pulmonary hypertension in neonates (PPHN) is a critical condition caused by a failure
in normal cardiac-pulmonary adjustment after birth; many factors can interfere
with this process, such as meconium aspiration, Parenchyma lung disease,
sepsis, intrauterine and/or prenatal
hypoxia, and abnormal pulmonary development.
Objectives: This study was conducted to evaluate the effect of magnesium sulfate
(MgSO4) as a treatment for persistent pulmonary hypertension of the
newborn (PPHN) and its outcome.
treatment of persistent acute pulmonary hypertension of newborn remains
controversial and has been tried in
various treatment modalities. This study was conducted to evaluate the effect
of magnesium sulfate (MgSO4)
as a treatment for persistent pulmonary hypertension of the newborn (PPHN) and its outcome.
study is a retrospective review of a neonate with PPHN treated with magnesium
sulfate (MgSO4) at King Hussein Medical Centre (KHMC)
neonatal intensive care units during the period of January to December of 2018.
Our sample covers nineteen newborn babies admitted to the neonatal intensive
care units (NICU) out of 10155 deliveries, with respiratory failure and
profound hypoxemia resulting from persistent pulmonary hypertension, were
enrolled in the study.
patients underwent the following tests: full blood count, kidney function test,
arterial blood gas, blood culture, chest x-ray, and echocardiograms. All
patients with congenital heart disease excluded from this study.
and data described in terms of median, mean ± standard deviation
(± SD) frequencies and percentages. Statistical calculations were carried
out using Microsoft Excel 2010 computer programs and the Statistical Package
for the Social Sciences (SPSS) version 18.
The total number
of 19 cases of PPHN from 10155 deliveries, by year, admitted to neonatal units
at KHMC during 2018. Male newborns with PPHN were 10 (53%), while the female
newborns were 9 (47%). The number of newborns with lung hypoplasia was 4 (21%),
prematurity was 7 (37%), respiratory distress syndrome (RDS) was 12 (63%),
sepsis was 9 (47%), congenital
diaphragmatic hernia was 2 (10%), birth asphyxia was 2 (10%). Sildenafil used
in 4 (23 %) cases treated with magnesium sulfate. The number of deaths was 7
Conclusion: This study provides evidence that magnesium sulfate can play a part in the therapy of PPHN. It is a non-aggressive treatment of short-duration and low cost.
Keywords: Persistent pulmonary hypertension in the newborn (PPHN), magnesium sulfate, Sildenafil, pulmonary arterial pressure (PAP).
JRMS August 2020; 27(2): 10.12816/0055806
Persistent pulmonary hypertension of the newborn (PPHN) is described as a persistence of the fetal circulatory pattern of right-to-left shunting across the patent’s ducts arteriosus and patent foramen oval
as a result of excessive pulmonary artery resistance(1). This, in turn, leads to extreme hypoxemia that might not respond to standard respiratory support.
There are many factors and causes
that lead to newborns with high pulmonary artery pressure, including a primary cause (very rare) or secondary
lung disease (e.g. meconium aspiration syndrome, surfactant
infection (e.g. pneumonia),
perinatal asphyxia, structural
abnormalities (e.g. congenital heart
disease, congenital diaphragmatic hernia) (2). The incidence is
1/500-1,500 live births, with a wide variation among clinical centers, with an estimated mortality of 10-20% (3) and
approximately 25% of survivors of neonatal display significant
neurodevelopmental impairment when tested
at 12 to 24 months of age (4).
The initial finding of PPHN is respiratory distress
and cyanosis, and this may occur despite adequate ventilation, in addition to
tachypnoea, retraction and may have a significant decrease in pulse oximetry
reading with routine nursing care or
Other clinical findings are highly variable depending
on the severity, stage and other associated disorders (particularly pulmonary
and cardiac disease) (5).
The diagnostic criteria of PPHN include (6):
(1) severe hypoxia (PaO2<50 mm Hg in 100% inspired oxygen and
(2) supra systemic pulmonary blood pressure (can be
estimated by echocardiography). (3) Normal cardiac anatomy: cyanotic congenital
heart defect should be excluded by
echocardiography. (4) Evidence of right-to-left shunting: bidirectional flow
across a patent ductus arteriosus or foramen oval on echocardiography.
