Newly Published
Perioperative Medicine  |   May 2019
Midazolam Sedation Induces Upper Limb Coordination Deficits That Are Reversed by Flumazenil in Patients with Eloquent Area Gliomas
Author Notes
  • 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.); and the Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California (A.W.G.).
  • This work was presented in a poster session at the Society for Neuroscience in Anesthesiology and Critical Care 45th annual meeting in Boston, Massachusetts, on October 20, 2017.
    This work was presented in a poster session at the Society for Neuroscience in Anesthesiology and Critical Care 45th annual meeting in Boston, Massachusetts, on October 20, 2017.×
  • Submitted for publication on September 20, 2018. Accepted for publication on February 22, 2019.
    Submitted for publication on September 20, 2018. Accepted for publication on February 22, 2019.×
  • Acknowledgments: The authors thank the neurosurgical team at Beijing Titan Hospital, Capital Medical University (Beijing, China) led by Yanhui Sun, M.D., Song Lin, M.D., and Zhixian Gao, M.D., for helping to identify the glioma patients and providing unconditional support in allowing consistent access to their patients, and Aidong Wang, M.D., and Mrs. Shirong Peng (nurse-in-charge) for their help in coordinating the study and the operative procedures.
    Acknowledgments: The authors thank the neurosurgical team at Beijing Titan Hospital, Capital Medical University (Beijing, China) led by Yanhui Sun, M.D., Song Lin, M.D., and Zhixian Gao, M.D., for helping to identify the glioma patients and providing unconditional support in allowing consistent access to their patients, and Aidong Wang, M.D., and Mrs. Shirong Peng (nurse-in-charge) for their help in coordinating the study and the operative procedures.×
  • Research Support: This work was funded by the National Natural Science Foundation of China (Beijing, China; grant No. 81701038); the Beijing Municipal Administration of Hospitals’ Youth Program (Beijing, China; grant No. QML20160503), the Ascent Plan (grant No. DFL20180502), and was also supported by the Beijing Municipal Administration of Hospitals’ Clinical Medicine Development of Special Funding (Beijing, China; grant No. ZYLX201708).
    Research Support: This work was funded by the National Natural Science Foundation of China (Beijing, China; grant No. 81701038); the Beijing Municipal Administration of Hospitals’ Youth Program (Beijing, China; grant No. QML20160503), the Ascent Plan (grant No. DFL20180502), and was also supported by the Beijing Municipal Administration of Hospitals’ Clinical Medicine Development of Special Funding (Beijing, China; grant No. ZYLX201708).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Reproducible Science: Full protocol available at: linnan127@gmail.com. Raw data available at: linnan127@gmail.com.
    Reproducible Science: Full protocol available at: linnan127@gmail.com. Raw data available at: linnan127@gmail.com.×
  • Correspondence: Address correspondence to Dr. Gelb: Department of Anesthesia and Perioperative Care, University of California San Francisco, 500 Parnassus Ave, MUE 404, San Francisco, California 94143. Adrian.gelb@ucsf.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Central and Peripheral Nervous Systems / Pharmacology
Perioperative Medicine   |   May 2019
Midazolam Sedation Induces Upper Limb Coordination Deficits That Are Reversed by Flumazenil in Patients with Eloquent Area Gliomas
Anesthesiology Newly Published on May 13, 2019. doi:10.1097/ALN.0000000000002726
Anesthesiology Newly Published on May 13, 2019. doi:10.1097/ALN.0000000000002726
Abstract

Editor’s Perspective:

What We Already Know about This Topic: Sedation is known to unmask focal neurologic deficits in patients with supratentorial brain tumors but the mechanism is unclear

What This Article Tells Us That Is New: When induced with midazolam, these deficits can be reversed by flumazenil, suggesting a γ-aminobutyric acid–mediated mechanism

Background: Midazolam 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.

Methods: This 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.

Results: Thirty-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.

Conclusions: In 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.