In vitro evaluation of the potential role of sulfite radical in morphine-associated histamine release.
BACKGROUND
Intravenous morphine use is associated with elevated histamine release leading to bronchoconstriction, edema and hemodynamic instability in some patients. This study evaluated the possibility that sulfite, which is present as a preservative in many morphine preparations, might contribute to histamine release in vitro.


RESULTS
The human mast cell line, HMC-1, was exposed to various morphine concentrations, in the absence of sulfite, under cell culture conditions. Clinically attained concentrations of morphine (0.018microg/ml and 0.45microg/ml) did not cause increased histamine release from mast cells. There was a significant increase in histamine release when the morphine concentration was increased by 1184-fold (668microg/ml morphine). Histamine release from mast cells exposed to morphine and/or sulfite required the presence of prostaglandin H synthetase. Histamine release in experiments using sulfite-containing morphine solutions was not statistically different from that observed in morphine-only solutions.


CONCLUSIONS
Sulfite in sulfite-containing morphine solutions, at concentrations seen clinically, is not responsible for histamine release in in vitro experiments of the human mast cell line, HMC-1. This does not preclude the fact that sulfite may lead to elevation of histamine levels in vivo.
Division of Pediatric Pharmacology and Critical Care, Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA. emma.gordon@case.edu
Emma M
EM
Gordon
Carolyn
C
Myers
Jeffrey
J
Blumer
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D005609:Free Radicals / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D013447:Sulfites / Q000494:pharmacology*
D000701:Analgesics, Opioid; D005609:Free Radicals; D013447:Sulfites; D009020:Morphine