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Management of Patient with Anaphylactic Shock

and Laryngeal Edema
Laksmi Sasyarini
INTRODUCTION
Anaphylaxis is the clinical syndrome that represents the most severe systemic allergic
reaction. It results from the immunologically induced release of mast cell and/or basophil
mediators after exposure to a specific antigen in previously sensitized individuals.
Anaphylaxis is a medical emergency that requires immediate attention. If medical attention is
delayed, death may occur most commonly from cardiovascular collapse or airway obstruction,
or both. Although any substance has the potential to cause anaphylaxis, the most common
causes of IgE-mediated anaphylaxis are insect stings, medications, latex, peanuts and tree nuts
(e.g., walnuts, hazelnuts, almonds, cashews, pecans and pistachios), shellfish and fish, milk,
eggs and wheat (Ellis AK, et al, 2003).
Anaphylaxis occurs in an acute and unexpected manner. The true incidence is
unknown, but still remains an important cause of mortality. Of 164 fatal reactions identified
between 1992 and 1998 in the United Kingdom, around half were iatrogenic (McLean-Tooke
APC et al, 2003).
Adverse drug reactions are uncommon, but only 6 % to 10% are immunologically
mediated. Unlikely most adverse drug reactions, allergic drug reactions are unpredictable.
Symptoms of adverse drug reactions in descending order include: skin reactions (80%),
anaphylaxis (9 - 15%), respiratory symptoms (6 - 9%), and drug fever (2 - 6%). Fatalities as a
result of drug-induced anaphylaxis have been recorded in several studies. The most common
drug causes were anesthetics, antibiotics, and contrast media. Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) commonly are implicated in allergic reactions and
anaphylaxis. Bronchospasm is common in patients with reactive airway disease and nasal
polyps (Gruchalla RS, 2003; Krause RS, 2005).
We would like to report a case of male with anaphylactic shock that underwent
tracheostomy due to laryngeal edema.
Case Report Depart. of Internal Medicine Airlangga University School of Medicine
Dr. Soetomo Teaching Hospital, Surabaya August, 8, 2008

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CASE
Male, 58 years old, was consulted to the Department of Internal Medicine with susp.
Acute epiglotitis + laryng edema + urticaria + post tracheostomy.
Heteroanamnesis :
He had history of difficulty in swallowing since 2 days before admission. He got the
medication from Mojokertos hospital such as injection of novalgin (consist of metamizole
sodium). Two hours later he felt shortness of breath, irritable, and fell into unconsciousness.
He also had urticaria that developing all over his body, hypotension, tachycardia, and also
cyanosis. He referred to Dr. Soetomos hospital, and in the Emergency Unit this patient has
already given 2 ampules of kalmethasone every 30 minutes (totally 6 ampules). Because there
was no clinically improvement, the doctors from ENT department decided to do tracheostomy
and then he was taken place in Observation Intensive Room. After that episodes, he was
consulted to department of Internal Medicine.
History of asthma, rhinosinusitis, food or drug allergy was denied.
Physical examination :
Glascow Coma Scale of 4 x 6, Blood pressure was 80/60 mmHg, Heart rate was 100x/minute
regular, Respiratory rate was using ventilator, and temperature was 37,3C.
There was no anemia, jaundice, cyanosis, or angioedema, tracheostomy was placed, chest
region revealed rhoncy in the both of lungs, and there was no wheezing. Abdomen revealed
no abnormalities. There was papulae erythematosus in all of his body.
Direct laryngoscope showed epiglottis and larynk edema.
Initial laboratory results showed haemoglobin level of 17,7 g/dl, leucocyte was 39.200/mm,
thrombocyte was 301.000/mm. Blood sugar was 103 mg/dl, BUN 23 mg/dl, creatinin serum
1,9 mg/dl, AST 44 U/l, ALT 52 U/l, albumin 5,8 g/dl, natrium 144,7 mmol/l, potassium 5,02
mmol/l.
Cervical X- ray revealed narrowing at C4-C5. Chest X-ray showed infiltrate in the right
paracardial with homogen opacity in the left phrenicocostalis angle.
Pulmonology consultation with lung tuberculosis, which still necessitate further evaluation.
Initial assessment was anaphylactic shock with post tracheostomy. We advised to give
injection of adrenalin 1:1000 dilution, 0.3 mL subcutaneously and the dose might be repeated
at 15 minutes interval. Intravenous fluid support with Ringer lactate solution,
dyphenhidramine 25-50 mg i.v every 6 hours, ranitidine 50 mg i.v, methyl prednisolone 125
mg i.v every 8 hours. If there was severe hypotension, we advised to give dopamine 5
g/kgBW/minute as a starting dose.

