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Medical treatment of SUNCT and SUNA: a prospective open-label study including single-arm meta-analysis.
Lambru, G, Stubberud, A, Rantell, K, Lagrata, S, Tronvik, E, Matharu, MS
Journal of neurology, neurosurgery, and psychiatry. 2021;(3):233-241
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INTRODUCTION The management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) remains challenging in view of the paucity of data and evidence-based treatment recommendations are missing. METHODS In this single-centre, non-randomised, prospective open-label study, we evaluated and compared the efficacy of oral and parenteral treatments for SUNCT and SUNA in a real-world setting. Additionally, single-arm meta-analyses of the available reports of SUNCT and SUNA treatments were conducted. RESULTS The study cohort comprised 161 patients. Most patients responded to lamotrigine (56%), followed by oxcarbazepine (46%), duloxetine (30%), carbamazepine (26%), topiramate (25%), pregabalin and gabapentin (10%). Mexiletine and lacosamide were effective in a meaningful proportion of patients but poorly tolerated. Intravenous lidocaine given for 7-10 days led to improvement in 90% of patients, whereas only 27% of patients responded to a greater occipital nerve block. No statistically significant differences in responders were observed between SUNCT and SUNA. In the meta-analysis of the pooled data, topiramate was found to be significantly more effective in SUNCT than SUNA patients. However, a higher proportion of SUNA than SUNCT was considered refractory to medications at the time of the topiramate trial, possibly explaining this isolated difference. CONCLUSIONS We propose a treatment algorithm for SUNCT and SUNA for clinical practice. The response to sodium channel blockers indicates a therapeutic overlap with trigeminal neuralgia, suggesting that sodium channels dysfunction may be a key pathophysiological hallmark in these disorders. Furthermore, the therapeutic similarities between SUNCT and SUNA further support the hypothesis that these conditions are variants of the same disorder.
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Interventions for itch in people with advanced chronic kidney disease.
Hercz, D, Jiang, SH, Webster, AC
The Cochrane database of systematic reviews. 2020;(12):CD011393
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BACKGROUND Itch in patients with chronic kidney disease (CKD) is common, often very distressing and associated with depression, reduced quality of life, and increased death. The most common first-line treatment has been the use of antihistamines despite the lack of substantial evidence for its use for uraemic itch. Few recommendations and guidelines exist for treatment. OBJECTIVES We aimed to determine: 1) the benefits and harms (both absolute and relative) of all topical and systemic interventions for the treatment of uraemic itch, either alone or in combination, when compared with placebo or standard care; and, 2) the dose strength or frequency, stage of kidney disease or method of dialysis used (where applicable) in cases where the effects of these interventions vary depending on co-interventions. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 17 December 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials (RCTs) in adults with CKD stages 4 or 5 comparing treatments (pharmacological, topical, exposure, dialysis modality) for CKD associated itch to either placebo or other established treatments. DATA COLLECTION AND ANALYSIS Two authors independently abstracted study data and assessed study quality. Data were analysed using a random effects meta-analysis design estimating the relative effects of treatment versus placebo. Estimates of the relative effects between treatments are included where possible. For continuous measures of severity of itch up to three months, mean difference (MD) or standardised mean difference (SMD) were used. When reported, adverse effects were tabulated. The certainty of the evidence was estimated using GRADE. MAIN RESULTS Ninety-two RCTs, randomising 4466 participants were included. Fifty-eight studies (3285 participants) provided sufficient data to be meta-analysed. Of these, 30 compared an intervention to a placebo or control. The 10 cm Visual Analogue Scale (VAS) was the dominant instrument utilized for itch reporting and the Duo score was used in a minority of studies. GABA analogues including, gabapentin and pregabalin, reduce itch in patients with CKD (5 studies, 297 participants: 4.95 cm reduction, 95% CI 5.46 to 4.44 lower in VAS compared to placebo; high certainty