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Fluid and electrolyte replacement during the post-transplant period aims to maintain an adequate intravascular volume to ensure renal perfusion so immediate graft function is optimized. To achieve this goal, an adequate understanding and management of fluid therapy is essential; a major surgery is commonly associated to renal insufficiency and electrolytic disorders such as hyperkalemia that should be prevented and the function of the graft needs to be warranted. Delayed graft function is a term used to describe acute renal failure after transplantation and may be defined by the need for dialysis during the first postoperative week.

Delayed graft function is important predictor of the subsequent clinical course of the graft. This choice has been based on the belief that the use of potassium containing replacement fluids could produce hyperkalemia. However, there are views that attribute to NS an increase of serum chlorine that predispose to the development of metabolic acidosis and the generation of hyperkalemia through a transcellular movement of ions.

This concept has been that basis for the elaboration of several studies during the last decade comparing the use of NS and balanced crystalloid solutions including potassium in their formulation during the perioperative period of renal transplantation. The present short reviews is brief pathophysiological assessment of this concept as well as a description of the publications in the current medical literature.. Intravenous fluids are separated into 2 types: crystalloids and colloids.

Crystalloids are made of sterile water and electrolytes and sometimes contain glucose as a source of calories. Colloids are solutions containing high molecular weight particles that increase oncotic pressure and are added to a crystalloid. This group includes albumin, gelatins, dextrans and starches derived from corn and potato. The increase in oncotic pressure increases intravascular fluid retention capacity as compared to crystalloids.

This theory is based on the theoretical premise that larger particles are trapped in the intravascular space by an intact endothelial barrier for longer period of time. However, it is necessary to consider that a colloid only behaves as a colloid that is, increasing oncotic pressure when the glycocalyx is intact. Furthermore, the use of colloids increases the cost, have limited availability the case of albumin, which is a blood product and are associated with clotting disorders that may cause persistent renal damage, mainly observed with the use of hydroxy-ethyl starches.

These details may have led clinicians to choose crystalloids as the first option in the postoperative period of renal transplantation.. Crystalloids are classified into 2 large groups. Unbalanced and balanced crystalloids; the NS is considered unbalanced fluid.. From the standpoint of renal hemodynamics, it tends to reduce the volume of diuresis, prolonging it over time.

The activity of natriuretic factors, the inhibition of antinatriuretic system and the effect on cardiac output is similar to that of balanced solutions, 24 but the water management is different from unbalanced crystalloid solution. With very large volumes of infusion and in the absence of spurious stimuli of ADH, it tends to produce hypernatremia. By contrast, the infusion of discreetly hypotonic solutions in large quantities favors hyponatremia more than hypernatremia.

With regard to glomerular filtration, the infusion of NS, by distending the right cardiac cavities, increases the secretion of atrial natriuretic peptide, which dilates the afferent artery and inhibits the sodium channels of the collecting tubule. Therefore, the delay in the initiation of diuresis is a tubular effect, secondary to the activation of ADH due to a relative hypertonicity, so it requires a considerable volume of infusion.

Hypovolemia due to situations as surgical interventions, forced diuresis, development of a third space or drainage, produce activation of the renin-angiotensin-aldosterone axis and increase in thirst. Such salt depletion may increase the dependence of glomerular filtration on an intact renin-angiotensin system and sensitize the patient to the development of acute renal failure. According to the Stewart model, the physical—chemical approach to the analysis of acid-base balance confers a predominant role to chloride, and hyperchloremia. Apart from the clinical effects of acidosis reduction of cardiac contractility, reduction of catecholamine effects, alterations in coagulation or platelet function 33 , it is necessary to recall its effect on the regulation of serum potassium..

Therefore, small changes in intracellular potassium will have a significant effect on extracellular potassium levels. Effect of hyperchloremic acidosis on serum potassium concentration. Source : Modified from Santi et al.

Simulation of the expected changes in the serum levels of chloride, bicarbonate, pCO 2 , pH and potassium of a standard subject treated with progressive volume expansion.. It is assumed 12 L of extracellular volume for a 70 kg subject. In the case of infusion of balanced solutions with buffer capacity, the presence of lactate or acetate will result in equivalent amounts of bicarbonate, which will prevent or minimize hyperchloremic acidosis.

In fact, if such buffered solutions did not contain potassium in their formulation, the dilution effect on serum potassium concentration would cause hypokalemia by dilution.. At this point, it is important to note that the theoretical pathophysiological models support that the metabolism of lactate and acetate to achieve the production of bicarbonate differ in several aspects.

