Extracorporeal Carbon Dioxide Removal for Acute Respiratory Distress Syndrome

Intermountain Health Care, Inc.

Status and phase: Completed; Phase 3

Conditions: Lung Diseases; Acute Respiratory Distress Syndrome

Treatments: Procedure: extracorporeal membrane oxygenation (CO2 removal); Procedure: positive-pressure ventilation

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00000572

R01HL036787 (U.S. NIH Grant/Contract)

210

Details and patient eligibility

About

To compare conventional therapy using low frequency positive pressure ventilation with extracorporeal CO2 removal for the treatment of adult respiratory distress syndrome (ARDS).

Full description

BACKGROUND:

It is estimated that at least 150,000 individuals die each year of adult respiratory distress syndrome. Treatment remains largely supportive. The National Heart, Lung, and Blood Institute (NHLBI) conducted the Extracorporeal Support for Respiratory Insufficiency (ECMO, Extracorporeal Membrane Oxygenation) trial from June 1974 through 1978. In ECMO, 90 patients were randomized to either extracorporeal membrane oxygenation plus conventional therapy or to conventional therapy. Survival rates were less than ten percent in both groups. The failure of the trial to demonstrate the superiority of ECMO over conventional ventilatory support resulted in the virtual elimination of the use of ECMO in clinical medicine.

In the earlier NHLBI trial, ECMO was implemented with a veno-arterial shunt which approximated 90 percent of the baseline cardiac output. Ventilation of the lungs was continued with reduced function of inspiration oxygen. Thus, the lungs were deprived of the principle source of blood supply while continuously exposed to potentially injurious ventilatory pressures and gas composition. The present patient trial used a new form of therapy developed by Dr. Gattinoni and co-workers in Milan, Italy with the collaboration of Dr. Kolobow at the National Institutes of Health in Bethesda. The authors reported a 77 percent survival rate for the new therapy. In Step 1 of the new therapy, the patient was initially ventilated with pressure-controlled, inverted ratio ventilation. If the patient did not improve, Step 2 using extracorporeal perfusion was performed with a veno-venous shunt in contrast to a veno-arterial shunt. The veno-venous shunt preserved pulmonary blood flow whereas the veno-arterial shunt diminished it. Step 3 was reserved for those patients who did not meet the therapeutic criteria of Step 2. They underwent low frequency positive-pressure ventilation and extracorporeal CO2 removal involving veno-venous bypass via the internal jugular and femoral or bilateral saphenous veins.

DESIGN NARRATIVE:

Randomized, fixed sample. Patients were stratified by age (under and over 40 years) and by the presence or absence of trauma. Patients were assigned to conventional positive pressure ventilation therapy or to a three-step therapeutic program employing pressure-controlled-inverted-ratio-ventilation, continuous positive airway pressure, and low-frequency positive pressure ventilation-extracorporeal CO2 removal. The main outcome measure was survival at 30 days after randomization. Secondary outcome measures included hospital costs, physiologic data, length of hospital stay, and blood product consumption. Follow-up took place during the year after hospital discharge.

Enrollment: 40 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Men and women with acute respiratory distress syndrome.

Inclusion Criteria: ECMO ENTRY CRITERIA (PaO2 < 50 mm Hg -REPEATED THREE TIMES):

Rapid entry: 2 hours at fraFIO2=1.00 and PEEP>5 cm H2O with PaCO2=30-45 mmHg

Slow entry: 12 hours at fraction of inspired oxygen (FIO2)>0.60 and positive end-expiratory pressure (PEEP)>5 cm H2O with PaCO2=30-45 mmHg and right to Left shunt fraction >0.30

Exclusion Criteria:

1. Contraindication to anti-coagulation (for example, gastrointestinal bleeding, recent cerebrovascular accident, or chronic bleeding disorder).

2. Pw > 25 mm Hg (superseded by our screening criterion that Pw ~ 15 mm Hg).

3. Mechanical ventilation >21. days.

4. Severe chronic systemic disease or another clinical condition that, in itself,greatly limits survival; for example,

   1. Irreversible central nervous system disease
   2. Severe chronic pulmonary disease (forced expiratory volume in 1 second (FEV1)<1 L, FEV1/FVC(forced vital capacity) <0.3 of predicted, chronic PaCO2 >45 mm Hg, chest x-ray evidence of overinflation or interstitial infiltration, or previous hospitalization for chronic respiratory insufficiency)
   3. Total-body surface burns> 40%
   4. Rapidly fatal malignancy
   5. Chronic left ventricular failure
   6. Chronic renal failure (we required serum creatlnlne ~ 2 mg/dl or chronic dialysis therapy)
   7. Chronic liver failure (we required total serum bilirubin;?; 2 mg/dl)
   8. Immunosuppressed patients and patients with a positive human immu.. nodeficiency virus test

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Extracorporeal membrane oxygenation (CO2 removal)

Experimental group

Description:

Detailed Electronic Protocol Controlled Extracorporeal CO2 Removal with reduced positive-pressure ventilation

Treatment:

Procedure: extracorporeal membrane oxygenation (CO2 removal)

Protocol Controlled positive-pressure vent

Active Comparator group

Description:

Detailed Electronic Protocol Controlled positive-pressure ventilation

Treatment:

Procedure: positive-pressure ventilation