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Cerebrovascular Response to Propofol, Fentanyl, and Midazolam in Moderate/Severe Traumatic Brain Injury: A Scoping Systematic Review of the Human and Animal Literature.

ABSTRACT: Intravenous propofol, fentanyl, and midazolam are utilized commonly in critical care for metabolic suppression and anesthesia. The impact of propofol, fentanyl, and midazolam on cerebrovasculature and cerebral blood flow (CBF) is unclear in traumatic brain injury (TBI) and may carry important implications, as care is shifting to focus on cerebrovascular reactivity monitoring/directed therapies. The aim of this study was to perform a scoping review of the literature on the cerebrovascular/CBF effects of propofol, fentanyl, and midazolam in human patients with moderate/severe TBI and animal models with TBI. A search of MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and the Cochrane Library from inception to May 2020 was performed. All articles were included pertaining to the administration of propofol, fentanyl, and midazolam, in which the impact on CBF/cerebral vasculature was recorded. We identified 14 studies: 8 that evaluated propofol, 5 that evaluated fentanyl, and 2 that evaluated midazolam. All studies suffered from significant limitations, including: small sample size, and heterogeneous design and measurement techniques. In general, there was no significant change seen in CBF/cerebrovascular response to administration of propofol, fentanyl, or midazolam during experiments where PCO₂ and mean arterial pressure (MAP) were controlled. This review highlights the current knowledge gap surrounding the impact of commonly utilized sedative drugs in TBI care. This work supports the need for dedicated studies, both experimental and human-based, evaluating the impact of these drugs on CBF and cerebrovascular reactivity/response in TBI.

SUBMITTER: Froese L

PROVIDER: S-EPMC7685293 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To evaluate the clinical effectiveness of bolus-dose fentanyl and midazolam to treat episodic intracranial hypertension in children with severe traumatic brain injury.Retrospective cohort.PICU in a university-affiliated children's hospital level I trauma center.Thirty-one children 0-18 years of age with severe traumatic brain injury (Glasgow Coma Scale score of ? 8) who received bolus doses of fentanyl and/or midazolam for treatment of episodic intracranial hypertension.None.The area under the curve from high-resolution intracranial pressure-time plots was calculated to represent cumulative intracranial hypertension exposure: area under the curve for intracranial pressure above 20 mm Hg (area under the curve-intracranial hypertension) was calculated in 15-minute epochs before and after administration of fentanyl and/or midazolam for the treatment of episodic intracranial hypertension. Our primary outcome measure, the difference between predrug and postdrug administration epochs (?area under the curve-intracranial hypertension), was calculated for all occurrences. We examined potential covariates including age, injury severity, mechanism, and time after injury; time after injury correlated with ?area under the curve-intracranial hypertension. In a mixed-effects model, with patient as a random effect, drug/dose combination as a fixed effect, and time after injury as a covariate, intracranial hypertension increased after administration of fentanyl and/or midazolam (overall aggregate mean ?area under the curve-intracranial hypertension = +17 mm Hg × min, 95% CI, 0-34 mm Hg × min; p = 0.04). The mean ?area under the curve-intracranial hypertension increased significantly after administration of high-dose fentanyl (p = 0.02), low-dose midazolam (p = 0.006), and high-dose fentanyl plus low-dose midazolam (0.007). Secondary analysis using age-dependent thresholds showed no significant impact on cerebral perfusion pressure deficit (mean ?area under the curve-cerebral perfusion pressure).Bolus dosing of fentanyl and midazolam fails to reduce the intracranial hypertension burden when administered for episodic intracranial hypertension. Paradoxically, we observed an overall increase in intracranial hypertension burden following drug administration, even after accounting for within-subject effects and time after injury. Future work is needed to confirm these findings in a prospective study design.

Project description:BackgroundPatients in the intensive care unit (ICU) are often under stress and fail to cooperate well with invasive treatments. Analgesia and sedation are of great significance for reducing the suffering of patients and ensuring the application and effectiveness of treatment. For better clinical choice, we aimed to explore the effect of the combination of propofol + fentanyl or midazolam + fentanyl on the short-term prognosis of hospitalized patients in the ICU.MethodsAccording to the inclusion and exclusion criteria, we retrospectively included patients in the MIMIC-IV database receiving midazolam + fentanyl or propofol + fentanyl analgesic and sedative treatment using Structured Query Language (SQL) to extract clinical data from the MIMIC-IV database. The primary endpoint was the death rate within 28 days after the patient was admitted to the ICU. Doubly robust estimation was used to infer the relationship between sedation and analgesia and 28 days outcome. The gradient boosted model (GBM) was used to estimate the propensity score (PS) of the patient's sedation and analgesia program, PS was used as the weight, and the inverse probabilities weighting (IPW) model was used to generate a weighted cohort.ResultsIn total, 4,188 cases were included, with 2,174 (51.9%) in the propofol group and 2,014 (48.1%) in the midazolam group. In the PS score matching cohort, the 28-day mortality of patients in the midazolam group was 30.8%, and the 28-day mortality of patients in the propofol group was 25.5%. The adjusted odds ratio (OR) value was 1.421 [95% confidence interval (CI): 1.118-1.806, P<0.001]. Patients in the propofol group did not use vasoactive drugs for a longer period of time than the midazolam group, and patients in the propofol group received significantly more fluids than those in the midazolam group in the first three days after admission to the ICU.ConclusionsCompared with midazolam combined with fentanyl, propofol combined with fentanyl for sedation and analgesia can reduce the risk of short-term death in ICU patients.

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Cerebrovascular Response to Propofol, Fentanyl, and Midazolam in Moderate/Severe Traumatic Brain Injury: A Scoping Systematic Review of the Human and Animal Literature.

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