Efficacy of Ultrasound-Guided Serratus Anterior Plane Block for Postoperative Analgesia in Patients Undergoing Breast Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Objective. Serratus anterior plane block (SAPB) provides effective thoracic analgesia. This systematic review and meta-analysis was conducted to assess the safety and efficacy of SAPB for postoperative analgesia after breast surgery. Methods. A systematic literature search was performed using Embase, PubMed, Web of Science, and the Cochrane Library for eligible randomised controlled trials. The primary outcomes involved the administration of intraoperative and postoperative opioids. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence for making recommendations. Results. Overall, 13 studies comprising 826 patients met the inclusion criteria (412 in the SAPB group and 414 in the control group). Patients treated with SAPB exhibited a significantly lower postoperative opioid consumption (mean difference, −38.51 mg of oral morphine equivalent; 95% confidence interval (CI), −60.97 to −16.05; P < 0.01 ; I2 = 100%), whereas no difference was observed in the intraoperative opioid consumption (mean difference, −9.85 mg of oral morphine equivalent; 95% CI, −19.52 to −0.18; P = 0.05 ; I2 = 94%). In addition, SAPB significantly decreased the occurrence of postoperative nausea and vomiting (risk ratio, 0.32; 95% CI, 0.19–0.55; P < 0.05 ;I2 = 38%) and reduced pain scores during the postoperative period (1 h: standardised mean difference (SMD), −1.23; 95% CI, −2.00 to −0.45; I2 = 92%; 2 h: SMD, −0.71; 95% CI, −1.00 to −0.41; I2 = 48%; 4 h: SMD, −1.52; 95% CI, −2.77 to −0.27; I2 = 95%; 6 h: SMD, −0.80; 95% CI, −1.51 to −0.08; I2 = 81%; 8 h: SMD, −1.12; 95% CI, −1.98 to −0.27; I2 = 92%; 12 h: SMD, −0.78; 95% CI, −1.21 to −0.35; I2 = 83%; and 24 h: SMD, −0.71; 95% CI, −1.20 to −0.23; I2 = 87%; P < 0.05 for all). Conclusion. SAPB was safe and effective after breast surgery to relieve postsurgical pain. However, additional well-developed trials are required to validate these findings.

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Protective Treatments against Endothelial Glycocalyx Degradation in Surgery: A Systematic Review and Meta-Analysis

Applied Sciences ◽

10.3390/app11156994 ◽

2021 ◽

Vol 11 (15) ◽

pp. 6994

Author(s):

Hasnain Q. R. B. Khan ◽

Gwendolen C. Reilly

Keyword(s):

Systematic Review ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Mean Difference ◽

The Body ◽

Endothelial Glycocalyx ◽

Controlled Trials ◽

Post Operation ◽

Mean Differences ◽

Randomised Controlled

The aim was to explore the body of literature focusing on protective treatments against endothelial glycocalyx degradation in surgery. A comprehensive systematic review of relevant articles was conducted across databases. Inclusion criteria: (1) treatments for the protection of the endothelial glycocalyx in surgery; (2) syndecan-1 used as a biomarker for endothelial glycocalyx degradation. Outcomes analysed: (1) mean difference of syndecan-1 (2) correlation between glycocalyx degradation and inflammation; (3) correlation between glycocalyx degradation and extravasation. A meta-analysis was used to present mean differences and 95% confidence intervals. Seven articles with eight randomised controlled trials were included. The greatest change from baseline values in syndecan-1 concentrations was generally from the first timepoint measured post-operatively. Interventions looked to either dampen the inflammatory response or fluid therapy. Methylprednisolone had the highest mean difference in plasma syndecan-1 concentrations. Ulinastatin showed correlations between alleviation of degradation and preserving vascular permeability. In this systematic review of 385 patients, those treated were more likely than those treated with placebo to exhibit less shedding of the endothelial glycocalyx. Methylprednisolone has been shown to specifically target the transient increase of glycocalyx degradation immediately post-operation and has displayed anti-inflammatory effects. We have proposed suggestions for improved uniformity and enhanced confidence for future randomised controlled trials.

