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.

Incidence and related factors for intraoperative failed spinal anaesthesia for lower limb arthroplasty.

BACKGROUND: Spinal anaesthesia is the preferred choice for total hip- and knee arthroplasty (THA/TKA), due to the claimed superior outcome profile, relative simple technique and without the need for advanced airway support. However, choosing and informing about spinal anaesthesia should also include the risk for intraoperative failed spinal anaesthesia with associated pain, discomfort and suboptimal settings for airway management. Small-scale studies suggest incidences from 1 to 17%; however, no multi-institutional large data exists on failed spinal incidence and related factors during THA/TKA, hindering evidence-based information and potential anaesthesia stratification. METHODS: In a sub-analysis, data from a prospective study on spinal anaesthesia for THA/TKA were examined for incidence of intraoperative conversion to general anaesthesia. Potential perioperative factors (age, gender, American Society of Anaesthesiologist (ASA) score, height, weight, BMI, procedure, bupivacaine dosage and duration of time from spinal administration until end of surgery) were analysed with logistic regression for relation to failed spinal anaesthesia. RESULTS: In all, 1451 patients were included for analysis, whereof 57 (3.9%) had failed spinal anaesthesia. Spinal failure patients were significantly younger (61 vs. 67 years, P = 0.003), and operation time longer in the failed spinal group vs no-failure, respectively (133 vs. 89 min, P < 0.001). No significant differences were found with regard to bupivacaine volume, gender, ASA-score, height, weight, BMI or THA vs. TKA. CONCLUSION: Failed spinal anaesthesia for THA and TKA is a relatively frequent occurrence and identification of risk patients is not feasible. These results should be considered when choosing anaesthesia and included in the information to patients.

No cases of perioperative allergy to local anaesthetics in the Danish Anaesthesia Allergy Centre.

BACKGROUND: Local anaesthetics (LA) are often suspected as possible causes of allergic reactions. The Danish Anaesthesia Allergy Centre (DAAC) is the national reference centre for investigation of perioperative allergic reactions. The purpose of this study was to investigate the incidence of IgE-mediated immediate type perioperative allergic reactions to LA. METHODS: In the period 2004-2013, a total of 409 patients (244 women/165 men; median age 49 years, range 1-86 years) were investigated in DAAC on suspicion of allergy associated with anaesthesia and surgery. A total of 162 (40%) patients were exposed to one or more LA. Suspected allergy to LA was investigated by prick test, intradermal test and subcutaneous provocation with the suspected drug. Patients with positive skin tests still underwent subcutaneous provocation, as false positive skin tests can occur. RESULTS: A total of 203 test series with LA were carried out on 162 patients (89 women/73 men; mean age 49 years, range 2-85 years) with the following drugs: Lidocaine n = 80 (49%), bupivacaine n = 82 (51%), ropivacaine n = 31 (19%) and mepivacaine n = 10 (6%). All 162 patients had negative subcutaneous provocation for all tested LA (95% CI: 0-1.8%). Investigations revealed another allergen in 52 of 162 patients. CONCLUSION: None of the 162 patients with suspected perioperative allergic reactions and exposure to LA reacted on subcutaneous provocation with the relevant LA. Thus, no patients have been diagnosed with allergy to LA in DAAC in the period 2004-2013 and allergy to LA must be considered very rare in this population.

No evidence for contraindications to the use of propofol in adults allergic to egg, soy or peanut†.

