Magnesium Sulfate - PPHN
Conditions
Keywords
PPHN, magnesium sulfate, Neonates
Brief summary
we conducted this study to compare between effect of nebulized and intravenous magnesium sulfate (MgSO₄) for better treatment of persistent pulmonary hypertension of neonates with less side effects.
Detailed description
Persistent pulmonary hypertension of the newborn (PPHN) is a serious syndrome characterized by sustained fetal elevation of pulmonary vascular resistance (PVR) at birth. The syndrome is seen in two of 1000 live-born infants and is associated with anormal or low systemic vascular resistance. Pulmonary hypertension is defined as a mean pulmonary artery pressure greater than 25 mmHg at rest and \> 30 mmHg during exercise. PPHN-targeted therapy is used for infants with PPHN who fail to respond to general cardiopulmonary supportive care. Oxygen and inhaled Nitric Oxide (iNO) are the only well-studied pulmonary vasodilators in neonates with PPHN. Magnesium is a potent vasodilator and hence has the potential to reduce the high pulmonary arterial pressures as it's able to dilate constricted muscles in the pulmonary arteries. However, its action is not specific and when given via an intravenous infusion, it will act on other muscles in the body including other arteries. Excessive magnesium causes hypotonia, hypotension, and cardiorespiratory failure. However, no studies have demonstrated long-term benefit. Delivering magnesium sulfate by nebulization may enhance effectiveness and minimizes systemic adverse effects.
Interventions
MgSO₄'s mechanism in PPHN includes activating cellular processes, modulating membrane excitability, and acting as a physiological calcium antagonist. It exerts sedative, muscle relaxant, and bronchodilatory properties, while concurrently inducing a state of alkalosis.
DRUGInhalational magnesium sulfate
It gives us the same mechanism of action as IV MgSO4 with less side effects.
Sponsors
Benha University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Hours to 3 Days
Healthy volunteers
No
Inclusion criteria
* Newborns with documented persistent pulmonary hypertension as confirmed by echocardiography. * Neonates born at ≥ 35 wk. gestation with a birth weight of 2.5-4 kg * Neonates have to be connected to mechanical ventilation with an oxygenation index (OI) \>30 on two occasions at least 15 min apart. * The echocardiogram had to show a predominant right-to-left or bidirectional shunt (through ductus arteriosus and/or foramen oval) and/or tricuspid regurgitant jet with a pressure gradient ≥ 2/3 of the systemic systolic blood pressure.
Exclusion criteria
* Infants of parents who refuse to give informed consent. * Infants of mothers who receive magnesium sulfate within 48 h before labor. * Congenital heart diseases other than patent ductus arteriosus (PDA) and foramen ovale. * Major congenital anomalies, including congenital diaphragmatic hernia and lung hypoplasia. * Prior need for cardiopulmonary resuscitation * Mean arterial blood pressure (MABP) \< 35 mmHg despite therapy with volume infusions and vasoactive inotropes. * Impaired kidney function; and prior administration of pulmonary vasodilators or prior administration of surfactant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Airway Pressure (cm H2O) | from baseline to 12 and 24 hours after administering the study drug | — |
| Fraction of Inspired Oxygen (FiO2) (%) | from baseline to 12 and 24 hours after administering the study drug | — |
| PaO2 (mmHg) | from baseline to 6, 12 and 24 hours after administering the study drug | kPa x 7.5 converts to the equivalent PaO2 in mmHg |
| Tracking Changes in the Oxygenation Index (OI) | from baseline to 12 and 24 hours after administering the study drug | OI evaluates both oxygenation and ventilatory support, aiding decisions on Extracorporeal Membrane Oxygenation (ECMO) necessity in newborns with PPHN. OI calculated as (Mean Airway Pressure (cm H2O) x Fraction of Inspired Oxygen (%) x 100) ÷ (PaO2 (kPa) x 7.5). OI is routinely used as an indicator of severity of hypoxemic respiratory failure (HRF) in neonates, with an arbitrary cutoff of 15 or less for mild HRF, between 16 and 25 for moderate HRF, between 26 and 40 for severe HRF, and more than 40 for very severe HRF |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the Variations in Mean Arterial Blood Pressure (MABP) | at 0, 12, and 24 hours post administration of the study drug relative to baseline | Both systolic and diastolic pressure are used to calculate MABP. |
| the Alterations in Serum Magnesium Levels (mmol/L) | from baseline to 12 hours following the administration of the study drug. | — |
Countries
Egypt
Participant flow
Pre-assignment details
The total number of neonates who admitted at Benha University hospital diagnosed as PPHN during study period was 158. 95 was excluded as they did not meet inclusion criteria. 23 parents refused to participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| Nebulized Magnesium (NebMag) Group 1 NebMag group (n=20) was administered nebulized isotonic magnesium (64 mg/mL). For nebulization, an isotonic MgSO₄ solution (64 mg/mL) was formulated by diluting a 10% intravenous preparation of MgSO₄ heptahydrate with sterile distilled water. 4 mL aliquots of the isotonic MgSO₄ solution (containing 256 mg of MgSO₄) were administered every 15 minutes through the jet nebulizer connected to the ventilator during the 24 hour study period.
