Sodium Lactate Infusion Research Articles

The acute hemodynamic effects of sodium lactate infusion: increased cardiac output and decreased afterload in a randomized trial in pigs

Abstract Background Lactate is traditionally acknowledged as a by-product of anaerobic glucose metabolism. Recently, however, lactate has been proven to be a preferred oxidative substrate for stressed myocardium. Studies have shown that exogenous lactate infusion provides beneficial hemodynamic effects including increased cardiac output (CO). Nevertheless, the exact mechanism of action underlying the hemodynamic effects of lactate infusion has not been fully elucidated. Aim To identify the cardiovascular mechanisms behind the acute hemodynamic effects of exogenous sodium lactate infusion in an experimental model of healthy human-sized pigs. Methods We performed a randomized, assessor-blinded crossover study in eight female 60 kg pigs. In randomized order, the pigs received an infusion with 1 M sodium lactate for two hours and a control infusion with iso-osmolar and isovolumetric sodium chloride for two hours. The two infusion periods were separated by a one-hour washout period. We measured CO and pulmonary pressures hourly with a pulmonary artery catheter. A pressure-volume admittance catheter was inserted in the left ventricle to assess measures of cardiac efficiency, contractility, afterload, and preload. Hemodynamic measures as arterial blood pressure, heart rate, and mixed venous saturation (SvO2) were measured hourly as well. The study followed the principles of laboratory animal care (NIH Publication no. 85-23 revised 1985) and national and European legislations. Results Lactate levels increased by 9.9 mmol/L (95% CI 9.1 to 11.0) and CO increased by 2.0 L/min (95% CI 1.2 to 2.8) during lactate infusion as compared with the control period (figure 1). During lactate infusion, ejection fraction increased by 16.0 percentage points (95% CI 1.9 to 31.0) and heart rate by 21 bpm (95% CI 9 to 32) compared with control. Arterial elastance decreased by -1.1 mmHg/ml (95% CI -2.1 to -0.18). Lactate infusion also increased cardiac efficiency, SvO2, arterial pH, and arterial glucose concentration significantly. The infusion of lactate led to no changes in systemic arterial pressure nor pulmonary pressures including pulmonary artery wedge pressure. Also, no changes were found in left ventricle end systolic elastance (contractility). Futhermore, no change in left ventricle end-diastolic volume or -pressure (preload) were observed during lactate infusion compared with the control (figure 2). Conclusion High dose lactate infusion increased cardiac output by reducing afterload. No changes in left ventricular contractility or -preload were observed.Fig 1:Lactate concentration and COFig 2:Changes of endpoint parameters

Effects of Sodium Lactate Infusion in Two Girls with Glucose Transporter 1 Deficiency Syndrome.

Glucose is an important fuel for the brain. In glucose transporter 1 deficiency syndrome (GLUT1DS), the transport of glucose across the blood-brain barrier is limited. Most individuals with GLUT1DS present with developmental problems, epilepsy, and (paroxysmal) movement disorders, and respond favorably to the ketogenic diet. Similar to ketones, lactate is an alternative energy source for the brain. The aim of this study is to investigate whether intravenous infusion of sodium lactate in children with GLUT1DS has beneficial effects on their epilepsy. We performed a proof of principle study with two subjects with GLUT1DS who were not on a ketogenic diet and suffered from absence epilepsy. After overnight fasting, sodium lactate (600 mmol/L) was infused during 120 minutes, under video electroencephalographic (EEG) recording and monitoring of serum lactate, glucose, electrolytes, and pH. Furthermore, the EEGs were compared with pre-/postprandial EEGs of both subjects, obtained shortly before the study. Fasting EEGs of both subjects showed frequent bilateral, frontocentral polyspike and wave complexes. In one subject, no more epileptic discharges were seen postprandially and after the start of lactate infusion. The EEG of the other subject did not change, neither postprandially nor after lactate infusion. Serum pH, lactate, and sodium changed temporarily during the study. This study suggests that sodium lactate infusion is possible in individuals with GLUT1DS, and may have potential therapeutic effects. Cellular abnormalities, beyond neuronal energy failure, may contribute to the underlying disease mechanisms of GLUT1DS, explaining why not all individuals respond to the supplementation of alternative energy sources.

