Measurement of mean systemic filling pressure after severe hemorrhagic shock in swine anesthetized with propofol-based total intravenous anesthesia: implications for vasopressor-free resuscitation

Abstract

Background:Mean systemic filling pressure (Pmsf) is a quantitative measurement of a patient's volume status and represents the tone of the venous reservoir. The aim of this study was to estimate Pmsf after severe hemorrhagic shock and cardiac arrest in swine anesthetized with propofol-based total intravenous anesthesia, as well as to evaluate Pmsf's association with vasopressor-free resuscitation. Methods: Ten healthy Landrace/Large-White piglets aged 10-12 weeks with average weight 20 ± 1 kg were used in this study. The protocol was divided into four distinct phases: stabilization, hemorrhagic, cardiac arrest, and resuscitation phases. We measured Pmsf at 5-7.5 seconds after the onset of cardiac arrest and then every 10 seconds until 1 minute postcardiac arrest. During resuscitation, lactated Ringers was infused at a rate that aimed for a mean right atrial pressure of ≤ 4 mm Hg. No vasopressors were used. Results: The mean volume of blood removed was 860 ± 20 ml (blood loss, ~61%) and the bleeding time was 43.2 ± 2 minutes while all animals developed pulseless electrical activity. Mean Pmsf was 4.09 ± 1.22 mm Hg, and no significant differences in Pmsf were found until 1 minute postcardiac arrest (4.20±0.22 mm Hg at 5-7.5 seconds and 3.72±0.23 mm Hg at 55-57.5 seconds; P=0.102). All animals achieved return of spontaneous circulation (ROSC), with mean time to ROSC being 6.1 ±1.7 minutes and mean administered volume being 394 ±20 ml. Conclusions: For the first time, Pmsf was estimated after severe hemorrhagic shock. In this study, Pmsf remained stable during the first minute post-arrest. All animals achieved ROSC with goal-directed fluid resuscitation and no vasopressors.

Resuscitative Effect of Centhaquine (Lyfaquin®) in Hypovolemic Shock Patients: A Randomized, Multicentric, Controlled Trial

“…Based on the mechanism of action, centhaquine increases venous return to the heart and increases cardiac output and tissue perfusion, making it an ideal candidate for use as a resuscitative agent in treating patients with hypovolemic patients. The venous system is critical following haemorrhage in mobilizing unstressed blood volume to preserve or increase venous blood return to the heart and increase cardiac output [ 37 , 38 ]. Centhaquine helps the venous system convert unstressed blood volume to stressed blood volume and optimize cardiac output to maintain blood circulation in a state of shock.…”

A Multicentric, Randomized, Controlled Phase III Study of Centhaquine (Lyfaquin®) as a Resuscitative Agent in Hypovolemic Shock Patients

“…In total, 60–70% of the total blood volume pooled in the venous system is adjustable [ 54 ]. The venous system is critically important following hemorrhage because it can be used to mobilize pooled (unstressed) blood volume towards systemic (stressed) circulation [ 35 , 55 ]. In a patient with hypovolemic shock, centhaquine converts the venous unstressed blood volume to stressed blood volume and improves cardiac output and blood circulation, making it an ideal candidate for the resuscitation of patients.…”

“…Patients with uncontrolled bleeding undergo damage-control resuscitation to stop blood loss and initiate resuscitation, keeping in mind permissive hypotension targeting a mean arterial pressure of 65 mmHg [ 67 , 68 ]. Resuscitation with centhaquine is likely to limit the use of vasopressors and may help achieve resuscitation free of arterial constriction [ 35 ]. If required, a balanced resuscitation may be followed by blood or blood product transfusion in a ratio similar to that of whole blood [ 67 ].…”

“…Stimulation of α 2B adrenergic receptors, located on the smooth muscle cells [ 32 ], produced dose-dependent constriction of human veins [ 33 ]. Centhaquine is a novel first-in-class resuscitative agent that acts on α 2B adrenergic receptors to produce venous constriction and increase venous return to the heart, resulting in increased cardiac output [ 34 , 35 ]. It also has little action on α 2A adrenergic receptors to reduce sympathetic drive and decrease systemic vascular resistance [ 36 ], contributing to improved tissue blood perfusion.…”

A Critical Appraisal of the Effects of Anesthetics on Immune-system Modulation in Critically Ill Patients With COVID-19

“…98 Inhibition of the development of severe inflammation and the enhancement of inflammation resolution by anesthetics may be a promising alternative approach to limiting severe organ damage and improving outcomes in patients with COVID-19. 102 Based on current evidence, midazolam, propofol, ketamine, dexmedetomidine, opioids, rocuronium, cisatracurium, and succinylcholine may have favorable immunomodulatory effects when used in the induction or maintenance of anesthesia. However, etomidate may be harmful, and its use may be questionable.…”