Anaphylaxis

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.

Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis.

Numerous methods for causality assessment of adverse drug reactions (ADRs) have been published The aim of this review is to provide an overview of these methods and discuss their strengths and weaknesses We conducted electronic searches in MEDLINE (via PubMed), EMBASE and the Cochrane databases to find all assessment methods Thirty-four different methods were found, falling into three broad categories: expert judgement/global introspection, algorithms and probabilistic methods (Bayesian approaches) Expert judgements are individual assessments based on previous knowledge and experience in the field using no standardized tool to arrive at conclusions regarding causality Algorithms are sets of specific questions with associated scores for calculating the likelihood of a cause-effect relationship Bayesian approaches use specific findings in a case to transform the prior estimate of probability into a posterior estimate of probability of drug causation The prior probability is calculated from epidemiological information and the posterior probability combines this background information with the evidence in the individual case to come up with an estimate of causation As a result of problems of reproducibility and validity, no single method is universally accepted Different causality categories are adopted in each method, and the categories are assessed using different criteria Because assessment methods are also not entirely devoid of individual judgements, inter-rater reliability can be low In conclusion, there is still no method universally accepted for causality assessment of ADRs

Methods for causality assessment of adverse drug reactions: a systematic review.

We performed a prospective study of anaphylaxis in 25 consecutive patients. Three distinct clinical patterns were observed: uniphasic, biphasic, and protracted anaphylaxis. Thirteen patients (52%) experienced a single episode. Biphasic anaphylaxis occurred in five patients (20%), two episodes of hypotension or laryngeal edema separated by asymptomatic intervals of 1 to 8 hours. Initial therapy included large doses of glucocorticoids in three of the five patients. Seven patients (28%) suffered hypotension, lower respiratory obstruction, or laryngeal obstruction that persisted 5 to 32 hours despite vigorous therapy that included systemic glucocorticoids. Recurrent or prolonged reactions were 2.8-fold more likely if the onset was 30 or more minutes after exposure to the stimulus or if the offending agent had been administered by mouth ( p

https://www.jacionline.org/article/0091-6749(86)90117-X/pdf

Biphasic and protracted anaphylaxis

Observations in 205 patients with cardiovascular manifestations of anaphylactic shock confirmed the belief that adrenaline is the drug of first choice in management and that colloid solutions are preferable to crystalloid solutions in volume replacement. Arrhythmias and elevated filling pressures are more common in patients with cardiac disease but the sympathetic response appears to override the cardiac effects of histamine in healthy patients.

Clinical observations on the pathophysiology and treatment of anaphylactic cardiovascular collapse.

In 2 clinical studies in 40 conscious human volunteers and 164 orthopedic patients histamine-release responses were diagnosed, defined and classified. Polygeline (Haemaccel) in its now outdated formulation [40] was chosen as a clinical histamine releaser. The main interest was not concentrated on the extreme, the “classical” anaphylactic response, but on theaverage histamine-release response found in clinical experiments with so many drugs in the last 10 years. In human volunteers 600 ng/kg histamine was i. v. injected. Indicants for a systemic anaphylactoid reaction with the highest incidence ratio were tachycardia, plasma histamine levels >1 ng/ml, “metallic taste”, flush, congestion of head, “wet eyes” and tears, hypertension and headache. Following polygeline none of these subjects developed a life-threatening reaction, but 12 showed a systemic response, 11 a cutaneous reaction and 17 were non-responders. Indicants for a systemic anaphylactoid reaction with the highest incidence ratio were plasma histamine levels >1 ng/ml, tachycardia, wheals, sensation of heat, narrowness of throat, hypertension, headache and wet eyes or tears. In a prolective, cohort study in the orthopedic patients 3 subjects with life-threatening reactions, 27 with systemic response, 96 with cutaneous reaction and 38 non-responders were included. Indicants with the highest incidence ratio were tachycardia, plasma histamine levels >1 ng/ml, erythema and wheals, cough, flush, stuffy nose and facial oedema. With this trial the indicants for diagnosing a systemic histamine release response in volunteers were validated in patients to a large extent. Thus the average histamine-release response was defined by clinical signs such as tachycardia and mild hypertension, scattered hives such as spots of erythema and wheals, respiratory symptoms in the laryngeal and nasal region, such as cough, narrowness in the throat, stuffy nose and sneezingand by pathological plasma histamine levels (>1 ng/ml). In addition histamine-release responses were differentiated as cutaneous responses, systemic responses and life-threatening responses by clinical and operational criteria and by plasma histamine levels. Using clinical trials and medical decision making procedures the incidence of systemic histamine-release responses in patients higher by two orders of magnitude than in other studies reported hitherto.

