Centhaquine Increases Stroke Volume and Cardiac Output in Patients with Hypovolemic Shock

Abstract

Background: Centhaquine is a resuscitative agent that acts on alpha-2B adrenergic receptors to enhance venous return in hypovolemic shock. The effect of centhaquine on cardiac output in patients with hypovolemic shock has not been reported. Methods: Trans-thoracic echocardiography was utilized to measure stroke volume (SV), cardiac output (CO), left ventricular outflow tract-velocity time integral (LVOT-VTI), left ventricular outflow tract diameter (LVOTd), heart rate (HR), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (FS) and inferior vena cava (IVC) diameter before (0 min) and after centhaquine (0.01 mg/kg, iv infusion over 60 min) treatment (60 min, 120 min, and 300 min) in 12 randomly selected patients with hypovolemic shock enrolled in a prospective, multicenter, open-label phase IV clinical study (NCT05956418) of centhaquine in patients with hypovolemic shock. Results: A significant increase in SV (mL) was observed after 60, 120, and 300 minutes of centhaquine treatment. CO (mL/min) increased significantly at 120 and 300 min despite a decrease in HR at these times. A significant increase in IVC diameter and LVOT-VTI (mL) at these time points was observed, which indicated increased venous return. The LVEF and FS did not change, while the mean arterial pressure (MAP, mmHg) increased in patients after 120 and 300 minutes of centhaquine treatment. Positive correlations between IVC diameter and SV (R2 = 0.9556) and between IVC diameter and MAP (R2 = 0.8928) were observed, which indicated the effect of centhaquine mediated increase in venous return on SV, CO, and MAP. Conclusions: Centhaquine mediated increase in venous return appears to play a critical role in enhancing SV, CO, and MAP in patients with hypovolemic shock; these changes could be pivotal for reducing shock-mediated circulatory failure, promoting tissue perfusion, and improving patient outcomes. Trial registration: The phase IV trial reported in this study has Clinical Trials Registry, India; ctri.icmr.org.in, CTRI/2021/01/030263; clinicaltrials.gov, NCT05956418.