Context Droperidol is widely used for the prevention of postoperative nausea and vomiting (PONV) in European countries. It is unclear how efficacious low-dose droperidol is in the prevention of PONV. Objectives To test the efficacy of low-dose droperidol in the prevention of PONV in adults and to test for dose-responsiveness. Design Systematic review of randomised controlled trials with meta-analyses. Data Sources Comprehensive search in electronic databases (Medline, Embase, Central) up to June 2011. Additional trials were obtained from bibliographies of retrieved reports. No language restriction was applied. Eligibility Criteria Randomised trials testing prophylactic intravenous droperidol ≤1 mg or ≤15 μg kg−1 compared with placebo (or no treatment) in adults undergoing general anaesthesia and reporting on PONV. Results We analysed 25 trials (2957 patients). Doses varied from 0.25 to 1.0 mg. For prevention of early nausea (within 6 h postoperatively), relative risk (RR) was 0.45 (95% CI, 0.35 to 0.58); number needed to treat (NNT) was 7, 4, and 2 for low, medium and high baseline risk (i.e. control event rate 25, 50, 75%). For prevention of early vomiting, RR was 0.65 (95% CI, 0.57 to 0.74), NNT 11, 6, and 4. For prevention of late nausea (within 24 h), RR was 0.74 (95% CI, 0.62 to 0.87), NNT 15, 8, and 5. For prevention of late vomiting, RR was 0.61 (95% CI, 0.47 to 0.80), NNT 10, 5, and 3. Droperidol decreased the risk of headache but increased the risk of restlessness. For these outcomes there was no evidence of dose-responsiveness. There were no differences in the incidences of sedation or dizziness. Two patients receiving droperidol 0.625 mg had extrapyramidal symptoms. Cardiac toxicity data were not reported. Conclusion Prophylactic doses of droperidol of 1 mg or below are antiemetic. Because adverse drug reactions are likely to be dose-dependent, there is an argument to stop using doses of more than 1 mg.
To study whether systematic reviewers apply procedures to counter-balance some common forms of research malpractice such as not publishing completed research, duplicate publications, or selective reporting of outcomes, and to see whether they identify and report misconduct.
Design
Cross-sectional analysis of systematic reviews and survey of their authors.
Participants
118 systematic reviews published in four journals (Ann Int Med, BMJ, JAMA, Lancet), and the Cochrane Library, in 2013.
Main outcomes and measures
Number (%) of reviews that applied procedures to reduce the impact of: (1) publication bias (through searching of unpublished trials), (2) selective outcome reporting (by contacting the authors of the original studies), (3) duplicate publications, (4) sponsors' and (5) authors' conflicts of interest, on the conclusions of the review, and (6) looked for ethical approval of the studies. Number (%) of reviewers who suspected misconduct are reported. The procedures applied were compared across journals.
Results
80 (68%) reviewers confirmed their data. 59 (50%) reviews applied three or more procedures; 11 (9%) applied none. Unpublished trials were searched in 79 (66%) reviews. Authors of original studies were contacted in 73 (62%). Duplicate publications were searched in 81 (69%). 27 reviews (23%) reported sponsors of the included studies; 6 (5%) analysed their impact on the conclusions of the review. Five reviews (4%) looked at conflicts of interest of study authors; none of them analysed their impact. Three reviews (2.5%) looked at ethical approval of the studies. Seven reviews (6%) suspected misconduct; only 2 (2%) reported it explicitly. Procedures applied differed across the journals.
Conclusions
Only half of the systematic reviews applied three or more of the six procedures examined. Sponsors, conflicts of interest of authors and ethical approval remain overlooked. Research misconduct is sometimes identified, but rarely reported. Guidance on when, and how, to report suspected misconduct is needed.
