- Email: [email protected]
Comparison of Postoperative Analgesic Requirements in Living Donors and Patients Undergoing Similar Surgical Procedures
Comparison of Postoperative Analgesic Requirements in Living Donors and Patients Undergoing Similar Surgical Procedures J. Wanga, Y. Fua, T. Yuanb, and N. Wangb,* a Department of Urology, First Hospital of Jilin University, Changchun, China; and bDepartment of Anaesthesiology, First Hospital of Jilin University, Changchun, China
ABSTRACT Background. More factors affect pain perception of donors than patients. We prospectively evaluated postoperative pain intensity and analgesic requirements in living kidney donors and patients with renal cell carcinoma undergoing laparoscopic nephrectomy with similar surgical procedures. Material and Methods. The study included 30 living kidney donors and 30 patients with renal cell carcinoma undergoing laparoscopic nephrectomy from March 2013 to August 2014. All of the participants underwent similar surgical procedures under general anesthesia. Data including participants’ demographics, surgical data, postoperative analgesic requirements, visual analog scale scores at rest and during coughing at postoperative 0.5, 2, 4, 8, 12, 24, and 48 hours, side effects, and overall satisfaction degree were compared between the 2 groups. Results. Time to the first tramadol request was significantly shorter in the donors. The donors received more intravenous doses of tramadol than the patients. Visual analog scale scores at 2 and 4 hours at rest and at 2, 4, and 8 hours during coughing after extubation were significantly higher in the donors. There were no significant differences between the groups according to the number of participants given pethidine, time to pethidine rescue, and adverse effects. The overall satisfaction degree was comparable between the 2 groups. Conclusions. There were significant differences with respect to postoperative pain intensity and analgesic requirements in living kidney donors and patients undergoing retroperitoneal laparoscopic nephrectomy with similar surgical procedures.
S
UCCESSFUL transplantations improve both the lifespan and life quality of patients with end-stage kidney disease. Renal grafts from living donors provide better chances of survival than cadaveric grafts and can relieve the graft shortage to some extent. A choice of an appropriate surgical technique and adequate pain relief during and after living donor nephrectomy are likely to make the procedure more appealing to kidney donors [1]. Laparoscopic living donor nephrectomy, which is now the preferred method and gold standard operation for kidney donation, reduces postoperative pain and morphine consumption [2]. Nonetheless, some patients undergoing laparoscopic living donor nephrectomy still suffer significant postoperative pain, to the point where opioids are necessary. In our country, most urologists perform
laparoscopic nephrectomies through a retroperitoneal approach different from a transperitoneal laparoscopic approach, which is widely used and reported in other countries [3]. More factors affect donors’ pain perception than patients’ in certain social environments and cultural backgrounds. Thus, we need to reassess postoperative pain management for this unique donor population. In this prospective clinical trial, we tested the hypothesis that living renal donors and patients undergoing retroperitoneal laparoscopic nephrectomy had different postoperative pain experiences and analgesic requirements. *Address correspondence to Na Wang, Department of Anaesthesiology, First Hospital of Jilin University, Changchun, China, 130021. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.04.088
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1896
Transplantation Proceedings, 47, 1896e1900 (2015)
POSTOPERATIVE ANALGESIC REQUIREMENTS
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Table 1. Demographic Data and Surgical Characteristics of Patients and Donors
Left/right nephrectomy (n) M/F (n) Age (y) Weight (kg) Duration of surgery (min) Duration of anesthesia (min) Intraoperative blood loss (mL) Intraoperative fluid administration (mL)* Intraoperative urinary output (mL)*
Group D
Group P
25/5 13/17 48.6 9.6 60.4 5.2 106.7 24.1 142.7 36.4 132.5 45.2
21/9 14/16 45.7 11.4 62.3 4.4 112.9 22.2 145.9 45.3 144.3 36.6
P
.329 .795 .290 .132 .304 .764 .271
1072.7 243.6 2122.9 614.3 <.005 323.3 56.6 1012.1 263.7 <.005
Note. Values are presented as mean SD and no. of patients (%). Abbreviations: M, male; F, female. *P < .05 compared with the counterpart of the Group P.
