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Case
3
An unpleasant surprise
SUMMARY
A 30-year-old lady develops acute shortness of
breath following administration of amoxicillin.
What would you do?
Medical history
You checked the medical history before administering the
amoxicillin and so you know that the patient is a well-
controlled asthmatic taking salbutamol on occasions. She
also suffers from eczema, as do her mother and her two
children, and uses a topical steroid cream as required. The
patient has had antibiotic cover before and refuses treat-
ment without. See Case 44 for further discussion.
Dental history
The patient has been a regular attender for a number of
years. She has had previous courses of penicillin from her
general medical practitioner for chest infections.
What is the likely diagnosis?
Anaphylaxis, arising from hypersensitivity to the amoxicillin.
Examination
The patients face is shown in Figure 3.1. What do you see?
There is patchy erythema. In the most infamed areas there
are well-defned raised oedematous weals, for instance at the
corner of the mouth and on the side of the chin. This is a
typical urticarial rash and indicates a type 1 hypersensitivity
reaction.
What would you do immediately?
Reassure the patient.
Assess the vital signs including blood pressure, pulse and
respiratory rate.
Lie the patient fat (as there is no difculty breathing).
Call for help.
Obtain oxygen and your practice emergency drug box.
What are the signs and symptoms of anaphylaxis?
The signs and symptoms vary with severity. The classical
picture is of:
a red urticarial rash
oedema that may obstruct the airway
hypotension due to reduced peripheral resistance
hypovolaemia due to the movement of fuid out of the
circulation into the tissues
small airways obstruction caused by oedema and
bronchospasm.
Involvement of nasal and ocular tissue may cause rhinitis and
conjunctivitis. There may also be nausea and vomiting.
What does urticarial mean?
The word urticarial comes from the Latin for nettle rash. An
urticarial rash has superfcial oedema that may form separate
fat raised blister-like patches (as in Fig. 3.1) or be difuse. In
the head and neck it is often difuse because the tissues are
lax. Markedly oedematous areas may become pale by
compression of their blood supply but the background is
erythematous. Patients often know an urticarial rash by the
lay term hives.
Fig. 3.1 The patients face as she starts to feel unwell.
History
Complaint
The patient complains that she feels unwell, hot and
breathless.
History of complaint
The patient has an appointment for routine dental treatment
involving scaling and a restoration under local anaesthesia
and antibiotic prophylaxis. She took a 3 g oral dose of amox-
icillin 45 minutes ago.
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Allow the patient to adopt the most comfortable position for
breathing and give oxygen (5 litres per minute) by facemask.
Because there is bronchospasm, give the following drugs in
order:
Adrenaline (epinephrine) 1 : 1000, 500 micrograms
intramuscularly. The easiest form to administer is a preloaded
EpiPen or Anapen, which are available for both adults (300
micrograms/dose) and children (150 micrograms/dose).
Alternatively, a Min-I-Jet prepacked syringe and needle
assembly or a standard vial of adrenaline solution, both
containing 1 milligram in 1 millilitre (1 : 1000), may be used.
However, both of these latter methods require a delay in
administration to prepare the injection. You need to be
familiar with whichever form is held in your practice as delay
in calculating doses and volumes is clearly undesirable.
Adrenaline (epinephrine) may also be given subcutaneously
but the absorption is slower and this route is no longer
recommended. Note that autoinjectors are designed for
self-administration and so provide a slightly lower dose than
is recommended. The recommended site for the
intramuscular injection is the anterolateral aspect of the
middle of the thigh, where there is most muscle bulk. If
clothing prevents access, the upper lateral arm, into the
deltoid muscle, is an alternative site. In an emergency it may
be necessary to inject through clothing but this is not
recommended. In the past the tongue has been proposed a
potential site because it is familiar to dentists, but it is highly
vascular allowing rapid uptake of drug and unlikely to be
acceptable to the conscious patient.
Chlorphenamine (chlorpheniramine) 10mg intravenously
will counteract the efects of histamine.
Hydrocortisone 100200mg intravenously or
intramuscularly.
Intravenous fuid. Only required if hypotension develops. A
suitable regime would be 1 litre of normal saline infused over
5 minutes with continuous monitoring of the vital signs.
The last three actions require intravenous access and this
may be difcult to achieve in an individual with reduced
circulatory volume and hypotension. Finding and entering
a collapsed vein is difcult even for the experienced and is
best attempted as soon as adrenaline has taken effect. If
necessary massage the arm towards the hand to try to
inate the vein. The importance of gaining venous access
depends on circumstances. If medical or paramedical help
is likely to arrive quickly, no more than adrenaline may be
required. If not, these extra drugs may be important. Though
the circulation may be maintained effectively by adrenaline,
its action is short lived and you will only have a limited
number of doses available. It is probably worthwhile insert-
ing a Venon-type intravenous cannula or at least a but-
tery needle for any patient that develops difculty
breathing. If the reaction becomes more severe, it may be
more difcult to insert later.
The presentation of drugs useful for anaphylaxis is
shown in Figure 3.3.
Why must the drugs be given in this order?
