Xiomara Garcia

Rapid reduction in donor-specific anti-human leukocyte antigen antibodies and reversal of antibody-mediated rejection with bortezomib in pediatric heart transplant patients.

Background. High titer donor-specific antibodies (DSA) and positive crossmatch in cardiac transplant recipients is associated with increased mortality from antibody-mediated rejection (AMR). Although treatment to reduce anti-human leukocyte antigen antibodies using plasmapheresis, intravenous immunoglobulin, and rituximab has been reported to be beneficial, in practice these are often ineffective. Moreover, these interventions do not affect the mature antibody producing plasma cell. Bortezomib, a proteasome inhibitor active against plasma cells, has been shown to reduce DSA in renal transplant patients with AMR. We report here the first use of bortezomib for cardiac transplant recipients in four pediatric heart recipients with biopsy-proven AMR, hemodynamic compromise, positive crossmatch, and high titer class I DSA. Methods. Patients received four intravenous dose of bortezomib (1.3 mg/m2) over 2 weeks with plasmapheresis and rituximab. DSA specificity and strength (mean fluorescence intensity) was determined with Luminex. All had received previous treatment with plasmapheresis, intravenous immunoglobulin, and rituximab that was ineffective. Results. AMR resolved in all patients treated with bortezomib with improvement in systolic function, conversion of biopsy to C4d negative in three patients and IgG negative in one patient, and a prompt, precipitous reduction in DSAs. In three patients who received plasmapheresis before bortezomib, plasmapheresis failed to reduce DSA. In one case, DSA increased after bortezomib but decreased after retreatment. Conclusions. Bortezomib reduces DSA and may be an important adjunct to treatment of AMR in cardiac transplant recipients. Bortezomib may also be useful in desensitization protocols and in prevention of AMR in sensitized patients with positive crossmatch and elevated DSA.

Preemptive Gastrostomy Tube Placement after Norwood Operation

OBJECTIVE Because infants undergoing a Norwood operation have poor interstage weight gain, we hypothesized that preemptive gastrostomy tube (GT) placement would result in earlier discharge, improved growth, and higher survival to stage 2. STUDY DESIGN Records of 74 neonates who underwent a Norwood operation were reviewed until stage 2 palliation. The patients were divided into conventional (n = 43) and preemptive GT groups (n = 31). Data included demographics, cardiac surgery, feeding strategy, length of hospitalization, and mortality. RESULTS Transplant-free survival to stage 2 was significantly higher in the preemptive group, but there were no significant differences in survival to discharge after stage 1, length of hospitalization, and weight-for-age z-score at discharge and at stage 2 palliation. In the conventional group, 27 of 43 underwent GT placement, all via laparotomy, 23 with Nissen fundoplication. In the preemptive group, all underwent GT placement (21 laparoscopic, 10 laparotomy), 7 with Nissen fundoplication. A second gastric intervention was performed in 11 of 21 with laparoscopic GT (7 conversion to gastrojejunostomy tube, 4 Nissen fundoplication). CONCLUSION Preemptive GT placement is associated with improved survival to stage 2 after a Norwood operation but not with shorter hospitalization or better growth. A thorough gastrointestinal evaluation must be performed before GT placement to avoid additional surgery.

Prophylactic amiodarone reduces junctional ectopic tachycardia after tetralogy of Fallot repair

OBJECTIVE Junctional ectopic tachycardia is common after pediatric heart surgery. After tetralogy of Fallot repair, the incidence of junctional ectopic tachycardia may be as high as 15% to 20%. We introduced prophylactic amiodarone for tetralogy repair. This study was conducted to evaluate the effectiveness of the prophylactic amiodarone. METHODS A continuous infusion of amiodarone was started in the operating room at the time of rewarming during cardiopulmonary bypass at a rate of 2 mg/kg/d and continued for 48 hours. Between November 2005 and November 2009, 63 consecutive patients underwent primary repair of tetralogy, of whom 20 had prophylactic amiodarone (amiodarone group) and 43 did not (control group). Variables studied included demographic and bypass data, surgical procedure details (transannular or nontransannular patch), preoperative and postoperative echocardiography findings, and postoperative inotropic support. Univariate and stepwise multivariate analyses were conducted to determine factors associated with the occurrence of junctional ectopic tachycardia. RESULTS The incidence of junctional ectopic tachycardia was 37% in the control group and 10% in the amiodarone group. The groups were similar in age, weight, bypass time, rate of transannular patch usage, and preoperative and postoperative gradient through the right ventricular outflow tract. Prophylactic amiodarone was significantly negatively associated with junctional ectopic tachycardia by both univariate (P = .039) and multivariate (P = .027) analyses. There were no adverse events attributable to prophylactic amiodarone use. CONCLUSIONS Prophylactic amiodarone is well tolerated and significantly associated with a decreased incidence of junctional ectopic tachycardia after tetralogy repair.