1660-P: Lactate Inhibits Lipolysis in Healthy Males—A Randomized Crossover Trial

Background: The intermediary metabolite lactate has signaling capacities through the lactate specific receptor GPR81/HCA1. Ex-vivo, lactate inhibits lipolysis through GPR81, but in-vivo human data are scarce. Lactate-mediated inhibition of lipolysis could improve insulin sensitivity. The aim of the study was to investigate if hyperlactatemia at physiological concentrations inhibits palmitate lipolysis and affects glucose metabolism in healthy males. Methods: In a randomized cross-over design, eight healthy men were studied after an overnight fast on two occasions 1) during a sodium-lactate infusion (LAC) and 2) during a NaCl infusion (CTL). Both study days comprised a 3-hour basal period followed by a 3-hour hyperinsulinemic euglycemic clamp (HEC) period. Lipolysis rate and endogenous glucose production (EGP) were evaluated using [9,10-3H]-palmitate and [3H]-glucose tracers. Average glucose infusion rate (mg/kg/min) during the last 30 min of the HEC (M-value) was used as a measure of insulin sensitivity. Data are mean±SD Results: Plasma lactate increased to 2.6 ±0.6 mmol/L during LAC vs. 0.8 ±0.3 mmol/L during CTL (p<0.001). At the end of the basal period, palmitate flux was 30% lower during LAC compared with CTL (84 ±32 μmol/min vs. 120 ±35 μmol/min, p=0.003). At the end of the HEC, palmitate flux was similarly suppressed during both interventions (p=0.7). Plasma FFA were lower during LAC compared with CTL (0.2 ±0.1 mmol/L vs. 0.3 ±0.1 mmol/L, p=0.03) at the end of the basal period and equally suppressed during both interventions at the end of the HEC (p=0.7). EGP was unaffected by LAC compared with CTL at the end of the basal period (p=1.0) and suppressed at the end of the HEC during both interventions (p=1.0). M-value was unaffected by LAC compared with CTL (p=0.8). Conclusion: Lactate inhibits palmitate lipolysis by 30 %, an effect which per se may improve insulin sensitivity. Hyperlactatemia did not affect EGP or insulin sensitivity, possibly because lactate intrinsically may induce insulin resistance. Disclosure M.G.B.Pedersen: None. N.Rittig: Research Support; ARLA. E.Søndergaard: None. L.C.Gormsen: None. N.Møller: Other Relationship; Aarhus University/Ketlace.

Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest

IntroductionPrognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA.MethodsAfter a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C.ResultsThirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls.ConclusionsIn this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.

The lactate receptor GPR81 is predominantly expressed in type II human skeletal muscle fibers: potential for lactate autocrine signaling.

Gi-coupled protein receptor 81 (GPR81) was first identified in adipocytes as a receptor for l-lactate, which upon binding inhibits cyclicAMP (cAMP)-protein kinase (PKA)-cAMP-response element binding (CREB) signaling. Moreover, incubation of myotubes with lactate augments expression of GPR81 and genes and proteins involved in lactate- and energy metabolism. However, characterization of GPR81 expression and investigation of related signaling in human skeletal muscle under conditions of elevated circulating lactate levels are lacking. Muscle biopsies were obtained from healthy men and women at rest, after leg extension exercise, with or without venous infusion of sodium lactate, and 90 and 180 min after exercise (8 men and 8 women). Analyses included protein and mRNA levels of GPR81, as well as GPR81-dependent signaling molecules. GPR81 expression was 2.5-fold higher in type II glycolytic compared with type I oxidative muscle fibers, and the expression was inversely related to the percentage of type I muscle fibers. Muscle from women expressed about 25% more GPR81 protein than from men. Global PKA activity increased by 5%-8% after exercise, with no differences between trials. CREBS133 phosphorylation was reduced by 30% after exercise and remained repressed during the entire trials, with no influence of the lactate infusion. The mRNA expression of vascular endothelial growth factor (VEGF) and peroxisome-proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) were increased by 2.5-6-fold during recovery, and that of lactate dehydrogenase reduced by 15% with no differences between trials for any gene at any time point. The high expression of GPR81-protein in type II fibers suggests that lactate functions as an autocrine signaling molecule in muscle; however, lactate does not appear to regulate CREB signaling during exercise.

Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes

IntroductionImpaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased...

Comparison of Sodium Lactate Infusion and Carbon Dioxide Inhalation Panic Provocation Tests: A Meta-analysis.

Sodium lactate (NaL) infusion and carbon dioxide (CO2) inhalation are proven to provoke acute panic attacks (PAs) in patients with panic disorder (PD). A systematic literature search and meta-analysis were performed to compare the effect sizes of these methods. Odds ratios were calculated for each of the original studies and were pooled using the random-effects model. Either NaL or CO2 provocations significantly increased the rates of PAs in individuals with PD compared to those in healthy controls. However, the effect size of NaL infusion (OR=25.13, 95% CI=15.48-40.80) was significantly greater than that of CO2 inhalation (OR=10.58, 95%CI=7.88-14.21). The evidence for the efficacy of the two panic provocation tests is very strong. Yet, the results support the superiority of NaL infusion over CO2 inhalation challenge as a panic provocation test. Thus, lactate seems a much stronger stimulus than CO2 for the brain suffocation detector.

Molar Sodium Lactate Attenuates the Severity of Postcardiac Arrest Syndrome: A Preclinical Study.

To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure. Randomized blinded study (animal model). University animal research facility. Twenty-four adult male "New Zealand White" rabbits. Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period. Pupillary reactivity (primary outcome), levels of S100β protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100β protein levels (189 ± 42 vs 412 ± 63 pg/mL, p < 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p > 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ± 2 vs 29 ± 3 mm Hg; p < 0.05], higher cardiac output [108 ± 4 vs 58 ± 9 mL/min; p < 0.05], higher left ventricle surface shortening fraction [38% ± 3% vs 19% ± 3%; p < 0.05], and lower left ventricular end-diastolic pressure [3 ± 1 vs 8 ± 2 mm Hg; p < 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ± 3 mL/kg; p < 0.01) due to lower diuresis. Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest.

Effect on cerebral metabolites of hypertonic sodium lactate infusion after resuscitation in an experimental model of cardiac arrest

Background: Among cardiac arrest (CA) survivors, hypoxic brain injury is responsible for poor outcome.1,2 In the context of traumatic brain injury, Hypertonic sodium lactate (HSL) could be beneficial as lactate is used as an alternative energetic substrate,3–6 but in the setting of global cerebral ischemia following CA, no studies have investigated the impact of HSL on cerebral metabolites.

Pharmacological modulation of the lactate fuelling of neuron by astrocytes after an experimental cardiac arrest in rabbits

Rapid induction of therapeutic hypothermia is known to prevent neurological sequelae after cardiac arrest. Its mechanism of action could involve a preservation of astrocytes function, which are known to fuel neuron with lactate in stress conditions. We investigated whether a specific stimulation of astrocyte metabolism by pyruvate administration could induce lactate release and exacerbate the neuronal death as compared to direct stimulation of neurons by lactate administration. Eighteen rabbits were anesthetized and instrumented for cerebral microdialysis and evaluation of cerebral consumption of O 2 , lactate and glucose. After 10 min of ventricular fibrillation and resuscitation, animals received an intravenous infusion of saline (control group, n = 6), sodium lactate (5 mg/kg/min, Lac group, n = 6) or pyruvate (5 mg/kg/min, Py group, n = 6). Neuronal death was quantified by fluorojade C staining after 240 min of follow-up. After cardiac arrest, cerebral concentration of lactates and glucose increased in all groups, with a concomitant decreased oxygen consumption and increased lactate and glucose consumption. In the Py group, pyruvate was reduced in lactate as suggested by a significant increase in cerebral lactate concentration in Py group vs others (8.0 ± 0.8, 3.5 ± 0.5 vs 4.4 ± 1.2 μmol/L in Py, Lac and Control groups at 30 min post-cardiac arrest, respectively). This led to a greater neuronal death (25 ± 6, 34 ± 6 vs 50 ± 6 dead neurons per field, in Control, Lac and Py groups, respectively), suggesting that astrocyte fuelling with pyruvate is worse than direct neuronal fuelling with lactate. Neuron fuelling with lactate after cardiac arrest is deleterious for neurons. Specific stimulation of astrocytes by pyruvate administration enhances lactate production and worsen the neurological death.

