Persistently high venous-to-arterial carbon dioxide differences during early resuscitation are associated with poor outcomes in septic shock

Abstract

Introduction: Venous-to-arterial carbon dioxide difference (Pv-aCO2) may reflect the adequacy of blood flow during shock states. We sought to test whether the development of Pv-aCO2 during the very early phases of resuscitation is related to multi-organ dysfunction and outcomes in a population of septic shock patients resuscitated targeting the usual oxygen-derived and hemodynamic parameters.

Methods: We conducted a prospective observational study in a 60-bed mixed ICU in a University affiliated Hospital. 85 patients with a new septic shock episode were included. A Pv-aCO2 value ≥ 6 mmHg was considered to be high. Patients were classified in four predefined groups according to the Pv-aCO2 evolution during the first 6 hours of resuscitation: (1) persistently high Pv-aCO2 (high at T0 and T6); (2) increasing Pv-aCO2 (normal at T0, high at T6); (3) decreasing Pv-aCO2 (high at T0, normal at T6); and (4) persistently normal Pv-aCO2 (normal at T0 and T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a Kaplan Meier curve was constructed to show the survival probabilities at day-28 using a log-rank test to evaluate differences between groups. A Spearman-Rho was used to test the agreement between cardiac output and Pv-aCO2. Finally, we calculated the mortality risk ratios at day-28 among patients attaining normal oxygen parameters but with a concomitantly increased Pv-aCO2.

Results: Patients with persistently high and increasing Pv-aCO2 at T6 had significant higher SOFA scores at day-3 (p < 0.001) and higher mortality rates at day-28 (log rank test: 19.21, p < 0.001) compared with patients who evolved with normal Pv-aCO2 at T6. Interestingly, a poor agreement between cardiac output and Pv-aCO2 was observed (r2 = 0.025, p < 0.01) at different points of resuscitation. Patients who reached a central venous saturation (ScvO)2 ≥ 70% or mixed venous oxygen saturation (SvO2) ≥ 65% but with concomitantly high Pv-aCO2 at different developmental points (i.e., T0, T6 and T12) had a significant mortality risk ratio at day-28.

Conclusion: The persistence of high Pv-aCO2 during the early resuscitation of septic shock was associated with more severe multi-organ dysfunction and worse outcomes at day-28. Although mechanisms conducting to increase Pv-aCO2 during septic shock are insufficiently understood, Pv-aCO2 could identify a high risk of death in apparently resuscitated patients.

Figures

Figure 1

Sequential Organ Failure Assessment scores at day 3 by the early development (first 6 hours) of mixed venous-to-arterial carbon dioxide difference. Kruskal–Wallis test, P <0.001. **Significant differences between persistently high mixed venous-to-arterial carbon dioxide difference (Pv-aCO2) and low Pv-aCO2 group; and between persistently high Pv-aCO2 and decreasing Pv-aCO2 group after Bonferroni correction. H-H, Pv-aCO2 high at Time 0 (T0) and 6 hours later (T6); L-H, Pv-aCO2 normal at T0 and high at T6; H-L, Pv-aCO2 high at T0 and normal at T6; and L-L, Pv-aCO2 normal at T0 and T6. SOFA, Sequential Organ Failure Assessment.

Figure 2

Survival probabilities at day 28 by the development of mixed venous-to-arterial carbon dioxide difference during the first 6 hours of resuscitation. Log-rank, Mantel–Cox: 19.21, P <0.001. H-H, mixed venous-to-arterial carbon dioxide difference (Pv-aCO2) high at Time 0 (T0) and 6 hours later (T6); L-H, Pv-aCO2 normal at T0 and high at T6; H-L, Pv-aCO2 high at T0 and normal at T6; and L-L, Pv-aCO2 normal at T0 and T6.

Figure 3

Scatter plot between cardiac index and mixed venous-to-arterial carbon dioxide difference. All patients at Time 0 (T0) and 6 hours (T6), 12 hours (T12) and 24 hours (T24) later. Pearson correlation: 0.16; r2 = 0.025; P <0.01. CI, confidence interval; Pv-aCO2, mixed venous-to-arterial carbon dioxide difference.

Figure 4

Lactate clearance (%) 6 and 12 hours after Time 0 for patients with normal or high mixed venous-to-arterial carbon dioxide difference at 6 hours. Significant differences for lactate clearance (Time 0 (T0) to 6 hours later (T6) and T0 to 12 hours later (T12)) between patients with persistently high (that is, high-to-high and normal-to-high groups) and normalized mixed venous-to-arterial carbon dioxide difference at T6 (high-to-normal and persistently low groups). A negative percent clearance indicates a reduction in lactate levels. Black bars: High Pv-aCO2 at T6; Gray bars: Low Pv-aCO2 at T6.

Figure 5

Correlation between mixed venous carbon dioxide pressure and central venous-to-arterial carbon dioxide difference. Scatter plot representing the mixed-venous to arterial carbon dioxide (Pvm-aCO2) difference versus the central-venous to arterial carbon dioxide difference (Pvc-aCO2). Pearson correlation: 0.71 (95% confidence interval: 0.47 to 0.86); R2 = 0.55, P <0.001.