Measurement of lung liquid and outcome after congenital cardiac surgery

Congenital heart defects (CHD) are classified as acyanotic and cyanotic. In cyanotic CHD, a mixing of deoxygenated in oxygenated blood reduces arterial oxygenation and the child may be cyanotic, i.e., bluish. Many children with CHD need cardiac surgery. Congenital cardiac surgery often aims to restore normal circulation and correct the defect as seen in vast majority of pulmonary atresia with ventricular septal defect (PA+VSD), but palliative surgery may also be needed or may be the only possible treatment strategy. After congenital cardiac surgery excessive extravascular lung water (EVLW) may appear and impair optimal gas exchange. Effective clearance of EVLW and lung edema rests on active airway epithelial Na+ transport. Postoperative lung edema after congenital cardiac surgery has principally been assessed by chest radiography (CXR), which may be inaccurate and causes irradiation. Excessive EVLW promotes appearance of artifacts called B-lines in lung ultrasound (US), whereas lung compliance associates negatively with increased EVLW. In this thesis the effect of chronic hypoxemia on lung liquid transport was studied in children with CHD. Second, feasibility of lung US and lung compliance in assessment of EVLW and in predicting short-term clinical outcome was tested after congenital cardiac surgery. Third, the long-term survival of a cyanotic CHD was retrospectively evaluated in patients with PA+VSD. According to our findings, the airway epithelial Na+ transport was impaired in profoundly hypoxemic children with cyanotic CHD. After congenital cardiac surgery, lung US B-line score and static lung compliance correlated with CXR lung edema assessment. However, ventilator-derived dynamic lung compliance may not reflect the state of lung parenchyma similar to static compliance. Furthermore, both early postoperative lung US B-line and CXR lung edema scorings predicted short-term outcome interpreted as length of postoperative mechanical ventilation and intensive care. Among factors affecting the long-term survival of PA+VSD the primary anatomy of pulmonary circulation and achievement of repair were most important. In summary, our results emphasize the effect of postoperative pulmonary complications on short-term outcome after congenital cardiac surgery. Our data suggests that hypoxemia may attenuate the constitutional mechanism of the lung to prevent excessive lung liquid accumulation. To detect this, lung US can be used to complement CXR when assessing EVLW in children undergoing cardiac surgery. This may be particularly useful in profoundly hypoxemic children with cyanotic CHD and may promote early recognition of postoperative pulmonary complications. Although primary anatomical factors affect long-term outcome of PA+VSD, an important form of cyanotic heart disease, the treatment should aim for corrective surgery in all PA+VSD patients.Syanoottisessa synnynnäisessä sydänviassa vähähappinen laskimoveri ja hapekas valtimoveri pääsevät sekoittumaan aiheuttaen valtimoveren happipitoisuuden alenemisen (hypoksemia), kun taas asyanoottisessa sydänviassa valtimoveren happipitoisuus on normaali. Merkittävä osa synnynnäisistä sydänvioista vaatii kirurgista hoitoa. Hoidon tavoitteena on usein normaalin verenkierron palauttaminen kuten on tässä kirjassa tarkemmin käsiteltävän syanoottisen synnynnäisen sydänvian, pulmonaaliatresia yhdistettynä kammioväliseinäaukkoon (PA+VSD), tapauksessakin. Kuitenkin osassa synnynnäisistä sydänvioista verenkierto voidaan korjata vain osittain palliatiivisen kirurgian keinoin. Synnynnäisen sydänvian leikkaushoidon jälkeen hengitysteihin voi kertyä liiallista nestettä eli keuhkoödeemaa, joka hankaloittaa keuhkojen pääasiallista tehtävää eli kaasujen vaihtoa. Ylimääräisen keuhkonesteen kuljetus pois ilmatilasta perustuu hengitysteiden pintasolukon (epiteelin) aktiivisen Na+-ionien kuljetukseen. Sydänleikkauksen jälkeen keuhkoödeeman kuvantaminen perustuu sydän-keuhkokuvaan (thorax-kuva), joka aiheuttaa säteilyä ja voi olla epätarkka. Keuhkojen ultraäänitutkimuksella todettavien ns. B-viivojen on todettu olevan merkki keuhkojen lisääntyneestä nestemäärästä. Ja toisaalta keuhkojen venyvyyttä kuvaavan keuhkokomplianssin on todettu heikentyvän keuhkojen nestemäärän lisääntyessä. Tutkimme sydänleikkaukseen saapuvilla lapsilla keuhkoödeema-alttiuteen vaikuttavia tekijöitä ja keuhkojen ultraäänen ja keuhkokomplianssin mahdollisuuksia keuhkoödeeman ja toisaalta leikkauksen jälkeisen lyhytaikaisennusteen arvioimisessa. Syanoottisen synnynnäisen sydänvian pitkäaikaisennustetta arvioitiin retrospektiivisesti kattavan PA+VSD-potilaiden pitkäaikaisseurannan perusteella. Osoitimme ensimmäistä kertaa keuhkoödeeman poistumisessa keskeisen hengitystie-epiteliaalisen Na+-ionien kuljetuksen olevan heikentynyt hypoksemisilla syanoottista sydänvikaa sairastavilla lapsilla. Sydänleikkauksen jälkeinen keuhkojen ultraäänilöydös ja staattinen keuhkokomplianssi korreloivat thorax-kuvan nesteisyysarvion kanssa. Hengityskoneen automaattisesti mittaama dynaaminen keuhkokomplianssi sen sijaan vaikutti kuvaavan eri asiaa kuin staattinen keuhkokomplianssi. Leikkauksen jälkeinen thorax-kuvasta tai keuhkojen ultraäänestä tehty arvio keuhkojen nesteisyydestä oli itsenäinen leikkauksen jälkeiseen lyhytaikaisennusteen vaikuttava tekijä. Puolestaan pitkäaikaisennusteeseen PA+VSD potilailla vaikuttivat tärkeimpinä tekijöinä alkuvaiheen keuhkoverenkierron anatomia ja onnistunut kirurginen korjaus. Tulokset korostavat sydänleikkauksen jälkeisten keuhkopulmien vaikutusta sydänleikkauksesta toipumiseen. Havaintomme perusteella syanoottista synnynnäistä sydänvikaa sairastavilla lapsilla voi olla suurentunut riski sydänleikkauksen jälkeiselle keuhkoödeemalle ja keuhkonesteen määrää voidaan sydänleikatuilla lapsilla arvioida thorax-kuvan ohella myös keuhkojen ultraäänitutkimuksella. Keuhkovaurion aktiivinen kuvantaminen sydänleikkauksen jälkeen voi olla hyödyksi potilaan lyhytaikaisennusteen parantamisessa ja tehohoidon keston minimoimisessa. Vaikka keuhkoverenkierron anatomia vaikuttaa PA+VSD potilaiden ennusteeseen, on kirurgiseen korjaukseen pyrkiminen ensiarvoisen tärkeää ennusteen kannalta

