Anaesthetic allergy: Overview

Abstract
Objective: The Drug Lymphocyte Stimulation Test (DLST), recognized for its safety as an allergy diagnostic modality, has been acknowledged for its utility in diagnosing drug-induced pathological conditions. However, reports elucidating DLST outcomes concerning local anesthetics are notably scarce.

Materials and methods: An exhaustive analysis was conducted on the DLST results pertaining to local anesthetics derived from 571 patients presenting with suspected allergies to these specific agents.

Results: Remarkably, Stimulation Index (SI) > 1.8 was discerned in 11.4% and 7.8% of patients exhibiting hives or swelling subsequent to the administration of local anesthetics, surpassing the incidence observed in those experiencing post-injection discomfort. Additionally, SI > 3.0 was observed in 3 cases with lidocaine, 3 cases with prilocaine, and 1 case with mepivacaine. The distribution of SI exhibited a non-normal pattern for all three tested local anesthetics. Noteworthy is the case of a singular patient registering an SI of 1.84, who also yielded a positive challenge test, conclusively confirming an allergy to lidocaine.

Conclusions: The DLST, holding promise as a potentially invaluable tool in identifying the causative factors behind adverse reactions to dental local anesthetics, lacks sufficient evidence to substantiate its efficacy definitively at present.

Clinical relevance: DLST, coupled with intradermal testing and challenge testing, may be elucidated in patients exhibiting indicators of suspected local anesthetic allergy.

Abstract
Background: As the primary Ca2+ release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, triggering agents including halogenated volatile anaesthetics bias RyR1 to an open state resulting in uncontrolled Ca2+ release, increased sarcomere tension, and heat production. Propofol does not trigger MH and is commonly used for patients at risk of MH. The atomic-level interactions of any anaesthetic with RyR1 are unknown.

Methods: RyR1 opening was measured by [3H]ryanodine binding in heavy SR vesicles (wild type) and single-channel recordings of MH mutant R615C RyR1 in planar lipid bilayers, each exposed to propofol or the photoaffinity ligand analogue m-azipropofol (AziPm). Activator-mediated wild-type RyR1 opening as a function of propofol concentration was measured by Fura-2 Ca2+ imaging of human skeletal myotubes. AziPm binding sites, reflecting propofol binding, were identified on RyR1 using photoaffinity labelling. Propofol binding affinity to a photoadducted site was predicted using molecular dynamics (MD) simulation.

Results: Both propofol and AziPm decreased RyR1 opening in planar lipid bilayers (P<0.01) and heavy SR vesicles, and inhibited activator-induced Ca2+ release from human skeletal myotube SR. Several putative propofol binding sites on RyR1 were photoadducted by AziPm. MD simulation predicted propofol KD values of 55.8 μM and 1.4 μM in the V4828 pocket in open and closed RyR1, respectively.

Conclusions: Propofol demonstrated direct binding and inhibition of RyR1 at clinically plausible concentrations, consistent with the hypothesis that propofol partially mitigates MH by inhibition of induced Ca2+ flux through RyR1.

Abstract
Perioperative anaphylaxis is a potentially life-threatening emergency that requires prompt recognition and institution of life-saving therapy. The Australian and New Zealand College of Anaesthetists and Australian and New Zealand Anaesthetic Allergy Group have partnered to develop the anaphylaxis management guideline along with crisis management cards that are recommended for use in suspected anaphylaxis in the perioperative setting. This is the third version of these guidelines with the second version having been published in 2016. This article contains the revised Australian and New Zealand Anaesthetic Allergy Group/Australian and New Zealand College of Anaesthetists perioperative anaphylaxis management guideline, with a brief review of the current evidence for the management of anaphylaxis in the perioperative environment.