Clinical trial NCT04295993: Methylene Blue and Microcirculation in Septic Shock
Official title: The Effect of Methylene Blue on Microcirculation in Patients With Septic Shock: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Septic Shock
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2020-03-05
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Septic shock
* The patient is on norepinephrine infusion

Exclusion Criteria:

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

Primary outcomes:
measure: Microvascular flow index
timeFrame: 6 hours
Secondary outcomes:
measure: Total vessel density
timeFrame: 6 hours
measure: Perfused vessel density
timeFrame: 6 hours
measure: Proportion of perfused vessel
timeFrame: 6 hours
measure: mean arterial pressure
timeFrame: 24 hours
measure: serum lactate
timeFrame: 6 hours
measure: length of stay in the intensive care unit
timeFrame: 28 days
measure: cardiac output
timeFrame: 24 hours
measure: total consumption of norepinephrine
timeFrame: 6 hours
measure: incidence of mortality
timeFrame: 28 days
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cairo University
Study officials:
affiliation: Professor of anesthesia
name: Ahmed Mukhtar, Professor
role: PRINCIPAL_INVESTIGATOR
References: