No abstract

The metabolism of catecholamines (CA) in non-selected patients with chronic renal failure and under hemodialysis (CRFh) was studied by measuring the concentration of plasma free, sulfo- and glucuroconjugated CA, dopamine (DA), norepinephrine (NE), and epinephrine (EPI). Our data demonstrate a statistically significant increase of free DA and free NE concentration in CRFh, while that of free EPI was not different from controls. However a careful scrutiny of 35 individual data suggests that sub-groups of patients with either high normal or low plasma-free NE concentration could exist; this likely heterogeneity could be a good explanation for conflicting conclusions provided by previous reports. Suspecting that conjugated CA might be altered in CRFh, plasma sulfo- and glucuro-conjugated DA, NE and EPI were also measured. We have found a predictable and highly significant increase of sulfo-conjugated CA; plasma concentration of glucuro-conjugated DA and NE in CRFh was not different from controls, while that of glucuro-conjugated EPI was significantly increased. The physiological meaning, if any, of these new observations on conjugated CA cannot be assessed at the moment. The effects of hemodialysis were also investigated. Measurements on the arterial and on the venous line showed highly significant differences for tyrosine, free and sulfo-conjugated CA, and a lack of difference for glucuro-conjugated CA. Thus tyrosine, free and sulfo-conjugated CA were eliminated by the artificial kidney, but not glucuro-conjugated amines.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or resistance to warfarin is unlikely if the above doses of vitamin K are used. Vitamin K is less effective for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than after treatment with warfarin.

The levels of free and sulfoconjugated catecholamines were measured in the plasma of fasting, recumbent normal subjects before and after an oral load of the catecholamine precursors tyrosine or L-dopa. Basal values of sulfoconjugated catecholamines, measured in plasma samples diluted 1:100 were 7998 +/- 540 pg/ml for dopamine sulfate, 2938 +/- 281 pg/ml for norepinephrine sulfate, and 2958 +/- 288 pg/ml for epinephrine sulfate (n = 37 tests in 15 men); these basal values are higher than those reported previously. Neither free nor sulfoconjugated catecholamine concentrations were changed by a tyrosine load (100 mg/kg) that induced a doubling of the plasma tyrosine level or by a meal low in phenylalanine and tyrosine (but otherwise supplying constituents of normal nourishment) that induced a greater than 50% reduction in the plasma tyrosine concentration. After an oral load of L-dopa (125 mg) the following were observed. (1) An extremely large increase (greater than 100-fold) in dopamine sulfate levels was noted, an increase that was less marked in the same subjects given L-dopa (125 mg) plus the peripheral dopa-decarboxylase inhibitor carbidopa (12.5 mg); as expected, free dopamine concentration also was increased. (2) Neither free nor sulfoconjugated norepinephrine concentrations were altered. (3) Epinephrine sulfate but not free epinephrine concentration was increased (more than ten-fold) after L-dopa ingestion alone; this result was unexpected and has to be confirmed before considering its physiological meaning, if any.