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Comparison of Postoperative Morphine Requirements in Renal Donors and Patients With Renal Carcinoma Undergoing Laparoscopic Nephrectomy
Comparison of Postoperative Morphine Requirements in Renal Donors and Patients With Renal Carcinoma Undergoing Laparoscopic Nephrectomy J. Wanga, H. Mab, Y. Fua, and N. Wangb,* a Department of Urology, the First Hospital of Jilin University, Changchun, China; and bDepartment of Anesthesiology, the First Hospital of Jilin University, Changchun, China
ABSTRACT Objective. The objective of this study was to evaluate postoperative pain intensity and morphine consumption between living renal donors and patients with renal cell carcinoma undergoing laparoscopic nephrectomy. Methods. The clinical trial enrolled 25 living renal donors and 25 patients with renal cell carcinoma undergoing laparoscopic nephrectomy. All underwent similar surgical procedures under general anesthesia. After surgery, morphine patient-controlled analgesia (PCA) was applied to all of them. Data including demographics, surgical details, postoperative morphine consumption, visual analog scale (VAS) 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. Donors received more intravenous doses of morphine than patients. VAS scores at 2 and 4 hours at rest and during coughing after extubation were significantly higher in donors. The overall satisfaction degree was higher in patients. Conclusions. Living-renal donors suffer more pain and are associated with more morphine consumption than patients with cancer.
L
IVING kidney transplantation produces a better chance of survival rate of grafts compared with cadaveric transplantation and can partially relieve the graft shortage. Adequate postoperative analgesia is likely to make the donation more appealing to kidney donors [1]. Laparoscopic nephrectomy is now widespread for kidney donation because it decreases postoperative pain and morphine consumption [2]. Many factors influence donors’ pain perception, including perioperative medications, social environment, education, and cultural background. Our previous study indicates that renal donors have a decreased postoperative analgesic requirement compared with patients with renal carcinoma without patient-controlled analgesia (PCA) [3]. In this prospective clinical trial, the hypothesis was tested that livingrenal donors and patients undergoing laparoscopic nephrectomy had different PCA morphine consumption. MATERIAL AND METHODS After approval of the institutional Ethics Committee and written informed consent from the participants, 25 kidney donors (Group D) ª 2016 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 48, 31e34 (2016)
and 25 patients (Group P) with renal cell carcinoma staged II or below were enrolled in this study. All participants were scheduled for laparoscopic nephrectomy with similar surgical procedures. Exclusion criteria included substance abuse, known allergy to study drugs, inability to comprehend verbal instructions, morbid obesity, liver or renal dysfunction, conversion to open surgery, and excessive bleeding. One day before operation, all subjects were given instructions on the usage of the PCA device and pain assessment with the visual analog scale (VAS; values from 0 to 10; 0, no pain and 10, the most severe pain). When arriving at the operating theater without premedication, the participants were monitored with electrocardiography (ECG), noninvasive blood pressure (BP), pulse oximetry (SpO2),
This clinical trial was supported by the First Hospital of Jilin University. *Address correspondence to Na Wang, Department of Anesthesiology, the First Hospital of Jilin University, No. 71 Xinmin Street, Changchun City, Jilin Province, China 130021. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2015.12.032
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32
WANG, MA, FU ET AL Table 1. Demographic Data and Surgical Details
Left/right nephrectomy (n) Male/female (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 (n ¼ 25)
Group P (n ¼ 24)
P
18/7 12/13 45.7 10.2 61.6 9.3 115.3 22.8 135.3 32.7 156.9 52.3 2342.1 587.7 1019.6 321.4
13/11 17/7 51.4 12.4 65.4 9.1 112.3 17.2 147.4 35.6 164.8 60.4 1179.5 236.4 458.9 63.5
.243 .148 .084 .155 .606 .221 .626 <.005 <.005
Note: Data are presented as mean standard deviation, median (range), or number of patients.
