Curtis Kennedy

Cardiac Structural and Functional Alterations in Infants and Children with Biliary Atresia, Listed for Liver Transplantation

BACKGROUND & AIMS Cirrhotic liver diseases are associated with abnormalities in cardiac geometry and function in adults (cirrhotic cardiomyopathy) but rarely explored in cirrhotic infants or children. We proposed that features of cirrhotic cardiomyopathy are present in infants with cirrhosis due to biliary atresia (BA) as early as the time of evaluation for liver transplant and will correlate with mortality and postoperative morbidity. METHODS Two-dimensional echocardiography (2DE) of infants with BA (n=40; median age, 8 months), listed for transplantation at the Texas Childrens Hospital from 2004 to 2010, were reviewed and compared with age- and sex-matched infants without cardiac or liver disease (controls). Length of stay and correlation with 2DE results were assessed. RESULTS Compared with controls, children with BA had significant increases in multiple 2DE parameters, notably left ventricle wall thickness (23% increase), left ventricular (LV) mass indexed to body surface area (51% increase), and LV shortening fraction (8% increase). Overall, features of cirrhotic cardiomyopathy were observed in most infants (29/40; 72%); 17 had hyperdynamic contractility, and 24 had altered LV geometry. After liver transplantation (33), infants with abnormal 2DE results had longer stays in the intensive care unit (median, 6 vs 4 days) and the hospital (21 vs 11 days) compared with infants who had normal 2DE reports. On univariate analysis, the length of hospital stay correlated with LV mass index. CONCLUSIONS Cardiomyopathy is a prevalent condition in infants with end-stage cirrhotic liver disease due to BA (>70%). This underrecognized condition likely contributes to the prolongation of posttransplant hospitalization.

Resuscitation Bundle in Pediatric Shock Decreases Acute Kidney Injury and Improves Outcomes

OBJECTIVE To investigate the impact of an early emergency department (ED) protocol-driven resuscitation (septic shock protocol [SSP]) on the incidence of acute kidney injury (AKI). STUDY DESIGN This was a retrospective pediatric cohort with clinical sepsis admitted to the pediatric intensive care unit (PICU) from the ED before (2009, PRE) and after (2010, POST) implementation of the SSP. AKI was defined by pRIFLE (pediatric version of the Risk of renal dysfunction; Injury to kidney; Failure of kidney function; Loss of kidney function, End-stage renal disease creatinine criteria). RESULTS A total of 202 patients (PRE, n = 98; POST, n = 104) were included (53% male, mean age 7.7 ± 5.6 years, mean Pediatric Logistic Organ Dysfunction [PELOD] 8.9 ± 12.7, mean Pediatric Risk of Mortality score 5.3 ± 13.9). There were no differences in demographics or illness severity between the PRE and POST groups. POST was associated with decreased AKI (54% vs 29%, P < .001), renal-replacement therapy (4 vs 0, P = .04), PICU, and hospital lengths of stay (LOS) (1.9 ± 2.3 vs 4.5 ± 7.6, P < .01; 6.3 ± 5.1 vs 15.3 ± 16.9, P < .001, respectively), and mortality (10% vs 3%, P = .037). The SSP was independently associated with decreased AKI when we controlled for age, sex, and PELOD (OR 0.27, CI 0.13-0.56). In multivariate analyses, the SSP was independently associated with shorter PICU and hospital LOS when we controlled for AKI and PELOD (P = .02, P < .001, respectively). CONCLUSION A protocol-driven implementation of a resuscitation bundle in the pediatric ED decreased AKI and need for renal-replacement therapy, as well as PICU and hospital LOS and mortality.

