Living kidney donor evaluation and safety assessment
van Londen, Marco
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van Londen, M. (2019). Living kidney donor evaluation and safety assessment. Rijksuniversiteit Groningen.
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CHAPTER 8
Chronic Pain after Living Donor
Nephrectomy
Marcel Zorgdrager, MD1*, Marco van Londen, MD2*, Lisa B. Westenberg1, Gertrude J. Nieuwenhuijs-Moeke, MD, PhD3, Johan F.M. Lange, MD, PhD4, Martin H. de Borst, MD, PhD2, Stephan J.L. Bakker, MD, PhD2, Henri G.D. Leuvenink, MSc, PhD4, Robert A. Pol, MD, PhD4
Submitted
1 Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
2 Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
3 Department of Anesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
4 Department of Surgery, Division of Transplant Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Abstract
Background and study aims: Little is known about chronic pain after living kidney
donation. The aim of this study is to assess the incidence of chronic pain after hand-assisted laparoscopic nephrectomy using a validated questionnaire.
Patients and methods: We included 333 living kidney donors who donated between
2011-2017 at the University Medical Center Groningen. Post-donation pain and movement disabilities were assessed using the Carolinas Comfort Scale (CCS) and the Visual Analogue Scale (VAS). We report the prevalence, severity of pain and the need for analgesics.
Results: Donors were 56±11 years old, 162 (48.6%) were male. At time of measurement,
at a median time of 19 [10-33] months post-donation, 82 (25%) donors had a CCS score >0, of which 58 (71%) had a CCS ≥2, and 57 (70%) reported movement limitations. One-hundred-and-ten (33%) donors had a VAS score >0. Complaints occurred during ‘bending over’ (12.3%) and ‘exercising’ (12.0%). Thirty-two (9.7%) donors required analgesics during follow-up between donation and time of measurement and 6% reported chronic inguinal pain. In multivariable analysis, donor age (OR 0.97 [95% CI 0.95-0.99], P=0.02) and hospital length of stay (HLOS, OR 1.23 [95% CI 1.00-1.51], P=0.049) were independently associated with chronic pain.
Conclusions: This study shows that 25% of donors experience chronic post-donation
pain or discomfort, of which 71% experienced bothersome complaints and 10% required analgesics. Complaints occur during bending over and exercising. Younger donors and donors with a longer HLOS had more complaints. These data can be used in donor education and help develop interventions for pain reduction in living kidney donors.
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Introduction
Transplantation with a kidney from a living donor is the best treatment for patients with end-stage renal disease and leads to a better survival rate and quality of life when compared to transplantation with a kidney from a deceased donor1,2.
Previous studies have shown that hand-assisted laparoscopic (HAL) donor nephrectomy is a safe procedure with good outcomes in terms of quality of life and quick recovery3,4. Outcomes after laparoscopic nephrectomy are superior to open procurement in terms of blood loss, hospital length of stay and postoperative pain5. However, a number of donor patients suffer from chronic pain after HAL donor nephrectomy with incidences reported between 3.7-33%. This poses an important barrier for living kidney donor programs6–9. Generally kidney donation leads to an increase in perceived quality of life by living kidney donors, but occurrence of chronic postoperative pain can importantly impair quality of life in these otherwise healthy subjects10,11. Despite the fact that the importance of pain management in this procedure is widely recognized6,7, little is known about location and precipitating causes of chronic pain after kidney donation.
We previously reported about chronic inguinal pain after kidney transplantation, which affected about one third of the transplant patients12. There, we hypothesized that this pain could have the same etiology as in inguinal herniorrhaphy and that identification and sparing of the three inguinal nerves (n. ilioinguinalis, n. iliohypogastricus and n. genitofemoralis) during surgery could lead to a lower incidence of chronic pain in recipients12. A similar strategy of sparing the three inguinal nerves may also benefit living kidney donors.
For a systematic approach to reduce chronic pain after donation, valid and standardized assessment of pain is necessary. However, a validated approach is lacking and studies investigating pain after donation mainly have focused on short-term postoperative pain13,14. The purpose of this study is to assess the incidence, location and precipitating causes of chronic pain lasting at least 3 months after HAL donor nephrectomy, using a validated questionnaire.
