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.

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.

Methoxyflurane Versus Standard of Care for Acute Trauma-Related Pain in the Emergency Setting: Protocol for a Randomised, Controlled Study in Italy (MEDITA).

INTRODUCTION: Low-dose methoxyflurane, administered via a hand-held inhaler, has been used for short-term pain relief in emergency medicine in Australia and New Zealand for over 40 years, and was recently approved in Europe for the rapid relief of moderate-to-severe trauma-related pain in adults. There is currently a lack of data for methoxyflurane versus active comparators, therefore this trial will investigate the efficacy and safety of inhaled methoxyflurane compared with standard of care (SoC) in the treatment of acute trauma-related pain in pre-hospital and ED settings in Italy. METHODS: MEDITA (Methoxyflurane in Emergency Department in ITAly) is a Phase IIIb, prospective, randomised, active-controlled, parallel-group, open-label, multicentre trial. A total of 272 adult patients with moderate-to-severe pain [score ≥ 4 on the Numerical Rating Scale (NRS)] due to limb trauma will be randomised 1:1 to receive 3 mL methoxyflurane (self-administered by the patient via inhalation under supervision of a trained person) or medications that currently comprise the SoC in Italy [intravenous (IV) morphine for severe pain (NRS ≥ 7); IV paracetamol or ketoprofen for moderate pain (NRS 4-6)], administered as soon as possible after randomisation. PLANNED OUTCOMES: Pain intensity will be measured using a 100-mm visual analogue scale (VAS) at baseline (time of randomisation) and at intervals up to 30 min. Time of onset of pain relief as reported by the patient and use of rescue medication will be recorded. The patient will rate the efficacy and the healthcare professional will rate the practicality of study treatment at 30 min after randomisation using a 5-point Likert scale. Adverse events will be recorded until safety follow-up at 14 ± 2 days. Vital signs will be measured at baseline, 10 and 30 min. The primary aim is to demonstrate non-inferiority of methoxyflurane versus SoC for the change in VAS pain intensity from baseline (randomisation) to 3, 5 and 10 min. TRIAL REGISTRATION: EudraCT number: 2017-001565-25. Clinicaltrials.gov identifier: NCT03585374. FUNDING: Mundipharma Pharmaceuticals srl.

A randomised, double-blind, placebo-controlled study to assess the safety and efficacy of methoxyflurane for procedural pain of a bone marrow biopsy.

CONTEXT: Pain during bone marrow biopsy (BMB) under local anaesthesia (LA) is reported in 70% of patients, of whom 35% rate the pain as severe. Pain is experienced during both the biopsy and the marrow aspiration. Many medical centres use conscious sedation involving benzodiazepines and/or opioids administered orally or intravenously for BMB analgesia. Methoxyflurane (MEOF) is self-administered by a handheld device (the Penthrox inhaler), which is licensed in Australia for the relief of pain associated with short surgical procedures. OBJECTIVES: To evaluate the efficacy and safety of MEOF analgesia in patients with cancer undergoing BMB. METHODS: Patients received LA plus either MEOF or placebo. The primary endpoint was worst pain intensity measured with the Numerical Rating Scale. Anxiety was assessed with the State Trait Anxiety Inventory (STAI-Y-1). Patients, operators and the research nurse rated global medication performance using a 5-point Likert scale. RESULTS: Forty-nine of the 50 patients randomised to MEOF and 48 of the 50 patients randomised to placebo effectively received the allocated intervention. Mean±SD worst pain overall was 4.90±2.07 in MEOF group and 6.0±2.24 in placebo group (p=0.011). Worst pain during the aspiration was 3.3±2.0 in MEOF group and 5.0±2.4 in placebo group (p<0.001). 49% of patients treated with MEOF rated the medication as very good or excellent compared with 16.5% of the patients treated with placebo (p=0.005). 20.4% of patients treated with MEOF had an adverse event (AE) compared with 4.2% in the placebo arm (p=0.028). All AEs were grade 1. CONCLUSIONS: MEOF was safe and performed better than placebo for analgesia in BMB procedures.

Energy metabolism in anesthetized children with burns.

Energy dynamics in 10 burned children were studied to determine cause and effect relationships between rates of heat production, heat loss and plasma catecholamine concentrations when thermoregulatory responses were depressed by methoxyflurane anesthesia. Rapid cooling of the burned children was due to increased heat loss during the period of anesthesia. Heat production increased significantly, although not enough to counterbalance the increased heat loss reflecting a block in central thermoregulation by general anesthesia. Mean plasma catecholamine concentrations decreased during general anesthesia as compared with baseline values. Heat production attempted to track heat loss during a period in which plasma catecholamine levels declined. An increased rate of heat loss is concluded to be primary stimulus for increased metabolic acitvity after thermal injury.