BACKGROUND: Propofol is thought to be a potential cause of allergic reactions in patients allergic to egg, soy or peanut, since current formulations contain an emulsion that includes egg lecithin and soybean oil. However, other than six case reports lacking in confirmatory evidence of an allergic reaction, there is no evidence linking the two types of allergies. The aim of this study was to examine the frequency of propofol allergy and to investigate if patients with specific immunoglobulin E (IgE) to egg, soy or peanut tolerated propofol. METHODS: Study A examined the frequency of propofol allergy in 273 patients systematically investigated for suspected perioperative allergic reactions. Of these, 153 had been exposed to propofol and underwent skin tests and intravenous provocation. Study B retrospectively investigated propofol exposure and tolerance in 520 adult patients with a positive specific IgE to egg, soy or peanut. RESULTS: Four of the 153 propofol-exposed patients (2.6%) investigated in study A were diagnosed with propofol allergy. Of these, three tested positive only on intravenous provocation. None of the four had allergic symptoms when eating egg, soy or peanut and none had detectable levels of specific IgE to egg or soy in their serum. In study B we found no signs of allergic reactions towards propofol in 171 retrieved anaesthetic charts from 99 patients with specific IgE to egg, soy or peanut. CONCLUSION: No connection between allergy to propofol and allergy to egg, soy or peanut was found. The present practice of choosing alternatives to propofol in patients with this kind of food allergy is not evidence based and should be reconsidered.

Oxytocin use during Caesarean sections in Denmark - are we getting the dose right?

BACKGROUND: In Denmark, an iv bolus of 10 IU oxytocin was traditionally given after delivery to prevent atony during caesarean sections. Randomized controlled trials have shown that lower iv bolus doses have same efficacy with fewer side effects and many countries now recommend a 5 IU maximum dose. The aims of this study were to investigate whether patients referred for allergy testing after oxytocin exposure had dose-related side effects to oxytocin rather than true allergic reactions and to investigate whether updated international recommendations on lower bolus doses had been implemented in practice. METHODS: Medical notes of patients tested with oxytocin as part of investigations in the Danish Anaesthesia Allergy Centre from May 2004 to January 2014 were reviewed retrospectively. A telephone survey of on-duty obstetricians at all Danish obstetric departments was performed and most recent online recommendations from the Danish societies of obstetrics and anaesthesia about the use of oxytocin were identified. RESULTS: In total 30 women were tested with oxytocin as part of investigations. None were allergic to oxytocin but 19 had symptoms consistent with dose-related side effects on iv provocation. The telephone survey revealed that iv doses of 10 IU oxytocin were still used and recommendations on the websites were not updated. CONCLUSION: Too high oxytocin doses are still used in Denmark leading to dose-related side effects mimicking allergic reactions. Coordination between obstetricians and anaesthesiologists on producing common updated guidelines on the administration of oxytocin and dissemination of this information to obstetric and anaesthetic departments in Denmark is needed.

Clinical and diagnostic features of perioperative hypersensitivity to cefuroxime.

INTRODUCTION: The Danish Anaesthesia Allergy Centre (DAAC) investigated 89 adult patients with suspected perioperative cefuroxime-associated hypersensitivity reactions between 2004 and 2013. The goals were to determine whether the time to index reaction after cefuroxime exposure could be used to implicate cefuroxime as the cause of the reactions and explore different test modalities in diagnosing cefuroxime hypersensitivity. METHOD: Skin tests, in vitro tests, and titrated provocations were used to determine cefuroxime hypersensitivity. Patients were deemed cefuroxime positive on the basis of at least two positive tests and/or a positive provocation. RESULTS: One or more tests were positive for cefuroxime in 24 of 89 (27.0%) patients. One was only specific IgE positive and was deemed cefuroxime negative. Twenty-three (25.8%) were deemed cefuroxime positive. There were four specific IgE-, 4 histamine release test-, 13 skin test-, and 14 provocation positive patients. There were eight (34.8%) patients who were only provocation positive. Data on time to index reaction after cefuroxime exposure were available for 80 patients (22 in the positive group and 58 in the negative group), 22 of 22 (100%) of positive patients reacted in <15 min vs. only 38 of 58 (65.5%) of negative patients. CONCLUSION: All patients with confirmed hypersensitivity to cefuroxime reacted within 15 min of administration, but so did 65.5% of Cefuroxime negative patients, making timing of administration an unreliable predictor of causation in the perioperative setting. Provocations were always positive when carried out in skin test positive patients; however, eight patients had positive provocations only, highlighting the need for provocation in skin test negative patients.

