• Anesthesiology · Jul 2019

    Midazolam Sedation Induces Upper Limb Coordination Deficits That Are Reversed by Flumazenil in Patients with Eloquent Area Gliomas.

    • Nan Lin, Ruquan Han, Xuan Hui, Kaiying Zhang, and Adrian W Gelb.
    • From the Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Fengtai District, Beijing, China (N.L., R.H., K.Z.) the Department of Public Health Sciences, University of Chicago, Chicago, Illinois (X.H.) the Department of Anesthesiology, University of Texas Health Science Center at Houston, Houston, Texas (K.Z.) the Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California (A.W.G.).
    • Anesthesiology. 2019 Jul 1; 131 (1): 36-45.

    BackgroundMidazolam has been found to exacerbate or unmask limb motor dysfunction in patients with brain tumors. This study aimed to determine whether the exacerbated upper limb motor-sensory deficits are mediated through benzodiazepine sites by demonstrating reversibility by flumazenil in patients with gliomas in eloquent areas.MethodsThis was an interventional, parallel assignment, nonrandomized trial. Study subjects were admitted in the operating room. Patients with supratentorial eloquent area gliomas and volunteers of similar age without neurologic disease were sedated with midazolam, but still responsive and cooperative. Motor and sensory functions for upper extremities were evaluated by the Nine-Hole Peg Test before and after midazolam, as well as after flumazenil reversal.ResultsThirty-two cases were included: 15 in the glioma group and 17 in the control group. The total dose of midazolam and flumazenil were comparable between the groups. In the glioma group, the times to task completion after midazolam in the contralateral hand (P = 0.001) and ipsilateral hand (P = 0.002) were 26.5 (95% CI, 11.3 to 41.7) and 13.7 (95% CI, 5.0 to 22.4) seconds slower than baseline, respectively. After flumazenil reversal, the contralateral hand (P = 0.99) and ipsilateral hand (P = 0.187) performed 1.2 (95% CI, -3.3 to 5.8) and 1.5 (95% CI, -0.5 to 3.5) seconds slower than baseline, respectively. In the control group, the dominant (P < 0.001) and nondominant hand (P = 0.006) were 2.9 (95% CI, 1.4 to 4.3) and 1.7 (95% CI, 0.5 to 2.9) seconds slower than baseline, respectively. After flumazenil, the dominant hand (P = 0.99) and nondominant hand (P = 0.019) performed 0.2 (95% CI, -0.7 to 1.0) and 1.3 (95% CI, -0.2 to 2.4) seconds faster than baseline, respectively.ConclusionsIn patients with eloquent area gliomas, mild sedation with midazolam induced motor coordination deficits in upper limbs. This deficit was almost completely reversed by the benzodiazepine antagonist flumazenil, suggesting that this is a reversible abnormality linked to occupation of the receptor by midazolam.

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