and end-tidal carbon dioxide pressure. General anesthesia was induced with 0.05 mg/kg midazolam, 3 mg/kg fentanyl, 2 mg/kg propofol, and 0.15 mg/kg cisatracurium. Anesthesia was maintained with a continuous intravenous infusion of 6e8 mg/kg/h propofol and 0.012 mg/kg/h remifentanil to maintain bispectral index between 45 and 60. Cisatracurium was administrated intermittently as needed. During the surgery, Ringer’s lactate was administered at the rate of 8 mL/kg/h in Group P, and 16 mL/kg/h in Group D. Donors were given 40 mg furosemide in 100 mL normal saline, which was administered intravenously over 20 minutes before the clamping of renal artery. Pneumoperitoneum was established by carbon dioxide insufflation with limiting pressure from 12 to 14 mm Hg. Local anesthetic infiltration into port sites and incision were performed by the same surgeon with 20 mL 0.5% ropivacaine. Thirty minutes before the end of surgery, all participants received intravenous 4 mg ondansetron and 3 mg morphine. The participants were extubated on meeting the standard criteria for extubation in the operating theater and then transferred to the postanesthesia care unit. All of the participants received intravenous morphine PCA after extubation from a PCA device (Aipeng ZZB-I Pump, Nantong Apon Medical Appliance Co Ltd, Rudong, China). PCA was set on the demand mode without loading dose or background infusion. The dose of morphine was set at 1 mg with a time-lock interval of 10 minutes and a 4-hour maximum dose of 15 mg. Perioperative data and postoperative assessments were done by a researcher blinded to each patient’s group who was not involved in the patient management. VAS scores at rest and during coughing were evaluated at 0.5, 2, 4, 8, 12, 24, and 48 hours after extubation of the participants. When sufficiently awake, participants were asked to evaluate their pain intensity using the VAS. Intravenous 1.5 mg/kg tramadol was given as rescue analgesia if the VAS score
Fig 1. Cumulative intravenous morphine consumption (mg) delivered by PCA until 48 h after extubation in Group D and Group P. Data are means standard deviation. *P < .05 between the 2 groups.
at rest was more than 3 over 15 minutes. The number of participants to whom tramadol was administrated during the postoperative period was noted. In addition, the overall satisfaction degree was also measured at the end of the study as follows: poor, moderate, good, and excellent. Additional administration of tramadol, postoperative pain intensity, and cumulative morphine consumption were documented. Side effects were observed and recorded at 48 hours, including nausea, vomiting, hypotension, bradycardia, allergic reactions, drowsiness, paresthesia, and respiratory depression. The incidence of adverse effects was assessed with “yes” or “no”. The primary endpoint was the amount of morphine needed for postoperative analgesia. After a pilot trial of 5 participants in each group, a variance of 23% in postoperative morphine consumption was noted. Twenty-two participants were required for each group, with a significance level of .05 and a power of 90% in a 2-sided test of hypothesis. Twenty-five participants in each group were enrolled for possible dropouts. Data were analyzed using SPSS 17 (SPSS Inc, Chicago, Ill, United States). The data of normal distribution were compared using Student t test. VAS scores were compared using MannWhitney U test. The categorical data were analyzed with the chi-square test or the Fisher exact test, as appropriate. Statistical significance was defined as P < .05.
RESULTS
Forty-nine patients finished the clinical trial. One patient in Group P was excluded from this study because of massive bleeding. Except for intraoperative fluid administration and urine output, which were larger in Group D, there were no
MORPHINE REQUIREMENTS IN DONORS AND PATIENTS
33
Fig 2. VAS scores at rest and during coughing at various time points postoperatively. Box plots of postoperative VAS scores at rest. Results are expressed in median. The top and bottom of each box indicate 75th and 25th percentiles and the error bars indicate 10th and 90th percentiles.
