Case Presentation
By
Dr Ahmaed Nabil
Assistant Lecturer Of
Anesthesia
Ain Shams University
Case :



A 23-years-old man is scheduled to undergo an ORIF
of a carpal scaphoid fracture, using a bone graft to be
harvested from the iliac crest.
Induction of general anesthesia and intubation were
uneventful.
When cefazolin 1 g is administered intravenously a
rash appears over the face and chest. The heart rate is
135 beats per minute and the blood pressure drops to
70/40 mmHg
Questions



What is the mechanism of anaphylaxis? What is the
difference between anaphylactic and anaphylactoid
reactions?
What treatment should be administered to this patient?
What else should be checked on physical
examination?
What are the medications most often implicated in
anaphylaxis? In anaphylactoid reactions?
Questions


What is the percentage of patients allergic to penicillin
who will have a reaction when challenged with a
cephalosporin?
What antibiotic would you use for “clean” orthopedic
surgery in a patient reporting a penicillin allergy or a
reaction to cephalosporins?
What is the mechanism of anaphylaxis?


Anaphylaxis is an IgE-mediated allergic
reaction.
The most common mechanism for an
anaphylactic reaction is the degranulation of
mast cells and basophils with the subsequent
release of inflammatory mediators, which are
responsible for the symptoms and signs.
What is the difference between
anaphylactic and anaphylactoid reactions?


Anaphylactoid
reactions
are
clinically
indistinguishable from anaphylaxis. However,
the mechanism of action differs in that IgE is
not involved.
Anaphylactoid reactions are a result of direct
degranulation of mast cells and basophils with
release of the same mediators as in
anaphylactic reactions
Anaphylactoid reaction



In practice, it does not matter whether or not
the reaction is IgE or non-IgE mediated.
The immediate management of the patient is
the same
the patient will need to avoid the drug in the
future, irrespective of the mechanism of the
reaction
What else should be
physical examination?
checked
on
1st we have to know that true anaphylaxis during
anesthesia is very rare.
 Many anesthetists may never see such a
reaction and few will see more than one during
their working life.
 However, because the consequences of
anaphylaxis can be serious and potentially lifethreatening, it is important for anaesthetists to
know what the clinical signs are and how to
deal with them.
Physical Examination

The reported incidence of anaphylactic
reactions during general anaesthesia varies
considerably between 1 in 950 to 1 in 20,000
anaesthetic procedures.
Physical Examination





Clinically, a mild reaction is manifested as:
flushing
urticaria
redness
localized edema.
Physical Examination
While a severe reaction is manifested by:
 shock (severe hypotension)
 bronchospasm
 widespread edema
 massive intravascular fluid
loss resulting in dramatically
reduced filling of the heart
and subsequent severe hypotension

What treatment should be
administered to this patient?




Causes need to be excluded first;
Exaggerated hypotensive response to the
induction agent
Bronchospasm resulting from the mechanical
effects
of
endotracheal
intubation
in
susceptible patients
Vagal response causing severe bradycardia
(e.g. During laparoscopy , ophthalmic
procedures, etc);
Other causes;



Covert hemorrhage.
Unexpectedly extensive sympathetic blockade
during epidural or intrathecal neuraxial
anesthesia;
Acute exacerbation of pre-existent asthma
independent of an aesthesia;
For treatment:
1.Call for help and inform the surgical team
2.Stop administration of the drug(s) likely to have
caused the reaction. It is recommended to stop
all the drugs that are possible to stop, as at this
time the causative agent can not be
determined.
3.(ABC) , Maintain airway: give 100% oxygen.
4.Lie patient flat with feet raised
Epinephrine
Is the drug of choice when resuscitating
patients during anaphylactic shock
Epinephrine

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

Epinephrine acts by two mechanisms:
It reverses vasodilatation by its α-agonist
effects
It blocks further degranulation of mast cells or
basophiles through its β-agonist effects.
It may also improve cerebral perfusion
independent of its effect on blood pressure by
β2-mediated vasodilatation, and it is very
effective in the treatment of bronchospasm.
For treatment (cont’d);
5.Give adrenaline (epinephrine):
 50–100 μg (0.5–1 mL of a 1:10,000 solution found in
pre-filled syringes,
 or 0.05–0.1 mL of the more commonly used 1:1,000
solution), or 0.01 mg/kg in children.
 Should be administered subcutaneously if the patient
is merely hypotensive, and may be repeated as
needed.
 Higher doses and the intravenous route should be
used if the reaction is severe, or if cardiac arrest
supervenes.
For treatment (cont’d);

The European guidelines say that
 Intravenous administration should be done
instead of the subcutaneous route ;
 Titrated doses (10-20mic for moderate cases
and 100-200 mic for severe cases) are given
 To be repeated every one to two minutes until
restoration of arterial blood pressure.
For treatment (cont’d);



