Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis

Rossella Marino, Joachim Struck, Alan S Maisel, Laura Magrini, Andreas Bergmann, Salvatore Di Somma, Rossella Marino, Joachim Struck, Alan S Maisel, Laura Magrini, Andreas Bergmann, Salvatore Di Somma

Abstract

Introduction: The incidence of death among patients admitted for severe sepsis or septic shock is high. Adrenomedullin (ADM) plays a central role in initiating the hyperdynamic response during the early stages of sepsis. Pilot studies indicate an association of plasma ADM with the severity of the disease. In the present study we utilized a novel sandwich immunoassay of bioactive plasma ADM in patients hospitalized with sepsis in order to assess the clinical utility.

Methods: We enrolled 101 consecutive patients admitted to the emergency department with suspected sepsis in this study. Sepsis was defined by fulfillment of at least two systemic inflammatory response syndrome (SIRS) criteria plus clinical suspicion of infection. Plasma samples for ADM measurement were obtained on admission and for the next four days. The 28-day mortality rate was recorded.

Results: ADM at admission was associated with severity of disease (correlation with Acute Physiology and Chronic Health Evaluation II (APACHE II) score: r = 0.46; P <0.0001). ADM was also associated with 28-day mortality (ADM median (IQR): survivors: 50 (31 to 77) pg/mL; non-survivors: 84 (48 to 232) pg/mL; P <0.001) and was independent from and additive to APACHE II (P = 0.02). Cox regression analysis revealed an additive value of serial measurement of ADM over baseline assessment for prediction of 28-day mortality (P < 0.01). ADM was negatively correlated with mean arterial pressure (r = -0.39; P <0.0001), and it strongly discriminated those patients requiring vasopressor therapy from the others (ADM median (IQR): no vasopressors 48 (32 to 75) pg/mL; with vasopressors 129 (83 to 264) pg/mL, P <0.0001).

Conclusions: In patients admitted with sepsis, severe sepsis or septic shock plasma ADM is strongly associated with severity of disease, vasopressor requirement and 28-day mortality.

Figures

Figure 1
Figure 1
Plasma Adrenomedullin (ADM) concentrations depending on severity of disease. ADM concentrations are shown for patients with sepsis and severe sepsis/septic shock on admission.
Figure 2
Figure 2
Association of Adrenomedullin (ADM) with vasopressor treatment. ADM concentrations are shown for patients who received (yes) or did not receive (no) vasopressor treatment on admission.
Figure 3
Figure 3
Association of Adrenomedullin (ADM) with cause of death. Admission ADM concentrations are shown for patients depending on their intra-hospital cause of death.
Figure 4
Figure 4
Illustration of added value of serial Adrenomedullin (ADM) measurement. Kaplan-Meier Plots for survival are shown for patients with ADM values above or below 70 pg/mL on admission (left) and for the subgroup of patients, who were above 70 pg/mL on admission and spread into those with ADM values above or below 70 pg/mL 4 days later (right).

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