Congenital heart disease: pulmonary hypertension treatment


Pulmonary hypertension (PHT) in Congenital Heart Disease (CHD) is a common problem. It can occur secondaary to volume or pressure overload secondary to CHD or can develop after vascular injury related with cardiopulmonary bypass and lung injury. Depending on the severity of pulmonary hypertension, patients may develop right ventricle overload, ischemia and dysfunction.

Perioperative management:


Triggers: fever, pain, anemia, sepsis, acidosis, dehydration, hypercarbia

a. Management:

  • Provide adequate FIO2
  • Maintain normal Functional Residual Capacity
  • Provide adequate level of sedation / anesthesia
  • May require moderate hyperventilation
  • Treat metabolic acidosis
  • Optimal use of inotropics (if required )
  • Optimal hematocrit level
  • Ensure AV synchrony and control arrythmias

b. Avoid:

  • Alveolar hypoxemia
  • Atelectasis/ alveolar distension
  • Vasoconstrictors
  • Stimulation and agitation
  • Acidosis
  • Polycythemia
  • Hypothermia
  • Low Cardiac Output
  • Low coronary perfusion


Mechanism of actions of current medications are based on modulation of the intracellular calcium through enhancement of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP)

a.    Inhalation therapies:

Inhaled Nitric Oxide (NO): Activates Guanylyl cyclase; that transforms GTP (guanosyn triphosphate) into cGMP. cGMP activates Protein kinase G (PKG). PKG has several actions: it can directly decrease the entrance of calcium into the muscle cell, decreases the release of calcium from the sarcoplasmic reticulum (SR). It also phosphorylates the kinase that transforms light myosin chains in activated chains. All of this results in decreased intracellular calcium in the muscle cell and causes relaxation

Prostacyclin analogs (Iloprostol): mimetic PGE2 actions. Activate adenyl cyclase increasing cAMP . cAMP activates protein kinase A. PKA has several actions: phosphorylation of several membrane proteins that produce relaxation; inactivates the kinase that phosphorylates the transformation of the light chain of myosin in its active form. It also phosphorylates the phopholambam (PLN) increasing the retention of the calcium into the SER.

b.    Intravenous and oral Vasodilators: a.    Prostacyclin analogs (Epoprosterenol): increases cAMP for activation of the adenyl cyclase b. Nitrodilators (Nitroprusside, Nytroglycerin) : Increases release of nitric oxide from the endothelium or form NO from enzymatic activity c. Endotelin receptor antagonist: Bosentan. The endothelin is a peptidic hormone that attaches to endotelin receptors type A in the smooth muscle producing vasoconstriction. d.    Phosphodiesterase inhibitors: i.    Milrinone increases cyclic AMP. It inhibits Phosphodiesterase III. (PPDIII transform cAMP to ATP) ii.    Sildenafil increases cyclic GMP. It inhibits phosphodiesteraseV; (PPDV inactivates cGMP transforming it into the GTP) . c.    Calcium channel blockers: inhibit directly influx calcium in the cell

Extracorporeal Life Support is an alternative as a life saving rescue when medical therapy is ineffective Lung Transplantation and atrial septostomy are surgical treatments

Pulmonary hypertension is associated with significant morbidity and mortality following congenital heart surgery. Miller et al. randomized 124 infants to inhaled 10 ppm NO continuously after surgery until just before extubation, vs. placebo, and the NO group had fewer pulmonary hypertensive crises was eligible to extubate sooner [Miller OI et al. Lancet 356: 1464, 2000].



Keyword history




  1. Farber H.W. and Loscalzo J. Drug Therapy: Treatment of Pulmonary Arterial Hypertension New England Journal of Medicine 2004; 351:1655-1665