Perioperative Hypersensitivity Research Articles

Perioperative Hypersensitivity Evaluation: Too-Often Overlooked but Effective at Promoting the Safe Passage of Future Procedures

Perioperative Hypersensitivity Evaluation: Too-Often Overlooked but Effective at Promoting the Safe Passage of Future Procedures

Perioperative hypersensitivity in children: A prospective multidisciplinary study.

There are few studies of perioperative hypersensitivity reactions in children. The diagnosis of perioperative hypersensitivity reactions may be under estimated because it is difficult to recognize the reactions. Anaphylaxis may go unnoticed because of patient unconsciousness. Urticaria may be missed due to sterile drapes. The aim of this study was to prospectively evaluate perioperative hypersensitivity reactions. In this prospective study, patients with suspected perioperative hypersensitivity reactions aged 0-18 years who underwent surgery at the Department of Pediatric Surgery, Cerrahpasa Faculty of Medicine, between 2019 and 2021 were investigated. Suspected reactions in the perioperative period were graded according to the Ring and Messmer scale. Patients with suspected reactions were examined 4-6 weeks after the reaction. If necessary, specific IgE and basophil activation tests were performed. Reactions of grades III-IV were considered anaphylaxis. If one test modality was strongly positive and there was a relevant time point or repeated allergic reactions, or at least two test modalities were positive, hypersensitivity was confirmed. In all patients, serum tryptase levels were analyzed at the time of the reaction, 2 h after the reaction, and 4-6 weeks after the reaction as part of the allergic evaluation. A total of 29 patients (8 female, 21 male) suspected of having an intraoperative reaction during the study were included in the analysis. Perioperative hypersensitivity reactions were noted in 1 patient. The incidence of perioperative hypersensitivity reactions was reported to be 0.03% (n = 1/2861). While anaphylaxis was confirmed in 1 patient, 5 patients were considered possible anaphylaxis cases. Perioperative hypersensitivity reactions can be life-threatening and may recur with further administration. Collaboration between pediatric surgeons, anesthesiologists, and allergists can prevent further reactions. All suspected cases should be evaluated by an experienced allergist soon after the initial reaction.

Investigating the optimal diagnostic value of histamine for diagnosing perioperative hypersensitivity: a prospective, observational study.

Although several guidelines recommend measuring blood tryptase and histamine concentrations to diagnose perioperative anaphylaxis (POA), tryptase measurement is more common. The appropriate timing of blood collection and the diagnostic threshold for histamine measurement are still controversial. To address these issues, histamine concentrations in patients with anaphylaxis and those with anaphylaxis-uncertain were compared in our previous study, the Japanese Epidemiologic Study for Perioperative Anaphylaxis (JESPA). However, because we could not rule out the possibility that the anaphylactic-uncertain group included anaphylactic patients, histamine concentrations were measured in patients who underwent general anesthesia with no complications as controls in the present study. Histamine levels were measured at anesthesia induction (baseline), 30min (first point), and 2h (second point) after the start of surgery in 30 control patients. Histamine concentrations in controls were lower than in patients with POA in JESPA at the first and second points. At the first point, a threshold of 1.5ng/ml resulted in sensitivity of 77% and specificity of 100%. A threshold of 1.1ng/ml at the second point resulted in sensitivity of 67% and specificity of 87%. Measurement of histamine concentrations within two hours after symptom onset might help diagnose POA.

Comparison of the passive mast cell activation test with the basophil activation test for diagnosis of perioperative rocuronium hypersensitivity

BackgroundRocuronium is a major cause of perioperative hypersensitivity (POH). Skin tests (STs) and quantification of specific immunoglobulin E antibodies (sIgEs) can yield incongruent results. In such difficult cases, the basophil activation test (BAT) can be helpful. Here, we evaluated the passive mast cell activation test (pMAT) as a substitute of BAT as part of the diagnostic tests for rocuronium allergy. MethodsSera from patients with a suspected POH reaction potentially related to rocuronium were included. All patients had a complete diagnostic investigation, including STs, quantification of sIgEs to morphine and rocuronium, and BAT. For execution of pMAT, human mast cells were generated from healthy donor peripheral blood CD34+ progenitor cells and sensitised overnight with patient sera. ResultsIn total, 90 sera were studied: 41 from ST+sIgE+ patients, 13 from ST–sIgE– patients, 20 from ST+sIgE– patients, and 16 from ST–sIgE+ patients. According to BAT results, patients were further allocated into subgroups. Of the 38 BAT+ patients, 25 (66%) showed a positive pMAT as well. Of the 44 BAT– patients, 43 (98%) also showed a negative pMAT. Mast cells that were not passively sensitised did not respond to rocuronium. ConclusionsWe show that the pMAT, in many cases, can substitute for BAT in the diagnosis of rocuronium hypersensitivity and advance diagnosis in difficult cases with uncertain ST or sIgE results when BAT is not locally available.

