Anesth Pain. 2013;2(3):119-122. DOI: 10.5812/aapm.7790 Anesthesiology Pain Medicine KOWSAR www.AnesthPain.com The Effect of EMLA Cream on Patient-Controlled Analgesia with Remifentanil in ESWL Procedure: A Placebo-Controlled Randomized Study Arzu Acar 1, Elvan Erhan 1, M. Nuri Deniz 1*, Gulden Ugur 1 1 Department of Anaesthesiology and Reanimation, School of Medicine, Ege University, Izmir, Turkey A R T I C L E I N F O A B S T R A C T Article type: Background: To alleviate stinging pain in the skin entry area and visceral discomfort in Research Article patients who are undergoing ESWL. Objectives: This study was designed to investigate the effectiveness of the EMLA cream in Article history: combination with remifentanil patient-controlled analgesia (PCA) in patients undergo- Received: 19 Aug 2012 ing ESWL treatment. Revised: 01 Sep 2012 Patients and Methods: Sixty patients were divided into two double-blind random- Accepted: 10 Oct 2012 ized groups. Those in the first group were administered 3-5mm of EMLA 5% cream on a marked area; the second group received, as a placebo, a cream with no analgesic effect in Keywords: the same amount. All patients were administered a remifentanil bolus with a PCA device. Lithotripsy Arterial blood pressure, oxygen saturation, and respiratory rate were recorded through- Remifentanil out the procedure; postoperative side effects, agitation, and respiratory depression were Analgesia, Patient-Controlled measured after. Visual Analogue Scale (VAS) scores were taken preoperatively, periopera- EMLA tively, directly postoperatively, and 60 minutes subsequent to finishing the procedure. Results: There were no statistically significant differences in the frequency of PCA de- mands and delivered boluses or among perioperative VAS. No significant side effects were noted. Patient satisfaction was recorded high in both groups. Conclusions: EMLA cream offered no advantage over the placebo cream in patients un- dergoing ESWL with remifentanil PCA. Published by Kowsar Corp, 2013. cc 3.0. Implication for health policy/practice/research/medical education: Several drugs and methods are being evaluated for aimed at pain control for renal stones during ESWL. This study investigates the effect of EMLA cream on patient-controlled analgesia with remifentanil during the ESWL procedure. Please cite this paper as: Acar A, Erhan E, Nuri Deniz M, Ugur G. The Effect of EMLA Cream on Patient-Controlled Analgesia with Remifentanil in ESWL Proce- dure: A Placebo-Controlled Randomized Study. Anesth Pain. 2013;2(3):119-22. DOI: 10.5812/aapm.7790 1. Background pain receptors are held responsible for the pain (2, 3). Other imperative factors include individual differences, the type of Extracorporeal shock wave lithotripsy (ESWL), the most com- lithotripter, site and size of the stones, and pressure of shock monly used procedure for the treatment of kidney stones, is waves (2, 4). During ESWL, general anaesthesia, regional an- painful based on the power of the acoustic shock waves ap- aesthesia, intravenous anaesthesia or analgesia and sedation plied (1). Though believed to be multifactorial, the pathogen- can be performed (5, 6). For this purpose, several studies using esis of the pain during ESWL remains to be elucidated. The cu- opioids such as fentanyl, alfentanil, sufentanil, and remifen- taneous superficial skin nociceptors and visceral nociceptors tanil have been conducted (7, 8). Since 1986, various studies such as periosteal, pleural, peritoneal and/or musculoskeletal * Corresponding author: M. Nuri Deniz, Department of Anaesthesiology and Reanimation, School of Medicine, Ege University, 35100, Izmir, Turkey. Tel: +90- 2323902140, Fax: +90-2323397687, E-mail: [email protected] DOI: 10.5812/aapm.7790 © 2013 Iranian Society of Regional Anesthesia and Pain Medicine; Published by Kowsar Corp. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Acar A et al. The Effect of EMLA Cream in ESWL Procedure have been reported on the use of infiltrative or topical local tion of stone, maximum energy and the number of shock anesthetics for analgesic purposes. The use of local anesthet- waves were similar between the groups (Table 1). Preopera- ics during ESWL has been demonstrated to be effective in tive, perioperative and postoperative VAS and VRS scores achieving analgesia (9, 10). showed similar differences over time (Figures 1 and 2). The remifentanil consumption and the incidence of side ef- 2. Objectives fects due to the use of remifentanil were similar between the groups. Both groups had similar number of PCA de- The purpose of this double-blind randomized study was to mands and PCA deliveries (Table 2). investigate the effects of the combined use of remifentanil used for pain management in patients who planned to un- dergo ESWL, and the use of EMLA, a topical local anaesthetic. Table 1. Demographic Data Group E Group P P 3. Patients and Methods (n = 30) (n = 30) value After the approval of the Ethics Committee of University Age, y, Mean ± SD 48.5 ± 2.2 43.4 ± 2.5 0.13 Faculty of Medicine and the informed consent of patients, a Male/Female, No. 17/13 16/14 total of 60 ASA I-II patients with renal stone disease between Height, cm, Mean ± SD 165.6 ± 1,7 167.9 ± 1.6 0.4 18-70 years of age who were scheduled to undergo elective Weight, kg, Mean ± SD 70.7 ± 2.1 69.5 ± 2.3 0.7 ESWL using the Dornier® lithotripsy (Donier MedTech, Duration of The ESWL Pro- Germany) were enrolled in the study. The exclusion criteria 26.1 ± 8.1 30.3 ± 8.8 0.06 cedure, min, Mean ± SD were patients with opioid allergy, obesity (BMI > 30), methe- Location of Stone: moglobinemia, liver disease, alcohol consumption, patients Renal Pelvic 9 8 using preoperative opioids and derivatives, cardiovascular Upper calyx 6 8 and neuropsychiatric medications, pregnant and nursing Middle calyx 4 2 mothers. No preoperative sedative-hypnotic drugs or anti- emetic agents were used. Prior to the ESWL procedure, the Lower calyx 8 8 data recorded for each patient included age, sex, ASA status, Ureter 3 4 and location and diameter of stones. The patients were dou- Shock Waves, No. 1988.3 2000 0.46 ble-blindedly randomized into two groups: the first group maximum energy, mv 21.1 21 0.32 (group E, n = 30) was administered a total of 10 gr of 5% EMLA cream in the thickness of 3-5 mm on a marked area 10 cm 5 4.5 VAS Placebo by 15 cm; the second group (group P, n = 30) was adminis- 4 VAS EMLA tered a cream with no analgesic effect in the same amount 3.5 and quality as a placebo one hour before the ESWL. Prior to 3 tphaein p frroocmed tuhreei,r e kaicdhn peayt sietonnt ewsa osn a sak VeAdS t aon sdco VrReS t h(Veeirr bleavl eRl aotf- Scores 2.52 ing Scale 0-3). Standard monitorization included electrocar- 1.5 1 diography, heart rate, non-invasive arterial blood pressure, 0.5 respiratory rate and SpO and all patients were administered 2 0 O via a facial mask at a rate of 6 liters/min and Remifentanil Preop Perop 10 Perop 20 Perop 30 Perop 0 Perop 30 Perop 60 2 PCA with a dose of 10 µgr (patient-controlled analgesia, Ab- Time bott) (in a bolus of 10 µg, with a lock-out time of 5 minutes) and the patients were asked to press the button when he or Figure 1. VAS Score Differences Comparing EMLA and Placebo she felt pain. During the procedure, vital parameters and 1.8 VAS and VRS values were recorded for each patient every 10 VAS Placebo 1.6 minutes. Remifentanil administration was discontinued 3 VAS EMLA 1.4 minutes before the termination of the ESWL procedure and 1.2 PCA demands and deliveries were recorded for each patient. es An unpaired t-test was used to compare demographic data cor 1 S0.8 and Bonferroni’s test to compare the pain scores between 0.6 the two groups. 