MATERIALS AND METHODS After approval of the institutional Ethics Committee and written informed consent from the participants, this study enrolled 30 kidney donors (Group D) and 30 patients (Group P) with renal cell carcinoma staged II or below. All participants underwent retroperitoneal laparoscopic nephrectomy with similar surgical procedures. Donors and patients with histories of substance abuse and mental illness, who have allergic reactions to study drugs, with liver or renal dysfunctions, and American Society of Anesthesiologists (ASA) physical status III or above were excluded from the study. Donors or patients in whom the laparoscopic procedure had to be converted to open nephrectomy were not included in this study for further assessment. Routine monitoring (electrocardiogram, noninvasive blood pressure, and pulse oxymeter) was performed for participants taken to the operation theater without premedication. With a 16-gauge intravenous canula sited, all participants received total intravenous anesthesia and mechanical ventilation. Anesthesia induction was performed with 2 mg$kg1 propofol, 3 mg$kg1 fentanyl, and 0.15 mg$kg1 cisatracurium. Anesthesia was maintained with continuous
infusions of propofol and remifentanil at the rates of 6 to 8 mg$kg1$h1 and 0.012 mg$kg1$h1, respectively; cisatracurium was administrated intermittently as needed. Lactated Ringer’s solution was given at the rate of 8 mL$kg1$h1 in Group P and 16 mL$kg1$h1 in Group D. Furosemide 40 mg in 100 mL normal saline was administrated intravenously for 20 minutes just before the clamping of the renal artery. Pneumoperitoneum was established by CO2 insufflation with limiting pressure from 12 to 14 mm Hg. Thirty minutes before the approximated end of surgery, the participants received intravenous 100 mg$kg1 ondansetron and intravenous 3 mg morphine in both groups. All of the participants were extubated on meeting the standard criteria for extubation in the operating theater and shifted to the postanesthesia care unit. An independent anesthesia registrar who was unaware of the grouping situation recorded pain intensity evaluated by a linear 10cm visual analog scale (VAS; 0, no pain; 10, worst imaginable pain). Pain assessment was done at rest (supine) and during coughing at 0.5, 2, 4, 8, 12, 24, and 48 hours after extubation of the participants. In addition, the overall satisfaction degree was also measured at the end of the study. The overall satisfaction degree was divided as follows: poor, moderate, good, and excellent. The first rescue analgesia (intravenous injection of tramadol 1.5 mg$kg1) was given if the VAS score was more than 4. If the pain persisted even after 30 minutes of intravenous tramadol administration, a single dose of intramuscular pethidine l mg$kg1 was given (the second rescue analgesic agent). No other mode of analgesia was used in this study, except for 3 mg morphine administered 30 minutes before the end of surgery, postoperative tramadol, and pethidine. The time from extubation of the participant to administration of the first dose of rescue analgesic was recorded. The number of participants to whom tramadol or/and pethidine was administrated during the postoperative period was noted. Side effects were specifically observed and recorded for a total period of 48 hours, including nausea, vomiting, hypotension, bradycardia, allergic reactions, drowsiness, paresthesia, and respiratory depression. The incidence of adverse effects was evaluated with “yes” or “no”. Nausea was defined as a subjective unpleasant sensation associated with the awareness of the urge to vomit. Vomiting was defined as the forceful expulsion of liquid gastric contents.
Fig 1. VAS scores at rest at various time points (in hours) postoperatively. Box plots of postoperative VAS scores at rest and during coughing. Results are expressed in median. The top and bottom of each box indicate 75th and 25th percentiles and the error bars 10th and 90th percentiles. *P < .05 compared with the counterpart of Group P.
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WANG, FU, YUAN ET AL
Fig 2. VAS scores during coughing at various time points (in hours) postoperatively. Box plots of postoperative VAS scores at rest and during coughing. Results are expressed in median. The top and bottom of each box indicate 75th and 25th percentiles and the error bars 10th and 90th percentiles. *P < .05 compared with the counterpart of Group P.
The primary end point was the time to the first analgesic request. The number of subjects required for the study was calculated to detect a 30 minute difference in time to the first analgesic request. Twenty-three participants were needed for each group to detect a significant difference between the 2 groups with a .05 level and 90% power in 2-sided test of hypothesis. We enrolled 30 participants in each group to allow for possible dropouts. The normally distributed data were compared using independent t test. VAS scores, which showed nonparametric characteristics, were compared between the 2 groups using Mann-Whitney U test. The qualitative data were analyzed with the chi-square test or the Fisher exact test, as appropriate. Statistical analysis was performed using SPSS 17 (SPSS Inc, Chicago, Ill, United States). Statistical significance was defined as P < .05.
of postoperative VAS scores at rest and during coughing is depicted in Figs 1 and 2. All participants received tramadol analgesia. Time from extubation to administration of the first dose of tramadol (time to the first analgesic request) was significantly shorter in group D. The number of tramadol doses administered was significantly higher in group D. The number of participants requiring pethidine analgesia and time to pethidine rescue analgesia were comparable between the 2 groups (Table 2). The overall satisfaction degree was higher in Group P, but not statistically significant (P ¼ .094; Table 3). No significant difference was noted in side effects between the 2 groups (Table 4).
