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Comparison of fluid balance and hemodynamic and metabolic effects of sodium lactate versus sodium bicarbonate versus 0.9% NaCl in porcine endotoxic shock: a randomized, open-label, controlled study.

ABSTRACT: Sodium lactate has been shown to improve hemodynamics and avoid fluid overload. The objective of this study was to confirm a beneficial effect on fluid balance with sodium lactate infusion and to specify whether the advantage of lactate is related to a negative chloride balance, its particular metabolism, or simply its energy load.This was an interventional, randomized, open-label, controlled experimental study. Fifteen female "large white" pigs (2 months old) were challenged with intravenous infusion of Escherichia coli endotoxin. Three groups of five animals were randomly assigned to receive different fluids: a treatment group received sodium lactate 11.2% (SL group); an isotonic control group received 0.9% NaCl (NC group); and a hypertonic control group, with the same amount of osmoles and sodium as the SL group, received sodium bicarbonate 8.4% (SB group). In order to provide the same energy load in the three groups, control groups were perfused with an equivalent energy supply. Statistical analysis was performed with non-parametric tests and the Dunn correction for multiple comparisons at p?

SUBMITTER: Duburcq T

PROVIDER: S-EPMC5438514 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Comparison of fluid balance and hemodynamic and metabolic effects of sodium lactate versus sodium bicarbonate versus 0.9% NaCl in porcine endotoxic shock: a randomized, open-label, controlled study.

Duburcq Thibault T Durand Arthur A Dessein Anne-Frédérique AF Vamecq Joseph J Vienne Jean-Claude JC Dobbelaere Dries D Mention Karine K Douillard Claire C Maboudou Patrice P Gmyr Valery V Pattou François F Jourdain Mercé M Tamion Fabienne F Poissy Julien J Mathieu Daniel D Favory Raphaël R

Critical care (London, England) 20170519 1

<h4>Background</h4>Sodium lactate has been shown to improve hemodynamics and avoid fluid overload. The objective of this study was to confirm a beneficial effect on fluid balance with sodium lactate infusion and to specify whether the advantage of lactate is related to a negative chloride balance, its particular metabolism, or simply its energy load.<h4>Methods</h4>This was an interventional, randomized, open-label, controlled experimental study. Fifteen female "large white" pigs (2 months old) ...[more]

PMID: 28526086

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Project description:BackgroundIntravenous fluid therapy represents the most common intervention critically ill patients are exposed to. Hyperchloremia and metabolic acidosis associated with 0.9% sodium chloride have been observed to lead to worse outcomes, including mortality. Balanced solutions, such as Plasma-Lyte 148 and Compound Sodium Lactate, represent potential alternatives but the evidence on optimal fluid choices in critically ill children remains scarce. This study aims to demonstrate whether balanced solutions, when used as intravenous fluid therapy, are able to reduce the incidence of a rise in serum chloride level compared to 0.9% sodium chloride in critically ill children.MethodsThis is a single-centre, open-label randomized controlled trial with parallel 1:1:1 assignment into three groups: 0.9% sodium chloride, Plasma-Lyte 148, and Compound Sodium Lactate solutions for intravenous fluid therapy. The intervention includes both maintenance and bolus fluid therapy. Children aged < 16 years admitted to intensive care and receiving intravenous fluid therapy during the first 4 h of admission are eligible. The primary outcome measure is a ≥ 5mmol/L increase in serum chloride level within 48 h post-randomization. The enrolment target is 480 patients. The main analyses will be intention-to-treat.DiscussionThis study tests three types of intravenous fluid therapy in order to compare the risk of hyperchloremia associated with normal saline versus balanced solutions. This pragmatic study is thereby assessing the most common intervention in paediatric critical care. This is a single-centre open-label study with no blinding at the level of delivery of the intervention. Certain paediatric intensive care unit (PICU) patient groups such as those admitted with a cardiac condition or following a traumatic brain injury are excluded from this study.Trial registrationThe study has received ethical approval (HREC/19/QCHQ/53177: 06/06/2019). It is registered in the Australian New Zealand Clinical Trials Registry ( ACTRN12619001244190 ) from 9th September 2019. Recruitment commenced on 12th November 2019. The primary results manuscript will be published in a peer-reviewed journal.

Project description:Background: The role of sodium bicarbonate therapy (SBT) remains controversial. This study aimed to investigate whether hemodynamic status before SBT contributed to the heterogeneous outcomes associated with SBT in acute critically ill patients. Methods: We obtained data from patients with metabolic acidosis from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score matching (PSM) was applied to match the SBT group with the control group. Logistic regression and Cox regression were used to analyze a composite of newly "developed or exacerbated organ dysfunction" (d/eOD) within 7 days of ICU admission and 28-day mortality associated with SBT for metabolic acidosis. Results: A total of 1,765 patients with metabolic acidosis were enrolled, and 332 pairs obtained by PSM were applied to the final analyses in the study. An increased incidence of newly d/eOD was observed in the SB group compared with the control group (54.8 vs. 44.6%, p < 0.01). Multivariable logistic regression indicated that the adjusted OR of SBT for this composite outcome was no longer significant [OR (95% CI): 1.39 (0.9, 1.85); p = 0.164]. This effect of SBT did not change with the quintiles stratified by pH. Interestingly, SBT was associated with an increased risk of the composite of newly d/eOD in the subgroup of patients with worsening hemodynamics before SBT [adjusted OR (95% CI): 3.6 (1.84, 7.22), p < 0.001]. Moreover, the risk potential for this composite of outcomes was significantly increased in patients characterized by both worsening [adjusted OR (95% CI): 2.91 (1.54, 5.47), p < 0.001] and unchanged hemodynamics [adjusted OR (95% CI): 1.94 (1.01, 3.72), p = 0.046] compared to patients with improved hemodynamics before SBT. Our study failed to demonstrate an association between SBT and 28-day mortality in acute critically ill patients with metabolic acidosis. Conclusions: Our findings did not demonstrate an association between SBT and outcomes in critically ill patients with metabolic acidosis. However, patients with either worsening or unchanged hemodynamic status in initial resuscitation had a significantly higher risk potential of newly d/eOD subsequent to SBT.

