Emergency. 2017; 5 (1): e82 http://dx.doi.org/10.22037/emergency.v5i1.18894 OR I G I N A L RE S E A RC H Intravenous Lidocaine Compared to Fentanyl in Renal Colic Pain Management; a Randomized Clinical Trial Hassan Motamed1, Mohammadreza Maleki Verki1∗ 1. Emergency Medicine Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Received: September 2017; Accepted: October 2017; Published online: 23 October 2017 Abstract: Introduction: Using alpha blockers such as intravenous (IV ) lidocaine has been deemed effective in controlling acute pain. Therefore, the current study was designed with the aim of evaluating the efficiency of IV lidocaine in comparison to IV fentanyl in pain management of patients with renal colic in emergency department (ED). Methods: In this double blind clinical trial, 18-65 year old patients that presented to ED with colicky flank pain and met the inclusion criteria of the study were allocated to either lidocaine or fentanyl group using block ran- domization and compared regarding pain severity 5, 10, 15, and 30 minutes after drug administration. Results: 90 patients with the mean age of 35.75±8.87 years were divided into 2 groups of 45 (90% male). The 2 groups were not significantly different regarding the studied baseline variables. Pain severity was not significantly dif- ferent between the 2 groups at various times after injection. Treatment failure rate 15 minutes after injection was 44.4% (20 cases) in IV lidocaine and 17.8% (8 cases) in IV fentanyl group (p = 0.006). These rates were 26.6% (12 patients) versus 22.2% 30 minutes after injection (p = 0.624). Absolute risk increase of treatment failure in case of using lidocaine was 26.7 (95% CI: 8.3-44.9) in the 15th minute and 4.4 (95% CI: 13.3-22.2) 30 minutes after injection. Number needed to harm (NNH) in treatment with lidocaine 15 and 30 minutes after injection were 4 (95% CI: 2.2-12.0) and 23, respectively. Conclusion: Although mean pain severity was not significantly different between IV fentanyl and lidocaine at various times after injection, treatment failure rate was significantly higher in the IV lidocaine group 15 minutes after injection. Keywords: Fentanyl; lidocaine; renal colic; pain management; analgesia; emergency service, hospital © Copyright (2017) Shahid Beheshti University of Medical Sciences Cite this article as: Motamed H, Maleki Verki M. Intravenous Lidocaine Compared to Fentanyl in Renal Colic Pain Management; a Random- ized Clinical Trial. Emergency. 2017; 5(1): e82. 1. Introduction R Renal colic is one of the most common clinical mani- festations of a stone being present in the urinary sys- tem, which presents as sudden and severe flank pain (1). In the United States, the prevalence of renal colic has in- creased from 5.2% during 1994-1998 to 8.8% in 2007-2010 (2, 3). One of the major duties of emergency department (ED) is reducing patients’ pain and suffering before taking any treat- ment or surgical measures. Recently, using alpha blockers such as intravenous (IV ) lido- caine, nifedipine and nerve blockers in the intercostal area has been deemed effective in reducing renal colic pain (4-6). When narcotic drugs lack the required effectiveness and lead ∗Corresponding Author: Mohammadreza Maleki Verki; Emergency Depart- ment, Golestan Hospital, Ahvaz, Iran. Tel: 00989122782787 Email: dr- malaki676@yahoo.com to undesirable side effects, lidocaine can be a good choice. IV lidocaine has been deemed effective in controlling neuro- pathic pains such as diabetic neuropathy, post-surgery pains, bone fracture pain, headache and nervous system malignan- cies (7-10). Continuous infusion of IV lidocaine during and after abdominal surgery has accelerated patient recovery and reduced length of hospital stay (11). Using opioids has some dangers due to reasons such as in- hibition of respiratory center in medulla region and activa- tion of vomiting center (12). These drugs are used as an ap- propriate analgesic in ED either alone or along with mida- zolam (13). Finding an effective analgesic with minimal side effects has been continuously desired by the physicians in- volved with these patients. Therefore, the current study was designed with the aim of evaluating the efficiency of IV lido- caine in comparison to IV fentanyl in pain management of patients with renal colic. