Methylene blue

Introduction

Methylene blue

Clinical data
Pharmacodynamics
Pharmacokinetics
Physical and chemical data
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Classically methylene blue is utilized as a dye in various procedures in aid in identification of anatomic structures. However, methylene blue has also been increasingly utilized in the setting of vasoplegic/distributive shock

Uses

Methylene blue is a heterocyclic aromatic molecule that produces a blue color when mixed with water. It can aid in the identification of various structures during surgical procedures, for example urological surgery to identify ureter. It has also been utilized in the treatment of methemoglobinemia. Additional it is proposed to have vasoconstrictive effects that lend utility in vasodilatory states including distributive shock.

Distributive shock can include multiple different etiologies such as sepsis, neurogenic, and anaphylactic. However the ultimate result if inadequate end organ perfusion pressure secondary to lack of vascular tone. Increasing vascular tone via the many vasoconstricting agents available can assist in increasing organ perfusion. Methylene blue can antagonize the profound vasodilation seen in such states. Purported uses include vasoplegia in the setting of cardiac surgery, liver transplantation, and septic shock.

Contraindications

Absolute contraindications

• History of hypersensitivity or anaphylaxis to methylene blue
• Glucose-6-phosphate dehydrogenase deficiency due to susceptibility of hemolytic anemia
• Pregnancy: currently class X rating secondary to intestinal atresia
• Methylene blue can also function as a monoamine oxidase inhibitor (MAOI). If given with medications causing increased serotonin, it may precipitate serotonin syndrome

Precautions

• Interference with pulse oximeter sensor

Pharmacology

Metabolism: Likely undergoes first pass metabolism or distribution; peripheral reduction to leukomethylene blue

Half-life elimination: 5-6 hours

Mechanism of action

Nitric oxide, produces by nitric oxide synthase induces smooth muscle relaxation via production of cGMP. Methylene blue may restore vascular tone by inhibition of endothelial nitric oxide synthase.

In low concentrations methylene blue can hasten the conversion of methemoglobin to hemoglobin

Evidence

Septic shock:

Kirov et al. randomized twenty patients with septic shock to methylene blue versus normal saline in addition to standard ionotropes. Methylene blue reduced the requirement for norepinephrine, epinephrine, and dopamine by as much as 87%, 81%, and 40%, respectively. The mortality rate in the methylene blue arm was 58%, as compared to 75% in the saline group (p = 0.65) [Kirov et al. Crit Care Med 29: 180, 2001]

Cardiac surgery:

Levin et al. randomized 56 vasoplegic patients (defined as hypotensive, with low filling pressures, low peripheral vascular resistance, and elevated or normal cardiac index despite significant vasopressor requirements) following cardiopulmonary bypass to methylene blue versus placebo. Patients who received methylene blue had a significant reduction in mortality (0% versus 21.4% [6 of 28 patients], p = 0.01), as well as in the incidence of renal failure (0 vs. 14%, p = 0.05), respiratory failure (0 vs. 14%, p = 0.05), supraventricular tachycardias (7% vs 28%, p = 0.03), sepsis (0% vs 25%, p = 0.005), and multiorgan failure (0% vs 25%, p = 0.005). [Levin RL et al. Ann Thorac Surg 77: 496, 2004]