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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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Abstract
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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Comparative Efficacy of 6 Topical Pharmacological Agents for Preventive Interventions of Postoperative Sore Throat After Tracheal Intubation: A Systematic Review and Network Meta-analysis.
Wang, G, Qi, Y, Wu, L, Jiang, G
Anesthesia and analgesia. 2021;(1):58-67
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BACKGROUND Topical pharmacological agents typically used to treat postoperative sore throat (POST) after tracheal intubation include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, lidocaine, Glycyrrhiza (licorice), and N-methyl-d-aspartate (NMDA) receptor antagonists (including ketamine and magnesium). However, the optimal prophylactic drug remains elusive. METHODS The literature published before September 8, 2019 was searched on the PubMed, the Embase, the Web of Science, and the Cochrane Library. Randomized controlled trials (RCTs) covering topical prophylactic medications for patients with POST were included. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the quality of evidence. The primary outcome is the risk of POST. Combining both direct and indirect evidence, a network meta-analysis was performed to assess odds ratios (ORs) between the topical pharmacological agents and surface under the cumulative ranking (SUCRA) curve for the treatment-based outcomes. This study is registered with PROSPERO, number CRD42020158985. RESULTS Sixty-two RCTs (at least 73% of which were double blinded) that included a total of 6708 subjects and compared 6 categories of drugs and/or placebos were ultimately enrolled. All preventive interventions except lidocaine were more effective than placebo at the 4 time intervals. Lidocaine (OR: 0.35, 95% credible interval [CrI], 0.16-0.79) has a greater POST preventative intervention effect than the placebo at a time interval of only 2 to 3 hours after surgery. Relative to lidocaine, the risk of POST except 2 to 3 hours was lower for the following treatments: corticosteroids, ketamine, magnesium, NSAIDs, and Glycyrrhiza. The NMDA receptor antagonists studied here included ketamine and magnesium. Magnesium generally demonstrated greater benefit than ketamine at 24 hours postsurgery/extubation (OR: 0.41, 95% CrI, 0.18-0.92). Compared with ketamine, corticosteroids were associated with a reduced risk of POST during the 4 to 6 hours (OR: 0.40, 95% CrI, 0.19-0.83) and 24 hours (OR: 0.34, 95% CrI, 0.16-0.72) time intervals. During the 2 to 3 hours time interval, Glycyrrhiza (OR: 0.38, 95% CrI, 0.15-0.97) was more efficacious than magnesium. CONCLUSIONS Our analysis shows that, among the 6 topical medications studied, lidocaine is not optimal for topical use to prevent POST. Glycyrrhizin, corticosteroids, NSAIDs, and NMDA receptor antagonists (ketamine and magnesium) are associated with a reduced postoperative pharyngeal pain across the 4 postsurgical time intervals studied, all of which can be chosen according to the clinical experience of the anesthesiologists and the patient preferences and are recommended for the reduction of postoperative throat pain.
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The Analgesic Benefits of Ketorolac to Local Anesthetic Wound Infiltration Is Statistically Significant But Clinically Unimportant: A Comprehensive Systematic Review and Meta-Analysis.
