Lampard, Andrina

Manidakis, Nikolaos

Mohanlal, Paras

Polyzois, Ioannis

Tsiridis, Eleftherios

Tsiridis, Evgenios

English

PubMed

Springer - Publisher Connector

BioMed CentralCases Journal
ssOpen AcceCase Report
Intraoperative anaphylaxis due to gelofusine in a patient undergoing 
intramedullary nailing of the femur: a case report
Ioannis Polyzois1, Andrina Lampard1, Paras Mohanlal1, Evgenios Tsiridis2, 
Nikolaos Manidakis1 and Eleftherios Tsiridis*1
Address: 1Academic Orthopaedic Unit, Leeds General Infirmary, Leeds School of Medicine, Leeds, LS1 3EX, UK and 2Blue Cross Hospital, Cardio-
Thoracic Anaesthetic Unit, Thessaloniki, Greece
Email: Ioannis Polyzois - polyzois@hotmail.co.uk; Andrina Lampard - andrinalampard@hotmail.com; 
Paras Mohanlal - drmpkumar@hotmail.com; Evgenios Tsiridis - etsiridis@hotmail.com; Nikolaos Manidakis - nimanidakis@hotmail.com; 
Eleftherios Tsiridis* - etsiridis@doctors.org.uk
* Corresponding author    
Abstract
Background: Although uncommon, anaphylaxis due to a colloid plasma expander can occur peri-
operatively
Case presentation: We present a case of an intra-operative cardiac arrest in a 72 year old
Caucasian male patient who underwent prophylactic intramedullary nailing for a proximal femoral
metastasis from prostate cancer. The patient was resuscitated successfully and the procedure was
completed uneventfully. Elevated serum tryptase levels confirmed the diagnosis of an anaphylactic
reaction and positive allergy skin prick testing identified gelofusine as the causative agent.
Conclusion: A high index of suspicion, prompt diagnosis and rapid institution of treatment are
essential for a safe outcome following such reactions. To our knowledge, this is the first published
report of such a severe reaction to gelofusine infusion that occurs during an orthopaedic
procedure.
Background
Colloid plasma expanders are widely used during surgery
and play a key role in resuscitation of the severely hypo-
volaemic patient [1]. They provide intravascular volume
expansion and help reduce transfusion requirements
whilst also allowing time for full blood cross matching to
be carried out. Anaphylactoid reaction to Gelofusine, that
contains succinylated gelatin and other plasma expanders
carries an estimated incidence of 0.07–0.15% [1,2]. How-
ever, this can prove life-threatening if not promptly recog-
nized and accordingly treated.
These reactions are normally type I, IgE-mediated and
cause production of antibodies through prior sensitiza-
tion, although in many cases they may occur without any
previous documented exposure. The reaction is termed
anaphylactoid when there is no known prior exposure for
the production of the antibody-antigen reaction of true
anaphylaxis [1,3].
Case presentation
A 72 year old male Caucasian patient was referred to our
unit with a metastatic bony deposit involving his left
proximal femur from a known primary prostatic carci-
noma. Commonly, prostatic metastases are sclerotic in
nature. However detailed radiological evaluation demon-
strated a large lytic lesion in this case (Figure 1). Due to
the high risk of an impending pathological fracture, the
Published: 6 January 2009
Cases Journal 2009, 2:12 doi:10.1186/1757-1626-2-12
Received: 4 November 2008
Accepted: 6 January 2009
This article is available from: http://www.casesjournal.com/content/2/1/12
© 2009 Polyzois et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 4
(page number not for citation purposes)
Cases Journal 2009, 2:12 http://www.casesjournal.com/content/2/1/12decision was taken to perform prophylactic intramedul-
lary nailing of the left femur (Figure 2). In order to reduce
the increased intramedullary pressure during nail inser-
tion, venting of the distal end of the femur was performed
(Figure 3).
The patient did not have any other significant past medi-
cal history and he was not known to be allergic to any
medication. He had surgical procedures for other condi-
tions in the past requiring general anaesthesia and had an
uneventful recovery in every case.
During the procedure, the patient suffered a cardiac arrest.
Fat embolism was initially thought to be the cause of this
event due to the increased intramedullary pressure during
reaming and nail insertion. Following successful resusci-
tation, a marked generalized erythematous rash was
noticed which lasted for about thirty minutes. This raised
the concern of a possible hypersensitivity reaction to one
of the anaesthetic agents. Our patient received in total
eight different drugs namely propofol, atracurium, mor-
phine, ondansentron, dexamethasone, gelofusine, para-
