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Severity of asphyxia is a covariate of phenobarbital clearance in newborns undergoing hypothermia
P. Pokorná, L. Posch, M. Šíma, P. Klement, O. Slanar, J. van den Anker, D. Tibboel, K. Allegaert,
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články
- MeSH
- analýza rozptylu MeSH
- antikonvulziva aplikace a dávkování farmakokinetika MeSH
- Apgar skóre MeSH
- asfyxie novorozenců komplikace terapie MeSH
- fenobarbital aplikace a dávkování farmakokinetika MeSH
- lidé MeSH
- metabolická clearance MeSH
- mozková hypoxie a ischemie etiologie terapie MeSH
- novorozenec MeSH
- prospektivní studie MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci * MeSH
- terapeutická hypotermie metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články 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.
Citace poskytuje Crossref.org
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- $a Pokorná, Pavla $u a Department of Pediatrics, First Faculty of Medicine , Charles University in Prague and General University Hospital , Prague , Czech Republic. b Institute of Pharmacology, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Prague , Czech Republic. c Intensive Care and Department of Pediatric Surgery , Erasmus MC, Sophia Children's Hospital , Rotterdam , The Netherlands.
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- $a Severity of asphyxia is a covariate of phenobarbital clearance in newborns undergoing hypothermia / $c P. Pokorná, L. Posch, M. Šíma, P. Klement, O. Slanar, J. van den Anker, D. Tibboel, K. Allegaert,
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- $a 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.
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- $a Posch, Lenka $u a Department of Pediatrics, First Faculty of Medicine , Charles University in Prague and General University Hospital , Prague , Czech Republic.
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- $a van den Anker, John $u c Intensive Care and Department of Pediatric Surgery , Erasmus MC, Sophia Children's Hospital , Rotterdam , The Netherlands. d Departments of Pediatrics, Pharmacology and Physiology , George Washington University School of Medicine and Health Sciences , Washington , DC , USA. 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. g Division of Paediatric Pharmacology and Pharmacometrics , University of Basel Children's Hospital , Basel , Switzerland.
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- $a Tibboel, Dick $u a Department of Pediatrics, First Faculty of Medicine , Charles University in Prague and General University Hospital , Prague , Czech Republic. c Intensive Care and Department of Pediatric Surgery , Erasmus MC, Sophia Children's Hospital , Rotterdam , The Netherlands.
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