Full text of DOI:10.1007/BF03019670

890
CLINICAL REPORT
Rocuronium anaphylax-
is and multiple neuro-
muscular blocking drug
sensitivities
Peter Matthey MB FFARCSI,*
Pei Wang MB FFARCSI,†
Barry A Finegan MB FRCPC,*
Maria Donnelly MB FFARCSI†
Purpose: To report a case of anaphylaxis to rocuronium and the sensitivities to multiple neuromuscular blocking
drugs in a patient with no previous exposure to this group of drugs. We describe the current recommendations
for both intraoperative and postoperative testing of these patients.
Clinical Features: A 36-yr-old man was admitted for repair of a ruptured Achilles tendon. Following induction
of general anesthesia with fentanyl and propofol, 60 mg of rocuronium were given to facilitate tracheal intubation.
He immediately became profoundly hypotensive with impalpable pulses, and blood pressure could not be
recorded. Airway pressure increased markedly, and hand ventilation of the lungs became very difficult. His airway
was secured and he was successfully resuscitated with 3 mg epinephrine and three litres crystalloid and colloid
intravenous fluid therapy. His recovery in the intensive care unit was uneventful and the operation was performed
four days later under spinal anesthesia. Subsequent skin prick testing, performed six weeks later, demonstrated
strong positive weal and flare reactions to rocuronium, vecuronium and pancuronium, and some cross-reactivity
with the benzylisoquinolinium group of muscle relaxants.
Conclusion: Muscle relaxants are responsible for 61.6% of cases of anaphylaxis during general anesthesia.
Cross-reactivity is common, as this group of drugs share a quaternary ammonium group. It is mandatory that
patients be tested for both the agent responsible and cross-reactivity following an anaphylactic response. We sug-
gest a protocol for investigation of suspected anaphylaxis.
Objectif : Rendre compte d’un cas d’anaphylaxie au rocuronium et de sensibilité à de multiples myorelaxants
chez un patient non exposé auparavant à ce genre de médicaments. Décrire les recommandations courantes de
tests peropératoires et postopératoires à réaliser dans de tels cas.
Éléments cliniques : Un homme de 36 ans a été admis pour la réparation d’une rupture de tendon d’Achille.
Après l’induction de l’anesthésie générale avec du fentanyl et du propofol, on a administré 60 mg de rocuronium
pour faciliter l’intubation endotrachéale. Une importante hypotension s’est immédiatement installée, les pouls
étaient impalpables et la pression sanguine ne pouvait être enregistrée. La pression a beaucoup augmenté dans les
voies aériennes et la ventilation manuelle des poumons est devenue très difficile. On a libéré les voies aériennes et
le patient a été réanimé avec succès suivant l’administration intraveineuse de 3 mg d’épinéphrine et de 3 L de
cristalloïde et de colloïde. La récupération s’est déroulée sans incident à l’unité des soins intensifs et l’opération a
été réalisée quatre jours plus tard sous rachianesthésie. Le test de cutiréaction pratiqué ultérieurement, six semaines
après l’opération, a montré une réaction papulo-érythémateuse fortement positive au rocuronium, au vécuro-
nium et au pancuronium ainsi qu’une réaction croisée avec les myorelaxants du groupe benzylisoquinolinium.
Conclusion : Les myorelaxants sont responsables de 61,6 % des cas d’anaphylaxie pendant l’anesthésie
générale. La réaction croisée est courante, car ce type de médicaments partage un groupe d’ammonium quater-
naire commun. Il faut absolument que les patients subissent des tests pour vérifier la réaction croisée et la sensi-
bilité à l’agent responsable d’anaphylaxie. Nous recommandons un protocole d’examen dans les cas d’anaphylaxie
présumée.
From the Department of Anesthesia and Intensive Care, Adelaide and Meath Hospitals,† Incorporating The National Children’s Hospital,
Dublin, Ireland and Department of Anesthesia, Walter C. Mackenzie Health Sciences Centre,* University of Alberta, Edmonton, Canada.
Address correspondence to: Peter Matthey MB, Department of Anesthesia, 3B2.32 Walter C Mackenzie Health Sciences Centre,
University of Alberta, Edmonton, T6G 2B7 Canada. Phone: 780-407-8861; Fax: 780-407-3200; E-mail: pmatthey@ualberta.ca
Accepted for publication June 15, 2000.
CAN J ANESTH 2000 / 47: 9 / pp 890–893

Matthey et al.: ROCURONIUM ANAPHYLAXIS
891
OCURONIUM is an aminosteroid non-
the event could not be processed due to a storage
error. The operation was performed four days after the
initial event under spinal anesthesia, using 0.5% bupi-
vacaine, without incident.
depolarising muscle relaxant and shares
many pharmacological features with
vecuronium. Rocuronium’s main benefits
R
are rapid onset of neuromuscular blockade with mini-
mal cardiovascular side-effects and negligible hista-
mine release.1,2
We report a patient who developed anaphylactic
shock following administration of rocuronium.