Standardized testing with chlorhexidine in perioperative allergy--a large single-centre evaluation.

BACKGROUND: Perioperative allergic reactions to chlorhexidine are often severe and easily overlooked. Although rare, the prevalence remains unknown. Correct diagnosis is crucial, but no validated provocation model exists, and other diagnostic tests have never been evaluated. The aims were to estimate (i) the prevalence of chlorhexidine allergy in perioperative allergy and (ii) the specificity and sensitivity for diagnostic tests for chlorhexidine allergy. METHODS: We included all patients investigated for suspected perioperative allergic reactions in the Danish Anaesthesia Allergy Centre during 2004-2012. The following tests were performed: specific IgE (Immunocap® ; Phadia AB, Sweden), histamine release test (HR) (RefLab ApS, Denmark), skin prick test (SPT) and intradermal test (IDT). Positivity criteria were as follows: specific IgE >0.35 kUA/l; HR class 1-12; SPT mean wheal diameter ≥3 mm; IDT mean wheal diameter ≥ twice the diameter of negative control. Chlorhexidine allergy was post hoc defined as a relevant clinical reaction to chlorhexidine combined with two or more positive tests. Based on this definition, sensitivity and specificity were estimated for each test. RESULTS: In total, 22 of 228 patients (9.6%) met the definition of allergy to chlorhexidine. Estimated sensitivity and specificity were as follows: specific IgE (sensitivity 100% and specificity 97%), HR (sensitivity 55% and specificity 99%), SPT (sensitivity 95% and specificity 97%) and IDT (sensitivity 68% and specificity 100%). CONCLUSIONS: In patients investigated for suspected perioperative allergic reactions, 9.6% were diagnosed with allergy to chlorhexidine. Using our definition of chlorhexidine allergy, the highest combined estimated sensitivity and specificity was found for specific IgE and SPT.

Transfusion-associated anaphylaxis during anaesthesia and surgery--a retrospective study.

BACKGROUND AND OBJECTIVES: Transfusion-associated anaphylaxis (TAA) is a severe adverse reaction reported to occur in 1:9000-90,000 transfusions. According to the Danish Registration of Transfusion Risks (DART), the frequency is 1:300,000 transfusions, which suggests insufficient reporting of TAA in Denmark. Our aims were to identify possible cases of TAA, to characterize their symptoms and tryptase levels and to investigate the reporting of TAA to the haemovigilance systems. MATERIAL AND METHODS: We reviewed 245 patients with suspected allergic reactions during anaesthesia and surgery, investigated at the Danish Anaesthesia Allergy Centre (DAAC). Based on the outcome of this investigation, the patients were classified as DAAC positive (confirmed hypersensitivity to identified agent, n = 112), or DAAC negative (no confirmed hypersensitivity, n = 133). Data on case history, details of blood transfusion and results of laboratory and clinical investigations were collected. TAA cases were identified according to the recommendations of the International Society of Blood Transfusion (ISBT). RESULTS: Ten possible TAA cases (30% of all transfused patients) were identified, all DAAC negative. The frequency of elevated serum tryptase, hypotension and male sex was significantly higher among these cases compared with the remaining DAAC negative (P < 0·05), but not different from the DAAC-positive patients. One case had been reported to the Blood Bank haemovigilance system and none to DART. CONCLUSION: We identified unreported cases of possible TAA, which resembled the DAAC-positive patients with respect to elevated tryptase and symptoms. By applying the ISBT criteria of adverse transfusion reactions, we conclude that TAA during anaesthesia and surgery is likely to be underreported in Denmark.

Scandinavian Clinical Practice Guidelines on the diagnosis, management and follow-up of anaphylaxis during anaesthesia.

