although renal parenchymal damage occurs during this procedure , it has been demonstrated that renal parenchymal function preserved after pcnl ( 1 ) . this operation may be performed under general or spinal anesthesia ; spinal anesthesia is as effective and safe as general anesthesia ( 2 ) . although this is a safe procedure , it is not recommended in cases using room air to opacify the collecting system ( 3 ) . postoperative pain is less intense after minimally invasive surgeries than open surgery but these surgeries , for example , pcnl are not pain - free ; however , several attempts like using epidural analgesia , patient controlled analgesia and local anesthetics or opioid infiltration ( 4 - 6 ) have been performed . among local anesthetics , although low - dose bupivacaine is commonly used with proper outcome , the use of high - dose bupivacaine may lead to cardiovascular side effects ( 7 ) . ropivacaine is another local anesthetic agent structurally similar to bupivacaine because of having s ( - ) enantiomer compounds , but without cardiovascular complications as well as higher sensory - motor blocking ( 8 , 9 ) . extensive researches have been performed on the clinical efficacy of ropivacaine on relieving labor pain and reducing postoperative pain in both children and adults ( 10 - 12 ) . in total , for analgesic effect and cardiac complication , ropivacaine has a higher efficacy compared to other similar anesthetics such as bupivacaine ( 13 ) . postoperative analgesic effects of intravenous or subcutaneous wound infiltration of opioids have been demonstrated in various urological surgeries ( 5 , 14 ) ; however , the beneficial effect of ropivacaine on postoperative pain relief in urological surgeries such as tubeless percutaneous nephrolithotomy ( pcnl ) has remained uncertain . as general anesthesia is commonly used for this procedure , it seems that using local anesthetics , intensity and duration of analgesia may be improved . hence , the present study aimed to assess the efficacy of ropivacaine on postoperative pain severity in patients undergoing tubeless pcnl procedure . following the approval of university ethics committee , this randomized double - blinded clinical trial was performed on 55 patients aged 15 to 60 years undergoing tubeless pcnl surgery in the urology ward of sina hospital , a university affiliated hospital of tehran university of medical sciences . after the research was approved by the ethics committee of tehran university of medical sciences , registered at irct under number irct201307153773n8 . the exclusion criteria were body weight lower than 40 kg , presence of excessive surgical punctures on skin during pcnl ( increased risk of drug toxicity ) or presence of ureteral or urinary tract stones remaining in surgical zone needing higher doses of analgesic . after including eligible patients , informed consent was obtained from them and randomly assigned to two intervention and placebo groups using block randomization sampling method . initially , all patients were pre - medicated by fentanil 1 g / kg plus midazolam 0.02 mg / kg and then anesthesia was induced by thiopental 5 mg / kg plus atracurium 0.5 mg / kg ; the patients were then intubated . after the administration of anesthesia , patients were laid on the operating table in the supine position , they were placed in the lithotomy position and a 22 f cystoscope inserted transurethrally and an open - ended 6f ureteral catheter was advanced up to the kidney with a stone . then , the patients were placed in the prone position . under the guidance of fluoroscopy an 18 g shiba needle was advanced into the calyx through which maximal number of stones could be retrieved with minimal risk of bleeding . after the observation of urine outflow through the needle , guidewire was delivered through the needle into the pelvicalyceal system . the skin was incised with 20 g scalpel . over the guidewire , 6f ureteral catheter , co - axial or one shut dilators stones were either extracted by forceps or fragmented with pneumatic lithotripter and extracted with a forceps . if necessary , for complete stone clearance , more than one entry was achieved . at the end of the operation , the nephrostomy tube was withdrawn . after ensuring lack of remnants of stone by fluoroscopy , the intervention group instilled with 30 ml of ropivacaine 0.2% at surgical zones including the renal puncture site ( 10 ml ) , nephrostomy tract ( 15 ml ) and skin ( 5 ml ) by a nelaton catheter 8f . the placebo group received only 30 ml of isotonic normal saline with the same protocol . twenty minutes before transferring patients to the recovery room , both groups received 1 g apotel intravenously . the patients received apotel three times a day . at the request of the patient due to feeling pain , meperidine ( 0.5 mg / kg ) could be administered . visual analogue scale ( vas ) for assessing pain severity ( 0 - 10 numeric pain rating scale ) and peak expiratory flow ( pef ) ( for assessing person s ability to breathe out air ) ( 15 ) were measured 4 and 6 hours after completing the procedure . moreover , the amounts of opioids or analgesics administered within 6 hours after the operation were recorded . results were presented as mean  standard deviation ( sd ) for quantitative variables and summarized