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Assessment of Opioid Cross-reactivity and Provider Perceptions in Hospitalized Patients With Reported Opioid Allergies
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Design
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Single-center, retrospective cohort study
N= 499
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Objective
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To characterize the incidence of newly suspected IgE-mediated reactions (IMRs) based on clinical criteria among patients with a chart-documented opioid allergy and to assess clinician perceptions of opioid allergies
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Study Groups
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Historical IgE-mediated reaction (H-IMR; n= 212)
Historical intolerance (n= 249)
Undetermined reaction (n= 38)
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Inclusion Criteria
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Patients aged 18 to 89 years who self-reported or had a chart documented history of an opioid allergy on admission and subsequently received an opioid medication during their stay
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Exclusion Criteria
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Pregnancy; prisoners; cognitively challenged patients; patients receiving concomitant nonopioid medications for which they had a documented allergy; patients admitted for the primary diagnosis of anaphylaxis, angioedema, or any other allergic condition
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Methods
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Patients' electronic healthcare records were retrospectively reviewed to identify historically documented opioid allergy
and then classify as a possible historical IgE-mediated reaction (H-IMR) or an intolerance reaction based on temporal association and symptomatic presentation. Newly suspected IgE-mediated reactions were defined based on the following criteria immediately after opioid administration: the appearance of rash, urticaria, pruritus, or throat swelling; or the requirement of treatment with epinephrine, diphenhydramine, or steroids; or a new ICD-9 code for anaphylaxis.
Patients who developed an IMR after receiving an opioid from a different class than the opioid previously documented as H-IMR were considered to be cross-reactive. Of note, hydrocodone belongs to semisynthetic and tramadol belongs to synthetic classification.
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Duration
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January 1, 2013, to December 31, 2017
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Outcome Measures
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Incidence of allergic cross-reactivity between the 3 different clinical classes of opioid medications (natural, semisynthetic, and synthetic); incidence of opioid intolerance reactions being incorrectly documented as opioid allergies
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Baseline Characteristics
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H-IMR
(n= 212)
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Historical intolerance
(n= 249) |
Undetermined
reaction (n= 38) |
p-value |
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Age, years
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56.4 ± 16 |
62 ± 15.3 |
60 ± 13.5 |
0.01 |
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Female
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77.4% |
70.7% |
65.7% |
> 0.05 |
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Length of hospital stay, days
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4.8 ± 5.12 |
5.5 ± 5.4 |
5.5 ± 5.4 |
0.4 |
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Number of concurrent allergies
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2.6 ± 2.8 |
1.97 ± 2.6 |
2.5 ± 3.6 |
0.06 |
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Historical allergy documentation*
Natural chart allergy
Semisynthetic chart allergy
Synthetic chart allergy
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154 (72.6%)
63 (30.0%)
60 (28.3%)
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172 (69.1%)
82 (32.9%)
41 (16.5%)
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25 (65.8%)
7 (18.4%)
11 (28.9%)
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0.57
0.16
0.005
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*Percentages are determined by proportion of each allergy classification (H-IMR, historical intolerance, or undetermined) that was observed for each opioid class with reported allergy. Some patients reported allergies to opioids from multiple classes, which accounts for the percentage totals above 100% in each column.
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Results
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Opioid Cross-reactivity Rates Among Patients With H-IMRs
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No IMR
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IMR
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Rate
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p-value |
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Patients with H-IMR to natural opioid (n= 154)
Natural readministration
Semisynthetic administration
Synthetic administration
Administration of any opioid of another class
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15
125
83
134
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1
4
2
4
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6.7%
3.2%
2.4%
2.9%
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N/A
0.45
0.41
0.43
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Patients with H-IMR to semisynthetic opioid (n= 63)
Natural readministration
Semisynthetic administration
Synthetic administration
Administration of any opioid of another class
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14
43
38
47
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0
4
3
3
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0
6.9%
7.9%
6.4%
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0.57
N/A
> 0.99
0.71
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Patients with H-IMR to synthetic opioid (n= 60)
Natural readministration
Semisynthetic administration
Synthetic administration
Administration of any opioid of another class
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11
52
25
63
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0
0
0
0
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0
0
0
0
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> 0.99
> 0.99
N/A
> 0.99
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Reaction Rates on Opioid Readministration as Classified by Chart Allergy History.
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No reaction
(n= 462) |
Suspected IMR
(n= 8) |
Intolerance
(n= 29) |
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Allergy history
Any historically reported opioid IgE allergy (n= 212)
Any historically reported opioid intolerance (n= 249)
Unclassified historical opioid reaction (n= 38)
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189 (89.2%)
235 (94.4%)
38 (100%)
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6 (2.8%)
2 (0.8%)
0
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17 (8%)
12 (4.8%)
0
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P-values compare the incidence of newly suspected IMR to the same class of the documented opioid allergy with the incidence of newly suspected IMR to a different opioid class. Some patients concomitantly received opioids from 2 or more classes prior to reaction, in which each medication was considered an individual incidence.
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Adverse Events
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See results |
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Study Author Conclusions
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The risk of IMRs caused by opioids is low in patients with H-IMRs to opioids. Opioid allergy documentations may propagate alert fatigue and unwarranted prescribing changes.
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InpharmD Researcher Critique
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Although specific cross-reactivity between hydrocodone and tramadol was not explicitly evaluated, patients with H-IMR to semisynthetic opioids had a relatively low risk of IMR to synthetic administration. The retrospective nature of the study may impair the accuracy of previously documented H-IMR, and the overall low rates of reactions reported in the study may further limit the implication of cross-reactivity among different classes.
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