Adrenaline is the life-saving drug and must be given straight
away, before circulatory collapse. It is rapidly acting.
What is the pathogenesis of anaphylaxis?
Anaphylaxis is an acute type 1 hypersensitivity reaction
triggered in a sensitized individual by an allergen. The
allergen enters the tissues and binds to immunoglobulin E
(IgE) that is already bound to the surface of mast cells,
present in almost all tissues. Binding of allergen to IgE induces
degranulation and the release of large amounts of
infammatory mediators, particularly histamine. This causes
the vasodilatation, increased capillary permeability and
bronchospasm.
Type 1 hypersensitivity is also known as immediate
hypersensitivity but onset was delayed for 45 minutes.
Why?
Acute anaphylactic reactions may occur within seconds or
may be delayed for up to an hour depending on the nature
of the allergen and the route of exposure. It takes time for an
oral dose of antibiotic to be absorbed and pass through the
circulation to the tissues, in this case 45 minutes. The reaction
would be expected about 30 minutes after intramuscular
administration of an allergen but almost instantaneously after
intravascular administration. The time of onset is
unpredictable. Some allergens such as peanuts and latex can
cause rapid reactions despite being applied topically. The
variability in onset of reactions explains why patients should
be observed for an hour after administration of antibiotic
cover.
On examining for the signs noted above you discover that
the patient is breathless and a wheeze can be heard during
both inspiration and expiration indicating small airways
obstruction. She feels hot and has a pulse rate of 120 beats
per minute and blood pressure of 120/80 mmHg. She is
conscious but the effects are becoming more severe and the
rash now affects all the face and neck region and has spread
onto the upper aspect of the thorax. The appearance of one
arm is shown in Figure 3.2.
Treatment
What treatment would you perform?
Before the breathing problems were noted you correctly laid
the patient fat. However, their lungs must now be raised
above the rest of their body to prevent oedema fuid
collecting in the lungs.
Fig. 3.2 The patients arm 5 minutes later.
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Continue to administer oxygen.
Arrange transfer of the patient to an appropriate
secondary care facility.
Advise the patient of the need for formal investigation of
their probable allergy.
Can you relax now the immediate crisis is over?
No, defnitely not. The response of the patient needs to be
closely observed. Adrenaline (epinephrine) is highly efective
but has a very short half-life. Recurrence of bronchospasm, a
Chlorphenamine (chlorpheniramine) is less potent and slower
acting and cannot alone counteract pulmonary oedema or
bronchospasm, which indicate a severe reaction.
Hydrocortisone is the lowest priority; it takes up to 6 hours to
act and is not immediately life saving.
After giving all three drugs, the patient recovers. What
would you do next?
Abandon dental treatment.
Continue to monitor the vital signs.
A
B
C
D
E
F
Fig. 3.3 Typical presentations of drugs used to treat anaphylaxis.
A. Oxygen mask.
B. Hydrocortisone. Vials of lyophilised powder for reconstitution in water for injection, NOT saline. Administer with a conventional
syringe and needle.
C. Adrenaline* in an Epipen disposable autoinjector spring-loaded syringe, boxed, and below with the plastic covers removed from
each end. Press directly onto the skin and the spring-loaded needle is unsheathed and the drug is injected automatically. A similar
device, the Anapen, has a spring-loaded needle that springs out when a button at the opposite end is pressed. Both deliver 300
micrograms of adrenaline.
D. Adrenaline in Min-I-Jet format. The yellow plastic cover is removed from the back (right hand end) of the syringe barrel and front of
the glass cartridge and the cartridge is screwed into the syringe barrel. Available in two types, with needle ftted (left,
recommended) and with luer lock ftting for a conventional needle (slower to use). After removing front cover and ftting needle, if
required, use as a conventional syringe. Versions with fner needles for subcutaneous administration are available but the
intramuscular route is preferred and the version with the larger 21 gauge needle should be used.
E. Adrenaline as traditional ampoule, ready to inject with a conventional syringe.
F. Chlorpheniramine as traditional ampoule, ready to inject with a conventional syringe.
*Note that epinephrine is now the recommended name for adrenaline internationally but that adrenaline is still the most widely used name in
the UK.
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predisposition to explain why only a few individuals develop
hypersensitivity.
Can patients be tested for penicillin allergy?
Yes, but it carries a risk of anaphylaxis and must be performed
with care in a specialized centre. Only 1020% of patients
who report penicillin allergy are actually hypersensitive but
not all can be tested. It is recommended that testing be
reserved only for those who give a convincing history of a
type 1 reaction and who also have a defnite requirement for
penicillin. In most cases a safe alternative antibiotic, for
example clindamycin, is available and so testing is not
performed.
Why is there no corticosteroid or antihistamine in my dental
emergency drugs box; it is claimed to contain the
recommended drugs?
The Resuscitation Council UK has published guidance on
medical emergencies and resuscitation, revised in May 2008.
