Drug-specific effects of anxiety on high-dose oxycodone: age as a modifier for oxycodone response

Area of Science:

• Anesthesiology
• Pain Management
• Genomics

Background:

• Preoperative anxiety is a common concern in patients undergoing surgery.
• Opioid tolerance can complicate postoperative pain management.
• Understanding factors influencing opioid tolerance is crucial for effective pain control.

Purpose of the Study:

• To examine the relationship between preoperative anxiety and opioid tolerance in hip arthroplasty patients.
• To investigate how different opioid types (morphine, oxycodone, tramadol) influence this association.
• To explore the age-specific effects and potential molecular mechanisms.

Main Methods:

• Retrospective cohort study of 1763 hip arthroplasty patients from the MIMIC-IV database.
• Identified anxious patients (n=198) based on admission diagnosis.
• Analyzed opioid dosage patterns using multivariable logistic regression, Johnson-Neyman, and restricted cubic spline analyses.
• Utilized rat neuropathic pain model transcriptomic data (GSE53897) for mechanistic insights.

Main Results:

• Preoperative anxiety was significantly associated with high-dose oxycodone use (ORs ranging from 1.679 to 2.025).
• No significant association was found between anxiety and high-dose morphine or tramadol.
• The anxiety-oxycodone association was age-specific, significant only in patients ≤75 years old.
• Mechanistic analysis indicated distinct gene profiles and pathways for morphine vs. oxycodone treatments.

Conclusions:

• Preoperative anxiety is an independent risk factor for oxycodone tolerance in hip arthroplasty patients.
• This effect is age-modulated, primarily impacting patients 75 years or younger.
• Integrating psychological status and age into pain management protocols may improve outcomes.