To what extent is hyperlactatemia fundamentally integrated into the definition of septic shock? : Review Article

Abstract

Under the international consensus definitions (Sepsis-3), diagnosing septic shock requires comprising two specific clinical criteria after adequate fluid resuscitation. Persistent hypotension requiring titrated doses of vasopressors (norepinephrine) to maintain a mean arterial pressure (MAP) of 65 mm Hg or greater and elevated serum lactate levels greater than 2 mmol/L (>18 mg/dL) independent of hypovolemia. However, the rise in the blood lactate levels in the septic shock are due to increased production and reduced clearance, largely independent of simple oxygen deprivation. Hyperlactatemia is deeply integrated into the current definition of septic shock, but it is not biologically synonymous with septic shock. Nevertheless, lactate is not specific for septic shock, tissue hypoxia, or oxygen debt. In addition, it not only   occurs secondary to the impaired perfusion and oxygen delivery, but it may also result from adrenergically mediated exaggerated aerobic glycolysis, altered metabolic flux, impaired hepatic or renal clearance, mitochondrial and microcirculatory abnormalities, medications and other causes of type B hyperlactatemia. Even High doses of propofol infusion more than 5mg/kg/hour for over 48 hours can lead to PARIS syndrome, that causes mitochondrial dysfunction and halts effective adenosine triphosphate (ATP) production, and use of sodium bicarbonate to counter the metabolic acidosis, and medications like metformin, paracetamol, albuterol, sodium valproate, salicylates involved in the hyperlactatemia. Therefore, lactate levels may be spuriously high in severe septic shock under all these conditions. Contemporary, guidelines themselves recognize that lactate does not directly measure tissue perfusion and recommend its use within broader clinical assessment. Hyperlactatemia has been witnessed in almost all type of shocks (cardiogenic, vasoplegic, hypovolemic hemorrhagic, obstructive and cryptic), and not an integrated part of septic shock. Therefore, lactate should be regarded as an important prognostic and physiological signal encased within the current operational definition, bearing in mind that its biological specificity for shock remains limited. Serum lactate is a surrogate marker rather than an inherent, defining element of the pathophysiology of septic shock.