Inhaled Analgesia in Dermatologic Settings: A Comprehensive Overview of Methoxyflurane.

Pain management is an important aspect of dermatologic procedures, which are typically performed on awake patients in outpatient settings. The first-line modalities for procedural analgesia during most dermatologic procedures are topical and injectable local anesthetics, such as lidocaine. However, in some medical and cosmetic dermatologic procedures, pain cannot be effectively managed with local anesthetics due to procedure-specific lack of efficacy, large treatment surface areas, high dosage requirements, allergies, or other contraindications. In these circumstances, methoxyflurane inhalers may be highly beneficial. Methoxyflurane (Penthrox®) has demonstrated efficacy for providing pain relief in randomized controlled trials in patients who presented to emergency departments with acute trauma-related pain, as well as in patients undergoing painful procedures for other medical indications. The limited side effect profile, ease of patient self-administration, rapid onset and quick resolution of central nervous system effects following cessation makes methoxyflurane an ideal choice for analgesia during outpatient dermatologic procedures. This review provides an overview of the supporting evidence for methoxyflurane inhalers and clinical commentary on potential indications for methoxyflurane use in dermatology.

Literature review on the use of methoxyflurane in the management of pain in cancer-related procedures.

INTRODUCTION: Self-administered methoxyflurane, also known as Penthrox, at a sub-anesthetic dose is a short-term, fast-acting, and safe analgesic that may provide suitable pain relief for cancer patients. This review aims to compile the existing evidence on methoxyflurane and its efficacy in reducing pain during cancer-related procedures. METHODS: A literature search was conducted through OVID Medline and Embase. The search was limited to articles published between 2012 and 2021 and studies were included if they assessed the efficacy of methoxyflurane to reduce pain in cancer-related procedures. All types of cancer were included. RESULTS: The literature search yielded seven studies published between 2012 and 2021. The studies analyzed assessed methoxyflurane use in prostate biopsy, colonoscopy, removal of brachytherapy rods, and bone marrow biopsy. Various research designs were employed, including three randomized controlled trials, two prospective observational studies, one retrospective, and one non-randomized controlled trial. In all, methoxyflurane has a demonstrated ability to reduce pain in these procedures. CONCLUSION: In the limited studies available in evaluating the efficacy of methoxyflurane for reducing procedural pain during cancer-related procedures, all have demonstrated clinical equivalency or superiority. Pain relief appears to be equivalent however methoxyflurane overcomes the standard limitations of respiratory sedation and has demonstrated quicker procedural recovery times than traditional sedation methods. The accumulated data to date supports the use of methoxyflurane which can supplement or supplant current methods of analgesia in cancer-related procedures.

How I Do It: Penthrox in Urology.

Penthrox is a portable handheld inhaler that delivers a low dose of methoxyflurane - an anesthetic with analgesic effects, rapid onset of action, and a favorable side-effect profile. It has been widely used for acute pain management in Australia for the past 40 years. Currently, it is approved for use in over 55 countries, including Canada. Prospective randomized studies highlight Penthrox analgesic effectiveness and safety profile for emergency, prehospital and outpatient settings. In addition, the use of multimodal analgesia, specifically Penthrox, can play an important role in the analgesic management of urological procedures, such as prostatic biopsies and office-based minimally invasive surgical therapies. Herein readers will familiarize themselves with Penthrox, significant studies, and technique used for outpatient urological procedures.

Efficacy and safety of methoxyflurane (Penthrox) for pain control during water vapor thermal therapy (Rezum) for benign prostatic enlargement.

INTRODUCTION: The safety and efficacy of low dose methoxyflurane disposable inhaler (Penthrox) was assessed in this study of men undergoing Rezum water vapor thermal therapy (WVTT). MATERIAL AND METHODS: An open-labeled, single-center study was conducted to demonstrate the safety and efficacy of using methoxyflurane inhaler during a Rezum procedure. Patients assessed current pain intensity using a 10-point Visual Analog Scale (VAS) of Pain at 4 timepoints including (1) before any medication, (2) initially after insertion of the rigid cystoscope and before any Rezum treatment, (3) immediately after final injection of Rezum treatment and (4) at discharge. Patients were asked to fill out the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4) and one question about pain relief at discharge. Treating physician also completed the TSQM 1.4. RESULTS: Ten patients were recruited. Median prostate volume was 53.4 cc (range 24-158 cc). Patients received a median of 10.5 Rezum injections, with a median procedure time of 4.5 minutes. Median VAS scores were 0, 0.1, 0 (primary efficacy outcome) and 0 (out of scale of 10) at the 4 timepoints, respectively. TSQM scores on effectiveness, side effects, convenience and global median satisfaction rated by patients were respectively 69.4, 100.0, 77.8 and 82.1 (out of scale of 100). Treatment satisfaction on pain relief was rated as 4.0 (very good). There were no observed adverse events. CONCLUSIONS: Methoxyflurane inhaler (Penthrox) was low cost, rapid, feasible and easy to administer as a pain management strategy for Rezum therapy. Further data from a larger comparative study will be conducted.

