Use of the Schelin Catheter for transurethral intraprostatic anesthesia prior to Rezum treatment.

Minimally invasive surgery techniques (MIST) have become newly adopted in urological care.  Given this, new analgesic techniques are important in optimizing patient outcomes and resource management. Rezum treatment (RT) for BPH has emerged as a new MIST with excellent patient outcomes, including improving quality of life (QoL) and International Prostate Symptom Scores (IPSSs), while also preserving sexual function.  Currently, the standard analgesic approach for RT involves a peri-prostatic nerve block (PNB) using a transrectal ultrasound (TRUS) or systemic sedation anesthesia.  The TRUS approach is invasive, uncomfortable, and holds a risk of infection.  Additionally, alternative methods such as, inhaled methoxyflurane (Penthrox), nitric oxide, general anesthesia, as well as intravenous (IV) sedation pose safety risks or mandate the presence of an anesthesiology team.  Transurethral intraprostatic anesthesia (TUIA) using the Schelin Catheter (ProstaLund, Lund, Sweden) (SC) provides a new, non-invasive, and efficient technique for out-patient, office based Rezum procedures.  Through local administration of an analgesic around the prostate base, the SC has been shown to reduce pain, procedure times, and bleeding during MISTs.  Herein, we evaluated the analgesic efficacy of TUIA via the SC in a cohort of 10 patients undergoing in-patient RT for BPH.

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.

Environmental impact of low-dose methoxyflurane versus nitrous oxide for analgesia: how green is the 'green whistle'?

BACKGROUND: The NHS has the target of reducing its carbon emission by 80% by 2032. Part of its strategy is using pharmaceuticals with a less harmful impact on the environment. Nitrous oxide is currently used widely within the NHS. Nitrous oxide, if released into the atmosphere, has a significant environmental impact. Methoxyflurane, delivered through the Penthrox 'green whistle' device, is a short-acting analgesic and is thought to have a smaller environmental impact compared with nitrous oxide. METHODS: Life cycle impact assessment (LCIA) of all products and processes involved in the manufacture and use of Penthrox, using data from the manufacturer, online sources and LCIA inventory Ecoinvent. These data were analysed in OpenLCA. Impact data were compared with existing data on nitrous oxide and morphine sulfate. RESULTS: This LCIA found that Penthrox has a climate change effect of 0.84 kg carbon dioxide equivalent (CO2e). Raw materials and the production process contributed to majority of the impact of Penthrox across all categories with raw materials accounting for 34.40% of the total climate change impact. Penthrox has a climate change impact of 117.7 times less CO2e compared with Entonox. 7 mg of 100 mg/100 mL of intravenous morphine sulfate had a climate change effect of 0.01 kg CO2e. CONCLUSIONS: This LCIA has shown that the overall 'cradle-to-grave' environmental impact of Penthrox device is better than nitrous oxide when looking specifically at climate change impact. The climate change impact for an equivalent dose of intravenous morphine was even lower. Switching to the use of inhaled methoxyflurane instead of using nitrous oxide in certain clinical situations could help the NHS to reach its carbon emission reduction target.

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.

Efficacy and Safety of Methoxyflurane for Treatment of Acute Traumatic Pain by EMTs during Alpine Rescue Operations: The "PainDrop" Trial.

Background: Treatment of acute traumatic pain is a core task for mountain rescue services. Intravenous access, however, is often difficult, and the vast majority of missions are carried out without a physician at the scene. The spectrum of analgesics available for use by non-physician personnel is limited. Inhaled analgesics, such as methoxyflurane, might prove useful, but currently no data exist on their application by non-physicians in the alpine setting.Methods: This prospective observational alpine field study was conducted over a period of 15 months. Patients suffering traumatic injuries with moderate to severe pain (pain score ≥ 5) after downhill bike accidents in the Tyrol mountains (1,362 m to 2,666 m above sea level) were enrolled. Teams of four mountain rescue service members, one of them a trained EMT, treated the patients with 3 ml of methoxyflurane by inhaler. We measured efficacy as reduction in pain from baseline to 15 minutes after treatment on a numerical rating scale. Safety was assessed by change in vital signs or occurrence of side-effects. Sample-size calculations were based on the efficacy outcome and yielded a need for 20 patients at a power of 0.8.Results: From June 29, 2020 to September 30, 2021, a total of 20 patients (two females; mean age 37 years) were included. The mean initial pain score was 7.2 (SD 1.0) points. After 15 minutes, pain was significantly reduced by a mean of 2.9 (SD 1.4) points. No major adverse events or relevant changes in vital signs were observed.Conclusion: The use of methoxyflurane by EMTs during alpine rescue operations in our study proved to be safe and efficient. We observed no reduction in the efficacy of the inhaler device at moderate altitude.