significant differences between the 2 groups based on demographic data and surgical details (Table 1). The amount of morphine consumption for the first 8 hours was significantly lower in Group P than Group D, and then comparable from 8 hours to 48 hours: 26.5 10.9 mg in Group D versus 21.5 13.3 mg in Group P (P ¼ .157) between the 2 groups (Fig 1). VAS score at rest at 2 and 4 hours, and during coughing at 2 and 4 hours were greater in Group D than in Group P (Figs 2 and 3). No difference was noted on the incidence of rescue analgesia or any side effects between the 2 groups (Table 2). No respiratory depression was found. More participants were satisfied in Group P (P ¼ .011; Table 3). DISCUSSION
Laparoscopic nephrectomies are commonly performed through retroperitoneal approach in our country, not the transperitoneal approach [2], thus no participants in this study were observed with shoulder tip pain resulting from
diaphragmatic irritation by pneumoperitoneum, because carbon dioxide gas for pneumoperitoneum will not get into the peritoneal cavity. On the basis of these results and the current literature, postoperative pain and pain management in this unique population need to be assessed. In this clinical trial, the 2 groups had comparable demographic and surgical details, but postoperative VAS scores and morphine consumption were significantly different. The result is consistent with the previous study [3]. Morphine is given intravenously to all participants to alleviate postoperative pain by PCA. Excessive urinary output and the use of furosemide may speed up morphine metabolism in donors, so donors experience more serious pain. It can be explained that the donors consume more morphine than patients in the first 8 hours, and then a comparable amount of morphine in the rest of the time of this study between the 2 groups. Moreover, donor nephrectomy is an operation on healthy people to benefit another individual, so there may be differences between donors and patients in pain perception. Donors may feel more painful than
Fig 3. VAS scores at rest and during coughing at various time points postoperatively. Box plots of postoperative VAS scores at rest. Results are expressed in median. The top and bottom of each box indicate 75th and 25th percentiles and the error bars indicate 10th and 90th percentiles.
34
WANG, MA, FU ET AL
Table 2. Rescue Analgesia and Side Effects After Extubation in 48 Hours Rescue Analgesia Nausea Vomiting Dizziness Itching
Group D (n ¼ 25) Group P (n ¼ 24) P
3 (12) 2 (8) 1.000
5 (20) 2 (8) .417
0 (0) 1 (4) .489
3 (12) 1 (4) .609
0 (0) 1 (4) .489
Note: Data are presented as number of patients (%).
patients about the same pain stimuli. In addition, doctors and nurses may pay more attention to donors than patients, which is reflected in earlier and greater administration of analgesics to donors. Although laparoscopic nephrectomy yields a faster recovery and less pain compared with an open operation, sometimes the postoperative pain is still significant to patients [4]. Inadequately controlled postoperative pain may have harmful physiological and psychological consequences, which potentially increase morbidity and mortality [5]. It had been recognized that inadequately treated postoperative pain might result in chronic pain, which was often misdiagnosed and neglected [6]. In this study, donors were not as satisfied as patients, so intensified pain management was necessary for donors. Exposing a donor to a painful experience not only leads to increased morbidity, but also discourages potential donors. It seems that careful attention and maximal effort need be applied to minimize postoperative pain for donors. The major limitation of this study is that it is not a doubleblind trial.
Table 3. Patients’ Satisfaction, Number of Patients (%) Group D (n ¼ 25) Group P (n ¼ 24)
Poor
Moderate
Good
Excellent
6 (24) 3 (12)
13 (52) 4 (16)
4 (16) 11 (46)
2 (8) 6 (25)
P ¼ .011 (P < .05), no significant difference between the 2 groups.
In conclusion, living-renal donors suffer more pain and are associated with more morphine consumption than patients undergoing laparoscopic nephrectomy.
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(6):1344e6. [2] Perry KT, Freedland SJ, Hu JC, Phelan MW, Kristo B, Gritsch AH, 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(6):2018e21. [3] Wang J, Fu Y, Yuan T, Wang N. Comparison of postoperative analgesic requirements in living donors and patients undergoing similar surgical procedures. Transplant Proc 2015;47(6):1896e900. [4] Dillenburg W, Poulakis V, Skriapas K, de Vries R, Ferakis N, Witzsch U, 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. [5] Joshi GP. Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol Clin North America 2005;23(1):185e202. [6] Nikolajsen L, Sørensen HC, Jensen TS, Kehlet H. Chronic pain following Caesarean section. Acta Anaesthesiol Scand 2004;48(1):111e6.