by absolute frequencies and percentages for categorical variables . categorical variables were compared using chi - square test or fisher s exact test when more than 20% of cells with the expected count of less than 5 were observed . continuous variables were compared using one - way analysis of t test and/or non - parametric mann - whitney test when data had not normal distribution . the trend of changes in the values of study endpoints was assessed using repeated measure anova test . all statistical analyses were performed using spss software ( version 21.0 , spss inc . , all statistical tests were two - sided and differences with probability values < 0.05 were considered statistically significant . results were presented as mean  standard deviation ( sd ) for quantitative variables and summarized by absolute frequencies and percentages for categorical variables . categorical variables were compared using chi - square test or fisher s exact test when more than 20% of cells with the expected count of less than 5 were observed . continuous variables were compared using one - way analysis of t test and/or non - parametric mann - whitney test when data had not normal distribution . the trend of changes in the values of study endpoints was assessed using repeated measure anova test . all statistical analyses were performed using spss software ( version 21.0 , spss inc . , all statistical tests were two - sided and differences with probability values < 0.05 were considered statistically significant . in total , 25 patients ( mean age of 48.20  13.53 years , 60.0% male ) received ropivacaine as the case group and 30 patients in the placebo group ( mean age of 47.20  14.93 years , 70.0% male ) received normal saline . the two groups were similar in sex distribution ( p = 0.272 ) , average age ( p = 0.713 ) as well as other baseline parameters including mean weight , mean height , mean body mass index , history of cardiovascular disorders and hypertension ( table 1 ) . regarding intraoperative characteristics ( table 2 ) , there were no significant differences in the number of holes on the skin for entering the catheter ( intercostal or subcostal ) or history of pcnl between the two groups . the two groups were similar in the mean operation duration , administration of analgesics or opioids during recovery time , number of analgesic request during 6 hours after the operation and mean doses of pethidine or morphine administered during 6 hours after the operation ( table 2 ) . the groups were also similar in prevalence of residual kidney stone after the operation as well as the prevalence of horseshoe kidney . we found no significant difference in the mean pain severity score between the groups 4 hours ( 5.80  2.12 versus 5.43  1.76 , p = 0.332 ) and 6 hours ( 4.88  2.18 versus 4.80  1.72 , p = 0.830 ) after the operation . the mean pef at baseline was similar in case and control groups ( 328.20  130.67 versus 320.00  125.55 , p = 0.738 ) . moreover , no significant difference was revealed in pef index 4 hours ( 205.00  99.94 versus 187.33  115.39 , p = 0.398 ) and 6 hours ( 210.60  105.85 versus 187.33  115.39 , p = 0.335 ) after pcnl . assessing the trend of changes in postoperative pain score showed that in the both groups , the mean pain severity score improved from 4 to 6 hours ( p < 0.001 in the both groups ) ( figure 1 ) . moreover , in the both groups , pef index increased from 4th to 6th hour with a mild gradient after the operation ( figure 2 ) . based on most previous studies on postoperative pain , some local anesthetics have been demonstrated to be more effective than common and traditional medications such as bupivacaine and ropivacaine with more therapeutic effects and less postoperative analgesics need , but some studies had no impact on pain scores ( 16 ) . the present study did not show the beneficial effects of ropivacaine on postoperative pain relief and pef improvement . by administrating ropivacaine 0.2% ( 30 ml ) via nephrostomy , patterns of changes in both pain severity and pef were similar in both ropivacaine and placebo groups . the difference in pain severity from the fourth hour after the operation to 2 hours later was not significant between the groups . different results were found in some previous studies , while there were differences in the methods of these studies . in parikh s studies ( 6 , 17 - 19 ) on patients undergoing elective pcnl , visual analogue scale and d - vas in the bupivacaine group were significantly higher than the ropivacaine group during a few hours after the operation . in another study , the above mentioned criteria were higher in the placebo group than the ropivacaine . in another study , the above mentioned criteria were higher in the ropivacaine group than the ropivacaine and morphine groups . in these studies , in contrast to our study , nephrostomy tube was not withdrawn at the end of operation and postponed to a later time ( on day 2 ) . moreover , in one of these studies , no comparison was made between a local anesthetic and a placebo ( 18 ) . in one investigation , although the mean number of doses of tramadol and total consumption of tramadol in 24 hours were less in the ropivacaine group , the difference was not significant ( 19 ) . in another study ( 6 ) , vas at rest as well as during