The effect of old age and frailty on intravenous fentanyl and midazolam pharmacodynamics — The Association Specialists
  1. Schedule
  2. Posters - Wednesday
  3. The effect of old age and frailty on intravenous fentanyl and midazolam pharmacodynamics

The effect of old age and frailty on intravenous fentanyl and midazolam pharmacodynamics (346)

Luke S Harb 1 2 , Claire F Johnston 1 3 , Peter R Carroll 2 3 , Slade T Matthews 2 3 , Sarah N Hilmer 1 3
  1. Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital and Kolling Institute of Medical Research, St Leonards, NSW, Australia
  2. Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia
  3. Sydney Medical School, The University of Sydney, Sydney, NSW, Australia

Introduction. Extensive variability in physiology, pharmacokinetics and pharmacodynamics is observed in older persons aged 65+ years, and may be partially explained by frailty. Plasma concentrations of interleukin (IL)-6, C-reactive protein (CRP) and albumin may be useful biomarkers of frailty in conjunction with clinical measures. The clearance of iv fentanyl and midazolam is reduced in old age. The impact of frailty on pharmacodynamic sensitivity to the sedative and chronotropic effects of these drugs is unknown.

Aims. (1) Evaluate the use of IL-6, CRP and albumin as biomarkers of frailty; (2) Compare changes in sedation and heart rate between young non-frail, old non-frail and old frail patients receiving iv fentanyl and midazolam for sedation during endoscopy.

Methods. Patients aged over 45 years were recruited from the endoscopy unit at Royal North Shore Hospital, Sydney. Baseline blood was used to measure CRP and albumin (by hospital pathology) and IL-6 (using ELISA). Frailty was assessed using the Reported Edmonton Frail Scale (REFS). Heart rate and Ramsay sedation score were measured at baseline and at regular intervals for 2 h after drug administration.

Results. Plasma CRP, IL-6 and albumin concentrations were not significantly different between the groups. CRP positively correlated with REFS score (P<0.05) but not age. IL-6 and albumin did not correlate with age or REFS score. Old frail patients received lower doses of midazolam compared to old non-frail patients (P<0.05). Heart rate significantly reduced over 2 h in all groups and was not affected by age or frailty. Maximum sedation score was significantly predicted by total weight-adjusted midazolam dose and age-frailty group (P<0.05), and correlated with CRP (P<0.05).

Discussion. In this cohort, CRP, IL-6 and albumin were not useful as biomarkers of frailty. Old age and frailty were associated with altered sensitivity to the sedative but not chronotropic effects of fentanyl and midazolam.