Pulmonary hypertension in neonates

Dr Varsha Atul Shah

What is the problem?

• PPHN / PFC : Persistence of the pattern of fetal circulation postnatally due to a sustained elevation of pulmonary vascular resistance, with right-to-left shunt at the ductus arteriosus or foramen ovale in the absence of structural heart disease

• Incidence: About 1 per 1000. Exact incidence unknown in the absence of ICD coding or a “gold standard” for diagnosis

• Mortality and Morbidity: Mortality rate of > 50% in the absence of ECMO, and >10-20% with ECMO; >20% severe handicap/intracranial hemorrhage/deafness

(Walsh-Sukys M C: Persistent pulmonary hypertension of the newborn. The black box revisited.

Clin Perinatol 20: 127-143, 1993)

Causes of PPHN(Geggel RL, Reid LM:The structural basis of PPHN.Clin Perinatol 11:525-549, 1984)

PPHN

Normal Arterial Number Decreased Arteries e.g. CDH

Normal muscularization Increased muscularization

Developmentalimmaturity

Maladaptation dueto acute injury (commonest) e.g.Sepsis, Meconiumaspiration synd., asphyxia

Chronic injurywith vascularremodeling

Malform-ation

Clinical features of PPHN

• Usually a term infant, with risk factors of asphyxia, elective C/section without labor, meconium stained fluid, sepsis, diaphragmatic hernia etc. Some infants have no obvious risk factors (idiopathic PPHN).

• Cyanosis due to shunting of blood from right to left (pulmonary to systemic circulation) “persistence of fetal circulation”, causing mixing of deoxygenated with oxygenated blood

Clinical features of PPHN

• Right to left shunting of blood occurs most often through the ductus arteriosus, and hence saturation will be lower (by 10-15% or more) in legs (+ left upper limb) as compared to right upper limb and head

• In some infants, shunting of blood also occurs within the heart at the foramen ovale level, and hence SpO2 is the same in all limbs

• Confirmation of the diagnosis is by echocardiogram, which will demonstrate R to L shunting, elevated R sided pressures, and absence of structural heart disease

Current management

Confirm diagnosis of PPHNCorrect underlying abnormalities (hypothermia, acidosis, hypocalcemia, hypoglycemia, polycythemia); Oxygen by hood

Conservative mechanical ventilationTrial of hyperventilation

If low PO2, trial of rescue therapies

Metabolic HFV Surfactant Vasodilators ECMOAlkalosis NO, PGD2,

PGI2, Tolazoline,

Adenosine

Pathophysiological basis of current management

• Mechanical ventilation: Ventilation-Perfusion (V/Q) matching to

improve oxygenation respiratory alkalosis to reduce Pulmonary

Vascular Resistance (PVR)• Metabolic alkalosis: effect of pH on PVR• Vasodilators: specific relaxation of the

pulmonary vasculature. Most experience with Nitric Oxide

• ECMO: modified long-term cardio-pulmonary bypass

Other support measures

• Cardiac strategies: Support of cardiac output and SVR with

dopamine, fluid infusions

• Environmental strategies: Sedation with fentanyl or morhphine Avoidance of noise and light stress

Ventilatory managementVentilatory management

• ventilator management controversial• FiO2 adjusted to maintain PaO2 80-

100 to minimize hypoxia-mediated pulmonary vasoconstriction

• ventilatory rates and pressures adjusted to maintain mild alkalosis (pH 7.5-7.6), usually combined with bicarbonate infusion

• avoid low PaCO2 (<20 mm Hg) to prevent cerebral vasoconstriction

Nursing care of infant with PPHN

• Sedation (+ muscle relaxant) initially, wean as condition improves. Too rapid or too slow weaning are both bad.

• Minimal stimulation• Close monitoring, esp. SpO2, PaO2, PaCO2.