deep breathing and coughing were significantly lower in ropivacaine group during the first 24 hours . the mean time of the first rescue analgesic in the ropivacaine group was also longer than the control group . the mean number of doses of tramadol in 24 hours in ropivacaine group was less than the placebo group . the mean total amount of tramadol in 24 hours in the ropivacaine was also lower than the placebo group . in parikh s studies , a spinal needle was inserted up to the renal capsule under ultrasonographic guidance along the nephrostomy tract at two positions and not at the main nephrostomy tube ; so the probability of drug dilution by urine was less . the operation method was classic pcnl ( which nephrostomy tube saves for several days ) and patients having supracostal puncture and more than one puncture were excluded from the study . in a study by gokten et al , there was no significant analgesic effect of levobupivacaine compared to the placebo ; however , only levobupivacaine infiltration through the nephrostomy tract in combination with intravenous paracetamol infusion was safe and efficacious as an analgesia method ( 20 ) . moreover , they did not perform any measurements on the respiratory system , which might be affected by pain . they did not use any quantity criteria ( only vas which is a quality criterion in fact ) . in another study by ugras et al . ( 4 ) , at the end of the operation , 30 ml of either 0.2% ropivacaine or saline was instilled into the renal puncture site , nephrostomy tract and skin . vas at 6 hours , time to first analgesic demand and total analgesic need were significantly lower in the ropivacaine group , whereas pef at 2 and 6 hours were significantly higher . ( 4 ) study , as in their study , nephrostomy tube was withdrawn on the second day ( in contrast to our study , in which nephrostomy tube was withdrawn at the end of operation ) . ( 4 ) were different compared to our study and this may be due to the presence of differences , especially in the mentioned type of surgery . urine leak into the injection site , nephrostomy tract is a tract reaching the calyx . acidified urine ( in the calyx ) may neutralize ( chemical neutralization ) the ropivacaine . the glomerular filtrate of blood plasma is usually acidified by renal tubules and collecting ducts ( 21 ) . the ph of medium containing local anesthetic affects drug activity by altering relative percentage of base and protonated forms . for example , in inflamed tissues , the ph is lower than normal and local anesthetics are more protonated than normal tissue and consequently penetrate the tissue more slowly ( 22 ) . the surface activities for uncharged anesthetics became higher than the charged ones ( 23 ) . at lower ph than that corresponding to the pka value of the local anesthetic , the amount of anesthetic adsorbed depended greatly to the membrane surface charge ( 24 ) . in conclusion , our study showed that instillation of ropivacaine 0.2% ( 30 ml ) at whole surgical zones including renal puncture site ( 10 ml ) , nephrostomy tract ( 15 ml ) and skin within tubeless pcnl surgery may not be effective on postoperative pain relief and improvement of pef within 6 hours after the operation .
background : postoperative analgesic effects of ropivacaine have been demonstrated in various surgical procedures ; however , its beneficial effect on postoperative pain relief and ability to breathe out air in urological surgeries , particularly in local interventions such as percutaneous nephrolithotomy ( pcnl ) , has remained uncertain.objectives:the aim of this study was to assess the efficacy of ropivacaine on postoperative pain severity and peak expiratory flow ( pef ) in patients undergoing pcnl procedure.patients and methods : this randomized double - blinded clinical trial was performed on 55 consecutive adult patients aged 15 to 60 years who underwent tubeless pcnl surgery . the patients were randomly assigned to instill 30 ml of ropivacaine 0.2% or 30 ml of isotonic saline with the same protocol . 
 the parameters of visual analogue scale ( vas ) ( for assessment of pain severity ) and pef ( for assessment of ability to breathe out air ) were measured 4 and 6 hours after completing the procedure . moreover , 
 the amounts of opioids or analgesics administered within 6 hours after the operation were recorded.results:we found no difference in the mean pain severity score between the case and control groups 4 hours ( p = 0.332 ) and 6 hours ( p = 0.830 ) after the operation . 
 the mean pef at baseline was similar in case and control groups ( p = 0.738 ) . 
 moreover , no difference was revealed in pef index 4 hours ( p = 0.398 ) and 6 hours ( p = 0.335 ) after pcnl between the groups . 
 the mean vas scores 4 hours after the operation slightly decreased 2 hours later ( p < 0.001 ) in the both groups . moreover , in the both groups , a sudden decrease in pef index was observed within 4 hours after the operation and increased with a mild gradient for the next 2 hours . 
 no difference was found in the amount of postoperative analgesic used in the both groups.conclusions:instillation of ropivacaine 0.2% ( 30 ml ) within tubeless pcnl surgery does not have a significant effect on postoperative pain relief and improvement of pef within 6 hours after the operation .