Severity of asphyxia is a covariate of phenobarbital clearance in newborns undergoing hypothermia
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
- Keywords
- Newborn, asphyxia, hypothermia, pharmacodynamics, pharmacokinetics, phenobarbital,
- MeSH
- Analysis of Variance MeSH
- Anticonvulsants administration & dosage pharmacokinetics MeSH
- Apgar Score MeSH
- Asphyxia Neonatorum complications therapy MeSH
- Phenobarbital administration & dosage pharmacokinetics MeSH
- Humans MeSH
- Metabolic Clearance Rate MeSH
- Hypoxia-Ischemia, Brain etiology therapy MeSH
- Infant, Newborn MeSH
- Prospective Studies MeSH
- Case-Control Studies MeSH
- Severity of Illness Index * MeSH
- Hypothermia, Induced methods MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anticonvulsants MeSH
- Phenobarbital MeSH
AIM: Phenobarbital (PB) pharmacokinetics (PK) in asphyxiated newborns show large variability, not only explained by hypothermia (HT). We evaluated potential relevant covariates of PK of PB in newborns treated with or without HT for hypoxic-ischemic encephalopathy (HIE). METHODS: Clearance (CL), distribution volume (Vd) and elimination half-life (t1/2) were calculated using one-compartment analysis. Covariates were clinical characteristics (weight, gestational age, hepatic, renal, and circulatory status), comedication and HIE severity [time to reach normal aEEG pattern (TnormaEEG), dichotomous, within 24 h] and asphyxia severity [severe aspyhxia = pH ≤7.1 + Apgar score ≤5 (5 min), dichotomous]. Student's t-test, two-way ANOVA, correlation and Pearson's chi-square test were used. RESULTS: Forty newborns were included [14 non-HT; 26 HT with TnormaEEG <24 h in 14/26 (group1-HT) and TnormaEEG ≥24 h in 12/26 (group2-HT)]. Severe asphyxia was present in 26/40 [5/14 non-HT, 11/14 and 10/12 in both HT groups]. PB-CL, Vd and t1/2 were similar between the non-HT and HT group. However, within the HT group, PB-CL was significantly different between group1-HT and group2-HT (p = .043). ANOVA showed that HT (p = .034) and severity of asphyxia (p = .038) reduced PB-CL (-50%). CONCLUSION: The interaction of severity of asphyxia and HT is associated with a clinical relevant reduced PB-CL, suggesting the potential relevance of disease characteristics beyond HT itself.
e Division of Clinical Pharmacology Children's National Health System Washington DC USA
f Intensive Care Erasmus MC Sophia Children's Hospital Rotterdam The Netherlands
h Department of Development and Regeneration KU Leuven Leuven Belgium
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