Preoperative survey to evaluate the patients' allergy list and its relevance to perioperative care.

INTRODUCTION: Perioperative hypersensitivity and allergic reactions can result in significant morbidity and mortality. For routine anesthetic care, allergies are determined from a review of the electronic medical record supplemented by a detailed patient history. Although the electronic medical record is generally assumed to be accurate, it may be that allergies are erroneously listed or not based on sound medical practice. The purpose of the current study is to evaluate allergies listed in the electronic medical record of children presenting for surgery and determine their origin, authenticity, and impact on perioperative care. METHODS: Eligible patients included those presenting for a surgical procedure in the main operating room, who were ≤ 21 years of age, with a drug allergy listed on the EMR. Prior to intraoperative care, an electronic survey questionnaire containing questions related to medication allergies was provided to a guardian or parent. Two anesthesiology physicians reviewed the survey responses to determine the validity of any reported allergies. A second electronic survey was given postoperatively to the attending anesthesiologist to determine whether the documented allergy impacted anesthetic care. RESULTS: The study cohort included 250 patients, ranging in age from 5 to 14 years (median age 9 years). All of the patients had at least one allergy listed on the electronic medical record. Seventy of the 250 patients (28%) had more than one drug allergy listed for a total of 351 medication allergies. The majority of the listed allergies were related to antibiotics including 155 (44%) from the penicillin family, 26 (7%) cephalosporins, 16 (5%) sulfonamides, and 36 (10%) other antimicrobial agents. Other commonly listed allergies were 27 (8%) nonsteroidal anti-inflammatory agents and 15 (4%) opioids. The remaining 76 (22%) included a miscellaneous list of other medications. On further review of the allergies, the survey was completed for 301 medications. After physician review, 135 of 301 (45%) responses were considered consistent with IgE reactions "true allergy," 73 (24%) were deemed less relevant to IgE reactions "unlikely true allergy," and 93 (31%) were not related to IgE reactions "not an allergy." Care alterations during surgery were uncommon regardless of whether the issue was assessed as a true allergy (11%), unlikely to be a true allergy (3%), or not a true allergy (13%). CONCLUSION: A significant portion of the documented allergies in children are not true allergies, but rather recognized adverse effects (apnea from an opioid, renal failure from an NSAIDs) or other nonallergic concerns (gastrointestinal upset such as nausea). Erroneously listed allergies may lead to unnecessary alterations in patient care during perioperative care. A careful analysis of the allergy list on the EMR should be supplemented by a thorough patient history with specific questions related to the drug allergy. Once this is accomplished, the allergy listed should be updated to avoid its erroneous impact on perioperative care.

Non-IgE-mediated hypersensitivity induced by multivitamins containing Tween-80.

Multivitamins have been widely used for years. Adverse reactions, especially hypersensitivity, to multivitamins are becoming noteworthy. However, the classification of hypersensitivity is confusing, and the trigger is unknown. Multivitamins consist of two vials labelled vial 1 containing Tween-80 and vial 2. Multivitamins without Tween-80 were used as a contrast. Behaviouristics, histamine, IgE, and blood pressure of beagle dogs and guinea-pigs were investigated by observation, ELISA and sphygmomanometer, and degranulation and apoptotic of RBL-2H3 cells were assayed by spectrophotometry and flow cytometry. The results showed that dogs suffered from multiorgan anaphylactoid symptoms, and dramatically decreased blood pressure, and high plasma concentrations of histamine after the first administration of multivitamins and multivitamins vial 1, which contains Tween-80, compared to the control, multivitamins vial 2 or multivitamins without Tween-80. In anaphylaxis assay, guinea-pigs did not display any anaphylaxis symptoms and there were no changes in plasma histamine and IgE concentrations in the multivitamins and multivitamins vial 1 groups or in the multivitamins vial 2 and multivitamins without Tween-80 groups except ovalbumin. Compared to the control, the release of ß-hexosaminidase and histamine, and the apoptosis of non-antigen-sensitized RBL-2H3 cells significantly increased in the Tween-80 and multivitamins and multivitamins vial 1 groups in a concentration-dependent manner. However, there was no alteration in multivitamins vial 2 and multivitamins without Tween-80 groups. The results indicate that the hypersensitivity induced by multivitamins may be anaphylactoid reaction, but not anaphylaxis. Multivitamin-induced release of inflammatory factors is triggered by Tween-80 through a non-IgE-mediated pathway.