Neurosurgical treatment for dystonia: Long-term outcome in a case series of 80 patients

INTRODUCTION In this study, we assessed the outcomes of patients with dystonia who underwent surgery treatment following the same algorithm. PATIENTS AND METHODS Eighty consecutive patients with dystonia were submitted to neurosurgical management by means of intrathecal pump implantation, pallidotomy or deep brain stimulation (GPi or VIM). These patients included 48 patients with primary dystonia and 32 patients with secondary dystonia. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to access pre- and post-operative outcomes. Patients were followed from 12 to 114 months. RESULTS Mean improvement in BFMDRS score among patients with PrD was 87.54% and 42.21% for SeD. Hemidystonic patients in both groups (PrD, SeD) showed a mean improvement in BFMDRS of 71.05% with GPiDBS. Patients with SeD due to previous perinatal insults showed a mean improvement in BFMDRS of 41.9%, with better results in purely dyskinetic patients (mean improvement of 61.2%). CONCLUSION Use of the proposed algorithm facilitated surgical decision planning, which translated in improved diagnostic rates, earlier interventions, appropriate management plans, and outcomes for both groups (PrD, SeD). Therefore, neuroimaging findings had a positive prognostic significance in the response to treatment in patients with primary dystonia compared with patients with secondary dystonia or distortion of basal ganglia anatomy. However, further studies in this line are warranted.

Neonatal herpes virus infection and extracorporeal life support.

Objectives: To investigate outcomes among neonates with herpes virus infection reported to the Extracorporeal Life Support Organization (ELSO) Registry and analyze factors associated with death before hospital discharge with this virus. Currently, scant data exist regarding extracorporeal membrane oxygenation support in neonates with herpes virus infection. Design: Retrospective analysis of ELSO Registry data set from 1985 to 2005. Setting: A total of 114 extracorporeal membrane oxygenation centers contributing data to the ELSO Registry. Patients: Patients, 0 to 31 days of age, with herpes simplex virus infection supported with extracorporeal membrane oxygenation and reported to the ELSO Registry. Interventions: None. Measurements and Main Results: Clinical characteristics, outcomes, and factors associated with death before hospital discharge were investigated for patients in the virus group. Kaplan-Meier estimates of survival to hospital discharge according to virus type were investigated. Newborns with herpes simplex virus infection requiring extracorporeal membrane oxygenation support demonstrated much lower hospital survival rates (25%). Clinical presentation with septicemia/shock was significantly associated with mortality for the herpes simplex virus group on multivariate analysis. There was no difference in herpes simplex virus mortality when comparing two eras (≥2000 vs. <2000). Conclusions: In this cohort of neonatal patients with overwhelming infections due to herpes simplex virus who were supported with extracorporeal membrane oxygenation, survival was dismal. Patients with disseminated herpes simplex virus infection presenting with septicemia/shock are unlikely to survive, even with aggressive extracorporeal support.

A Novel Paradigm for Providing Improved Care to Chronic Patients in Cardiac Intensive Care Unit

OBJECTIVE Evaluate the impact of chronic cardiac care team (CCCT) on hospital course of patients, their families, and nursing staff. DESIGN Retrospective observational study in children with hospital stay of ≥6 weeks in a pediatric cardiac intensive care unit (CICU) at a tertiary care childrens hospital. Before and after care, survey of the nurses and patients family was also performed. RESULTS The CCCT provided care for 68 patients of which 44 survived to discharge. Median age at admission was 19 days (range 0-20.6 years); 18 (26%) were admitted at birth. Cardiac diagnosis included single ventricle in 27, heart failure/cardiac transplantation in 37, others in 6. The CCCT was involved in follow-up for vitamin and endocrine deficiencies, updating immunization status, optimizing nutritional intake, growth parameters, assess feeding issues, and providing end-of-life discussions in all those who died. One year after implementation, 85% nurses indicated improved understanding of patient problems, 57% reported improved working relationship with families, and 87% reported improved team communication. Family survey indicated that implementation of the model led to significantly improved opinion of parents in their ability to participate in the plan of care (28% vs. 70%, P = 0.019) and better relationship with the CICU staff caring for their child (57% vs. 100%, P = 0.008). CONCLUSION The CCCT provides a new team-based paradigm for improving continuity of care in chronic CICU patients by supplementing medical care and facilitates end-of-life discussions. The CCCT bridges communication gap between CICU staff and families.

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.

Adrenal Insufficiency in Hemodynamically Unstable Neonatesafter Open-Heart Surgery

