Simulation of Health and Economic Benefits of Extended Observation of Resolved Anaphylaxis

Marcus Shaker,David B K Golden,Matthew Greenhawt,John Oppenheimer,Dana Wallace

doi:10.1001/jamanetworkopen.2019.13951

Abstract

Biphasic anaphylaxis may occur in up to 20% of patients with anaphylaxis; however, the optimal observation time of patients with resolved anaphylaxis is unknown. To characterize the cost-effectiveness of short vs prolonged medical observation times after resolved anaphylaxis. An economic evaluation was performed of computer-simulated adult patients observed in outpatient allergy clinics and emergency departments, with rates of biphasic anaphylaxis derived from a 2019 meta-analysis. Computer-simulated patients (10 000 per strategy) were randomized to undergo 1 hour of medical observation (associated with 95% negative predictive value of biphasic anaphylaxis) or 6 or more hours of observation (associated with a 97.3% negative predictive value of biphasic anaphylaxis). Cost-effectiveness of 6- to 24-hour medical observation of resolved anaphylaxis evaluated at willingness-to-pay thresholds of $10 000 per case of biphasic anaphylaxis observed and $10 million per death prevented, assuming that observation is associated with a 10- to 1000-fold reduction in the risk of death due to biphasic anaphylaxis. Biphasic anaphylaxis occurred after hospital discharge in 365 patients observed for 1 hour and in 213 patients undergoing prolonged observation. From a health care sector perspective, with medical observation costs of $286.92 per hour, the incremental cost of extended medical observation of resolved anaphylaxis (1 hour vs 6 hours) was $62 374 per case of biphasic anaphylaxis identified ($68 411 from the societal perspective). In Monte Carlo simulations, with hourly costs ranging from $100 to $500 and extended observation ranging from 6 to 24 hours (health care sector perspective), the mean (SD) costs were $295.36 ($81.22) for 1 hour of observation vs $3540.42 ($1626.67) for extended observation. The incremental cost-effectiveness ratio was $213 439 per biphasic anaphylaxis observed ($230 202 from the societal perspective). A 6-hour observation could be cost-effective if the risk of biphasic anaphylaxis after 1-hour observation of resolved anaphylaxis was 17% or if hourly observation costs were less than $46 in the base case. Cost-effectiveness could also be achieved (willingness-to-pay of $10 million per death prevented, health care sector perspective) when a baseline fatality rate of 0.33% per biphasic anaphylactic event was assumed, with a no greater than 24% relative risk of fatality associated with 6-hour observation. This study indicates that prolonged medical observation (6-24 hours) for resolved anaphylaxis may not be cost-effective for patients at low risk for biphasic anaphylaxis; however, in particular clinical circumstances of low observation costs, high postdischarge risk of biphasic anaphylaxis, or large incremental fatality risk reduction associated with extended observation, longer medical observation can be justified.

Highlights

Anaphylaxis is an acute event that represents a life-threatening emergency.[1]
Biphasic anaphylaxis occurred after hospital discharge in 365 patients observed for 1 hour and in 213 patients undergoing prolonged observation
This study indicates that prolonged medical observation (6-24 hours) for resolved anaphylaxis may not be cost-effective for patients at low risk for biphasic anaphylaxis; in particular clinical circumstances of low observation costs, high

Summary

Introduction

Anaphylaxis is an acute event that represents a life-threatening emergency.[1]. estimates vary, the lifetime prevalence of anaphylaxis ranges between 1.6% to 5.1%, with an incidence of 42 cases per 100 000 person-years.[1,2,3,4] Leading causes of anaphylaxis include medications, foods, and stinging insects, many cases are idiopathic.[1,2,5,6,7,8,9] Fatal anaphylaxis is rare, with an overall estimated prevalence of 0.47 to 0.69 cases per million persons.[10,11,12] anaphylaxis-associated hospitalizations have increased, case-fatality rates have remained stable at 0.25% to 0.33% of hospitalizations or emergency department (ED) visits for anaphylaxis.[13]Biphasic anaphylaxis is a potential sequela of resolved anaphylaxis, by definition occurring after anaphylaxis has been treated and completely resolved for at least 1 hour.[14,15] Biphasic anaphylaxis can be life-threatening and has been reported to occur up to 78 hours after the initial episode of anaphylaxis.[15]. It is important to distinguish biphasic anaphylaxis from a protracted (incompletely responsive) initial anaphylactic episode, as well as to differentiate repeated anaphylactic episodes from subsequent reexposure to an unidentified trigger.[16,17] Biphasic anaphylaxis may occur in less than 1% to 20% of individuals with anaphylaxis, and its occurrence is difficult to predict with any certainty.[14,18,19] Specific treatments for biphasic anaphylaxis have not been well studied, but at present, standard practice focuses on management with rapid administration of intramuscular epinephrine—management identical to the treatment of index anaphylaxis.[15,20] antihistamines and glucocorticoids are frequently used in an attempt to prevent biphasic anaphylaxis, clear evidence supporting a benefit associated with this practice is scant.[16,20,21,22,23] In the community setting, epinephrine autoinjectors in the United States are administered as a twinpack (2 devices) only, secondary to the risk of a poorly responsive primary reaction or the risk of a biphasic reaction, and individuals are advised to carry both units on their person at all times.[24]

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