cetamol and diclofenac. Interestingly, it was noted that
the cardiac arrest occurred following a dose of atracurium
and an infusion of gelofusine. Consequently, it was
thought that either one of those two agents could have
been responsible for the anaphylactic response.
Serum mast cell tryptase levels taken one hour following
the event, demonstrated a level of 190 ng/ml, which
dropped to 60 ng/ml upon repeating the levels twelve
hours later (normal range 3–23 ng/ml). The raised levels
of mast cell tryptase were consistent with mast cell degran-
ulation. The latter strongly suggested a hypersensitivity
reaction. Furthermore, allergy skin prick tests were per-
formed to all the drugs used during the procedure. Inter-
estingly, they showed a positive reaction to gelofusine
only, confirming it as the causative agent.
Discussion
Plasma expanders play an important role in trauma resus-
citation as well as during the peri-operative period. How-
Anteroposterior (AP) view radiograph of the left femur dem-o strating he large lytic met stasis in the subtronchanteric areaFigu e 1
Anteroposterior (AP) view radiograph of the left 
femur demonstrating the large lytic metastasis in the 
subtronchanteric area.
AP and lateral image intensifier views showing optimal posi-tioni g of the proximal locking scre s and the intra edullary nail  the left proxi al femurFigure 2
AP and lateral image intensifier views showing opti-
mal positioning of the proximal locking screws and 
the intramedullary nail in the left proximal femur.Page 2 of 4
(page number not for citation purposes)
Cases Journal 2009, 2:12 http://www.casesjournal.com/content/2/1/12ever there is controversy regarding the relative merits of
colloid versus crystalloid solutions as colloids can induce
an anaphylactoid reaction which could potentially prove
life threatening if left untreated [4].
Such reactions are more common in male patients with
atopy and often occur within ten minutes of commencing
the infusion, hence the need for early and frequent moni-
toring [1]. The reactions are graded in severity on a scale
of I-V and tend to be under-reported [2]. Nevertheless,
with the increasing use of these agents there are sporadic
reports of such adverse reactions in the literature [3,5-7].
In a large multi-centre prospective trial conducted by Ring
and Messner which involved 200,906 infusions of colloid
substitutes, sixty-nine cases of anaphylactoid reactions
were observed. Specifically, the incidence of severe reac-
tions including shock, cardiac and/or respiratory arrest
was found to be 0.003% for plasma protein solutions,
0.006% for hydroxylethylstarch, 0.008% for dextran and
0.038% for gelatin solutions [2].
Not all gelatins share the same molecular structure;
Haemaccel and Plasmagel are urea-linked, whilst Gelofu-
sine is a succinate-linked gelatin. Hepner and Castells
stated that there is no known cross-reactivity between dif-
ferent colloids, so a particular allergy to one should not
preclude the use of another [8]. Whilst this is probably
true of colloids of highly differing chemical composition,
it is not the case between Haemaccel and Gelofusine
which differ only in their linkage to urea or succinate.
Cross-reactivity between these two colloids has been doc-
umented by intradermal skin prick testing [9]. Conse-
quently, any patient known to be allergic to one should be
assumed as being allergic to the other until proven other-
wise.
There have been case reports of anaphylactoid reactions to
all of the gelatin-based colloids, with varying degrees of
response severity. In 1979 Freeman reported a case of
severe anaphylaxis to Haemaccel which unfortunately
resulted in death. Autopsy findings of mucus in the bron-
chioles, indicating severe anaphylactic bronchospasm
were attributed to reaction to the infused colloid, though
no concrete evidence of the role of Haemaccel was found
[6]. Often, due to polypharmacy during anaesthesia it is
difficult to elucidate a single agent causing the anaphylac-
tic response. In severe reactions it may become necessary
to abandon the operative procedure until the patient has
been resuscitated and conduct further investigations to
identify the cause [5]. Great care must be taken once there
is a suspicion of allergy due to the possibility of reaction
to other gelatin-based colloids or escalating anaphylactic
response with further infusion [7]. This scenario was
exemplified by Vervloet et al, who described three cases of
anaphylaxis due to modified fluid gelatin Plasmagel. One
of these occurred during an operative procedure which
had to be abandoned and in one patient a repeat infusion
