Mild Sedation Exacerbates or Unmasks Focal Neurologic Dysfunction in Neurosurgical Patients with Supratentorial Brain Mass Lesions in a Drug-specific Manner

Abstract

Background Sedation is commonly used in neurosurgical patients but has been reported to produce transient focal neurologic dysfunction. The authors hypothesized that in patients with frontal–parietal–temporal brain tumors, focal neurologic deficits are unmasked or exacerbated by nonspecific sedation independent of the drug used. Methods This was a prospective, randomized, single-blind, self-controlled design with parallel arms. With institutional approval, patients were randomly assigned to one of the four groups: “propofol,” “midazolam,” “fentanyl,” and “dexmedetomidine.” The sedatives were titrated by ladder administration to mild sedation but fully cooperative, equivalent to Observer’s Assessment of Alertness and Sedation score = 4. National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurologic function before and after sedation. The study’s primary outcome was the proportion of NIHSS-positive change in patients after sedation to Observer’s Assessment of Alertness and Sedation = 4. Results One hundred twenty-four patients were included. Ninety had no neurologic deficits at baseline. The proportion of NIHSS-positive change was midazolam 72%, propofol 52%, fentanyl 27%, and dexmedetomidine 23% (P less than 0.001 among groups). No statistical difference existed between propofol and midazolam groups (P = 0.108) or between fentanyl and dexmedetomidine groups (P = 0.542). Midazolam and propofol produced more sedative-induced focal neurologic deficits compared with fentanyl and dexmedetomidine. The neurologic function deficits were mainly limb motor weakness and ataxia. Patients with high-grade gliomas were more susceptible to the induced neurologic dysfunction regardless of the sedative. Conclusions Midazolam and propofol augmented or revealed neurologic dysfunction more frequently than fentanyl and dexmedetomidine at equivalent sedation levels. Patients with high-grade gliomas were more susceptible than those with low-grade gliomas.

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

“…In our previous investigation, we found motor function and limb ataxia were the most affected. 6 In order to more accurately detect and quantify this deficit, the Nine-hole Peg Test has good reliability for testing upper limb dexterity, motor coordination, and hand-eye coordination, as well as patient ability to follow simple directions. 7,10 It therefore goes beyond assessing a single neurologic function confined to the tumor and its surroundings, but also assesses multiple functions reflecting the network connections between cortical and subcortical regions.…”

“…We speculated in our previous investigation that mild sedation-induced focal neurologic function worsening in patients with supratentorial intracranial lesions was likely transient and would return to baseline once the medications were no longer present on relevant receptors. 6 The sedative we used in this study is a specific benzodiazepine agonist: midazolam. It is a GABAergic agent that we previously found to most impair neurologic function, compared with other agents that have other pharmacologic mechanisms.…”

“…5 In our previous study, we found that midazolam sedation profoundly exacerbates or unmasks motor deficits in patients with supratentorial mass lesions. These deficits primarily involved limb motor function or ataxia as assessed using the National Institutes of Health Stroke Scale 6 ; however, neither the mechanism nor the reversibility of effects aBStract 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.…”

Sevoflurane versus PRopofol Combined with Remifentanil Anesthesia Impact on Postoperative Neurologic Function in Supratentorial Gliomas (SPRING): Protocol for a Randomized Controlled Trial

“…Patients with neurological diseases, e.g., brain tumors, are usually excluded in studies examining the correlation between anesthesia and neural function [8], as those diseases are major confounders leading to nervous system dysfunction, however, anesthetic effects on neural function cannot be ignored in neurosurgical patients, let alone the previously mentioned "vulnerable" brain tumor patient who is even more susceptible to anesthetics [9]. Recent findings have reported patients with supplementary motor area (SMA) lesions presenting with intraoperative neurological deficits for awake craniotomy which could not be explained anatomically by their intact corticospinal tracts as detected by cortical stimulation or cortical mapping [10,11], and these deficits were reversible after operations over time without further intervention.…”

“…It has been reported that in some supratentorial brain mass patients, a small plasma concentration of sedative could significantly worsen neurologic deficits before any operative intervention [9], but there is no evidence related to how residual anesthetics affect neurologic deficits after operations. are eligible for the study.…”