Incidence of perioperative hypersensitivity reactions: Asingle-center, prospective, US cohort experience.

A previous study, using administrative data, reported an incidence of perioperative anaphylaxis (POA) of 1:6537 procedures in the United States. We sought to determine the incidence of POA in a prospective US cohort. Adult participants undergoing a procedure at a single tertiary care center were studied prospectively between April 2018 and January 2022. Subinvestigators recorded vital signs and skin checks preoperatively, 15 minutes into induction, and hourly thereafter until 1 hour into the postoperative period. If participants developed an adverse reaction, additional variables were documented: causal agent(s) exposure, type of nonallergic adverse reaction, Sixth National Audit Project severity score, evidence of mast cell activation by serum acute and baseline tryptase pairing, Allergy consult, and causal agent identification. Among 939 procedures (mean age, 59.25± 14.78 years; 58% females; 87% White), there were 12 (1.3%) cases with an identified adverse reaction. Nine cases were classified as nonhypersensitivity adverse reactions (1%) and 3 as possible hypersensitivity reactions (0.3%); 1 case was classified as suspected perioperative hypersensitivity and 2 as POA (0.2%). Both POA cases were males, had previous procedures, had evidence of mast cell activation, had a Sixth National Audit Project score of 3, and were referred to Allergy for further evaluation. There were 9 participants who developed a nonhypersensitivity adverse reaction: relative overdose of anesthetic (n= 6), transient rash (n= 2), and isolated bronchospasm (n= 1). All transient rashes were observed during undraping protocol. In our prospective study, the incidence of POA is 1:470 procedures. Our study suggests that the incidence of POA may be higher than previously reported.

Perioperative Hypersensitivity Evaluation and Management: A Practical Approach

Perioperative Hypersensitivity Evaluation and Management: A Practical Approach

Allergy identification for neurosurgical patients: updates for management.

Allergic reactions in neurosurgical procedures are uncommon, but they are detrimental to a patient's prognosis and recovery. By synthesizing data collected from other surgical fields, possible triggers and alternatives have been identified. Current treatment guidelines involve stabilizing the patient in emergency situations, symptom management, and identification of causative allergens. Preoperative allergy screening is uncommon due to the low prevalence of perioperative hypersensitivity reactions. However, preoperative questionnaire screening can identify when preoperative allergy screening, premedication, or use of a material alternative is necessary. Greater emphasis on material alternatives, increased preoperative screening, and more data can improve the prognosis of neurosurgical patients at risk of perioperative allergic complications.

Perioperative Hypersensitivity Evaluation and Management: A Practical Approach

Perioperative hypersensitivity (POH) is an uncommon, potentially life-threatening event. Identification of POH can be difficult given the lack of familiarity, physiological effects of anesthesia, draping of the patient during surgery, and potential nonimmunological factors contributing to signs and symptoms. Given the unique nature and large number of medications administered in the perioperative setting, evaluation of POH can be challenging. In this paper, we present a practical approach to management with an emphasis on understanding what happens in the operating room, the overlap of signs and symptoms between nonimmunological and immunological reactions, acute management, and subsequent evaluation. In addition, we provide a strategy for further review of an initially negative evaluation and emphasize the importance of establishing management plans for the patient as well as providing recommendations to the medical, anesthesia, and surgical teams for future surgeries. A critical factor for successful management at all points in the process is a close collaboration between the anesthesia and the allergy teams.

Diagnostic value of a medical algorithm for investigation of perioperative hypersensitivity reactions.

