# Severe Anaphylaxis to Volplex, a Colloid Solution during Cesarean Section: A Case Report and Review

Authors: K. Karri; R. Raghavan; J. Shahid
Journal: Obstetrics and Gynecology International
 (2009)

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## Abstract

Anaphylaxis is a life-threatening event that can occur anytime during pregnancy. It has been reported following administration of various substances with adverse maternal and neonatal consequences. It should be considered in the differential diagnosis of intrapartum collapse. We encountered a case of severe anaphylactic reaction following a routine cesarean section. It is very important that all members of the perinatal team are aware of early recognition and management of anaphylactic reaction. We think that it is important to highlight this as a further case report of severe anaphylactic reaction to a colloid solution and discuss the pathophysiology and
management.


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## Body

## 1. Introduction

Anaphylaxis
is an acute systemic reaction with life-threatening consequences. Anaphylaxis
although uncommon can lead to adverse maternal and fetal consequences if it occurs
during pregnancy. It can be severe, can occur within minutes after initial
exposure to the offending agent,  and can occur with no history of known allergy.
In United States, it has been estimated that 1 to 17% of the population are at
risk of anaphylaxis and of these 0.002% are at risk of fatal reactions [1]. Incidence among inpatients
has been reported to be 3–5 per 10 000 [2]. The estimated incidence
of intra-operative anaphylaxis is between 1:3500 and 1:20 000 [3, 4]. Anaphylaxis can result in significant long-term morbidity, mainly related to
cerebral hypoxia after an ineffective resuscitation. It
is very important that the members of the perinatal team are aware of the
symptoms and signs of anaphylactic reaction and are familiar with the
management of anaphylactic shock. We report a case of anaphylactic reaction to
Volplex, a commonly used colloid solution, in the immediate postoperative
period following cesarean section and reviewed the literature on pregnancy and
anaphylaxis.


## 2. Case History

A
34-year-old primigravida underwent a cesarean section for failed induction of
labour under spinal anesthesia. She booked with a Body mass Index of 31. She
was diabetic on insulin and was on methyl dopa in view of essential
hypertension. The surgery was uneventful until the very end. Towards the end of
the procedure, the systolic component of the blood pressure dropped to 85 mm Hg.
She was given 500 mL of Volplex, a gelatin-based colloid. Within few minutes,
she developed tingling, itching around face including tongue and lips. Then she
complained of difficulty in breathing and blood pressure dropped to 65 mm Hg systolic.
The colloid was stopped. She was given adrenaline 100μg intravenously and
following that she was given hydrocortisone 100 mg and chlorphenaramine 10 mg. With
these medications, the blood pressure improved and there was marked improvement
in her symptoms. She was well oxygenated
and did not need intubation.  She responded well to resuscitation and was
transferred to Intensive care unit. Serum tryptase was
sent one hour postincident and was 41.6 which is consistent with anaphylaxis.
Repeat value of Tryptase on the next day was 11. She had no previous incidents
of anaphylaxis and no history of any known allergies. Skin prick testing to
ascertain the causative agent was undertaken and anaphylactic reaction due to a gelatin-based colloid
was confirmed.


## 3. Pathophysiology

Anaphylaxis is a rapid systemic
hypersensitivity reaction to a substance in a sensitised individual with
potentially life-threatening consequences. Anaphylaxis is mediated by IgE
antibodies, which can cause histamine and other vasoactive mediators to be
released from mast cells and basophills [5]. IgE immunoglobulins
are found in plasma and are the only antibodies in man to produce anaphylactic
reactions,  for example,  immediate hypersensitivity. The antibodies are generated on
exposure to a defined stimulus. These Mast cells are wandering cells that are
found in most tissues but are most abundant in connective tissue. These cells
liberate histamine in the tissues as part of the inflammatory reaction. These
mediators produce respiratory, circulatory, cutaneous, and gastrointestinal
effects. Increased vascular permeability and peripheral vasodialation reduce
venous return and cardiac output. A mild reaction is manifested as Flushing,
urticaria, redness,  and localized oedema. More serious reaction is manifested as
shock, bronchospasm, laryngeal oedema,  and angioedema. Anaphylactic reaction is
usually precipitated by blood products, vaccines, insect bites, latex rubber,
skin antiseptics, and certain drugs such as antibiotics, Opioid analgesics, and
neuromuscular blocking agents. It is more likely to occur after parenteral
administration and atopic individuals are particularly susceptible because of
their hereditary predisposition to anaphylactic reactions.


