Is there any dose of benzodiazepines safe for delirium in the PICU? A secondary analysis of the PICU Up! pilot trial dataset

Authors

• Isabella Blackman, Johns Hopkins University School of Medicine, Baltimore, MD.
• Rachel De Armas, Johns Hopkins University School of Medicine, Baltimore, MD.
• Sofia Padilla, Advocate Health - MidwestFollow
• Sarah Goldberg, Department of Cardiology, Boston Children's Hospital, Boston, MA.
• Samer Abu-Sultaneh, Department of Pediatrics, Division of Pediatric Critical Care, Indiana University School of Medicine, Indianapolis, IN.
• Michelle Piole, Department of Pediatrics, Division of Pediatric Critical Care, SSM Health Cardinal Glennon Children's Hospital, St. Louis, MO.
• Megan Geno, Department of Physical Therapy and Occupational Therapy Services, Boston Children's Hospital, Boston, MA.
• Mary-Jeanne Manning, Department of Critical Care Medicine, Boston Children's Hospital, Boston, MA.
• Kate Madden, Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, MA.
• Erik Madsen, Department of Pediatrics, Division of Pediatric Critical Care, SSM Health Cardinal Glennon Children's Hospital, St. Louis, MO.
• Deanna Behrens, Advocate Health - MidwestFollow
• Danielle Maue, Department of Pediatrics, Division of Pediatric Critical Care, Indiana University School of Medicine, Indianapolis, IN.
• Kelechi Iheagwara, Our Lady of the Lake Regional Medical Center, Baton Rouge, LA.
• Colleen Mennie, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
• Sukaina Furniturewala, Department of Pediatrics, Icahn School of Medicine at Mount Sinai (NYC Health and Hospitals: Elmhurst), New York, NY.
• Ronke Awojoodu, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
• Elizabeth Colantuoni, Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
• Dale Needham, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
• Sapna R. Kudchadkar, Departments of Anesthesiology and Critical Care Medicine, Pediatrics, and Physical Medicine and Rehabilitation, Johns Hopkins School of Medicine, Baltimore, MD.
• Razvan Azamfirei, Johns Hopkins University School of Medicine, Baltimore, MD.

Recommended Citation

Blackman I, De Armas R, Padilla S, et al. Is There Any Dose of Benzodiazepines Safe for Delirium in the PICU? A Secondary Analysis of the PICU Up! Pilot Trial Dataset. Crit Care Explor. 2026;8(4):e1389. Published 2026 Mar 31. doi:10.1097/CCE.0000000000001389

Affiliations

Advocate Children's Hospital, Park Ridge

Abstract

Importance: A better understanding of the relationship between sedative dose and PICU delirium is crucial for delirium prevention.

Objectives: To identify risk factors for delirium in critically ill children and characterize the dose-response relationship between benzodiazepine administration and next-day delirium in the PICU.

Design, setting, and participants: A secondary analysis of 10,644 patient-days from prospectively collected data, including sedative and analgesic use and delirium screening from the multicenter, randomized PICU Up! pilot trial, including seven PICUs and 1,006 patients.

Main outcomes and measures: Delirium odds were evaluated using a multivariable logistic regression model adjusted for known delirium risk factors.

Results: Benzodiazepines, opioids, and dexmedetomidine were commonly used in the PICU. A higher previous-day benzodiazepine dose was associated with increased odds of delirium on a given day with an adjusted odds ratio (aOR) of 1.12 per midazolam milligram equivalent per kilogram (95% CI, 1.02-1.25; p = 0.020). The most pronounced increase in delirium risk occurred at the lowest doses, between 0 and 0.01 mg/kg (p = 0.010), with risk continuing to rise at higher doses. Previous-day opioid dose was not associated with changes in the odds of delirium (aOR, 1.00; 95% CI, 1.00-1.00; p = 0.892). Any previous-day dexmedetomidine administration was associated with increased odds of next-day delirium (aOR, 1.26; 95% CI, 1.04-1.52; p = 0.019). Additionally, same-day physical restraint use was associated with increased odds of delirium (aOR, 1.72; 95% CI, 1.27-2.31; p < 0.001).

Conclusions and relevance: No safe benzodiazepine threshold was identified in critically ill children, with delirium risk increased even at minimal doses. The greatest increase in odds occurred at the lowest doses. Hence, regardless of dose, benzodiazepine use should be minimized or eliminated whenever possible. Physical restraints and dexmedetomidine use were also associated with increased risk of delirium; thus, a tailored approach for each patient with an emphasis on judicious use is critical.

Type

Article

PubMed ID

41915588