No abstract

We conclude that the described method of automatic detection and removal of artifacts in AEP recordings effectively improves the quality of the resulting AEP waveform, without excessive rejection of artifact-free signal periods. The signal variables used in this method seem appropriate for distinguishing artifact-free signal periods from periods containing artifacts for the types of artifact that were studied.

No abstract

BackgroundKetorolac, a potent non-steroidal anti-in-flammatory drug, is a chiral substance. Racemic ketorolac clearance is significantly higher at delivery, but S-ketorolac disposition determines the analgesic effects. We aimed to document the impact of pregnancy and postpartum on enantiomer-specific (S and R) ketorolac pharmacokinetics (PK) in young women.MethodsObservations shortly following caesarean de-livery (n=39) were pooled with data in subgroup of these women (n=8/39) four months afterwards (‘postpartum’) and with 8 healthy female volunteers, resulting in 47 un-paired and 8 paired PK estimates. All women received single intravenous bolus of ketorolac tromethamine (30 mg). Five (at 1, 2, 4, 6, 8 hour) plasma samples were collected and plasma concentrations were determined using HPLC method. Enantiomer-specific PKs were calculated using PKSolver.ResultsUnpaired analysis documented that median distribution volume at steady state (Vss) for S-and R-ke-torolac was significantly higher in women following cae-sarean delivery (n=31) compared to postpartum (n=8) (S-ketorolac: 12.79 vs. 7.84 L, p=0.011; R-ketorolac: 8.96 vs. 5.86 L, p=0.001) or to healthy female volunteers (n=8).(S-ketorolac: 12.79 vs. 9.14 L, p=0.002; R-ketorolac: 8.96 vs. 5.51 L, p<0.001). When corrected for BW, median Vss for both S-and R-ketorolac were significantly higher in women shortly following caesarean delivery compared to those in healthy female volunteers (S-ketorolac: 0.18 vs. 0.15 L/kg, p=0.037; R-ketorolac: 0.12 vs. 0.09 L/kg, p=0.001). The median clearance (CL) for S-and R-ketoro-lac was significantly higher in women following caesarean delivery compared to postpartum (S-ketorolac: 6.49 vs. 3.73 L/h, p<0.001; R-ketorolac: 2.14 vs. 1.43 L/h, p=0.002) or to healthy female volunteers (S-ketorolac: 6.49 vs. 3.60 L/h, p<0.001; R-ketorolac: 2.14 vs. 0.99 L/h, p=0.001). After taking the body size differences into account, CL to body weight (CL/BW) and CL to body surface area (CL/BSA) for S-and R-ketorolac were also higher following caesar-ean delivery compared to observations in postpartum (S-ketorolac:+33.3%, L/h·kg,+38.6%, L/h·m2; R-ketorolac:+33.3%, L/h·kg,+31.4%, L/h·m2) and in healthy female volunteers (S-ketorolac:+33.3%, L/h·kg,+48.4%, L/h·m2; R-ketorolac:+33.3%, L/h·kg,+56.8%, L/h·m2). In addition, S/R-ketorolac CL/BSA ratio was significantly higher at de-livery compared to postpartum (3.07 vs. 2.73, p=0.020). Paired PK analysis in 8 women following delivery or post-partum showed the same pattern. Finally, the simultane-ous increase in CL and Vss resulted in similar estimates for elimination half-life in both unpaired and paired analysis.ConclusionPregnancy affects S-, R-and S/R-ketorolac disposition. This is of clinical relevance since S-ketorolac (analgesia) CL is even more increased compared to R-ke-torolac CL and S/R-ketorolac CL ratio is higher following delivery compared to postpartum or to healthy female volunteers. For definitive physiological state-specific dos-ing recommendations in women, we encourage future repeated dos...