Effects of methylene blue on microcirculatory alterations following cardiac surgery

Abstract

BACKGROUND Methylene blue is used as rescue therapy to treat catecholamine-refractory vasoplegic syndrome after cardiac surgery. However, its microcirculatory effects remain poorly documented.OBJECTIVE We aimed to study microcirculatory abnormalities in refractory vasoplegic syndrome following cardiac surgery with cardiopulmonary bypass and assess the effects of methylene blue.DESIGN A prospective open-label cohort study.SETTING 20-Bed ICU of a tertiary care hospital.PATIENTS 25 Adult patients receiving 1.5 mg kg À1 of methylene blue intravenously for refractory vasoplegic syndrome (defined as norepinephrine requirement more than 0.5 mg kg À1 min À1 ) to maintain mean arterial pressure (MAP) more than 65 mmHg and cardiac index (CI) more than 2.0 l min À1 m À2 .MAIN OUTCOME MEASURES Complete haemodynamic set of measurements at baseline and 1 h after the administration of methylene blue. Sublingual microcirculation was investigated by sidestream dark field imaging to obtain microvascular flow index (MFI), total vessel density, perfused vessel density and heterogeneity index. Microvascular reactivity was assessed by peripheral near-infrared (IR) spectroscopy combined with a vascular occlusion test. We also performed a standardised measurement of capillary refill time.RESULTS Despite normalised CI (2.6 [2.0 to 3.8] l min À1 m À2 ) and MAP (66 [55 to 76] mmHg), patients with refractory vasoplegic syndrome showed severe microcirculatory alterations (MFI < 2.6). After methylene blue infusion, MFI significantly increased from 2.0 [0.1 to 2.5] to 2.2 [0.2 to 2.8] (P ¼ 0.008), as did total vessel density from 13.5 [8.3 to 18.5] to 14.9 [10.1 to 14.7] mm mm À2 (P ¼ 0.02) and perfused vessel density density from 7.4 [0.1 to 11.5] to 9.1 [0 to 20.1] mm mm À2 (P ¼ 0.02), but with wide individual variation. Microvascular reactivity assessed by tissue oxygen resaturation speed also increased from 0.5 [0.1 to 1.8] to 0.7 [0.1 to 2.7]% s À1 (P ¼ 0.002). Capillary refill time remained unchanged throughout the study.CONCLUSION In refractory vasoplegic syndrome following cardiac surgery, we found microcirculatory alterations despite normalised CI and MAP. The administration of methylene blue could improve microvascular perfusion and reactivity, and partially restore the loss of haemodynamic coherence.

Prophylactic Administration with Methylene Blue Improves Hemodynamic Stabilization During Obstructive Jaundice–Related Diseases’ Operation: a Blinded Randomized Controlled Trial

“…It was found that microcirculatory is still abnormal despite normalization of blood pressure by vasopressors under this condition, which is considered the primary cause of kidney and hepatic dysfunction, and cardiac injury after the operations. 23 Methylene blue has been suggested as an adjuvant treatment in the setting of refractory hypotension. 24,25 Methylene blue reduces nitric oxide-mediated vasodilation via direct inhibitory of iNOS and soluble guanylate cyclase, 26 which attenuates remarkably low response to vasoconstrictor.…”

“…Methylene blue is recommended as an effective treatment of refractory hypotension which is not sensitive to catecholamine in the international guidelines. 27 Recently, it has been reported that methylene blue improved both macro-circulation and micro-circulation, and thus attenuates mismatch between macro-circulation and micro-circulation induced by administration with high dose of catecholamine, 23 which was regarded to contribute to improve hepatic and kidney function, and attenuated myocardium ischemic damage. It has been reported that methylene blue is routinely administrated as rescue therapy for catecholamine-refractory hypotension in the setting of cardiac surgery, sepsis shock, and liver transplantation.…”