Elevated plasma lactate levels via exogenous lactate infusion do not alter resistance exercise-induced signaling or protein synthesis in human skeletal muscle.

Lactate has been implicated as a potential signaling molecule. In myotubes, lactate incubation increases mechanistic target of rapamycin complex 1 (mTORC1)- and ERK-signaling and induces hypertrophy, indicating that lactate could be a mediator of muscle adaptations to resistance exercise. However, the potential signaling properties of lactate, at rest or with exercise, have not been explored in human tissue. In a crossover design study, 8 men and 8 women performed one-legged resistance exercise while receiving venous infusion of saline or sodium lactate. Blood was sampled repeatedly, and muscle biopsies were collected at rest and at 0, 90, and 180 min and 24 h after exercise. The primary outcomes examined were intracellular signaling, fractional protein synthesis rate (FSR), and blood/muscle levels of lactate and pH. Postexercise blood lactate concentrations were 130% higher in the Lactate trial (3.0 vs. 7.0 mmol/L, P < 0.001), whereas muscle levels were only marginally higher (27 vs. 32 mmol/kg dry wt, P = 0.003) compared with the Saline trial. Postexercise blood pH was higher in the Lactate trial (7.34 vs. 7.44, P < 0.001), with no differences in intramuscular pH. Exercise increased the phosphorylation of mTORS2448 (∼40%), S6K1T389 (∼3-fold), and p44T202/T204 (∼80%) during recovery, without any differences between trials. FSR over the 24-h recovery period did not differ between the Saline (0.067%/h) and Lactate (0.062%/h) trials. This study does not support the hypothesis that blood lactate levels can modulate anabolic signaling in contracted human muscle. Further in vivo research investigating the impact of exercised versus rested muscle and the role of intramuscular lactate is needed to elucidate its potential signaling properties.

Effects Of Lactate Infusion On Resistance Exericse Induced MTORC1-signaling And Protein Synthesis In Human Muscle

Lactate has recently been highlighted as a potential signaling molecule. In myotubes, lactate incubation increase mTORC1-signaling, reduce myostatin expression and induce myotube growth. This indicates that lactate could be a potential mediator of muscle adaptations to resistance exercise. PURPOSE: Here we wanted to study the acute molecular response in human skeletal muscle to resistance exercise performed with our without a venous infusion of lactate. The primary outcomes of the study was intracellular signaling, rate of protein synthesis (FSR) and blood/muscle levels of lactate and pH. METHODS: 16 healthy females and males participated in the study which consisted of two resistance exercise sessions performed under venous infusion of sodium lactate or saline, in a randomized, blinded and counterbalanced fashion. In the overnight fasted state infusion was employed during ~60 min of rest and unilateral knee-extension exercise. Blood was sampled repeatedly during trials and muscle biopsies were collected at rest and at 0, 90, 180 min and 24 h after exercise. Oral D2O ingestion was used to determine FSR during 24 h of recovery. RESULTS: With saline, blood lactate levels reached 3.0 mmol/l post exercise, while lactate infusion resulted in 130% greater lactate levels post exercise that also remained higher than at rest and saline up to 90 min of recovery. Post exercise muscle levels of lactate were 20% higher with lactate compared to saline infusion (32 vs 27 mmol/kg d.w). Lactate infusion had an alkalizing effect in blood with pH being 7.44 after exercise with lactate and 7.34 with saline. This effect was not noted in muscle were pH was reduced by 0.06 units after exercise in both trials. Exercise increased the phosphorylation of mTORS2448 (~40%), S6K1T389 (~3-fold) and S6S240/244 (~9-fold) during recovery, without any differences between trials. Effects of exercise without any influence of lactate infusion was also noted for eEF2T56, AMPKT172, PRAS40T246 and p44T202/T204. FSR over 24h of recovery did not differ between saline (0.067 %/h) and lactate infusion (0.060 %/h). CONCLUSIONS: In this model blood lactate levels did not modulate resistance exercise induced mTORC1-signaling or FSR. As only small differences were noted for muscle levels of lactate, its potential role as signaling molecule should not be discarded.

