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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 14  |  Issue : 4  |  Page : 306-312

The role of povidone-iodine in prevention of lymphorrhea after kidney transplant surgery - A prospective, pilot study


1 Department of Urology, IPGMER, Kolkata, West Bengal, India
2 Department of Pathology, IPGMER, Kolkata, West Bengal, India

Date of Submission08-Aug-2020
Date of Acceptance22-Nov-2020
Date of Web Publication30-Dec-2020

Correspondence Address:
Prof. Dilip Kumar Pal
Department of Urology, IPGMER, 242, AJC Bose Road, Kolkata - 700 020, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_96_20

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  Abstract 


Objective: Lymphatic complications (lymphorrhea or lymphocele) are one of the most common and frustrating complications of renal transplantation. It was well documented in literatures that excessive lymphatic leak in the early postoperative period leads to lymphorrhea, which may transform into lymphocele. Povidone-iodine has been used as a sclerosant in lymphocele management for the past 30 years. In this study, our aim is to establish the role of povidone-iodine to prevent lymphorrhea after kidney transplant surgery. Materials and Methods: A total of 106 (live donor transplant patient = 63 and deceased donor transplant patient 43) patients had undergone renal transplantation from May 2019 to May 2020. Those patients were randomized into three groups – Group A (n = 35): where 1% povidone-iodine was used, Group B (n = 35): where 5% povidone-iodine was used, and Group C (n = 36): control group, where povidone-iodine was not used. Fifty milliliters of 1% or 5% povidone-iodine was used to wash the bed and kept for 5 min in contact with the bed and again 1% (Group A) or 5% (Group B) povidone-iodine wash was given after completion of ureteroneocystostomy and was kept for 5 min. Results: On postoperative day 6, there is a statistically significant decrease in drain output in the 5% and 1% povidone-iodine groups in comparison with the control group, but no statistically significant difference exists between 5% versus 1% povidone-iodine group. Conclusion: Intraoperative instillation povidone-iodine is a cheap, safe, and very effective procedure to prevent lymphorrhea following renal transplant surgeries.

Keywords: Lymphocele, lymphorrhea, povidone-iodine, renal transplantation


How to cite this article:
Pal DK, Roy P, Chatterjee A, Jana D, Mandal D. The role of povidone-iodine in prevention of lymphorrhea after kidney transplant surgery - A prospective, pilot study. Indian J Transplant 2020;14:306-12

How to cite this URL:
Pal DK, Roy P, Chatterjee A, Jana D, Mandal D. The role of povidone-iodine in prevention of lymphorrhea after kidney transplant surgery - A prospective, pilot study. Indian J Transplant [serial online] 2020 [cited 2021 Apr 10];14:306-12. Available from: https://www.ijtonline.in/text.asp?2020/14/4/306/305442




  Introduction Top


Kidney transplantation is the only definitive treatment for patients with end-stage renal disease. Postoperative complications give a negative impact to the procedure. Lymphatic complications are one of the most common and frustrating complications of renal transplantation. Lymphatic complication may occur in the form of either lymphorrhea or lymphocele. Lymphorrhea is defined as excessive lymph leak through surgical wound or abdominal drain.[1],[2],[3] However, the amount of lymph drainage or duration of lymph drainage is not universally defined. Sureka et al. defined significant lymphorrhea as a drain output of more than 50 ml after 5 days of renal transplant surgery,[4] whereas lymphocele was defined as lymph-filled collection, covered with a fibrous capsule without any epithelial lining.[2],[3]

The exact incidence of lymphorrhea is not reported in available literatures, but the incidence of lymphoceles was reported as 0.6%–51% among published literatures.[2] Majority of the lymphoceles are asymptomatic. The incidence of symptomatic lymphocele was reported as 0.03%–26% with a mean 5.2%.[5],[6],[7],[8] Lymphocele generally occurs after 2 weeks to 6 months of renal transplant surgery.[9]

