Year : 2022 | Volume
| Issue : 1 | Page : 38-44
Crystalloid fluids and delayed graft function in kidney transplant: A cohort study
Amr ALKouny1, Mohammed K ALHarbi2, Abdulrahman R ALTheaby3, Ghaleb Aboalsamh4, Amel Fayed5
1 Department of Anesthesia, King Abdul Aziz Medical City, Riyadh, Saudi Arabia
2 Department of Anesthesiology, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences, Riyadh, Saudi Arabia
3 Department of Adult Nephrology and Renal Transplantation, King Abdul Aziz Medical City, Riyadh, Saudi Arabia
4 Department of Organ Transplantation and Hepatobiliary Surgery, King Abdul Aziz Medical City, Riyadh, Saudi Arabia
5 College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
Department of Anesthesia, King Abdul Aziz Medical City, Riyadh
Source of Support: None, Conflict of Interest: None
|Date of Submission||12-May-2021|
|Date of Decision||07-Jun-2021|
|Date of Acceptance||08-Jun-2021|
|Date of Web Publication||04-Jan-2022|
Background: Normal saline is commonly used in the perioperative kidney transplant period; its high chloride content can cause hyperchloremic metabolic acidosis giving a possible advantage to balanced electrolyte solutions due to their lower chloride content. The evidence regarding the best practices in fluid management during kidney transplantation and its effect on the incidence of delayed graft function (DGF) is still limited. Materials and Methods: One hundred thirty-eight patients were included and followed up for seven days after surgery. Administered crystalloid type and volume were compared among patients with and without DGF, along with additional patient and surgical variables. To investigate whether intraoperative fluid type/amount influence DGF, patients were categorized into three groups: those who received mainly (>50%) lactated Ringer's solution, normal saline, or plasmaLyte. A logistic regression analysis was used to define variables independently correlated with DGF, and odds ratios (OR) with a 95% confidence interval (CI) were reported. Results: The incidence of DGF was 8.7%. Cold ischemia time independently increased the odds of DGF (OR = 1.006 (95% CI: 1.002–1.011) while fluid type (saline versus PlasmaLyte OR = 5.28, 95% CI: 0.76–36.88) or amount (OR = 1.00, 95% CI: 1.00–1.01) did not significantly modify the odds of DGF. Central venous pressure, systolic blood pressure, and mean arterial pressure were higher in the non-DGF group, but this was not statistically significant (P > 0.05). Significant intraoperative acidosis developed in patients who received normal saline compared to those in PlasmaLyte and lactated Ringer's groups; however, acid–base balance and electrolytes did not vary significantly between the DGF and non-DGF groups. Conclusion: DGF was primarily influenced by surgical factors such as cold ischemia time, whereas intraoperative fluid type or amount did not affect DGF incidence.
Keywords: Delayed graft function, intraoperative fluid administration, kidney transplant
|How to cite this article:|
ALKouny A, ALHarbi MK, ALTheaby AR, Aboalsamh G, Fayed A. Crystalloid fluids and delayed graft function in kidney transplant: A cohort study. Saudi J Anaesth 2022;16:38-44
|How to cite this URL:|
ALKouny A, ALHarbi MK, ALTheaby AR, Aboalsamh G, Fayed A. Crystalloid fluids and delayed graft function in kidney transplant: A cohort study. Saudi J Anaesth [serial online] 2022 [cited 2022 Nov 30];16:38-44. Available from: https://www.saudija.org/text.asp?2022/16/1/38/334745
| Introduction|| |
Kidney transplant is the treatment of choice for patients with end-stage renal disease (ESRD) as the recipients will have an improved life quality with freedom from dialysis. Despite improvements in renal transplantation outcomes, delayed graft function (DGF) still represents a substantial complication and a prognosticator of the patient and graft outcome. DGF is defined as failure of the transplanted kidney to function normally within the first week after transplantation, necessitating dialysis. The most common cause of DGF is acute tubular necrosis (ATN). Any factor that causes graft oxygen consumption–delivery mismatch, like the ischemia time and preservation techniques, may cause ATN., The recipient's hemodynamics and fluid management also affect DGF and long-term transplant outcomes.[5–7] Normal saline has long been considered as the fluid of choice in kidney transplant. However, it was found that the administration of big volumes of normal saline causes a relative increase in plasma chloride ions compared to sodium ions leading to a reduction in the plasma strong ion difference and hence to metabolic acidosis. Renal vasoconstriction and a lower glomerular filtration rate were observed after infusion of chloride-rich fluids into denervated animal kidneys. When comparing normal saline with balanced crystalloids in non-kidney transplant patients, there was a greater incidence of serious adverse kidney events following normal saline administration.
