BACKGROUND:Topical local anaesthetics provide effective analgesia for patients undergoing numerous superficial procedures, including repair of dermal lacerations. The need for cocaine in topical anaesthetic formulations has been questioned because of concern about adverse effects, thus novel preparations of cocaine-free anaesthetics have been developed. This review was originally published in 2011 and has been updated in 2017. OBJECTIVES:To assess whether benefits of non-invasive topical anaesthetic application occur at the expense of decreased analgesic efficacy. To compare the efficacy of various single-component or multi-component topical anaesthetic agents for repair of dermal lacerations. To determine the clinical necessity for topical application of the ester anaesthetic, cocaine. SEARCH METHODS:For this updated review, we searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11), Cumulative Index to Nursing and Allied Health Literature (CINAHL; 2010 to December 2016), Embase (2010 to December 2016) and MEDLINE (2010 to December 2016). We did not limit this search by language or format of publication. We contacted manufacturers, international scientific societies and researchers in the field. Weemailed selected journalsand reviewed meta-registers of ongoing trials. For the previous version of this review, we searched these databases to November 2010. SELECTION CRITERIA:We included randomized controlled trials (RCTs) that evaluated the efficacy and safety of topical anaesthetics for repair of dermal laceration in adult and paediatric participants. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information when needed. We collected adverse event information from trial reports. We assessed methodological risk of bias for each included study and employed the GRADE approach to assess the overall quality of the evidence. MAIN RESULTS:The present updated review included 25 RCTs involving 3278 participants. The small number of trials in each comparison group and the heterogeneity of outcome measures precluded quantitative analysis of data for all but one outcome: pain intensity. In two pooled studies, the mean self-reported visual analogue scale (VAS; 0 to 100 mm) score for topical prilocaine-phenylephrine (PP) was higher than the mean self-reported VAS (0 to 100 mm) score for topical tetracaine-epinephrine-cocaine (TAC) by 5.59 points (95% confidence interval (CI) 2.16 to 13.35). Most trials that compared infiltrated and topical anaesthetics were at high risk of bias, which is likely to have affected their results. Researchers found that several cocaine-free topical anaesthetics provided effective analgesic efficacy. However, data regarding the efficacy of each topical agent are based mostly on single comparisons in trials with unclear or high risk of bias. Mild, self-limited erythematous skin induration occurred in one of 1042 participants who had undergone application of TAC. Investigators reported no serious complications among any of the participants treated with cocaine-based or cocaine-free topical anaesthetics. The overall quality of the evidence according to the GRADE system is low owing to limitations in design and implementation, imprecision of results and high probability of publication bias (selective reporting of data). Additional well-designed RCTs with low risk of bias are necessary before definitive conclusions can be reached. AUTHORS' CONCLUSIONS:We have found two new studies published since the last version of this review was prepared. We have added these studies to those previously included and have conducted an updated analysis, which resulted in the same review conclusions as were presented previously.Mostly descriptive analysis indicates that topical anaesthetics may offer an efficacious, non-invasive means of providing analgesia before suturing of dermal lacerations. Use of cocaine-based topical anaesthetics might be hard to justify, given the availability of other effective topical anaesthetics without cocaine. However, the overall quality of the evidence according to the GRADE system is low owing to limitations in design and implementation, imprecision of results and high probability of publication bias (selective reporting of data). Additional well-designed RCTs with low risk of bias are necessary before definitive conclusions can be reached.

