Adult Urology Comparing Two Local Anesthesia Techniques for Extracorporeal Shock Wave Lithotripsy Erkan Demir, Mete Kilciler, Selahattin Bedir, Koray Erten, and Yasar Ozgok OBJECTIVES
METHODS
RESULTS
CONCLUSIONS
To evaluate the efficacy of a eutectic mixture of local anesthetics (EMLA) cream compared with dimethyl sulfoxide (DMSO) with lidocaine during extracorporeal shock wave lithotripsy (ESWL) in a prospective randomized study. Of 167 patients, 85 received 10 g of EMLA cream (EMLA group) and 82 received 10 g of 40% DMSO (DMSO group) with an amount of lidocaine equal to that in the lidocaine gel, applied to the skin of the flank at the area of entry of the shock wave marked by the urologist. A second-generation lithotriptor Siemens Lithostar was used. The degree of pain was rated by the patients using a 10-point visual analog scale. In 80 patients in the EMLA group (94%), the entire procedure was performed with no, minor, or tolerable pain after the application of EMLA cream (pain score 5.2 ⫾ 1.3). In 5 EMLA patients (6%), EWSL was interrupted because of intolerable pain. Of the 82 DMSO patients, 80 (98%) underwent the entire procedure with no, minor, or tolerable pain after the application of DMSO with lidocaine (pain score 3.7 ⫾ 1.1). In 2 DMSO patients (2%), EWSL was interrupted because of intolerable pain. The pain scores were significantly lower for the DMSO group than for the EMLA group (P ⫽ 0.011). Our findings have indicated that the pain scores were significantly lower for the DMSO group than for the EMLA group. In addition to the local anesthetic effect of DMSO, diuretic, anti-inflammatory, muscle relaxant, and hydroxyl radical scavenger effects can be important for patients undergoing ESWL. These effects should be evaluated with new studies of patients undergoing ESWL. UROLOGY 69: 625– 628, 2007. © 2007 Elsevier Inc.
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hock wave lithotripsy has become a routine procedure for the treatment of urinary stones. With the additional development of shock wave lithotripsy technology, analgesic requirements during the procedure have decreased, but nevertheless continue. Since 1986, several studies have investigated the effect of different local anesthetic substances on therapy-dependent pain with varying results.1–5 The effectiveness of local anesthesia for extracorporeal shock wave lithotripsy (ESWL) is reported to be good, and general anesthesia is necessary for only 5% to 10% of patients.1 Most centers today use general anesthesia only for children. A eutectic mixture of local anesthetics (EMLA cream) is a topical anesthetic drug designed for use on intact skin. DMSO is quickly absorbed through the skin and relieves musculoskeletal pain when applied topically to painful areas. The aim of the present prospective ranFrom the Department of Urology, Gulhane Military Medical Academy School of Medicine, Ankara, Turkey Reprint requests: Erkan Demir, M.D., Department of Urology, Gulhane Military ¨ roloji AD. Etlik, Ankara 06018, Medical Academy School of Medicine, GATA U Turkey. E-mail:
[email protected] Submitted: July 23, 2006; accepted (with revisions): January 3, 2007
© 2007 Elsevier Inc. All Rights Reserved
domized study was to evaluate the efficacy of EMLA cream compared with DMSO with lidocaine in patients undergoing ESWL.