evidence). Kappa opioid agonists, including nalfurafine also reduced itch in this population (6 studies, 661 participants: 1.05 cm reduction, 95% CI 1.40 to 0.71 lower in VAS compared to placebo; high certainty evidence). Ondansetron had little or no effect on itch scores (3 studies, 183 participants: 0.38 cm reduction, 95% CI 1.04 lower to 0.29 higher in VAS compared to placebo; high certainty evidence). Reduction in the severity of itch was reported with oral montelukast, turmeric, zinc sulfate and topical capsaicin. For all other interventions, the certainty of the evidence was low to moderate, and the interventions had uncertain effects on uraemic pruritus. Six studies have disclosed significant financial support from their respective manufacturers, six were affected by lack of blinding, and 11 studies have 15 participants or less. Older, smaller RCTs often failed to follow intention-to-treat protocols with unexplained dropouts after randomisation. Adverse effects were generally poorly and inconsistently reported across all RCTs. No severe adverse events were reported for any intervention. AUTHORS' CONCLUSIONS The RCTs of this meta-analysis contain a large array of interventions with a diverse set of comparators. For many interventions, trials are sparse. This served to make informative meta-analysis challenging. Of all treatments for uraemic pruritus, gabapentinoids (gabapentin and pregabalin) were the most studied and show the greatest reduction in itch scores. Further RCTs, even of the scale of the largest trials included in this review, are unlikely to significantly change this finding. Kappa-opioid agonists (mainly nalfurafine) also may reduce itch, but indirect comparison suggests a much more modest effect in comparison to GABA analogues. Evidence for oral montelukast, turmeric, zinc sulfate, and topical capsaicin also showed an itch score reduction. However, these reductions were reported in small studies, and warrant further investigation. Ondansetron did not reduce itch. It is somewhat unlikely that a further study of ondansetron will change this result.
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Efficacy and safety of over-the-counter analgesics for primary dysmenorrhea: A network meta-analysis.
Nie, W, Xu, P, Hao, C, Chen, Y, Yin, Y, Wang, L
Medicine. 2020;(19):e19881
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BACKGROUND Primary dysmenorrhea is common and troublesome. The comparative efficacy of over-the-counter analgesics (OTCAs) for dysmenorrhea is unclear. This study was aimed at conducting a network meta-analysis to assess the efficacy and safety of 5 OTCAs - naproxen, ibuprofen,diclofenac, aspirin, and ketoprofen - in patients with primary dysmenorrhea. METHODS The study was registered with PROSPERO (number: CRD42019133556). The search strategy involved a review of PubMed, Embase, Cochrane Library, Web of Science, and CINAHL for relative randomized controlled trials of the 5 analgesics from the date of database establishment to July 2019. The outputs are presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities. RESULTS Thirty-five trials with 4383 participants were included in our study. As for efficacy outcomes, all the included analgesics except aspirin were more effective than placebo in treating dysmenorrhea [naproxen (OR 3.99, 95% CI 2.18-7.30), ibuprofen (OR 10.08, 95% CI 3.29-30.85), diclofenac (OR 11.82, 95% CI 2.66-52.48), and ketoprofen (OR 5.12, 95% CI 1.57-16.69). The OTCAs were superior to the placebo in terms of pain relief in primary dysmenorrhea. Aspirin was less effective than ibuprofen (OR 0.17, 95% CI 0.04-0.73) and diclofenac (OR 1.17, 95% CI 0.02-0.85). The SUCRA curves showed that diclofenac and ibuprofen were the most and second most effective (85.1% and 83.8%, respectively), followed by ketoprofen, naproxen, and aspirin. Regarding safety, there was no significant difference between the 5 OTCAs included and the placebo. Diclofenac versus ibuprofen (OR 4.31, 95% CI 1.18-15.67), ketoprofen versus diclofenac (OR 0.18, 95% CI 0.04-0.78), and ketoprofen versus aspirin (OR 0.41, 95% CI 0.18-0.97) presented statistically significant differences. Ketoprofen and ibuprofen were ranked the best (SUCRA 90.6% and 79.6%), followed by naproxen, aspirin, and diclofenac. CONCLUSION Considering the efficacy and safety, ibuprofen is recommended as the optimal OTCA for primary dysmenorrhea. Further well-designed studies that directly compare these analgesics are needed to support our conclusion.
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Drugs for Acute Attack of Pediatric Migraine: A Network Meta-analysis of Randomized Controlled Trials.
