To investigate the increase in plasma cyclic GMP (cGMP) concentrations in humans with hyperkinetic septic shock (SS) and to evaluate its relationship to low systemic vascular resistance (SVR).

Prospective clinical investigation.

Medical intensive care unit of a university hospital.

22 patients with documented SS requiring hemodynamic resuscitation, respiratory support and —in some cases — hemodialysis.

Hemodynamic data were recorded at admission time and then twice a-day during the following 72 h. We simultaneously measured cyclic GMP, atrial natriuretic peptides (ANP), creatininemia and platelet counts. At admission time, higher plasma cGMP concentrations were observed in patients with SS (11.84±1.52 pmol·ml⁻¹) than in healthy controls (1.77±0.18 pmol·ml⁻¹,p<0.0001), in septicemia patients without circulatory failure (3.28±0.36 pmol·ml⁻¹,p<0.005) or in patients with hyperkinetic non-septic shock (3.6±0.7 pmol·ml⁻¹,p<0.02). In contrast, there was no significant difference between patients with SS and controls with anuria from non-septic origin. Also ANP concentrations were higher in patients with SS than in others. In addition, cGMP levels correlated negatively with SVR during the first 48 h of the study, and positively with creatininemia later when renal function worsened. However, they did not correlate significantly with ANP.

These data demonstrate that a significant increase in plasma cGMP concentrations occurs during human SS and that it correlates with the decline in peripheral vascular resistance in the absence, but not in the presence, of severe renal failure. Furthermore, the increase in cGMP levels cannot be ascribed solely to enhanced ANP-induced particulate guanylyl cyclase activity. Thus, our results suggest the occurrence of another endogenous source of cGMP during hyperkinetic SS.