Abstract
IntroductionThe 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.MethodsWe 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.ResultsADM 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).ConclusionsIn patients admitted with sepsis, severe sepsis or septic shock plasma ADM is strongly associated with severity of disease, vasopressor requirement and 28-day mortality.
Highlights
The incidence of death among patients admitted for severe sepsis or septic shock is high
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
Using a novel ADM sandwich immunoassay, which selectively detects the bioactive C-terminally amidated ADM variant, this study demonstrates that plasma ADM levels in septic patients admitted to the Emergency Department (ED) increase with the severity of disease, correlate with the requirement for vasopressor therapy, and are associated with the 28-day mortality rate similar to APACHE II
Summary
The incidence of death among patients admitted for severe sepsis or septic shock is high. 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. The global incidence of severe sepsis is greater than of either cancer or myocardial infarction, with a mortality rate estimated at 40% [1,2,3] This high mortality is in many cases linked to multi-organ hypoperfusion and hypotension associated with the development of septic shock. Previous studies indicate that ADM plays a major role in initiating the hyperdynamic response during the early stages of polymicrobial sepsis [13,14]. Our study aimed to explore the clinical utility of basal and serial plasma ADM assessments in patients hospitalized for sepsis using this new assay
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