PRESYNCOPE DURING PROGRESSIVE HYPOVOLEMIA SIMULATED BY LOWER-BODY NEGATIVE-PRESSURE IS NOT PREVENTED BY HIGH-DOSE NALOXONE

Background. The haemodynamic response to progressive hypovolaemia, whe ther simulated by lower body negative pressure (LBNP) or head-up tilt, or induced by haemorrhage or haemodialysis, has a typical biphasic pa ttern: a first, sympathoexcitatory, phase of vasoconstriction, tachyca rdia, and stable blood pressure, and a second, sympathoinhibitory, pha se 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 huma ns, this finding could not be confirmed. We hypothesized that this cou ld result from inadequate dosing. Methods. Six healthy subjects underw ent LBNP at -45 mmHg until presyncope before and after administration of naloxone 2 mg/kg. During the study, blood pressure, heart rate, vas cular resistance, cardiac output, and plasma beta-endorphin were measu red. Results. LBNP caused an immediate increase in vasoconstriction an d 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 seco nd phase of the circulatory response, and tolerance to LBNP even tende d to decrease (hypotension after 7.5 +/- 2.0 min, NS). Pre-LBNP plasma beta-endorphin as well as hypotensive levels were increased after nal oxone. Conclusions. Our results suggest that naloxone, in a sufficient dose to interfere with the opioid system, does not influence the circ ulatory 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 n ot useful to treat the latter form of hypotension.