Clinical Determinants and Perioperative Allergic Reactions (CADECAP Study) (CADECAP)

Clinical Determinants in Perioperative Allergic Immediate Hypersensitivity

The clinical presentation of perioperative allergic and non-allergic clinical reactions is often considered undistinguishable while the accurate analysis of clinical cases shows striking clinical differences which might be predictive of the etiological diagnosis (allergic versus non-allergic).

The four-step Ring and Messmer clinical scale helps to guide acute management of immediate hypersensitivity accordingly to the clinical presentation although this scale does not take into account the mechanism involved (i.e. allergic versus non-allergic). Non-allergic clinical reactions are usually non-life-threatening and may, sometimes, spontaneously resolve in contrast to allergic reactions which are mainly severe and life-threatening conditions, typically called anaphylaxis.

The cornerstones of anaphylaxis management are fluid therapy and epinephrine. However, poor outcome has been reported as a result of delayed treatment and/or inappropriate management of perioperative anaphylaxis.

Study Overview

• Status: Completed
• Conditions: Hypersensitivity, Immediate; Perioperative Period

Detailed Description

The main objectives of this study are to: i) characterize the clinical and paraclinical determinants of IgE-mediated allergy that could be correlated to the ultimate diagnosis; and ii) elaborate a decision-making algorithm for clinical patterns identification of perioperative allergic reactions to guide acute management, thus potentially decreasing the related morbidity and mortality.

The secondary objectives are to: i) suggest a modification of the Ring and Messmer scale according to the phenotypes involved; ii) identify the clinical characteristics of isolated non-allergic bronchospasm; iii) compare the most frequent agents involved in perioperative IgE-mediated allergy to those reported in the international studies; iv) identify the negative predictive values of skin tests in allergic and non-allergic patients; v) compare the therapeutic modalities used to those recommended in the literature; vi) describe the cases of morbidity and mortality and identify the potential risk factors.

The Ring and Messmer scale is used to quote the clinical features occurring in drug- or latex-induced immediate hypersensitivity and has been adapted to the perioperative setting as follows:

Grade I: Muco-cutaneous signs only (generalized erythema and/or extensive urticaria and/or angioedema) Grade II: Mucocutaneous signs, hypotension, tachycardia and/or moderate bronchospasm Grade III: Mucocutaneous signs, cardiovascular collapse, tachycardia or bradycardia, bronchospasm, digestive signs Grade IV: Cardiac arrest Grade V: Death

Perioperative immediate hypersensitivity reaction requires further allergologic assessment.

The allergologic assessment is performed a few weeks after the reaction to confirm or disprove an allergic mechanism behind the reaction (i.e. allergy versus non-allergy), and to identify culprit agent(s) and safe drugs, including suitable alternatives. It is based on the review of the details of the reaction along with histamine and/or tryptase levels and specific Immunoglobulin E levels (when available) and skin tests results.

Plasma histamine and/or tryptase levels and Immunoglobulin E levels are measured at the time of the reaction. Acute tryptase levels are compared to baseline tryptase measured at least 24 hours after the reaction or when the patient is referred for allergological investigation. Skin tests, including prick-tests and intradermal tests, are performed during the allergological assessment.

• Study Type: Observational
• Enrollment (Actual): 153

Contacts and Locations

Study Locations

• France
  • Paris, France, 75004
    • Assistance Publique-Hopitaux de Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients having experienced a perioperative immediate hypersensitivity where the allergological assessment was performed by the collaborators of this study

Description

Inclusion criteria:

• Patients having experienced a perioperative immediate hypersensitivity (including the obstetrical setting) according to one grade of the Ring and Messmer clinical scale, for whom:
• The clinical history is known and has been related to perioperative immediate hypersensitivity;
• The biological assessment including plasma histamine and/or tryptase (and serum IgE when available) was performed after the onset of immediate hypersensitivity according to current guidelines;
• The allergological assessment including skin tests performed by the collaborators of this study was carried out according to current guidelines in surviving patients