First, it is considered that the production of bicarbonate from acetate is faster, with less oxygen consumption and not dependent exclusively on hepatic metabolism. Second, it does not interfere with gluconeogenesis and it is not a marker of tissue hypoxia, unlike lactate. The presence of calcium in the fluids may be responsible for significant clinical differences.. The effect of saline versus a calcium-balanced crystalloid was compared in an animal model subjected to uncontrolled bleeding produced by similar vascular lesions and with a therapeutic objective of maintaining a stable blood pressure.

It was observed that the therapeutic goal was achieved with less volume infusion of the balanced crystalloid. Bleeding animals receiving saline have more blood losses than those treated with calcium. It is evident that the presence calcium modified the hemostasis of the animals. And, reasonably, the volume of diuresis was related to the volumes infused as the blood pressure remained constant. However, other authors have criticized this presence of calcium in some balanced crystalloids, arguing that they can facilitate microthrombi if they are used in large quantities in patients receiving multiple transfusions, since calcium antagonizes the effect of citrate.

The perioperative period in renal transplantation has traditionally been a period of time in which large amounts of resuscitation fluids are administered, with the ultimate aim of ensuring the function of the graft after renal transplantation. In the last decade, several studies have compared changes the ionic and acid—base produced by different crystalloids administration during the perioperative period of renal transplantation.

After searching the databases Medline, Embase, Cochrane Database and Lilacs, we describe, according to year of publication, the most relevant studies in this regard:. Study carried out in 51 patients including live donors or cadaveric transplants. Twenty-five patients were randomized to the balanced crystalloid group and 26 to the NS group. The primary endpoint of the study was to determine differences in serum creatinine on the third postoperative day.. Hadimioglu et al. All 90 patients received live donor organ.

The primary objectives of the study were to analyze: total daily urinary volume, serum creatinine on the third postoperative day, pH, bicarbonate and potassium levels during surgery and in the postoperative period, as well as creatinine, BUN, chloride, urinary output and creatinine clearance on days 1, 2, 3 and Results showed a statistically significant reduction in pH, in excess of alkali and a significant increase in serum chloride levels in patients receiving NS during surgery. Potassium levels did not show significant changes in any group.

Khajavi et al. Lactated Ringer's during renal transplantation. Randomized, double-blind study conducted in 52 patients with live donor grafts. The primary objectives were to find differences in serum potassium and pH at the end of surgery. Modi et al. The primary objectives were to compare urinary output intraoperatively and during the first postoperative day, serum creatinine values on the first postoperative day, changes in pH, bicarbonate, potassium and chloride during surgery and in the postoperative period.

The anesthesia protocol was to maintain the central venous pressure between 12 and 15 mmHg.. The pH decreased from 7. The mean value of serum creatinine on the first day after surgery was 2. The serum potassium reached 3. The serum chloride level was Kim et al. The fluids were administered to maintain central venous pressure between 12 and 15 mmHg.

Arterial blood samples were collected after induction of anesthesia T0 , immediately before the anastomosis of the iliac vein T1 , 10 min after reperfusion T2 and at the end of surgery T3 to measure pH, PaCO 2 , excess bases, bicarbonate, sodium, potassium, chloride, lactate, phosphate and albumin.

The water balance was calculated during the study, as well as serum levels of chloride and creatinine at 24 h and at days 1, 2 and 7. The acid-base state was analyzed using the physicochemical model of Stewart.. Postoperative serum chloride levels were not different between the 2 groups. Serum creatinine and h urine volume were similar between groups.. Potura et al. A prospective, randomized, controlled trial including patients, 74 received NS and 76 a crystalloid solution balanced with acetate during and after renal cadaver transplantation.

More patients in the saline group, compared to the balancing group, required the administration of catecholamines for circulatory support. The difference was statistically significant.. Recently, the results of a meta-analysis with 4 of the previously described articles have been published. Results of the comparative meta-analysis of the Ringer's solution and the SSN, in relation to the development of hyperkalemia.

Source : Taken from Trujillo-Zea et al. Results of the comparative meta-analysis of the Ringer's solution and the NS, in relation to the development of hyperchloremia. First, despite the results of the studies described above, it should be emphasized that number of studies presently available is not sufficient to make a entirely correct choice of fluids in the perioperative period of renal transplantation. In addition, the studies described so far include a low number of patients, with different periods of observation and post-transplant follow-up and the variables evaluated are not always the same; these are premises that limit the interpretation of the data..

However, it can be concluded that the use of balanced crystalloids that include potassium in their formulation, during the perioperative period of renal transplantation, appear to be safe with respect to the control of serum potassium concentration. In addition, with the use balanced solutions there seems to be a better control of acid-base balance. No significant changes in serum creatinine have been observed during the perioperative period, neither at 3 nor at 7 days. Hyperchloremia caused by infusion of NS causes hyperchloremic metabolic acidosis.. Hyperchloremic metabolic acidosis may favor an increase in serum potassium concentration..

