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Journal of Pain Research 2021Compared to low concentrations of local anesthetics with opioids for labor epidural analgesia, very high concentrations of local anesthetics are associated with an...
A Systematic Review and Meta-Analysis of Randomized Controlled Trials of Labor Epidural Analgesia Using Moderately High Concentrations of Plain Local Anesthetics versus Low Concentrations of Local Anesthetics with Opioids.
PURPOSE
Compared to low concentrations of local anesthetics with opioids for labor epidural analgesia, very high concentrations of local anesthetics are associated with an increased risk of assisted vaginal delivery. We aimed to investigate if moderately high concentrations of plain local anesthetics are also associated with this risk.
METHODS
We searched for published randomized controlled trials that compared moderately high concentrations of plain local anesthetics (>0.1% but ≤0.125% bupivacaine, >0.1% but ≤0.125% levobupivacaine, or >0.17% but ≤0.2% ropivacaine) to low concentrations of local anesthetics (≤0.1% bupivacaine, ≤0.1% levobupivacaine, or ≤0.17% ropivacaine) with opioids for labor analgesia. Meta-analyses were performed to compare the risk of assisted vaginal delivery and other perinatal outcomes between these two groups.
RESULTS
We identified nine randomized controlled trials with a total of 1334 participants. Meta-analysis of these nine trials showed no differences in the risks of assisted vaginal delivery (odds ratio [OR] = 1.18; 95% confidence interval [CI], 0.93-1.49) or Cesarean delivery (OR = 0.96; 95% CI, 0.71-1.29) between the two groups. The incidence of motor block was higher in the group of moderately high concentrations (OR = 4.05; 95% CI, 2.19-7.48), while the incidence of pruritus was lower (OR = 0.07; 95% CI, 0.03-0.16).
CONCLUSION
This systematic review and meta-analysis suggests that the current evidence is inadequate to support that moderately high concentrations of plain local anesthetics increase the risk of assisted vaginal delivery compared to low concentrations of local anesthetics with opioids.
PubMed: 34054305
DOI: 10.2147/JPR.S305838 -
BMC Urology Jan 2015Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). However, tramadol may cause addiction and difficulty in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). However, tramadol may cause addiction and difficulty in breathing and the beneficial effect of tramadol in PE is yet not supported by a high level of evidence. The purpose of this study was to systematically review the evidence from randomised controlled trials (RCT) for tramadol in the management of PE.
METHODS
We searched bibliographic databases including MEDLINE to August 2014 for RCTs. The primary outcome was intra-vaginal ejaculatory latency time (IELT). Methodological quality of RCTs was assessed. Between-group differences in IELT and other outcomes were pooled across RCTs in a meta-analysis. Statistical and clinical between-trial heterogeneity was assessed.
RESULTS
A total of eight RCTs that evaluated tramadol against a comparator were included. The majority of RCTs were of unclear methodological quality due to limited reporting. Pooled evidence (four RCTs, 721 participants), suggests that tramadol is significantly more effective than placebo at increasing IELT over eight to 12 weeks (p = 0.0007). However, a high level of statistical heterogeneity is evident (I-squared = 74%). Single RCT evidence indicates that tramadol is significantly more effective than paroxetine taken on-demand, sildenafil, lidocaine gel, or behavioural therapy on IELT in men with PE. Tramadol is associated with significantly more adverse events including: erectile dysfunction, constipation, nausea, headache, somnolence, dry mouth, dizziness, pruritus, and vomiting, than placebo or behavioural therapy over eight to 12 weeks of treatment. However, addiction problems or breathing difficulties reported by patients for PE is not assessed in the current evidence base.
CONCLUSIONS
Tramadol appears effective in the treatment of PE. However, these findings should be interpreted with caution given the observed levels of between-trial heterogeneity and the reporting quality of the available evidence. The variability across placebo-controlled trials in terms of the tramadol dose evaluated and the treatment duration does not permit any assessment of a safe and effective minimum daily dose. The long-term effects and side effects, including addiction potential, for men with PE have not been evaluated in the current evidence base.
TRIAL REGISTRATION
The review is registered on PROSPERO 2013: CRD42013005289 .
