Peritoneal catheters in neonates undergoing complex cardiac surgery: a multi-centre descriptive study.

BACKGROUND: The use of peritoneal catheters for prophylactic dialysis or drainage to prevent fluid overload after neonatal cardiac surgery is common in some centres; however, the multi-centre variability and details of peritoneal catheter use are not well described. METHODS: Twenty-two-centre NEonatal and Pediatric Heart Renal Outcomes Network (NEPHRON) study to describe multi-centre peritoneal catheter use after STAT category 3-5 neonatal cardiac surgery using cardiopulmonary bypass. Patient characteristics and acute kidney injury/fluid outcomes for six post-operative days are described among three cohorts: peritoneal catheter with dialysis, peritoneal catheter with passive drainage, and no peritoneal catheter. RESULTS: Of 1490 neonates, 471 (32%) had an intraoperative peritoneal catheter placed; 177 (12%) received prophylactic dialysis and 294 (20%) received passive drainage. Sixteen (73%) centres used peritoneal catheter at some frequency, including six centres in >50% of neonates. Four centres utilised prophylactic peritoneal dialysis. Time to post-operative dialysis initiation was 3 hours [1, 5] with the duration of 56 hours [37, 90]; passive drainage cohort drained for 92 hours [64, 163]. Peritoneal catheter were more common among patients receiving pre-operative mechanical ventilation, single ventricle physiology, and higher complexity surgery. There was no association with adverse events. Serum creatinine and daily fluid balance were not clinically different on any post-operative day. Mortality was similar. CONCLUSIONS: In neonates undergoing complex cardiac surgery, peritoneal catheter use is not rare, with substantial variability among centres. Peritoneal catheters are used more commonly with higher surgical complexity. Adverse event rates, including mortality, are not different with peritoneal catheter use. Fluid overload and creatinine-based acute kidney injury rates are not different in peritoneal catheter cohorts.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

BACKGROUND: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS: We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS: A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS: In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Tolvaptan increases serum sodium in pediatric patients with heart failure.

This study aimed to evaluate the use of tolvaptan in a consecutive series of pediatric patients with heart failure. Patients 18 years of age or younger with heart failure prescribed tolvaptan between January 2009 and October 2011 were retrospectively identified at Children's Medical Center Dallas. Laboratory parameters, urine output, fluid balance, and concurrent medications were recorded at baseline and at specified intervals after a single dose of tolvaptan. The 28 patients in the study had a median age of 2 years (range 1 month-18 years). The median tolvaptan dose administered was 0.3 mg/kg (range 0.1-1.3 mg/kg). The study patients had a median baseline serum sodium concentration of 127 mmol/L, and the increases in sodium were 2.5 mmol/L at 12 h, 5 mmol/L at 24 h, 4 mmol/L at 48 h, and 5 mmol/L at 72 h (all p < 0.001). Urine output was increased at 24 h (p < 0.001) and 48 h (p = 0.03), and fluid balance changes were significantly different at 24 h (p = 0.004). The changes in potassium, blood urea nitrogen, and serum creatinine were not significant at any interval. When controlling for traditional diuretic therapy, increases in serum sodium concentration and urine output remained statistically significant. A single dose of tolvaptan increased serum sodium concentrations for the majority in this small series of pediatric patients with heart failure. These results suggest that tolvaptan can be safely and effectively administered to pediatric patients. Prospective, randomized controlled trials are needed to evaluate the safety and efficacy of its use further.

Protecting the future: neuroprotective strategies in the pediatric intensive care unit.

PURPOSE OF REVIEW: Brain injury is the leading cause of death in pediatric intensive care units, and improvements in therapy and in understanding the pathogenesis are urgently needed. This review presents recent advances in the understanding of neuroprotective therapy and brain-specific monitoring for critically ill pediatric patients. RECENT FINDINGS: Two neuroprotective strategies are becoming increasingly accepted as they are applied to different mechanisms of brain injury. The rapid application of hypothermia and avoidance of hyperoxia after cardiac arrest and other brain injuries are each being more commonly used as both human and animal data advocating for these approaches accumulate. In addition, more advanced and noninvasive technologies are emerging that are designed to serve as surrogates for brain function and may be used to help predict outcome. Near-infrared spectroscopy is one such commonly used technique that has prompted many studies to understand how to incorporate it into practice. SUMMARY: Protection of the pediatric brain from both a primary insult and the common subsequent secondary injury is essential for improving long-term neurologic outcomes. Whereas monitoring technology is being constantly modified, it must be proven efficacious in order to understand the utility of new and presumed neuroprotective therapies like hypothermia and avoidance of hyperoxia.