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After given adrenalin and other drugs that mentioned above, the patient was in a stable
condition. The ventilator was weaned off, and the patient was removed to the ward.
DISCUSSION
The term anaphylaxis describes allergic, IgE-mediated, immediate hypersensitivity
reactions to protein substances. Anaphylactoid responses are clinically indistinguishable
reactions that are not IgE-mediated. The term anaphylaxis will be used to refer to both IgEand non IgE-mediated reactions, as their presentation and management are virtually identical;
however, hypotension and associated cardiac adverse events are less common in
anaphylactoid reactions (ODowd LC et al, 2007).
The most common identifiable causes of anaphylaxis in adults include : (1) Drugs
(including beta-lactam antibiotics, nonsteroidal anti-inflammatory agents (NSAIDs), and
antineoplastic compounds); (2) Insect stings/bites (including yellow jackets, wasps, kissing
bugs, and imported fire ants); (3) Foods (including seafood, fish, peanuts, and tree nuts); (4)
Immunotherapy injections; (5) Radiocontrast media; (6) Exercise (alone and in combination
with eating); (7) Latex. However, no specific trigger can be identified in up to 60 percent of
patients referred to Allergy/Immunology specialty clinics following anaphylaxis, and the
diagnosis of idiopathic anaphylaxis is assigned (AHA, 2006; ODowd LC et al, 2007).
Penicillins are the most common cause of drug-induced anaphylaxis. Cephalosporins,
which share a common beta-lactam ring with penicillins, are also frequently implicated.
Aspirin and other NSAIDs are the second most-commonly implicated class of medications
causing anaphylaxis. NSAIDs cause a variety of hypersensitivity reactions, some of which
will occur with several different NSAID agents, and others which are specific to a single drug.
Approximately 30 40% of adults with asthma and rhinosinusitis are sensitive to
aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). If exposed, they develop
symptoms ranging from increased nasal congestion to severe asthma and anaphylaxis. Rarely,
patients have anaphylactic sensitivity to aspirin and NSAIDs without the triad symptoms.
The mechanism may be blockade of the cyclo-oxygenase enzyme with resultant
overproduction of leukotrienes, especially LT3, 4 and 5. These are potent bronchoconstrictors.
This sensitivity appears to be related only to blocking the COX I isoform of the enzyme, as
patients with aspirin-induced asthma have been shown to tolerate COX II inhibitors. Why
only a subset of patients have this sensitivity to aspirin and NSAIDs is not known.
Unfortunately, it is a class effect, but some drugs induce more severe symptoms. This appears
to be related to the strength of the enzyme blockade. Patients may tolerate weaker COX I
inhibitors, such as acetaminophen or salisalate, but usually these do not provide adequate

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symptom relief (Biercher AJ, 1999; Shepherd GM, 2003). Since acetaminophen is a weak
inhibitor of the COX-1 enzyme, patients with aspirin-induced asthma should not take more
than 1000 mg of acetaminophen in a single dose (Knowles SR et al, 2007).
NSAID sensitivity is not always IgE-mediated, so skin testing is not an effective
means of ruling out the diagnosis (Craig TJ, 1999). However, note that in rare cases, patients
can have what are thought to be true IgE-mediated anaphylactic reactions to a specific NSAID
(Anand MK, 2007). In select cases, it is possible to desensitize patients with severe triad
symptoms to aspirin and maintain them on a regular daily dose. This has been associated with
clinical improvement in these patients. One study documented successful oral challenge
desensitization over several hours in 11 patients with aspirin- or NSAID-induced angioedema
and urticaria. Leukotriene inhibitors blocking lipoxygenase activating factor or LT4 receptors
have also helped some of these patients, but have not been shown, so far, to block specific
aspirin or NSAID sensitivity (Shepherd GM, 2003).
The likelihood of an individual experiencing an anaphylactic reaction to a particular
agent is influenced by gender, atopy, the route of exposure, a history of prior exposure, and a
history of prior anaphylactic episodes.
This patient denied any kind history of allergic disease.
There are several grading scales for anaphylaxis in the literature. The simplest and
probably most practical is one by Ringer and Messmer (Crump V, 2006) :
Grade 1: Skin reaction only
Grade 2: Systemic, non-life-threatening reaction
Grade 3: Life-threatening reaction
Grade 4: Cardiopulmonary arrest
After exposure to an inciting antigen, patients generally develop symptoms within 5 to
60 minutes, with earlier onset generally following parenteral introduction of the allergen. Less
commonly, the onset of anaphylaxis may be delayed several hours after exposure. The
manifestations of anaphylaxis vary widely. Death most commonly results from intractable
bronchospasm, asphyxiation from upper airway edema, or cardiovascular collapse. The most
common symptoms seen in anaphylaxis are urticaria (hives) and angioedema, which are seen
in 88 percent of individuals. These often occur after a period of generalized pruritus, flushing,
and the development of a sense of impending doom. Respiratory tract involvement and
complaints of shortness of breath, wheezing (particularly in persons with a history of asthma),
or laryngeal edema occur in approximately 50 percent of patients. Chest radiographs may
reveal hyperinflation, while functional measurements may demonstrate reduced values of
peak flow and FEV1 along with elevated airway resistance. The latter may result in increased

