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Serum lactate levels are a useful tool in managing critically ill septic patients, but the levels are often not routinely drawn or rapidly available in some institutions. As sepsis or SIRS-related disease is time-crucial with the administration of antibiotics and early goal directed therapy important to overall mortality, this delay could potentially translate into a patient care issue for the Emergency Physician.
 
Taking this into account, this study attempted to determine whether a readily available test, the anion gap (AG), could be used as a marker for abnormal lactate levels in ED patients at risk for sepsis. The authors enrolled 1419 adult patients prospectively with clinically suspected infection who had chemistry panels, calculated AG and lactate levels drawn in the ED. The mean AG was 11.8 and the mean lactate was 2.1. For an abnormal AG greater than 12, the mean lactate was 2.9, compared with 1.8 for an AG less than 12. The sensitivity of an elevated AG (greater than 12) in predicting elevated lactate levels (greater than 4 mmol/L) was 80% and the specificity was 69%. Patients with a gap greater than 12 had a 7-fold increased risk of having a lactate greater than 4 mmol/L.
 
The authors concluded that an elevated AG “is a moderately sensitive and specific means to detect elevated lactate levels in ED patients at risk for sepsis. This information may be somewhat helpful to Emergency Physicians to risk-stratify their patients to provide more aggressive early resuscitation.”
 
Elevated lactate levels are a surrogate for the outcomes of interest: death and organ failure. Lactate levels do correlate with sepsis-related mortality with levels above 4.0 mmol/L demonstrating 36% sensitivity and 92% specificity for all-cause mortality (Shapiro et al. Annals Emergency Medicine 2005; 45: 524-528). A single lactate is non-specific for sepsis. Since many conditions can produce hyperlacticacidemia, such as end-stage liver disease, alcoholic ketoacidosis, and toxic ingestions (James et al, Lancet 1999; 354: 505-508), serial lactate levels may have greater prognostic accuracy.
Nguyen (Crit Care Med 2004; 32: 1637-1642) noted that a failure to reduce lactate levels by >10% at six-hours (a measurement dubbed the “lactime”) is associated with increased mortality (sensitivity 44%, specificity 84%) from 42% to 67%.
 
Like lactate, an elevated anion gap has a wide differential diagnosis and is non-specific for hypo-perfusion or sepsis. The current study would have been more useful if the anion gap had been correlated with sepsis or the systemic inflammatory response syndrome and sepsis-related mortality. Furthermore, the prognostic test characteristics (sensitivity, specificity, likelihood ratios) of serial anion gap measurements to correlate with sepsis-related mortality would also be of interest.
 
This study is good news for those emergency physicians practicing where lactate levels may take a couple hours or may not be available at all, such as in some low to moderate volume community EDs. Now there is evidence that the anion gap may be used to help assist clinical decisions while patient dispositions are made. The bottom line: if lactate levels at your institution are unavailable or have a prolonged turn-around time, take a second look at the anion gap for your patient with possible SIRS or sepsis.


The Study
Berkman M, Ufberg J, Nathanson LA, Shapiro NI: Anion Gap as a Screening Tool for Elevated Lactate in Patients with an Increased Risk of Developing Sepsis in the Emergency Department. JEM 2009; 36(4):391-394.

 

Comments   

# MD, Faculty Brown Medical School, Dept. of EMJon Valente 2009-09-15 18:06
Will this prompt you to do EGDT more?

Nice review.
At centers with poor access to lactate levels, this could prompt the clinician to use more aggressive management i.e. EGDT, considering admission to higher level of care, etc. A high AG (>12) just might be the "red flag" or "ticket" to persuade you or the admitting physician to admit your patient.
Other questions to consider:
1. Will repeating the lab and improving your AG correlate with improving lactate and improving morbidity and mortality? Possibly, but this data to my knowledge is not available.
2. How good is lactate for predicting sepsis? What is lactic acid's sensitivity? (In this study, the AG is only being used as a surrogate marker for another test).
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