Intra-operative protective mechanical ventilation in lung transplantation: a randomised, controlled trial.

Primary graft dysfunction occurs in up to 25% of patients after lung transplantation. Contributing factors include ventilator-induced lung injury, cardiopulmonary bypass, ischaemia-reperfusion injury and excessive fluid administration. We evaluated the feasibility, safety and efficacy of an open-lung protective ventilation strategy aimed at reducing ventilator-induced lung injury. We enrolled adult patients scheduled to undergo bilateral sequential lung transplantation, and randomly assigned them to either a control group (volume-controlled ventilation with 5 cmH2 O, positive end-expiratory pressure, low tidal volumes (two-lung ventilation 6 ml.kg-1 , one-lung ventilation 4 ml.kg-1 )) or an alveolar recruitment group (regular step-wise positive end-expiratory pressure-based alveolar recruitment manoeuvres, pressure-controlled ventilation set at 16 cmH2 O with 10 cmH2 O positive end-expiratory pressure). Ventilation strategies were commenced from reperfusion of the first lung allograft and continued for the duration of surgery. Regular PaO2 /FI O2 ratios were calculated and venous blood samples collected for inflammatory marker evaluation during the procedure and for the first 24 h of intensive care stay. The primary end-point was the PaO2 /FI O2 ratio at 24 h after first lung reperfusion. Thirty adult patients were studied. The primary outcome was not different between groups (mean (SD) PaO2 /FI O2 ratio control group 340 (111) vs. alveolar recruitment group 404 (153); adjusted p = 0.26). Patients in the control group had poorer mean (SD) PaO2 /FI O2 ratios at the end of the surgical procedure and a longer median (IQR [range]) time to tracheal extubation compared with the alveolar recruitment group (308 (144) vs. 402 (154) (p = 0.03) and 18 (10-27 [5-468]) h vs. 15 (11-36 [5-115]) h (p = 0.01), respectively). An open-lung protective ventilation strategy during surgery for lung transplantation is feasible, safe and achieves favourable ventilation parameters.

Carbon-11 labeled tracers for in vivo imaging P-glycoprotein function: kinetics, advantages and disadvantages.

P-glycoprotein (P-gp) is a drug efflux transporter with broad substrate specificity localized in the blood-brain barrier and in several peripheral organs. In order to understand the role of P-gp in physiological and patho-physiological conditions, several carbon-11 labelled P-gp tracers have been developed and validated. This review provides an overview of the spectrum of radiopharmaceuticals that is available for this purpose. A short overview of the physiology of the blood-brain barrier in health and disease is also provided. Tracer kinetic modelling for quantitative analysis of P-gp function and expression is highlighted, and the advantages and disadvantages of the various tracers are discussed.