The treatment approach for PPHN is still controversial,
and various modalities
of treatment have been tried, including; supplemental oxygen, intubation, mechanical
ventilation, nitric oxide, sedation and analgesia, pharmacological agents
(dopamine, epinephrine, Sildenafil, magnesium sulfate)
and extracorporeal membrane oxygenation (ECMO) (7).
Neonates who develop PPHN are at
approximately 20% risk of rehospitalization within one year of discharge and
have a 20% to 46% risk of audiology, neurodevelopmental, or cognitive
This study is
a retrospective review of a neonate with PPHN treated with magnesium sulfate (MgSO4) in the neonatal
intensive care units at KHMC during
the period of January to December of 2018.
The diagnosis of PPHN was
considered when there was persistent hypoxemia (PaO2 of
mm Hg or
6.67 kPa) not proportionate to the degree of severity on the chest radiograph,
despite the adequate ventilator support and/or
important liability of oxygenation with significant variations in PAO2 without
changes in ventilator settings.
Congenital cyanotic heart disease
excluded and pulmonary hypertension always confirmed by echocardiography (9) through
measurement of their estimated pulmonary arterial pressure (EPAP). Neonates
with EPAP more than 50 mm Hg included.
Mean Apgar scores were seven at one minute and nine at five
minutes. Gestational age, type of delivery, birth
weight, primary diagnosis, ventilator settings, arterial blood gas, magnesium,
calcium, electrolytes, and vital signs were measured.
All patients were first given routine supportive treatment, including (1) hemodynamic support by volume expansion up to
20 to 30 ml/kg and, if necessary, with a continuous dopamine infusion at 2 to
20 mcg/kg/minute; (2) sedation with morphine infusion at 10 to 20 mg/kg/hour
and; (3) appropriate ventilatory support (Nasal continuous positive
airway pressure (NCPAP), Synchronized
Intermittent-Mandatory Ventilation (SIMV), High
frequency oscillatory ventilation (HFOV).
Before MgSO4 infusion was begun, all infants were ventilated with 100% FiO2 at a rate of 45
breaths/minute with high peak inspiratory pressure (PIP) of 25 cm H2O
and positive end-expiratory pressure (PEEP) of 3-5 cm H2O (10). A loading dose of 200 mg/kg MgSO4
diluted to 8-10% in sterile water was given intravenously over 30 minutes,
followed by a continuous infusion of 20 to 50 mg/kg/hour, to obtain a magnesium
blood concentration between 1.5-2.5 mg/dl. Magnesium blood concentrations were monitored before and every 6 hours after
we gave magnesium sulfate, within the first
24 hours, and every 12 hours after stabilization. Before and during MgSO4
treatment, heart rate, mean arterial blood pressure (MAP), temperature, and
ventilator settings with inspired oxygen fraction (FIO2),
respiratory rate, peak inspiratory pressure (PIP), positive end-expiratory
pressure (PEEP), and mean airway pressure (MAP) recorded at two-hour intervals,
during the first day of treatment, and then four to six times a day.
depend on three indicators for the treatment responder (1) pulmonary arterial
pressure (PAP). (2) Continuous pulse oximetry recorded serial rise to≥90%. (3) Repeated arterial blood
gas measurement recorded at PaO2> 60 mm Hg.
The total number of 19 cases of PPHN from 10155
deliveries, by year, admitted to neonatal units at
KHMC during 2018.
Table 1 shows the descriptive study data, such as gender
distribution, gestational ages, and delivery modes. Male newborns with PPHN
were 10 (52.63%), while the female newborns were 9 (47.37%). Full-term cases
(>37weeks) were 9 (47.37%), the number of 30-37 weeks was 4 (21.05%), and
the number of less than 30weeks was 6 (31.58%). The normal delivery number was
7 (36.84%) while the cesarean section number was 12 (63.16%). Babies with a
birth weight higher than 2.4 kg were 8 (42.10%), while babies with a birth
weight less than 2.4 kg were 11 (57.89%).
Table I: Summary of sex distribution, gestational ages and delivery modes of neonates with PPHN
FT (37 weeks)
Less than 30 weeks
Mode of Delivery
Higher than 2.4 kg
Less than 2.4 kg
Regarding PPHN clinical diagnosis, this study candidate presented with
lung hypoplasia, prematurity, respiratory distress syndrome (RDS), sepsis, congenital diaphragmatic hernia and birth asphyxia (Table II).
