Plasma-Lyte 148 vs. Hartmann's solution for cardiopulmonary bypass pump prime: a prospective double-blind randomized trial.

BACKGROUND: The mechanisms of acid-base changes during cardiopulmonary bypass (CPB) remain unclear. We tested the hypothesis that, when used as CPB pump prime solutions, Plasma-Lyte 148 (PL) and Hartmann's solution (HS) have differential mechanisms of action in their contribution to acid-base changes. METHODS: We performed a prospective, double-blind, randomized trial in adult patients undergoing elective cardiac surgery with CPB. Participants received a CPB prime solution of 2000 mL, with either PL or HS. The primary endpoint was the standard base excess (SBE) value measured at 60 minutes after full CPB flows (SBE60min). Secondary outcomes included changes in SBE, pH, chloride, sodium, lactate, gluconate, acetate, strong ion difference and strong ion gap at two (T2min), five (T5min), ten (T10min), thirty (T30min) and sixty (T60min) minutes on CPB. The primary outcome was measured using a two-tailed Welch's t-test. Repeated measures ANOVA was used to test for differences between time points. RESULTS: Twenty-five participants were randomized to PL and 25 to HS. Baseline characteristics, EURO and APACHE scores, biochemistry, hematology and volumes of cardioplegia were similar. Mean (SD) SBE at T60min was -1.3 (1.4) in the PL group and -0.1 (2.7) in the HS group; p=0.55. No significant differences in SBE between the groups was observed during the first 60 minutes (p=0.48). During CPB, there was hyperacetatemia and hypergluconatemia in the PL group and hyperlactatemia and hyperchloremia in the HS group. No significant difference between the groups in plasma bicarbonate levels and total weak acid levels were found. Complications and intensive care unit and hospital length of stays were similar. CONCLUSIONS: During CPB, PL and HS did not cause a significant metabolic acidosis. There was hyperacetatemia and hypergluconatemia with PL and hyperchloremia and hyperlactatemia with HS. These physiochemical effects appear clinically innocuous.

Effects of intraoperative and early postoperative normal saline or Plasma-Lyte 148® on hyperkalaemia in deceased donor renal transplantation: a double-blind randomized trial.

BACKGROUND: Administration of saline in renal transplantation is associated with hyperchloraemic metabolic acidosis, but the effect of normal saline (NS) on the risk of hyperkalaemia or postoperative graft function is uncertain. METHODS: We compared NS with Plasma-Lyte 148® (PL) given during surgery and for 48 h after surgery in patients undergoing deceased donor renal transplantation. The primary outcome was hyperkalaemia within 48 h after surgery. Secondary outcomes were need for hyperkalaemia treatment, change in acid-base status, and graft function. RESULTS: Twenty-five subjects were randomized to NS and 24 to PL. The incidence of hyperkalaemia in the first 48 h after surgery was higher in the NS group; 20 patients (80%) vs 12 patients (50%) in the PL group (risk difference: 0.3; 95% confidence interval: 0.05, 0.55; P=0.037). The mean (sd) peak serum potassium was NS 6.1 (0.8) compared with PL 5.4 (0.9) mmol litre-1 (P=0.009). Sixteen participants (64%) in the NS group required treatment for hyperkalaemia compared with five (21%) in the PL group (P=0.004). Participants receiving NS were more acidaemic [pH 7.32 (0.06) vs 7.39 (0.05), P=0.001] and had higher serum chloride concentrations (107 vs 101 mmol litre-1, P<0.001) at the end of surgery. No differences in the rate of delayed graft function were observed. Subjects receiving PL who did not require dialysis had a greater reduction in creatinine on day 2 (P=0.04). CONCLUSIONS: Compared with PL, participants receiving NS had a greater incidence of hyperkalaemia and hyperchloraemia and were more acidaemic. These biochemical differences were not associated with adverse clinical outcomes. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000023853.

Effect of 0.9% Saline or Plasma-Lyte 148 as Crystalloid Fluid Therapy in the Intensive Care Unit on Blood Product Use and Postoperative Bleeding After Cardiac Surgery.

