Date of Award

10-12-2009

Document Type

Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Charles R. Wira, MD

Abstract

Severe sepsis and septic shock comprise a significant number of emergency department (ED) admissions annually. With the advent of early goal directed therapies, early identification and intervention have become paramount in this population. Few studies, however, have examined the role of serum lactate as a predictor of mortality or endpoint to resuscitation among this population. We aimed to show that improved lactate clearance is associated with decreased 28-day in-hospital mortality. We retrospectively examined data from the Yale Sepsis Registry for patients with severe sepsis or septic shock who had lactate levels that were measured initially in the ED and subsequently when the patient arrived on the floor. This study received institutional review board approval. Lactate clearance was calculated as a percentage, and comparison between patients who cleared lactate and those who did not were made for mortality data as well as baseline characteristics and interventions required between the two groups. 207 patients (110 male) with mean age and standard deviation (SD) of 63.17 ± 17.9 years were examined. 136 patients (65.7%) were diagnosed with severe sepsis and 71 patients (34.3%) had septic shock. Of those with identified sources of infection, pneumonia was the most common (54 patients, 26.1%). There were 171 patients in the clearance group and 36 patients in the non-clearance group, all of whom had a mean time of 9 hours 8 minutes ± 4 hours 6 minutes between lactate measurements. 28-day mortality rates were 15.2% (26 patients) in the lactate clearance group and 36.1% (13 patients) in the non-clearance group (p<0.01). Vasopressor support within 72 hours of admission was initiated among 61.1% (22 patients) in the non-clearance group compared with 36.8% (63 patients) in the clearance group (p<0.01). Mechanical ventilation was required for 36.3% (62 patients) in the clearance group and 66.7% (24 patients) in the non-clearance group (p=0.001). Rates of severe sepsis, mean number of SIRS and organ dysfunction criteria, and initial creatinine were similar between the two groups; however, only 86.1% (31 patients) in the non-clearance group received intravenous fluids in the ED compared with 98.8% (169 patients) in the clearance group (p=0.002). 33.3% (12 patients) in the non-clearance group had chronic obstructive pulmonary disease (COPD) compared with 15.2% (26 patients) in the clearance group (p<0.05). The mean Mortality in Emergency Department Sepsis (MEDS) scores were 8.78 ± 3.96 for the clearance group and 10.4 ± 4.48 for the non-clearance group (95% CI, -3.1 to -.14, p<0.05). These results show significantly higher mortality rates among patients who do not clear their lactate in the ED. Additionally, these patients require vasopressor support and mechanical ventilation more often. Lactate clearance was significantly associated with receipt of fluids and may also reflect lower MEDS score. Our findings suggest lactate clearance could be used as an endpoint for ED resuscitation and in stratifying mortality risk among patients with severe sepsis or septic shock. Future studies might seek to prospectively validate these findings and incorporate multivariate analysis to determine factors affecting lactate clearance.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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