Subsequent testing revealed sensitivity to many of the
non-depolarising muscle relaxants in current use.
The results and implications of this event were
explained to the patient and arrangements were made
for him to have a further series of skin prick tests on
his return home. A Medic-Alert bracelet was supplied.
More extensive skin prick testing was performed in
his local hospital six weeks later. This revealed strong
positive weal and flare reactions to rocuronium, vecuro-
nium and pancuronium. A 3 mm weal developed in
response to cisatracurium, demonstrating cross-reactiv-
ity with the benzylisoquinolinium group of muscle
relaxants. Tests for succinylcholine were negative.
Case Report
A 36-yr-old, 80 kg healthy male tourist was scheduled to
undergo repair of a ruptured Achilles tendon under gen-
eral anesthesia. He had undergone previous uneventful
dental anesthesia and had no history of allergies or atopy.
Patient monitoring included continuous electrocardiog-
raphy (ECG), non-invasive blood pressure monitoring,
Discussion
Muscle relaxants are the commonest group of anes-
thetic drugs implicated in perioperative anaphylaxis. A
recent report from the French Perioperative
Anaphylactoid Reactions Study Group found that
61.6% of anaphylactic reactions were due to muscle
relaxants, with vecuronium, atracurium and succinyl-
choline responsible for 30.5%, 25.1%, and 24.8%
respectively.3
Clinically, it is not possible to differentiate anaphy-
lactoid from anaphylactic shock and histamine is
involved in both processes, though an IgE mechanism
predominates in allergic reactions to non-depolarising
muscle relaxants.4 The main antigenic determinants of
non-depolarising muscle relaxants are the tertiary and
quaternary ammonium groups, which are common to
all of this class of drugs. Consequently the potential
for cross reactivity exists, though it is unusual to be
allergic to all non-depolarising muscle relaxants.5,6 To
date only three cases of rocuronium anaphylaxis have
been reported.4,7 In one case report a patient suffered
an anaphylactic reaction to rocuronium but negative
results were obtained in response to testing with
vecuronium, pancuronium, pipercuronium, d-tubocu-
rarine and atracurium. The case described in our
report is unusual in that sensitivity to many of the
non-depolarising muscle relaxants in common use
today occurred.
pulse oximetry (SpO , airway pressure and end-tidal car-
bon dioxide (ETCO )measurement.
2 )
2
Anesthesia was induced with 100 µg fentanyl and
150 mg propofol with 20 mg lidocaine. Once the abil-
ity to ventilate the lungs had been confirmed, 60mg
rocuronium were administered to facilitate tracheal
intubation.
Immediately following rocuronium administration
the lungs became extremely difficult to ventilate with
bag and mask. Emergency intubation was performed
and auscultation revealed bronchospasm. Concomitant
with this a supraventricular tachycardia of 180
beats·min-1 was noted on ECG. Pulses were impalpable
and SpO and ETCO were unrecordable. Profound
2
bradycardia of 30 beat2s·min-1 followed and cardiopul-
monary resuscitation was promptly initiated. Atropine,
0.6 mg, 3 mg epinephrine in divided doses and volume
loading with two litres of saline and one litre of gelo-
fusin were given over the next 20 min. At this point,
blood pressure returned, but an adrenalin infusion at 7
µg·kg–1·min– 1 was required to maintain a systolic pres-
sure of greater than 80 mmHg. Hydrocortisone, 200
mg, was also administered.
The procedure was canceled and the patient was
transferred to the intensive care unit (ICU). By this
time generalized edema, more prominent in the facial
area, was noted. The epinephrine infusion was discon-
tinued 60 min after ICU admission. Tracheal extuba-
tion was achieved three hours later. Subsequent
recovery was uneventful.
Skin prick testing, performed two days later,
demonstrated a strong reaction to rocuronium bro-
mide, with negative results for fentanyl, propofol and
lidocaine. Serum tryptase levels taken at the time of
Cross-reactivity of rocuronium has recently been
evaluated in a series of thirty-one patients known to
have had hypersensitivity reactions to a variety of neu-
romuscular blocking agents.8 Ten of these patients
exhibited the presence of specific IgE against the qua-
ternary ammonium group on radioimmunoassay
(QAS-RIA), but cross-reactivity could not be demon-
strated using intradermal and in vitro leukocyte hista-
mine release (LHRT) testing for rocuronium. The

892
CANADIAN JOURNAL OF ANESTHESIA
LHRT test had demonstrated 83% specificity for eval-
uating in vitro cross-reactivity between steroid muscle
relaxant drugs in this series. Laxenaire et al. conclud-
ed that rocuronium had a low potential for anaphylax-
is and suggested that it could be considered as an
alternative agent in those known to be allergic to
other muscle relaxants, provided that intradermal test-
ing was negative.