The present approach to the diagnosis, management and follow-up of anaphylaxis during anaesthesia varies in the Scandinavian countries. The main purpose of these Scandinavian Clinical Practice Guidelines is to increase the awareness about anaphylaxis during anaesthesia amongst anaesthesiologists. It is hoped that increased focus on the subject will lead to prompt diagnosis, rapid and correct treatment, and standardised management of patients with anaphylactic reactions during anaesthesia across Scandinavia. The recommendations are based on the best available evidence in the literature, which, owing to the rare and unforeseeable nature of anaphylaxis, mainly includes case series and expert opinion (grade of evidence IV and V). These guidelines include an overview of the epidemiology of anaphylactic reactions during anaesthesia. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline (epinephrine) and fluid therapy as first-line treatment. Recommendations for primary and secondary follow-up are given, bearing in mind that there are variations in geography and resources in the different countries. A list of National Centres from which anaesthesiologists can seek advice concerning follow-up procedures is provided. In addition, an algorithm is included with advice on how to manage patients with previous suspected anaphylaxis during anaesthesia. Lastly, Appendix 2 provides an overview of the incidence, mechanisms and possibilities for follow-up for some common drug groups.

Allergic reactions in anaesthesia: are suspected causes confirmed on subsequent testing?

BACKGROUND: The aim of this retrospective survey of possible allergic reactions during anaesthesia was to investigate whether the cause suspected by anaesthetists involved corresponded with the cause found on subsequent investigation in the Danish Anaesthesia Allergy Centre (DAAC). METHODS: Case notes and anaesthetic charts from 111 reactions in 107 patients investigated in the DAAC were scrutinized for either suspicions of or warnings against specific substances stated to be the cause of the supposed allergic reaction. RESULTS: In 67 cases, one or more substances were suspected. In 49 of these (73%) the suspected cause did not match the results of subsequent investigation, either a different substance being the cause or no cause being found. Only five cases (7%) showed a complete match between suspected cause and investigation result. In the remaining 13 cases (19%) there was a partial match, the right substance being suspected, but investigations showed an additional allergen or several substances, including the right substance being suspected. CONCLUSIONS: An informed guess is not a reliable way of determining the cause of a supposed allergic reaction during anaesthesia and may put a significant number of patients at unnecessary risk. Some patients may be labelled with a wrong allergy, leading to unnecessary warnings against harmless substances, and some patients may be put at risk of subsequent re-exposure to the real allergen. Patients with suspected allergic reactions during anaesthesia should be referred for investigation in specialist centres whenever possible.

Seizures in a 77-year-old-woman after a bolus dose of remifentanil.

Seizures in patients with no history of epilepsy has been associated with administration of remifentanil in two previous case reports. We present a case where a bolus dose of remifentanil (50 micrograms/kg) was followed by a self terminating generalised tonic-clonic seizure in a patient admitted for acute hip surgery, and no previous history of epilepsy.

Polyamines in nerve terminals and secretory granules isolated from neurohypophyses.

In isolated nerve terminals from ox neurohypophyses the following concentrations of polyamines [pmol (microgram protein)-1 (mean +/- SEM)] were found: spermine: 2.07 +/- 0.14 (n = 3), spermidine: 0.22 +/- 0.01 (n = 4), putrescine: 0.20 +/- 0.01 (n = 4). In secretory granules isolated from the same tissue, the concentrations were: spermine: 0.57 +/- 0.02 (n = 3), spermidine: 0.07 +/- 0.04 (n = 3), putrescine: 0.13 +/- 0.04 (n = 3). After incubation of isolated nerve terminals with the polyamines, they were taken up as a function of time and concentration, approaching saturation at high concentrations. The kinetic parameters of their synthesizing enzyme, ornithine decarboxylase, in ox neurohypophyseal nerve terminals (apparent Km 0.75 mM and Vmax 22.5 pmol mg protein-1 h-1) were comparable to those previously found in cerebral cortex of rats. When isolated, hemilobes from rat neurohypophyses were incubated in a medium which contained spermidine (5 mM), and were stimulated by 56 mM K+, release of vasopressin was smaller than in control experiments. However, after removal of spermidine and after restimulation, 50 min after initial stimulation, the release was significantly elevated. It is suggested that polyamines may take part in modulation of vasopressin release.