title: Extracorporeal membrane oxygenation in severe influenza infection with respiratory failure: A systematic review and meta-analysis.
abstract: BACKGROUND
  Extracorporeal membrane oxygenation (ECMO) has been extensively used for potentially reversible acute respiratory failure associated with severe influenza A (H1N1) pneumonia; however, it remains an expensive, resource-intensive therapy, with a high associated mortality. This systematic review and meta-analysis aims to summarize and pool outcomes data available in the published literature to guide clinical decision-making and further research.
  
  
  METHODS
  We conducted a systematic search of MEDLINE (1966 to April 15, 2015), EMBASE (1980 to April 15, 2015), CENTRAL, and Google Scholar for patients with severe H1N1 pneumonia and respiratory failure who received ECMO. The study validity was appraised by Newcastle-Ottawa Scale. The primary outcome was all-cause mortality. The secondary outcomes were duration of ECMO therapy, mechanical ventilation, and Intensive Care Unit (ICU) length of stay.
  
  
  RESULTS
  Of 698 abstracts screened and 142 full-text articles reviewed, we included 13 studies with a total of 494 patients receiving ECMO in our final review and meta-analysis. The study validity was satisfactory. The overall mortality was 37.1% (95% confidence interval: 30-45%) limited by underlying heterogeneity (I2 = 65%, P value of Q statistic = 0.006). The median duration for ECMO was 10 days, mechanical ventilation was 19 days, and ICU length of stay was 33 days. Exploratory meta-regression did not identify any statistically significant moderator of mortality (P < 0.05), except for the duration of pre-ECMO mechanical ventilation in days (coefficient 0.19, standard error: 0.09, Z = 2.01, P < 0.04, R2 = 0.16). The visual inspection of funnel plots did not suggest the presence of publication bias.
  
  
  CONCLUSIONS
  ECMO therapy may be used as an adjunct or salvage therapy for severe H1N1 pneumonia with respiratory failure. It is associated with a prolonged duration of ventilator support, ICU length of stay, and high mortality. Initiating ECMO early once the patient has been instituted on mechanical ventilation may result in improved survival.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, John H Stroger, Jr. Hospital of Cook County, Chicago, Illinois, USA.
authors.forename: Shashvat
authors.initials: S
authors.lastname: Sukhal
authors.affiliation: Department of Internal Medicine, John H Stroger, Jr. Hospital of Cook County, Chicago, Illinois, USA.
authors.forename: Jaskaran
authors.initials: J
authors.lastname: Sethi
authors.affiliation: Department of Internal Medicine, John H Stroger, Jr. Hospital of Cook County, Chicago, Illinois, USA.
authors.forename: Malini
authors.initials: M
authors.lastname: Ganesh
authors.affiliation: Division of Cardiovascular Diseases, Montefiore Medical Center, Albert Einstein College of Medicine, New York, USA.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Villablanca
authors.affiliation: Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Anita K
authors.initials: AK
authors.lastname: Malhotra
authors.affiliation: Department of Anesthesiology, Mayo Clinic College of Medicine, Scottsdale; Department of Anesthesiology, Mayo Clinic, Phoenix, AZ 85054, USA.
authors.forename: Harish
authors.initials: H
authors.lastname: Ramakrishna
mesh_terms: D015199:Extracorporeal Membrane Oxygenation / Q000379:methods*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000150:complications* / Q000628:therapy*; D007902:Length of Stay / Q000706:statistics & numerical data; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D012131:Respiratory Insufficiency / Q000150:complications* / Q000628:therapy*