Kiberd et al. explained the formation of lymphocele in a step-wise manner; excessive lymphatic leak leads to lymphorrhea that ultimately transforms into lymphocele.[10] There are some data which show that if the lymphatic leak in the early postoperative period is prevented, lymphocele formation can be prevented afterward.[10] It is also reported that leakage cannot be solely prevented by meticulous surgical ligations of lymphatic vessels.[11] Almost all the published studies have described the management of lymphocele, where Sureka et al. described the plan of management of lymphorrhea.[4] Hence, the hypothesis of this study was that the prevention of lymphatic leak is the key to prevent lymphocele formation, and the purpose of the study was:

  1. To determine the efficacy of instillation of povidone-iodine during intraoperative period in recipients of renal transplant in preventing lymphorrhea
  2. To compare the efficacy of 1% povidone-iodine with 5% povidone-iodine in the prevention of lymphorrhea after renal transplant
  3. To find out any complications of using povidone-iodine as an agent in preventing lymphorrhea by estimating urine iodine level in postoperative day 1 (POD1) and POD5.



  Materials and Methods Top


The study was conducted in a tertiary care center of West Bengal in the patients of end-stage renal disease undergoing live or deceased donor renal transplantation. It was a prospective study conducted during the period from May 2019 to May 2020.

Inclusion and exclusion criteria

All patients undergoing live or deceased donor transplantation and willing to give informed consent; the patients not willing to give consent and patients with history of severe iodine toxicity were excluded from the study.

Study design

This study is a pilot study. Google Scholar database was searched for relevant literature. After thorough literature search, we had not found a single article where povidone-iodine was used for intraoperative instillation to prevent lymphatic complications in renal transplant surgery. In all available studies, povidone-iodine was used to treat lymphatic complications, and to the best of our knowledge, there is no article available where two concentrations of povidone-iodine were compared. Hence, in this study, we had fixed a time frame of 1 year to analyze the interim result.

Study techniques

  1. Patients were divided into three groups as per card randomization process
  2. First group (Group A) comprised patients in which, after preparation of recipient bed, 50 ml of 1% povidone-iodine was used to wash the bed and kept for 5 min and again 1% povidone-iodine wash was given after completion of ureteroneocystostomy and was kept for 5 min
  3. Second group (Group B) comprised patients in which, after preparation of recipient bed, 50 ml of 5% povidone-iodine was used to wash the bed and was kept for 5 min in contact with the bed and again 50 ml of 5% povidone-iodine wash was given after completion of ureteroneocystostomy and was kept for 5 min
  4. Third group (Group C) was control group in which, after preparation of recipient bed, no povidone-iodine was used to wash the bed or after completion of ureteroneocystostomy
  5. Drain output was measured on day 1 (POD1), day 4 (POD4), and on the day of removal of drain (POD6)
  6. In case of excess drain output, biochemical tests were performed to differentiate between lymphocele and urinoma. In those cases, drain fluid creatinine level was measured to differentiate between lymphatic leak and urinoma. If drain fluid creatinine was three times the serum creatinine, it was considered as urinary leak
  7. Significant lymphocele was defined as drain output of more than 50 ml on POD6
  8. On POD1 and POD5, urine iodine estimation was done in the Department of Biochemistry using Sandell–Kolthoff method to rule out systemic iodine absorption from povidone-iodine.


Statistical analysis

Data were entered into a Microsoft Excel spreadsheet and then analyzed by SPSS (version 25.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism version 5. Data had been summarized as mean and standard deviation for numerical variables and count and percentages for categorical variables. One-way analysis of variance (one-way ANOVA) was a technique used to compare means of three or more samples for numerical data (using the F distribution), and Bonferroni test was performed for pair-wise comparison between group means. P ≤ 0.05 was considered statistically significant.

