Pulmonary Hypertension is defined by:
In adults, upper limit of pulmonary artery pressures are 25/10 mmHg
In pediatric patients, generally referenced to systemic pressures with > 1/3 systemic pressures considered elevated (often not clinically significant in the PICU until >1/2 systemic or more)
Indicates increased PVR in the setting of normal pulmonary capillary wedge (LA) pressures
Cardiac catheterization allows measurement of actual pressures (rarely done in PICU patients)
Swan-Ganz PA catheter also allows direct measurements (rarely done in pediatric patients)
RV hypertrophy or dilation
Ventricular septal position
TR Jet: The TR jet allows estimation of the RV pressure during systole by measuring the velocity of the tricuspid regurgitant jet. Hence, assuming no significant pulmonary valve stenosis, it allows an estimation of PA pressure. the calculation (which depends on the presence of a TR jet as well as capturing the maximal velocity (depending on the angle of the ultrasound wave in relation to the TR jet). The modified Bernoulli equation 4v2 where v= velocity of TR jet gives an estimate of the pressure differential between RV and RA. Hence, the estimated RV and thereby the PA pressure in systole = 4v2+ RA pressure
Signs/Symptoms of PH:
Fatigue, dyspnea, syncope
RVH via EKG or CXR
Enlarged PA's on CXR
RV strain pattern on EKG (ST depression and/or T wave inversion in leads V1-V4, II, III, AVF)
Of note, PH does NOT typically cause hypoxemia unless there is a R to L shunt (ie PDA, ASD, etc.)
Can lead to RV failure over time
JVD, loud S2 (corresponding to pulmonary valve closure at higher pressure), pulmonary regurgitation, hepatomegaly, ascites
While the final common pathway for PH results in restricted flow through the pulmonary arterial circulation with eventual development of right heart failure, it can result from a variety of causes
The WHO classifies PH into various etiologies (See Figure below)
A number of mediators have been shown to influence the balance of pulmonary vasodilation and vasoconstriction. These include Endothelin-I, Prostacyclin (PGI2), and nitric oxide, among others. See Figure below:
Pathophysiology of Pulmonary Hypertension & Targets for Therapy (From Humbert et al, NEJM 2004)
Pulmonary vascular resistance (PVR) is also affected by pH, PCO2, PaO2
PVR is also affected by lung volumes, with corner and septal capillaries demonstrating different PVR at different lung volumes. The aggregate is that PVR is least at Functional Residual Capacity (FRC). (see Figure below)
Pulmonary vascular resistance varies with lung volumes and is minimized at FRC
Treatment of an acute episode (ie pulmonary hypertensive crisis or "snit"):
100% Oxygen (potent pulmonary vasodilator)
Hyperventilation (pulmonary vessels vasodilate in response to alkalemia)- ie via BMV
Sedation, decreasing adrenergic tone
iNO, Direct pulmonary vasodilator
Fluid bolus (ie if associated with dynamic RV outflow tract obstruction- "Tet Spell")
Treatment targets the imbalance of pulmonary vasodilators and vasoconstrictors:
Calcium Channel Blockers: Rarely used in pediatric patients, but used in adult patients who respond to vasodilator (i.e. iNO or prostacyclin) testing during cardiac catheterization (response is defined as 20% decrease in PA pressure or a decrease of at least 10 mmHg to below 40 mmHg for mean PAP.
Prostacyclin (PGI2): Epoprostenol (Flolan): Improves survival in patients with severe PAH, issues include need for IV administration and short half life (3-6 minutes) that can lead to life threatening rebound pulmonary hypertension if the infusion is stopped inadvertently (ie broviac catheter breaks), medication must also be refrigerated and so patients must keep ice packs with them. Treprostinil is given via subcutaneous infusion but injection site pain is a significant limiting factor in pediatric patients.Inhaled iloprost is also an option but due to its short half life, must be inhaled up to 6-12 times/day, making it useful in a limited population of pediatric patients.
If a patient on epoprostenol comes in with a disruption in their infusion, start iNO and work on immediate access to restart the epoprostenol infusion
Endothelin Receptor Antagonists: Bosentan: oral endothelin A and B receptor antagonist. Elevated LFT's a limiting factor and seems to be dose dependent. Ambrisentan is a potential alternative.
Nitric Oxide: stimulates cGMP and functions as a direct vasodilator. Given in inhaled form and leads to selective pulmonary vasodilation (improves VQ matching as well as PVR). Used in acute situations.
Often initiated at 20-40 ppm and can be titrated to effect (ie oxygen saturation or echocardiographic evidence of reduced PA pressures). Weans generally in a pattern of 20,15,10,5,4,3,2,1 with several hours between each wean
Sildenafil: Phosphodiesterase 5 inhibitor, inhibiting the breakdown of cGMP and thereby producing vasodilation. Commonly used oral medication in pediatric pulmonary hypertension. Some controversy after the STARTS-2 trial (STARTS-1 conducted by Barst et al and published in Circulation 2012 was a dose response randomized control trial demonstrating improved survival with sildenafil vs. placebo) demonstrated a higher mortality in the high dose sildenafil group. However, many criticize the conclusion as physicians were allowed to adjust dosing after STARTS-1, leading to the conclusion that it was likely sicker patients that ended up on higher doses of sildenafil and hence, the increased mortality seen in that group
Combination therapy: May show synergystic effects by targeting multiple mechanisms, although clear data is lacking at this time
Heart Lung transplant: Due to generally poor outcomes (~50% 3 year survival overall) and few centers which do heart-lung transplants, this is reserved for refractory cases of pulmonary hypertension with estimated 2 year survival <50%.
From Ivy et al, JACC 2013