Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside

Abstract

Lactic acidosis is a very common biological issue for shock patients. Experimental data clearly demonstrate that metabolic acidosis, including lactic acidosis, participates in the reduction of cardiac contractility and in the vascular hyporesponsiveness to vasopressors through various mechanisms. However, the contributions of each mechanism responsible for these deleterious effects have not been fully determined and their respective consequences on organ failure are still poorly defined, particularly in humans. Despite some convincing experimental data, no clinical trial has established the level at which pH becomes deleterious for hemodynamics. Consequently, the essential treatment for lactic acidosis in shock patients is to correct the cause. It is unknown, however, whether symptomatic pH correction is beneficial in shock patients. The latest Surviving Sepsis Campaign guidelines recommend against the use of buffer therapy with pH ≥7.15 and issue no recommendation for pH levels <7.15. Furthermore, based on strong experimental and clinical evidence, sodium bicarbonate infusion alone is not recommended for restoring pH. Indeed, bicarbonate induces carbon dioxide generation and hypocalcemia, both cardiovascular depressant factors. This review addresses the principal hemodynamic consequences of shock-associated lactic acidosis. Despite the lack of formal evidence, this review also highlights the various adapted supportive therapy options that could be putatively added to causal treatment in attempting to reverse the hemodynamic consequences of shock-associated lactic acidosis.

Figure 1

Description of the principal pathophysiological effects of severe metabolic acidosis with pH <7.2 on a muscle cell. Transient calcium amplitude: the increase in Ca²⁺ transient amplitude is the net consequence of the inhibitory effect of low intracellular pH on RyRs, NCX and I_Ca, and the stimulatory effects of low intracellular pH on NHE, NBC, TRVP-1 and sarcoplasmic reticulum Ca². Myofilament Ca²⁺ sensitivity: due to the low intracellular pH, Ca²⁺ binding to troponin is altered and myofilament Ca²⁺ sensitivity decreased. Cellular hyperpolarization: intracellular acidosis also enhances hyperpolarization through K⁺ extrusion. Apoptosis: intracellular acidosis has stimulatory effects on BNIP3, promoting apoptosis. Adrenoreceptors: extracellular and intracellular acidosis reduces the number of adrenoreceptors on the cell membrane. Ica, L-type Ca²⁺ channel; IP3-R, inositol-1,4,5-triphosphate receptor; NBC, Na⁺/HCO₃ ⁻ co-transport; NCX, Na⁺/Ca²⁺ exchange; NHE, Na⁺/H⁺ exchange; pHe, extracellular pH; pHi, intracellular pH; PLB, phospholamban; Ry-R, ryanodine receptor; SERCA, sarco/endoplasmic reticulum Ca²⁺-ATPase; SR, sarcoplasmic reticulum; TRVP-1, transient receptor potential channels-1.

Figure 2

Schematic representation of cellular and functional consequences in myocardial and vascular smooth muscle cells in instances of severe lactic acidosis. The same mechanisms are involved in both cell types but with specific functional consequences. PFK, phospho-fructo-kinase; pHe, extracellular pH; pHi, intracellular pH.