Nebulized morphine for analgesia in an emergency setting

Abstract

Objective: To evaluate the efficacy and safety of inhaled morphine delivered in patients experiencing severe acute pain in an emergency setting.Patients and Methods: Patients were eligible for inclusion if they were aged 18 years or older, with a severe acute pain defined by a numerical rating scale (NRS) score of 60/100 or higher. The intervention involved administering a single dose of 0.2 mg/kg morphine nebulized using a Misty-Neb nebulizer system. NRSs were recorded and were repeated at 1, 3, 5, and 10 minute after the end of inhalation (T10). The protocol-defined primary outcome measure was pain relief (defined by an NRS score of 30/100 or lower) at T10. Secondary outcomes included differences between pain scores at baseline and at T10 and incidence of adverse events.Results: A total of 28 patients were included in this study. No patient experienced pain relief 10 minutes after the end of inhalation, and no adverse effects were recorded. Respective initial and final median NRS scores were 80 (70-90) and 70 (60-80), p < 0.0001. Despite achieving statistical significance, the value of this point estimate is less than the 14 NRS difference that was defined a priori as representing a minimum clinically significant difference in pain severity.Conclusion: 0.2 mg/kg nebulized morphine is not effective in managing acute pain in an emergency setting. In spite of the potential advantages of the pulmonary route of administration, opioids should be intravenous prescribed at short fixed intervals to control severe acute pain in an emergency setting.

Pharmacokinetic modeling of morphine and its glucuronides: Comparison of nebulization versus intravenous route in healthy volunteers

“…5 The lack of homogenous aerosol techniques (doses, administration routes, and duration time), evaluation goals, and available data in the literature make it difficult to assess the effectiveness and appropriateness of NEB administration. [6][7][8] Moreover, pharmacological studies conducted in healthy volunteers lack relevance for clinical objectives and there is currently no gold-standard pain model. The need for stronger fundamentals, especially regarding routine devices, is essential to improve our knowledge and challenge i.v.…”

Bedside Evaluation of Early VAS/NRS Based Protocols for Intravenous Morphine in the Emergency Department: Reasons for Poor Follow-Up and Targeted Practices

“…The need for venous access and a nurse exclusively dedicated to titration (high level of resources) could be organizational barriers, leading to therapeutic alternatives, more available, resulting in a morphine-saving strategy, especially in case of ED crowding. Other routes of administration could be interesting alternatives [ 51 , 52 , 53 ], still, so far, underprescription of IV morphine protocols has been poorly investigated regarding routine organizational constraints in the ED (e.g., logistics and nurse availability). Moreover, the state of knowledge in the field of opioid management has changed considerably since 2010.…”

Nebulized versus intravenous morphine titration for the initial treatment of severe acute pain in the emergency department: study protocol for a multicenter, prospective randomized and controlled trial, CLIN-AEROMORPH

“…The majority of clinical studies involve patients in long-stay medical departments who have dyspnea and not pain (cancer or chronic respiratory insufficiency [21–26]). Some work has been carried out in pediatric EDs [27] or only in trauma patients [28–30]. Some protocols have tested inhaled morphine hydrochloride, and others fentanyl [27, 31].…”

“…Moreover, analysis of the literature shows that previous protocols involving nebulized morphine for pain relief in the ED aimed to evaluate a weight-associated “loading dose” rather than a morphine titration protocol. For example, a recent study tested an emergency dose of 0.2 mg/kg of morphine, unsuccessfully [28]. Although morphine is probably absorbed via the ear-nose-throat and bronchopulmonary systems, the variability of the pharmacodynamic effects of morphine for the same plasma concentration is unlikely to be modified [32–34] and remains a central parameter.…”

“…The ideal times of the aerosol bolus and between each aerosol bolus have not been tested yet and cannot be deduced from what is proposed intravenously. Some clinical studies have tended to show relief, especially at the beginning of nebulization, in the first 5 min (when measured), and others have shown a greater rapidity of appearance of metabolites of morphine in the blood than in other routes of administration but without studying pain relief parallelism [27, 28, 35, 36]. Again, the data are insufficient and deserve to be completed.…”