Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock

Abstract

Rationale: Changes in plasma cytokine levels may predict mortality, and therapies (vasopressin versus norepinephrine) could change plasma cytokine levels in early septic shock.

Objectives: Our hypotheses were that changes in plasma cytokine levels over 24 hours differ between survivors and nonsurvivors, and that there are different effects of vasopressin and norepinephrine on plasma cytokine levels in septic shock.

Methods: We studied 394 patients in a randomized, controlled trial of vasopressin versus norepinephrine in septic shock. We used hierarchical clustering and principal components analysis of the baseline cytokine concentrations to subgroup cytokines; we then compared survivors to nonsurvivors (28 d) and compared vasopressin- versus norepinephrine-induced changes in cytokine levels over 24 hours.

Measurements and main results: A total of 39 plasma cytokines were measured at baseline and at 24 hours. Hierarchical clustering and principal components analysis grouped cytokines similarly. Survivors (versus nonsurvivors) had greater decreases of overall cytokine levels (P < 0.001). Vasopressin decreased overall 24-hour cytokine concentration compared with norepinephrine (P = 0.037). In less severe septic shock, the difference in plasma cytokine reduction over 24 hours between survivors and nonsurvivors was less pronounced than that seen in more severe septic shock. Furthermore, vasopressin decreased interferon-inducible protein 10 and granulocyte colony-stimulating factor more than did norepinephrine in less severe septic shock, whereas vasopressin decreased granulocyte-macrophage colony-stimulating factor in patients who had more severe shock.

Conclusions: Survivors of septic shock had greater decreases of cytokines, chemokines and growth factors in early septic shock. Vasopressin decreased 24-hour plasma cytokine levels more than did norepinephrine. The vasopressin-associated decrease of cytokines differed according to severity of shock. Clinical trial registered with www.controlled-trials.com (ISRCTN94845869).

Figure 1.

Principal components analysis (PCA) of baseline plasma cytokine concentrations in patients who had septic shock. The axes represent the loadings of first three principal components after varimax rotation.

Figure 2.

Hierarchical clustering of baseline plasma cytokine concentrations in patients who had septic shock. Each patient is in each column and each cytokine is in each row. The color code shows log 10 plasma cytokine concentrations below (blue tones), at the median (black tones), or above (yellow tones) the median. The vertical axis on the left shows the color code of each cytokine classified as proinflammatory, antiinflammatory, chemokine, growth factor, pleiotropic, and unclassified.