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.

Consequences of proceeding with surgery after resuscitation from intra-operative anaphylaxis.

Intra-operative acute hypersensitivity reactions require a decision to be made regarding whether to proceed with or abandon the planned surgical procedure once the patient has stabilised. Using retrospective case controls, we examined all cases (223) of proven acute hypersensitivity reactions from 2005 to 2014 in Western Australia, in which the syndrome was recognised by the treating clinician before or during surgery, to determine whether recovery outcomes were adversely affected by proceeding with the planned procedure. Surgery proceeded in 104 patients (47%) and was abandoned in 119 (53%). The severity of acute hypersensitivity reactions was Société Française d'Anesthésie et de Réanimation grade 1 or 2 in 56 patients (25%), grade 3 in 128 (56%) and grade 4 in 39 (17%). Abandoning surgery was more common in patients with increasing severity of hypersensitivity. The rate of major hypersensitivity-related complications for all patients was zero for grade 1 and 2 reactions, 4.7% for grade 3 and 12.8% for grade 4. There were no deaths. Patients in whom surgery was completed were not observed to have a higher frequency of major hypersensitivity-related complications when compared with cases of similar severity in whom surgery was abandoned. For patients admitted to the intensive care unit, proceeding with surgery was not associated with an increased duration of mechanical ventilation of the lungs. Our results suggest that, once initial resuscitation has been achieved and if resuscitative efforts can be re-instituted if required, continuing with planned surgery in grade 1, 2 and 3 immediate hypersensitivity was not associated with poorer outcomes. After grade 3 reactions, there was a significant incidence of complications attributable to acute hypersensitivity regardless of whether surgery proceeded or was abandoned. Surgery was frequently abandoned in grade 4 immediate hypersensitivity and was associated with a high rate of complications.

Cefalotin as antimicrobial prophylaxis in patients with known intraoperative anaphylaxis to cefazolin.

BACKGROUND: The most common trigger for intraoperative anaphylaxis in Western Australia for the period 2014-5 was an antibiotic used for surgical prophylaxis, cefazolin. In these patients who subsequently present for surgery, alternative cephalosporins are forbidden by current guidelines because of concerns regarding an increased risk of anaphylaxis. However, consideration of the structure-activity relationships relevant to anaphylaxis suggests that cefalotin is a safe alternative because of structural dissimilarities, although there are no pubished clinical data relevant to the perioperative setting. METHODS: Patients diagnosed with intraoperative anaphylaxis to cefazolin at the Western Australian Anaesthetic Allergy Clinic were tested with intradermal cefalotin and, if negative, subsequently challenged i.v. If tolerated, cefalotin was recommended for subsequent surgery, and subjects were followed up to determine the safety of subsequent intraoperative doses. RESULTS: Twenty-one subjects diagnosed with immediate hypersensitivity to cephazolin, including 19 subjects with confirmed anaphylaxis, participated. None tested positive to intradermal cefalotin, and all received a graded i.v. challenge to cefalotin without developing signs or symptoms of anaphylaxis. Three subjects subsequently received intraoperative cefalotin 12-139 days later without adverse events. CONCLUSIONS: A negative intradermal cefalotin skin test has a good negative predictive value in patients who have previously suffered anaphylaxis to cefazolin, allowing the rational and desirable use of this alternative cephalosporin for future surgery and the avoidance of less desirable antimicrobial agents.

Efficacy of sugammadex in rocuronium-induced or antibiotic-induced anaphylaxis. A case-control study.

We report 13 cases of presumed rocuronium-induced anaphylaxis in which sugammadex was administered with the intention of reversing the immunological reaction. Of these 13 cases, eight (62%) were later confirmed to be type-1 hypersensitivity reactions to rocuronium, three (23%) were triggered by an antibiotic and two (15%) were non-immunologically mediated. Response to treatment was scored by the treating anaesthetist, and compared with haemodynamic and inotrope measurements from the resuscitation and anaesthetic records. Haemodynamic improvement was seen in only six (46%) cases, three of which were associated with a non-rocuronium trigger. Of the three cases in which the treating anaesthetist thought that sugammadex had been beneficial, one was not caused by rocuronium, one had no improvement in blood pressure and one required 8.5 times as much adrenaline in boluses after, compared with the period before, sugammadex administration. These data suggest that sugammadex does not modify the clinical course of a suspected hypersensitivity reaction.

Survival from perioperative anaphylaxis in Western Australia 2000-2009.

