Management of acute pain in patients using opioids


The overall aim of this PhD is to describe and improve the management of acute pain in patients with a chronic use of opioids. Three studies are outlined in the following:  

Study I
Chronic opioid users in the emergency department: a descriptive nationwide study in Denmark

Study II
Acute pain management for patients with chronic use of opioids in the ED: a cross-sectional study.

Study III
Ketamine for acute pain in opioid-tolerant patients in the ED, a randomized, controlled, double-blinded, superiority trial.


Denmark has one of the highest rates of opioid consumption in the world with 3-5 % of the population using opioids daily or regularly. Adding to this are individuals who misuse opioids and patients in substitution programs with e.g. methadone. This group of patients seek medical help much more often than non-opioid users, i.e. in the Emergency Departments (ED) .

The ED, the entrance to the hospital, is a medical treatment facility, specializing in the care of patients with acute illness and/or pain. It is the responsibility of the emergency physician to assess and evaluate, and if appropriate, safely and effectively reduce pain. Care should be tailored to the patient based on their specific acute painful condition and underlying risk factors and comorbidities. This can be a challenge in many cases, but especially in patients who presents a physiology already adapted to opioids. While opioids remain a mainstay of treatment for many patients, there is a need for safe and even better alternatives.


Study I
All adult (aged ≥ 18 years) residents in Denmark from 2016 to 2019 with one or more contacts to an ED in Denmark during 1st January to 31st December 2018 will be identified in the Danish National Patient Register.

Study II
From the dataset in Study I, a subpopulation will be extracted including all adults (aged ≥18) with a chronic use of opioids and one or more contacts to the ED at Aarhus University Hospital (AUH) or the ED at The Regional Hospital West (HEV) from 1st of january to 30th of Juni 2018.

Study III
Adults with a chronic use of opioids (defined as a daily dose of 30 mg over at least 2 weeks) presenting with acute pain, in two of the largest EDs in Denmark between 1st January 2022 to 31st August 2022. Patients will be screened during daytime and evening hours on weekdays. Patients are eligible for inclusion if they complain of pain with an intensity of > 4 on a numeric rating scale.

Intervention group:
Ketamine 1 mg will be injected iv plus fentanyl equivalent to 10 % of the total 24-hour opioid consumption.

Control group:
Placebo (saline) plus fentanyl equivalent 10 % of the total 24-hour opioid use. In case of insufficient pain relief (Numeric Rating Scale (NRS)>3 after 20 min), repeated doses of fentanyl (each half the initial dose) can be used as rescue medication.

Data sources

Study I
This nationwide population-based cohort study will be based on several Danish registers: The Danish Civil Registration System, the Danish National Patient Register, The Cancer Registry, the Danish Register of Medicinal Product Statistics and Statistics Denmark

Study II
The following information will be retrieved from the Danish Register of Medicinal Product Statistics and the Electronic Medical Record (EPJ):

  • Cause of contact and diagnosis
  • Daily use of opioids before contact to the ED
  • First on demand opioid dose in the ED, AUH
  • Total dose during contact
  • Characteristics of the patients (gender, age, time and cause of contact, reason for having a chronic use of opioid (malignant/non-malignant pain)

Information regarding the opioid administrated at the ED will be retrieved from each department via Central Denmark Regions “Datawarehouse”. Information regarding socio-economic relations will be obtained from Statistics Denmark.


Study III
The primary outcome measurement is pain relief after 10 min assessed on a 5-point Lickert scale. Secondary outcomes include the need of rescue fentanyl within the first 60 min after administration of study medication, pain intensity after 10, 20, 30 and 60 min and side effects. Richmond Agitation-Sedation Scale (RASS) will be used to evaluate agitation or sedation. TOKS (tidlig opsporing af kritisk sygdom) will be used to evaluate differences in vital parameters. Provider Satisfaction Score will be used after drug administration to evaluate provider's clinical experience with the analgesic and a questionnaire will evaluate patients satisfaction and side-effects.


This project will fill in several gaps in the existing literature concerning patients using opioids, regardless of reason (pain, addiction, or as part of substitution treatment). It provides highly relevant possibilities for a new way of treating a large group of patients with severe pain in the Danish EDs. This will increase the patients safety, ease the treatment for the medical provider and possibly decrease the length of hospital stay.