Derivation of an occupational exposure limit for an inhalation analgesic methoxyflurane (Penthrox(®)).

Methoxyflurane (MOF) a haloether, is an inhalation analgesic agent for emergency relief of pain by self administration in conscious patients with trauma and associated pain. It is administered under supervision of personnel trained in its use. As a consequence of supervised use, intermittent occupational exposure can occur. An occupational exposure limit has not been established for methoxyflurane. Human clinical and toxicity data have been reviewed and used to derive an occupational exposure limit (referred to as a maximum exposure level, MEL) according to modern principles. The data set for methoxyflurane is complex given its historical use as anaesthetic. Distinguishing clinical investigations of adverse health effects following high and prolonged exposure during anaesthesia to assess relatively low and intermittent exposure during occupational exposure requires an evidence based approach to the toxicity assessment and determination of a critical effect and point of departure. The principal target organs are the kidney and the central nervous system and there have been rare reports of hepatotoxicity, too. Methoxyflurane is not genotoxic based on in vitro bacterial mutation and in vivo micronucleus tests and it is not classifiable (IARC) as a carcinogenic hazard to humans. The critical effect chosen for development of a MEL is kidney toxicity. The point of departure (POD) was derived from the concentration response relationship for kidney toxicity using the benchmark dose method. A MEL of 15 ppm (expressed as an 8 h time weighted average (TWA)) was derived. The derived MEL is at least 50 times higher than the mean observed TWA (0.23 ppm) for ambulance workers and medical staff involved in supervising use of Penthrox. In typical treatment environments (ambulances and treatment rooms) that meet ventilation requirements the derived MEL is at least 10 times higher than the modelled TWA (1.5 ppm or less) and the estimated short term peak concentrations are within the MEL. The odour threshold for MOF of 0.13-0.19 ppm indicates that the odour is detectable well below the MEL. Given the above considerations the proposed MEL is health protective.

MethOxyfluraNe in InTerventiOnal Radiology (MONITOR): A randomised controlled trial.

INTRODUCTION: Procedural sedation and pain management in interventional radiology (IR) are of critical importance to successful outcomes but remain under-researched. Methoxyflurane has been previously used in some minor procedures with several advantages including rapid onset and offset and a good safety profile. The purpose of this study was to evaluate methoxyflurane for procedures in IR. METHODS: A randomised, double-blind, placebo-controlled trial was performed between October 2021 and November 2022. Patients presenting for portacath insertion, portacath removal or solid organ biopsy were randomised to either methoxyflurane or placebo. Three hundred and fourteen patients were enrolled in total. Patients were supplied with one Penthrox inhaler containing either 3 mL methoxyflurane or placebo. The primary endpoints of the study were change in pain and anxiety scores compared with baseline, measured on a standardised visual analogue scale (VAS) pre-procedure, at 5-min intervals during the procedure and post-procedure. Baselines scores were controlled for in the statistical analysis. Safety analysis was also performed. RESULTS: One hundred and sixty-nine patients received methoxyflurane and 145 received placebo. Baseline characteristics were similar between the two groups. The methoxyflurane group had lower pain and anxiety scores throughout the procedure (P < 0.001) with 2.5 times less pain (VAS 1.08/10) and 1.6 times less anxiety (VAS 0.97/10) on average. Lower post-procedure pain (mean 0.72 vs 1.44; P < 0.001) and anxiety (mean 0.55 vs 1.13; P = 0.008) were also observed with methoxyflurane. There were no drug or major procedure-related adverse events. CONCLUSION: The results of this study suggest that methoxyflurane provides safe and effective analgesia and anxiolysis for some procedures in IR.

Inhaled methoxyflurane (Penthrox®) as a novel pain relief for outpatient hysteroscopy and other gynaecological procedures.

