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.

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.

Timing of onset of gastrointestinal bleeding in the ICU: Protocol for a preplanned observational study.

BACKGROUND: Critically ill patients are at risk of gastrointestinal bleeding, but clinically important gastrointestinal bleeding is rare. The majority of intensive care unit (ICU) patients receive stress ulcer prophylaxis (SUP), despite uncertainty concerning the balance between benefit and harm. For approximately half of ICU patients with gastrointestinal bleeding, onset is early, ie within the first two days of the ICU stay. The aetiology of gastrointestinal bleeding and consequently the balance between benefit and harm of SUP may differ between patients with early vs late gastrointestinal bleeding. METHODS: This is a protocol and statistical analysis plan for a preplanned exploratory substudy of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) randomized clinical trial, comparing intravenous pantoprazole (40 mg once daily) with placebo in 3350 acutely ill adult ICU patients. We will describe baseline characteristics and assess the time to onset of the first clinically important episode of GI bleeding accounting for survival status and allocation to SUP or placebo. In addition, we will describe differences in therapeutic and diagnostic procedures used in patients with clinically important gastrointestinal bleeding according to early vs late bleeding and 90-day vital status. CONCLUSIONS: The study outlined in this protocol will provide detailed information on patient characteristics and the timing of onset of gastrointestinal bleeding in the patients enrolled in the SUP-ICU trial. This may provide additional knowledge and incentives for future studies on which patients benefit from SUP.

Stress ulcer prophylaxis in the intensive care unit trial: detailed statistical analysis plan.

BACKGROUND: In this statistical analysis plan, we aim to provide details of the pre-defined statistical analyses of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial. The aim of the SUP-ICU trial is to assess benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the intensive care unit (ICU). METHODS: The SUP-ICU trial is an investigator-initiated, international, multicentre, randomised, blinded, parallel-group trial of intravenously pantoprazole 40 mg once daily vs. placebo in 3350 acutely ill adult ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support, serious adverse reactions, 1-year mortality, and a health economic analysis. Two formal interim analyses will be performed. The statistical analyses will be conducted according to the outlined pre-defined statistical analysis plan. The primary analysis will be a logistic regression analysis adjusted for stratification variables comparing the two intervention groups in the intention-to-treat population. In a secondary analysis, we will additionally adjust the primary outcome for potential random differences in baseline characteristics. The conclusion will be based on the intention-to-treat population. CONCLUSION: Stress ulcer prophylaxis is standard of care in ICUs worldwide, but has never been tested in large high-quality randomised placebo-controlled trials. The SUP-ICU trial will provide important high-quality data on the balance between the benefits and harms of stress ulcer prophylaxis in adult critically ill patients.

Six years without pholcodine; Norwegians are significantly less IgE-sensitized and clinically more tolerant to neuromuscular blocking agents.

BACKGROUND: As a strong inducer of IgE antibodies to substituted ammonium ion epitopes (QAI), pholcodine (PHO) is a postulated cause of allergic anaphylaxis to neuromuscular blocking agents (NMBAs). Three years after withdrawal of PHO in Norway, a significant reduction in IgE sensitization and anaphylaxis reporting was seen. OBJECTIVE: Six-year follow-up study on the effects of PHO withdrawal on IgE sensitization and anaphylaxis reporting. METHODS: From 650 acute consecutive reports (2005-2013) to the Norwegian Network for Anaphylaxis under Anaesthesia (NARA), total number of reports on suspected anaphylactic reactions, number of reactions where NMBAs were administered, number of reactions where serum IgE antibodies (≥0.35 kUA /l) to suxamethonium (SUX) and PHO were present at time of reaction and anaphylaxis severity grades were retrieved. In addition, NMBA sales and prevalence of IgE sensitization to PHO and SUX among 'allergics' were monitored. RESULTS: From baseline period P0 (PHO on the market) through the first (P1) and second (P2), three-year periods after withdrawal, significant falls in total reports (P < 0.001) and reports with IgE antibodies to PHO (P = 0.008) and SUX (P = 0.001) at time of reaction were found. Total NMBA sales in P2 were 83% of P0, and SUX and rocuronium (ROC) together made up 86% of sales throughout the study. Five NMBA-related anaphylactic deaths occurred during P0 and P1 and, however, none during P2. Prevalence of IgE sensitization to SUX in 'allergics' fell to 0% at 4 and 5 years after withdrawal. CONCLUSIONS: Six years after PHO withdrawal, the Norwegian population has become significantly less IgE-sensitized and clinically more tolerant to NMBAs.