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com H. Motamed and M. Maleki Verki 2 2. Methods 2.1. Study design and setting In this double blind clinical trial, the effectiveness of IV lido- caine and IV fentanyl was evaluated and compared in pain management of patients with renal colic admitted to ED of Golestan Hospital, Ahwaz, Iran, in 2015. The study was ap- proved by the ethics committee of Ahwaz University of Med- ical Sciences under the number “ajums.REC.1392.324” and the researchers adhered to all the principles stated in the dec- laration of Helsinki regarding ethical practice and confiden- tiality of patient data. Informed consent was obtained from all the participants for taking part in the study. All the ex- penses of patients’ treatment were covered by the project ex- ecutive and no additional fees were inflicted upon the pa- tients. This study was registered on the Iranian registry of clinical trials under the number IRCT2017081415446N12. 2.2. Participants Patients in the 18-65 years age range that had presented to the ED with colicky flank pain and lacked histories such as: cardiac dysrhythmia and ischemia, parenchymal tissue problems in liver and kidney, and history of using mono amino oxidase (MAO) inhibitor drugs in the last 2 weeks, were included in the study. In addition, patients with a his- tory of allergy to morphine or other opiates, definite or pos- sible pregnancy, lactating women, addiction to opiates, and receiving analgesics in the last 6 hours were excluded from the study. To confirm absence of dysrhythmia or underly- ing ischemic disease, electrocardiogram was used on admis- sion. All the clinical examinations were done by 2 physicians, one senior resident of emergency medicine and one senior resident of urology. Clinical diagnoses were confirmed by performing ultrasonography or spiral computed tomography (CT) scan, or presence of hematuria in urinalysis after man- agement of the patient’s pain and those who did not have definitive evidence of stone in evaluations were excluded from the study. 2.3. Intervention Patients were allocated to a group receiving either lidocaine (1.5 mg/kg) or fentanyl (1.5 µg/kg) via block randomiza- tion. Drug prescriptions were as IV infusion during 2 minutes while patients were under cardiac monitoring. For patients who still had moderate to severe pain 30 minutes after injec- tion, morphine sulfate with the standard dose of 0.1 mg/kg was prescribed as additional analgesic. The physician pre- scribing the drug and the patient were blind to the prescribed drug. Drugs were prepared by a nurse in syringes with the same volume and color in the absence of the physician and were then given to the physician. Figure 1: Comparison of pain severity between the 2 studied groups 5 (p = 0.113), 10 (p = 0.056), 15 (p = 0.137) and 30 (p = 0.291) minutes after drug injection. 2.4. Outcome The primary outcome of this study was evaluating the pain score of patients based on visual analog pain scale (VAS) 5, 10, 15, and 30 minutes after injection. 3 points pain reduction based on VAS was considered as clinically significant pain re- duction. Therefore, lack of 3 points pain reduction 15 and 30 minutes after injection were considered as treatment failure. 2.5. Data gathering Demographic data (age, sex, weight) and data regarding pain severity on admission to ED and 5, 10, 15, and 30 minutes after injection were gathered using a checklist. The senior emergency medicine resident was responsible for data gath- ering and was blind to the drug received by the patient. 2.6. Statistical Analysis Sample size was estimated to be 40 for each group consider- ing 95% confidence interval and type 2 error of 0.2% (4). Data analysis was done using SPSS 21 software. Quantitative data were reported based on mean ± standard deviation and qual- itative ones based on frequency and percentage. Chi square test, Fisher’s exact test and t-test were used for comparisons. P values less than 0.05 were considered significant. 