/pdf/definition-and-classification-of-the-histamine-release-5dyv2reifp.pdf

Definition and Classification of the Histamine-Release Response to Drugs in Anaesthesia and Surgery: Studies in the Conscious Human Subject* **

To demonstrate the efficacy of a premedication with H1- + H2-receptor antagonists against histamine-release responses in anaesthesia and surgery 3 randomized controlled trials were conducted in patients, volunteers and experimental animals (dogs). Cutaneous anaphylactoid reactions following infusion of polygeline (Haemaccel) in orthopedic patients were successfully abolished by premedication with 0.1 mg/kg dimethpyrindene (Fenistil) and 5 mg/kg cimetidine (Tagamet). Chlorpheniramine (Piriton) was also useful, but dimethpyrindene was more effective in the doses recommended and used. Side-effects of the premedication were not observed when the 2 drugs were slowly administered (2 min each). Systemic anaphylactoid reactions following infusion of polygeline were completely prevented in volunteers by the same premedication (0.1 mg/kg dimethpyrindene and 10 mg/kg cimetidine). Life-threatening reactions could not be tested in human subjects, but were elicited in experimental animals (dogs). In this species which resembles man in its sensitivity against histamine, in plasma histamine levels and in response to polygeline life-threatening reactions were prevented or in especially severe cases diminished to such an extent by the premedication with H1- + H2-blockers that this premedication was finally judged to be very effective against histamine-release responses of any grade of severity. To confirm this clinically very important hypothesis more clinical trials in patients at risk for anaphylactoid reactions to drugs are urgently needed.

/pdf/prophylaxis-of-anaphylactoid-reactions-to-a-polypeptidal-2cwgq5kuo9.pdf

Prophylaxis of anaphylactoid reactions to a polypeptidal plasma substitute by H1- plus H2-receptor antagonists: Synopsis of three randomized controlled trials

A computer-aided model for the prediction of pseudoallergic reactions was developed using prospective data collected from 581 patients in a controlled clinical trial examining pseudoallergic reactions to the plasma substitute Haemaccel (outdated formulation). The multivariate analysis of 22 proposed risk factors was performed using Bayes theorem. This enabled the accurate prediction of 86% of the patients who had a systemic reaction. The clinical use of such system would enable a selection of patients to receive the effective prophylactic measure of pretreatment with H1 plus H2-receptor antagonists.

Prediction of risk for pseudoallergic reactions and histamine release in patients undergoing anaesthesia and surgery: a computer-aided model using independence-Bayes.

Definition of histamine release in human subjects and experimental animals using plasma histamine determinations in the whole individual

The application of a drug or plasma substitute to a patient carries the risk of an unwanted and unexpected reaction. The reactions we are interested in are the allergic/pseudoallergic reactions to drugs. Both types follow a similar clinical picture but have different initiating reaction mechanisms. In allergic reactions specific antibodies (IgE) are involved whereas in pseudoallergic reactions the drug acts directly on the same cells (mast cells, basophils) without the involvement of antibodies (1).

B. Schöning

Papers

Definition and Classification of the Histamine-Release Response to Drugs in Anaesthesia and Surgery: Studies in the Conscious Human Subject* **

Prophylaxis of anaphylactoid reactions to a polypeptidal plasma substitute by H1- plus H2-receptor antagonists: Synopsis of three randomized controlled trials

Prediction of risk for pseudoallergic reactions and histamine release in patients undergoing anaesthesia and surgery: a computer-aided model using independence-Bayes.

Definition of histamine release in human subjects and experimental animals using plasma histamine determinations in the whole individual

Computer-Aided Predictions of Pseudoallergic Reactions to Plasma Substitutes: A Model Using HaemaccelR