Peri-Operative Anaphylaxis—An Investigational Challenge

Patients with suspected peri-operative anaphylaxis (POP) require thorough investigation to identify underlying trigger(s) and enable safe anesthesia for subsequent surgery. The changing epidemiology of POP has been striking. Previous estimates of the incidence of POP have ranged between 1:6,000 and1:20,000 anesthetics, but more recent data from France and the United Kingdom suggest an estimated incidence of 1:10,000. Other important changes include a change in the hierarchy of well-recognized triggers, with antibiotics (beta-lactams) supplanting neuromuscular blockers (NMB) as the leading cause of POP. The emergence of chlorhexidine, patent blue dye, and teicoplanin as important triggers have also been noteworthy findings. The mainstay of investigation revolves around critical analysis of the time-line of events leading up to anaphylaxis coupled with judicious skin testing. Skin tests have limitations with respect to unknown predictive values for most drugs/agents and therefore, knowledge of background positivity in healthy controls, test characteristics of individual drugs and the use of non-irritant concentrations is essential to avoid both false-positive and false-negative results. Specific IgE assays for individual drugs are available only for a limited number of agents and are not a substitute for skin testing. Acute serum total tryptase has a high specificity and positive predictive value in IgE-mediated POP anaphylaxis but is limited by its moderate sensitivity and negative predictive value. Planning for safe anesthesia in this group of patients is particularly challenging and consequently anesthetists need to be alert to the possibility of repeat episodes of anaphylaxis. Because of the limitations of current investigations for POP, collecting systematic data on the outcome of repeat anesthesia is valuable in validating current investigatory approaches. This paper reviews the changing epidemiology of POP with reference to the main triggers, and the investigation and outcome of subsequent anesthesia

Exploring facilitators and barriers in asthma management in rural, semi-urban and urban populations in Vellore, India:an interview study of patients and primary care physicians

Summary box In India, there are deficits in asthma self-management and asthma training for primary care physicians. We advocate culturally tailored interventions for patients and clinically oriented training for primary care physicians.<br/

Effects of short-term exposure to nitrogen dioxide and ozone on human airways

The studies presented in this thesis have examined the plausible mechanisms underlying development of airway inflammation soon after short-term exposure to ozone at peak ambient levels and NO2 at peak indoor levels on human airways.The study presented in chapter 3 has shown that short-term exposure of healthy human subjects to 2 ppm NO2 induces an acute inflammatory response characterised by secretion of IL-8 at 1.5 hours and this is followed by influx of PMNs at 6 hours in the bronchial wash (BW) following exposure. No changes were seen in the inflammatory cell numbers or in the expression of leucocyte endothelial adhesion molecules (LECAMs) in the bronchial mucosa suggesting that NO2 induces an inflammatory response mainly in the peripheral conducting airways.In order to study (chapter 4) the role of the LECAMs in ozone-induced acute inflammatory response, fibre-optic bronchoscopy (FOB) was performed 1.5 hours following exposure to ozone (0.12 ppm). No changes were seen in total and differential cell counts, albumin and total protein in BW and bronchoalveolar lavage (BAL) fluid. A significant increase was seen in the expression of P-selectin staining blood vessels in the bronchial submucosa following ozone exposure. However, no changes were seen in the numbers of neutrophils and the expression of other LECAMs including ICAM-1, E-selectin and VCAM-1 in bronchial submucosa. In the absence of an overt inflammatory response the upregulation of P-selectin could represent one of the earliest events in the inflammatory response such as 'rolling' of neutrophils on the vessel wall prior to transendothelial migration.In conclusion, these studies have shown that short-term exposure to ozone (healthy and asthmatic airways) and NO2 (in healthy airways) induces an acute inflammatory response characterised by PMN influx and at least at the dose and time points studied the inflammatory response occurs mainly in the peripheral conducting airways. In addition, exposure to ozone in healthy subjects induces epithelial damage, stimulates subepithelial sensory nerves to release SP and secretion of chemokines which contribute to development of inflammation.</p

Peri-Operative Anaphylaxis-An Investigational Challenge.

Patients with suspected peri-operative anaphylaxis (POP) require thorough investigation to identify underlying trigger(s) and enable safe anesthesia for subsequent surgery. The changing epidemiology of POP has been striking. Previous estimates of the incidence of POP have ranged between 1:6,000 and1:20,000 anesthetics, but more recent data from France and the United Kingdom suggest an estimated incidence of 1:10,000. Other important changes include a change in the hierarchy of well-recognized triggers, with antibiotics (beta-lactams) supplanting neuromuscular blockers (NMB) as the leading cause of POP. The emergence of chlorhexidine, patent blue dye, and teicoplanin as important triggers have also been noteworthy findings. The mainstay of investigation revolves around critical analysis of the time-line of events leading up to anaphylaxis coupled with judicious skin testing. Skin tests have limitations with respect to unknown predictive values for most drugs/agents and therefore, knowledge of background positivity in healthy controls, test characteristics of individual drugs and the use of non-irritant concentrations is essential to avoid both false-positive and false-negative results. Specific IgE assays for individual drugs are available only for a limited number of agents and are not a substitute for skin testing. Acute serum total tryptase has a high specificity and positive predictive value in IgE-mediated POP anaphylaxis but is limited by its moderate sensitivity and negative predictive value. Planning for safe anesthesia in this group of patients is particularly challenging and consequently anesthetists need to be alert to the possibility of repeat episodes of anaphylaxis. Because of the limitations of current investigations for POP, collecting systematic data on the outcome of repeat anesthesia is valuable in validating current investigatory approaches. This paper reviews the changing epidemiology of POP with reference to the main triggers, and the investigation and outcome of subsequent anesthesia

Fatal drug reaction to andexanet alfa:a case report

Andexanet alfa is a recombinant, modified factor Xa (FXa) molecule that is used for the reversal of the anticoagulant effect of oral anti-FXa anticoagulants in patients with major haemorrhage. Here we present a case of an 85-year-old man taking rivaroxaban for atrial fibrillation, who presented with an acute, upper gastrointestinal bleed. He was stabilised with red cell transfusion and then received a 400 mg bolus of andexanet alfa. Within minutes of this, he developed chest tightness, shortness of breath, ischaemic electrocardiographic changes, and then cardiac arrest from which he could not be resuscitated. The onset of symptoms was clearly temporally related to andexanet alfa administration and the differential diagnosis includes anaphylaxis with Kounis syndrome, or myocardial infarction. Although infusion site reactions have been reported and are relatively common, this is to date the first case of a fatal drug reaction andexanet alfa. This knowledge can be factored into physicians’ risk-benefit decisions when treating patients with oral anti-FXa anticoagulant-associated major haemorrhage