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Article Review/Hyperlink
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Blowey DL, Balfe JW, Gupta I, Gajaria MM, Koren G
Midodrine efficacy and pharmacokinetics in a patient with
recurrent intradialytic hypotension
Am J Kidney Dis
(Jul) 28:132-136 1996

How to treat dialysis patients with refractory hypotension is an important
clinical problem. Given
recent data that expected increases in plasma vasopressin or norepinephrine
levels fail to occur,
and that there is paradoxic withdrawal of peroneal nerve sympathetic tone
during or just prior to
hypotensive episodes, predialysis administration of phenylephrine, amezinium,
or vasopressin has
been tried. Midodrine is an alpha-agonist prodrug with high oral
bioavailability which is
metabolized to its active component, de-glymidodrine, the latter having a
plasma half-life of about
3 hours in patients with normal renal function (but which is prolonged in
ESRD). Midodrine has been used successfully to treat to
treat idiopathic orthostatic hypotension and hypotension in Shy Drager
syndrome.
In his paper, Blowey et al had an 18 year old patient with ESRD and who also
had Bardet-Biedl
syndrome (polydactyly, obesity, tapetoretinal degeneration, mental
retardation, hypogonadism, and
renal involvement) who had precipitous, symptomatic falls in BP during
dialysis, which persisted
even after use of ramped sodium dialysis and use of cool dialysate. A tilt
table test showed marked
hypotension within 20 min of tilting, even when 2 kg over dry weight. The
intradialytic hypotension
was improved markedly with 5 mg administration of midodrine predialysis, and
completely resolved
when the dose was increased to 10 mg. After 4 months, the midodrine was
tapered and then
discontinued, without recurrence of the hypotension. Pharmacokinetic studies
also were done.
Plasma half-life was 10 hours off dialysis and 1.4 hours during dialysis.
Continuous ambulatory BP
monitoring showed that the mean interdialytic BP was significantly increased.
This, and the long
plasma half-life in this patient off dialysis probably warrant some caution
in chronic use of this agent.
Comment:
Recurrent hypotensive episodes during dialysis have been
associated with poor outcome. However, it is not clear if chronic midodrine
administration to such
patients would increase their survival or decrease morbidity. The
encouraging results in this paper are preliminary, but suggest that further
trials of midodrine are warranted in hypotension-prone dialysis patients. It
is unclear to me why the patient unltimately improved and eventually no
longer required midodrine.
(John T. Daugirdas, M.D., University of Illinois at Chicago)
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