Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies

Abstract

Objective To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome (MODS) presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Data Sources Literature review, research data, and expert opinion. Study Selection Not applicable. Data Extraction Moderated by an expert from the field, issues relevant to the association of MODS with a variety of conditions were presented, discussed and debated with a focus on identifying knowledge gaps and research priorities. Data Synthesis Summary of presentations and discussion supported and supplemented by relevant literature. Conclusions Among critically ill children, MODS is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this manuscript, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of MODS. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anti-cytokine therapies, anti-toxin treatments, anti-oxidant approaches and multiple forms of exogenous steroids. For the field to advance, these and other therapies must be assessed in rigorous manner and implemented accordingly.

Mortalidad y morbilidad en choque séptico según aporte calórico recibido durante su fase inicial en pacientes pediátricos admitidos en unidad de cuidados intensivos

“…De igual forma Wegner y cols. Informaron una mayor mortalidad a 90 días mayor en pacientes fue menor en pacientes con aporte calórico bajo comparados con aquellos que recibieron un aporte calórico estándar (33,34).…”

Refining the Pediatric Multiple Organ Dysfunction Syndrome

“…Examples include early initiation of antibiotic therapy and source control in cases of sepsis; optimal medication dosing, as MODS affects pharmacokinetics and pharmacodynamics of drugs; nutritional support (preference for the enteral route); glycemic control; and fluid management aimed at maintaining intravascular volume while minimizing fluid overload. 63 The majority of these therapeutic strategies are used to limit secondary insults rather than mitigate mechanisms of the underlying MODS state. Therapeutic plasma exchange for TAMOF, for example, is an intervention used to reverse a cause of MODS.…”

Pathophysiology of Pediatric Multiple Organ Dysfunction Syndrome

“…PAMPs and DAMPs activate immune cells via Toll-like receptors leading to the production of reactive oxygen species (ROS) that promote endothelial dysfunction by the oxidation of crucial cellular signaling proteins (73). Although ROS are important in killing pathogens, excessive or unchecked ROS lead to tissue injury (85). In particular, cytokine and hypoxia-induced production of ROS leads to mitochondrial dysfunction with subsequent development of cellular dysfunction and organ failure (86).…”