Inhalational magnesium sulfate: It gives us the same mechanism of action as IV MgSO4 with less side effects. | 20 |
| Intravenous Magnesium (IVMag) Group 2 IVMag group (n=20) received intravenous magnesium. For intravenous administration, a 10% MgSO₄ solution was prepared by diluting a 50% intravenous formulation of MgSO₄ heptahydrate with 5% glucose and administrated in a loading dose of 2 mL/kg over 30 minutes (equivalent to 200 mg/kg of MgSO₄), followed by a continuous infusion at a rate of 0.5 mL/kg/h (equivalent to 50 mg/kg/h of MgSO₄) over the 24 hour study period.
IV Magnesium Sulfate: MgSO₄'s mechanism in PPHN includes activating cellular processes, modulating membrane excitability, and acting as a physiological calcium antagonist. It exerts sedative, muscle relaxant, and bronchodilatory properties, while concurrently inducing a state of alkalosis. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Intravenous Magnesium (IVMag) Group 2 | Total | Nebulized Magnesium (NebMag) Group 1 |
|---|---|---|---|
| Age, Continuous | 37.2 gestional weeks STANDARD_DEVIATION 1.1 | 37.15 gestional weeks STANDARD_DEVIATION 1 | 37.1 gestional weeks STANDARD_DEVIATION 0.9 |
| Body weight (kg) | 3.1 kg STANDARD_DEVIATION 0.3 | 3.1 kg STANDARD_DEVIATION 0.3 | 3.1 kg STANDARD_DEVIATION 0.3 |
| mode of delivery caesarean delivery | 15 Participants | 28 Participants | 13 Participants |
| mode of delivery vaginal delivery | 5 Participants | 12 Participants | 7 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Egypt | 20 participants | 40 participants | 20 participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 10 Participants | 21 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Fraction of Inspired Oxygen (FiO2) (%)
Time frame: from baseline to 12 and 24 hours after administering the study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebulized Magnesium (NebMag) Group 1 | Fraction of Inspired Oxygen (FiO2) (%) | baseline | 100 percentage | Standard Deviation 0 |
| Nebulized Magnesium (NebMag) Group 1 | Fraction of Inspired Oxygen (FiO2) (%) | at 12h | 96.5 percentage | Standard Deviation 5.8 |
| Nebulized Magnesium (NebMag) Group 1 | Fraction of Inspired Oxygen (FiO2) (%) | at 24h | 96 percentage | Standard Deviation 5.9 |
| Intravenous Magnesium (IVMag) Group 2 | Fraction of Inspired Oxygen (FiO2) (%) | baseline | 100 percentage | Standard Deviation 0 |
| Intravenous Magnesium (IVMag) Group 2 | Fraction of Inspired Oxygen (FiO2) (%) | at 12h | 97.5 percentage | Standard Deviation 4.4 |
| Intravenous Magnesium (IVMag) Group 2 | Fraction of Inspired Oxygen (FiO2) (%) | at 24h | 97 percentage | Standard Deviation 5.7 |
p-value: 0.46Chi-squared
Primary
Mean Airway Pressure (cm H2O)
Time frame: from baseline to 12 and 24 hours after administering the study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebulized Magnesium (NebMag) Group 1 | Mean Airway Pressure (cm H2O) | Baseline | 14.1 (cm H2O) | Standard Deviation 1.29 |
| Nebulized Magnesium (NebMag) Group 1 | Mean Airway Pressure (cm H2O) | At 12h | 13.7 (cm H2O) | Standard Deviation 1 |
| Nebulized Magnesium (NebMag) Group 1 | Mean Airway Pressure (cm H2O) | At 24h | 14 (cm H2O) | Standard Deviation 1.27 |
| Intravenous Magnesium (IVMag) Group 2 | Mean Airway Pressure (cm H2O) | Baseline | 13.8 (cm H2O) | Standard Deviation 1.18 |
| Intravenous Magnesium (IVMag) Group 2 | Mean Airway Pressure (cm H2O) | At 12h | 13.25 (cm H2O) | Standard Deviation 0.9 |
| Intravenous Magnesium (IVMag) Group 2 | Mean Airway Pressure (cm H2O) | At 24h | 13.8 (cm H2O) | Standard Deviation 1.24 |
p-value: 0.83Chi-squared
Primary
PaO2 (mmHg)
kPa x 7.5 converts to the equivalent PaO2 in mmHg
Time frame: from baseline to 6, 12 and 24 hours after administering the study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebulized Magnesium (NebMag) Group 1 | PaO2 (mmHg) | Baseline | 38.45 (mmHg) | Standard Deviation 2 |
| Nebulized Magnesium (NebMag) Group 1 | PaO2 (mmHg) | 12H | 54.8 (mmHg) | Standard Deviation 5.43 |