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The Effects of Modified Simiao Decoction in the Treatment of Gouty Arthritis: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/6037037 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Ya-Fei Liu ◽

Ying Huang ◽

Cai-Yu-Zhu Wen ◽

Jun-Jun Zhang ◽

Guo-Lan Xing ◽

...

Keyword(s):

Systematic Review ◽

Uric Acid ◽

Adverse Effects ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Gouty Arthritis ◽

Mean Difference ◽

Controlled Trials ◽

Randomised Controlled ◽

Anti Inflammation

The modified Simiao decoctions (MSD) have been wildly applied in the treatment of gouty arthritis in China. However, the evidence needs to be evaluated by a systematic review and meta-analysis. After filtering, twenty-four randomised, controlled trials (RCTs) comparing the effects of MSD and anti-inflammation medications and/or urate-lowering therapies in patients with gouty arthritis were included. In comparison with anti-inflammation medications, urate-lowering therapies, or coadministration of anti-inflammation medications and urate-lowering therapies, MSD monotherapy significantly lowered serum uric acid (p<0.00001, mean difference = −90.62, and 95% CI [−128.38, −52.86];p<0.00001, mean difference = −91.43, and 95% CI [−122.38, −60.49];p=0.02, mean difference = −40.30, and 95% CI [−74.24, −6.36], resp.). Compared with anti-inflammation medications and/or urate-lowering therapies, MSD monotherapy significantly decreased ESR (p<0.00001; mean difference = −8.11; 95% CI [−12.53, −3.69]) and CRP (p=0.03; mean difference = −3.21; 95% CI [−6.07, −0.36]). Additionally, the adverse effects (AEs) of MSD were fewer (p<0.00001; OR = 0.08; 95% CI [0.05, 0.16]). MSD are effective in the treatment of gouty arthritis through anti-inflammation and lowering urate. However, the efficacy of MSD should be estimated with more RCTs.

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Oral Bicarbonate Therapy in Non-Haemodialysis Dependent Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Journal of Clinical Medicine ◽

10.3390/jcm8020208 ◽

2019 ◽

Vol 8 (2) ◽

pp. 208 ◽

Cited By ~ 8

Author(s):

May Khei Hu ◽

Miles D. Witham ◽

Roy L. Soiza

Keyword(s):

Systematic Review ◽

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Mean Difference ◽

Controlled Trials ◽

Bicarbonate Therapy ◽

Randomised Controlled

Metabolic acidosis is a common complication in chronic kidney disease (CKD) patients, and is associated with an accelerated decline in renal function. Oral bicarbonate therapy has been used to counteract metabolic acidosis in CKD for decades. However, until recently, there have been very few intervention studies testing the effectiveness of bicarbonate therapy at improving metabolic acidosis or its consequences in patients with CKD. In this systematic review and meta-analysis, we aimed to examine the outcomes of all published randomised controlled trials (RCTs) that investigated the effect of oral bicarbonate therapy in adults with CKD. Ovid MEDLINE®, EMBASE® and Cochrane Library were searched in mid-October 2018 for English literature, with no restrictions applied to the publication status or date. Seven RCTs that recruited 815 participants met our inclusion criteria after full text review. Oral bicarbonate supplementation resulted in a slightly higher estimated glomerular filtration rate (eGFR) (mean difference 3.1 mL/min per 1.73 m2; 95% CI 1.3–4.9) and serum bicarbonate levels (mean difference 3.4 mmol/L; 95% CI 1.9–4.9) at the end of follow-up (three months to five years) compared to those given placebo or conventional CKD treatment. When limited to studies reporting outcomes at one year, the positive effect of oral bicarbonate therapy on eGFR was attenuated. There were no significant treatment effects in other parameters such as systolic blood pressure (BP) and weight. These findings should be interpreted with caution and further trial evidence is needed to establish the net overall benefit or harm of oral bicarbonate therapy in CKD.

