Microcirculatory changes during open label magnesium sulphate infusion in patients with severe sepsis and septic shock

Andrius Pranskunas,Vidas Pilvinis,Matty Koopmans,E Christiaan Boerma,Namkje Ar Vellinga

doi:10.1186/1471-2253-11-12

Abstract

BackgroundMicrocirculatory alterations play a pivotal role in sepsis and persist despite correction of systemic hemodynamic parameters. Therefore it seems tempting to test specific pro-microcirculatory strategies, including vasodilators, to attenuate impaired organ perfusion. As opposed to nitric oxide donors, magnesium has both endothelium-dependent and non-endothelium-dependent vasodilatory pathways.MethodsIn a single-center open label study we evaluated the effects of magnesium sulphate (MgS) infusion on the sublingual microcirculation perfusion in fluid resuscitated patients with severe sepsis and septic shock within the first 48 hours after ICU admission. Directly prior to and after 1 hour of magnesium sulphate (MgS) infusion (2 gram) systemic hemodynamic variables, sublingual SDF images and standard laboratory tests, were obtained.ResultsFourteen patients (12 septic shock, 2 severe sepsis) with a median APACHE II score of 20 were enrolled. No significant difference of the systemic hemodynamic variables was found between baseline and after MgS infusion. We did not observe any significant difference pre and post MgS infusion in the primary endpoint microvascular flow index (MFI) of small vessels: 2.25(1.98-2.69) vs. 2.33(1.96-2.62), p = 0.65. Other variables of microcirculatory perfusion were also unaltered. In the overall unchanged microvascular perfusion there was a non-significant trend to an inverse linear relationship between the changes of MFI and its baseline value (y = -0.7260 × + 1.629, r2 = 0.270, p = 0.057). The correlation between baseline Mg concentrations and the change in MFI pre- and post MgS infusion was non-significant (rs = -0.165, p = 0.67).ConclusionsIn the setting of severe sepsis and septic shock sublingual microcirculatory alterations were observed despite fulfillment of sepsis resuscitation guidelines. After infusion of a limited and fixed dose of MgS, microcirculatory perfusion did not improve over time.Trial registrationClinicalTrials.gov NTC01332734.

Highlights

Microcirculatory alterations play a pivotal role in sepsis and persist despite correction of systemic hemodynamic parameters
Our study aims to test the hypothesis that magnesium sulphate (MgS) infusion may improve sublingual microcirculatory perfusion in patients with severe sepsis and septic shock
Hospital mortality was 57% and all patients survived the first day after MgS infusion

Summary

Introduction

Microcirculatory alterations play a pivotal role in sepsis and persist despite correction of systemic hemodynamic parameters. It seems tempting to test specific pro-microcirculatory strategies, including vasodilators, to attenuate impaired organ perfusion. Vasodilators should be able to increase blood flow via a change in vessel diameter at the entrance of the microcirculation and recruit microcirculatory perfusion in volume resuscitated patients [6]. Stimulation of endothelium-dependent vasodilation by topical application of acetylcholine was effective in the recruitment of shut-down capillaries in septic patients, challenging the concept of vasoplegia [7]. It suggested that endothelial vasodilatory response is intact in sepsis and microvascular thrombosis is not the predominant factor in the observed decrease in microcirculatory blood flow. A recent randomized clinical trial could not confirm the previous observation, that nitroglycerin improved microvascular perfusion in an open label setting [10]

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