Material and methods
Study design
Between January 2011 and December 2016 a total of 419 consecutive patients who underwent a HAL donor nephrectomy were asked to complete questionnaires regarding chronic pain. In accordance with our donor selection criteria, potential donors with a
history of diabetes, kidney disease or cardiovascular events were excluded from the donation program. Hypertension was accepted under the condition that blood pressure was adequately regulated with a maximum of two antihypertensive drugs. Exclusion criteria for the current study were age <18 years, incapability to fill out the questionnaire (e.g. foreign language) and dead at time of inquiry. Informed consent was obtained from all participants. The study was approved by the institutional ethical review board (METc 2014/077). All procedures were conducted in accordance with the declarations of Helsinki and Istanbul.
Donor nephrectomy procedure
All patients underwent hand-assisted laparoscopic donor nephrectomy, either transperitoneal (HAL) or retroperitoneal (HARN). The main difference between a HAL and a HARN procedure is the retroperitoneal approach in HARN compared to the transperitoneal approach in HAL15. Conversion to an open procedure was necessary in 1 patient. Wound infiltration prior to surgery was performed with 10cc 0.25% Marcaine in all patients. A suprapubic transvers incision was made for access of the Gelport® (Applied medical®) in both surgical procedures. All trocars (Applied Medical®) were positioned under view of the camera. One 10 mm trocar was placed in the iliac fossa (left or right depending on the side of the kidney to be donated), one 10 mm trocar periumbilical for the 30° video port and one 5mm trocar subcostal/ epigastric (left or right depending on the side of the kidney to be donated). The kidney was dissected from surrounding tissues and the ureter and hilar vessels were identified. The ureter and artery were clipped (Ligaclip Ethicon®) and cut and the vein was stapled and cut (Medtronic Covedien Endo GIATM 30–2.5). After removal of the kidney via the suprapubic incision, the suprapubic fascia was closed using a running absorbable suture. The 12 mm trocar port sites were closed at the fascia level by interrupted absorbable sutures.
Preoperative all patients were given acetaminophen 1000mg. Intraoperative analgesia was managed with remifentanil or sufentanil using ml/h or a TCI system (pharmacokinetic-dynamic model respectively)16,17. Patients were given pritramide/morphine 0.1 mg/kg 30-45 min before end of surgery. Postoperative pain management consisted of acetaminophen 1000 mg 4 times/daily and piritramide (Dipidolor®) or morphine using a patient controlled analgesia (PCA) technique. Non-steroidal anti-inflammatory drugs were avoided because of its nephrotoxic effects. During the use of PCA at the ward pain management was conducted by the acute pain service of the anesthesiology department.
Clinical data collection
Collected data consisted of age, gender, body mass index (BMI; weight in kg/height in meters squared), measured glomerular filtration rate (GFR, 125-iothalamate) pre-donation, surgical complications according to the Clavien-Dindo classification, type of donor (related, unrelated, altruistic), type of nephrectomy (HAL or HARN), site of nephrectomy, duration of
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surgery (minutes), conversion rate (to open or from HARN to HAL), blood loss (mL), need for re-intervention and hospital length of stay (HLOS, days). Data regarding pain medication at hospital discharge were obtained from patient medical records.
Questionnaire
The questionnaire consisted of the modified Carolina Comfort scale12,15, the Visual Analog Scale (VAS-scale)18 and questions regarding the medical history and use of analgesics (appendix I). The CCS is originally validated for pain assessment after inguinal hernia repair with use of a mesh and was modified in our previous study on chronic pain in kidney recipients12. The questionnaires were sent by mail and all non-repliers were contacted by phone after 4 weeks. General questions were added to the enquiry to assess potential confounding factors.
Chronic pain was defined by complaints or pain in the inguinal region or flank at time of survey, which was assessed ≥3 months after surgery. Patients with a CCS>0 were scored as positive for pain (in the CCS indicated as ‘patients with complaints’). Patients with a CCS≥2 in one of the subcategories were considered patients with ‘significant and bothersome complaints’ according to the CCS classification. In a subgroup of donors (n=218), who also participated in the TransplantLines study (registered at clinicaltrials.gov NCT03272841), additional data regarding pain were collected along with the CCS at clinical follow-up visits after nephrectomy. These additional data consisted of a detailed pain history, taken by a trained researcher, and involved questions about the type of pain, intensity of pain using the Numeric Pain Rating Scale18,19, the location, referred pain, signs of sympathetic nerve activation and the influence of perceived pain on sleep and activities of daily life.
