Perioperative Anaphylaxis Research Articles

Skin Test Reactivity After Food-Induced Anaphylaxis: A 5 Year Retrospective Review

Allergy skin prick testing (SPT) is commonly used in the evaluation of food allergy (FA). In cases of anaphylaxis, there is practice variability regarding the appropriate timing of SPT post reaction. Some providers test shortly after anaphylaxis, while others defer SPT due to a potential refractory period and resulting false negative (FN) results, as described in venom and perioperative anaphylaxis.

Patent Blue Dye: Allergen Increasing

Patent blue dye (PBD) is one of the most used dyes to identify the sentinel lymph node during breast cancer surgery. It is estimated as the culprit in 5% of peri-operative anaphylaxis. We present two cases of peri-operative anaphylaxis. The first, it is a 62 year old woman who presents a widespread violaceous wheal eruption immediately after anesthetic induction and dye infiltration. The second, it is a 69 year old woman who presents, after 20 minutes of the surgery beginning, abrupt hypotension refractory to treatment and forehead and hands angioedema.

Relationship of perioperative anaphylaxis to neuromuscular blocking agents, obesity, and pholcodine consumption: a case-control study

BackgroundThe observation that patients presenting for bariatric surgery had a high incidence of neuromuscular blocking agent (NMBA) anaphylaxis prompted this restricted case-control study to test the hypothesis that obesity is a risk factor for NMBA anaphylaxis, independent of differences in pholcodine consumption. MethodsWe compared 145 patients diagnosed with intraoperative NMBA anaphylaxis in Western Australia between 2012 and 2020 with 61 patients with cefazolin anaphylaxis with respect to BMI grade, history of pholcodine consumption, sex, age, comorbid disease, and NMBA type and dose. Confounding was assessed by stratification and binomial logistic regression. ResultsObesity (odds ratio [OR]=2.96, χ2=11.7, P=0.001), ‘definite’ pholcodine consumption (OR=14.0, χ2=2.6, P<0.001), and female sex (OR=2.70, χ2=9.61, P=0.002) were statistically significant risk factors for NMBA anaphylaxis on univariate analysis. The risk of NMBA anaphylaxis increased with BMI grade. Confounding analysis indicated that both obesity and pholcodine consumption remained important risk factors after correction for confounding, but that sex did not. The relative rate of rocuronium anaphylaxis was estimated to be 3.0 times that of vecuronium using controls as an estimate of market share, and the risk of NMBA anaphylaxis in patients presenting for bariatric surgery was 8.8 times the expected rate (74.9 vs 8.5 per 100 000 anaesthetic procedures). ConclusionsObesity is a risk factor for NMBA anaphylaxis, the risk increasing with BMI grade. Pholcodine consumption is also a risk factor, and this is consistent with the pholcodine hypothesis. Rocuronium use is associated with an increased risk of anaphylaxis compared with vecuronium in this population.

Perioperative anaphylaxis in children: A report from the Wake-Up Safe collaborative.

Anaphylactic reactions to antigens in the perioperative environment are uncommon, but they have a potential to lead to serious morbidity and/or mortality. The incidence of anaphylactic reactions is 1:37000 pediatric anesthetics, and substantially less than the 1:10000 to 1:20000 incidence in the adult population. Neuromuscular blocking agents, latex, and antibiotics are the most frequently cited triggers. To date, there is no comprehensive report on perioperative anaphylactic reactions in children in the United States. Using the Wake-up Safe database, we examined the incidence and consequences of reported perioperative anaphylaxis events. We reviewed the Wake-up Safe database from 2010 to 2017 and identified all reported instances of anaphylaxis. The triggering agent, timing, and location of the registered event, severity of patient harm, and preventability were identified. Narrative review of free-text comments entered by reporting centers was performed to determine presenting symptoms, and interventions required. Type of case was identified from procedure codes provided in mandatory fields. Among 2261749 cases reported to the Wake-up Safe database during the study period, perioperative anaphylactic reactions occurred in 1:36479 (0.003%). Antibiotics, neuromuscular blocking agents, and opioid analgesics were the main triggers. Forty-nine cases (79%) occurred in the operating room, and 13 cases (21%) occurred in off-site locations. Seven (11%) patients required cardiopulmonary resuscitation following the onset of symptoms. Thirty-five (57%) patients were treated with epinephrine or epinephrine plus other medications, whereas 5% were managed only with phenylephrine. Most cases (97%) required escalation of care after the event. Regarding case preventability, 91% of cases were marked as either "likely could not have been prevented" or "almost certainly could not have been prevented." The estimated incidence of anaphylaxis and inciting agents among the pediatric population in this study were consistent with the most recent published studies outside of the United States; however, new findings included need for cardiopulmonary resuscitation in 11% of cases, and estimated fatality of 1.6%. The management of perioperative anaphylaxis could be improved for some cases as epinephrine was not administered, or its administration was delayed. Fewer than half of reported cases had additional investigation to formally identify the responsible agent.