ABSTRACT Objective. The objective of this study was to evaluate postoperative pain intensity and morphine consumption between living renal donors and patients with renal cell carcinoma undergoing laparoscopic nephrectomy. Methods. The clinical trial enrolled 25 living renal donors and 25 patients with renal cell carcinoma undergoing laparoscopic nephrectomy. All underwent similar surgical procedures under general anesthesia. After surgery, morphine patient-controlled analgesia (PCA) was applied to all of them. Data including demographics, surgical details, postoperative morphine consumption, visual analog scale (VAS) 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. Donors received more intravenous doses of morphine than patients. VAS scores at 2 and 4 hours at rest and during coughing after extubation were significantly higher in donors. The overall satisfaction degree was higher in patients. Conclusions. Living-renal donors suffer more pain and are associated with more morphine consumption than patients with cancer.
L
IVING kidney transplantation produces a better chance of survival rate of grafts compared with cadaveric transplantation and can partially relieve the graft shortage. Adequate postoperative analgesia is likely to make the donation more appealing to kidney donors [1]. Laparoscopic nephrectomy is now widespread for kidney donation because it decreases postoperative pain and morphine consumption [2]. Many factors influence donors’ pain perception, including perioperative medications, social environment, education, and cultural background. Our previous study indicates that renal donors have a decreased postoperative analgesic requirement compared with patients with renal carcinoma without patient-controlled analgesia (PCA) [3]. In this prospective clinical trial, the hypothesis was tested that livingrenal donors and patients undergoing laparoscopic nephrectomy had different PCA morphine consumption. MATERIAL AND METHODS After approval of the institutional Ethics Committee and written informed consent from the participants, 25 kidney donors (Group D) ª 2016 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 48, 31e34 (2016)
and 25 patients (Group P) with renal cell carcinoma staged II or below were enrolled in this study. All participants were scheduled for laparoscopic nephrectomy with similar surgical procedures. Exclusion criteria included substance abuse, known allergy to study drugs, inability to comprehend verbal instructions, morbid obesity, liver or renal dysfunction, conversion to open surgery, and excessive bleeding. One day before operation, all subjects were given instructions on the usage of the PCA device and pain assessment with the visual analog scale (VAS; values from 0 to 10; 0, no pain and 10, the most severe pain). When arriving at the operating theater without premedication, the participants were monitored with electrocardiography (ECG), noninvasive blood pressure (BP), pulse oximetry (SpO2),
This clinical trial was supported by the First Hospital of Jilin University. *Address correspondence to Na Wang, Department of Anesthesiology, the First Hospital of Jilin University, No. 71 Xinmin Street, Changchun City, Jilin Province, China 130021. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2015.12.032
31
32
WANG, MA, FU ET AL Table 1. Demographic Data and Surgical Details
Left/right nephrectomy (n) Male/female (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 (n ¼ 25)
Group P (n ¼ 24)
P
18/7 12/13 45.7 10.2 61.6 9.3 115.3 22.8 135.3 32.7 156.9 52.3 2342.1 587.7 1019.6 321.4
13/11 17/7 51.4 12.4 65.4 9.1 112.3 17.2 147.4 35.6 164.8 60.4 1179.5 236.4 458.9 63.5
.243 .148 .084 .155 .606 .221 .626 <.005 <.005
Note: Data are presented as mean standard deviation, median (range), or number of patients.
