Cindy S. Barrett

Neurological injury after extracorporeal membrane oxygenation use to aid pediatric cardiopulmonary resuscitation.

Objectives: Extracorporeal membrane oxygenation (ECMO) to aid failed cardiopulmonary resuscitation (CPR) in children is associated with a high incidence of neurologic injury. We sought to identify risk factors for acute neurologic injury in children undergoing ECMO to aid CPR (E-CPR). Design: Retrospective cohort study using data reported to the Extracorporeal Life Support Organization registry. Setting: Multi-institutional data. Patients: Patients <18 years of age undergoing E-CPR during 1992–2005. Interventions: None. Measurements and Results: We defined acute neurologic injury as the occurrence of brain death, brain infarction, or intracranial hemorrhage identified by ultrasound or computerized tomography imaging. Of 682 E-CPR patients, 147 (22%) patients had acute neurologic injury. Brain death occurred in 74 (11%), cerebral infarction in 45 (7%), and intracranial hemorrhage in 45 (7%). The in-hospital mortality rate in patients with acute neurologic injury was 89%. In a multivariable logistic regression model, pre-ECMO factors including cardiac disease (odds ratio [OR] 0.46 [95% confidence interval {CI} 0.28–0.76]) and pre-ECMO blood pH ≥6.865 (≥6.865–7.120; OR 0.49 [95% CI 0.25–0.94]; pH >7.120; OR 0.47 [95% CI 0.26–0.85]) compared with pH <6.865 were associated with decreased odds of neurologic injury. During ECMO, neurologic injury was associated with ECMO complications including pulmonary hemorrhage (OR 1.93, 95% CI 1.1–3.4), dialysis use (OR 2.36, 95% CI 1.4–4.0), and CPR during ECMO support (OR 2.08, 95% CI 1.6–3.8). Conclusions: Neurologic injury is a frequent complication in children undergoing E-CPR. Children with cardiac disease, less severe metabolic acidosis before ECMO, and an uncomplicated ECMO course have decreased odds of sustaining neurologic injury. Providing effective CPR and inclusion of brain protective therapies on ECMO should be considered in the future to improve neurologic outcomes for patients undergoing E-CPR.

Pediatric ECMO outcomes: comparison of centrifugal versus roller blood pumps using propensity score matching.

Centrifugal blood pumps are being increasingly utilized in children supported with extracorporeal membrane oxygenation (ECMO). Our aim was to determine if survival and ECMO-related morbidities in children supported with venoarterial (VA) ECMO differed by blood pump type.Children aged less than 18 years who underwent VA ECMO support from 2007 to 2009 and reported to the Extracorporeal Life Support Organization registry were propensity score matched (Greedy 1:1 matching) using pre-ECMO characteristics.A total of 2,656 (centrifugal = 2,231, roller = 425) patients were identified and 548 patients (274 per pump type) were included in the propensity score-matched cohort. Children supported with centrifugal pumps had increased odds of hemolysis (odds ratio [OR], 4.03 95% confidence interval [CI], 2.37–6.87), hyperbilirubinemia (OR, 5.48; 95% CI, 2.62–11.49), need for inotropic support during ECMO (OR, 1.54; 95% CI, 1.09–2.17), metabolic alkalosis (blood pH > 7.6) during ECMO (OR, 3.13; 95% CI, 1.49–6.54), and acute renal failure (OR, 1.61; 95% CI, 1.10–2.39). Survival to hospital discharge did not differ by pump type.In a propensity score-matched cohort of pediatric ECMO patients, children supported with centrifugal pumps had increased odds of ECMO-related complications. There was no difference in survival between groups.

Extracorporeal membrane oxygenation support after the Fontan operation

OBJECTIVE Extracorporeal membrane oxygenation has been used to support children with cardiac failure after the Fontan operation. Mortality is high, and causes of mortality remain unclear. We evaluated the in-hospital mortality and factors associated with mortality in these patients. METHODS Extracorporeal Life Support Organization registry data on patients requiring extracorporeal membrane oxygenation after the Fontan operation from 1987 to 2009 were retrospectively analyzed. Demographics and extracorporeal membrane oxygenation data were compared for survivors and nonsurvivors. A multivariable logistic regression model was used to identify factors associated with mortality. RESULTS Of 230 patients, 81 (35%) survived to hospital discharge. Cardiopulmonary resuscitation was more frequent (34% vs 17%, P = .04), and median fraction of inspired oxygen concentration was higher (1 [confidence interval, 0.9-1.0] vs 0.9 [confidence interval, 0.8-1.0], P = .03) before extracorporeal membrane oxygenation in nonsurvivors compared with survivors. Extracorporeal membrane oxygenation duration and incidence of complications, including surgical bleeding, neurologic injury, renal failure, inotrope use on extracorporeal membrane oxygenation, and bloodstream infection, were higher in nonsurvivors compared with survivors (P < .05 for all). In a multivariable model, neurologic injury (odds ratio, 5.18; 95% confidence interval, 1.97-13.61), surgical bleeding (odds ratio, 2.36; 95% confidence interval, 1.22-4.56), and renal failure (odds ratio, 2.81; 95% confidence interval, 1.41-5.59) increased mortality. Extracorporeal membrane oxygenation duration of more than 65 hours to 119 hours (odds ratio, 0.33; 95% confidence interval, 0.14-0.76) was associated with decreased mortality. CONCLUSIONS Cardiac failure requiring extracorporeal membrane oxygenation after the Fontan operation is associated with high mortality. Complications during extracorporeal membrane oxygenation support increase mortality odds. Prompt correction of surgical bleeding when possible may improve survival.

