Gerald W. Volcheck

The incidence of anaphylaxis following intravenous phytonadione (vitamin K1): a 5-year retrospective review.

BACKGROUND Phytonadione (vitamin K1) administered intravenously (i.v.) has been associated with anaphylaxis, although the incidence is not known. The anaphylaxis is thought to be attributable to the solubilizing vehicle, polyethoxylated castor oil (Cremophor EL, BASF AG, Ludwingshafen, Germany). OBJECTIVE To estimate the incidence of anaphylaxis after i.v. administration of phytonadione. METHODS A retrospective review of anaphylaxis after i.v. phytonadione over a 58-month period at a large academic center was performed. During the period of the study a protocol for the administration of i.v. phytonadione was in place. A review of computerized records and survey of staff identified cases of anaphylaxis meeting predefined inclusion criteria. In addition, a literature review was performed for articles concerning anaphylaxis after i.v. phytonadione. RESULTS Over the 58 months of the study, a total of 6,572 doses of i.v. phytonadione were administered. Two cases of anaphylaxis after i.v. phytonadione were identified. The incidence of anaphylaxis was 3 per 10,000 doses with 95% confidence intervals of 0.04 to 11 per 10,000 doses. The literature review identified 14 cases meeting inclusion criteria with no reviews of the literature or estimates of incidence. CONCLUSIONS The incidence of anaphylaxis after i.v. phytonadione is overall comparable or slightly less than other drugs known to cause anaphylaxis. We do not recommend routine pretreatment with antihistamines or corticosteroids before administration of phytonadione.

Exercise-Induced Urticaria and Anaphylaxis

Exercise-induced urticaria and anaphylaxis have become increasingly recognized during the past 2 decades as more people participate in physical activities. These syndromes can be categorized as cholinergic urticaria or exercise-induced anaphylaxis based on the clinical manifestation. Newer subsets such as food-dependent and familial exercise-induced anaphylaxis have also been recognized. Further studies are needed to characterize the variables involved in mast cell activation and mast cell mediator release in these syndromes. The management strategy for patients who have exercise-induced syndromes with skin manifestations only differs from the management for those with systemic symptoms. Currently, antihistamines, as a single agent or in combination with other agents, may be helpful prophylactically in both groups. Avoidance of precipitating factors, modification of exercise, and use of a self-injectable epinephrine kit are recommended for patients with anaphylaxis.

Anaphylaxis to intravenous cyclosporine and tolerance to oral cyclosporine : case report and review

BACKGROUND Hypersensitivity reactions to cyclosporine are rare. The mechanism of the reaction and guidelines for subsequent use of cyclosporine are not well defined. OBJECTIVE To investigate the mechanisms involved in hypersensitivity reactions to cyclosporine and determine the feasibility of future cyclosporine use. METHODS We report a patient who had an anaphylactic reaction during the intravenous infusion of cyclosporine. Skin-prick tests were performed for the antibiotics he received earlier in the day and the cyclosporine. A MEDLINE search identified all the reported cases of hypersensitivity reactions to cyclosporine. Each was analyzed to determine a mechanism of the hypersensitivity reaction and subsequent management outcomes. RESULTS Intradermal tests to intravenous cyclosporine formulation (1 mg/mL) were positive in the patient and negative in two controls. There was no reaction to the antibiotics. The literature search revealed 22 cases of hypersensitivity reaction to cyclosporine. The clinical setting and diagnostic evaluation suggest multiple mechanisms for the hypersensitivity response. All seven patients who were given an oral formulation of cyclosporine tolerated it well after a reaction to the intravenous infusion. Two patients who initially reacted to an oral solution formulation subsequently tolerated the corn oil-based soft gelatin capsule. CONCLUSIONS Hypersensitivity reactions to cyclosporine are due to Cremophor EL. There is direct and indirect evidence for various immunologic and nonimmunologic pathways precipitating the reaction. This case suggests a role for IgE in the hypersensitivity reaction. Fortunately, a hypersensitivity reaction to one formulation of cyclosporine does not preclude use of a different formulation. The corn oil-based soft gelatin capsule appears to be the safest formulation.

Allergic reactions during anesthesia at a large United States referral center.

BACKGROUND: The types of agents implicated to trigger intraoperative anaphylactic reactions vary among reports, and there are no recent series from the United States. In this retrospective study, we examined perioperative anaphylactic reactions that occurred at a major tertiary referral academic center. METHODS: To characterize perioperative allergens associated with anaphylactic reactions, we reviewed the Mayo Clinic Division of Allergic Diseases skin test database between 1992 to 2010. The records of all patients who were tested for perioperative and anesthetic medications were reviewed. Charts that included a detailed history obtained by an allergist, skin test results, and tryptase measurements when available were reviewed and categorized. RESULTS: Thirty-eight patients were found to have an anaphylactic reaction during anesthesia, of which 18 were immunoglobulin (Ig)E-mediated anaphylactic reactions (likely causative agent identified by skin test), 6 were non–IgE-mediated anaphylactic reactions (elevated tryptase levels and negative skin test), and 14 were probable non–IgE-mediated anaphylactic reactions (tryptase levels normal or not obtained and negative skin test). Of the IgE-mediated anaphylactic reactions, antibiotics were the most prevalent likely causative agent (50%) whereas neuromuscular blocking drugs were implicated as a likely causative agent in 11% of reactions. CONCLUSION: Antibiotics were the most common likely causative agent associated with IgE-mediated anaphylactic reactions; however, for 52.6% of reactions, a causative agent could not be determined, suggesting a non–IgE-mediated anaphylactic reaction. The undiagnosed allergic reactions place patients at risk of a subsequent reexposure to the same allergen, or lead to unnecessary avoidance of needed medications.

