Lung separation in children: Options and impact on gas exchange and lung compliance.

BACKGROUND: One-lung ventilation is a challenging airway technique in the pediatric population. Multiple airway devices can be employed, but there is no consensus as to the most reliable and physiologically advantageous method. This report is a review of the methods of one-lung ventilation in children in our practice, as well as an analysis of the impact of airway device type, patient age, and duration of lung separation on respiratory mechanics and gas exchange. METHODS: The records of all pediatric patients undergoing procedures requiring one-lung ventilation in a single center over an 18-month period were reviewed. Demographics, time required to achieve lung separation (anesthesia ready-time), and duration of one-lung ventilation were collected. Data from arterial blood gas analysis and ventilator parameters were collected at three time points: 15 minutes prior to one-lung ventilation (pre-OLV), 15 minutes after initiation of one-lung ventilation (during OLV), and 15 minutes after one-lung ventilation was ended (post-OLV). Standard equations for calculating compliance, the ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen, and the alveolar-arterial oxygen gradient were used. RESULTS: Forty-six patients were identified with a mean age of 9.3 (inner quartile range 3-15) years. All patients had significant changes in pulmonary function when comparing pre-OLV with during OLV and when comparing during OLV with post-OLV. There were no significant changes from pre- to post-OLV. On further analysis, there were more pronounced changes in compliance and gas exchange in older patients (P = 0.003; 95% CI: -0.62 to -0.14). There was also a significant decrease in post-OLV compliance with a longer duration of OLV (P = 0.018; 95% CI: -0.02 to <-0.01). Airway device type did not have significant impact on the parameters examined. CONCLUSION: Our report demonstrates significant changes in lung function during one-lung ventilation. One particular device does not seem to be superior. Though pre-OLV measures of pulmonary function correlate closely with post-OLV, older age and a prolonged duration of one-lung ventilation did impact compliance.

The association between brain injury, perioperative anesthetic exposure, and 12-month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study.

BACKGROUND: Adverse neurodevelopmental outcomes are observed in up to 50% of infants after complex cardiac surgery. We sought to determine the association of perioperative anesthetic exposure with neurodevelopmental outcomes at age 12 months in neonates undergoing complex cardiac surgery and to determine the effect of brain injury determined by magnetic resonance imaging (MRI). METHODS: Retrospective cohort study of neonates undergoing complex cardiac surgery who had preoperative and 7-day postoperative brain MRI and 12-month neurodevelopmental testing with Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Doses of volatile anesthetics (VAA), benzodiazepines, and opioids were determined during the first 12 months of life. RESULTS: From a database of 97 infants, 59 met inclusion criteria. Mean ± sd composite standard scores were as follows: cognitive = 102.1 ± 13.3, language = 87.8 ± 12.5, and motor = 89.6 ± 14.1. After forward stepwise multivariable analysis, new postoperative MRI injury (P = 0.039) and higher VAA exposure (P = 0.028) were associated with lower cognitive scores. ICU length of stay (independent of brain injury) was associated with lower performance on all categories of the Bayley-III (P < 0.02). CONCLUSIONS: After adjustment for multiple relevant covariates, we demonstrated an association between VAA exposure, brain injury, ICU length of stay, and lower neurodevelopmental outcome scores at 12 months of age. These findings support the need for further studies to identify potential modifiable factors in the perioperative care of neonates with CHD to improve neurodevelopmental outcomes.

Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease.