The association of carotid artery cannulation and neurologic injury in pediatric patients supported with venoarterial extracorporeal membrane oxygenation

Objectives: To describe the prevalence of neurologic injury in a recent cohort of patients 18 years old or younger cannulated for venoarterial extracorporeal membrane oxygenation. To evaluate the association of carotid artery cannulation with neurologic injury when compared with other cannulation sites. To determine if age impacts the association of carotid artery cannulation with neurologic injury. Design: Retrospective analysis of data from the Extracorporeal Life Support Organization registry. Setting: Neonatal and pediatric medical/surgical and cardiac ICUs of 118 international tertiary care centers worldwide. Patients: Pediatric patients 18 years old or younger cannulated for venoarterial extracorporeal membrane oxygenation and reported to the Extracorporeal Life Support Organization registry during 2007 and 2008. Interventions: None. Measurements and Main Results: Two thousand nine hundred seventy-seven patients underwent venoarterial extracorporeal membrane oxygenation during the study period. Indications for extracorporeal membrane oxygenation included pulmonary (n = 1,390, 47%), cardiac (n = 1,168, 39%), extracorporeal membrane oxygenation during cardiopulmonary resuscitation (n = 418, 14%), and unknown (n = 1). Arterial cannulation sites were aorta (n = 938, 32%), femoral artery (n = 118, 4%), and carotid artery (n = 1,921, 64%). Overall, 611 patients (21%) had evidence of neurologic injury defined as seizures, infarction, and/or hemorrhage. The occurrence of neurologic injury varied significantly by cannulation site: femoral artery (n = 18, 15%), aorta (n = 160, 17%), and carotid artery (n = 433, 23%); p equals 0.001. Neonates represented the largest group of patients cannulated for venoarterial extracorporeal membrane oxygenation (n = 1,807, 61%), the majority of patients cannulated via the carotid artery (n = 1,276, 66%), and had the highest burden of neurologic injury (n = 398, 22%). Age, preextracorporeal membrane oxygenation high-frequency oscillatory ventilation use, preextracorporeal membrane oxygenation arterial pH and serum bicarbonate level, and preextracorporeal membrane oxygenation cardiac arrest were independently associated with neurologic injury in a covariate model. Carotid artery cannulation site was added to this adjusted model and found to independently increase odds of neurologic injury (odds ratio, 1.4 [95% CI, 1.01–1.69]). An interaction term containing age and cannulation site was not associated with neurologic injury (odds ratio, 1.06 [95% CI, 0.84–1.34]). Conclusions: Carotid artery cannulation for venoarterial extracorporeal membrane oxygenation in patients 18 years old or younger is associated with statistically significant increased odds of neurologic injury. These increased odds are present across all age groups.

Outcomes of Neonates Undergoing Extracorporeal Membrane Oxygenation Support Using Centrifugal Versus Roller Blood Pumps

BACKGROUND Advances in centrifugal blood pump technology have led to increased use of centrifugal pumps in extracorporeal membrane oxygenation (ECMO) circuits. Their efficacy and safety in critically ill neonates remains unknown. Blood cell trauma leading to hemolysis may result in end-organ injury in critically ill neonates receiving centrifugal pump ECMO. We hypothesized that neonates undergoing ECMO support using centrifugal pumps were at increased odds of hemolysis and subsequent end-organ injury. METHODS Children 30 days of age or younger who received support with venoarterial ECMO and were reported to the Extracorporeal Life Support Registry during 2007 to 2009 underwent propensity score matching (Greedy matching 1:1) using pre-ECMO support characteristics. RESULTS A total of 1,592 neonates receiving ECMO (centrifugal pump = 163 and roller pump = 1,492) were identified. Significant differences in demographic, presupport, and cannulation variables were present before matching. One hundred seventy-six neonates who were supported using either centrifugal (n = 88) or roller pumps (n = 88) were matched using propensity scoring. No significant differences in demographic, presupport, or cannulation variables were present after matching. Neonates undergoing support using centrifugal pumps had increased odds of hemolysis (odds ratio [OR], 7.7 [2.8-21.2]), hyperbilirubinemia (OR, 20.8 [2.7-160.4]), hypertension (OR, 3.2 [1.3-8.0]), and acute renal failure (OR, 2.4 [1.1-5.6]). Survival to discharge was not different between pump types. CONCLUSIONS Use of ECMO using centrifugal pumps is associated with increased odds of hemolysis that likely contributes to other end-organ injury. Research into the optimal use of centrifugal pumps and strategies to prevent support-related complications need to be investigated.