0.4 0.2 4. Results 0 Preop Perop 10 Perop 20 Perop 0 Perop 30 Perop 60 The results are presented as mean ± standard value and a P value of < 0.05 was considered statistically significant. Time Demographic data, duration of ESWL procedure, loca- Figure 2. VRS Score Differences Comparing EMLA and Placebo 120 Anesth Pain.2013;2(3) The Effect of EMLA Cream in ESWL Procedure Acar A et al. Table 2. Data Concerning Remifentanil and PCA, VAS Pain Scores Group E (n = 30) Group P (n = 30) P value Remifentanil dose, µg, Mean ± SD 17.3 ± 15.5 21.3 ± 12.8 0.29 Number of PCA demands, Mean ± SD 5.9 ± 6.3 5.2 ± 8.3 0.79 Number of PCA deliveries, Mean ± SD 2.1 ± 1.5 1.7 ± 1.1 0.72 Preoperative VAS, Mean ± SD 1.2 ± 0.8 1.0 ± 0 0.16 Peroperative VAS, Mean ± SD 3.9 ± 0.9 4.1 ± 0.4 0.84 Postoperative VAS (0 min), Mean ± SD 1.1 ± 0.3 1.7 ± 1.7 0.72 Postoperative VAS (60 min), Mean ± SD 1.0 ± 0.5 1.0 ± 0.0 1.00 Postoperative Side effects, yes/no Hypotension 0/30 0/30 Respiratory depression 0/30 0/30 Nausea and Vomiting 3/30 3/30 Dizziness 3/30 4/30 Abbreviations: PCA, Patient controlled analgesia; VAS, Visual Analogue Scale. 5. Discussion (15) reported a 23% lower use of fentanyl and lower pain scores compared to placebo, however, the results did not ESWL is a commonly used treatment for patients with reach statistical significance. Monk et al. (6) compared kidney and uretheric stones, offering a high efficacy and EMLA cream with IV fentanyl and reported that even a low complication rate and is performed on an outpa- though the application of EMLA cream produced cutane- tient basis in most centers. ESWL uses acoustic shock ous analgesia, it failed to produce an opioid-sparing an- waves to break up kidney stones, during which pain at algesic effect, and was not superior to placebo. They also the entry site of shock waves and deep visceral discom- reported that EMLA cream produced no decrease in post- fort is experienced (11). For this reason, there are numer- operative side effects and recovery times. In conclusion, ous studies using opioids (1, 11, 12). Even though opioids considering EMLA’s slow onset, the inability to identify are used extensively because of their high efficiency, their the precise entrance site for the shock waves and the high side effects such as bradychardia, hypotension, respira- cost of the drug, the routine use of EMLA was not recom- tory depression, sedation, nausea-vomiting, and itching mended by the authors (6). Barcena et al. (16) conducted can lengthen their hospital stay which has led clinicians a study on 20 patients who had been unable to tolerate to seek alternatives. Several studies on this issue have pain without IV analgesia during ESWL. In this study, 10 attempted to determine various regimens of remifen- gr of EMLA cream was applied on the skin over the area tanil; the optimal bolus dose and infusion rate of remi- of 64-100 cm 2 60 minutes before the second session. De- fentanil in itself or compared with other opioids such as spite higher voltages, lower pain scores were found in pa- sufentanil, alfentanil and fentanyl (11, 12). These studies tients for whom EMLA cream was used and only two pa- compared a remifentanil bolus of 10 µg and remifentanil tients required further analgesia. In addition, all patients infusions of 0.05 µg/kg/min and 0.1 µg/kg/min and dem- required additional fentanyl in the first session without onstrated that the administration of bolus combined EMLA. In a study by Ganapathy et al (17), one group re- with low dose infusion had a beneficial analgesic effect ceived 30 gr EMLA cream and the other