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

BackgroundDespite dexmedetomidine may be neuroprotective in patients undergoing cranial surgery by inhibiting neuroinflammation; however, it reduces cardiac output and cerebral blood flow. We proposed that dexmedetomidine infusion combined with goal-directed hemodynamic therapy (GDHT) could improve cranial surgery neurological outcomes without hemodynamic perturbation.MethodsA randomized, double-blind trial was conducted. One hundred sixty adult patients undergoing elective cranial surgery received either dexmedetomidine (0.5 μg kg−1 h−1) or saline during surgery. The goal-directed hemodynamic therapy was used for stroke volume optimization. The proportion of patients who developed postoperative new neurological deficits was compared. The severities of new neurological deficit were assessed by using in-hospital Barthel index changes and the 30-day modified Rankin Scale (mRS). Postoperative delirium was identified using the Intensive Care Delirium Screening Checklist (ICSDC) criteria. The level of a perioperative serum neuroinflammatory mediator, high motility group box 1 protein (HMGB1), was compared.ResultsThe dexmedetomidine group exhibited 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. Fewer patients in the dexmedetomidine group developed new postoperative deficits (26.3% versus 43.8%; p = 0.031) but numbers of patients remained symptomatic neurological deficit before discharge were comparable between the two groups (23.8% vs. 38.8%; p= 0.060). In addition, an attenuated Barthel index decline (−6.3 ± 20.4 vs. −13.6 ± 24.8; p = 0.043), a more favorable 30-day mRS profile (p = 0.013), and a higher incidence of postoperative delirium-free (ICDSC scored 0: 84.6% versus 64.2%; p = 0.012) were observed in the dexmedetomidine group. Furthermore, dexmedetomidine induced a significant decline in perioperative serum HMGB1 level (222.5 ± 408.3 vs. 152.2 ± 280.0 ng mL−1; p = 0.0033).ConclusionsDexmedetomidine infusion combined with GDHT mitigates neuroinflammation during cranial surgery without hemodynamic perturbation, thus achieving neuroprotective effects.Clinical Trial RegistrationProspectively registered at clinicaltrials.gov. (identifier NCT02878707, date of registration: August 25, 2016)