Continuous ventilation during intubation through a supraglottic airway device guided by fiberoptic bronchoscopy: a observational assessment.

INTRODUCTION: supraglottic airway devices remain, despite advances in video laryngoscopy, important tools in the management of unexpected difficult airways. Intubation through a functioning supraglottic airway device with the aid of a fiberoptic bronchoscope is a well-known technique usually performed in apnoea. With a simple modification, the patient can be ventilated during this procedure. METHODS: In this observational study, Tracheal intubation Assisted by Bronchoscopy And Sad during Continuous Oxygenation (TABASCO) was performed as part of department training routine in 26 elective, fasted patients. A supraglottic airway device was used as a conduit for an endotracheal tube. RESULTS: All patients were easily intubated and ventilation was maintained during the procedure. The gap between the outer diameter of the fiberoptic bronchoscope and the inner diameter of the endotracheal tube was more than 2 mm in 25 of 26 patients. Effective ventilation was confirmed by clinical signs, capnography and pressure-volume curves. No signs of airtrapping occurred. DISCUSSION: No adverse events were observed during this form of airway management in this small series of elective and fasted patient when performed by an anaesthesiologist experienced in fiberoptic intubation. A gap between fiberoptic bronchoscope and endotracheal tube inner lumen seems to be prerequisite for easy ventilation through the supraglottic airway. In trained hands, this technique can be a means to secure an airway with an intubating bronchoscope without pausing ventilations. A prerequisite for this is a well-functioning supraglottic airway device.

Salivary IgA from the sublingual compartment as a novel noninvasive proxy for intestinal immune induction.

Whole-saliva IgA appears like an attractive noninvasive readout for intestinal immune induction after enteric infection or vaccination, but has failed to show consistent correlation with established invasive markers and IgA in feces or intestinal lavage. For reference, we measured antibodies in samples from 30 healthy volunteers who were orally infected with wild-type enterotoxigenic Escherichia coli. The response against these bacteria in serum, lavage, and lymphocyte supernatants (antibody-in-lymphocyte-supernatant, ALS) was compared with that in targeted parotid and sublingual/submandibular secretions. Strong correlation occurred between IgA antibody levels against the challenge bacteria in sublingual/submandibular secretions and in lavage (r=0.69, P<0.0001) and ALS (r=0.70, P<0.0001). In sublingual/submandibular secretions, 93% responded with more than a twofold increase in IgA antibodies against the challenge strain, whereas the corresponding response in parotid secretions was only 67% (P=0.039). With >twofold ALS as a reference, the sensitivity of a >twofold response for IgA in sublingual/submandibular secretion was 96%, whereas it was only 67% in the parotid fluid. To exclude that flow rate variations influenced the results, we used albumin as a marker. Our data suggested that IgA in sublingual/submandibular secretions, rather than whole saliva with its variable content of parotid fluid, is a preferential noninvasive proxy for intestinal immune induction.

Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries.

BACKGROUND: Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries. METHODS: Adult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups. RESULTS: Ninety-seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2-receptor antagonists were used 31% (30/97) of the units. Twenty-three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP. CONCLUSIONS: In this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications.

Intravenous fluorescein as a cause of immunoglobulin E-mediated anaphylactic shock.

We report a patient with severe anaphylactic shock immediately after injection of i.v. fluorescein. The patient recovered without sequela. Immunoglobulin E (IgE) mechanism was highly suggestive with significant increase in serum tryptase, positive basophil allergen threshold sensitivity (CD-sens) and histamine release tests towards fluorescein. This is, to our knowledge, the first report where CD-sens has been used to aid in diagnosing an IgE-mediated anaphylactic shock caused by fluorescein.

Implementation of nutritional guidelines in a university hospital monitored by repeated point prevalence surveys.