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.

Peri-prostatic nerve block using Clarius EC7 HD3 handheld ultrasound guidance.

Transrectal ultrasound (TRUS) is a common modality used during urological procedures that require real-time visualization of the prostate, such as prostate biopsy and peri-prostatic nerve blocks (PNB) for surgical procedures. Current practice for TRUS-guided PNB requires use of costly, fixed, and non-portable ultrasound machinery that can often limit workflow. The Clarius endocavity EC7 probe, a digital, handheld and pocket-sized endocavity ultrasound (US) device, is an alternative, portable technology which was recently shown to accurately visualize and measure prostate dimensions and volume. Moreover, in recent years, there has been a renaissance of office-based treatments for minimally invasive surgical therapies (MIST) for the treatment of benign prostate hyperplasia (BPH). More specifically, the Rezum procedure has been demonstrated to offer men a short, outpatient therapy with excellent 5-year outcomes in durability and preservation of antegrade ejaculation. While other anesthetic techniques have been described for Rezum, including inhaled methoxyflurane (Penthrox), nitrous oxide, IV sedation and general anesthesia (which often mandate the presence of an anesthesiology team), US-guided local blocks offer the urologist an independent method for pain management. While most urologists may not have direct access to expensive, cart-based ultrasound systems, point of care ultrasound (POCUS) technology, such as Clarius (Vancouver, BC, Canada) and Butterfly (Butterfly Network, Inc, Guilford, CT, USA), can provide high-resolution imaging in combination with smart phone technology. Herein, we sought to describe the technique for using Clarius EC7 for TRUS-guided PNB and its use in urological application with the Rezum BPH procedure.

Real world safety of methoxyflurane analgesia in the emergency setting: a comparative hybrid prospective-retrospective post-authorisation safety study.

BACKGROUND: Low-dose analgesic methoxyflurane (Penthrox®) was approved in Europe for emergency relief of moderate to severe pain in conscious adults with trauma in 2015. A comparative post-authorisation safety study (PASS) was conducted to assess the risk of hepatotoxicity and nephrotoxicity with methoxyflurane during routine clinical practice. METHODS: This was a comparative hybrid prospective-retrospective cohort study. The comparative cohorts consisted of adults who were given methoxyflurane (methoxyflurane cohort) or another analgesic (concurrent cohort) routinely used for moderate to severe trauma and associated pain in the emergency setting (ambulance and Emergency Department) in the UK between December 2016 and November 2018. Hepatic and renal events were captured in the ensuing 12 weeks. A blinded clinical adjudication committee assessed events. A historical comparator cohort (non-concurrent cohort) was identified from patients with fractures in the English Hospital Episode Statistics (HES) accident and emergency database from November 2013 and November 2015 (before commercial launch of methoxyflurane). Hepatic and renal events were captured in the ensuing 12 weeks via linkage with the Clinical Practice Research Datalink (CPRD) and HES hospital admissions databases. RESULTS: Overall, 1,236, 1,101 and 45,112 patients were analysed in the methoxyflurane, concurrent and non-concurrent comparator cohorts respectively. There was no significant difference in hepatic events between the methoxyflurane and concurrent cohorts (1.9% vs. 3.0%, P = 0.079) or between the methoxyflurane and non-concurrent cohorts (1.9% vs. 2.5%, P = 0.192). Renal events were significantly less common in the methoxyflurane cohort than in the concurrent cohort (2.3% vs. 5.6%, P < 0.001). For methoxyflurane versus non-concurrent cohort the lower occurrence of renal events (2.3% vs. 3.2%, P = 0.070) was not statistically significant. Multivariable adjustment did not change these associations. CONCLUSIONS: Methoxyflurane administration was not associated with an increased risk of hepatotoxicity or nephrotoxicity compared with other routinely administered analgesics and was associated with a reduced risk of nephrotoxicity compared with other routinely administered analgesics. TRIAL REGISTRATION: Study registered in the EU PAS Register (ENCEPP/SDPP/13040).