BACKGROUND: The mortality from perioperative anaphylaxis has recently been quoted in a range between 3 and 9%. However, it was our impression in Western Australia that we had had no deaths from perioperative anaphylaxis for over a decade. As we have comprehensive processes in place to investigate both perioperative anaphylaxis and anaesthesia-related deaths, we undertook this study to determine our actual perioperative anaphylaxis mortality rate. METHODS: We obtained the number of deaths related to perioperative anaphylaxis for the decade 2000-2009 from the database of the West Australian Anaesthetic Mortality Committee; in Western Australia it is a legal requirement to report all deaths that occur within 48 h of an anaesthetic, and all deaths due to a complication of an anaesthetic. We obtained the number of cases of perioperative anaphylaxis for the same period from the database of the West Australian Anaesthetic Drug Reaction Clinic. RESULTS: From 2000 to 2009, there were 45 anaesthesia-related deaths in Western Australia, but none of these involved anaphylaxis. Over this period, there were 264 cases classified by the West Australian Anaesthetic Drug Reaction Clinic as anaphylaxis. The 95% confidence interval for the observed 0/264 mortality rate is 0-1.4%. There were about three million anaesthetics administered in Western Australia over the decade, giving a perioperative anaphylaxis rate of ~1:11,000. CONCLUSIONS: Our incidence of perioperative anaphylaxis was within expectations, but our mortality rate was lower than recently quoted figures. It is likely that the current true perioperative anaphylaxis mortality rate is within the range 0-1.4%.

Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011.

BACKGROUND: Neuromuscular blocking drugs (NMBDs) are the most common cause of intraoperative anaphylaxis in Western Australia. Differences in the rates of anaphylaxis between individual agents have been surmised in the past, but not proven, and are an important consideration if agents are otherwise equivalent. METHODS: We estimated a rate of anaphylaxis to NMBDs by analysing cases of NMBD anaphylaxis referred to the only specialized diagnostic centre in Western Australia over a 10 yr period. Exposure was approximated by analysing a 5 yr period of NMBD ampoule sales data. Agents were also ranked according to the prevalence of cross-reactivity in patients with previous NMBD anaphylaxis. RESULTS: Rocuronium was responsible for 56% of cases of NMBD anaphylaxis, succinylcholine 21%, and vecuronium 11%. There was no difference in the severity of reactions for different NMBDs. Rocuronium had a higher rate of IgE-mediated anaphylaxis compared with vecuronium (8.0 vs 2.8 per 100,000 exposures; P=0.0013). The prevalence of cross-reactivity after NMBD anaphylaxis suggested that succinylcholine also has a high risk of triggering anaphylaxis. Cisatracurium had the lowest prevalence of cross-reactivity in patients with known anaphylaxis to rocuronium or vecuronium. CONCLUSIONS: Rocuronium has a higher rate of IgE-mediated anaphylaxis compared with vecuronium, a result that is statistically significant and clinically important. Cisatracurium had the lowest rate of cross-reactivity in patients who had previously suffered anaphylaxis to rocuronium or vecuronium.

The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model.

The availability of sugammadex as a selective encapsulating agent for rocuronium has led to speculation that it may be useful in mitigating rocuronium-induced anaphylaxis. Off-label use of sugammadex for this indication has already been documented in case reports although there are theoretical objections to the likelihood of an allergen-binding agent's being able to attenuate the immunological cascade of anaphylaxis. Using a cutaneous model of anaphylaxis in rocuronium-sensitised patients, we were unable to demonstrate that sugammadex was effective in attenuating the type-1 hypersensitivity reaction after it has been triggered by rocuronium, but we were able to demonstrate that these patients are anergic to sugammadex-bound rocuronium. These findings demonstrate that a cyclodextrin can bind an allergen and exclude it from interacting with the immune system, and may potentially lead to novel applications in other allergic diseases. However, there is no evidence that sugammadex should be used for the treatment of rocuronium-induced anaphylaxis, and clinical management should follow established protocols.

Sugammadex in the management of rocuronium-induced anaphylaxis.

Anaphylaxis during anaesthesia is a rare event that in ∼60-70% of cases is secondary to neuromuscular blocking agents. It has been suggested previously that the recent introduction of sugammadex may provide a novel therapeutic approach to the management of rocuronium-induced anaphylaxis. We describe the case of a 33-yr-old female who suffered a severe anaphylactic reaction to rocuronium, presenting with cardiovascular collapse on induction of anaesthesia. After 19 min of traditional management, she was given a bolus of sugammadex 500 mg. This was associated with an improvement in the adverse haemodynamic state. The underlying reasons for this are unclear, but sugammadex may potentially be a useful adjunct in the management of rocuronium-induced anaphylaxis.

