Central venous oxygen saturation in septic shock - a marker of cardiac output, microvascular shunting and/or dysoxia?

Shock therapy aims at increasing central venous oxygen saturation (ScvO2), which is a marker of inadequate oxygen delivery. In this issue of Critical Care, Textoris and colleagues challenge this notion by reporting that high levels of ScvO2 are associated with mortality in patients with septic shock. This is of obvious interest, but as their retrospective design has inherent limitations, the association should be confirmed in a prospective, multicenter study with protocolized ScvO2 measurements and detailed registration of potentially confounding factors.

In this issue of Critical Care, Textoris and colleagues [1] report that high levels of central venous oxygen saturation (ScvO 2 ) are associated with mortality in patients with septic shock. ScvO 2 is easily measured in most ICU patients and thus represents a convenient therapeutic marker in the resuscitation of the critically ill patient. Low ScvO 2 is a valid therapeutic target in early septic shock [2,3] and a diagnostic marker for low cardiac output [4]. ScvO 2 itself is a surrogate marker of mixed venous oxygen saturation, which in theory refl ects the balance between global oxygen delivery and consumption, so that low ScvO 2 is a marker of inadequate oxygen delivery. Still we do not fully understand the pathophysio logical and clinical meaning of altered ScvO 2 .
So far, the focus has mostly been on low levels of ScvO 2 , but Textoris and co-workers [1] have focused on higher levels of ScvO 2 in septic shock patients. Th ey hypothesise that levels of ScvO 2 above 80% correlate with increased mortality and that this correlation is likely due to impaired ability to extract oxygen. In a retrospective design, they identifi ed all adult ICU patients with septic shock in a 2-year period and registered lowest and highest ScvO 2 measurements during the fi rst 3 days in the ICU. Th ey found that the maximum ScvO 2 was signifi cantly higher in the patients that died in hospital than in those who survived (85% versus 79%, P = 0.009). In contrast, the minimum ScvO 2 did not diff er between these groups. Th e association between maximum ScvO 2 and mortality persisted in a multivariate analysis adjusting for other variables that diff ered between the survivors and non-survivors.
Th is is of obvious interest, but the study has several limitations, as the authors point out. Th e retrospective design carries an inherent risk of selection bias since patients with mild disease or early death might not have had any ScvO 2 measurements and were then excluded from the study. Furthermore, ScvO 2 might have been measured more frequently in the most severely ill patients, increasing the chance for a high ScvO 2 measurement, especially as ScvO 2 varies over time.
Th e interpretation of ScvO 2 remains a challenge. ScvO 2 depends on arterial oxygen saturation, cardiac output, oxygen consumption, haemoglobin levels and shunting. Th e ability of ScvO 2 to refl ect systemic oxygen delivery/ consumption is not constant in time as it depends on many conditions, including sedation, ventilator treatment [5], redistribution of blood as seen in shock [6] and thus shock severity, the position of the catheter tip, which depends on the body position [7], and so on. Th us, the complex mechanisms infl uencing ScvO 2 hamper the interpretation.
Textoris and co-workers hypothesise that the high ScvO 2 in the non-survivor group is likely due to impaired oxygen extraction, but there may be other explanations. It is likely that very aggressive resuscitation with high doses of fl uid, vasopressors, inotropes and blood resulting in supranormal oxygen delivery, and thus high ScvO 2 , negatively impacts on survival [8]. Alternatively, impaired regulation of the microcirculation might have resulted in shunting and thus high ScvO 2 . Other, un known confounders may also have existed. Th e current data cannot distinguish between these alternative hypo the ses as discussed by the authors.
If high ScvO 2 associates with increased mortality in sepsis, it may have clinical implications. But the hypothesis should be evaluated in a prospective, multicentre study with protocolized ScvO 2 measurements and detailed registration of potentially confounding factors, including use of fl uid, vasopressors, inotropes and blood, to reduce the risk of bias. Results from such a study have the potential to infl uence the design of further clinical trials evaluating ScvO 2 as a target for shock therapy.