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

Lin, Nan; Han, Ruquan; Hui, Xuan; Zhang, Kaiying; Gelb, Adrian W.

doi:10.1097/aln.0000000000002726

Cited by 13 publications

(23 citation statements)

References 23 publications

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“…In this issue of Anesthesiology, Lin et al report midazolam-induced upper limb motor deficits in patients with supratentorial gliomas. 2 This aligns with previous work demonstrating that GABAergic agonism unmasks neurologic deficits in patients with brain tumors or cerebrovascular disease. 1,3,4 What is unique in the current study by Lin et al 2 is the demonstration that flumazenil reverses these pharmacologically induced deficits, supporting a GABAergic mechanism.…”

supporting

confidence: 90%

“…2 This aligns with previous work demonstrating that GABAergic agonism unmasks neurologic deficits in patients with brain tumors or cerebrovascular disease. 1,3,4 What is unique in the current study by Lin et al 2 is the demonstration that flumazenil reverses these pharmacologically induced deficits, supporting a GABAergic mechanism. Interestingly, motor dysfunction was not restricted to the contralateral limb in this study; ipsilateral motor dysfunction was observed as well, and flumazenil restored baseline function bilaterally.…”

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confidence: 90%

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Pharmacologic Unmasking of Neurologic Deficits

Vlisides

Mashour

2019

Anesthesiology

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Neuroplasticity remains one of the most intriguing aspects of modern neuroscience and is of clinical relevance to anesthesiology. Indeed, the brain possesses a remarkable ability to adapt to various perturbations via structural and functional alterations. For example, stroke patients demonstrate signs of adaptation by regaining neurologic function after injury, without regeneration of the original lesion per se. However, such adaptations can be reversed pharmacologically, with relative selectivity by agents that potentiate the transmission of gamma-aminobutyric acid (GABA) compared with agents that antagonize the cholinergic system. 1 Understanding the interactions of brain dysfunction, adaptive changes, and pharmacology is important for the field of anesthesiology. Studying the effects of our drugs on neurologic function in surgical patients may provide a unique window into prior neurologic injury, subsequent neuroplastic changes, and associated clinical vulnerability, particularly in those with known or suspected neuropathology.

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confidence: 90%

supporting

confidence: 90%

Pharmacologic Unmasking of Neurologic Deficits

Vlisides

Mashour

2019

Anesthesiology

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“…One previous study reported that BZD use was a trigger for post-stroke recrudescence ( 15 ). Further, akin to the present work, transient worsening has been noted in patients with space-occupying lesions or an ischemic event specifically with midazolam usage ( 16 – 19 ). Moreover, there is evidence to support a phenomenon whereby neurological deficits associated with space-occupying lesions or ischemic events from which patients recovered are unmasked by BZD sedation.…”

Section: Discussionsupporting

confidence: 60%

“…Previous studies have reported upon an association between midazolam use and transient unmasking of past neurological deficits ( 17 – 21 ). Notably, one study demonstrated reversibility of worsened deficits by treatment with flumazenil ( 16 ). This body of literature has been summarized in greater detail within a recent systematic review on this topic ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Benzodiazepine Sedation and Postoperative Neurological Deficits after Awake Craniotomy for Brain Tumor – An Exploratory Retrospective Cohort Study

et al. 2022

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An awake craniotomy is a common neurosurgical procedure for excising brain tumor(s) located near or in eloquent areas. The use of benzodiazepine (BZD) for sedation in some patients with neuropathological conditions (e.g., stroke, brain tumors) has been previously linked with re-appearance of neurological deficits including limb incoordination, ataxia, and motor weakness, resulting in complications for the patient along with procedural challenges. Whether or not these findings can be extrapolated to patients undergoing brain tumor resection is largely unknown. The current work primarily sought to compare neurological outcome(s) in the immediate postoperative period between BZD-free and BZD-based sedation techniques in patients undergoing awake craniotomy. Using a database composed of awake craniotomies conducted within a single center and by a single surgeon, patients were retrospectively classified based on midazolam administration into BZD-free sedation (n=125) and BZD-based sedation (n=416) groups. Patients from each group were matched based on age, sex, tumor location, tumor grade, preoperative neurological deficits, non-operative BZD use, and Karnofsky Performance Scale scores, resulting in 108 patients within each group. Postoperative neurological deficits were recorded. Logistic regression analyses were conducted comparing postoperative neurological deficits between the matched groups. Postoperative neurological deficits were more prevalent within the BZD-based sedation group compared to the BZD-free sedation group (adjusted odds ratio (aOR)=1.903, 95% CI=1.018-3.560, p=0.044). In addition, subgroup analysis of the matched cohort showed a relationship between preoperative neurological symptoms and postoperative neurological deficits in the BZD-based sedation group (aOR=3.756, 95% CI=1.390-10.147, p=0.009). Our findings support the notion that the increased incidence of postoperative neurological deficits with BZD sedation may in part be related to the unmasking of preoperative neurological deficits. Further studies are required to confirm this phenomenon.

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“…Lin et al studied 15 adult patients with eloquent area glioma scheduled for elective resection of the tumors. 1 Prior to induction of anesthesia, motor coordination and eye-hand coordination of upper extremity (contralateral or ipsilateral to tumor location) were evaluated using Nine-Hole Peg Test in three phases: baseline (before midazolam), sedation (after midazolam), and reversal (after reversal of midazolam with flumazenil). Endpoint of midazolam administration was to achieve Observer Assessment of Alertness and Sedation score (OAAS) of 4 (i.e., sedated, but arousable and fully cooperative), and the endpoint of flumazenil reversal was to achieve OAAS score of 5 (i.e., fully alert).…”

Section: Reversal Of Midazolam-induced Motor Deficits By Flumazenil In Patients With Eloquent Area Gliomamentioning

confidence: 99%

Year in Review: Synopsis of Selected Articles in Neuroanesthesia and Neurocritical Care from 2019

Leong

Dalby

Venkatraghavan

2020

Journal of Neuroanaesthesiology and Critical Care

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This review is a synopsis of selected articles from neuroscience, neuroanesthesia, and neurocritical care from 2019 (January–November 2019). The journals reviewed included anesthesia journals, critical care medicine journals, neurosurgical journals, as well as high-impact medical journals such as the Lancet, Journal of American Medical Association, New England Journal of Medicine, and Stroke. This summary of important articles will serve to update the knowledge of anesthesiologists and other perioperative physicians who provide care to neurosurgical and neurocritical cases.

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

Abstract: This article is featured in "This Month in Anesthesiology," page 1A. This article is accompanied by an editorial on p. 5. This article has a related Infographic on p. 17A. This article has an audio podcast.

Cited by 13 publications

References 23 publications

Pharmacologic Unmasking of Neurologic Deficits

Pharmacologic Unmasking of Neurologic Deficits

Benzodiazepine Sedation and Postoperative Neurological Deficits after Awake Craniotomy for Brain Tumor – An Exploratory Retrospective Cohort Study

Year in Review: Synopsis of Selected Articles in Neuroanesthesia and Neurocritical Care from 2019

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