Dopamine vs. Norepinephrine in Term and Late Preterm Neonates With Hypoxemic Respiratory Failure and Systemic Hypotension Due to Pulmonary Hypertension: A Pilot Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- SAP/PAP ratio
研究概览
简要总结
This pilot randomized clinical trial compares dopamine and norepinephrine as first-line vasoactive therapies in term and late preterm neonates with pulmonary hypertension associated with hypoxemic respiratory failure and systemic hypotension. Systemic hypotension is a common and clinically significant complication of persistent pulmonary hypertension of the newborn (PPHN) and frequently requires vasopressor support to maintain adequate systemic perfusion. Dopamine is commonly used in this setting; however, prior animal experimental and clinical data suggest it may increase pulmonary vascular resistance, potentially worsening right ventricular afterload and hypoxemia. Norepinephrine may preferentially increase systemic vascular resistance with less effect on the pulmonary circulation. This study evaluates short-term hemodynamic and oxygenation responses following initiation of dopamine or norepinephrine.
详细描述
Persistent pulmonary hypertension of the newborn (PPHN) is a serious cardiopulmonary disorder characterized by sustained elevation of pulmonary vascular resistance, leading to right-to-left shunting, impaired oxygenation, and increased morbidity and mortality. In addition to hypoxemic respiratory failure, many infants with PPHN develop systemic hypotension. Management of systemic hypotension in this population is complex, as vasoactive medications may have differing effects on systemic and pulmonary circulations.
Dopamine is widely used as first-line therapy for neonatal hypotension because of its dose-dependent dopaminergic and adrenergic effects. However, both animal models and clinical observations suggest that dopamine may increase pulmonary vascular resistance in neonates with PPHN. Norepinephrine, a predominantly alpha-adrenergic agonist with modest beta-adrenergic activity, may provide more selective augmentation of systemic vascular resistance while exerting less influence on pulmonary vascular tone. Despite the increasing clinical use of norepinephrine in neonatal intensive care units, there are no prospective trials comparing dopamine and norepinephrine in neonates with PPHN.
This is a single-center, cluster-randomized, pilot clinical trial enrolling term and late preterm neonates with hypoxemic respiratory failure, echocardiographic evidence of pulmonary hypertension, and systemic hypotension that persists despite initial fluid resuscitation. Eligible infants are assigned by time-based cluster randomization to receive either dopamine or norepinephrine as first-line vasoactive therapy, consistent with standard clinical practice in the neonatal intensive care unit. Informed consent is obtained for research-specific procedures, including serial targeted neonatal echocardiography, while vasoactive medication use follows established clinical protocols.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- — 至 28 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Postmenstrual age > 34 6/7 weeks and Postnatal age ≤ 28 days
- •On respiratory support (Invasive mechanical ventilation, NIPPV, CPAP, HFNC ≥ 2 LPM) and FiO2 ≥ 0.3
- •Echocardiographic evidence of pulmonary hypertension
- •Mean arterial pressure below the threshold for gestational age despite a 10-20 mL/kg fluid bolus
- •Permissible Comorbidities: CDH, trisomy 21, HIE on hypothermia, PDA, PFO/ASD, VSD < 2 mm
排除标准
- •Gestational age < 32 weeks
- •Severe hypoxic respiratory failure (OI > 35 or SpO2 < 75% on 100% FiO2 for > 60 minutes)
- •Lethal anomalies (e.g., trisomy 13 or 18)
- •Complex congenital heart disease beyond specified criteria
研究组 & 干预措施
Dopamine Arm
Infants in this group will receive dopamine as their first-line vasopressor. Continuous intravenous dopamine infusion will be initiated at 5 mcg/kg/min and titrated to achieve gestational age appropriate mean arterial blood pressure targets (maximum 20 mcg/kg/min).
干预措施: Dopamine administration (Drug)
Norepinephrine Arm
Infants in this group will receive norepinephrine as their first-line vasopressor. Continuous intravenous norepinephrine infusion initiated at 0.02 mcg/kg/min and titrated to achieve gestational age appropriate mean arterial blood pressure targets (maximum 1 mcg/kg/min).
干预措施: Norepinephrine (Drug)
结局指标
主要结局
SAP/PAP ratio
时间窗: Within 30 hours of vasopressor initiation.
Ratio of systemic arterial pressure to pulmonary arterial pressure (SAP/PAP)
LV Cardiac output
时间窗: Within 30 hours of vasopressor initiation
Left Ventricular Cardiac Output calculated with echocardiography
Oxygenation Indices
时间窗: Within 30 hours of vasopressor initiation
FiO₂ (fraction of inspired oxygen), SpO₂ (peripheral oxygen saturation), PaO₂ (arterial oxygen partial pressure), OI (oxygenation index), OSI (oxygen saturation index)
次要结局
- Use of inhaled nitric oxide (iNO)(Within 30 hours of vasopressor initiation)
- Need for additional vasoactive agents(Within 30 hours of vasopressor initiation)
- Echocardiographic markers of heart function(Within 30 hours of vasopressor initiation)
研究者
Deepika Sankaran
Associate Professor
University of California, Davis