[Establishment of new evaluation standards for systemic anaphylactoid reactions using mouse model].

The detection of drug-induced anaphylactoid reactions remains a global challenge,still lacking mature and reliable animal models or test methods. Therefore,the purpose of this paper is to explore and establish the test methods and evaluation standards for anaphylactoid reactions that apply to injection drugs. Based on the anaphylactoid reaction symptoms of mice induced by intravenous injection drugs C48/40 and Tween 80,a list of systemic anaphylactoid reaction symptoms in mice was sorted out and an evaluation standard of anaphylactoid reactions symptoms was established by applying symptom intensity coefficient K( that can represent these verity of anaphylactoid reaction symptoms) and its calculation formula Accordingly,histamine,tryptase,and Ig E were selected as blood indicators of anaphylactoid reactions,so that a test method combining symptoms evaluation and blood makers detection was established.This test method could be used to evaluate the characteristics of anaphylactoid reactions: coefficient K,blood histamine levels were highly and positively correlated with C48/80 and Tween 80 dose; The log value of histamine was highly and positively correlated with K; tryptase level may rise,or remain steady,or drop,possibly associated with the characteristics of the tested object and time for blood taking; and Ig E level would drop or remain steady,but it would not rise,which can be clearly distinguished from type I allergic reactions. On this basis,tiohexol,iopromide,paclitaxel,Xuesaitong Injection,Shuanghuanglian Injection and Shengmai Injection were used to investigate the applicability. The testing results showed a high degree of consistency with the actual clinical situation. The results suggest that the method of systemic anaphylaxis test in mice has high sensitivity,specificity and good consistency with clinical practice.It is suggested to be further validated and popularized.

Typical antimicrobials induce mast cell degranulation and anaphylactoid reactions via MRGPRX2 and its murine homologue MRGPRB2.

Mast cells are unique immune cells that function as sentinels in host defence reactions, including immediate hypersensitivity responses and allergic responses. The mast cell-specific receptor named MAS-related G protein-coupled receptor X2 (MRGPRX2) triggers mast-cell degranulation, a key process in anaphylactoid reactions. It is widely observed that antimicrobials can induce pseudo-allergic reactions (i.e. IgE-independent mechanism) with symptoms ranging from skin inflammation to life-threatening systemic anaphylaxis. However, their direct involvement and the mechanisms underlying anaphylactoid reactions caused by antimicrobials have not been demonstrated. Structurally different antimicrobials were screened by Ca2+ imaging using MRGPRX2 overexpressing HEK293 cells. MRGPRX2 related anaphylactoid reactions induced by these components were investigated by body temperature drop and mast cell degranulation assays. We showed that MRGPRX2 is involved in allergic-like reactions to three types of antimicrobials in a dose-dependent manner. However, mast cells lacking the receptor show reduced degranulation. Furthermore, mice without MAS-related G protein-coupled receptor B2 (the orthologous gene of MRGPRX2) exhibited reduced substance-induced inflammation. Interestingly, ß-lactam and antiviral nucleoside analogues did not induce anaphylactic reactions, which were also observed in vitro. These results should alarm many clinicians that such drugs might induce anaphylactoid reactions and provide guidance on safe dosage of these drugs.

Allergic-like contrast media reaction management in children.

The use of contrast materials as part of imaging examinations is common in children of all ages, as these compounds increase image contrast, lesion detection and lesion characterization. Though modern iodinated, gadolinium-based and ultrasound microbubble contrast materials generally are quite safe, acute physiological and allergic-like reactions are possible. The majority of acute contrast reactions in children are mild and self-limited; however, life-threatening reactions can occur. It is our obligation as radiologists to recognize and manage these adverse reactions. The objective of this article is to review the frequency, manifestations and appropriate treatment of acute contrast reactions in the pediatric population.