Their recommendations have been endorsed by the General
Dental Council. They state that the emergency drugs listed in
Table 3.1 should be available in all dental surgeries in the UK:
Of the drugs recommended for this case, only oxygen and
adrenaline are included. The guidance specifcally notes that
antihistamines and corticosteroids are not frst line drugs for
treatment of anaphylaxis. As noted above, this is true, but this
drug box is a minimum specifcation for general practice only.
Much more diverse emergency drug boxes are used by those
working in hospitals, health clinics and some specialist
practices, where dentists may be trained in advanced trauma
life support (ATLS) or have other specialist skills through their
involvement with conscious sedation or special care dentistry.
The list must also be modifed to circumstances. In remote
areas where medical help may be delayed, it will be essential
to have these additional drugs for longer term treatment and
also for the dentist to be able to gain venous access. These
drugs and skills should be within the remit and capabilities of
any dental practitioner.
Dentists must be familiar with the actions and efects of
drugs they may need to use, so it is the dentists responsibility
to ensure that they are properly informed about any
additional drugs they elect to hold. The General Dental
Council also provides guidance that every practice should
have two people available and trained in medical
emergencies whenever treatment is being carried out. All the
dental team must practice simulated emergencies together
on a regular basis.
drop in blood pressure or worsening oedema indicates a
need for further adrenaline (epinephrine). This is likely to be
needed about 5 minutes after the previous administration
and it can be repeated again as often as necessary. However,
the chlorphenamine (chlorpheniramine) will start to become
efective and no more than two doses of adrenaline
(epinephrine) should be necessary.
Late relapse, hours later, is also possible. Mast cells also
release other potent infammatory mediators and some have
long half-lives. The hydrocortisone prevents this late relapse.
Can an anaphylactic reaction be controlled without
adrenaline (epinephrine)?
If the only features are a rash and mild swelling not involving
the airway it may be appropriate to give chlorphenamine
(chlorpheniramine) and hydrocortisone in the frst instance
and observe the response. However, if bronchospasm,
hypotension or oedema around the airway develops,
adrenaline (epinephrine) will be needed. Adrenaline
(epinephrine) should be administered as early as possible to
be efective and it is better not to delay unless the signs and
symptoms are very mild.
Further points
Why is adrenaline (epinephrine) efective?
Adrenaline (epinephrine) is the prototypical adrenergic
agonist and has both alpha and beta receptor activity. Alpha
receptor-mediated action on arterioles causes
vasoconstriction and thus reverses oedema. Beta receptor-
mediated actions include increasing the cardiac output by
increasing the force of contraction and heart rate (beta 1) and
bronchodilatation (beta 2). Mast cell degranulation is also
suppressed.
Why was this patient at high risk of anaphylaxis?
She has a history of asthma and a family history of eczema.
This indicates atopy and an increased risk of developing
hypersensitivity to a wide range of substances. It is important
to take a thorough allergy history, particularly regarding
drugs, rubber and other dental materials in all patients. No
patient should be exposed to a possible allergen until you
have sought advice.
Why had this patient no history of allergy to penicillin?
The patient may have been sensitized by the previous courses
of penicillins. This underlines the unpredictability of allergic
reactions. Patients who have been administered any
medication should be monitored for an appropriate time in
case of acute adverse efects, the period depending on the
route of administration (see above).
How can penicillin allergy develop in patients who have
never taken penicillins?
It is thought that sensitization may also develop in response
to very small quantities of penicillins in the environment.
Veterinary uses of penicillins leave residues in meat and milk,
and these may pass to babies via their mothers milk.
Penicillins are ubiquitous and there is probably a genetic
Table 3.1 Emergency drugs
Drug Dose
Glyceryl trinitrate spray 400 micrograms/dose
Salbutamol aerosol inhaler 100 micrograms/puf
Adrenaline injection 1 : 1000 1mg/ml
Aspirin dispersible 300mg
Glucagon injection 1mg
Oral glucose solution Gel, tablets or powder
Midazolam 5mg/ml or 10mg/ml
Oxygen
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Suppose the patient had been a child?
Allergy in children is usually triggered by dietary allergens
rather than drugs but latex allergy is possible and children
with frequent medical exposure to latex, as in catheters, are at
risk. Doses of adrenaline are reduced to 250 micrograms for
ages 612 years and 120 micrograms for ages 6 months to 6
years. Giving these doses might prove difcult if you do not
have specifc paediatric formulations in your emergency drug
kit. Autoinjectors provide 300 or 150 micrograms and
Min-I-Jet devices are designed to give a full adult dose.
Children with severe allergies may carry autoinjection devices
with the correct paediatric dose and should be asked to bring
them when they attend for dental treatment.
Other possibilities
If you discovered that you had just administered a penicillin
orally to a patient known to be allergic to penicillins, what
would you do?
Absorption of only a very small amount of the penicillin is
needed to trigger an allergic response so there is no point in
thinking that inducing vomiting would be helpful. The best
thing to do would be to administer the chlorphenamine
(chlorpheniramine) and steroid immediately, prepare the
adrenaline (epinephrine) and oxygen and administer the
adrenaline (epinephrine) immediately any signs begin to
develop. The patient would still have to seek medical care as
soon as possible because the late phases of the reaction
might still develop even if the immediate phases were
prevented.
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