| Nebulized Magnesium (NebMag) Group 1 | PaO2 (mmHg) | 24H | 69.45 (mmHg) | Standard Deviation 7.56 |
| Intravenous Magnesium (IVMag) Group 2 | PaO2 (mmHg) | Baseline | 38.35 (mmHg) | Standard Deviation 1.63 |
| Intravenous Magnesium (IVMag) Group 2 | PaO2 (mmHg) | 12H | 51.45 (mmHg) | Standard Deviation 3.46 |
| Intravenous Magnesium (IVMag) Group 2 | PaO2 (mmHg) | 24H | 60.75 (mmHg) | Standard Deviation 5.9 |
p-value: 0.008Chi-squared
Primary
Tracking Changes in the Oxygenation Index (OI)
OI evaluates both oxygenation and ventilatory support, aiding decisions on Extracorporeal Membrane Oxygenation (ECMO) necessity in newborns with PPHN. OI calculated as (Mean Airway Pressure (cm H2O) x Fraction of Inspired Oxygen (%) x 100) ÷ (PaO2 (kPa) x 7.5). OI is routinely used as an indicator of severity of hypoxemic respiratory failure (HRF) in neonates, with an arbitrary cutoff of 15 or less for mild HRF, between 16 and 25 for moderate HRF, between 26 and 40 for severe HRF, and more than 40 for very severe HRF
Time frame: from baseline to 12 and 24 hours after administering the study drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebulized Magnesium (NebMag) Group 1 | Tracking Changes in the Oxygenation Index (OI) | Baseline | 34.3 index | Standard Deviation 2.4 |
| Nebulized Magnesium (NebMag) Group 1 | Tracking Changes in the Oxygenation Index (OI) | 12h | 24.2 index | Standard Deviation 2.6 |
| Nebulized Magnesium (NebMag) Group 1 | Tracking Changes in the Oxygenation Index (OI) | 24h | 19.75 index | Standard Deviation 2.9 |
| Intravenous Magnesium (IVMag) Group 2 | Tracking Changes in the Oxygenation Index (OI) | Baseline | 34.1 index | Standard Deviation 2.2 |
| Intravenous Magnesium (IVMag) Group 2 | Tracking Changes in the Oxygenation Index (OI) | 12h | 25.1 index | Standard Deviation 2.4 |
| Intravenous Magnesium (IVMag) Group 2 | Tracking Changes in the Oxygenation Index (OI) | 24h | 22.1 index | Standard Deviation 2.19 |
p-value: 0.032Chi-squared
Secondary
the Alterations in Serum Magnesium Levels (mmol/L)
Time frame: from baseline to 12 hours following the administration of the study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebulized Magnesium (NebMag) Group 1 | the Alterations in Serum Magnesium Levels (mmol/L) | Baseline | 0.92 (mmol/L) | Standard Deviation 0.1 |
| Nebulized Magnesium (NebMag) Group 1 | the Alterations in Serum Magnesium Levels (mmol/L) | At 12h | 1.2 (mmol/L) | Standard Deviation 0.17 |
| Intravenous Magnesium (IVMag) Group 2 | the Alterations in Serum Magnesium Levels (mmol/L) | Baseline | 0.93 (mmol/L) | Standard Deviation 0.1 |
| Intravenous Magnesium (IVMag) Group 2 | the Alterations in Serum Magnesium Levels (mmol/L) | At 12h | 3.6 (mmol/L) | Standard Deviation 0.18 |
p-value: <0.001Chi-squared
Secondary
the Variations in Mean Arterial Blood Pressure (MABP)
Both systolic and diastolic pressure are used to calculate MABP.
Time frame: at 0, 12, and 24 hours post administration of the study drug relative to baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebulized Magnesium (NebMag) Group 1 | the Variations in Mean Arterial Blood Pressure (MABP) | Baseline | 45.8 mmHg | Standard Deviation 2.7 |
| Nebulized Magnesium (NebMag) Group 1 | the Variations in Mean Arterial Blood Pressure (MABP) | 12h | 53.6 mmHg | Standard Deviation 3.2 |
| Nebulized Magnesium (NebMag) Group 1 | the Variations in Mean Arterial Blood Pressure (MABP) | 24h | 56.8 mmHg | Standard Deviation 3.3 |
| Intravenous Magnesium (IVMag) Group 2 | the Variations in Mean Arterial Blood Pressure (MABP) | Baseline | 45.7 mmHg | Standard Deviation 2.7 |
| Intravenous Magnesium (IVMag) Group 2 | the Variations in Mean Arterial Blood Pressure (MABP) | 12h | 48.6 mmHg | Standard Deviation 2.3 |
| Intravenous Magnesium (IVMag) Group 2 | the Variations in Mean Arterial Blood Pressure (MABP) | 24h | 53.6 mmHg | Standard Deviation 2.4 |
p-value: <0.001Chi-squared