OBJECTIVE: Penthrox® (methoxyflurane) is a convenient, portable, self-administered disposable single-use handheld inhaler licenced as an emergency, rapid-onset, short-acting, analgesic in adult trauma patients. Outpatient hysteroscopy is one of the commonest procedures in contemporary gynecology but it can be associated with significant pain leading to poor patient experience and failed procedures. We evaluated the feasibility and acceptability of Penthrox® in women undergoing outpatient hysteroscopic procedures and its potential efficacy to reduce pain and improve patient experience. STUDY DESIGN: We conducted a prospective observational cohort study on women undergoing hysteroscopy or other intrauterine procedures, such as coil fitting, endometrial biopsy, polypectomy, endometrial ablation and manual vacuum aspiration in an outpatient setting. Women were offered Penthrox® inhalers for pain control, instructed how to use it and asked to record the intra-procedural pain they expected and actually experienced using a 10 cm Visual Analogue Scale. The acceptability, side effects and ease of use of the Penthrox® device were also recorded. RESULTS: 122/146 (83.6 %) women chose to use Penthrox®. 116 out of the 122 (95.1 %) underwent an intrauterine procedure, including 59 hysteroscopic polypectomies and 34 global endometrial ablations. The average pain expected during the procedure was 6.0 (SD = 2.8) and the pain experienced during the procedure was 5.1 (SD = 2.8). The intended procedure was completed in 117 (96 %) women. Penthrox® was considered easy to use by 118 (97 %) women and 111 (91 %) would use it again, although 22 (18 %) women would prefer general anaesthesia in the future. No adverse events occurred but 88 (72 %) women reported mild, self-limiting side effects. CONCLUSION: Penthrox® appears safe, feasible and acceptable as a pain relief option during outpatient hysteroscopy and other intrauterine procedures. The effectiveness of Penthrox® should be evaluated against conventional pain control in an adequately powered multicentre randomised controlled trial.

Deployed Combat Use of Methoxyflurane for Analgesia.

BACKGROUND: The U.S. Military needs fast-acting, non-opioid solutions for battlefield pain. The U.S. Military recently used morphine auto-injectors, which are now unavailable. Off-label ketamine and oral transmucosal fentanyl citrate use introduces challenges and is therefore uncommon among conventional forces. Sublingual suftentanil is the only recent pain medication acquired to fill this gap. Conversely, methoxyflurane delivered by a handheld inhaler is promising, fast-acting, and available to some partner forces. We describe methoxyflurane use reported in the Department of Defense Trauma Registry (DODTR). METHODS: We requested all available DODTR encounters from 2007 to 2023 with a documented intervention or assessment within the first 72 hours of care. We analyzed casualties who received methoxyflurane in the prehospital setting using descriptive statistics. RESULTS: There were 22 encounters with documented methoxyflurane administration. The median patient age was 23 (range 21-31) years. All were men. The largest proportion was partner force (50%), followed by U.S. Military (27%). Most (64%) sustained battle injuries. Explosives were the most common mechanism of injury (46%), followed by firearms (23%). The median injury severity score was 5 (range 1-17). The most frequent injuries were serious injuries to the extremities (27%), and 23% of patients (5) received a tourniquet. One-half of the casualties received concomitant pain medications. Only three casualties had multiple pain scores measured, with a median pain score change of -3 on a scale of 10. CONCLUSION: Methoxyflurane use in deployed combat shows both feasibility and usability for analgesia.

Pain and symptom relief using inhaled methoxyflurane for gynecologic brachytherapy applicator removal.

Purpose: Intra-cavitary brachytherapy forms an essential part of the curative treatment of cervical and vaginal cancer, and can be used for cure or palliation in endometrial and vulval cancers. Removal of brachytherapy applicators is often performed after anaesthesia has worn off and can be an uncomfortable and anxiety-provoking procedure. In this paper, we present our experience in a series of patients before and after the introduction of inhaled methoxyflurane (IMF, Penthrox™). Material and methods: Questionnaires were sent to patients prior to the introduction of IMF to retrospectively score pain and anxiety during the brachytherapy procedure. Following successful review by the local drugs and therapeutic committee as well as staff training, IMF was introduced and offered to patients during applicator removal. Prospective pain scores and retrospective questionnaires were collected. Pain was rated on a scale of 0 to 10, with zero being no pain and 10 being extreme pain. Results: Thirteen patients returned retrospective questionnaires prior to IMF introduction and seven patients following IMF introduction. After the first brachytherapy insertion, the mean recollected pain score during applicator removal decreased from 6/10 to 1/10 (p = 0.002). The mean recollected pain score one hour after applicator removal reduced from 3/10 to 0 (p = 0.04). Prospective measurements for 77 insertions in 44 patients receiving IMF reported a median pain score of 1/10 immediately before applicator removal (range, 0-10), and 0/10 immediately after applicator removal (range, 0-5). Conclusions: Inhaled methoxyflurane is easily administered and effective method of decreasing pain during applicator removal following gynecologic brachytherapy.

