Evaluating in Cirrhotics With Refractory Vasoplegia the Effect of Methylene Blue

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

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.

Inclusion Criteria:

1. Adult patients (>18 years )
2. Refractory septic shock (Noradrenaline >0.5mcg/kg/mt )

Exclusion Criteria:

1. Declined consent
2. Pregnancy
3. Less than 18 years old
4. Immunosuppressant patients (e.g. on steroid medication, active anti-cancer chemotherapeutic agent, etc.)
5. Glucose-6-phosphate dehydrogenase deficiency
6. Medication of Serotonin modulator/SSRI
7. Pre-existing Pulmonary Hypertension
8. CKD-Stage IV/V
9. Patients with GI bleed
10. Patients on DNR
11. Patients declared Brain dead