Stability of diluted neuromuscular blocking agents utilized in perioperative hypersensitivity evaluation

101

This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. AbstractThe specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules.This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring Zuzana Diamanthttps://orcid.org/0000-0003-0133-0100Thomas Eiwegger https://orcid.org/0000-0002-2914-7829Wytske J. Fokkens https://orcid.org/0000-0003-4852-229X

Section: New Approaches To the Diagnosis And Treatment Of Drug Hypementioning

confidence: 99%

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

Breiteneder

Diamant

Eiwegger

et al. 2019

101

“…17,19 Moreover, factors such as dilution can affect drug stability and therefore the rate of positivity, as demonstrated with neuromuscular blocking agents (NMBA). 20 The time interval between the reaction and the study 21 and the latency for reading the STs 22 can also affect the likelihood for obtaining positive results in ST. 21 This leads to a high heterogeneity in current practice. 5,18 Moreover, differences in the sensitivity of the tests and the diagnostic approach exist due to different regional consumption patterns and to the introduction of new drugs.…”

Section: Box 2 Major Milestone Discoveriesmentioning

confidence: 99%

“…For other drugs, nonirritating concentrations are used, although in many cases they are not standardized 17,19 . Moreover, factors such as dilution can affect drug stability and therefore the rate of positivity, as demonstrated with neuromuscular blocking agents (NMBA) 20 . The time interval between the reaction and the study 21 and the latency for reading the STs 22 can also affect the likelihood for obtaining positive results in ST 21 .…”

Section: In Vivo Diagnosismentioning

confidence: 99%

Advances and novel developments in drug hypersensitivity diagnosis

Ariza

Mayorga

Bogas

et al. 2020

The diagnosis of drug hypersensitivity reactions (DHRs) has important implications for both patients and health system. 1 Mainly because an allergy label, whether true or not, implies the avoidance of medications that may be essential, the performance of unnecessary desensitization procedures, or the use of alternative medications. All these alternatives can lead to a less effective treatment, more potential adverse effects, and costs for health systems. 2 Moreover, in the case of antibiotics, it results in bacterial resistance. 3 Considering that there are no specific tests to distinguish between a viral infection and DHRs in the acute phase, a diagnostic work-up should be performed to remove a false label of hypersensitivity. 4 DHRs diagnosis is complex, time consuming, needs to be done by trained staff, and it is not standardized for many drugs. It is mainly based on skin testing (ST) and drug provocation tests (DPTs),

“…For most clinicians dealing with the management of anaphylaxis induced by neuromuscular blocking drugs (NMBDs), diagnosis and prevention of subsequent reactions usually rest on a detailed history and appropriate skin tests that are cheap, generally reliable, easy to perform with the free drugs, and do not require special equipment . An aspect of skin testing with NMBDs that has been somewhat neglected is the stability of the dilutions employed for testing, the subject of the recent communication to the journal by Gonzalez‐Estrada et al . In their letter, the authors carelessly state, “A previous manuscript has recommended storing diluted NMBAs up to 3 months at 4°C” and incorrectly attribute this recommendation to the text book of Baldo and Pham .…”

mentioning

confidence: 99%

“…Apart from manufacturers’ recommendations on storage and shelf life of NMBDs in solution (generally, restriction of storage to 24 hours at 2‐8°C once the container is opened; see for example references 5 and 6) and a number of detailed studies on the stability of succinylcholine, the study by Gonzalez‐Estrada et al provides some welcome quantitative measurements of potencies of NMBD solutions at dilutions beyond those routinely administered to induce neuromuscular block. Given the variables and uncertainties inherent in exposure times to light (pancuronium, vecuronium, atracurium, cisatracurium and mivacurium should be protected from light) and different temperatures, the employment of different diluents and containers, adsorption of drugs to contacted materials, and the frequent absence of aseptic methods in the preparation of test solutions, the demonstration of decreased drug stability at high dilutions further supports the need for an always prudent approach in the testing and storage of NMBD skin test solutions.…”

mentioning

confidence: 99%

Stability of neuromuscular blocking drugs used for skin testing

Baldo

2019

For most clinicians dealing with the management of anaphylaxis induced by neuromuscular blocking drugs (NMBDs), diagnosis and prevention of subsequent reactions usually rest on a detailed history and appropriate skin tests that are cheap, generally reliable, easy to perform with the free drugs, and do not require special equipment. 1 An aspect of skin testing with NMBDs that has been somewhat neglected is the stability of the dilutions employed for testing, the subject of the recent communication to the journal by Gonzalez-Estrada et al. 2 In their letter, the authors carelessly state, "A previous manuscript has recommended storing diluted NMBAs up to 3 months at 4°C" and incorrectly attribute this recommendation to the text book of Baldo and Pham. 3 In fact, in considering skin testing as one of the diagnostic procedures for the diagnosis of suspected anaphylaxis to NMBDs, we concluded: "Information on the shelf life of diluted NMBD preparations is lacking, an indication that solutions for skin testing should be freshly prepared at the time of testing and rejected upon completion but, except for atracurium, cisatracurium, mivacurium and rocuronium, each of which should be freshly diluted, storage of test solutions for up to 3 months at 4°C has been suggested by some." [Emphasis added]. In fact, the source of the recommendation is the published guidelines for clinical practice for reducing the risk of anaphylaxis during anaesthesia implemented in France under the auspices of the Société Française d'Anesthésie et de Réanimation according to the French National Agency of Evaluation of Medicine. This published recommendation for storage of NMBD test solutions has been repeated a number of times in the literature. 4 Apart from manufacturers' recommendations on storage and shelf life of NMBDs in solution (generally, restriction of storage to 24 hours at 2-8°C once the container is opened; see for example references 5 and 6) and a number of detailed studies on the stability of succinylcholine, 7,8 the study by Gonzalez-Estrada et al 2 provides some welcome quantitative measurements of potencies of NMBD solutions at dilutions beyond those routinely administered to induce neuromuscular block. Given the variables and uncertainties inherent in exposure times to light (pancuronium, vecuronium, atracurium, cisatracurium and mivacurium should be protected from light) and different temperatures, the employment of different diluents and containers, adsorption of drugs to contacted materials, and the frequent absence of aseptic methods in the preparation of test solutions, the demonstration of decreased drug stability at high dilutions further supports the need for an always prudent approach in the testing and storage of NMBD skin test solutions. Add to that the rare occurrence of NMBD-induced anaphylaxis and long intervals between cases, NMBD skin test solution dilutions should not be stored for extended periods even in a refrigerator. As a general rule it is recommended that, for all NMBDs, skin test solution dilutions are fre...