group received a and a low incidence of side effects (12). In this study, we placebo 60-90 minutes before the procedure. All patients used remifentanil and patient controlled analgesia com- received 5 mcg/kg of alfentanil via a PCA machine with bined with remifentanil bolus of 10 µg. Since 1986, vari- a lockout time of 3 minutes and no significant differ- ous studies have been conducted on the use of local anes- ences were noted in pain scores, side effects and duration thetics for analgesic purposes during treatment (9). Local of stay in the post anaesthesia care unit between EMLA anesthetics were also shown to be effective in achieving cream and placebo. In a double-blind randomized con- analgesia during ESWL and only 5% of these patients re- trolled study of 60 ASA I-III patients between 18-70 years quired general anaesthesia (9). There are a number of of age, aiming at investigating the effect of EMLA cream studies concerning the use of topical EMLA cream for this in lithotripsy by Terri et al. (6), one group received 30 gr purpose (9, 13). Even though the skin is where the pain is of EMLA cream applied to a 15x20 cm area of skin 90 min- experienced most intensely as a result of the shock waves utes prior the procedure and the other group received during the procedure (6, 14) and EMLA cream is effective placebo with the same appearance and consistency and in relieving pain, patients usually require additional an- patients with pain received an additional bolus of alfen- algesia since the pain related to ESWL has both cutaneous tanil 5 µg/kg and an infusion of 0.5 µg/kg/min. The dose and visceral components (2, 3). A study by Bierkens et al. Anesth Pain.2013;2(3) 121 Acar A et al. The Effect of EMLA Cream in ESWL Procedure of alfentanil was doubled in those patients with continu- Funding/Support ing pain. They also reported that there was no change in None declared. pain scores at energy levels of 10,12,15 mV but there was a significant decrease in pain at energy levels of 18 and 20 References mV in the EMLA group. However, no significant differenc- es were noted in alfentanil use between the two groups. 1. Burmeister MA, Brauer P, Wintruff M, Graefen M, Blanc I, Standl TG. A comparison of anaesthetic techniques for shock wave lith- In the present study, similar to those of Ganapathy and otripsy: the use of a remifentanil infusion alone compared to in- Terri (6, 17), 10 gr of EMLA cream was applied to a 10x15 termittent fentanyl boluses combined with a low dose propofol cm area of skin 1 hour before the procedure. Both authors infusion. Anaesthesia. 2002;57(9):877-81. preferred alfentanil as the opioid. In this study, we pre- 2. Gupta NP, Kumar A. Analgesia for pain control during extra- corporeal shock wave lithotripsy: Current status. Indian J Urol. ferred remifentanil, which has a short duration. We ad- 2008;24(2):155-8. ministered remifentanil at a bolus dose of 10 µg with a 3. Weber A, Koehrmann KU, Denig N, Michel MS, Alken P. What are lockout time of 5 minutes. As in the study by Ganapathy the parameters for predictive selection of patients requiring anesthesia for extracorporeal shockwave lithotripsy? Eur Urol. et al., no basal infusion was administered. Thus, keeping 1998;34(2):85-92. the dose of remifentanil at the lowest tolerable level, we 4. Basar H, Yilmaz E, Ozcan S, Buyukkocak U, Sari F, Apan A, et al. tried to assess how effective EMLA cream was. In this ap- Four analgesic techniques for shockwave lithotripsy: eutec- plication, no hypotension or respiratory depression due tic mixture local anesthetic is a good alternative. J Endourol. 