Penthrox® (Methoxyflurane) as an Analgesic for Removal of Circular External Fixators and Minor Procedures during the COVID-19 Pandemic.

Introduction: Methoxyflurane has excellent analgesic properties and is approved for use in the United Kingdom and Ireland since 2015. It is currently used in emergency departments for analgesia during fracture reductions. During the COVID-19 pandemic, with theatre access severely restricted, Penthrox® had the potential to provide adequate pain relief to aid frame and wire removal in the clinic setting. Materials and methods: Patients presenting to the limb reconstruction service elective clinic and requiring frame removal or minor procedures were included in the study. Patients with renal, cardiac or hepatic disease, a history of sensitivity to fluorinated anaesthetic agents and those on any nephrotoxic or enzyme-inducing drugs were excluded. All procedures were performed in an appropriate isolated room in the clinic. Patient demographics, procedure details, visual analogue score, Richmond Agitation Scale and patient satisfaction were recorded. Results: A total of 39 patients were included in the study of which 17 had Ilizarov frames removed, 10 had hexapod removals, nine had heel rings removed and three had an external fixator removed. Eleven patients received additional pain relief in the form of oral analgesia. All patients were satisfied or very satisfied with the experience. One patient required a general anaesthetic for the removal of a wire that could not be removed in the clinic due to bony overgrowth. Conclusion: Patient satisfaction was very high (>95%), and it was possible to perform frame removals and minor procedures in the clinic environment during the COVID-19 pandemic. We see potential for regular use of Penthrox® in the future for the removal of external fixation outside of the operating theatre. Clinical significance: Penthrox as an analgesic for frame adjustments and removals is safe and has the potential for significant financial savings for the National Health Service (NHS). How to cite this article: Debuka E, Birkenhead P, Shah S, et al. Penthrox® (Methoxyflurane) as an Analgesic for Removal of Circular External Fixators and Minor Procedures during the COVID-19 Pandemic. Strategies Trauma Limb Reconstr 2023;18(2):82-86.

Penthrox enables quicker management of fractures, dislocations and more: learning lessons from expedited care of trauma patients during the COVID-19 pandemic.

INTRODUCTION: Methoxyflurane is an historical anaesthetic agent that has undergone a renaissance with the introduction of a smaller dose in a handheld 'Penthrox' device. The benefits of Penthrox include its ease of use, with disposable individual packets, and the need for less monitoring and staff, when compared with deeper sedation. The literature acknowledges its use for analgesia and in the management of anterior shoulder dislocation but in no other procedural orthopaedic circumstance. METHODS: Following institutional approval, we undertook a retrospective review of all incidences of Penthrox use to facilitate minor procedures within a 2-month period starting 24 March 2020. Time to procedure and success were recorded using the surrogate markers of patient attendance and x-Ray occurrence times. RESULTS: Some 101 Penthrox doses were given to 89 patients over 97 unique episodes between 24 March and 26 May 2020. No complications were recorded following the use of Penthrox during this period. Patient demographics were explored. Fracture manipulations and casting (n=54) had a 100% success rate in achieving adequate and safe reduction. Joint dislocations (n=34) were treated with varying success. Native elbow dislocations were reduced most successfully (4/4, 100%). Native shoulder dislocations were seen in 17 patients and successful relocation was seen in 11 cases, giving a success rate of 65%. CONCLUSIONS: This is the first study, outside anterior shoulder dislocations, to report on the efficacy of Penthrox within emergent orthopaedic scenarios. We have demonstrated Penthrox to be a safe tool for helping to manage trauma procedures in the emergency department.

Ambulance nurses' experiences of pain management with Penthrox® in Swedish ambulance care: A mixed method study.