Harpagoside-induced anaphylactic reaction in an IgE-independent manner both in vitro and in vivo.

BACKGROUND: Harpagoside (HAR) is an active component of Scrophularia ningpoensis (SN), which has anti-inflammatory and anti-immune effects. SN is used widely in China to treat various diseases. Recently, SN has been used as a traditional Chinese medicine injection and used clinically. However, allergic responses to these injections are frequently reported. AIM: We examined whether the main component of SN, HAR, is associated with the allergic reaction to SN. METHODS: This study assessed the effects of HAR in mice and mast cell activation to characterize its anaphylactic effects and underlying mechanisms. Mice hindpaw swelling, serum allergy factor detection, enzyme-linked immunosorbent assays, and degranulation assays were performed to measure allergic mediators both in vivo and in vitro. RESULTS: The present study indicated that HAR induced paw swelling, interleukin-6, inositol triphosphate, tumor necrosis factor-α, and histamine increases in mice. Our in vitro data also showed that HAR induced ß-hexosaminidase, inositol triphosphate, and interleukin-6 release, leading to mast cell degranulation. In contrast, neither C48/80 nor HAR induced local anaphylaxis in STOCK KitW-sh/HNihrJaeBsmJNju mice. CONCLUSIONS: HAR is a potential sensitization compound in SN, and these results provide information for the safe clinical use of SN.

Rapid Desensitization to Overcome Contrast Allergy Prior to Urgent Coronary Angiography.

Allergic reactions to contrast media are a frequently reported complication of coronary angiography. The majority of patients experience mild, self-limited episodes, but in rare cases patients may experience severe, persistent symptoms. A strategy of premedication with corticosteroids and anti-histamines and an optimal selection of contrast agent is almost always successful in averting contrast reactions, yet a select few patients will continue to have breakthrough events. This is a case of recurrent, severe allergy to contrast media despite standard precautions complicating the treatment of non-ST elevation myocardial infarction (NSTEMI). Our patient was successfully managed with a strategy of rapid desensitization to iodinated contrast media achieved by administering progressively incremental doses of the media.

Kounis syndrome, a disease to know: Case report and review of the literature.

The case deals with an anaphylactoid reaction to intravenous ampicillin/sulbactam resulting in cardiogenic syncope and myocardial damage. Symptoms and ECG modifications promptly disappeared after corticosteroids administration. The Kounis syndrome is an acute coronary syndrome, including coronary spasm, acute myocardial infarction and stent thrombosis, resulting from an anaphylactic or anaphylactoid or allergic or hypersensitivity insult. First described in 1991, it can be caused by a lot of substances, particularly antibiotics. The management should be directed to both the allergic reaction and the myocardial damage. The Kounis syndrome is a not rare disease that every physician should know because of the wideness of triggers and the possible fatal evolution if not promptly recognized.

Allergens in red ginseng extract induce the release of mediators associated with anaphylactoid reactions.

BACKGROUND: Anaphylactoid reactions induced by preparations containing red ginseng have been reported. The aim of this study is to evaluate the allergenicity and screen potential allergens in red ginseng extract thoroughly. METHODS: Red ginseng extract (RGE) and different fractions of RGE were prepared and evaluated by measuring the degranulation and viability of rat basophilic leukemia 2H3 (RBL-2H3) cells. Potential allergens were screened by RBL-2H3 cell extraction and allergenicity verified in RBL-2H3 cells, mouse peritoneal mast cells, Laboratory of Allergic Disease 2 (LAD2) human mast cells and mice, respectively. RESULTS: 80% ethanol extract of red ginseng extract induced mast cell degranulation with less cytotoxicity, but 40% ethanol extract could not. Ginsenoside Rd and 20(S)-Rg3 could induce a significant increase in ß-hexosaminidase release, histamine release and translocation of phosphatidylserine in RBL-2H3 cells. Ginsenoside Rd and 20(S)-Rg3 also increased ß-hexosaminidase release and the intracellular Ca2+ concentration in mouse peritoneal mast cells and LAD2 cells. In addition, histamine levels in serum of mice were elevated dose-dependently. CONCLUSIONS: Ginsenoside Rd and 20(S)-Rg3 are potential allergens that induce the release of mediators associated with anaphylactoid reactions. Our study could guide optimization of methods associated with Rd/20(S)-Rg3-containing preparations and establishment of quality standards for safe application of Traditional Chinese Medicines.

