Methoxyflurane analgesia for outpatient hysteroscopy: A double-blind, randomised, controlled trial.

BACKGROUND: Despite clinical and economic benefits, pain during outpatient hysteroscopy (OPH) remains a barrier to use. There is a lack of evidence to support routine use of one analgesic over another versus no analgesic. AIMS: To study the efficacy and safety of methoxyflurane analgesia during OPH. MATERIALS AND METHODS: A single-centre, randomised, double-blind, placebo-controlled experiment was performed; 90 patients were randomly assigned (1:1). Participants allocated to the treatment group (cases) received 3 mL of methoxyflurane through an inhaler. The control group received a placebo. The primary outcome was a mean difference in pain, via a change in Visual Analog Scale (VAS) score from baseline at diagnostic hysteroscopy. Secondary outcomes were a mean difference in VAS score with any subsequent operative procedures; a mean difference in VAS score at 15 min post-procedure; participant and clinician-reported adverse effects and events; and participant-reported procedure acceptability, adjuvant nitrous oxide (N2O2) use and a composite of 'distress'. RESULTS: During diagnostic hysteroscopy, there was a mean difference of 11.5 mm/100 (95% confidence interval (CI) 0.08-22.95), P = 0.05, with the lower score in the cases, compared with controls. During subsequent operative procedures, there was a mean difference of 15 mm/100 (95% CI 2.71-28.22), P = 0.02, with the lower pain score in the cases, compared with controls. There was no significant difference in pain 15 min post-procedure, participant- and clinician- reported adverse effects and events, procedure acceptability and the 'distress' composite. CONCLUSIONS: Methoxyflurane significantly reduced pain during OPH compared with placebo, for diagnostic as well as operative procedures. Furthermore, methoxyflurane was well tolerated, with no adverse events.

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.

Skeletal fluorosis secondary to methoxyflurane use for chronic pain.

Skeletal fluorosis is rare and occurs secondary to chronic high amounts of fluoride consumption, manifesting as diffuse osteosclerosis, skeletal pain, connective tissue calcification, and increased fracture risk. Methoxyflurane is a volatile, fluorinated hydrocarbon-inhaled analgesic, and the maximum recommended dose is 15 mL (99.9 % w/w) per wk. A rodent study found increased skeletal fluoride after methoxyflurane exposure. However, skeletal fluorosis secondary to methoxyflurane use in humans has rarely been reported. We present the case of a 47-yr-old female with diffuse osteosclerosis secondary to fluorosis from methoxyflurane use for chronic pain, presenting with 3 yr of generalized bony pain and multiple fragility fractures. Lumbar spine BMD was elevated. CT and radiographs demonstrated new-onset marked diffuse osteosclerosis, with calcification of interosseous membranes and ligaments, and a bone scan demonstrated a grossly increased uptake throughout the skeleton. Biochemistry revealed an elevated alkaline phosphatase and bone turnover markers, mild secondary hyperparathyroidism with vitamin D deficiency, and mild renal impairment. Zoledronic acid, prescribed for presumed Paget's disease, severely exacerbated bony pain. Urinary fluoride was elevated (7.3 mg/L; reference range < 3.0 mg/L) and the patient revealed using methoxyflurane 9 mL per wk for 8 yr for chronic pain. A decalcified bone biopsy revealed haphazardly arranged cement lines and osteocytes lacunae and canaliculi, which was consistent with an osteosclerotic process. Focal subtle basophilic stippling around osteocyte lacunae was suggestive of fluorosis. Although fluorosis is not a histological diagnosis, the presence of compatible histology features was supportive of the diagnosis in this case with clinical-radiological-pathological correlation. Skeletal fluorosis should be considered as a cause of acquired diffuse osteosclerosis. Methoxyflurane should not be recommended for chronic pain. The risk of repeated low-dose exposure to fluoride from methoxyflurane use as analgesia may be greater than expected, and the maximum recommended dose for methoxyflurane may require re-evaluation to minimize skeletal complications. Abbreviated abstract: Skeletal fluorosis is rare and occurs secondary to chronic high amounts of fluoride consumption, manifesting as diffuse osteosclerosis, skeletal pain, connective tissue calcification, and increased fracture risk. We present the case of a 47-yr-old female with skeletal fluorosis secondary to long-term methoxyflurane for chronic pain. The risk of repeated low-dose exposure to fluoride from methoxyflurane use for analgesia may be greater than expected, and the maximum recommended dose for methoxyflurane may require re-evaluation to minimize skeletal complications.