Approach to Perioperative Anaphylaxis in 2020: Updates in Diagnosis and Management.

The goal of the paper is to review the epidemiology, pathogenesis, diagnosis, and manifestations of perioperative anaphylaxis (POA). We seek to review the most common culprits of POA and different diagnostic modalities for evaluation. Specific IgE testing has a limited role in POA evaluation due to lack of widespread availability and low sensitivity. Basophil activation testing is complementary to skin tests and can assist NMBA sensitivity diagnosis in complex cases. In the past years, there has been an exponential increase in suspected teicoplanin allergic reactions in the European Union. Chlorhexidine is also being increasingly implicated as a culprit in POA. Multiple classes of perioperative medications cause POA. Diagnostic modalities available include skin testing with nonirritating concentrations, basophil activation tests, specific IgE, and drug provocation testing. An accurate record and critical analysis of perioperative events is more important than isolated test results. Future studies evaluating the pathophysiology of these reactions and other therapeutic strategies, such as targeting the MRGPRX2 receptor, are needed.

Diagnosis and Management of Rocuronium-induced Perioperative Anaphylaxis

Introduction - Perioperative anaphylaxis is a hypersensitivity reaction that occurs after exposure to drugs used for anaesthesia during a surgical procedure. The most common triggers are neuromuscular blocking agents and antibiotics. Case report - A 71-old man, with a history of anaphylaxis during previous anaesthesia, was scheduled for elective coronary surgery. The clinical signs included skin rash, swelling of the upper part of the body with angioedema of the eyelids and lips, without bronchospasm. Based on the assumption that rocuronium was the most likely causative agent, percutaneous coronary intervention was performed during the same hospitalization. After recovery, he was sent for a prick skin test and intradermal test, where sensitivity to rocuronium and insensitivity to the anaesthetics used were determined. Two months later, he developed an acute myocardial infarction. Chronic total occlusive percutaneous coronary intervention was attempted, but without optimal results, so the patient was prepared for elective surgery. Due to potential further complications during anaesthesia, the medical team decided to send him for a skin allergy test for neuromuscular blocking agents. The only neuromuscular relaxant available was Cisatracurium, and it was tested for sensitivity by intradermal test. The intradermal test showed insensitivity to Cisatracurium and Suxamethonium chloride. Conclusion - Early recognition and management of anaphylaxis is based on clinical presentation. The diagnosis by in-vivo and in-vitro tests is useful to determine the cause of anaphylactic reaction and safe alternatives for future anaesthesia.

Perioperative anaphylaxis: A five-year review in a tertiary paediatric hospital.

Making a diagnosis of perioperative anaphylaxis and identifying culprit drugs are diagnostic challenges. The aim of this study is to describe the perioperative presentation of anaphylaxis and results of patients who underwent allergy evaluation. This is a retrospective review of perioperative anaphylaxis of severity Grade 2 and above based on the Australian and New Zealand Anaesthetic Allergy Group criteria from 2015 to 2019 in a tertiary paediatric hospital. Data collected were demographics, clinical features, investigations and management. Of the 35,361 cases of paediatric anaesthesia, there were 15 cases of perioperative anaphylaxis, giving an incidence of four in 10,000. The median age was seven years (interquartile range four-15 years) with a male predominance of 86.7% (13/15). The severity of anaphylaxis was Grade 2 in 33.3% (5/15) and Grade 3 in 66.7% (10/15). The commonest presenting feature was hypotension (13/15, 86.7%) while the earliest symptom was respiratory change (9/15, 60.0%). Dynamic tryptase was raised in 75% (6/8) of the patients with adequate tryptase samples. Eight patients (53.3%) completed allergy testing, of whom five patients (62.5%) had IgE-mediated anaphylaxis with skin test positive to cefazolin (n = 3), atracurium (n = 1) and rocuronium (n = 1). Three patients (25.0%) had non-IgE-mediated reactions with negative skin tests. Although only half the patients completed allergy evaluation, a culprit drug could be identified in 62.5%, with antibiotics being the commonest. This emphasises the need for appropriate evaluation in cases of suspected perioperative anaphylaxis.

