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

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 mu g 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, highmobility 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 +/- 1.81 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.