Evaluation of perioperative hypersensitivity (POH) is challenging, and accurate screening tools are needed to optimize the diagnostic process. We aimed to assess and validate the diagnostic value of a published algorithm (using tryptase and clinical presentation) to identify appropriate individuals for further testing for IgE-mediated POH. We analysed the clinical presentation (tryptase elevation, cardiovascular, respiratory, skin involvement) of patients proceeding to testing for possible IgE-mediated POH at a single tertiary referral centre, relative to subsequent skin testing and specific IgE results. Clinical presentations by drug class were also determined. In 293 consecutive patients, the use of a published algorithm based on one or more of; (i) defined increase in serum tryptase, (ii) involvement of at least two-organ systems, or (iii) presentation with new urticaria and/or angioedema; was highly sensitive [98.8% (CI95: 95.7-99.9%)] but less specific [34.6% (CI95: 25.7-44.4%)] in identifying patients testing positive on skin testing and/or specific IgE. Presentation with cardiovascular symptoms was also sensitive [89.8%(CI95: 84.2-94.0%)], while the combination of respiratory symptoms and increased tryptase was most specific [85.9%(CI95:76.6-92.5%)]. Respiratory involvement was more common in neuromuscular blocking agent allergy, while urticaria/angioedema was more common in antibiotic allergy. The published algorithm (of tryptase rise, two-organ involvement or new urticaria/angioedema) is highly sensitive, and appropriate as a screening tool to identify patients suitable for testing for IgE-mediated POH.

Agreement of a clinical scoring system with allergic anaphylaxis in suspected perioperative hypersensitivity reactions: prospective validation of a new tool

BackgroundA clinical scoring system to estimate the likelihood that a reaction represents a perioperative immediate hypersensitivity reaction has been devised using a Delphi consensus process. Agreement of this clinical scoring system with the outcome of allergological assessment would allow the use of this tool in post-resuscitation and subsequent management of suspected perioperative immediate hypersensitivity reaction and potentially as a new standard reference for clinical investigations. MethodsWe prospectively scored 301 cases of suspected perioperative immediate hypersensitivity reaction according to the Hypersensitivity Clinical Scoring Scheme. Classification of cases was by allergological workup based on immediate and delayed investigations. The discrimination and calibration of the Hypersensitivity Clinical Scoring Scheme was compared with results from an expert panel of allergologists, skin testing, mast cell tryptase ratios, and specific IgE assays, as was agreement by Cohen's kappa coefficient. ResultsThe Hypersensitivity Clinical Scoring Scheme predicted cases of allergic perioperative immediate hypersensitivity reaction with comparable discrimination to an expert panel, mast cell tryptase formula, and specific IgE assays in anaphylaxis to neuromuscular blocking drugs. Using a score threshold of 15 or greater to indicate allergic perioperative immediate hypersensitivity reaction, the sensitivity was 88.9%, with a specificity of 79.4%. Prospectively, the Hypersensitivity Clinical Scoring Scheme correctly classified a greater number of subjects than the expert panel and the optimal post hoc binary logistic regression model (86% vs 85% vs 84%), however it was inferior to skin testing. ConclusionThe Hypersensitivity Clinical Scoring Scheme predicts allergic perioperative immediate hypersensitivity using features of the acute syndrome. This approach could guide algorithms for the post-resuscitative management of suspected perioperative immediate hypersensitivity, and identify patients requiring drug provocation challenge.

Anesthetic management of allergic hypersensitivity during a surgical procedure: A case report and literature review

Introduction: Perioperative anaphylaxis is a rare but serious, life-threatening condition that presents challenges in diagnosis and management. The incidence of severe perioperative reactions is estimated to be approximately 1:7,000–10,000. Case report: A 75-year-old patient underwent a surgical procedure due to adhesions of previous surgeries. She had a serious anaphylactic reaction in the intraoperative period, which was quickly addressed with fluid and adrenaline administration. Discussion: Proper management involves both immediate stabilization of the patient and identification of the causing agent. This identification is essential to avoid the recurrence of the event in other surgeries. A previous history of perioperative hypersensitivity reaction is the main risk factor for anaphylaxis.

