942 | 1Department of Urologic Surgery, Henan Provincial People's Hospital, 7 Weiwu Road, Zhengzhou, Henan, China 2Yun-Jiang Zang, Depart- ment of Urologic Surgery, Weifang People's Hospital, 151 Guangwen Street, Kuiwen District, Weifang, Shandong, China Jianjun Liu,1 Yun-Jiang Zang2 Comparative Study between Three Analgesic Agents for the Pain Management during Extracorporeal Shock Wave Lithotripsy Corresponding Author: Yun-Jiang Zang, MD Department of Urologic Surgery, Weifang People's Hospital, 151 Guangwen Street, Kuiwen District, Wei- fang, Shandong, China Tel: +13869652099 E-mail: yunshanzang@ gmail.com Received June 2012 Accepted January 2013 Purpose: To compare the clinical efficacy between locally applied diclofenac diethylamine gel, EMLA cream and systemically given diclofenac sodium for the pain relief during extracorporeal shock wave lithotripsy (SWL) using Dornier Delta Compact Lithotripter. Material and Methods: One hundred five patients with renal stones were randomly divided in to 3 groups. Group A was given intramuscular diclofenac sodium (1 mg/kg), 45 minutes before the procedure. In group B, 10 gm of eutectic mixture of local anesthetic (EMLA) cream and in group C, 15 gm of diclofenac diethylamine gel was applied locally 45 minutes before the procedure. Ten-score linear and visual analogue scale (VAS) was used to assess the severity of pain during the procedure. Analysis of variance (ANOVA) test was used to compare various parameters and analyzed statistically. Results: All the three groups were not statistically different with respect to age, weight, stone size, number of shock wave delivered and maximum voltage used (P > .05). The mean pain score in group A was 4.48, in group B was 3.60 and in group C was 3.95, which were not significantly different (P = 1.34). Complication like skin lesion was found only in injection diclofenac sodium group whereas cold sensation at the local site was typically found in diclofenac diethylamine gel group. Conclusion: Although not statistically significant, the mean pain score in locally applied analgesic agents (EMLA and diclofenac diethylamine gel) is lower as compared to intramuscularly given di- clofenac sodium. Among these two locally acting drugs, diclofenac diethylamine gel is an equally effective alternative to EMLA. ENDOUROLOGY AND STONE DISEASE Endourology and Stone Disease 943Vol. 10 | No. 3 | Summer 2013 |U R O LO G Y J O U R N A L INTRODUCTION Extracorporeal shock wave lithotripsy (SWL) is well known for its noninvasiveness, effectiveness and minimal morbidity for the management of re- nal and ureteric stones.(1,2) Older lithotripter were associ- ated with more pain as compared to modern day lithotripter and it was impossible to carry out stone fragmentation with- out the need of anesthesia, now with the advent of mod- ern lithotripters we can break the stones even on outpatient basis. Although the pain intensity and severity has been decreased from original HM3 lithotripter to present day modern lithotripter, still most of the patients require some form of analgesic agents to decrease their pain during SWL. Various analgesics and anesthetics agent has been tried to decrease pain, still we don’t have any guidelines for the pain management.(3,4) The present study aimed to compare the clinical efficacy between the three drugs, two of which are applied locally at the site of the entry of shock wave like Eutectic mixture of local anesthetic agents (EMLA) cream and diclofenac diethylamine gel, third drug is diclofenac sodium which is given intramuscularly. This study is using locally applied diclofenac diethylamine gel for the first time and compared its clinical efficacy with that of EMLA and injection di- clofenac sodium. MATERIALS AND METHODS This was a prospective and randomized study conducted in our institute from January 2011 to August 2011 after obtain- ing ethical clearance from the institute and written consent from the patients. These patients were recruited from the urology department outpatient clinic. Our institute being a secondary referral center, we get frequent cases of renal stones and so more cases of those undergoing an interven- tion for this disorder. Following inclusion criteria were used: renal stone of size less than 2cm, no previous surgery and no previous expo- sure of SWL. Exclusion criteria used in the study were: stone size more than 2cm, pregnancy, bleeding disorders, active urinary tract infection, age less than 18 years and al- lergy to one of the study medications. We recruited 105 patients out of 156 patients with renal stones fulfilling the inclusion and exclusion criteria. En- rolled patients were evaluated in detailed with clinical ex- amination, family history, baseline biological and hemato- logical tests, urine microscopy with culture and sensitivity. An intravenous urogram (IVU) was done in all the cases to assess the anatomical and functional aspects of the urinary system along with stone characteristics like stone size and position. Recruited 105 outpatients of renal stones were randomly di- vided in to three groups. Right sided renal stone was found in 54 patients and 51patient had stone on the left side. Ran- domization was done by simple randomization using the random number generator. Procedure was conducted us- ing third generation lithotripter (Dornier delta compact, Germany). Group A (n=35) were given diclofenac sodium at the dose of 1 mg/kg, intramuscularly 45 minutes before the procedure. In group B (n=34), 10 gm of eutectic mix- ture of local anaesthetic (EMLA) cream (2.5% lignocaine and 2.5% prilocaine) was applied locally at the site of the entry of shock wave, 60 minutes before the procedure. In group C (n=36), 15 gm of diclofenac diethylamine gel was applied locally at the site of the entry of shock wave, 45 minutes before the procedure. Pain assessment was done with the 10-score linear visual analogue pain scale and was compared between the