II

ALLERGIC REACTIONS IN ANAESTHESIA

A. Criado *, A. Seiz *, JR. Ortiz **
* Department of Anesthesiology and Reanimation. Hospital Universitario "La Paz".
Madrid. ** Department of Anesthesiology and Reanimation. Clínica Universitaria
de Navarra. Pamplona.
INTRODUCTION Anesthesiology delivers a special drug in the practice of medicine.
Most drugs used are non-therapeutic, potentially lethal and have a margin or th
erapeutic index / toxic narrow. In addition, they all have a potential to cause
adverse reactions. Many of the drugs used in anesthesia, other than inhalation a
gents can induce histamine release and be responsible for allergic reactions. Th
ese responses may be due to an adverse drug reaction (anaphylactoid reaction), o
r an immune mechanism mediated by IgE antibodies, which require prior exposure t
o the molecule responsible for the sensitization (anaphylactic reaction). Clinic
ally the most important mediator in anaphylactoid reactions is histamine, while
the true anaphylactic reactions, the contact of the sensitizer molecule (hapten)
with IgE antibodies formed by previous exposure, can trigger a large release of
mediators (leucotrienios , prostaglandins, serotonin, etc.).. Anaphylactic reac
tions are usually the most severe and serious (1). The incidence of severe aller
gic reactions in anesthesia is 1/3.500 anesthesia with a mortality of 5-6%. 60%
are anaphylactic. Its diagnosis can only be done by immunoallergic studies (2,3)
.
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A. Criado, A. Seiz, JR. Ortiz
DRUG REACTIONS Adverse reactions The risk of an adverse reaction is an inevitabl
e consequence of the proper administration of the drug. Some studies show that u
p to 30% of medical patients admitted, develop some type of adverse drug reactio
n during their hospitalization. These adverse reactions in 80% of cases are pred
ictable, and are due to action of the drug itself. They tend to be dose-dependen
t and correspond with the side effects described for each drug. Allergic reactio
ns account for 20% of drug reactions. Usually are not predictable, nor are dose-
dependent, or associated with the pharmacological action of the drug. They are u
sually related to an individual's immune response. When the allergic reaction is
called antibody-mediated anaphylactic. When antibodies are not responsible for
the reaction or may not be shown are known as anaphylactoid. Clinically it is im
possible to distinguish the two reactions and the diagnosis must be made in immu
noallergic techniques. According to these criteria, allergic reactions are class
ified as anaphylactic reactions and IgE-mediated anaphylactoid reactions not med
iated by IgE (leukocyte activation, release of histamine). IgE anaphylactic reac
tion is required prior contact of antigen with the body, causing sensitization w
ith IgE antibody production that will be located in mast cells and basophilic ce
lls. In a subsequent contact Ag-Ab complex causes leukocyte activation with rele
ase of histamine and numerous chemical mediators (leucotrienios, prostaglandins,
kinins, etc..) From the granules of mast cells and basophils develop anaphylact
ic table. The severity and onset of symptoms is related to the specificity of th
e mediators in the target organs (cardiovascular, pulmonary and cutaneous). Ther
e are individual variations in clinical manifestations and severity of anaphylax
is. Allergic reactions are not IgE mediated Some mechanisms can trigger release
of mediators and cause similar clinical symptoms to anaphylactic: * Activation o
f neutrophil leukocytes may occur through the activation of complement by immune
mechanism (IgM, IgG) or non-immunological (endotoxins , heparin-protamine compl
ex, etc.).. The fractions of complement C3 and C5, also known as anaphylatoxins,
are capable, when activated, to cause the release of histamine from mast cells
and basophilic cells that produce increased
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Allergic reactions in anesthesia
capillary permeability and smooth muscle contraction. The fraction C5a causes ac
tivation and aggregation of leukocytes and platelets, which aggregate trigger re
lease of various mediators. These mechanisms have been attributed to reactions t
o transfusions and protamine.€* Histamine release by non-immune Many drugs admin
istered perioperatively release histamine in relation to dose and without the in
volvement of immunological mechanisms. Have been implicated in the onset of degr
anulation of mast cells without activation of basophils and the participation of
some opioid receptors. The administration of morphine, atracurium, and vancomyc
in can release histamine producing vasodilation and urticaria along the vein adm
inistered.
Effect on outpatient anesthesia up to 10% of patients will complain of any aller
gies to any drug and are particularly attributed to antibiotics (40-50%) and pai
n (15-25%). Only 10% is referred to anesthetics. However, Allergy studies perfor
med in these patients, indicate that most of the pictures described are due to a
dverse drug reactions and that only 3-10% are true allergic reactions (4-12). Pr
obably the incidence of allergic reactions in anesthesia is the 0.5-2% and in se
vere anaphylactic frame 1/3.000 to 1/10.000 anesthesia (1,12). There are predisp
osing factors that increase the risk of anaphylactic reactions (Table I).