3. Results 3.1. Baseline characteristics 90 patients with the mean age of 35.75±8.87 years (20-55) were randomly divided into 2 groups of IV lidocaine (45 pa- tients) and IV fentanyl (45 patients) (90% male). Table 1 has compared the baseline characteristics of the 2 groups. As can be seen, the 2 groups are not significantly different regarding studied baseline variables. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 3 Emergency. 2017; 5 (1): e82 Table 1: Comparison of baseline characteristics between the 2 studied groups Variable IV fentanyl IV lidocaine P value Sex Male 39 (86.7) 42 (93.3) 0.292 Female 6 (13.3) 3 (6.7) Age (year) 39.08 ± 6.64 34.08 ± 9.49 0.112 Weight (kg) 80.93 ± 15.27 82.85 ± 15.83 0.572 Pain severity on admission Moderate 2 (4.4) 2 (4.4) 1.000 Severe 43 (95.6) 43 (95.6) Data are presented as frequency (%) or mean ± standard deviation. IV: intravenous. Table 2: Comparison of pain severity between the 2 studied groups at various times after drug injection Time IV fentanyl IV lidocaine P value 5 minutes Mild 8 (17.8) 7 (15.6) 0.302 Moderate 17 (37.8) 11 (24.4) Severe 20 (44.4) 27 (60.0) 10 minutes Mild 14 (31.1) 11 (24.4) 0.310 Moderate 18 (40.0) 14 (31.1) Severe 13 (28.9) 20 (44.4) 15 minutes Mild 20 (44.4) 14 (31.1) 0.405 Moderate 14 (31.1) 16 (35.6) Severe 11 (24.4) 15 (33.3) 30 minutes Mild 25 (55.6) 22 (48.9) 0.679 Moderate 7 (15.6) 10 (22.2) Severe 13 (28.9) 13 (28.9) Data are presented as frequency (%). IV: intravenous. 3.2. Pain management Table 2 and figure 1 compare pain severity between the 2 groups 5, 10, 15, and 30 minutes after drug injection. Pain severity was not significantly different between the 2 groups at various times after injection. Treatment failure rate 15 minutes after injection was 44.4% (20 cases) in IV lidocaine and 17.8% (8 cases) in IV fentanyl group (p = 0.006). These rates were 26.6% (12 cases) versus 22.2% (10 cases), 30 min- utes after injection (p = 0.624). Therefore, the absolute risk increase of treatment failure in case of using lidocaine was 26.7 (95% CI: 8.3-44.9) in the 15th minute and 4.4 (95% CI: 13.3-22.2) 30 minutes after injection. Number needed to harm (NNH) in treatment with lidocaine 15 and 30 minutes after injection were 4 (95% CI: 2.2-12.0) and 23, respectively. 4. Discussion Based on the findings of the present study, although mean pain severity was not significantly different between IV fen- tanyl and IV lidocaine groups at various times after injec- tion, treatment failure rate was significantly higher in the li- docaine group 15 minutes after injection. In addition, the absolute risk increase of treatment failure in case of using lidocaine 15 and 30 minutes after injection were 26.7 and 4.4 percent, respectively. Renal colic is caused due to increased pressure in the upper urinary tract or dilatation of kidney capsule following urinary retention. In a study by Khaniha et al. on evaluating the effect of various drugs in relieving renal colic, the results showed that pethi- dine 10 to 45 minutes after injection, methadone 30-60 min- utes and morphine 1.5 to 30 minutes after injection showed their analgesic effects (14). Using intranasal fentanyl led to an effective sedation in pa- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com H. Motamed and M. Maleki Verki 4 tients 30 minutes after administration (15). In another study that had compared the effectiveness of lidocaine and mor- phine, the findings showed that lidocaine is a safe, effective and cheap method for induction of analgesia in patients with renal colic compared to morphine, which lacks the side ef- fects of morphine such as nausea and vomiting. Time needed for induction of analgesia when using morphine alone and morphine with lidocaine were reported to be 100 and 87 min- utes after injection, respectively (16). In another study, 240 patients aged 18 to 65 years presenting to Imam Reza Hospi- tal, Tabriz, Iran, with renal colic were randomly divided into 2 groups receiving either IV morphine or IV lidocaine. The results indicated effectiveness of IV lidocaine in comparison to morphine (4). Based on the results of this study, it seems that IV lidocaine has proper ability in controlling renal colic during 30 min- utes. However, if the speed of analgesia induction is of higher priority for the physician and patient compared to probable side effects, considering the high rate of treatment failure of IV lidocaine in 15 minutes (44.4% vs 17.8% for fentanyl), it cannot be a good choice for this purpose. 