RESULTS
Except for intraoperative fluid administration and urine output, which were extremely larger in Group D than in Group P, there were no significant differences between the 2 groups based on demographic data and surgical characteristics (Table 1). There was no need for blood transfusion or conversion to open surgery. There were significant differences in VAS score at rest at 2 and 4 hours, and during coughing at 2, 4, and 8 hours between Group D and Group P after extubation. VAS scores at these time points were significantly higher in Group D. Comparison
DISCUSSION
Most laparoscopic nephrectomies are performed through a retroperitoneal approach in our country, not the transperitoneal approach reported in most other countries [2e4], so the type and intensity of pain are not similar. Part of the external oblique, internal oblique, and transverse muscles, which contribute to body supporting, are dissected in retroperitoneal laparoscopic nephrectomy, therefore, this may cause more pain from the incision than in transperitoneal laparoscopic nephrectomy. The reported incidence of shoulder tip
Table 2. Rescue Analgesia in 48 Hours Time to the first analgesic request (min)* Average no. of doses of tramadol* Pethidine rescue analgesia: no. of patients (%) Time of administration of pethidine (min) Note. Values are presented as mean SD and no. of patients (%). *P < .05 compared with the counterpart of the Group P.
Group D
Group P
P
156.6 92.5 2.8 1.3 7 (23%) 536.7 132.3
203.4 76.5 2.1 0.9 4 (13%) 603.7 157.2
.037 .011 .506 .468
POSTOPERATIVE ANALGESIC REQUIREMENTS
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Table 3. Patients’ Satisfaction
Group D Group P
Poor
Moderate
Good
Excellent
4 (13) 1 (3)
10 (33) 4 (13)
10 (33) 15 (30)
6 (20) 10 (53)
Note. Values are presented as no. of patients (%), and P ¼ .094, no significant difference is found between the 2 groups.
pain is as high as 30.7% after transperitoneal laparoscopic nephrectomy [4]. But none of the participants in this study were found with shoulder tip pain resulting from diaphragmatic irritation caused by pneumoperitoneum, because CO2 gas for pneumoperitoneum will not get into the peritoneal cavity in retroperitoneal laparoscopic nephrectomy. On the basis of these results and the current literature, postoperative pain and pain management in this unique population need to be reassessed. In the present study, 2 groups had similar demographic profile, similar surgical procedures, and comparable duration time of surgery and anesthesia, but the result was significantly different between the donors and patients. According to the result, the donors were associated with higher VAS scores at rest at 2 and 4 hours and during coughing at 2, 4 and 8 hours, shorter time to the first analgesic request, and more doses of tramadol administered than patients. The specific mechanism was unclear. One possible reason was that 3 mg morphine was administered intravenously half an hour before the expected completion of surgery to all participants for postoperative pain. Morphine was metabolized primarily by the liver; however, morphine metabolites were found in urine, indicating the existence of an extrahepatic morphine metabolic pathway [5]. A large volume of urinary output and the use of furosemide might alter and even speed up the morphine metabolism in donors, so the postoperative pain occurred earlier and was intensified. Moreover, the donor nephrectomy was a kind of operation carried out to benefit another individual, so there might be differences between donors and patients according to pain perception. Donors might feel more painful than patients about the same pain stimuli. Besides, doctors and nurses might pay more attention to donors than patients, which could result in more and earlier administration of analgesics to donors. According to this study, there were as high as 46% donors and 16% patients who regarded the postoperative pain management as poor or moderate. The inadequate pain control of this simple analgesic mode might lead to the comparable satisfaction degree between the 2 groups.
Table 4. Side Effects in 48 Hours After Extubation
Group D Group P P
Nausea
Vomiting
Dizziness
Itching
7 (23) 4 (13) .506
0 (0) 1 (3) 1.000
6 (20) 3 (10) .471
0 (0) 1 (3) 1.000
Note. Values are presented as no. of patients (%).
