Related Experiment Video
Updated: Jan 27, 2026
Author Spotlight: Exploring Venous Waveforms for Non-Invasive Respiratory Monitoring in Pigs
Published on: March 8, 2024
Morphine Dose Optimization in Critically Ill Pediatric Patients With Acute Respiratory Failure: A Population
Athena F Zuppa1,2, Giselle R Benitez3, Nicole R Zane2
1Department of Pediatric Anesthesia and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA.
Insights
This study modeled morphine pharmacokinetics in critically ill children, finding weight and age predict drug levels. Prolonged ventilation impacts morphine metabolism, but genetic factors were not identified in this cohort.
Area of Science:
- Pharmacology
- Pediatric Critical Care
- Pharmacogenomics
Background:
- Critically ill children require precise medication dosing.
- Morphine is commonly used for pain and sedation in pediatric intensive care units (PICUs).
- Understanding morphine's disposition is crucial for optimizing therapy in vulnerable pediatric populations.
Purpose of the Study:
- To develop a pharmacokinetic-pharmacogenomic population model for morphine in critically ill children.
- To identify factors influencing morphine and its metabolite concentrations.
- To explore potential genetic influences on morphine metabolism.
Main Methods:
- Prospective observational study in 13 US PICUs.
- Included 66 mechanically ventilated pediatric patients receiving morphine infusions.
- Utilized serial blood sampling for drug/metabolite quantification and genotyping; analyzed using nonlinear mixed-effects modeling.
Main Results:
- Body weight and postmenstrual age were significant predictors of morphine and metabolite pharmacokinetics.
- Mechanical ventilation duration >= 10 days reduced metabolite formation/elimination by over 30%.
- No heritable factors (e.g., UGT2B7) were identified due to sample size and population heterogeneity.
Conclusions:
- Established a pharmacokinetic model for morphine in critically ill children, highlighting nonheritable factors.
- Provides a foundation for future research into genetic influences on morphine metabolism.
- Emphasizes the impact of ventilation duration on morphine disposition in pediatric patients.
Objective:
To develop a pharmacokinetic-pharmacogenomic population model of morphine in critically ill children with acute respiratory failure.
Design:
Prospective pharmacokinetic-pharmacogenomic observational study.
Setting:
Thirteen PICUs across the United States.
Patients:
Pediatric subjects (n = 66) mechanically ventilated for acute respiratory failure, weight greater than or equal to 7 kg, receiving morphine and/or midazolam continuous infusions.
Interventions:
Serial blood sampling for drug quantification and a single blood collection for genomic evaluation.
Measurements And Main Results:
Concentrations of morphine, the two main metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were quantified by high-performance liquid chromatography tandem mass spectrometry/mass spectroscopy. Subjects were genotyped using the Illumina HumanOmniExpress genome-wide single nucleotide polymorphism chip. Nonlinear mixed-effects modeling was performed to develop the pharmacokinetic-pharmacogenomic model. A two-compartment model with linear elimination and two individual compartments for metabolites best describe morphine disposition in this population. Our analysis demonstrates that body weight and postmenstrual age are relevant predictors of pharmacokinetic parameters of morphine and its metabolites. Furthermore, our research shows that a duration of mechanical ventilation greater than or equal to 10 days reduces metabolite formation and elimination upwards of 30%. However, due to the small sample size and relative heterogeneity of the population, no heritable factors associated with uridine diphosphate glucuronyl transferase 2B7 metabolism of morphine were identified.
Conclusions:
The results provide a better understanding of the disposition of morphine and its metabolites in critically ill children with acute respiratory failure requiring mechanical ventilation due to nonheritable factors. It also provides the groundwork for developing additional studies to investigate the role of heritable factors.
More Related Videos
05:16Cutoff Value of Phase Angle by Bioelectrical Impedance Analysis at Admission as a Prognostic Factor in Patients with Acute Heart Failure
Published on: June 10, 2025
04:05Author Spotlight: Unveiling Prognostic Indicators in Heart Failure - The Role of Phase Angle and Bioelectrical Impedance Analysis
Published on: June 30, 2023
Related Concept Videos
01:21Acute Respiratory Failure-I
Definition: It is defined by specific criteria based on blood gas measurements. Hypoxemia happens when the partial pressure of oxygen (PaO2) falls below 60 mmHg. At the same time,...
01:21Acute Respiratory Failure-II
The underlying physiological abnormalities that contribute to hypoxemic respiratory failure include:
01:29Acute Respiratory Failure-V
Ensure that patients are monitored continuously for their response to therapy, including changes in...
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
01:30Acute Respiratory Failure-III
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution