Much has been made over measurement of serum lactate over the last several years– primarily focusing on whether we should be measuring it in the first place, and what the significance (and etiology) of elevations in serum lactate is, and what role it should play in diagnosis and risk stratification. Back in 2010, Scott Weingert was organizing the New York Sepsis Collaborative, and produced this podcast covering the basics of lactate measurement, with a particular bent towards sepsis. He did a great job covering the essential take-home of the data that existed thus far, and addressed a lot of points of confusion many people have about lactate — namely, the idea that it results from hypoxia/hypoxemia or anaerobic respiration, and covers some of the alternative etiologies of hyperlactatemia, i.e. any beta agonist, whether endogenous catecholamines or exogenous, such as albuterol or epinephrine being used as a vasopressor. The takeaway from this, echoed in sepsis care guidelines issued by many other organizations since and in the policies and protocols in many hospitals and emergency departments, is that elevated lactate is a marker of increased mortality, and may be an early alarm that someone is in septic shock or headed towards it.
I wanted to cover two studies — one by Shapiro et al. (a big name in sepsis research), and the other by del Portal et al– that looked at this question in the ED. These were prospective and retrospective cohort studies respectively, and both looked at over 1,000 emergency department patients and evaluated the prognostic significance of elevated venous lactate measurements. In the first study by Shapiro et al, they evaluated all patients admitted to the hospital with an infection-related diagnosis. In the second study, they looked at older adults admitted to the hospital with any diagnosis, though a very large proportion of patients were excluded. Reasons for exclusion (they excluded >14,000 of 16,886 total admissions , so I think this really affects the robustness of this paper) were things like being a sick trauma patient, transfers out, LWBS or leaving AMA — those are all reasonable, but they also excluded all patients in whom a lactate was not drawn in the ED. Without providing the numbers to break this down, it’s tough to say how generalizable these conclusions are, or if lactates were only obtained in patients that the providers thought were sick/potentially septic in the first place (which was the protocol at the hospital conducting the study by Shapiro et al.).
As one might expect, both studies found that hyperlactatemia correlates with badness in the form of increased mortality. The relationship is linear, and statistically significant. The authors also stratified the mortality by time — in Shapiro et al. by 28d in-hospital v. death within 3 days (top graph), and in del Portal’s study by in-hospital, 30 day and 60 day mortality (bottom):
Note the similar trend and the steep upward trajectory of the relationship — these results have been paralleled in the critical care literature, and have led to the commonly-accepted idea that a lactate > 4.0 is a threshold above which one should be concerned for hypoperfusion or shock, even in the absence of hypotension. These studies do not, and no studies have, established a causal relationship between lactate elevation and increased mortality– nor have they shown that trying to “clear” lactate will lead to better outcomes than trending alternative markers of perfusion (though several studies have looked at this question, without any definite conclusions). They also did not establish that one need only be worried about lactate > 4.0 — multiple studies including this one have shown that infected patients with lactate in the 2.0–3.9 mmol ⁄ L range have a risk of mortality that is approximately twice that of patients with a lactate level of < 2.0 mmol ⁄ L. They also have not established that we need not be worried about patients without hyperlactatemia — so-called “occult” sepsis.
More recent studies have questioned the relationship between hyperlactatemia and hypoperfusion per se by looking at changes in microcirculation, but I think it’s safe to say that an elevated lactate in a patient with suspected infection should still ring alarm bells in your head. Having these mortality “buckets” in mind when mentally risk stratifying patients or prioritizing them for workup or interventions can also help — particularly when these patients might otherwise look well and thereby fly under the radar.
In my mind, an elevated serum lactate must be explained — sometimes, the explanation is that they just got a nebulizer treatment, are in alcoholic ketoacidosis (which along with the production of ketones, leads to an accumulation in reduced nicotinamide adenine dinucleotide (NADH), which then results in impaired conversion of lactate to pyruvate or preferential conversion of pyruvate to lactate, both resulting in increased lactic acid level), or seized. But these are diagnoses of exclusion, and one must assume until proven otherwise that this represents their body’s sympathetic accelerator pedal being pushed to the floor and that they are needing resuscitation and provision of care with the mentality that this is a sick patient.