Exclusion criteria:

• Patients who decline to be involved in the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Perioperative immediate hypersensitivity; Patients having experienced perioperative immediate hypersensitivity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of the predictive muco-cutaneous signs of perioperative allergic immediate hypersensitivity as assessed by the Ring and Messmer clinical scale	muco-cutaneous signs (generalized erythema and/or extensive urticaria and/or angioedema)	From date of the perioperative clinical reaction up to 6 hours
Identification of the predictive heart rate of perioperative allergic immediate hypersensitivity as assessed by the Ring and Messmer clinical scale	heart rate (beat/min.)	From date of the perioperative clinical reaction up to 6 hours
Identification of the predictive arterial pressure of perioperative allergic immediate hypersensitivity as assessed by the Ring and Messmer clinical scale	arterial pressure (mmHg)	From date of the perioperative clinical reaction up to 6 hours
Identification of the predictive upper gastrointestinal symptoms of perioperative allergic immediate hypersensitivity as assessed by the Ring and Messmer clinical scale	digestive signs (vomiting)	From date of the perioperative clinical reaction up to 6 hours
Identification of the predictive lower gastrointestinal symptoms of perioperative allergic immediate hypersensitivity as assessed by the Ring and Messmer clinical scale	digestive signs (diarrhea)	From date of the perioperative clinical reaction up to 6 hours
Identification of recurrence of perioperative allergic immediate hypersensitivity as assessed by the Ring and Messmer clinical scale	recurrence of symptoms following a symptom-free response	From date of the perioperative clinical reaction up to 6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drugs involved in adverse reactions as assessed by the Ring and Messmer clinical scale	To identify the drugs involved in the onset of perioperative allergic clinical reactions and compare our results to those provided in the different international epidemiologic studies regarding perioperative immediate hypersensitivity.	From date of the perioperative clinical reaction and up to 100 months
Negative predictive values of skin tests in allergic and non-allergic patients	Negative skin-tested agents administered according to the results of allergological follow-up during subsequent anesthetics in allergic and non-allergic patients	Up to 5 years after the allergologic follow-up
Participants with treatment-related adverse events as assessed by by CTCAE v4.0 and fluid therapy	To identify the number of patients who received fluid therapy (volume, type) in allergic hypersensitivity	Through study completion, an average of 2 years
participants with treatment-related adverse events as assessed by CTCAE v4.0 and vasoconstrictive agents	To identify the number of patients who received vasoconstrictive agents (ephedrine, neosynephrine, epinephrine, norepinephrine) and corresponding cumulative doses	Through study completion, an average of 2 years
participants with treatment-related adverse events as assessed by CTCAE v4.0 and salbutamol and/or steroids	To identify the number of patients who received salbutamol, steroids and corresponding doses	Through study completion, an average of 2 years
Participants with treatment-related adverse events as assessed by CTCAE v4.0 and intensive care unit admission	To identify the number of patients who were admitted in intensive care unit	Through study completion, an average of 2 years
Participants with treatment-related adverse events as assessed by CTCAE v4.0 and morbidity	To report the morbidity cases including cardiac and/or renal and/or hepatic and/or neurologic failure(s) after perioperative allergic immediate hypersensitivity	Through study completion, an average of 2 years
Participants with treatment-related adverse events as assessed by CTCAE v4.0 and mortality	To report the mortality cases after perioperative allergic immediate hypersensitivity	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Chair: Pascale Dewachter, M.D., Ph.D., Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2018
• Primary Completion (Actual): November 5, 2018
• Study Completion (Actual): March 22, 2019

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Hypersensitivity, Immediate; Morbidity; Mortality; Epinephrine; Perioperative Period; Anaphylaxis; Skin Tests; Tryptases
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Hypersensitivity, Immediate
• Other Study ID Numbers: 2018-043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No