Preoperative evaluation of patients with history of allergy to penicillin: Comparison of 2 models of practice

OBJECTIVE To study whether allergy consultation and penicillin allergy skin testing affects the selection of antibacterial prophylaxis perioperatively in surgical patients with history of allergy to penicillin (HOAP). PATIENTS AND METHODS From January 1 through June 30, 2004, we compared 2 different models of practice at our institution. At the Preoperative Evaluation Clinic (POEC), all patients with HOAP are evaluated by an allergist and undergo skin testing for allergy to penicillin. At other (non-POEC) preoperative evaluation settings (OPES), patients with HOAP do not undergo allergy consultation and penicillin skin testing before surgery. Of the 4889 patients screened at the POEC during the study period, 412 consecutive patients with HOAP were included in the study. Of the 416 patients screened at OPES, 69 consecutive patients with HOAP were studied. Logistic regression was used to assess whether allergy consultation was associated with the choice of antibiotic for antibacterial prophylaxis perioperatively, after adjusting for age, sex, and type of surgery. RESULTS Perioperative cephalosporin use was greater among patients screened at POEC vs those screened at OPES (70% vs 39%, P<.001 unadjusted; P=.04 adjusted for age, sex, and type of surgery). Vancomycin use was lower for patients screened at POEC vs those screened at OPES (10% vs 28%, P<.001 unadjusted; P=.03 adjusted). CONCLUSION For patients with HOAP, evaluation at the POEC was associated with increased use of cephalosporin and decreased use of vancomycin.

Formulating an effective and efficient written asthma action plan.

Written asthma action plans (WAAPs) are recommended by national and international guidelines to help patients recognize and manage asthma exacerbations. Despite this recommendation, many patients with asthma do not have a WAAP. In addition, WAAPs vary widely in their readability and usability. To promote issuance and patient use, the WAAP should clearly define the decision (action) points, expected response, and expected time of response. The WAAP should also be easily integrated into a physicians busy practice. Herein, we describe the key elements of an effective WAAP, including concise, detailed recommendations regarding asthma exacerbation recognition (patient self-monitoring) and treatment.

Epidemiology of perioperative anaphylaxis

Anaphylactic reactions may be either of immune (allergy, usually IgE-mediated, sometimes IgG-mediated) or non-immune origin. The incidence of anaphylactic reactions during anaesthesia varies between countries ranging from 1/1250 to 1/18,600 per procedure. In France, the estimated incidence of allergic reactions is 100.6 [76.2-125.3]/million procedure with a high female predominance (male: 55.4 [42.0-69.0], female: 154.9 [117.2-193.1]). The proportion of IgE-mediated allergic reactions seems to be relatively similar between countries, ranging from 50 to 60%. Substantial geographical variability regarding the different drugs or substances involved is reported. Reactions involving neuromuscular blocking agents are a major cause in several countries but are less frequently reported in the United States or Denmark. Reactions involving antibiotics, dyes or chlorhexidine are reported with a high and sometimes increasing frequency in most series. Reactions to latex are rapidly decreasing as a result of primary and secondary prevention policy. Regional differences are a strong incentive for repeated epidemiological surveys in different countries.

The risk of asthma exacerbation after reducing inhaled corticosteroids: A systematic review and meta-analysis of randomized controlled trials

Asthma guidelines suggest reducing controller medications when asthma is stable.

Local and General Anesthetics Immediate Hypersensitivity Reactions

Intraoperative anaphylaxis and hypersensitivity reactions in the setting of anesthesia contribute significantly to the morbidity and mortality of surgeries and surgical procedures. Because multiple medications and products are given in a short period of time, identifying the specific cause can be difficult. Neuromuscular blocking agents, antibiotics, and latex are the most common causes of anesthesia-related reactions, though other medications or exposures could be involved. Careful review of anesthetic charts and allergy testing can help identify the underlying cause. The identification of the cause and subsequent prevention of reactions are critical to reduce overall mortality and morbidity related to anesthesia.

Preventing and Managing Drug-Induced Anaphylaxis

Drug-induced anaphylaxis and anaphylactoid reactions have increased in frequency with more widespread use of pharmaceutical agents. Anaphylaxis is a systemic, severe immediate hypersensitivity reaction caused by immunoglobulin (Ig) E-mediated immunological release of mediators of mast cells and basophils. An anaphylactoid reaction is an event similar to anaphylaxis but is not mediated by IgE.The incidence of anaphylactic or anaphylactoid reactions differs amongst classes of medications. Antibacterials are the most usual offenders, and penicillins are the most studied. Other compounds commonly causing reactions include nonsteroidal anti-inflammatory drugs, anaesthetics, muscle relaxants, latex and radiocontrast media.Prevention, if possible, is the purpose of detailed patient history taking and physical examination. Simple strategies can be employed to decrease the risk of anaphylaxis. These include consideration of the route of drug administration, identification of patients with known causes of anaphylaxis, and the knowledge that certain medications cross react and are contraindicated in those with known history of anaphylaxis. Tests are available, and include IgE-specific skin tests and radioallergosorbent tests. Penicillins are the only compounds whose antigenic determinants are well documented, it is therefore difficult to determine the negative predictive value of other compounds tested. Oral challenge remains an alternative, though entails risk. Desensitisation procedures, as well as gradual dose escalation protocols, are available and can be implemented based on patient history and diagnostic testing.The management of anaphylaxis is based on control of the airway, breathing and circulation. Treatment consists of epinephrine (adrenaline) and supportive measures. Rapid diagnosis and intervention are important in these life-threatening reactions. After stabilisation, all individuals with a documented history of anaphylaxis require a Medic-Alert bracelet or necklace, and an identification card for their wallet or purse.