Prompt and effective analgesia is often recommended in patients with acute trauma pain in both pre-hospital and hospital settings.
Low-dose methoxyflurane showed
superior and faster onset of pain relief compared with standard of care
analgesics, therefore should be considered for the management of acute
trauma-related pain in emergency settings.
Prompt and effective analgesia is often recommended in patients with acute trauma pain in both pre-hospital and hospital settings. Despite these recommendations, many patients remain under treated leading to dissatisfaction, unnecessary patient suffering and prolonged hospital stay. Several analgesics available in a variety of formulations and routes of administration are widely used in the pre-hospital and emergency care departments. Therefore, it is challenging for health care providers to assess the most suitable and effective treatment. Also, the use of analgesics is correlated with some factors which lead to oligoanalgesia among patients with moderate-to-severe trauma pain. These factors include difficulties with intravenous administration, adverse events, limited efficacy of weak analgesics, logistical constraints and the high administrative burden associated with controlled drugs.
Low-dose methoxyflurane is a non-opioid analgesic that is provided to patients under medical supervision. It is usually self-administered using a handheld inhaler, which is compact, easy to use and also helps to control the level of analgesia. It exhibits several features which makes it an attractive and reliable option for analgesia in emergency and hospital settings. It provides rapid pain relief and if used continuously, this pain-relieving effect can last for 25–30 minutes and can be longer with intermittent use. The adverse events associated with methoxyflurane are also transient and mild which resolves quickly after stopping inhalation. It does not affect cardiovascular function and did not cause respiratory depression.
It is widely prescribed for treating acute pain in adults and children in Australia. However, in Europe, it is approved for the treatment of moderate-to-severe trauma pain in adults. This approval was granted based on the randomized, double-blind, placebo-controlled trial (STOP trial), which indicated statistically and clinically significant reductions in pain intensity with low-dose methoxyflurane. Also, it was found to be more effective than standard of care analgesics for the management of moderate and severe acute trauma pain.
Rationale behind research
There is a need to conduct high-quality analysis for evaluating the efficacy and safety of analgesics in acute trauma-related pain to help healthcare providers in treatment-related decision making. Therefore, this study was conducted.
Objective
The purpose of this study was to
compare the safety and efficacy of low-dose methoxyflurane and standard of care
analgesics in patients with emergency trauma-related pain.
Literature search
Clinical databases such as MEDLINE and Embase were searched for relevant articles using search terms methoxyflurane AND emergency AND randomi*. The PICO (population, interventions, comparisons, and outcome) framework was used to define eligibility criteria.
Inclusion criteria
The studies were eligible for inclusion if:
Study selection and Data extraction
Independent screening of all the titles and abstracts which were identified in the search was done. The full text of eligible abstracts was further screened and reviewed. The articles which met the eligibility criteria after full-text screening were enrolled. Data related to demographics, pain intensity scores, exposure, time to pain relief, treatment satisfaction, and AEs was extracted from included studies by two reviewers independently. A third reviewer was referred for resolving any disagreement.
Statistical Analysis
Individual patient data was used to carry out analysis with the one-step approach. A repeated-measures analysis of variance (ANOVA) model was used to compare differences in pain intensity. This model includes the study, nominal time point, treatment, and the interaction between treatment and nominal time point. Evaluation of heterogeneity between the studies and consolidation of results was done using a two-step approach. Repeated measures ANOVA was used to interpret each data set separately. The weighted average of treatment effects with a random-effects model was used to combine the treatment effects across studies.
Quality assessment
Risk of Bias
The pain intensity was recorded on a 100 mm VAS [where 0=no pain and 100=worst pain imaginable] in most of the studies. The association between NRS at randomization and the closest value in the VAS was evaluated to assess potential bias regarding the use of NRS.
Study outcomes
Outcomes
Study characteristics:
Study quality:
Effect of intervention on the outcome:
The present meta-analysis confirmed the superior efficacy of low dose methoxyflurane over a range of standard of care analgesics for the treatment of acute trauma pain in emergency care settings. It has also demonstrated the faster onset of pain relief among patient administered with low dose methoxyflurane. The superior analgesic effect of low-dose methoxyflurane was consistent for a range of other endpoints, including response criteria and time to pain relief.
Patients administered with low dose methoxyflurane also reported greater treatment satisfaction compared to standard of care analgesics. The adverse event profile of all the analgesics was also comparable. The incidence of mild transient dizziness and somnolence was higher with low-dose methoxyflurane. Also, the efficacy of low dose methoxyflurane was comparable in patients aged ≥65 years and the overall population, but the data in the elderly subgroup should be interpreted with caution due to low patient numbers.
Along with faster pain relief,
methoxyflurane exhibits additional benefits over other short-acting analgesics
such as a non-opioid mechanism of action, ease of use, and the ability to
self-titrate for pain control. This study also established the use of low-dose
methoxyflurane as a highly effective short-term treatment option, thereby
providing reassurance to healthcare providers in emergency settings.
For self-administration, it is
essential to coach patients for inhaler use. Methoxyflurane should be added to
the inhaler through a one-way valve and absorbed by a polypropylene wick. After
absorption, the methoxyflurane vaporizes and therefore can be easily inhaled
through the mouthpiece. At first, patients are advised to take gentle breaths
and inhale intermittently for adequate analgesia. Any exhaled methoxyflurane
will be captured in an activated chamber, thereby reducing the exposure risk.
Low-dose methoxyflurane can be considered as an effective
alternative to the standard of care analgesics due to its superior efficacy for
treating acute trauma-related pain in pre-hospital and hospital settings.
Dove Press
Low-Dose Methoxyflurane versus Standard of Care Analgesics for Emergency Trauma Pain: A Systematic Review and Meta-Analysis of Pooled Data
Andrea Fabbri et al.
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