Effect of half-molar sodium lactate infusion on biochemical parameters in critically ill patients

ObjectiveTo evaluate the impact of the infusion of sodium lactate 500ml upon different biochemical variables and intracranial pressure in patients admitted to the intensive care unit. DesignA prospective experimental single cohort study was carried out. ScopePolyvalent intensive care unit of a university hospital. PatientsCritical patients with shock and intracranial hypertension. ProcedureA 500ml sodium lactate bolus was infused in 15min. Plasma levels of sodium, potassium, magnesium, calcium, chloride, lactate, bicarbonate, PaCO2, pH, phosphate and albumin were recorded at 3 timepoints: T0 pre-infusion; T1 at 30min, and T2 at 60min post-infusion. Mean arterial pressure and intracranial pressure were measured at T0 and T2. ResultsForty-one patients received sodium lactate: 19 as an osmotically active agent and 22 as a volume expander. Metabolic alkalosis was observed: T0 vs. T1 (p=0.007); T1 vs. T2 (p=0.003). Sodium increased at the 3 timepoints (T0 vs. T1, p<0.0001; T1 vs. T2, p=0.0001). In addition, sodium lactate decreased intracranial pressure (T0: 24.83±5.4 vs. T2: 15.06±5.8; p<0.001). Likewise, plasma lactate showed a biphasic effect, with a rapid decrease at T2 (p<0.0001), including in those with previous hyperlactatemia (p=0.002). ConclusionsThe infusion of sodium lactate is associated to metabolic alkalosis, hypernatremia, reduced chloremia, and a biphasic change in plasma lactate levels. Moreover, a decrease in intracranial pressure was observed in patients with acute brain injury.

PL - 035 Effects of lactate infusion on the molecular response to resistance exercise in men and women

PL - 035 Effects of lactate infusion on the molecular response to resistance exercise in men and women

Effect of lactate administration on brain lactate levels during hypoglycemia in patients with type 1 diabetes

Administration of lactate during hypoglycemia suppresses symptoms and counterregulatory responses, as seen in patients with type 1 diabetes and impaired awareness of hypoglycemia (IAH), presumably because lactate can substitute for glucose as a brain fuel. Here, we examined whether lactate administration, in a dose sufficient to impair awareness of hypoglycemia, affects brain lactate levels in patients with normal awareness of hypoglycemia (NAH). Patients with NAH (n = 6) underwent two euglycemic-hypoglycemic clamps (2.8 mmol/L), once with sodium lactate infusion (NAH w|lac) and once with saline infusion (NAH w|placebo). Results were compared to those obtained during lactate administration in patients with IAH (n = 7) (IAH w|lac). Brain lactate levels were determined continuously with J-difference editing 1H-MRS. During lactate infusion, symptom and adrenaline responses to hypoglycemia were considerably suppressed in NAH. Infusion of lactate increased brain lactate levels modestly, but comparably, in both groups (mean increase in NAH w|lac: 0.12 ± 0.05 µmol/g and in IAH w|lac: 0.06 ± 0.04 µmol/g). The modest increase in brain lactate may suggest that the excess of lactate is immediately metabolized by the brain, which in turn may explain the suppressive effects of lactate on awareness of hypoglycemia observed in patients with NAH.

