Preoperative high-dose glucocorticoids for early recovery after liver resection: randomized double-blinded trial

Abstract

Background Glucocorticoids modulate the surgical stress response. Previous studies showed that high-dose preoperative glucocorticoids reduce levels of postoperative inflammatory markers and specific biomarkers of liver damage compared with placebo, and suggested a reduced complication rate and shorter hospital stay after liver surgery. However, there are no studies with a clinical primary outcome or of early recovery outcomes. The aim of this study was to investigate whether a single high dose of preoperative glucocorticoid reduces complications in the immediate postoperative phase after liver surgery. Methods This was a single-centre, double-blinded, parallel-group RCT investigating preoperative methylprednisolone 10 mg/kg (high dose) versus dexamethasone 8 mg (standard-dose postoperative nausea prophylaxis) in patients scheduled for open liver resection. The primary outcome was number of patients with a complication in the postanaesthesia care unit; secondary outcomes included duration of hospital stay, pain and nausea during admission, and 30-day morbidity. Results A total of 174 patients (88 in high-dose group, 86 in standard-dose group) were randomized and analysed (mean(s.d.) age 65(12) years, 67.2 per cent men); 31.6 per cent had no serious co-morbidities and 25.3 per cent underwent major liver resection. Complications occurred in the postanaesthesia care unit in 51 patients (58 per cent) in the high-dose group and 58 (67 per cent) in the standard-dose group (risk ratio 0.86, 95 per cent c.i. 0.68 to 1.08; P = 0.213). Median duration of hospital stay was 4 days in both groups (P = 0.160). Thirty-day morbidity and mortality rates were similar in the two groups. Conclusion A high dose of preoperative glucocorticoids did not reduce acute postoperative complications after open liver resection compared with a standard dose. Registration number: NCT03403517 (http://www.clinicaltrials.gov); EudraCT 2017–002652-81 (https://eudract.ema.europa.eu/).

High‐dose preoperative glucocorticoid for prevention of emergence and postoperative delirium in liver resection: A double‐blinded randomized clinical trial substudy

“…All patients included in the main study during the first 7 months (January 2018 to July 2018) were also included in this predefined substudy. 19 Acknowledging an unbalanced distribution of potential important confounders, we refrained from the planned primary outcome analysis of a chi-square test for differences in the occurrence of ED between intervention groups. Secondary outcomes of PACU LOS were analyzed with the chi-square test for the difference in the occurrence of POD between intervention groups.…”

“…This study was a predefined exploratory substudy to form the basis for future potential more extensive studies, and as such, there was no separate sample size calculation. All patients included in the main study during the first 7 months (January 2018 to July 2018) were also included in this predefined substudy 19 …”

“…24 Postoperative complications were registered for all patients at 30 days follow-up and are presented in the main study. 19…”

“…Patients were enrolled as in the original study, 19 but only during the first 7 months when dedicated staff for the current sub study was available (January–July 2018) as defined in the study protocol of the original study: All patients at the department of surgical gastroenterology were consecutively screened for study eligibility if >18 years of age and planned for open liver resection. Further inclusion criteria were the ability to understand Danish or English and provide informed oral and written consent.…”

Impact of high-dose glucocorticoid on endothelial damage after liver resection – a double-blinded randomized substudy

“…This was a predefined exploratory substudy from a randomized double-blind clinical trial (RCT) of the impact of high-dose glucocorticoid on acute complications after major liver resection [14].…”