Wang, G, Tan, T, Liu, Y, Hong, P
Clinical neurology and neurosurgery. 2020;:105853
Abstract
Migraine in pediatric is a common neurological disease, and its prevalence is varying widely. The medication for the acute attack of pediatric migraine is various. we take advantage of network meta-analysis to address the efficacy and rank of these medications. Database including Pubmed and Cochrane Library were queried using a specific searching strategy. The quality of trials enrolled was assessed according to the Cochrane collaboration'tool for assessing risk of bias. The data analysis was conducted by using the core software for Cochrane reviews (Rev Man 5.3) and the Aggregate Data Drug Information System (Addis v1.16.8). The outcomes were pain-free and pain relief at 2 hours post-dose. Totally, twenty trials with high quality including 6029 migraineurs with 6912 attacks randomly assigned to 14 different drugs. The data of ketorolac and prochlorperazine were missing. We found that sumatriptan nasal spray and zolmitriptan nasal spray were superior to placebo in the two efficacy outcomes, whereas almotriptan, rizatriptan, sumatriptan with naproxen sodium, ibuprofen and ibuprofen suspension were superior to placebo only in one of the efficacy outcomes. And in network meta-analysis, we found the best 3 treatments were ibuprofen, sumatriptan with naproxen sodium and ibuprofen suspension in achieving pain-free. Meanwhile, the best 3 treatments were ibuprofen suspension, ibuprofen, and rizatriptan in achieving pain relief. In conclusion, in acute treatments of pediatric migraine, most triptans and NSAIDS were effective to achieve pain-free or pain-relief. And the most effective treatment to achieve pain-free is sumatriptan with naproxen sodium. Ibuprofen and ibuprofen suspension were the most effective treatments to achieve pain-relief.
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Systematic review of analgesics and dexamethasone for post-tonsillectomy pain in adults.
Tolska, HK, Hamunen, K, Takala, A, Kontinen, VK
British journal of anaesthesia. 2019;(2):e397-e411
Abstract
BACKGROUND Intense pain can last several days after tonsillectomy. It is often undertreated and improved analgesic strategies that can be safely used at home are needed. METHODS We conducted a systematic review and meta-analysis on the effectiveness of systemic medications used for post-tonsillectomy pain in adult and adolescent (13 yr old) patients. Studies were identified from PubMed, the Cochrane Library, and by hand searching reference lists from studies and review articles. Randomised, double-blind, placebo-controlled studies reporting on pain intensity or use of rescue analgesia were included. RESULTS Twenty-nine randomised controlled trials representing 1816 subjects met the inclusion criteria. Follow-up time was ≤24 h in 15 studies, in which the majority were taking nonsteroidal anti-inflammatory drugs. Thirteen studies were suitable for meta-analysis. In pooled analysis, paracetamol, dexamethasone, and gabapentinoids reduced pain intensity on the day of operation. In individual studies, ketoprofen, ibuprofen, lornoxicam, parecoxib, rofecoxib, indomethacin and dextromethorphan reduced pain intensity, need for rescue analgesics, or both on the day of operation. Oral celecoxib for 2 postoperative weeks or i.v. ketamine on the day of operation were not effective at the studied doses. Dexamethasone in multiple doses provided analgesia beyond 1 postoperative day. Pain was moderate to strong in both study and control groups during the first postoperative week. CONCLUSIONS Single analgesics and dexamethasone provide only a weak to moderate effect for post-tonsillectomy pain on the day of operation and thus a multimodal analgesic strategy is recommended. Short follow-up times and clinical heterogeneity of studies limit the usefulness of results.
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Analgesic Effects of Locally Administered Ketorolac-based Analgesics After Breast Surgery: A Meta-Analysis of Randomized Controlled Trials.