Topics: Drug Administration Schedule; Evidence-Based Medicine; Humans; Male; Off-Label Use; Orgasm; Patient Satisfaction; Premature Ejaculation; Prevalence; Randomized Controlled Trials as Topic; Tramadol; Treatment Outcome
PubMed: 25636495
DOI: 10.1186/1471-2490-15-6 -
The Cochrane Database of Systematic... Oct 2012Traditional epidural techniques have been associated with prolonged labour, use of oxytocin augmentation and increased incidence of instrumental vaginal delivery. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traditional epidural techniques have been associated with prolonged labour, use of oxytocin augmentation and increased incidence of instrumental vaginal delivery. The combined spinal-epidural (CSE) technique has been introduced in an attempt to reduce these adverse effects. CSE is believed to improve maternal mobility during labour and provide more rapid onset of analgesia than epidural analgesia, which could contribute to increased maternal satisfaction.
OBJECTIVES
To assess the relative effects of CSE versus epidural analgesia during labour.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 September 2011) and reference lists of retrieved studies. We updated the search on 30 June 2012 and added the results to the awaiting classification section.
SELECTION CRITERIA
All published randomised controlled trials (RCTs) involving a comparison of CSE with epidural analgesia initiated for women in the first stage of labour. Cluster-randomised trials were considered for inclusion. Quasi RCTs and cross-over trials were not considered for inclusion in this review.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed the trials identified from the searches for inclusion, assessed trial quality and extracted the data. Data were checked for accuracy.
MAIN RESULTS
Twenty-seven trials involving 3274 women met our inclusion criteria. Twenty-six outcomes in two sets of comparisons involving CSE versus traditional epidurals and CSE versus low-dose epidural techniques were analysed.Of the CSE versus traditional epidural analyses five outcomes showed a significant difference. CSE was more favourable in relation to speed of onset of analgesia from time of injection (mean difference (MD) -2.87 minutes; 95% confidence interval (CI) -5.07 to -0.67; two trials, 129 women); the need for rescue analgesia (risk ratio (RR) 0.31; 95% CI 0.14 to 0.70; one trial, 42 women); urinary retention (RR 0.86; 95% CI 0.79 to 0.95; one trial, 704 women); and rate of instrumental delivery (RR 0.81; 95% CI 0.67 to 0.97; six trials, 1015 women). Traditional epidural was more favourable in relation to umbilical venous pH (MD -0.03; 95% CI -0.06 to -0.00; one trial, 55 women). There were no data on maternal satisfaction, blood patch for post dural puncture headache, respiratory depression, umbilical cord pH, rare neurological complications, analgesia for caesarean section after analgesic intervention or any economic/use of resources outcomes for this comparison. No differences between CSE and traditional epidural were identified for mobilisation in labour, the need for labour augmentation, the rate of caesarean birth, incidence of post dural puncture headache, maternal hypotension, neonatal Apgar scores or umbilical arterial pH.For CSE versus low-dose epidurals, three outcomes were statistically significant. Two of these reflected a faster onset of effective analgesia from time of injection with CSE and the third was of more pruritus with CSE compared to low-dose epidural (average RR 1.80; 95% CI 1.22 to 2.65; 11 trials, 959 women; random-effects, T² = 0.26, I² = 84%). There was no significant difference in maternal satisfaction (average RR 1.01; 95% CI 0.98 to 1.05; seven trials, 520 women; random-effects, T² = 0.00, I² = 45%). There were no data on respiratory depression, maternal sedation or the need for labour augmentation. No differences between CSE and low-dose epidural were identified for need for rescue analgesia, mobilisation in labour, incidence of post dural puncture headache, known dural tap, blood patch for post dural headache, urinary retention, nausea/vomiting, hypotension, headache, the need for labour augmentation, mode of delivery, umbilical pH, Apgar score or admissions to the neonatal unit.
AUTHORS' CONCLUSIONS
There appears to be little basis for offering CSE over epidurals in labour, with no difference in overall maternal satisfaction despite a slightly faster onset with CSE and conversely less pruritus with low-dose epidurals. There was no difference in ability to mobilise, maternal hypotension, rate of caesarean birth or neonatal outcome. However, the significantly higher incidence of urinary retention, rescue interventions and instrumental deliveries with traditional techniques would favour the use of low-dose epidurals. It is not possible to draw any meaningful conclusions regarding rare complications such as nerve injury and meningitis.
Topics: Analgesia, Epidural; Analgesia, Obstetrical; Anesthesia, Epidural; Anesthesia, Spinal; Female; Humans; Labor, Obstetric; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 23076897
DOI: 10.1002/14651858.CD003401.pub3 -
The Cochrane Database of Systematic... Mar 2012The pain that women experience during labour is affected by multiple physiological and psychosocial factors and its intensity can vary greatly. Most women in labour... (Review)
Review
BACKGROUND
The pain that women experience during labour is affected by multiple physiological and psychosocial factors and its intensity can vary greatly. Most women in labour require pain relief. Pain management strategies include non-pharmacological interventions (that aim to help women cope with pain in labour) and pharmacological interventions (that aim to relieve the pain of labour).
