Related Experiment Video
Updated: Feb 11, 2026
How to Administer Near-Infrared Spectroscopy in Critically ill Neonates, Infants, and Children
Published on: August 19, 2020
Benzodiazepines and Development of Delirium in Critically Ill Children: Estimating the Causal Effect
Kalgi Mody1, Savneet Kaur2, Elizabeth A Mauer3
1Department of Pediatrics, Mount Sinai School of Medicine, New York, NY.
Insights
Benzodiazepine use in pediatric intensive care units (PICUs) significantly increases the risk of delirium in critically ill children. Limiting benzodiazepine dosage may reduce delirium rates.
Area of Science:
- Pediatric Critical Care Medicine
- Neuroscience
- Pharmacology
Background:
- Benzodiazepines are commonly used sedatives in pediatric intensive care units (PICUs).
- A potential association exists between benzodiazepine administration and the development of delirium in critically ill children.
- Current guidelines consider benzodiazepines a first-line sedative choice despite this concern.
Purpose of the Study:
- To investigate the temporal relationship between benzodiazepine administration and delirium in critically ill children.
- To control for time-varying covariates, including mechanical ventilation and opiate use.
- To evaluate the association between benzodiazepine dosage and the subsequent risk of delirium.
Main Methods:
- Retrospective observational study design.
- Prospective screening for delirium using the Cornell Assessment for Pediatric Delirium.
- Multivariable mixed effects modeling and marginal structural modeling to control for confounding variables.
Main Results:
- Benzodiazepine use was strongly associated with an increased risk of delirium, more than quadrupling delirium rates (OR, 4.4).
- After controlling for time-dependent confounders, the association remained significant (OR, 3.3).
- A dose-response relationship was observed, with increased benzodiazepine dosage correlating with a higher risk of delirium.
Conclusions:
- Benzodiazepines are an independent and modifiable risk factor for delirium in critically ill children.
- The findings suggest a causal link between benzodiazepine exposure and pediatric delirium.
- Limiting benzodiazepine use in PICUs may be a strategy to reduce delirium incidence.
Objectives:
Benzodiazepine use may be associated with delirium in critically ill children. However, benzodiazepines remain the first-line sedative choice in PICUs. Objectives were to determine the temporal relationship between administration of benzodiazepines and delirium development, control for time-varying covariates such as mechanical ventilation and opiates, and evaluate the association between dosage of benzodiazepines and subsequent delirium.
Design:
Retrospective observational study.
Setting:
Academic tertiary care PICU.
Patients:
All consecutive admissions from January 2015 to June 2015.
Interventions:
Retrospective assessment of benzodiazepine exposure in a population that had been prospectively screened for delirium.
Measurements And Main Results:
All subjects were prospectively screened for delirium throughout their stay, using the Cornell Assessment for Pediatric Delirium, with daily cognitive status assigned as follows: delirium, coma, or normal. Multivariable mixed effects modeling determined predictors of delirium overall, followed by subgroup analysis to assess effect of benzodiazepines on subsequent development of delirium. Marginal structural modeling was used to create a pseudorandomized sample and control for time-dependent variables, obtaining an unbiased estimate of the relationship between benzodiazepines and next day delirium. The cumulative daily dosage of benzodiazepines was calculated to test for a dose-response relationship. Benzodiazepines were strongly associated with transition from normal cognitive status to delirium, more than quadrupling delirium rates (odds ratio, 4.4; CI, 1.7-11.1; p < 0.002). Marginal structural modeling demonstrated odds ratio 3.3 (CI, 1.4-7.8), after controlling for time-dependent confounding of cognitive status, mechanical ventilation, and opiates. With every one log increase in benzodiazepine dosage administered, there was a 43% increase in risk for delirium development.
Conclusions:
Benzodiazepines are an independent and modifiable risk factor for development of delirium in critically ill children, even after carefully controlling for time-dependent covariates, with a dose-response effect. This temporal relationship suggests causality between benzodiazepine exposure and pediatric delirium and supports limiting the use of benzodiazepines in critically ill children.
More Related Videos
10:11Portable Intermodal Preferential Looking IPL: Investigating Language Comprehension in Typically Developing Toddlers and Young Children with Autism
Published on: December 14, 2012
04:55Handheld Metal Detector Screening for Metallic Foreign Body Ingestion in Children
Published on: September 11, 2018
Related Concept Videos
01:21Causality in Epidemiology
01:19Sedatives and Hypnotics Drugs: Benzodiazepines
Benzodiazepines work by enhancing the effects of the inhibitory neurotransmitter GABA. They bind to the GABAA receptor, increasing its affinity for GABA, which opens chloride...
01:14CNS Depressants: Barbiturates and Benzodiazepines
01:29Anxiolytic Drugs: Benzodiazepines and Buspirone
01:16Critical Region, Critical Values and Significance Level
In hypothesis testing, a sample statistic is converted to a test statistic using z, t, or chi-square distribution. A critical region is an area under the curve in probability distributions demarcated by the critical value. When the test statistic falls in this region, it suggests that the null hypothesis must be rejected. As this region contains all those values of the...
01:31Critical Values