Ventilator-derived dynamic respiratory system compliance : Comparison with static compliance in children

Measurement of dynamic lung compliance during breathing requires measurement of esophageal pressure, whereas static respiratory system compliance (Crs) method requires several airway occlusions. Despite their precision these compliance methods are cumbersome and not suitable for evaluation of pulmonary system in intensive care. The current ventilators display dynamic Crs, which, however, is seldom utilized in clinical practice. We studied the feasibility of ventilator-derived dynamic Crs measurement in pulmonary evaluation after congenital cardiac surgery in children. In 50 children static Crs was measured by double-occlusion technique, and compared with simultaneous ventilator-derived dynamic Crs values. The early postoperative dynamic and static Crs showed a correlation (r = 0.57, p <0.0001), but static Crs was 48% higher than dynamic (p <0.0001). Dynamic Crs measurement showed no correlation with radiographic lung edema findings, whereas the static Crs showed a negative correlation with radiographic lung edema scoring (r = -0.50, p = 0.0002). Thus ventilator-derived dynamic Crs seems less reliable in postoperative pulmonary evaluation than static Crs.Peer reviewe

Postnatal gene expression of airway epithelial sodium transporters associated with birth stress in humans

IntroductionLung fluid clearance is essential for successful postnatal pulmonary adaptation. The epithelial sodium channel (ENaC) and Na-K-ATPase, induced by serum- and glucocorticoid-inducible kinase 1 (SGK1) as well as aquaporins (AQP), represent key players in the switch from fetal lung fluid secretion to absorption and in early postnatal lung fluid balance. Birth stress, including a surge in catecholamines, promotes pulmonary adaptation, likely through the augmentation of epithelial sodium reabsorption. ObjectivesWe sought to determine the changes in the airway gene expression of molecules vital to epithelial sodium transport during early pulmonary adaptation, and the association with birth stress reflected in the norepinephrine concentration in the cord blood in humans. MethodsWe included 70 term newborns: 28 born via vaginal delivery and 42 via elective cesarean section. We determined the norepinephrine concentrations in the cord blood using tandem mass spectrometry and collected nasal epithelial cell samples at 2min, 1h, and 24h postnatally to quantify ENaC, Na-K-ATPase, AQP5, and SGK1 mRNAs using RT-PCR. ResultsThe molecular gene expression involved in airway epithelium sodium transport changed markedly within the first hour postnatally. Newborns born via elective cesarean section exhibited a lower expression of ENaC, Na-K-ATPase, and SGK1. Significant correlations existed between the expressions of ENaC, Na-K-ATPase, and SGK1, and the concentration of norepinephrine in the cord blood. ConclusionsThe association of ENaC, Na-K-ATPase, and SGK1 expression with the cord blood norepinephrine concentration points to the importance of birth stress in promoting lung fluid clearance during early postnatal pulmonary adaptation.Peer reviewe

Postnatal decrease of cystic fibrosis transmembrane conductance regulator gene expression in nasal epithelium of healthy newborn infants

