Haemodynamic effects of selective venoconstriction with centhaquine in spontaneously breathing patients with mixed hypovolaemic-vasodilatory shock

Abstract

Circulatory shock remains difficult to manage because fluid resuscitation and catecholamines may exacerbate vascular dysfunction and tissue hypoperfusion. This prospective physiological analysis, embedded within a multicentre phase IV study, examined whether selectively targeting the venous circulation with centhaquine improves circulatory dynamics in spontaneously breathing patients with mixed hypovolaemic–vasodilatory shock (MHVS). Fifteen spontaneously breathing adults with MHVS received centhaquine (0.01 mg kg⁻¹) in addition to standard care. Over 300 min, mean circulatory filling pressure analogue increased from 6.03 ± 0.22 to 7.28 ± 0.21 mmHg and driving pressure for venous return from 5.88 ± 0.22 to 7.16 ± 0.21 mmHg (adjusted P < 0.001 for both), while estimated central venous pressure remained near atmospheric pressure and resistance to venous return remained unchanged. Cardiac output increased from 5.62 ± 0.22 to 6.80 ± 0.24 L min⁻¹ and mean arterial pressure from 56.8 ± 1.5 to 69.8 ± 2.0 mmHg (adjusted P < 0.001 for both). Effective arterial elastance and systemic vascular resistance did not significantly change over time. Patients received 677 ± 79 mL of crystalloids during the study period, and no drug-related adverse events were observed. The findings of this preliminary physiological study suggest that selective venoconstriction may augment venous return and systemic haemodynamics in spontaneously breathing patients with MHVS without evidence of major adverse haemodynamic effects.