and end-tidal carbon dioxide pressure. General anesthesia was induced with 0.05 mg/kg midazolam, 3 mg/kg fentanyl, 2 mg/kg propofol, and 0.15 mg/kg cisatracurium. Anesthesia was maintained with a continuous intravenous infusion of 6e8 mg/kg/h propofol and 0.012 mg/kg/h remifentanil to maintain bispectral index between 45 and 60. Cisatracurium was administrated intermittently as needed. During the surgery, Ringer’s lactate was administered at the rate of 8 mL/kg/h in Group P, and 16 mL/kg/h in Group D. Donors were given 40 mg furosemide in 100 mL normal saline, which was administered intravenously over 20 minutes before the clamping of renal artery. Pneumoperitoneum was established by carbon dioxide insufflation with limiting pressure from 12 to 14 mm Hg. Local anesthetic infiltration into port sites and incision were performed by the same surgeon with 20 mL 0.5% ropivacaine. Thirty minutes before the end of surgery, all participants received intravenous 4 mg ondansetron and 3 mg morphine. The participants were extubated on meeting the standard criteria for extubation in the operating theater and then transferred to the postanesthesia care unit. All of the participants received intravenous morphine PCA after extubation from a PCA device (Aipeng ZZB-I Pump, Nantong Apon Medical Appliance Co Ltd, Rudong, China). PCA was set on the demand mode without loading dose or background infusion. The dose of morphine was set at 1 mg with a time-lock interval of 10 minutes and a 4-hour maximum dose of 15 mg. Perioperative data and postoperative assessments were done by a researcher blinded to each patient’s group who was not involved in the patient management. VAS scores at rest and during coughing were evaluated at 0.5, 2, 4, 8, 12, 24, and 48 hours after extubation of the participants. When sufficiently awake, participants were asked to evaluate their pain intensity using the VAS. Intravenous 1.5 mg/kg tramadol was given as rescue analgesia if the VAS score
Fig 1. Cumulative intravenous morphine consumption (mg) delivered by PCA until 48 h after extubation in Group D and Group P. Data are means standard deviation. *P < .05 between the 2 groups.
at rest was more than 3 over 15 minutes. The number of participants to whom tramadol was administrated during the postoperative period was noted. In addition, the overall satisfaction degree was also measured at the end of the study as follows: poor, moderate, good, and excellent. Additional administration of tramadol, postoperative pain intensity, and cumulative morphine consumption were documented. Side effects were observed and recorded at 48 hours, including nausea, vomiting, hypotension, bradycardia, allergic reactions, drowsiness, paresthesia, and respiratory depression. The incidence of adverse effects was assessed with “yes” or “no”. The primary endpoint was the amount of morphine needed for postoperative analgesia. After a pilot trial of 5 participants in each group, a variance of 23% in postoperative morphine consumption was noted. Twenty-two participants were required for each group, with a significance level of .05 and a power of 90% in a 2-sided test of hypothesis. Twenty-five participants in each group were enrolled for possible dropouts. Data were analyzed using SPSS 17 (SPSS Inc, Chicago, Ill, United States). The data of normal distribution were compared using Student t test. VAS scores were compared using MannWhitney U test. The categorical data were analyzed with the chi-square test or the Fisher exact test, as appropriate. Statistical significance was defined as P < .05.
RESULTS
Forty-nine patients finished the clinical trial. One patient in Group P was excluded from this study because of massive bleeding. Except for intraoperative fluid administration and urine output, which were larger in Group D, there were no
MORPHINE REQUIREMENTS IN DONORS AND PATIENTS
33
Fig 2. VAS scores at rest and during coughing at various time points postoperatively. Box plots of postoperative VAS scores at rest. Results are expressed in median. The top and bottom of each box indicate 75th and 25th percentiles and the error bars indicate 10th and 90th percentiles.