Table I Risk factors for allergic Age between 30-50 years Females: 4:1 History o
f atopy States hiperansiedad Repeated exposure to allergens
1. Age: more common in young people between 30-50 years. Are less common in chil
dren because of the immaturity of the immune system and the lower probability of
previous exposures. 2. Sex: they are four times more common in women than in me
n, perhaps because of increased exposure to allergens (dyes, detergents, rubber
gloves, etc.).. 3. History of atopy (asthma, hay fever, food allergy, etc.).. 4.
Anxiety states. 5. Repeated exposure to drugs or allergens, especially with int
ervals of more than two weeks.
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A. Criado, A. Seiz, JR. Ortiz
In any case, in these risk groups there is no indication of Allergy exhaustive s
tudies, provocation test, even prophylaxis against the risk of possible reaction
s not found. There are factors or situations when the allergic reaction associat
ed with increasing severity, as in patients treated with beta-blockers, reaction
s in the course of an epi or spinal anesthesia for sympathetic blockade added, a
nd bronchial asthma in which unreasonably increases the degree of bronchospasm.
Virtually all drugs used in anesthesia, both anesthetics, and other common use (
antibiotics, colloids, blood products, latex, etc..) Have been implicated in all
ergic reactions (Tables II and III). In these reactions, 30% were anaphylactic (
specific IgE-mediated), 45% is non-specific histaminoliberación and 25% did not
identify the mechanism (11).
Table II allergic reactions in anesthesia. Epidemiological study in France (Laxe
naire2) 1984-9 muscle relaxing agent Latex Colloids Antibiotics Other Opioids Hy
pnotics n = 821 81% 0.5 11 3 0.5 2 2 1990-1 n = 813 70% 12.5 6 1.7 4 6 2.6 2.6 n
= 1030 1992-3 60% 19 8 3.5 5 3.1 1.4
Table III
Muscle relaxants and suxamethonium anaphylaxis Atracurium Vecuronium Pancuronium
alcuronium 42% 23% 21% 8% 6%
The highest incidence of allergic reactions to anesthetics is due to muscle rela
xants (60%), especially when suxamethonium, atracurium and vecuronium, although
its distribution is due to the frequency of use of each. It has been found cross
-sensitivity between relaxants in 60-80% of patients due to their common chemica
l structure of the ammonium ion. Many cosmetics, detergents, dyes and quaternary
ammonium compounds have in their composition and can act as sensitizers, which
explains anaphylactic reactions at first exposure to muscle relaxants and their
greater incidence in women (6,12,15,16). Among the barbiturates have been observ
ed cross-reactivity between them and the previous exposure is a predisposing fac
tor.
22
Allergic reactions in anesthesia
Allergy to local anesthetics has been described for the ester group (procaine),
but are exceptional for the amide group (lidocaine and bupivacaine MEPI). Its in
cidence is very low (0.5%) and sometimes the reactions have been attributed to p
reservatives and additives (methylparaben and metabisulfite). There is no cross-
reactivity between both groups (10-17). The incidence of latex allergy has incre
ased in recent years especially in people with chronic history of contact with m
aterials that have latex in patients with multiple interventions (spina bifida a
nd genitourinary malformations) among health workers and between workers of oper
ating rooms rubber (18-20).€Should always be suspected in patients reporting all
ergies to fruits (chestnut, banana, kiwi, avocado) or contact dermatitis to rubb
er products. Its real incidence is underestimated, because many of its clinical
intraoperative go unnoticed or undiagnosed.
CLINICAL clinical symptoms is often independent of the reaction mechanism, altho
ugh anaphylactic reactions (IgE immunologic mechanism) does not depend on the do
se administered, and the reaction can become self-perpetuating indicating greate
r amount of adrenaline to block the activation circle of mediators. Anaphylactoi
d reactions tend to be self-limiting (the cessation of administration of the ant
igen), the short half-life of histamine. Symptoms usually appear within minutes
of drug administration. When there are more late in the maintenance phase of ane
sthesia, we must suspect a reaction to latex. Some reactions have been described
at the end of orthopedic surgery after the release of the tourniquet and are du
e to the antibiotics used to disinfect the wound. The first signs of anaphylaxis
occur in areas with higher concentrations of mast cells, as in skin and mucous
membranes, lungs, cardiovascular system and digestive tract. Muco-cutaneous sign
s appear in 70% of reactions, the involvement circulatory (hypotension and tachy
cardia) in 85% and 35% bronchospasm. In less severe forms predominantly hypotens
ion and tachycardia with cutaneous preferably in the chest, but can be generaliz
ed quickly. In severe forms can be triggered an anaphylactic shock box where mor
tality is 5-6% (7,11,13,14). Generally, with the administration of epinephrine,
reverts to the clinic after 1 hour without sequelae, but in some cases the shock
is refractory to epinephrine, especially in patients treated with beta-blockers
, requiring significant time infusion of fluids and high doses of adrenaline. Pr
ogress will depend on how early and effectiveness of treatment initiated. The cl
inical signs of hypotension, tachycardia, laryngospasm can persist for hours des
pite treatment. Anaphylactic shock can be replayed within 24 hours to 20% of pat
ients, so it must remain guarded in a reanimation unit.
