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British Journal of Anaesthesia 97 (5): 6349 (2006)

doi:10.1093/bja/ael237

Advance Access publication September 1, 2006

CLINICAL PRACTICE
Anaesthetists responses to patients self-reported drug allergies
R. D. MacPherson1 *, C. Willcox2, C. Chow2 and A. Wang1
1

Department of Anaesthesia and Pain Management and 2Department of Pharmacy,


Royal North Shore Hospital, Pacific Highway, St Leonards, NSW 2065, Australia
*Corresponding author. E-mail: RMacpher@nsccahs.health.nsw.gov.au
Background. Patients with drug allergies are commonplace in anaesthetic practice. We investigated the incidence and nature of drug allergies reported by surgical patients attending a
hospital pre-admission clinic, and went on to ascertain to what degree drug allergies recorded
in the records influenced drug prescribing during the patients hospital stay and determine
whether any adverse events occurred in relation to drug prescribing in this population.

Results. Of 1260 patients attending the Pre-admission clinic during the study period 420 (33.4%)
claimed to have a total of 644 individual drug allergies. The most common agents implicated were
antibiotics (n=272), opioid analgesics (n=118) and NSAIDs (n=62); the most common form of
these reactions were dermatological (n=254) and nausea and vomiting (n=124). There were 41
self-reports specifically of anaphylaxis and a further 61 where there was significant respiratory
system involvement.
Conclusions. The majority of the self-reported allergies were in fact simply accepted adverse effects
of the drugs concerned. The patients reported drug allergy history was generally well respected by
anaesthetists and other medical staff. There were 13 incidents, mainly involving morphine, where
patients were given a drug to which they had claimed a specific allergy. There were 101 incidents in 89
patients where drugs of the same pharmacological group as that of their allergic drug were used. There
were no untoward reactions in 84 patients who had claimed a prior adverse reaction to penicillin who
were given cephalosporins. There were no sequelae from any other events. While anaesthetists
generally respected patients self-reported allergies, more attention needs to be paid to the accurate
recording of patients events and a clear distinction should be made both in medical records and to the
patient between true drug allergy and simple adverse drug reactions.
Br J Anaesth 2006; 97: 6349
Keywords: complications, adverse drug reaction; complications, allergy
Accepted for publication: June 29, 2006

Taking a drug history is an integral part of any medical


admission, and within that history it is important to elicit
from the patient reports of previous adverse drugs effects or
drug allergies, as these details will obviously influence drug
selection and therapeutic decision making. Unfortunately,
the reliability and details of such self-reported allergies are
often questionable, and furthermore these details are often
recorded in a perfunctory manner.
The aims of the present study were 3-fold. First, to examine in detail self-reported drug allergies in a surgical patient
population, and to determine the extent to which these

events were likely to be true drug allergy as opposed to a


simple adverse drug effect. Then, by examination of patient
medical records, to ascertain to what degree patient reported
allergy had influenced prescribing and whether any adverse
events occurred because of inappropriate prescribing.

Methods
After approval from the Hospital Ethics Committee, as part
of their routine admission, all patients attending the PreAdmission Clinic at this hospital were questioned by an

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Methods. Patients attending for anaesthetic assessment at a Pre-Admission Clinic over a 30 week
period were questioned concerning drug allergies. Medical records of these patients were then
examined after their hospitalization to assess medications prescribed during that period.

Anaesthesia and drug allergies

attending pharmacist (C. W. or C. C.) using a formatted


questionnaire as to whether they had any drug allergies to
report. If the response was positive, patient characteristic
data were recorded, and the exact nature of the reaction and
how long ago the reaction occurred. These patient allergies
were recorded in the usual manner on the Patient Medication
Chart. After discharge from hospital, the medical records of
these patients were examined to ascertain what drugs were
administered during their admission and whether any of
these medications might conflict with those reported as
allergies from the patient allergy list.