Time to Reconsider Analgesia in Mass Casualty Incidents.

The provision of analgesia in mass casualty incidents has traditionally been viewed as low-priority and reserved for later stages of care. Poor pain management is commonplace in trauma victims, and inadequate acute pain management can hinder evacuation efforts and may lead to the development of chronic pain and posttraumatic stress disorder. New, safe, and simple methods for administering quality analgesia have proven to be safe and effective in the prehospital setting and, as such, could easily be implemented into mass casualty incident protocols and allow for analgesia at earlier stages in such incidents, thereby improving patient care.

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.

Analgesic agents administered by ambulance personnel to mountain bikers and hikers on trails in Western Australia.

Objective: To describe the types of analgesic medications administered to patients who were attended by ambulance on recreational trails while mountain biking or hiking and report on the reduction in pain by these agents. Methods: This is a retrospective cohort study of patients attended by ambulance (2015-2021) after mountain biking or hiking, on Western Australia (WA) trails. All data were extracted from electronic patient care records created by ambulance personnel who attended the patient. We compared patient and case characteristics between mountain bikers and hikers and the reduction in pain scores achieved by different analgesics. Results: A total of 717 patients were included. Paramedics reported traumatic aetiology for mountain bikers in 92 % of cases and hikers in 58 % of cases. A pain score out of 10 was recorded for 538 (75 %) patients. The median (inter-quartile range) initial pain score was 6 (2-8) and the median final pain score was 3 (1-5). Around 48 % of these 538 patients reported ≥25 % reduction in their pain score. A reduction of ≥25 % in their pain score was greatest in those patients who received intravenous fentanyl (81 %), followed by patients administered multiple analgesics (72 %) and methoxyflurane only (52 %). Even 37 % of 134 patients who received no analgesia still reported ≥25 % reduction in their pain score by hospital arrival. Conclusion: Trauma was the most common reason mountain bikers and hikers on trails called an ambulance and a large proportion of these patients were in pain on ambulance arrival. Further work assessing the effectiveness of safe, non-opioid analgesics, additional to methoxyflurane, is needed to ensure non-registered practitioners such as first aid providers and event medical teams can offer suitable safe analgesics to these patients. Additionally, among patients given no pharmacological analgesic agent, almost half still achieved a >25 % reduction in their pain scores which reiterates the importance of non-pharmacological pain reduction strategies.

Comparison of three regimens with inhalational methoxyflurane versus intranasal fentanyl versus intravenous morphine in pre-hospital acute pain management: study protocol for a randomized controlled trial (PreMeFen).

BACKGROUND: Pre-hospital pain management has traditionally been performed with intravenous (IV) morphine, but oligoanalgesia remain a recognized problem. Pain reduction is essential for patient satisfaction and is regarded as a measure of successful treatment. We aim to establish whether non-invasive methods such as inhalation of methoxyflurane is non-inferior to intranasal fentanyl or non-inferior to the well-known IV morphine in the pre-hospital treatment of acute pain. METHOD/DESIGN: The PreMeFen study is a phase three, three-armed, randomized, controlled, non-inferiority trial to compare three regimens of analgesics: inhalation of methoxyflurane and intranasal (IN) fentanyl versus IV morphine. It is an open-label trial with a 1:1:1 randomization to the three treatment groups. The primary endpoint is the change in pain numeric rating scale (NRS) (0-10) from baseline to 10 min after start of investigational medicinal product administration (IMP). The non-inferiority margin was set to 1.3, and a sample size of 270 patients per protocol (90 in each treatment arm) will detect this difference with 90% power. DISCUSSION: We chose a study design with comparison of analgesic regimens rather than fixed doses because of the substantial differences in drug characteristics and for the results to be relevant to inform policymakers in the pre-hospital setting. We recognize that easier administration of analgesics will lead to better pain management for many patients if the regimens are as good as the existing, and hence, we chose a non-inferiority design. The primary endpoint, the change in pain (NRS) after 10 min, is set to address the immediate need of pain reduction for patients with acute prehospital pain. On a later stage, more analgesic methods are often available. PreMeFen is a non-inferiority randomized controlled trial comparing three analgesic regimens aiming to establish whether inhalation of methoxyflurane or intranasal fentanyl is as good as IV morphine for fast reduction of acute pain in the prehospital setting.

