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Environmental Health Perspectives Jun 1976Investigations of methoxyflurane-induced nephrotoxicity in man have been extensively aided by the use of an animal model. To be of value the animal model must share...
Investigations of methoxyflurane-induced nephrotoxicity in man have been extensively aided by the use of an animal model. To be of value the animal model must share similar metabolic pathways with man and have the same clinical manifestations of the diseases process. The Fischer 344 rat appears to meet these criteria. The predominant factors in the production of methoxyflurane nephrotoxicity appear to be high methoxyflurane dosage and serum inorganic fluoride concentration. It is likely that secondary factors include: (1) a high rate of methoxyflurane metabolism and sepsitivity of the kidney to inorganic fluoride toxicity: (2) concurrent treatment with other nephrotoxic drugs; (3) preexisting renal disease; (4) surgery of the urogenital tract, aorta, or renal vasculative; (5) repeat administration of methoxyflurane due to accumulation of inorganic fluoride and, perhaps, methoxyflurane induction of its own metabolism: and (6) concurrent treatment with enzyme-inducing drugs such as phenobarbital.
Topics: Age Factors; Animals; Child; Dose-Response Relationship, Drug; Fluorides; Gentamicins; Humans; Kidney Diseases; Kidney Tubules; Methoxyflurane; Oxalates; Rats
PubMed: 1001288
DOI: 10.1289/ehp.7615111 -
The Lancet. Planetary Health Jul 2023There is increasing concern within the health-care community about the role care delivery plays in environmental degradation, sparking research into how to reduce... (Review)
Review
There is increasing concern within the health-care community about the role care delivery plays in environmental degradation, sparking research into how to reduce pollution from clinical practice. Inhaled anaesthetics is a particular research area of interest for two reasons. First, several gases are potent greenhouse gases, and waste gas is mostly emitted directly to the environment. Second, there are options to reduce gas waste and substitute medications and procedures with fewer embodied emissions while delivering high-quality care. Performance improvements are contingent on a proper understanding of the emission estimates and climate metrics used to ensure consistent application in guiding mitigation strategies and accounting at various scales. We review the current literature on the environmental impact and the estimation of the potential climate forcing of common inhaled anaesthetic drugs: desflurane, sevoflurane, isoflurane, methoxyflurane, and nitrous oxide.
Topics: Anesthetics, Inhalation; Climate; Methoxyflurane; Isoflurane; Sevoflurane; Gases
PubMed: 37438003
DOI: 10.1016/S2542-5196(23)00084-0 -
Scandinavian Journal of Trauma,... Dec 2021Clinically meaningful pain reduction with respect to severity and the adverse events of drugs used in prehospital pain management for children are areas that have not... (Review)
Review
BACKGROUND
Clinically meaningful pain reduction with respect to severity and the adverse events of drugs used in prehospital pain management for children are areas that have not received sufficient attention. The present systematic review therefore aims to perform a comprehensive search of databases to examine the preferable drugs for prehospital pain relief in paediatric patients with acute pain, irrespective of aetiology.
METHODS
The systematic review includes studies from 2000 and up to 2020 that focus on children's prehospital pain management. The study protocol is registered in PROSPERO with registration no. CRD42019126699. Pharmacological pain management using any type of analgesic drug and in all routes of administration was included. The main outcomes were (1) measurable pain reduction (effectiveness) and (2) no occurrence of any serious adverse events. Searches were conducted in PubMed, Medline, Embase, CINAHL, Epistemonikos and Cochrane library. Finally, the risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist and a textual narrative analysis was performed due to the heterogeneity of the results.
RESULTS
The present systematic review on the effectiveness and safety of analgesic drugs in prehospital pain relief in children identified a total of eight articles. Most of the articles reviewed identified analgesic drugs such as fentanyl (intranasal/IV), morphine (IV), methoxyflurane (inhalational) and ketamine (IV/IM). The effects of fentanyl, morphine and methoxyflurane were examined and all of the included analgesic drugs were evaluated as effective. Adverse events of fentanyl, methoxyflurane and ketamine were also reported, although none of these were considered serious.