MATERIAL AND METHODS After informed consent was obtained, 167 patients with kidney stones were randomized to receive EMLA cream (EMLA group, 85 patients) or DMSO with lidocaine (DMSO group, 82 patients). The EMLA group received 10 g of EMLA (AstraZeneca LP, Wilmington, Del; 1 g contains 25 mg lidocaine and 25 mg prilocaine), and the DMSO group received 10 g 40% DMSO (prepared in our pharmacology section) with an amount of lidocaine equal to that in the lidocaine gel applied to the skin of the flank at the area of entry of the shock wave marked by the urologist. The cream covered approximately 200 cm2. The EMLA cream was applied for at least 60 minutes (range 60 to 110). The DMSO with lidocaine was applied 10 minutes before starting the treatment. No patient was given intravenous anesthesia. A second-generation lithotriptor, Siemens Lithostar, was used. The urinary stones were treated at a power setting of 13 to 19 kV, and 800 to 3500 shock waves were applied. At 10 minutes after beginning ESWL, the degree of pain was rated by the patients using a 10-point visual analog scale. After the 0090-4295/07/$32.00 doi:10.1016/j.urology.2007.01.003
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Table 1. Comparison of clinical parameters for both groups during ESWL* Parameter Age (yr) Mean Range Sex (n) Male Female Weight (kg) Mean Range Mean stone burden (n) Stone localization (n) Renal Ureter Shock waves (n) Mean Range Mean shock energy (kV) Duration of ESWL (min) Mean Range
EMLA Group (n ⫽ 85)
DMSO Group (n ⫽ 82)
31.4 ⫾ 11.2 19–63
33.8 ⫾ 10.4 20–71
71 14
72 10
78 ⫾ 3 46–97 9.5 ⫾ 4.2
73 ⫾ 4 54–91 9.1 ⫾ 4.1
79 6
78 4
2608 ⫾ 302 800–3500 17.2 ⫾ 2.3
2636 ⫾ 311 800–3500 17.4 ⫾ 2.1
42 ⫾ 4 25–95
46 ⫾ 3 20–100
EMLA ⫽ eutectic mixture of local anesthetics; DMSO ⫽ dimethyl sulfoxide; ESWL ⫽ extracorporeal shock wave lithotripsy. * For all parameters, P ⬎0.05.
procedure, the patients were asked to complete a self-administered questionnaire. Also, patients were asked about the experience and to rate the intensity of pain as no, minor, tolerable, and intolerable. The stone fragmentation rate of the EMLA and DMSO groups was determined by comparing the pretreatment and posttreatment x-ray findings. Differences in pain score, number of shock waves, duration of treatment, and weight were evaluated using the Mann-Whitney U test. The chi-square test was used for statistical analysis of differences for skin changes and gender.
Table 2. Results of pain questionnaire and visual analog scale for both groups Variable
EMLA Group (n ⫽ 85)
DMSO Group (n ⫽ 82)
Questionnaire (n) No pain Minor pain Tolerable pain Intolerable pain Mean visual analog scale score*
0 34 46 5 5.2 ⫾ 1.3
2 58 20 2 3.7 ⫾ 1.1
Abbreviations as in Table 1. * Statistically significant (P ⫽ 0.011).
entire procedure. After treatment, 66 (82%) of the 80 patients were stone-free by x-ray, 7 (9%) had residual fragments, and 7 (9%) had no sign of stone disintegration. Although in the DMSO group, the stone-free rate was greater (82% versus 70%) and the percentage of residual fragments was lower (9% versus 24%) than in the EMLA group, these differences were not statistically significant (P ⫽ 0.14). In 80 (94%) of the 85 EMLA patients, the entire procedure was performed with no, minor, or tolerable pain after the application of EMLA cream. However, in 5 patients (6%), therapy was interrupted because of intolerable pain. In 80 (98%) of the 82 DMSO patients, the entire procedure was with no, minor or tolerable pain after the application of DMSO with lidocaine. In 2 patients (2%), therapy was interrupted because of intolerable pain. The pain scores were significantly lower for the DMSO group than for the EMLA group (Table 2). No significant differences between the two groups were found with regard to post-ESWL skin changes (redness, petechia, paleness, and edema), and no serious side effects occurred in either group.
