A controlled comparison between single doses of intravenous and intramuscular morphine with respect to analgesic effects and patient safety

Tveita, T.; Thoner, J; Klepstad, Pål; Dale, Ola; Jystad, Åse; Borchgrevink, Petter C.

doi:10.1111/j.1399-6576.2008.01608.x

Cited by 45 publications

(24 citation statements)

References 18 publications

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“…This is consistent with the rapid onset of pain relief reported by Johnston et al in their study of pre-hospital analgesia for visceral pain, which found a mean reduction in visual/verbal analog scale pain score (0–10 scale) with methoxyflurane of 2.0 (95% CI: 1.7, 2.2) after 5 min and 2.5 (95% CI: 2.1–2.9) on arrival at hospital, compared with 1.6 (95% CI: 1.4, 1.8) and 3.2 (95% CI: 2.9, 3.5), respectively, for intranasal fentanyl [19]. The onset of pain relief with methoxyflurane is also similar to that reported by Tveita et al for a 10 mg bolus dose of IV morphine [32]. Although methoxyflurane is currently only licensed for emergency relief of pain due to trauma in Europe, several studies in Australia and New Zealand have also demonstrated its effectiveness as a procedural analgesic [21, 33–36].…”

Section: Discussionsupporting

confidence: 71%

Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!)

et al. 2016

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IntroductionAcute pain remains highly prevalent in the Emergency Department (ED) setting. This double-blind, randomized, placebo-controlled UK study investigated the efficacy and safety of low-dose methoxyflurane analgesia for the treatment of acute pain in the ED in the adult population of the STOP! trial.MethodsPatients presenting to the ED requiring analgesia for acute pain (pain score of 4–7 on the Numerical Rating Scale) due to minor trauma were randomized in a 1:1 ratio to receive methoxyflurane (up to 6 mL) or placebo (normal saline), both via a Penthrox® (Medical Developments International Limited, Scoresby, Australia) inhaler. Rescue medication (paracetamol/opioids) was available immediately upon request. Change from baseline in visual analog scale (VAS) pain intensity was the primary endpoint.Results300 adult and adolescent patients were randomized; data are presented for the adult subgroup (N = 204). Mean baseline VAS pain score was ~66 mm in both groups. The mean change from baseline to 5, 10, 15 and 20 min was greater for methoxyflurane (−20.7, −27.4, −33.3 and −34.8 mm, respectively) than placebo (−8.0, −11.1, −12.3 and −15.2 mm, respectively). The primary analysis showed a highly significant treatment effect overall across all four time points (−17.4 mm; 95% confidence interval: −22.3 to −12.5 mm; p < 0.0001). Median time to first pain relief was 5 min with methoxyflurane [versus 20 min with placebo; (hazard ratio: 2.32; 95% CI: 1.63, 3.30; p < 0.0001)]; 79.4% of methoxyflurane-treated patients experienced pain relief within 1–10 inhalations. 22.8% of placebo-treated patients requested rescue medication within 20 min compared with 2.0% of methoxyflurane-treated patients (p = 0.0003). Methoxyflurane treatment was rated ‘Excellent’, ‘Very Good’ or ‘Good’ by 77.6% of patients, 74.5% of physicians and 72.5% of nurses. Treatment-related adverse events (mostly dizziness/headache) were reported by 42.2% of patients receiving methoxyflurane and 14.9% of patients receiving placebo; none caused withdrawal and the majority were mild and transient.ConclusionThe results of this study support the evidence from previous trials that low-dose methoxyflurane administered via the Penthrox inhaler is a well-tolerated, efficacious and rapid-acting analgesic.FundingMedical Developments International (MDI) Limited and Mundipharma Research GmbH & Co.KG.Trial registrationClinicaltrials.gov identifier: NCT01420159, EudraCT number: 2011-000338-12.