Results

Preoperative assessment
A total of 644 reactions were reported by the 420 patients
finally enrolled in the study. Mild reactions such as rash
or pruritus (n=254) or nausea and vomiting (n=124) constituted the bulk of reports (Table 1). Of the serious reports,
there were 41 self-reports specifically of anaphylaxis
[penicillins (n=21); sulphonamides (n=4); NSAIDs (n=2)]
and a further 61 reports of potentially serious events
involving respiratory distress, upper airway obstruction or
oro-facial oedema. Although there is clearly considerable
possibility of crossover between the anaphylaxis and
Table 1 Nature of adverse reactions to drugs as described by patients
(n=number of reports)
Type of reaction

Rash/pruritis
Nausea/vomiting
CNS/hallucinations
Oedema/swelling
Anaphylaxis
Extrapyramidal symptoms
Other reactions
Could not recall

254
124
64
61
41
8
54
38

Postoperative assessment
The aim of this part of the study was to examine to what
degree patients self-reported drug allergies were respected
with regard to medication prescription. Of the original
420 patients enrolled in the study, records for 400 were selected for further examination. Twenty patients were excluded from the second part of the study either because the
patient did not proceed to surgery (n=9), or because the
patient medical record could not be located (n=11).
In the majority of cases (n=298), patients were not given
drugs to which they had stated a specific drug allergy. There
were 101 instances in 89 individuals where drugs were selected from related groups, presumably in an effort to avoid
the allergic drug (Table 3). The most common event was
Table 2 Drugs to which patients claimed they had previous adverse or allergic
reactions (n=number of individual reports)
Drug

Antibiotic
Penicillin
Sulphonamides
Cephalosporins
Erythromycin
Tetracyclines
Other
Opioids
NSAIDs
Iodine
Vaccines
Phenothiazines
Tramadol
Steroids
Other

272
147
60
15
12
8
30
118
62
24
14
13
12
7
122

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During the 30 week period, a total of 1260 patients attended


the Hospital PAC for assessment before surgery. Of these
431 (29.1%) claimed to have at least one drug allergy and
underwent further assessment by a pharmacist. Eleven
patients were excluded. In nine patients this was because
their allergy was not to a drug but rather to either surgical
dressings or foodstuffs. The remaining 2 cases were patients
who each claimed to have more than 40 different drug
allergies. Unfortunately, of the list presented, in many
instances these patients had not received all of these
drugs at all, but rather had created lists of drugs to which
they felt they might be allergic. It proved impossible to
determine from these patients histories which drugs they
had been exposed to and which ones were simply suspected allergens. Therefore 420 patients were finally admitted
to the study. The patient characteristics of the group showed
a female preponderance (females 269, males 139) with a
mean overall age of 62.6 yr (range 1995 yr).

breathing/oedema categories, only patients who specifically stated anaphylaxis as their type of reaction were
included in the former category. Of this group, the most
common drugs implicated again were antibiotics with 31
reports [penicillins (n=14); sulphonamides (n=12), other
antibiotics (n=5)], non-steroidal anti-inflammatory drugs
(n=8) and opioids (n=3). There were 38 cases in which
the patient stated they had suffered an adverse reaction to
a particular drug, but had forgotten details of the event and
could offer no further information.
Table 2 shows the most common drugs implicated in
these reactions with antibiotics (n=272) and opioid analgesics (n=118) being the most common. Of importance to
anaesthetists, other common agents to which allergy was
reported included NSAIDs (62), phenothiazines (13) and
tramadol (12). Of six patients who claimed to be allergic
to general anaesthesia, all in fact were reporting postoperative nausea and vomiting. The time course of these reactions was also investigated. Although the majority (n=317)
had occurred within the last 10 yr, patients continued to
report reactions that had occurred 30 (n=570), 40 (n=47)
or even 50 yr earlier (n=37). In 124 cases, the patient could
not recall when the reaction had occurred.

MacPherson et al.