Hourly, shift, or daily ranges and plan essential.• Do not suction unless necessary! (e.g. MAS,

thick secretions). Suctioning can cause pain, fighting ventilator, atelectasis, loss of lung volume

• Cannot hear heart sounds/breath sounds/bowel sounds when on HFV. Use monitors!

Ventilator settings: PIPVentilator settings: PIP

• affects MAP (PO2) and VT (PCO2)• PIP required depends largely on

compliance of respiratory system• Clinical: gentle rise of chest with

breath, similar to spontaneous breath• Minimum effective PIP to be used. No

relation to weight or airway resistance

• Neonate with PPHN: 15-30 cm H2O. Start low and increase.

Ventilator settings: PEEPVentilator settings: PEEP

• affects MAP (Paffects MAP (POO22), affects V), affects VTT (P (PCOCO22) ) depending on position on P-V curvedepending on position on P-V curve

• older infants (e.g. BPD) tolerate higher older infants (e.g. BPD) tolerate higher levels of PEEP (6-8 cm Hlevels of PEEP (6-8 cm H22O) betterO) better

• RDS: minimum 2-3, maximum 6 cm HRDS: minimum 2-3, maximum 6 cm H22O. O.

Pressure

Volume

PEEP PIP

Ventilator settings: RateVentilator settings: Rate

• affects minute ventilation (PCO2)• In general, rate ---> PCO2

• Rate changes alone do not alter MAP (with constant I:E ratio) or change PO2 , unless PVR changes with changes in pH

• However, if rate --> TE < 3TC --> gas trapping--> decreased VT--> PCO2

• Minute ventilation plateaus, then falls with rate

Ventilator settings: TVentilator settings: TII and T and TEE

• Need to be 3-5 TC for complete Need to be 3-5 TC for complete inspiration and expiration (Note: TC exp inspiration and expiration (Note: TC exp = TC insp)= TC insp)

• Usual ranges:Usual ranges: T TII sec sec TTEE secsec RDS RDS 0.2-0.45 0.2-0.45 0.4-0.6 0.4-0.6 BPDBPD 0.4-0.8 0.4-0.8 0.5-1.50.5-1.5 PPHNPPHN 0.3-0.8 0.3-0.8 0.5-1.00.5-1.0

• Chest wall motion / VChest wall motion / VTT may be useful in may be useful in determining optimal Tdetermining optimal TII and T and TEE

Ventilator settings: I:E ratioVentilator settings: I:E ratio

• When corrected for the same MAP, When corrected for the same MAP, changes in I:E ratio do not affect gas changes in I:E ratio do not affect gas exchange as much as changes in PIP or exchange as much as changes in PIP or PEEPPEEP

• Changes in TChanges in TII or T or TEE do not change V do not change VTT or or PPCOCO2 2 unless they are too short (< 3 TC)unless they are too short (< 3 TC)

• Reversed I:E ratio: No change in mortality Reversed I:E ratio: No change in mortality or morbidity noted in studies. Not often or morbidity noted in studies. Not often used. May improve V/Q matching and Pused. May improve V/Q matching and POO22 at risk of at risk of venous return and gas venous return and gas trappingtrapping

Ventilator settings: FiOVentilator settings: FiO22

• affects oxygenation directly• with FiO2 <0.6-0.7, risk of oxygen

toxicity less than risk of barotrauma• to improve oxygenation, increase

FiO2 to 0.7 before increasing MAP• during weaning, once PIP is low

enough, reduce FiO2 from 0.7 to 0.4. Maintenance of adequate MAP and V/Q matching may permit a reduction in FiO2

Ventilator settings: FlowVentilator settings: Flow

• affects pressure waveformaffects pressure waveform• minimal effect on gas exchangeminimal effect on gas exchange as as

long as sufficient flow usedlong as sufficient flow used• increased flow--> turbulenceincreased flow--> turbulence• higher flow required if TI short, to higher flow required if TI short, to

maintain TVmaintain TV• flow of 8-10 lpm usually sufficientflow of 8-10 lpm usually sufficient• change of flow may affect delivery change of flow may affect delivery

of NO or anesthesia gasesof NO or anesthesia gases

High frequency ventilationHigh frequency ventilation

HFPPV HFJV HFFI HFOV

VT >dead sp > or < ds > or <ds <ds?

Exp passive passive passive active

Wave- variable triangular triangular sine wave

Form

Entrai- none possible none none

ment

Freq. 60-150 60-600 300-900 300-3000

(/min)

High Frequency Ventilation in PPHN

• V/Q matching to improve oxygenation

• Respiratory alkalosis to reduce PVR• Improved response to inhaled NO• “Rescue” for air leak syndromes

High frequency ventilation

•HFPPV conventional ventilators with low-

compliance tubing ventilatory rates of 60-150/min not very effective: minute ventilation

decreases with high frequencies [If TI < 3 TC, VT decreases.]

(Boros et al. Pediatrics 74: 487-492, 1984 )

ventilator and circuit design are not optimal for use at high frequencies

HFPPV

HFPPV

Jet ventilation (HFJV)

Oscillator (HFOV)

Flow interrupter (HFFI)

Which is best: HFOV, HFJV, HFFI, HFPPV ?

• No good animal or human comparisons; animal studies suggest HFV causes less lung damage than CMV

• Many centers now use HFOV for term infants with PPHN, rather than HFFI or HFJV

• Not possible to state if one type of HFV is better in human infants

ECMO

Hyperventilation in PPHN

No HV/Alk HV Alk HV+Alk p

Mortality% 4.4 6.8 9.5 9.8 0.67ECMO% 33.3 13.6 44.6 34.2 0.01Duration 7.8 7.2 7.8 12.6 0.001ventilator (d)Duration O2 (d) 11.1 11.5 11.9 17.5

0.001O2 at 28 d 2.7 2.8 6.8 16.7 0.1

(Walsh-Sukys et al. Pediatrics 105:14-20, 2000)

HFV Indications

• Usually used as “rescue” therapy for infants not improving/deteriorating on conventional ventilator

• Response to HFJV or HFOV may depend on disease pathophysiology: Pneumonia and RDS more likely to respond (70-

90%) MAS (50%) and CDH (20%) less likely to respond

(Baumgart et al. Pediatrics 89:491, 1992; Paranka et al. Pediatrics 95: 400, 1995; Stewart et al. Eur Respir J 9:1257, 1996)

HFV techniques: HFOV• MAP: start 1-3 cm H2O higher than on IMV:

controls V/Q matching and oxygenation• Frequency: 8-12 Hz• Inspiratory time: 33%• Amplitude: sufficient for visible chest

motion: main determinant of CO2 elimination

• Target ABG: pH 7.45-7.55, PaCO2 30-40,

PaO2 80-100, HCO3 26-30

HFV techniques

• “High volume strategy” often used Useful in animal models and preterm infants with

RDS Assessment of lung volume a problem (chest X-

Rays not accurate) Initial MAP 10-20% more than MAP on IMV. Increase MAP in 1-3 cm H2O increments until

oxygenation and a/A ratio improve or cardiac compromise occurs

FiO2 can then be weaned to 0.3-0.4. As lungs improve, wean MAP slowly (MAP changes may take > 1 hr to affect PaO2). If air leak, wean FiO2 later.

HFV + NO; HFV+ Surfactant

• The combination of HFOV and NO is more effective than HFOV alone or NO alone

• HFV and surfactant prevent lung injury synergistically, combination: prolongs efficacy of surfactant reduces number of surfactant doses reduces pulmonary morbidity

Summary

• PPHN is a rare but serious illness in newborn infants

• Close monitoring and a staged approach (oxygen by hood IMV HFV / NO ECMO) improve outcomes

• Most infants (>85%) now have normal outcomes, except for infants with diaphragmatic hernias.