Jonathan W. Byrnes

Hemolysis during cardiac extracorporeal membrane oxygenation: a case-control comparison of roller pumps and centrifugal pumps in a pediatric population.

Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy, which has been used for the support of children with a broad range of diseases. Two pumps of differing mechanisms have been used to generate the extracorporeal flow: roller-head pumps and centrifugal pumps. Seven patients supported during ECMO with Levitronix Centrimag (Centrimag group [CG]) were matched to 14 patients supported with Stockert-Shiley SIII (Stockert-Shiley group [SSG]) at a single institution from July 2007 to July 2009. We hypothesized that hemolysis as measured by plasma-free hemoglobin (PFH) is elevated in the SSG versus the CG during cardiac ECMO. Categorical data were analyzed using Fishers exact test. Plasma-free hemoglobin differences between groups were analyzed using both Wilcoxon rank sum and beta regression. Overall, SSG patients had two times the odds of having a higher PFH than CG patients adjusting for repeated measures (odds ratio [OR] = 1.96, 95% confidence interval [CI]: [1.15–3.34], p < 0.014). Differences between circuit failure in the first 168 hours did not reach statistical significance (1/7 CG vs. 7/14 SSG; p = 0.174). In this population of cardiac patients requiring ECMO support, more hemolysis occurred in the SSG, a roller-head pump supported group, when compared with the CG, a centrifugal pump supported group. Differences in circuit life did not reach statistical significance. This pilot study contrasts with past studies, which have demonstrated more hemolysis occurring with centrifugal pumps when compared with roller-head pumps.

Incremental reduction in the incidence of stroke in children supported with the Berlin EXCOR ventricular assist device.

BACKGROUND Cerebrovascular events (CVEs) are common among children supported with the Berlin EXCOR (Berlin Heart GmbH, Berlin, Germany) ventricular assist device (VAD). Given the high incidence of CVEs associated with this device, we sought to describe our institutional experience in incrementally reducing CVEs in children supported with the Berlin EXCOR VAD. METHODS We collected pertinent data on 39 consecutive patients who underwent Berlin EXCOR VAD implantation at a single center. Frequency of CVEs was described in risk per implantation, per day, and in reference to the time of therapeutic anticoagulation. Risk factors were analyzed for association with CVEs. RESULTS Of the initial 39 Berlin EXCOR VAD implantations, 16 CVEs occurred in 12 patients. The incidence of CVEs decreased with institutional experience per patient (R(2) = 0.6909, p = 0.007) and per patient-day (R(2) = 0.8051, p = 0.002). CVEs occurred more frequently before therapeutic anticoagulation targets were achieved (4.1%/day) compared with after therapeutic anticoagulation targets were achieved (0.9%/day; p = 0.044). CONCLUSIONS Incidence of CVEs decreased with institutional experience. The risk of CVE is highest in the immediate postoperative period before therapeutic anticoagulation is achieved. Further studies are warranted in pediatric patients supported with the Berlin EXCOR VAD to confirm our findings in a larger cohort.

Antithrombin III supplementation on extracorporeal membrane oxygenation: impact on heparin dose and circuit life.

Antithrombin III (ATIII) is used during extracorporeal membrane oxygenation (ECMO) based on physiologic rationale and studies during cardiopulmonary bypass. In February 2008, our institution began using ATIII as replacement for low ATIII activity (<70%) in patients supported with ECMO. We hypothesized that ATIII supplementation would reduce heparin infusion rates, increase unfractionated heparin anti-Xa levels, and prolong ECMO circuit life. Data from 40 consecutive patients (45 deployments) requiring ECMO support for >72 hours with venoarterial ECMO from January 1, 2007, through December 31, 2008, were collected. Antithrombin III concentrate was administered for ATIII activity <70% at the discretion of the attending physician. The primary outcome was whether the heparin infusion rate was reduced by 10% or more as a result of ATIII administration. No difference in heparin infusion rate (p = 0.245) as a result of ATIII administration was observed. Anti-Xa levels were lower before ATIII administration (p< 0.001) and were increased after ATIII administration (p < 0.001). There was an increased frequency of circuit failure in ATIII treatment group compared with nontreatment group (p = 0.018). Neither heparin responsiveness nor circuit life was enhanced by daily ATIII supplementation for activity <70%. Future studies are warranted to evaluate the effectiveness of antithrombin replacement.

Unfractionated heparin activity measured by anti-factor Xa levels is associated with the need for extracorporeal membrane oxygenation circuit/membrane oxygenator change: a retrospective pediatric study.