Extracorporeal membrane oxygenation in patients undergoing superior cavopulmonary anastomosis

OBJECTIVE Patients who have undergone the superior cavopulmonary anastomosis (Glenn procedure) have unique cardiopulmonary-cerebral physiology that may limit the success of cardiopulmonary resuscitation and extracorporeal membrane oxygenation (ECMO). Limited data published to date suggest grim morbidity and mortality when ECMO is used. We utilized the Extracorporeal Life Support Organization registry database to more thoroughly assess outcomes in these patients. METHODS Data from the Extracorporeal Life Support Organization registry from 1999 to 2012 for children with Glenn physiology aged 3 months to 1 year were retrospectively analyzed. Demographics and ECMO characteristics were compared between survivors and nonsurvivors. Factors associated with mortality were evaluated using multivariate logistic regression. RESULTS Of 103 infants, 42 (41%) survived to hospital discharge. Neurologic complications (eg, seizure, hemorrhage, or embolic stroke) were documented in 23% of patients (24 of 103) and 14% of survivors (6 of 42). In univariate analysis, inotropic requirement before ECMO, duration of ECMO, mechanical complications with the ECMO circuit, renal failure, and pulmonary hemorrhage or pneumothorax were predictors of mortality. In multivariate logistic regression, inotrope requirement (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.3-9.8), longer duration of ECMO support (OR, 7.2; 95% CI, 1.8-28), combined cardiopulmonary indication for ECMO (OR, 3.7; 95% CI, 1.4-9.7), and renal failure (OR, 4.2; 95% CI, 1.5-12) were associated with mortality. CONCLUSIONS Mortality in infants with Glenn physiology supported with ECMO is lower than that previously reported, but the incidence of neurologic injury is high. These data support use of ECMO in patients with Glenn physiology with refractory cardiopulmonary failure.

Neurologic injury in neonates with congenital heart disease during extracorporeal membrane oxygenation: an analysis of extracorporeal life support organization registry data.

The aim of this article is to describe the epidemiology and factors associated with acute neurologic injury in neonates with congenital heart disease (CHD) undergoing extracorporeal membrane oxygenation (ECMO). It is a retrospective cohort study. Multi-institutional data for purposes of this study were obtained from the extracorporeal life support organization registry Neonates with CHD supported with ECMO during 2005–2010. Of 1,898 neonates with CHD supported with ECMO, 273 (14%) had neurologic injury. Birth weight less than 3 kg (odds ratio [OR]: 1.5; 95% confidence intervals [CI]: 1.1–1.9), pre-ECMO blood pH ⩽ 7.15 (OR: 1.5, 95% CI: 1.1–2.1) need for cardiopulmonary resuscitation before ECMO (OR: 1.7, 95% CI: 1.5–2.0) increased neurologic injury. In-hospital mortality was higher in patients with neurologic injury compared with those without (73% vs. 53%; p < 0.001). Neonates with CHD undergoing ECMO are highly vulnerable to acute neurologic injury regardless of cardiac lesion-specific physiology or the occurrence of cardiac surgery. The incidence of neurologic injuries in this population is higher in sicker patients. Severity of illness should therefore become the main target for improvement. Timely deployment of ECMO may therefore influence the development of ECMO complications.

Improved Nutrition Delivery and Nutrition Status in Critically Ill Children With Heart Disease

BACKGROUND: This initiative sought to improve nutrition delivery in critically ill children with heart disease admitted to the cardiac ICU (CICU) and neonates undergoing stage 1 palliation (S1P) for single-ventricle physiology through interdisciplinary team interventions. Specific goals were increased caloric and protein delivery for all patients and a more nourished state for infants with single ventricles at the time of discharge. METHODS: We developed a nutrition flow sheet in the electronic health record to track whether daily nutrition goals were met. Interventions included nurses reporting daily whether caloric and protein goals were met, mandatory involvement of feeding specialists, and introduction of an enteral nutrition guideline. For infants undergoing S1P, weight-for-age z score (as an indicator for assessing malnutrition) was calculated at admission and discharge. RESULTS: The percentage of patient days per month when daily caloric goals were met increased from 50.1% to 60.7%, and protein goals met increased from 51.6% to 72.7%. Hospital length of stay, need for ventilation, and mortality did not differ. Patients undergoing S1P demonstrated a statistically significant improvement in weight-for-age z score compared with the preintervention group (P = .003). Thirteen S1P patients were discharged undernourished in the preintervention group; 5 were severely undernourished. In the intervention group, 4 patients were discharged undernourished, and none were severely undernourished. CONCLUSIONS: This initiative resulted in improved nutrition delivery for a heterogeneous population of cardiac patients in the CICU as well as significant improvements in weight gain and nourishment status at discharge in infants undergoing S1P.

