Robert Jan Houmes

Haemofiltration in newborns treated with extracorporeal membrane oxygenation: a case-comparison study

IntroductionExtracorporeal membrane oxygenation is a supportive cardiopulmonary bypass technique for patients with acute reversible cardiovascular or respiratory failure. Favourable effects of haemofiltration during cardiopulmonary bypass instigated the use of this technique in infants on extracorporeal membrane oxygenation. The current study aimed at comparing clinical outcomes of newborns on extracorporeal membrane oxygenation with and without continuous haemofiltration.MethodsDemographic data of newborns treated with haemofiltration during extracorporeal membrane oxygenation were compared with those of patients treated without haemofiltration in a retrospective 1:3 case-comparison study. Primary outcome parameters were time on extracorporeal membrane oxygenation, time until extubation after decannulation, mortality and potential cost reduction. Secondary outcome parameters were total and mean fluid balance, urine output in mL/kg/day, dose of vasopressors, blood products and fluid bolus infusions, serum creatinin, urea and albumin levels.ResultsFifteen patients with haemofiltration (HF group) were compared with 46 patients without haemofiltration (control group). Time on extracorporeal membrane oxygenation was significantly shorter in the HF group: 98 hours (interquartile range (IQR) = 48 to 187 hours) versus 126 hours (IQR = 24 to 403 hours) in the control group (P = 0.02). Time from decannulation until extubation was shorter as well: 2.5 days (IQR = 0 to 6.4 days) versus 4.8 days (IQR = 0 to 121.5 days; P = 0.04). The calculated cost reduction was €5000 per extracorporeal membrane oxygenation run. There were no significant differences in mortality. Patients in the HF group needed fewer blood transfusions: 0.9 mL/kg/day (IQR = 0.2 to 2.7 mL/kg/day) versus 1.8 mL/kg/day (IQR = 0.8 to 2.9 mL/kg/day) in the control group (P< 0.001). Consequently the number of blood units used was significantly lower in the HF group (P< 0.001). There was no significant difference in inotropic support or other fluid resuscitation.ConclusionsAdding continuous haemofiltration to the extracorporeal membrane oxygenation circuit in newborns improves outcome by significantly reducing time on extracorporeal membrane oxygenation and on mechanical ventilation, because of better fluid management and a possible reduction of capillary leakage syndrome. Fewer blood transfusions are needed. All in all, overall costs per extracorporeal membrane oxygenation run will be lower.

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.

Sevoflurane therapy for life-threatening asthma in children

BACKGROUND Asthma is a common disease in children and often develops early in life. This multicentre retrospective case series describe the use and effectiveness of sevoflurane inhalation therapy in a series of children with severe asthma in the paediatric intensive care unit (PICU). METHODS Seven children ranging from 4 to 13 yr of age admitted to the PICU of two tertiary care hospitals in the Netherlands were included. They all were admitted with the diagnosis of severe asthma requiring invasive mechanical ventilation and were treated with sevoflurane inhalation therapy. RESULTS The median (range) Pco2 level at the start, after 2 h, and at the end of sevoflurane treatment were 14 (5.1-24.8), 9.8 (5.4-17.0), and 6.2 (4.5-11.4) kPa (P=0.05) while the median (range) pH was 7.02 (6.97-7.36), 7.18 (7.04-7.35), and 7.43 (7.15-7.47) kPa (P=0.01), respectively. The median (range) peak pressure values declined from 30 (23-56) to 20.4 (14-33) cm H2O (P=0.03). No severe adverse effects besides hypotension, with sufficient response to norepinephrine treatment, were seen. CONCLUSIONS Sevoflurane inhalation corrects high levels of Pco2 and provides clinical improvement in mechanically ventilated children with life-threatening asthma who fail to respond to conventional treatment.

Risk and relevance of open lung biopsy in pediatric ECMO patients: the Dutch experience

BACKGROUND Open lung biopsy can help differentiate between reversible and irreversible lung disease and may guide therapy. To assess the risk-benefit ratio of this procedure in pediatric extracorporeal membrane oxygenation (ECMO) patients, we reviewed data of all patients who underwent an open lung biopsy during ECMO in one of the two pediatric ECMO centers in a nationwide study in the Netherlands. RESULTS In nineteen neonatal and six pediatric patients (0-15.5years), twenty-five open lung biopsies were performed during the study period. In 13 patients (52%), a classifying diagnosis of underlying lung disease could be made. In another nine patients (36%), specific pathological abnormalities were described. In three patients (12%), only nonspecific abnormalities were described. The histological results led to withdrawal of ECMO treatment in 6 neonates with alveolar capillary dysplasia/misalignment of pulmonary veins (24%) and in another 6 patients, corticosteroids were started (24%). All patients survived the biopsy procedure. Hemorrhagic complications were rare. CONCLUSION An open lung biopsy during an ECMO run in neonates and children is a safe procedure with a minimum risk for blood loss and biopsy-related death. It can be very useful in diagnosing the underlying pathology and can guide cessation of ECMO treatment and thereby avoid continuation of futile treatment, especially in neonatal patients. LEVEL OF EVIDENCE III. TYPE OF STUDY Diagnostic study.