Objective: Investigate whether anti-Factor Xa levels are associated with the need for change of circuit/membrane oxygenator secondary to thrombus formation in pediatric patients. Design and Settings: Retrospective single institution study. Patients: Retrospective record review of 62 pediatric patients supported with extracorporeal membrane oxygenation from 2009 to 2011. Interventions: Data on standard demographic characteristics, indications for extracorporeal membrane oxygenation, duration of extracorporeal membrane oxygenation, activated clotting time measurements, anti-Factor Xa measurements, and heparin infusion rate were collected. Generalized linear models were used to associate anti-Factor Xa concentrations and need for change of either entire circuit/membrane oxygenator secondary to thrombus formation. Measurements and Main Results: Sixty-two patients met study inclusion criteria. No-circuit change was required in 45 of 62 patients. Of 62 patients, 17 required change of circuit/membrane oxygenator due to thrombus formation. Multivariate analysis of daily anti-Factor Xa measurements throughout duration of extracorporeal membrane oxygenation support estimated a mean anti-Factor Xa concentration of 0.20 IU/mL (95% CI, 0.16, 0.24) in no-complete-circuit group that was significantly higher than the estimated concentration of 0.13 IU/mL (95% CI, 0.12, 0.14) in complete-circuit group (p = 0.001). A 0.01 IU/mL decrease in anti-Factor Xa increased odds of need for circuit/membrane oxygenator change by 5% (odds ratio = 1.105; 95% CI, 1.00, 1.10; p = 0.044). Based on the observed anti-Factor Xa concentrations, complete-circuit group had 41% increased odds for requiring circuit/membrane oxygenator change compared with no-complete-circuit group (odds ratio = 1.41; 95% CI, 1.01, 1.96; p = 0.044). Mean daily activated clotting time measurement (p = 0.192) was not different between groups, but mean daily heparin infusion rate (p < 0.001) was significantly different between the two groups. Conclusions: Higher anti-Factor Xa concentrations were associated with freedom from circuit/membrane oxygenator change due to thrombus formation in pediatric patients during extracorporeal membrane oxygenation support. Activated clotting time measurements did not differ significantly between groups with or without circuit/membrane oxygenator change. This is the first study to link anti-Factor Xa concentrations with a clinically relevant measure of thrombosis in pediatric patients during extracorporeal membrane oxygenation support. Further prospective study is warranted.

Successful intra-arterial thrombolytic therapy for a right middle cerebral artery stroke in a 2-year-old supported by a ventricular assist device

Embolic stroke is a common complication in patients on ventricular assist devices in both adults and children. The reported incidence of strokes in children supported by VAD’s varies from 7 to 38%. The rapid increase in recent years in the availability of both adult and pediatric VADs will likely add to the overall prevalence of strokes in patients being bridged to heart transplant. Strokes in this population can be lethal as they frequently necessitate withdrawal of the extracorporeal device support and withdrawal from the organ transplant waiting list. We present a case of a fully anti‐coagulated 29‐month‐old supported on a Berlin EXCOR LVAD (Berlin, Germany) with embolic stroke which was treated successfully with direct thrombolysis with recombinant tissue plasminogen activator. This is the first report which uses intra‐arterial thrombolytics while on a ventricular assist device in a pediatric patient.

Abdominal compartment syndrome in newborns and children supported on extracorporeal membrane oxygenation.

The objective of this study was to investigate the effect of timely peritoneal dialysis (PD) catheter in children with abdominal compartment syndrome (ACS) while supported on extracorporeal membrane oxygenation (ECMO). We present a case series of four patients who developed significant intraperitoneal fluid accumulation and ACS at the general pediatric and cardiac intensive care units in a tertiary children’s hospital. The hospital’s ECMO database was queried for patients supported on ECMO who required PD catheter placement. These patients were assessed for clinical characteristics and outcomes. Four patients were identified with capillary leak syndrome associated with a primary diagnosis: cardiac transplant rejection in one, septic shock and acute respiratory distress syndrome in two, and neonatal hydrops fetalis in one patient. In each of these patients, a PD catheter was placed for severe abdominal distension and proven/suspected ACS. There was dramatic improvement in venous return after drainage of peritoneal fluid. Two patients were subsequently able to be separated successfully from ECMO support. One patient died of acute neurologic complication and the other because of severe gastrointestinal bleeding. After ruling out common causes for decreased venous return, ACS should be suspected as one of the important causes, especially in patients with massive capillary leak and increasing abdominal distension, among patients supported on ECMO. Timely placement of a PD catheter in patients who develop abdominal distension and ACS can substantially improve venous return and thus help maintain adequate tissue perfusion by improving ECMO flows.

Noncardiac Challenges in the Cardiac ICU: Feeding, Growth and Gastrointestinal Complications, Anticoagulation, and Analgesia.