BACKGROUND/OBJECTIVES: Malnutrition is present in 20-50% of hospitalized patients, and nutritional care is a challenge. The aim was to evaluate whether the implementation of a nutritional strategy would influence nutritional care performance in a university hospital. SUBJECTS/METHODS: This was a prospective quality improvement program implementing guidelines for nutritional care, with the aim of improving nutritional practice. The Nutrition Risk Screening (NRS) 2002 was used. Point prevalence surveys over 2 years to determine whether nutritional practice had improved. RESULTS: In total, 3604 (70%) of 5183 eligible patients were screened and 1230 (34%) were at nutritional risk. Only 53% of the at-risk patients got nutritional treatment and 5% were seen by a dietician. The proportion of patients screened increased from the first to the eighth point prevalence survey (P=0.012), but not the proportion of patients treated (P=0.66). The four initial screening questions in NRS 2002 identified 92% of the patients not at nutritional risk. CONCLUSIONS: Implementation of nutritional guidelines improved the screening performance, but did not increase the proportion of patients who received nutritional treatment. Point prevalence surveys were useful to evaluate nutritional practice in this university hospital. In order to improve practice, we suggest using only the four initial screening questions in NRS 2002 to identify patients not at risk, better education in nutritional care for physicians and nurses, and more dieticians employed. Audit of implementation of guidelines, performed by health authorities, and specific reimbursement for managing nutrition may also improve practice.

Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients.

BACKGROUND: Low plasma glutamine concentration is an independent prognostic factor for an unfavourable outcome in the intensive care unit (ICU). Intravenous (i.v.) supplementation with glutamine is reported to improve outcome. In a multi-centric, double-blinded, controlled, randomised, pragmatic clinical trial of i.v. glutamine supplementation for ICU patients, we investigated outcomes regarding sequential organ failure assessment (SOFA) scores and mortality. The hypothesis was that the change in the SOFA score would be improved by glutamine supplementation. METHODS: Patients (n=413) given nutrition by an enteral and/or a parenteral route with the aim of providing full nutrition were included within 72 h after ICU admission. Glutamine was supplemented as i.v. l-alanyl-l-glutamine, 0.283 g glutamine/kg body weight/24 h for the entire ICU stay. Placebo was saline in identical bottles. All included patients were considered as intention-to-treat patients. Patients given supplementation for >3 days were considered as predetermined per protocol (PP) patients. RESULTS: There was a lower ICU mortality in the treatment arm as compared with the controls in the PP group, but not at 6 months. For change in the SOFA scores, no differences were seen, 1 (0,3) vs. 2 (0.4), P=0.792, for the glutamine group and the controls, respectively. CONCLUSION: In summary, a reduced ICU mortality was observed during i.v. glutamine supplementation in the PP group. The pragmatic design of the study makes the results representative for a broad range of ICU patients.

Suspected allergy to local anaesthetics: follow-up in 135 cases.

BACKGROUND: Local anaesthetics (LA) are generally considered safe with respect to allergy. However, various clinical reactions steadily occur. Even though most reactions are manifestations of reflexes to perceptive stimuli, uncertainty often remains regarding a possible allergic mechanism. This uncertainty later leads to an avoidance of local anaesthesia and unnecessarily painful interventions, resource-consuming general anaesthesia or even the risk of re-exposure to other yet unidentified allergens. In the present study, follow-up procedures at an allergy clinic were analysed to examine the frequency of identified causative agents and pathogenetic mechanisms and evaluate the strength of the diagnostic conclusions. METHOD: The medical records of 135 cases with alleged allergic reactions to LA were reviewed. Diagnoses were based on case histories, skin tests, subcutaneous challenge tests and in vitro IgE analyses. RESULTS: Two events (1.5%) were diagnosed as hypersensitivity to LA, articaine-adrenaline and tetracaine-adrenaline, respectively. Ten reactions (7%) were diagnosed as IgE-mediated allergy to other substances including chlorhexidine, latex, triamcinolone and possibly hexaminolevulinate. As challenge testing was not consistently performed with the culprit LA compound, follow-ups were short of definitely refuting hypersensitivity in 61% of the cases. The reported clinical manifestations were in general diagnostically unspecific, but itch and generalised urticaria were most frequent in test-positive cases. CONCLUSION: Reactions during local anaesthesia are rarely found to be an IgE-mediated LA allergy. Whenever the clinical picture is compatible with allergy, other allergens should also be tested.

Anaphylaxis to Patent Blue V. I. Clinical aspects.

