title: Dose-response relationship between opioid use and adverse effects after ambulatory surgery.
abstract: This health outcomes analysis based on data from a randomized, double-blind, placebo-controlled trial determined dose-response relationship between opioid use and related symptoms. All patients received intravenous fentanyl on demand for pain predischarge, and oral acetaminophen 500 mg/hydrocodone 5 mg every 4-6 hours as needed postdischarge for up to 7 days postsurgery. Patients completed an opioid-related Symptom Distress Scale (SDS) questionnaire every 24 hours postdischarge for 7 days, which assessed 12 opioid-related symptoms by 3 ordinal measures: frequency, severity, and bothersomeness. Clinically meaningful events (CMEs) were defined based on the responses to this questionnaire. Opioid use was converted to morphine equivalent dose (MED). The dose-response relationship between composite SDS scores and MED on Day 1, on Days 0 and 1, and on Days 1-4, was assessed. SDS scores for all 12 symptoms within the 3 dimensions were significantly associated with MED on Day 1 (F-value=1.56; P=0.04), as well as cumulative MED used on Days 0 and 1 (F-value=1.85; P<0.01). Patients with a specific CME used a higher MED than those without a CME on Day 1 (P<0.001). Between Days 1 and 4, patients with a higher number of patient-CME-days used a significantly higher MED. Regression analyses suggested that once the MED reached a threshold, approximately every 4 mg increase in MED was related to 1 additional patient-CME-day (P<0.01). A dose-response relationship empirically exists between MED and directly assessed opioid-related CMEs after ambulatory laparoscopic cholecystectomy. Once daily MED reaches a threshold, every 3-4 mg increase will be associated with 1 additional clinically meaningful opioid-related symptom, or 1 additional patient-day with an opioid-related CME.
authors.affiliation: Global Health Outcomes Research, Pfizer, Inc., Peapack, New Jersey, USA.
authors.forename: Sean Z
authors.initials: SZ
authors.lastname: Zhao
authors.forename: Frances
authors.initials: F
authors.lastname: Chung
authors.forename: David B
authors.initials: DB
authors.lastname: Hanna
authors.forename: Anna L
authors.initials: AL
authors.lastname: Raymundo
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Cheung
authors.forename: Connie
authors.initials: C
authors.lastname: Chen
mesh_terms: D000328:Adult; D000556:Ambulatory Surgical Procedures; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl