TL;DR: ⚪ Definitive null — cardiac output-guided hemodynamic therapy did not reduce postoperative infection in major GI surgery (P=0.71); the smaller original OPTIMISE trial's signal did not replicate at scale.
1. Publication
- Title: Cardiac output-guided haemodynamic therapy for patients undergoing major gastrointestinal surgery: OPTIMISE II randomised clinical trial
- Acronym: OPTIMISE II
- Year & Journal: BMJ, published December 3, 2024 (387:e080439)
- Citation: OPTIMISE II Trial Group. BMJ. 2024;387:e080439. doi:10.1136/bmj-2024-080439
2. Context & Rationale
Background: Goal-directed hemodynamic therapy has long been proposed to reduce perioperative complications, but evidence remains mixed. The original OPTIMISE trial suggested benefit; OPTIMISE II was designed as a larger, definitive confirmatory test.
Research Question/Hypothesis: In older adults undergoing major elective GI surgery, does a perioperative cardiac output-guided fluid/low-dose-inotrope algorithm reduce postoperative infection within 30 days compared with usual care?
3. Design & Methods
- Study Type: Multicenter RCT
- Setting & Centers: 55 hospitals worldwide; January 2017–September 2022
- Population: 2498 adults ≥65y, ASA ≥II, undergoing major elective GI surgery
- Intervention: Minimally invasive cardiac output-guided IV fluid therapy with low-dose inotrope infusion, intraoperatively and for 4h postoperatively
- Comparator: Usual care without cardiac output monitoring
- Statistical Power & Follow-Up: Primary: postoperative infection within 30 days.
4. Key Results
2498 patients across 55 hospitals.
Outcome | Cardiac Output-Guided Therapy | Usual Care | p-value | Notes |
Postoperative infection within 30 days (primary) | Not significantly reduced | — | 0.71 | Clear null result |
Other secondary outcomes | No significant differences | — | — | Consistent null pattern |
5. Internal Validity Assessment
Large (2498-patient), multicenter, international RCT — among the largest perioperative hemodynamic-optimization trials to date. Overall: Strong — definitive, well-powered null result (P=0.71) directly addressing whether the original smaller OPTIMISE trial's positive signal would replicate at scale; it did not.
6. External Validity Assessment
55-hospital, worldwide population of older, higher-risk (ASA≥II) major GI surgery patients — excellent generalizability given the scale and international scope.
7. Strengths & Limitations
Strengths: Very large, definitive, international trial; directly tests replication of a previously suggestive smaller trial; comprehensive secondary outcome assessment.
Limitations: As with many perioperative optimization trials, evolving background "usual care" (already incorporating some hemodynamic optimization principles) may narrow the achievable contrast between arms.
8. Interpretation & Practice Impact
Does not support routine cardiac output-guided hemodynamic therapy for reducing postoperative infection in major GI surgery — a definitive null result tempering enthusiasm from the smaller, earlier OPTIMISE trial.
9. Controversies & Subsequent Evidence
Contrasts with the original, smaller OPTIMISE trial's more favorable signal; this larger, more definitive confirmatory trial did not replicate that finding — an instructive example of "regression to the null" as trials scale up, a recurring theme across perioperative hemodynamic optimization research (echoing similar patterns as ESCAPE/PAC-guided therapy trials).
10. Summary & Executive Takeaway
Summary: OPTIMISE II, a large international RCT, randomized 2498 older adults undergoing major GI surgery to cardiac output-guided hemodynamic therapy or usual care. Postoperative infection within 30 days was not significantly reduced (P=0.71), with no differences in other secondary outcomes.
Overall Takeaway: This large, definitive trial does not support routine cardiac output-guided perioperative hemodynamic therapy for reducing postoperative infection in major GI surgery — the smaller original OPTIMISE trial's positive signal did not replicate at scale.
11. Bibliography
- Pearse RM, et al. Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes (original OPTIMISE trial).