Purpose: We set out to assess the resuscitation fluid requirements and physiological and clinical responses of intensive care unit (ICU) patients resuscitated with 20% albumin versus 4-5% albumin. Methods:We performed a randomised controlled trial in 321 adult patients requiring fluid resuscitation within 48 h of admission to three ICUs in Australia and the UK. Results:The cumulative volume of resuscitation fluid at 48 h (primary outcome) was lower in the 20% albumin group than in the 4-5% albumin group [median difference − 600 ml, 95% confidence interval (CI) − 800 to − 400; P < 0.001]. The 20% albumin group had lower cumulative fluid balance at 48 h (mean difference − 576 ml, 95% CI − 1033 to − 119; P = 0.01). Peak albumin levels were higher but sodium and chloride levels lower in the 20% albumin group. Median (interquartile range) duration of mechanical ventilation was 12.0 h (7.6, 33.1) in the 20% albumin group and 15.3 h (7.7, 58.1) in the 4-5% albumin group (P = 0.13); the proportion of patients commenced on renal replacement therapy after randomization was 3.3% and 4.2% (P = 0.67), respectively, and the proportion discharged alive from ICU was 97.4% and 91.1% (P = 0.02). Conclusions:Resuscitation with 20% albumin decreased resuscitation fluid requirements, minimized positive early fluid balance and was not associated with any evidence of harm compared with 4-5% albumin. These findings support the safety of further exploration of resuscitation with 20% albumin in larger randomised trials.

ObjectiveCurrently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement.MethodsFollowing third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured. Placental function was then assessed in terms of (i) chorionic plate artery agonist responses and length-tension characteristics using wire myography and (ii) production and release of placentally derived hormones (by quantitative polymerase chain reaction and enzyme linked immunosorbant assay of villous tissue and explant conditioned culture medium).ResultsPlacentas from pregnancies ending in adverse outcome (N = 23) were ~25% smaller in weight, volume, length, width and disc area (all p<0.0001) compared with those from normal outcome pregnancies. Villous and trophoblast areas were unchanged, but villous vascularity was reduced (median (interquartile range): adverse outcome 10 (10–12) vessels/mm2 vs. normal outcome 13 (12–15), p = 0.002). Adverse outcome pregnancy placental arteries were relatively insensitive to nitric oxide donated by sodium nitroprusside compared to normal outcome pregnancy placental arteries (50% Effective Concentration 30 (19–50) nM vs. 12 (6–24), p = 0.02). Adverse outcome pregnancy placental tissue contained less human chorionic gonadotrophin (20 (11–50) vs. 55 (24–102) mIU/mg, p = 0.007) and human placental lactogen (11 (6–14) vs. 27 (9–50) mg/mg, p = 0.006) and released more soluble fms-like tyrosine kinase-1 (21 (13–29) vs. 5 (2–15) ng/mg, p = 0.01) compared with normal outcome pregnancy placental tissue.ConclusionThese data provide a description of the placental phenotype of adverse outcome in late pregnancy. Antenatal tests that accurately reflect elements of this phenotype may improve its prediction.