Hypothermia's Impact on Pharmacology (HIP)
Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics
Descripción general del estudio
Estado
Condiciones
Descripción detallada
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
Tipo de estudio
Inscripción (Actual)
Contactos y Ubicaciones
Ubicaciones de estudio
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Alabama
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Birmingham, Alabama, Estados Unidos, 35294
- University of Alabama at Birmingham
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District of Columbia
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Washington, District of Columbia, Estados Unidos, 20010
- Children's National Medical Center
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Kentucky
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Louisville, Kentucky, Estados Unidos, 40202
- University of Louisville
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- Univeristy of Michigan
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Ohio
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Columbus, Ohio, Estados Unidos, 43205
- Nationwide Children's Medical Center
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Pennsylvania
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Hershey, Pennsylvania, Estados Unidos, 19104
- Pennsylvania State University Hersey Medical Center
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- The Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Estados Unidos, 15224
- University of Pittsburgh
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Washington
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Seattle, Washington, Estados Unidos, 98105
- Seattle Children's Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
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 de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / 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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Impact of genetic factors
Periodo de tiempo: 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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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Manifestations of hypothermia
Periodo de tiempo: 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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Athena F Zuppa, MD MSCE, Children's Hospital of Philadelphia
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 12-009214
- RO1HL11274501A1 (Otro identificador: NIHLBI)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
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