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Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis

The British Journal of Psychiatry ◽

10.1192/bjp.bp.109.067710 ◽

2010 ◽

Vol 197 (3) ◽

pp. 174-179 ◽

Cited By ~ 130

Author(s):

Surendra P. Singh ◽

Vidhi Singh ◽

Nilamadhab Kar ◽

Kelvin Chan

Keyword(s):

Randomised Controlled Trials ◽

Selective Serotonin Reuptake Inhibitors ◽

Negative Symptoms ◽

Rating Scales ◽

Meta Analysis ◽

Chronic Schizophrenia ◽

Mean Difference ◽

Controlled Trials ◽

Clinical Issue ◽

Randomised Controlled

BackgroundTreatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue.AimsTo analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia.MethodSystematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms.ResultsThere were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (–0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin.ConclusionsAntidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.

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Analgesic efficacy of cannabinoids for acute pain management after surgery: a systematic review and meta-analysis

Regional Anesthesia and Pain Medicine ◽

10.1136/rapm-2020-101340 ◽

2020 ◽

Vol 45 (7) ◽

pp. 509-519 ◽

Cited By ~ 5

Author(s):

Faraj W Abdallah ◽

Nasir Hussain ◽

Tristan Weaver ◽

Richard Brull

Keyword(s):

Postoperative Pain ◽

Meta Analysis ◽

Oral Morphine ◽

Analgesic Efficacy ◽

Acute Postoperative Pain ◽

Acute Pain Management ◽

Cannabinoid Compounds ◽

Oral Morphine Equivalent ◽

Morphine Equivalent

BackgroundEvidence regarding the role of cannabinoids in managing acute postoperative pain is conflicting. The purpose of this systematic review and meta-analysis was to determine the analgesic efficacy of perioperative cannabinoid compounds for acute pain management after surgery.MethodsOriginal research articles evaluating the addition of cannabinoids to standard opioid-based systemic analgesia (Control) in the postoperative period were sought. Our primary outcomes were cumulative oral morphine equivalent consumption and rest pain severity at 24 hours postoperatively. We also assessed analgesic consumption in the postanesthesia care unit (PACU), pain scores in PACU, 6 and 12 hours postoperatively, and opioid-related and cannabinoid-related side effects, patient satisfaction, and quality of recovery as secondary outcomes.ResultsEight randomized controlled trials (924 patients) and four observational studies (4259 patients) were analyzed and included. There were insufficient data to pool for quantification of differences in cumulative oral morphine equivalent consumption and rest pain severity at 24 hours postoperatively with the addition of cannabinoids in comparison to Control. Qualitative synthesis revealed no differences in cumulative oral opioid consumption or pain at rest 24 hours postoperatively with the addition of cannabinoids in comparison to Control. Patients receiving cannabinoids appeared to have an increased weighted mean difference 95% CI of pain at 12 hours by 0.83 cm (0.04 to 1.63) (p=0.04). Patients receiving cannabinoids also appeared to have 3.24 times increased odds of developing hypotension postoperatively (95% CI 1.12 to 9.36) (p=0.03). Qualitative and quantitative synthesis revealed no differences in any other secondary outcomes.ConclusionsOur quantitative and qualitative review of the literature suggests that the analgesic role of perioperative cannabinoid compounds is limited, with no clinically important benefits detected when cannabinoids are added to traditional systemic analgesics compared with traditional systemic analgesics alone. Notably, there appears to be a signal towards increased postoperative pain and hypotension associated with the addition of perioperative cannabinoids to traditional systemic analgesics. These results do not support the routine use of cannabinoids to manage acute postoperative pain at the present time.

