Methylene Blue and Microcirculation in Septic Shock

Septic Shock Clinical Trial

Official title:

The Effect of Methylene Blue on Microcirculation in Patients With Septic Shock: a Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04295993
• Other study ID #: N-13-2019
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 10, 2020
• Est. completion date: September 20, 2020

Study information

• Verified date: March 2020
• Source: Cairo University
• Contact: kareman abdelghaffar, Demonstrator
• Phone: +201223931469
• Email: kareman_86[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 32
• Est. completion date: September 20, 2020
• Est. primary completion date: September 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Septic shock

• The patient is on norepinephrine infusion

Exclusion Criteria:

• Elevated serum creatinine (above 1.4 mg/dL)

• Pregnancy

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Drug:
• Methylene Blue
The patient will receive Methylene Blue bolus with a dose of 2 mg/kg over 10 minutes.
• Norepinephrine infusion
The patient will receive norepinephrine infusion to maintain mean arterial pressure above 65 mmHg

Locations

Country	Name	City	State
Egypt	Cairo University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

Outcome

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