Pulmonary vascular resistance after cardiopulmonary bypass in infants: Effect on postoperative recovery

AbstractObjective: We sought to define the contemporary clinical effect of increased pulmonary vascular resistance in infants after congenital heart operations with cardiopulmonary bypass. Methods: Fifteen infants (median age, 0.31 years; median weight, 5.1 kg) underwent cardiac operations involving cardiopulmonary bypass (range, 49-147 minutes). Pulmonary vascular resistance was measured in the immediate postoperative period in the intensive care unit by means of the direct Fick principle, with respiratory mass spectrometry to measure oxygen consumption. The effect of ventilation with an inspired oxygen fraction of 0.65, with additional infusion of L -arginine, substance P, and inhaled nitric oxide, was assessed and subsequently correlated with the length of mechanical ventilation from the end of cardiopulmonary bypass to successful extubation. Results: Overall, pulmonary vascular resistance at baseline (11.7 ± 5.6 WU · m2) could be reduced to a minimum of 6.1 ± 3.5 WU · m2. The ventilatory time was 0.86 to 14.9 days (median, 1.75 days) and correlated directly with the lowest pulmonary vascular resistance value achieved during the pulmonary vascular resistance study (r 2 = 0.64, P <.01). The patient subgroup with mechanical ventilation of greater than 2 days had significantly higher pulmonary vascular resistance at all stages of the study protocol, and in this group there was a correlation of cardiopulmonary bypass time and ventilatory support time (r 2 = 0.48, P <.05). Conclusion: Increased pulmonary vascular resistance, either directly or as a surrogate of the systemic inflammatory response after cardiopulmonary bypass, continues to have a significant effect on postoperative recovery of infants after cardiac operations. (J Thorac Cardiovasc Surg 2001;121:1033-9

The endothelin antagonist BQ123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease

AbstractObjective: Postoperative pulmonary hypertension in children after surgical intervention for congenital heart disease has been attributed to failure of the pulmonary endothelium to provide adequate vasodilation. Although we have shown that the impaired vasodilatory component attributable to the l-arginine-nitric oxide pathway is almost completely reversible, a nonrestorable component persists, implying an additional vasoconstrictive mechanism in postoperative pulmonary endothelial dysfunction. In this study of children after surgical intervention for congenital heart disease, we measured endothelin-1 levels and used BQ123, a selective endothelin-A receptor antagonist, together with inhaled nitric oxide to discriminate dysfunctional pulmonary endothelial vasodilation from endothelin-mediated pulmonary vasoconstriction. Methods: All children were examined early after surgical intervention in the intensive care unit. Pulmonary vascular resistance (with respiratory mass spectrometry), as well as arterial and venous endothelin-1 levels (measured by means of a quantitative enzyme-linked immunosorbent assay), were determined in 7 children (age range, 3.3-13.7 months; median age, 6.3 months) with intracardiac shunting defects at baseline and during ventilation with a fraction of inspired oxygen of 0.65, with additional BQ123 (0.1 mg/kg infused over 20 minutes), and with inhaled nitric oxide (20 ppm). Results: Pulmonary vascular resistance decreased from 7.7 ± 3.4 at baseline to 6.1 ± 2.8 Woods units · m−2 (P =.022) at a fraction of inspired oxygen of 0.65 and to 4.7 ± 2.7 Woods units · m−2 (P =.013) during BQ123 infusion. Inhaled nitric oxide had no further effect on pulmonary vascular resistance. Left atrial endothelin-1 levels (1.35-5.12 pg/mL; mean, 2.4 pg/mL) correlated significantly with the decrease in pulmonary vascular resistance in response to BQ123 infusion (r2 = 0.89, P =.003). Conclusion: Postoperative elevation of pulmonary vascular resistance in children after surgical intervention for congenital heart disease is responsive to endothelin-A blockade with BQ123. Increased levels of endothelin-1 predict the response to this therapy, which might become an important addition to the clinical armamentarium in postoperative pulmonary hypertensive disease.J Thorac Cardiovasc Surg 2002;124:435-4

The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part II: Medical Treatment - Study Results

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death

The Adult Patient with Eisenmenger Syndrome: A Medical Update After Dana Point Part I: Epidemiology, Clinical Aspects and Diagnostic Options

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death

The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part III: Specific Management and Surgical Aspects

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death

Motor outcome, executive functioning, and health‐related quality of life of children, adolescents, and young adults after ventricular assist device and heart transplantation

Objective The aim of the current study is to measure long‐term executive function, motor outcome, and QoL in children, adolescents, and young adults after VAD and Htx. Methods Patients were examined during routine follow‐up. Investigation tools were used as follows: Examination for MND of motor outcomes, Epitrack® for attention and executive functioning, and Kidscreen‐52 and EQ‐5D‐5L questionnaires for QoL. Additional data were retrospectively obtained by an analysis of patient medical records. Results Out of 145 heart transplant recipients at the department of pediatric cardiology of the University Hospital Munich, 39 were implanted with a VAD between 1992 and 2016. Seventeen (43.6%) patients died before or after Htx; 22 (56.4%) patients were included in our study. Mean age at transplant was 9.52 years (range: 0.58‐24.39 years, median 9), and the mean follow‐up time after Htx was 6.18 years (range: 0.05‐14.60 years, median 5.82). MND examination could be performed in 13 patients (normal MND: n = 11, simple MND: n = 1, complex MND: n = 1). Executive functioning was tested in 15 patients. Two (13.3%) patients had good results, six (40%) average results, three (20%) borderline results, and four (26.7%) impaired results. QoL (Kidscreen n = 7, EQ‐5D‐5L n = 8) was similar to a healthy German population. Conclusion Motor outcome, executive functioning and QoL in survivors of VAD bridging therapy and Htx can be good, though underlying diseases and therapies are associated with a high risk of cerebral ischemic or hemorrhagic complications