5. Limitation Stone size, history of kidney stone, and ethnic characteris- tics were not evaluated in this study, but they may affect pain severity and response to analgesics used. 6. Conclusion The absolute risk increase of renal colic management failure with IV lidocaine 15 and 30 minutes after injection were 26.7 and 4.4, respectively. It seems that IV lidocaine cannot be a good choice when quick pain control is of higher priority for the physician. 7. Appendix 7.1. Acknowledgements All staffs who helped to establish the trial, are acknowledged. 7.2. Author contribution All the authors met the standard criteria of authorship based on the recommendations of international committee of med- ical journal editors. 7.3. Funding/Support No funds have been received for doing this project. 7.4. Conflict of interest Hereby the authors declare that there is no conflict of interest regarding the present study. References 1. Edwards J, Sloan E, Eder S, Chan S. Renal colic patient pain management in the emergency department. Annals of Emergency Medicine. 2004;44(4):S58. 2. Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC. Time trends in reported prevalence of kid- ney stones in the United States: 1976–1994. Kidney inter- national. 2003;63(5):1817-23. 3. Scales CD, Smith AC, Hanley JM, Saigal CS, Project UDiA. Prevalence of kidney stones in the United States. Euro- pean urology. 2012;62(1):160-5. 4. Soleimanpour H, Hassanzadeh K, Vaezi H, Golzari SE, Esfanjani RM, Soleimanpour M. Effectiveness of intra- venous lidocaine versus intravenous morphine for pa- tients with renal colic in the emergency department. BMC urology. 2012;12(1):13. 5. Dellabella M, Milanese G, Muzzonigro G. Random- ized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol in medical expulsive therapy for distal ureteral calculi. The Journal of urology. 2005;174(1):167- 72. 6. Iguchi M, Katoh Y, Koike H, Hayashi T, Nakamura M. Ran- domized trial of trigger point injection for renal colic. In- ternational journal of urology. 2002;9(9):475-9. 7. Barzegari H, Motamed H, Ziapour B, Hajimohammadi M, Kadkhodazadeh M. Intranasal Lidocaine for Primary Headache Management in Emergency Department; a Clinical Trial. Emergency. 2017;5(1):e79. 8. Ferrini R, Paice J. How to initiate and monitor infusional lidocaine for severe and/or neuropathic pain. The jour- nal of supportive oncology. 2004;2(1):90. 9. Afhami M, Salmasi P. Studying analgesic effect of preinci- sional infiltration of lidocaine as a local anesthetic with different concentrations on postoperative pain. Pak J Med Sci. 2009;25(5):821-4. 10. Forouzan A, Barzegari H, Motamed H, Khavanin A, Shiri H. Intravenous Lidocaine versus Morphine Sulfate in Pain Management for Extremity Fractures; a Clinical Trial. Emergency. 2017;5(1):e68. 11. Marret E, Rolin M, Beaussier M, Bonnet F. Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. British Journal of Surgery. 2008;95(11):1331-8. 12. Ockerblad NF, Carlson HE, Simon JF. The Effect of Mor- phine Upon the Human Ureter. The Journal of Urology. 1935;33(4):356-62. 13. Marx J, Walls R, Hockberger R. Rosen’s Emergency Medicine-Concepts and Clinical Practice E-Book: Else- vier Health Sciences; 2013. 14. Khaniha RB, Safarinezhad MR, Markazi Moghadam N, Valimanesh HA, Abd Elahian M. The comparison of the This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 5 Emergency. 2017; 5 (1): e82 efficacy of common pain management in acute renal colic. Annals of Military and Health Sciences Research 2004;2(3):381-6. 15. Belkouch A, Zidouh S, Rafai M, Chouaib N, Sirbou R, El- bouti A, et al. Does intranasal fentanyl provide efficient analgesia for renal colic in adults? The Pan African med- ical journal. 2015;20. 16. Firouzian A, Alipour A, Dezfouli HR, Kiasari AZ, Baradari AG, Zeydi AE, et al. Does lidocaine as an adjuvant to morphine improve pain relief in patients presenting to the ED with acute renal colic? A double-blind, random- ized controlled trial. The American journal of emergency medicine. 2016;34(3):443-8. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com Introduction Methods Results Discussion Limitation Conclusion Appendix References