TABLE Investigation protocol for suspected anaphylaxis
1. Do not attempt any investigations until emergency treatment
has been completed.
2. Make a detailed written record of all events, including timing
of administration of drugs in relation to the onset of the reaction.
3. Draw blood samples for serum ß-tryptase at 1, 3 and 24 hours
after onset of reaction. Use serum collection tube. Separate
blood as quickly as possible. Store separated serum at -20°C
unless it can be processed immediately.
The clinical features, response to treatment and
subsequent test results suggest that our patient suf-
fered an anaphylactic response to rocuronium.
Unfortunately, we were unable to prove this conclu-
sively in the absence of serum tryptase levels. The
striking feature of this case was the presence of multi-
ple allergies to muscle relaxants.
4. Draw blood sample for plasma histamine. Process immediately.
5. Collect urine for determination of urinary methyl-histamine
concentrations. Timed collection. Requires acetic acid bottle.
6. Perform intradermal testing four to six weeks after the event to
identify the agent responsible for the reaction. Current recom-
mended dilutions are 10– 1 to 10– 4 for intradermal testing, and
10– 1 for skin prick testing. Ideally these tests should be per-
formed in an allergy clinic by experienced personnel.
7. In the case of muscle relaxants, identify any cross-reactivity.
8. Explain the importance of the reaction to the patient and pro-
vide a Medic-Alert bracelet.
As anaphylactic reactions are uncommon, this case
also serves to highlight the importance of having a pro-
tocol in place to guide the clinician in performing the
appropriate laboratory tests at the time of a suspected
reaction (Table). These tests will subsequently aid in
confirming or refuting a diagnosis of anaphylaxis. As
these tests are specialized and reactions may occur out-
side of normal laboratory working hours, correct stor-
age and processing of samples is vital. Immunological
and biochemical proof of anaphylaxis requires elevated
levels of histamine and tryptase, together with demon-
stration of specific IgE. Serum ß-tryptase, plasma hist-
amine and urinary methyl-histamine levels are the most
useful immediate tests. Elevated ß-tryptase concentra-
tions demonstrate that mast-cell activation with medi-
ator release has occurred, the level generally reflecting
the severity of the reaction. The initial sample must be
obtained within one to two hours of the reaction and
a further sample is usually obtained five to six hours
later. ß-tryptase serum samples remain stable for sever-
al days when correctly stored. Plasma histamine con-
centrations return to baseline within 30 to 60 min of
the reaction and must therefore be drawn immediately.
Sample processing must not be delayed, as sponta-
neous basophil histamine release will occur, resulting in
falsely elevated histamine levels. Urinary methyl-hista-
mine remains elevated for longer and may thus be
more useful.9
9. Report the event to the appropriate regulatory body.
With respect to muscle relaxants, Laxenaire et al.
suggest performing intradermal tests on the back
using 10–4 to 10–1 dilutions of the commercially avail-
able drug preparations. Injections are given every 15-
20 min starting with a 10–4 dilution when a prick test,
using undiluted drug, is positive and starting with a
10–3 dilution when the prick test is negative, and end-
ing with the lowest dilution as long as the results seem
negative. A positive prick test is deemed to have
occurred if the resulting wheal is at least half the diam-
eter of that produced by a control test using 9%
codeine phosphate solution. Skin tests are interpreted
after 15 min: a positive reaction results in a pale pink
wheal and surrounding flare. Intradermal tests are
positive when the diameter of the wheal is more than
5 mm with a surrounding flare.8
Other tests for cross-reactivity include LHRT and
QAS-RIA but, as they do not have a higher sensitivity
than intradermal testing and are considerably more
difficult to perform, they are more useful in confirm-
ing the results of skin tests in dubious cases.
It is considered mandatory that attempts are made
to identify the drug responsible for an anaphylactic
reaction, and that any cross-reactivity among muscle
relaxants is also identified.
Intradermal testing is the method of choice for this,
though skin prick testing has also been shown to have a
sensitivity and specificity of over 95% for succinylcholine,
pancuronium and vecuronium.1 0 – 1 2 Intradermal testing
is best performed approximately one month after the ini-
tial episode.1 3
In conclusion, drug related anaphylactic reactions in
anesthesia are uncommon, but are most frequently due
to the aminosteroid group of non-depolarising muscle
relaxants. Cross-sensitivity can occur and must be iden-
tified. The patient should be advised with respect to
future options once the results of testing are available.

Matthey et al.: ROCURONIUM ANAPHYLAXIS
893
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