OBJECTIVES
To summarise the evidence from Cochrane systematic reviews on the efficacy and safety of non-pharmacological and pharmacological interventions to manage pain in labour. We considered findings from non-Cochrane systematic reviews if there was no relevant Cochrane review.
METHODS
We searched the Cochrane Database of Systematic Reviews (The Cochrane Library 2011, Issue 5), The Cochrane Database of Abstracts of Reviews of Effects (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (1966 to 31 May 2011) and EMBASE (1974 to 31 May 2011) to identify all relevant systematic reviews of randomised controlled trials of pain management in labour. Each of the contributing Cochrane reviews (nine new, six updated) followed a generic protocol with 13 common primary efficacy and safety outcomes. Each Cochrane review included comparisons with placebo, standard care or with a different intervention according to a predefined hierarchy of interventions. Two review authors extracted data and assessed methodological quality, and data were checked by a third author. This overview is a narrative summary of the results obtained from individual reviews.
MAIN RESULTS
We identified 15 Cochrane reviews (255 included trials) and three non-Cochrane reviews (55 included trials) for inclusion within this overview. For all interventions, with available data, results are presented as comparisons of: 1. Intervention versus placebo or standard care; 2. Different forms of the same intervention (e.g. one opioid versus another opioid); 3. One type of intervention versus a different type of intervention (e.g. TENS versus opioid). Not all reviews included results for all comparisons. Most reviews compared the intervention with placebo or standard care, but with the exception of opioids and epidural analgesia, there were few direct comparisons between different forms of the same intervention, and even fewer comparisons between different interventions. Based on these three comparisons, we have categorised interventions into: " What works" ,"What may work", and "Insufficient evidence to make a judgement".WHAT WORKSEvidence suggests that epidural, combined spinal epidural (CSE) and inhaled analgesia effectively manage pain in labour, but may give rise to adverse effects. Epidural, and inhaled analgesia effectively relieve pain when compared with placebo or a different type of intervention (epidural versus opioids). Combined-spinal epidurals relieve pain more quickly than traditional or low dose epidurals. Women receiving inhaled analgesia were more likely to experience vomiting, nausea and dizziness.When compared with placebo or opioids, women receiving epidural analgesia had more instrumental vaginal births and caesarean sections for fetal distress, although there was no difference in the rates of caesarean section overall. Women receiving epidural analgesia were more likely to experience hypotension, motor blockade, fever or urinary retention. Less urinary retention was observed in women receiving CSE than in women receiving traditional epidurals. More women receiving CSE than low-dose epidural experienced pruritus. WHAT MAY WORKThere is some evidence to suggest that immersion in water, relaxation, acupuncture, massage and local anaesthetic nerve blocks or non-opioid drugs may improve management of labour pain, with few adverse effects. Evidence was mainly limited to single trials. These interventions relieved pain and improved satisfaction with pain relief (immersion, relaxation, acupuncture, local anaesthetic nerve blocks, non-opioids) and childbirth experience (immersion, relaxation, non-opioids) when compared with placebo or standard care. Relaxation was associated with fewer assisted vaginal births and acupuncture was associated with fewer assisted vaginal births and caesarean sections.INSUFFICIENT EVIDENCEThere is insufficient evidence to make judgements on whether or not hypnosis, biofeedback, sterile water injection, aromatherapy, TENS, or parenteral opioids are more effective than placebo or other interventions for pain management in labour. In comparison with other opioids more women receiving pethidine experienced adverse effects including drowsiness and nausea.
AUTHORS' CONCLUSIONS
Most methods of non-pharmacological pain management are non-invasive and appear to be safe for mother and baby, however, their efficacy is unclear, due to limited high quality evidence. In many reviews, only one or two trials provided outcome data for analysis and the overall methodological quality of the trials was low. High quality trials are needed.There is more evidence to support the efficacy of pharmacological methods, but these have more adverse effects. Thus, epidural analgesia provides effective pain relief but at the cost of increased instrumental vaginal birth.It remains important to tailor methods used to each woman's wishes, needs and circumstances, such as anticipated duration of labour, the infant's condition, and any augmentation or induction of labour.A major challenge in compiling this overview, and the individual systematic reviews on which it is based, has been the variation in use of different process and outcome measures in different trials, particularly assessment of pain and its relief, and effects on the neonate after birth. This made it difficult to pool results from otherwise similar studies, and to derive conclusions from the totality of evidence. Other important outcomes have simply not been assessed in trials; thus, despite concerns for 30 years or more about the effects of maternal opioid administration during labour on subsequent neonatal behaviour and its influence on breastfeeding, only two out of 57 trials of opioids reported breastfeeding as an outcome. We therefore strongly recommend that the outcome measures, agreed through wide consultation for this project, are used in all future trials of methods of pain management.
