Neuroprotective effects of intraoperative dexmedetomidine versus saline infusion combined with goal-directed haemodynamic therapy for patients undergoing cranial surgery: A randomised controlled trial

Abstract

Background: By inhibiting neuroinflammation dexmedetomidine may be neuroprotective in patients undergoing cranial surgery, but it reduces cardiac output and cerebral blood flow.

Objective: To investigate whether intra-operative dexmedetomidine combined with goal-directed haemodynamic therapy (GDHT) has neuroprotective effects in cranial surgery.

Design: A double-blind, single-institution, randomised controlled trial.

Setting: A single university hospital, from April 2017 to April 2020.

Patients: A total of 160 adults undergoing elective cranial surgery.

Intervention: Infusion of dexmedetomidine (0.5 μg kg-1 h-1) or saline combined with GDHT to optimise stroke volume during surgery.

Main outcome measures: The proportion who developed postoperative neurological complications was compared. Postoperative disability was assessed using the Barthel Index at time points between admission and discharge, and also the 30-day modified Rankin Scale (mRS). Postoperative delirium was assessed. The concentration of a peri-operative serum neuroinflammatory mediator, high-mobility group box 1 protein (HMGB1), was compared.

Results: Fewer patients in the dexmedetomidine group developed new postoperative neurological complications (26.3% vs. 43.8%; P = 0.031), but the number of patients developing severe neurological complications was comparable between the two groups (11.3% vs. 20.0%; P = 0.191). In the dexmedetomidine group the Barthel Index reduction [0 (-10 to 0)] was less than that in the control group [-5 (-15 to 0)]; P = 0.023, and there was a more favourable 30-day mRS (P = 0.013) with more patients without postoperative delirium (84.6% vs. 64.2%; P = 0.012). Furthermore, dexmedetomidine induced a significant reduction in peri-operative serum HMGB1 level from the baseline (222.5 ± 408.3 pg ml-1) to the first postoperative day (152.2 ± 280.0 pg ml-1) P = 0.0033. There was no significant change in the control group. The dexmedetomidine group had a lower cardiac index than did the control group (3.0 ± 0.8 vs. 3.4 ± 1.8 l min-1 m-2; P = 0.0482) without lactate accumulation.

Conclusions: Dexmedetomidine infusion combined with GDHT may mitigate neuroinflammation without undesirable haemodynamic effects during cranial surgery and therefore be neuroprotective.

Trial registration: Clinicaltrials.gov Identifier: NCT02878707.