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peak airway pressures in intubated patients. Respiratory failure can result from airflow
obstruction, cardiogenic or non-cardiogenic pulmonary edema, or the acute respiratory
distress syndrome (ARDS). Anaphylactic shock occurs in 30 percent of cases. Cardiovascular
collapse results from hypovolemia (due to increased vascular permeability and loss of up to
50 percent of blood volume), alterations in peripheral vascular resistance, and myocardial
depression. The cardiac output is initially elevated but may become depressed. The pulmonary
and systemic vascular resistances are usually low, but may be elevated in some patients due to
maximal vasoconstriction in response to the loss of intravascular volume. These latter patients
may be unresponsive to pressor agents alone because they are already maximally
vasoconstricted. EKG monitoring may demonstrate tachycardia, relative bradycardia,
arrhythmias, or ST-T wave changes. Multifocal premature ventricular contractions are the
most commonly reported arrhythmia. Gastrointestinal symptoms, such as nausea, vomiting,
diarrhea, and abdominal or uterine cramping, are reported by 30 percent of patients (Dreskin
SC et al, 2005; ODowd LC et al, 2007).
Two hours after he got the medication (Novalgin injection), this patient felt shortness
of breath, irritable, and fell into unconsciousness. He also had urticaria that developing all
over his body, hypotension, tachycardia, and also cyanosis.
The clinical syndrome of anaphylaxis primarily results from activation and release of
mediators from mast cells and basophils. These cells can degranulate in response to multiple
triggers acting through a number of different mechanisms. These include the cross-linking of
mast cell-bound IgE with antigen, and stimulation by the anaphylatoxin complement
components C3a, C4a, and C5a. Other agents (eg, NSAIDs) initiate anaphylactic reactions
through alterations in arachidonic acid metabolism. Proper stimulation causes the release of
preformed mediators from mast cells and basophils, and promotes the rapid synthesis of other
active substances. During the initial minutes of the reaction, the liberated agents include
histamine, tryptase, prostaglandins (PGD2, PGF2a), leukotrienes (LTB4, LTC4, LTD4,
LTE4), and platelet-activating factor. Hours later, these same cells release newly synthesized
cytokines, such as IL-4, tumor necrosis factor, and IL-13. Mast cell and basophil-derived
mediators promulgate a number of physiologic changes. These include: pruritus, increases in
vascular permeability, vasodilation (leading to hypotension, and tachycardia), respiratory
smooth muscle contraction, stimulation of the autonomic nervous system, mucus secretion,
enhanced gut motility, platelet aggregation, and recruitment of inflammatory cells (ODowd
LC et al, 2007).
Symptoms of anaphylaxis generally have their onset within minutes, but occasionally
occur as late as 1 hour after exposure to the offending antigen. The signs and symptoms may

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follow a uniphasic course, with resolution of symptoms within hours of treatment, but about
20% of anaphylactic reactions will follow a biphasic course. Because the initial report by
Stark and Sullivan described asymptomatic periods of 18 hours, this is the time frame often
quoted in the medical literature, although some authors report a smaller window of 13 hours
based on another case series. Recently, the mean time to onset of second-phase reactivity has
been documented to be 10 hours.A number of cases have been documented of biphasic
reactivity occurring as late as 2438 hours after the initial manifestation of the anaphylactic
reaction. We have found that about one-third of the second-phase reactions were more severe
than the initial reaction, onethird were similar and one-third were milder. Mortality from
biphasic reactions is possible but is not adequately documented in the literature (Ellis AK, et
al, 2003)..

