Propofol-containing sedatives increase levels of parathyroid hormone.
OBJECTIVE
To evaluate the effects of propofol and propofol containing disodium edetate (ethylenediaminetetraacetic acid [EDTA]) on the parathyroid-calcium axis in normal subjects.


METHODS
Randomised, double-blind, age-stratified, crossover trial.


METHODS
Single centre.


METHODS
A total of 50 healthy subjects.


METHODS
Each subject was randomised to receive propofol or propofol containing EDTA on day 1 and the alternate treatment between days 15 and 29, with a 2-week wash-out period in between. On the day of treatment, subjects received a bolus of trial medication (1 or 2 mg/kg) followed by a 60-minute observation period. At the end of 60 minutes, subjects received trial medication infused for 60 minutes at 1 of 4 randomised infusion rates (25, 50, 100, or 200 microg/kg per min). Subjects were monitored for an additional 60 minutes following the infusion.


RESULTS
Blood pressure, heart rate, respiratory rate, oxygen saturation, blood ionised calcium concentration, serum total magnesium concentration, serum intact parathyroid hormone (PTH) level, and plasma EDTA level were assessed at periodic intervals during and following the bolus and continuous infusion of trial medication. Mean arterial pressure significantly decreased (p < 0.05) following the bolus injection of both trial medications and returned to baseline at 60 minutes; it significantly decreased again during the continuous infusion and returned to baseline during recovery. Heart rate and respiratory rate fluctuated in both groups with significant increases and decreases throughout the study period following the bolus injection; both returned to baseline during the recovery period in each group. Ionised calcium and total magnesium concentrations remained within normal limits and were unchanged in response to both study medications. PTH levels significantly increased following the bolus injection of both study drugs. The increase in PTH levels was greater with higher doses of study medication during the infusion period. There was no difference in the response of blood pressure, heart rate, respiratory rate, or PTH levels between propofol and propofol with EDTA. EDTA levels increased significantly during the infusion of propofol with EDTA, reaching mean levels of 240 ng/mL.


CONCLUSIONS
The results of this study indicate that propofol increases PTH levels in normal subjects; however, propofol with EDTA does not alter ionised calcium or total magnesium concentrations.
Zaloga
G P
GP
Critical Care Medicine, Suburban Hospital, Bethesda, MD 20817, USA. gzaloga@aol.com
Youngs
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D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002614:Chelating Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004492:Edetic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008274:Magnesium / Q000097:blood; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D002614:Chelating Agents; D010281:Parathyroid Hormone; D011310:Preservatives, Pharmaceutical; D004492:Edetic Acid; D008274:Magnesium; D002118:Calcium; D015742:Propofol