ABSTRACT
BACKGROUND: Perioperative myocardial injury after noncardiac surgery is associated with postoperative mortality. Heart rate (HR) is an independent risk factor for perioperative myocardial injury. In this pilot trial we tested the feasibility of a randomised, placebo-controlled trial of personalised HR-targeted perioperative ivabradine. METHODS: This was a single-centre, randomised, placebo-controlled, double-blind, parallel group, feasibility pilot trial conducted at Geneva University Hospitals. We included patients ≥75 yr old or ≥45 yr old with cardiovascular risk factors planned for intermediate- or high-risk surgery. Patients were randomised to receive ivabradine (2.5, 5.0, or 7.5 mg) or placebo according to their HR, twice daily, from the morning of surgery until postoperative day 2. Primary outcomes were appropriate dosage and blinding success rates. RESULTS: Between October 2020 and January 2022, we randomised 78 patients (recruitment rate of 1.3 patients week-1). Some 439 of 444 study drug administrations were adequate (99% appropriate dosage rate). The blinding success rate was 100%. There were 137 (31%) administrations of Pill A (placebo in both groups for HR ≤70 beats min-1). Nine (11.5%) patients had a high-sensitive cardiac troponin T elevation ≥14 ng L-1 between any two measurements. The number of bradycardia episodes was eight in the placebo group and nine in the ivabradine group. CONCLUSIONS: This pilot study demonstrates the feasibility of, and provides guidance for, a future trial testing the efficacy of personalised perioperative ivabradine. Future studies should include patients at higher risk of cardiac complications. CLINICAL TRIAL REGISTRATION: NCT04436016.
ABSTRACT
BACKGROUND: The increase in intra-abdominal pressure (IAP) during closed abdominal hyperthermic intraperitoneal chemotherapy (HIPEC) leads to major haemodynamic changes and potential organ dysfunction. We investigated these effects on hepatic blood flow (HBF) and liver function in patients undergoing HIPEC following cytoreductive surgery and fluid management guided by dynamic preload indices. METHODS: In this prospective observational clinical study including 15 consecutive patients, we evaluated HBF by transesophageal echocardiography and liver function by determination of the indocyanine green plasma disappearance rate (ICG-PDR). Friedman's two-way analysis of variance by ranks and Wilcoxon signed-rank test were performed for statistical analysis. RESULTS: During HIPEC, HBF was markedly reduced, resulting in the loss of any pulsatile Doppler flow signal in all but one patient. The ICG-PDR, expressed as median (interquartile 25-75), decreased from 23 (20-30) %/min to 18 (12.5-19) %/min (p < 0.001). Despite a generous crystalloid infusion rate (27 (22-35) ml/kg/h), cardiac index decreased during the increased IAP period, inferior vena cava diameter decreased, stroke volume variation and pulse pressure variation increased, lung compliance dropped, and there was an augmentation in plateau pressure. All changes were significant (p < 0.001) and reversed to baseline values post HIPEC. CONCLUSION: Despite optimizing intravenous fluids during closed abdominal HIPEC, we observed a marked decrease in HBF and liver function. Both effects were transient and limited to the period of HIPEC but could influence the choice between closed or open abdominal cavity procedure for HIPEC and should be considered in similar clinical situations of increased IAP.
