Pulmonary Hypertension in

Newborns with Meconium

Aspiration
New Therapeutic Aspects
Pekka Kp, MD
Research Centre of Applied and
Preventive Cardiovascular
Medicine,
University of Turku

PERSISTENT PULMONARY
HYPERTENSION OF THE NEWBORN
(PPHN)

High pulmonary artery pressure

Right-to-left shunting

Hypoxemia

Low systemic arterial pressure

PULMONARY HYPERTENSION
OF THE NEWBORN

Incidence > 1:1000 births

Mortality 30-50%

Neurological sequelae 10-30%

Chronic lung injury ca. 25%

DIAGNOSIS OF PULMONARY
HYPERTENSION

Clinical signs (hypoxemia)

Clinical tests (pre-postductal pO2)

Doppler/ultrasound examinations

Catheterization

PULMONARY HYPERTENSION
OF THE NEWBORN

Obstruction of the pulmonary vessels:

Idiopathic
RDS
Aspiration
Infection

Pulmonary vascular hypoplasia

High blood viscosity:

Infants of diabetic mothers

MECONIUM ASPIRATION
SYNDROME

Meconium-stained amniotic fluid in

10-15% of deliveries

Respiratory failure in 5% of infants,

often connected with pulmonary
hypertension

Mortality up to 40%

PATHOPHYSIOLOGY OF
MECONIUM ASPIRATION
SYNDROME
Airway

occlusion
Direct tissue injury
Pulmonary hypertension
Inflammation
Surfactant dysfunction

PULMONARY RESPONSES IN
MECONIUM ASPIRATION

Immediate ventilation/perfusion
mismatch - concentration dependent

Progressive pulmonary hypertension from

2 hours on - concentration dependent

Inflammatory changes and surfactant

dysfunction in 4-6 hours

Tissue necrosis after 24-48 hours

TREATMENT STRATEGIES IN
MECONIUM ASPIRATION

Ventilatory assistance / oxygenation

Vasodilatory treatment

Anti-inflammatory drugs

Surfactant administration / lavage

ECMO

TREATMENT STRATEGIES OF
PULMONARY HYPERTENSION
IN MECONIUM ASPIRATION

Ventilatory assistance / oxygenation

Vasodilatory treatment (-> NO)

Anti-inflammatory drugs (-> Dexa)

ECMO

PULMONARY VASODILATORY
TREATMENT

Tolazoline (1 mg/kg/h)
not selective, dilatory effect poor
hemorrhagies, hypotension, renal
failures in 50-70%

Prostacyclin(PGI2)(10-60 ng/kg/min)

systemic hypotension

Inhaled nitric oxide (INO)

INHALED NITRIC OXIDE (INO)

IN MECONIUM ASPIRATION

Selective pulmonary vasodilation

Modulation of endothelial
permeability

Attenuation of leucocyte function

Inhibition of platelet aggregation

Nitric oxide
in MAS

Nitric oxide
in MAS

INO IN EXPERIMENTAL
MECONIUM ASPIRATION

Author ModelINO Response

-----------------------------------------------------Barrington
Piglet 5-80ppm SO2 ,PAP
1995
Rais-Bahrami
1997

Piglet 10-40ppm SO2, PAP

Cuesta 1998

Lamb 20ppm

Holopainen
1999

Piglet 1, 10 ppm PO2,PAP

PO2, PAP

INO IN EXPERIMENTAL
MECONIUM ASPIRATION

Transient or short-term improvement of

oxygenation

Small or no reduction in pulmonary

hypertension

Effects similar at different doses (5-80 ppm)

No clear effect on the ventilatory

parameters or inflammatory lung tissue
response

INO IN CLINICAL MECONIUM

ASPIRATION SYNDROME

Variable improvement of
oxygenation (in about 50%)

Decreased need for ECMO

No reduction in mortality
Cochrane Database 2001
Weinberger et al., Pharmacol Ther 2001

INO IN MECONIUM
ASPIRATION

Improves ventilation/perfusion matching

Effect on oxygenation and pulmonary

vascular resistance variable

Severity of the parenchymal disease

critical in the responsiveness to INO

--> Experimental mode of treatment

TREATMENT STRATEGIES OF
PULMONARY HYPERTENSION
IN MECONIUM ASPIRATION

Ventilatory assistance / oxygenation

Vasodilatory treatment (-> NO)

Anti-inflammatory drugs (-> Dexa)

ECMO

Steroids
in MAS

Steroids
in MAS

STEROIDS IN EXPERIMENTAL
MECONIUM ASPIRATION
Author
Model Steroid
Response
----------------------------------------------------Franz 1975 Rabbit
HC
survival
Soukka 1997 Pig

MP (pre)

Khan 1999

Piglet

Dexa

Wu 1999

Piglet

Dexa PAP

Holopainen

Piglet

Dexa (pre) FiO2,PAP PVR

2000

FiO2,PAP ,PVR
FiO2,compliance

STEROIDS IN CLINICAL
MECONIUM ASPIRATION

No effect on oxygenation, ventilation

or survival
(Yeh et al., 1977)

Improvement of oxygenation
(da Costa et al., 2001)

STEROIDS IN MECONIUM
ASPIRATION

Early steroid administration may improve

the pulmonary function and oxygenation

Steroids may attenuate the inflammatory

lung injury

Potential side-effects: hypertension,

immunosuppression, poor neurological
development (?)

--> Experimental treatment

THERAPEUTIC APPROACH TO
MECONIUM ASPIRATION
WITH PPHN

Therapeutic effect of INO or steroids

variable and generally poor

Combination of therapies, or
addition of exogenous surfactant
may be more effective

Potential side-effects may limit the

use

POOR THERAPEUTIC RESPONSE

OF PULMONARY HYPERTENSION
IN MECONIUM ASPIRATION

Selectivity of the vasodilators poor

Treatment of the lung disease

insufficient

Continuous systemic hypotension

FUTURE THERAPEUTIC
ASPECTS OF MECONIUM
ASPIRATION SYNDROME

New modes of therapy:

surfactant lavage
liquid ventilation

Early start of the therapy:

prophylactic
at birth / first hours

Preventive measures

RESEARCH GROUP
Hanna Soukka, MD
Kalle Korhonen, MD
Minna Aaltonen, MD
Jaakko Kytl, MD
Heikki Lukkarinen, BM
Jani Lehtonen, BM
Aida Steiner, BM