Nephrology Dialysis Transplantation, Vol 13, Issue 2 396-401, Copyright © 1998 by Oxford University Press
G Ligtenberg, P Blankestijn and H Koomans
Background. The haemodynamic response to progressive
hypovolaemia, whether simulated by lower body negative pressure (LBNP) or
head-up tilt, or induced by haemorrhage or haemodialysis, has a typical
biphasic pattern: a first, sympathoexcitatory, phase of vasoconstriction,
tachycardia, and stable blood pressure, and a second, sympathoinhibitory,
phase of vasodilatation, bradycardia, and hypotension. The opioid system is
involved in this response, since animal studies showed that opioid
antagonism by naloxone can attenuate hypovolaemic hypotension. In humans,
this finding could not be confirmed. We hypothesized that this could result
from inadequate dosing. Methods. Six healthy subjects
underwent LBNP at -45 mmHg until presyncope before and after administration
of naloxone 2 mg/kg. During the study, blood pressure, heart rate, vascular
resistance, cardiac output, and plasma {beta}-endorphin were measured.
Results. LBNP caused an immediate increase in
vasoconstriction and heart rate, resulting in stable blood pressure. After
12±3.5 min, vasodilatory hypotension followed, accompanied by a
modest increase in plasma {beta}-endorphin. Naloxone did not alter the
first or the second phase of the circulatory response, and tolerance to
LBNP even tended to decrease (hypotension after 7.5±2.0 min,
NS). Pre-LBNP plasma {beta}-endorphin as well as hypotensive levels were
increased after naloxone. Conclusions. Our results
suggest that naloxone, in a sufficient dose to interfere with the opioid
system, does not influence the circulatory response to simulated
hypovolaemia in humans is not influenced by naloxone. Given the mechanistic
resemblance of LBNP hypotension to dialysis-induced hypotension, we propose
that high-dose naloxone is not useful to treat the latter form of
hypotension. Keywords: {beta}-endorphin;
hypotension; lower body negative pressure; naloxone; opioid system;
progressive hypovolaemia
ORIGINAL ARTICLES
Presyncope during progressive hypovolaemia simulated by lower body negative pressure is not prevented by high-dose naloxone
Department of Nephrology and Hypertension, University Hospital Utrecht, Room F03.226, PO Box 85500, 3508 GA Utrecht, The Netherlands; Corresponding author
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