Time series analysis as input for clinical predictive modeling: Modeling cardiac arrest in a pediatric ICU

BackgroundThousands of children experience cardiac arrest events every year in pediatric intensive care units. Most of these children die. Cardiac arrest prediction tools are used as part of medical emergency team evaluations to identify patients in standard hospital beds that are at high risk for cardiac arrest. There are no models to predict cardiac arrest in pediatric intensive care units though, where the risk of an arrest is 10 times higher than for standard hospital beds. Current tools are based on a multivariable approach that does not characterize deterioration, which often precedes cardiac arrests. Characterizing deterioration requires a time series approach. The purpose of this study is to propose a method that will allow for time series data to be used in clinical prediction models. Successful implementation of these methods has the potential to bring arrest prediction to the pediatric intensive care environment, possibly allowing for interventions that can save lives and prevent disabilities.MethodsWe reviewed prediction models from nonclinical domains that employ time series data, and identified the steps that are necessary for building predictive models using time series clinical data. We illustrate the method by applying it to the specific case of building a predictive model for cardiac arrest in a pediatric intensive care unit.ResultsTime course analysis studies from genomic analysis provided a modeling template that was compatible with the steps required to develop a model from clinical time series data. The steps include: 1) selecting candidate variables; 2) specifying measurement parameters; 3) defining data format; 4) defining time window duration and resolution; 5) calculating latent variables for candidate variables not directly measured; 6) calculating time series features as latent variables; 7) creating data subsets to measure model performance effects attributable to various classes of candidate variables; 8) reducing the number of candidate features; 9) training models for various data subsets; and 10) measuring model performance characteristics in unseen data to estimate their external validity.ConclusionsWe have proposed a ten step process that results in data sets that contain time series features and are suitable for predictive modeling by a number of methods. We illustrated the process through an example of cardiac arrest prediction in a pediatric intensive care setting.

The Centers for Disease Control and Prevention's New Definitions for Complications of Mechanical Ventilation Shift the Focus of Quality Surveillance and Predict Clinical Outcomes in a PICU.

Objectives: The Centers for Disease Control and Prevention shifted the focus of surveillance paradigm for adult patients receiving mechanical ventilation, moving from the current standard of ventilator-associated pneumonia to broader complications. The surveillance definitions were designed to enable objective measures and efficient processes, so as to facilitate quality improvement initiatives and enhance standardized benchmark comparisons. We evaluated the surveillance definitions in term of their ability to predict clinical outcomes and ease of surveillance in a PICU. Design: Retrospective cohort study. Setting: A PICU at a university-affiliated children’s hospital. Patients: Eight hundred thirty-six patients receiving mechanical ventilation over 1-year period. Interventions: None. Measurements and Main Results: We applied the definition for ventilator-associated condition (i.e., a sustained increase in ventilator setting after a period of stable or decreasing support) to our database. Of total 606 patients, 14.5% had ventilator-associated condition (20.9/1,000 ventilator days) and 8.1% had an infection-related ventilator-associated condition (12.9/1,000 ventilator days). The patients with infection-related ventilator-associated condition were classified into probable pneumonia (55%), possible pneumonia (28.6%), and undetermined infection (16.3%). A large portion of patients with ventilator-associated condition (44%) had other noninfectious etiologies (e.g., atelectasis, pulmonary edema, and shock). Patients who developed ventilator-associated condition had significantly longer ventilatory, ICU, and hospital days compared with those who did not. The ventilator-associated condition group had increased hospital mortality compared with the non–ventilator-associated condition group (19.3% vs 6.9%; p = 0.0007). Multivariate regression analysis identified ventilator-associated condition as one of the predictors of hospital mortality with an adjusted odds ratio of 2.14 (95% CI, 1.03–4.42). Risk factors for developing a ventilator-associated condition included immunocompromised status (odds ratio, 2.90; 95% CI, 1.57–5.33), tracheostomy dependence (odds ratio, 2.78; 95% CI, 1.40–5.51), and chronic respiratory disease (odds ratio, 1.85; 95% CI, 1.03–3.3). Conclusions: The definitions for the various ventilator-associated conditions are good predictors of outcomes in children and adults and are amenable to automated surveillance. Based on the study findings, we suggest consideration for shifting the focus of surveillance for ventilator-associated events from only pneumonia to a broader range of complications.

