Intrapleural Methylprednisolone Injection for Multiple Organ Failure With Acute Respiratory Distress Syndrome

Phase 2

Completed

• Conditions: Acute Respiratory Distress Syndrome (ARDS); Multiple Organ Failure
• Interventions: Drug: conventional ECMO with intravenous steroid; Drug: solumedrol

• Registration Number: NCT01423864
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

Acute respiratory distress syndrome (ARDS) in combination with multi-organ dysfunction syndrome (MODS) is a life-threatening condition, particularly when treatment modalities such as extracorporeal membrane oxygenation (ECMO) and catecholamine administration have failed to treat the severe condition. In this study, the investigators report patients who responded to intrapleural steroid instillation (IPSI) while being unresponsive to conventional treatment (use of intravenous steroids, nitric oxide inhalation, high-frequency oscillatory ventilation, or ECMO) for treatment of critical illnesses such as ARDS in combination with MODS.

Detailed Description

Acute respiratory distress syndrome (ARDS) with multi-organ dysfunction syndrome (MODS) are common debilitating postoperative complications, which also result from shock and trauma. However, despite the use of ECMO, mortality rate among hypoxia patients remains high in such critical care conditions. Corticosteroid therapy inhibits ongoing inflammation and abnormal deposition of collagen. However, intravenous administration of corticosteroids may be harmful because it may increase the risk of associated neuromyopathy in critically ill patients. Although intrapleural instillation of steroids has been employed in several pleural diseases,little is known about the therapeutic effects of this treatment method on ARDS in combination with MODS. Therefore, in the present pilot study, the investigators hypothesized that timely initiation of intrapleural steroid instillation (IPSI) will positively influence ventilation in and survival of patients with ARDS in combination with MODS.

The investigators conducted a retrospective study on ninety-two of the 467 ECMOs performed between 2005 and 2009 were on ARDS patients. Analyses of gas exchange, tidal volumes, airway pressures, respiratory frequency, and vasopressor and sedation requirements were performed before and after intervention.

The indication for IPSI was unresponsive severe ARDS in combination with MODS when all the other treatment modalities such as intravenous steroid administration, nitric oxide inhalation, high-frequency oscillatory ventilation, or ECMO performed within 2 days were unsuccessful.

An experienced team performed thoracic catheterization of the patients under ultrasound evaluation. Patients with severe pleural adhesion were considered unsuitable for IPSI. The dosage of the intrapleural steroid was determined on the basis of the chest radiographic examination, inspired oxygen concentration, and positive end-expiratory pressure (PEEP) of the ventilator.

Study Timeline

• Study Start: 2005-06
• Primary Completion: 2009-06
• Study Completion: 2009-06
• Status Verified: 2011-08
• Study First Submitted: 2011-08-18
• Study First Submitted QC: 2011-08-25
• Last Update Submitted: 2011-08-25
• Study First Posted: 2011-08-26
• Last Update Posted: 2011-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

1. All of the patients had failure of at least 2 organs acquiring arteriovenous or venovenous ECMO support

2. All of the patients met the criteria as below:

   • blood gas parameters of PaO2/FiO2 < 100

   • bilateral pulmonary infiltration on chest radiographic images

   • 100% oxygen demand in case of ventilation and ECMO flow

   • hemodynamic instability requiring high catecholamine infusion

   • All the patients had scoring system, which were calculated by the physician within 24 h of admission of the patients into the hospital.

     • sequential organ failure assessment score (SOFA) ≥ 10
     • Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 20
     • inotropic score ≥ 10
     • multiple organ dysfunction (MOD) score ≥ 10

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Exclusion Criteria

1. uncontrollable underlying disease
2. life expectancy of less than 24 h
3. immunosuppression
4. neutrophil count of less than 0.3 × 109/L
5. brainstem death
6. history of long-term corticosteroid use during the past 6 months.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
conventional ECMO with intravenous steroid	conventional ECMO with intravenous steroid	refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome unresponsive to conventional extracorporeal membrane oxygenation
Drug: intrapleural steroid instillation	solumedrol	refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome unresponsive to conventional extracorporeal membrane oxygenation

Primary Outcome Measures

Name	Time	Method
survival until discharge from the hospital	2005~2009 (up to 4 years)	Comparing the difference between two groups about the survival ratio of discharge from the hospital

Secondary Outcome Measures

Name	Time	Method
Incidence of complications	12 weeks	complication of the interventional treatment will be followed for the duration of hospital stay
the effects on tidal volumes	up to 12 weeks	the therapeutic effects in the improvement of tidal volumes, followed for the duration of ventilator usage
the therapeutic effects on oxygenation	up to 12 weeks	the therapeutic effects in the improvement of oxygenation, followed for the duration of hospital stay

Trial Locations

Locations (1)

Department of Surgery, National Taiwan University Hospital; 🇨🇳 7, Chung-Shan S. Rd, Taipei 10002, Taiwan., Taiwan