CONCLUSION
The systematic review revealed that fentanyl, morphine, methoxyflurane and combination drugs are effective analgesic drugs for children in prehospital settings. No serious adverse events were reported following the administration of fentanyl, methoxyflurane and ketamine. Intranasal fentanyl and inhalational methoxyflurane seem to be the preferred drugs for children in pre-hospital settings due to their ease of administration, similar effect and safety profile when compared to other analgesic drugs. However, the level of evidence (LOE) in the included studies was only three or four, and further studies are therefore necessary.
Topics: Acute Pain; Analgesics; Analgesics, Opioid; Child; Emergency Medical Services; Fentanyl; Humans
PubMed: 34895311
DOI: 10.1186/s13049-021-00974-3 -
British Journal of Anaesthesia Sep 1965
Review
Topics: Anesthesia, Inhalation; Humans; Methoxyflurane
PubMed: 5320092
DOI: 10.1093/bja/37.9.706 -
Open Access Emergency Medicine : OAEM 2018Methoxyflurane is an inhaled analgesic administered via a disposable inhaler which has been used in Australia for over 40 years for the management of pain associated... (Review)
Review
Methoxyflurane is an inhaled analgesic administered via a disposable inhaler which has been used in Australia for over 40 years for the management of pain associated with trauma and for medical procedures in children and adults. Now available in 16 countries worldwide, it is licensed in Europe for moderate to severe pain associated with trauma in conscious adults, although additional applications are being made to widen the range of approved indications. Considering these ongoing developments, we reviewed the available evidence on clinical usage and safety of inhaled analgesic methoxyflurane in trauma pain and in medical procedures in both adults and children. Published data on methoxyflurane in trauma and procedural pain show it to be effective, well tolerated, and highly rated by patients, providing rapid onset of analgesia. Methoxyflurane has a well-established safety profile; adverse events are usually brief and self-limiting, and no clinically significant effects on vital signs or consciousness levels have been reported. Nephrotoxicity previously associated with methoxyflurane at high anesthetic doses is not reported with low analgesic doses. Although two large retrospective comparative studies in the prehospital setting showed inhaled analgesic methoxyflurane to be less effective than intravenous morphine and intranasal fentanyl, this should be balanced against the administration, supervision times, and safety profile of these agents. Given the limitations of currently available analgesic agents in the prehospital and emergency department settings, the ease of use and portability of methoxyflurane combined with its rapid onset of effective pain relief and favorable safety profile make it a useful nonopioid option for pain management. Except for the STOP! study, which formed the basis for approval in trauma pain in Europe, and a few smaller randomized controlled trials (RCTs), much of the available data are observational or retrospective, and further RCTs are currently underway to provide more robust data.
PubMed: 30410414
DOI: 10.2147/OAEM.S181222 -
British Journal of Anaesthesia May 2018Methoxyflurane 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.... (Review)
Review
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.
Topics: Ambulatory Care; Analgesia; Anesthetics, Inhalation; Female; Humans; Male; Methoxyflurane; Outpatients; Treatment Outcome
PubMed: 29661381
DOI: 10.1016/j.bja.2018.01.011 -
Pain and Therapy Jun 2021Evidence on the use of inhaled methoxyflurane in the management of trauma pain is conflicting and obfuscated. This study aimed to determine the efficacy and safety of...
INTRODUCTION
Evidence on the use of inhaled methoxyflurane in the management of trauma pain is conflicting and obfuscated. This study aimed to determine the efficacy and safety of inhaled methoxyflurane for trauma pain on the basis of published randomized controlled trials (RCTs).
METHODS
RCTs assessing the efficacy of methoxyflurane in adults or adolescents with acute trauma pain published in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar were searched. The control groups were those that received placebo or standard analgesic treatment (SAT). The primary outcome was the change from baseline in pain scores during the first 30 min of treatment. Secondary outcomes included time to first pain relief, the proportion of patients experiencing pain relief, rescue analgesia rate, the treatment satisfaction of patients and investigators, and the methoxyflurane-related treatment-emergent adverse events (TEAEs).
