Brief Research Report
Serum Lactate as a Predictor of Mortality in Emergency Department Patients with Infection

https://doi.org/10.1016/j.annemergmed.2004.12.006Get rights and content

Study objective

Little is known about risk-stratification biomarkers in emergency department (ED) patients with suspected infection, and lactate is a biologically plausible candidate. We determine whether a serum venous lactate is associated with an increased risk of death in ED patients with infection.

Methods

This was a prospective cohort study in an urban, academic medical center with 50,000 annual ED visits. A total of 1,278 consecutive patient visits met enrollment criteria between July 24, 2003, and March 24, 2004, and all patients were enrolled. Inclusion criteria were age 18 years or older, serum lactate level obtained, and admission to the hospital with an infection-related diagnosis. The main outcome measure was all-cause 28-day inhospital mortality and death within 3 days of presentation.

Results

Among 1,278 patient visits, there were 105 (8.2%) deaths during hospitalization, with 55 (4.3%) of 1,278 deaths occurring in the first 3 days. Mortality rates increased as lactate increased: 43 (4.9%) of 877 of patients with a lactate level between 0 and 2.5 mmol/L died, 24 (9.0%) of 267 patients with a lactate level between 2.5 and 4.0 mmol/L died, and 38 (28.4%) of 134 patients with a lactate level greater than or equal to 4.0 mmol/L died. Lactate level greater than or equal to 4.0 mmol/L was 36% (95% confidence interval [CI] 27% to 45%) sensitive and 92% (95% CI 90% to 93%) specific for any death; it was 55% (95% CI 41% to 68%) sensitive and 91% (95% CI 90% to 93%) specific for death within 3 days.

Conclusion

In this cohort of ED patients with signs and symptoms suggestive of infection, our results support serum venous lactate level as a promising risk-stratification tool. Multicenter validation, as well as comparison of the lactate level with clinical predictors, needs to be done before widespread implementation.

Introduction

Bacteremia and sepsis are responsible for significant morbidity, mortality, and costs to patients in our health care system. There are an estimated 751,000 cases of severe sepsis per year in the United States,1 with a hospital case mortality rate between 30% and 50%.2, 3, 4 The therapies of activated protein C and early goal-directed therapy have been recently shown to reduce mortality in patients with severe sepsis.2, 4, 5 Although these therapies are effective, early goal-directed therapy is resource intensive, activated protein C is expensive, and all aggressive therapies carry risk. Thus, it is important to select patients who may benefit most. Additionally, the early presentation of sepsis can be subtle and difficult to detect, which also represents a challenge to the clinician.

A number of laboratory tests and markers have been proposed to assist in risk stratification of patients with infection. Leukocytosis, bandemia, thrombocytopenia, elevated C-reactive protein, elevated sedimentation rates, and elevated procalcitonin have all been suggested; however, there is no single reliable test. Serum lactate offers theoretical promise as a risk-stratification tool in patients with infection. Impaired tissue oxygenation is a hallmark of shock, but blood pressure, pulse rate, and urine output are insensitive markers for this disturbance, and many patients have clinically unapparent shock. However, tissue hypoxia causes cellular metabolism to shift to the anaerobic pathway, increasing lactate production; at the same time, sepsis impairs lactate clearance, which may lead to an increase in circulating lactate levels, even when vital signs are not yet compromised. In practice, determination of circulating lactate levels is technically feasible, commonly used, and clinically available with rapid turnaround times. Finally, lactate has been evaluated as a prognostic tool in a number of critical-care patient populations, including patients with septic shock, recent surgery, burns, and trauma, and has been found to predict mortality among these very ill patients.

Despite its routine use in ICU patients already identified to be seriously ill, measurement of a serum lactate as a risk-stratification tool in patients with infection is relatively limited in most emergency departments (EDs). Given its ability to detect patients with tissue hypoxia and increased metabolic demands resulting from sepsis, we hypothesized that the serum lactate level is a useful screen to identify patients in the ED with increased risk of death. Accordingly, the objective of this study is to determine the ability of a serum lactate level to predict death in ED patients with infection.

Section snippets

Study Design

This was a prospective, observational, cohort study of consecutive ED patients with infection who had a serum lactate level obtained. All adult patients (aged 18 years or older) who presented to the ED between July 24, 2003, and March 24, 2004, were eligible. The ED, with 50,000 annual visits, serves an urban, academic teaching hospital with 490 beds. The study was approved by the institutional review board, and a waiver of consent was obtained.

The study inclusion criteria were age 18 years or

Results

A total of 1,278 patients met criteria, and all were enrolled. There were 105 (8.2%) of 1,278 inhospital deaths, of which 55 (4.3%) of 1,278 patients died within 3 days of admission (early death). The mean lactate level of 4.0 mmol/L (95% confidence interval [CI] 3.4 to 4.7 mmol/L) in those who died was higher than 2.2 mmol/L (95% CI 2.1 to 2.3 mmol/L) in those who lived (Figure 1). The mortality rates for the low, medium, and high groups were 43 of 877 (4.9%; 95% CI 3.5% to 6.3%), 24 of 267

Limitations

This study is a preliminary examination and has several important limitations. Because this was a preliminary study, we collected no data about hemodynamics, comorbidities, or other clinical conditions. We did not describe our patient population in terms of proportions of patients with conditions such as systemic inflammatory response syndrome, severe sepsis, or septic shock. It is also possible that lactate is a covariate of some other measurable clinical factor. There are also patients in our

Discussion

Our data demonstrate that in a large cohort of ED patients with signs and symptoms of infection, a single measurement of venous lactate provides risk-stratification information about inhospital mortality and mortality within 3 days. We measured lactate in a systematic fashion and used the objective endpoint of all-cause mortality. The mortality rate of 28% for patients with a lactate level greater than or equal to 4.0 mmol/mm3 clearly demonstrates that a lactate level may be helpful in

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Author contributions: NIS, MDH, and DT were involved in all phases of idea conception, study design, data collection, analysis, and manuscript preparation. LAN was involved in study design, data collection, and manuscript review. AL, REW, and JWW were involved in study design and manuscript preparation. NIS, MH, and DT take responsibility for the paper as a whole.

Funding and support: The authors report this study did not receive any outside funding or support.

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