## 4. Clinical Manifestations

Symptoms
can vary in onset, appearance, and course. Cardiovascular and cutaneous symptoms
are more common and account for about three quarters of the manifestations (see
Table1). Mild reactions are manifested in the form of pruritus, rash, flushing
of the skin, urticaria, tachycardia, and hypotension. More serious
manifestations include urticaria, flush, hypotension, bronchospasm, angioedema,
shock, and cardiac arrest. Many present with only one or two of these features.
In most cases, the more rapid the onset of symptoms is,  the more severe the
reaction is. It is very important to stop the administration of the drug or agent
at the earliest after the onset of symptoms.Table 1
Clinical manifestations of drug hypersensitivity [22].
Cardiovascular symptoms
74.7%
Cutaneous symptoms
71.9%
Cardiovascular collapse
50.8%
Bronchospasm
39.8%
Hypotension
17.3%
Angioedema
12.3%
Cardiac arrest
5.9%


## 5. Diagnosis of Anaphylaxis

History of atopy is present in fewer than 50% of
patients. Clinical recognition of manifestations is very important. Serial
serum Tryptase estimations are helpful in diagnosis of anaphylaxis [6]. Tryptase enzyme is released from mast
cells and it parallels histamine release. Peak concentrations well above 20 ng/mL indicate true anaphylaxis/anaphylactic reaction. The peak value of
tryptase in the serum occurs between 30 minutes to 6 hours after an
anaphylactic reaction. The value of skin tests, and especially the prick test,
has been shown in extensive studies [7]. This demonstrates the
presence of specific IgE antibodies. In our reported case, elevated Tryptase
levels and skin test confirmed the diagnosis and proved the allergen.


## 6. Treatment

Abrupt
cessation of administration of medication is warranted. Treatment should be
aimed to maintain good cardiorespiratory support. Epinephrine is the mainstay
of the treatment. Hypotension should be corrected by rapid intravascular volume
expanders like crystalloids. If colloid is suspected to be the causative agent,
it should be replaced by a crystalloid. In patient with cardiovascular collapse, additional
doses of epinephrine may be needed. Severe anaphylaxis during antepartum or
intrapartum period can result in severe maternal hypotension and this in turn
can lead to severe brain damage of the fetus as a consequence of intrapartum
hypoxia. Gei et al. reported use of continous infusion of Epinephrine to
correct hypotension and fetal bradycardia following anaphylactic shock
secondary to Ampicillin during labour [8]. Chaudhuri et al. have reported an
allergic reaction to Penicillin in a Primigravida who needed incremental doses
of epinephrine for stabilization of blood pressure and the baby was diagnosed
with neurological damage [9]. In
pregnant patients, continous electronic fetal monitoring is advocated during
the event as fetus is very sensitive to maternal changes in blood pressure. The treatment has been
summarised in Table 2.Table 2
Treatment of anaphylaxis [21].
(1)
Stop administration of the drug(s) likely to have caused the reaction.
(2)
First line of treatment includes restoration of blood pressure by making the
patient lie flat, raising the foot end and lateral tilt of the patient if
occurs antepartum.
(3)
Maitain airway: give 100% oxygen.
(4)
Adrenaline is given intramuscularly 0.5–1.0 mg{0.5–1 mL adrenaline injection 1
in 1000}. This can be repeated every 10 minutes until improvement occurs. If
hemodyanamic instability persists, a continuous drip may be needed. One mg of
epinephrine is diluted in 250 mL of saline, starts at 15 mL/hr (1μg /mt),  and
titrated according to clinical response.
(5) Administer
crystalloid or colloid for rapid intravascular volume expansion. If colloid has
been given prior to the reaction, change to crystalloid
since the causative agent might have been the colloid.
Secondary
therapy
(1) Antihistamine,
for example,  Chlorphenaramine over 1 minute 10–20 mg diluted in a syringe with normal saline or water given slowly intravenously.
(2) Corticosteroids
(100–500 mg Hydrocortisone IV) is of use in severely affected patients.
(3)
Bronchodialators may be required for persistent bronchospasm.
(4) Prolonged
monitoring in the Intensive care unit.Studies in animals have demonstrated the generation
of nitric oxide during anaphylaxis. Inhibition of nitric oxide synthase
improves survival in an animal model of anaphylaxis. Nitric oxide causes
vasodilation indirectly by increasing the activation of guanylyl cyclase.
Methylene blue is an inhibitor of guanylyl cyclase, which increases systemic
vascular resistance and reverses shock in animal studies. Treatment with methylene blue should be considered in patients with
anaphylactic hypotension that have not responded to other interventions but
there have been no reports of its use in the peripartum period [10].


