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Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury.

Publication ,  Journal Article
Welch, TP; Wallendorf, MJ; Kharasch, ED; Leonard, JR; Doctor, A; Pineda, JA
Published in: Crit Care Med
April 2016

OBJECTIVE: To evaluate the clinical effectiveness of bolus-dose fentanyl and midazolam to treat episodic intracranial hypertension in children with severe traumatic brain injury. DESIGN: Retrospective cohort. SETTING: PICU in a university-affiliated children's hospital level I trauma center. PATIENTS: 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. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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 (Δarea 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 Δarea 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 Δarea under the curve-intracranial hypertension = +17 mm Hg × min, 95% CI, 0-34 mm Hg × min; p = 0.04). The mean Δarea 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 Δarea under the curve-cerebral perfusion pressure). CONCLUSIONS: 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.

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Published In

Crit Care Med

DOI

EISSN

1530-0293

Publication Date

April 2016

Volume

44

Issue

4

Start / End Page

809 / 818

Location

United States

Related Subject Headings

  • Treatment Failure
  • Retrospective Studies
  • Midazolam
  • Male
  • Intracranial Pressure
  • Intracranial Hypertension
  • Infant, Newborn
  • Infant
  • Hypnotics and Sedatives
  • Humans
 

Citation

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Chicago
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Welch, T. P., Wallendorf, M. J., Kharasch, E. D., Leonard, J. R., Doctor, A., & Pineda, J. A. (2016). Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury. Crit Care Med, 44(4), 809–818. https://doi.org/10.1097/CCM.0000000000001558
Welch, Timothy P., Michael J. Wallendorf, Evan D. Kharasch, Jeffrey R. Leonard, Allan Doctor, and Jose A. Pineda. “Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury.Crit Care Med 44, no. 4 (April 2016): 809–18. https://doi.org/10.1097/CCM.0000000000001558.
Welch TP, Wallendorf MJ, Kharasch ED, Leonard JR, Doctor A, Pineda JA. Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury. Crit Care Med. 2016 Apr;44(4):809–18.
Welch, Timothy P., et al. “Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury.Crit Care Med, vol. 44, no. 4, Apr. 2016, pp. 809–18. Pubmed, doi:10.1097/CCM.0000000000001558.
Welch TP, Wallendorf MJ, Kharasch ED, Leonard JR, Doctor A, Pineda JA. Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury. Crit Care Med. 2016 Apr;44(4):809–818.

Published In

Crit Care Med

DOI

EISSN

1530-0293

Publication Date

April 2016

Volume

44

Issue

4

Start / End Page

809 / 818

Location

United States

Related Subject Headings

  • Treatment Failure
  • Retrospective Studies
  • Midazolam
  • Male
  • Intracranial Pressure
  • Intracranial Hypertension
  • Infant, Newborn
  • Infant
  • Hypnotics and Sedatives
  • Humans