Efficacy of Epinephrine versus Nor-epinephrine as the initial vasoactive agent in Paediatric hematoncology patients with shock- A Feasibility Pilot study

There are thought to be key differences in pathophysiology of shock in children compared to adults. Unlike adults who usually have a compensatory mechanism to maintain adequate cardiac output, children often exhibit a “low cardiac output†state secondary to severe myocardial depression. (1) Early manifestations of shock in children include tachycardia, cold peripheries, prolonged CFT, narrow pulse pressure and late signs include altered mental status and hypotension.

Early recognition of shock and appropriate interventions are associated with favourable outcomes (2-5). Management of a child in shock includes optimizing the macro- and micro-circulation. Fluid therapy constitutes the first step in the management of a child in shock (16). Though correcting hypovolemia is important, the risk of fluid overload is to be borne in mind as this can lead to worse outcomes (6). After initial fluid resuscitation, if a child continues to be in shock and is determined not to be fluid responsive or the benefits of giving further fluids are going to be counterproductive, one needs to optimise cardiac output by improving the cardiac contractility and/or attempting to normalize the systemic vascular resistance. Inotropes and vasoactive drugs need to be optimised from this point onwards to achieve shock resolution (7, 8). Vasoactive drugs include vasopressors and vasodilators. As inotropes increase the contractility, Inodilators are another class of drugs that improve both contractility and cause systemic vasodilation (7).

Dopamine has long been used as a first line inotrope of choice in paediatric shock (7,8). Recent evidence, including an Indian trial has shown that dopamine is associated with more tachyarrhythmias and increased incidence of health care associated infections and higher mortality (9, 10). The most recent paediatric Surviving Sepsis Guidelines (pSSC) 2020 recommends one of 2 catecholamines, viz, epinephrine or norepinephrine as the first line vasoactive-inotrope in paediatric fluid refractory shock (10), based on the caregiver’s decision. Further, the pSSC has de-emphasized cold vs warm shock pathway, considering evidence (11,2) showing that even with overt cold shock, a vasodilatory state can exist with wide pulse pressures, decreased SVR and increased cardiac index. Regarding epinephrine versus norepinephrine; both are found to be equally efficacious with epinephrine reported to cause more drug related side effects in adult patients (12-14). However, the majority of these reports are derived from adult studies and it is important to note that there are no published studies comparing the epinephrine vs norepinephrine in children till date.

 Cardiac dysfunction is relatively common in oncology patients admitted in PICU with shock that leads to higher risk of morbidity and mortality in these children (1). The cardiac dysfunction in these children can be due to lot of reasons including underlying hematologic/oncologic condition, chemotherapeutic agents, bone marrow transplantation, cytokine release syndrome. This also makes this subset of children different from the other paediatric patients.

 In this context, our aim is to compare epinephrine and norepinephrine as first-line agents for shock among paediatric hematoncology patients.