Although balanced electrolyte solutions produce less metabolic acidosis, which is a potential benefit in ESRD, the best fluid practices for kidney transplantation are still not certain.,
| Materials and Methods|| |
Study participants and design
This study is a retrospective cohort study involving 138 consecutive patients who underwent kidney transplantation between March 2018 and January 2020. Ethical approval was obtained from Institutional Review Board (approval number RC 19/424/R) and the requirement of consent was waived by the ethical committee as all data were collected anonymously from electronic medical records. The study involved adult patients who were receiving a kidney from a living or deceased donor.
Data were retrieved from electronic medical records and included recipient demographics (age, gender, and body mass index (BMI)) as well as comorbid conditions like hypertension, ischemic heart diseases, diabetes mellitus, and liver diseases), kidney-transplant related data as the underlying causes of kidney disease, cold ischemia time (CIT), and warm ischemia time.
Other data related to anesthesia management as monitors, type and volume of fluid administration, and blood products transfusion were collected additionally, whereas laboratory data, such as glomerular filtration rate, urea, creatinine, potassium, sodium, chloride, and bicarbonate, were abstracted.
To investigate the effect of fluid type/amount on DGF, patients were categorized into those who received mainly (more than 50%) lactated Ringer's solution, normal saline, or PlasmaLyte.
Intraoperative changes in hemodynamics and arterial blood gases were retrieved from medical records. Additionally, postoperative fluid administration over the first 3 days was reported along with changes in electrolytes and kidney function parameters over the first week after surgery.
DGF, identified as the need for renal dialysis within 7 days of transplantation, was the primary outcome in this study. Secondary outcomes included the immediate postoperative outcomes as urine output, sodium, potassium, bicarbonate, and chloride levels.
Sampling technique and sample size
A consecutive nonprobability sampling technique was adopted to collect data. A priori sample size was calculated, assuming the prevalence of DGF varying around 15±10%, using power of 80% (beta = 20%) and a level of confidence of 95% (alpha = 0.05), and the minimal sample size was 120.
Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 23.0 (Armonk, NY, USA: IBM Corp.). Descriptive statistics of numeric variables were reported as the median and interquartile range [IQR], and categorical variables as frequency and percentage. Mann–Whitney test was used to compare patients with and without DGF and Kruskal–Wallis test was used when comparing patients receiving different fluids. At the same time, Chi-square or Fisher's exact tests were used to test the association between categorical variables. To investigate the associations between DGF and possible risk factors, logistic regression models were used to estimate crude and adjusted odds ratios (OR) with 95% confidence intervals (95% CI). A P value of less than 0.05 was considered statistically significant.
| Results|| |
[Table 1] displays the characteristics of the participating patients; a total of 138 patients were included in the current study, whose median age was 46 [IQR: 31.5,59.5] years, with male majority (64%), nonsmokers (85.6%), and BMI of 28.67 [IQR: 24.59, 32.40) kg/m2. The most common cause of ESRD was diabetes (34.1%) followed by hypertension (14.5%); however, 16.7% were with unknown causes. The majority of patients were on hemodialysis (88.5%), 27.4% were insulin-dependent diabetic, 45.3% were hypertensive, and 31.7% had dyslipidemia. On average, the surgery time was 240 min [IQR: 210,270), blood loss was 200 ml [IQR: 100,200), cold ischemia time was 240 min [IQR: 210,180), and 74.6% had living donors.