Statistical Analysis
Categorical variables are presented as numbers or percentages and analyzed with a χ2 test or Fisher’s exact test. Continuous variables are presented as mean ± SD for normally distributed variables and tested with the Student t test, or as median ± interquartile range (IQR) for skewed variables and tested with a Mann- Whitney U test.
Univariable and multivariable analysis on factors associated with a higher CCS score and sensitivity analyses were performed using logistic regression. Variables that were analyzed consisted of sex, age, body mass index, systolic blood pressure, measured glomerular filtration rate, altruistic donor, side of nephrectomy, type of donor procurement, blood loss, hospital stay and complications. Characteristics that were univariably associated with the CCS score or had a univariable P-value below 0.20 were added to a multivariable model. We used multiple imputation using the fully conditional specification method to correct for missing data, as described previously20. Two-tailed P-values were used throughout and
significance was set at P<0.05. The statistical analyses were done with the Statistical Package for the Social Sciences (SPSS 23, SPSS, Chicago, IL, USA, 2015).
Results
Study population
Of the 419 donor approached for this study with a median time of 19 [10;33] months after nephrectomy, 333 donors filled in the study questionnaires (response rate 79%), and formed the basis for this analysis. Mean age at time of donation was 56±11 years, 49% were male. Mean BMI at donor screening was 26±3 kg/m2. All baseline characteristics are shown in Table 1.
Outcomes Carolina Comfort Scale and Visual Analogue Scale
Eighty-two (25%) donors reported a CCS score >0 at time of completing the surveys , indicating the presence of pain symptoms. Fifty-eight patients (17%) experienced bothersome complaints on at least one of the subcategories (CCS score ≥2), which equals to 71% of donors with pain. The median CCS score in these donors was 6 [4;12]. Pain was most often reported while bending over (12%) and during exercise (13%). Other pain-provoking factors are shown in Table 2. Fifty-seven donors (17%) reported movement limitations in the questionnaire. These movement limitations also occurred most frequently during bending over (10%) and exercising (12%). One-hundred-and-ten donors (33%) reported a VAS score >0, with a median VAS of 4 [1;16] in these donors. Donors experiencing pain were younger (53±11 vs. 57±11, P=0.01) and had a longer HLOS (4.8±1.4 vs. 4.5±1.1 days, P=0.03), but otherwise did not significantly differ from donors without pain symptoms (Table 1). Regarding the pain location: the abdominal region (36%), the site of nephrectomy (14%) and the inguinal region (7%) were most frequently reported. This rather varied distribution of pain could be explained by the fact that most patients (94%) underwent transperitoneal donor procurement instead of retroperitoneal approach.
Determinants of chronic pain
In univariable logistic regression, age was a significant determinant of pain, with younger donors more frequently experiencing pain (OR per year 0.97 [95% CI 0.95-0.99], P=0.01). Furthermore, a longer HLOS was associated with a higher risk of developing chronic pain during follow-up (OR 1.24, P=0.04). Altruistic donors showed a trend towards a lower pain incidence (OR 0.33 [95% CI 0.10-1.13], P=0.08) and ‘living related’ donation showed a trend toward a higher pain incidence (OR 1.65 [0.99-2.73], P=0.05).
