Hypothermia's Impact on Pharmacology (HIP)
Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics
Aperçu de l'étude
Statut
Les conditions
Description détaillée
Background:
Therapeutic hypothermia is used in the pediatric intensive care unit, and is being studied in the setting of pediatric cardiac arrest. Following cardiac arrest, multiple organ dysfunction syndrome, especially renal and hepatic dysfunction, is common and affects the metabolism and excretion of drugs. In addition, very little is known about the impact of hypothermia on a child's ability to metabolize medications. Dose adjustments may be required in the setting of hypothermia to avoid under-dosing and over-dosing of medications. Improper dosing and drug accumulation of sedatives and opiates can worsen existing neurologic, circulatory and respiratory failure. The measurement of the actual drug and metabolite concentrations in the body (pharmacokinetics) provides information on how a child metabolizes medications. In addition, variability in these concentrations after the administration of equal doses to different children may result from genetically driven differences in drug metabolizing systems (pharmacogenetics). Finally, these genetic differences may respond differently to hypothermia. Our overarching hypothesis is that morphine and midazolam disposition will be affected by temperature management even when accounting for potentially confounding quantifiable factors of organ dysfunction and genetic differences.
Objectives:
The objectives of this study, Hypothermia's Impact on Pharmacology 2, are
- To estimate the impact of hypothermia on the variability in morphine and midazolam pharmacokinetics in children after cardiac arrest and
- To estimate the impact of genetic factors on the variability in morphine and midazolam pharmacokinetics, specifically in the setting of hypothermia.
Sophisticated modeling and simulation techniques will be utilized to examine the highly dynamic changes in physiology associated with critical illness, drug disposition, pharmacogenetics and temperature modulation. The models created using this approach will be implemented to optimize the prospective treatment of these critically ill children.
Study Design:
Prospective pharmacokinetic study
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
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Alabama
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Birmingham, Alabama, États-Unis, 35294
- University of Alabama at Birmingham
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District of Columbia
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Washington, District of Columbia, États-Unis, 20010
- Children's National Medical Center
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Kentucky
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Louisville, Kentucky, États-Unis, 40202
- University of Louisville
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Michigan
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Ann Arbor, Michigan, États-Unis, 48109
- Univeristy of Michigan
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Ohio
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Columbus, Ohio, États-Unis, 43205
- Nationwide Children's Medical Center
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Pennsylvania
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Hershey, Pennsylvania, États-Unis, 19104
- Pennsylvania State University Hersey Medical Center
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Philadelphia, Pennsylvania, États-Unis, 19104
- The Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, États-Unis, 15224
- University of Pittsburgh
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Washington
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Seattle, Washington, États-Unis, 98105
- Seattle Children's Hospital
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria:
- Be greater than or equal to three (3) kg
- Receiving or have received morphine and/or midazolam as part of clinical care
- Receiving hypothermia after any cardiac arrest
- Provide Informed Consent
Exclusion Criteria:
- Receiving renal replacement therapy [example Continuous Veno-Venous Hemofiltration (CVVH), Continuous Veno-Venous Hemodialysis (CVVHD), and Continuous Veno-Venous Hemodiafiltration (CVVHDF)]
- Receiving plasmapheresis
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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Pediatric after Cardiac Arrest
Pediatric patients greater than 3 kg.
and less than 18 years suffering cardiac arrest who have been given or currently receiving morphine and/or midazolam and receiving hypothermia.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam
Délai: 2.5 years
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The objective of this aim is to identify the physiologic manifestations of cardiac arrest and MODS that underlie the variability in morphine and midazolam pharmacokinetics.
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2.5 years
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Impact of genetic factors
Délai: 2.5 years
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The objective of this aim is to estimate the impact of genetic factors that underlie the variability in morphine and midazolam pharmacokinetics (PK), specifically in the setting of pediatric cardiac arrest.
In this aim we will investigate the effect of genotype on pharmacokinetic parameters for morphine and midazolam.
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2.5 years
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Manifestations of hypothermia
Délai: 2.5 years
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The objective of this aim is to identify the manifestations of hypothermia that underlie the variability in morphine and midazolam pharmacokinetics in children after cardiac arrest.
In this aim we will investigate the effect of body temperature on PK parameters for morphine and midazolam.
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2.5 years
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Athena F Zuppa, MD MSCE, Children's Hospital of Philadelphia
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 12-009214
- RO1HL11274501A1 (Autre identifiant: NIHLBI)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
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