Although laparoscopic nephrectomy facilitated a faster recovery and produced less pain as compared with an open operation [6], some patients undergoing laparoscopic nephrectomy still suffered postoperative pain, to the point where they required parenteral opioids. Pain at the inner surgical site, the laparoscopic port sites, and incision, organ nociception, ureteric colic, and lower urinary tract discomfort associated with an indwelling urinary catheter contributed to the total pain experience in the postoperative period, so some patients might require more analgesics compared with open nephrectomy in the first 24 hours [7]. Based on the assumption that minimally invasive approaches were less traumatic, some units avoided opioids and neuraxial techniques [8]. Pain had a wide spectrum of effects on the body. Inadequately controlled postoperative pain might have harmful physiological and psychological consequences, which potentially increased the morbidity and mortality [9]. It had been recognized that inadequately treated postoperative pain might result in chronic pain, which was often misdiagnosed and neglected [8]. The significance of this acknowledgment was confirmed in other studies on patients undergoing caesarean section and inguinal hernia repair [10,11]. So intensified pain management was necessary for all of the donors and patients after laparoscopic nephrectomy, especially for donors. Living donor transplantation is gaining popularity because not only has it helped to partially relieve the refractory shortage of donor grafts, but also kidneys from living donors offer a better chance of long-term graft survival than cadaveric kidney grafts. However, living related donation exposes healthy donors to a certain risk of morbidity and even mortality. Subjecting a donor to a painful experience leads to increased morbidity, and discourages potential donors. It seemed that careful attention and maximal effort should be applied to minimize the postoperative pain for donors. There are some limitations in this study. First of all, it was not a double-blind trial or a single-blind trial. Patients and donors understood why they underwent surgery and some of them would casually offer information about their grouping situation to the registrar who recorded VAS scores. The VAS score might not be affected because it was decided by the participants and not by the registrar. The doctors who prescribed analgesics to participants knew the grouping situation. They might give more analgesics to the donors than to the patients. Second, although postoperative analgesia with tramadol and pethidine was widely used in most hospitals in our country, it was not a multimodal analgesia or a satisfactory regimen with respect to the results. So it might not translate to other groups. Third, we found that the satisfaction degree in the donors was lower but not significantly lower than in the patients, not like VAS scores, which were significantly different. A simple classification with only 4 grades might be the reason. In further research we will modify the classification of the overall satisfaction. In conclusion, it is indicated in this study that living kidney donors suffer more pain and are involved in more
1900
analgesic consumption than patients undergoing similar surgical procedures. REFERENCES [1] Chung E, Grant AB, Hibberd AD, Sprott P. Why potential live renal donors prefer laparoscopic nephrectomy: a survey of live donor attitudes. BJU Int 2007;100:1344e6. [2] Perry KT, Freedland SJ, Hu JC, et al. Quality of life, pain and return to normal activities following laparoscopic donor nephrectomy versus open mini-incision donor nephrectomy. J Urol 2003;169:2018e21. [3] Aboutaleb E, Herbert P, Crane J, Hakim N. Mini-incision donor nephrectomy techniques: a systematic review. Exp Clin Transplant 2010;8(3):189e95. [4] Singh R, Sen I, Wig J, Minz M, Sharma A, Bala I. An acetazolamide based multimodal analgesic approach versus conventional pain management in patients undergoing laparoscopic living donor nephrectomy. Indian J Anaesth 2009;53(4):434e41. [5] Bodenham A, Quinn K, Park GR. Extrahepatic morphine metabolism in man during the anhepatic phase of orthotopic liver transplantation. Br J Anaesth 1989;63:380.
WANG, FU, YUAN ET AL [6] Dillenburg W, Poulakis V, Skriapas K, et al. Retroperitoneoscopic versus open surgical radical nephrectomy for large renal cell carcinoma in clinical stage cT2 or cT3a: quality of life, pain and reconvalescence. Eur Urol 2006;49(2): 314e22. [7] Bachmann A, Wolff T, Giannini O, et al. How painful is donor nephrectomy? Retrospective analysis of early pain and pain management in open versus laparoscopic versus retroperitoneoscopic nephrectomy. Transplantation 2006;81(12): 1735e8. [8] Williams M, Milner QJW. Postoperative analgesia following renal transplantationdcurrent practice in the UK. Anaesthesia 2003;58(7):712e3. [9] Joshi GP. Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol Clin North America 2005;23(1):185e202. [10] Nikolajsen L, Sørensen HC, Jensen TS, Kehlet H. Chronic pain following Caesarean section. Acta Anaesthesiol Scand 2004;48(1):111e6. [11] Bay-Nielsen M, Perkins FM, Kehlet H. Pain and functional impairment 1 year after inguinal herniorrhaphy: a nationwide questionnaire study. Ann Surg 2001;233(1):1e7.
