Vasopressor-Sparing Action of Methylene Blue in Severe Sepsis and Shock: A Narrative Review

Abstract

Shock is a serious acute circulatory failure leading to inadequate oxygen delivery to the cells. Its treatment is mainly based on circulating fluid optimization, and vasopressors to provide an adequate mean arterial pressure and microcirculatory flow. Norepinephrine is the drug of choice, but high dosages may be responsible for several side effects, including increased myocardial oxygen consumption, dysrhythmias, and peripheral and organ ischemia. Moreover, some patients are ''non-responders'' to first-line norepinephrine treatment. Hence, other drugs have been proposed to reach and maintain the hemodynamic target. In general, they are described as catecholaminesparing agents. Among others, the most used are vasopressin, corticosteroids, and angiotensin II. Methylene blue (MB) represents a further option, even though its use is still a topic of controversy. This review article tries to summarize what is known and unknown about the actions of MB in patients in shock. It reduces excessive production of nitric oxide via blockade of guanylate cyclase in shock states. At present, it appears the MB provides positive results in septic shock, if administered early. Further randomized controlled trials are warranted regarding its use to provide more precise indications to physicians involved in the treatment of such patients.

Vazopresino Panaudojimas Klinikinėje Praktikoje

“…Dėl to sutrinka deguonies pristatymas į ląsteles, vystosi dauginis organų nepakankamumas. Vazopresoriai yra pagrindiniai vaistai, skiriami vazodilataciniam šokui, ypač septiniam, gydyti, kai nėra atsako į adekvačią skysčių terapiją [2,4,8,9]. Pirmo pasirinkimo vazopresorius − norepinefrinas (NE).…”

Methylene blue for vasodilatory shock in the intensive care unit: a retrospective, observational study

“…Refractory vasodilatory shock, or vasoplegia, is a state of uncontrolled vasodilation thought to be chiefly mediated by dysregulation of nitric oxide (NO) and soluble guanylate cyclase (sGC) and likely also associated with underlying inflammation and endothelial dysregulation [ 1 , 2 ]. NO is generated via nitric oxide synthase and results in vasodilation due to the production of cyclic guanosine monophosphate production (cGMP) which subsequently mediates vascular smooth muscle relaxation [ 1 , 3 ]. Definitions of vasoplegia vary, but most sources define it as requiring vasopressor doses ranging from above 0.2 mcg/kg/min to 0.5 mcg/kg/min of norepinephrine equivalents or more, with a cardiac index (CI) of at least 2.2 L/min/m 2 and difficulty maintaining a mean arterial pressure (MAP) above 65 mmHg [ 2 , 4 , 5 ].…”

“…Rescue therapy for vasoplegia refractory to catecholamines includes vasopressin, methylene blue (MB), corticosteroids, angiotensin II, ascorbic acid, and hydroxocobalamin [ 1 , 3 , 5 ]. The routine use of these adjunct agents has not been standardized due to limited, inconsistent data and cost.…”

“…Methylene blue (ProvayBlue™) inhibits endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), sGC, and cytokines such as tumor necrosis factor-α (TNF-α) [ 1 , 6 , 7 ]. MB restores vascular tone and due to the selective blockade of both sGC and iNOS, and it is considered more targeted to the dysregulation of the microcirculation in the setting of NO upregulation [ 3 ].…”

Cox-LASSO Analysis for Hospital Mortality in Patients With Sepsis Received Continuous Renal Replacement Therapy: A MIMIC-III Database Study

“…Sepsis is a major condition with high morbidity and mortality in intensive care unit (ICU) patients (1). Severe sepsis and septic shock are characterized by vasoplegia and alterations of microcirculation, resulting in aggressively hemodynamic alterations that render the patient hypotensive or with organ dysfunction (2)(3)(4)(5). During sepsis, fluid responsiveness or the use of vasopressors could guide fluid administration (6), but the response to therapy is highly variable (7,8).…”