BMJ Open BMJ Open: first published as 10.1136/bmjopen-2016-015002 on 4 May 2017. Downloaded from Non-steroidal anti-inflammatory drugs (NSAIDS) versus opioids (update) and NSAIDS versus paracetamol in the management of acute renal colic-Protocol for a systematic review and meta-analysis For peer review only Journal: BMJ Open Manuscript ID bmjopen-2016-015002 Article Type: Protocol Date Submitted by the Author: 01-Nov-2016 Complete List of Authors: Pathan, Sameer; Hamad Medical Corp, Emergency Department; Monash University School of Public Health and Preventive Medicine, Mitra, Biswadev; Monash University, Romero, Lorena ; The Ian Potter Library, Ground Floor, AMREP Building, The Alfred Cameron, Peter; Monash University, Department of Epidemiology and Preventive Medicine <b>Primary Subject Emergency medicine Heading</b>: Secondary Subject Heading: Evidence based practice, Medical management, Urology http://bmjopen.bmj.com/ Renal colic, Urolithiasis < UROLOGY, NSAIDS, Paracetamol, Opioids, Keywords: Analgesia on September 25, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 21 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2016-015002 on 4 May 2017. Downloaded from 1 2 3 Non-steroidal anti-inflammatory drugs (NSAIDS) versus opioids (update) and NSAIDS 4 5 versus paracetamol in the management of acute renal colic-Protocol for a systematic 6 7 review and meta-analysis 8 9 10 Authors’ names and degrees 11 1,2,3 12 1. Dr. Sameer A. Pathan MBBS, CABEM, MRCEM 13 2,3,4 14 2. A/Prof. Biswadev Mitra MBBS, MHSM, PhD, FACEM 15 For peer5 review only 16 3. Ms. Lorena Romero BA, MBIT 17 2,3,4 18 4. Prof. Peter A. Cameron MBBS, MD, FACEM 19 20 21 Affiliations 22 23 1 Emergency Department, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar 24 2 25 Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia. 26 3 National Trauma Research Institute, The Alfred Hospital, Melbourne, Australia. 27 4 28 Emergency & Trauma Centre, The Alfred Hospital, Melbourne, Australia. 29 5 Alfred Health, The Ian Potter Library, Melbourne, Australia. 30 31 32 33 Corresponding author http://bmjopen.bmj.com/ 34 Dr. Sameer A. Pathan 35 36 P.O.BOX. 50107, Mesaieed Post Office, Qatar. 37 38 Email: [email protected] 39 40 Telephone: 00974 6685 7650 41 on September 25, 2021 by guest. Protected copyright. 42 43 Word count: Abstract- 300, Manuscript – 2224 44 45 46 47 Registration: This systematic review is registered on the PROSPERO international 48 49 prospective register of systematic reviews (PROSPERO 2016:CRD42016047559). 50 51 Amendments: Any change(s) in the protocol will be updated in the PROSPERO registry. 52 The amendments will be accompanied by the information regarding time, date, 53 54 description of changes, and rationally behind the changes made. 55 56 Support: This systematic review is non-funded. 57 58 59 60 1 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 21 BMJ Open: first published as 10.1136/bmjopen-2016-015002 on 4 May 2017. Downloaded from 1 2 3 ABSTRACT 4 5 Introduction 6 7 Patients with renal colic, present to the emergency department in excruciating pain. 8 9 There is uncertainty and wide variability among the choice of initial analgesic to be used 10 11 in renal colic. The aim of this review is to assess the efficacy and safety of NSAIDS, 12 13 opioids, and paracetamol use in renal colic pain management. 14 15 Methods andFor analysis peer review only 16 17 This is the protocol for a systematic review, comparing efficacy of NSAIDS, opioids, and 18 19 paracetamol in renal colic studied under randomized controlled trial design. We will 20 conduct a comprehensive literature search for both peer-reviewed and grey literature 21 22 published until 1st October 2016. Using a predefined search strategy MEDLINE, Embase, 23 24 Cochrane Central Register of Controlled Trials will be searched. Additional searches will 25 26 include WHO International Clinical Trials Registry Platform, abstract list of relevant 27 28 major conferences and the reference lists of relevant publications. Two authors will 29 30 independently screen and identify the studies to be included. The RCT comparing 31 32 NSAIDS versus opioids or paracetamol will be included in the review, if the age of 33 http://bmjopen.bmj.com/ 34 participants in the study was >16 years, and they presented with moderate to severe 35 renal colic. Any disagreement between the screening authors will be resolved through 36 37 discussion and reaching to consensus, if not, a third reviewer will arbitrate. Quantitative 38 39 data from homogenous studies will be pooled in the meta-analysis using RevMan 5.3 40 41 software. The findings of this review will be presented according to guidelines in the on September 25, 2021 by guest. Protected copyright. 