three groups. Age, sex, weight, stone size, total shock waves given and voltage used for each pa- tient were recorded. Statistical analysis was done using one way ANOVA and results were compared between the three groups. A P value of less than .05 was considered to be sta- tistically significant. RESULTS The patients mean age, sex distribution in each group, weight (kg), stone size (mm), number of shock wave de- livered and voltage level used in each group was recorded and presented in Table 1. Mean VAS score in group A was 4.48 ± 2.01, in group B was 3.60 ± 2.21 and in group C was 3.95 ± 2.5, and the P-value was 1.34 (Table 2). Thus the difference was insignificant and each drug was equally effective in decreasing the pain during SWL. If we see com- plication then cold sensation at the site of the entry of shock wave was the most common complication associated with Pain Management during SWL | Liu et al 944 | diclofenac diethylamine gel. It was present in 20 out of 36 patients. Whereas skin lesion was present only in 2 out of 35 patient’s injection diclofenac sodium group, it was not seen in other two locally applied agents. DISCUSSION Extracorporeal shock wave lithotripsy (SWL) is a non- invasive and effective mode of treatment for the urinary stones. As it is associated with minimum morbidity, it can be perform in an outpatient setting. Earlier first generation lithotripter were associated with severe pain during the pro- cedure so general or regional anesthesia was considered essential, but with the advent of modern third generation lithotripter now it is possible to complete the procedure without the need of anesthesia. This general or regional anesthesia has been replaced by opioids, sedatives, non- steroidal anti-inflammatory drugs (NSIADs) and topical anesthetics. Various analgesic agents that has been tried are opioids (morphine, fentanyl, and pethidine), NSAIDS (diclofenac, ketorolac and piroxicam), local anesthetic agents like EMLA (eutectic mixture of lignocaine 2.5% and prilocaine 2.5%) and Dimethyl sulfoxide (DMSO) in combination with lignocaine and various other combination drugs. Still we don’t have any guidelines regarding the use of analge- sic agents during SWL. Opioids like fentanyl, morphine and pethidine are well established for the management of pain during SWL but they are associated with dose related profound decrease in breathing rate, tidal volume, nausea, vomiting, broncospasm and respiratory depression.(5) So to prevent these side effects various centers started using other alternatives like NSAID and topical anesthetic agents. Non steroidal anti inflammatory drugs like diclofenac sodi- um and ketorolac have been proven as effective analgesics for the pain relief during the SWL.(6) Its main action is by anti inflammatory effect secondary to prostaglandin synthe- sis inhibition. Various routes has been tried for diclofenac like oral, intramuscular and rectal, but in this study it was used as a locally applied gel for the first time.(7) In our study we used diclofenac as intramuscular injection as well as lo- cally applied gel and comparison was made among them as well as with topical EMLA cream. Kumar et al used Oral diclofenac in their study to compare it with EMLA and combination of oral diclofenac sodium and EMLA. They suggested combination of oral diclofenac and occlusive dressing of EMLA provides adequate analgesia for SWL. (8) Eryidilium et al. compared the efficacy of EMLA cream, diclofenac sodium and EMLA+ diclofenac sodium for the pain management during SWL. Their study showed that di- clofenac sodium was more effective than EMLA cream, but in our study we find both are equally effective in reducing the pain of SWL.(9) EMLA cream is a eutectic mixture of lignocaine (2.5%) and prilocaine (2.5%), and has been used as topical anesthetic agent for venous catheterization, condyloma acuminatum excision, phimosis and preparation of skin grafts in various studies.(10,11) To achieve its maximum anesthetic effect, it should be applied 45-60 minutes before the procedure,(8) and this property of EMLA cream made it, an effective agent for pain reduction during SWL in various studies. Bierkens and associates reported reduced opoid require- ment when EMLA was used as a supplement during SWL. (12) Tritrakarn and associates also reported in their study that EMLA is a safe, effective and economical method to reduce pain during SWL.(13) McDonald and Berry found EMLA cream as an ineffective agent for the pain management dur- Endourology and Stone Disease Table 1. Demographic characteristics Variables Group A (Diclofenac injection) Group B (EMLA) Group C (Diclofenac gel) P value Age 38.5±12.0 37.5±13.5 37.5±14.5 5.5 Sex (M:F) 21:14 18:16 21:15 .99 Weight 61.0±8.2 58.6±9.4 58.3±9.9 .8 Stone size 10.3±3.3 10.4±2.8 10.9±2.3 .4 No. of shock waves 1580±408 1682±301 1800±322 3.5 Used voltage 1-2 1-2 1-2 .07 Table 1. Demographic characteristics Variables Group A (Diclofenac injection) Group B (EMLA) Group C (Diclofenac gel) P value VAS SCORE 4.48 3.60 3.90 1.34 945Vol. 10 | No. 3 | Summer 2013 |U R O LO G Y J O U R N A L ing SWL as compared to placebo.(14) In our study we found EMLA cream equally effective to intramuscular diclofenac sodium and locally applied diclofenac diethylamine gel in controlling pain of the intervention CONCLUSION The EMLA cream, diclofenac gel and intramuscular di- clofenac sodium produce similar results for pain scores during SWL. Further studies with larger sample sizes are needed to extrapolate these results. CONFLICT OF INTEREST None declared. Pain Management during SWL | Liu et al REFERENCES 1. Chaussy C, Brendel W, Schmiedt E. Extracorporeal induced destruction of kidney stones by shock waves. Lancet. 1980;2:1265–8. 2. Chaussy GC, Fuchs GJ. Current state and future develop- ments of noninvasive treatment of urinary stones with ex- tracorporeal shock wave lithotripsy. 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