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

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.

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.

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

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.

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

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

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

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

secondary outcomes combine the occurrence of side effects requiring discontinuation of treatment such as: dizziness, dyspnea, cutaneous rush, vomiting, nausea and pruritus.

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

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.