Amniotic fluid embolism: Pathophysiology from the perspective of pathology.

Amniotic fluid embolism (AFE) is recognized as a type of syndrome characterized by the abrupt onset of hypoxia, hypotension, seizures, or disseminated intravascular coagulopathy (DIC), occurring during labor, delivery, or immediately postpartum, caused by the inflow of amniotic components into the maternal circulation. AFE is a rare condition but one of the most serious obstetrical complications, resulting in a high mortality rate among pregnant women. Despite earlier recognition and intensive critical management, we often encounter patients who unfortunately do not recover from the exacerbation of AFE-related conditions. A major concern is that there are no effective evidence-based therapies for AFE, because its pathophysiology is still not well understood. This article reviewed AFE, focusing on the pathology and currently proposed pathophysiology.

Immunology of infusion reactions in the treatment of patients with acute lymphoblastic leukemia.

Infusion reactions are potentially dose-limiting adverse events associated with intravenous administration of several common agents used to treat patients with acute lymphoblastic leukemia. True clinical hypersensitivity reactions are antibody-mediated and can occur only after repeated exposure to an antigen. Conversely, anaphylactoid infusion reactions are nonantibody-mediated and often occur on the initial exposure to a drug. Cytokine-release syndrome comprises a subset of nonantibody-mediated infusion reactions associated with the use of monoclonal antibodies and immune therapies. Clinical symptoms of hypersensitivity reactions and nonantibody-mediated infusion reactions heavily overlap and can be difficult to distinguish in practice. Regardless of the underlying mechanism, any infusion reaction can negatively affect treatment efficacy and patient safety. These events require prompt response, and potentially, modification of subsequent therapy.

Clinical course of disseminated intravascular coagulopathy-type amniotic fluid embolism: A report of three cases.

Amniotic fluid embolism (AFE) is a rare complication of pregnancy and its mortality rate is high. There have been few reports of AFE with presence of severe coagulopathy and incoagulable bleeding, and absence of cardiopulmonary symptoms or limited cardiopulmonary symptoms, followed by massive blood loss during delivery. Such cases have been referred to as disseminated intravascular coagulopathy-type AFE, and the characteristics of this condition have been presented previously. Here we report three cases that fulfilled the diagnostic characteristics of disseminated intravascular coagulopathy-type AFE.

A Reliable Method for the Evaluation of the Anaphylactoid Reaction Caused by Injectable Drugs.

Adverse reactions of injectable drugs usually occur at first administration and are closely associated with the dosage and speed of injection. This phenomenon is correlated with the anaphylactoid reaction. However, up to now, study methods based on antigen detection have still not gained wide acceptance and single physiological indicators cannot be utilized to differentiate anaphylactoid reactions from allergic reactions and inflammatory reactions. In this study, a reliable method for the evaluation of anaphylactoid reactions caused by injectable drugs was established by using multiple physiological indicators. We used compound 48/80, ovalbumin and endotoxin as the sensitization agents to induce anaphylactoid, allergic and inflammatory reactions. Different experimental animals (guinea pig and nude rat) and different modes of administration (intramuscular, intravenous and intraperitoneal injection) and different times (15 min, 30 min and 60 min) were evaluated to optimize the study protocol. The results showed that the optimal way to achieve sensitization involved treating guinea pigs with the different agents by intravenous injection for 30 min. Further, seven related humoral factors including 5-HT, SC5b-9, Bb, C4d, IL-6, C3a and histamine were detected by HPLC analysis and ELISA assay to determine their expression level. The results showed that five of them, including 5-HT, SC5b-9, Bb, C4d and IL-6, displayed significant differences between anaphylactoid, allergic and inflammatory reactions, which indicated that their combination could be used to distinguish these three reactions. Then different injectable drugs were used to verify this method and the results showed that the chosen indicators exhibited good correlation with the anaphylactoid reaction which indicated that the established method was both practical and reliable. Our research provides a feasible method for the diagnosis of the serious adverse reactions caused by injectable drugs which could be used in the clinical practice.

