Perioperative fluid management in kidney transplantation: What’s new and future directives?

Abstract

Kidney transplantation is a moderate to high-risk surgery, and postoperative outcome is closely related to good intraoperative fluid management. Suboptimal fluid management is adversely associated with poor graft and recipient outcomes. Hence, meticulous intraoperative fluid management is essential and requires in-depth knowledge of newly added fluids and hemodynamic tools for fluid monitoring. Over the years, fluid management during kidney transplant has significantly changed with the inclusion of newer fluids and dynamic indices of volume responsiveness. In this review, we will discuss the different types of fluids and hemodynamic tools available for perioperative fluid management in kidney transplantation and their pros and cons on postoperative outcomes.

Key Words: Fluid therapy; Kidney transplantation; Perioperative period; Crystalloid solutions; Haemodynamic; Central venous pressure

Core Tip: Fluid therapy is one of the core domains of intraoperative anaesthesia management in kidney transplantation. Newer advancements in recent years have changed the outlook of intraoperative hemodynamic monitoring, resulting in better transplant outcomes. In this review, we focused on discussing newer indices of fluid responsiveness and their utility in kidney transplant surgery, as well as newer crystalloids and colloids and their impact on metabolic profile and post-transplant graft outcomes.

INTRODUCTION

Fluid therapy is an essential part of perioperative anaesthetic management for intermediate to high-risk surgeries, including cardiac, transplant, polytrauma, major abdominal, and vascular. Optimal fluid management in the perioperative period is required for enhanced patient recovery, as it is closely associated with postoperative surgical outcomes. Euvolemia is highly desired, as improper fluid therapy by means of the wrong fluid type or poor monitoring guidance may lead to adverse consequences related to both hypovolemia and hypervolemia. Hypovolemia increases the risk of organ hypoperfusion, hypotension, lactic acidosis, increased need for vasopressors, infections, and organ failure, while hypervolemia enhances the risk of cardiopulmonary complications, tissue oedema, poor wound healing, postoperative ileus, mechanical ventilation, and coagulopathy[1,2].

In kidney transplantation, postoperative graft function and patient recovery depend on perioperative fluid management; hence, meticulous fluid therapy is highly recommended. In this review, we highlighted the different aspects of fluid therapy, including types of fluids (crystalloids vs colloids), monitoring tools, and hemodynamic targets during kidney transplantation based on recent literature.

LITERATURE REVIEW

The medical literatures were searched for data using search engines (PubMed, Scopus, Google Scholar, and Cochrane Library) for recent practices in perioperative fluid management during kidney transplantation. The key terms used for search included (kidney transplant OR kidney transplantation OR renal transplant OR renal transplantation) AND (normal saline OR lactated ringer OR plasmaLyte A OR hydroxyethyl starch OR albumin OR central venous pressure OR mean arterial pressure OR pulse pressure variation OR stroke volume variation OR transoesophageal doppler OR perioperative goal directed fluid therapy OR floTrac OR hypotension prediction index OR delayed graft function). We included data from randomized controlled trials and retrospective studies in this review and excluded the case reports, case studies, review articles, meta-analysis, and protocols observing simultaneous multiple interventions and outcomes in perioperative period as shown in Figure 1.

Figure 1  Preferred reporting items for systematic reviews and meta-analyses diagram of study protocol.

Primary outcome included was delayed graft function (DGF) while urine output, change in postoperative creatinine level, requirements of intraoperative fluids, metabolic changes (serum electrolytes and acid/base), and postoperative complications were as secondary outcomes.

The levels of evidence and strength of recommendations were determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Evidence quality was classified as high, moderate, low, or very low, based on the available literature. Generally, multiple randomized controlled trials with consistent outcomes or systematic reviews were rated as high quality, whereas observational studies, particularly retrospective ones, were considered low or very low quality. The strength of recommendations was graded as strong or weak, depending on whether they supported or opposed an intervention. Strong recommendations were given when benefits clearly outweighed risks (or vice versa), while weak recommendations were made when evidence was limited and decisions needed to be individualized.