Table 3 The left column (Stated allergy) lists drugs to which patients had
claimed a previous adverse reaction. The middle column shows drugs of similar
pharmacological activity administered to these patients. The right column lists
number of instances
Stated allergy

Drug given

Penicillin
Penicillin
Penicillin
Prochlorperazine
Pethidine
Atropine
Atropine
Antibiotics
Anaesthetics
Codeine
Omeprazole
Indomethacin
Indomethacin

Cephazolin
Cefotetan
Ceftriaxone
Metoclopramide
Morphine
Hyoscine
Glycopyrrolate
Gentamicin
GA
Tramadol
Esomprazole
Rofecoxib
Diclofenac

n
73
7
4
2
2
1
1
1
6
1
1
1
1

Discussion
An integral part of the medical or anaesthetic assessment is
an appraisal of any previous drug allergies or adverse drug
reactions (ADRs). In the hospital setting, these same questions are often asked by multiple members of the health care
team including nursing staff and pharmacists, but despite
this, accurate recording of details does not always occur.1
While such data are usually then summarized as a simple
list, further analysis often gives useful insight into the nature
of these reactions. An ADR has been defined2 as any noxious, unintended and undesired side effect of a drug that
occurs at doses used for prevention, diagnosis and treatment.
However, Rawlins and Thompson3 have expanded this concept, and classified ADRs into two main categories, depending on their aetiology.
Type A reactions are common and predictable. These are
usually dose dependent and are produced by known and
understood pharmacological actions of a drug. They include
the effects of excessive dosage and secondary effects such as
diarrhoea related to antibiotic use.4 Drug intolerance (an
undesired effect produced by a drug at therapeutic or
sub-therapeutic doses) is also included in this category.
Type B reactions are defined as uncommon, usually
unpredictable and dose-independent events. A range of

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the use of cephalosporins in patients who self-reported a preexisting adverse reaction to penicillin (n=84).
However, in a small number of cases (n=13) there was
evidence that the patient was administered either the drug to
which they had claimed they were allergic or an agent of
very close pharmacological similarity. In six of these cases,
morphine was administered to patients who had claimed a
previous allergy to the drug. In the other cases, penicillin
was given to two patients with a claimed penicillin allergy,
and codeine (three), tramadol (one) and aspirin (one) were
administered under similar circumstances. In none of these
cases was there any evidence of any subsequent adverse
reaction after administration.

other descriptors have been used to describe these events


including idiosyncratic reactions (uncharacteristic reactions
that are not explicable in terms of a drugs pharmacological
action) and allergic or hypersensitivity reactions.5 Recently,
the whole question as to what criteria should be present to
constitute an allergic reaction has been re-examined. Expert
groups6 7 have suggested that the term drug hypersensitivity should be used as an umbrella term to cover the gamut of
reactions, especially those involving the skin and mucous
membranes. The term allergy should be used only to
describe reactions that have been demonstrated to be
immunologically mediated, with all other events referred
to as non allergic hypersensitivity.
There is no doubt that analysis of ADRs and hence comparisons between studies have become more difficult. This is
because of what one author8 has called a Tower of Babel
terminology, where over time definitions and terms have
changed, with some categories (e.g. pseudo-allergy) being
declared obsolete while other new categories (e.g. allergic
protein contact dermatitis) have emerged. In part these
changes reflect the growing understanding in the area of
clinical immunology.
Despite the limitations of the Rawlinson and Thompson
classification, it remains in use by many authors as a means
to simply classify ADRs.9 It has been suggested that in
addition to the Type A and B reactions outlined above, a
third group needs to be acknowledged. These are patients
who experience an adverse event, such as nausea or vomiting, and wrongly ascribe this as being because of medication, when in fact it may be part of the disease process.
The incidence of drug allergies and the distribution of
Types A and B reactions using the Rawlins and Thompson
classification has been widely studied. Taken in the broadest
context, most studies have found that the incidence of selfreported drug allergy is in the order of between 25 and
39%.1012
In one of these studies11 the rates of reported ADRs were
assessed on admission. In 915 patients admitted over a 13
month period, 78 (8.5%) reported a total of 102 ADRs and
102 reactions. In 45 cases in this study, the adverse drug
event was directly responsible for the patients admission.
The most common drugs implicated were diuretics, analgesics, especially NSAIDs, and anti-psychotic agents. In
another study, Jones and Como12 found the ADR rate in
their sample (n=133) to be 39% with beta-lactam antibiotics
(12.6%), sulphonamides (9.1%) and opioids (4.4%) being
the most commonly implicated agents.
When these ADRs are further examined, most studies
have concluded that the majority of the self-reported drug
reactions are of the Type A category. These constitute
between 70 and 80% of reports13 14 with an undetermined
group of about 10%. Our study supports these findings with
Category A reactions (n=386) exceeding Category B reactions (n=152). In the remainder of cases (n=106) it was
not possible to determine the nature of the reaction from
the data supplied. The most common types of reactions were