Project description:BACKGROUND:Infusion therapy is one of the most frequently prescribed medications in hospitalized patients. Currently used crystalloid solutes have a variable composition and may therefore influence acid-base status, intracellular and extracellular water content and plasma electrolyte compositions and have a major impact on organ function and outcome. The aim of our study was to investigate whether use of acetate-based balanced crystalloids leads to better hemodynamic stability compared to 0.9% saline. METHODS:We performed a sub-analysis of a prospective, randomized, controlled trial comparing effects of 0.9% saline or an acetate-buffered, balanced crystalloid during the perioperative period in patients with end-stage renal disease undergoing cadaveric renal transplantation. Need for catecholamine therapy and blood pressure were the primary measures. RESULTS:A total of 150 patients were included in the study of which 76 were randomized to 0.9% saline while 74 received an acetate-buffered balanced crystalloid. Noradrenaline for cardiocirculatory support during surgery was significantly more often administered in the normal saline group, given earlier and with a higher cumulative dose compared to patients receiving an acetate-buffered balanced crystalloid (30% versus 15%, p = 0.027; 68 ± 45 µg/kg versus 75 ± 60 µg/kg, p = 0.0055 and 0.000492?µg/kg body weight/min, ±0.002311 versus 0.000107?µg/kg/min, ±0.00039, p = 0.04, respectively). Mean minimum arterial blood pressure was significantly lower in patients randomized to 0.9% saline than in patients receiving the balanced infusion solution (57.2 [SD 8.7] versus 60.3 [SD 10.2] mm?Hg, p = 0.024). CONCLUSION:The use of an acetate-buffered, balanced infusion solution results in reduced need for use of catecholamines and cumulative catecholamine dose for hemodynamic support and in less occurrence of arterial hypotension in the perioperative period. Further research in the field is strongly encouraged.

Project description:RationaleSalt sensitivity of blood pressure affects >30% of the hypertensive and >15% of the normotensive population. Variants of the electrogenic sodium bicarbonate cotransporter NBCe2 gene, SLC4A5, are associated with increased blood pressure in several ethnic groups. SLC4A5 variants are also highly associated with salt sensitivity, independent of hypertension. However, little is known about how NBCe2 contributes to salt sensitivity, although NBCe2 regulates renal tubular sodium bicarbonate transport. We hypothesized that SLC4A5 rs10177833 and rs7571842 increase NBCe2 expression and human renal proximal tubule cell (hRPTC) sodium transport and may be a cause of salt sensitivity of blood pressure.ObjectiveTo characterize the hRPTC ion transport of wild-type (WT) and homozygous variants (HV) of SLC4A5.Methods and resultsThe expressions of NBCe2 mRNA and protein were not different between hRPTCs carrying WT or HV SLC4A5 before or after dopaminergic or angiotensin (II and III) stimulation. However, luminal to basolateral sodium transport, NHE3 protein, and Cl-/HCO3- exchanger activity in hRPTCs were higher in HV than WT SLC4A5. Increasing intracellular sodium enhanced the apical location of NBCe2 in HV hRPTCs (4.24±0.35% to 11.06±1.72% (P<0.05, N = 3, 2-way ANOVA, Holm-Sidak test)) as determined by Total Internal Reflection Fluorescence Microscopy (TIRFM). In hRPTCs isolated from kidney tissue, increasing intracellular sodium enhanced bicarbonate-dependent pH recovery rate and increased NBCe2 mRNA and protein expressions to a greater extent in HV than WT SLC4A5 (+38.00±6.23% vs HV normal salt (P<0.01, N = 4, 2-way ANOVA, Holm-Sidak test)). In hRPTCs isolated from freshly voided urine, bicarbonate-dependent pH recovery was also faster in those from salt-sensitive and carriers of HV SLC4A5 than from salt-resistant and carriers of WT SLC4A5. The faster NBCe2-specific bicarbonate-dependent pH recovery rate in HV SCL4A5 was normalized by SLC4A5- but not SLC4A4-shRNA. The binding of purified hepatocyte nuclear factor type 4A (HNF4A) to DNA was increased in hRPTCs carrying HV SLC4A5 rs7571842 but not rs10177833. The faster NBCe2-specific bicarbonate-dependent pH recovery rate in HV SCL4A5 was abolished by HNF4A antagonists.ConclusionNBCe2 activity is stimulated by an increase in intracellular sodium and is hyper-responsive in hRPTCs carrying HV SLC4A5 rs7571842 through an aberrant HNF4A-mediated mechanism.

Dataset Information

Comparison of fluid balance and hemodynamic and metabolic effects of sodium lactate versus sodium bicarbonate versus 0.9% NaCl in porcine endotoxic shock: a randomized, open-label, controlled study.

Publications

Comparison of fluid balance and hemodynamic and metabolic effects of sodium lactate versus sodium bicarbonate versus 0.9% NaCl in porcine endotoxic shock: a randomized, open-label, controlled study.

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