Titrated Versus High and Low Dose Nebulized Morphine to Reduce Pain in Emergency Settings (TIMORNEB)

Efficacy and Safety of Nebulized Morphine Given at Two Different Doses Compared to Intravenous Morphine in Post-traumatic Acute Pain: a Randomized Controlled Double Blind Study

The investigators test a different technique using morphine to improve pain relief in patient visiting the emergency department with acute trauma pain, for this we are comparing three different methods of morphine administration:

• intravenous titrated morphine
• low dose nebulized morphine and
• high dose nebulized morphine

Study Overview

• Status: Completed
• Conditions: Acute Pain; Post-Traumatic Headache
• Intervention / Treatment: Drug: IV titrated morphine; Drug: Low dose nebulised morphine; Drug: High dose nebulised morphine

Detailed Description

Trauma patients are frequent in emergency department settings, and often require urgent care.

taking care of this patients consists on taking care of their pain and then the specific treatment of their traumatic lesions.

actually, the most used medicine and most efficient one in treating pain is morphine, it's mechanism of action is by acting on receptors located on neuronal cell membranes and inhibit neurotransmitter release.

The most applied administration root of morphine is by intravenous (IV) titration or IV continuous perfusion, but until now, there is no clear recommendation concerning the superiority of this root over other administration techniques such as nebulization.

In this study we aimed to investigate the efficiency, the feasibility and the tolerance of three morphine administration roots in patients with acute traumatic pain and to clarify the most adequate one to apply in emergency department settings.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Tunisia
  • Monastir, Tunisia, 5000
    • Emergency department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 50 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients older than 8 years and less than 50 years
• patients who consult emergency department for sever pain after an immediately trauma

Exclusion Criteria:

• Glasgow coma scale <14
• inability to cooperate
• hypotension with systolic blood pressure< 90mmhg
• bradypnea<12cpm
• SAO2<90%
• polytrauma
• nasal trauma
• rhinitis
• nasal obstruction
• allergy to opioids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: IV titrated morphine; patient will receive 2 mg morphine each 5 min, associated to continuous nebulisation of saline serum (placebo). Morphine administration is stopped when VAS becomes under 50% and treatment failure is defined as VAS > 50%, 30 minutes after the beginning of the protocol.	Drug: IV titrated morphine; Intravenous morphine : 2 mg every 5 minutes by IV root and nebulized placebo: SS nebulised : 5 ml SS nebulised over 10 minutes and repeated 3 times; Other Names: IV morphine group
EXPERIMENTAL: Low dose nebulised morphine; patient will receive 10 mg of morphine prepared with 4 ml saline serum (SS) and nebulised with 6 l/min flow during 10 minutes. Nebulisation will be repeated 3 times, in addition, patients receive 2 ml IV SS every 5 minutes as placebo	Drug: Low dose nebulised morphine; 10 mg morphine in 4 ml Serum Saline(SS) nebulised over 10 minutes and repeated 3 times, and SS IV placebo : 2 ml by IV root every 5 minutes; Other Names: Neb10
EXPERIMENTAL: High dose nebulised morphine; patient will receive 20 mg of morphine prepared with 3 ml saline serum (SS) and nebulised with 6 l/min flow during 10 minutes. Nebulisation will be repeated 3 times, in addition, patients receive 2 ml IV SS every 5 minutes as placebo.	Drug: High dose nebulised morphine; 20 mg morphine in 3 ml serum saline (SS) nebulised over 10 minutes and repeated 3 times, and SS IV placebo : 2 ml by IV root every 5 minutes; Other Names: Neb20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain resolution	primary end point defined by the decrease in intensity pain objectified by a decline in visual analogy pain scale greater than or equal to 50% of its initial value	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
side effects	secondary outcomes combine the occurrence of side effects requiring discontinuation of treatment such as: dizziness, dyspnea, cutaneous rush, vomiting, nausea and pruritus.	30 minutes

Collaborators and Investigators

• Sponsor: University of Monastir

Publications and helpful links

General Publications

• Grissa MH, Boubaker H, Zorgati A, Beltaief K, Zhani W, Msolli MA, Bzeouich N, Bouida W, Boukef R, Nouira S. Efficacy and safety of nebulized morphine given at 2 different doses compared to IV titrated morphine in trauma pain. Am J Emerg Med. 2015 Nov;33(11):1557-61. doi: 10.1016/j.ajem.2015.06.014. Epub 2015 Jun 14.

Helpful Links

• official department site

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: July 22, 2014
• First Submitted That Met QC Criteria: July 24, 2014
• First Posted (ESTIMATE): July 25, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): December 2, 2014
• Last Update Submitted That Met QC Criteria: November 26, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: post traumatic pain; titrated morphine; nebulised morphine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders; Headache Disorders, Secondary; Headache; Acute Pain; Post-Traumatic Headache; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: TIMORNEB