42 43 Cochrane Handbook of Systematic Reviews of Interventions and PRISMA statement. 44 45 Ethics and dissemination 46 47 Formal ethics approval is not required for a systematic review. We plan to publish the 48 49 result of this review in a peer-review journal. We believe that the results of this review 50 51 will provide robust evidence in deciding superiority among commonly used analgesics, 52 and help to improve guidance for protocolised analgesia in renal colic. 53 54 55 56 57 58 59 60 2 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 21 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2016-015002 on 4 May 2017. Downloaded from 1 2 3 INTRODUCTION 4 5 6 Kidney stones are very common in the “stone belt” region, which extends over America 7 8 (Southeast), Africa (North), Middle East, Asia (Southeast), and Australia (Northeast). 1 9 10 Globally, the lifetime prevalence of stone disease is 10-15%, and it counts for millions of 11 1 2 12 patient visits to the emergency departments (ED) or the outpatient clinics. The acute 13 14 painful presentation is commonly known as renal colic, and movement of stone in the 15 For peer review only 16 urinary tract produce this excruciating pain. The National Health Service (NHS) England, 17 18 statistics for year 2012-13, estimated the cost for renal colic was nearly £20 million, 19 3 20 where median patient stay in the hospital was 1 day. In the management of renal colic, 21 one of the priorities in the ED is to provide quick, safe and effective analgesia to the 22 23 patients. 24 25 26 27 The most commonly prescribed analgesics in renal colic are non-steroidal anti- 28 4 5 29 inflammatory drugs (NSAIDS), opioids and paracetamol. The important factors in the 30 31 selection of first-line analgesic in ED are efficacy, safety, the ease and rapid 32 33 administration, and the logistics involved around it. Effective ongoing analgesia can be http://bmjopen.bmj.com/ 34 35 practically challenging to deliver in an ED with a diverse population, and a high volume 36 of patients being managed concurrently.6 The previously published meta-analysis 37 38 comparing NSAIDS with opioids suggested NSAIDS to be better than opioids in terms of 39 40 requiring lesser rescue analgesia and having fewer side effect. However, it did not 41 on September 25, 2021 by guest. Protected copyright. 42 establish superior efficacy of either drug group.5 7 The use of intravenous opioids, as the 43 44 first-line analgesic in renal colic, continues to be a common practice in many developed 45 46 countries. However, the logistical delay involved in intravenous administrations, dose- 47 48 dependent side-effects, need for titrating dosage, and overly bureaucratic restrictions 49 50 are some of the challenges associated with the IV opioid use as the first-line analgesic in 51 8 9 10 52 the busy ED. Routine use of NSAIDS has been limited because of the fear of 53 gastrointestinal (GI) and renal complications. In addition, there has been undue 54 55 emphasis placed on the possibility of abscess and muscle necrosis secondary to 56 57 intramuscular injection, given the extremely low level of documented cases. 58 59 60 3 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 21 BMJ Open: first published as 10.1136/bmjopen-2016-015002 on 4 May 2017. Downloaded from 1 2 3 4 5 The obvious limitations of previous studies and systematic reviews may partly explain 6 7 the continued clinical orthodoxy of intravenous opioid use as the first analgesic in many 8 9 settings. Firstly, this review was conducted and published in 2004 and the studies 10 11 included were published between 1982-1999. 5 In the last 15 years, newer, well 12 13 powered, pragmatic, clinical trials have been published with clinically relevant outcomes 14 15 in renal colicFor management. peer Secondly, reviewmost studies in the reviewonly only included patients 16 17 who had confirmed renal calculi on subsequent testing. This may limit the applicability 18 19 of evidence in routine clinical practice where patients are treated with a clinical picture 20 of renal colic well before any imaging can be performed. Thirdly, significant 21 22 heterogeneity between the studies included, did not allow pooled analysis to conclude 23 24 the superiority of a drug based on efficacy. 4 5 A pooled analysis of NSAIDS other than 25 26 Ketorolac in the review showed pain reduction of 4.6mm (on VAS 0-100) only, which is 27 11 28 minimal compared to the newer trial results. Fourthly, as 12 of the 20 included trials 29 30 used pethidine as their opioid arm, which is not a commonly used opioid in current 31 5 32 practice.