Adrenal insufficiency in neonates undergoing cardiopulmonary bypass and postoperative hypothalamic-pituitary-adrenal function after prophylactic glucocorticoids.

OBJECTIVES: Determine incidence of preoperative adrenal insufficiency in neonates >35 weeks gestation with congenital heart disease undergoing cardiothoracic surgery with bypass and effects of prophylactic methylprednisolone on postoperative hypothalamic-pituitary-adrenal function and hemodynamic stability. DESIGN: Prospective observational study in 36 neonates with preoperative adrenocorticotrophic hormone stimulation tests and serial total cortisol and adrenocorticotrophic hormone measurements before and after surgery. Data analyses: analysis of variance and regression. RESULTS: Baseline circulating adrenocorticotrophic hormone and cortisol were unchanged 4-20 days postnatal (P > 0.1); however, cortisol levels rose with increasing adrenocorticotrophic hormone, P = 0.02. Ten neonates (29%) demonstrated preoperative adrenal insufficiency (∆cortisol ≤9 µg/dl); one had postoperative hemodynamic instability. Growth-restricted neonates had lower baseline cortisol, but normal stimulation tests and responded well to surgical stresses. Seventy-five percent of neonates receiving perioperative methylprednisolone demonstrated postoperative hypothalamic-pituitary-adrenal inhibition. CONCLUSION: Adrenal insufficiency appears common in neonates >35 weeks gestation with congenital heart disease, but did not contribute to postoperative hemodynamic instability despite hypothalamic-pituitary-adrenal inhibition.

Pediatric cardiac arrest due to drowning and other respiratory etiologies: Neurobehavioral outcomes in initially comatose children.

AIM: To describe the 1-year neurobehavioral outcome of survivors of cardiac arrest secondary to drowning, compared with other respiratory etiologies, in children enrolled in the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial. METHODS: Exploratory analysis of survivors (ages 1-18 years) who received chest compressions for ≥2min, were comatose, and required mechanical ventilation after return of circulation (ROC). Participants recruited from 27 pediatric intensive care units in North America received targeted temperature management [therapeutic hypothermia (33°C) or therapeutic normothermia (36.8°C)] within 6h of ROC. Neurobehavioral outcomes included 1-year Vineland Adaptive Behavior Scales, Second Edition (VABS-II) total and domain scores and age-appropriate cognitive performance measures (Mullen Scales of Early Learning or Wechsler Abbreviated Scale of Intelligence). RESULTS: Sixty-six children with a respiratory etiology of cardiac arrest survived for 1-year; 60/66 had broadly normal premorbid functioning (VABS-II≥70). Follow up was obtained on 59/60 (30 with drowning etiology). VABS-II composite and domain scores declined significantly from premorbid scores in drowning and non-drowning groups (p<0.001), although declines were less pronounced for the drowning group. Seventy-two percent of children had well below average cognitive functioning at 1-year. Younger age, fewer doses of epinephrine, and drowning etiology were associated with better VABS-II composite scores. Demographic variables and treatment with hypothermia did not influence neurobehavioral outcomes. CONCLUSIONS: Risks for poor neurobehavioral outcomes were high for children who were comatose after out-of-hospital cardiac arrest due to respiratory etiologies; survivors of drowning had better outcomes than those with other respiratory etiologies.

Brief exposure to hyperoxia depletes the glial progenitor pool and impairs functional recovery after hypoxic-ischemic brain injury.

Patterns of hypoxic-ischemic brain injury in infants and children suggest vulnerability in regions of white matter development, and injured patients develop defects in myelination resulting in cerebral palsy and motor deficits. Reperfusion exacerbates the oxidative stress that occurs after such injuries and may impair recovery. Resuscitation after hypoxic-ischemic injury is routinely performed using 100% oxygen, and this practice may increase the oxidative stress that occurs during reperfusion and further damage an already compromised brain. We show that brief exposure (30 mins) to 100% oxygen during reperfusion worsens the histologic injury in young mice after unilateral brain hypoxia-ischemia, causes an accumulation of the oxidative metabolite nitrotyrosine, and depletes preoligodendrocyte glial progenitors present in the cortex. This damage can be reversed with administration of the antioxidant ebselen, a glutathione peroxidase mimetic. Moreover, mice recovered in 100% oxygen have a more disrupted pattern of myelination and develop a static motor deficit that mimics cerebral palsy and manifests itself by significantly worse performance on wire hang and rotorod motor testing. We conclude that exposure to 100% oxygen during reperfusion after hypoxic-ischemic brain injury increases secondary neural injury, depletes developing glial progenitors, interferes with myelination, and ultimately impairs functional recovery.