Conclusions remained unaltered for the “day of surgery admission” sensitivity analysis. This further highlights the high likelihood of cost-effectiveness of the interventions across a variety of assumptions.Subgroup protein inhibitors analysis of the effects of cardiac risk, heart failure grade and type of surgery showed no evidence of interaction with the main effect of the intervention (data not shown).DiscussionThe study demonstrated a non-significant trend towards a reduction of hospital length of stay with a mean difference of 5.50 (-0.44, 11.44) days (median 2.20 days). This direction of effect was also observed when considering total duration of hospital stay and days from study randomisation until hospital discharge.

Observed differences towards improvements in secondary outcome measures also support the proposition that fluid loading is likely to be beneficial by showing that pre-operative fluid loading tended towards reduced serious adverse events that prolonged hospital stay and resulted in a non-significant reduction in post-operative morbidity (at seven days). The finding of the economic analysis was that fluid loading results in, on average, lower costs and greater benefits than no fluid loading. Cost savings associated with the intervention were mainly driven by longer post-operative inpatient length of stay in the fluid control group (data not shown). Based on the balance of probabilities; there is a high probability that fluid loading is cost-effective compared to fluid control.

The fluid interventionThe fluid loading group received a median of 1,875 ml of Ringer’s solution in the pre-operative period compared to a median of 0 ml in the control; this correlates well with the 25 ml/kg protocolised target pre-operative fluid load. This fluid was delivered over a six-hour period before surgery. With clinical practice changing towards day of surgery admission in many countries, future studies in this area may find it difficult to deliver this intervention and may choose to consider testing whether shorter periods of fluid administration are appropriate; for instance, delivery of the fluid intervention in a two-hour period rather than six. It is important to identify that our sensitivity analysis suggests that the intervention is still highly likely to be cost-effective even if patients, who would normally be admitted on the day of surgery, had to be admitted to hospital up to 12 hours earlier (that is, the night before surgery) to receive the intervention.With regard to the choice of fluid used, we chose Ringer’s solution due to our desire to select a crystalloid and use a balanced solution. We believe this was the appropriate Cilengitide choice and would be unlikely to change this selection in a future study.