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. 2015 Jan 22;2015(1):CD010381. doi: 10.1002/14651858.CD010381.pub2

Morris 1994.

Methods This randomized, controlled, non‐cross‐over clinical trial was carried out in the United States (Shock Trauma/Intermountain Respiratory ICU, LOS Hospital, Salt Lake City).
Participants were treated with pressure‐controlled inverse ratio ventilation followed by VV extracorporeal CO2 removal compared with continuous positive‐pressure ventilation.
Inclusion criteria: PaO2 < 50 mmHg with FiO2 1.0 and PEEP ≥ 5 cm H2O for 2 hours OR PaO2 < 50 mmHg for > 12 hours with FiO2 0.6 and PEEP ≥ 5 cm H2O with a shunt fraction above 30%.
Exclusion criteria: age < 12 or > 65 years; mechanical ventilation > 21 days; immunosuppression; positive human immunodeficiency virus test.
Participants Patients with ARDS. ARDS was defined by the presence of all of the following: P(a/A)O2 < 0.2, bilateral chest radiographic infiltrates, CTH < 50 mL/cm H2O and PW < 15 mmHg (or no clinical evidence of heart failure). Patients with severe ARDS who met ECMO entry and exclusion criteria were considered candidates for the clinical trial.
249 patients with ARDS were identified, and 41 met ECMO entry criteria. 40 participants were enrolled (1 with no consent) and were randomly assigned from August 25, 1987, to April 24, 1991. Of these 40 randomly assigned participants, 5 were originally admitted to the LDS Hospital and 35 were transferred there from other hospitals: 6 from Salt Lake City hospitals, 6 from Utah hospitals outside Salt Lake City and 23 by air from out‐of‐state hospitals. Patient referrals were actively solicited from within the LDS Hospital and from other medical centres. All patients at the LDS Hospital were screened for ARDS.
Interventions Researchers constructed an extracorporeal system with a parallel and series configuration of two 3.5‐m2 Sci‐Med membrane lungs for gas and blood flow, respectively. If PCIRV support failed, LFPPV‐ECCO2R was initiated. Failure of PCIRV was based on failure to maintain PaO2 or failure to maintain pHa.
21 participants received the intervention (LFPPV‐ECCO2R). 3 to 6 hours after initiation of LFPPV‐ECCO2R, the Ppeak was 45.4 ± 1.7 cm H2O (mean ± SEM, with the number of observations in parentheses) for the 19 new therapy participants supported extracorporeally (35.8 ± 0.5 cm H2O for the first 10 participants). The desired low Ppeak goal was maintained for the first day of LFPPVECCO2R, as Ppeak was only 41.2 cm H2O 24 to 27 hours after initiation of LFPPV‐ECCO2R in the first 10 LFPPV‐ECCO2R participants. During the entire LFPPV‐ECCO2R period, the Ppeak was 54.1 ± 0.2 cm H2O (2865). VR was reduced to 3 to 5/min in all participants during LFPPV‐ECCO2R initiation and was kept at 3.3 ± 0.1/min during the first 3 to 6 hours of LFPPV‐ECCO2R in all participants.
For all 21 participants receiving new therapy, Ppeak during all mechanical ventilation support modes grouped together (PCIRVb + LFPPV‐ECCO2R + CPAP) was 49.5 ± 0.2 (6331). For the 19 control participants, Ppeak during the entire CPPV period was 57.8 ± 0.2 cm H2O. For all participants, arterial oxygenation protocols consistently reduced FiO2 and PEEP to the lowest values necessary to maintain the common PaO2 endpoint of 59 mmHg.
Outcomes Primary outcome: survival
Secondary outcomes: hospital costs; physiological data; length of hospital stay and blood product consumption
Notes The trial was stopped after 40 participants with the conclusion that the difference between new and traditional therapies was too small for a significant survival difference to be demonstrated with 60 randomly assigned participants.
The study was supported by Grant No. HL36787 from the National Institutes of Health, and by the Deseret Foundation, the Respiratory Distress Syndrome Foundation and LDS Hospital/IHC, Inc.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk "Blinded randomization with blocking was used, and patients were assigned to receive either control therapy or the new therapy"
Allocation concealment (selection bias) Unclear risk "Blinded randomization with blocking was used, and patients were assigned to receive either control therapy or the new therapy"
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk Blinding of outcome assessment was not reported. However, it was judged unlikely that outcome assessment was influenced by lack of blinding: "The end point of this analysis was the time until death occurred"
Incomplete outcome data (attrition bias) 
 All outcomes Low risk "We randomized all patients who met entry criteria, despite the gravity of their clinical state (1 new therapy patient died rapidly before we could initiate LFPPV‐ECCO2R, and 2 patients died within 1 day after initiating LFPPV‐ECCO2R). We observed the "intention‐to‐treat" principle in our evaluation of this new therapy in the clinical trial"
Selective reporting (reporting bias) Unclear risk Information was insufficient to permit a judgement
Other bias Unclear risk "We used a minimum VT of 4 ± 0.5 ml/kg BWp rather than a Ppeak limit. We abandoned use of the Ppeak limit because of difficulty in maintaining a VT > 100 ml in some patients after several days of extracorporeal support. After the first 10 patients, we were advised to insist upon a minimum VT of about 250 ml (A. Pesenti, personal communication). Of 6 survivors receiving LFPPV‐ECCO2R, 3 were maintained with the Ppeak limit and 3 with the minimum VT after we abandoned the Ppeak limit"
"We used explicit protocols to ensure uniformity of care, with equal frequency of monitoring, consistent decision‐making logic for the management of arterial oxygenation, and common PaO end points for all randomized ARDS patients from the time of randomization to extubation or death, regardless of the therapy limb"