Current and future strategies in the treatment of childhood pulmonary hypertension
Introduction
Treatment strategies for pulmonary hypertension in children will vary with the acuity or chronicity of the hypertensive disorder. The underlying cause of pulmonary hypertension may be idiopathic (primary) or it may arise secondary to a wide variety of childhood disorders, particularly congenital heart disease or interventions associated with repair or palliation of structural heart disease. Treatment of acute life threatening pulmonary hypertension is focused on principles of perioperative and critical care, while the underpinning for new treatments of chronic (including primary) pulmonary hypertension emphasizes discoveries in genetics and vascular biology which may permit new vessel growth, repair or remodeling, even normalization of abnormal vessels in the lung. The following discussion addresses first the critical care strategies aimed at treating pulmonary hypertension, primarily among children with congenital heart disease. Much of the discussion relates to the comparative effects of inhaled nitric oxide among these patients. This is followed by a review of (outpatient) treatment options for patients with chronic pulmonary hypertension, predominantly those with primary pulmonary hypertension. Here the clinical discussion centers on the recent findings and hopeful promise of prostacyclin and innovative applications of new findings in vascular biology.
Section snippets
Diversity in diagnoses
Pulmonary hypertension frequently confronts the critical care practitioner. It is present in the neonatal period as a life threatening pathologic entity associated with persistent pulmonary hypertension of the newborn and other forms of acute hypoxemic respiratory failure. Later, infants with lung hypoplasia and reduced microvascular cross-sectional area in the lungs invariably have difficulty with pulmonary hypertension if they survive the neonatal period; they face further exacerbations of
Secondary pulmonary hypertension
Rare forms of chronic pulmonary hypertension in children are diverse and therapy should be tailored to the underlying disease when known [218]. Avoidance of circumstances that are known to incite or aggravate pulmonary hypertension (high altitude, extreme exercise, pregnancy, birth control pills, etc.) is sound and obvious advice.
Adequate repair (not palliation) of congenital heart disease very early in life is the best solution to preventing the development of progressive pulmonary vascular
References (280)
- et al.
Repair of truncus arteriosus in the neonate
J Thorac Cardiovasc Surg
(1993) - et al.
The pulmonary hemodynamic response to perioperative anesthesia in the treatment of high-risk infants with congenital diaphragmatic hernia
J Pediatr Surg
(1984) - et al.
Randomized trial of fentanyl anesthesia in preterm neonates undergoing surgery: effects on the stress response
Lancet
(1987) - et al.
Pharmacokinetics of alfentanil before and after cardiopulmonary bypass in pediatric patients undergoing cardiac surgery: part I
J Cardiothorac Vasc Anesth
(1992) - et al.
Plasma fentanyl levels in infants undergoing extracorporeal membrane oxygenation
J Thorac Cardiovasc Surg
(1993) - et al.
Effect of pH and Pco2 on pulmonary and systemic hemodynamics after surgery in children with congenital heart disease and pulmonary hypertension
J Pediatr
(1988) - et al.
The independent effects of hyperventilation, tolazoline, and dopamine on infants with persistent pulmonary hypertension
J Pediatr
(1981) - et al.
Physiologic factors affecting pulmonary artery pressure in infants with persistent pulmonary hypertension
J Pediatr
(1978) - et al.
Efficacy and neurologic outcome of profound hypocapneic alkalosis for the treatment of persistent pulmonary hypertension in infancy
J Pediatr
(1984) - et al.