Declaration of Patient consent

The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity

Ethical clearance

Institute ethics board IPGME and R/IEC/2019/298approved this analysis on April 10, 2019.. All protocols as per Declaration of Helsinki were followed. The authors confirm the availability of, and access to, all original data reported in this study


  Results Top


A total of 106 (live donor transplant patient = 63 and deceased donor transplant patient = 43) patients had undergone renal transplantation from May 2019 to May 2020. No patient was excluded as per the exclusion criteria. Those patients were randomized into three groups.

  • Group A (n = 35): where 1% povidone-iodine was used. Among 35 patients, 21 patients underwent live donor renal transplant and 14 patients underwent deceased donor renal transplant surgery
  • Group B (n = 35): where 5% povidone-iodine was used. Among 35 patients, 21 patients underwent live donor renal transplant and 14 patients underwent deceased donor renal transplant surgery
  • Group C (n = 36): where povidone-iodine was not used. Among 36 patients, 21 patients underwent live donor renal transplant and 15 patients underwent deceased donor renal transplant surgery.


The mean drain output at day 1 was higher in the 5% group as compared to the 1% and control groups. The difference of mean drain output at the 1st day in the three groups was statistically significant (P = 0.001). The mean drain output at day 4 was lowest in the 5% group as compared to the 1% and control groups. The difference of mean drain output at the 4th day in the three groups was statistically significant (P < 0.001). The mean drain output at day 6 was lowest in the 5% group as compared to the 1% and control groups. The difference of mean drain output at the 6th day in the three groups was statistically significant (P < 0.001) [Table 1] and [Figure 1].
Table 1: Distribution of mean drain output among different groups

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Figure 1: Bar diagram showing distribution of mean drain output (in milliliters) among groups

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  1. When Bonferroni post hoc test was applied, the results were [Table 2]:


    • Statistically significant (P = 0.001) increase in drain output was found on POD1 in the 5% povidone-iodine group compared to the control group. However, there was no difference between 5% versus 1% povidone-iodine group and 1% povidone-iodine versus control group
    • On POD4, no significant difference was found between 5% versus 1% povidone-iodine group. However, there was a statistically significant decrease in drain output in the 5% povidone-iodine group (P = 0.000) and the 1% povidone-iodine group (P = 0.003) in comparison with the control group
    • On POD6, there is no difference between 5% versus 1% povidone-iodine group. However, there was a statistically significant decrease in drain output in the 5% and 1% povidone-iodine groups compared to the control group (P < 0.001).


  2. Among the live donor renal transplant patients, results are as follows [Table 3]:


    • Statistically significant increase in drain output was found on POD1 in the 5% povidone-iodine group and 1% povidone-iodine group in comparison with the control group. However, there was no difference between 5% versus 1% povidone-iodine group
    • On POD4, although the mean drain output was more in the control group, no statistically significant difference was found between 5% versus 1% povidone-iodine group, 1% povidone-iodine versus control group, and 5% povidone-iodine versus control group
    • On POD6, there was no statistically significant difference between 5% versus 1% povidone-iodine group. However, there was a statistically significant decrease in drain output in the 5% and 1% povidone-iodine groups in comparison with the control group.


  3. Among the deceased donor renal transplant patients, results are as follows [Table 4]:


    • No statistically significant difference was found on POD1 in the 1% and 5% povidone-iodine groups in comparison with the control group
    • On POD4, there was no difference between 5% versus 1% povidone-iodine group. However, there was a statistically significant decrease in drain output in the 1% and 5% povidone-iodine groups compared to the control group
    • On POD6, no statistically significant difference was found between 5% versus 1% povidone-iodine group. However, there was a statistically significant decrease in drain output in the 5% and 1% povidone-iodine groups as compared to the control group (P < 0.001).
Table 2: Comparison drain output in 1% versus 5% povidone-iodine group, control group versus 1% povidone-iodine group and control group versus 1% povidone-iodine group on postoperative days 1, 4, and 6

