morphine in subjects without cardiovascular disease and not receiving prior ... Serum histamine concentration increased 2, 5, and 10 min after the morphine.
Role of histamine in the hemodynamic and plasma
catecholamine responses to morphine The role of histamine in the hemodynamic and plasma catecholamine responses to intravenous
morphine in subjects without cardiovascular disease and not receiving prior medication has not been reported. Systemic hemodynamics and serum histamine and plasma catecholamine concentrations were measured in 10 subjects before and 2, 5, 10, and 20 min after, 0.3 mg kg' IV morphine. Serum histamine concentration increased 2, 5, and 10 min after the morphine. Systolic and mean arterial pressures and systemic vascular resistance decreased and cardiac output increased because of increases in heart rate and stroke volume. The most important changes in hemodynamic function occurred after 2 min in association with a 400% increase in serum histamine concentration; these variables, together with serum histamine concentration, returned toward baseline values after 20 min. There was a negative correlation between peak increase in serum histamine concentration and maximum decrease in systemic vascular resistance. Plasma epinephrine concentrations were elevated 5, 10, and 20 min after morphine injection, suggesting activation of the adrenal medulla by histamine. Our data suggest that histamine plays an important role in the acute hemodynamic and plasma epinephrine response to morphine.
Nabil R. Fahmy, M.D., Neelakantan Sunder, M.D., and Nicholas A. Soter, M.D. Boston, Mass. Anaesthesia Services at Massachusetts General Hospital and lmmunodermatology Section of the
Department of Rheumatology and Immunology at Brigham and Women's Hospital, and the Departments of Anaesthesia and Dermatology, Harvard Medical School
Evidence for morphine-induced histamine release has been based on clinical observations, notably flushing, generalized warmth, and pruritus. Histamine exerts important effects in man and in the experimental animal and may be responsible for the hemodynamic effects associated with the drugs.'° Recently, Fahmy5 and Supported in part by grants Al 18139 and Al 10356 from the National Institutes of Health. Received for publication Sept. 30, 1982. Accepted for publication Nov. 19, 1982. Reprint requests to: Nabil R. Fahmy, M.D., Department of Anesthesia, Massachusetts General Hospital, Boston, MA 02114.
Philbin et a1.'5 reported changes in plasma histamine levels and hemodynamic variables associated with morphine. The former report described an anaphylactoid reaction to morphine that was associated with a 3000% increase in plasma histamine concentration; in the latter, however, a number of factors, including the simultaneous administration of metocurine (a histamine-releasing drug) and morphine, ventilation with nitrous oxide and oxygen, propranolol, presence of cardiac disease, and phenylephrine infusion, could have modified the observations. We quantified the changes in 615
Clin. Pharmacol. Ther. May 1983
Fahmy et al.
616
Table I. Hemodynamic variables and serum histamine and plasma catecholamine levels before and after intravenous morphine in 10 patients Morphine administration Minutes after
Variable
Before
Arterial blood pressure (mm Hg) Systolic Diastolic Mean Cardiac output (1
5
126.5 ± 7.2 78.2 ± 5.1 94.8 ± 6 5.1 ± 0.6
114.5 ± 6.8* 73.3 ± 5.4 87.0 ± 5.4* 6.9 ± 0.81:
117.9 ± 6.6* 75.0 ± 4.2 89.3 ± 5* 6.7 ± 0.9t
63 ± 3 1388 ± 110
78 ± 51
916 ± 85$
72 ± 963 ± 92$
8.0 ± 1.1
8.5 ± 1.0
3.32 ± 0.2*
2.28 ± 0.41:
min')
Heart rate (bpm-1) Systemic vascular resistance (dynes sec cm-5) Right atrial sure (mm Hg) Serum histamine
pres-6.5 ±
0.9
0.93 ± 0.10
20
10
2
120.2 ± 77.0 ± 91.4 ± 6.4 ±
8.9 3.2 5 0.61:
68 ± 3* 1036 ± 1061:
8±
1.1
124.1 ± 1.0 77.6 ± 5.1 93.1 ± 6
5.4 ± 0.5 65 ± 3 1274 ± 122
7
± 0.9
2.00 ± 0.181:
1.66 ± 0.3
140 ± 221:
427 ± 361:
208 ± 41
187 ± 32
206 ± 29
24 ± 6
21 ± 6
(ng m1-1)
epineph-64 ± norepi-221 ±
Plasma rine (pg m1-') Plasma nephrine (pg
12
42
49 ± 10 191
± 37
94 ±
151:
ml-') Plasma dopamine (Pg
26 ± 8
26 ± 7
21
±
7
1111-')
Values are mean
*P < 0.05; tP