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Table 1. Donor characteristics
Variable All donors Donors
with no pain with painDonors P value
Age, years 56 ± 11 57 ± 11 53 ± 11 0.01 Sex, n (%) Male Female 162171(49%)(51%) 121130(48%)(52%) 41 41 (50%)(50%) 0.80 Length, cm 175 ± 9 175 ± 9 175 ± 10 0.69 Weight, kg 801 ± 13 81 ± 12 82 ± 14 0.45 BMI, kg/m2 26.4 ± 3.3 26.4 ± 3.2 26.6 ± 3.5 0.62 Blood pressure, mmHg Systolic Diastolic 12776± 12± 9 12876± 12± 9 12576± 11± 8 0.13 0.97 GFR, mL/min 111 ± 22.2 110 ± 20.8 114 ± 26.2 0.20 Type of donor, n (%) Living related Living unrelated Altruistic 138 146 28 (42%) (44%) (9%) 97 112 25 (39%) (45%) (10%) 41 34 3 (50%) (42%) (1%) 0.17
Side donor nephrectomy, n (%) Right Left 25380(24%)(76%) 18863 (5%)(75%) 1765(21%)(79%) 0.46 Surgical technique, n (%) HAL HARN Open 312 18 1 (94%) (5%) (0.3%) 235 13 1 (97%) (5%) (0.4%) 77 5 0 (94%) (6%) (0%) 0.81 Blood loss, mL 0 [0-100] 0 [0-100] 0 [0-100] 0.67
Duration surgery, minutes 187 ± 42 186 ± 42 187 ± 43 0.88
HLOS (days) 4.6 ± 1.2 4.5 ±1.1 4.8 ±1.4 0.03
Complications <30 days, n (%)
Clavien Dindo grade III-IV 27 (12%) 19 (10%) 8 (15%) 0.45
Conversion rate, n (%) No conversion, primary HAL No conversion, primary HARN
Conversion HARN to HAL Conversion HAL to open
9 311 11 8 1 (3%) (94%) (3%) (2%) (0.3%) 5 235 9 4 1 (2%) (94%) (4%) (2%) (0.4%) 4 76 2 4 0 (5%) (93%) (2%) (5%) (0%) 0.34 0.92 0.68 0.11 1.00
Need for reoperation, n (%) 2 (1%) 2 (1%) 0 (0%) 1.00
Follow-up, months 19 [10-33] 20 [12-33] 16 [8-32] 0.10
Donor characteristics at time of surgery. BMI, Body Mass Index (kg/m2); GFR, Glomerular Filtration Rate (mL/min); HAL, Hand-Assisted Laparoscopy; HARN, Hand-Assisted Retroperitoneal Nephrectomy; Clavien Dindo grade III-IV, any complication which requires surgical, endoscopic or radiological
Table 2. Analysis of pain and complaints in living kidney donors
Variable Prevalence
Complaints, n (%) CCS>0
VAS>0 11082(24.6%)(33.1%) Complaints ≥1 year post-donation, n (%)
CCS>0 VAS>0 47 67 (20.4%) (29.3%) Pain, n (%) Situational, n (%) Lying down Bending over Sitting up Activities daily life Coughing or deep breathing Walking
Walking up the stairs Exercising 82 25 41 25 29 21 31 30 40 (24.6%) (7.5%) (12.3%) (7.5%) (8.7%) (6.3%) (9.3%) (9.0%) (12.7%) Movement limitations, n (%) Situational, n (%) Bending over Sitting up Activities daily life Coughing or deep breathing Walking
Walking up the stairs Exercising 57 33 22 24 11 20 25 35 (17.2%) (10.0%) (6.6%) (7.3%) (3.3%) (6.0%) (7.5%) (11.2%) Pain ≥1 year post-donation, n (%)
Situational, n (%) Lying down Bending over Sitting up Activities daily life Coughing or deep breathing Walking
Walking up the stairs Exercising 47 14 20 16 18 14 22 19 25 (20%) (6.1%) (8.6%) (7.0%) (7.8%) (6.1%) (9.5%) (8.2%) (10.9%) Movement limitations ≥1 year post-donation, n (%)
Situational, n (%) Bending over Sitting up Activities daily life Coughing or deep breathing Walking
Walking up the stairs Exercising 34 13 10 12 6 14 16 24 (14.8%) (5.7%) (4.3%) (5.2%) (2.6%) (6.1%) (7.0%) (10.7%) Analgesic use for any indication, n (%) 32 (9.7%) Location of pain, n (%) Inguinal At site of wound Abdomen other Extra-abdominal Not specified 6 10 26 8 32 (7.3%) (12.2%) (31.7%) (9.8%) (39.0%) CCS, Carolina Comfort Scale; VAS, Visual Analogue Scale.
The CCS measures the severity of pain and movement limitations, indicated on a scale from 0 (no pain/ movement limitations) to 5 (severe pain/movement limitations).
