Arno van Heijst

Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.

Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe

Congenital diaphragmatic hernia (CDH) is associated with high mortality and morbidity. To date, there are no standardized protocols for the treatment of infants with this anomaly. However, protocols based on the literature and expert opinion might improve outcome. This paper is a consensus statement from the CDH EURO Consortium prepared with the aim of achieving standardized postnatal treatment in European countries. During a consensus meeting between high-volume centers with expertise in the treatment of CDH in Europe (CDH EURO Consortium), the most recent literature on CDH was discussed. Thereafter, 5 experts graded the studies according to the Scottish Intercollegiate Guidelines Network (SIGN) Criteria. Differences in opinion were discussed until full consensus was reached. The final consensus statement, therefore, represents the opinion of all consortium members. Multicenter randomized controlled trials on CDH are lacking. Use of a standardized protocol, however, may contribute to more valid comparisons of patient data in multicenter studies and identification of areas for further research.

Use of evidence based practices to improve survival without severe morbidity for very preterm infants: results from the EPICE population based cohort

Objectives To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity. Design Prospective multinational population based observational study. Setting 19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project. Participants 7336 infants born between 24+0 and 31+6 weeks’ gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission. Main outcome measures Combined use of four evidence based practices for infants born before 28 weeks’ gestation using an “all or none” approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital. Results Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality (risk ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants. Conclusions More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity.

Motor performance in five-year-old extracorporeal membrane oxygenation survivors: A population-based study

IntroductionVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a cardio-pulmonary bypass technique to provide life support in acute reversible cardio-respiratory failure when conventional management is not successful. Most neonates receiving ECMO suffer from meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), sepsis or persistent pulmonary hypertension (PPH). In five-year-old children who underwent VA-ECMO therapy as neonates, we assessed motor performance related to growth, intelligence and behaviour, and the association with the primary diagnosis.MethodsIn a prospective population-based study (n = 224) 174 five-year-old survivors born between 1993 and 2000 and treated in the two designated ECMO centres in the Netherlands (Radboud University Medical Centre Nijmegen and Sophia Childrens Hospital, Erasmus MC – University Medical Center Rotterdam) were invited to undergo follow-up assessment including a paediatric assessment, the movement assessment battery for children (MABC), the revised Amsterdam intelligence test (RAKIT) and the child behaviour checklist (CBCL).ResultsTwenty-two percent of the children died before the age of five, 86% (n = 149) of the survivors were assessed. Normal development in all domains was found in 49% of children. Severe disabilities were present in 13%, and another 9% had impaired motor development combined with cognitive and/or behavioural problems. Chi-squared tests showed adverse outcome in MABC scores (P < 0.001) compared with the reference population in children with CDH, sepsis and PPH, but not in children with MAS. Compared with the Dutch population height, body mass index (BMI) and weight for height were lower in the CDH group (P < 0.001). RAKIT and CBCL scores did not differ from the reference population. Total MABC scores, socio-economic status, growth and CBCL scores were not related to each other, but negative motor outcome was related to lower intelligence quotient (IQ) scores (r = 0.48, P < 0.001).ConclusionsThe ECMO population is highly at risk for developmental problems, most prominently in the motor domain. Adverse outcome differs between the primary diagnosis groups. Objective evaluation of long-term developmental problems associated with this highly invasive technology is necessary to determine best evidence-based practice. The ideal follow-up programme requires an interdisciplinary team, the use of normal-referenced tests and an international consensus on timing and actual outcome measurements.

Conventional Mechanical Ventilation Versus High-frequency Oscillatory Ventilation for Congenital Diaphragmatic Hernia: A Randomized Clinical Trial (The VICI-trial).

