Methylene Blue and Microcirculation in Septic Shock

Phase 3

• Conditions: Septic Shock
• Interventions: Drug: Methylene Blue; Drug: Norepinephrine infusion

• Registration Number: NCT04295993
• Lead Sponsor: Cairo University

Brief Summary

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.

Detailed 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.

Study Timeline

• Status Verified: 2020-03
• Study First Submitted: 2020-03-03
• Study First Submitted QC: 2020-03-03
• Last Update Submitted: 2020-03-03
• Study First Posted: 2020-03-05
• Last Update Posted: 2020-03-05
• Study Start: 2020-03-10
• Primary Completion: 2020-09-10
• Study Completion: 2020-09-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Septic shock
• The patient is on norepinephrine infusion

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
methylene blue group	Norepinephrine infusion	The patients in this group will receive methylene blue bolus in addition to the norepinephrine infusion.
Norepinephrine group	Norepinephrine infusion	The patients in this group will receive norepinephrine infusion.
methylene blue group	Methylene Blue	The patients in this group will receive methylene blue bolus in addition to the norepinephrine infusion.

Primary Outcome Measures

Name	Time	Method
Microvascular flow index	6 hours	The image will be divided into four quadrants and the vessels \<20 μ m diameter will be assigned a score based on the predominant flow characteristics of the vessels in that quadrant (0 = absent flow; 1 = intermittent; 2 = sluggish; 3 = normal). The values in each quadrant will be averaged to give an microvascular flow index for each sublingual site at each time point. To determine heterogeneity of perfusion, the flow heterogeneity index will be calculated as the highest microvascular flow index minus the lowest microvascular flow index divided by the mean microvascular flow index.

Secondary Outcome Measures

Name	Time	Method
Proportion of perfused vessel	6 hours	The number of vessels with flows 2 and 3 divided by the total number of vessels and multiplied by 100.
serum lactate	6 hours	the value of lactate in the serum measured in milligrams per liter
length of stay in the intensive care unit	28 days	the duration of stay in the intensive care unit measured in days
incidence of mortality	28 days	The number of dead patients divided by the total number of patients
Perfused vessel density	6 hours	The number of vessels multiplied by the fraction of perfused vessels
Total vessel density	6 hours	The number of vessels per millimeters squared.
mean arterial pressure	24 hours	the mean arterial blood pressure measured in mmHg
cardiac output	24 hours	The amount of blood ejected by the heart in one minute measured in liters
total consumption of norepinephrine	6 hours	the total consumption of norepinephrine in 6 hours measured in micrograms.

Trial Locations

Locations (1)

Cairo University; 🇪🇬 Cairo, Egypt