ABSTRACT Background. More factors affect pain perception of donors than patients. We prospectively evaluated postoperative pain intensity and analgesic requirements in living kidney donors and patients with renal cell carcinoma undergoing laparoscopic nephrectomy with similar surgical procedures. Material and Methods. The study included 30 living kidney donors and 30 patients with renal cell carcinoma undergoing laparoscopic nephrectomy from March 2013 to August 2014. All of the participants underwent similar surgical procedures under general anesthesia. Data including participants’ demographics, surgical data, postoperative analgesic requirements, visual analog scale scores at rest and during coughing at postoperative 0.5, 2, 4, 8, 12, 24, and 48 hours, side effects, and overall satisfaction degree were compared between the 2 groups. Results. Time to the first tramadol request was significantly shorter in the donors. The donors received more intravenous doses of tramadol than the patients. Visual analog scale scores at 2 and 4 hours at rest and at 2, 4, and 8 hours during coughing after extubation were significantly higher in the donors. There were no significant differences between the groups according to the number of participants given pethidine, time to pethidine rescue, and adverse effects. The overall satisfaction degree was comparable between the 2 groups. Conclusions. There were significant differences with respect to postoperative pain intensity and analgesic requirements in living kidney donors and patients undergoing retroperitoneal laparoscopic nephrectomy with similar surgical procedures.
S
UCCESSFUL transplantations improve both the lifespan and life quality of patients with end-stage kidney disease. Renal grafts from living donors provide better chances of survival than cadaveric grafts and can relieve the graft shortage to some extent. A choice of an appropriate surgical technique and adequate pain relief during and after living donor nephrectomy are likely to make the procedure more appealing to kidney donors [1]. Laparoscopic living donor nephrectomy, which is now the preferred method and gold standard operation for kidney donation, reduces postoperative pain and morphine consumption [2]. Nonetheless, some patients undergoing laparoscopic living donor nephrectomy still suffer significant postoperative pain, to the point where opioids are necessary. In our country, most urologists perform
laparoscopic nephrectomies through a retroperitoneal approach different from a transperitoneal laparoscopic approach, which is widely used and reported in other countries [3]. More factors affect donors’ pain perception than patients’ in certain social environments and cultural backgrounds. Thus, we need to reassess postoperative pain management for this unique donor population. In this prospective clinical trial, we tested the hypothesis that living renal donors and patients undergoing retroperitoneal laparoscopic nephrectomy had different postoperative pain experiences and analgesic requirements. *Address correspondence to Na Wang, Department of Anaesthesiology, First Hospital of Jilin University, Changchun, China, 130021. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.04.088
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1896
Transplantation Proceedings, 47, 1896e1900 (2015)
POSTOPERATIVE ANALGESIC REQUIREMENTS
1897
Table 1. Demographic Data and Surgical Characteristics of Patients and Donors
Left/right nephrectomy (n) M/F (n) Age (y) Weight (kg) Duration of surgery (min) Duration of anesthesia (min) Intraoperative blood loss (mL) Intraoperative fluid administration (mL)* Intraoperative urinary output (mL)*
Group D
Group P
25/5 13/17 48.6 9.6 60.4 5.2 106.7 24.1 142.7 36.4 132.5 45.2
21/9 14/16 45.7 11.4 62.3 4.4 112.9 22.2 145.9 45.3 144.3 36.6
P
.329 .795 .290 .132 .304 .764 .271
1072.7 243.6 2122.9 614.3 <.005 323.3 56.6 1012.1 263.7 <.005
Note. Values are presented as mean SD and no. of patients (%). Abbreviations: M, male; F, female. *P < .05 compared with the counterpart of the Group P.
