Intravenous Methylene Blue for Treating Refractory Neonatal Septic Shock
Preterm infants (born at less than 37 weeks of pregnancy) sometimes develop a serious blood infection leading to low blood pressure, which does not respond to saline or to the standard medicines for increasing blood pressure, such as dopamine and epinephrine. The goal of this research study is to compare the effect of giving an injectable medicine called Methylene blue (MB) versus not giving MB to such preterm infants who are unresponsive to standard treatment. The main questions that this study aims to answer is:

Whether MB treatment reduces death to any cause as compared to no MB treatment.
Whether treatment with MB reduces the time to achieve normal blood pressure
Whether treatment with MB reduces the time to stoppage of all blood pressure medications, steroids and normal saline.
Whether treatment with MB improves heart function as measured by echocardiography at 24 and 48 hours.
- EligibilityCriteria: 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  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.  Shock: adapted from the definition given by Davis et al 2017  Either SBP < age and gestation appropriate cut-off OR 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 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:  G6PD deficient or family history of G6PD deficiency Potentially lethal malformation Congenital heart disease Severe acute kidney injury Family history of allergy to methylene blue or food dyes - HealthyVolunteers: No - Gender: All - MinimumAge: 0 Days - MaximumAge: 28 Days - StdAgeList: Child