RESULTS No significant differences were found between the two groups concerning patient age, sex, weight, stone burden, stone location, or session duration of the ESWL (all P ⬎0.05; Table 1). Of the 85 patients in the EMLA group, 71 were men and 14 were women, with a mean age of 31.4 ⫾ 11.2. Of the 85 stones, 79 were located in the kidney and 6 in the upper ureter, with a mean size of 9.5 ⫾ 4.2 mm (right 40, left 45). Of the 82 patients in the DMSO with lidocaine group, 72 were men and 10 were women, with a mean age of 33.8 ⫾ 10.4. Of the 82 stones, 78 were located in the kidney and 4 in the upper ureter, with a mean size of 9.1 ⫾ 4.1 cm (right 38, left 44). The average number of applied shock waves was 2608 (range 800 to 3500) in the EMLA group and 2636 (range 800 to 3500) in the DMSO group with lidocaine. In the EMLA group, 80 patients had completed the entire procedure. After treatment, 56 (70%) of the 80 patients were stone-free by x-ray, 19 (24%) had residual fragments, and 5 (6%) had no sign of stone disintegration. In the DMSO group, 80 patients completed the 626
COMMENT Although a number of procedures are available for the treatment of urinary stones, ESWL is now considered one of the most important standard treatments and is performed on an ambulatory basis. Shock wave-related pain is one of the most significant side effects of ESWL. Improvements in the technology have made it possible to perform ESWL in an outpatient setting without the need for general or spinal anesthesia. However, ESWL without anesthesia demands proper pain management to ensure success and patient satisfaction. The patient’s relaxation and cooperation during treatment is crucial in maintaining stone localization for optimal fragmentation. Various sedative and analgesic medications have been used for ESWL. However, variable results relating to the efficacy of local and topical anesthesia with EMLA cream have been reported.2,4,6 In one of the studies, the EMLA group was reported to need less fentanyl (23%) and have less pain than those receiving placebo, but the difference was not statistically significant.7 Monk et al.,8 comparing UROLOGY 69 (4), 2007
intravenous fentanyl with EMLA during ESWL, reported that EMLA cream provided cutaneous analgesia but demonstrated no opioid-sparing effect. McDonald and Berry6 did not recommend topical anesthesia for treatment with a first-generation lithotripter and found EMLA and placebo to be comparable. The pharmacologic actions of DMSO have stimulated much research. Ten minutes after cutaneous application in the rat, radioactivity was measured in the blood. In humans, radioactivity appeared in the blood 5 minutes after cutaneous application. We applied DMSO only 10 minutes before the procedure, and EMLA was applied 60 minutes or more before EWSL. Although we did not calculate the length of stay in our hospital for patients undergoing the outpatient ESWL procedure, the DMSO group might have had a shorter length of stay in the hospital. Formanek and Kovak9 showed that topically applied DMSO inhibited the traumatic edema induced by intrapedal injection of autologous blood in the leg of a rat. Gorog and Kovacs10 demonstrated that DMSO exerted minimal anti-inflammation effects on the edema induced by carrageen administration. These investigators also studied the anti-inflammatory potential of DMSO in adjuvant-induced polyarthritis of rats. Topical DMSO showed potent anti-inflammatory properties in this model. Immersion of the sciatic nerve in 6% DMSO decreases the conduction velocity by 40%. This effect is totally reversed by washing the nerve in a buffer for 1 hour.11 Shealy12 studied peripheral small fiber after discharge in the cat. Concentrations of 5% to 10% DMSO eliminated the activity of C fibers within 1 minute. The activity of the fibers returned after the DMSO was washed away. Haigler13 concluded that DMSO is a drug that produces analgesia by acting both locally and systemically. The analgesia appeared to be unrelated to that produced by morphine, although the two appear to be of a comparable magnitude. DMSO had a longer duration of action than morphine, 6 versus 2 hours, respectively.13 Formanek and Suckert14 studied the diuretic effects of DMSO administered topically to rats five times daily in a dosage of 0.5 mL of 90% DMSO per animal. The urine volume was increased 10-fold and, with the increase in urine volume, the sodium and potassium excretion increased. This effect might be important for patients’ stone-free rates after ESWL. In the present study, the DMSO group had a greater stone-free rate (82% versus 70%) and lower percentage of residual fragments (9% versus 24%) than the EMLA group; however, the differences were not statistically significant. Additional studies of more patients are needed before conclusions can be drawn. DMSO applied topically to the skin of patients produces electromyographic evidence of muscle relaxation 1 hour after application.15 Furthermore, one of the significant sites at which hydroxyl radicals can form after ischemia is in the mitochondria. DMSO is known to be UROLOGY 69 (4), 2007
