Echocardiographic characteristics in neonates with septic shock.

Clinical parameters used for hemodynamic assessment and titration of vasopressor therapy in neonates with septic shock have several limitations. Functional echocardiography is an emerging tool for bedside assessment of cardiac function and may be useful for diagnosis of shock and assessing the response to therapy. Data regarding echocardiographic parameters in neonates with shock is lacking. This prospective observational study was conducted in a Level III NICU with the primary objective of comparing echocardiographic characteristics of neonates with septic shock at diagnosis, following fluid boluses, and after maximum inotropic support [A1]. Additionally, we compared these characteristics with those of healthy stable neonates who were gestation and postnatal age-matched. A total of 36 neonates with septic shock and 30 gestation and postnatal age-matched controls were enrolled. The mean (SD) gestation and birth weight of neonates with septic shock were 30.6 (4.0) weeks and 1538 (728) g, respectively. Gram-negative bacilli constituted 78.9% of all isolates. At presentation, there was no significant difference between neonates with shock and controls in terms of ventricular outputs, shortening fraction, ratio of early to late diastolic trans-mitral flow velocity, and myocardial performance indices. The distensibility index of inferior vena cava was higher in neonates with shock compared to controls, (17% vs 10%, (p < 0.01)). Left ventricular output was 209 (92) and 227 (102) ml/kg/min (p = 0.53) and right ventricular output was 427 (203) and 459 (227) ml/kg/min, (p = 0.03), respectively, before and after inotropic therapy.     Conclusion: Echocardiographic parameters may not differentiate neonates with septic shock from hemodynamically stable neonates. Neonates with shock associated with predominantly gram-negative sepsis are not able to augment cardiac functions, either at the onset or after administration of inotropes.      Trial registration: (CTRI/2017/12/010766). What is known: • For neonates with shock, echocardiography is becoming increasingly popular as an objective method of evaluating hemodynamics. • In healthy preterm neonate, cardiac output has been known to increase in response to altered hemodynamics during states of increased oxygen demand. What is new: •  In the setting of septic shock induced by gram-negative organisms, echocardiographic parameters are less likely to assist in the assessment of the response to vasoactive agents. Cytokines, induced by gram-negative organisms, may alter adrenoreceptors in myocardium and vasculature.

Role of next generation sequencing in diagnosis and management of critically ill children with suspected monogenic disorder.

Next generation sequencing based diagnosis has emerged as a promising tool for evaluating critically ill neonates and children. However, there is limited data on its utility in developing countries. We assessed its diagnostic rate and clinical impact on management of pediatric patients with a suspected genetic disorder requiring critical care. The study was conducted at a single tertiary hospital in Northern India. We analyzed 70 children with an illness requiring intensive care and obtained a precise molecular diagnosis in 32 of 70 probands (45.3%) using diverse sequencing techniques such as clinical exome, whole exome, and whole genome. A significant change in clinical outcome was observed in 13 of 32 (40.6%) diagnosed probands with a change in medication in 11 subjects and redirection to palliative care in two subjects. Additional benefits included specific dietary management (three cases), avoidance of a major procedure (one case) and better reproductive counseling. Dramatic therapeutic responses were observed in three cases with SCN1A, SCN2A and KCNQ2-related epileptic encephalopathy. A delayed turn-around for sequencing results was perceived as a major limiting factor in the study, as rapid and ultra-rapid sequencing was not available. Achieving a precise molecular diagnosis has great utility in managing critically ill patients with suspected genetic disorders in developing countries.