significant differences between the 2 groups based on demographic data and surgical details (Table 1). The amount of morphine consumption for the first 8 hours was significantly lower in Group P than Group D, and then comparable from 8 hours to 48 hours: 26.5 10.9 mg in Group D versus 21.5 13.3 mg in Group P (P ¼ .157) between the 2 groups (Fig 1). VAS score at rest at 2 and 4 hours, and during coughing at 2 and 4 hours were greater in Group D than in Group P (Figs 2 and 3). No difference was noted on the incidence of rescue analgesia or any side effects between the 2 groups (Table 2). No respiratory depression was found. More participants were satisfied in Group P (P ¼ .011; Table 3). DISCUSSION
Laparoscopic nephrectomies are commonly performed through retroperitoneal approach in our country, not the transperitoneal approach [2], thus no participants in this study were observed with shoulder tip pain resulting from
diaphragmatic irritation by pneumoperitoneum, because carbon dioxide gas for pneumoperitoneum will not get into the peritoneal cavity. On the basis of these results and the current literature, postoperative pain and pain management in this unique population need to be assessed. In this clinical trial, the 2 groups had comparable demographic and surgical details, but postoperative VAS scores and morphine consumption were significantly different. The result is consistent with the previous study [3]. Morphine is given intravenously to all participants to alleviate postoperative pain by PCA. Excessive urinary output and the use of furosemide may speed up morphine metabolism in donors, so donors experience more serious pain. It can be explained that the donors consume more morphine than patients in the first 8 hours, and then a comparable amount of morphine in the rest of the time of this study between the 2 groups. Moreover, donor nephrectomy is an operation on healthy people to benefit another individual, so there may be differences between donors and patients in pain perception. Donors may feel more painful than
Fig 3. VAS scores at rest and during coughing at various time points postoperatively. Box plots of postoperative VAS scores at rest. Results are expressed in median. The top and bottom of each box indicate 75th and 25th percentiles and the error bars indicate 10th and 90th percentiles.
34
WANG, MA, FU ET AL
Table 2. Rescue Analgesia and Side Effects After Extubation in 48 Hours Rescue Analgesia Nausea Vomiting Dizziness Itching
Group D (n ¼ 25) Group P (n ¼ 24) P
3 (12) 2 (8) 1.000
5 (20) 2 (8) .417
0 (0) 1 (4) .489
3 (12) 1 (4) .609
0 (0) 1 (4) .489
Note: Data are presented as number of patients (%).
patients about the same pain stimuli. In addition, doctors and nurses may pay more attention to donors than patients, which is reflected in earlier and greater administration of analgesics to donors. Although laparoscopic nephrectomy yields a faster recovery and less pain compared with an open operation, sometimes the postoperative pain is still significant to patients [4]. Inadequately controlled postoperative pain may have harmful physiological and psychological consequences, which potentially increase morbidity and mortality [5]. It had been recognized that inadequately treated postoperative pain might result in chronic pain, which was often misdiagnosed and neglected [6]. In this study, donors were not as satisfied as patients, so intensified pain management was necessary for donors. Exposing a donor to a painful experience not only leads to increased morbidity, but also discourages potential donors. It seems that careful attention and maximal effort need be applied to minimize postoperative pain for donors. The major limitation of this study is that it is not a doubleblind trial.
Table 3. Patients’ Satisfaction, Number of Patients (%) Group D (n ¼ 25) Group P (n ¼ 24)
Poor
Moderate
Good
Excellent
6 (24) 3 (12)
13 (52) 4 (16)
4 (16) 11 (46)
2 (8) 6 (25)
P ¼ .011 (P < .05), no significant difference between the 2 groups.
In conclusion, living-renal donors suffer more pain and are associated with more morphine consumption than patients undergoing laparoscopic nephrectomy.
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(6):1344e6. [2] Perry KT, Freedland SJ, Hu JC, Phelan MW, Kristo B, Gritsch AH, 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(6):2018e21. [3] Wang J, Fu Y, Yuan T, Wang N. Comparison of postoperative analgesic requirements in living donors and patients undergoing similar surgical procedures. Transplant Proc 2015;47(6):1896e900. [4] Dillenburg W, Poulakis V, Skriapas K, de Vries R, Ferakis N, Witzsch U, 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. [5] Joshi GP. Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol Clin North America 2005;23(1):185e202. [6] Nikolajsen L, Sørensen HC, Jensen TS, Kehlet H. Chronic pain following Caesarean section. Acta Anaesthesiol Scand 2004;48(1):111e6.