α-Atrial natriuretic peptide, cyclic guanosine monophosphate, and endothelin in plasma as markers of myocardial depression in human septic shock

Objective: To assess the value of alpha -atrial natriuretic peptide (alpha -ANP), second messenger cyclic guanosine monophosphate (cGMP,) and endothelin as markers of myocardial depression in septic shock. Design: Prospective observational study. Setting: Medical intensive care unit (ICU) of a university hospital. Patients: Fourteen consecutive patients with septic shock and arterial and pulmonary artery catheters in place. Measurements and Main Results: Hemodynamic variables and plasma levels of alpha -ANP, cGMP, and endothelin were measured every 6 hrs for 3 days after admission. Eight patients died from shock in the ICU. The nadir left ventricular stroke work index (LVSWI) was below 35 g/m(2) in all patients, and the median peak circulating alpha -ANP (n < 68 pg/mL) was 276 pg/mL (range, 79-1056), the median peak cGMP (n < 2.1 ng/ml) was 8.1 ng/mL (range, 3.2-29.7), and the median peak endothelin (n < 5.3 pg/mL) was 15.5 pg/mL (range, 8.5-33.9), supranormal in all patients. Outcome groups differed in the course of cardiac index and LVSWI, which were lower in nonsurvivors despite similar filling pressures and more intensive inotropic treatment (p < .01). The course of alpha -ANP, cGMP, and endothelin plasma levels also differed between groups, with higher levels in nonsurvivors (p < .05). As for pooled data, the mean daily or nadir LVSWI inversely related to mean daily or peak <alpha>-ANP, cGMP, and endothelin levels, respectively (p < .05). The area under the receiver operating characteristic curve for myocardial depression (LVSWI < 35 g/m(2)) was for alpha -ANP and endothelin 0.77, and for cGMP 0.85 (p < .01). The optimum cutoff values for <alpha>-ANP, cGMP, and endothelin were 172 pg/mL, 4.5 ng/mL, and 10.0 pg/mL, respectively. The sensitivity for myocardial depression of alpha -ANP, cGMP, and endothelin was 68%, 77%, and 72%, and the specificity was 82%, 93%, and 69%, respectively. Conclusions: circulating alpha -ANP, endothelin, and, particularly, cGMP may be markers of the myocardial depression of human septic shock, which is associated with mortality.