Perioperative allergy and anaphylaxis: An anesthesiologist’s nightmare

Perioperative anaphylactic reactions though rarer than in adults, result in severe morbidity in children. There is a shift in the most commonly implicated agents causing anaphylaxis from neuromuscular blocking agents and latex to antibiotics. The allergy work up for children can be tedious due to the necessity to perform skin prick tests which are the gold standard. Anaesthesia for children with documented hypersensitivity to various foodstuffs and drugs can be fraught with difficulties due to airway hyperreactivity, need to avoid culprit drugs and possibility of biphasic reaction if epinephrine is not administered on time. We describe perioperative management of three cases with history of allergies and their implications.

Evolution of the medical devices for the protection of healthcare workers. Prevention of hemocontact infections in patients with an uncertain status

Background. Personal protective equipment (PPE) is an item of clothing designed to protect healthcare workers (HCW) or others from infection. PPE includes gloves, masks, gowns, respirators, goggles, face shields, headgear, boot covers, rubber shoes, and more.&#x0D; Objective. To describe the evolution of medical devices for HCW protection.&#x0D; Materials and methods. Review of literature data on this issue.&#x0D; Results and discussion. Medical gloves are divided into sterile and non-sterile. The purpose of wearing non-sterile gloves is to prevent contamination of the hands of HCW with microorganisms. They should be worn when there is a risk of contact with blood or other body fluids, patient secretions, or contaminated equipment. Gloves do not protect against contamination and after their use it is still necessary to treat hands with antiseptic. Latex gloves have good elasticity and flexibility, are convenient and anatomically suitable for hands, have a good sensitivity to touch. However, they can cause allergies or skin irritation. Latex allergy is the most common cause of perioperative anaphylaxis in children. It is recommended to use powder-free gloves. Nitrile gloves for examination manufactured by “Yuria-Pharm” are characterized by high toughness, elongated cuff, and special texture facilitating holding the instruments. Surgical masks consist of three layers of thermoplastic polymer located between the layers of nonwoven fabric. They are designed to protect against pathogens (mainly bacteria) transmitted in large droplets (&gt;5 μm). The Cochrane review did not show any convincing effect of wearing of surgical masks on reducing the risk of infectious complications during sterile surgical procedures. WHO recommends wearing surgical masks to prevent the transmission of coronavirus disease (COVID-19). N95 or FFP3 class respirators are recommended for aerosol-generating procedures (tracheal intubation, bronchoscopy) and for dangerous infections. N95 respirators are the standard for working with patients with COVID-19 in USA. They can be with a valve or without it. These respirators consist of thermoplastic polymer and nonwoven fabric and filter 95 % of particles sized ≥0.3 μm. They should tightly fit to the face and be tested for leaks before the contact with patient. A similar tactic should be used when wearing FFP3 respirator. Valve respirators are easier to use because the presence of a valve facilitates exhalation. The valve also increases comfort and prevents excessive accumulation of moisture under the respirator. Such respirators do not filter the exhaled air, so they do not protect others from infection. Another field of PPE application is its usage in hematocontact infections caused by hepatitis B/C virus and human immunodeficiency virus. The risk of HCW infection is associated with pricks, cuts, contact with the patient’s body fluids, and any invasive diagnostic or treatment procedures. The risk of patient’s infection is present in case of the improper instruments sterilization, use of non-sterile infusion solutions, transfusion of blood and its components, transplantation, and contact with biological fluids of the infected HCW. To reduce the risk of HCW infection, always wear gloves if there is a risk of contact with blood or other body fluids; never put the cap on the needle after using it; always keep a container for sharp objects on hand; carry out the necessary vaccinations; use PPE and safety needles, scalpels and syringes.&#x0D; Conclusions. 1. Wearing masks reduces the risk of COVID-19 transmission. 2. During aerosol-generating procedures it is necessary to use all available PPE. 3. When wearing a respirator, it is advisable to check its tightness. 4. The number of extra injections should be minimized.

