Intravenous Methylene Blue for Treating Refractory Neonatal Septic Shock

Screening Criteria: preterm infants (\<37 weeks, \<28 days) clinically diagnosed to have septic shock will be screened for inclusion Inclusion criteria: Subjects must fulfill all the following 1. Definite/probable sepsis :Clinical syndrome of sepsis for which bedside neonatologist starts intravenous antibiotics AND either a positive culture of otherwise sterile body fluid OR presence of any 2 or more of the following five markers of sepsis: (a) C-reactive protein \>10 mg/dL; (b) procalcitonin as per age-appropriate cut-off (c) total leukocyte count and absolute neutrophilic count beyond acceptable range (d) chest X-ray adjudged as pneumonia by two independent Neonatologists. 2. Shock: adapted from the definition given by Davis et al 2017 1. Either SBP \< age and gestation appropriate cut-off OR 2. Presence of any 2 of the following 6 parameters i. HR \>205/min ii. Central pulses either week OR bounding iii. CRT \>3 sec OR flash refill (\<1 sec) iv. skin mottled/cool OR flushed v. urine output \<0.5 ml/kg/h in the preceding 6 hours vi. DBP \< age and gestation appropriate cut-off 3. Fluid and catecholamine-resistant shock: received fluid boluses up to a maximum of 40 ml/kg followed by catecholamine infusion titrated up to the maximum dose. The catecholamine infusion could be either dopamine (maximum dose 20 µg/kg/min) or epinephrine (maximum dose 0.4 µg/kg/min) or norepinephrine (maximum dose 0.4 µg/kg/min). Exclusion Criteria: excluded if ≥1 criterion positive: 1. G6PD deficient or family history of G6PD deficiency 2. Potentially lethal malformation 3. Congenital heart disease 4. Severe acute kidney injury 5. Family history of allergy to methylene blue or food dyes