IDEAL PERIOPERATIVE FLUIDS

Postoperative graft and recipient outcomes are affected by the type of fluid used and should be considered in anaesthesia planning beforehand. However, the selection of fluids (crystalloids or colloids) during kidney transplantation is highly controversial, and practices vary among anaesthesiologists.

Crystalloids

Normal saline, Ringer lactate, and low chloride solutions are commonly used crystalloids in kidney transplantation and have differences in solute contents. Normal saline is a potassium-free crystalloid and has been considered an ideal fluid during kidney transplantation by anaesthesiologists since decades, but recent evidence discourages intraoperative use of normal saline in large volumes, as it is associated with increased risk of hyperchloremic metabolic acidosis due to supraphysiologic levels of chloride (154 mmol/L) compared to plasma (96-108 mmol/L)[3-7]. Hyperchloremic metabolic acidosis eventually causes hyperkalaemia by outward movement of K⁺ ions from the cells, afferent renal vasoconstriction mediated through tubulo-glomerular feedback mechanism related to delivery of high chloride to distal tubules, reduced glomerular filtration rate (GFR), urine production, acute kidney injury (AKI), DGF, requirement of renal replacement therapy[8-12]. Balanced low chloride crystalloids (e.g., Kabilyte, Plasma-Lyte A, and Physiomax) are isotonic to plasma and contain chloride in physiological concentration to plasma (98 mmol/L vs 96-108 mmol/L) and acetate as a buffer[13-17]. In kidney transplantation, numerous studies have concluded that balanced low chloride solutions reduce the risk of hyperchloremia, hyperkalaemia, metabolic acidosis, AKI, and DGF as compared to normal saline. However, balanced low chloride solutions have not shown any benefit in terms of vasopressor requirement, length of intensive care unit stay, and postoperative creatinine level[18-22].

Ringer lactate is a slightly hypotonic crystalloid containing lactate as a buffer and potassium (4 mmol/L) with an inherent theoretical risk of lactic acidosis and hyperkalaemia. But recent studies have shown favourable metabolic outcomes as compared to 0.9% saline with less metabolic acidosis and hyperkalaemia in kidney transplantation[23-25].

Recommendations: Based on recent evidence, balanced low chloride solutions are strongly recommended for kidney transplantation and must be considered as crystalloids of choice in perioperative periods (GRADE high-quality of evidence, strong recommendation).

Colloids

The use of intraoperative colloids (starches, gelatin, and albumin) in kidney transplantation has many controversies among perioperative physicians and area of debate. There is very scarce evidence in support of perioperative use of colloids.

Colloids containing starches have shown increased risk of kidney injury, need for renal replacement therapy, and coagulation abnormalities in critically ill patients[26,27]. The proposed mechanisms of kidney injury include osmotic nephrosis-like lesions, cytoplasmic vacuolisation, and tubular swelling by tissue uptake of starches[28,29]. Administration of hydroxyethyl starches (HES) in brain-dead donor management is associated with increased incidence of DGF in kidney transplant recipients due to effects on graft quality[30-32]. However, studies on recipients during kidney transplant did not reveal any significant negative impact on postoperative kidney function as compared to crystalloids and gelatin[33,34].

Intravenous administration of human albumin plays potential roles, including increasing plasma oncotic pressure, antioxidant effects, immunomodulation, protection from ischaemia-reperfusion injury, and decreasing the requirement of crystalloids and vasopressors[35,36]. However, studies have shown either no benefit or an increased risk of postoperative complications, pulmonary oedema, and mortality. Also, human albumin is associated with increased risk of disease transmission, immunogenicity, and high cost[37-40]. In kidney transplantation, 20% albumin does not have any advantage on early graft functions as compared to crystalloids[41,42]. Table 1 outlines different types of intravenous fluids used during kidney transplantation.