Yan, R, Fu, X, Ren, YF, Liu, H, You, FM, Shi, W, Jiang, YF
Advances in wound care. 2021;(11):583-595
Abstract
Objective: Even though ketorolac-infiltration is said to provide superior postoperative analgesic benefits in different surgical procedures, its safety and efficacy remain to be validated because of the lack of high-quality evidence. We aimed to summarize the efficacy and safety of ketorolac-infiltration based on published randomized-controlled trials (RCTs). Approach: This work followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, assessing the methodological quality of systematic reviews and the Cochrane Collaboration recommendations. We searched for RCTs evaluating the efficacy of ketorolac-infiltration in adults in the PubMed, Web of Science, Embase, Cochrane Library, Chinese databases, and Google Scholar. The two co-primary outcomes of this meta-analysis were rescue analgesic consumption in the 24-h postoperative period and rest pain scores. Results: Twelve trials (761 patients) were analyzed. Ketorolac-infiltration provided a clinically unimportant benefit in morphine consumption (mean difference, -2.81 mg; 95% confidence interval [CI], -5.11 to -0.50; p = 0.02; moderate-quality evidence). Low-to-moderate quality evidence supported a brief (2-6 h), clinically subtle, but statistically consistent effect of surgical site ketorolac-infiltration in reducing wound pain at rest. High-quality evidence supported shorter hospital stays for surgical patients receiving local ketorolac-infiltration when compared to controls (mean difference, -0.12 days; 95% CI, -0.17 to -0.08; p < 0.00001). Further, ketorolac-infiltration does not improve any opioid-related side effects. Innovation: Ketorolac-infiltration provides statistically significant but clinically unimportant benefits for improving postoperative wound pain. Conclusion: Overall, despite the fact that current moderate-to-high quality of evidence does not support routine using of ketorolac as an adjuvant to local anesthetic for wound infiltration, these findings underscore the importance of optimizing agents and sustained delivery parameters in postoperative local anesthetic practice. Clinical Trials.gov ID: CRD42021229095.
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Efficacy of intracuff lidocaine in reducing coughing on tube: a systematic review and meta-analysis.
Peng, F, Wang, M, Yang, H, Yang, X, Long, M
The Journal of international medical research. 2020;(2):300060520901872
Abstract
OBJECTIVE To investigate the efficacy of intracuff lidocaine in reducing coughing and other endotracheal tube side effects and so ensure a smooth extubation process. METHOD PubMed, EMBASE, and Cochrane Library databases were systematically searched for all randomised controlled trials (RCTs) published before June 30, 2019 that investigated the efficacy of intracuff lidocaine, with or without sodium bicarbonate, in reducing coughing and other complications related to endotracheal intubation. A random-effects model was used to conduct a meta-analysis to assess the relative risks (RRs) of the incidence of these intubation-related side effects. RESULTS 11 studies involving 843 patients were included in the meta-analysis. Compared with control groups (i.e., saline or air), intracuff lidocaine groups (alkalinized or non-alkalinized) had a significantly reduced incidence of coughing on tube. Similarly, intracuff lidocaine groups were more effective than control groups in reducing the incidence of other intubation-related complications. CONCLUSION Intracuff alkalinized or non-alkalinized lidocaine significantly reduced coughing and other intubation-related complications during the extubation process.
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Epidural corticosteroid injections for lumbosacral radicular pain.
Oliveira, CB, Maher, CG, Ferreira, ML, Hancock, MJ, Oliveira, VC, McLachlan, AJ, Koes, BW, Ferreira, PH, Cohen, SP, Pinto, RZ
The Cochrane database of systematic reviews. 2020;(4):CD013577
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Abstract
BACKGROUND Lumbosacral radicular pain (commonly called sciatica) is a syndrome involving patients who report radiating leg pain. Epidural corticosteroid injections deliver a corticosteroid dose into the epidural space, with the aim of reducing the local inflammatory process and, consequently, relieving the symptoms of lumbosacral radicular pain. This Cochrane Review is an update of a review published in Annals of Internal Medicine in 2012. Some placebo-controlled trials have been published recently, which highlights the importance of updating the previous review. OBJECTIVES To investigate the efficacy and safety of epidural corticosteroid injections compared with placebo injection on pain and disability in patients with lumbosacral radicular pain. SEARCH METHODS We searched the following databases without language limitations up to 25 September 2019: Cochrane Back and Neck group trial register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and two trial registers. We also performed citation tracking of included studies and relevant systematic reviews in the field. SELECTION CRITERIA We included studies that compared epidural corticosteroid injections of any corticosteroid drug to placebo injections in patients with lumbosacral radicular