Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial

Abstract

Background: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery.

Methods: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery.

Results: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis.

Conclusions: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications.

Clinical trial registration: NCT03021525.

Keywords: anaesthesia; cardiac output; cardiovascular dynamics; haemodynamic monitoring; individualised; morbidity; mortality; randomised controlled trial.

Fig 1

Treatment algorithms. Treatment algorithm 1 illustrates determination of the optimised postinduction cardiac index at which pulse pressure variation was <12% after induction of general anaesthesia. Clinicians were asked to maintain optimised postinduction cardiac index during surgery according to treatment algorithm 2. During the first 8 h after surgery, cardiac index-guided therapy was performed according to treatment algorithm 2 in subjects on controlled mechanical ventilation or according to treatment algorithm 3 in spontaneously breathing subjects. CI, cardiac index; PPV, pulse pressure variation.

Fig 2

Subject flow chart. Flow chart illustrating subject screening, enrolment, randomisation, and reasons for exclusion.

Fig 3

Primary outcome. Forest plots showing the effect of cardiac index-guided therapy compared with routine care on the composite primary outcome and individual complications within 28 days after surgery. ∗Statistical tests were restricted to complications with at least two events per treatment group owing to model computability.