Results of 102 cases of complete repair of congenital heart defects in patients weighing 700 to 2500 grams
J Thorac Cardiovasc Surg
(1999)
Selective pulmonary and systemic vasodilator effects of amrinone in children: new therapeutic implications
J Am Coll Cardiol
Use of amrinone in cardiac surgery patients
J Cardiothorac Vasc Anesth
Amrinone and dobutamine as primary treatment of low cardiac output syndrome following coronary artery surgery: a comparison of their effects on hemodynamics and outcome
J Cardiothorac Vasc Anesth
Effect of inhaled nitric oxide on endothelin-1 and cyclic guanosine 5′-monophosphate plasma concentrations in newborn infants with persistent pulmonary hypertension
J Pediatr
Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow
J Thorac Cardiovasc Surg
Pulmonary vasodilatory effects of 12 and 60 parts per million inhaled nitric oxide in children with ventricular septal defect
Am J Cardiol
Inhaled nitric oxide and hemodynamic evaluation of patients with pulmonary hypertension before transplantation
J Am Coll Cardiol
Inhaled nitric oxide in children with pulmonary hypertension and congenital mitral stenosis
Am J Cardiol
Inhaled nitric oxide in the treatment of postoperative graft dysfunction after lung transplantation
Ann Thorac Surg
Inhaled nitric oxide in persistent pulmonary hypertension of the newborn
Lancet
Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide
J Pediatr
Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: dose response
J Pediatr
Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man
Lancet
Endogenous nitric oxide and pulmonary vascular tone in the neonate
J Pediatr Surg
Regulation of pulmonary vascular resistance by endogenous and exogenous nitric oxide
Ann Thorac Surg
Abnormalities in von Willebrand factor and antithrombin III after cardiopulmonary bypass operations for congenital heart disease
J Thorac Cardiovasc Surg
Pulmonary sequelae of prolonged total venoarterial bypass: Evaluation with a new experimental model
Ann Thorac Surg
Inhaled nitric oxide selectively decreases pulmonary vascular resistance following acute massive pulmonary microembolism in piglets
Chest
Nitric oxide improves hypoxaemia following reperfusion oedema after pulmonary thromboendarterectomy
Br J Anaesth
Inhaled nitric oxide as an adjunct to pulmonary thromboendarterectomy
Ann Thorac Surg
Effect of baffle fenestration on outcome of the modified Fontan operation
Circulation
Blunting of stress responses in the pulmonary circulation of infants by fentanyl
Anesth Analg
Halothane-morphine compared to high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery
N Engl J Med
Pulmonary and systemic hemodynamic responses to fentanyl in infants
Anesth Analg
Pulmonary and systemic hemodynamic effects of nitrous oxide in infants with normal and elevated pulmonary vascular resistance
Anesthesiology
Hemodynamic effects of ketamine in children with congenital heart disease
Anesth Analg
Hemodynamic effects of ketamine in children undergoing cardiac catheterization
Pediatr Cardiol
Fentanyl-air-oxygen anesthesia for ligation of patent ductus arteriosus in preterm infants
Anesth Analg
Fentanyl- and sufentanil- oxygen- pancuronium anesthesia for cardiac surgery in infants
Anesth Analg
Hemodynamic and anesthetic effects of sufentanil as the sole anesthetic for pediatric cardiovascular surgery
Anesthesiology
Pharmacodynamics and pharmacokinetics of high-dose sufentanil in infants and children undergoing cardiac surgery
Anesth Analg
Anesthesia for hypoplastic left heart syndrome: high dose fentanyl in 30 neonates
Anesth Analg
Pulmonary and systemic hemodynamic responses to ketamine in infants with normal and elevated pulmonary vascular resistance
Anesthesiology
Effect of anesthetic induction regimens on oxygen saturation in cyanotic congenital heart disease
Anesthesiology
The dose response to fentanyl in neonatal surgery [Abstract]
Anesthesiology
Pharmacokinetics of continuous infusions of fentanyl in critically ill children
Crit Care Med
Alfentanil-induced rigidity in newborn infants
Anesth Analg
Response to the pulmonary circulation to hypoxia and H+ ion changes
J Clin Invest
Pulmonary vascular resistance in infants after cardiac surgery: role of carbon dioxide and hydrogen ion
Crit Care Med
Long-term follow-up of newborns with persistent pulmonary hypertension
Crit Care Med
Cited by (18)
Critical Care After Surgery for Congenital Cardiac Disease
2011, Pediatric Critical Care: Expert Consult Premium EditionCritical Care After Surgery for Congenital Cardiac Disease
2011, Pediatric Critical CareUnidirectional Monovalve Homologous Aortic Patch for Repair of Ventricular Septal Defect With Pulmonary Hypertension
2007, Annals of Thoracic SurgeryCitation Excerpt :Cardiopulmonary bypass, infusion of protamine, and other factors that could cause the release of vasoactive substances such as thromboxane A2 and catecholamine could result in pulmonary vasoconstriction and acute pulmonary hypertension [15–17]. Pulmonary hypertensive crisis can be associated with acute congestive heart failure, which is the main cause of death [18–21]. Fifteen years ago, we used nonfenestrated patch closure for children less than six years old with severe pulmonary hypertension and resistance, but the operative mortality was very high.
Cardiac Intensive Care
2006, Pediatric Critical CarePulmonary Hypertension
2006, Nadas' Pediatric CardiologyIntensive Care Unit
2006, Nadas' Pediatric Cardiology