pain. We accepted all three anatomical approaches (caudal, interlaminar, and transforaminal) to delivering corticosteroids into the epidural space. We considered trials that included a placebo treatment as delivery of an inert substance (i.e. one with no pharmacologic activity), an innocuous substance (e.g. normal saline solution), or a pharmacologically active substance but not one considered to provide sustained benefit (e.g. local anaesthetic), either into the epidural space (i.e. to mimic epidural corticosteroid injection) or adjacent spinal tissue (i.e. subcutaneous, intramuscular, or interspinous tissue). We also included trials in which a local anaesthetic with a short duration of action was used as a placebo and injected together with corticosteroid in the intervention group. DATA COLLECTION AND ANALYSIS Two authors independently performed the screening, data extraction, and 'Risk of bias' assessments. In case of insufficient information, we contacted the authors of the original studies or estimated the data. We grouped the outcome data into four time points of assessment: immediate (≤ 2 weeks), short term (> 2 weeks but ≤ 3 months), intermediate term (> 3 months but < 12 months), and long term (≥ 12 months). We assessed the overall quality of evidence for each outcome and time point using the GRADE approach. MAIN RESULTS We included 25 clinical trials (from 29 publications) investigating the effects of epidural corticosteroid injections compared to placebo in patients with lumbosacral radicular pain. The included studies provided data for a total of 2470 participants with a mean age ranging from 37.3 to 52.8 years. Seventeen studies included participants with lumbosacral radicular pain with a diagnosis based on clinical assessment and 15 studies included participants with mixed duration of symptoms. The included studies were conducted mainly in North America and Europe. Fifteen studies did not report funding sources, five studies reported not receiving funding, and five reported receiving funding from a non-profit or government source. Eight trials reported data on pain intensity, 12 reported data on disability, and eight studies reported data on adverse events. The duration of the follow-up assessments ranged from 12 hours to 1 year. We considered eight trials to be of high quality because we judged them as having low risk of bias in four out of the five bias domains. We identified one ongoing trial in a trial registry. Epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing leg pain at short-term follow-up (mean difference (MD) -4.93, 95% confidence interval (CI) -8.77 to -1.09 on a 0 to 100 scale; 8 trials, n = 949; moderate-quality evidence (downgraded for risk of bias)). For disability, epidural corticosteroid injections were probably slightly more effective compared to placebo in reducing disability at short-term follow-up (MD -4.18, 95% CI -6.04 to -2.17, on a 0 to 100 scale; 12 trials, n = 1367; moderate-quality evidence (downgraded for risk of bias)). The treatment effects are small, however, and may not be considered clinically important by patients and clinicians (i.e. MD lower than 10%). Most trials provided insufficient information on how or when adverse events were assessed (immediate or short-term follow-up) and only reported adverse drug reactions - that is, adverse events that the trialists attributed to the study treatment. We are very uncertain that epidural corticosteroid injections make no difference compared to placebo injection in the frequency of minor adverse events (risk ratio (RR) 1.14, 95% CI 0.91 to 1.42; 8 trials, n = 877; very low quality evidence (downgraded for risk of bias, inconsistency and imprecision)). Minor adverse events included increased pain during or after the injection, non-specific headache, post-dural puncture headache, irregular periods, accidental dural puncture, thoracic pain, non-local rash, sinusitis, vasovagal response, hypotension, nausea, and tinnitus. One study reported a major drug reaction for one patient on anticoagulant therapy who had a retroperitoneal haematoma as a complication of the corticosteroid injection. AUTHORS' CONCLUSIONS This study found that epidural corticosteroid injections probably slightly reduced leg pain and disability at short-term follow-up in people with lumbosacral radicular pain. In addition, no minor or major adverse events were reported at short-term follow-up after epidural corticosteroid injections or placebo injection. Although the current review identified additional clinical trials, the available evidence still provides only limited support for the use of epidural corticosteroid injections in people with lumbosacral radicular pain as the treatment effects are small, mainly evident at short-term follow-up and may not be considered clinically important by patients and clinicians (i.e. mean difference lower than 10%). According to GRADE, the quality of the evidence ranged from very low to moderate, suggesting that further studies are likely to play an important role in clarifying the efficacy and tolerability of this treatment. We recommend that further trials should attend to methodological features such as appropriate allocation concealment and blinding of care providers to minimise the potential for biased estimates of treatment and harmful effects.