Original Contribution
End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis

https://doi.org/10.1016/j.ajem.2012.05.034Get rights and content

Abstract

Objective

Exhaled end-tidal carbon dioxide (Etco2) concentration is associated with lactate levels in febrile patients. We assessed the association of Etco2 with mortality and lactate levels in patients with suspected sepsis.

Methods

This was a prospective observational study. We enrolled 201 adult patients presenting with suspected infection and 2 or more systemic inflammatory response syndrome criteria. Lactate and Etco2 were measured and analyzed with patient outcomes.

Results

The area under the receiver operator characteristics curve (AUC) was 0.75 (confidence interval [CI], 0.65-0.86) for lactate and mortality and 0.73 (CI, 0.61-0.84) for Etco2 and mortality. When analyzed across the different categories of sepsis, the AUCs for lactate and mortality were 0.61 (CI, 0.36-0.87) for sepsis, 0.69 (CI, 0.48-0.89) for severe sepsis, and 0.74 (CI, 0.55-0.93) for septic shock. The AUCs for Etco2 and mortality were 0.60 (CI, 0.37-0.83) for sepsis, 0.67 (CI, 0.46-0.88) for severe sepsis, and 0.78 (CI, 0.59-0.96) for septic shock. There was a significant inverse relationship between Etco2 and lactate in all categories, with correlation coefficients of − 0.421 (P < .001) in the sepsis group, − 0.597 (P < .001) in the severe sepsis group, and − 0.482 (P = .011), respectively. Adjusted odds ratios were calculated, demonstrating 3 significant predictors of mortality: use of vasopressors 16.4 (95% CI, 1.80-149.2), mechanical ventilation 16.4 (95% CI, 3.13-85.9), and abnormal Etco2 levels 6.48 (95% CI, 1.06-39.54).

Conclusions

We observed a significant association between Etco2 concentration and in-hospital mortality in emergency department patients with suspected sepsis across a range of disease severity.

Introduction

Severe sepsis and septic shock are responsible for significant morbidity and mortality among patients admitted to the emergency department (ED) [1]. Early identification and treatment of these disorders have been shown to improve survival [2], [3]. A hallmark of septic shock is hypoperfusion leading to end-organ damage and cardiovascular collapse [1], [4]. Lactic acidosis is a well-accepted marker for disease severity in this population [4], [5] and has been shown to predict mortality in ED patients with infection [6]. The physiologic response to metabolic acidosis is a compensatory respiratory alkalosis for maintenance of homeostasis. Capnography, a noninvasive, real-time method of determining exhaled end-tidal carbon dioxide (Etco2), has been shown to predict severe metabolic acidosis in diabetic ketoacidosis [7], [8] and gastroenteritis [9]. Recently, Etco2 levels were associated with lactic acidosis and organ dysfunction in febrile patients admitted to the ED [10].

Mortality rates have been shown to decrease as much as 16% when early goal-directed therapy is initiated [2]. A challenge in implementing early and aggressive therapy has been properly identifying appropriate patients because hemodynamic compensation may mask the severity of underlying disease. Although lactate levels provide a reliable insight into disease severity, they may not be rapidly or easily attainable. One group noted a period of up to 172 minutes from the time of ED triage for a whole blood lactate value to be obtained in patients with sepsis [11]. Such delay may prevent prompt initiation of treatment in a condition that is amenable to improved outcomes with early interventions. Faster, point-of-care lactate tests have shown promise in expediting this process but have not yet been widely implemented [11], [12]. A real-time, noninvasive marker of disease severity in patients with suspected sepsis may expedite recognition, triage, and therapeutic intervention in this patient population.

We examined a prospective cohort of patients presenting to a tertiary referral ED with suspected sepsis to investigate the association of Etco2 with both direct (mortality) and indirect (lactic acidosis) outcome measures. We hypothesized that lower Etco2 levels would be associated with mortality and that Etco2 levels would decline with more severe lactic acidosis.

Section snippets

Design and setting

We performed a prospective convenience sampling of ED patients presenting with suspected sepsis. Institutional review board at the participating hospital approved the study protocol. Written consent was waived by the institutional review board because capnography is considered standard of care for many circumstances in our ED. Patient enrollment occurred between January 1, 2009, and October 31, 2010.

The study was conducted in the ED of a large adult tertiary hospital with an annual census of

Results

For 22 months, we enrolled a total of 201 patients with a mean age of 65 years (range, 18-99 years). Across all subjects, the mean length of stay was 8.6 days (range, 1-54 days), in-hospital mortality was 14%, 36% were admitted to the ICU, 24% were put on vasopressors, and 31% were blood culture positive (see Table 1). As a group, nonsurviving patients presented with higher respiratory rates and lower systolic and diastolic blood pressures, as well as lower oxygen saturations (see Table 1).

Discussion

This study suggests that Etco2 concentration may perform similarly to lactate levels as a predictor for mortality in patients with suspected sepsis. This performance was comparable across sepsis categories, as well as in both spontaneously breathing patients and those who required emergent intubation upon presentation to the ED. Furthermore, when we controlled for potential predictors of mortality, such as age, use of pressors, admission to the ICU, mechanical ventilation, positive blood

Conclusions

In conclusion, in patients admitted to the hospital with suspected sepsis, a single Etco2 measurement in the ED may predict mortality. Capnography is fast, noninvasive, and relatively inexpensive. Further studies are necessary to determine if Etco2 can be used to decrease time to recognition and therapy of patients with sepsis, and if prehospital Etco2 levels can be used to expedite care.

Acknowledgments

We thank all members of the ED staff for their assistance.

References (18)

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    End-tidal carbon dioxide measurement (ETCO2) might be able to add valuable information to trauma risk stratification. Below normal ETCO2 has been shown to be associated with worse outcomes in sepsis and trauma patients as compared to patients with normal ETCO2 [12-17]. ETCO2 less than 35 has been shown to have a strong association with hemorrhagic shock and massive transfusion protocol initiation in trauma patients independent of injury severity score (ISS), age, and/or systolic blood pressure (SBP) < 90 [18].

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