Chen, JY, Feng, IJ, Loh, EW, Wang, LK, Lin, CC, Tam, KW
The Clinical journal of pain. 2018;(6):577-584
Abstract
OBJECTIVE Reducing postoperative pain following breast surgery is crucial for rapid recovery and shortening hospital stay. Ketorolac, a nonsteroidal anti-inflammatory drug, has been used as a postoperative analgesic in many surgical procedures. We conducted a systemic review and meta-analysis on the efficacy of locally administered ketorolac-based analgesics in managing pain after breast surgery. METHODS We searched the PubMed, Embase, Cochrane Library, Scopus, and ClinicalTrials.gov registry for randomized control trials (RCTs) published up to September 2016. The primary outcome was pain level assessed using a visual analog scale (VAS) at 1 and 6 hours following breast surgery. RESULTS We reviewed 4 RCTs with 255 patients. For meta-analysis, VAS at 1 and 6 hours of 3 similar RCTs were compared. At 1 hour, VAS scores were significantly lower in patients administered a ketorolac solution [weighted mean difference (WMD)=-2.04; 95% confidence interval (CI): -3.08 to -1.00] or ketorolac-bupivacaine solution (WMD=-2.30; 95% CI, -4.07 to -0.54) than in controls. At 6 hours, the ketorolac-bupivacaine solution reduced VAS scores significantly (WMD=-1.40; 95% CI, -2.48 to -0.32) compared with controls. However, at 1 hour, the ketorolac solution was significantly more effective than the bupivacaine solution was (WMD=-1.70; 95% CI, -2.81 to -0.59). DISCUSSION The effects of ketorolac-based analgesics vary as per the surgery and disease type. Locally administered ketorolac-based analgesics decreased postoperative pain in breast surgery patients, and the effect of local ketorolac was better than local bupivacaine. Therefore, ketorolac-based analgesics demonstrate considerable local infiltration during pain management after breast surgery.
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Baseline Morphine Consumption May Explain Between-Study Heterogeneity in Meta-analyses of Adjuvant Analgesics and Improve Precision and Accuracy of Effect Estimates.
Doleman, B, Sutton, AJ, Sherwin, M, Lund, JN, Williams, JP
Anesthesia and analgesia. 2018;(2):648-660
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BACKGROUND Statistical heterogeneity can increase the uncertainty of results and reduce the quality of evidence derived from systematic reviews. At present, it is uncertain what the major factors are that account for heterogeneity in meta-analyses of analgesic adjuncts. Therefore, the aim of this review was to identify whether various covariates could explain statistical heterogeneity and use this to improve accuracy when reporting the efficacy of analgesics. METHODS We searched for reviews using MEDLINE, EMBASE, CINAHL, AMED, and the Cochrane Database of Systematic Reviews. First, we identified the existence of considerable statistical heterogeneity (I > 75%). Second, we conducted meta-regression analysis for the outcome of 24-hour morphine consumption using baseline risk (control group morphine consumption) and other clinical and methodological covariates. Finally, we constructed a league table of adjuvant analgesics using a novel method of reporting effect estimates assuming a fixed consumption of 50 mg postoperative morphine. RESULTS We included 344 randomized controlled trials with 28,130 participants. Ninety-one percent of analyses showed considerable statistical heterogeneity. Baseline risk was a significant cause of between-study heterogeneity for acetaminophen, nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, tramadol, ketamine, α2-agonists, gabapentin, pregabalin, lidocaine, magnesium, and dexamethasone (R = 21%-100%; P < .05). There was some evidence that the methodological limitations of the trials explained some of the residual heterogeneity. Type of surgery was not independently associated with analgesic efficacy. Assuming a fixed baseline risk of 50 mg (in order of efficacy), gabapentin, acetaminophen, α2-agonists, nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, pregabalin, tramadol, magnesium, and lidocaine demonstrated moderate clinically significant reductions (>10 mg). We could not exclude a moderate clinically significant effect with ketamine. Dexamethasone demonstrated a small clinical benefit (>5 mg). CONCLUSIONS We empirically identified baseline morphine consumption as the major source of heterogeneity in meta-analyses of adjuvant analgesics across all surgical interventions. Controlling for baseline morphine consumption, clinicians can use audit data to estimate the morphine-reducing effect of adding any adjuvant for their local population, regardless which surgery they undergo. Moreover, we have utilized these findings to present a novel method of reporting and an amended method of graphically displaying effect estimates, which both reduces confounding from variable baseline risk in included trials and is able to adjust for other clinical and methodological confounding variables. We recommend use of these methods in clinical practice and future reviews of analgesics for postoperative pain.