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Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials

British Journal Of Nutrition ◽

10.1017/s0007114513000548 ◽

2013 ◽

Vol 110 (7) ◽

pp. 1178-1187 ◽

Cited By ~ 241

Author(s):

Nassib Bezerra Bueno ◽

Ingrid Sofia Vieira de Melo ◽

Suzana Lima de Oliveira ◽

Terezinha da Rocha Ataide

Keyword(s):

Body Weight ◽

Randomised Controlled Trials ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Mean Difference ◽

Weighted Mean ◽

Low Fat Diet ◽

Low Carbohydrate ◽

Randomised Controlled

The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30 % of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect, Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was body weight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure, glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis, five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference − 0·91 (95 % CI − 1·65, − 0·17) kg, 1415 patients), TAG (weighted mean difference − 0·18 (95 % CI − 0·27, − 0·08) mmol/l, 1258 patients) and diastolic blood pressure (weighted mean difference − 1·43 (95 % CI − 2·49, − 0·37) mmHg, 1298 patients) while increased HDL-C (weighted mean difference 0·09 (95 % CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95 % CI 0·04, 0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the long term; hence, a VLCKD may be an alternative tool against obesity.

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Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: meta-analysis of randomised controlled trials

BMJ ◽

10.1136/bmj.l1328 ◽

2019 ◽

pp. l1328 ◽

Cited By ~ 32

Author(s):

Giovanni Musso ◽

Roberto Gambino ◽

Maurizio Cassader ◽

Elena Paschetta

Keyword(s):

Type 1 Diabetes ◽

Randomised Controlled Trials ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Insulin Dose ◽

Mean Difference ◽

Controlled Trials ◽

Weighted Mean ◽

Randomised Controlled

AbstractObjectiveTo assess the efficacy and safety of dual sodium glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin in type 1 diabetes mellitus.DesignMeta-analysis of randomised controlled trials.Data sourcesMedline; Cochrane Library; Embase; international meeting abstracts; international and national clinical trial registries; and websites of US, European, and Japanese regulatory authorities, up to 10 January 2019.Eligibility criteria for selecting studiesRandomised controlled trials evaluating the effect of sotagliflozin versus active comparators or placebo on glycaemic and non-glycaemic outcomes and on adverse events in type 1 diabetes in participants older than 18. Three reviewers extracted data for study characteristics, outcomes of interest, and risk of bias and summarised strength of evidence using the grading of recommendations assessment, development, and evaluation approach. Main outcomes were pooled using random effects models.ResultsOf 739 records identified, six randomised placebo controlled trials (n=3238, duration 4-52 weeks) were included. Sotagliflozin reduced levels of glycated haemoglobin (HbA1c; weighted mean difference −0.34% (95% confidence interval −0.41% to −0.27%), P<0.001); fasting plasma glucose (−16.98 mg/dL, −22.1 to −11.9; 1 mg/dL=0.0555 mmol/L) and two hour-postprandial plasma glucose (−39.2 mg/dL, −50.4 to −28.1); and daily total, basal, and bolus insulin dose (−8.99%, −10.93% to −7.05%; −8.03%, −10.14% to −5.93%; −9.14%, −12.17% to −6.12%; respectively). Sotagliflozin improved time in range (weighted mean difference 9.73%, 6.66% to 12.81%) and other continuous glucose monitoring parameters, and reduced body weight (−3.54%, −3.98% to −3.09%), systolic blood pressure (−3.85 mm Hg, −4.76 to −2.93), and albuminuria (albumin:creatinine ratio −14.57 mg/g, −26.87 to −2.28). Sotagliflozin reduced hypoglycaemia (weighted mean difference −9.09 events per patient year, −13.82 to −4.36) and severe hypoglycaemia (relative risk 0.69, 0.49 to 0.98). However, the drug increased the risk of ketoacidosis (relative risk 3.93, 1.94 to 7.96), genital tract infections (3.12, 2.14 to 4.54), diarrhoea (1.50, 1.08 to 2.10), and volume depletion events (2.19, 1.10 to 4.36). Initial HbA1c and basal insulin dose adjustment were associated with the risk of diabetic ketoacidosis. A sotagliflozin dose of 400 mg/day was associated with a greater improvement in most glycaemic and non-glycaemic outcomes than the 200 mg/day dose, without increasing the risk of adverse events. The quality of evidence was high to moderate for most outcomes, but low for major adverse cardiovascular events and all cause death. The relatively short duration of trials prevented assessment of long term outcomes.ConclusionsIn type 1 diabetes, sotagliflozin improves glycaemic and non-glycaemic outcomes and reduces hypoglycaemia rate and severe hypoglycaemia. The risk of diabetic ketoacidosis could be minimised by appropriate patient selection and down-titration of the basal insulin dose.