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Table 3. Univariable analysis of variables associated with the different categories of the Carolina Comfort Scale (CCS) CCS domain
Age Sex BMI SBP GFR Altruistic donor Related donor Side (left) HAL vs. Other Blood loss HLOS Complications Total OR [95%CI] 0.97* [0.95-0.99] 1.10 [0.67-1.82] 1.00 [0.91-1.10] 0.99 [0.97-1.01] 1.01 [1.00-1.02] 0.33 [0.10-1.13] 1.65 [0.99-2.73] 0.73 [0.39-1.36] 0.96 [0.34-2.70] 1.00 [1.00-1.00] 1.24* [1.01-1.52] 1.52 [0.44-5.25] Lying OR [95%CI] 0.95** [0.61-0.98] 1.37 [0.60-3.12] 0.96 [0.82-1.12] 0.99 [0.97-1.01] 1.00 [0.97-1.03] 0.42 [0.05-3.17] 0.78 [0.34-1.83] 0.41 [0.12-1.42] 1.31 [0.29-5.97] 1.00 [1.00-1.00] 1.20 [0.88-1.65] 1.69 [0.47-6.15] Bending OR [95%CI] 0.96** [0.93-0.99] 1.18 [0.61-2.30] 0.98 [0.85-1.13] 0.99 [0.97-1.01] 1.00 [0.99-1.02] 0.51 [0.12-2.25] 1.49 [0.77-2.89] 0.42 [0.16-1.1 1] 0.35 [0.05-2.65] 1.00 [0.99-1.00] 1.20 [0.93-1.56] 1.49 [0.45-4.94] Sitting OR [95%CI] 0.95** [0.91-0.98] 0.81 [0.36-1.85] 1.04 [0.90-1.20] 0.98 [0.95-1.01] 1.01 [0.99-1.03] 0.41 [0.05-3.17] 0.94 [0.41-2.16] 0.59 [0.20-1.76] 1.31 [0.29-5.97] 1.00 [0.99-1.00] 1.17 [0.85-1.61] 1.10 [0.23-5.36] Daily OR [95%CI] 0.96* [0.93-0.99] 1.05 [0.49-2.29] 1.05 [0.92-1.20] 0.98 [0.96-1.01] 1.01 [0.99-1.02] 0.78 [0.18-3.49] 1.46 [0.67-3.18] 0.61 [0.17-1.51] 0.52 [0.07-4.04] 1.00 [1.00-1.00] 1.19 [0.88-1.61] 1.32 [0.33-5.28] Cough OR [95%CI] 0.95** [0.91-0.99] 1.05 [0.44-2.50] 1.07 [0.92-1.24] 0.96 [0.93-0.99] 1.02 [1.00-1.04] 0.48 [0.06-3.68] 2.16 [0.89-5.20] 1.21 [0.46-3.21] 1.52 [0.33-7.00] 1.00 [1.00-1.00] 1.25 [0.90-1.74] 2.1 1 [0.59-7.49] W alking OR [95%CI] 0.98 [0.94-1.01] 0.85 [0.41-1.79] 0.98 [0.88-1.09] 0.99 [0.97-1.01] 1.00 [0.99-1.02] 0.32 [0.04-2.46] 1.19 [0.56-2.50] 0.59 [0.22-1.58] 0.47 [0.06-3.59] 1.00 [1.00-1.00] 1.23 [0.93-1.64] 1.16 [0.35-3.88] Stairs OR [95%CI] 0.96* [0.93-0.99] 1.42 [0.67-3.02] 0.99 [0.79-1.24] 0.99 [0.97-1.02] 1.01 [1.01-1.03] 0.36 [0.04-2.56] 1.47 [0.69-3.1 1] 0.78 [0.31-1.98] 0.48 [0.06-3.73] 1.00 [1.00-1.00] 1.18 [0.87-1.58] 1.21 [0.30-4.94] Exercise OR [95%CI] 0.98 [0.95-1.00] 1.1 1 [0.59-2.05] 0.99 [0.88-1.12] 0.99 [0.96-1.01] 1.01 [0.99-1.03] 0.58 [1.15-2.25] 0.95 [0.50-1.81] 0.55 [0.24-1.22] 1.18 [0.37-3.82] 1.00 [1.00-1.00] 1.23 [0.97-1.55] 1.45 [0.49-4.32] Bothersome OR [95%CI] 0.97* [0.95-0.99] 1.07 [0.94-1.48] 0.98 [0.89-1.09] 0.99 [0.97-1.01] 1.01 [1.00-1.02] 0.36 [0.1 1-1.23] 1.47 [0.88-2.47] 0.81 [0.44-1.51] 1.05 [0.37-2.96] 1.00 [1.00-1.00] 1.26* [1.02-1.47] 1.42 [0.42-4.77]
* P<0.05; ** P<0.01, *** P<0.001 OR, Odds Ratio for CCS>0; [95% CI], 95% Confidence Interval of Odds Ratio; BMI, Body Mass Index; SBP
, Systolic Blood Pressure; GFR, measured Glomerular Filtration