This Month in Anesthesiology

This Month in Anesthesiology

Recognition, treatment, and prevention of perioperative anaphylaxis: a narrative review

<abstract> <p>Perioperative anaphylaxis events are allergic reactions which occur in the perioperative period when patients are exposed to a multitude of agents, received anesthesia, and undergo a procedure. These reactions are rare and can be life-threatening, with the common signs being hypotension, hypoxia, elevated airway pressures and urticaria. Perioperative anaphylaxis can be mediated by immunoglobulin E (IgE) or non-IgE mechanisms. Globally, the incidence of reactions and frequency of specific triggers varies considerably. Perioperative anaphylaxis events often result in discontinuation of surgery, extended hospital stays, unanticipated intensive care admissions and increased morbidity and mortality. Common causative agents include neuromuscular blocking agents (NMBA's), beta-lactam antibiotics, chlorhexidine, and latex. The primary treatment of perioperative anaphylaxis is removal of the offending agent, epinephrine, and adequate fluid resuscitation. Post-operative workup involves serial serum tryptase measurements, skin testing, in-vitro testing and challenges to determine the culprit agent. Several countries including the UK, Spain, France, Australia, and New Zealand have established guidelines, reporting systems, and specialized clinics dedicated to perioperative hypersensitivity reactions. Future efforts should address diagnostic challenges as well as increasing awareness of other perioperative anaphylaxis triggers. This narrative review will provide an overview of the epidemiology, diagnosis, management, and prevention of perioperative anaphylaxis events.</p> </abstract>

Specific and non-specific perioperative drug reactions

Perioperative hypersensitivity reactions pose a complex clinical problem. The combination of surgical intervention, the simultaneous action of several drugs, including anesthesia, and comorbidity of the patient complicates the assessment of perioperative urgent events. To date, there are no clear international and national recommendations on standardized preoperative examinations of patients to prevent drug allergies. The article presents modern data on the mechanisms of causes and the possibility of preventing perioperative allergic reactions.

Quality, safety and efficacy in a communication protocol between the anesthesiologist and the allergist in perioperative hypersensitivity reactions

Quality, safety and efficacy in a communication protocol between the anesthesiologist and the allergist in perioperative hypersensitivity reactions

Diagnostic performance of serial serum total tryptase measurement to differentiate positive from negative allergy testing among patients with suspected perioperative hypersensitivity.

Serum total tryptase has been shown to increase during acute allergic reactions (acute tryptase, TA ); however, few studies have investigated the values of TA or a combination of TA and baseline tryptase (TB ) to discriminate positive from negative testing in perioperative hypersensitivity reaction (POH) allergy work-up. The aim of this study was to determine the diagnostic performance of TA in order to differentiate positive from negative allergy testing suspected POH and analyse the diagnostic performance of serial tryptase levels using several formulas. All patients from the University hospital of Montpellier and Strasbourg, France, who presented with suspected POH and underwent complete drug allergy work-up between March 2011 and December 2019 with available TA and TB were included. Four formulas, including a change in TA >11 (F1), or >2+1.2×TB (F2), or >3+TB (F3), or >120%TB (F4), were applied. One hundred and sixty-two patients were included, and 131 of them (80.8%) had Grade III or IV reactions. Ninety patients had positive allergy testing. The optimal cut-off value of TA to distinguish positive from negative allergy testing patients was 9.8μg/L with an AUC of 0.817 (95% CI: 0.752-0.882, p<.001). The 93% PPV threshold for TA was 33μg/L (95.8% specificity). Paired tryptase levels according to formulas F2 and F3 yielded the highest Youden index (0.54 and 0.53, respectively). The optimal cut-off point for TA for distinguishing positive from negative allergy testing suspected POH was 9.8μg/L. TA value of 33μg/L was required to achieve >90% PPV.

Reliability of Early and Late Testing for Suspected Perioperative Hypersensitivity

The optimal timing of diagnostic testing for perioperative hypersensitivity (POH) remains unknown. It has been recommended that investigation is best carried out at least 4 to 6 weeks after the event. On the other hand, guidelines discourage the use of invitro tests later than 3 years after the index reaction. This retrospective study aimed to assess the reliability of early and late skin tests (STs). It also attempted to verify whether discouraging late exvivo and invitro tests is substantiated. For the first aim, patients were stratified over three epochs: an early timing group, with investigations performed within 6 weeks; a recommended timing group, with tests performed between 6 weeks and 6 months; and a late timing group, tested later than 6 months after the event. For the second study purpose, we studied the reliability of specific IgE quantification and basophil activation test rocuronium within 6 weeks and after 3 years in patients who experienced an ST-proven POH to rocuronium. A total of 677 patients were included. Based on a positive ST result, a causative agent was found in 74.2% of the early timing group, 62.6% of the recommended timing group, and 50% of the late timing group. A positive specific IgE for rocuronium or morphine was found in 80% of patients tested within 6 weeks, 63% of patients tested between 6 weeks and 3 years, and 50% of patients tested more than 3 years after the event. A positive basophil activation test was found in 83.3%, 51%, and 20%, respectively, of patients. Our data confirm that evaluation of drug allergy for suspected POH can be performed before 6 weeks after the event, and there is no maximal upper time limit disclosing exvivo and invitro testing.

