Continuous non-invasive advanced hemodynamic monitoring versus standard care for the management of pediatric septic shock - A pilot randomized control trial

Septic shock is a leading cause of childhood morbidity and mortality. Pathophysiology includes a combination of fluid depletion, heterogenous vasodilatation, capillary leak and myocardial dysfunction, with varying contributions over time. Accurate hemodynamic assessments are necessary to guide therapy (including fluids, vasoactives, inotropes) and traditional clinical monitoring is not accurate enough. Invasive cardiac output monitoring with pulmonary artery catheter, though believed to be gold standard, is associated with significant risks and is not routinely employed. Continuous non-invasive advanced hemodynamic monitoring based on electrical cardiometry has been validated in children and adults. However, whether it will provide better real-time guidance regarding pediatric septic shock management as compared to current standard care, to facilitate optimal fluid administration and/or drug titrations for time-sensitive, goal directed resuscitation is not known, and whether this will translate into better patient-centered outcomes like reduced mortality and morbidity has not been studied. Hence we designed this pilot open-label, parallel-arm, randomized control trial. We hypothesize that a protocol on continuous non-invasive advanced hemodynamic monitoring to guide management of pediatric septic shock is feasible and that the intervention will lead to lesser organ dysfunction, earlier shock resolution and better patient outcomes as compared to current standard management. Our feasibility objectives include determination of recruitment, consent, treatment protocol adherence and retention/follow-up rates. Primary clinical objective is survival free of organ dysfunction censored at 28 days. Other objectives include comparison of mortality, time to shock resolution, organ supports, fluid overload and long-term functional outcomes and quality of life between the two groups. We would randomize 60 children (30 in each arm, with 1:1 ratio), aged 2 months – 18 years with diagnosis of septic shock, unresolved after initial 20ml/kg isotonic fluid bolus. Those in the intervention arm would be connected to continuous non-invasive advanced hemodynamic monitor based on electrical cardiometry, which will provide measurements of cardiac output, stroke volume variability, systemic vascular resistance, index of contractility and thoracic fluid content. There measures along with standard clinical monitoring would be used to guide further fluid bolus, selection and titration of vasoactive agents. Those in the control arm will be managed as per standard institutional protocols. All the patients will be followed up to 28 days or death, whichever is earlier and then at 6 months to study outcomes. The study findings may facilitate better understanding of pediatric septic shock phenotypes, response to treatment, and will inform a future larger multicenter trial. Institute ethics approval will be sought and informed consent will be obtained from all participants.