Objectives:To determine the optimal initial ventilation mode in congenital diaphragmatic hernia. Background:Congenital diaphragmatic hernia is a life-threatening anomaly with significant mortality and morbidity. The maldeveloped lungs have a high susceptibility for oxygen and ventilation damage resulting in a high incidence of bronchopulmonary dysplasia (BPD) and chronic respiratory morbidity. Methods:An international, multicenter study (NTR 1310), the VICI-trial was performed in prenatally diagnosed congenital diaphragmatic hernia infants (n = 171) born between November 2008 and December 2013, who were randomized for initial ventilation strategy. Results:Ninety-one (53.2%) patients initially received conventional mechanical ventilation and 80 (46.8%) high-frequency oscillation. Forty-one patients (45.1%) randomized to conventional mechanical ventilation died/ had BPD compared with 43 patients (53.8%) in the high-frequency oscillation group. An odds ratio of 0.62 [95% confidence interval (95% CI) 0.25–1.55] (P = 0.31) for death/BPD for conventional mechanical ventilation vs high-frequency oscillation was demonstrated, after adjustment for center, head-lung ratio, side of the defect, and liver position. Patients initially ventilated by conventional mechanical ventilation were ventilated for fewer days (P = 0.03), less often needed extracorporeal membrane oxygenation support (P = 0.007), inhaled nitric oxide (P = 0.045), sildenafil (P = 0.004), had a shorter duration of vasoactive drugs (P = 0.02), and less often failed treatment (P = 0.01) as compared with infants initially ventilated by high-frequency oscillation. Conclusions:Our results show no statistically significant difference in the combined outcome of mortality or BPD between the 2 ventilation groups in prenatally diagnosed congenital diaphragmatic hernia infants. Other outcomes, including shorter ventilation time and lesser need of extracorporeal membrane oxygenation, favored conventional ventilation.

Therapeutic drug monitoring of voriconazole in a child with invasive aspergillosis requiring extracorporeal membrane oxygenation.

We describe a patient with invasive pulmonary aspergillosis on extracorporeal membrane oxygenation therapy in which therapeutic drug monitoring and individualization of therapy by measuring voriconazole plasma concentrations were performed.

Neuropsychological Follow-up After Neonatal ECMO

OBJECTIVE: To assess the longitudinal development of intelligence and its relation to school performance in a nationwide cohort of neonatal extracorporeal membrane oxygenation (ECMO) survivors and evaluate predictors of outcome at 8 years of age. METHODS: Repeated measurements assessed intelligence of neonatal ECMO survivors at 2, 5, and 8 years (n = 178) with the use of validated, standardized instruments. Selective attention (n = 148) and type of education were evaluated in the 8-year-olds. RESULTS: Intelligence remained stable and average across development (mean ± SD IQ: at 2 years, 102 ± 18; at 5 years, 100 ± 17; and at 8 years, 99 ± 17 [P = .15]). Children attending regular education without the need for help (n = 101; mean z score: –1.50 ± 1.93) performed significantly better on the selective attention task compared with those children who needed extra help (n = 65; mean z score: –2.54 ± 3.18) or those attending special education (n = 13; mean z score: –4.14 ± 3.63) (P = .03). However, only children attending special education had below-average intelligence (mean IQ: 76 ± 15), compared with average intelligence for those attending regular education, both with help (mean IQ: 95 ± 15) and without help (mean IQ: 105 ± 16). Compared with children with other diagnoses, children with congenital diaphragmatic hernia (CDH) scored significantly lower on both IQ (CDH, mean IQ: 93 ± 20; meconium aspiration syndrome, mean IQ: 100 ± 15; other diagnoses, mean IQ: 100 ± 19 [P = .04]) and selective attention (CDH, mean z score: –3.48 ± 3.46; meconium aspiration syndrome, mean z score: –1.60 ± 2.13; other diagnoses, mean z score: –1.65 ± 2.39 [P = .002]). CONCLUSIONS: For the majority of neonatal ECMO survivors, intelligence testing alone did not identify those at risk for academic problems. We propose internationally standardized follow-up protocols that focus on long-term, problem-oriented neuropsychological assessment.

Brain injury associated with neonatal extracorporeal membrane oxygenation in the Netherlands: a nationwide evaluation spanning two decades.

