Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations.

Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.

Consensus clinical scoring for suspected perioperative immediate hypersensitivity reactions.

BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.

Neuromuscular blocking agents induced anaphylaxis: Results and trends of a French pharmacovigilance survey from 2000 to 2012.

BACKGROUND: Perioperative anaphylaxis mainly involves neuromuscular blocking agents (NMBAs) with an IgE-mediated mechanism. In France, this life-threatening condition is reported by anesthetists and allergologists, and two safety alerts concerning suxamethonium were raised in 2011 and 2012. This led to start a national survey over the 2000-2012 period which objectives were to provide a descriptive analysis, to estimate incidence rates, and to analyze the trends over this period. METHODS: The French pharmacovigilance database was retrospectively queried for all the available NMBAs. Anaphylaxis cases with elevated tryptase and positive skin tests were qualified as "confirmed cases." Subgroup analysis compared atracurium and cisatracurium vs suxamethonium and rocuronium. RESULTS: A total of 680 confirmed cases and 944 nonconfirmed cases were identified. Suxamethonium was the most implied NMBA (64%). Incidence rates (according to sales data) of suxamethonium and rocuronium were, respectively, 10- and 13-folds higher than those of the others NMBAs, regardless the confirmed/nonconfirmed status. Cisatracurium incidence rates remained stable over the period, while suxamethonium and atracurium increased and rocuronium first decreased but re-increased after 2006. Male patients were more frequent in the subgroup "atracurium-cisatracurium" (P = .019), whereas obesity and emergency setting were more frequent in the subgroup "rocuronium-suxamethonium." Shared characteristics were the poorly documented previous exposure to NMBA(s) and an insufficient adherence of patients to perform skin tests, showing the need to improve this procedure. CONCLUSION: Suxamethonium and rocuronium are markedly more involved in perioperative anaphylaxis than the other available NMBAs. Patients should be more informed about their perioperative anaphylaxis and its consequences.

Anaesthetic hypersensitivity reactions in France between 2011 and 2012: the 10th GERAP epidemiologic survey.

BACKGROUND: Immediate hypersensitivity reactions during anaesthesia are rare but potentially life-threatening. The epidemiology changes with time and evolving professional practice, and hence needs to be monitored. Our objective was to follow this epidemiology. METHODS: This was a retrospective, observational study in French hospital clinics, conducted by GERAP members (Groupe d'Étude des Réactions Anaphylactoïdes Périopératoires). Consecutive patients seen in allergo-anaesthesia outpatient clinics, who had experienced a hypersensitivity reaction during anaesthesia between 1 January 2011 and 31 December 2012, were included. Demographic data, allergy history, drugs received before the reaction, symptoms of the reaction, results of blood samples (histamine, tryptase, IgE-specific assays), and results of the allergy assessment were recorded. RESULTS: The most common causes of allergic reactions were (Neuromuscular Blocking Agents) NMBAs (N = 302; 60.6%), antibiotics (N = 91, 18.2%, Cephalosporin N = 49, 10%) and dyes (N = 27; 5.4%). Latex as an allergic agent was involved in 26 cases (5.2%), hypnotics in 11 cases (2.2%) and opioids in seven cases (1.4%). Of the NMBAs, Rocuronium had the highest proportion of reactions (13.8 reactions/100,000 vials sold) followed by Suxamethonium (13.3/100,000 vials sold). Cisatracurium had the lowest proportion of reactions (0.4/100,000 vials sold). Patients were sensitized to two or more NMBAs in 48.9% of cases and without testing, cross-sensitivity cannot be predicted. CONCLUSIONS: When compared with the previous GERAP studies, NMBAs are still the most frequently triggering allergens, with marked differences between individual NMBAs, but they are now followed by antibiotics (of which greater than 50% were cephalosporins) and dyes. Anaesthetists must be aware of the differences between drugs and of the pattern of emerging allergens. For the future of safe anaesthesia, allergy assessment is essential.

Anaphylactic bronchospasm during general anesthesia is not related to asthma.

In the general population, a history of asthma (HA) is associated with a higher risk of mortality of anaphylactic shock (AS), but it is unknown whether this association remains valid for intra-operative AS. The goal of this retrospective study was to investigate whether a HA was associated with a higher risk of bronchospasm during intra-operative AS. We analyzed 106 patients (January 2009-December 2012) with intra-operative AS: 57% of them had a confirmed IgE-mediated reaction and 27% had a HA. On logistic regression, the only factor statistically associated with bronchospasm was a neuromuscular blocking drug, with both IgE- or non-IgE-mediated reactions. These results suggest that the mechanisms of bronchospasm in AS may be different from those of asthma and that, in the presence of bronchospasm during anesthesia, AS should be considered to be the most likely cause.

Fatal anaphylaxis with neuromuscular blocking agents: a risk factor and management analysis.