[Table 2] shows the intraoperative fluid administration and changes in hemodynamics and blood gases in patients with and without DGF. Out of 138 patients, 12 patients (8.7%) developed DGF. PlasmaLyte was the most used fluid (100 patients, 74.6%), followed by normal saline (33 patients, 21.4%), whereas only 5 patients received lactated Ringer's solution—all of whom did not develop DGF. Neither intraoperative fluid type nor amount differed significantly between patients with and without DGF (P > 0.05). Central venous pressure (CVP) did not vary significantly between DGF and non-DGF groups at the start of surgery or at reperfusion, whereas by the end of surgery, it was higher among the non-DGF group; however, this difference was not statistically conclusive. On average, patients with DGF had lower systolic blood pressure (SBP) and mean arterial blood pressure (MAP), yet, this variation was not statistically significant. (P > 0.05). Amongst the two groups, acid–base balance and electrolytes did not differ significantly.
|Table 2: Intraoperative Fluid Administration, Hemodynamics, and Arterial Blood Gas Changes in Patients With and Without Delayed Graft Function (DGF)|
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At the end of surgery, laboratory outcomes were compared among different groups of patients according to the type of intraoperative fluid administration [Table 3]. The amount of intraoperative fluids in the three groups were nearly equivalent (median was around 5000 ml, P = 0.95). Significant intraoperative acidosis developed in the normal saline group. Differences among the three groups did not reach statistically significant levels in all the other outcomes.
|Table 3: End of Surgery Laboratory Parameters According to Intraoperative Fluid Type|
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[Table 4] shows the crude and adjusted odds ratios of various factors for developing DGF. Out of all studied factors, five factors had a crude association with risk of developing DGF; having a deceased donor (OR = 3.34; 95% CI = 1.02–11.16), increasing the CIT (OR = 1.003; 95% CI = 1.001–1.006), higher blood loss (OR = 1.006; 95%CI = 1.001–1.011), longer surgery (OR = 1.012; 95%CI = 1.001–1.022), and intraoperative administration of normal saline (OR = 3.48; 95% CI = 1.04–11.67). After adjusting these crude associations, an independent association was defined only between DGF and CIT time (OR = 1.006; 95%CI = 1.002–1.011).
|Table 4: Univariate and Multivariate Association of DGF With Patient-Related and Surgery-Related Factors|
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The postoperative fluid administration, electrolyte changes, and kidney function parameters among patients with and without DGF are shown in [Supplementary File 1]. Significant difference between the two groups was evident in some parameters as early as day zero of surgery like the urine output; this discrepancy increased dramatically between the two groups with each day after the surgery as measured by all variables. Fluids administration was adjusted for each patient according to their kidney function, like urine output and creatinine level; therefore, the amount of fluids was significantly lower in the DGF group compared to those without DGF.
| Discussion|| |
In a kidney transplant, maintaining intravascular volume primarily with isotonic crystalloid solutions is critical to ensure optimal graft perfusion and avoid DGF, but different crystalloids can affect electrolytes and acid–base balance in various ways, raising the question whether this could affect the patient or the graft outcome.
The current study found no association between the crystalloid type and DGF. In one of the earliest studies comparing normal saline and balanced crystalloid solutions (lactated Ringer's solution) in kidney transplantation, insignificant difference in postoperative serum creatinine taken as a primary outcome was found between the two groups; some patients in the saline group developed moderate hyperkalemia and metabolic acidosis, which required intervention and the study was stopped early due to safety concerns, concluding that although normal saline does not detrimentally affect renal function in kidney transplant patients, lactated Ringer's solution seemed safe and superior. This safety was challenged by another group of investigators who used the same study design, due to the development of hypercoagulability, vascular graft thrombosis, and graft loss in the lactated Ringer's solution group despite lower serum potassium level and less acidosis. Hadimioglu et al. found that normal saline, lactated Ringer's solution, and PlasmaLyte can all be used safely in kidney transplants, with PlasmaLyte tending to have the best metabolic profile. In this study, significant intraoperative acidosis developed in the normal saline group and in the immediate postoperative serum chloride level was considerably higher. Kim et al. found a significantly higher serum chloride in the normal saline group, but postoperative urine output, serum creatinine, and graft failure were not significantly different between the groups. A Cochrane meta-analysis was uncertain whether lower chloride solutions had more advantage compared to normal saline in terms of improved graft outcomes.