Table II: Clinical diagnosis of neonates with PPHN.
congenital Diaphragmatic hernia
The number of newborns with lung hypoplasia was 4
(21.05%), prematurity was 7 (36.84%), RDS was 12 (63.16%), sepsis was 9
(47.36%), the congenital
diaphragmatic hernia was 2 (10.53%), and birth asphyxia was 2 (10.53%).
Hypotension is the only side effect registered in our
cases with a total numer of 8 and a percentage of (42.11%) of the cases using magnesium
sulfate. Sildenafil used in 4 (21.05%) cases treated with magnesium sulfate. The
number of deaths was 7 (36.84%).
Neonates showed a significant drop of pulmonary
artery pressure (PAP) at 48 hours and five days after initiation of magnesium sulfate therapy, compared to baseline PAP.
Significantly lower in PAP (P3) of 23.7 ± 3.7 mm Hg five days after
therapy (Table III).
Table III: Estimated Pulmonary Artery Pressure (EPAP) in the Study candidates.
EPAP before treatment
EPAP (48 hours after treatment)
EPAP (after five days of treatment)
An essential factor indicating an improvement
of the patient is the time interval to normalization
of oxygen saturation (SaO2) and arterial blood gases (ABG). Neonates
treated with magnesium sulfate therapy
showed a significantly shorter interval to oxygen saturation normalization, arterial blood gases, and
duration of ventilation (Table IV).
Table IV: Duration of SaO2 Improvement, ABG and Duration of Ventilation by Days.
to SaO2 normalization (days)
Time interval to ABG normalization(days)
Seven (36.8%) babies died, 2 showed congenital diaphragmatic hernia, and 5 showed sepsis.
Figure 1: Mortality Rate in PPHN After We Used Magnesium Sulfate.
PPHN is an important neonatal emergency contributing
to neonatal hypoxia, which is often associated
with high mortality. Most types of PPHN treatments, including nitric oxide and
ECMO, are effective but not available in our country.
Hence the search for other options is crucial this study aimed at assessing
the role of magnesium sulfate in the
treatment of PPHN in neonates and concluded that magnesium sulfate is effective and relatively safe compared
to outcome rates of adverse effects.
limited information on the use of MgSO4 to treat PPHN. Several
clinical studies reviewed. Some of these studies
performed on infants in the full term. All of these studies used a
comparable dose plan, with a loading dose of 200 mg/kg over 20-30 minutes,
followed by continuous infusion of 20 - 150 mg/kg/hour, given for up 5 days (11-13).
The serum magnesium level
measured in the present study; however, blood pressure and the response to
hypotension were monitored, MgSO4 infusion discontinued temporarily,
and the saline infusion was given. Hypotension observed in 8 (42.1%)
neonates; this percentage was higher than the result reported by Daffa and
Milaat (11). Abu-Osba observed transient bradycardia (15),
which is not seen in the present study.
Flaccidity was seen in one of the study
other side effects of MgSO4 (hypocalcemia and GIT disturbance) not
found in the present work, which is in agreement with other studies (11,14-16).
study, patients not monitored for negative neurological effects, but previous
studies have found that patients have a normal neurological examination in one
year (11, 14).
outcome measure reported a drop in EPAP by echocardiographic evaluation. Not
all other studies followed up with echocardiography of patients. Abu-Osba (15)
reported a comparable rate of improvement.
outcome measure showed oxygenation improvement by changes in partial
oxygenation pressure and ventilatory requirements, where significant
improvement of patients’ oxygenation parameters was
observed at 48 hours, which is in line with previous studies (13-14).
Seven (36.8%) neonates died,
while 12 (63.2%) survived, after treatment with magnesium sulfate.
Abu-Osba reported (15) that the survival rate was 7 out of 9. Daffa (11)
recorded a survival rate of 7 out of 8. However, Tolsa et al. (16) and Chandran et al. (14)
all included studies patients have survived. Seven of the study patients, who
died, suffered sepsis (5 patients), 2 (congenital diaphragmatic hernia) and this
cannot be considered therapy failure
diaphragmatic hernia has remained the most challenging condition to treat
successfully despite all the advances in neonatal critical care (17).
concluded that magnesium sulfate (MgSO4) could be used as a safe and effective method of treating PPHN. It may have a
place in the treatment of PPHN, especially in areas where NO and ECMO are not
The MgSO4 treatment showed good results with regard to survival rates and side effects.
PAP was significantly reduced after five
days of therapy in neonates receiving MgSO4.
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