Intrapleural Methylprednisolone Injection for Multiple Organ Failure With Acute Respiratory Distress Syndrome - Full Text View

Purpose

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.

Condition	Intervention	Phase
Acute Respiratory Distress Syndrome (ARDS) Multiple Organ Failure	Drug: conventional ECMO with intravenous steroid Drug: solumedrol	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Retrospective Study of Intrapleural Methylprednisolone Injection for Multiple Organ Failure With Acute Respiratory Distress Syndrome

Resource links provided by NLM:

Drug Information available for: Hydrocortisone acetate Hydrocortisone Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Hydrocortisone sodium succinate Prednisolone phosphate Hydrocortisone cypionate Prednisolone sodium succinate Methylprednisolone sodium succinate Hydrocortisone butyrate Hydrocortisone valerate Hydrocortisone probutate

U.S. FDA Resources

Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:

survival until discharge from the hospital [ Time Frame: 2005~2009 (up to 4 years) ] [ Designated as safety issue: No ]
Comparing the difference between two groups about the survival ratio of discharge from the hospital

Secondary Outcome Measures:

Incidence of complications [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
complication of the interventional treatment will be followed for the duration of hospital stay
the effects on tidal volumes [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
the therapeutic effects in the improvement of tidal volumes, followed for the duration of ventilator usage
the therapeutic effects on oxygenation [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]
the therapeutic effects in the improvement of oxygenation, followed for the duration of hospital stay

Enrollment:	29
Study Start Date:	June 2005
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Sham Comparator: conventional ECMO with intravenous steroid refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome unresponsive to conventional extracorporeal membrane oxygenation	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 Other Name: Solu-Cortef
Experimental: Drug: intrapleural steroid instillation refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome unresponsive to conventional extracorporeal membrane oxygenation	Drug: 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.

Arms

Assigned Interventions

Sham Comparator: conventional ECMO with intravenous steroid

refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome unresponsive to conventional extracorporeal membrane oxygenation

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

Other Name: Solu-Cortef

Experimental: Drug: intrapleural steroid instillation

refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome unresponsive to conventional extracorporeal membrane oxygenation

Drug: 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.

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.

Eligibility

Ages Eligible for Study:	16 Years to 87 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01423864

Locations

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

Sponsors and Collaborators

National Taiwan University Hospital

Investigators

Principal Investigator:

Pei-Ming Huang, MD, MS

National Taiwan University Hospital and National Taiwan University College of Medicine

More Information

Publications:

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. Epub 2010 Jan 7.

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Biffl WL, Moore FA, Moore EE, Haenel JB, McIntyre RC Jr, Burch JM. Are corticosteroids salvage therapy for refractory acute respiratory distress syndrome? Am J Surg. 1995 Dec;170(6):591-5; discussion 595-6.

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.

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

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.

Dagenais A, Denis C, Vives MF, Girouard S, Massé C, Nguyen T, Yamagata T, Grygorczyk C, Kothary R, Berthiaume Y. Modulation of alpha-ENaC and alpha1-Na+-K+-ATPase by cAMP and dexamethasone in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2001 Jul;281(1):L217-30.

Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut 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.

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.

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.

Broccard AF. Prone position in ARDS: are we looking at a half-empty or half-full glass? Chest. 2003 May;123(5):1334-6. No abstract available.

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.

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.

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.

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

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.

Bernard GR. Acute respiratory distress syndrome: a historical perspective. Am J Respir Crit Care Med. 2005 Oct 1;172(7):798-806. Epub 2005 Jul 14.

Annane D, Sebille V, Bellissant E; Ger-Inf-05 Study Group. Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med. 2006 Jan;34(1):22-30.

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.

Responsible Party:	National Taiwan University Hospital
ClinicalTrials.gov Identifier:	NCT01423864 History of Changes
Other Study ID Numbers:	200906014R
Study First Received:	August 18, 2011
Last Updated:	August 25, 2011
Health Authority:	Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:

Acute Respiratory Distress Syndrome
Multi-organ Dysfunction Syndrome
Extracorporeal Membrane Oxygenation

Additional relevant MeSH terms:

Multiple Organ Failure
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Shock
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate

Methylprednisolone acetate
Prednisolone acetate
Hydrocortisone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Hydrocortisone-17-butyrate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on May 19, 2013

Intrapleural Methylprednisolone Injection for Multiple Organ Failure With Acute Respiratory Distress Syndrome (IP steroid)