Figure 1. Schematic representation of a biphasic anaphylactic reaction

Due to the potentially life-threatening nature of anaphylaxis, prompt treatment is

required. The patient's airway and cardiopulmonary status should be rapidly assessed. If there
is airway involvement or significant edema of the facial or neck tissues, preparations for
possible intubation should be made. Careful monitoring of cardiopulmonary status, including
frequent vital signs, telemetry, and pulse oximetry, is required for the duration of the reaction.
Depending on the severity of clinical findings, patients may require treatment with
epinephrine, intravenous fluids, antihistamines, bronchodilators, or corticosteroids (Crump
2006, ODowd LC et al, 2007).
The primary medication for acute anaphylaxis is epinephrine. All other therapies are
adjunctive, including antihistamines, corticosteroids, and albuterol. Dopamine may be

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required to maintain blood pressure, and glucagon can be used in patients taking beta-blockers
who have refractory anaphylaxis (Dreskin SC, 2005).
Epinephrine is the drug of choice for anaphylaxis because it can reverse associated
hypotension and bronchospasm. Epinephrine should be given to patients presenting with
bronchospasm, significant gastrointestinal symptoms, laryngeal edema (hoarse voice,
difficulty swallowing, stridor), hypotension (lightheadedness, collapse), or any rapidly
progressing reaction. We recommend: 0.3 to 0.5 mL of 1:1000 (1 mg/mL) epinephrine
intramuscularly into the anterior or lateral thigh. This may be repeated every 5 to 15 minutes.
Shorter intervals between doses (such as every three to five minutes) may be appropriate
based upon response and clinical severity. If there is no response to the first or second doses
of epinephrine, fluid resuscitation should be initiated because one explanation for nonresponse to a vasoconstrictor is intravascular volume depletion (McLean-Tooke APC et al,
2003; ODowd LC et al, 2007).
First drug thats been used for this patient was not epinephrine but corticosteroid.
Because the symptoms of bronchospasm was not relieved by this drug, so tracheostomy was
done.
Antihistamines should be given to all patients with anaphylaxis. However, these
agents are considered second-line treatment after the administration of injected epinephrine. A
combination of H1 and H2 blockers may be superior to either agent alone.
Inhaled bronchodilators, such as albuterol, should be used as needed for the treatment of
bronchospasm. These agents are second-line treatment after the administration of injected
epinephrine. Corticosteroids are not helpful in the treatment of acute anaphylaxis. However,
based upon their efficacy in preventing late phase reactions in other IgE-mediated diseases
such as asthma, corticosteroids are often given for anaphylaxis with the goal of preventing or
ameliorating biphasic reactions. Vasopressor medications should be utilized in patients with
persistent hypotension despite intravenous fluid administration. In addition to epinephrine,
dopamine (5 to 20 micrograms/kg/min), norepinephrine (0.5 to 30 micrograms/min), or
phenylephrine (30 to 180 micrograms/min) are effective for this indication (Lieberman P et al,
2005; ODowd LC et al, 2007) .
We advised to give injection of adrenalin 1:1000 dilution, 0.3 mL subcutaneously and
the dose might be repeated at 15 minutes interval. Intravenous fluid support with Ringer
lactate solution, dyphenhidramine 25-50 mg i.v every 6 hours, ranitidine 50 mg i.v, methyl
prednisolone 125 mg i.v every 8 hours. If there was severe hypotension, we advised to give
dopamine 5 g/kgBW/minute as a starting dose. After given those drugs, there were clinically
improvement. The ventilator was weaned off and the patient was removed to the ward.

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Tracheostomy is an operative procedure that creates a surgical airway in the cervical
trachea. In the case of upper airway obstruction, tracheostomy provides a path of low
resistance for air exchange. The indications of tracheostomy was to bypass obstruction, neck
trauma that results in severe injury to the thyroid or cricoid cartilages, hyoid bone, or great
vessels, subcutaneous emphysema, facial fractures that may lead to upper airway obstruction,
edema due to trauma, burns, infection, or anaphylaxis, or to provide a long-term route for
mechanical ventilation in cases of respiratory failure. No absolute contraindications exist to
tracheostomy. The tracheostomy tube should be removed as soon as is feasible and, therefore,
should be downsized as quickly as possible. This allows the patient to resume breathing
through the upper airway and reduces dependence (psychological and otherwise) on the lesser
resistance of the tracheostomy tube. Decannulation may be performed when the patient can
tolerate plugging of the tracheostomy tube overnight while asleep without oxygen
desaturation (Lindman JP, 2006).
It should be remained that the most important medication for the treatment of
anaphylaxis is epinephrine. Tracheostomy will not be necessitated to be done in this situation,
if this patient got epinephrine as the first drug.
SUMMARY
It had been reported a patient with drug-induced anaphylaxis. The identifiable causes
was novalgin injection (consist of metamizole Na) and categorized into non-steroidal anti
inflammation drugs. First drug thats been used for this patient was not epinephrine but
corticosteroid. Because the symptoms of bronchospasm was not relieved by this drug, so
tracheostomy was done. After given those drugs, there were clinically improvement so the
ventilator was weaned off and the patient was removed to the ward.
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