BACKGROUND: Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages. OBJECTIVES: The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease. METHODS: Phase 2, open-label trial in children (ages, 28 days to <18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis. PRIMARY ENDPOINT: a composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy. RESULTS: From 2017 to 2021, 192 participants were randomized, 129 apixaban and 63 SOC. Diagnoses included single ventricle (74%), Kawasaki disease (14%), and other heart disease (12%). One apixaban participant (0.8%) and 3 with SOC (4.8%) had major or clinically relevant nonmajor bleeding (% difference -4.0 [95% CI: -12.8 to 0.8]). Apixaban incidence rate for all bleeding events was nearly twice the rate of SOC (100.0 vs 58.2 per 100 person-years), driven by 12 participants with ≥4 minor bleeding events. No thromboembolic events or deaths occurred in either arm. Apixaban pediatric PK steady-state exposures were consistent with adult levels. CONCLUSIONS: In this pediatric multinational, randomized trial, bleeding and thromboembolism were infrequent on apixaban and SOC. Apixaban PK data correlated well with adult trials that demonstrated efficacy. These results support the use of apixaban as an alternative to SOC for thromboprophylaxis in pediatric heart disease. (A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist [VKA] or Low Molecular Weight Heparin [LMWH] in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation; NCT02981472).

Design and methods for the training in exercise activities and motion for growth (TEAM 4 growth) trial: A randomized controlled trial.

BACKGROUND: Growth is often impaired in infants with congenital heart disease. Poor growth has been associated with worse neurodevelopment, abnormal behavioral state, and longer time to hospital discharge. Nutritional interventions, drug therapy, and surgical palliation have varying degrees of success enhancing growth. Passive range of motion (PROM) improves somatic growth in preterm infants and is safe and feasible in infants with hypoplastic left heart syndrome (HLHS), after their first palliative surgery (Norwood procedure). METHODS: This multicenter, Phase III randomized control trial of a 21-day PROM exercise or standard of care evaluates growth in infants with HLHS after the Norwood procedure. Growth (weight-, height- and head circumference-for-age z-scores) will be compared at 4 months of age or at the pre-superior cavopulmonary connection evaluation visit, whichever comes first. Secondary outcomes include neonatal neurobehavioral patterns, neurodevelopmental assessment, and bone mineral density. Eligibility include diagnosis of HLHS or other single right ventricle anomaly, birth at ≥37 weeks gestation and Norwood procedure at <30 days of age, and family consent. Infants with known chromosomal or recognizable phenotypic syndromes associated with growth failure, listed for transplant, or expected to be discharged within 14 days of screening are excluded. CONCLUSIONS: The TEAM 4 Growth trial will make an important contribution to understanding the role of PROM on growth, neurobehavior, neurodevelopment, and BMD in infants with complex cardiac anomalies, who are at high risk for growth failure and developmental concerns.

Bradycardia during induction of anesthesia with sevoflurane in children with Down syndrome.

BACKGROUND: Bradycardia is a complication associated with inhaled induction of anesthesia with halothane in children with Down syndrome. Although bradycardia has been reported after anesthetic induction with sevoflurane in these children, the incidence is unknown. OBJECTIVES: In this study we compared the incidence and characteristics of bradycardia after induction of anesthesia with sevoflurane in children with Down syndrome to healthy controls. METHODS: We reviewed electronic anesthetic records of 209 children with Down syndrome and 268 healthy control patients who had inhaled induction of anesthesia with sevoflurane over an 8-year period. Data extracted from the medical record included demographics, history of congenital heart disease, heart rate, oxyhemoglobin saturation, expired sevoflurane concentrations, arterial blood pressure, and any treatment of bradycardia during the first 360 seconds after the start of induction of anesthesia. Bradycardia and hypotension were defined as heart rate and arterial blood pressure below the critical limits recommended for activating a pediatric rapid response team to the bedside of a hospitalized child for quick intervention. Factors associated with bradycardia were identified in a univariate analysis. A step-wise backward multiple logistic regression model was used to identify independent factors. Differences between the 2 groups were computed using Fisher's exact test or χ(2) tests for categorical data and t tests for continuous data. RESULTS: Univariate analysis demonstrated that Down syndrome, low ASA physical status, congenital heart disease, and mean sevoflurane concentrations were factors associated with bradycardia. However, multivariate analysis showed that only Down syndrome and low ASA physical status remained as independent factors associated with bradycardia. CONCLUSION: Bradycardia during anesthetic induction with sevoflurane was common in children with Down syndrome, with and without a history of congenital heart disease.

