Serum phosphate modifies the vascular response to vitamin D receptor activation in chronic kidney disease (CKD) patients.

BACKGROUND AND AIMS: Vitamin D receptor activation (VDRA) ameliorates endothelial dysfunction in CKD patients but also increases phosphate and FGF-23, which may attenuate the beneficial effect of VDRA on endothelial function. METHODS AND RESULTS: This is a pre-specified secondary analysis of the PENNY trial (NCT01680198) testing the effect of phosphate and FGF-23 on the flow mediated vasodilatory (FMD) response to paricalcitol (PCT, 2 µg/day) and placebo over a 12-weeks treatment period. Eighty-eight stage G3-4 CKD patients were randomized to PCT (n = 44) and Placebo (n = 44). Endothelial function was assessed by measuring endothelium dependent forearm blood flow (FBF) response to ischemia. The FMD response was by the 61% higher in PCT treated patients than in those on placebo (P = 0.01). Phosphate (+11%, P = 0.039), calcium (+3%, P = 0.01) and, particularly so, FGF23 (+164%, P < 0.001) increased in PCT treated patients. Changes in FMD by PCT associated inversely with phosphate (r = -0.37, P = 0.01) but were independent of FGF-23, calcium and PTH changes. The response to PCT was maximal in patients with no changes in phosphate (1st tertile), attenuated in those with mild-to-moderate rise in phosphate (2nd tertile) and abolished in those with the most pronounced phosphate increase (3rd tertile) (effect modification P = 0.009). No effect modification by FGF-23 and other variables was observed. CONCLUSIONS: The beneficial effect of PCT on endothelial function in CKD is maximal in patients with no or minimal changes in phosphate and it is abolished in patients with a pronounced phosphate rise. These findings generate the hypothesis that the endothelium protective effect by VDRA may be potentiated by phosphate lowering interventions.

[Clinical experience with atracurium--a continuous infusion technic]. / Kliniese ondervinding met atrakurium--'n aanhoudende infusie-tegniek.

A continuous infusion technique for atracurium was investigated. It provided a stable neuromuscular block, with a mean infusion rate of 0.008 mg/kg/min after an initial bolus of 0.5 mg/kg. A wide individual response was found and an arbitrary infusion rate based on mass alone is therefore not possible. The above rate is thus a starting point and should be adjusted according to individual requirements, preferably by using a peripheral nerve stimulator. The technique obviates the need for repeated increments of atracurium during lengthy surgical procedures.

Comparison between atracurium and alcuronium for muscle relaxation during laparoscopy.

Atracurium 0.3 mg/kg was compared with alcuronium 0.25 mg/kg as the sole muscle relaxant for tracheal intubation and abdominal relaxation for gynaecological laparoscopy in 46 patients during nitrous oxide, oxygen and halothane anaesthesia. Speed of onset, intubation conditions, effect on blood pressure and pulse rate, and ease of reversal were compared. Alcuronium had a significantly faster onset of action than atracurium; intubation conditions were adequate and abdominal relaxation was satisfactory for both drugs. The effect of atracurium was readily reversible within 10 minutes; in contrast alcuronium was significantly more resistant and mean recovery time was 28.03 minutes. Although alcuronium provided good muscle relaxation, it is not suitable for short procedures because of difficulty in reversing its action. Atracurium allowed earlier and more complete reversal of neuromuscular block.