Pharmacokinetic and clinical profile of a novel formulation of bosentan in children with pulmonary arterial hypertension: the FUTURE-1 study

center dot Exposure to bosentan was lower in paediatric pulmonary arterial hypertension (PAH) patients treated with the marketed adult formulation at a dose of about 2 mg kg-1 when compared with adult PAH patients. center dot In healthy adult subjects, bosentan pharmacokinetics are less than dose-proportional at doses of >= 500 mg. WHAT THIS STUDY ADDS center dot The pharmacokinetics of a new paediatric bosentan formulation were characterized in paediatric PAH patients. center dot The level of exposure to bosentan as observed in adult PAH patients cannot be reached in paediatric patients with b.i.d. dosing. center dot In paediatric PAH patients, nondose-proportional pharmacokinetics of bosentan occur at lower doses when compared with healthy adult subjects. AIM To show equivalent bosentan exposure in paediatric patients with pulmonary arterial hypertension (PAH) when compared with a cohort of historical controls of adult PAH patients using a newly developed paediatric formulation. METHODS Thirty-six paediatric PAH patients were enrolled in this multicentre, prospective, open-label, noncontrolled study and treated for 4 weeks with bosentan 2 mg kg-1 b.i.d. and then for 8 weeks with 4 mg kg-1 b.i.d. Blood samples were taken for pharmacokinetic purposes. Exploratory efficacy measurements included World Health Organization (WHO) functional class and parent's and clinician's Global Clinical Impression scales. RESULTS Comparing children with a historical group of adults, the geometric mean ratio (90% confidence interval) of the area under the plasma concentration-time curve was 0.54 (0.37, 0.78), i.e. children had lower exposure to bosentan than adults. Bosentan concentrations following doses of 2 and 4 mg kg-1 were similar. Improvements in WHO functional class and the Global Clinical Impression scales occurred mainly in bosentan-naive patients, whereas the rare worsenings occurred in patients already on bosentan prior to study initiation. The paediatric formulation was well accepted and bosentan well tolerated in this study. No cases of elevated liver enzymes or anaemia were reported. CONCLUSIONS Exposure to bosentan, as shown comparing the results from this study with those from a study in adults, was different in paediatric and adult PAH patients. Since FUTURE-1 and past studies suggest a favourable benefit-risk profile for bosentan at 2 mg kg-1 b.i.d., this dose is recommended for children with PAH. The new paediatric formulation was well tolerate

Postoperative pulmonalen Hypertension nach Korrektur angeborener Herzfehler

Die postoperative pulmonale Hypertension (PHT) bei Kindern nach chirurgischer Korrektur eines angeborenen Herzfehlers ist mit einer erhöhten postoperativen Morbidität und Mortalität assoziiert. Sie kann in lebensbedrohliche pulmonalhypertensive Krisen exazerbieren. Eine systematische Untersuchung der zugrundeliegenden Pathophysiologie sowie mögliche Behandlungsformen der postoperativen PHT ist Gegenstand dieser Arbeiten. Alle Untersuchungen wurden im Rahmen der klinischen Routine an sedierten und zumeist intubierten und mechanisch beatmeten Kindern mit angeborenen Herzfehlern durchgeführt, sowohl präoperativ im Herzkatheterlabor, als auch postoperativ auf der Intensivstation. Es wird die Anwendung von inhalatorischem NO und aerosolisiertem PGI2 zur Diagnostik und Therapie der prä- und postoperativen PHT bei Patienten mit angeborenen Herzfehlern konkret entwickelt und dargestellt. Die Bedeutung von pulmonalem endothelialen Versagen, zirkulierenden plasmatischen Endothelinen und vaskulo-bronchialen Interaktionen für Ausprägung der postoperativen PHT und den klinischen Verlauf des Patienten werden hier erstmals dargestellt. Insgesamt werden hierdurch neue Therapieansätze aufgezeigt, welche bereits im Einsatz sind oder in naher Zukunft umgesetzt werden.Postoperative pulmonary hypertension in children after congenital heart surgery is associated with increased postoperative morbidity and mortality. This state may exacerbate in livethreatening pulmonary hypertensive crises. A systematic assessment of the underlying pathophysiology and possible treatment options was the object of this work. All studies were done within the clinical routine in sedated and mostly intubated and mechanically ventilated children with congenital heart disease, during preoperative evaluation in the cardiac catheter laboratory, and during their postoperative recovery on the intensive care unit. The application of inhaled nitric oxide and aerosolised prostacyclin for the preoperative evaluation and postoperative treatment of pulmonary hypertension is described. The impact of pulmonary endothelial dysfunction, circulating endothelins, and vasculo-bronchial interactions for the development and perpetuation of postoperative pulmonary hypertension and the clinical course of the patient is delineated for the first time. Thus, novel therapeutic options are demonstrated which may be already in use or will be applied in the near future