Is There an Ideal Dose of Intravenous Fentanyl in the Prehospital Setting

Is There an Ideal Dose of Intravenous Fentanyl in the Prehospital Setting: A Prospective Cluster-randomized Comparison of 2 vs. 3 μg/kg/Transport

In a previous study the investigators evaluated the apparent efficacy and safety of intravenous fentanyl administered by ambulance personnel and found that 58.4% (CI 56.4-60.4) out of 2348 prehospital patients treated with fentanyl still experienced moderate to severe pain [numeric rating scale (NRS, 0-10) > 3] at hospital arrival. The number of patients with possible fentanyl-related side effects was low.

Therefore, the aim of the present study is to explore the efficacy and safety of a liberalized pain treatment protocol for ambulance personnel (a total of 3 μg/kg per transport) compared with existing restrictive protocol (a total of 2 μg/kg per transport). The investigators hypothesize that:

• A higher proportion of patients will experience sufficient pain relief at hospital admission (NRS < 4) using the liberalized protocol and
• There will be no differences in the proportion of potential fentanyl related side-effects are observed.

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Other: Fentanyl

Detailed Description

A prospective cluster-randomized trial observing proportional differences in sufficient pain relief at hospital admission (NRS < 4) and potential fentanyl related side-effects between patients treated by ambulance personnel applying either:

• a more liberal treatment approach (a total of 3 μg/kg per transport) or
• existing treatment approach (a total of 2 μg/kg per transport).

The Ambulance stations and their affiliated ambulance personnel are stratified into 5 clusters according to size/average transports per month and randomized to either liberal or existing treatment approach within each cluster. As patients are not randomized on an individual level baseline differences between the two groups and its patients are adjusted statistically with relevant confounders on 3 overall levels:

1. Patients: Charlson Comorbidity Index Score, main overall diagnose category, inhospital surrogate measures of disease severity (intensive care unit admission and 30-day mortality).
2. Ambulance personnel: Years of experience and preinterventional cumulative fentanyl administration and
3. Ambulance stations and geographical factors: prehospital time measures and geographical distance from site of emergency to hospital.

These covariates are obtained from the Danish National Patient Registry, the Danish Civil Registration System and the electronic prehospital patient journal.

• Study Type: Interventional
• Enrollment (Actual): 7093
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 110 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with acute pain treated with intravenous fentanyl by ambulance personnel

Exclusion Criteria:

• Reduced conscious level (GCS < 15) before initiation of fentanyl treatment
• Reduced respiratory rate (< 10/minute) before initiation of fentanyl treatment
• Patient weight < 30 kg
• Known opioid allergy
• Women in labour
• Chronic pain conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Existing treatment; Business as usual: Ambulance personnel use existing treatment approach (a total of 2 μg/kg fentanyl per transport)
Experimental: More liberal treatment; Ambulance personnel use a more liberal treatment approach (a total of 3 μg/kg fentanyl per transport)	Other: Fentanyl; Change in protocol from 2 to a total of 3 μg/kg fentanyl per transport

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with sufficient pain relief (NRS < 4) at hospital arrival	Up to 6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with reduced Glasgow Coma Scale (<15) after fentanyl administration and at any given point during transport		Up to 6 hours
Proportion of patients with reduced respiratory rate (<10/minute) after fentanyl administration and at any given point during transport		Up to 6 hours
Proportion of patients with reduced peripheral oxygen saturation (< 90%) after fentanyl administration and at any given point during transport		Up to 6 hours
Proportion of patients with hypotension after fentanyl administration and at any given point during transport	Hypotension defined as a drop in mean arterial pressure (MAP) >= 10 mmHg to a MAP < 70 mmHg	Up to 6 hours

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Central Denmark Region
• Investigators: Study Chair: Hans Kirkegaard, Professor, Aarhus University Hospital; Principal Investigator: Kristian Friesgaard, MD, PhD Student, University of Aarhus; Study Chair: Lone Nikolajsen, DmSc, Aarhus University Hospital; Study Chair: Erika Frischknecht Christensen, Professor, Northern Denmark Region; Study Chair: Matthias Giebner, MD, Central Denmark Region; Study Chair: Claus-Henrik Rasmussen, MD, Central Denmark Region

Publications and helpful links

General Publications

• Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health. 2011 Jul;39(7 Suppl):30-3. doi: 10.1177/1403494811401482.
• Schmidt M, Pedersen L, Sorensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014 Aug;29(8):541-9. doi: 10.1007/s10654-014-9930-3. Epub 2014 Jun 26.
• Friesgaard KD, Nikolajsen L, Giebner M, Rasmussen CH, Riddervold IS, Kirkegaard H, Christensen EF. Efficacy and safety of intravenous fentanyl administered by ambulance personnel. Acta Anaesthesiol Scand. 2016 Apr;60(4):537-43. doi: 10.1111/aas.12662. Epub 2015 Nov 27.
• Friesgaard KD, Kirkegaard H, Rasmussen CH, Giebner M, Christensen EF, Nikolajsen L. Prehospital intravenous fentanyl administered by ambulance personnel: a cluster-randomised comparison of two treatment protocols. Scand J Trauma Resusc Emerg Med. 2019 Feb 7;27(1):11. doi: 10.1186/s13049-019-0588-4.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: September 12, 2016
• First Submitted That Met QC Criteria: September 22, 2016
• First Posted (Estimate): September 26, 2016

Study Record Updates

• Last Update Posted (Actual): October 27, 2017
• Last Update Submitted That Met QC Criteria: October 25, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Emergency Medical Services; Analgesics
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: AU-PHA2V3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO