Mechanical Circulatory Support in Refractory Vasodilatory Septic Shock: a Randomized Controlled Porcine Study

Abstract

As controversy persists regarding the benefits of mechanical circulatory support in septic shock with a predominantly vasoplegic phenotype, preclinical studies may provide a useful alternative to fill the actual knowledge gap. Here, we investigated the physiologic responses to venoarterial extracorporeal membrane oxygenation therapy (VA-ECMO) in a clinically relevant porcine peritonitis-induced model of refractory vasodilatory septic shock. In 12 anesthetized, mechanically ventilated, and instrumented domestic pigs, septic shock was induced by intraperitoneally inoculating autologous feces. After reaching the threshold for refractory vasodilatory shock (norepinephrine dose ≥1 μg/kg/min), the pigs were randomized into the conservative treatment group (control) or the VA-ECMO group (target flow 100 mL/kg/min). The time to develop refractory vasodilatory shock was similar in both groups (18.8 h in the ECMO group, 18.1 h in the control group). There was no difference between the groups in terms of time to death measured from the point of reaching the predefined vasopressor threshold (7.1 h for the ECMO group, 7.9 h for the control group). The initiation of ECMO resulted in a markedly increased fluid and vasopressor support. Although treatment with ECMO compromised neither renal nor carotid blood flow initially, both progressively decreased later during the experiment. The pattern of sepsis-induced multiorgan injury, alterations in energy metabolism, and the systemic inflammatory response were remarkably similar between both groups. In conclusion, the application of VA-ECMO in this model of peritonitis-induced refractory vasodilatory septic shock aggravated hemodynamic deterioration. Our findings contribute to increasing equipoise with respect to the clinical utility of VA-ECMO in refractory vasodilatory shock.

Clinical Pearls of Venoarterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock

“…However, the evidence of its benefits in adult patients is weak, particularly in cases of refractory septic shock 34). Controversies surrounding the benefits of ECMO in septic shock with a predominantly vasoplegic phenotype persist 35). Favorable outcomes of VA ECMO in patients with septic shock combined with heart failures have been reported for recent years 36)37)38)39)…”

Angiotensin II for Vasodilatory Hypotension in Patients Requiring Mechanical Circulatory Support

“…Although these devices are used in the setting of cardiac and/or respiratory failure, and they increase circulatory blood flow (depending on configuration), they themselves do not reverse hypotension. 2 In fact, exposure to the nonbiological, non-endothelialized surfaces of the devices activates inflammatory pathways invoking a state mimicking the systemic inflammatory response syndrome thereby inducing hypotension. 13 There may be biological plausibility for increased response and favorable outcome to angiotensin II treatment in these patients.…”

“…1 These devices may be deployed as a temporary intervention to bridge to recovery or transplantation, or as a form of durable support for the remainder of a patient's life. Although these devices restore circulatory blood flow, they do not reverse vasodilatory shock, 2 a common, yet devastating syndrome with death rates of 30% to 50% depending on the underlying etiology. 3–5 Attention to correcting underlying pathologies responsible for shock (eg, sepsis) is paramount to achieving a positive outcome.…”

Mechanical circulatory support with Impella 5.0 in septic shock

“…Data from studies involving septic patients receiving temporary MCS with ECMO show very high (64%‐93%) mortality rates 1 . A recent experimental study has further confirmed these clinical observations 2 . The Impella 5.0 is a temporary left ventricular assist device, which has shown favorable outcomes in terms of hemodynamic recovery in cardiogenic shock 3 .…”