Methylene Blue and Microcirculation in Septic Shock

Cairo University (CU)

Status and phase: Unknown; Phase 3

Conditions: Septic Shock

Treatments: Drug: Methylene Blue; Drug: Norepinephrine infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT04295993

N-13-2019

Details and patient eligibility

About

This trial aims to identify the effects of methylene blue infusion on the the micro-circulation in patients with septic shock. The investigators will evaluate various indices of micro-circulation such as: microvascular flow index, the flow heterogeneity index, the total vessel density, the perfused vessel density, and the proportion of perfused vessels.

Full description

The mortality rate of patients with septic shock remains very high. Arterial hypotension, related to arteriolar vasodilation and myocardial depression are the mainstays of septic shock pathology.

At the level of the micro-circulation, there is insufficient delivery of oxygen to organs and tissues which results in organ dysfunction and potential organ necrosis.One key factor leading to vascular dysfunction is the inappropriately increased production of nitric oxide within the blood vessel endothelium. Elevated levels of nitric oxide results in the blood vessel endothelium receiving direct vasodilator input, as well as the inability to respond to norepinephrine-mediated vasoconstriction. Nitric oxide activates the soluble isoform of the enzyme guanylatecyclase, which in turn increases production of cyclic guanosine monophosphate. Nitric oxide has other beneficial effects which are mediated via other pathways than guanylatecyclase; therefore, administration of a guanylate cyclase inhibitor such as methylene blue could be a safer therapeutic option than the inhibition of nitric oxide production.

These effects of methylene blue could be related to vasoconstriction and positive inotropic effects as well to an increase in blood volume, itself related to a decrease in vascular permeability. The use of methylene blue has been recently advocated as a potential adjunct in the treatment of shock states. However, the effect of MB at the level of the capillary bed, where vital exchange of oxygen and nutrients occurs, is unknown. Thus in this study, the investigators will investigate the effect of methylene blue in combination with NE at the microvascular level in septic shock.

Enrollment: 32 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Septic shock
• The patient is on norepinephrine infusion

Exclusion criteria

• Elevated serum creatinine (above 1.4 mg/dL)
• Pregnancy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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32 participants in 2 patient groups

methylene blue group

Experimental group

Description:

The patients in this group will receive methylene blue bolus in addition to the norepinephrine infusion.

Treatment:

Drug: Norepinephrine infusion

Drug: Methylene Blue

Norepinephrine group

Active Comparator group

Description:

The patients in this group will receive norepinephrine infusion.

Treatment:

Drug: Norepinephrine infusion