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Section: Discussionsupporting

confidence: 71%

Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!)

et al. 2016

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“…In addition, the median time to first pain relief for the methoxyflurane group was 4 min. This compares favourably with a median time to onset of meaningful pain relief of 11 min with intranasal fentanyl (IF),19 16 min with oromucosal fentanyl,19 and 5 min with intravenous morphine sulfate 20. There was a higher occurrence of AEs in methoxyflurane-treated patients than in those treated with placebo; however, in general, methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action.…”

Section: Discussionmentioning

confidence: 94%

STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain

et al. 2014

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ObjectiveTo evaluate the short-term efficacy and safety of methoxyflurane for the treatment of acute pain in patients presenting to an emergency department (ED) with minor trauma.MethodsSTOP! was a randomised, double-blind, multicentre, placebo-controlled study conducted at six sites in the UK. A total of 300 patients, 90 of whom were adolescent patients (age 12–17 years), were randomised 150:150 to receive either methoxyflurane via a Penthrox inhaler or placebo. The primary end point of the study was the change in pain intensity as measured using the visual analogue scale (VAS) from baseline to 5, 10, 15 and 20 min after the start of study drug inhalation. Patients were supplied with one inhaler containing 3 mL methoxyflurane or 5 mL placebo after enrolment and initial assessments. Age group (adolescent/adult) and baseline VAS score were controlled for in the statistical analyses.ResultsA total of 149 patients received methoxyflurane, and 149 patients received placebo. Demographic and baseline characteristics were comparable between the groups. Methoxyflurane reduced pain severity significantly more than placebo (p<0.0001) at all time points tested, with the greatest estimated treatment effect of −18.5 mm (adjusted change from baseline) seen at 15 min after the start of treatment. Methoxyflurane was well tolerated, with the majority of adverse reactions being mild, transient and in line with anticipated pharmacological action.ConclusionThe results of this study suggest that methoxyflurane administered via the Penthrox inhaler is an efficacious, safe, and rapidly acting analgesic.Trial registration number:NCT01420159.

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“…Emphasis was placed on intravenous and intranasal methods of administration given their shorter onset of action as opposed to intramuscular and oral analgesia. 28 Pain reduction and the prevalence of serious adverse events (SAEs), including hypotension, hypoventilation, allergy, hypoxia, and/or altered level of consciousness, were considered important outcomes. The panel considered minor adverse events (AEs), such as nausea, dizziness, bad taste, and pruritus, as outcomes of lesser importance.…”

Section: What Is the Basis Of Suggesting Morphine And Fentanyl For Pamentioning

confidence: 99%

“…28,[31][32][33]35 There were few direct comparisons made between IV morphine and IV fentanyl, although a number of studies compared IN fentanyl with IM or IV morphine. [29][30][31][32]36 Intravenous administration was the most commonly researched route for fentanyl, but in a few observational studies, intranasal delivery appeared to be safe, effective, and less painful than intravenous cannulation.…”

Section: Routesmentioning

confidence: 99%

An Evidence-based Guideline for Prehospital Analgesia in Trauma

Gausche‐Hill¹,

Brown²,

Oliver³

et al. 2013

Prehospital Emergency Care

119

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Background. The management of acute traumatic pain is a crucial component of prehospital care and yet the assessment and administration of analgesia is highly variable, frequently suboptimal, and often determined by consensus-based regional protocols. Objective. To develop an evidence-based guideline (EBG) for the clinical management of acute traumatic pain in adults and children by advanced life support (ALS) providers in the prehospital setting. Methods. We recruited a multi-stakeholder panel with expertise in acute pain management, guideline development, health informatics, and emergency medical services (EMS) outcomes research. Representatives of the National Highway Traffic Safety Administration (sponsoring agency) and a major children's research center (investigative team) also contributed to the process. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to guide the process of question formulation, evidence retrieval, appraisal/synthesis, and formulation of recommendations. The process also adhered to the National Prehospital Evidence-Based Guideline (EBG) model process approved by the Federal Interagency Council for EMS and the National EMS Advisory Council. Results. Four strong

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A controlled comparison between single doses of intravenous and intramuscular morphine with respect to analgesic effects and patient safety

Cited by 45 publications

References 18 publications

Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!)

Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!)

STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain

An Evidence-based Guideline for Prehospital Analgesia in Trauma

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