Outcomes following cardiac intensive care unit (CICU) admission are influenced by many factors including initial cardiac diagnosis, surgical complexity, and burden of critical illness. Additionally, the presence of noncardiac issues may have a significant impact on outcomes and the patient experience during and following an intensive care unit stay. This review focuses on three common noncardiac areas which impact outcomes and patient experience in and beyond the CICU: feeding and growth, pain and analgesia, and anticoagulation. Growth failure and feeding dysfunction are commonly encountered in infants requiring cardiac surgery and have been associated with worse surgical and developmental outcomes. Recent studies most notably in the single ventricle population have demonstrated improved weight gain and outcomes when feeding protocols are implemented. Children undergoing cardiac surgery may experience both acute and chronic pain. Emerging research is investigating the impact of sedatives and analgesics on neurodevelopmental outcomes and quality of life. Improved pain scores and standardized management of pain and withdrawal may improve the patient experience and outcomes. Effective anticoagulation is a critical component of perioperative care but may be complicated by inflammation, multiorgan dysfunction, and patient factors. Advances in monitoring of anticoagulation and emerging therapies are reviewed.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Anticoagulation and Thrombolysis

Objective: Thrombotic complications are increasingly being recognized as a significant cause of morbidity and mortality in pediatric and congenital heart disease. The objective of this article is to review the medications currently available to prevent and treat such complications. Data Sources: Online searches were conducted using PubMed. Study Selection: Studies were selected for inclusion based on their scientific merit and applicability to the pediatric cardiac population. Data Extraction: Pertinent information from each selected study or scientific review was extracted for inclusion. Data Synthesis: Four classes of medications were identified as potentially beneficial in this patient group: anticoagulants, antiplatelet agents, thrombolytic agents, and novel oral anticoagulants. Data on each class of medication were synthesized into the follow sections: mechanism of action, pharmacokinetics, dosing, monitoring, reversal, considerations for use, and evidence to support. Conclusions: Anticoagulants, antiplatelet agents, and thrombolytic agents are routinely used successfully in the pediatric patient with heart disease for the prevention and treatment of a wide range of thrombotic complications. Although the novel oral anticoagulants have been approved for a limited number of indications in adults, studies on the safety and efficacy of these agents in children are pending.

Risk Factors for Prolonged Mechanical Ventilation for Children on Ventricular Assist Device Support

BACKGROUND Patients with end-stage heart failure possess many attributes that place them at risk for prolonged mechanical ventilation (MV). However, there are only limited data on MV support among children after ventricular assist device (VAD) implantation. We report the duration of MV after VAD placement, indications for respiratory support in the postimplantation period, and associated patient factors. METHODS This single-center retrospective study included 43 consecutive children (aged <18 years) with end-stage heart failure who were supported with a VAD as a bridge to transplantation from January 2005 to December 2011. Multivariable analysis was performed using the multiple Poisson regression model for the duration of MV. RESULTS Overall, 33% (n = 14) remained on MV until heart transplant or death. Of those requiring pre-VAD extracorporeal membrane oxygenation (ECMO) support, 63% (n = 12 of 19) remained on MV until heart transplant or death compared with 8% (n = 2 of 24) among those not on ECMO before VAD (p < 0.001). Patients with moderate or severe mitral regurgitation while on VAD support had 1.7-times more MV days compared with those with none or trivial on-VAD mitral regurgitation. In addition, previous support on ECMO, those with moderate or severe tricuspid regurgitation, and those with only left VAD implants had an increased risk of prolonged MV. CONCLUSIONS Our results suggest that VAD recipients previously supported on ECMO, those with moderate or severe mitral regurgitation, moderate or severe tricuspid regurgitation, and those with only left VAD implants had an increased risk of prolonged MV. Future studies in larger cohorts are necessary to confirm the findings from this single-institutional experience.

Hemorrhage requiring surgical intervention among children on pulsatile ventricular assist device support

Bleeding complications are a source of morbidity after Berlin EXCOR VAD implantation yet remain poorly characterized. We evaluated our experience to describe the bleeding complications among pediatric VAD recipients. We hypothesized that those with bleeding requiring exploration had abnormal coagulation profile compared with those without bleeding. The retrospective study included 43 consecutive patients with end‐stage heart failure supported on pediatric mechanical cardiac support as a bridge to transplantation. Day‐/event‐based analysis on factors below associated with (i) bleeding and (ii) bleeding in next 48 h. Cases with bleeding were compared with day‐matched patients without bleeding complications. Among 43 subjects bleeding occurred in 47% of cases, which necessitated exploration or chest tube placement. Twenty of 34 interventions for bleeding occurred in the first seven post‐operative days. No differences in coagulation parameters or use of antiplatelet agents were noted among those who had bleeding vs. those who did not. Our results indicate that (i) re‐bleeding requiring re‐exploration was common, (ii) most of the bleeding occurred early post‐implantation, (iii) there were no differences in coagulation parameters or the use of antiplatelet agents within 48 h of bleeding compared with those who did not bleed on each successive post‐operative day.