Table 1 Different types of perioperative fluids in kidney transplantation.

Type of fluid	Pros	Cons
Normal saline	Less expensive, easily available, potassium free	Potentially hypertonic, Risk of hyperchloremic metabolic acidosis, hyperkalemia, decreased GFR and urine output, AKI, and DGF large volume infusion should be avoided
Low chloride solutions (e.g., Kabilyte, Plasm-Lyte A)	Physiologically like plasma, no risk of hyperkalemia, metabolic acidosis, and DGF. Fluid of choice during kidney transplant	More expensive than other crystalloids
Ringer lactate	Balanced crystalloid, isotonic, has buffering capacity, is cost-effective, and safe	Theoretical risk of lactic acidosis and hyperkalemia
Hydroxyethyl starch	Volume expander, easily available	Risk of AKI, renal replacement therapy, and coagulopathy
Albumin	Increases plasma oncotic pressure, antioxidant properties, immunomodulation, protection from ischemia-reperfusion injury, less requirement of crystalloids, and vasopressors	Increased cost, risk of allergic reactions, and disease transmission. No benefit or increased risk of volume-related complications in recipients with cardio-pulmonary compromise. Routine use is not recommended

GFR: Glomerular filtration rate; AKI: Acute kidney injury; DGF: Delayed graft function.

Recommendations: Recent evidence suggests no benefit of routine use of albumin in kidney transplantation and use should be individualized based on serum albumin level (GRADE moderate-quality evidence, weak recommendation). Studies on recipients did not reveal any significant negative impact of HES on postoperative kidney function. Still, routine use of HES is not recommended for kidney transplantation and should be avoided in the perioperative period (GRADE moderate-quality of evidence, weak recommendation).

HEMODYNAMIC MONITORING FOR VOLUME RESPONSIVENESS

Haemodynamic monitoring is the cornerstone of fluid therapy in kidney transplantation to maintain optimal volume status and for excellent postoperative graft function. Suboptimal fluid management (hypovolemia or hypervolemia) has detrimental effects on postoperative graft and recipient outcomes. Excessive volume administration may cause tissue oedema, pulmonary oedema, the requirement of mechanical ventilation, dilutional coagulopathy, poor wound healing, postoperative ileus, and/or multi-organ dysfunction, while inadequate fluid volume results in hypotension, increased need for inotropes or vasopressors, metabolic acidosis, poor perfusion to the grafted kidney, AKI, and DGF. In the initial days of kidney transplantation, fluid administration was considered till no further response, but supranormal volume loading is not warranted in recent studies[43,44]. Over the decades, a lot has changed in perioperative fluid monitoring, and it is discussed here one by one.

Central venous pressure

Older studies have recommended monitoring of central venous pressure (CVP) to assess volume responsiveness during kidney transplantation to guide intraoperative fluids, but there were no uniformities among authors for upper and lower CVP targets, and it ranged between 1-2 kPa[44-46]. CVP is a static parameter and poorly predicts volume status. It has many limitations, including complications associated with central venous catheters (injury to major vessels, haematoma, haemothorax, infection, difficult cannulation in kidney recipients, etc.) and erroneous results (valvular regurgitation, pulmonary hypertension, right heart disease, etc.). Recent studies have not shown any advantages of CVP monitoring on post-transplant renal functions; hence, routine use of CVP for fluid management during kidney transplantation is highly discouraged due to the availability of newer and better haemodynamic tools to assess volume responsiveness[47-50].

Recommendations: Recent evidence suggested that there are no advantages of CVP monitoring on post-transplant renal functions; hence, routine use of CVP for fluid management during kidney transplantation is not recommended (GRADE moderate-quality evidence, strong recommendation).