[A high content screening method for detection of anaphylactoid reaction of injection formulations].

Anaphylactoid reaction (AR) is the most common adverse reaction of injection formulations, however, there are obvious drawbacks in available methods for AR detection. A novel in vitro detection method for AR was established based on fluorescent labeling and high content screen (HCS) system in present study. With the use of RBL-2H3 cells degranulation model, positive cell count was determined with specific cellular membrane fluorescent dye FM4-64 labeling vesicle recycle, and total cells count was determined with specific nucleus fluorescent dye Hochest 3334, and then the ratio of cells degranulation after drug stimulation was calculated. In order to verify the reliability of this HCS method, positive drug Compound 48/80 was first used to confirm the consistence of HCS method with the traditional ß-hexosaminidase release test and the Evans blue staining ears test in mice. The results showed high consistence between HCS method and traditional testing methods, and the HCS method showed higher sensitivity than the other two tests. Then 30 samples of Danhong injection (DHI) with clinical allergy symptoms further were used to confirm the reliability of this HCS method. The HCS results showed high consistence with the clinical report, and the HCS method had the advantage in reducing the interference by drug color. Therefore, this HCS method is reliable, sensitive, simple and high-throughput method in detection of AR, applicable for the AR evaluation of injection formulations, and can provide guidance for safety of clinical application in clinical practice.

Tween-80 and impurity induce anaphylactoid reaction in zebrafish.

A number of recent reports suspected that Tween-80 in injectable medicines, including traditional Chinese medicine injections could cause life-threatening anaphylactoid reaction, but no sound conclusion was drawn. A drug-induced anaphylactoid reaction is hard to be assayed in vitro and in conventional animal models. In this study, we developed a microplate-based quantitative in vivo zebrafish assay for assessing anaphylactoid reaction and live whole zebrafish mast cell tryptase activity was quantitatively measured at a wavelength of 405 nm using N-benzoyl-dl-arginine p-nitroanilide as a substrate. We assessed 10 batches of Tween-80 solutions from various national and international suppliers and three Tween-80 impurities (ethylene glycol, 2-chloroethanol and hydrogen peroxide) in this model and found that three batches of Tween-80 (nos 2, 20080709 and 20080616) and one Tween-80 impurity, hydrogen peroxide (H2 O2 ), induced anaphylactoid reactions in zebrafish. Furthermore, we found that H2 O2 residue and peroxide value were much higher in Tween-80 samples 2, 20080709 and 20080616. These findings suggest that H2 O2 residue in combination with oxidized fatty acid residues (measured as peroxide value) or more likely the oxidized fatty acid residues in Tween-80 samples, but not Tween-80 itself, may induce anaphylactoid reaction. High-throughput zebrafish tryptase assay developed in this report could be used for assessing safety of Tween-80-containing injectable medicines and potentially for screening novel mast cell-modulating drugs.

Anaphylactoid-like Reaction to Midazolam During Oral and Maxillofacial Surgery.

We experienced a case of life-threatening hypotension and bronchoconstriction associated with edema in a patient undergoing resection of a tumor of the right mandible following intravenous midazolam for induction of general anesthesia. We decided to postpone surgery for further examination of a possible drug-induced allergic reaction, and we rescheduled surgery for 1 week later. After administering H1 and H2 histamine antagonists, we administered a slow induction with sevoflurane in nitrous oxide and oxygen plus intravenous atropine sulfate after performing a test dose injection. We safely induced and maintained anesthesia with nitrous oxide, oxygen, and sevoflurane.