The intraoperative crystalloid volume was similar in patients who developed or did not develop DGF, and this was similar to the findings of a recent multicenter pilot study. In the present study, CVP was slightly elevated at the end of surgery in the non-DGF group, but this was not statistically conclusive. Studies on CVP as a volume guide in kidney transplant showed inconsistent results, with many studies advising maximal hydration and high CVP to ensure good graft function, whereas other studies observed an association between high CVP and DGF and advised against supranormal volume loading, especially in cardiac patients with poor myocardial function. As a result, the target CVP in a kidney transplant seems elusive, keeping in mind the intraoperative factors that may alter its readings leading to incorrect decision making. These factors include operating table position, which is not always flat and the surgeon may left or right tilt it to have more access to the iliac vessels, the pressure effect of surgical retractors on the abdominal viscera and venous return, and the positive pressure ventilation during the procedure that can also affect venous return. Systematic reviews revealed a weak correlation between CVP and blood volume, as well as CVP's inability to predict hemodynamic responses to a fluid challenge.,
Although statistically insignificant, the current study patients with DGF had an average lower SBP and MAP. Blood pressure targets and thresholds are different between studies., Campos et al. found that MAPmore than93 mmHg led to greater graft survival. In a previous study, Tóth et al. observed a significantly higher MAP in patients with good graft function. Unfortunately, since the ideal measurement to assess kidney microcirculation is still unknown, these associations do not mean that increasing blood pressure restores renal function. Furthermore, the ideal MAP that prevents acute kidney injury during different medical conditions is unknown.
Fluid requirements among transplant patients are highly variable and traditional parameters such as heart rate, blood pressure, CVP, pulmonary artery pressure, and urine output to direct fluid therapy in kidney transplantation are not very reliable. An individualized approach tailored for each patient's physiologic needs will be more beneficial than a standardized algorithm.
The incidence of DGF in our study was 8.7%, which corresponds with other published literatures that show an incidence of 1%–18% with living donors, and 10%–60% with deceased donors kidney transplant., In accordance with other researches, CIT was independently associated with DGF. CIT is one of the most crucial predictors of short- and long-term graft survivals. There is a significant proportionate escalation in the risk of graft failure for each added hour of CIT and shortening of CIT will reduce DGF rates and the occurrence of acute rejection and graft loss.
Despite the known limitation of the retrospective design and the relatively small sample size of the study, the detailed reporting of perioperative variables and outcomes adds to the strengths of our study. Moreover, we are planning for a future larger prospective study to confirm our results and clarify the definitive effect of fluid management on DGF.
Declaration of patient consent
Consent was waived by the ethical committee as all data were retrieved anonymously from electronic medical records.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Andre M, Huang E, Everly M, Bunnapradist S. The UNOS Renal Transplant Registry: Review of the Last Decade. Clin Transpl 2014;1-12.
Schnuelle P, Johannes van der Woude F. Perioperative fluid management in renal transplantation: A narrative review of the literature. Transpl Int 2006;19:947-59.
Massberg S, Messmer K. The nature of ischemia/reperfusion injury. Transplant Proc 1998;30:4217-23.
Perico N, Cattaneo D, Sayegh MH, Remuzzi G. Delayed graft function in kidney transplantation. Lancet (London, England) 2004;364:1814-27.
Campos L, Parada B, Furriel F, Castelo D, Moreira P, Mota A. Do intraoperative hemodynamic factors of the recipient influence renal graft function? Transplant Proc 2012;44:1800-3.
Bacchi G, Buscaroli A, Fusari M, Neri L, Cappuccilli ML, Carretta E, et al
. The influence of intraoperative central venous pressure on delayed graft function in renal transplantation: A single-center experience. Transplant Proc 2010;42:3387-91.
Aulakh NK, Garg K, Bose A, Aulakh BS, Chahal HS, Aulakh GS. Influence of hemodynamics and intra-operative hydration on biochemical outcome of renal transplant recipients. J Anaesthesiol Clin Pharmacol 2015;31:174-9.
] [Full text]
Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol 1983;61:1444-61.
Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest 1983;71:726-35.
Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, et al
. Balanced crystalloids versus saline in noncritically ill adults. N Engl J Med 2018;378:819-28.
