Pharmacokinetics of Morphine and Oxycodone in Frail Elderly Undergoing Cardiac Surgery

Completed

• Conditions: Opioid Use; Side Effect of Drug; Postoperative Pain

• Registration Number: NCT04696445
• Lead Sponsor: St. Antonius Hospital

Brief Summary

* 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

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.

Study Timeline

• Study Start: 2020-10-01
• Study First Submitted: 2020-10-22
• Study First Submitted QC: 2021-01-05
• Study First Posted: 2021-01-06
• Primary Completion: 2021-11-26
• Study Completion: 2021-11-26
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-16
• Last Update Posted: 2022-06-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
M6G concentration in blood over time	Until three consecutive days after ICU discharge	Analysis of serum concentrations of M6G, metabolite of morphine, for pharmacokinetic modelling
Noroxycodone concentration in blood over time	Until three consecutive days after ICU discharge	Analysis of serum concentrations of Noroxycodone, metabolite of oxycodone, for pharmacokinetic modelling
Oxymorphone concentration in blood over time	Until three consecutive days after ICU discharge	Analysis of serum concentrations of Oxymorphone, metabolite of oxycodone, for pharmacokinetic modelling
M3G concentration in blood over time	Until three consecutive days after ICU discharge	Analysis of serum concentrations of M3G, metabolite of morphine, for pharmacokinetic modelling

Secondary Outcome Measures

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

Trial Locations

Locations (1)

St Antonius hospital; 🇳🇱 Nieuwegein, Netherlands