Haemodynamic effects of methoxyflurane versus fentanyl and placebo in hypovolaemia: a randomised, double-blind crossover study in healthy volunteers.

Background: Methoxyflurane is approved for relief of moderate to severe pain in conscious adult trauma patients: it may be self-administrated and is well suited for use in austere environments. Trauma patients may sustain injuries causing occult haemorrhage compromising haemodynamic stability, and it is therefore important to elucidate whether methoxyflurane may adversely affect the haemodynamic response to hypovolaemia. Methods: In this randomised, double-blinded, placebo-controlled, three-period crossover study, inhaled methoxyflurane 3 ml, i.v. fentanyl 25 µg, and placebo were administered to 15 healthy volunteers exposed to experimental hypovolaemia in the lower body negative pressure model. The primary endpoint was the effect of treatment on changes in cardiac output, while secondary endpoints were changes in stroke volume and mean arterial pressure and time to haemodynamic decompensation during lower body negative pressure. Results: There were no statistically significant effects of treatment on the changes in cardiac output, stroke volume, or mean arterial pressure during lower body negative pressure. The time to decompensation was longer for methoxyflurane compared with fentanyl (hazard ratio 1.9; 95% confidence interval 0.4-3.4; P=0.010), whereas there was no significant difference to placebo (hazard ratio -1.3; 95% confidence interval -2.8 to 0.23; P=0.117). Conclusions: The present study does not indicate that methoxyflurane has significant adverse haemodynamic effects in conscious adults experiencing hypovolaemia. Clinical trial registration: ClinicalTrials.gov (NCT04641949) and EudraCT (2019-004144-29) https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004144-29/NO.

Pain Management with Inhalation of Methoxyflurane Administrated by Non-Medical Ski Patrol: A Quality Assessment Study.

INTRODUCTION: Pain management can be challenging, especially in remote locations where first responders are not certified health care personnel. In these settings, traditional intravenous administration of analgesics is not feasible. In this study, we explore the feasibility of using methoxyflurane as a first-line analgesic in ski-related traumas, administered by the ski patrol, acting as the municipality physician's aiding personnel. METHODS: This is a quality assessment of a project aimed at improving pain management in trauma patients at the largest ski resort in Norway. Members of the ski patrol were trained and delegated administration of methoxyflurane on behalf of the municipality physician. Patients > 18 years with ski-related trauma and pain Numeric Rating Scale (NRS) of 6 or more were included. The patients received inhalational methoxyflurane on site, with continued administration during transport. Data were collected by the ski patrol and entered into a quality register. RESULTS: In total, 53 patients (18 to 76 years, 32 (60%) males) accepted to be registered. The injuries were fractures in 35 (66%), joint luxation in seven (13%), combination of fracture and luxation in seven (13%), and blunt soft tissue damage in four (8%) cases. Median NRS before administration of methoxyflurane was 8 decreasing to median NRS 5 after 5-10 min. The median NRS reduction of 3 (25-75% percentiles 2-5) was significant, p < 0.001. Patients rated the perceived effect as good in 40 (80%) moderate in nine (18%) and no effect in 1 (2%). Side effects were mild: Six patients (11%) experienced dizziness, one patient (2%) was considered drowsy. CONCLUSIONS: Methoxyflurane is feasible as a first-line analgesic administered by a non-medical ski patrol in a responsibly organized system. Early pain management with inhalation of methoxyflurane provides good perceived effect with mild adverse events and can be of great value in settings where few alternatives for pain management are available.

Pain Self-Management with Inhaled Methoxyflurane by Emergency Department Trauma Patients: A Prospective, Interventional, Single-Center Study.

