Neuroprotective Effects of Intraoperative Dexmedetomidine Infusion Combined With Goal-directed Hemodynamic Therapy for Patients Undergoing Cranial Surgery: A Double-blinded Randomized Controlled Trial

Abstract

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)

Neuroprotective effects of dexmedetomidine combined with goal-directed haemodynamic therapy for patients undergoing cranial surgery

“…We read with great interest the article of Chen et al 1 that evaluated the neuroprotective effect of intra-operative dexmedetomidine (DEX) infusion combined with goal-directed haemodynamic therapy (GDHT) in patients undergoing cranial surgery. The author concluded that DEX combined with GDHT could attenuate postoperative disability and prevention of delirium through mitigation of neuro-inflammation during cranial surgery.…”