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A. Criado, A. Seiz, JR. Ortiz
DIAGNOSIS (Table IV)
Table IV diagnostic Guideline IMMEDIATE anaphylaxis XXXX XX 1 TIME 6-8 WEEKS
Serum tryptase, plasma histamine Metilhistamlna urinary specific IgE skin tests
Ac
X X
The first objective is to show the mechanism involved in the reaction, confirmin
g a diagnosis of anaphylaxis, by evidence confirming the degranulation of mast c
ells. Basically we measured: 1. Serum tryptase. It is a protease present in mast
cells is higher after degranulation, reaches the peak hour, decreased at 10 hou
rs and returned to baseline levels (<1 ng / ml) at 24 hours of the reaction. It
is also detectable postmortem. 2. Plasma histamine. It stands at 5 minutes of re
action and goes quickly to 15 to 20 minutes, except when the shock is severe, si
nce their metabolism is slowed. Concentrations above 100 ng / ml suggest a diagn
osis of allergic reaction. 3. Metilhistamina urine. It is the main metabolite of
histamine. It is detected in the first void and remains elevated at 24 h of rea
ction. It is a good indicator of histamine release in plasma. In case you can no
t make these determinations must immediately freeze samples of serum, plasma and
urine at -20 ° C, for further studies. The second objective is to identify diag
nostic agents responsible. This study was performed delayed 6-8 weeks by: 1. Tit
ration of specific IgE. This is done by radioimmunoassay (RAST) incubating patie
nt sera with IgE antibodies on a solid phase fixed leading cause of potential an
tigens. There are currently marketed for muscle relaxants kit, latex, thiopental
, propofol, morphine, pethidine, protamine, gelatin and antibiotics. This test h
as a high sensitivity and specificity and correlates well with skin tests. 2. Sk
in tests. Should be performed on non-pigmented skin and next to the target subst
ance, it makes a positive control with histamine and negative saline. The readin
g was performed at 15 minutes. Usually performed two types of tests: a) Prick te
st. It consists of inoculating the undiluted drug in the forearm. It is consider
ed positive when the edema of the skin is> 2 mm or more than 50% of positive con
trol.€When epidermal puncture allergen does not pass into the bloodstream, there
being no risk of anaphylaxis or sensitization. b) skin test. Is usually done in
the back by intradermal injection of 0.05 to 1 ml of various dilutions of the s
ubstance or drug. It conside24
Allergic reactions in anesthesia
ra positive a wheal> 9 mm. There may be false positives with histamine-releasing
drugs. Skin tests can identify the causative agent in 75-90% of cases. The sens
itivity to muscle relaxants is up 98%. Challenge tests are almost discouraged, e
xcept for local anesthetics (1,12,17). Allergy diagnosis always has a core suppo
rt in the medical record in the sequence of events and their causality. The test
s in vivo or in vitro used to confirm clinical diagnoses. In all cases, patients
must provide a full report of the officers responsible, the type of reaction an
d alternative or safe drugs.
Initial treatment should be aimed at identifying the responsible agent (anesthet
ic, colloids, blood, latex, etc..), To suppress his administration and stabilize
the cardiovascular and respiratory symptoms. (Table V).
Table V INITIAL identify and suppress antigen administration Maintain airway and
100% O2 expansion volume (2-4 L crystalloid if hypotension) Adrenaline: 5-10 mg
bolus if hypotension 0.1-0.5 mg iv if cardiovascular collapse anesthetic agents
SECONDARY Remove from 0.25 to 1 g of hydrocortisone methylprednisolone 1-2 g of
bicarbonate (0.5-1 mEq / kg) hypotension and acidosis adrenaline infusion: 0.1
to 1 mg / kg / min effect as bronchodilators: aminophylline iv and / or salbutam
ol aerosol Antihistamines: 0.5-1 mg / kg diphenhydramine assess airway after ext
ubation Corticosteroids: Treatment of anaphylactic reaction
The volume replacement should be fast and energetic (crystalloids and colloids)
to offset the sharp drop in peripheral vascular resistance. Place the patient in
Trendelenburg position may facilitate venous return. Epinephrine is the drug of
choice for the treatment of hypotension, bronchospasm and angioedema. Occasiona
lly when the shock is refractory associate is needed infusion of noradrenaline (
0.1-1 mg / kg / min) to preserve cerebral and coronary risk. Patients with sympa
thetic blockade by epi or spinal anesthesia, require for their control, very hig
h doses of catecholamines and aggressive replacement of blood volume.