2003;17(1):3-6. to remifentanil was observed. Side effects such as nau- 5. Monk TG, Boure B, White PF, Meretyk S, Clayman RV. Comparison sea-vomiting and dizziness were similarly low in both of intravenous sedative-analgesic techniques for outpatient im- groups. No patients had severe pain necessitating the mersion lithotripsy. Anesth Analg. 1991;72(5):616-21. 6. Monk TG, Ding Y, White PF, Albala DM, Clayman RV. Effect of topi- administration of other analgesics or the termination of cal eutectic mixture of local anesthetics on pain response and the procedure. Even though it has been suggested that analgesic requirement during lithotripsy procedures. Anesth topical anesthetics used for the elimination of cutaneous Analg. 1994;79(3):506-11. component of pain can provide a more comfortable anal- 7. Coloma M, Chiu JW, White PF, Tongier WK, Duffy LL, Armbruster SC. Fast-tracking after immersion lithotripsy: general anesthesia gesia by reducing the use of opioids and their side effects, versus monitored anesthesia care. Anesth Analg. 2000;91(1):92-6. we demonstrated in this study that EMLA cream did not 8. Rosow C. Remifentanil: a unique opioid analgesic. Anesthesiol- lead to a decrease in the dose of remifentanil compared ogy. 1993;79(5):875-6. to a placebo during ESWL. In conclusion, we found that 9. Aeikens B, Fritz KW, Hoehne E. Initial experience with local anesthesia in extracorporeal shock wave lithotripsy. Urol Int. EMLA cream combined with PCA using remifentanil was 1986;41(4):246-7. not significantly superior to a placebo in ESWL and did 10. Demir E, Kilciler M, Bedir S, Erten K, Ozgok Y. Comparing two lo- not lead to a decrease in the dose of remifentanil used cal anesthesia techniques for extracorporeal shock wave litho- tripsy. Urology. 2007;69(4):625-8. during ESWL. However, there are different application 11. Beloeil H, Corsia G, Coriat P, Riou B. Remifentanil compared with schemes for EMLA. We do consider that the investigation sufentanil during extra-corporeal shock wave lithotripsy with of the use of EMLA cream alone or combined with other spontaneous ventilation: a double-blind, randomized study. Br IV analgesia regimens will be able to give further insight J Anaesth. 2002;89(4):567-70. 12. Medina HJ, Galvin EM, Dirckx M, Banwarie P, Ubben JF, Zijlstra into the efficacy of EMLA cream. FJ, et al. Remifentanil as a single drug for extracorporeal shock wave lithotripsy: a comparison of infusion doses in terms of an- Acknowledgments algesic potency and side effects. Anesth Analg. 2005;101(2):365-70, table of contents. None declared. 13. Tiselius HG. Cutaneous anesthesia with lidocaine-prilocaine cream: a useful adjunct during shock wave lithotripsy with an- algesic sedation. J Urol. 1993;149(1):8-11. Authors’ Contribution 14. Malhotra V, Long CW, Meister MJ. Intercostal blocks with local Arzu Acar; Study design, Conduct of the study, Data col- infiltration anesthesia for extracorporeal shock wave lithotripsy. Anesth Analg. 1987;66(1):85-8. lection, Data analysis and Manuscript preparation. MNuri 15. Bierkens AF, Maes RM, Hendrikx JM, Erdos AF, de Vries JD, De- Deniz; Data collection, Data analysis and Manuscript prep- bruyne FM. The use of local anesthesia in second generation aration. Elvan Erhan; Study design, Data collection, Data extracorporeal shock wave lithotripsy: eutectic mixture of local anesthetics. J Urol. 1991;146(2):287-9. analysis and Manuscript preparation. Gulden Ugur; Data 16. Barcena M, Rodriguez J, Gude F, Vidal MI, Fernandez S. EMLA analysis and Manuscript preparation. cream for renal extracorporeal shock wave lithotripsy in ambu- latory patients. Eur J Anaesthesiol. 1996;13(4):373-6. Financial Disclosure 17. Ganapathy S, Razvi H, Moote C, Parkin J, Yee I, Gverzdys S, et al. Eutectic mixture of local anaesthetics is not effective for extra- None declared. corporeal shock wave lithotripsy. Can J Anaesth. 1996;43(10):1030- 4. 122 Anesth Pain.2013;2(3)