Rate; HAL, Hand-Assisted Laparoscopy; HLOS, Hospital Length of Stay
Secondary analysis
Younger age was associated with increased pain in the following subdomains; lying down (OR 0.95 [95% CI 0.61-0.98], P=0.003), bending over (OR 0.96 [95% CI 0.93-0.99], P=0.007), sitting (OR 0.95 [95% CI 0.91-0.98], P=0.002), activities of daily life (OR 0.96 [95% CI 0.93-0.99], P=0.01), coughing (OR 0.95 [95% CI 0.91-0.93-0.99], P=0.006) and climbing stairs (OR 0.96 [95% CI 0.93-0.99], P=0.02). In linear regression, donor age (St. β -0.06, P=0.29), donor type (St. β -0.94, P=0.35) and admission days were not associated with the donors VAS score (St. β -0.05, P=0.96 respectively). In donors experiencing pain opioids were prescribed more frequently at discharge from the hospital after nephrectomy, compared to donors without pain (Supplementary Table S1). In multivariable analysis, donor age (OR 0.97 [95% CI 0.95-0.99], P=0.02) and HLOS (OR 1.23 [1.00-1.51], P=0.049) remained independent associates of pain (Table 4).
Detailed analysis of pain
In a subgroup of donors (n=218), we performed a more detailed analysis of the pain symptoms. One hundred thirty-seven (63%) of these donors had a follow-up of >5 years post-donation. Of these donors 46 (21%) experienced pain in their lower thorax/abdominal region with emphasis on the hypogastric (37%), umbilical (13%) or lower left and right abdominal quadrant (11% and 11%). Twenty-seven donors (63%) ascribed their pain to the nephrectomy. The pain was most often described as ‘stabbing’ (37%), ‘deep/nagging’ (32%) or ‘burning’ (12%). The median intensity (NRS) of the pain was 4/10 [2/10;6/10] and referred pain in the stomach or back was described in 17%. Eight (20%) donors described continuous pain symptoms. Three donors (8%) experienced vegetative symptoms like sweating, nausea and paleness during pain episodes and 12 (27%) reported interference with their sleep. As with the CCS score, donors most often described the pain during bending over (20%). Most donors (54%) experiencing pain reported no limitations in daily activities, but 6 donors (13%) experienced medium impairment and 3 (7%) severe impairment in their daily life.
Discussion
This study shows that 25% of donors experience chronic pain or discomfort after HAL donor nephrectomy, of which 71% experienced bothersome complaints (CCS ≥ 2). Complaints occur most often during bending over and exercising and required analgesia in a minority of cases. To our knowledge this is the first study that describes chronic pain in detail in a donor nephrectomy cohort. These data can be used to raise awareness and develop individualized interventions for pain reduction in living kidney donors that focus on specific activities provoking these symptoms.