It is necessary to perform clinical studies in these patients, in which variables of a greater clinical impact are evaluated.. The corresponding author, Dr. The rest of the authors declare no conflict of interest.. Home Articles in press Archive. ISSN: Previous article Next article. November - December Pages Choice of fluids in the perioperative period of kidney transplantation.

Download PDF. Alejandro Gonzalez-Castro. Corresponding author. This item has received. Under a Creative Commons license. Article information. Show more Show less. Table 1. Simulation of the expected changes in the serum levels of chloride, bicarbonate, pCO2, pH and potassium of a standard subject treated with progressive volume expansion.. These solutions do not affect serum potassium levels any more than normal saline, whilst maintaining a better acid—base balance in these patients. Kidney transplantation.

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Palabras clave:. Trasplante renal. Introduction Fluid and electrolyte replacement during the post-transplant period aims to maintain an adequate intravascular volume to ensure renal perfusion so immediate graft function is optimized. Type of fluids Intravenous fluids are separated into 2 types: crystalloids and colloids.

Unbalanced and balanced crystalloids; the NS is considered unbalanced fluid. Simulation of the expected changes in the serum levels of chloride, bicarbonate, pCO 2 , pH and potassium of a standard subject treated with progressive volume expansion. Schnuelle, J.

Perioperative fluid management in renal transplantation. Transpl Int, 19 , pp. Halloran, L. Delayed graft function: state of the art, November 10—11, Am J Transpl, 1 , pp. Impact of delayed graft function and acute rejection on kidney graft survival. Clin Transpl, 6 , pp. Brennan, C. Freise, F. Fuller, A. Bostrom, S. Tomlanovich, S. Early graft function after living donor kidney transplantation predicts rejection but not outcomes. Am J Transpl, 4 , pp.

Kidney transplantation: recent developments and recommendations for anesthetic management. Anesthesiol Clin North Am, 22 , pp. Frumento, E. Intravenousfluid therapy in renal transplant recipients: results of a US survey. Transpl Proc, 34 , pp. Frumento, M. Hardy, A. Benvenisty, T. Brentjens, J. Mercer, et al. A randomized, double-blind comparison of lactated Ringer's solution and 0.

Anesth Analg, , pp. Khajavi, F. Etezadi, R.

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Moharari, F. Imani, A. Meysamie, P. Khashayar, et al. Effects of normal saline vs. Ren Fail, 30 , pp. Modi, K. Vora, G. Parikh, V. A comparative study of impact of infusion of Ringer's lactate solution versus normal saline on acid—base balance and serum electrolytes during live related renal transplantation. Saudi J Kidney Dis Transpl, 23 , pp. Hadimioglu, I. Saadawy, T. Saglam, Z. Ertug, A. The effect of different crystalloid solutions on acid—base balance and early kidney function after kidney transplantation.

Potura, G. Lindner, P. Biesenbach, G. Funk, C. Reiterer, B. Kabon, et al.

Value of Managing Fluid Overload in Critically Ill Patients

An acetate-buffered balanced crystalloid versus 0. Med Clin Barc , , pp. Raghunathan, M. During this period, 28 patients 7. Of patients with available premorbid creatinine levels, NUF rates greater than 1. Net ultrafiltration rate was significantly associated with risk of death in the presence of cumulative fluid balance aHR, 1. In the propensity score—matched cohort matched pairs , an NUFrate greater than 1. An NUF rate greater than 1. Using maximum values, an NUF rate greater than 2. After excluding 92 patients with NUF rates less than 0.

The association persisted when the nodes in the Gray model were increased aHR, 1. Of patients with negative fluid balance, the cutoff values were NUF rates less than 1. Using logistic regression, an NUF rate greater than 1. However, every 0. Using subgroup analyses, an NUFrate greater than 1. Among patients Compared with an NUFrate less than 0. An NUFrate greater than 1. More patients with NUF rates greater than 1. These findings are aligned with several recent studies in outpatients with end-stage renal disease 10 - 13 that found that higher NUF rates are associated with decreased survival.

Our findings have several implications. First, the attributable risk associated with an NUF rate greater than 1. Moreover, there was an interaction between the NUF rate and cumulative fluid balance that considerably increased this risk, which may explain the high mortality among patients treated with CVVHDF. Notably, this risk was present only after day 7 and is easily modifiable by slowing the NUF rate to less than 1.

There are many possible biological explanations for late mortality. Decreased circulating volume is associated with decreased coronary perfusion and myocardial ischemia. Hypotension associated with a high NUF rate may result in administration of fluid with subsequent fluid overload, which is associated with ventricular hypertrophy and fibrosis, predisposing the patient to heart failure and sudden death.

