PLE was evacuated in all groups, at which point fluid loading was discontinued whereas norepinephrine infusion continued at the maximal infusion rate.
Oxytocin exposure during labour was studied as a binary variable and also with three quantitative variables: total dose (in international unit), maximal infusion rate (in milli international units per minute) and total duration of infusion (in minutes).
However, when the level of oxytocin exposure was considered, the risk of severe PPH appeared significantly higher for women in the most exposed categories: the adjusted OR was 2.1 (95% CI 1.3 to 3.3) for a total dose of >4 IU and 1.7 (95% CI 1.1 to 2.5) for a maximal infusion rate of >15 mIU/ml.
Similarly, the association of severe PPH with the maximal infusion rate of oxytocin appeared dose related: the adjusted OR was 2.2 (95% CI 1.3 to 3.8) for a maximal rate between 10 and 15 mIU/min and 3.2 (95% CI 1.7 to 6.1) for a maximal rate of >15 mIU/min (table 4).
The maximal infusion rates associated with survival were 50 mg h epinephrine, 140 mg h norepinephrine and 25 mg h isoprenaline.
After 10 units injection, time to lispro plasma peak (Tmax) was similar (48.3 vs. 55.7 min; control subjects versus type 2 diabetic subjects), although maximal concentration (Cmax)/dose was 41% lower in subjects with type 2 diabetes, with lower and delayed maximal glucose infusion rate (GIRmax: 9.0 vs. 0.6 mg/kg/min, P < 0.0001, 69 vs. 130 min, P < 0.0001, respectively).
In the six patients the maximal glucose infusion rate was associated with a wide range of insulin concentrations, suggesting a saturable toxic mechanism at these high concentrations.
The maximal naloxone infusion rate was associated with an R, S-methadone concentration ranging from 400 to 1,200 ng/ml, suggesting a saturation of the mu-opioid receptors at these concentrations.
Supporting this assumption is the finding that the maximal glucose infusion rate in the study of Luzio et al. was ∼9 pmol/kg/min, which was equivalent to the largest glucose infusion rate occurring in this study after a 4-fold higher dose of glargine (2.0 units/kg).
However, euglycaemia could not be achieved even at maximal glucose infusion rates in Ucn3+ mice at this standard high physiological insulin dose (~450 pmol/l [ 21]), whereas euglycaemia was achieved in controls (Fig. 4d).
Increases in glucose flux revealed no discernible peak and were modest with maximal glucose infusion rates of 9.4, 6.6, 5.5, and 2.8 μmol/kg/min for the 2.0, 1.0, 1.0, and 0.5 units/kg doses, respectively.