Using time series analysis to predict cardiac arrest in a PICU

Objectives: To build and test cardiac arrest prediction models in a PICU, using time series analysis as input, and to measure changes in prediction accuracy attributable to different classes of time series data. Design: Retrospective cohort study. Setting: Thirty-one bed academic PICU that provides care for medical and general surgical (not congenital heart surgery) patients. Subjects: Patients experiencing a cardiac arrest in the PICU and requiring external cardiac massage for at least 2 minutes. Interventions: None. Measurements and Main Results: One hundred three cases of cardiac arrest and 109 control cases were used to prepare a baseline dataset that consisted of 1,025 variables in four data classes: multivariate, raw time series, clinical calculations, and time series trend analysis. We trained 20 arrest prediction models using a matrix of five feature sets (combinations of data classes) with four modeling algorithms: linear regression, decision tree, neural network, and support vector machine. The reference model (multivariate data with regression algorithm) had an accuracy of 78% and 87% area under the receiver operating characteristic curve. The best model (multivariate + trend analysis data with support vector machine algorithm) had an accuracy of 94% and 98% area under the receiver operating characteristic curve. Conclusions: Cardiac arrest predictions based on a traditional model built with multivariate data and a regression algorithm misclassified cases 3.7 times more frequently than predictions that included time series trend analysis and built with a support vector machine algorithm. Although the final model lacks the specificity necessary for clinical application, we have demonstrated how information from time series data can be used to increase the accuracy of clinical prediction models.

The Use of Nesiritide in Children With Congenital Heart Disease.

Objective: We evaluated the use of nesiritide in children with critical congenital heart disease, pulmonary congestion, and inadequate urine output despite conventional diuretic therapy. Design: We conducted a retrospective analysis of 26 consecutive patients, comprising 37 infusions occurring during separate hospitalizations. Hemodynamic variables, urine output, and serum creatinine levels were monitored prior to and throughout the duration of therapy with nesiritide. In addition, the stage of acute kidney injury was determined prior to and throughout the duration of the therapy using a standardized definition of acute kidney injury—The Kidney Disease: Improving Global Outcomes criteria. Setting: Cardiac ICU. Patients: Pediatric patients with critical congenital heart disease, pulmonary congestion, and inadequate urinary output despite diuretic therapy. Intervention: Nesiritide infusion. Measurements and Main Results: The use of nesiritide was associated with a significant decrease in the central venous pressure and heart rate with a trend toward a significant increase in urine output. During the course of therapy with nesiritide, the serum creatinine and stage of acute kidney injury decreased significantly. The decrease in stage of acute kidney injury became significant by day 4 (p = 0.006) and became more significant with time (last day of therapy compared with baseline; p < 0.001). During 12 of the 37 infusions, the stage of acute kidney injury decreased by two or more (p < 0.001). Conclusions: Nesiritide had a favorable impact on hemodynamics and urine output in children with critical congenital heart disease and pulmonary congestion, and there was no worsening of renal function.

Epilepsy is associated with ventricular alterations following convulsive status epilepticus in children

Convulsive status epilepticus can exert profound cardiovascular effects in adults, including ventricular depolarization–repolarization abnormalities. Whether status epilepticus adversely affects ventricular electrical properties in children is less understood. Therefore, we sought to characterize ventricular alterations and the associated clinical factors in children following convulsive status epilepticus.

Clinical Consequences of Cardiomyopathy in Children with Biliary Atresia Requiring Liver Transplantation

