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

Multiple Organ Failure Clinical Trial

— IP steroid  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01423864
• Other study ID #: 200906014R
• Status: Completed
• Phase: Phase 2
• First received: August 18, 2011
• Last updated: August 25, 2011
• Start date: June 2005
• Est. completion date: June 2009

Study information

• Verified date: August 2011
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 87 Years

Eligibility

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

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome (ARDS)
• Multiple Organ Failure
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• conventional ECMO with intravenous steroid
refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome treated with intravenous steroid, Solu-Cortef 50mg q6h taper down when hemodynamic stable
• solumedrol
Initially, intrapleural steroid administration was performed using 40 mg solumedrol q6h (for both the pleural cavities). If chest radiography showed an improvement in consolidation, i.e., 0.8 > FiO2 = 0.5 and 5 = PEEP = 10, the dosage of solumedrol was reduced to 40 mg q12h. When FiO2 was below 0.5 and the PEEP was below 10, the dosage of solumedrol was lowered to 40 mg qd for 3 days and then its administration was discontinued.

Locations

Country	Name	City	State
Taiwan	Department of Surgery, National Taiwan University Hospital	7, Chung-Shan S. Rd, Taipei 10002, Taiwan.

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (19)

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Annane D, Sébille V, Charpentier C, Bollaert PE, François B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troché G, Chaumet-Riffaud P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. Erratum in: JAMA. 2008 Oct 8;300(14):1652. Chaumet-Riffaut, Philippe [corrected to Chaumet-Riffaud, Philippe]. — View Citation

Beiderlinden M, Eikermann M, Boes T, Breitfeld C, Peters J. Treatment of severe acute respiratory distress syndrome: role of extracorporeal gas exchange. Intensive Care Med. 2006 Oct;32(10):1627-31. Epub 2006 Jul 28. — View Citation

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Broccard AF. Prone position in ARDS: are we looking at a half-empty or half-full glass? Chest. 2003 May;123(5):1334-6. — View Citation

Brunet F, Mira JP, Belghith M, Monchi M, Renaud B, Fierobe L, Hamy I, Dhainaut JF, Dall'ava-Santucci J. Extracorporeal carbon dioxide removal technique improves oxygenation without causing overinflation. Am J Respir Crit Care Med. 1994 Jun;149(6):1557-62. — View Citation

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Dünser M, Hasibeder W, Rieger M, Mayr AJ. Successful therapy of severe pneumonia-associated ARDS after pneumonectomy with ECMO and steroids. Ann Thorac Surg. 2004 Jul;78(1):335-7. — View Citation

Gerlach H, Keh D, Semmerow A, Busch T, Lewandowski K, Pappert DM, Rossaint R, Falke KJ. Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study. Am J Respir Crit Care Med. 2003 Apr 1;167(7):1008-15. — View Citation

Lee HS, Lee JM, Kim MS, Kim HY, Hwangbo B, Zo JI. Low-dose steroid therapy at an early phase of postoperative acute respiratory distress syndrome. Ann Thorac Surg. 2005 Feb;79(2):405-10. — View Citation

Lewandowski K, Rossaint R, Pappert D, Gerlach H, Slama KJ, Weidemann H, Frey DJ, Hoffmann O, Keske U, Falke KJ. High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation. Intensive Care Med. 1997 Aug;23(8):819-35. — View Citation

North SA, Au HJ, Halls SB, Tkachuk L, Mackey JR. A randomized, phase III, double-blind, placebo-controlled trial of intrapleural instillation of methylprednisolone acetate in the management of malignant pleural effusion. Chest. 2003 Mar;123(3):822-7. — View Citation

Shinozaki M. [Respiratory and cadiovascular management of septic ALI-ARDS and shock]. Nihon Rinsho. 2004 Dec;62(12):2301-7. Review. Japanese. — View Citation

Suchyta MR, Clemmer TP, Orme JF Jr, Morris AH, Elliott CG. Increased survival of ARDS patients with severe hypoxemia (ECMO criteria). Chest. 1991 Apr;99(4):951-5. — View Citation

Tomiyama H, Takara I, Tokumine J, Sugahara K. [Sivelestat sodium hydrate was effective for ARDS in a patient suffering from chronic rheumatoid arthritis with acute exacerbation after failing to respond to high dose steroid pulse therapy]. Masui. 2004 Sep;53(9):1042-6. Japanese. — View Citation

Wiener-Kronish JP, Broaddus VC. Interrelationship of pleural and pulmonary interstitial liquid. Annu Rev Physiol. 1993;55:209-26. Review. — View Citation

Zemans RL, Matthay MA. Bench-to-bedside review: the role of the alveolar epithelium in the resolution of pulmonary edema in acute lung injury. Crit Care. 2004 Dec;8(6):469-77. Epub 2004 Jun 30. Review. — View Citation

Zhang J, Wang W, Sun J, Li Q, Liu J, Zhu H, Chen T, Wang H, Yu S, Sun G, Chen W, Yi D. Gap junction channel modulates pulmonary vascular permeability through calcium in acute lung injury: an experimental study. Respiration. 2010;80(3):236-45. doi: 10.1159/000274384. Epub 2010 Jan 7. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	survival until discharge from the hospital	Comparing the difference between two groups about the survival ratio of discharge from the hospital	2005~2009 (up to 4 years)	No
Secondary	Incidence of complications	complication of the interventional treatment will be followed for the duration of hospital stay	12 weeks	Yes
Secondary	the effects on tidal volumes	the therapeutic effects in the improvement of tidal volumes, followed for the duration of ventilator usage	up to 12 weeks	Yes
Secondary	the therapeutic effects on oxygenation	the therapeutic effects in the improvement of oxygenation, followed for the duration of hospital stay	up to 12 weeks	Yes