Improving long-term outcomes after extracorporeal membrane oxygenation: from observational follow-up programs towards risk stratification.

Since the introduction of extracorporeal membrane oxygenation (ECMO), more neonates and children with cardiorespiratory failure survive. Interest has therefore shifted from reduction of mortality toward evaluation of long-term outcomes and prevention of morbidity. This review addresses the changes in ECMO population and the ECMO-treatment that may affect long-term outcomes, the diagnostic modalities to evaluate neurological morbidities and their contributions to prognostication of long-term outcomes. Most follow-up data have only become available from observational follow-up programs in neonatal ECMO-survivors. The main topics are discussed in this review. Recommendations for long-term follow up depend on the presence of neurological comorbidity, the nature and extent of the underlying disease, and the indication for ECMO. Follow up should preferably be offered as standard of care, and in an interdisciplinary, structured and standardized way. This permits evaluation of outcome data and effect of interventions. We propose a standardized approach and recommend that multiple domains should be evaluated during long-term follow up of neonates and children who needed extracorporeal life support.

Liquid ventilation in congenital diaphragmatic hernia: Back on stage?

www.pccmjournal.org November 2014 • Volume 15 • Number 9 In congenital diaphragmatic hernia (CDH), lung hypoplasia and pulmonary hypertension are the main causes of neonatal mortality (1). Mortality significantly decreased during the past 10 years, after the introduction of the gentle ventilation strategy and the development of international standards for postnatal therapy (2). Still, ventilator-induced lung injury is largely responsible for the development of chronic lung disease in children with CDH (3). In this issue of Pediatric Critical Care Medicine, HerberJonat et al (4) present the results of a well-performed laboratory study in rabbits with induced CDH. CDH was induced by fetal surgery and 5 days later perfluorooctylbromide, a perfluorocarbon, was instilled into the lungs of randomly selected fetal rabbits; other fetal rabbits received saline. A third group were nonoperated fetuses who served as controls. Fetal instillation of perfluorooctylbromide was associated with improvement of lung-to-body weight ratio, total lung capacity, and lung compliance when compared with fetal instillation of saline. Second, at messenger RNA (mRNA) level only, expression of genes involved in extracellular matrix formation and remodeling in the hypoplastic lung was increased. However, surfactant protein expression, distal airway size, mean linear intercept, and airspace and tissue fractions were similar between the two groups and also similar to fetuses who were not operated upon. The authors concluded that fetal perfluorooctylbromide treatment resulted in improved lung growth, lung mechanics, and extracellular matrix remodeling. Extrapulmonary effects of perfluorooctylbromide, such as effects on neuronal cell alteration and effects in the brain, should be determined in future studies before this therapy can be studied in human prenatal studies. A ventilation technique known as liquid ventilation stems from the year 1929, when Von Neergard incidentally found that filling the lungs with saline solution dramatically improved the static pulmonary compliance in cats (5). After further investigation of different types of liquids, Clark and Gollan (6) received fame for their experiments of liquid ventilation using perfluorocarbon in mice for the first time. In 1989, liquid ventilation showed its potential in a first trial in prematurely born neonates (7). In CDH, Hirschl et al (8) conducted a randomized trial in sheep and concluded that partial liquid ventilation (PLV) during extracorporeal membrane oxygenation may have beneficial effects on pulmonary function and gas exchange. Pranikoff et al (9) applied PLV with the use of perflubron in four patients with CDH who required extracorporeal life support postnatally. They concluded that this therapy was possibly associated with improvement in gas exchange and lung compliance. Later on Hirschl et al (10) conducted a randomized trial in 13 CDH infants who were randomized to either PLV perfluorocarbon-induced lung growth or conventional mechanical ventilation. They found that perfluorocarbon-induced lung growth can be performed safely. However, when this trial was still ongoing, in 2001 the Food and Drug Administration decided that all clinical trials with perflubron had to be discontinued until safely data were available. That decision was based on findings that adults with acute respiratory distress syndrome randomized to PLV had no improved outcome and experienced more adverse events such as more pneumothoraces, hypoxic episodes, and hypotensive episodes (11). Nevertheless in China, adults with acute respiratory distress syndrome are currently recruited in a randomized controlled trial of perfluorocarbon instillation (NCT01391481). In normal fetal lung development, the lungs are liquid-filled, and fluid secretion and fetal breathing movements are necessary for lung maturation (12). In abnormal situations such as in prematurely born neonates in which transition from liquid-breathing to an air-breathing situation takes place prematurely, and in fetuses with an amniotic fluid-deficient environment, lung development is likely to be immature resulting in lung-related problems postnatally. Instillation of perfluorooctylbromide in the trachea approximately to functional residual capacity can simulate the antenatal situation of liquid-filled airway branches. Thereafter, gas tidal volumes are delivered using a mechanical conventional ventilator. This is called PLV. In total liquid ventilation, the lungs are completely filled with a liquid, whereas in PLV the lungs are filled until functional residual capacity. Perfluorocarbons have a high solubility for respiratory gases (6). By eliminating the air–liquid interface, lung compliance can be improved (13). Because of their dense characteristics, perfluorooctylbromide gravitate to dependent part of the lungs, and collapsed regions can be re-opened and ventilation/perfusion ratio may be improved (13). Next to these advantages, pulmonary inflammation and injury may be reduced as a result of decreased cytokine production. Moreover, in pigs receiving PLV, a redistribution of pulmonary blood flow away from the dependent region of the lung was found, as well as increased vascular resistance and pulmonary artery pressure (14). In line with the experiments of the article from Herber-Jonat et al (4), we know that a complete obstruction of the fetal airways Copyright