Amniotic fluid embolism: pathophysiology and new strategies for management.

The registry program of amniotic fluid embolism (AFE) in Japan started in 2003. More than 400 hundred clinical diagnosed amniotic fluid embolism has been accumulated. Those data showed that there were two etiologies of AFE: the fetal materials create physical obstructions in the maternal microvessels in various organs, such as the lung; and (ii) the liquids cause an anaphylactoid reaction that leads to pulmonary vasospasm and activation of platelets, white blood cells and/or complements. The clinical findings showed that AFE was characterized mainly by cardiopulmonary collapse, the other involves the presence of disseminated intravascular coagulation (DIC) and atonic bleeding. Zinc coproporphyrin-1, sialyl Tn antigen (STN), complement C3, C4 and interleukin-8 have been used as serum markers of AFE. The levels of zinc coproporphyrin-1 and STN were increased in cardiopulmonary collapse type AFE, and a marked reduction of C3 and C4 was observed in DIC type AFE. At the primary medical institution, initial treatments for shock airway management, vascular management, fluid replacement, administration of anti-DIC therapy such as antithrombin, and administration of fresh frozen plasma should be provided. C1 esterase inhibitor activity in AFE cases was significantly lower than those of normal pregnant women. C1 esterase inhibitor may be a promising candidate of treatment of AFE.

Clinical Case Report: Neonatal Mesenteric Traction Syndrome During Surgery for Congenital Duodenal Stenosis.

Mesenteric traction syndrome (MTS) is a common complication of major abdominal surgery, characterized by flushing, hypotension, and tachycardia. However, its occurrence in neonates has not yet been documented. This report details a neonatal case of MTS that emerged during surgery for congenital duodenal stenosis. The patient was a two-day-old girl, born at 39 weeks and three days of gestation via vaginal delivery, weighing 2708 g. She underwent general anesthesia for the surgery, and continuous IV administration of remifentanil at 0.2 µg/kg/min was commenced minutes before the surgery began. Initially, her arterial pressure was 60-70/40-50 mmHg. However, shortly after bowel manipulation began, her blood pressure rapidly declined to 31/25 mmHg. Concurrently, her heart rate increased from 120 to 170 beats per minute, and she displayed facial and upper body flushing. Arterial blood gas analysis indicated a PaO2 drop from 124 to 61 mmHg at an FiO2 of 0.3. Treatment consisted of infusion loading and two bolus doses of 2.5 µg of phenylephrine (diluted to 2.5 µg/mL), which normalized her blood pressure within approximately 10 minutes. The facial flushing gradually subsided and disappeared after 40 minutes. Subsequent circulatory stability allowed for the successful completion of the surgery. There was no alteration in airway pressure, and hemodynamic stability was only compromised following the commencement of bowel manipulation. Given the serious risks associated with prolonged hemodynamic instability in neonates, the potential for MTS should be considered during anesthetic management in such cases.

Vancomycin Anaphylaxis and Kounis Syndrome Case Report.

Preoperative antibiotic administration has become a standard practice to mitigate the risk of surgical site infections; however, it is not devoid of potential complications. This report delves into the case of a 67-year-old male who underwent a routine preoperative vancomycin infusion prior to an elective total knee arthroplasty and subsequently experienced an unexpected adverse reaction including diaphoresis, cutaneous flushing, hypotension, and eventually unresponsiveness involving cardiovascular collapse and non-ST-segment elevation myocardial infarction (NSTEMI), despite minimal underlying coronary artery disease. The report focuses on the management of the emergent condition at our facility, highlighting the immediate response and following management of additional complications. The successful management led to a full recovery with the electrocardiogram (EKG) returning to the preoperative baseline of sinus rhythm with first-degree atrioventricular (AV) block within two hours of the event. This study contributes valuable insights into the complexities associated with preoperative antibiotic use, underscores the importance of understanding individual patient profiles, and raises awareness of potential risks and strategies to be used for antibiotic administration from a healthcare professional perspective.