Dynamic indices of fluid responsiveness

Pulse pressure variation (PPV) is a dynamic index of volume responsiveness derived from cardiorespiratory interaction. It is a minimally invasive and easily measured parameter of volume responsiveness. Recent evidence has shown that postoperative renal function is better in recipients who received fluid by PPV guidance, with a lower incidence of DGF in comparison to CVP. Also, the intraoperative need for crystalloids is significantly less[51-53]. Suggested targets for PPV were between 6% to 15%, but upper and lower limits varied among authors. Similarly, stroke volume variation (SVV) predicts better preload status in comparison to CVP during kidney transplantation and has a good correlation to change in cardiac index[54-56]. High risk kidney transplant recipients like patients with dilated cardiomyopathy (ejection fraction < 40%), coronary artery disease, severe pulmonary hypertension etc. have low safety of margin and prone to higher fluid related complications. Goyal et al[57] in their retrospective study in patients with dilated cardiomyopathy observed decreased incidence of immediate post-transplant complication when fluids were guided using SVV as compared to CVP[56,57]. These dynamic indices are easy to interpret and guide fluids, as fluid is stopped once the value is below the lower limit, and a fluid bolus (250-500 mL of crystalloid or colloid) is infused when the upper limit is crossed. A few limitations, including low tidal volume ventilation (< 8 mL/kg), spontaneous ventilation, and arrhythmias, must be considered during PPV or SVV-guided fluid therapy. Currently, lung protective ventilation (< 8 mL/kg) is no more of a limitation with the use of SVV or PPV if the tidal volume challenge strategy is considered during kidney transplantation[58].

Less studied dynamic indices during kidney transplantation are stroke volume and Transoesophageal Doppler (TED), and have also shown promising results. Perioperative goal-directed fluid therapy with stroke volume optimization protocol effectively reduces the postoperative complications and DGF[59]. TED-guided fluid therapy during kidney transplantation has also shown a reduced requirement of intraoperative fluids along with decreased fluid-related postoperative complications, including postoperative dyspnoea and tissue oedema, compared to CVP[60].

Recommendations: Recent evidence has shown that postoperative renal function is better in recipients who received fluid by PPV/SVV guidance, with a lower incidence of DGF in comparison to CVP (GRADE high-quality evidence, strong recommendation).

Stroke volume optimization and TED have effectively reduced the DGF and fluid related postoperative complications (GRADE low-quality evidence, weak recommendation).

Mean arterial pressure

Intraoperative hypotension (IOH) during kidney transplant is closely associated with poor postoperative graft outcomes, including AKI, DGF, increased incidence of rejection, and poor long-term graft survival. Monitoring systemic arterial pressure is vital, as perfusion of the renal graft largely depends on pressure due to loss of autoregulation by ischaemia-reperfusion injury and denervation of the explanted kidney. Post-ischaemic tissue oedema can further deteriorate the perfusion of the graft[61]. Hence, higher mean arterial pressure (MAP) targets are necessary for adequate perfusion of the graft, and these targets are widely affected by donor (age, live/brain dead/donation after cardiac death, hypertensive, number of vessels) and recipient characteristics (preoperative blood pressure, dialysis, comorbidities, etc.). Exposure to MAP below the threshold (magnitude as well as the duration) is directly related to the increased incidence of DGF. Intraoperative target MAP varies among institutions; however, the MAP ≥ 11 kPa after reperfusion is generally recommended. Perioperative use of vasopressors (preferred agents and dosing) to increase MAP to the target level is not well studied, and further work is needed to find optimal strategies. However, large doses of vasopressors should be avoided due to the inherent risk of intrarenal vasoconstriction and impaired graft perfusion[62,63].

MAP at reperfusion is advocated to be related to early recovery of graft function, but Oh et al[64], in a retrospective study, concluded that high baseline MAP is directly associated with early recovery of eGFR and urine output[64-66]. Also, the practice of arterial pressure monitoring, either invasive or non-invasive, depends on the anaesthesiologist's discretion and is a subject of controversy. Table 2 outlines the intraoperative haemodynamic monitoring to assess fluid responsiveness.