'Pain-free TRUS B': a phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasonography-guided prostate biopsy (ANZUP 1501).

OBJECTIVE: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. PATIENTS AND METHODS: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. RESULTS: The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events. CONCLUSIONS: We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

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.

Usability and effectiveness of inhaled methoxyflurane for prehospital analgesia - a prospective, observational study.

BACKGROUND: Pain relief in the prehospital setting is often insufficient, as the administration of potent intravenous analgesic drugs is mostly reserved to physicians. In Australia, inhaled methoxyflurane has been in routine use by paramedics for decades, but experience in Central European countries is lacking. Thus, we aimed to assess whether user friendliness and effectiveness of inhaled methoxyflurane as sole analgesic match the specific capabilities of local ground and air-based EMS systems in Austria. METHODS: Observational study in adult trauma patients (e.g. dislocations, fracture or low back pain following minor trauma) with moderate to severe pain (numeric rating scale [NRS] ≥4). Included patients received a Penthrop® inhaler containing 3 mL of methoxyflurane (maximum use 30 min). When pain relief was considered insufficient (NRS reduction < 3 after 10 min), intravenous analgesics were administered by an emergency physician. The primary endpoint was effectiveness of methoxyflurane as sole analgesic for transport of patients. Secondary endpoints were user friendliness (EMS personell), time to pain relief, vital parameters, side effects, and satisfaction of patients. RESULTS: Median numeric pain rating was 8.0 (7.0-8.0) in 109 patients. Sufficient analgesia (reduction of NRS ≥3) was achieved by inhaled methoxyflurane alone in 67 patients (61%). The analgesic effect was progressively better with increasing age. Side effects were frequent (n = 58, 53%) but mild. User satisfaction was scored as very good when pain relief was sufficient, but fair in patients without benefit. Technical problems were observed in 16 cases (14.7%), mainly related to filling of the inhaler. In every fifth use, the fruity smell of methoxyflurane was experienced as unpleasant. No negative effects on vital signs were observed. CONCLUSION: In prehospital use, inhaled methoxyflurane as sole analgesic is effective for transport of trauma patients (62%) with moderate to severe pain. Older patients benefit especially from inhaled methoxyflurane. Side effects are mild and vital parameters unaffected. Thus, inhaled methoxyflurane could be a valuable device for non-physician EMS personnel rescue services also in the central Europe region.

Evaluation of the effectiveness and costs of inhaled methoxyflurane versus usual analgesia for prehospital injury and trauma: non-randomised clinical study.

BACKGROUND: We aimed to investigate clinical benefits and economic costs of inhaled methoxyflurane when used by ambulance staff for prehospital emergency patients with trauma. Comparison is to usual analgesic practice (UAP) in the UK in which patient records were selected if treatment had been with Entonox® or intravenous morphine or intravenous paracetamol. METHODS: Over a 12-month evaluation period, verbal numerical pain scores (VNPS) were gathered from adults with moderate to severe trauma pain attended by ambulance staff trained in administering and supplied with methoxyflurane. Control VNPS were obtained from ambulance database records of UAP in similar patients for the same period. Statistical modelling enabled comparisons of methoxyflurane to UAP, where we employed an Ordered Probit panel regression model for pain, linked by observational rules to VNPS. RESULTS: Overall, 96 trained paramedics and technicians from the East Midlands Ambulance Service NHS Trust (EMAS) prepared 510 doses of methoxyflurane for administration to a total of 483 patients. Comparison data extracted from the EMAS database of UAP episodes involved: 753 patients using Entonox®, 802 patients using intravenous morphine, and 278 patients using intravenous paracetamol. Modelling results included demonstration of faster pain relief with inhaled methoxyflurane (all p-values < 0.001). Methoxyflurane's time to achieve maximum pain relief was estimated to be significantly shorter: 26.4 min (95%CI 25.0-27.8) versus Entonox® 44.4 min (95%CI 39.5-49.3); 26.5 min (95%CI 25.0-27.9) versus intravenous morphine 41.8 min (95%CI 38.9-44.7); 26.5 min (95%CI 25.1-28.0) versus intravenous paracetamol 40.8 (95%CI 34.7-46.9). Scenario analyses showed that durations spent in severe pain were significantly less for methoxyflurane. Costing scenarios showed the added benefits of methoxyflurane were achieved at higher cost, eg versus Entonox® the additional cost per treated patient was estimated to be £12.30. CONCLUSION: When administered to adults with moderate or severe pain due to trauma inhaled methoxyflurane reduced pain more rapidly and to a greater extent than Entonox® and parenteral analgesics. Inclusion of inhaled methoxyflurane to the suite of prehospital analgesics provides a clinically useful addition, but one that is costlier per treated patient.

