Errors in estimating neonatal production of glucose with stable isotopes during "approximate steady state"

In studies of glucose metabolism in neonates, a commonly used approach is b ased on constant rate infusion of glucose labelled with a stable isotope in order to reach an approximate steady state with regard to isotopic enrichm ent in plasma. Under presumed conditions of a glucose steady state. the rat es of appearance and disappearance of glucose can. in principle, be calcula ted with use of a simple steady-state formula, However, in the neonate, ste ady-state conditions do not generally prevail and results derived on such a ssumptions are questionable. In the present study, we have taken a pragmati c approach and compared estimates obtained from the conventional formula wi th values calculated with Steele's nonsteady-state method. The results show that the estimated glucose appearance and disappearance rates change more or less over the observed time period in all the typical cases studied, and that "steady-state estimates" may differ from the corresponding non-steady -state values by up to 37%, In a sensitivity analysis, the value of the dis tribution volume factor was found to be non-critical, a circumstance that s upports the use of Steele's method. Thus, even though the classical Steele pool-fraction method for computation of rates of appearance and disappearan ce under non-steady-state conditions has been criticized, it is still the m ost realistic alternative to the frequently used simple steady-state formul a in applications to newborns.