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Remifentanil degradation in umbilical cord blood of preterm infants
Lars Welzing1, Sabine Ebenfeld, Verena Dlugay
1Department of Neonatology and Pediatric Intensive Care, University Hospital of Cologne, Cologne, Germany. lars.welzing@uk-koeln.de
Insights
Preterm infants possess high nonspecific esterase activity, similar to term infants, enabling rapid metabolism of remifentanil. This supports the safe clinical use of remifentanil in this vulnerable pediatric population.
Area of Science:
- Neonatal Pharmacology
- Pediatric Anesthesiology
- Drug Metabolism
Background:
- Limited pharmacokinetic data exists for remifentanil in preterm infants, a vulnerable population.
- Ethical constraints on blood sampling in preterm infants hinder pharmacokinetic studies.
- Remifentanil is increasingly used in preterm neonates despite data gaps.
Purpose of the Study:
- To investigate the activity of nonspecific esterases in preterm and term infant umbilical cord serum.
- To determine if gestational age influences the activity of blood esterases responsible for remifentanil metabolism.
Main Methods:
- Umbilical cord serum from preterm and term infants was collected.
- Remifentanil degradation was assessed in serum samples at various time points using liquid chromatography-mass spectrometry.
- Nonspecific esterase activity was measured by quantifying remifentanil and its metabolite GR90291.
Main Results:
- Degradation rates of remifentanil were comparable between preterm and term infants.
- The median degradation half-life of remifentanil was 143 minutes, with no significant difference based on gestational age.
- Remifentanil concentrations remained stable in control samples lacking serum.
Conclusions:
- Very preterm infants demonstrate high nonspecific esterase activity in umbilical cord blood, similar to term infants.
- This comparable esterase activity suggests rapid remifentanil metabolism in preterm infants.
- Findings support the clinical use of remifentanil in preterm infants, indicating no prolonged side effects due to metabolism.
Background:
No pharmacokinetic data about remifentanil in preterm infants exist, although remifentanil is increasingly used in this especially vulnerable subgroup of pediatric patients. Unfortunately, ethical restrictions in the volume of blood that can be withdrawn for kinetic sampling nearly prohibit pharmacokinetic studies in preterm infants.
Methods:
Because remifentanil is rapidly metabolized by nonspecific blood esterases, we collected umbilical cord serum of preterm and term infants to investigate whether the activity of nonspecific blood esterases depends on gestational age. Umbilical cord serum, buffer solution, ascorbic acid, and remifentanil were mixed in a glass vial placed in a shaking water bath at 37°C. Subsequently, serum samples were subjected to liquid chromatography-mass spectrometry-based analysis of remifentanil and its metabolite GR90291 after 0, 30, 60, 100, and 150 min.
Results:
We analyzed umbilical cord serum samples of 34 preterm infants (24-36 gestational weeks) and six term infants. The degradation rates of remifentanil to its major metabolite GR90291 were comparable in preterm and term infants. The overall median degradation half-life of remifentanil was 143 ± (interquartile range) 47 min (minimum, 76 min; maximum, 221 min) without significant differences between very preterm infants (less than 28 gestational weeks) and term infants. The remifentanil concentration remained stable in control runs without serum.
Conclusions:
Our study demonstrates that very preterm infants exhibit a high nonspecific esterase activity in umbilical cord blood that is comparable with that of term infants. These results support clinical experiences that remifentanil is rapidly metabolized by preterm infants without prolonged side effects.
