title: Measurement of extravascular lung water following human brain death: implications for lung donor assessment and transplantation.
abstract: OBJECTIVE
  The measurement of extravascular lung water could aid the assessment and guide the management of potential lung donors following brain death. We therefore sought to validate a single indicator thermodilution extravascular lung water index (EVLWI-T) measurement using gravimetry and to assess the impact and clinical correlates of elevated EVLWI-T in potential lung donors and transplant recipients.
  
  
  METHODS
  In a prospective study, we measured serial EVLWI-T and haemodynamic and oxygenation data in 60 potential lung donors. To validate the EVLWI-T measurement, we measured in vivo thermodilution EVLWI (EVLWI-T) and gravimetric ex vivo EVLWI (EVLWI-G) in donor lungs rejected for transplant using the Holcroft and Trunkey modification of Pearce's method. We assessed the clinical correlates of elevated lung water and measured interleukin-8 and hepatocyte growth factor in bronchoalveolar lavage (BAL) fluid.
  
  
  RESULTS
  The mean EVLWI-T (n = 60) was 9.7 (4.5) ml kg(-1), being >7-10 ml kg(-1) in 23/60 and >10 ml kg(-1) in 16/60 potential donors. Donor lungs with EVLWI >10 ml kg(-1) were more likely to be receiving norepinephrine (P = 0.04), have higher pulmonary capillary wedge pressures (P = 0.008), be unsuitable for transplantation (P = 0.007) and, if transplanted, have worse survival (P = 0.04). Lungs submitted to gravimetric analysis [n = 20 in 11 donors (9 double and 2 single)] had EVWLI-T of 10.8 (2.7) and EVLWI-G was 10.1 (2.5). There was a strong correlation between EVLW-T and EVLW-G (r = 0.7; P = 0.014), but EVLWI-T over-predicted the EVLWI-G by ≈ 1 ml kg(-1) (EVLW-T = 1.05 × EVLW-G). Cytokine levels in BAL fluid were elevated.
  
  
  CONCLUSIONS
  Elevated lung water is found in >50% of potential lung donors, predicts lung suitability for transplant and may adversely affect recipient outcome. Although EVLWI-T intrinsically overestimates gravimetric lung water, its measurement may aid the assessment of organ suitability. Lung water accumulation and the proinflammatory response may both be targets for modifying therapy.
authors.affiliation: Department of Heart and Lung Transplantation, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Rajamiyer V
authors.initials: RV
authors.lastname: Venkateswaran
authors.forename: Vamsidhar
authors.initials: V
authors.lastname: Dronavalli
authors.forename: Val
authors.initials: V
authors.lastname: Patchell
authors.forename: Ian
authors.initials: I
authors.lastname: Wilson
authors.forename: Jorge
authors.initials: J
authors.lastname: Mascaro
authors.forename: Richard
authors.initials: R
authors.lastname: Thompson
authors.forename: John
authors.initials: J
authors.lastname: Coote
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bonser
mesh_terms: D000328:Adult; D001926:Brain Death / Q000378:metabolism*; D015633:Extravascular Lung Water / Q000378:metabolism*; D005260:Female; D006652:Histological Techniques; D006801:Humans; D008168:Lung / Q000378:metabolism; D016040:Lung Transplantation / Q000379:methods* / Q000592:standards*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D018709:Statistics, Nonparametric; D013815:Thermodilution; D014019:Tissue Donors; D016896:Treatment Outcome
keywords: Donor management; Extravascular lung water; Gravimetric lung water; Lung transplantation; Lung water