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Nuts and their Effect on Gut Microbiota, Gut Function and Symptoms in Adults: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Nutrients ◽

10.3390/nu12082347 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2347 ◽

Cited By ~ 1

Author(s):

Alice C. Creedon ◽

Estella S. Hung ◽

Sarah E. Berry ◽

Kevin Whelan

Keyword(s):

Systematic Review ◽

Gut Microbiota ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Mean Difference ◽

Controlled Trials ◽

Faecal Microbiota ◽

Gut Function ◽

Randomised Controlled ◽

The Impact

Nuts contain fibre, unsaturated fatty acids and polyphenols that may impact the composition of the gut microbiota and overall gut health. This study aimed to assess the impact of nuts on gut microbiota, gut function and gut symptoms via a systematic review and meta-analysis of randomised controlled trials (RCTs) in healthy adults. Eligible RCTs were identified by systematic searches of five electronic databases, hand searching of conference abstracts, clinical trials databases, back-searching reference lists and contact with key stakeholders. Eligible studies were RCTs administering tree nuts or peanuts in comparison to control, measuring any outcome related to faecal microbiota, function or symptoms. Two reviewers independently screened papers, performed data extraction and risk of bias assessment. Outcome data were synthesised as weighted mean difference (WMD) or standardised mean difference (SMD) using a random effects model. This review was registered on PROSPERO (CRD42019138169). Eight studies reporting nine RCTs were included, investigating almonds (n = 5), walnuts (n = 3) and pistachios (n = 1). Nut consumption significantly increased Clostridium (SMD: 0.40; 95% CI, 0.10, 0.71; p = 0.01), Dialister (SMD: 0.44; 95% CI, 0.13, 0.75; p = 0.005), Lachnospira (SMD: 0.33; 95% CI, 0.02, 0.64; p = 0.03) and Roseburia (SMD: 0.36; 95% CI, 0.10, 0.62; p = 0.006), and significantly decreased Parabacteroides (SMD: −0.31; 95% CI, −0.62, −0.00; p = 0.05). There was no effect of nuts on bacterial phyla, diversity or stool output. Further parallel design RCTs, powered to detect changes in faecal microbiota and incorporating functional and clinical outcomes, are needed.

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Efficacy of vision-based treatments for children and teens with amblyopia: a systematic review and meta-analysis of randomised controlled trials

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2020-000657 ◽

2021 ◽

Vol 6 (1) ◽

pp. e000657

Author(s):

Taylor Adrian Brin ◽

Amy Chow ◽

Caitlin Carter ◽

Mark Oremus ◽

William Bobier ◽

...