Background Intravenous lidocaine is increasingly used in surgical patients. As it has neuromuscular blocking effects, we tested the impact of an intravenous lidocaine infusion on the time course of a rocuronium‐induced neuromuscular block. Methods Fifty‐two adults undergoing surgery were randomly allocated to intravenous lidocaine 1.5 mg/kg followed by a continuous infusion of 2 mg/kg/h or physiological saline (control) throughout surgery. Anaesthesia was induced and maintained with a target‐controlled propofol infusion and sufentanil. After loss of consciousness, rocuronium 0.6 mg/kg was given. Neuromuscular transmission was measured using train‐of‐four ( TOF )‐watch SX (Organon, Swords Co., D ublin, I reland) acceleromyography. Results Onset time (to 95% depression of first twitch) was on average 113.9 s (standard deviation 35.3) with lidocaine and 119.5 s (44.9) with saline ( P = 0.618). Total recovery time ( TOF ratio 0.9) was on average 58.1 min (15.1) with lidocaine and 54.3 min (16.9) with saline ( P = 0.394). Clinical duration (until first twitch has recovered to 25%) was on average 33.3 min (7.2) with lidocaine and 30.6 min (8.1) with saline ( P = 0.21). Recovery index (time between 25% and 75% recovery of the first twitch) was on average 11.5 min (5.0) with lidocaine and 10.6 min (4.1) with saline ( P = 0.458). Recovery time (between 25% recovery of the first twitch and TOF ratio 0.9) was on average 24.8 min (9.3) with lidocaine and 23.2 min (9.2) with saline ( P = 0.541). Conclusion A continuous intravenous infusion of lidocaine has no impact on the time course of the neuromuscular blockade induced by a standard intubation dose of rocuronium.
Since 2010, the European Journal of Anaesthesiology has required the reporting of five items concerning ethical approval in articles describing human research: ethics committee's name and address, chairperson's name, study's protocol number and approval date. We aimed to assess whether this requirement has helped to identify and to contact the referenced ethics committees. In this cross-sectional study, we analysed articles requiring ethical approval, according to the Swiss federal law for human research and published in the European Journal of Anaesthesiology in 2011. Ethics committees were searched through our institutional Internet access based on information provided in the articles. The last search was performed in November 2015. Numbers (%) of items reported, of ethics committees identified, and of those that confirmed having provided ethical approval are reported. Of 76 articles requiring ethical approval, 74 (97%) declared it. Ethics committees' names and addresses were mentioned in 63/74 (85%), protocol numbers in 51/74 (69%), approval dates in 48/74 (65%), and chairpersons' names in 45/74 (61%). We could identify 44/74 (59%) committees; 36/74 (49%) answered our inquiry and 24/74 (32%) confirmed their role. Thirty-four of 74 articles (46%) reported all five items; in 25/34 (74%), we were able to identify an ethics committee, 18/34 (53%) answered our inquiry, and 15/34 (44%) confirmed their role. Forty of 74 articles (54%) reported ≤4 items; in 19/40 (48%), we were able to identify an ethics committee, 18/40 (45%) answered our inquiry, and 9/40 (23%) confirmed their role. Reporting five items significantly increased identification of ethics committees (p = 0.023) and their confirmation of ethical approval (p = 0.048). Twelve of 74 ethics committees (16%) were unable to confirm their role in approving the study. Even when details concerning ethical approval were reported in these studies of human research, we were unable to identify almost half of the ethics committees concerned. The reporting of five items, compared with reporting ≤4, was associated with facilitated identification of ethics committees, and increased the likelihood that they would be able to confirm the study's approval. Future research should identify which information facilitates identification of, and contact with, ethics committees.
