Hypothermia's Impact on Pharmacology (HIP)
Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics
Studieoversikt
Status
Forhold
Detaljert beskrivelse
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
Studietype
Registrering (Faktiske)
Kontakter og plasseringer
Studiesteder
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Alabama
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Birmingham, Alabama, Forente stater, 35294
- University of Alabama at Birmingham
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District of Columbia
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Washington, District of Columbia, Forente stater, 20010
- Children's National Medical Center
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Kentucky
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Louisville, Kentucky, Forente stater, 40202
- University of Louisville
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Michigan
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Ann Arbor, Michigan, Forente stater, 48109
- Univeristy of Michigan
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Ohio
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Columbus, Ohio, Forente stater, 43205
- Nationwide Children's Medical Center
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Pennsylvania
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Hershey, Pennsylvania, Forente stater, 19104
- Pennsylvania State University Hersey Medical Center
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Philadelphia, Pennsylvania, Forente stater, 19104
- The Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Forente stater, 15224
- University of Pittsburgh
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Washington
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Seattle, Washington, Forente stater, 98105
- Seattle Children's Hospital
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Prøvetakingsmetode
Studiepopulasjon
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / Kohort |
|---|
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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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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam
Tidsramme: 2.5 years
|
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.
|
2.5 years
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Impact of genetic factors
Tidsramme: 2.5 years
|
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.
|
2.5 years
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Manifestations of hypothermia
Tidsramme: 2.5 years
|
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.
|
2.5 years
|
Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: Athena F Zuppa, MD MSCE, Children's Hospital of Philadelphia
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 12-009214
- RO1HL11274501A1 (Annen identifikator: NIHLBI)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
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