BACKGROUND: Methoxyflurane (MTX) is an inhalation agent that has several potential benefits for limiting various types of pain in ambulance care. AIM: To elucidate how ambulance nurses experience the characteristics of MTX in an ambulance care setting. METHOD: This cross-sectional study applied a mixed-methods approach, using a questionnaire together with complementary interviews. The questionnaire survey was analyzed using descriptive statistics (10-point Likert scale and question index values [Q-IV], range: 0-1.0). The interviews were analyzed using directed content analysis. Study results were reported following the STROBE statement. RESULTS: The ambulance nurses' overall general satisfaction with the MTX concept had a median of 7.0 (IQR 5-8), corresponding to a mean Q-IV of 0.84 (very good experience). The qualitative part was divided into three categories: sense of security, patient participation, and general usefulness. The results revealed varying experiences of usefulness, including pain-relieving effect and the possibility of patient participation. The perceived strong odor of MTX seemed to concern the ambulance nurses and their patients. CONCLUSION: In general, MTX was experienced as a safe and effective analgesic. However, the experiences of the overall usefulness varied, particularly since the product had a perceived strong odor. Increasing knowledge of using MTX, could likely increase the overall usefulness.

Conservative Management of the Ring and Little Finger Carpometacarpal Joint Dorsal Dislocations.

This is a case of right ring and little finger carpometacarpal joint dislocation managed with conservative care following early presentation and accurate identification of the injury. It is a rare injury that can be easily missed with the need for operative intervention if there is a delayed diagnosis. The dislocation was reduced and retained with an ulnar gutter splint using plaster of Paris extending from the mid-forearm to the metacarpophalangeal joints. Caution and repeated radiological assessment are advised to ensure that the reduction has been maintained. Follow-up at one week and four weeks post injury showed no pain or deformity, with a normal range of motion in the affected joints.

Comparison of inhalational methoxyflurane (Penthrox®) and intramuscular tramadol for prehospital analgesia.

INTRODUCTION: Treatment of pain is an important component of prehospital care. Inhalational analgesia agents have attractive strengths, but there is a paucity of studies comparing these with more conventional agents. We aimed to compare inhalational methoxyflurane and intramuscular (IM) tramadol as first-contact analgesia in the Singapore national ambulance service. METHODS: Ambulances were randomised to carry either methoxyflurane or IM tramadol for the first six months and crossed over to the other arm after six months. Patients aged ≥ 16 years, with acute pain arising from musculoskeletal trauma with Numerical Rating Scale (NRS) score ≥ 3 were enrolled. Variables included NRS reduction, time variables, adverse effects, Ramsay Sedation Scores, and patient and paramedic satisfaction scores on a Likert scale. RESULTS: A total of 369 patients were enrolled into this study, but 26 patients were excluded due to missing data. The methoxyflurane arm had a shorter median time taken from arrival at the scene to drug administration (9.0 [interquartile range 6.0-14.0] minutes vs. 11.0 [interquartile range 8.0-15.0] minutes). For patients who achieved reduction in NRS ≥ 3 within 20 minutes, those in the methoxyflurane arm took a shorter time. However, the methoxyflurane (46.7%) arm experienced lower proportion of patients not achieving NRS reduction ≥ 3 when compared to the tramadol (71.6%) arm after over 20 minutes. The methoxyflurane arm had significantly higher paramedic and patient satisfaction scores. CONCLUSION: For the doses of medication used in this implementation study, methoxyflurane was superior in efficacy, speed of onset and administration, but had more minor adverse effects when compared to IM tramadol.

Pain management with methoxyflurane (Penthrox®) in Swedish ambulance care - An observational pilot study.

BACKGROUND: In ambulance care, patients are often classified as high-risk, particularly when they are in immediate need of pain relief. It has been shown that, after ambulance nurses administer intravenous analgesic drugs, patients delivered to the emergency department tend to complain of moderate to severe pain. AIMS AND OBJECTIVES: The present study aimed to evaluate the overall patient-perceived pain during treatment with methoxyflurane (MTX) in an ambulance-care setting. We also explored potential demographic variations. METHODS: This prospective observational study included 50 patients in need of ambulance care that perceived acute pain, defined as a Numeric Rating Scale (NRS) value ≥4 (scale range: 1-10). We monitored the vital parameters of patients and MTX treatment characteristics, including the total number of inhaled MTX breaths and the average number of treatment sequences. RESULTS: Among the 50 patients initially assessed, we excluded 8 patients (16%), due to MTX contraindications. We excluded 10 patients (24%), due to discontinued treatment. The remaining cohort (n = 32) that fulfilled the pain-relieving procedure, included equal numbers of men and women. The average time spent in ambulance care was 29 ±â€¯15 min. The NRS scores for pain measured at the scene (median 8.0, interquartile range [IQR]: 7.25-10.0) were significantly higher than those measured at hospital admission (median 5.0, IQR: 4.0 7.0; p = .001). The median NRS scores measured at the hospital were different between sexes (men: 6.0, IQR: 5-7.25; women: 4.0, IQR: 3.76-6.0; p = .036). The average number of treatment sequences was 2. The overall average number of inhaled breaths was 17 ±â€¯9. CONCLUSION: This study demonstrates that MTX provided clinically significant lower pain scores among patients in ambulance care without significant effects on vital parameters. However, the pharmacological characteristics of MTX appeared to affect the potential of achieving standardized treatment objectives.