OBJECTIVE: To evaluate the effect of Plasma-Lyte 148 (PL-148) compared with 0.9% saline (saline) on blood product use and postoperative bleeding in patients admitted to the intensive care unit (ICU) following cardiac surgery. DESIGN: A post hoc subgroup analysis conducted within a multicenter, double-blind, cluster-randomized, double-crossover study (study 1) and a prospective, single-center nested-cohort study (study 2). SETTING: Tertiary-care hospitals. PARTICIPANTS: Adults admitted to the ICU after cardiac surgery requiring crystalloid fluid therapy as part of the 0.9% saline vs. PL-148 for ICU fluid therapy (SPLIT) trial. INTERVENTIONS: Blinded saline or PL-148 for 4 alternating 7-week blocks. MEASUREMENTS AND MAIN RESULTS: 954 patients were included in study 1; 475 patients received PL-148, and 479 received saline. 128 of 475 patients (26.9%) in the PL-148 group received blood or a blood product compared with 94 of 479 patients (19.6%) in the saline group (OR [95% confidence interval], 1.51 [1.11-2.05]; p = 0.008). In study 2, 131 patients were allocated to PL-148 and 120 patients were allocated to saline. There were no differences between groups in chest drain output from the time of arrival in the ICU until 12 hours postoperatively (geometric mean, 566 mL for the PL-148 group v 547 mL in the saline group; p = 0.60). CONCLUSIONS: The findings did not support the hypothesis that using PL-148 for fluid therapy in ICU following cardiac surgery reduces transfusion requirements compared to saline. The significantly increased proportion of patients receiving blood or blood product with allocation to PL-148 compared to saline was unexpected and requires verification through further research.

Plasma-Lyte-148 Versus Normal Saline 0.9% in Diabetic Ketoacidosis Management: A Review.

Diabetic ketoacidosis (DKA) is a critical complication of diabetes mellitus characterized by hyperglycemia, ketonemia, circulatory collapse, hypokalemia, and metabolic acidosis. The therapeutic management of DKA includes vigilant fluid resuscitation to address dehydration and electrolyte imbalances and restore hemodynamic stability. The choice of fluid, either isotonic saline or a balanced electrolyte solution like Plasma-Lyte 148 (PL), is pivotal in the clinical outcomes of DKA patients. Recent studies have compared the effectiveness of these fluid solutions in DKA management, focusing on different clinical outcomes such as the resolution of metabolic acidosis, electrolyte imbalances, the incidence of acute kidney injury, and length of hospital stay. This review examines the literature comparing isotonic saline and balanced electrolyte solutions for fluid resuscitation in DKA, analyzing the associated clinical outcomes. Through synthesizing research findings, this review aims to elucidate the efficacy and potential advantages of utilizing PL as an alternative to traditional isotonic saline for fluid resuscitation in treating DKA. This would further facilitate evidence-based decision-making among healthcare professionals and contribute to optimizing DKA management strategies. Understanding the intricacies and implications of fluid resuscitation is crucial, given its profound impact on patient outcomes in DKA management.

Statistical analysis plan for Better Evidence for Selecting Transplant Fluids (BEST-Fluids): a randomised controlled trial of the effect of intravenous fluid therapy with balanced crystalloid versus saline on the incidence of delayed graft function in deceased donor kidney transplantation.

BACKGROUND: Delayed graft function, or the requirement for dialysis due to poor kidney function, is a frequent complication of deceased donor kidney transplantation that is associated with inferior outcomes. Intravenous fluids with a high chloride content, such as isotonic sodium chloride (0.9% saline), are widely used in transplantation but may increase the risk of poor kidney function. The primary objective of the BEST-Fluids trial is to compare the effect of a balanced low-chloride crystalloid, Plasma-Lyte 148 (Plasmalyte), versus 0.9% saline on the incidence of DGF in deceased donor kidney transplant recipients. This article describes the statistical analysis plan for the trial. METHODS AND DESIGN: BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-centre, double-blind, randomised controlled trial. Eight hundred patients (adults and children) in Australia and New Zealand with end-stage kidney disease admitted for a deceased donor kidney transplant were randomised to intravenous fluid therapy with Plasmalyte or 0.9% saline in a 1:1 ratio using minimization. The primary outcome is delayed graft function (dialysis within seven days post-transplant), which will be modelled using a log-binomial generalised linear mixed model with fixed effects for treatment group, minimization variables, and ischaemic time and a random intercept for study centre. Secondary outcomes including early kidney transplant function (a ranked composite of dialysis duration and the rate of graft function recovery), treatment for hyperkalaemia, and graft survival and will be analysed using a similar modelling approach appropriate for the type of outcome. DISCUSSION: BEST-Fluids will determine whether Plasmalyte reduces the incidence of DGF and has a beneficial effect on early kidney transplant outcomes relative to 0.9% saline and will inform clinical guidelines on intravenous fluids for deceased donor kidney transplantation. The statistical analysis plan describes the analyses to be undertaken and specified before completion of follow-up and locking the trial databases. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12617000358347 . Prospectively registered on 8 March 2017 ClinicalTrials.gov identifier NCT03829488 . Registered on 4 February 2019.

