Potentiation of Vancomycin-Induced Histamine Release by Muscle Relaxants and Morphine in Rats

Abstract

The intravenous injection of vancomycin sometimes causes anaphylactoid reactions, in which histamine release may play a major role. These reactions are more frequently manifested when vancomycin is injected into anesthetized patients. We examined the vancomycin-induced histamine release and the interaction of vancomycin with muscle relaxants or opioid in rats. In an in vitro study with rat peritoneal mast cells, treatment with vancomycin at concentrations of greater than 1.25 mM produced significant histamine release. Tubocurarine, vecuronium, pancuronium, succinylcholine, and morphine up to concentrations of 0.25, 1, 5, 30, and 5 mM, respectively, produced no significant histamine release. However, the nonsignificant histamine release induced by 0.5 mM vancomycin was clearly enhanced by combining vancomycin with any of these agents. In the in vivo study, the intravenous injection of vancomycin significantly increased the plasma histamine levels in rats when vancomycin was injected at 200 mg/kg of body weight (63.2 ± 34.0 ng/ml [mean ± standard deviation]) but not when it was injected at 100 mg/kg (30.8 ± 20.2 ng/ml) compared with that in the saline-treated rats (22.5 ± 11.4 ng/ml). Although the subcutaneous administration of morphine (10 mg/kg) never increased the plasma histamine levels, the intravenous injection of vancomycin (100 mg/kg) 30 min after this morphine treatment markedly increased the plasma histamine levels (56.0 ± 26.9 ng/ml). These findings provide experimental evidence that the combination of muscle relaxants or an opioid with vancomycin may increase the risk of anaphylactoid reactions by enhancing the release of histamine.

Different Patterns of Mast Cell Activation by Muscle Relaxants in Human Skin

“…17,24 However, despite their low potency, there might be an interaction with opioids or antibiotics, which can enhance the mast cell degranulation. 25 Atracurium and even more mivacurium provoked mast cell activation very potently, again confirming previous in vivo studies in which systemic histamine release was measured. 10,26 -28 Furthermore, the ratio between peak plasma concentration and ED 50 for histamine release of mivacurium and atracurium was found to be significantly lower when compared with all other muscle relaxants (table 3).…”

Development and validation of a liquid-chromatography tandem mass spectrometry method to determine in vitro and in vivo histamine release

“…Basal levels of histamine in the rat plasma were typically under 100 ng/mL (Fig. 5), which is consistent with known literature values (Shuto et al, 1999) [28]. Treatment with a drug suspected of causing anaphylactic type reactions resulted in plasma histamine levels above 3000 ng/mL (Fig.…”

Quantification of gadolinium in nephrogenic systemic fibrosis: Re-examination of a reported cohort with analysis of clinical factors

“…23 It is well recognized that vancomycin infusions, often augmented by other ubiquitous medications of hospitalization, such as opioids, can induce histamine release; histamine impacts vascular permeability and tissue edema. 25,26 It is possible that vancomycin exacerbated renal dysfunction, leading to increased accumulation or reduced clearance of gadolinium in tissue or, alternatively, it impaired other homeostatic processes or induced further endothelial dysfunction. Sepsis and infection (viral, bacterial, and parasitic) can alter expression of cytokines that impact the endothelium, such as endothelin-1 and vascular endothelial growth factor.…”