Sophie Orlowski

Background: Refractory cardiac arrest management relies on extracorporeal cardiopulmonary resuscitation (ECPR), requiring the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Circulatory flow recovery can be associated with an ischemia–reperfusion injury, leading to vasoplegia and vasopressor requirement. The aim of this work was to evaluate the impact on hemodynamics of a methylene blue bolus infusion in a porcine model of ischemic refractory cardiac arrest. Methods: Ischemic refractory cardiac arrest was induced in 20 pigs. After a low flow period of 30 min, VA-ECMO was initiated and the pigs were randomly assigned to the standard care group (norepinephrine + crystalloids) or methylene blue group (IV 2 mg·kg⁻¹ bolus of methylene blue over 30 min + norepinephrine and crystalloids). Macrocirculatory parameters and lactate clearance were measured. Sublingual microcirculation was evaluated with sidestream dark field (SDF) imaging. The severity of the ischemic digestive lesions was assessed according to the histologic Chiu/Park scale. Results: Eighteen pigs were included. The total crystalloid load (5000 (6000–8000) mL vs. 17,000 (10,000–19,000) mL, p = 0.007, methylene blue vs. standard care group) and catecholamine requirements (0.31 (0.14–0.44) μg·kg⁻¹·min⁻¹ vs. 2.32 (1.17–5.55) μg·kg⁻¹·min⁻¹, methylene blue vs. standard care group, p = 0.004) were significantly reduced in the methylene blue group. There were no significant between-group differences in lactate clearance, sublingual capillary microvascular parameters assessed by SDF or histologic Chiu/Park scale. Conclusions: In our refractory cardiac arrest porcine model treated with ECPR, methylene blue markedly reduced fluid loading and norepinephrine requirements in comparison to standard care during the first 6 h of VA-ECMO.

Administration of a selective β1-blocker, such as esmolol, in human septic shock has demonstrated cardiovascular protective effects related to heart rate reduction. Certain experimental data also indicate that esmolol exerts systemic anti-inflammatory and beneficial effects on vascular tone. Thus, the present study aimed to determine whether a non-chronotropic dose of esmolol maintains its protective cardiovascular and anti-inflammatory effects in experimental septic shock. Four hours after cecal ligation and puncture (CLP), Wistar male rats were randomly allocated to the following groups (n = 8): CLP, CLP + E-1 (esmolol: 1 mg.kg−1.h−1), CLP + E-5 (esmolol: 5 mg.kg−1.h−1), CLP + E-18 (esmolol: 18 mg.kg−1.h−1). An additional eight rats underwent sham operation. All rats received a continuous infusion of saline, analgesic and antibiotics 4 hours after the surgery. Assessment at 18 hours included in vivo cardiac function assessed by echocardiography and ex vivo vasoreactivity assessed by myography. Circulating cytokine levels (IL-6 and IL-10) were measured by ELISA. Cardiac and vascular protein expressions of p-NF-κB, IκBα, iNOS, p-AKT/AKT and p-eNOS/eNOS were assessed by western blotting. CLP induced tachycardia, hypotension, cardiac output reduction, hyperlactatemia and vascular hypo-responsiveness to vasopressors. Compared to CLP animals, heart rate was unchanged in CLP + E-1 and CLP + E-5 but was reduced in CLP + E-18. Stroke volume, cardiac output, mean arterial pressure and lactatemia were improved in CLP + E-1 and CLP + E-5, while vascular responsiveness to phenylephrine was only improved in CLP + E-5 and CLP + E-18. Plasma IL-6 levels were decreased in all esmolol groups. p-NF-κB was decreased in both cardiac and vascular tissues in CLP + E-5 and CLP + E-18. In experimental septic shock, low doses of esmolol still improved cardiac function and vasoreactivity. These benefits appear to be associated with a modulation of inflammatory pathways.