[Volatile anesthetics for prehospital analgesia by paramedics-An overview]. / Volatile Anästhetika zur präklinischen Analgesie durch Rettungssanitäter ­ Eine Übersicht.

Treatment of acute pain is a central task in emergency medicine. Yet, prehospital pain relief is often insufficient or delayed since the administration of potent intravenous analgesic drugs (such as opioids) is mostly limited to physicians due to legal restrictions or training deficiencies in Germany and Austria. Frequently, prehospitally operating emergency physicians have to be demanded later for anguished patients limiting disposability of physicians for patients who are in a potentially life-threatening condition. Thus, inhaled analgesics could represent an interesting alternative.A mixture of 50% nitrous oxide and 50% oxygen (N2O, Livopan®) has been available in Germany and Austria for several years; however, prehospital use of Livopan has been merely realized and only one trial has been published. In addition, methoxyflurane (Penthrop®), a volatile anesthetic from the group of the dialkyl esters (2-dichloro-1:1-difluoroethyl-methyl-ester) was approved for the treatment of moderate to severe pain following trauma in adults in many European countries in recent years and was brought onto the market in Austria in 2018. Several in-hospital trials demonstrated high effectiveness in this setting.This article discusses the effects and prehospital areas of application of both substances in the light of the existing literature. We provide a narrative overview of the current study situation and report on a recently performed prehospital application study of methoxyflurane (Penthrop®) from Austria.The need for pressurized gas cylinders for the use of N2O represents a certain limitation in prehospital use. Furthermore, in certain injuries such as of the inner ear or a pneumothorax N2O should not be used and the risk of diffusion hypoxemia has to be addressed. Users should be particularly careful and limit the use in alcohol addicts and vegans. The advances of N2O are that it is odorless, has a fast onset of action, the usability in patients over 1 month old and has stabilizing effects on the circulation. Plenty of literature regarding prehospital as well as in-hospital use of nitrous oxide in emergency, obstetric and pediatric settings show its effectiveness as a single drug as well as in combination with other analgesics, such as paracetamol or various opioids. Its long tradition in Anglo-American countries is also based on its safety and low rate of side effects.Methoxyflurane is easier to store and handle and may be slightly more effective in severe pain after trauma; however, its approval is restricted to adults, where it works significantly better with increasing age, based on the declining minimal alveolar concentration (MAC) of all inhaled anesthetics with increasing age. Furthermore, decades of use of inhaled methoxyflurane in Australia have shown the drug is effective, safe and low in side effects and has a broad spectrum of applications. The use of methoxyflurane is limited in patients with severe hepatic or renal insufficiency and the characteristic odor has been described as unpleasant by some patients. In Europe, three large in-hospital trials showed strong pain relief in trauma patients, even comparable to opioids.Overall, based on the current evidence, the use of nitrous oxide and even more of methoxyflurane may be recommended also for prehospital use by skilled paramedics.

Determination of equi-analgesic doses of inhaled methoxyflurane versus intravenous fentanyl using the cold pressor test in volunteers: a randomised, double-blinded, placebo-controlled crossover study.