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Decreased airway epithelial ion transport was associated with the severity of the respiratory syncytial virus infection and complications in infants

Abstract The respiratory syncytial virus (RSV) primarily infects airway epithelial cells. It also decreases airway epithelial sodium transport, especially through the epithelial sodium channel (ENaC) (1), which is crucial for osmosis-based fluid absorption across respiratory epithelium. Meanwhile, the electrochemical balance is maintained by secretion of chloride ions through apical chloride channels, including the cystic fibrosis transmembrane conductance regulator (CFTR) (1). In animals, ENaC inhibition has caused middle ear fluid collection in acute otitis media (AOM) (2).Peer reviewe

Long-term outcome after treatment of pulmonary atresia with ventricular septal defect : nationwide study of 109 patients born in 1970-2007

OBJECTIVES: Treatment of pulmonary atresia with ventricular septal defect (PA + VSD) has evolved during recent decades, but it still remains challenging. This study evaluated 41-year experience of outcome, survival and treatment of PA + VSD patients. METHODS: Patient records and angiograms of 109 patients with PA + VSD born in Finland between 1970 and 2007, and treated at the Children's Hospital, Helsinki University Central Hospital, were retrospectively analysed in this nationwide study. RESULTS: Of the 109 patients, 66 (61%) had simple PA + VSD without major aortopulmonary collateral arteries (MAPCAs). Although we observed no difference in overall survival between those with or without MAPCAs, the patients without MAPCAs had better probability to achieve repair (64 vs 28%, P <0.0003). Only 3 patients were treated by compassionate care. Overall survival was affected by the size of true central pulmonary arteries on the first angiogram (P = 0.001) and whether repair was achieved (P <0.0001). After successful repair, the survival rate was 93% at 1 year, 91% from the second year, and functional capacity as assessed by New York Heart Association (NYHA) I-II remained in 85% of patients alive at the end of follow-up. Palliated patients at 1, 5, 10 and 20 years of age had Kaplan-Meier estimated survival rates of 55, 42, 34 and 20%, respectively. Patients who underwent repair attempts but were left palliated with right ventricle (RV)-pulmonary artery connection and septal fenestration had better survival than the rest of the palliated patients (P = 0.001). Further, the McGoon index improved after implementation of a systemic-pulmonary artery shunt in the overall PA + VSD population (P <0.0001). CONCLUSIONS: These findings show that achievement of repair and initial size of true central pulmonary arteries affect survival of patients with PA + VSD. Although the overall survival of patients with MAPCAs showed no difference compared with simple PA + VSD patients, they had a higher risk of remaining palliated. However, palliative surgery may have a role in treatment of PA + VSD because the size of pulmonary arteries increased after placement of systemic-pulmonary artery shunt. In addition, subtotal repair by a RV-pulmonary artery connection and septal fenestration improved survival over extracardiac palliation.Peer reviewe

Heart Transplantation for Early-Onset Anthracycline-Induced Cardiomyopathy Within 5 Months of Chemotherapy Completion

Publisher Copyright: © 2021 The AuthorsA 9-year-old boy developed progressive anthracycline-induced cardiomyopathy three months after completion of chemotherapy for osteosarcoma. Five months after completion of chemotherapy, at the age of 10 years, heart transplantation was performed. At 29 months since transplantation, the patient remains free of rejection and recurrence of osteosarcoma. (Level of Difficulty: Intermediate.)Peer reviewe

Lung Injury After Neonatal Congenital Cardiac Surgery Is Mild and Modifiable by Corticosteroids

Objectives: The present study was performed to determine whether lung injury manifests as lung edema in neonates after congenital cardiac surgery and whether a stress-dose corticosteroid (SDC) regimen attenuates postoperative lung injury in neonates after congenital cardiac surgery. Design: A supplementary report of a randomized, double-blinded, placebo-controlled clinical trial. Setting: A pediatric tertiary university hospital. Participants: Forty neonates (age Measurements and Main Results: The chest radiography lung edema score was lower in the SDC than in the placebo group on the first postoperative day (POD one) (p = 0.03) and on PODs two and three (p = 0.03). Furthermore, a modest increase in the edema score of 0.9 was noted in the placebo group, whereas the edema score remained at the preoperative level in the SDC group. Postoperative dynamic respiratory system compliance was higher in the SDC group until POD three (p < 0.01). However, postoperative oxygenation; length of mechanical ventilation; and tracheal aspirate biomarkers of inflammation and oxidative stress, namely interleukin-6, interleukin-8, resistin, and 8-isoprostane, showed no differences between the groups. Conclusions: The SDC regimen reduced the development of mild and likely clinically insignificant radiographic lung edema and improved postoperative dynamic respiratory system compliance without adverse events, but it failed to improve postoperative oxygenation and length of mechanical ventilation. (C) 2021 The Authors. Published by Elsevier Inc.Peer reviewe

Unravelling associations between maternal health and congenital heart defect risk in the offspring-the FINNPEDHEART study

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