Histamine Release by Four Narcotics

Abstract

FLACKE, JW, FL.ACKE WE, BLOOR BC, VAN E'lTEN AP, KRIPKE BJ. Histamine release by four narcotics: a double-blind study in humans. Anesth Analg 1987;66:723-30. Histamine release and hemodynamic changes associated w'th four narcotics were studied in 60 adults (28 men, 32 women) scheduled for general surgery under balanced anesthesia. Under doublt-blind conditions, insremental equiptent doses of meperidine, morphine, fentanyl, or sufentanil were administered IV for induction of anesthesia, prior to thiopental, succinylcholine, and intubation. Arterial blood samples were drawn before and I, 6 , and 20 min after narcotic administration. Of the 16 patients given meperidine (mean dose 4.3 2 0.2 (SEM) mglkg), five (31 %) had clinical signs (hypotension, tachycardia, erythema) and e l m t i a s in plasma histamine levels rangingfrom 3.2 to 49.7 nglml 1 min after narcotic administration. Plasma epinephrine levels at this time were also elevated in these five patients. One of the ten patients given morphine (0.6 2 0.02 mglkg) developed hypotension, tachycardia, and an increase in plasma histamine level to 12.4 nglml. None of34 patientsgiven either fentanyl (7 2 0.4 pglkg) or sufentanil (1.3 f 0.1 kglkg) had clinical signs of histamine release or elevations of plasma histamine levels. In the six patients in whom histamine release occurred, there was a significant correlation between the histamine levels at 1 min and the magnitude of change in heart rate, blood pressure, and plasma epinephrine level. All six histamine releasers were young women, ranging in age from 18 to 35 yr. Histamine release occurred more frequently after meperidine than after the other narcotics, including morphine, and the degree of hemodynamic compromise was related to the increase in plasma histamine concentration.

Refractory Intracranial Hypertension Due to Fentanyl Administration Following Closed Head Injury

“…This was likely due to a rheologic reduction in cerebral blood volume rather than to osmotic diuresis as she did not have evidence of significant cerebral edema on imaging. While this may explain the sudden increase in ICP following morphine administration in our patient, it does not fully explain the reduction in ICP after discontinuation of fentanyl infusion as fentanyl does not typically trigger histamine release (Flacke et al, 1987). This mechanism is also made unlikely by the lack of significant hemodynamic change associated with the rise in ICP.…”

Effect of Meperidine on Equine Blood Histamine, Tryptase, and Immunoglobulin-E Concentrations

“…In humans, IV meperidine causes an increase in histamine plasma concentrations as early as 1 min following injection and lasting 6.5 min post injection. In these patients, signs of shock (hypotension, tachycardia) with erythema and a catecholamine surge were documented (24). In anesthetized dogs administered meperidine at 5 mg/kg IV, histamine concentrations increased 4-5 fold 1 min following injection and decreased to two to three times the baseline values after 5 min (30).…”

“…First, it is possible that the increase in histamine peaked and lasted <5 min. The authors chose a first sampling time point of 5 min in order to capture the window of elevation previously observed in dogs (30) and humans after IV injection (24). Typically, return to baseline of histamine plasma concentrations occurs 15-60 min post injection (31,32).…”

“…Reported adverse effects of intravenous (IV) administration of meperidine in horses include sweating, tachycardia, hypotension, and erythema (19,21,22). Such effects are presumed to be a result of mast cell degranulation, as meperidine is known to cause histamine release in dogs (23) and humans (24). However, this syndrome has not been confirmed in horses.…”

Evaluation of Therapies for Peripheral and Neuraxial Opioid-induced Pruritus based on Molecular and Cellular Discoveries

“…In humans, the neuraxial administration of fentanyl, a lipophilic and synthetic opioid, evokes pruritus, even though fentanyl does not cause mast cell degranulation and histamine release as morphine does. 60,[64][65][66] Furthermore, clinical plasma concentrations of morphine are orders of magnitude smaller than CSF concentrations after neuraxial morphine administration (less than 0.01%), 67,68 and the concentration of morphine detected in the plasma is likely insufficient to cause mast cell degranulation, as suggested by in vitro studies (fig. 2).…”