BACKGROUND: Inhaled methoxyflurane for acute pain relief has demonstrated an analgesic effect superior to placebo. Data comparing methoxyflurane to an opioid are needed. The aim of this study was to determine the equi-analgesic doses of inhaled methoxyflurane vs i.v. fentanyl. Both drugs have an onset within minutes and an analgesic effect of 20-30 min. METHODS: Twelve subjects were included in a randomised, double-blinded, placebo-controlled crossover study with four treatments: placebo (NaCl 0.9%), fentanyl 25 µg i.v., fentanyl 50 µg i.v., or inhaled methoxyflurane 3 ml. The subjects reported pain intensity using the verbal numeric rating scale (VNRS) from 0 to 10 during the cold pressor test (CPT). The CPT was performed before (CPT 1), 5 min (CPT 2), and 20 min (CPT 3) after drug administration. RESULTS: Inhaled methoxyflurane and fentanyl 25 µg reduced VNRS scores significantly compared with placebo at CPT 2 (-1.14 [estimated difference in VNRS between treatment groups with 95% confidence interval {CI}: -1.50 to -0.78]; -1.15 [95% CI: -1.51 to -0.79]; both P<0.001) and CPT 3 (-0.60 [95% CI: -0.96 to -0.24]; -0.84 [95% CI: -1.20 to -0.47]; both P<0.001). There were no significant differences between the two drugs. Methoxyflurane had significantly higher VNRS scores than fentanyl 50 µg at CPT 2 (0.90 [95% CI: 0.54-1.26]; P<0.001) and CPT 3 (0.57 [95% CI: 0.21-0.94]; P<0.001). CONCLUSIONS: Inhaled methoxyflurane 3 ml was equi-analgesic to fentanyl 25 µg i.v. at CPT 2. Both resulted in significantly less pain than placebo. Fentanyl 50 µg i.v. demonstrated analgesia superior to methoxyflurane. CLINICAL TRIAL REGISTRATION: NCT03894800.

Frequency and duration of ambulance officer exposure to nitrous oxide and methoxyflurane in New Zealand.

OBJECTIVE: Nitrous oxide (Entonox®) and methoxyflurane (Penthrox®) are inhaled analgesics administered in paramedicine. Occupational exposure to nitrous oxide has been associated with negative health effects, and may inhibit professional capability. The effect of occupational exposure to methoxyflurane has not yet been clearly determined. This study identifies the frequency and duration of ambulance officer (AO) occupational exposure to nitrous oxide and methoxyflurane to provide a foundation for future assessments of occupational toxicity risk. METHODS: A retrospective database review of Patient Report Forms (PRFs) in 11 months between February 2016 and February 2018 was conducted. Nitrous oxide was available for the first 5 months studied, followed by 6 months methoxyflurane availability. AO-specific measures of attendance, rate of inhaled analgesic use, and duration of analgesic use were determined. Subgroup analysis by AO qualification and rostered work hours was undertaken. RESULTS: A total of 46,759 PRFs were examined, identifying 1,033 cases of nitrous oxide administration and 1456 cases of methoxyflurane was administration. There was a significant increase in the proportion of cases where inhaled analgesia was administered following the replacement of nitrous oxide with methoxyflurane. Relative risk of exposure to methoxyflurane compared with nitrous oxide was 1.22, while median duration of each exposure remained unchanged (32 vs. 33 min). CONCLUSIONS: Methoxyflurane via the Penthrox® inhaler was more likely to be administered than nitrous oxide. Most AOs are infrequently exposed to inhaled analgesics and are exposed for durations slightly greater than previously reported. Relative risk of exposure was greatest for lower-qualified AOs. Peak number of exposures and duration values suggest a subset of AOs with higher occupational health risk.

Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments.

STUDY OBJECTIVE: The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe. METHODS: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score ≥4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2×3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief. RESULTS: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. CONCLUSION: These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain.

[Use of methoxyflurane on acute pain during burn dressing in adult consultation]. / Utilisation du méthoxyflurane sur la douleur aiguë lors du pansement en consultation des brûlés adultes.

