Introduction 1 2 5 6 7 8 9 7 10 The aim of this study was to compare the clinical efficacy of inhalational Entonox and pethidine for pain relief during outpatient ESWL. Methods A total of 150 patients (97 men and 53 women) with stones located in the renal pelvicalyceal system were prospectively randomized to receive Entonox (prefixed equimolar nitrous oxide and oxygen mixture), pethidine, or compressed air for sedoanalgesia during lithotripsy with a third generation electromagnetic lithotripter (Dornier Compact Delta magneto lithotripter). After institutional review board approval, written informed consent was obtained during the anesthesia consultation, which was performed at least 48 h before ESWL. During this consultation, the method of pain assessment was explained to the patients. Patients were asked to rate their pain on a scale from 0 (no pain) to 10 (worst possible pain). Patients were included in the study if they were older than 15 years of age, had pelvicalyceal stones, and understood the pain scoring. Patients were excluded from the trial if they had any of the following: (1) serum creatinine > 200 μmol/l; (2) history of chronic use of analgesics and/or sedatives; (3) allergy to any of the study medications; or (4) history of middle ear surgery within the previous month. Just before entering the lithotripsy room, the patients were randomly assigned to one of the three treatment groups (Entonox, pethidine, 1 mg/kg intravenously over 10 min, or compressed air, each to be provided if the patient asked for pain relief during ESWL) by opening a sealed envelope. All patients were assessed by a single physician who was blinded to the patient group assignment. All patients received no premedication and they were told not to eat or drink for at least 4 h prior to the procedure. The control group received compressed air, followed by Entonox gas if pain relief was considered inadequate by the patient. Pain was assessed before and 2 min after receiving pain medication by using a visual analogue scale (VAS) with two anchor points, zero denoting no pain and ten for the worst pain the patient had ever experienced. Statistical analysis t ® P Results 1 Table 1 Demographic data and ESWL variables in three different groups Groups Entonox Pethidine Control Age (years) 43.76 ± 11.89 45 ± 13.46 43.9 ± 14.21 Weight (kg) 75 ± 2 78 ± 3 79 ± 2 Height (cm) 165 ± 10 167 ± 12 164 ± 8 n 30/20 34/16 33/17 Stone location (%)   Renal 80 78 84   Ureteral 20 20 15   Both 0 2 1 Number of shocks delivered 2,010 ± 320 2,000 ± 560 2,500 ± 450 Maximum voltage (kV) used 4.04 ± 1.15 4.14 ± 0.75 4.51 ± 1.00 Past history of urinary calculi (%) 70 72 76 Past history of ESWL (%) 42 46 36 n No ESWL procedure had to be prematurely terminated because of inadequate analgesia. A patient in the Entonox group had mild nausea that subsided spontaneously. The other patients did not develop any complications. 2 2 Table 2 P VAS scores Entonox Pethidine Compressed air Entonox in the compressed air group Before administration 5.76 ± 1.92 6.04 ± 1.54 3.6 ± 1.1 4.96 ± 1.42 After administration 3.73 ± 2.13 4.11 ± 1.69 3.48 ± 1.3 3.8 ± 1.74 P 0.001 0.001 0.426 0.001 In control group, after testing with compressed air, we used Entonox. As can be seen in this group, like Entonox group, VAS score decreased significantly P P 1 Fig. 1 VAS scores in different groups before and after administration of Entonox, pethidine, and compressed air  Discussion 11 12 13 14 15 16 15 17 18 19 Several studies have compared different local and systemic analgesia regimens for pain relief during ESWL, but this, to our knowledge, is the first randomized clinical trial to evaluate the efficacy of Entonox in the treatment of ESWL-associated pain. 20 21 22 17 23 24 25 Conclusions Entonox can provide easy, rapid, and adequate pain relief for patients undergoing ESWL, and is associated with few and minimal side effects.