The passively sensitized mast cell activation test is a reliable diagnostic for chlorhexidine allergy

Chlorhexidine (CHX) is a synthetic cationic biguanide that harbors 2 biguanide groups both linked to a terminal 4-chlorophenyl group with the resultant chlorguanide structures connected by a hexamethylene bridge. Chlorhexidine can cause life-threatening anaphylaxis due to specific immunoglobulin E (sIgE) antibody–mediated activation of basophils and mast cells (MCs) and is generally associated with mucosal or parenteral exposure. Although it was originally thought to be very rare, in some countries, CHX has now become an important—often hidden and overlooked—cause of perioperative hypersensitivity (POH).

Mast Cell Activation During Suspected Perioperative Hypersensitivity: A Need for Paired Samples Analysis

Perioperative hypersensitivity (POH) reactions constitute a significant clinical and diagnostic challenge. A transient increase in serum tryptase during POH reflects mast cell activation (MCA) and helps to recognize an underlying hypersensitivity mechanism. To determine the diagnostic performance of different tryptase decision thresholds based on single and paired measurements to document MCA in suspected POH. Acute serum tryptase (aST) and baseline serum tryptase (bST) samples were obtained from patients referred to our outpatients clinic because of clinical POH. Tryptase samples from controls were obtained before induction (Tt0) and 1.5 hours after induction (Tt1) in uneventful anesthesia. Different cutoff points for tryptase increase over bST and the percentage increase in tryptase (%T) were calculated and compared with existing thresholds: aST > [1.2× (bST)+ 2] (consensus formula), aST higher than 11.4 ng/mL, and aST higher than 14 ng/mL. Patients with POH had higher bST and aST levels compared with controls (respectively 5.15 vs 2.28 ng/mL for bST and 20.30 vs 1.92 ng/mL for aST). The consensus formula and a tryptase increase over bST of greater than or equal to 3.2 ng/mL held the highest accuracies to document MCA in POH (respectively 81% and 82%). A bST of higher than 8 ng/mL was present in 4% of controls, 5% of patients with grade 1 POH, 24% of patients with grade 2 POH, 15% of patients with grade 3 POH, and 17% of patients with grade 4 POH. Our data endorse the consensus formula for detection of MCA in POH. Furthermore, it shows that a bST of higher than 8 ng/mL was associated with occurrence of anaphylaxis.

Comparison of immediate hypersensitivity reactions to preoperative antibiotics in patients labeled as penicillin allergic

BackgroundCefazolin is routinely recommended as the first-line agent for surgical antibiotic prophylaxis because it prevents more surgical site infections than second-line antibiotics. Clinicians often avoid administering cefazolin to patients who are labeled as penicillin allergic due to concerns of cross-reactivity. The aim of this study was to compare the incidence of hypersensitivity reactions between cefazolin and the second-line antibiotics vancomycin and clindamycin. MethodsThis retrospective study included patients who were labeled as penicillin allergic and received either cefazolin, clindamycin, or vancomycin as preoperative antibiotics. The primary outcome was intraoperative hypersensitivity reactions. ResultsA total of 734 surgical procedures in 690 patients were included. Fifteen immediate hypersensitivity reactions were identified. Probable hypersensitivity reactions occurred in 3 (0.9%) patients in the cefazolin group, 4 (1.4%) in the clindamycin group, and 1 (1.1%) in the vancomycin group. Seven of 8 patients reported allergies to additional medications beyond penicillin. There were seven cases of possible hypersensitivity reactions, 3 (0.9%) in the cefazolin group, 1 (1.1%) in the vancomycin group, and 3 (1.0%) in the clindamycin group. ConclusionOur data suggest that perioperative hypersensitivity reactions are uncommon in patients labeled as penicillin allergic. The frequency of immediate hypersensitivity reactions was not different between patients receiving cefazolin, clindamycin, or vancomycin. Avoiding cefazolin in patients labeled as penicillin allergic may not be warranted.