, and ≥90 mm Hg for high risk.
– Usual care: Standard management at the anesthesiologist’s discretion, generally avoiding MAP below 65 mm Hg without higher predefined targets.

The primary endpoint was functional disability at 6 months, measured by the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), a validated tool. Secondary outcomes encompassed a broad range of postoperative complications, quality of life measures, and mortality within 6 months.

Key Findings

The trial was stopped early for futility after enrolling 3,247 patients out of the planned 5,000. Among participants, 21% were classified as low risk, 56% as intermediate risk, and 23% as high risk for IOH. Initial median WHODAS scores were similar between groups (12.5 proactive vs 14.6 standard).

At 6 months, the proactive and standard groups had mean WHODAS scores of 17.7 and 18.2, respectively, with a mean difference of -0.5 points (95% credible interval, -1.9 to 0.9), well below the prespecified minimally clinically important difference of 5 points.

No statistically or clinically significant differences were found across 23 secondary outcomes, including quality of life, complication rates, or mortality.

Expert Commentary

The PRETREAT trial provides high-quality evidence that a proactive blood pressure management strategy individualized by hypotension risk does not improve postoperative functional disability in elective noncardiac surgery. These findings challenge the prevailing notion that preventing even mild intraoperative hypotension by targeting higher MAP thresholds confers meaningful long-term benefits. Clinicians must balance efforts to avoid hypotension carefully since aggressive blood pressure elevation may carry its own risks, including excessive vasopressor use and potential cardiac strain.

Limitations include early trial termination, which may reduce power to detect smaller effects, and the focus on elective noncardiac surgery limiting generalizability to emergency or cardiac cases. Additionally, while WHODAS 2.0 is validated for functional disability, it may not capture all dimensions of recovery affected by IOH. Future research could explore subgroup analyses or mechanistic studies examining whether specific patient populations benefit from tailored management.

Conclusion

The PRETREAT randomized clinical trial concludes that proactive intraoperative blood pressure management guided by individual hypotension risk does not improve functional disability at 6 months postoperatively when compared with usual anesthesiologist-directed care in elective noncardiac surgery. Standard approaches targeting a MAP above 65 mm Hg remain appropriate. These results underscore the complexity of IOH management and highlight the need for continued research to optimize intraoperative hemodynamic strategies for diverse surgical populations.

Funding and Trial Registration

This trial was conducted without mention of specific external funding. Trial registration: Overview of Medical Research in the Netherlands (CCMO): NL-OMON55117.

References

Kant M, van Klei WA, Hollmann MW, de Klerk ES, Otterspoor LC, Besselink MG, Kappen TH, Veelo DP; PRETREAT study group. Proactive vs Reactive Treatment of Hypotension During Surgery: The PRETREAT Randomized Clinical Trial. JAMA. 2025 Oct 12. doi: 10.1001/jama.2025.18007. Epub ahead of print. PMID: 41076587.