Intensive care units (ICUs) provide care for critically-ill patients who require constant monitoring and the availability of specialized equipment and personnel. In this environment, a high volume of information and a high degree of uncertainty present a burden to clinicians. In specialized cohorts, such as pediatric patients with congenital heart defects (CHDs), this burden is exacerbated by increased complexity, the inadequacy of existing decision support aids, and the limited and decreasing availability of highly-specialized clinicians. Among CHD patients, infants with single ventricle (SV) physiology are one of the most complex and severely-ill sub-populations. While SV mortality rates have dropped, patient deterioration may happen unexpectedly in the period before patients undergo stage-2 palliative surgery. Even in expert hands, critical and potentially catastrophic events (CEs), such as cardiopulmonary resuscitation (CPR), emergent endotracheal intubation (EEI), or extracorporeal membrane oxygenation (ECMO) are common in SV patients, and may negatively impact morbidity, mortality, and hospital length of stay. There is a clinical need of predictive tools that help intensivists assess and forecast the advent of CEs in SV infants. Although ubiquitous, widely adopted ICU severity-of-illness scores or early warning systems (EWS), e.g., PRISM and PIM, have not met this need. They are often v developed for general ICU use and do not generalize well to specialized populations. Furthermore, most EWS are developed for prediction of patient mortality. Among SV patients, however, death is semi-elective. On the other hand, prediction of CEs may help clinicians improve patient care by anticipating the advent of patient deterioration. In this dissertation, we aimed to develop and validate predictive models that achieve early and accurate prediction of CEs in infants with SV physiology. Such models may provide early and actionable information to clinicians and may be used to perform clinical interventions aimed at preventing CEs, and to reducing morbidity, mortality, and healthcare costs. We assert that our work is significant in that it addresses an unmet clinical need by achieving state-of-the-art, early prediction of patient deterioration in a challenging and vulnerable population. vi TABLE OF CONTENTS
Objective: Examine the relationship between perioperative renal regional oximetry (rSO2), urinary biomarkers, and acute kidney injury (AKI) in infants after congenital cardiac surgery with cardiopulmonary bypass. Design: Prospective, observational. Setting: Cardiac operating room and intensive care unit (CICU) Patients: Neonates and infants without history of kidney injury or anatomic renal abnormality. Interventions: None. Measurements and Main Results: Renal rSO2 was measured intraoperatively and for 48 hours postoperatively. Urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinases 2 (TIMP-2) together with insulin-like growth factor-binding protein 7 (IGFBP7) were measured preoperatively, 2, 12, and 24 hours postoperatively. Patients were categorized as no AKI, Stage 1, or Stage 2–3 AKI using KDIGO criteria with 43/70 (61%) meeting criteria for any stage AKI. Stage 2–3 AKI patients had higher [TIMP-2]•[IGFBP7] at 2 hours (0.3 vs. 0.14 for Stage 1 AKI and 0.05 for no AKI, P=0.052) and 24 hours postop (1.71 vs. 0.27 for Stage 1 AKI and 0.19 for no AKI, P=0.027) and higher NGAL levels at 24 hours postop (10.3 vs. 3.4 for Stage 1 AKI and 6.2 for no AKI, P=0.019). Stage 2–3 AKI patients had lower mean CICU renal rSO2 (66% vs. 79% for Stage 1 AKI and 84% for no AKI, P=0.038). Regression analyses showed that [TIMP-2]•[IGFBP7] at 2 hours postop and nadir intraoperative renal rSO2 to be independent predictors of postoperative kidney damage as measured by urinary NGAL. Conclusions: We observed modest differences in perioperative renal rSO2 and urinary biomarker levels compared between AKI groups classified by creatinine-dependent KDIGO criteria, but there were significant correlations between renal rSO2, [TIMP-2]•[IGFBP7], and postoperative NGAL levels. Kidney injury after infant cardiac surgery may be undetectable by functional assessment (creatinine) alone and continuous monitoring of renal rSO2 may be more sensitive to important subclinical AKI.
BackgroundThrombocytopenia-associated multi-organ failure (TAMOF) in children is a well-described factor for increased hospital mortality. Low cardiac output syndrome (LCOS) and the effects of cardiopulmonary bypass may manifest with several adverse physiologic and immunologic effects, with varying degrees of thrombocytopenia and multi-organ dysfunction, sometimes very similar to TAMOF. LCOS is a common occurrence in children with critical heart disease, presenting in as much as 23.8% of infants postoperative of congenital heart surgery. Therapeutic plasma exchange (TPE) has been offered as a promising therapy for TAMOF; however, the therapeutic implications of this modality in children with critical heart disease and a clinical diagnosis of TAMOF are unknown.ObjectivesWe describe our institutional experience with TPE as an adjuvant rescue therapy for children with critical heart disease and a clinical diagnosis of TAMOF, while supported by extracorporeal membrane oxygenation (ECMO).MethodsSingle-center retrospective analysis of children with critical heart disease admitted to the CICU and supported by ECMO, undergoing TPE for a clinical diagnosis of TAMOF between January 2006 and June 2015.ResultsForty-one patients were included for analysis. Median age and weight of patients was 0.6 years (range 0.0–17.2) and 8.5 kg (range 1.5–80.0). TPE was initiated at a median of 1 day (0–13) after initiation of ECMO. Modified organ failure index (MOFI) and platelet count improved after TPE start (p < 0.001). Patients with early TPE initiation after ECMO cannulation (<1 day) showed more improvement in MOFI and platelet counts than patients with late TPE initiation (p < 0.001 for each). Overall survival to hospital discharge was 53.7%. The within-groups hospital survival was 73.3% for patients with heart failure, 34.8% for patients with congenital heart disease, and 100% for those with other cardiac disease (p = 0.016).ConclusionIn children with critical cardiac disease and clinical diagnosis of TAMOF necessitating ECMO for hemodynamic support, concurrent TPE may be associated with an improvement in organ failure and platelet count, particularly when started early. Further studies are warranted to establish the most effective use of TPE and its effect on survival in this population.
The implementation of telemedicine-assisted interventions in a pediatric ECMO program delivered valuable diagnostic and therapeutic advice, was associated with significant changes in selection criteria and model of care, and an increased hospital survival.
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