INTRODUCTION: The objective was to compare the short-term efficacy of methoxyflurane vs. MEOPA on acute pain during burn dressing in consultation, the secondary outcome was to assess the patient's comfort and the quality of the dressing performed. MATERIALS AND METHODS: Monocentric, prospective study from April 2018 to January 2019. Men and women>18 years presenting acute burn on<10% SCT were included. A pain≥4 on the numerical scale (from 0 to 10) at the beginning of the treatment established the indication of methoxyflurane or MEOPA, with randomization done by a nurse. The following data were collected: burn description, performed debridement, pain assessment by numerical scale: on arrival, at the beginning of care, after 6 to 10 inhalations for methoxyflurane or 3 to 4minutes of inhalation for MEOPA and at the end of care. RESULTS: Sixty patients were included, 30 in each group. There was a decrease of -2.47 points of numerical scale when initiating methoxyflurane against -1.53 points for MEOPA (P=0.08). Patients were significantly less painful when stopping treatment in the methoxyflurane group -4 points vs -2 points (P=0.001). Methoxyflurane significantly improved the debridement of the burn (P=0.018). CONCLUSION: Methoxyflurane is more effective than MEOPA in acute pain in burn dressing, improved patient comfort, and improved dressing quality.

[Acute pain management†: the role of inhaled methoxyflurane in clinical practice]. / Traitement de la douleur aiguë†: la place du méthoxyflurane inhalé dans la pratique clinique.

Since 2018, a new analgesic drug has been made available in Switzerland : methoxyflurane. This halogenated gas, controlled by the patient, offers a very effective analgesic effect comparable to opiates. Known since the 1960s and used mainly in pre-hospital emergency medicine in Australia and New Zealand, its use in Europe is increasing alongside standard analgesic treatments in the traumatic setting. Administered by inhalation, it does not require an intravenous access, which is ideal in prehospital emergency situations. This treatment could be used for the management of acute pain of various origins, such as renal lithiasis, or to facilitate different procedures, such as closed fracture reduction or chest tube insertion. Its indications are growing and its use will probably become commonplace with clinicians in a near future.

Depuis 2018, une nouvelle modalité antalgique est disponible en Suisse : le méthoxyflurane. Ce gaz halogéné, contrôlé par le·la patient·e, offre une antalgie très efficace, comparable aux opiacés. Utilisé depuis les années 1960 en médecine préhospitalière dans les régions d'Australie et de Nouvelle-Zélande, il fait ses preuves en Europe où on l'emploie avec les différents antalgiques habituels dans les situations traumatiques d'urgence. Par son administration inhalée, il ne nécessite aucune perfusion. Ce traitement pourrait être utilisé pour la gestion de douleurs aiguës d'origines diverses, telles que la colique néphrétique, ou encore faciliter différentes procédures, comme la réduction fermée de fracture ou la pose de drains. Son indication thérapeutique est croissante et son utilisation deviendra vraisemblablement commune.

BET 1: Green or blue for you? Methoxyflurane (Penthrox) or nitrous oxide/oxygen 50% mixture (Entonox) for the management of acute pain in the ED.

A short-cut review of the literature was carried out to establish whether inhaled methoxyflurane (Penthrox) is comparable or superior with a standard inhalational analgesia for the management of acute pain. Only two papers were identified as suitable for inclusion using the reported search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. It is concluded that both methods of inhaled analgesia appear to be useful options for acute pain in the ED when compared with placebo. No evidence was found to suggest superiority of methoxypenflurane. International studies directly comparing the use of both drugs for in acute trauma are ongoing and will develop the evidence base.

A review of the safety and efficacy of inhaled methoxyflurane as an analgesic for outpatient procedures.

Methoxyflurane delivered via a hand-held inhaler is a proven analgesic which has been used in Australasia for emergency relief of trauma associated pain since the 1970s. The agent is self-administered by the patient under the supervision of trained personnel. More than 5 million patients have received inhaled methoxyflurane without significant side effects. Methoxyflurane is also licensed in Australasia for the relief of pain in monitored conscious patients requiring analgesia for minor surgical procedures. Recent clinical studies undertaken in a variety of outpatient settings, including colonoscopy, prostate biopsy, dental procedures, bone marrow biopsy, and the management of burns dressings, indicate that inhaled methoxyflurane has significant analgesic activity, without producing deep sedation or respiratory depression. Return to full psychomotor activity is rapid. Thus, methoxyflurane may be a suitable and well-tolerated alternative to traditional i.v. sedative agents for outpatient medical and surgical procedures. There are direct advantages to the patient in terms of rapid recovery and an early return to normal activities, and significant benefits for outpatient departments in terms of cost saving and rate of throughput. Further randomised controlled trials comparing the efficacy, safety, and cost-effectiveness of inhaled methoxyflurane against traditional i.v. sedative techniques are currently in progress.