Streptokinase Versus Unfractionated Heparin Nebulization in Patients With Severe Acute Respiratory Distress Syndrome (ARDS): A Partially Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 60
- 主要终点
- Change in PaO2/FiO2 ratio
研究概览
简要总结
Background: Intra-alveolar clotting and alveolar collapse in ARDS is due to alveolar capillaries epithelial and leakage. Subsequently, collapse induces hypoxemia that is resistant to recruitment (RM). Heparin and Streptokinase may prevent or dissolve intra-alveolar fibrin clot respectively helping alveolar re-expansion. We examined and compared the effect of nebulizing Heparin versus Streptokinase on reversing this pathology.
Methods: Sixty severe ARDS (PaO2/FiO2<100) patients and failure of RM, prone position (PP) and neuromuscular block (NMB) were partially randomised into Group (I): (n=20) received nebulized Heparin 10000 IU/4h. Group (II): (n=20) received nebulized Streptokinase 250,000 IU/4h. Group (III): (n=20) received conservative management. Randomization to either Heparin or Streptokinase groups was applied to patients whom guardian accepted participation, while those who declined participation were followed-up as a control. The primary outcome was the change in PaO2/FiO2; the secondary outcomes included the change in compliance, plateau pressure, ventilation-off days, coagulation and ICU mortality.
详细描述
Methods:
The current study was carried out in the Intensive Care Unit of a tertiary University Hospital following approval by the local Research and Ethics Committee and after obtaining of a written informed consent from the first of kin of the recruited patients.
The guardians of the patients with severe ARDS fulfilling the inclusion criteria of our study were offered to participate in the trial. Randomization to either Heparin or Streptokinase groups was applied to patients whom first of kin agreed to participate in the trial, while patients whom first of kin declined to participate were followed up as a control group. Written informed consent to participate in the trial and to undergo randomization to either Heparin or Streptokinase group was signed by the guardians who approved their patients to participate. Written informed consent to use patients data was signed by the guardians who declined their patients to participate.
Adult patients aged 21-60 years and admitted to our ICU with the diagnosis of ARDS according to Berlin definition (12) were examined and followed up for the presence of the following inclusion criteria;
- Severe ARDS with PO2/FiO2 ratio<100.
- Failure of Recruitment Maneuver (RM), (13) Prone Position (PP) (14) or Neuro-Muscular Block (NMB) (15) to improve hypoxemia.
- No contraindications to thrombolytic or anticoagulant therapy (e.g. Coagulopathy, Heparin-Induced Thrombocytopenia, Previous administration of streptokinase, Known or suspected allergy to heparin or streptokinase, History of intracranial hemorrhage in the past 12 months, Patients with an epidural catheter in place or likely to be placed within the next 48 h.).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Investigators prepared and administered the study medication. participants, ICU physician and nurses, and the outcomes assessor were blinded to the two randomized groups
入排标准
- 年龄范围
- 21 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Severe ARDS with PO2/FiO2 ratio<
- •Failure of Recruitment Maneuver (RM), Prone Position (PP) or Neuro-Muscular Block (NMB) to improve hypoxemia.
- •No contraindications to thrombolytic or anticoagulant therapy (e.g. Coagulopathy, Heparin-Induced Thrombocytopenia, Previous administration of streptokinase, Known or suspected allergy to heparin or streptokinase, History of intracranial hemorrhage in the past 12 months, Patients with an epidural catheter in place or likely to be placed within the next 48 h.).
- •Static compliance <50 ml/cmH2O
排除标准
- •PO2/FiO2 ratio>
- •The success of Recruitment Maneuver (RM), Prone Position (PP) or Neuro-Muscular Block (NMB) to improve hypoxemia.
- •Contraindications to thrombolytic or anticoagulant therapy (e.g. Coagulopathy, Heparin-Induced Thrombocytopenia, Previous administration of streptokinase, Known or suspected allergy to heparin or streptokinase, History of intracranial hemorrhage in the past 12 months, Patients with an epidural catheter in place or likely to be placed within the next 48 h.)
- •Static compliance >50 ml/cmH2O
研究组 & 干预措施
Group I: Heparin nebulized group
Group (I): 20 patients received inhaled Unfractionated Heparin at a dose of 10000 IU/4h by nebulizer, with the total daily dose of nebulized Unfractionated Heparin 60,000 IU
干预措施: Unfractionated heparin (Drug)
Group II: Streptokinase group
Group (II): 20 patients received inhaled Streptokinase at a dose of 250,000 IU/4h by nebulizer, with the total daily dose of nebulized Streptokinase 1,500,000 IU.
干预措施: Streptokinase (Drug)
结局指标
主要结局
Change in PaO2/FiO2 ratio
时间窗: daily over eight days
Change in the ratio of arterial oxygen tension to fraction of inspired oxygen from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.
次要结局
- ICU survival rate(At the end of ICU stay up to one year after the start of recruitment)
- Tracheostomy rate(During ICU stay up to one month after the start of recruitment)
- Change in the plateau pressure(daily over eight days)
- Change in the pulmonary compliance(daily over eight days)
- ICU length of stay(At the end of ICU stay up to one year after the start of recruitment)
研究者
Ahmed Abdelaal Ahmed Mahmoud
Associate Professor of Anesthesiology
Beni-Suef University