MATERIALS AND METHODS After approval of the institutional Ethics Committee and written informed consent from the participants, this study enrolled 30 kidney donors (Group D) and 30 patients (Group P) with renal cell carcinoma staged II or below. All participants underwent retroperitoneal laparoscopic nephrectomy with similar surgical procedures. Donors and patients with histories of substance abuse and mental illness, who have allergic reactions to study drugs, with liver or renal dysfunctions, and American Society of Anesthesiologists (ASA) physical status III or above were excluded from the study. Donors or patients in whom the laparoscopic procedure had to be converted to open nephrectomy were not included in this study for further assessment. Routine monitoring (electrocardiogram, noninvasive blood pressure, and pulse oxymeter) was performed for participants taken to the operation theater without premedication. With a 16-gauge intravenous canula sited, all participants received total intravenous anesthesia and mechanical ventilation. Anesthesia induction was performed with 2 mg$kg1 propofol, 3 mg$kg1 fentanyl, and 0.15 mg$kg1 cisatracurium. Anesthesia was maintained with continuous
infusions of propofol and remifentanil at the rates of 6 to 8 mg$kg1$h1 and 0.012 mg$kg1$h1, respectively; cisatracurium was administrated intermittently as needed. Lactated Ringer’s solution was given at the rate of 8 mL$kg1$h1 in Group P and 16 mL$kg1$h1 in Group D. Furosemide 40 mg in 100 mL normal saline was administrated intravenously for 20 minutes just before the clamping of the renal artery. Pneumoperitoneum was established by CO2 insufflation with limiting pressure from 12 to 14 mm Hg. Thirty minutes before the approximated end of surgery, the participants received intravenous 100 mg$kg1 ondansetron and intravenous 3 mg morphine in both groups. All of the participants were extubated on meeting the standard criteria for extubation in the operating theater and shifted to the postanesthesia care unit. An independent anesthesia registrar who was unaware of the grouping situation recorded pain intensity evaluated by a linear 10cm visual analog scale (VAS; 0, no pain; 10, worst imaginable pain). Pain assessment was done at rest (supine) and during coughing at 0.5, 2, 4, 8, 12, 24, and 48 hours after extubation of the participants. In addition, the overall satisfaction degree was also measured at the end of the study. The overall satisfaction degree was divided as follows: poor, moderate, good, and excellent. The first rescue analgesia (intravenous injection of tramadol 1.5 mg$kg1) was given if the VAS score was more than 4. If the pain persisted even after 30 minutes of intravenous tramadol administration, a single dose of intramuscular pethidine l mg$kg1 was given (the second rescue analgesic agent). No other mode of analgesia was used in this study, except for 3 mg morphine administered 30 minutes before the end of surgery, postoperative tramadol, and pethidine. The time from extubation of the participant to administration of the first dose of rescue analgesic was recorded. The number of participants to whom tramadol or/and pethidine was administrated during the postoperative period was noted. Side effects were specifically observed and recorded for a total period of 48 hours, including nausea, vomiting, hypotension, bradycardia, allergic reactions, drowsiness, paresthesia, and respiratory depression. The incidence of adverse effects was evaluated with “yes” or “no”. Nausea was defined as a subjective unpleasant sensation associated with the awareness of the urge to vomit. Vomiting was defined as the forceful expulsion of liquid gastric contents.
Fig 1. VAS scores at rest at various time points (in hours) postoperatively. Box plots of postoperative VAS scores at rest and during coughing. Results are expressed in median. The top and bottom of each box indicate 75th and 25th percentiles and the error bars 10th and 90th percentiles. *P < .05 compared with the counterpart of Group P.
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Fig 2. VAS scores during coughing at various time points (in hours) postoperatively. Box plots of postoperative VAS scores at rest and during coughing. Results are expressed in median. The top and bottom of each box indicate 75th and 25th percentiles and the error bars 10th and 90th percentiles. *P < .05 compared with the counterpart of Group P.
The primary end point was the time to the first analgesic request. The number of subjects required for the study was calculated to detect a 30 minute difference in time to the first analgesic request. Twenty-three participants were needed for each group to detect a significant difference between the 2 groups with a .05 level and 90% power in 2-sided test of hypothesis. We enrolled 30 participants in each group to allow for possible dropouts. The normally distributed data were compared using independent t test. VAS scores, which showed nonparametric characteristics, were compared between the 2 groups using Mann-Whitney U test. The qualitative data were analyzed with the chi-square test or the Fisher exact test, as appropriate. Statistical analysis was performed using SPSS 17 (SPSS Inc, Chicago, Ill, United States). Statistical significance was defined as P < .05.
of postoperative VAS scores at rest and during coughing is depicted in Figs 1 and 2. All participants received tramadol analgesia. Time from extubation to administration of the first dose of tramadol (time to the first analgesic request) was significantly shorter in group D. The number of tramadol doses administered was significantly higher in group D. The number of participants requiring pethidine analgesia and time to pethidine rescue analgesia were comparable between the 2 groups (Table 2). The overall satisfaction degree was higher in Group P, but not statistically significant (P ¼ .094; Table 3). No significant difference was noted in side effects between the 2 groups (Table 4).