an effective hydroxyl radical scavenger.16 –18 Because it has been shown that DMSO can improve mitochondrial oxidative phosphorylation, it has been suggested that DMSO may act to neutralize the cytotoxic effects of hydroxyl radicals in mitochondria themselves.19 Oxidative phosphorylation is one of the primary biochemical activities to be negatively affected after ischemic injury. DMSO has also been reported to reduce adenosine triphosphatase activity in submitochondrial particles, an effect that can lower oxygen use during cellular ischemia.20,21
CONCLUSIONS Our findings have shown that the pain scores were significantly lower for the DMSO group than for the EMLA group. In addition to the local anesthetic effect of DMSO, diuretic, anti-inflammatory, muscle relaxant, and hydroxyl radical scavenger effects could be important for ESWL patients. These effects should be evaluated with new studies of ESWL patients. References 1. Aeikens B, Fritz KW, and Hoehne E: Initial experience with local anesthesia in extracorporeal shock wave lithotripsy. Urol Int 41: 246 –247, 1986. 2. Honnens de Lichtenberg M, Miskowiak J, Mogensen P, et al: Local anesthesia for extracorporeal shock wave lithotripsy: a study comparing eutectic mixture of local anesthetics cream and lidocaine infiltration. J Urol 147: 96 –97, 1992. 3. Loening S, Kramolowsky EV, and Willoughby B: Use of local anesthesia for extracorporeal shock wave lithotripsy. J Urol 137: 626 – 628, 1987. 4. Tiselius HG: Cutaneous anesthesia with lidocaine-prilocaine cream: a useful adjunct during shock wave lithotripsy with analgesic sedation. J Urol 149: 8 –11, 1993. 5. London RA, Kudlak T, and Riehle RA: Immersion anesthesia for extracorporeal shock wave lithotripsy: review of two hundred twenty treatments. Urology 28: 86 –94, 1986. 6. McDonald PF, and Berry AM: Topical anaesthesia for extracorporeal shock wave lithotripsy. Br J Anaesth 69: 399 – 400, 1992. 7. Bierkens AF, Maes RM, Hendrikx JM, et al: The use of local anesthesia in second generation extracorporeal shock wave lithotripsy: eutectic mixture of local anesthetics. J Urol 146: 287–289, 1991. 8. Monk TG, Ding Y, White PF, et al: Effect of topical eutectic mixture of local anesthetics on pain response and analgesic requirement during lithotripsy procedures. Anesth Analg 79: 506 –511, 1994. 9. Formanek K, and Kovac W: DMSO bei experimentellen Rattenpfotenodemen, in Laudahn G and Gertich K (Eds): DMSO Symposium, Vienna, 1966. Berlin, Saladruck, 1966, p 18. 10. Gorog P, and Kovacs IB: Effect on dimethyl sulfoxide (DMSO) on various experimental inflammations. Curr Ther Res 10: 486 – 492, 1968. 11. Sams WM: The effects of dimethyl sulfoxide on nerve conduction. Ann NY Acad Sci 141: 242–247, 1967. 12. Shealy CN: The physiological substrate of pain. Headache 6: 101–108, 1966. 13. Haigler HJ: Comparison of the analgesic effects of dimethyl sulfoxide and morphine. Ann NY Acad Sci 411: 19 –27, 1983. 14. Formanek K, and Suckert R: Diuretische Wirkung von DMSO, in Laudahn G, and Gertich K (Eds): DMSO Symposium, Vienna, 1966. Berlin, Saladruck, 1966, p 21. 15. Birkmayer W, Danielczyk W, and Werner H: DMSO bei spondylogenen neuropathien, in Laudahn G, and Gertich K (Eds): DMSO Symposium, Vienna, 1966. Berlin, Saladruck, 1966, p 134.
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16. Del Maestro R, Thaw HH, Bjork J, et al: Free radicals as mediators of tissue injury. Acta Physiol Scand 492: 43–57, 1980. 17. Panganamala RV, Sharma HM, and Heikkila RE: Role of hydroxyl radical scavengers, dimethyl sulfoxide, alcohols, and methional in the inhibition of prostaglandin synthesis. Prostaglandins 11: 599 – 607, 1976. 18. Ashwood-Smith MJ: Current concepts concerning radioprotective and cryroprotective properties or dimethyl sulfoxide in cellular systems. Ann NY Acad Sci 243: 246 –256, 1975.
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19. Schlafer M, Kane PF, and Kirsch M: Effects of dimethyl sulfoxide on the globally ischemic heart: possible general relevance to hypothermic organ preservation. Cryobiology 19: 61– 69, 1982. 20. Ghosh AK, Ito T, Ghosh S, et al: Effects of dimethyl sulfoxide on metabolism of isolated perfused rat brain. Biochem Pharmacol 25: 115–117, 1976. 21. Conover TE: Influence of nonionic organic solutes on various reactions of energy conservation and utilization. Ann NY Acad Sci 243: 24 –37, 1975.
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