Topics: Acupuncture Analgesia; Administration, Inhalation; Analgesia, Epidural; Analgesia, Obstetrical; Analgesics; Cesarean Section; Female; Humans; Immersion; Labor Pain; Massage; Patient Satisfaction; Pregnancy; Relaxation Therapy; Review Literature as Topic
PubMed: 22419342
DOI: 10.1002/14651858.CD009234.pub2 -
The Cochrane Database of Systematic... Dec 2011Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily affects the genital area and around the anus, where it causes persistent itching and soreness. Scarring after inflammation may lead to severe damage by fusion of the vulval lips (labia); narrowing of the vaginal opening; and burying of the clitoris in women and girls, as well as tightening of the foreskin in men and boys, if treatments are not started early. Affected people have an increased risk of genital cancers.
OBJECTIVES
To assess the effects of topical interventions for genital lichen sclerosus and adverse effects reported in included trials.
SEARCH METHODS
We searched the following databases up to 16 September 2011: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (from 1982), CINAHL (from 1981), British Nursing Index and Archive (from 1985), Science Citation Index Expanded (from 1945), BIOSIS Previews (from 1926), Conference Papers Index (from 1982), and Conference Proceedings Citation Index - Science (from 1990). We also searched ongoing trial registries and scanned the bibliographies of included studies, published reviews, and papers that had cited the included studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of topical interventions in genital lichen sclerosus.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion.
MAIN RESULTS
We included 7 RCTs, with a total of 249 participants, covering 6 treatments. Six of these RCTs tested the efficacy of one active intervention against placebo or another active intervention, while the other trial tested three active interventions against placebo.When compared to placebo in one trial, clobetasol propionate 0.05% was effective in treating genital lichen sclerosus in relation to the following outcomes: 'participant-rated improvement or remission of symptoms' (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.45 to 5.61) and 'investigator-rated global degree of improvement' (standardised mean difference (SMD) 5.74, 95% CI 4.26 to 7.23).When mometasone furoate 0.05% was compared to placebo in another trial, there was a significant improvement in the 'investigator-rated change in clinical grade of phimosis' (SMD -1.04, 95% CI -1.77 to -0.31).Both trials found no significant differences in reported adverse drug reactions between the corticosteroid and placebo groups. The data from four trials found no significant benefit for topical testosterone, dihydrotestosterone, and progesterone. When used as maintenance therapy after an initial treatment with topical clobetasol propionate in another trial, topical testosterone worsened the symptoms (P < 0.05), but the placebo did not.One trial found no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (itching) (SMD -0.33, 95% CI -0.99 to 0.33) and burning/pain (SMD 0.03, 95% CI -0.62 to 0.69). However, pimecrolimus was less effective than clobetasol propionate with regard to the 'investigator-rated global degree of improvement' (SMD -1.64, 95% CI -2.40 to -0.87). This trial found no significant differences in reported adverse drug reactions between the pimecrolimus and placebo groups.
AUTHORS' CONCLUSIONS
The current limited evidence demonstrates the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital lichen sclerosus. Further RCTs are needed to determine the optimal potency and regimen of topical corticosteroids, examine other topical interventions, assess the duration of remission or prevention of flares, evaluate the reduction in the risk of genital squamous cell carcinoma or genital intraepithelial neoplasia, and examine the efficacy in improving the quality of the sex lives of people with this condition.
Topics: Adult; Anti-Inflammatory Agents; Child; Clobetasol; Dermatologic Agents; Dihydrotestosterone; Female; Genital Diseases, Male; Humans; Lichen Sclerosus et Atrophicus; Male; Mometasone Furoate; Pregnadienediols; Randomized Controlled Trials as Topic; Tacrolimus; Testosterone Propionate; Vulvar Lichen Sclerosus
PubMed: 22161424
DOI: 10.1002/14651858.CD008240.pub2