Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue

Study Overview
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Brief Summary
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Mortality rates associated septic shock remains unacceptably high, around 20-50%, with refractory hypotension in half of these patients. Widespread vasodilatation involves the activation of the soluble intracellular enzyme guanylate cyclase (GC) by nitric oxide (NO), resulting in the production of cyclic guanosine monophosphate (cGMP). Initially discovered as an endothelium-derived relaxing factor in blood vessels, NO is made by the enzyme nitric oxide synthase (NOS). It has been suggested that the inhibition of NO generation might be a treatment option for sepsis and septic shock. Methylene blue (MB) is a dye that easily crosses cell membranes, inhibits iNOS, and is capable of inhibiting the GC enzyme in vascular smooth muscle cells.Early use of MB can block the progressive decrease in systemic vascular resistance of patients unresponsive to noradrenaline and mitigate the need for prolonged vasoconstrictor use. The investigators propose to study the effect of methylene blue on cirrhotic adults with sepsis, with refractory vasoplegia unresponsive to maximum doses of noradrenaline and vasopressin.

Official Title
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Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue in Sepsis: A Randomized Controlled Trial

Conditions
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Septic Shock, Vasoplegia, Cirrhosis, Liver, Refractory Shock

Intervention / Treatment
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* Drug: Methylene Blue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (>18 years ) Refractory septic shock (Noradrenaline >0.5mcg/kg/mt ) Exclusion Criteria: Declined consent Pregnancy Less than 18 years old Immunosuppressant patients (e.g. on steroid medication, active anti-cancer chemotherapeutic agent, etc.) Glucose-6-phosphate dehydrogenase deficiency Medication of Serotonin modulator/SSRI Pre-existing Pulmonary Hypertension CKD-Stage IV/V Patients with GI bleed Patients on DNR Patients declared Brain dead

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylene Blue<br>Methylene Blue intravenous route, 2 mg/kg Loading Dose over 30 minutes, followed by 0.5 mg/kg/hr for 6 hours | Drug: Methylene Blue<br> <br> |
| No Intervention: Standard Treatment<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival in both groups |  | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic Vascular Resistance | Change in SVR | 6 hours | 
| Mean Arterial Pressure | Improvement in MAP | 6 hours | 
| Decrease of vasopressor dose of 20 percent from time of start of test drug. | Effect on decreasing vasopressor doses | 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methylene Blue, Septic Shock, Vasoplegia, Cirrhosis