The aim of this systematic review was to indirectly compare the efficacy of any intervention, administered perioperatively, on acute and persistent pain after breast surgery.We searched for randomized trials comparing analgesic interventions with placebo or no treatment in patients undergoing breast surgery under general anaesthesia. Primary outcome was intensity of acute pain (up to 6 hr postoperatively). Secondary outcomes were cumulative 24-hr morphine consumption, incidence of postoperative nausea and vomiting (PONV), and chronic pain. We used an original three-step approach. First, meta-analyses were performed when data from at least three trials could be combined; secondly, trial sequential analyses were used to separate conclusive from unclear evidence. And thirdly, the quality of evidence was rated with GRADE.Seventy-three trials (5,512 patients) tested loco-regional blocks (paravertebral, pectoralis), local anaesthetic infiltrations, oral gabapentinoids or intravenous administration of glucocorticoids, lidocaine, N-methyl-D-aspartate antagonists or alpha2 agonists. With paravertebral blocks, pectoralis blocks and glucocorticoids, there was conclusive evidence of a clinically relevant reduction in acute pain (visual analogue scale > 1.0 cm). With pectoralis blocks, and gabapentinoids, there was conclusive evidence of a reduction in the cumulative 24-hr morphine consumption (> 30%). With paravertebral blocks and glucocorticoids, there was conclusive evidence of a relative reduction in the incidence of PONV of 70%. For chronic pain, insufficient data were available.Mainly with loco-regional blocks, there is conclusive evidence of a reduction in acute pain intensity, morphine consumption and PONV incidence after breast surgery. For rational decision making, data on chronic pain are needed.This quantitative systematic review compares eight interventions, published across 73 trials, to prevent pain after breast surgery, and grades their degree of efficacy. The most efficient interventions are paravertebral blocks, pectoralis blocks and glucocorticoids, with moderate to low evidence for the blocks. Intravenous lidocaine and alpha2 agonists are efficacious to a lesser extent, but with a higher level of evidence. Data for chronic pain are lacking.
Abstract Ketamine is often added to opioids in patient-controlled analgesia devices. We tested whether in surgical patients, ketamine added to an opioid patient–controlled analgesia decreased pain intensity by ≥25%, cumulative opioid consumption by ≥30%, the risk of postoperative nausea and vomiting by ≥30%, the risk of respiratory adverse effects by ≥50%, and increased the risk of hallucination not more than 2-fold. In addition, we searched for evidence of dose-responsiveness. Nineteen randomized trials (1349 adults, 104 children) testing different ketamine regimens added to various opioids were identified through searches in databases and bibliographies (to 04.2016). In 9 trials (595 patients), pain intensity at rest at 24 hours was decreased by 32% with ketamine (weighted mean difference −1.1 cm on the 0-10 cm visual analog scale [98% CI, −1.8 to −0.39], P < 0.001). In 7 trials (495 patients), cumulative 24 hours morphine consumption was decreased by 28% with ketamine (weighted mean difference −12.9 mg [−22.4 to −3.35], P = 0.002). In 7 trials (435 patients), the incidence of postoperative nausea and vomiting was decreased by 44% with ketamine (risk ratio 0.56 [0.40 to 0.78], P < 0.001). There was no evidence of a difference in the incidence of respiratory adverse events (9 trials, 871 patients; risk ratio 0.31 [0.06 to 1.51], P = 0.08) or hallucination (7 trials, 690 patients; odds ratio 1.16 [0.47 to 2.79], P = 0.70). Trial sequential analyses confirmed the significant benefit of ketamine on pain intensity, cumulative morphine consumption, and postoperative nausea and vomiting and its inability to double the risk of hallucination. The available data did not allow us to make a conclusion on respiratory adverse events or to establish dose-responsiveness.
Background Dr. Scott Reuben allegedly fabricated data. The authors of the current article examined the impact of Reuben reports on conclusions of systematic reviews. Methods The authors searched in ISI Web of Knowledge systematic reviews citing Reuben reports. Systematic reviews were grouped into one of three categories: I, only cited but did not include Reuben reports; II, retrieved and considered, but eventually excluded Reuben reports; III, included Reuben reports. For quantitative systematic reviews (i.e., meta-analyses), a relevant difference was defined as a significant result becoming nonsignificant (or vice versa) by excluding Reuben reports. For qualitative systematic reviews, each author decided independently whether noninclusion of Reuben reports would have changed conclusions. Results Twenty-five systematic reviews (5 category I, 6 category II, 14 category III) cited 27 Reuben reports (published 1994-2007). Most tested analgesics in surgical patients. One of 6 quantitative category III reviews would have reached different conclusions without Reuben reports. In all 6 (30 subgroup analyses involving Reuben reports), exclusion of Reuben reports never made any difference when the number of patients from Reuben reports was less than 30% of all patients included in the analysis. Of 8 qualitative category III reviews, all authors agreed that one would certainly have reached different conclusions without Reuben reports. For another 4, the authors' judgment was not unanimous. Conclusions Carefully performed systematic reviews proved robust against the impact of Reuben reports. Quantitative systematic reviews were vulnerable if the fraudulent data were more than 30% of the total. Qualitative systematic reviews seemed at greater risk than quantitative.
