Impaired β-adrenergic receptor stimulation of cyclic adenosine monophosphate in human septic shock: Association with myocardial hyporesponsiveness to catecholamines

Objectives: To determine whether myocardial hyporesponsiveness to administered catecholamines occurs in human sepsis and whether this phenomenon is associated with impaired β-adrenergic receptor stimulation of cyclic adenosine monophosphate. Design: Prospective study. Setting: Medical ICU in a university hospital. Patients: Normal human volunteers (n = 7), critically ill patients who were not septic (n = 9), septic patients not in shock (n = 16), and septic patients in shock (n = 17). Measurements and Main Results: Pulmonary artery catheter-derived hemodynamic data were obtained in patients with sepsis and septic shock. Isoproterenol and sodium fluoride- stimulated cyclic adenosine monophosphate accumulations were measured in circulating lymphocytes. The hemodynamic response to sequential infusions of dobutamine, 5 and 10 μg/kg/min, was obtained in septic and septic shock patients. Baseline hemodynamic values for mean arterial pressure, cardiac index, left ventricular stroke work index, and oxygen delivery index at approximately 2 days after the onset of sepsis were significantly lower in septic shock patients compared with septic (nonshock) patients (p < .01, p < .05, p < .001, p < .01, respectively). Isoproterenol- and sodium fluoride- stimulated cyclic adenosine monophosphate accumulations were significantly reduced in septic shock patients compared with those accumulations observed in septic patients (p < .01 and p < .001, respectively). The heart rate response to 10 μg/kg/min of dobutamine was significantly (p < .01) lower in septic shock patients compared with septic patients. Conclusions: In patients with septic shock, impaired β-adrenergic receptor stimulation of cyclic adenosine monophosphate is associated with myocardial hyporesponsiveness to catecholamines, suggesting that β-adrenergic receptor dysfunction may contribute to the reduced myocardial performance observed in this shock state.