Keyword(s):

Randomised Controlled Trials ◽

Meta Analysis ◽

Linear Regression Analysis ◽

Treatment Success ◽

Indirect Comparison ◽

Mean Difference ◽

Cochrane Library ◽

Controlled Trials ◽

Standard Mean Difference ◽

Randomised Controlled

ObjectiveTo identify differences in efficacy between vision-based treatments for improving visual acuity (VA) of the amblyopic eye in persons aged 4–17 years old.Data sourcesOvid Embase, PubMed (Medline), the Cochrane Library, Vision Cite and Scopus were systematically searched from 1975 to 17 June 2020.MethodsTwo independent reviewers screened search results for randomised controlled trials of vision-based amblyopia treatments that specified change in amblyopic eye VA (logMAR) as the primary outcome measure. Quality was assessed via risk of bias and GRADE (Grading of Recommendations, Assessment, Development, and Evaluations).ResultsOf the 3346 studies identified, 36 were included in a narrative synthesis. A random effects meta-analysis (five studies) compared the efficacy of binocular treatments versus patching: mean difference −0.03 logMAR; 95% CI 0.01 to 0.04 (p<0.001), favouring patching. An exploratory study-level regression (18 studies) showed no statistically significant differences between vision-based treatments and a reference group of 2–5 hours of patching. Age, sample size and pre-randomisation optical treatment were not statistically significantly associated with changes in amblyopic eye acuity. A network meta-analysis (26 studies) comparing vision-based treatments to patching 2–5 hours found one statistically significant comparison, namely, the favouring of a combination of two treatment arms comparing combination and binocular treatments, against patching 2–5 hours: standard mean difference: 2.63; 95% CI 1.18 to 4.09. However, this result was an indirect comparison calculated from a single study. A linear regression analysis (17 studies) found a significant relationship between adherence and effect size, but the model did not completely fit the data: regression coefficient 0.022; 95% CI 0.004 to 0.040 (p=0.02).ConclusionWe found no clinically relevant differences in treatment efficacy between the treatments included in this review. Adherence to the prescribed hours of treatment varied considerably and may have had an effect on treatment success.

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Inhaled methoxyflurane (Penthrox) for analgesia in trauma: a systematic review protocol

Systematic Reviews ◽

10.1186/s13643-021-01600-0 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Michael M. Eager ◽

Grant S. Nolan ◽

Kathryn Tonks ◽

Anoopama Ramjeeawon ◽

Natalie Taylor

Keyword(s):

Systematic Review ◽

Pain Relief ◽

Standard Care ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Mean Difference ◽

Controlled Trials ◽

Acute Trauma ◽

Patient Reported ◽

Randomised Controlled

Abstract Background More than 75% of patients presenting to the Emergency Department are suffering symptoms of pain. Despite this, 67% will not receive any analgesia. Methoxyflurane is a fluorinated hydrocarbon gas which has analgesic properties when inhaled. Penthrox is a methoxyflurane autoinhaler recently licenced in Europe. Its ease of administration, safety, and fast onset of action make it of particular relevance to emergency medicine. Additionally, outside the hospital, it has the advantage of increased temperature stability and portability over current standard care. New evidence of its efficacy is emerging; however, currently, its use in Europe is not widespread. The objective of this study will be to systematically evaluate the evidence on inhaled methoxyflurane to determine if it is a superior analgesia in the acute trauma setting. Methods We designed and registered a study protocol for a systematic review and meta-analysis on randomised controlled trials, comparing inhaled methoxyflurane and either placebo or standard care. A comprehensive search will be conducted from database inception onwards in MEDLINE, Embase, and the Cochrane CENTRAL database, concurrent with a search of the grey literature for other relevant studies, including clinical trial databases. Only randomised controlled trials will be included. No limitations will be imposed on publication status or language of publication. The primary outcome will be mean difference in patient-reported pain at time points within the first 30 min of administration. Secondary outcomes will be mean difference in time to clinically significant pain relief and relative risk of adverse effects. Two reviewers will independently screen all returned studies and collect data. Disagreements will be resolved through discussion or referral to a third reviewer. Individual study methodological quality will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis; if this is not possible, we will construct a narrative synthesis. Discussion This systematic review will summarise the best available evidence and definitively establish if inhaled methoxyflurane is a superior analgesia to standard care in the acute trauma setting. This knowledge will directly impact emergency care in the UK and worldwide and may require amendments to European pain relief guidelines. Systematic review registration PROSPERO CRD42020189119.

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