The coronavirus disease 2019 (COVID-19) pandemic has led to overcrowding in many emergency departments (EDs). The present single-center, prospective, interventional study (conducted at Bichat University Medical Center (Paris, France)) was designed to assess the impact of self-administered, inhaled, low-dose methoxyflurane on trauma pain in a pre-ED fast-track zone dedicated to the management of lower-acuity non-COVID-19 patients. In the first phase of the study, the control group consisted of patients with mild-to-moderate trauma pain, for whom the triage nurse initiated pain management (based on the World Health Organization (WHO)'s analgesic ladder). In the second phase, the intervention group consisted of similar patients who self-administered methoxyflurane as an adjuvant to the standard analgesic ladder. The primary endpoint was the numerical pain rating scale (NPRS) score (from 0 to 10) recorded at different time points during the patient's care (T0: arrival in the ED, T1: exit from the triage box, T2: in the radiology department, T3: clinical examination, and T4: discharge from the ED). The level of agreement between the NPRS and the WHO analgesic ladder was assessed by the calculation of Cohen's kappa. Pairwise comparisons of continuous variables were performed with Student's t-test or a non-parametric Mann-Whitney U test. Changes over time in the NPRS were analyzed in an analysis of variance (with Scheffe's post hoc test if a pairwise comparison was significant) or a non-parametric Kruskal-Wallis H test. In all, 268 and 252 patients were included in the control and intervention groups, respectively. The two groups had similar characteristics. The level of agreement between the NPRS score and the analgesic ladder was high in both the control and intervention groups (Cohen's kappa: 0.74 and 0.70, respectively). The NPRS score decreased significantly between T0 and T4 in both groups (p < 0.001), but the decrease between T2 and T4 was significantly greater in the intervention group (p < 0.001). The proportion of patients still in pain on discharge was significantly lower in the intervention group than in the control group (p = 0.001). In conclusion, a combination of self-administered methoxyflurane and the WHO analgesic ladder improves pain management in the ED.

Clinical assessment and risk stratification for prehospital use of methoxyflurane versus standard analgesia in adult patients with trauma pain.

Oligoanalgesia, the undertreatment of trauma-related pain using standard analgesics in prehospital and emergency departments, has been extensively documented as one of the major challenges affecting the effective treatment of trauma-related pain. When administered in low doses, methoxyflurane has been highlighted by numerous medical works of literature to provide an effective, nonopioid, nonnarcotic treatment alternative to standard analgesics for prehospital and emergency department use. Low-dose methoxyflurane has been associated with fast-pain relief in adult patients manifesting moderate-to-severe pain symptoms. This systematic review and meta-analysis aimed to assess the clinical implication of low-dose methoxyflurane use in prehospital and emergency departments in adult patients with moderate-to-severe trauma-related pain. Moreover, the review aimed at assessing the risk stratification associated with using low-dose methoxyflurane in prehospital and emergency departments. The systematic review and meta-analysis performed a comprehensive search for pertinent literature assessing the implications and risks of using low-dose methoxyflurane in adult patients exhibiting moderate-to-severe trauma-related pain in prehospital settings. A comparison between the use of low-dose methoxyflurane and standard-of-care analgesics, placebo, in prehospital settings was reported in four clinically conducted randomized controlled trials (RCTs). These RCTs included the STOP! trial, InMEDIATE, MEDIATA, and the PenASAP trials. A meta-analysis comparing the time taken to achieve first pain relief on initial treatment of patients with moderate-to-severe trauma-related pain favored the use of low-dose methoxyflurane to the standard-of-care analgesics (mean difference = -6.63, 95% confidence interval = -7.37, -5.09) on time taken to establish effective pain relief. Low-dose methoxyflurane has been associated with superior and faster pain relief in prehospital and emergency departments in adult patients exhibiting moderate-to-severe trauma-related pain compared to other standard analgesics.

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.

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.

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.

El resurgimiento del metoxiflurano en México / The resurgence of methoxyflurane in Mexico

Resumen: El metoxiflurano es un anestésico halogenado que se utilizó hace varias décadas para anestesia general balanceada y que actualmente está indicado para otorgar sedación controlada por el paciente. Este medicamento se encuentra actualmente a la venta en la República Mexicana, por lo que recordar las características que lo hacen diferente a otros halogenados, su farmacocinética y su utilidad para distintos escenarios proporciona el conocimiento adecuado para su uso en la práctica clínica.

Abstract: Methoxyflurane is a halogenated anesthetic that was used decades ago for a balanced general anesthesia and is currently indicated for patient-controlled sedation. This drug is currently on sale in the Mexican Republic, so remembering the characteristics that make it different from other halogenated drugs, its pharmacokinetics and its usefulness for different scenarios provides knowledge for use in clinical practice.

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.

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.

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.

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.

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.