BACKGROUND: Anaphylactic reactions to neuromuscular blocking agents (NMBAs) can be severe and even fatal. Our aim was to evaluate mortality rate in France from anaphylactic reactions to NMBAs, to identify risk factors for a fatal outcome, and to describe management of the cases that proved fatal. METHODS: The French National Pharmacovigilance Database was queried for reports of NMBA anaphylaxis that occurred between January 2000 and December 2011. A questionnaire was sent to regional pharmacovigilance centers to obtain further information on the management of cases with a fatal outcome. RESULTS: Two thousand and twenty-two cases of NMBA hypersensitivity were retrieved, of which 84 were fatal (4.1%). Among the 1247 cases of severe NMBA anaphylaxis (grades 3 and 4), independent risk factors associated with a fatal outcome in a multivariate analysis were male gender (female gender: OR = 0.4; 95% CI 0.2-0.7; P = 0.0004), an emergency setting (OR = 2.6; 95% CI 1.5-4.6; P = 0.0007), a history of hypertension (OR = 2.5; 95% CI 1.5-4.4; P = 0.0010) or of other cardiovascular disease (OR = 4.4; 95% CI 2.4-8.1; P < 0.0001), obesity (OR = 2.4; 95% CI 1.1-5.3; P = 0.0376), and ongoing beta-blocker treatment (OR = 4.2; 95% CI 1.8-9.8; P = 0.0011). All 31 patients with a fatal outcome received epinephrine in a titrated manner according to international guidelines. CONCLUSION: Obese males with a history of cardiovascular disease receiving ongoing beta-blocker treatment and undergoing surgery in an emergency setting were at high risk of a fatal outcome after NMBA-induced anaphylaxis. Some epinephrine-resistant cases may play a role in our high mortality rate. New therapeutic approaches need to be developed to treat these cases.

Prevalence of IgE against neuromuscular blocking agents in hairdressers and bakers.

BACKGROUND: Allergic IgE-mediated reactions to neuromuscular blocking agents (NMBAs) are the main cause of immediate hypersensitivity reactions in anaesthesia; their predominant occurrence in the absence of previous exposure to NMBAs suggests a risk related to environmental exposure. OBJECTIVE: To investigate the prevalence of specific IgE to quaternary ammonium ions in two populations professionally exposed to quaternary ammonium compounds, in the north-eastern France. METHODS: The study had a retrospective follow-up design whereby apprentices were assessed after their 2-year training period as apprentices. The professionally exposed hairdresser populations (n = 128) were compared with baker/pastry makers (n = 108) and 'non-exposed' matched control subjects (n = 379). RESULTS: We observed a 4.6-fold higher frequency of positive IgE against quaternary ammonium ions in hairdressers (HD), compared with baker/pastry makers (BP) and control (C) groups. The competitive inhibition of quaternary ammonium Sepharose radioimmunoassay (QAS-IgE RIA) with succinylcholine was significantly higher in HD, compared with BP and C groups, with inhibition percentage of 66.2 ± 7.4, 39.7 ± 6.0 and 43.8 ± 9.9, respectively (P < 0.001). The specific IgE against quaternary ammonium ions recognized also two compounds widely used by hairdressers, benzalkonium chloride and polyquaternium-10, in competitive inhibition of IgE RIA. When considering the whole study population, hairdresser professional exposure and total IgE > 100 kU/L were the two significant predictors of IgE-sensitization against quaternary ammonium ions in the multivariate analysis of a model that included age, sex, professional exposure, increased concentration of total IgE (IgE > 100 kU/L) and positive IgE against prevalent allergens (Phadiatop(®) ; P = 0.019 and P = 0.001, respectively). CONCLUSION AND CLINICAL RELEVANCE: The exposure to hairdressing professional occupational factors increases IgE-sensitization to NMBAs and quaternary ammonium ion compounds used in hairdressing. Besides the pholcodine hypothesis, our study suggests that repetitive exposure to quaternary ammonium compounds used in hairdressing is a risk factor for NMBAs sensitization.

Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper.

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

Reducing the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical practice.

These guidelines represent the updated consensus of experts in the field of immediate hypersensitivity reactions occurring during anesthesia. They provide a series of valid, widely accepted, effective, and easily teachable guidelines that are the fruit of current knowledge, research, and experience. The guidelines are based on the findings of international scientific research and have been implemented in France under the auspices of the French Society for Anaesthesia and Intensive Care (Société Française d'Anesthésie et de Réanimation [SFAR]) and the French Society of Allergology (Société Française d'Allergologie [SFA]). The members of the European Network for Drug Allergy approved the guidelines. This paper presents the most relevant clinical implications of the guidelines.

Hypersensitivity reactions to blood components: document issued by the allergy committee of the French medicines and healthcare products regulatory agency.

These guidelines represent a consensus among experts on hypersensitivity reactions occurring after transfusion of blood components. They cover recognition, investigation, treatment, and prevention of such reactions. Implemented in France under the auspices of the French Medicines and Healthcare Products Regulatory Agency (AFSSAPS) and based on current knowledge, research, and experience, they aim to provide effective and easily teachable means of further improving the quality of hemovigilance databases, promote interest in this field, and help identify possible mechanisms and at-risk patient groups.