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Table 3: Comparison of drain output in 1% versus 5% povidone-iodine group, control group versus 1% povidone-iodine group, and control group versus 1% povidone-iodine group on postoperative days 1, 4, and 6 in live donor renal transplant patients only

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Table 4: Comparison of drain output in 1% versus 5% povidone-iodine group, control group versus 1% povidone-iodine group, and control group versus 1% povidone-iodine group on postoperative days 1, 4, and 6 in deceased donor renal transplant patients only

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  Discussion Top


The lymphatic complications are multifactorial in origin. It is believed that surgical factors are more responsible for the occurrence.[12] Surgical causes are dissection of iliac, mainly external iliac vessels,[13] and dissection of allograft hilar vessels during retrieval or during bench preparation. In general, lymphatic leak occurs if those delicate lymphatics are not ligated meticulously.[14],[15] Sansalone et al. showed that when a common iliac vessel was used for vascular anastomosis, lymphatic leaks were less, as there was minimal lymphatic dissection,[16] however, in all our cases, we used external iliac vessels for anastomosis as per the institutional protocol. Similarly, Saidi et al. demonstrated that laparoscopic organ procurement causes more lymphatic complications as all fragile lymphatics cannot be ligated during the surgery.[17] However, on the other hand, various studies have demonstrated that there is no difference in the occurrence of lymphatic complication among various surgical techniques and among surgeons with different grades of experience.[18],[19],[20] In our study, organ procurement was mixed, with some cases having open and some laparoscopic organ procurement. It is also proved that lymphoceles can occur weeks after surgery due to leakage from allograft lymphatics. In addition, prolonged graft anoxia during procurement is also responsible for more lymphatic leak.[21] Apart from surgical factors, there are various medical factors which are responsible for the same. The important medical factors are certain immunosuppressive drugs, mainly mammalian target of rapamycin inhibitors, obesity, diabetes, coagulopathy, delayed graft function, and rejection episodes.[22],[23] After analyzing the various published articles, we have noticed that lymphatic complication is very much unpredictable. Even after adhering to the proper surgical technique by the most experienced transplant surgeon, lymphatic leak can happen.

Lymphocele deteriorates allograft function due to the compression effect on ureter or renal vasculature.[24],[25] The compression effect exerted by the lymphocele generally depends on their size and location.[6] The reported complications of lymphocele are pelvic pain, increased urinary frequency (due to compression effect on the bladder), abdominal distension, tenesmus, deep vein thrombosis, and allograft failure.[26] Veeramani et al. reported that 10-year graft survival is significantly lower in patients with lymphocele compared to patients not having lymphatic complications.[27]

The management options for lymphocele are simple aspiration, aspiration with or without sclerotherapy, and more invasive procedures, i.e., laparoscopic/open surgery for fenestration of lymphocele to the peritoneal cavity.[14] With the advancement of radiological technologies in recent years, percutaneous drainage with sclerosant instillation became the first-line management of lymphocele among various transplant centers. Various sclerosants used for this purpose are povidone-iodine, fibrin glue, ethanol, fibrinogen, tetracycline, and sodium tetradecyl sulfate.[13],[28],[29],[30],[31]