Inhaled methoxyflurane (Penthrox) for analgesia in trauma: a systematic review protocol.

BACKGROUND: More than 75% of patients presenting to the Emergency Department are suffering symptoms of pain. Despite this, 67% will not receive any analgesia. Methoxyflurane is a fluorinated hydrocarbon gas which has analgesic properties when inhaled. Penthrox is a methoxyflurane autoinhaler recently licenced in Europe. Its ease of administration, safety, and fast onset of action make it of particular relevance to emergency medicine. Additionally, outside the hospital, it has the advantage of increased temperature stability and portability over current standard care. New evidence of its efficacy is emerging; however, currently, its use in Europe is not widespread. The objective of this study will be to systematically evaluate the evidence on inhaled methoxyflurane to determine if it is a superior analgesia in the acute trauma setting. METHODS: We designed and registered a study protocol for a systematic review and meta-analysis on randomised controlled trials, comparing inhaled methoxyflurane and either placebo or standard care. A comprehensive search will be conducted from database inception onwards in MEDLINE, Embase, and the Cochrane CENTRAL database, concurrent with a search of the grey literature for other relevant studies, including clinical trial databases. Only randomised controlled trials will be included. No limitations will be imposed on publication status or language of publication. The primary outcome will be mean difference in patient-reported pain at time points within the first 30 min of administration. Secondary outcomes will be mean difference in time to clinically significant pain relief and relative risk of adverse effects. Two reviewers will independently screen all returned studies and collect data. Disagreements will be resolved through discussion or referral to a third reviewer. Individual study methodological quality will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis; if this is not possible, we will construct a narrative synthesis. DISCUSSION: This systematic review will summarise the best available evidence and definitively establish if inhaled methoxyflurane is a superior analgesia to standard care in the acute trauma setting. This knowledge will directly impact emergency care in the UK and worldwide and may require amendments to European pain relief guidelines. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020189119 .

Penthrox: a breath of PHEC air for the military?

Prehospital analgesia is vital to good clinical care and inhaled methoxyflurane (Penthrox) would be a valuable addition to the armed forces medical armoury. Penthrox would provide strong, fast-acting, self-administered and safe analgesia to patients with moderate to severe injuries. In addition, it would provide an option for strong analgesia which would not be subject to the regulations that govern controlled or accountable drugs which gives it a unique position as the military moves its focus from large enduring operations to small short-term training teams supported by lone combat medics in remote locations across the globe.

Non-interventional study evaluating exposure to inhaled, low-dose methoxyflurane experienced by hospital emergency department personnel in France.

OBJECTIVES: Low-dose methoxyflurane is a non-opioid, inhaled analgesic administered via the Penthrox inhaler and was recently licensed in Europe for emergency relief of moderate-to-severe trauma-associated pain in conscious adults. This non-interventional study investigated occupational exposure to methoxyflurane in the hospital emergency department (ED) personnel during routine clinical practice. SETTING AND PARTICIPANTS: The study was conducted in two hospital ED triage rooms in France over a 2-week and 3-week period, respectively. Low-dose methoxyflurane analgesia was self-administered by patients via the inhaler under the supervision of nursing staff, per routine clinical practice. An organic vapour personal badge sampler was attached to the uniform of the nurses working in the treatment rooms throughout an 8-hour shift (total of 140 shifts during the study period). Seven-day ambient air monitoring of each treatment room was also performed. Methoxyflurane levels adsorbed in each badge sampler were measured by a central laboratory. The primary objective was to evaluate methoxyflurane exposure experience by the hospital ED nurses during an 8-hour shift. RESULTS: In 138 badge samplers, the median (range) concentration of methoxyflurane present following 8-hour nursing shifts was 0.017 (0.008, 0.736) ppm. This level was almost 900-fold lower than the previously reported 8-hour-derived maximal exposure level of 15 ppm; methoxyflurane exposure approaching this threshold was not documented in any badges. There was no correlation between the number of applications of low-dose methoxyflurane administered during a shift (range 0-5) and the vapour exposure measured on the personal badge samplers. CONCLUSIONS: This study indicates that nurses working in hospital EDs experience very low levels of occupational exposure to methoxyflurane vapour during routine clinical practice. These real-world data can provide reassurance to healthcare providers supervising patients receiving low-dose methoxyflurane analgesia via a Penthrox inhaler; further studies may inform exposure in other hospital ED settings.