Anaesthesia and drug allergies

patients (mean age 61.7), reflecting changes in prescribing


patterns. While occasional dermatological reactions such as
StevensJohnson syndrome can be potentially life threatening, most common skin and gastrointestinal complaints to
this drug group are generally minor. There is some disagreement concerning the incidence of cross-sensitivity between
sulphonamides and other agents with structural similarities.
While it is known that the para-amino benzoic acid moiety
found in sulphonamides is also found in a range of other
drugs such as COX-2 inhibitors, thiazide diuretics, sulphonylurea oral hypoglycaemic agents and diazoxide, it has
been suggested that the risk of cross-reactivity would seem
to be more of a theoretical rather than a clinical consideration.30 This is because the sulphonamide antibiotics contain
an aromatic amine on the N4 position, necessary both for the
drugs antimicrobial activity and allergenic propensity, a side
chain that is lacking in these other drugs.31
NSAIDS are common producers mainly of gastrointestinal upset, a typical Type A reaction. While true allergic
reactions are uncommon,32 this group of drugs has been
implicated in more serious reactions such as NSAID induced asthma and urticaria/angio-oedema. Aseptic meningitis
and hypersensitivity pneumonitis are other rare immunerelated reactions that have been reported.33 34
With regard to opioids, the majority of reactions are
clearly of the Type A category and include, nausea, vomiting sedation and pruritus. These are clearly not allergic in
nature but it can be problematic to administer the drug again.
Most anaesthetists in our study chose to avoid the offending
drug (usually morphine) and selected another opioid. However, with the current trend against the use of meperidine35
the possibilities are becoming more limited.
It is of interest to note that in our study, seven patients
reported a reaction to corticosteroids (rash, 2; facial swelling, 2; hallucinations, 1; could not recall, 1). Steroid hypersensitivity reactions although rare are not unknown. In one
review36 the authors noted that steroid reactions can vary
from minor dermatological effects to complete cardiovascular collapse. The mechanisms involved are probably multiple with some being of a classic IgE response and some
pseudo-allergic in nature.
In this study, a total of 644 reactions were reported by
420 patients seen in a Pre-Admission Clinic, a result that
concords with those of previous reports that suggest that
approximately one-third of hospital patients will report at
least one drug allergy. Patients have a tendency to venerate
their drug allergies, with many of the reported reactions
being of dubious importance and many having occurred
more than 40 yr ago. Importantly, the most commonly reported drugs, antibiotics, opioids and analgesic agents such as
NSAIDs and tramadol, are those that would normally be
given as part of the anaesthetic or surgical admission. When
called to anaesthetize these patients, the anaesthetist must
decide whether to avoid reported allergic drugs completely
and use alternative agents or whether to investigate the selfreported allergy in more detail. If further investigation

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generally minor with dermatological and gastrointestinal