O'Malley CM, Frumento RJ, Hardy MA, Benvenisty AI, Brentjens TE, Mercer JS, et al
. A randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl during renal transplantation. Anesth Analg 2005;100:1518-24.
Hadimioglu N, Saadawy I, Saglam T, Ertug Z, Dinckan A. The effect of different crystalloid solutions on acid-base balance and early kidney function after kidney transplantation. Anesth Analg 2008;107:264-9.
Khajavi MR, Etezadi F, Moharari RS, Imani F, Meysamie AP, Khashayar P, et al
. Effects of normal saline vs. lactated ringer's during renal transplantation. Ren Fail 2008;30:535-9.
Kim SY, Huh KH, Lee JR, Kim SH, Jeong SH, Choi YS. Comparison of the effects of normal saline versus Plasmalyte on acid-base balance during living donor kidney transplantation using the Stewart and base excess methods. Transplant Proc 2013;45:2191-6.
Wan S, Roberts MA, Mount P. Normal saline versus lower-chloride solutions for kidney transplantation. Cochrane Database Syst Rev 2016:CD010741. doi: 10.1002/14651858.CD010741.pub2.
Efune GE, Zerillo J, Zhou G, Mazzeffi MA, Demaria S, Wang C. Intravenous fluid management practices in kidney transplant patients: A multicenter observational cohort pilot study. Semin Cardiothorac Vasc Anesth 2020;24:256-64.
Othman MM, Ismael AZ, Hammouda GE. The impact of timing of maximal crystalloid hydration on early graft function during kidney transplantation. Anesth Analg 2010;110:1440-6.
Carlier M, Squifflet JP, Pirson Y, Gribomont B, Alexandre GP. Maximal hydration during anesthesia increases pulmonary arterial pressures and improves early function of human renal transplants. Transplantation 1982;34(4):201-4.
De Gasperi A, Narcisi S, Mazza E, Bettinelli L, Pavani M, Perrone L, et al
. Perioperative fluid management in kidney transplantation: Is volume overload still mandatory for graft function? Transplant Proc 2006;38:807-9.
Aref A, Zayan T, Sharma A, Halawa A. Utility of central venous pressure measurement in renal transplantation: Is it evidence based? World J Transplant 2018;8:61-7.
Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest 2008;134:172-8.
Eskesen TG, Wetterslev M, Perner A. Systematic review including re-analyses of 1148 individual data sets of central venous pressure as a predictor of fluid responsiveness. Intensive Care Med 2016;42:324-32.
Snoeijs MGJ, Wiermans B, Christiaans MH, Van Hooff JP, Timmerman BE, Schurink GWH, et al
. Recipient hemodynamics during non-heart-beating donor kidney transplantation are major predictors of primary nonfunction. Am J Transplant 2007;7:1158-66.
Tóth M, Réti V, Gondos T. Effect of recipients' peri-operative parameters on the outcome of kidney transplantation. Clin Transplant 1998;12:511-7.
Calixto Fernandes MH, Schricker T, Magder S, Hatzakorzian R. Perioperative fluid management in kidney transplantation: A black box. Crit Care (London, England) 2018;22:14.
Gopalakrishnan N, Dineshkumar T, Dhanapriya J, Sakthirajan R, Balasubramaniyan T, Srinivasa Prasad ND, et al
. Deceased donor renal transplantation: A single center experience. Indian J Nephrol 2017;27:4-8.
] [Full text]
Park HS, Hong YA, Kim HG, Choi SR, Sun IO, Chung BH, et al
. Delayed graft function in living-donor renal transplantation: 10-year experience. Transplant Proc 2012;44:43-6.
Quiroga I, McShane P, Koo DD, Gray D, Friend PJ, Fuggle S, et al
. Major effects of delayed graft function and cold ischaemia time on renal allograft survival. Nephrol Dial Transplant 2006;21:1689-96.
Mikhalski D, Wissing KM, Ghisdal L, Broeders N, Touly M, Hoang AD, et al
. Cold ischemia is a major determinant of acute rejection and renal graft survival in the modern era of immunosuppression. Transplantation 2008;85(7 Suppl):S3-9.
[Table 1], [Table 2], [Table 3], [Table 4]