The PartnerREC network at the Geneva University Hospitals aims to facilitate the collaboration between researchers and patient partners in any type of clinical research, mainly those led at the HUG. It is the result of a coconstruction process initiated in 2019 by physicians, research professionals, cantonal research ethics committee members, a lawyer, and patient partners. The network implemented four initiatives: a) a website providing information to researchers and patients participating to research projects; b) personalized counseling for researchers to explore partnership opportunities in their own research projects; c) a training program related to patient partnership in research developed together with different partners in French-speaking Switzerland and d) its own research program on partnership in clinical research.
Failure to report complete and important information regarding the design and conduct of a clinical experimental or observational study decreases the informative value and usefulness of a publication.1,2 To try to overcome this significant problem, guidelines have been developed which aim to help authors of research articles to report their findings clearly and completely. One of the first guidelines which was developed was the CONsolidated Standards Of Reporting Trials (CONSORT) statement for the reporting of randomised controlled trials (RCTs) which has been endorsed by many scientific journals. Since then, other guidelines have been, and continue to be, established and promoted to improve the completeness of reporting of various study designs. The Enhancing the QUAlity and Transparency Of health Research (EQUATOR) network (http://www.equator-network.org/home/) has been working very hard to improve the quality of research reporting. This international initiative, which brings together researchers, peer-reviewers, journal editors and guideline developers, has emerged following the work initiated by the CONSORT group. From 2006, EQUATOR has centralised most of what has been achieved around the theme of ‘good and transparent research reporting’. The EQUATOR website has become an extraordinary source of precious information for researchers, peer-reviewers and journal editors. We can only encourage authors who wish to publish their work in the European Journal of Anaesthesiology to spend some time on the EQUATOR website to grasp an idea of the extent of the educational material which is now (freely) available. Almost everything you need to know about the adequate reporting of a research article may be found through the EQUATOR network. However, to remain practical and oriented towards the European Journal of Anaesthesiology, we shall briefly describe a few guidelines which focus on the design of articles that are most commonly published in the journal. In a previous Editorial, we described the adherence of our authors to the CONSORT statement.3 We screened all the issues of the European Journal of Anaesthesiology from January 2010 to December 2010 and found 129 original research articles, 50 of which (39%) were RCTs. Only 12 of the 50 RCTs (24%) reported at least 50% of the CONSORT items which led us to conclude that there was room for improvement.3 For the purpose of the present essay, we broaden the issue of adequate data reporting to all 129 original research articles. In addition to the 50 RCTs, there were 26 (20.1%) cohort studies, 21 (16.3%) animal studies and nine (7.0%) surveys; the remaining 23 reports (17.8%) included studies on diagnostic accuracy, cross-sectional and case–control trials, case series and systematic reviews with or without meta-analyses (Table 1).Table 1: Designs of reports of original research published in the European Journal of Anaesthesiology in 2010Specific reporting guidelines are available for each of these study designs (Table 2).4–6 These can be summarised briefly as follows.Table 2: Reporting guidelines for various forms of study design: links and referencesThe reporting guideline for RCTs is the CONSORT statement, an evidence-based, 25-item set of recommendations which are summarised in a ‘checklist’, with instructions on how to draw a flow diagram. Each item of the CONSORT statement is described clearly, with helpful examples in an ‘Explanation and Elaboration’ document which is freely accessible online (http://www.consort-statement.org/consort-statement/). The main CONSORT statement provides advice for the reporting of a standard two-group, parallel, randomised study design. Extensions to the CONSORT statement are available for slightly different designs such as cluster or equivalence designs and for trials reporting on non-pharmacological interventions, or on harm. An extension also exists regarding what to include in an abstract.7 The CONSORT statement changes as new evidence emerges; the last version to date is CONSORT 2010. We encourage authors of RCTs to consult the CONSORT website for up-to-date information. The recommended reporting