I.V infusion at a dose of 0.05 to 0.1 mic /kg might be
used instead of repeated bolus administration of
epinephrine.
If I.V route is not immediately availbale, the I.M route
can be used(0.3-0.5 mg) with injection to be repeated
every 5-10 minutes depending on the patient
hemodynamic status.
In the same situation, the intra tracheal route can be
used if the trachea is intubated knowing that one third
of the dose will enter the circulation
For treatment (cont’d);

High doses of epinephrine are more efficacious
but cases of myocardial ischemia or even
infarction after epinephrine administration
have been reported.
Other measures include



Start rapid i.v volume expansion with
crystalloid or colloid.
Increased vascular permeability can transfer
50% of intravascular fluid into the extravascular
space within 10 minutes.
The amount of fluid administered should be
based on hemodynamic parameter
Other measures include



Intravenous steroids
(e.g.,
methylprednisolone
1–2
mg/kg
intravenously or hydro cortisone 100-500mg
(I.V); repeat q4–6 hourly as needed).
Steroids may have no effect for 4–6 hours, but
may
prevent
persistent
or
biphasic
anaphylaxis.
Other measures include



Anti-H1 medications (e.g., diphenhydramine
25– 100 mg IV).
Anti-H2 medications (e.g., ranitidine 1 mg/kg
IV).
Glucagon (1–5 mg IV)
in severe reactions. Glucagon directly activates adenyl
cyclase and bypasses the β-adrenergic receptor. It
may
reverse
refractory
hypotension
and
bronchospasm. Glucagon or atropine should be used
in β-blocked patients to increase an inappropriately
slow heart rate.
Other measures include

In case of refractory hypotension, military
antishock trousers (MAST) may significantly
improve hemodynamics.
Other measures include

Save any blood samples that have been
collected prior to or during the procedure.
These may be required for testing.
Other measures include

If cardiac arrest supervenes, advanced
cardiac life support (ACLS) protocols should be
followed, including epinephrine, atropine, etc.

Prolonged
resuscitative
efforts
are
encouraged, since recovery is more likely to
be successful in anaphylaxis, in which the
subject is often a young individual with a
healthy cardiovascular system
Further management



The chest should be auscultated since bronchospasm
is often triggered by anaphylactic or anaphylactoid
reactions.
If bronchospasm does not respond to the treatment
administered for anaphylaxis, inhaled β2-agonists and
possibly aminophylline should be added to the
regimen.
Volatile anesthetics can also be used (if that is not
already the case, and if the blood pressure allows) for
their bronchodilating properties.
Note



If pregnant;
start with ephedrine(10 mg to be repeated
every 1-2 minutes)because of the risk of
hypoperfusion of the placenta caused by
epinephrine and the patient should be placed
in the left lateral decubitus.
In case of ineffectiveness, switch to
epinephrine
To summarize:

Immediate measures
a. Assess airway, breathing, circulation
b. Administer epinephrine SQ 50–100 μg or 0.01 mg/kg in
children; repeat as needed(or iv/im)

General measures
a. Expedite surgery; position the patient supine; elevate
lower extremities
b. Administer 100% oxygen
c. Administer normal saline or colloids if there is severe
hypotension
To summarize:

Specific measures
a. Glucocorticoids: methylprednisolone 1–2 mg/kg IV;
repeat q 4–6 hourly as needed
b. H1 antagonists: diphenhydramine 25–100 mg IV
c. H2 antagonists: ranitidine 1 mg/kg IV
d. Glucagon: 1–5 mg IV
e. Nebulized β2-agonists
f. Aminophylline: 5 mg/kg IV over 30 min, then 0.9
mg/kg/hr IV; follow serum levels (therapeutic range 8–
15 μg/mL)
g. Military antishock trousers (MAST)
To summarize:
Supervening cardiac arrest, in addition to
ACLS protocol
a. Rapid volume expansion
b. Prolonged resuscitative efforts

What are the medications most often
implicated in anaphylaxis? In anaphylactoid
reactions?

