Lactic acidosis: Clinical implications and management strategies
ABSTRACTIn hospitalized patients, elevated serum lactate levels are both a marker of risk and a target of therapy. The authors describe the mechanisms underlying lactate elevations, note the risks associated with lactic acidosis, and outline a strategy for its treatment.
KEY POINTS
- Serum lactate levels can become elevated by a variety of underlying processes, categorized as increased production in conditions of hypoperfusion and hypoxia (type A lactic acidosis), or as increased production or decreased clearance not due to hypoperfusion and hypoxia (type B).
- The higher the lactate level and the slower the rate of normalization (lactate clearance), the higher the risk of death.
- Treatments differ depending on the underlying mechanism of the lactate elevation. Thus, identifying the reason for hyperlactatemia and differentiating between type A and B lactic acidosis are of the utmost importance.
- Treatment of type A lactic acidosis aims to improve perfusion and match oxygen consumption with oxygen delivery by giving fluids, packed red blood cells, and vasopressors or inotropic agents, or both.
- Treatment of type B involves more specific management, such as discontinuing offending medications or supplementing key cofactors for anaerobic metabolism.
OTHER MEASURES TO OPTIMIZE OXYGEN DELIVERY
In circulatory shock from any cause, tissue oxygen demand exceeds oxygen delivery. Once arterial oxygenation and hemoglobin levels (by packed red blood cell transfusion) have been optimized, cardiac output is the critical determinant of oxygen delivery. Cardiac output may be augmented by ensuring adequate preload (by fluid resuscitation) or by giving inotropes or vasodilators.
The optimal cardiac output is difficult to define, and the exact marker for determining when cardiac output should be augmented is unclear. A strategy of increasing cardiac output to predefined “supranormal” levels was not associated with a lower mortality rate.49 Therefore, the decision to augment cardiac output must be individualized and will likely vary in the same patient over time.23
A reasonable approach to determining when augmentation of cardiac output is necessary was proposed in a study by Rivers et al.50 In that study, in patients randomized to early goal-directed therapy, inotropes were recommended when the central venous oxygenation saturation (Scvo2) was below 70% despite adequate fluid resuscitation (central venous pressure ≥ 8 mm Hg) and hematocrits were higher than 30%.
When an inotrope is indicated to improve cardiac output, dobutamine is usually the preferred agent. Dobutamine has a shorter half-life (allowing for easier titration) and causes less hypotension (assuming preload has been optimized) than phosphodiesterase type III inhibitors such as milrinone.
Mechanical support devices, such as intra-aortic balloon counterpulsation, and vasodilators can also be used to improve tissue perfusion in selected patients with low cardiac output syndromes.
USING LACTATE LEVELS TO GUIDE THERAPY
Lactate levels above 4.0 mmol/L
Lactate may be a useful marker for determining whether organ dysfunction is present and, hence, what course of therapy should be given, especially in sepsis. A serum lactate level higher than 4.0 mmol/L has been used as the trigger to start aggressive resuscitation in patients with sepsis.50,51
Traditionally, as delineated by Rivers et al50 in their landmark study of early goal-directed therapy, this entailed placing an arterial line and a central line for hemodynamic monitoring, with specific interventions directed at increasing the central venous pressure, mean arterial pressure, and central venous oxygen saturation.50 However, a recent study in a similar population of patients with sepsis with elevated lactate found no significant advantage of protocol-based resuscitation over care provided according to physician judgment, and no significant benefit in central venous catheterization and hemodynamic monitoring in all patients.51
Lactate clearance: 10% or above at 8 hours?
Regardless of the approach chosen, decreasing lactate levels can be interpreted as an adequate response to the interventions provided. As a matter of fact, several groups of investigators have also demonstrated the merits of lactate clearance alone as a prognostic indicator in patients requiring hemodynamic support.
McNelis et al52 retrospectively evaluated 95 postsurgical patients who required hemodynamic monitoring.52,53 The authors found that the slower the lactate clearance, the higher the mortality rate.