Incidence of and risk factors for perioperative or periprocedural anaphylaxis in the United States from 2005 to 2014

BackgroundThe estimated worldwide incidence of perioperative or periprocedural anaphylaxis (PA) is between 1 in 1250 and 1 in 20,000 procedures. ObjectiveTo evaluate the incidence of PA in the United States and compare patient characteristics and underlying risk factors using a large national database. MethodsUsing deidentified data from the nationwide inpatient sample from 2005 to 2014, we identified cases of PA through the International Classification of Diseases, Ninth Revision, Clinical Modification codes and conducted a retrospective analysis. ResultsAmong 35,647,347 surgeries and procedures, there were 5458 (0.015%) PA cases identified. The incidence of PA was 15.3 cases per 100,000 procedures. When compared with controls, PA cases had an increased mortality (3.4% vs 1.4%; P < .001), median length of stay (5 vs 3 days; P < .001), and median hospital cost ($45,155 vs $24,734; P < .001). The age group between 18 and 34 years (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.13-1.58; P < .001) and female sex (OR, 1.40; 95% CI, 1.31-1.49; P < .001) were associated with increased odds of PA. Transplant (OR, 3.35; 95% CI, 2.59-4.34; P < .001), hematologic (OR, 1.63; 95% CI, 1.30-2.05; P < .001), vascular (OR, 1.49; 95% CI, 1.30-1.67; P < .001), and cardiac (OR, 1.47; 95% CI, 1.30-1.67; P < .001) procedures were at increased risk for PA. Several comorbidities were associated with PA including chronic pulmonary disease (OR, 1.41; 95% CI, 1.31-1.51; P < .001). ConclusionThe incidence of PA is 1 in 6531 procedures, with a mortality of 1 in 191,652 procedures. PA has worsening outcomes compared with controls. The risk factors of PA include age, sex, procedure type, and comorbidities.

A survey of anesthetists’ experience and perspectives of perioperative anaphylaxis at an Australian tertiary hospital

Background : Anaphylaxis is a life-threatening emergency that requires prompt recognition and institution of life-saving therapy. Perioperative Anaphylaxis Management Guidelines have been developed by the Australian and New Zealand College of Anaesthetists and Australian and New Zealand Anaesthetic Allergy Group and anesthetic societies worldwide to facilitate diagnosis and management of this rare, but severe complication. Objectives : To perform a cross-sectional survey of the anesthetists’ experience of perioperative anaphylaxis at a single centre and its effect on their practice. Design : Survey questionnaire constructed in Survey Monkey® and sent via e-mail link to all anesthetists. This questionnaire included qualitative and quantitative questions. Setting : Royal Brisbane and Women’s Hospital, a tertiary referral hospital in Queensland. Methods : Anesthetic specialists and provisional fellows at The Royal Brisbane and Women’s Hospital were surveyed using an online platform regarding their experiences of managing anaphylaxis, referral for testing, formal incident reporting and knowledge of existing departmental protocol. We also asked if their experience of anaphylaxis modified their clinical practice. Results : Forty-five out of 102 (44%) of the specialists and provisional fellows surveyed responded. Of these, 17 (38%) had been involved as primary anesthetist and 20 (44.5%) indirectly in at least one suspected case of perioperative anaphylaxis in the past 12-months. Most anesthetists were aware of the resources available in this crisis and appropriate referral for testing had occurred. There was poor local and national reporting of anaphylaxis as a critical incident. Conclusion : A large percentage of the anesthetists surveyed had seen a case of perioperative anaphylaxis in the past year. Managing this life-threatening event has led to practice change for many anesthetists. There is a requirement for further education around incident reporting.