Electroencephalographic seizures after neonatal cardiac surgery with high-flow cardiopulmonary bypass.

BACKGROUND: Postoperative electroencephalographic (EEG) seizures are reported to occur in 14% to 20% of neonates after cardiac surgery with cardiopulmonary bypass (CPB). EEG seizures are associated with prolonged deep hypothermic circulatory arrest and with adverse long-term neurodevelopmental outcomes. We performed video/EEG monitoring before and for 72 hours after neonatal cardiac surgery, using a high-flow CPB protocol and cerebral oxygenation monitoring, to ascertain incidence, severity, and factors associated with EEG seizures. METHODS: The CPB protocol included 150 mL/kg/min flows, pH stat management, hematocrit >30%, and high-flow antegrade cerebral perfusion. Regional cerebral oxygen saturation (rSo(2)) was monitored, with a treatment protocol for rSo(2) <50%. EEG was assessed for seizures. RESULTS: Sixty-eight patients (36 single ventricle [SV] and 32 2-ventricle [2V]) were monitored for a total of 4824 hours. The total midazolam dose was 2.4 mg/kg (1.5-7.3 mg/kg) (median, 25th-75th percentile) for the SV group and 1.3 mg/kg (1.0-2.7 mg/kg) for the 2V group (P = 0.009). One SV patient experienced 2 brief EEG seizures postoperatively (1.5% incidence; 95% confidence interval: 0.3%-7.9%). The SV patients experienced a significant incidence of cerebral desaturation (rSo(2) <45% for >240 minutes total) perioperatively (18 of 36 SV vs 0 of 32 2V patients, P < 0.001). This difference did not affect electrographic seizure occurrence or other EEG characteristics. CONCLUSIONS: EEG seizures are infrequent in neonates undergoing surgery with high-flow CPB. Cerebral desaturation did not affect EEG seizure occurrence; however, benzodiazepines may play a role in suppressing postoperative seizures caused by cerebral hypoxemia in this patient population. Using this anesthetic and surgical protocol, EEG seizures are a poor surrogate marker for acute neurological injury in this population.

Erythropoietin neuroprotection in neonatal cardiac surgery: a phase I/II safety and efficacy trial.

OBJECTIVES: Neonates undergoing complex congenital heart surgery have a significant incidence of neurologic problems. Erythropoietin has antiapoptotic, antiexcitatory, and anti-inflammatory properties to prevent neuronal cell death in animal models, and improves neurodevelopmental outcomes in full-term neonates with hypoxic ischemic encephalopathy. We designed a prospective phase I/II trial of erythropoietin neuroprotection in neonatal cardiac surgery to assess safety and indicate efficacy. METHODS: Neonates undergoing surgery for D-transposition of the great vessels, hypoplastic left heart syndrome, or aortic arch reconstruction were randomized to 3 perioperative doses of erythropoietin or placebo. Neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development III was performed at age 12 months. RESULTS: Fifty-nine patients received the study drug. Safety profile, including magnetic resonance imaging brain injury, clinical events, and death, was not different between groups. Three patients in each group died. Forty-two patients (22 in the erythropoietin group and 20 in the placebo group; 79% of survivors) returned for 12-month follow-up. In the group receiving erythropoietin, mean Cognitive Scale scores were 101.1 ± 13.6, Language Scale scores were 88.5 ± 12.8, and Motor Scale scores were 89.9 ± 12.3. In the group receiving placebo, Cognitive Scale scores were 106.3 ± 10.8 (P = .19), Language Scores were 92.4 ± 12.4 (P = .33), and Motor Scale scores were 92.6 ± 14.1 (P = .51). CONCLUSIONS: Safety profile for erythropoietin administration was not different than placebo. Neurodevelopmental outcomes were not different between groups; however, this pilot study was not powered to definitively address this outcome. Lessons learned suggest optimized study design features for a larger prospective trial to definitively address the utility of erythropoietin for neuroprotection in this population.