reactions being the most common.
Others have found conflicting results. In one study15 the
investigators examined more than 1800 patients and found
that 28% claimed to have one or more allergies. There was a
clear female preponderance (60.3%). Commonly implicated
drugs were antibiotics (50%), opioids (27%) and NSAIDs
(10%). The rate of probably true allergic (Type B) reaction
was higher than most at 50%. In another large prospective
study of hospital admissions 366 cases of suspected drug
allergy were reported during a 2 yr period16 and found
the majority (57.4%) to be true allergic reactions, 19.7%
idiosyncratic and 19.1% coincidental reactions.
Despite changes in prescribing patterns over time, the
most commonly reported drugs in our study are common
to other earlier studies and include antibiotics and analgesics
including opioids and NSAIDs,12 with the most common
reactions being dermatological, another finding common to
previous studies.14 16 17
It is generally accepted that penicillins are the most common cause of allergic drug reactions and anaphylaxis,18 with
an incidence across the population as a whole of between
1 and 10%. However, it has been suggested that the vast
majority of patients who report a penicillin allergy are not
truly allergic19 and could safely receive the drug. Another
large scale prospective study showed that of 1790 people
with claimed penicillin allergy, only 57 (3.2%) demonstrated true penicillin allergy of which 4 were anaphylactic
in nature.20
Much has been written on penicillin allergy and its consequences. It is clearly important to correctly identify the
true nature of reactions in patients claiming penicillin
allergy. Validation of true allergy using skin prick testing
should be instituted where possible, as patients self-labelled
as allergic may be treated with inappropriate antibiotics and
hasten the spread of multiple drug resistant organisms.19
Anaphylactic reactions to penicillin, while still very rare,5
continue to account for more than 75% of all fatal anaphylactic drug reactions.21 22 When this reaction does
occur, it is mainly in adults aged 2049 yr.23 Interestingly,
with the passage of time the risk associated with readministration of the drug decreases,24 with the incidence
of positive skin test responses in previous anaphylaxis
patients reducing by about 10% annually. Skin testing itself
has a very variable sensitivity of between 20 and 70%
depending on the determinant.2527
The incidence of cross-sensitivity between penicillins and
cephalosporins has been the subject of continued interest.
The degree of cross-reactivity has been estimated at about
10% for first generation cephalosporins, but only 12% in
third generation agents.28 29 In our study a range of cephalosporins [cephazolin (n=73), cefotetan (n=7) and ceftriaxone (n=4)] were given to 84 patients who believed they
were allergic to penicillin with no adverse sequelae.
Sulphonamide antibiotics are rarely prescribed nowadays,
and most people stating allergy to these agents were older

MacPherson et al.

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suggests that the reaction simply represents an adverse drug


event, and there are no reasonable alternatives to the suspect
drug, then the use of the drug could be justified
after discussion with the patient. The risk, as always, is
that the prescriber will have little recourse in the unfortunate
situation should an untoward reaction occur.
The label of drug allergy needs to be applied with caution after the occurrence of an ADR. Patients should understand that unnecessarily labelling themselves as allergic
when it is not the case can result in the use of less appropriate medication in the future, as the allergic label will
restrict the prescribers choice. Even when the patient has
suffered a true allergic reaction subsequent investigations
may show that this was not caused by the drug thought to be
responsible at the time.37
A second approach is the replacement on medication
charts and anaesthetic record sheets of the work drug
allergy with ADR, which apart from being more correct
terminology, might give prescribers more leeway in deciding whether to administer the stated drug or not after consideration of previous events. In our hospital, adverse drug
events are recorded on a specific sheet, which is then transferred from the patients medical record to his or her medical
admission notes during subsequent admissions. Therefore
we have a permanent and ongoing record of previous
adverse drug events recorded by appropriate and identifiable
hospital personnel. We should also be aware that a large
proportion, if not the majority, of ADRs occur in the community, and not the hospital setting.38 Appropriate communication of such events7 represents another possible area of
improvement.
Should an adverse drug event occur during the perioperative period the anaesthetist should make a point of discussing this with the patient. If it is likely that a Type A reaction
has occurred the patient should be reassured that this does
not constitute an allergic reaction and does not preclude the
use of the drug in the future.
The results of the present study indicate that in general
anaesthetists take great care to avoid the administration of
medications to which a patient has claimed a stated allergy.
However, much of the information volunteered by patients
is unreliable, reflecting events of decades earlier. Ensuring
that patients are given accurate and preferably written
details of adverse drug events that occur during their hospital admission will help alleviate these problems in the
future.

Anaesthesia and drug allergies

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