Morphine-induced cardiovascular stimulation: the effects of two doses on healthy subjects.
In humans, morphine induces hypotension, probably because of histamine liberation. Earlier animal studies have, however, suggested that morphine can induce immediate cardiovascular stimulation when given as a sole medication. The aim of this study was to evaluate the initial effects of morphine on circulation, oxygen consumption, and plasma histamine and catecholamine concentrations. Oxycodone was used as a reference drug. Eight healthy volunteers received, in a random, cross-over, double-blinded fashion: 0.07 mg/kg morphine (M1); 0.14 mg/kg morphine (M2); 0.14 mg/kg oxycodone (O); and placebo (P) as a 2-min IV injection for pain. Mean arterial blood pressure (MAP), heart rate (HR), and oxygen consumption (VO(2)) were recorded. Plasma histamine and catecholamine concentrations were determined. Both M1 and M2 elicited an initial, but transient, increase in MAP from 84 +/- 5 to 96 +/- 9 mm Hg (P < 0.05) and from 83 +/- 8 to 100 +/- 10 mm Hg (P < 0.05), respectively. A parallel increase in HR was also seen after M1 (from 62 +/- 12 to 70 +/- 10 bpm, P < 0.05) and M2 (from 67 +/- 9 to 78 +/- 8 bpm, P < 0.05). After M2, this was accompanied by a simultaneous increase in VO(2) from 295 +/- 39 mL/min to 322 +/- 61 mL/min (P < 0.05). After O, as well as P, no increase in MAP or HR was detected. Plasma histamine and catecholamine concentrations were not clearly affected by any of the treatments. We conclude that the immediate effect of morphine on the hemodynamics of healthy volunteers was stimulation, not hypotension. This effect was not seen in conjunction with oxycodone, a morphine-like mu-receptor agonist.


CONCLUSIONS
In this double-blinded, randomized study, we evaluated whether morphine could induce immediate cardiovascular stimulation, as seen previously in animal studies. In healthy volunteers, during a painful stimulus, morphine caused an initial, transient hemodynamic stimulation, accompanied by increased oxygen consumption, without detectable release of histamine or catecholamines into the plasma. Oxycodone caused only minor hemodynamic alterations.
Mildh
L H
LH
Department of Anesthesia, Helsinki University Hospital, Finland. leena.mildh@hus.fi
Tuomisto
L M
LM
Scheinin
M
M
Kirvelä
O A
OA
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000097:blood; D006801:Humans; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010098:Oxycodone / Q000008:administration & dosage / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D013268:Stimulation, Chemical
D000701:Analgesics, Opioid; D002395:Catecholamines; D009020:Morphine; D006632:Histamine; D010098:Oxycodone