In this study, our main concern was to prevent the lymphatic complication rather than treating it. Chandrasekharan in his study used povidone-iodine to prevent lymphocele formation by instilling the same soon after transplantation, however, his method of instillation and protocol was different.[32] In this study, we also had used povidone-iodine instillation during intraoperative period to prevent early postoperative lymphatic leak. Here, povidone-iodine was instilled once after the preparation of bed and then again after ureteroneocystostomy, with the idea that the first instillation would sclerose the lymphatics of bed and next instillation would sclerose allograft lymphatics. We had used povidone-iodine as it is cheap, easily available, safe, and effective.[33],[34] Furthermore, the intraoperative instillation reduces the chances of infection. Pope et al. first used sclerotherapy as a treatment option for lymphocele.[35] Povidone-iodine as a sclerosant in lymphocele treatment was first described by Teurel et al.[14] There are various case reports and case series where povidone-iodine was used as a sclerosant in the treatment of lymphocele.[24],[33],[34],[35],[36],[37] It was postulated that povidone-iodine has local sclerosant property due to the inflammatory reaction incited by the free iodine release. Although it has antibacterial property, its use as a sclerosant cannot reduce the infection rate.[38] Although maximum published documents showed that the use of povidone-iodine as a sclerosant is safe, there are few case reports showing the complication of povidone-iodine instillation. Rivera et al. mentioned pericatheter infection as a complication of the procedure which was further supported by the systemic meta-review conducted by Lucewicz et al.[6],[38] However, the most significant complication was reported by Manfro et al.,[39] where allograft loss due to iodine-induced acute tubular necrosis occurred following povidone-iodine instillation in lymphocele. In that case, povidone-iodine was instilled twice daily manner for consecutive 7 days. There are also some reports of iodine-induced acute kidney injury following povidone-iodine oral ingestion and after mediastinal instillation during cardiac surgeries.[40] In our study, we had used povidone-iodine only once and during intraoperative period. So theoretically, there was no chance of pericatheter infection, and by reducing the number and frequency of instillation, we had tried to minimize the cumulative toxic effect of free iodine on graft kidney.

In this study, we had noticed a peculiar finding. There is increased drain output in POD1, where povidone-iodine was used. Sureka et al. explained that in initial 2–3 days, drain output largely consists of blood and serum, after that period lymph contributes the major portion in drain output.[4] Hence, the possible reason for this finding could be increased seroma formation in POD1 due to local inflammatory reaction caused by the povidone-iodine.

Although there are multiple studies on povidone-iodine as a sclerosant in lymphocele treatment, there is no consensus on the concentration and volume to be used. There are instances where as minimum as 0.5% to as maximum as 10% concentration of povidone-iodine has been used.[12],[38],[41] We found similar results in case of volume too. Among published literatures, as minimum as 20 ml to as maximum as half of the volume of the lymphocele was used.[33],[36] In our study, we had compared the efficacy of 1% and 5% povidone-iodine in preventing lymphatic leak and found that no significant difference exists between the two groups. As we had observed that 50 ml povidone-iodine was most commonly used among published reports, we also used 50 ml as volume.

In this study, in case of lymphatic leak, we could not find out the exact site of the leak. Pacovsky et al. demonstrated that by estimating the creatine kinase level in the collected lymph, the source of the leak can be identified. If creatine kinase level is <35 UI, more than 85% of the drain output is from the allograft lymphatic leak.[42]

In our study, we had not observed even a single case of significant lymphorrhea in the povidone-iodine groups. This high success rate could possibly be explained by keeping in mind that the lymphatic complication is multifactorial in origin (surgical as well as medical), and povidone-iodine can sclerose the lymphatic channels in allograft area, thus preventing any further leak even if some lymphatic channels were missed while clipping during intraoperative period.

In our study, we have not found a single case of iodine toxicity as measured by urinary iodine concentration in POD1 and POD5.

Limitation of the study

  1. The limitation of our study is the relatively small sample size, and this study was done in a single center
  2. In our study, we could not find out the exact cause of increased lymphatic leak in cases of lymphorrhea, and also, the incidence of lymphorrhea in laparoscopic and open organ procurement was not measured separately
  3. Direct exposure of povidone-iodine for 5 min was given to the allograft in this study, though after a 1-month follow-up, we saw no cases with graft failure in the povidone-iodine group, however, a long-term follow-up should be done for these cases.



  Conclusion Top


From this study, we can conclude that intraoperative instillation povidone-iodine is a cheap, safe, and very effective procedure to prevent the lymphatic leak following renal transplant surgeries. However, this must be remembered that proper and meticulous surgical technique is the most important key to reduce the lymphatic complications. Povidone-iodine can safely be used to improve the surgical outcome by reducing the unforeseen lymphatic complication.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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