Service Evaluation of Methoxyflurane Versus Standard Care for Overall Management of Patients with Pain Due to Injury.

INTRODUCTION: Inhaled methoxyflurane is an analgesic used for the emergency relief of moderate to severe pain in conscious adult patients with trauma and associated pain that is increasingly being used in hospital emergency departments to provide rapid analgesia. It is widely accepted that effective pain relief can facilitate patient care and flow through the emergency department (ED). The main aim of this evaluation was to assess the impact of inhaled methoxyflurane on patient length of stay (LOS) in the ED compared with standard care. METHODS: Adult patients with moderate to severe trauma pain and Glasgow coma score of 15 were included in the evaluation. Evaluation forms were completed for 79 patients who received methoxyflurane and were matched with 80 patients who received standard care. RESULTS: Overall the mean time spent in the ED was reduced by 71 min in those patients who were administered methoxyflurane compared with patients who received standard care. Furthermore, analysis of LOS by injury type demonstrated a reduction in ED LOS by 183 min for patients with shoulder dislocation who were treated with methoxyflurane compared with patients who received standard care. There was no reduction in ED LOS for patients with lower limb, hip or pelvic injuries between the two treatment groups. CONCLUSION: Use of methoxyflurane in adult patients with trauma pain significantly reduced the ED LOS and may potentially improve patient flow through the ED.

Low-dose methoxyflurane analgesia in adolescent patients with moderate-to-severe trauma pain: a subgroup analysis of the STOP! study.

INTRODUCTION: The undertreatment of acute pain presents a significant challenge in the Emergency Department. This post hoc subgroup analysis of a previously reported randomized controlled UK study reports the efficacy and safety of low-dose methoxyflurane analgesia in treating adolescent patients with moderate-to-severe trauma pain. PATIENTS AND METHODS: Three hundred patients (96 in the adolescent subgroup) aged ≥12 years requiring analgesia for acute trauma pain (pain score of 4-7 on the Numerical Rating Scale) at triage were randomized 1:1 to methoxyflurane (up to 6 mL) or placebo (normal saline), both administered using a Penthrox® inhaler. The patient could request rescue medication (paracetamol/opioids) at any time. The primary endpoint was the change from baseline in visual analog scale (VAS) pain intensity. RESULTS: Mean VAS pain score for the adolescent subgroup at baseline was ~ 61 mm. Adjusted mean change in VAS pain intensity from baseline to 5, 10, 15, and 20 minutes was -24.5, -28.1, -31.6, and -31.7 mm for methoxyflurane and -14.6, -18.8, -19.2, and -23.7 mm for placebo, with a statistically significant treatment effect in favor of methoxyflurane overall across all four time points (-9.9 mm; 95% CI: -17.4, -2.4 mm; P=0.0104). Median time to first pain relief was significantly shorter with methoxyflurane (1 minute) than placebo (3 minutes, P<0.0001). Pain relief was reported within 1-10 inhalations in 95.7% of methoxyflurane-treated patients and 64.6% of placebo-treated patients. Rescue medication was requested by two (4.3%) methoxyflurane-treated patients and three (6.3%) placebo-treated patients. Over 95% of patients, physicians, and nurses rated methoxyflurane treatment as "Excellent", "Very Good" or "Good" compared with between 64% and 68% for placebo. The incidence of adverse events was higher with methoxyflurane (51%) than placebo (42%), mostly comprising mild/transient dizziness and headache. CONCLUSION: This subgroup analysis shows that low-dose inhaled methoxyflurane is a rapid-acting and effective analgesic in adolescent patients presenting with moderate-to-severe trauma pain. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.