The
commonly
anaphylaxis are:

Antibiotics
Aprotinin
IV anaesthetics, e.g. thiopental, propofol, midazolam
Latex rubber
Local anaesthetics
Neuromuscular blocking agents (NMBAs)
Non-opioid analgesics, e.g. NSAIDs
Opioid analgesics, e.g. morphine, alfentanyl, fentany







used
drugs
during
Others
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Plasma volume expanders, e.g. gelatins,
starches
Pre-medication drugs
Preservatives
Protamine
Radiocontrast media
Skin antiseptics, e.g. chlorhexidine, iodine
Others


The rate of anaphylactic reactions with iodinated
contrast has significantly decreased because sensitive
individuals are being pretreated with steroids and
antihistamines, and non-ionic contrast with less
potential to cause allergic reactions is being used.
Latex has emerged as a cause of anaphylactic
reaction , probably because of the increasing use of
latex gloves and barriers. Patients
who have
undergone multiple surgeries, and healthcare workers
are especially at risk
Others

Anaphylactoid reactions are commonly
caused by morphine, d-tubocurarine, certain
antibiotics (e.g., vancomycin, ciprofloxacin),
aspirin (possibly through inhibition of
cyclooxygenase), and succinylcholine
What is the percentage of patients allergic to
penicillin who will have a reaction when
challenged with a cephalosporin?

In patients with true allergy to penicillin, a
3–7% rate of allergic reaction to cephalosporin
is expected, versus 1–2% in patients with no
history of penicillin allergy. History is the most
important element here.
What is the percentage of patients allergic to
penicillin who will have a reaction when
challenged with a cephalosporin?

A morbilliform rash (i.e., resembling
measles), consisting of macular lesions that
are red and are usually 2–10 mm in diameter
but may be confluent in places, is a benign
reaction that does not qualify as “allergic”. In a
patient who had a morbilliform rash,
cephalosporins can be given safely.
What antibiotic would you use for “clean”
orthopedic surgery in a patient reporting a
penicillin allergy or a reaction to cephalosporins?

If
true
allergy
to
penicillin
or
cephalosporins is reported, it is prudent to
use clindamycin 600 mg intravenously.
Vancomycin
1,000
mg
intravenously
administered over 30–60 minutes can be used
as well. Rapid vancomycin administration may
cause the “red man syndrome” secondary to a
non-immune-mediated release of histamine,
i.e.an anaphylactoid reaction.
Case (cont’d)

Once blood pressure and heart rate
returned to normal, the rash was subsiding
and the chest auscultation was clear.
Should surgery be allowed to proceed or
should the case be cancelled? What will
you tell the patient postoperatively?
Answer



The case can probably be allowed to
proceed after rapid resolution of the event.
Upper airway edema should be excluded prior
to extubation.
The presence of a leak around the
endotracheal tube should be determined by
deflating the endotracheal tube cuff and
occluding the tube manually.
Postoperative Recommendations



This patient should be told that the
administration of any β-lactam antibiotic might
be fatal.
He should be given a letter detailing the
reaction and specifically naming the medication
involved, and he should be instructed to wear a
bracelet indicating his allergy.
Allergy specialists sometimes perform skin
tests to identify the causative drug
Who are at risk for anaphylaxis
during anesthesia?



Patients who are allergic to one of the drugs or
products likely to be administered or used during
anaesthesia and for which the diagnosis had been
established by a previous allergy investigation(e.g
Deprivan and eggs).
Patients who have shown clinical signs suggesting
an allergic reaction during a previous anaesthesia.
Patients
who
have
experienced
clinical
manifestations of allergy when exposed to latex
Other patients


Children who have had multiple operations,
especially those with spina bifida, because of
the high rate of sensitization to latex
Patients who have experienced clinical
manifestations of allergy to kiwi, banana,
chestnut,buckwheat, etc., because of the high
rate of cross-reactivity with latex.
Others

Patients who are atopic (for example, those
with allergic asthma or hay fever) or those who
are allergic to a drug or other product that is
not likely to be used during the course of the
anesthesia are not to be considered at risk for
anaphylaxis during anesthesia
Note


For those patients who are at risk as defined
above , an allergy investigation looking for
specific sensitization should be proposed
before any anesthetic procedure.
Nevertheless, no matter which tests are used,
they do not guarantee an absolutely correct
diagnosis.
1ry prevention


Total avoidance of contact with latex from
the first surgical procedure and in the medical
environment of infants with spina bifida
prevents the acquisition of latex sensitivity .
There is actually no way to prevent primary
sensitization
to
muscle
relaxants.
Anaphylactic reactions to these agents can
occur in the absence of their prior
administration
2ry prevention



The only effective secondary preventive
measure is to IDENTIFY THE RESPONSIBLE
ALLERGEN and then completely avoid it.
For patients sensitized to latex, a latexfree
environment is effective for the prevention of
an anaphylactic reaction.
The latex-free environment must include the
operating rooms, the postoperative recovery
room and some other sectors of the hospital
Note


The
intravenous
administration
of
antibiotics for preoperative prophylaxis should
be started in the operating room with the
patient awake and being monitored, 5 to 10
minutes before anesthesia induction.
Because there is no evidence of crossreactivity
between propofol and muscle relaxants, the
use of propofol in patients allergic to a muscle
relaxant is not contraindicated.