Table 2 Intraoperative hemodynamic monitoring to assess fluid responsiveness.

Hemodynamic indices	Advantages and targets	Limitations
Central venous pressure	Relatively cheap, measures right atrial pressure to predict volume status 1-2 kPa, upper and lower limits vary among institutions	Static parameter, complications associated with central venous cannulation (injury to major vessels, haematoma, and infection, etc.), erroneous results in PAH, valvular heart disease, and pulmonary disease, etc., poorly predict volume status. No benefit in post-transplant renal function recovery
Pulse pressure variation/stroke volume variation	Dynamic indices, minimally invasive, easy to interpret, and high accuracy. Decreased incidence of DGF in postoperative periods. 6%-15% varies among institutions	Confounding factors: Low tidal volume (< 8 mL/kg), spontaneous ventilation, high PEEP, and arrhythmias
Stroke volume	Dynamic index, minimally invasive, easy to interpret, and more accurate. Reduced incidence of DGF in postoperative periods% change in stroke volume (</> 10%)	Confounding factors: Low tidal volume (< 8 mL/kg), spontaneous ventilation, high PEEP, and arrhythmias
Transoesophageal Doppler	Dynamic index, non-invasive, continuous, real-time, and more accurate reduces requirements of intraoperative fluids along with fluid-related complications (tissue edema, dyspnoea)	Equipment cost, operator dependent, requires training, risk of oesophageal injury
Invasive blood pressure	Beat-to-beat monitoring of arterial pressure, post reperfusion MAP ≥ 11 kPa, varies among institutions	Difficult arterial line placement due to AV fistula or objected by treating physicians, risk of infection, hematoma, etc. No specified targets, depends on donor and recipient’s characteristics (age, co-morbidities, and type of donation)

PAH: Pulmonary artery hypertension; PEEP: Positive end expiratory pressure; DGF: Delayed graft function; AV: Arterio-venous; MAP: Mean arterial pressure.

Recommendations: Recent evidence have shown that higher MAP (≥ 11 kPa) is necessary for adequate perfusion of the graft (GRADE high-quality evidence, strong recommendation).

FUTURE DIRECTIVES

As discussed, intraoperative fluid therapy is a key to good postoperative transplant outcomes. Over the decades, continuous evolutions in haemodynamic monitoring and incorporation of newer fluid compositions have drastically changed the graft and recipient survival. Continuous beat-to-beat arterial pressure monitoring is pivotal to detecting hypotension and taking reactive measures, but placement of an arterial cannula is challenging due to the presence of an AV fistula and is sometimes objected to by nephrologists. Kakuta et al[67] reported successful use of non-invasive continuous arterial pressure monitoring using ClearSight in kidney transplant recipients. Further studies with large numbers of patients are required to support its use in routine practice. Recently, the role of artificial intelligence in perioperative haemodynamic management to prevent IOH and its consequences came into focus. Goyal et al[68], in their retrospective study in kidney transplant recipients, have observed the role of the hypotension prediction index (HPI) and concluded that HPI provides superior haemodynamic management in terms of reduced incidence of severity, magnitude, and duration of IOH. This study is limited by the inconclusive effect on postoperative outcomes; hence, prospective trials are needed to establish the role of HPI in the reduction of postoperative transplant complications.

Early recovery of graft function largely depends on close adherence to intraoperative blood pressure targets. IOH requires urgent measures to hasten its impact on graft functioning, but the ideal strategy (fluid or vasopressors) to combat hypotension is not well defined. Also, the use of vasopressors during transplant is debatable due to their effect on renal perfusion and necessitates further studies to choose the ideal agent and dosing regimen.

CONCLUSION

In conclusion, perioperative fluid management during kidney transplantation is an important concern for the transplant team. Meticulous fluid therapy based on recent evidence and with the inclusion of newer fluids and haemodynamic tools will be helpful to improve postoperative outcomes further.