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Analgesic efficacy of preoperative dexketoprofen trometamol: A systematic review and meta-analysis.
Esparza-Villalpando, V, Pozos-Guillén, A, Masuoka-Ito, D, Gaitán-Fonseca, C, Chavarría-Bolaños, D
Drug development research. 2018;(2):47-57
Abstract
Post-Market Research Clinical evidence supports the use of dexketoprofen trometamol (DEX) to manage acute postoperative pain. However, controversies surround the impact of the use of this drug in preoperative analgesic protocols. The aim of the present meta-analysis was to evaluate the effectiveness of the preoperative administration of DEX under postoperative pain conditions. Electronic and manual searches were conducted through diverse electronic databases. A systematic review and meta-analysis to evaluate the analgesic efficacy of the preoperative administration of DEX was performed including Randomized Clinical Trials (RCTs) published between 2002 and 2017. Suitable individual studies were evaluated through a quality system, and the data were extracted and analyzed. Fourteen RTCs were included (12 parallel trials and 2 cross-over trials), published in the English and Turkish languages. Follow-up periods ranged from 4, 6, 8, 24, and 48 hr. All trials measured the outcome result as Acute Pain Level (APL) (VAS, NRS, VRS), time to requiring a second dose of DEX or analgesic emergency and consumption of opioids via patient-controlled analgesia. When the comparators were other drugs - paracetamol, Lornoxicam or placebo during the preoperative time, preoperative administration of DEX was superior. When the comparison comprised preoperative and postoperative DEX, both alternatives exhibited comparable analgesic effects. The analgesic efficacy of the preoperative administration of DEX when compared to placebo, lornoxicam, and paracetamol on postoperative pain was evident. Preoperative administration of DEX compared to its immediate postoperative administration showed a similar analgesic effect.
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Effect of preoperative oral analgesics on pulpal anesthesia in patients with irreversible pulpitis-a systematic review and meta-analysis.
Shirvani, A, Shamszadeh, S, Eghbal, MJ, Marvasti, LA, Asgary, S
Clinical oral investigations. 2017;(1):43-52
Abstract
OBJECTIVES The objectives of this study were to assess the efficacy of preemptive oral administration of single dose of non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on the local anesthetic success in adults with irreversible pulpitis and to find the possible covariates that could predict treatment effect. MATERIALS AND METHODS A systematic search using electronic databases up to March 2015 was conducted. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated using random and fixed-effect inverse variance method. Subgroup and meta-regression analyses were conducted to assess the potential source of heterogeneity. RESULTS Results showed that preemptive analgesics are more effective than placebo in increasing anesthetic success (OR = 0.30, CI% 0.24-0.39, p = 0.000) [Q = 55.860 (p = 0.001)]. In the subgroup analysis, administration of NSAIDs as monotherapy, ibuprofen as mono- vs. combination therapy, oxicam type drugs as monotherapy, and acetaminophen as combination therapy were significantly more effective in increasing anesthetic success OR = 0.25, CI% 0.16-0.38, p = 0.00, Q = 40.539 (p = 0.003); OR = 0.44, CI% 0.26-0.75, p = 0.00, Q = 12.833 (p = 0.011); OR = 0.48, CI% 0.30-0.74, p = 0.002, Q = 15.898 (p = 0.14); OR = 0.30, CI% 0.16-0.38, p = 0.001, Q = 7.506 (p = 0.02); OR = 0.10, CI% 0.16 0.38, p = 0.001, Q = 5.075 (p = 0.07), respectively. However, there was no significant difference in increasing anesthetic success between treatment and placebo arms when acetaminophen was administrated alone. In meta-regression analysis, an association between different types of NSAIDs (indomethacin, diclofenac potassium, and oxicam-type drugs) and articaine with treatment effect was observed. CONCLUSIONS The administration of preemptive analgesics can induce superior intraoperative analgesia for patients with irreversible pulpitis. However, strategies such as co-administration of certain types of analgesics and anesthetic solution might be predictors of treatment effect. Additionally, there was no association between different timing and dosage of analgesics and treatment effect. CLINICAL RELEVANCE When compared to placebo, preemptive oral analgesics are superior in achieving anesthetic success in inflamed pulp.
