Occurrence and determinants of poor response to short-term pre-operative erythropoietin treatment.

BACKGROUND: This study aimed to explore the occurrence and determinants of poor response to short-term pre-operative erythropoietin treatment and the effect of such poor response on transfusion in total hip arthroplasty patients. METHODS: We studied total hip arthroplasty patients who received erythropoietin before surgery. The primary outcome was the pre-operative increase in haemoglobin (delta haemoglobin) as response to erythropoietin therapy. Additionally, patients were classified in tertiles based on this delta haemoglobin: poor responders (cases), responders and good responders (controls) to erythropoietin. Patient characteristics, comedication and co-morbidity were collected as potential determinants of erythropoietin response. Regression techniques were used to estimate the strength of the associations and to assess the effect of poor response on transfusion requirement. RESULTS: A total of 379 patients receiving erythropoietin were eligible to enter the study. Mean delta haemoglobin was 19.3 g/l (standard deviation 9.4). Factors significantly associated with delta haemoglobin were the use of angiotensin II antagonists [-3.1 g/l; 95% confidence interval (CI) -5.7 to -0.6] and vitamin K antagonists (-6.9 g/l; 95% CI -10.0 to -0.2), together with body mass index (BMI) (-0.3 g/l per unit>; 95% CI -0.5 to -0.2). The additional case-control analysis yielded comparable results. Poor response to erythropoietin was associated with an increased transfusion risk (odds ratio 4.6, 95% CI 2.0-11). CONCLUSION: Use of angiotensin II receptor antagonists and vitamin K antagonists, and having a high BMI were determinants of poor response to short-term pre-operative erythropoietin treatment in total hip arthroplasty patients. Poor responders had a higher risk for perioperative blood transfusion.

Nonlinear first-pass metabolism of nifedipine in healthy subjects.

1. A dose-range study was carried out with nifedipine (NF) in 11 healthy subjects, who received orally 5, 10 and 20 mg in capsules (cap) and 20 mg as slow-release tablet. 2. The dose-normalized area under the curve (AUC) of NF showed significant nonlinearity: AUC of 5 mg (cap) was 312 +/- 179, of 10 mg (cap) 357 +/- 186 and of 20 mg (cap) 424 +/- 174 (ng.h/ml). The AUC of the tablet was significantly lower than that of 10 and 20 mg (cap), but not different from 5 mg (cap). 3. The dose-normalized AUC of the pyridine metabolite (M-0) significantly decreased with increasing dose: AUC of 5 mg (cap) was 244 +/- 88, of 10 mg (cap) 194 +/- 96 and of 20 mg (cap) 120 +/- 37 (ng.h/ml). 4. The excretion of M-I (which is ester-hydrolysed M-0) into urine was not different for any of the doses. 5. It is concluded that NF exhibits nonlinear first-pass metabolism, which concomitantly affects the formation of M-0, but not that of M-I.