Study Protocol for Better Evidence for Selecting Transplant Fluids (BEST-Fluids): a pragmatic, registry-based, multi-center, double-blind, randomized controlled trial evaluating the effect of intravenous fluid therapy with Plasma-Lyte 148 versus 0.9% saline on delayed graft function in deceased donor kidney transplantation.

BACKGROUND: Delayed graft function, the requirement for dialysis due to poor kidney function post-transplant, is a frequent complication of deceased donor kidney transplantation and is associated with inferior outcomes and higher costs. Intravenous fluids given during and after transplantation may affect the risk of poor kidney function after transplant. The most commonly used fluid, isotonic sodium chloride (0.9% saline), contains a high chloride concentration, which may be associated with acute kidney injury, and could increase the risk of delayed graft function. Whether using a balanced, low-chloride fluid instead of 0.9% saline is safe and improves kidney function after deceased donor kidney transplantation is unknown. METHODS: BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-center, double-blind, randomized controlled trial. The primary objective is to compare the effect of intravenous Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride solution, with the effect of 0.9% saline on the incidence of delayed graft function in deceased donor kidney transplant recipients. From January 2018 onwards, 800 participants admitted for deceased donor kidney transplantation will be recruited over 3 years in Australia and New Zealand. Participants are randomized 1:1 to either intravenous Plasmalyte or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid is no longer required; whichever comes first. Follow up is for 1 year. The primary outcome is the incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant. Secondary outcomes include early kidney transplant function (composite of dialysis duration and rate of improvement in graft function when dialysis is not required), hyperkalemia, mortality, graft survival, graft function, quality of life, healthcare resource use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. DISCUSSION: If using Plasmalyte instead of 0.9% saline is effective at reducing delayed graft function and improves other clinical outcomes in deceased donor kidney transplantation, this simple, inexpensive change to using a balanced low-chloride intravenous fluid at the time of transplantation could be easily implemented in the vast majority of transplant settings worldwide. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12617000358347. Registered on 8 March 2017. ClinicalTrials.gov: NCT03829488. Registered on 4 February 2019.

Effects of chloride content of intravenous crystalloid solutions in critically ill adult patients: a meta-analysis with trial sequential analysis of randomized trials.

BACKGROUND: Intravenous crystalloid solutions are administered commonly for critically ill patients. We performed this meta-analysis of randomized trials with trial sequential analysis (TSA) to evaluate effects of chloride content of intravenous crystalloid solutions on clinical outcomes among critically ill adult patients. METHODS: Electronic databases were searched up to June 1, 2018, for randomized trials of use of balanced crystalloids versus 0.9% saline solutions in critically ill adult patients. The outcome variables included mortality, renal outcomes, serum content alterations and organ function. Subgroup analysis was conducted according to patient settings, types or volume of crystalloid fluid, or among sepsis versus non-sepsis, TBI versus non-TBI or subpopulations by the categories of baseline kidney function. Random errors were evaluated by trial sequential analysis. RESULTS: Eight studies with 19,301 patients were analyzed. A trend of in-hospital survival benefit with no statistical difference could be observed with balanced crystalloids compared with 0.9% saline (RR 0.92, 95% CI 0.85-1.0, p = 0.06). The use of balanced crystalloid solutions was associated with longer RRT-free days (SMD 0.09, 95% CI 0.06-0.12, p < 0.001), less risk of increase in serum concentrations of chloride (SMD - 1.23, 95% CI - 1.59 to - 0.87, p < 0.001) and sodium (SMD - 1.28, 95% CI - 1.65 to - 0.92, p < 0.001), less risk of decline in serum base deficit (SMD - 0.58, 95% CI - 0.98 to - 0.18, p = 0.004), longer ventilator-free days (SMD 0.08, 95% CI 0.05-0.11, p < 0.001) and vasopressor-free days (SMD 0.04, 95% CI 0.00-0.07, p = 0.02). Subgroup analysis showed that balanced crystalloid solutions were associated with a reduced in-hospital mortality rate among septic patients (RR 0.86, 95% CI 0.75-0.98; p = 0.02) and non-traumatic brain injury patients (RR 0.90, 95% CI 0.82-0.99, p = 0.02), while the TSA results indicated a larger sample size is still in need. CONCLUSIONS: Limited evidence supported statistical survival benefit with balanced crystalloid solutions, while it benefited in reducing organ support duration and fluctuations in serum electrolyte and base excess and was associated with decreased in-hospital mortality in subpopulation with sepsis and non-TBI. Large-scale rigorous randomized trials with better designs are needed to provide robust evidence for clinical management. Trial registration The protocol for this meta-analysis was registered on PROSPERO: International prospective register of systematic reviews (CRD42018102661), https://www.crd.york.ac.uk/prospero/#recordDetails.