Anaphylaxis and other acute reactions following vaccination: Canadian Immunization Guide
Introduction
This chapter is intended as a guide for the assessment and initial management of vaccine recipients who develop acute adverse reactions in a community setting (e.g., schools, public health clinics, health centres).
Two types of adverse events are most likely to present acutely:
- Anxiety-related adverse events following immunization (AEFI) including fainting (vasovagal syncope), hyperventilation and breath-holding
- Anaphylaxis or other immediate hypersensitivity reactions to vaccine components or the container (e.g., latex).
Management and implications for future immunization are markedly different for these events and it is important to distinguish one from the other as quickly as possible without delaying appropriate therapeutic interventions.
See  for a side by side comparison of presenting features of anaphylaxis and vasovagal syncope.
Anxiety-related adverse events

# Breath-holding
Breath-holding episodes occur in some young children when they are upset and crying hard. The child suddenly becomes silent but remains agitated. Facial flushing and perioral cyanosis deepens as breath-holding continues. Some episodes end with resumption of crying, but others end with a brief period of unconsciousness during which breathing resumes. No treatment is required beyond reassurance of the child and parents.

# Hyperventilation
People experiencing anxiety may appear fearful, pale and diaphoretic. They may complain of lightheadedness, dizziness and numbness, as well as tingling of the face and extremities. Hyperventilation is usually evident. Treatment consists of reassurance and encouraging the individual to breathe slowly and deeply. Initiating a refocusing activity, such as asking the person to count to ten, may help. Should there be another condition causing the hyperventilation, such as asthma or heart attack, holding one's breath could worsen the condition.

# Vasovagal syncope (fainting)
Fainting itself has no adverse consequence but during a fall, severe head injuries could occur.
Fainting is common with at least one lifetime occurrence in about 3.5% of women and 3% of men. The exact frequency of fainting post-immunization is not known but the majority of syncope adverse event reports involve adolescents or adults. Fainting is rare in infants and children. Therefore, a sudden loss of consciousness in young children should be presumed to be anaphylaxis, especially if other clinical features of anaphylaxis are present.
Fainting usually occurs during immunization or within minutes of immunization. The individual may complain of feeling faint or light-headed, then suddenly become pale, lose consciousness and collapse to the ground. This may be accompanied by brief clonic seizure activity (i.e., rhythmic jerking of the limbs). As a general rule, the respiratory rate is normal and not laboured, but may be shallow. Cardiovascular signs include bradycardia and faint peripheral pulses but usually the carotid pulse is strong. In addition to pallor, the skin may be cool and clammy. There may be associated nausea and vomiting. Fainting is managed by placing the vaccinee in a supine (lying on their back) position and elevating the lower extremities. If vomiting has occurred or is imminent, position the vaccinee lying on one side. If the vaccinee is pregnant, position them lying on their left side. Recovery of consciousness and resolution of limb jerking usually occurs within a minute or two. The person may remain pale, diaphoretic and mildly hypotensive for several minutes. Continue monitoring and providing support to the vaccinee who has fainted until signs and symptoms have stabilized.
Adapted with permission from: Immunisation Section, South Australian Department for Health and Wellbeing.
For a more detailed list of system-specific manifestations of anaphylaxis, see .
For techniques to decrease anxiety and fainting, refer to  in Part 1.
Anaphylaxis
Anaphylaxis is a serious, potentially life-threatening allergic reaction to foreign antigens; it has been proven to be causally associated with vaccines with an estimated frequency of 1.3 episodes per million doses of vaccine administered. Anaphylaxis is preventable in many cases and treatable in all. It should be anticipated in every vaccinee.

# Pre-vaccination screening
Prevention of anaphylaxis is critically important. Pre-vaccination screening includes screening for a history of anaphylaxis and identification of potential risk factors. It should include questions about possible allergy to any component or container of the scheduled vaccine(s) in order to identify if there is a contraindication to administration.

## Post-vaccination observation
Most instances of anaphylaxis to a vaccine begin within 30 minutes after administration of vaccine. Therefore, vaccine recipients should be kept under observation for at least 15 minutes after immunization; 30 minutes is a safer interval when there is a specific concern about possible vaccine allergy. In low-risk situations, observation can include asking vaccinees to watch for symptoms and return immediately for assessment if they feel unwell.
 For information about reporting AEFI such as anaphylaxis, refer to  (AEFI).