Sodium lactate improves renal microvascular thrombosis compared to sodium bicarbonate and 0.9% NaCl in a porcine model of endotoxic shock: an experimental randomized open label controlled study

BackgroundSodium lactate seemed to improve fluid balance and avoid fluid overload. The objective of this study was to determine if these beneficial effects can be at least partly explained by an improvement in disseminated intravascular coagulation (DIC)-associated renal microvascular thrombosis.MethodsAncillary work of an interventional randomized open label controlled experimental study. Fifteen female “Large White” pigs (2 months old) were challenged with intravenous infusion of E. 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); a hypertonic control group, with the same amount of osmoles and sodium than SL group, received sodium bicarbonate 8.4% (SB group). Glomerular filtration rate (GFR) markers, coagulation and inflammation parameters were measured over a 5-h period. Immediately after euthanasia, kidneys were withdrawn for histological study. Statistical analysis was performed with nonparametric tests and the Dunn correction for multiple comparisons. A p < 0.05 was considered significant.ResultsThe direct immunofluorescence study revealed that the percentage of capillary sections thrombosed in glomerulus were significantly lesser in SL group [5 (0–28) %] compared to NC [64 (43–79) %, p = 0.01] and SB [64 (43–79), p = 0.03] groups. Alterations in platelet count and fibrinogen level occurred earlier and were significantly more pronounced in both control groups compared to SL group (p < 0.05 at 210 and 300 min). The increase in thrombin–antithrombin complexes was significantly higher in NC [754 (367–945) μg/mL; p = 0.03] and SB [463 (249–592) μg/mL; p = 0.03] groups than in SL group [176 (37–265) μg/mL]. At the end of the experiment, creatinine clearance was significantly higher in SL group [55.46 (30.07–67.85) mL/min] compared to NC group [1.52 (0.17–27.67) mL/min, p = 0.03].ConclusionsIn this study, we report that sodium lactate improves DIC-associated renal microvascular thrombosis and preserves GFR. These findings could at least partly explain the better fluid balance observed with sodium lactate infusion.

Balanced Crystalloid Solution Versus Normal Saline on Biochemical Outcomes in Acute Medical and Surgical Patients

Background: Concerns have been raised regarding the use of various intravenous fluids resulting in hyperchloremic acidosis and associated acute kidney injury; however, this has primarily been in the context of resuscitation and critical care, and not ward-based medical or surgical patients who receive lower volumes of infusion fluid. We aimed to determine whether normal saline use is more likely to produce hyperchloremic metabolic acidosis than compound sodium lactate, in acute general medical and surgical patients. Methods: This was a retrospective study, conducted in 2015 in a metropolitan hospital in Melbourne, Australia, and of 1,158 sequentially admitted general medical and surgical patients receiving either intravenous normal saline or compound sodium lactate. Demographics, admission diagnosis, comorbidities, and medications were compared. Serum biochemistry results 24 - 48 h post-infusion were analyzed. Primary outcome was incidence of serum hyperchloremia post-infusion. In addition, mean shift in serum chloride concentration as well as mean normalized chloride concentration (mmol/L per day per L of infusion) were calculated. Acute kidney injuries and deaths during admission were also reported. Results: A total of 221 patients (169 medical and 52 surgical patients) were included for analysis (mean age 71.6 years, 72% female), with 174 normal saline and 61 compound sodium lactate infusions. No difference in hyperchloremia rate was found (normal saline vs. compound sodium lactate; n = 8 (4.6%) vs. n = 2 (3.3%), P = 1.0). Post-infusion serum chloride concentration was also not significantly different (99.0 ± 5.1 mmol/L vs. 100.0 ± 3.4 mmol/L, P = 0.1700) between infusion groups. Normal saline infusions resulted in an increase of mean normalized chloride concentration compared to compound sodium lactate (1.2 ± 4.0 mmol/L per day/L vs. -0.3 ± 1.5, P = 0.0121). Conclusions: We conclude that 2 - 3 L normal saline infusions in this population do not appear to be associated with hyperchloremic acidosis more frequently than compound sodium lactate infusions, allaying concerns of normal saline use in wards. World J Nephrol Urol. 2018;7(2):39-44 doi: https://doi.org/10.14740/wjnu339w

Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation.

