Interaction of milrinone with extracorporeal life support.

Background: Milrinone is commonly prescribed to critically ill patients who need extracorporeal life support such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Currently, the effect of ECMO and CRRT on the disposition of milrinone is unknown.

Methods: Ex vivo ECMO and CRRT circuits were primed with human blood and then dosed with milrinone to study drug extraction by the circuits.

Interaction of azithromycin and methylprednisolone with ex-vivo extracorporeal membrane oxygenation circuits (ECMO).

Background: Azithromycin and methylprednisolone are two medications that are commonly used in patients who require ECMO support. Unfortunately, ECMO support can decrease drug concentrations through adsorption to circuit components. Such interactions have not been well described for either azithromycin or methylprednisolone.

Extraction of ketamine and dexmedetomidine by extracorporeal life support circuits★.

Background: Patients supported with extracorporeal life support (ECLS) circuits such as ECMO and CRRT often require high doses of sedatives and analgesics, including ketamine and dexmedetomidine. Concentrations of many medications are affected by ECLS circuits through adsorption to the circuit components, dialysis, as well as the large volume of blood used to prime the circuits. However, the impact of ECLS circuits on ketamine and dexmedetomidine pharmacokinetics has not been well described.

A physiologically-based pharmacokinetic modeling approach for dosing amiodarone in children on ECMO.

Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device commonly used to treat cardiac arrest in children. The American Heart Association guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care recommend using amiodarone as a first-line agent to treat ventricular arrhythmias in children with cardiac arrest. However, there are no dosing recommendations for amiodarone to treat ventricular arrhythmias in pediatric patients on ECMO.

Meropenem extraction by ex vivo extracorporeal life support circuits.

Background: Meropenem is a broad-spectrum carbapenem-type antibiotic commonly used to treat critically ill patients infected with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. As many of these patients require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), it is important to understand how these extracorporeal life support circuits impact meropenem pharmacokinetics. Based on the physicochemical properties of meropenem, it is expected that ECMO circuits will minimally extract meropenem, while CRRT circuits will rapidly clear meropenem.

Medication patterns and dosing guidance in pediatric patients supported with intermittent hemodialysis or continuous kidney replacement therapy.

Background: Hemodialysis is a life-saving technology used during periods of acute or chronic kidney failure to remove toxins, and maintain fluid, electrolyte and metabolic balance. While this technology plays an important role for pediatric patients with kidney dysfunction, it can alter the pharmacokinetic behavior of medications placing patients at risk for suboptimal dosing and drug toxicity. The ability to directly translate pharmacokinetic alterations into dosing recommendations has thus far been limited and dosing guidance specific to pediatric hemodialysis patients is rare.

Interaction of ceftazidime and clindamycin with extracorporeal life support.

Background: Ceftazidime and clindamycin are commonly prescribed to critically ill patients who require extracorporeal life support such as ECMO and CRRT. The effect of ECMO and CRRT on the disposition of ceftazidime and clindamycin is currently unknown.

Methods: Ceftazidime and clindamycin extraction were studied with ex vivo ECMO and CRRT circuits primed with human blood.

Cefepime Extraction by Extracorporeal Life Support Circuits.

Extracorporeal life support (ECLS) devices are lifesaving for critically ill patients with multi-organ dysfunction. Despite this, patients supported with ECLS are at high risk for ECLS-related complications, including nosocomial infections, and mortality rates are high in this patient population. The high mortality rates are suspected to be, in part, a result of significantly altered drug disposition by the ECLS circuit, resulting in suboptimal antimicrobial dosing.

Remdesivir and GS-441524 Extraction by Ex Vivo Extracorporeal Life Support Circuits.

Patients with severe, COVID-related multi-organ failure often require extracorporeal life support (ECLS) such as extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy (CRRT). An ECLS can alter drug exposure via multiple mechanisms. Remdesivir (RDV) and its active metabolite GS-441524 are likely to interact with ECLS circuits, resulting in lower than expected exposures.

Timing of Pediatric Palliative Care Consults in Hospitalized Patients with Heart Disease.

Pediatric palliative care (PPC) provides an extra layer of support for families caring for a child with complex heart disease as these patients often experience lifelong morbidities with frequent hospitalizations and risk of early mortality. PPC referral at the time of heart disease diagnosis provides early involvement in the disease trajectory, allowing PPC teams to longitudinally support patients and families with symptom management, complex medical decision-making, and advanced care planning. We analyzed 113 hospitalized pediatric patients with a primary diagnosis of heart disease and a PPC consult to identify timing of first PPC consultation in relation to diagnosis, complex chronic conditions (CCC), and death.

Embodied valuation: Directional action is associated with item values.

We have a lifetime of experience interacting with objects we value. Although many economic theories represent valuation as a purely cognitive process independent of the sensorimotor system, embodied cognitive theory suggests that our memories for items' value should be linked to actions we use to obtain them. Here, we investigated whether the value of real items was associated with specific directional movements toward or away from the body.

Early complement factors in the local tissue immunocomplex generated during intestinal ischemia/reperfusion injury.

Recent work reveals that the innate immune system is able to recognize self-targets and initiate an inflammatory response similar to that of pathogens. One novel example of this innate autoimmunity is ischemia/reperfusion (I/R) injury, in which reperfusion of the ischemic tissues elicits an acute inflammatory response activated by natural IgM (nIgM) binding to ischemia-specific self-antigens, which are non-muscle myosin heavy chains type II (NMHC-II) subtype A and C. Subsequently, the complement lectin pathway is activated and eventually tissue injury occurs.