of Plasmagel caused anaphylactic shock [5].
Diagnosis can be a challenge in such circumstances. Some
features of anaphylactic response to an agent are similar to
the effects of anaesthesia itself. Most anaesthetic agents
can cause vasodilation, hypotension and potential cardi-
opulmonary dysfunction due to their direct and indirect
effects on the cardiovascular system, and distinguishing
this from an anaphylactic reaction can prove difficult. In
our case, the cardiorespiratory arrest could have been due
to a number of different causes, including fat or pulmo-
nary embolus. It was only after careful observation that
the developing erythematous rash was noted and the pos-
sibility of anaphylaxis considered.
Elevated serum tryptase levels are indicative of mast cell
degranulation and are very helpful in the differential diag-
nosis of anaphylaxis. Concentrations peak one hour after
the hypersensitivity reaction and can usually last for sev-
AP views of the left distal femur demonstrating drilling and creation of a distal venting holeFigure 3
AP views of the left distal femur demonstrating drill-
ing and creation of a distal venting hole.Page 3 of 4
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eral hours thereafter. Comparison with the baseline val-
ues, taken a few weeks after the event, may confirm or
exclude the diagnosis. However this does not define the
causative agent. The standard diagnostic technique for
this is skin prick testing. This may be complemented by
detection of specific IgE by radioimmunoassay [10].
Apostolou et al have reported the use of in vitro basophil
activation test (BAT) as a safe and reliable assay test to
detect gelofusine sensitivity. This method uses detection
of surface expression of lysosomal membrane glycopro-
tein CD63 on activated basophils [11]. The leucocyte his-
tamine release test (LHR) which can measure histamine
release in response to gelatin solutions in vitro has been
described but remains mostly a research tool [5].
Conclusion
Even though colloid plasma expanders carry a risk of ana-
phylactoid reaction, this is small when compared to com-
mon drugs such as penicillin, which carries a risk of
adverse reaction from 1–5% [12]. Plasma expanders pro-
vide intravascular volume expansion and help reduce
transfusion requirements. However, the use of these
agents should be done with caution. A high index of sus-
picion and a prompt diagnosis should ensure successful
resuscitation in the event of anaphylaxis.
Consent
Written informed consent was obtained from the patient
for publication of this case report and accompanying
images in the Cases Journal.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
IP conducted a literature search and prepared the final
manuscript. AL conducted a literature search and contrib-
uted to preparation of the manuscript. PM prepared the
first draft of the manuscript. ET conducted a literature
search and contributed to preparation of the final manu-
script. NM contributed to the preparation of the final
manuscript. ET supervised the manuscript and treated the
patient. All authors contributed equally in collecting
patient data and editing radiographic images.
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Intraoperative anaphylaxis due to gelofusine in a patient undergoing intramedullary nailing of the femur: a case report

Ioannis Polyzois

Andrina Lampard

Paras Mohanlal

Evgenios Tsiridis

Nikolaos Manidakis

Eleftherios Tsiridis

Ioannis  Polyzois

Crossref

Adverse reactions to drugs. BMJ

Anaphylactic reactions to modified fluid gelatins. J Allergy Clin Immunol

Castells MC: Anaphylaxis during the perioperative period. Anesth Analg

Fatal reaction to haemaccel. Anaesthesia

Fenwick DG: Anaphylaxis to Haemaccel and cross reactivity to Gelofusin. Anaesth Intensive Care

GA: Three cases of anaphylactoid reaction to Haemaccel. Anaesth Intensive Care

Gelofusine allergy – the need for identification jewellery. Ann R Coll Surg Engl

I: Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials.

Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet

Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull World Health Organ

O'hehir RE: Anaphylaxis to Gelofusine confirmed by in vitro basophil activation test: a case series. Anaesthesia

Synthetic plasma volume expanders – their pharmacology, safety and clinical efficacy. Clin Haematol

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Intraoperative anaphylaxis due to gelofusine in a patient undergoing intramedullary nailing of the femur: a case report

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