Methods and analysis. (a) Schematic showing timing of serial skin biopsies before induction of anaesthesia and 48 h after the haemodynamic trial intervention. (b)Venn diagram showing primary and secondary outcome analyses. Blue shading/text denotes patients in whom oxygen delivery (DO2) remained low after intervention. Red shading/text denotes subjects in whom DO2 was normal after intervention. Primary outcome was comparison between proteins differentially expressed in patients with normal vs low DO2 after intervention. Grey shaded area highlights secondary pathway analyses which accounted for directional changes in protein expression for subjects with normal or low DO2 value. An increase/decrease was defined by fold-change >1.5, confidence score >20 and P-value <0.05 (analysis of variance, anova), as generated by Progenesis QI analysis software (Nonlinear Dynamics, Newcastle upon Tyne, UK).