Effect of norepinephrine challenge on cardiovascular determinants assessed using a mathematical model in septic shock: a physiological study

Abstract

BACKGROUND: The present study investigated the cardiovascular determinants of cardiac output (CO), mean systemic filling pressure analogue (Pmsa) derived by Geoffrey Parkin, efficiency of heart (Eh) and related parameters to a norepinephrine (NE) challenge [an increase of 10 mmHg mean arterial pressure (MAP) by NE] in septic shock patients using of a mathematical model. METHODS: Twenty-seven septic shock patients with pulse index continuous cardiac output (PiCCO) monitoring were enrolled. These patients required NE to maintain an individualized MAP for organ perfusion after early fluid resuscitation based on their clinical condition. NE was decreased to obtain a decrease of 10 mmHg from base MAP (MAP(-10mmHg)), and the NE doses were adjusted to return MAP to baseline (MAP(base)) and produce an increase of 10 mmHg from MAP(base) (MAP(+10mmHg)). Two NE challenge episodes were analyzed for each patient: from MAP(-10mmHg) to MAP(base) and from MAP(base) to MAP(+10mmHg). The Pmsa, pressure gradient for venous return (PG(vr)), and Eh (PGvr relative to Pmsa) were estimated using a mathematical model for the three MAP levels (MAP(-10mmHg), MAP(base) and MAP(+10mmHg)). RESULTS: A total of 54 episodes of NE challenges were obtained in 27 patients. Significant and consistent increases were observed in the central venous pressure (CVP), Pmsa, and PGvr in response during the NE titration. $Δ$CO negatively and significantly correlated with $Δ$CVP (r=-0.722, P<0.0001), $Δ$Pmsa (r=-0.549, P<0.0001), $Δ$Resistance of venous return (Rvr) (r=-0.597, P<0.0001), and $Δ$Resistance of systemic vascular beds (Rsys) (r=-0.597, P<0.0001). Episodes of decreasing CO/Eh were associated with a higher $Δ$CVP than the CO/Eh-increasing episodes. The area under the curve (AUC) of $Δ$CVP to predict decreased CO by the incremental NE was 0.86, and the AUC of $Δ$CVP to predict decreased Eh was 0.94. A cutoff of $Δ$CVP >1.5 mmHg for detecting decreased CO resulted in a sensitivity of 75% and a specificity of 94.1%. A cutoff of $Δ$CVP >1.5 mmHg for detecting decreased Eh resulted in a sensitivity of 64.3% and a specificity of 100%. CONCLUSIONS: There were a highly divergent response in Eh and CO to afterload challenge episodes of an NE-induced 10mmHg increase in MAP. An increase in CVP may be an early alarm to identify the reduction in CO/Eh during an NE-induced increase of MAP.