RESULTS
A total of nine RCTs (1806 patients) were identified. Results revealed that methoxyflurane provided a clinically unimportant benefit by improving the mean difference of change from baseline in pain intensity (from - 0.44 to - 1.23 cm, p < 0.001) at various time points within the first 20 min compared to control treatment. Besides, methoxyflurane decreased the time of onset of pain relief (mean difference - 5.29 min; 95% CI - 6.97 to - 3.62) and the proportion of patients who needed rescue analgesic medication (risk ratio 1.41; 95% CI 1.17-1.70) despite it increasing the risk of non-severe TEAEs (risk ratio 3.09; 95% CI 1.72-5.57). Notably, the benefit of almost all secondary pain-related outcomes was rendered clinically nonsignificant between methoxyflurane and SAT strata besides the time of onset of pain relief. The quality of evidence was low or very low in all outcomes.
CONCLUSIONS
In emergency situations without effective therapy, this systematic review and meta-analysis provides low-quality evidence that methoxyflurane can be used as a rapid-acting and effective treatment for acute trauma pain, although its utilization is associated a risk of non-severe TEAEs. However, the current evidence does not support the notion that inhaled methoxyflurane offered superior analgesic efficacy to SAT.
CLINICAL TRIAL NUMBER
PROSPERO registration number CRD42020223000.
PubMed: 33837931
DOI: 10.1007/s40122-021-00258-9 -
Asia-Pacific Journal of Ophthalmology...This study will provide a thorough review of systemic (and select intravitreal) medications, along with illicit drugs that are capable of causing various patterns of...
This study will provide a thorough review of systemic (and select intravitreal) medications, along with illicit drugs that are capable of causing various patterns of retinal toxicity. The diagnosis is established by taking a thorough medication and drug history, and then by pattern recognition of the clinical retinal changes and multimodal imaging features. Examples of all of these types of toxicity will be thoroughly reviewed, including agents that cause retinal pigment epithelial disruption (hydroxychloroquine, thioridazine, pentosan polysulfate sodium, dideoxyinosine), retinal vascular occlusion (quinine, oral contraceptives), cystoid macular edema/retinal edema (nicotinic acid, sulfa-containing medications, taxels, glitazones), crystalline deposition (tamoxifen, canthaxanthin, methoxyflurane), uveitis, miscellaneous, and subjective visual symptoms (digoxin, sildenafil). The impact of newer chemotherapeutics and immunotherapeutics (tyrosine kinase inhibitor, mitogen-activated protein kinase kinase, checkpoint, anaplastic lymphoma kinase, extracellular signal-regulated kinase inhibitors, and others), will also be thoroughly reviewed. The mechanism of action will be explored in detail when known. When applicable, preventive measures will be discussed, and treatment will be reviewed. Illicit drugs (cannabinoids, cocaine, heroin, methamphetamine, alkyl nitrite), will also be reviewed in terms of the potential impact on retinal function.
Topics: Humans; Retina; Retinal Diseases; Macular Edema; Uveitis; Illicit Drugs; Retinal Vein Occlusion; Intravitreal Injections; Tomography, Optical Coherence
PubMed: 36971705
DOI: 10.1097/APO.0000000000000605 -
Singapore Medical Journal Jun 2021Treatment of pain is an important component of prehospital care. Inhalational analgesia agents have attractive strengths, but there is a paucity of studies comparing... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Acute Pain; Ambulances; Analgesia; Anesthetics, Inhalation; Humans; Methoxyflurane; Pain Measurement; Tramadol
PubMed: 32179922
DOI: 10.11622/smedj.2020035 -
BMC Emergency Medicine Jul 2022We aimed to investigate clinical benefits and economic costs of inhaled methoxyflurane when used by ambulance staff for prehospital emergency patients with trauma.... (Clinical Trial)
Clinical Trial
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.
Topics: Acetaminophen; Administration, Inhalation; Adult; Ambulances; Analgesia; Analgesics; Anesthetics, Inhalation; Humans; Methoxyflurane; Morphine; Pain; Pain Measurement
PubMed: 35799131
DOI: 10.1186/s12873-022-00664-y