British Journal of Anaesthesia 88 (4): 600±2 (2002)

Anaphylaxis to rocuronium
C. Baillard1*, A. M. Korinek2, V. Galanton1, Y. Le Manach1, P. Larmignat1, M. Cupa1 and
C. M. Samama1
1
DeÂpartement d'anestheÂsie, HoÃpital Avicenne, 125 route de Stalingrad, F-93009 Bobigny Cedex, France.
2
DeÂpartement d'anestheÂsie, PitieÂ-SalpeÂtrieÁre Hospital, Paris, France
*Corresponding author

Reports about anaphylactic and anaphylactoid reactions to rocuronium have increased recently.
We report two new cases of documented grade III anaphylaxis, leading to death in one patient.
The ®rst case occurred in an 81-year-old ASA II woman scheduled for emergency abdominal
surgery. Severe hypotension and tachycardia were observed after rocuronium, without
bronchospasm. Neosynephrine allowed rapid resuscitation, and the patient recovered fully.
The second patient was a 64-year-old ASA II man scheduled for abdominal surgery. Severe hae-
modynamic instability and bronchospasm occurred after rocuronium. Despite immediate life
support, the postoperative period was complicated by persistent low systolic pressure, acute
respiratory distress syndrome, acute renal failure, disseminated intravascular coagulation and
pancreatitis, leading to the death of the patient.
Br J Anaesth 2002; 88: 600±2
Keywords: neuromuscular block, rocuronium; complications, anaphylaxis
Accepted for publication: December 12, 2002

Rocuronium has been available in France since 1994. It is a
widely used aminosteroidal non-depolarizing neuromuscu-
lar blocking agent that shares many pharmacological
features with vecuronium. It has the advantage of a more
rapid onset time,1 which has led many anaesthetists to use
rocuronium rather than vecuronium.2 Case reports,3±12 and
correspondence,13±14 about both anaphylaxis (characteristic
clinical symptoms, positive allergological tests) and ana-
phylactoid reactions (unusual clinical symptoms and reac-
tion not mediated by IgE) after rocuronium have increased
recently. Such reactions are often life-threatening and may
be fatal.1±14 One fatality following rocuronium has already
been reported.2 We report two new cases of documented
grade III anaphylaxis, leading to death in one patient.
Case reports
Case 1 was an 81-year-old ASA II woman scheduled
for emergency abdominal surgery in March 2000. Her
past medical history included a nervous breakdown and
atrial ®brillation. Her medication consisted of ¯uoxetine
and verapamil. She had previously undergone eight
general anaesthetic procedures, including orthopaedic
(knee and hip) surgery, and repair of a genital prolapse.
Induction was achieved with thiopental 350 mg and
succinylcholine 80 mg. Following loss of consciousness,
the trachea was intubated. Twenty min later and before
skin incision, rocuronium 30 mg and sufentanil 10 mg
were administered. One min later, the patient exhibited
narrow complex tachycardia (156 beat min±1), severe
hypotension (45/32 mm Hg), and weak chest erythema,
but did not develop bronchospasm. Incremental doses of
neosynephrine up to 200 mg were given, and both heart
rate and arterial pressure returned to basal values.
Because of the rapid resuscitation, surgery was not
cancelled. After surgery, the patient was transferred to
the recovery room and her trachea was extubated 1 h
later. She recovered fully and was discharged 6 days
later.
Blood samples obtained at 30 min and 1 h, and urine
sampled at 3 h after the reaction demonstrated increased
levels of histamine (19.7 and 6.7 nmol ml±1, respectively;
normal value <6 nmol ml±1), and tryptase (27.9 and
19.2 nmol ml±1, respectively; normal value <13.5 nmol ml±1)
but normal urinary methylhistamine. Speci®c IgE anti-
bodies against quaternary ammonium ions and rocuronium
measured during the reaction were negative. Cutaneous tests
were performed by an allergologist 6 weeks later. Skin-
prick testing produced wheals <3 mm in the negative control
and 1038 mm in the positive (codeine sulfate) control.
Skin-prick testing con®rmed the diagnosis of anaphylaxis to
rocuronium (837 mm). A positive skin test was also

Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2002
 Anaphylaxis to rocuronium
observed with the other aminosteroidal neuromuscular
blocking agents (pancuronium: 9310 mm; vecuronium:
839 mm), but not with the benzylisoquinolinium neuro-
muscular blocking agents (<3 mm). Intradermal tests were
positive to rocuronium (1:100 dilution),16 with a wheal of
11.5 mm and ¯are of 35 mm, but negative to succinylcho-
line (1:10 dilution).
Case 2 was a 64-year-old ASA II man scheduled for
hernia repair in November 2000. Previous general
anaesthesia for umbilical hernia repair and melanoma
resection had been uneventful. His medical history
included venous thromboembolism and obesity and he
was treated with oral anticoagulants (acenocoumarol).
Anaesthesia was induced with sufentanil 15 mg and
propofol 400 mg. Following loss of the eyelash re¯ex,
rocuronium 50 mg was administered and the trachea
was intubated. Shortly after rocuronium administration,
the patient developed bronchospasm, hypotension (50/
30 mm Hg), tachycardia (135 beat min±1), and general-
ized erythema. The patient was resuscitated with
epinephrine (up to 2 mg i.v., followed by a continuous
i.v. infusion of 0.5 mg h±1), hydrocortisone 200 mg and
colloid 2 litres i.v. Surgery was cancelled and the
patient was transferred to the intensive care unit. The
postoperative period was complicated by persistent low
systolic arterial pressure, acute respiratory distress syn-
drome, acute renal failure, disseminated intravascular
coagulation and pancreatitis, leading to death 7 days
later.
Blood samples obtained at 30 min and 1 h, and urine
sampled at 3 h after the reaction demonstrated elevated
levels of histamine (>100 and 44.6 nmol ml±1, respectively;
normal value <6 nmol ml±1), mast cell tryptase
(>200 nmol ml±1 for both blood samples; normal value
<13.5 nmol ml±1) and urinary methylhistamine (10
318 nmol litre±1 or 849 nmol mmol creatinine±1; normal
value <170 nmol mmol creatinine±1), in keeping with
anaphylaxis. Speci®c IgE antibodies against quaternary
ammonium compounds were detected (QAS-radioimmu-
noassay technique: 3.5%) with positive radioimmunoassay
inhibition by rocuronium (63%).15
Discussion
We report two more anaphylactic reactions to rocuronium,
leading to the death of one patient. According to the Ring
and Messmer classi®cation, these two cases were con-
sidered to be grade III.17
In the ®rst case, the patient did not exhibit any reaction
when she received succinylcholine whereas 20 min later,
she developed an anaphylactic reaction immediately after
rocuronium. Skin tests were highly positive (1/100) to
rocuronium, but negative to atracurium, a well-known
histamine-releasing drug, suggesting an IgE-mediated reac-
tion. The patient may have been previously sensitized to
steroidal neuromuscular blocking agents (she had already
601
undergone eight general anaesthetic procedures), without
cross-reactivity to atracurium or succinylcholine. Speci®c
IgE antibodies against quaternary ammonium ions were
negative. This negative result is not rare, as IgE may have
been consumed during the reaction. The technique has only
85% sensitivity.15 Therefore, the lack of speci®c IgE
detection during such an adverse effect does not rule out
an anaphylactic origin.
In contrast, there is no doubt that the second case
documents a typical anaphylactic reaction because of the
clinical presentation and the increase in mast cell tryptase
and speci®c IgE antibodies against rocuronium. Despite
rapid resuscitation, the patient died after developing mul-
tiple organ failure. Such a fatal event has already been
described with rocuronium and has been documented with
other neuromuscular blocking agents.2
The use of rocuronium is increasing and it is not
surprising that reports of side-effects such as anaphylaxis
increase concomitantly.2±14 A high `rocuronium-mediated
anaphylaxis rate' is suspected by some authors, 2 9±11 who
recommended close monitoring of such adverse events. We
agree with this recommendation. We would like also to
emphasize that neuromuscular blocking agents are the main
drugs responsible for life-threatening episodes during
anaesthesia, but such agents are not always necessary
surgically. There are several studies of the ability to intubate
without neuromuscular blocking agents.18 Between 1995
and 2000 the use of muscles relaxants in intubated patients
decreased from 100% to 25% in our institution, without any
related adverse events. We believe full reporting is import-
ant to study the potential risks of anaphylaxis to rocuronium.
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