National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study.

BACKGROUND: The aim of this study was to test, on a multinational level, the pholcodine (PHO) hypothesis, i.e. that the consumption of PHO-containing cough mixtures could cause higher prevalence of IgE antibodies to PHO, morphine (MOR) and suxamethonium (SUX). As a consequence the risk of anaphylaxis to neuromuscular blocking agents (NMBA) will be increased. METHODS: National PHO consumptions were derived from the United Nations International Narcotics Control Board (INCB) database. IgE and IgE antibodies to PHO, MOR, SUX and P-aminophenyl-phosphoryl choline (PAPPC) were measured in sera from atopic individuals, defined by a positive Phadiatop test (>0.35 kU(A)/l), collected in nine countries representing high and low PHO-consuming nations. RESULTS: There was a significant positive association between PHO consumption and prevalences of IgE-sensitization to PHO and MOR, but not to SUX and PAPPC, as calculated both by exposure group comparisons and linear regression analysis. The Netherlands and the USA, did not have PHO-containing drugs on the markets, although the former had a considerable PHO consumption. Both countries had high figures of IgE-sensitization. CONCLUSION: This international prevalence study lends additional support to the PHO hypothesis and, consequently, that continued use of drugs containing this substance should be seriously questioned. The results also indicate that other, yet unknown, substances may lead to IgE-sensitization towards NMBAs.

Pre-existing arterial stiffness can predict hypotension during induction of anaesthesia in the elderly.

BACKGROUND: The aim of the present study was to establish whether elevated carotid-femoral pulse wave velocity (c-fPWV), an indicator of aortic stiffness, assessed before surgery, is correlated with variations in arterial pressure (AP) during induction of anaesthesia in elderly patients undergoing non-cardiovascular surgery. METHODS: c-fPWV was measured with the PulsePen(®) device during pre-surgical anaesthetic evaluation. Monitoring included electrocardiography, pulse oximetry, non-invasive AP, heart rate, bispectral index (BIS), and oxygen concentration during induction of anaesthesia with propofol and remifentanil. Anaesthesia was induced so as to maintain BIS values between 40 and 50. RESULTS: Forty-five patients, aged [mean (sd)] 71.1 (5.8) yr, were studied. The mean value of c-fPWV was 12.1 (3.9) m s⁻¹. There was no correlation between hypotension during anaesthesia induction and total dosage or rate of administration of propofol or remifentanil. In univariate analysis, only age and PWV significantly correlated with the decreases in AP, and the association between c-fPWV and a decrease in AP was also seen in multivariate analysis (r = 0.36, P< 0.05). Patients classified as having 'high stiffness' (c-fPWV ≥ 12.9 m s⁻¹) had 25% further decrease in systolic AP during anaesthesia induction than those with lower PWV [75.2 (5.7) vs 60.2 (4.2) mm Hg, P < 0.05]. CONCLUSIONS: Increased aortic stiffness, as assessed by PWV measured during preoperative anaesthetic evaluation, is associated with more pronounced hypotension during induction of anaesthesia. Measurement of aortic stiffness in the elderly may thus represent a valid indicator of the risk of hypotension during anaesthesia induction.

Diagnostic Pitfall of Platypnea-Orthodeoxia Syndrome Caused by Atrial Septal Defect after Right Pneumonectomy.

We describe a case of platypnea-orthodeoxia syndrome (POS) due to atrial septal defect (ASD) occurring in the early postoperative course of a right pneumonectomy. Deformation of the atrial septum after right pneumonectomy deviates the blood from the inferior vena cava to ASD during the sitting position creating, a massive right-to-left shunt. Diagnosis can initially be missed by making contrast bubble test through the superior vena cava. The atrial septal defect was then closed using the surgical technique, allowing an instantaneous improvement of hematosis.

Pharmacovigilance of drug allergy and hypersensitivity using the ENDA-DAHD database and the GALEN platform. The Galenda project.

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.

Continuous intravenous lidocaine in the treatment of paralytic ileus due to severe spinal cord injury.

Paralytic ileus is a major concern in the acute phase of spinal cord injury. Classical treatment with neostigmine is often ineffective. Continuous intravenous (i.v.) lidocaine infusion has been previously proposed intra and post-operatively in order to decrease the duration of post-operative ileus after abdominal surgery. We report the cases of seven patients suffering from complete paralytic spinal cord injury-related ileus with colectasy resistant to neostigmine, who were treated by i.v. lidocaine infusion.

[TRALI and TACO: diagnostic and clinical management of patients]. / Trali et Taco: diagnostic et prise en charge clinique des patients.

Transfusion-related acute lung injury (TRALI) is the inflammatory, exudative form and Transfusion-associated cardiac overload (TACO) is the hydrostatic, transudative form of transfusion-induced acute pulmonary edema. The distinction between these two entities may be difficult, but important because of different clinical management strategies and different implications. There is no unique diagnostic tool. The diagnostic search should gather several clinical information and may be helped by various techniques listed in this article.