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Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.
Gajjar, K, Martin-Hirsch, PP, Bryant, A, Owens, GL
The Cochrane database of systematic reviews. 2016;(7):CD006120
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BACKGROUND Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the National Health Service (NHS) cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. OBJECTIVES To assess whether the administration of pain relief (analgesia) reduces pain during colposcopy treatment and in the postoperative period. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE (1950 to March week 3, 2016) and Embase (1980 to week 12, 2016) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. DATA COLLECTION AND ANALYSIS We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into Review Manager 5 and double checked it for accuracy. Where possible, we expressed results as mean pain score and standard error of the mean with 95% confidence intervals (CI) and synthesised data in a meta-analysis. MAIN RESULTS We included 19 RCTs (1720 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, buffered lignocaine with adrenaline, prilocaine with felypressin, oral analgesics (non-steroidal anti-inflammatory drugs (NSAIDs)), inhalation analgesia (gas mixture of isoflurane and desflurane), lignocaine spray, cocaine spray, local application of benzocaine gel, lignocaine-prilocaine cream (EMLA cream) and transcutaneous electrical nerve stimulation (TENS).Most comparisons were restricted to single trial analyses and were under-powered to detect differences in pain scores between treatments that may or may not have been present. There was no difference in pain relief between women who received local anaesthetic infiltration (lignocaine 2%; administered as a paracervical or direct cervical injection) and a saline placebo (mean difference (MD) -13.74; 95% CI -34.32 to 6.83; 2 trials; 130 women; low quality evidence). However, when local anaesthetic was combined with a vasoconstrictor agent (one trial used lignocaine plus adrenaline while the second trial used prilocaine plus felypressin), there was less pain (on visual analogue scale (VAS)) compared with no treatment (MD -23.73; 95% CI -37.53 to -9.93; 2 trials; 95 women; low quality evidence). Comparing two preparations of local anaesthetic combined with vasoconstrictor, prilocaine plus felypressin did not differ from lignocaine plus adrenaline for its effect on pain control (MD -0.05; 95% CI -0.26 to 0.16; 1 trial; 200 women). Although the mean (± standard deviation (SD)) observed blood loss score was less with lignocaine plus adrenaline (1.33 ± 1.05) compared with prilocaine plus felypressin (1.74 ± 0.98), the difference was not clinically as the overall scores in both groups were low (MD 0.41; 95% CI 0.13 to 0.69; 1 trial; 200 women). Inhalation of gas mixture (isoflurane and desflurane) in addition to standard cervical injection with prilocaine plus felypressin resulted in less pain during the LLETZ (loop excision of the transformation zone) procedure (MD -7.20; 95% CI -12.45 to -1.95; 1 trial; 389 women). Lignocaine plus ornipressin resulted in less measured blood loss (MD -8.75 ml; 95% CI -10.43 to -7.07; 1 trial; 100 women) and a shorter duration of treatment (MD -7.72 minutes; 95% CI -8.49 to -6.95; 1 trial; 100 women) than cervical infiltration with lignocaine alone. Buffered solution (sodium bicarbonate buffer mixed with lignocaine plus adrenaline) was not superior to non-buffered solution of lignocaine plus adrenaline in relieving pain during the procedure (MD -8.00; 95% CI -17.57 to 1.57; 1 trial; 52 women).One meta-analysis found no difference in pain using VAS between women who received oral analgesic and women who received placebo (MD -3.51; 95% CI -10.03 to 3.01; 2 trials; 129 women; low quality evidence).Cocaine spray was associated with less pain (MD -28.00; 95% CI -37.86 to -18.14; 1 trial; 50 women) and blood loss (MD 0.04; 95% CI 0 to 0.70; 1 trial; 50 women) than placebo.None of the trials reported serious adverse events and majority of trials were at moderate or high risk of bias (13 trials). AUTHORS' CONCLUSIONS Based on two small trials, there was no difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (MD -3.51; 95% CI -10.03 to 3.01; 129 women). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.