Figure 1Study flow chart. Ig, immunoglobulin; MODS, multiple organ dysfunction syndrome; SIRS, systemic inflammatory Vandetanib VEGFR response syndrome.Table 1Demographic characteristics of patients enrolled in the studyThe study end point was the kinetics of serum IgM upon progression from severe sepsis to septic shock in relation with final outcome. To reach this end point, a three-step approach was followed (Figure 1) (a) circulating IgM was compared between critically ill patients with varying severity; (b) circulating IgM was measured at baseline and on the first day of worsening; and (c) distribution of IgM was compared over time between survivors and non-survivors from septic shock.Median IgM was 44.1 mg/dl in healthy volunteers; 34.9 mg/dl in SIRS; 23.0 mg/dl in sepsis; 36.2 mg/dl in severe sepsis; and 21.
9 mg/dl in septic shock. Statistical analysis showed that serum IgM was decreased in septic shock compared to healthy volunteers (P = 0.001), to patients with SIRS (P = 0.028) and to patients with severe sepsis (P <0.0001) but not to patients with uncomplicated sepsis (P = 0.754) (Figure 2).Figure 2Circulating immunoglobulin M (IgM) at various stages of severity. IgM levels were measured in serum within the first 24 hours from diagnosis of systemic inflammatory response syndrome (SIRS) (n= 41), of sepsis (n= 100), of severe sepsis (n= 113) and of ...Paired comparisons of IgM were done for 83 patients at two specific time points: on initial diagnosis and on worsening.
These measurements involved: 13 patients initially diagnosed with uncomplicated sepsis who worsened into severe sepsis; 16 patients initially diagnosed with uncomplicated sepsis who worsened into septic shock; 49 patients initially diagnosed with severe sepsis who worsened into septic shock; and five patients initially diagnosed with septic shock who worsened into MODS (Figure 3). From all these paired comparisons, significant changes of circulating IgM were found only between severe sepsis and septic shock; IgM was significantly decreased upon worsening from severe sepsis into septic shock (P = 0.039).Figure 3Changes of circulating immunoglobulin M (IgM) upon worsening of sepsis. IgM was measured: in panel (A) in 13 patients within the first 24 hours from diagnosis of sepsis and repeated within the first 24 hours of worsening into severe sepsis; in panel …
Within the enrolled population with septic shock, serum IgM did not differ between survivors and non-survivors (median IgM of survivors Carfilzomib 23.1 mg/dl and of non-survivors 20.7 mg/dl, P = 0.442). The time curves of IgM were designed for 30 patients with severe sepsis who progressed into septic shock. Sampling was started on the day of the start of vasopressors and lasted for seven consecutive days. Separate curves were designed for survivors and non-survivors.
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