13 research outputs found
Pharmacokinetics of C1-inhibitor in patients with acute myocardial infarction
Nederlands Tijdschrift voor Klinische Chemie 27(2),69(2002) -- Nederlandse Vereniging voor Klinische Chemie en Laboratoriumgeneeskunde --
Pharmacokinetics of C1-inhibitor protein in patients with acute myocardial infarction
OBJECTIVES: C1-inhibitor protein (C1-INH) purified from pooled human plasma is used for the treatment of patients with hereditary angioedema. Recently, the beneficial effects of high-dose C1-INH treatment on myocardial ischemia or reperfusion injury have been reported in various animal models and in humans. We investigated the pharmacokinetic behavior of C1-INH in patients with acute myocardial infarction to calculate the amount of C1-INH required for optimal efficacy. METHODS: Twenty-two patients received an intravenous loading dose, followed by 48 hours of continuous infusion of C1-INH. Changes in the endogenous production of C1-INH were evaluated in 16 control patients with acute myocardial infarction. A 2-compartment model was used to estimate the fractional catabolic rate constant (FCR), transcapillary escape rate constant (TER), and extravascular return rate constant (ERR) of C1-INH. Software designed to analyze and fit measured data to unknown parameters in a system of differential equations was used to fit the experimental data against the 3-parameter model. RESULTS: With fixed TER and ERR values (0.014 h(-1) and 0.018 h(-1), respectively), 20 of the 22 cases yielded well-determined FCR values, and simultaneous fitting resulted in a median FCR of 0.011 h(-1) (95% confidence interval, 0.010 to 0.012 h(-1)) versus 0.025 h(-1) as reported in healthy control patients. Simultaneous estimation of TER, ERR, and FCR demonstrated weakly defined TER and ERR values, whereas the median FCR value remained unchanged. The use of a 2-compartment model resulted in a significantly better fit compared with the 1-compartment model. Physiologic explanations are offered for discrepancies in the literature. CONCLUSIONS: Dose calculation of C1-INH in patients treated with massive doses of C1-INH requires turnover parameters that differ from those found in healthy subjects, possibly because of suppression of continuous C1-INH consumption by target protease
Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study
Background: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage
hampers comparative studies and optimization of clinical management. The concept of persistent postpartum
haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common
definitions that are either based on estimations of blood loss or transfused units of packed red blood cells
(RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured
by these three types of definitions.
Methods: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive
women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical
characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum
haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h
following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation
and intensive care unit admission.
Results: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the
definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h
following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying
the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal
outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent
postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line
treatment.
Conclusion: The definition persistent postpartum haemo