Racial Variations in Extracorporeal Membrane Oxygenation Use Following Congenital Heart Surgery

Objectives: Previous studies demonstrate racial and ethnic disparities among children undergoing congenital heart surgery. Extracorporeal membrane oxygenation (ECMO) is used to support critically ill children after congenital heart surgery and improve survival. Thus, racial or ethnic variations in postoperative ECMO use following congenital heart surgery may be associated with racial/ethnic disparities in hospital survival. Methods: All children in the Pediatric Health Information Systems dataset undergoing congenital heart surgery from 2004 to 2015 were examined. Multivariable, multinomial regression models examining hospital survival without ECMO use, survival after ECMO, death after ECMO, and death without ECMO support were constructed. Results: Of 130,860 congenital cardiac surgery patients, 95.4% survived to hospital discharge without requiring ECMO support, whereas 1.3% survived after ECMO support, 1.3% died after ECMO support, and 1.9% died without receiving ECMO support. After adjustment for other covariates, black patients (odds ratio, 1.22; 95% confidence interval [CI], 1.05‐1.42) and patients of other race (odds ratio, 1.36; 95% CI, 1.17‐1.58) were at increased odds of mortality compared with white patients. In multivariable multinomial models, black patients had increased risk of death without ECMO support (relative risk, 1.31; 95% CI, 1.11‐1.56). Patients of other race (relative risk, 1.37; 95% CI, 1.10‐1.69) and governmental insurance (relative risk, 1.24; 95% CI, 1.12‐1.37) were also at increased risk of death without ECMO. Conclusions: Black children and children of other race are at increased odds of mortality after congenital heart surgery. These disparities can be traced to variations in ECMO utilization across racial/ethnic groups.

Metrics to assess extracorporeal membrane oxygenation utilization in pediatric cardiac surgery programs

Objectives: Only a small fraction of pediatric cardiac surgical patients are supported with extracorporeal membrane oxygenation following cardiac surgery, but extracorporeal membrane oxygenation use is more common among those undergoing higher complexity surgery. We evaluated extracorporeal membrane oxygenation metrics indexed to annual cardiac surgical volume to better understand extracorporeal membrane oxygenation use among U.S. cardiac surgical programs. Design: Retrospective analysis Setting: Forty-three U.S. Children’s Hospitals in the Pediatric Health Information System that performed cardiac surgery and used extracorporeal membrane oxygenation. Patients: All patients (< 19 yr) undergoing cardiac surgery during January 2003 to July 2014. Interventions: None. Measurements and Main Results: Both extracorporeal membrane oxygenation use and surgical mortality were risk adjusted using Risk Adjustment for Congenital Heart Surgery 1. Extracorporeal membrane oxygenation metrics indexed to annual cardiac surgery cases were calculated for each hospital and the metric values divided into quintiles for comparison across hospitals. Among 131,786 cardiac surgical patients, 3,782 (2.9%) received extracorporeal membrane oxygenation. Median case mix adjusted rate of extracorporeal membrane oxygenation use was 2.8% (interquartile range, 1.6–3.4%). Median pediatric cardiac case mix adjusted surgical mortality was 3.5%. Extracorporeal membrane oxygenation-associated surgical mortality was 1.3% (interquartile range, 0.7–1.6%); without extracorporeal membrane oxygenation, median case mix adjusted surgical mortality would increase from 3.5% to 5.0%. Among patients who died, 36.7% (median) were supported with extracorporeal membrane oxygenation. The median reduction in case mix adjusted surgical mortality from extracorporeal membrane oxygenation surgical survival was 30.1%. The median extracorporeal membrane oxygenation free surgical survival was 95% (interquartile range, 94–96%). Centers with less than 150 annual surgical cases had significantly lower median extracorporeal membrane oxygenation use (0.78%) than centers with greater than 275 cases (≥ 2.8% extracorporeal membrane oxygenation use). Extracorporeal membrane oxygenation use and mortality varied within quintiles and across quintiles of center annual surgical case volume. Conclusions: Risk adjusted extracorporeal membrane oxygenation metrics indexed to annual surgical volume provide potential for benchmarking as well as a greater understanding of extracorporeal membrane oxygenation utilization, efficacy, and impact on cardiac surgery mortality.