Pharmacokinetics of Morphine and Oxycodone in Frail Elderly Undergoing Cardiac Surgery

Study Overview
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Brief Summary
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Single centre observational cohort study. 20 older patients undergoing cardiac surgery who receive standard of care pain treatment. Postoperative ICU: blood sampling to determine morphine and metabolite (M3G, M6G, noroxycodone and oxymorphone) pharmacokinetics After ICU discharge on general ward: blood sampling to determine morphine, oxycodone and metabolite (M3G, M6G, noroxycodone and oxymorphone) pharmacokinetics During study monitoring of pain scores, total opioid consumption, side effects (e.g. nausea, vomiting, pruritus), sedation and delirium scores.

Detailed Description
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Postoperative pain after cardiac surgery in elderly patients is common and leads to postoperative complications. Opioids play an important role in treatment of postoperative pain after cardiac surgery. In frail elderly after cardiac surgery however dosing schemes for opioids are still unknown, potentially leading to inadequate treatment of pain and/or safety issues. Single center observational cohort study The study population includes frail patients ≥70 years undergoing elective cardiac surgery. Primary endpoints of this study is the concentration of morphine, oxycodone and metabolites in blood over time on behalf of pharmacokinetic modelling. Secondary endpoints of this study are the pharmacodynamic parameters of morphine, oxycodone and metabolites (M3G, M6G, noroxycodone and oxymorphone) in blood in frail patients; such as pain scores, postoperative opioid consumption, vital signs, side effects of opioids and the influence of covariates such as frailty, serum creatinine, Glomerular Filtration Rate (GFR) on the pharmacokinetics and pharmacodynamics of morphine and oxycodone.

Official Title
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Pharmacokinetics of Morphine and Oxycodone in Frail Elderly Undergoing Cardiac Surgery - AGE AWARE II

Conditions
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Opioid Use, Side Effect of Drug, Postoperative Pain

Intervention / Treatment
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* Drug: Morphine & Oxycodone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥70 years undergoing elective cardiac surgery. Exclusion Criteria: Patients undergoing transcatheter aortic valve replacement or mitral valve repair Contra-indication for morphine and/or oxycodone

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Morphine & Oxycodone|Morphine and Oxycodone are used in daily practice as part of standard care. Morphine and Oxycodone will be acquired through the clinical pharmacy of St Antonius and administered according to the standard postoperative pain protocol.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| M3G concentration in blood over time | Analysis of serum concentrations of M3G, metabolite of morphine, for pharmacokinetic modelling | Until three consecutive days after ICU discharge | 
| M6G concentration in blood over time | Analysis of serum concentrations of M6G, metabolite of morphine, for pharmacokinetic modelling | Until three consecutive days after ICU discharge | 
| Noroxycodone concentration in blood over time | Analysis of serum concentrations of Noroxycodone, metabolite of oxycodone, for pharmacokinetic modelling | Until three consecutive days after ICU discharge | 
| Oxymorphone concentration in blood over time | Analysis of serum concentrations of Oxymorphone, metabolite of oxycodone, for pharmacokinetic modelling | Until three consecutive days after ICU discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Rating Scale (NRS; 0-10, 0 = none, 10 = severe) | NRS as pain measurement scale, reported by nurse in standard care, for pharmacodynamic modelling | Until three consecutive days after ICU discharge | 
| Postoperative opioid consumption | Postoperative opioid consumption, mg per 24 hour, for pharmacodynamic modelling | Until three consecutive days after ICU discharge | 
| Side effects of opioids | Side effects of opioids (pruritis, vomiting, constipation, nausea), dichotomous (yes/no) each day by nurse/researcher, for pharmacodynamic modelling | Until three consecutive days after ICU discharge | 
| Vital sign observation: bloodpressure (in mmHg) by nurse | Systolic and diastolic bloodpressure (SBP, DBP), reported by nurse in standard care for pharmacodynamic modelling | Until three consecutive days after ICU discharge | 
| Vital sign observation: heartrate (in beats/minute) by nurse | Heartrate (HR) reported by nurse in standard care for pharmacodynamic modelling | Until three consecutive days after ICU discharge | 
| Vital sign observation: saturation (in %) by nurse | Saturation (SpO2), reported by nurse in standard care for pharmacodynamic modelling | Until three consecutive days after ICU discharge |