Objective: To determine the prevalence of and to classify ultrasound-proven brain injury during neonatal extracorporeal membrane oxygenation in The Netherlands. Design: Retrospective nationwide study (Rotterdam and Nijmegen), spanning two decades. Setting: Level III university hospitals. Subjects: All neonates who underwent neonatal extracorporeal membrane oxygenation from 1989 to 2010. Interventions: None. Measurements and Main Results: Cranial ultrasound images were reviewed independently by two investigators without knowledge of primary diagnosis, outcome, type of extracorporeal membrane oxygenation, or statistics. The scans were reviewed for lesion type and timing, with the use of a refined classification method for focal brain injury. Extracorporeal membrane oxygenation type was venoarterial in 88%. Brain abnormalities were detected in 17.3%: primary hemorrhage was most frequent (8.8%). Stroke was identified in 5% of the total group, with a notable significant preference for the left hemisphere (in 70%). Lobar hematoma (prevalence 2.2 %) was also significantly left predominant. Conclusion: The incidence of brain injury found with cranial ultrasound in The Netherlands of the patients treated with extracorporeal membrane oxygenation during the neonatal period was 17.3%. Primary hemorrhage was the largest group of lesions, not clearly side-specific except for lobar bleeding, most probably related to changes in venous flow. Arterial ischemic stroke occurred predominant in the left hemisphere.

Cardiac output measurement using an ultrasound dilution method: a validation study in ventilated piglets.

Objective: To assess agreement between a new method of cardiac output monitoring, using ultrasound dilution technology and ultrasound transit time-based measurement of pulmonary blood flow in a piglet model. Design: Prospective, experimental juvenile animal study. Setting: Animal laboratory of a university hospital. Subjects: Nine random-bred piglets. Interventions: After the animals received general anesthesia, we placed intravascular arterial and central venous catheters with the tip positioned in the abdominal aorta and the right atrium, respectively. The catheters were connected to the ultrasound dilution cardiac output monitor. An ultrasound transit time perivascular flow probe was positioned around the common pulmonary artery and served as the standard reference measurement. Cardiac output was manipulated during the experiment by creating hemorrhagic hypotension. Ultrasound dilution cardiac output was measured intermittently with injection volumes of 0.5 mL/kg and 1.0 mL/kg of isotonic saline at body temperature. Measurements and Main Results: Ultrasound dilution cardiac output (QUDCO) measurement was compared with pulmonary blood flow (QAPC). Bias, defined as QUDCO minus QAPC, was calculated for each measurement. Mean bias with standard deviation was calculated for measurements with volumes of injected saline, 0.5 mL/kg and 1.0 mL/kg, and compared using the Mann-Whitney U test. Mean bias (sd) between QUDCO and QAPC was 0.040 (0.132) and 0.058 (0.136) L/min for measurement with 0.5 mL/kg and 1.0 mL/kg of isotonic saline, respectively (no statistically significant difference). Conclusions: Ultrasound dilution cardiac output measurement is reliable in piglets with the use of a small volume of a nontoxic indicator (isotonic saline).

Long-term outcome of children treated with neonatal extracorporeal membrane oxygenation: Increasing problems with increasing age

As more and more critically ill neonates survive, it becomes important to evaluate long-term morbidity. This review aims to provide an up-to-date overview of medical and neurodevelopmental outcomes in children who as neonates received treatment with extracorporeal membrane oxygenation (ECMO). Most patients-except those with congenital diaphragmatic hernia-have normal lung function and normal growth at older age. Maximal exercise capacity is below normal and seems to deteriorate over time in the CDH population. Gross motor function problems have been reported until school age. Although mental development is usually favorable within the first years and cognition is normal at school age, many children experience problems with working speed, spatial ability tasks, and memory. In conclusion, children who survived neonatal treatment with ECMO often encounter neurodevelopmental problems at school age. Long-term follow-up is needed to recognize problems early and to offer appropriate intervention.