OBJECTIVE To investigate if the low dose (1 µg) ACTH stimulation test appropriately assesses adrenal responsiveness in neonates undergoing open-heart surgery requiring cardio-pulmonary bypass. DESIGN In this retrospective study, adrenal axis response was assessed on the first post-operative day with the low-dose (1 µg) ACTH stimulation test. Age, gender, weight, RACHS category, inotrope score, and baseline and post-stimulation cortisol levels were collected. The association between basal serum cortisol levels and degree of response to the ACTH stimulation test was also investigated. SETTING Tertiary care referral center. PATIENTS Twenty-one neonates who underwent neonatal cardiac surgery on cardiopulmonary bypass and underwent an ACTH stimulation test. Interventions.  Hydrocortisone 50 mg/m(2) bolus in four divided doses daily. OUTCOME MEASURES Response to the low dose (1 µg) ACTH stimulation was assessed. RESULTS All neonates with hemodynamic instability in the immediate post-operative period had low basal serum cortisol levels. The basal mean serum cortisol level for the 21 patients who underwent the low dose ACTH stimulation test was 7.3 µg/dL (median 2.2, range 0.7-42). The mean serum cortisol level increased after the ACTH stimulation test in the 21 patients to 39.6 µg/dL (median 38, range 79-17). The mean inotrope score in the first 24 hours after surgery was 24 (median 17.5, range 7-76.5) and decreased to 17 (median 14, range 5-52.3) 24-48 hours after surgery. At 48 hours post-surgery the mean arterial pressure in the groups with a serum cortisol increase after ACTH stimulation (<30 µg/dL vs. >50 µg/dL) was significantly different (P value 0.026). CONCLUSIONS The low dose (1 µg) ACTH stimulation test is a valid test to assess adrenal responsiveness among neonates after open heart surgery requiring CPB. Traditionally used basal serum cortisol level cutoff of <20 µg/dL used to define relative adrenal insufficiency may not be applicable in neonates undergoing open heart surgery on CPB thus indicating the need for re-defining adrenal insufficiency in this patient population.

Acute kidney injury is associated with increased in-hospital mortality in mechanically ventilated children with trauma.

BACKGROUND Acute kidney injury (AKI) is associated with significant morbidity and mortality in patients with critical illness; however, its impact on children with trauma is not fully unexplored. We hypothesized that AKI is associated with increased in-hospital mortality. METHODS A retrospective review of consecutive mechanically ventilated patients aged 0 years to 20 years from 2004 to 2007 with trauma hospitalized at our institution was performed. Univariate and multivariate analyses were performed to identify whether AKI was a risk factor for hospital mortality. RESULTS Eighty-eight patients met inclusion/exclusion criteria. The study cohort included 58 (66%) males with mean (SD) age of 11.6 (5.5) years (median, 13.25; range, 0.083–19.42 years) and mean (SD) Pediatric Expanded Logical Organ Dysfunction score of 24 (11) (median, 22; range 2–51). Mean pediatric intensive care unit length of stay (median, 11; range, 4–43) and duration of mechanical ventilation (median, 9; range, 3–34), was 13.5 (8.2) days and 11.2 (7.2) days, respectively. The mean (SD) Injury Severity Score for the cohort was 28 (14). Pediatric RIFLE identified those at risk (R), those with injury (I), or those with failure (F) in 30 (51%), 10 (17%), and 12 (21%) patients, respectively. There was a 10% (3 of 30 patients) mortality rate in those at risk, 30% (3 of 10 patients) in those with injury, and 33% (4 of 12 patients) in those with failure. AKI (injury and failure groups) was significantly associated with increased in-hospital mortality. CONCLUSION Development of AKI (injury or failure) is a significant risk factor associated with in-hospital mortality. Our study highlights the need to consider both urine output as well as creatinine-based components of the pRIFLE criteria to define AKI. LEVEL OF EVIDENCE Prognostic and epidemiological study, level II.

Aspergillus Infection and Extracorporeal Membrane Oxygenation Support

Background: The clinical characteristics of patients with Aspergillus isolation while supported on extracorporeal membrane oxygenator (ECMO) remain unclear. Objectives: We present a case report of angioinvasive Aspergillus infection on an infant supported on ECMO and also investigate outcomes among patients with Aspergillus infection reported to the Extracorporeal Life Support Organization (ELSO) registry. Design: Case report and retrospective analysis of ELSO registry data set from 1985 to 2009. Setting: One hundred and seventy ECMO centers contributing data to the ELSO registry. Patients: Single case report and patients 0 to 90 years of age with Aspergillus infection requiring ECMO support as reported to the ELSO registry. Methods: Besides presenting details of our institutional case, we compared clinical characteristics and outcomes between pediatric and adult patients with Aspergillus isolation. Risk factors for in-hospital mortality were investigated. Kaplan-Meier estimates for freedom from death on ECMO for pediatric and adult patients were investigated. Measurements and Main Results: (a) we report a case with Aspergillus supported on ECMO, (b) the ELSO registry yielded 46 patients with 59% (n = 27) in the pediatric data set (≤20 years of age) and 41% (n = 19) in the adult data set (>20 years of age) with Aspergillus infection requiring ECMO support. Overall survival to hospital discharge was 30% (14/46) with 22% (6/27) in children as compared to 42% (8/18) in adults (P = .19). Table 1 shows a comparison of clinical characteristics between children and adults. The comparison between adults and pediatric groups differed significantly in age (P = .0001), more use of venoarterial ECMO in children (P = .028). The median age of pediatric group was 1.95 years (range 0-17.3 years) versus 30.2 years (range 22-60 years) among adults. Conclusions: Aspergillus infection/colonization is associated with a 70% overall mortality among patients supported on ECMO. The ELSO registry data confirms that Aspergillus infection among ECMO supported patients occurs often in hosts who do not have known immunodeficiencies. The case stresses the need for a high level of suspicion for Aspergillus infection in nonimproving lung disease in patients on ECMO support.