Second, our study suggests that a more modest NUF rate less than 1. This finding is consistent with other studies in patients with end-stage renal disease, 13 , 36 , 37 in which lower rates and longer treatment duration were associated with survival. Nevertheless, randomized clinical trials are required to confirm our findings. Third, while a lower NUF rate might be associated with improved outcomes, it is likely to prolong treatment duration, and this has to be balanced against the need for fluid removal in a critically ill patient.

For example, pulmonary edema in a patient with severe heart failure or refractory hypoxemia in a patient with acute respiratory distress syndrome may need a greater NUF rate for a short period of time to prevent sudden death. Although the reason for the differences between the 2 studies is unclear, it is important to note that there are considerable differences in study design and patient population between them.

Nevertheless, these differential findings emphasize the need for randomized clinical trials to examine the relationship of NUF rates with outcomes. Our study has several limitations. First, findings may be biased by measured and unmeasured confounding at the patient and hospital levels. Nevertheless, the joint model matched propensity score analysis, and the logistic regression provided alternative methods to handle measured confounders and support the primary analysis. Third, there were 31 patients with missing treatment hours; however, including these patients in the analysis did not change the results.

Fourth, fluid balance prior to initiation of CVVHDF was unavailable, a limitation that was addressed using the organ edema variable as a surrogate for fluid overload. Given these limitations, the risk associated with an NUF rate greater than 1. Although the study design does not exclude the possibility of residual confounding owing to unmeasured risk factors, a randomized clinical trial is required to validate these findings before they can be applied to clinical practice.

Published: June 7, Author Contributions: Dr Murugan and Ms Kerti had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Critical revision of the manuscript for important intellectual content: All authors. Dr Chang reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Gallagher reported receiving speaking fees from Amgen outside the submitted work. Dr Kellum reported receiving personal fees from NxStage and grants and personal fees from Baxter International during the conduct of the study.

Dr Bellomo reported receiving grants from Baxter International outside the submitted work. No other disclosures were reported. Home Issues Specialties For Authors. All Rights Reserved. Download PDF Comment. View Large Download. Table 1. Joint Model eAppendix 5. Multivariable Logistic Regression Model eTable 1. Both positive and negative fluid balance may be associated with reduced long-term survival in the critically ill. Crit Care Med. Fluid overload is associated with an increased risk for day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study.

Crit Care.

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Fluid overload in the ICU: evaluation and management

Accessed May 1, Am J Kidney Dis. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int. An observational study of fluid balance and patient outcomes in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy trial.


Hemodialysis-induced repetitive myocardial injury results in global and segmental reduction in systolic cardiac function. Clin J Am Soc Nephrol. Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study. Net ultrafiltration intensity and mortality in critically ill patients with fluid overload. PubMed Google Scholar Crossref. Rapid fluid removal during dialysis is associated with cardiovascular morbidity and mortality. Association of ultrafiltration rate with mortality in incident hemodialysis patients.

Association between high ultrafiltration rates and mortality in uraemic patients on regular haemodialysis: a 5-year prospective observational multicentre study. Nephrol Dial Transplant. Longer treatment time and slower ultrafiltration in hemodialysis: associations with reduced mortality in the DOPPS. Intensity of continuous renal-replacement therapy in critically ill patients.

N Engl J Med. Ann Intern Med. Assessment and control for confounding by indication in observational studies. J Am Geriatr Soc. Use of multiple imputation method to improve estimation of missing baseline serum creatinine in acute kidney injury research. MICE: multivariate imputation by chained equations in R. J Stat Softw. Flexible methods for analyzing survival data using splines, with applications to breast cancer prognosis.

J Am Stat Assoc. Spline-based tests in survival analysis. Stat Med. Dynamic predictions and prospective accuracy in joint models for longitudinal and time-to-event data. A joint model for survival and longitudinal data measured with error. Hemodialysis-induced cardiac injury: determinants and associated outcomes. Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease.

Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction. J Am Coll Cardiol. Inhibition of mTOR signaling with rapamycin regresses established cardiac hypertrophy induced by pressure overload. The challenge of sudden death in dialysis patients.

Intensity of renal support in critically ill patients with acute kidney injury. Hypophosphatemia during continuous hemodialysis is associated with prolonged respiratory failure in patients with acute kidney injury. Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure.

Hypophosphatemia in critically ill patients with acute kidney injury treated with hemodialysis is associated with adverse events.

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  • Hypophosphatemia during continuous veno-venous hemofiltration is associated with mortality in critically ill patients with acute kidney injury. Shorter length dialysis sessions are associated with increased mortality, independent of body weight. Disentangling the ultrafiltration rate-mortality association: the respective roles of session length and weight gain. Get the latest research based on your areas of interest. Weekly Email. Monthly Email. Save Preferences.