ECMO Support in Drowning Victims

In extracorporeal membrane oxygenation (ECMO), or often interchangeably named extracorporeal life support (ECLS), a simplified form of cardiopulmonary bypass (CPB) is used to provide respiratory or both respiratory and circulatory support. CPB was developed earlier as a means to facilitate open heart surgery. Maintenance of pulmonary blood flow, lack of hemodilution, and inflammatory stimuli are the major differences between ECMO and CPB. These advantages reduce the need for anticoagulation and reduce the activation of immune and complement systems, as blood-tissue and blood-air contacts are absent. This reduces the need for anticoagulation and thus decreases the risk for bleeding making ECMO feasible for use in the ICU.

419 Sevoflurane Therapy for Life Threatening Asthma in Children

Background Severe asthma is treated with bronchodilators like salbutamol, corticosteroids, magnesium sulphate, and if necessary mechanical ventilation. If these options fail, volatile anesthetic agents can be used. This is the first multicentre case series that describes the effectiveness of sevoflurane therapy in children with life-threatening asthma. Methods Pediatric patients admitted to the pediatric intensive care unit (PICU) with severe asthma and sevoflurane treatment were included. A retrospective review of demographic, medical, laboratory and ventilation parameters was performed. Results 7 children from two PICU’s in the Netherlands with age ranging from 4 to 13 years were included. The mean length of PICU stay was 6.7 days (range 3–10). Mean (range) dose of sevoflurane and duration of treatment were 2.2% (1–4%) and 24h (0.5–90h). Mean (range) pH at the beginning and at the end of sevoflurane treatment were 7.11 (6.97–7.36) and 7.35 (7.15–7.47)kPa (p<0.01). Mean (range) pCO2 were respectively 14.3 (5.1–24.8) and 7.1 (4.5–11.4)kPa (p<0.05). Mean (range) peak pressure declined from 33 (23–56) to 22 (14–33) cmH2O (p<0.03). Four patients developed hypotension, which was successfully treated with norepinephrine. One patient (dotted line figure), was afterwards judged to suffer from ARDS and indeed failed to respond to sevoflurane therapy. Conclusion Mechanical ventilation with Sevoflurane inhalation is a safe and effective treatment for children with life-threatening asthma. Abstract 419 Figure 1 pCO2 before and after sevofl urane treatment

Het ernstig zieke of zwaargewonde kind op de eerste hulp

SamenvattingEen ernstig ziek of zwaargewond kind kan zich op elk moment presenteren op de eerste hulp van een algemeen ziekenhuis. De combinatie van de ernst van de situatie, die snel en adequaat handelen vereist, en de lage frequentie van voorkomen maakt dat specifieke voorzorgsmaatregelen moeten worden genomen. De voorzorgsmaatregelen betreffen verschillende aspecten, namelijk: 1) personeel, 2) materiaal, 3) voorzieningen, 4) toegankelijkheid, triage, overplaatsing en transport, 5) onderwijs en training en 6) administratieve ondersteuning. Al deze aspecten worden besproken met speciale aandacht voor de bekwaamheid van het personeel en het belang van een systematische aanpak van de acute opvang van een vitaal bedreigd kind.SummaryA critically ill or severely injured child can present itself at any time at the emergency department of a district general hospital. The seriousness of the situation, requiring rapid and adequate treatment, combined with the infrequent occurrence, asks for specific precautions. These precautions concern various aspects, i.e. 1) personnel, 2) equipment, 3) facilities, 4) access, triage, transfer and transport, 5) education and training, and 6) administrative support. These various aspects will be discussed, with special focus on the capability of personnel and the importance of a systematic approach to the critically ill or severely injured child.