RESULTS
Except for intraoperative fluid administration and urine output, which were extremely larger in Group D than in Group P, there were no significant differences between the 2 groups based on demographic data and surgical characteristics (Table 1). There was no need for blood transfusion or conversion to open surgery. There were significant differences in VAS score at rest at 2 and 4 hours, and during coughing at 2, 4, and 8 hours between Group D and Group P after extubation. VAS scores at these time points were significantly higher in Group D. Comparison
DISCUSSION
Most laparoscopic nephrectomies are performed through a retroperitoneal approach in our country, not the transperitoneal approach reported in most other countries [2e4], so the type and intensity of pain are not similar. Part of the external oblique, internal oblique, and transverse muscles, which contribute to body supporting, are dissected in retroperitoneal laparoscopic nephrectomy, therefore, this may cause more pain from the incision than in transperitoneal laparoscopic nephrectomy. The reported incidence of shoulder tip
Table 2. Rescue Analgesia in 48 Hours Time to the first analgesic request (min)* Average no. of doses of tramadol* Pethidine rescue analgesia: no. of patients (%) Time of administration of pethidine (min) Note. Values are presented as mean SD and no. of patients (%). *P < .05 compared with the counterpart of the Group P.
Group D
Group P
P
156.6 92.5 2.8 1.3 7 (23%) 536.7 132.3
203.4 76.5 2.1 0.9 4 (13%) 603.7 157.2
.037 .011 .506 .468
POSTOPERATIVE ANALGESIC REQUIREMENTS
1899
Table 3. Patients’ Satisfaction
Group D Group P
Poor
Moderate
Good
Excellent
4 (13) 1 (3)
10 (33) 4 (13)
10 (33) 15 (30)
6 (20) 10 (53)
Note. Values are presented as no. of patients (%), and P ¼ .094, no significant difference is found between the 2 groups.
pain is as high as 30.7% after transperitoneal laparoscopic nephrectomy [4]. But none of the participants in this study were found with shoulder tip pain resulting from diaphragmatic irritation caused by pneumoperitoneum, because CO2 gas for pneumoperitoneum will not get into the peritoneal cavity in retroperitoneal laparoscopic nephrectomy. On the basis of these results and the current literature, postoperative pain and pain management in this unique population need to be reassessed. In the present study, 2 groups had similar demographic profile, similar surgical procedures, and comparable duration time of surgery and anesthesia, but the result was significantly different between the donors and patients. According to the result, the donors were associated with higher VAS scores at rest at 2 and 4 hours and during coughing at 2, 4 and 8 hours, shorter time to the first analgesic request, and more doses of tramadol administered than patients. The specific mechanism was unclear. One possible reason was that 3 mg morphine was administered intravenously half an hour before the expected completion of surgery to all participants for postoperative pain. Morphine was metabolized primarily by the liver; however, morphine metabolites were found in urine, indicating the existence of an extrahepatic morphine metabolic pathway [5]. A large volume of urinary output and the use of furosemide might alter and even speed up the morphine metabolism in donors, so the postoperative pain occurred earlier and was intensified. Moreover, the donor nephrectomy was a kind of operation carried out to benefit another individual, so there might be differences between donors and patients according to pain perception. Donors might feel more painful than patients about the same pain stimuli. Besides, doctors and nurses might pay more attention to donors than patients, which could result in more and earlier administration of analgesics to donors. According to this study, there were as high as 46% donors and 16% patients who regarded the postoperative pain management as poor or moderate. The inadequate pain control of this simple analgesic mode might lead to the comparable satisfaction degree between the 2 groups.
Table 4. Side Effects in 48 Hours After Extubation
Group D Group P P
Nausea
Vomiting
Dizziness
Itching
7 (23) 4 (13) .506
0 (0) 1 (3) 1.000
6 (20) 3 (10) .471
0 (0) 1 (3) 1.000
Note. Values are presented as no. of patients (%).
