Combination of arterial lactate levels and venous-arterial CO2 to arterial-venous O 2 content difference ratio as markers of resuscitation in patients with septic shock

Abstract

Purpose: To evaluate the prognostic value of the Cv-aCO2/Da-vO2 ratio combined with lactate levels during the early phases of resuscitation in septic shock.

Methods: Prospective observational study in a 60-bed mixed ICU. One hundred and thirty-five patients with septic shock were included. The resuscitation protocol targeted mean arterial pressure, pulse pressure variations or central venous pressure, mixed venous oxygen saturation, and lactate levels. Patients were classified into four groups according to lactate levels and Cv-aCO2/Da-vO2 ratio at 6 h of resuscitation (T6): group 1, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 >1.0; group 2, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 ≤1.0; group 3, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 >1.0; and group 4, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 ≤1.0.

Results: Combination of hyperlactatemia and high Cv-aCO2/Da-vO2 ratio was associated with the worst SOFA scores and lower survival rates at day 28 [log rank (Mantel-Cox) = 31.39, p < 0.0001]. Normalization of both variables was associated with the best outcomes. Patients with a high Cv-aCO2/Da-vO2 ratio and lactate <2.0 mmol/L had similar outcomes to hyperlactatemic patients with low Cv-aCO2/Da-vO2 ratio. The multivariate analysis revealed that Cv-aCO2/Da-vO2 ratio at both T0 (RR 3.85; 95 % CI 1.60-9.27) and T6 (RR 3.97; 95 % CI 1.54-10.24) was an independent predictor for mortality at day 28, as well as lactate levels at T6 (RR 1.58; 95 % CI 1.13-2.22).

Conclusion: Complementing lactate assessment with Cv-aCO2/Da-vO2 ratio during early stages of resuscitation of septic shock can better identify patients at high risk of adverse outcomes. The Cv-aCO2/Da-vO2 ratio may become a potential resuscitation goal in patients with septic shock.

Figures

Fig. 1

Sequential Organ Failure Assessment (SOFA) scores at day 3 for predefined groups. Data presented as median (percentiles). Patients were separated into four groups according to lactate and Cv-aCO2/Da-vO2 ratio measured after the first 6 h of resuscitation: group 1, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 ratio >1.0; group 2, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 ratio ≤1.0; group 3, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 ratio >1.0; and group 4, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 ratio ≤1.0. Kruskal–Wallis one-way ANOVA, p < 0.001. **p < 0.01 by Tukey–Kramer showing differences between groups 1 vs. 3 and 1 vs. 4

Fig. 2

Survival probabilities up to day 28 according to lactate and Cv-aCO2/Da-vO2 after 6 h of resuscitation. Log rank (Mantel–Cox) = 31.39, p < 0.0001. Group 1, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 ratio >1.0; group 2, lactate ≥2.0 mmol/L and Cv-aCO2/Da-vO2 ratio ≤1.0; group 3, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 ratio >1.0; and group 4, lactate <2.0 mmol/L and Cv-aCO2/Da-vO2 ratio ≤1.0

Fig. 3

Receiver operating characteristics (ROC) curves for prediction of mortality at day 28 for models including or not Cv-aCO2/Da-vO2 ratio. The “large model” included Cv-aCO2/Da-vO2 + lactate levels. The “short model” included lactate levels but not Cv-aCO2/Da-vO2. Both models also included oxygen consumption (VO2), oxygen delivery (DO2), mixed-venous oxygen saturation (SvO2), cardiac index, APACHE II, age, time before T0, gender, fluids administered, norepinephrine dose, and mean arterial pressure. Likelihood ratio test, χ2 = 17.81, p < 0.001. Differences between AUCs, C statistic, χ2 4.52, p = 0.03