BACKGROUND: Midazolam is used as an anticonvulsant in neonatology, including newborns with perinatal asphyxia treated with hypothermia. Hypothermia may affect the safety and effectiveness of midazolam in these patients. OBJECTIVES: The objective was to evaluate the anticonvulsant effectiveness and hemodynamic safety of midazolam in hypothermic newborns and to provide dosing guidance. METHODS: Hypothermic newborns with perinatal asphyxia and treated with midazolam were included. Effectiveness was studied using continuous amplitude-integrated electroencephalography. Hemodynamic safety was assessed using pharmacokinetic-pharmacodynamic modeling with plasma samples and blood pressure recordings (mean arterial blood pressure) under hypothermia. RESULTS: No effect of therapeutic hypothermia on pharmacokinetics could be identified. Add-on seizure control with midazolam was limited (23% seizure control). An inverse relationship between the midazolam plasma concentration and mean arterial blood pressure could be identified. At least one hypotensive episode was experienced in 64%. The concomitant use of inotropes decreased midazolam clearance by 33%. CONCLUSIONS: Under therapeutic hypothermia, midazolam has limited add-on clinical anticonvulsant effectiveness after phenobarbital administration. Due to occurrence of hypotension requiring inotropic support, midazolam is less suitable as a second-line anticonvulsant drug under hypothermia.
BACKGROUND:Midazolam is used as an anticonvulsant in neonatology, including newborns with perinatal asphyxia treated with hypothermia. Hypothermia may affect the safety and effectiveness of midazolam in these patients. OBJECTIVES: The objective was to evaluate the anticonvulsant effectiveness and hemodynamic safety of midazolam in hypothermic newborns and to provide dosing guidance. METHODS:Hypothermic newborns with perinatal asphyxia and treated with midazolam were included. Effectiveness was studied using continuous amplitude-integrated electroencephalography. Hemodynamic safety was assessed using pharmacokinetic-pharmacodynamic modeling with plasma samples and blood pressure recordings (mean arterial blood pressure) under hypothermia. RESULTS: No effect of therapeutic hypothermia on pharmacokinetics could be identified. Add-on seizure control with midazolam was limited (23% seizure control). An inverse relationship between the midazolam plasma concentration and mean arterial blood pressure could be identified. At least one hypotensive episode was experienced in 64%. The concomitant use of inotropes decreased midazolam clearance by 33%. CONCLUSIONS: Under therapeutic hypothermia, midazolam has limited add-on clinical anticonvulsant effectiveness after phenobarbital administration. Due to occurrence of hypotension requiring inotropic support, midazolam is less suitable as a second-line anticonvulsant drug under hypothermia.
Authors: Laurent M A Favié; Floris Groenendaal; Marcel P H van den Broek; Carin M A Rademaker; Timo R de Haan; Henrica L M van Straaten; Peter H Dijk; Arno van Heijst; Sinno H P Simons; Koen P Dijkman; Monique Rijken; Inge A Zonnenberg; Filip Cools; Alexandra Zecic; Johanna H van der Lee; Debbie H G M Nuytemans; Frank van Bel; Toine C G Egberts; Alwin D R Huitema Journal: Neonatology Date: 2019-06-28 Impact factor: 4.035
Authors: Maria D Donovan; Brendan T Griffin; Liudmila Kharoshankaya; John F Cryan; Geraldine B Boylan Journal: Drugs Date: 2016-04 Impact factor: 9.546
Authors: Laurent M A Favié; Floris Groenendaal; Marcel P H van den Broek; Carin M A Rademaker; Timo R de Haan; Henrica L M van Straaten; Peter H Dijk; Arno van Heijst; Jeroen Dudink; Koen P Dijkman; Monique Rijken; Inge A Zonnenberg; Filip Cools; Alexandra Zecic; Johanna H van der Lee; Debbie H G M Nuytemans; Frank van Bel; Toine C G Egberts; Alwin D R Huitema Journal: PLoS One Date: 2019-02-14 Impact factor: 3.240
Authors: Christopher McPherson; Adam Frymoyer; Cynthia M Ortinau; Steven P Miller; Floris Groenendaal Journal: Semin Fetal Neonatal Med Date: 2021-06-23 Impact factor: 3.926