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

Abstract

Background: Sodium 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.

Methods: Ancillary 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 Immediately after euthanasia, kidneys were withdrawn for histological study.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.

Results: The 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].

Conclusions: In 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.

Keywords: Disseminated intravascular coagulation; Fluid resuscitation; Glomerular filtration rate; Lactate infusion; Renal histology; Septic shock.

Fig. 1

Study design. During preparation period, all animals received 25 mL/kg 0.9% NaCl to prevent hypovolemia. Measurements were taken over a 5-h period: at baseline (T0) and at 60 (T60), 120 (T120), 210 (T210) and 300 (T300) minutes. All animals were administered 5 μg/kg/min Escherichia coli lipopolysaccharide (LPS). The endotoxin was infused over a 30-min period intravenously. The SL group received 40.5 g lactate (3.61 kcal/g). NC and SB groups received an equivalent energy supply: 39 g glucose (3.75 kcal/g) as 780 mL 5% glucose solution from T30 to T300. To ensure the same fluid intake, the SL group received 780 mL sterile water for injection. If mean arterial pressure (MAP) felt below 65 mmHg, 2.5 mL/kg infusion of NaCl 0.9% was given as rescue therapy every 15 min. At the end of the study period, all animals were sacrificed with T61 administration. Immediately after euthanasia, renal biopsies were performed

Fig. 2

Histological comparison of NC and SL groups samples. Light microscopy (Masson’s trichrome, magnification ×400) (a) and immunofluorescence study with polyclonal antifibrinogen antibody (b) of a kidney section. In NC group sample, glomeruli showed signs of oedema uniformly, with glomerular capillary thrombosis well estimated by immunofluorescence study

Fig. 3

Changes in leucocyte, platelet count, fibrinogen, haemoglobin, TAT and vWF in the three groups. Considering the differences between groups for platelet count and fibrinogen at baseline, values are expressed as a percentage of the first value. Open circles and dotted line: NC group (n = 5); squares and grey line: SB group (n = 5); closed circles and black line: SL group (n = 5). Results are expressed as median with interquartile ranges. *p < 0.05, NC versus SL. ^#p < 0.05, SB versus SL. ^&p < 0.05, NC versus SB

Fig. 4

Changes in interleukin-6 and TNFα in the three groups. Open circles and dotted line: NC group (n = 5); squares and grey line: SB group (n = 5); closed circles and black line: SL group (n = 5). Results are expressed as median with interquartile ranges. *p < 0.05, NC versus SL. ^#p < 0.05, SB versus SL. ^&p < 0.05, NC versus SB

Fig. 5

Creatinine clearance (CrCl) and diuresis in the three groups. Open circles and dotted line: NC group (n = 5); squares and grey line: SB group (n = 5); closed circles and black line: SL group (n = 5). Results are expressed as median with interquartile ranges. *p < 0.05, NC versus SL. ^#p < 0.05, SB versus SL. ^&p < 0.05, NC versus SB