Potential Confounders in Study Concluding Higher Lactate at Vasopressin Initiation Is Associated With Higher Mortality in Septic Shock

Abstract

Sacha et al (1) concluded that higher norepinephrine-equivalent dose and higher lactate concentration at vasopressin initiation were each associated with higher inhospital mortality after vasopressin administration in patients with septic shock. When examining the population characteristics, it was noted that, in the survivor group, there were 13.2% patients with cirrhosis and 10% with hepatic failure, whereas in the nonsurvivor group, there were 19.5% patients with cirrhosis (p < 0.01) and 16.2% with hepatic failure (p < 001) (1). Cirrhosis and hepatic failure are crucial characteristics that were not taken into account in the discussion or limitations (1). Kluge et al (2) showed that lactate levels at admission to the ICU in cirrhotic patients in septic shock are significantly associated with the number of failing organs and mortality. Baseline lactate levels are an independent predictor for the severity of the underlying disease (2). Twelve-hour lactate clearance has a strong predictive prognosis for survival in patients with abnormal baseline lactate levels, with better outcomes associated with a greater decrease in lactate during the initial therapy (2). Evidently, cirrhotic patients have significantly higher lactate levels due to reduced hepatic clearance and, therefore, have a higher mortality rate during septic shock (2). So clearly, concluding that higher lactate levels at vasopressin initiation are associated with a higher inhospital mortality in septic shock patients who received vasopressin is not accurate when considering the confounding variables. The higher lactate levels are simply due to reduced liver clearance in the patients with cirrhosis and hepatic failure in the nonsurvivor group (1). In another study conducted by Yang and Hsu (3), patients in the nonsurvivor group had significantly higher serum lactate levels compared with the patients in the survivor group (adjusted hazard ratio = 1.03; p < 0.01), but in this study, chronic liver failure and cirrhosis and serum lactate were identified as independent prognostic factors in their multivariate regression model, further showing that these confounding variables have been already addressed in literature. In conclusion, assuming an association between inhospital mortality rate and lactate levels at vasopressin initiation when the nonsurvivor group has significantly more patients with cirrhosis and hepatic failure than the survivor group significantly reduces the reliability of the data.

Clinical value of CVP+VIVC in predicting fluid resuscitation in patients with septic shock

“…The static pressure index, which indirectly describes the level of cardiac preload through pressure, which is only applicable to the volume assessment of hypovolemic patients. Since the relationship between pressure and volume is not a simple linear relationship, its accuracy and reliability are not high 6 . The static volume index can reflect the cardiac preload more accurately than the pressure index.…”

The authors reply

“…We appreciate the interest by Honore et al (1) in our recently published article (2) in Critical Care Medicine , evaluating the association of catecholamine dose, lactate, and shock duration at vasopressin initiation with mortality in patients with septic shock. We agree with the posed comments and acknowledge the potential confounding associated with the patients in our study (2) who have either cirrhosis or hepatic failure as lactate concentrations have been shown to be associated with mortality and morbidity outcomes in this population (3).…”