Although laparoscopic nephrectomy facilitated a faster recovery and produced less pain as compared with an open operation [6], some patients undergoing laparoscopic nephrectomy still suffered postoperative pain, to the point where they required parenteral opioids. Pain at the inner surgical site, the laparoscopic port sites, and incision, organ nociception, ureteric colic, and lower urinary tract discomfort associated with an indwelling urinary catheter contributed to the total pain experience in the postoperative period, so some patients might require more analgesics compared with open nephrectomy in the first 24 hours [7]. Based on the assumption that minimally invasive approaches were less traumatic, some units avoided opioids and neuraxial techniques [8]. Pain had a wide spectrum of effects on the body. Inadequately controlled postoperative pain might have harmful physiological and psychological consequences, which potentially increased the morbidity and mortality [9]. It had been recognized that inadequately treated postoperative pain might result in chronic pain, which was often misdiagnosed and neglected [8]. The significance of this acknowledgment was confirmed in other studies on patients undergoing caesarean section and inguinal hernia repair [10,11]. So intensified pain management was necessary for all of the donors and patients after laparoscopic nephrectomy, especially for donors. Living donor transplantation is gaining popularity because not only has it helped to partially relieve the refractory shortage of donor grafts, but also kidneys from living donors offer a better chance of long-term graft survival than cadaveric kidney grafts. However, living related donation exposes healthy donors to a certain risk of morbidity and even mortality. Subjecting a donor to a painful experience leads to increased morbidity, and discourages potential donors. It seemed that careful attention and maximal effort should be applied to minimize the postoperative pain for donors. There are some limitations in this study. First of all, it was not a double-blind trial or a single-blind trial. Patients and donors understood why they underwent surgery and some of them would casually offer information about their grouping situation to the registrar who recorded VAS scores. The VAS score might not be affected because it was decided by the participants and not by the registrar. The doctors who prescribed analgesics to participants knew the grouping situation. They might give more analgesics to the donors than to the patients. Second, although postoperative analgesia with tramadol and pethidine was widely used in most hospitals in our country, it was not a multimodal analgesia or a satisfactory regimen with respect to the results. So it might not translate to other groups. Third, we found that the satisfaction degree in the donors was lower but not significantly lower than in the patients, not like VAS scores, which were significantly different. A simple classification with only 4 grades might be the reason. In further research we will modify the classification of the overall satisfaction. In conclusion, it is indicated in this study that living kidney donors suffer more pain and are involved in more
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analgesic consumption than patients undergoing similar surgical procedures. REFERENCES [1] Chung E, Grant AB, Hibberd AD, Sprott P. Why potential live renal donors prefer laparoscopic nephrectomy: a survey of live donor attitudes. BJU Int 2007;100:1344e6. [2] Perry KT, Freedland SJ, Hu JC, et al. Quality of life, pain and return to normal activities following laparoscopic donor nephrectomy versus open mini-incision donor nephrectomy. J Urol 2003;169:2018e21. [3] Aboutaleb E, Herbert P, Crane J, Hakim N. Mini-incision donor nephrectomy techniques: a systematic review. Exp Clin Transplant 2010;8(3):189e95. [4] Singh R, Sen I, Wig J, Minz M, Sharma A, Bala I. An acetazolamide based multimodal analgesic approach versus conventional pain management in patients undergoing laparoscopic living donor nephrectomy. Indian J Anaesth 2009;53(4):434e41. [5] Bodenham A, Quinn K, Park GR. Extrahepatic morphine metabolism in man during the anhepatic phase of orthotopic liver transplantation. Br J Anaesth 1989;63:380.
WANG, FU, YUAN ET AL [6] Dillenburg W, Poulakis V, Skriapas K, et al. Retroperitoneoscopic versus open surgical radical nephrectomy for large renal cell carcinoma in clinical stage cT2 or cT3a: quality of life, pain and reconvalescence. Eur Urol 2006;49(2): 314e22. [7] Bachmann A, Wolff T, Giannini O, et al. How painful is donor nephrectomy? Retrospective analysis of early pain and pain management in open versus laparoscopic versus retroperitoneoscopic nephrectomy. Transplantation 2006;81(12): 1735e8. [8] Williams M, Milner QJW. Postoperative analgesia following renal transplantationdcurrent practice in the UK. Anaesthesia 2003;58(7):712e3. [9] Joshi GP. Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol Clin North America 2005;23(1):185e202. [10] Nikolajsen L, Sørensen HC, Jensen TS, Kehlet H. Chronic pain following Caesarean section. Acta Anaesthesiol Scand 2004;48(1):111e6. [11] Bay-Nielsen M, Perkins FM, Kehlet H. Pain and functional impairment 1 year after inguinal herniorrhaphy: a nationwide questionnaire study. Ann Surg 2001;233(1):1e7.