Orexin neurons originating in the perifornical and lateral hypothalamic area are highly reactive to anxiogenic stimuli and have strong projections to anxiety and panic-associated circuitry. Recent studies support a role for the orexin system and in particular the orexin 1 receptor (OX1R) in coordinating an integrative stress response. However, no selective OX1R antagonist has been systematically tested in two preclinical models of using panicogenic stimuli that induce panic attack in the majority of people with panic disorder, namely an acute hypercapnia-panic provocation model and a model involving chronic inhibition of GABA synthesis in the perifornical hypothalamic area followed by intravenous sodium lactate infusion. Here we report on a novel brain penetrant, selective and high affinity OX1R antagonist JNJ-54717793 (1S,2R,4R)-7-([(3-fluoro-2-pyrimidin-2-ylphenyl)carbonyl]-N-[5-(trifluoromethyl)pyrazin-2-yl]-7-azabicyclo[2.2.1]heptan-2-amine). JNJ-54717793 is a high affinity/potent OX1R antagonist and has an excellent selectivity profile including 50 fold versus the OX2R. Ex vivo receptor binding studies demonstrated that after oral administration JNJ-54717793 crossed the blood brain barrier and occupied OX1Rs in the rat brain. While JNJ-54717793 had minimal effect on spontaneous sleep in rats and in wild-type mice, its administration in OX2R knockout mice, selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. JNJ-54717793 attenuated CO2 and sodium lactate induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. These data confirm that selective OX1R antagonism may represent a novel approach of treating anxiety disorders, with no apparent sedative effects.

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

BackgroundSodium 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.MethodsThis 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 < 0.05.ResultsFluid and chloride balance, hemodynamics, oxygenation markers, and microcirculatory parameters were measured over a 5-h period. Cumulative fluid balance was significantly lower in the SL group (550 (415–800) mL; median (interquartile range)) compared to the NC group (1100 (920–1640) mL, p = 0.01) and the SB group (935 (790–1220) mL, p = 0.03). Hemodynamics, cardiac efficiency, and microcirculation were significantly enhanced in the SL group, resulting in a significant improvement in oxygen delivery (SL group 417 (305–565) mL/min/m2 at 300 min versus the NC (207 (119–272) mL/min/m2, p = 0.01) and the SB (278, (211–315) mL/min/m2, p = 0.03) groups). Oxygenation markers (arterial oxygen partial pressure (PaO2)/inspired oxygen fraction (FiO2), mixed venous oxygen saturation (SvO2), and venoarterial carbon dioxide tension difference (Pv-aCO2) were enhanced with sodium lactate infusion. Chloride balance was equivalent in both hypertonic groups and significantly reduced compared to the NC group.ConclusionSodium lactate infusion improves fluid balance and hemodynamics. The advantage of lactate does not seem to be explained by its energy load or by the induced negative chloride balance with subsequent water movements.

Exogenous lactate infusion improved neurocognitive function of patients with mild traumatic brain injury.

Background:Many studies showed a better recovery of cognitive function after administration of exogenous lactate during moderate-severe traumatic brain injury. However, the study evaluating lactate effect on mild traumatic brain injury is still limited.Aims:To evaluate the effect of exogenous lactate on cognitive function in mild traumatic brain injury patients.Settings and Design:Prospective, single blind, randomized controlled study on 60 mild traumatic brain injury patients who were undergoing neurosurgery.Materials and Methods:Subjects were randomly assigned into hyperosmolar sodium lactate (HSL) group or hyperosmolar sodium chloride (HSS) group. Patients in each group received either intravenous infusion of HSL or NaCl 3% at 1.5 ml/KgBW within 15 min before neurosurgery. During the surgery, patients in both groups received maintenance infusion of NaCl 0.9% at 1.5 ml/KgBW/hour.Statistical Analysis:Cognitive function, as assessed by Mini-Mental State Examination (MMSE) score at 24 h, 30 and 90 days post-surgery, was analyzed by Anova repeated measures test.Results:The MMSE score improvement was significantly better in HSL group than HSS group (P < 0.001). In HSL group the MMSE score improved from 16.00 (13.75-18.00) at baseline to 21.00 (18.75-22.00); 25.00 (23.75-26.00); 28.00 (27.00-29.00) at 24 h, 30, 90 days post-surgery, respectively. In contrast, in HSS group the MMSE score almost unchanged at 24 h and only slightly increased at 30 and 90 days post-surgery.Conclusions:Hyperosmolar sodium lactate infusion during mild traumatic brain injury improved cognitive function better than sodium chloride 3%.