Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

Background

Pulmonary Hypertension may be a primary or secondary cause of hypoxia in the neonate.

The diagnostic evaluation should include

A. Central hematocrit, serum glucose and calcium levels, platelet count

B. Chest x-ray, EKG

C. Hyperoxia (100% oxygen) challenge test

D. Simultaneous pre- and postductal arterial PaO2 or TcPO2

E. Cardiology consult, if indicated for echocardiography to rule out cyanotic congenital heart disease.

MEDICAL MANAGEMENT of PPHN

  • Minimize Pulmonary Hypertension/Vasoconstriction
    • AVOID: HYPOXIA, HYPOTHERMIA, ACIDOSIS, ANEMIA,
    • HYPOTENSION AND STIMULATION !
     
  • Maximize Pulmonary Vasodilatation (Decrease pulmonary vascular resistance)
    • OXYGEN (FiO2 = 1.0)
    • ALKALINIZATION - METABOLIC ALKALOSIS (pH > 7.55)
     
  • Support Cardiac Output and Blood Pressure
    • VOLUME
    • INOTROPIC AGENTS: Dobutamine, Dopamine and Epinephrine
     
  • Relieve Pain and Anxiety
    • ANALGESIA: Morphine or Fentanyl
    • SEDATION: Lorazepam, Chloral Hydrate, Phenobarbital, Midazolam and Thorazine
    • PARALYSIS: Pavulon
     
  • Administer Pulmonary Vasodilating Agents
    • "INHALED NITRIC OXIDE"
    • TOLAZOLINE
    • PROSTAGLANDIN E1 p
    • ISOPROTERENOL
     
  • Avoid Barotrauma
    • Small tidal volumes with high rates (i.e., HFOV)
    • Avoid hyperventilation (pCO2 ² 30) to minimize barotrauma
     

Initial Therapeutic Guide

A. Correct hypothermia, hyperviscosity and metabolic problems. 

B. 100% oxygen and transient hyperventilation with goal of an arterial pH value greater than 7.55 (1), and PaCO2 of 30-35 mm Hg, and a PaO2 of 55 mm Hg or greater. This may transiently require rapid ventilation with rates of 60 to 80 BPM (I:E = 1:1). However, to avoid barotrauma alkalinize metabolically and then use gentler ventilation (PaCO2 ³ 35 mmHg) with HFOV. 

C. Alkalinization by metabolic means with the use of a bicarbonate infusion (1-2 meq/kg/hr) (2). 

D. Analgesia with morphine infusion (0.1 - 0.2 µg/kg/hr) and sedation with Lorazepam (0.1 - 0.3 mg/kg/dose PRN Q2H) or chloral hydrate (50 mg/kg/dose Q8H-Q12H). Consider transient neuromuscular blockade with Pavulon if infant is "fighting" the ventilator. 

E. Aggressively support blood pressure with appropriate volume and use Dobutamine (10-20 µg/kg/hr) and Dopamine (5-10 µg/kg/min). Consider NO if PaO2 < 70 on 100% O2. 

V. Start Nitric Oxide at 40 ppm as per experimental protocol if PaO2 < 55 mmHg. 

VI. Pharmacologic intervention with Priscoline (Tolazoline) may be indicated if ventilation, correction of acidosis, and treatment of the primary lung disorder do not lower pulmonary arterial pressure. 

A. Tolazoline is an alpha-adrenergic blocking agent. Given IV, the onset of action is within minutes. The biologic half-life is approximately two hours. It is excreted, largely in the unchanged form, by the renal tubules. 

B. Indications for use: 

1. Documented right-to-left shunt, with a PaO2 gradient >20 TORR 

2. ECHO documentation of pulmonary arterial hypertension. 

3. Failure of hyperventilation and metabolic alkalosis as initial therapy. 

4. Tolazoline should NOT be given without consultation with the staff Neonatologist. 

C. Dose: 1.0 mg/kg IV over 10 minutes followed by a constant infusion of 0.5-2.0 mg/kg/hour via a scalp, or an upper extremity, vein. The hourly dose is infused in the same volume of IV fluid that the infant has been previously receiving. 

D. During the infusion, monitor: 

1. Systemic blood pressure; if low, be ready to treat immediately with volume expansion 

2. Urine output

3. Heart rate 

4. Arterial blood gases pre- and postductal 

5. Evidence of GI hemorrhage

6. Platelet count

E. Consider starting Dopamine or Dobutamine at 5-10 ug/kg/min. prior to the use of Tolazoline to support systemic blood pressure.

F. If improvement is documented (an increase in PaO2 of 20 mm Hg, or a decrease in ventilator settings) within two hours, maintain the same dose. If no improvement is documented, slowly increase the dose of Tolazoline by increments of 0.5 mg/kg/hour. If no response is seen in another two hours, discontinue the infusion. 

G. Tolazoline is excreted by the kidney. If the infant is anuric or oliguric, caution must be used when administering this drug. 

Additional pharmacologic Therapy

A. Consider the use of other vasoactive drugs such as Isoproterenol, Nitroglycerin, Epinephrine, or PGE1 after consulting with the staff Neonatologist.

References:

  1. Perkins R.M. and Anas N.G. Pulmonary hypertension in pediatric patients. J Pediatr 1984;105:511-522.
  2. Dwortz A.R., et. al. Survival of infants with persistent pulmonary without extracorporeal membrane oxygenation. Pediatrics 1989;84:1-6.

 Treatment of Pulmonary Hypertension