Epinephrine (adrenaline) preventing recovery from intraoperative anaphylactic shock complicated by systolic anterior motion of the mitral valve with left ventricular outflow tract obstruction on transoesophageal echocardiography.

We describe a case of severe left ventricular outflow tract obstruction (LVOTO) with severe mitral incompetence due to systolic anterior motion of the anterior mitral leaflet (SAM) that was recognised thanks to the immediate availability of transoesophageal echocardiography during the resuscitation of anaphylactic shock. The patient rapidly responded to cessation of the epinephrine (adrenaline) infusion and intravascular volume expansion with intravenous crystalloid. The absence of risk factors for developing SAM/LVOTO serve as a warning to clinicians to consider this diagnosis in all cases of epinephrine non-responsive anaphylactic shock.

Recent clinical experience with etodolac in the treatment of osteoarthritis of the knee.

Interim results are reported for three double-blind clinical trials comparing etodolac, a new nonsteroidal anti-inflammatory drug (NSAID), with piroxicam, diclofenac, or naproxen in patients with osteoarthritis (OA) of the knee. Patients assigned to receive etodolac were given 200 mg three times a day in the diclofenac comparison and 300 mg twice a day in the other two studies. The comparator groups in the three studies received piroxicam 20 mg once a day, diclofenac 50 mg three times a day, or naproxen 500 mg twice a day. The length of the studies ranged from 6 to 12 weeks, and patients were seen at baseline and every 2 weeks thereafter. Etodolac, piroxicam, and diclofenac treatment consistently resulted in similar and statistically significant changes from baseline, indicative of improvement, in all primary efficacy variables (physicians' and patients' global assessments of improvement, pain intensity, and night pain) at every evaluation. In the comparison with naproxen, patients who received etodolac showed statistically significant improvement at most evaluations, whereas significant changes were less frequent in the naproxen group. Response rates in the three studies (response was defined as a decrease of 1 or more units in the patient's overall global evaluation, which is based on a 5-point scale ranging from 1 = very good to 5 = very poor) were as follows: etodolac 72%, piroxicam 75%; etodolac 66%, diclofenac 56%; and etodolac 40%, naproxen 16%. These interim results suggest that the efficacy of etodolac compares favorably with that of other NSAIDs in the treatment of OA of the knee.

Intraoperative anaphylaxis to sugammadex and a protocol for intradermal skin testing.

Sugammadex is a selective binding agent for aminosteroid neuromuscular blockers whose use is increasing in anaesthetic practice. We present three cases of severe anaphylaxis coincident with sugammadex administration. Subsequent intradermal testing confirmed sugammadex as the triggering agent, with all patients having positive skin responses to a 1:100 dilution of the standard 100 mg/ml solution and two out of three having a positive response to a 1:1000 dilution. As all patients were administered sugammadex to reverse neuromuscular blockade with rocuronium, we considered that sugammadex-rocuronium complexes were a potential unique allergen. In the two patients who were additionally tested with a rocuronium-sugammadex (3.6:1 molecular ratio) mixture, the wheal-and-flare response was significantly attenuated.

Systemic mastocytosis presenting as intraoperative anaphylaxis with atypical features: a report of two cases.

Two cases of perioperative cardiovascular collapse are presented that were associated with markedly elevated mast cell tryptase levels shortly after the event, leading to the assumption that an immunoglobin E-mediated, drug-induced anaphylaxis had occurred. However, the clinical picture in both cases was atypical and subsequent skin testing failed to identify a triggering drug. Further blood tests, some weeks later, revealed persistently elevated baseline levels of mast cell tryptase. In both cases bone marrow biopsy and genetic testing confirmed the diagnosis of mastocytosis. We present evidence and speculate that mast cell degranulation was triggered by tourniquet release in the first case and by exposure to peanuts in the second. An atypical presentation of anaphylaxis should alert the anaesthetist to the possibility of previously undiagnosed mastocytosis.

Quantification of volume loss and haemodynamic changes of Gelofusine-induced anaphylaxis during cardiopulmonary bypass.

A patient undergoing anaesthesia for coronary artery bypass surgery developed what was subsequently confirmed to be an anaphylactic reaction to succinylated gelatin (Gelofusine). By virtue of being on cardiopulmonary bypass, rapid detection, quantification and treatment of volume loss (by vasodilatation and extravasation) was possible. The patient required 51 ml/kg of resuscitative fluids in the 15 minutes after onset of anaphylaxis, or 73% of her calculated preoperative blood volume. Alpha-adrenoceptor agonists and vasopressin were required to manage ongoing vasoplegia. This case emphasises the importance of volume resuscitation and vasopressors in the treatment of anaphylaxis.