## 7. Discussion

Anaphylactic reactions to anaesthesia and associated
agents of anaphylaxis have been reported with increasing frequency [11]. 2000–2002 Confidential Enquiries into Maternal Deaths in the United Kingdom
looked into one of the case reports and
highlighted the “need for staff to able to manage anaphylaxis.” Volplex
is a sterile solution of chemically modified (succinylated) fluid gelatin
produced from bovine collagen. This colloid is given as intravenous infusion for
the lost blood volume. All available colloid volume substitutes carry the risk
of anaphylactic reactions. None of the colloids in clinical use (plasma protein
solution, gelatine, hydroxyethylstarch,  and dextran) is free from the risk of
anaphylactic reactions. Even though the incidence of anaphylactic reactions is
low (0.03%), lethal outcome might be encountered. Between the colloids
differences exist as far as manifestation (skin, circulatory and respiratory
system) and degree of severity of anaphylactic reactions are concerned. Since
the underlying pathomechanisms have not been elucidated yet, true prophylactic
measures are unknown. Therefore, it is mandatory to control the patient very
carefully at the beginning of infusion; early symptoms of anaphylactic
reactions should trigger immediate therapeutic measures. Studies of the adverse
reactions to gelatin plasma substitutes have concluded that, far from being
inert substances, gelatins can initiate a life-threatening anaphylactic
response [12]. Allergic reaction to
Hydroxyethylstarch (a colloid) has been reported during caesarean
delivery [13]. Other substances
reported to cause anaphylaxis in pregnancy are Laminaria insertion, Latex,
Ranitidine, Antibiotics, sodium ferric gluconate complex, Snake antivenom,
insect stings, local anaesthetics,  and induction of general anesthesia [14–20].


## 8. Conclusion

There must be a written emergency action plan for
the management of anaphylaxis. Accurate reporting and issue of Medic-Alert is
an important risk management issue. There is no valid predictor of drug
anaphylaxis. It is important to analyze circumstances leading to anaphylaxis and
maintain fatal anaphylactic register in a national data base [21].
Anaphylaxis can result in significant morbidity mainly related to cerebral
hypoxia after an ineffective resuscitation. These reactions can be life
threatening in particular if adequate treatment is not started quickly. Since
anaphylaxis can occur with any drug, all the members of the perinatal team
should be familiar with the recognition of symptoms and signs of anaphylactic
reaction.  Colloid solutions are used
very frequently for postpartum haemorrhage and sometimes antenatally for severe
haemorrhage. Anaphylaxis has been reported with commonly used substances like
latex, and very commonly used drugs like Oxytocin, antibiotics, and Ranitidine.
Colloid solution is a commonly used plasma expander in clinical practice. This
case report further highlights the fact that anaphylactic reactions can be
unpredictable and severe reactions manifested in the form of angioedema and
cardiovascular collapse need immediate and prompt treatment. As seen in the
reported case, severe anaphylactic reaction was well managed by the
anaesthetist as it happened during a surgical procedure. The importance of
awareness among the clinicians about the clinical signs and treatment measures
to be undertaken cannot be underestimated as reactions are being observed with
commonly used medications. Severe
reactions require early recognition and aggressive resuscitation. All
obstetricians and midwives should be trained to be able to identify and manage
this emergency.  The team should also
ensure the availability of these drugs in the labour ward as well as in the
antenatal and postnatal wards.  Every hospital should have a guideline
for anaphylaxis. This should be included in the Induction book as part of
protocols. Management of anaphylaxis should be included in the emergency drills
on a regular basis so that uncommon life-threatening event is tackled in the
most effective way.



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