Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis

Abstract

Study objective: Abnormal (both low and high) central venous saturation (ScvO(2)) is associated with increased mortality in emergency department (ED) patients with suspected sepsis.

Methods: This was a secondary analysis of 4 prospectively collected registries of ED patients treated with early goal-directed therapy-based sepsis resuscitation protocols from 4 urban tertiary care hospitals. Inclusion criteria were sepsis, hypoperfusion defined by systolic blood pressure less than 90 mm Hg or lactate level greater than or equal to 4 mmol/L, and early goal-directed therapy treatment. ScvO(2) levels were stratified into 3 groups: hypoxia (ScvO(2) <70%); normoxia (ScvO(2) 71% to 89%); and hyperoxia (ScvO(2) 90% to 100%). The primary exposures were initial ScvO(2) and maximum ScvO(2) achieved, with the primary outcome as inhospital mortality. Multivariate analysis was performed.

Results: There were 619 patients who met criteria and were included. For the maximum ScvO(2), compared with the mortality rate in the normoxia group of 96 of 465 (21%; 95% confidence interval [CI] 17% to 25%), both the hypoxia mortality rate, 25 of 62 (40%; 95% CI 29% to 53%) and hyperoxia mortality rate, 31 of 92 (34%; 95% CI 25% to 44%) were significantly higher, which remained significant in a multivariate modeling. When the initial ScvO(2) measurement was analyzed in a multivariate model, only hyperoxia was significantly higher.

Conclusion: The maximum ScvO(2) value achieved in the ED (both abnormally low and high) was associated with increased mortality. In multivariate analysis for initial ScvO(2), the hyperoxia group was associated with increased mortality, but not the hypoxia group. This study suggests that future research aimed at targeting methods to normalize high ScvO(2) values by therapies that improve microcirculatory flow or mitochondrial dysfunction may be warranted.

Figure 1. Maximum ScvO2 groups – The Association of Hypoxia, Normoxia, and Hyperoxia with Mortality

The figure above shows the mortality rates by ScvO2 groups of hypoxia (<70%), normoxia (70-90%), and hyperoxia (> 90%). There was a significant difference in comparing the mortality rates for the hypoxia group (40%; 29 – 53%) versus the normoxia group (21%; 17 - 25%) and hyperoxia group (34%; 25 – 44%) versus normoxia (21%; 17 – 25%).

Figure 2. Schema for Classification of Oxygen Supply and Utilization

This figure show one approach to a general classification of the components of oxygen supply and utilization. More specifically, it may be used to better understand the types of failure that can occur, leading to cellular hypoxia. Oxygen supply, represented by the macrocirculation, is the oxygen contained in the blood leaving the heart. It is calculated as cardiac output (CO) × oxygen carrying capacity of the hemoglobin (Hb) × arterial oxygen saturation (SaO2) × 13.4 (a constant). The microcirculation consists of the small arterioles and capillaries where oxygen exchange generally occurs, while the mitochondria are where the oxygen is processed once it reaches the cells. 1) Macrocirculatory failure occurs when there is not enough oxygen supplied to meet the needs of the cells and is usually caused by hypotension, anemia, or hypoxemia, often in the setting of increased oxygen demand of the tissues/vital organs. 2) Microcirculatory failure occurs when there is global, or more often regionalized, shunting of blood, producing a disruption in the ability of oxygen to flow through the microcirculation to reach metabolically active tissues. Finally, 3) Mitochondria failure occurs when oxygenated blood is delivered to the tissues but the mitochondria can not process the oxygen. The ScvO₂ measurement occurs after all three types of failure have occurred.