Given the prognostic implications of lactate clearance, investigators have evaluated whether lactate clearance could be used as a surrogate resuscitation goal for optimizing oxygen delivery. Using lactate clearance may have significant practical advantages over using central venous oxygen saturation, since it does not require a central venous catheter or continuous oximetric monitoring.
In a study comparing these two resuscitation end points, patients were randomized to a goal of either central venous oxygen saturation of 70% or more or lactate clearance of 10% or more within the first 6 hours after presentation as a marker of oxygen delivery.53 Mortality rates were similar with either strategy. Of note, only 10% of the patients actually required therapies to improve their oxygen delivery. Furthermore, there were no differences in the treatments given (including fluids, vasopressors, inotropes, packed red blood cells) throughout the treatment period.
These findings provide several insights. First, few patients admitted to the emergency department with severe sepsis and treated with an initial quantitative resuscitation protocol require additional therapy for augmenting oxygen delivery. Second, lactate clearance, in a setting where initial resuscitation with fluids and vasopressors restores adequate oxygen delivery for the majority of patients, is likely as good a target for resuscitation as central venous oxygen saturation.
This study, however, does not address the question of whether lactate clearance is useful as an additional marker of oxygen delivery (in conjunction with central venous oxygen saturation). Indeed, caution should be taken to target central venous oxygen saturation goals alone, as patients with septic shock presenting with venous hyperoxia (central venous oxygen saturation > 89%) have been shown to have a higher mortality rate than patients with normoxia (central venous oxygen saturation 71%–89%).54
This was further demonstrated by Arnold et al in a study of patients presenting to the emergency department with severe sepsis.15 In this study, significant discordance between central venous oxygen saturation and lactate clearance was seen, where 79% of patients with less than 10% lactate clearance had concomitant central venous oxygen saturation of 70% or greater.
Jansen et al18 evaluated the role of targeting lactate clearance in conjunction with central venous oxygen saturation monitoring. In this study, critically ill patients with elevated lactate and inadequate lactate clearance were randomized to usual care or to resuscitation to adequate lactate clearance (20% or more). The therapies to optimize oxygen delivery were given according to the central venous oxygen saturation. Overall, after adjustment for predefined risk factors, the in-hospital mortality rate was lower in the lactate clearance group. This may signify that patients with sepsis and central venous oxygen saturation of 70% or more may continue to have poor lactate clearance, warranting further treatment.
Taken together, serum lactate may be helpful for prognostication, determination of course of therapy, and quantification for tissue hypoperfusion for targeted therapies. Figure 2 presents our approach to an elevated lactate level. As performed in the study by Jansen et al,18 it seems reasonable to measure lactate levels every 2 hours for the first 8 hours of resuscitation in patients with type A lactic acidosis. These levels should be interpreted in the context of lactate clearance (at least 10%, but preferably 20%) and normalization, and should be treated with an approach similar to the one outlined in Figure 2.
TREATING TYPE B LACTIC ACIDOSIS (NORMAL PERFUSION AND OXYGENATION)
Treating type B lactic acidosis is quite different because the goal is not to correct mismatches in oxygen consumption and delivery. Since most cases are due to underlying conditions such as malignancy or medications, treatment should be centered around eliminating the cause (eg, treat the malignancy, discontinue the offending medication). The main reason for treatment is to alleviate the harmful effects of acidosis. For example, acidosis can result in a negative inotropic effect.
Sodium bicarbonate, dichloroacetate, carbicarb, and tromethamine have all been studied in the management of type B lactic acidosis, with little success.55,56
Renal replacement therapy has had some success in drug-induced lactic acidosis.57,58
l-carnitine has had promising results in treating patients with human immunodeficiency virus infection, since these patients are carnitine-deficient and carnitine plays an important role in mitochondrial function.59
Thiamine and biotin deficiencies can occur in patients receiving total parenteral nutrition without vitamins and in patients who drink alcohol heavily and can cause lactic acidosis. These nutrients should be supplemented accordingly.
Treatment of mitochondrial disorders includes antioxidants (coenzyme Q10, vitamin C, vitamin E) and amino acids (l-arginine).60
