No abstract

No abstract

Sacha et al (1) showed that vasopressin was utilized in 42.6% of acute kidney injury (AKI) before and increased to 54.6 % after rebranding, which seems to be high despite the cost increase. We reviewed potential justifications for the vasopressin increased use in AKI during septic shock (SS) after rebranding (2). Just after rebranding in 2016, Gordon et al (2) reported the results of the multicenter trial Vasopressin vs Norepinephrine as Initial Therapy in Septic Shock (VANISH), which compared the effect of these two vasopressors on AKI in adult patients with SS. Rationale for this study was the landmark Vasopressin and Septic Shock Trial (VASST), done in 2014 before rebranding. This study found an association between low-dose vasopressin (0.01-0.03 U/min) and decreased mortality in less severe SS but no difference between vasopressin and norepinephrine on global mortality or organ dysfunction rates (3). Post hoc analysis of the VASST study suggested that vasopressin treatment is associated with reduced progression to AKI, decreased need for renal replacement therapy (RRT), and reduced mortality in SS patients at risk of AKI (4). This concurred with earlier small clinical studies, demonstrating improvement in creatinine clearance (CCL) in vasopressin-treated patients (4). In the VANISH study, there were fewer RRTs in the vasopressin group (2).Unfortunately, the VANISH study did not find a difference in the number of kidney failure-free days in surviving patients receiving vasopressin or norepinephrine (2). The reduction in the number of RRTs in the vasopressin group but without any difference in the number of kidney failure-free days in survivors between groups had procured only some meager scientific solace (4). Many meta-analyses, however, did not reveal any significant improvements with vasopressin regarding AKI (4). Since rebranding, only one study has shown a favorable effect of vasopressin on AKI risk in sepsis. This was a study performed in an ovine model of sepsis by Okazaki et al (5). This study showed that vasopressin infusion did not significantly affect renal medullary perfusion or Po 2 and induced a sustained (6 hr) ~2.5-fold increase in CCL (5). Vasopressin reduced sepsis-induced mesenteric hyperemia (+61 ± 13 to +9% ± 6%) (5). Norepinephrine transiently (2 hr) improved CCL (by ~3.5-fold) but worsened renal medullary ischemia (to -64% ± 7%) and hypoxia (to -71% ± 6%) (5). Therefore, clearly, low-dose vasopressin (0.03 international units [IU]/min [0.03-0.05 IU/min]) as first vasopressor

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.

No abstract

No abstract

No abstract

No abstract