Clinical trial NCT01564420: Morphine Postoperative Analgesia and Pharmacokinetic/Pharmacodynamic Modeling
Official title: Pharmacokinetic/Pharmacodynamic Modeling of Morphine for Postoperative Analgesia Through a Patient Controlled Device After Coronary Artery Bypass Grafting. Intrathecal Morphine Significantly Reduces Drug Consumption
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiopulmonar Artery Bypass Grafting
Keywords: pharmacokinetic/pharmacodynamic modeling
intrathecal morphine
postoperative analgesia
patient-controlled analgesia device
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2012-03-27
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with coronary artery disease, eligible to cardiopulmonary artery bypass grafting surgery

Brief summary: The currently available data are insufficient to develop a model that achieves optimum morphine dose individualization at the postoperative period of coronary artery bypass grafting (CABG). Therefore, the objective of the study was to apply a PK/PD model that could justify morphine consumption, drug plasma concentration and pain intensity during the postoperative period after CABG and evaluate the post operative pain.

Detailed description: The protocol was a prospective, open-label study, approved by the institutional ethical committee of the hospital where the study was performed. Patients were randomly assigned to receive general anesthesia plus intrathecal morphine at a dosage of 400 mcg (morphine group) or general anesthesia alone (control group) according to a simple computer-generated list.

Eligibility criteria: Inclusion Criteria:

* eligible to cardiopulmonary artery bypass grafting surgery

Exclusion Criteria:

* fraction of ejection below 40%
* contraindications to neuraxial blockage
* coagulopathy
* use of low-weight heparin
* warfarin or a platelet aggregation inhibitor other than aspirin,
* systemic or local infection
* and patients with a specific contraindication on the medication employed in the study

Primary outcomes:
measure: Postoperative pain
timeFrame: two days
measure: PK/PD modelling
timeFrame: 2 days
Secondary outcomes:
measure: PK parameter: Cmax (peak plasma concentration)
timeFrame: 2 days
measure: PK parameter: Tmax (time to achieve the maximum concentration)
timeFrame: 2 days
measure: PK parameter: AUC (area under the plasma cocentration versus time curve)
timeFrame: 2 days
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: School of Pharmaceutical Science
Study officials:
affiliation: University of Sao Paulo
name: Silvia RCJ Santos, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: dos Santos LM, Santos VC, Santos SR, Malbouisson LM, Carmona MJ. Intrathecal morphine plus general anesthesia in cardiac surgery: effects on pulmonary function, postoperative analgesia, and plasma morphine concentration. Clinics (Sao Paulo). 2009;64(4):279-85. doi: 10.1590/s1807-59322009000400003.