Invasive pulmonary aspergillosis is associated with adverse clinical outcomes in critically ill patients receiving veno-venous extracorporeal membrane oxygenation

I Rodriguez-Goncer,S Thomas,M D Richardson,A Ashworth,C G Geraghty,E G Muldoon,T W Felton,J Barker,P Foden

doi:10.1007/s10096-018-3241-7

Abstract

To identify the incidence, risk factors and impact on long-term survival of invasive pulmonary aspergillosis (IPA) and Aspergillus colonisation in patients receiving vv-extracorporeal membrane oxygenation (ECMO). A retrospective evaluation was performed of patients receiving vv-ECMO at a tertiary hospital in Manchester (UK) between January 2012 and December 2016. Data collected included epidemiological data, microbiological cultures, radiographic findings and outcomes. Cases were classified as proven IPA, putative IPA or Aspergillus colonisation according to a validated clinical algorithm. One hundred thirty-four patients were supported with vv-ECMO, median age of 45.5 years (range 16.4–73.4). Ten (7%) patients had putative IPA and nine (7%) had Aspergillus colonisation. Half of the patients with putative IPA lacked classical host risk factors for IPA. The median number of days on ECMO prior to Aspergillus isolation was 5 days. Immunosuppression and influenza A infection were significantly associated with developing IPA in a logistic regression model. Cox regression model demonstrates a three times greater hazard of death associated with IPA. Overall 6-month mortality rate was 38%. Patients with putative IPA and colonised patients had a 6-month mortality rate of 80 and 11%, respectively. Immunosuppression and influenza A infection are independent risk factors for IPA. IPA, but not Aspergillus colonisation, is associated with high long-term mortality in patients supported with vv-ECMO.

Highlights

Study definitionsVeno-venous extracorporeal membrane oxygenation is an effective treatment to support patients with severe respiratory failure unresponsive to conventional therapies [1]
Respiratory infection was the most common indication for receiving vv-extracorporeal membrane oxygenation (ECMO) support with 74/134 (55%) patients with bacterial pneumonia, 23/74 (31%) of whom had Streptococcus pneumoniae isolated from broncho-alveolar lavage (BAL)
During a 5-year period, we found an incidence of putative invasive pulmonary aspergillosis (IPA) and Aspergillus colonisation in critically ill patients receiving vv-ECMO support of 7% each

Summary

Introduction

Veno-venous extracorporeal membrane oxygenation (vvECMO) is an effective treatment to support patients with severe respiratory failure unresponsive to conventional therapies [1]. Older age, being immunocompromised, longer duration of mechanical ventilation before vv-ECMO, neuromuscular blockade agents, nitric oxide use and increased extra-pulmonary organ failure are associated with worse outcomes [3–5]. Healthcare-associated infections occur in 26–45% of patients on vv-ECMO and are associated with high mortality and increased hospital stay [6–8]. Aspergillus spp. are identified more frequently in this group compared with those in other groups of critically ill patients [7]. Aspergillus in the airways of patients supported with ECMO may be associated with poorer outcomes [10–12]. Several major risk factors have been identified for developing invasive pulmonary aspergillosis (IPA) in critically ill patients not receiving vvECMO, such as influenza A infection, higher SOFA score and previous broad-spectrum antibiotic therapy [13–15]

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Conclusion