Cirrhotic cardiomyopathy (CCM), a comorbidity of end‐stage cirrhotic liver disease, remains uncharacterized in children, largely because of a lack of an established pediatric definition. The aim of this retrospective cohort analysis is to derive objective two‐dimensional echocardiographic (2DE) criteria to define CCM associated with biliary atresia (BA), or BA‐CCM, and correlate presence of BA‐CCM with liver transplant (LT) outcomes in this population. Using receiver operating characteristic (ROC) curve analysis, optimal cut‐off values for left ventricular (LV) geometrical parameters that were highly sensitive and specific for the primary outcomes: A composite of serious adverse events (CSAE) and peritransplant death were determined. These results were used to propose a working definition for BA‐CCM: (1) LV mass index (LVMI) ≥95 g/m2.7 or (2) relative wall thickness of LV ≥0.42. Applying these criteria, BA‐CCM was found in 34 of 69 (49%) patients with BA listed for LT and was associated with increased multiorgan dysfunction, mechanical and vasopressor support, and longer intensive care unit (ICU) and hospital stays. BA‐CCM was present in all 4 waitlist deaths, 7 posttransplant deaths, and 20 patients with a CSAE (P < 0.01). On multivariable regression analysis, BA‐CCM remained independently associated with both death and a CSAE (P < 0.01). Utilizing ROC analysis, LVMI was found to be a stronger predictor for adverse outcomes compared with current well‐established markers, including Pediatric End‐Stage Liver Disease (PELD) score. Conclusion: BA‐CCM is highly sensitive and specific for morbidity and mortality in children with BA listed for LT. 2DE screening for BA‐CCM may provide pertinent clinical information for prioritization and optimal peritransplant management of these children.

The use of nesiritide in patients with critical cardiac disease

OBJECTIVE We evaluated the use of nesiritide in children with critical CHD, pulmonary congestion, and inadequate urine output despite undergoing conventional diuretic therapy. DESIGN We conducted a retrospective analysis of 11 patients with critical CHD, comprising 18 infusions, each of which occurred during separate hospitalisations. Haemodynamic parameters were assessed, and the stage of acute kidney injury was determined before and throughout the duration of therapy using a standardised definition of acute kidney injury - The Kidney Disease: Improving Global Outcomes criteria. Patients Children with critical CHD, pulmonary congestion, and inadequate urinary output despite undergoing diuretic therapy were included. Measurements and main results The use of nesiritide was associated with a significant decrease in the maximum and minimum heart rate values and with a trend towards a significant decrease in maximum systolic blood pressure and maximum and minimum central venous pressures. Urine output increased but was not significant. Serum creatinine levels decreased significantly during the course of therapy (-0.26 mg/dl [-0.50, 0.0], p=0.02), and the number of patients who experienced a decrease in the stage of acute kidney injury of 2 or more - where a change in the stage of acute kidney disease of 2 or more was possible, that is, baseline stage >1 - was highly significant (five of 12 patients, 42%, p<0.001). CONCLUSIONS Nesiritide had a favourable impact on haemodynamics, and its use was not associated with deterioration of renal function in patients with critical CHD.

1298: ACUTE KIDNEY INJURY AND FLUID OVERLOAD MAY BE BETTER RECOGNIZED BY AUTOMATED SCREENING

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) water-inflatable cuff and the insertion of a fluid-filled pressure catheter. Renal autoregulation was assessed by recording the change in renal blood flow (RBF) in response to stepwise reductions in renal perfusion pressure. Sepsis was induced by fecal peritonitis. Treatment consisted of fluid administration to maintain pulmonary artery balloon-occluded pressure at baseline levels. After mean arterial pressure fell below 65 mmHg in the absence of fluid-responsiveness, the animals were randomized to receive NE or AVP to restore a blood pressure of 85-95 mmHg. Before switching to the second vasopressor, discontinuation of the first vasopressor for 30 min ensured a complete wash-out. Autoregulation was assessed at baseline, after 6 hours, and during vasopressor infusion. Data were analyzed using pairwise Student’s T-test with Bonferroni correction for multiple testing. Results: The model was characterized by a hyperdynamic pattern, associated with progressive renal vasodilation and increased RBF. The lower limit of renal autoregulation was unaffected at 6 hours (64 ± 7 vs. 63 ± 6 mmHg at baseline, p = 0.87). After shock, AVP was associated with a lower autoregulatory threshold, implying better renal autoregulation, compared to NE (59 ± 5 vs. 65 ± 7 mmHg, p = 0.07, N = 6 animals, study ongoing). Conclusions: In this clinically relevant animal model of septic shock, AVP seemed associated with better renal autoregulation than NE. This study supports the renal protective effects of vasopressin in septic shock.