BACKGROUND: The dye Patent Blue V (PBV) is increasingly used for staging procedures in operable breast cancer, but is reported to cause adverse reactions. The aim of this study was to present the clinical features and the results of follow-up examinations in patients with such reactions. METHODS: We studied nine patients with hypersensitivity reactions to PBV between 1999 and 2006 who were identified through the Norwegian network for reporting and investigating allergic reactions during anesthesia. RESULTS: We observed incidences of 0.5% (7/1418) for all kinds of PBV reactions and 0.4% (5/1418) for anaphylaxis. Typical clinical features included: (i) cardiovascular and/or cutaneous symptoms, (ii) a delay in symptoms, compared to the time of dye injection, (iii) poor response to ephedrine and intravenous fluid, and (iv) need for adrenaline administration, sometimes prolonged, for circulatory stabilization. Cutaneous manifestations were noted in five of the seven patients with anaphylaxis and two additional patients without circulatory instability. During anaphylactic reactions, serum tryptase was increased in six patients and normal in one. Serum tryptase was normal in one patient with skin symptoms only. Skin prick tests to PBV were positive in all eight patients tested, including the two with skin manifestations only. CONCLUSION: The clinical features and the results of follow-up studies strongly suggest that these reactions are IgE mediated.

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.

Anaphylaxis to Patent Blue V. II. A unique IgE-mediated reaction.

BACKGROUND: Patent Blue V (PBV) is injected in order to map sentinel nodes during cancer staging procedures. Anaphylactic reactions, allegedly IgE antibody mediated, have been reported. The aim of the study was to explore the immunological mechanism of anaphylaxis to PBV. METHODS: PBV allergen threshold basophil sensitivity, CD-sens, was performed on cells from nine patients diagnosed as having had adverse reactions to PBV. The mechanisms of the CD-sens were studied by immunological and immuno-chemical methods. RESULTS: Five of the nine patients had a positive CD-sens to PBV which was completely eliminated by washing the cells in phosphate buffered saline before allergen challenge. However, the positive CD-sens was completely reconstituted by incubating the cells in plasma or serum of that patient or the other PBV-anaphylactic patients for 15 min at room temperature. In some patients the factor mediating CD-sens was completely or partially destroyed by heating at +56 degrees C for 30 min or being exposed to the low pH used for elution from anti-Ig columns. A 1000-fold excess of monoclonal IgE blocked the reconstitution by approximately 50%. CONCLUSION: Anaphylactic reactions to PBV are mediated by IgE antibodies giving a classical CD-sens reaction. However, the allergenic configuration seems to constitute a structure completely dependent on PBV, as a hapten, linked to a, so far, unknown carrier that seems to be unique for patients having experienced a PBV-induced reaction. Further studies are needed to characterize the postulated carrier.

No consumption of IgE antibody in serum during allergic drug anaphylaxis.

BACKGROUND: The general understanding is that a blood sample for analysis of immunoglobulin (Ig) E antibodies to an allergen suspected to cause an anaphylaxis cannot be drawn until several weeks after the reaction. As this is most unpractical, the changes in IgE antibody levels during anaphylaxis were studied to evaluate the possibility of using samples drawn at the time of the reaction. METHODS: Immunoglobulin E antibodies to suxamethonium were quantitated with ImmunoCAP before, during and after an anaphylactic reaction occurring during anaesthesia using neuromuscular blocking agents. RESULTS: Serum IgE antibody concentrations against suxamethonium in blood samples collected up to 6 h after the reaction were not different from those in samples drawn before or days and weeks after the anaphylaxis. CONCLUSIONS: A serum sample intended to trace the drug involved in an IgE-mediated anaphylactic reaction can be drawn in direct relation to the reaction.

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.

A case of anaphylactic shock possibly caused by intravesical Hexvix.

BACKGROUND: We report a case of a 69-year-old Caucasian male who experienced a severe drop in blood pressure and a skin rash after fluorescence cystoscopy and transurethral resection of the prostate. The diagnostic agent used for fluorescence cystoscopy and suspected of causing the anaphylaxis was hexaminolevulinate hydrochloride (Hexvix). INCIDENT: A profound fall in blood pressure associated with atrial fibrillation, the appearance of a rash, vomiting and transient loss of consciousness occurred immediately after surgery. The hypotension persisted for several hours despite intensive treatment. The reaction commenced approximately 5 h after exposure to Hexvix. There was an increase in serum tryptase (almost nine-fold) and a positive skin prick test to undiluted Hexvix. CONCLUSION: The mechanism of the anaphylaxis is uncertain, but is considered likely to be a non-immunoglobulin E-mediated allergic reaction possibly caused by Hexvix. This is the first reported case of a severe allergic reaction after intravesical instillation of Hexvix.