Patient selection:

Patients aged >18yrs who are highly suspected or confirmed infection, the patients will be checked for volume responsiveness by straight leg rise and capillary refill time after adequate fluid resuscitation with 500ml bolus of balanced crystalloid, if found to have negative response. Patients are initiated on Norepinephrine to maintain MAP>65 mmHg, Patients are selected if time to vasopressor initiation <6hrs. All the components in exclusion criteria will be assessed before eligibility.

Randomisation, Intervention, Measurements:

             After informed consent the patients are randomized 1:1  to                                     methylene blue group or the standard group by computer generated simple randomization.

 Both the groups will continue to get similar standard of care according to protocol. When Norepinephrine dose reached >0.20 mcg/kg/min, Vasopressin is initiated at 0.03IU/min in both groups.

In the Methylene blue group, after test dose, the dosing regimen - Bolus of 2mg/kg followed by infusion of 0.25mg/kg/h in 0.9%Nacl solution for 6hrs for two consecutive days.

Physician-led vasopressor tapering protocol of norepinephrine titration at 15–20min intervals to maintain mean arterial pressure (MAP-70 mmHg) will be continued. Our standard protocol calls for the initiation of epinephrine, even after reaching the maximum dose requirement for dual vasopressors. Weaning of vasopressors will also be according to periodic intervals by withdrawal epinephrine followed by vasopressin and norepinephrine. Close monitoring of meth-hemoglobin levels will be done periodically to avoid complications.

Hydrocortisone at 50mg Q6hrly dose is also a standard in our unit,will be initiated and it is withheld after 24-h after discontinuation of all vasopressors.