Incidence of and risk factors for perioperative and periprocedural anaphylaxis in the United States

Incidence of and risk factors for perioperative and periprocedural anaphylaxis in the United States

Mast cell activation test in chlorhexidine allergy: a proof of concept

BackgroundImmediate drug hypersensitivity reactions are an increasing public health issue and a frequent cause of life-threatening anaphylaxis. Conventional confirmatory testing include skin tests and, for a few drugs, quantification of drug-specific immunoglobulin E (IgE) antibodies. However, none of these tests are absolutely predictive for the clinical outcome, and can yield false-negative and false-positive results. We performed a proof-of-concept study to assess whether a mast cell activation test could improve diagnosis of IgE-mediated chlorhexidine hypersensitivity, a common cause of perioperative anaphylaxis. MethodsHuman mast cells were generated from CD34+ progenitor cells and sensitised with patients' sera to become IgE+ human mast cells (dMCIgE+), and then incubated with chlorhexidine to assess degranulation. We compared the diagnostic performance of this mast cell activation test with serum from patients with and without positive skin test and basophil activation test to chlorhexidine. ResultsIn dMC sensitised with sera from patients with a positive skin test and basophil activation test to chlorhexidine showed drug-specific and concentration-dependent degranulation upon stimulation with chlorhexidine, determined by surface upregulation of the degranulation marker CD63. In contrast, dMC sensitised with sera from patients with a negative skin test and basophil activation test to chlorhexidine were unresponsive in the mast cell activation test. ConclusionsOur study suggests that the mast cell activation test can be used to diagnose IgE/FcεRI-dependent immediate drug hypersensitivity reactions. It also shows potential to assess the clinical relevance of drug-specific IgE antibodies in their ability to elicit mast cell degranulation, and therefore discriminate between allergy and sensitisation. Extended studies are required to verify whether this technique can be used in other causes of perioperative anaphylaxis.

Dobutamine-Induced Perioperative Anaphylaxis in a Dog

Dobutamine-Induced Perioperative Anaphylaxis in a Dog

Perioperative anaphylaxis: diagnostic challenges and management.

Perioperative hypersensitivity reactions can pose diagnostic and management challenges for the anaesthetist. Difficulties in diagnosing hypersensitivity reactions in the perioperative setting are highlighted and recommendations from recent guidelines on the acute management of life-threatening anaphylaxis are presented. Anaesthetists play a key role in investigating perioperative hypersensitivity reactions. During a suspected perioperative hypersensitivity event, a serum tryptase level should be measured to help with subsequent allergy investigation. Moreover, anaesthetists can ensure that a high-quality referral is made to allergy clinics by providing thorough documentation of the events, detailing symptoms, treatments, and the chronology of drug administrations. Perioperative hypersensitivity reactions are rare but can be life-threatening. A high index of suspicion should be maintained for their successful management. Whenever a perioperative hypersensitivity reaction is suspected, close collaboration between anaesthetist and the allergy team investigating the patient is paramount, in order for the patient to be appropriately investigated and have an uneventful anaesthetic in the future.

Perioperative Severe Anaphylaxis to Paracetamol in a Child.

The data on perioperative anaphylaxis (PA) in children is limited and usually reported with neuromuscular blocking agents and antibiotics. However we present a first pediatric case who developed PA with paracetamol unlike the literature.

Interpreting the results of early skin tests after perioperative anaphylaxis requires special attention: a case report and review of literature

Skin tests are the gold standard for detecting the culprit drug of anaphylaxis, and should ideally be performed after an interval of 4–6 weeks after the reaction to avoid false-negative results. However, when re-operation cannot be delayed and early allergy tests are necessary, special attention is required during subsequent anesthesia, because early skin tests tend to produce false-negative results. This report presents a case of rocuronium-induced anaphylaxis in which early skin tests showed negative results for all the drugs tested. The second anesthesia was safely performed by avoiding all the drugs used for the first anesthesia. Ultimately, skin tests and basophil activation tests (BATs) performed after re-operation demonstrated rocuronium as the drug responsible for anaphylaxis. We recommend performing BATs in addition to skin tests to improve the accuracy of diagnosis of anaphylaxis. In this report, we also discuss interpretation of the results of early skin tests and subsequent selection of drugs for anesthesia. After postponement of surgery due to anaphylaxis, we are often required to perform allergy tests at an early stage if re-operation cannot be delayed. In such cases, skin test results alone should not be used to guide subsequent anesthesia management to avoid recurrent anaphylaxis.

Multiple drug allergies: Recommendations for perioperative management.