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Table 4. Multivariable analysis of variables associated with the different categories of the Carolina Comfort Scale (CCS) CCS domain
Age SBP Altruistic donor Related donor HLOS Total OR [95%CI] 0.97 [0.95-0.99]* 0.99 [0.98-1.02] 0.31 [0.08-1.25] 1.14 [0.81-1.60] 1.23 [1.00-1.51]* Lying OR [95%CI] 0.95 [0.91-0.98]** 0.99 [0.97-1.02] 0.30 [0.03-3.03] 1.19 [0.96-2.63] 1.26 [0.91-1.74] Bending OR [95%CI] 0.96 [0.93-0.99]** 0.99 [0.97-1.01] 0.45 [0.08-2.39] 1.33 [0.87-2.03] 1.22 [0.94-1.58] Sitting OR [95%CI] 0.95 [0.91-0.98]** 0.98 [0.95-1.01] 0.68 [0.06-8.23] 0.85 [0.45-1.62] 1.16 [0.84-1.60] Daily OR [95%CI] 0.96 [0.92-0.99]* 0.98 [0.96-1.01] 1.34 [0.21-8.80] 0.84 [0.46-1.55] 1.16 [0.86-1.56] Cough OR [95%CI] 0.95 [0.91-0.99]* 0.96 [0.93-0.99]* 0.34 [0.01-13.19] 1.06 [0.55-2.05] 1.24 [0.89-1.75] W alking OR [95%CI] 0.98 [0.94-1.01] 1.00 [0.97-1.02] 0.32 [0.04-2.88] 1.10 [0.67-1.79] 1.22 [0.92-1.62] Stairs OR [95%CI] 0.96 [0.93-0.99]* 1.00 [0.97-1.02] 0.42 [0.05-3.86] 1.00 [0.59-1.69] 1.17 [0.88-1.57] Exercise OR [95%CI] 0.98 [0.95-1.01] 0.99 [0.97-1.01] 0.80 [0.16-3.97] 0.86 [0.64-1.36] 1.26 [0.99-1.60] Bothersome OR [95%CI] 0.97 [0.95-0.99]* 0.99 [0.98-1.02] 0.35 [0.09-1.42] 1.12 [0.79-1.59] 1.25 [1.01-1.54]*
* P<0.05; ** P<0.01 OR, Odds Ratio f
or CCS>0;
[95% CI], 95% Confidence Inter
val of Odds Ratio;
SBP
, Systolic Blood Pressure;
HLOS
, Hospital Length of Sta
The incidence of chronic pain was relatively high in younger patients. Previous studies reported similar results after inguinal hernia repair21,22. There is no clear explanation why younger patients, in a relatively healthy population, are prone to experience more pain, despite that elderly appear to have a higher threshold for low intensity pain23. The complaints during bending over are probably explained by the fact that younger patients have a more active lifestyle. But also differences in immune response can contribute to increased nociceptor activation which then can lead to “hyperalgesic priming” and/or “wind-up” and eventually to central sensitization through long term potentiation in the central nervous system24.
Altruistic donors showed a trend towards having chronic pain less frequently compared to other donors. It has been suggested that a specific neurocognitive pathway is activated in altruistic donors25, which may involve enhanced volume and function of the amygdala, thereby dampening the biological response to pain. Another possibility is that because altruistic donors in the Netherlands donate anonymously, a poor graft or recipient outcome does not psychologically affect the donor 4,11.
The hospital length of stay (HLOS) was higher in patients reporting chronic pain. Because no difference in complication rate was found, it might be possible that donors experiencing chronic pain had a longer HLOS because of a higher pain intensity directly after surgery26,27. Due to the retrospective nature of this study, we were not able to reliably estimate or collect
Figure 1. CCS subcategories in living kidney donors
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data on pain during the hospital admission. However, we were able to demonstrate that opiates were more frequently prescribed at hospital discharge in donors with chronic pain. Although the incidence of inguinal pain was relatively low, the CCS scores were comparable with VAS scores, which is frequently used in studies assessing chronic pain after donor nephrectomy28-31.
We found no difference in chronic pain in donors who underwent retroperitoneal nephrectomy compared to a transperitoneal dissection. However, the conversion rate from retroperitoneal to transperitoneal nephrectomy was rather high (n=8/19, 42%) which could have biased these results. We found no difference in incidence of chronic pain between donors with and without the need of conversion.