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A. Criado, A. Seiz, JR. Ortiz
Arrhythmias are usually secondary to hypoxemia, hypercapnia, catecholamine treat
ment or the presence of a cardiopathy. Your treatment will be symptomatic, attem
pting to eliminate the triggers and the most appropriate antiarrhythmic. Calcium
antagonists may be indicated by its antagonistic effect of arrhythmias caused b
y histamine. Bronchospasm can be a complication difficult to treat if not improv
ed with adrenaline. Salbutamol and aminophylline are used, halogenated anestheti
c agents be a good therapeutic alternative. Corticosteroids, although perhaps in
the acute phase are not too effective, they have very useful to inhibit the lat
e components of the reaction. Occasionally some signs and symptoms such as hypot
ension, right ventricular dysfunction, pulmonary hypertension, airway obstructio
n and stridor persist for 5-30 hours while maintaining treatment. Recurrences ma
y also occur, so it is advisable to maintain surveillance of these patients at l
east 24 hours in the reanimation unit (1.2 l).
PROPHYLAXIS IN PATIENTS ALLERGIC The only really effective measure to prevent an
anaphylactic reaction in allergic patients is to avoid contact with the offendi
ng agent, hence the importance of a careful history to exclude previous reaction
s, or to investigate cross-allergies in patients with intolerance to cosmetics,
dyes, detergents, and certain fruits. It is very important to distinguish previo
us allergic reactions to certain drugs intolerance which reflect their own pharm
acological effects or side effects. Serious hypersensitivity reactions occur mor
e frequently in patients with a history of allergy, atopy or bronchial asthma, h
owever, has been shown that premedication with corticosteroids in these patients
is not effective to prevent the possible occurrence of perioperative anaphylact
ic reactions. The preparation with steroids and antihistamine, is used in patien
ts allergic to complement activating substances or histamine-releasing, as with
iodinated contrast.€It has also been recommended for patients with latex allergy
because of the difficulty in the operating room to ensure an environment free o
f this allergen, despite the precautions are taken. Because latex allergy has in
creased in recent years, it is recommended to always have special equipment avai
lable in the surgical area of material including: circuit respirator, gloves, tr
acheal tubes, masks, serums systems, syringes, nasogastric tubes and bladder pre
ssure cuffs Stethoscopes and containing no latex in its composition, and avoid a
ny medication or multidose vial with a rubber stopper sera that should be tapped
. Drug prophylaxis (Table VI) may give a false sense of security, and that has n
ot been proven to prevent the occurrence of intraoperative anaphylaxis (22). In
diabetic patients receiving insulin-protamine (NPH), have a risk of 10-30
26
Allergic reactions in anesthesia
Table VI
Preoperative prophylaxis in patients at risk allergic Diphenhydramine Ranitidine
Prednisone 1-2 mg/kg/24 h (three doses) 4 mg/kg/24 h (4 doses) 3 mg / kg / 24 h
(3 doses)
Start prophylaxis prophylaxis 24 hours before 24 hours postoperatively Continue
anaphylactic reaction times when given protamine to reverse heparin. However, th
e incidence of severe reactions less than 2% (23). Antihistamines are advisable
to prevent the release of histamine, but do not prevent anaphylactic reactions A
g-Ab immune. Currently there are no effective drugs to prevent the synthesis of
histamine, but the cromoglicolato sodium (Intal ®) inhibits mast cell degranulat
ion. The most effective are antihistamines that block H1 receptors (Atarax ®, Tr
iludan ® and Hismanal ®). The use of anti H2 (cimetidine or ranitidine) is more
controversial because of its effects bronchial and by inhibition of hepatic micr
osomal enzyme system. In hiperansiedad states that favor the release of histamin
e, we recommend adequate premedication with benzodiazepines. Prophylaxis with co
rticosteroids is controversial. Only commonly used in allergy to iodinated contr
ast media and occasionally to latex. In patients at risk should be preferred his
taminoliberación inhalants and anesthetics less histamine (Table VII).
Table VII Halogenated inhalational anesthetics bit histaminoliberadores Hypnotic
s: etomidate, propofol and benzodiazepines morphine: fentanyl and alfentanil Neu
roleptics: droperidol relaxants: vecuronium and pancuronium amide local anesthet
ics: lidocaine and bupivacaine
Locoregional anesthetic techniques are a good alternative for patients allergic
to or predisposing factors. Epidural anesthesia has been recommended in combinat
ion with general, interventions that require muscle relaxation in patients with
allergy to muscle relaxants.
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