BACKGROUND:Topical local anaesthetics are recognized as providing effective analgesia for numerous superficial procedures, including repair of dermal lacerations. The need for cocaine in topical anaesthetic formulations has been questioned due to concern about adverse effects, and so novel preparations of cocaine-free anaesthetics have been developed. OBJECTIVES:To compare the efficacy and safety of infiltrated local anaesthetics with those of topical local anaesthetics for repair of dermal lacerations and to evaluate the efficacy and safety of various single or multi-component topical anaesthetics to identify cocaine-free topically applied local anaesthetics that may provide equivalent analgesia to those containing cocaine. SEARCH STRATEGY:We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10); MEDLINE (1966 to November 2010); EMBASE (1980 to November 2010); CINAHL (1982 to November 2010); and reference lists of articles. We also handsearched selected journals, reviewed abstracts presented at international society meetings, reviewed metaregisters of ongoing trials and contacted manufacturers and researchers in the field. SELECTION CRITERIA:We included randomized controlled trials (RCTs) that evaluated the efficacy and safety of topical anaesthetics for repair of torn skin in adult and paediatric patients. DATA COLLECTION AND ANALYSIS:Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse event information from the trials. MAIN RESULTS:We included 23 RCTs involving 3128 patients. The small number of trials in each comparison group and the heterogeneity of outcome measures precluded quantitative analysis of data in all but one outcome, pain scores using a visual analogue scale. The majority of trials that compared infiltrated and topical anaesthetics are at high risk of bias, which is likely to affect the interpretation of the results. Several cocaine-free topical anaesthetics were found to provide effective analgesic efficacy. However, the data regarding the efficacy of each topical agent is mostly based upon single comparisons, in trials that have unclear or high risk of bias. Mild, self-limited erythematous skin induration occurred in one case after application of topical tetracaine-adrenaline-cocaine (TAC) where a total of 1042 patients were exposed. No serious complications were reported in any of the patients treated with either cocaine-based or cocaine-free topical anaesthetics. AUTHORS' CONCLUSIONS:Based on mostly descriptive analysis, topical anaesthetics are possibly an efficacious, non-invasive means of providing analgesia prior to suturing of dermal lacerations. However, additional well designed RCTs with low risk of bias are necessary before definitive conclusions can be made.

This chapter explores the clinical trial design, with a particular focus on investigations of neuromodulation. The current hierarchy of clinical study design stratifies the scientific literature based upon its type and quality. It should be considered a general framework rather then an absolute ranking system, and clinicians should consider the results of the best available evidence while making evidence-based decisions. Randomized, double-blinded, controlled trials (RCT) are historically considered the least biased method of study design for assessing the efficacy of medical interventions. However, in trials evaluating the efficacy of interventional therapies, including neuromodulation, blinding is more challenging to accomplish. In fact, double-blinded trials of spinal cord stimulation are not feasible because of the paresthesiae normally present during such treatment. In situations where RCTs are not practical or feasible, observational trials that are rigorously designed may be an appropriate alternative to RCTs for determining therapeutic efficacy. Although the available evidence generally supports the use of neurostimulation, there is a paucity of high quality literature. It is therefore essential that those involved with neuromodulation, especially for chronic pain management, develop innovative studies with improved methodological quality in order to determine the value of this emerging therapy.

Optimized use of systemic analgesics fails to adequately control pain in some patients with cancer. Commonly used analgesics, including opioids, nonopioids (acetaminophen and non-steroidal anti-inflammatory drugs), and adjuvant analgesics (anticonvulsants and antidepressants), have limited analgesic efficacy, and their use is often associated with adverse effects. Without adequate pain control, patients with cancer not only experience the anguish of poorly controlled pain but also have greatly diminished quality of life and may even have reduced life expectancy. Interventional pain therapies are a diverse set of procedural techniques for controlling pain that may be useful when systemic analgesics fail to provide adequate control of cancer pain or when the adverse effects of systemic analgesics cannot be managed reasonably. Commonly used interventional therapies for cancer pain include neurolytic neural blockade, spinal administration of analgesics, and vertebroplasty. Compared with systemic analgesics, which generally have broad indications for control of pain, individual interventional therapies generally have specific, narrow indications. When appropriately selected and implemented, interventional pain therapies are important components of broad, multimodal cancer pain management that significantly increases the proportion of patients able to experience adequate pain control.