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

K J Steinthorsdottir, H N Awada, N A Schultz, P N Larsen, J G Hillingsø, Ø Jans, H Kehlet, E K Aasvang, K J Steinthorsdottir, H N Awada, N A Schultz, P N Larsen, J G Hillingsø, Ø Jans, H Kehlet, E K Aasvang

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/).

© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.

Figures

Fig. 1
Fig. 1
CONSORT flow chart for trial IDDM, insulin-dependent diabetes mellitus; ALPPS, associating liver partitition and portal vein ligation for staged hepatectomy.
Fig. 2
Fig. 2
Pain during admission a Average and b worst pain. Median value (bold line), i.q.r. (box), and range (error bars) excluding outliers (dots) are shown. Number of observations each day for each group is indicated below bars. SD, standard dose; HD, high dose; NRS, numerical rating scale; POD, postoperative day.
Fig. 3
Fig. 3
Alanine aminotransferase, prothrombin time, and bilirubin levels measured before surgery and on postoperative day 1 (all patients) and postoperative day 2–3 (major resections only) a Alanine aminotransferase, b prothrombin time, and c bilirubin. Values are mean(s.d.). Number of observations each day for each group is indicated below graph. SD, standard dose; HD, high dose; preop., before surgery (baseline); POD, postoperative day; INR, international normalized ratio. *P < 0.050, †P < 0.001 versus SD (Likelihood-ratio test).

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