Our results may be used for the counseling of future living kidney donors and their recipients. While generally kidney donation tends to increase donor quality of life10,11, the incidence of pain may have a reducing effect. While HAL nephrectomy greatly reduced the incidence of pain28-30, we show that it is still an important problem affecting 25% of donors. There is a strong relationship between acute postoperative pain and development of chronic pain and this transition is likely to be caused by sensitization of pain due to a complex process of psychosocial and biological factors32-35.Various interventions to prevent acute pain after laparoscopic donor nephrectomy are previously described, but their effect on chronic pain are not yet fully clarified. Perioperative administration of an alpha-2 agonist (e.g. clonidine), lidocaine infusion, pregabalin or ketamine are all described as effective methods in reducing acute postoperative pain and the need of opioid medication36-38. Effective intra-operative interventions consist of subfascial administration of bupivacaine, transversus abdominis plane block (TAP), low pressure pneumoperitoneum and deep neuromuscular blockade39-40. Future studies are needed to determine which approach is most appropriate and effective in living kidney donors.
This study has a few limitations that need to be addressed. The CCS score was primarily validated in studies reporting chronic pain after inguinal herniorrhaphy15 and the donor nephrectomy is performed at different anatomical plains. For example, the peritoneal cavity is opened during the HAL nephrectomy, which could lead to a different etiology, rather than chronic pain induced by inguinal nerve injury even though the same inguinal nerves are encountered at a more proximal location during donor nephrectomy. This is further underlined by our sub analysis in which the location of pain was evaluated in 46 patient. Only 7% of patients reported specific inguinal pain. Next to peritoneal visceral pain, the more localized pain in the abdomen or flank in donors could be explained by the dissection of perforating nerves around the kidney during procurement. These nerves are innervated by splanchnic nerve roots that originate in the aorticorenal ganglion which is located at the origin of the renal artery. This could suggest that local anesthetic infiltration or spraying at this level may be beneficial in reducing the incidence or severity of postoperative pain.
Other limitations are the retrospective design of our study and the relatively limited follow-up of our patients (maximal 6 years). One previous study reported an increased incidence of pain 10 years after donation, but that particular study had similar results compared to the general surgical population41. We also had some missing data in our study: 7% of patients did not completely fill in the questionnaire. We used multiple imputation to account for the missing data20. Because pain and movement disability are highly related to each other, we believe the bias from the missing questions was limited. In addition, we further reduced bias by using a binary outcome (pain or no pain) in the analyses. We collected data on opiate use at discharge after nephrectomy, which may have been subject to underreporting in the patient files. Finally, the enquiry was taken at different time points after surgery between patients, with a minimum of 3 months, which also could have led to bias. However, we found no relation between the duration of follow-up and incidence of chronic pain making this effect negligible.
In conclusion, we show that 25% of living kidney donors experience some form of chronic post-operative pain of which 10% still require analgesics after a median follow-up of 19 month. Complaints occur more often in younger donors, patients with along HLOS and most often during bending over and exercising. These data can be used in donor education, to optimize perioperative pain management and to develop individualized interventions for pain reduction in living kidney donors that focus on specific activities that provoke pain.
Acknowledgements
This study received no funding of any kind. The authors of this manuscript have no conflicts of interest to disclose. This study is part of the TransplantLines Biobank and Data Repository.
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Supporting Information
Table S1. Modified Carolina Comfort Scale While lying down, do you have
Pain 0 1 2 3 4 5 n/a
While bending over, do you have
Pain 0 1 2 3 4 5 n/a
Movement limitations 0 1 2 3 4 5 n/a While sitting up, do you have
Pain 0 1 2 3 4 5 n/a
Movement limitations 0 1 2 3 4 5 n/a While performing activities of daily life, do you have
Pain 0 1 2 3 4 5 n/a
Movement limitations 0 1 2 3 4 5 n/a While coughing or deep breathing, do you have
Pain 0 1 2 3 4 5 n/a
Movement limitations 0 1 2 3 4 5 n/a While walking, do you have
Pain 0 1 2 3 4 5 n/a
Movement limitations 0 1 2 3 4 5 n/a While walking up the stairs, do you have
Pain 0 1 2 3 4 5 n/a
Movement limitations 0 1 2 3 4 5 n/a While exercising, do you have
Pain 0 1 2 3 4 5 n/a
Movement limitations 0 1 2 3 4 5 n/a Table 1: 0= No symptoms; 1= Mild but not bothersome symptoms; 2= Mild and bothersome symptoms; 3= Moderate and/or daily symptoms; 4= Severe symptoms; 5= Disabling symptoms
