A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.
Serum lactate has been the darling of Emergency Medicine/Critical Care since Manny Rivers first introduced EGDT to the Emergency Department. Since then we have used it as a screening tool, a means to guide therapy and even to prognosticate outcomes. Despite our universal acceptance of its utility, very little high quality data has been published on its diagnostic properties. I reviewed this evidence in more depth in a past post and will limit this to the question, “Can serum lactate identify a group of patients who are in cryptic shock, despite clinically appearing well?” The Surviving Sepsis Campaign recommends using a lactate level of 4 mmol/L as the threshold for identifying cryptic shock, but lactate has a continuous curvilinear association with mortality and a 4 mmol/L threshold seems like an arbitrary cutoff.
In an attempt to answer this question Puskarich et al conducted a systematic review, published in the Journal of Critical Care, examining the ability of intermediate lactate values (2.0-3.9 mmol/L) to predict cryptic shock and death. Eight studies were included in this review. A total of 11,062 patients with intermediate lactate levels were examined. The authors appropriately decided that given the heterogeneity of these datasets, a formal meta-analysis was not appropriate. Instead they settled for descriptive statistics of each individual trial. In summary they found patients with intermediate lactate values who were normotensive had a 30 day mortality rate of 14.9% (mortality in individual trials ranged from 3.2-16.4%). Obviously the patients with intermediate lactate levels that were concurrently hypotensive fared far worse (30 day mortalities of 35-37%).
This review fails to define the clinical utility of the association between elevated lactate levels and risk of death. In the few studies included in this review which published diagnostic test characteristics, lactate performed surprisingly poorly. Howell et al found lactate had an AOC of 0.71 for predicting 30 day mortality. Shapiro et al reported a similar AOC of 0.67. In fact in the Shapiro study when a cutoff of 2.5 mmol/L was used as screening tool for cryptic shock, it had a sensitivity of 59% and a specificity of 71%. Even a threshold of 4 mmol/L though very specific (92%) had a sensitivity of 36%, a far lower sensitivity than one would be traditionally accepted for a screening test.
More importantly, this data does not allow us to determine how a lactate threshold of 2.5 mmol/L performs in the true cryptic shock patient. This is the patient who has end organ hypoperfusion without any clinically obvious signs. In most of the patients with elevated lactates, they appear clinically ill and thus the lactate is only confirming what we already know, that this patient needs aggressive intervention. If lactate is to prove useful as a true screening tool (at whatever threshold), it should be able to identify the patient clandestinely experiencing septic shock before any obvious signs of of end-organ damage (AMS, hypotension, AKI) become apparent. Unfortunately we have little data supporting its use in this manner. Even the secondary analysis of the Jones trial, finding similar mortalities between hypotensive patients and normotensive patients with elevated lactate (above 4mmol/L), fails to impress. Although the cryptic shock patients were not hypotensive in the strictest sense, they were by no means physiologically normal. On the contrary they were older, more tachycardic, with faster respiratory rates, and experienced significantly more intra-abdominal infections (30% vs 16%) than their hypotensive counterparts. And though they were not hypotensive (<90 mmHg), their blood pressures were not necessarily normal. The median blood pressure in the cryptic shock group was 108mmHG with an IQR of 92-126. To put it simply, these patients were sick. They did not require a lactate level to identify them as in need of aggressive therapy. There was nothing cryptic about them….
“Prognosis of Emergency Department Patients with Suspected Infection and Intermediate Lactate Levels: A Systematic Review”