Life-threatening hypersensitivity reactions are more likely to occur in patients with a history of allergy, atopy, or asthma. Hence, in a patient who presented with a history of multiple drug allergies (MDA), an allergological assessment should be performed prior to surgical procedure. Drug allergies, being one of the causes of catastrophic events occurring in the perioperative period, are of major concern to anesthesiologists. Neuromuscular blocking agents are regularly used during anesthesia and are one of the most common causes of perioperative anaphylaxis. They are estimated to be responsible for 50%-70% of perioperative hypersensitivity reactions. Antibiotics and latex represent the next two groups of drug allergy. Allergic reactions to propofol are rare with an incidence of 1:60,000 exposures. Although intraoperative drug anaphylaxis is rare, it contributes to 4.3% of deaths occurring during general anesthesia. These recommendations discuss pathophysiology of MDA, preoperative evaluation, and anesthesia considerations as well as the prevention and management of allergic reactions in anesthetized patients with a history of MDA.

A novel MRGPRX2-targeting antagonistic DNA aptamer inhibits histamine release and prevents mast cell-mediated anaphylaxis

Anaphylaxis during general anaesthesia is a significant clinical challenge for anaesthesiologists. Approximately 50% of perioperative anaphylaxis cases lack the presence of specific IgE antibodies. Mas-related G-protein coupled receptor X2 (MRGPRX2) in humans and its mouse orthologue Mas-related G-protein coupled receptor B2 (Mrgprb2) are crucial receptors in non-IgE-dependent histamine release. Anaesthetics such as rocuronium and atracurium cause perioperative anaphylaxis by activating histamine release via the Mrgprb2 pathway. We hypothesized that antagonistic DNA aptamers that target MRGPRX2 can prevent perioperative anaphylaxis. Selection of a DNA aptamer that specifically binds MRGPRX2 was achieved by using our modified Systematic Evolution of Ligands by Exponential enrichment (SELEX) approach. Our SELEX process used MRGPRX2-proteoliposomes synthesised by a wheat germ cell-free system as templates. The activity of the selected aptamer to inhibit histamine release from MRGPRX2-activated mast cells and in an anaphylaxis rat model transplanted with this cell line was examined. Our selection process identified aptamer-X35 with the sequence 5′-ATGACCATGACCCTCCACACTGTAGGCACCACGGGTCCCTGGCAGTTAAAAGTACGTTTGTCAGACTGTGGCAGGGAAACA-3'. In silico 2D modelling of aptamer-X35 revealed a structure with a small loop and a long stem. Aptamer-X35 inhibited histamine release from mast cells by 70%. Subcutaneous injection of 30 nmol of aptamer-X35 inhibited the anaphylactic reaction in the rat anaphylaxis model.This study demonstrated that aptamer-X35 selected by the modified SELEX approach reduced histamine release by inhibiting the MRGPRX2 pathway. Overall, our findings establish aptamer-X35 as a potential therapeutic candidate against perioperative anaphylaxis.

Perioperative anaphylaxis and investigations: a local study in Hong Kong

Data on local intraoperative anaphylaxis in Hong Kong is scarce, with few reviews available. We aimed to study the characteristics, presentations and workup results of cases referred to a local allergy clinic. A retrospective review was performed of patient referrals and workup results for suspected intraoperative anaphylaxis at Queen Mary Hospital drug allergy clinic in 2012-2016. Tryptase was checked in only 81.7% (49/60) of the cases, most of which showed elevation (71.4%, 35/49). Among the 59 patients who received a workup, 47 (79.7%) showed positive findings, with a particularly high yield in the tryptase-positive subgroup (88.6%, 31/35). Among the 54 patients who consented to skin tests (the most sensitive investigation), 43 (79.6%) cases were positive. Overall, neuromuscular blockers were the commonest cause (25.0%, 15/60) of intraoperative anaphylaxis, while antibiotics ranked second (23.3%, 14/60). The timing of reactions was an important indication of potential allergens. For example, the majority of the neuromuscular blocker allergies occurred during the induction phase, while all gelofusine allergic events were in the maintenance phase of anaesthesia. 13 (21.7%) out of 60 cases received subsequent general anaesthesia procedures, with no recurrence of allergic reactions. Proper workup after an intraoperative anaphylactic event has a fairly good chance of identifying the causative allergen. These results are useful for patient management and the planning of subsequent anaesthetic procedures.