Lactate in Critical Illness—Implications for Monitoring


2mEq/l. This clear association between lactate and SOFA score was strongest in the early phase of ICU care compared with later. This confirmed the relationship between blood lactate levels and injury severity and of the prognostic value of lactate clearance for the survival of severely injured patients.


determined that initial lactate levels were associated with mortality, independent of organ failure and shock. In this study of 830 patients admitted to the emergence department (ED) with severe sepsis, initial lactate was categorized as low (<2mEq/l), intermediate (2–3.9mEq/l), or high (≥4mEq/l). Mortality at 28 days was 8.7% (confidence interval [CI] 4.9–14.2), 16.4% (CI 12.5–20.9), and 31.8% (CI 24.6–39.7) for low, intermediate, and high lactate levels, respectively, in non-shock patients and 15.4% (CI 5.9–30.5), 37.3% CI 25–50.8), and 46.9% (CI 36.8–57.3) in the low, intermediate, and high lactate levels in patients with shock. A second important finding was related to the conventional lactate threshold of >4 mEq/l and that some risk for death is associated with lactate levels that are deemed ‘normal’.15


Mikkelsen et al.15


A recently published clinical study examining this association of ‘relative’ hyperlactatemia, (<2mEq/l), also found increased risk for hospital death to confirm these findings.9


neuro/trauma patients, followed by the medical, then surgical, then cardiac surgical patient groups. Higher lactate levels were found in patients with higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores,18


and increased with patient age. Among patients


who did not have elevated lactate on admission, subsequent hyperlactatemia occurred in 6%. Mortality was highest among all patient groups with hyperlactatemia on admission, (20% versus 5%; p<0.001). This affected medical patients most (47%) followed by neuro/trauma (25%), surgical (15%), and cardiac surgical (13%) patients (p<0.001). After controlling for confounding variables, increasing levels of hyperlactatemia at presentation were independently associated with stepwise increased risk for subsequent ICU-related mortality. Lactate concentrations of 2–5mEq/l conferred an increased risk for death (odds Ratio [OR] 1.94, 95% CI 1.62–2.32, while concentrations of 5–10mEq/l (OR 3.38, 95% CI 2.64–4.33); 10–15mEq/l (OR 4.41, 95% CI 2.99–6.50); 15–20mEq/l (OR 7.58, 95% CI 3.93–14.60) and >20mEq/l (OR 10.89, 95% CI 4.89–24.48), respectively.16


Howell et al.17 reported that patients with This retrospective


observational study of prospectively collected data from 7,155 consecutive critically ill patients admitted to the ICU examined the relationship of on admission, maximum, and time-weighted relative hyperlactatemia with hospital outcome. Findings concluded that even lactate concentrations >0.75mEq/l can be used by clinicians to identify patients at higher risk for death. These findings suggest that the current reference range for lactate levels that trigger EGDT in the critically ill may need to be reassessed.9


studied lactate levels in septic patients versus other patients with hemorrhage or conditions generally associated with low oxygen transport (LT) and in patients who were hemodynamically stable compared with those who were not. They found that a reduction in lactate concentration during the first 24 hours after ICU admission was associated with improved outcome in septic patients but not patients presenting with hemorrhage or LT, and that lactate on admission, not the reduction over time, predicted mortality in the hemorrhage and LT group. They hypothesized that the patients who experienced hemorrhage and LT and significantly higher lactate levels sustained a more severe insult and irreversible organ damage that would not respond to interventions designed to reduce lactate levels.16


Lactate as a Clinical Marker for Hypoxia Jansen et al.16


Lactate as a Predictor of Mortality


Significantly higher lactate levels in non-survivors have been reported in several studies,16,17


demonstrating that hyperlactatemia adds mortality risk to all critically ill patient populations regardless of admission diagnosis. In a study of 11,581 adult patients16


admitted to four ICUs


with serious medical, cardiac surgical, surgical, and neuro/trauma conditions, the incidence of one episode of high lactate (>2mEq/l) was present in 40% of patients and the average prevalence was 20 per 100 days of hyperlactatemia during the average ICU stay. The occurrence of hyperlactatemia varied significantly by admitting diagnostic category (p<0.001), with the highest cumulative incidence observed among the


US RESPIRATORY DISEASE Nguyen et al.21


further examined the clinical implications of clearance of high lactate levels on presentation to the ED. As the ED is frequently the initial point of care for patients with sepsis and shock, the hypothesis was that initiating early goal directed therapy to reduce lactate levels early in the course of therapy (prior to ICU admission) may improve outcomes from severe sepsis and septic shock. In this prospective observational study, therapy was initiated on recognition of sepsis in the ED and continued in the ICU. Survivors had a lactate clearance of 38.1 ± 34.6mEq/l compared with 12.0 ± 51.6mEq/l (p=0.005) in non-survivors. Multivariate logistic regression demonstrated lactate clearance had a


53


a lactate level ≥4mEq/l in the presence of normal blood pressure had a mortality rate of 15%, (95% CI 6.0–24), while patients who had either septic shock or lactate ≥4mEq/l had a mortality rate of 28.3% (21.3–35.3%), which was significantly higher than for those who had neither (2.5%, 1.6–3.4%). Additionally, patients with a lacate level of 2.5–4.0mEq/l had adjusted odds ratio of death of 2.2 (1.1–4.2) and those with lactate ≥4mEq/l had 7.1 (3.6–13.9) times the odds of experiencing death.17


Jansen et al.19 also found that mortality was significantly higher


in ED patients with lactate levels of ≥3.5mEq/l compared with those with lactate levels <3.5mEq/l at first measure (T1) and on ED arrival (T2); T1: 41 versus 12% and T2: 47 versus 15%).19


These findings suggest


that a clinical intervention for lactate concentration >4mEq/l may miss opportunities for preventing ICU death.


Early Lactate Clearance may Decrease Mortality Early studies of lactate clearance demonstrated that lactate metabolism and the time needed to normalize lactate levels is also an important prognostic factor for survival in severely injured patients.20


Serum


lactate levels and oxygen transport were measured from admission up to 48 hours in 76 consecutive patients with multiple trauma. Patients were analyzed with respect to survival and lactate clearance to normal (≤2mEq/l) by 24 and 48 hours. While there were no differences in interventions and severity scores, all patients whose lactate levels normalized in 24 hours survived. When lactate cleared to normal between 24 and 48 hours, the survival rate was 75%, and only three of the 22 patients who did not clear their lactate level at 48 hours survived, demonstrating that optimization of treatment of hypoxia and perfusion alone does not predict survival.20


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