guideline for cohort studies is the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement. This 22-item list is available on http://www.strobe-statement.org/. STROBE provides checklists for two additional major observational study designs, the case–control and cross-sectional design, and a checklist for the reporting of conference abstracts. Although some overlap exists between these different reporting guidelines, some issues are very specific to a given study architecture. These checklists are updated regularly in response to new emerging evidence as well as comments and critiques from users. The STROBE statement has been endorsed by a growing number of journals and is available from the website in many languages including Chinese, Spanish, German, Italian, Japanese, Persian and Portuguese. The Animal in Research: Reporting In Vivo Experiments (ARRIVE) guideline focuses on specific ethical and technical problems encountered in animal research. Obviously, this guideline addresses issues which are quite different from guidelines dealing with clinical research, such as the description of housing, type of cage, number of animals per cage and husbandry conditions. It is summarised as a 20-item checklist and is freely accessible online from the National Centre for the Replacement, Refinement and Reduction of Animals in Research in the UK (http://www.nc3rs.org.uk/page.asp?id=1357). This website also provides interesting information regarding different aspects of animal research (systematic reviews, experimental designs, pilot studies). In addition to the ARRIVE guidelines, the Gold Standard Publication Checklist (GSPC) for animal research has been published,4 together with a Commentary in the British Journal of Pharmacology.8 GSPC provides an even more detailed checklist of what should be included in reports of animal research with the aim of standardising data reporting in order to facilitate systematic reviews and meta-analyses in this area. Both guidelines pay particular attention to the need for justification of the use of animals for research. Interesting guidelines for the conduct and implementation of survey research were published in 2003,5 and more recently by the Canadian Medical Association in 2008.6 Although these articles do not focus exclusively on data reporting, the first provides an 18-item checklist of key points which need to be covered when reporting a survey. Some of these items are very specific to this study design, such as ‘how many and what type of attempts were made to contact subjects?’ or ‘what was the response rate?’. Other study designs published in the European Journal of Anaesthesiology in 2010 for which specific reporting guidelines exist included studies of diagnostic accuracy (STAndard for the Reporting of Diagnostic accuracy studies, STARD; http://www.stard-statement.org/), systematic reviews and meta-analyses (Preferred Reporting Items for Systematic reviews and Meta-Analyses, PRISMA; http://www.prisma-statement.org/) and further observational studies which are covered by STROBE as discussed above. All these guidelines, as well as many others, may be found through the EQUATOR website (http://www.equator-network.org/home/). The aim of this short essay is to remind readers, authors and peer-reviewers of the European Journal of Anaesthesiology that guidelines for data reporting are available. Events are moving fast in this area and we strongly encourage authors who are planning to submit a research article to the journal to spend some time visiting the EQUATOR website for recent updates and, most of all, to use these guidelines when writing their manuscripts. We also strongly encourage peer-reviewers to use these guidelines when reviewing research articles for us in order to help authors to complete missing, potentially important, information and, thus, to improve the quality and completeness of data reporting. Critics may argue that the strict and standardised formatting of research articles will eventually kill the creativity of authors. However, we do not believe that a research article is the appropriate place to express ‘creativity’ which should be left to authors of Editorials, Commentaries, Letters to the Editor or perhaps narrative, conventional, non-systematic reviews. When it comes to the reporting of a scientific experiment, performed in humans or animals, we need clarity, completeness and transparency to ensure that the methods are reproducible and that the reported data are informative, valid and useful for clinical decision making. This is why guidelines on adequate data reporting have been created and made available. Use them. Acknowledgements Assistance with the Editorial: none declared. Sources of funding: none declared. Conflicts of interest: none declared. NE and MRT are Editors of the European Journal of Anaesthesiology. Comment from the Editor: This article was checked and accepted by the Editors, but was not sent for external peer-review.
