There are some limitations in this study which need to be considered when interpreting the results. The kinetics of 3-OMG absorption have never been validated in the critically ill population. It is possible that kinetic variables, such as selleck bio the volume of distribution and renal clearance, may affect 3-OMG concentrations following ingestion. These effects are likely to vary between individuals and in the same individual over time. An increase in volume of distribution would reduce 3-OMG concentrations but it is unlikely that this could account for the marked reduction in 3-OMG concentrations observed in this study. Similarly, three patients in this study were receiving renal replacement therapy. It is not known how 3-OMG is cleared by dialysis and so the effect of this on the 3-OMG concentrations cannot be predicted.

Blood samples for the measurement of glucose and 3-OMG were taken from an arterial line in the patients and a venous line in healthy subjects. There is a difference in blood glucose concentrations between arterial and venous samples, but this difference is generally believed to be small [36,37]. As 3-OMG is not metabolised by tissues, there is unlikely to be a difference between arterial and venous samples, but this has not been documented.The number of subjects recruited was relatively small. Nevertheless, highly significant differences were observed between healthy subjects and critically ill patients, suggesting that a study with greater numbers is unlikely to generate different results. However, there was a difference in the age and gender ratio between the two groups.

In health, GE is probably slightly slower in pre-menopausal women than in age-matched men [38-40]. Interestingly, the largest study to date examining GE in critically ill patients suggests that gender has the opposite effect, in that women had a faster emptying rate [2], although this is not a consistent finding [41,42]. It is possible that normal hormonal effects are less evident in critically ill patients, because critical illness causes marked aberrations in hormonal activity so the gender effect on GE may be less important. It is also likely that other factors have a stronger influence on GE causing marked slowing in some cases and obscuring the more subtle hormonal effects. In this study, there was a greater proportion of women in the healthy group, which could have resulted in a slowing of GE in this cohort.

However, the current study demonstrated slowed GE in critically ill patients compared with healthy controls. We may have shown a greater difference if we had included more males in the control group.The effect of healthy ageing on GE is uncertain with inconsistent GSK-3 observations [43-49]. Extreme ageing is thought to be associated with a slowing of GE, which may reflect an increase in small intestinal nutrient feedback [50]. Studies on the elderly usually evaluate subjects in the age range 65 to 80 years.