# Signs and symptoms of anaphylaxis
In anaphylaxis, signs and symptoms onset suddenly and progress rapidly over several minutes and involves two or more body systems. The most frequently involved systems are skin (80% to 90% of anaphylaxis cases), respiratory (up to 70% of cases) and less often cardiovascular and gastrointestinal (each up to 45% of cases). Up to 15% of cases may also manifest central nervous system changes of uneasiness, altered mental status, dizziness, or confusion. Features of severe anaphylaxis include obstructive swelling of the upper airway, marked bronchospasm and hypotension. Hypotension can progress to cause shock and collapse.
Reproduced with permission from: Cheng A; Canadian Paediatric Society, Acute Care Committee. Emergency treatment of anaphylaxis in infants and children. Paediatr Child Health 2011;16(1):35-40. Reaffirmed February 2018.
It may be challenging to identify anaphylaxis in infants and young children (0-2 years of age) as they are unable to describe their symptoms. Infants may present with respiratory distress (e.g., increased work of breathing, cough, wheeze, stridor) or tachycardia rather than hypotension. Non-specific signs and symptoms may include sudden quietness or sleepiness, drooling, incontinence and behavioural changes such as inconsolable crying and irritability - all of which are common in this age group. Generalized urticaria, flushing, vomiting (including persistent vomiting), and angioedema are typically observed in this age group. Specific or non-specific signs or symptoms in two or more body organ systems are required for a clinical diagnosis of anaphylaxis.

# Risk factors for severe anaphylaxis
Anaphylaxis is a rare complication of immunization. Risk factors for increased severity of anaphylactic events include:
- very young or old age,
- pregnancy,
- severe or uncontrolled asthma,
- cardiovascular disease,
- chronic obstructive pulmonary disease,
- systemic mastocytosis,
- concurrent use of certain medications (e.g., angiotensin-converting enzyme  inhibitors and beta-blockers).

# Anaphylaxis management kits
Appropriate preparation is important for a good outcome in anaphylaxis. Anaphylaxis management kits should be readily available wherever vaccines are administered. EPINEPHrine in an autoinjector or in a vial may be used to treat anaphylaxis; however, vials of EPINEPHrine must be available for treatment of infants weighing less than 5 kg (refer to ). EPINEPHrine and other emergency supplies should be checked on a regular basis and replaced when outdated.
- EPINEPHrine dosage by weight and age
- Three extra 25 gauge needles of each different size: 5/8 inch, 1 or 1.25 inch, 1.5 inch
- Alcohol swabs
- Tongue depressors
- Pocket mask
- Wristwatch with second hand (for heart rate)
- Ready access to a phone to call emergency services
- Flashlight
- Oxygen and related equipment
- IV lines, fluids and related equipment
- Stethoscope
- Sphygmomanometer
All immunization sites should have the essential items. Optional items reflect variations in immunization sites some of which are equipped for advanced care.
 TALLMAN lettering is a method of applying upper-case lettering to sections of look-alike/sound-alike name attributes in efforts to avoid drug name confusion and potential medication incidents.

# Management of anaphylaxis
Anaphylaxis is a medical emergency, and rapid recognition and management can be life-saving. Every vaccine provider should be familiar with the signs and symptoms of anaphylaxis and be prepared to act quickly. The rate of progression or the severity of the anaphylactic episode can be difficult to predict at the start of anaphylaxis; however, rapid development of anaphylaxis following vaccination indicates that a more severe reaction is likely. Death can occur within minutes. EPINEPHrine is the only medication that reduces hospitalization and death and should be administered promptly following the onset of anaphylaxis.

## Protocols
All immunization providers should be trained to recognize anaphylaxis, to administer intramuscular (IM) EPINEPHrine and to initiate basic life-support measures such as cardio-pulmonary resuscitation (CPR) if indicated.
Vaccinees with severe allergic reaction or anaphylaxis should be transported to a hospital as soon as possible. The establishment of intravenous (IV) access for fluid resuscitation may be necessary, and endotracheal intubation and other advanced life-support interventions may be required. These interventions generally do not take place in community settings but may at times be performed by competent and trained staff in safe and appropriate care settings.
Advance preparation for emergency management of anaphylaxis is essential. It is recommended that vaccine providers develop, post, and regularly rehearse a written anaphylaxis emergency management protocol. Protocols should specify the necessary emergency equipment, drugs and dosages, and medical personnel necessary to safely and effectively manage anaphylaxis.

## Steps for basic management of anaphylaxis in a community setting
Rapid intervention is of paramount importance. Steps 1, 2, 3 and 4 should be done promptly and simultaneously.
- 1. Direct someone to call 911 (where available) or emergency medical services.
- 2. Assess airway, breathing, circulation, mental status, skin, and body weight (mass). Secure an oral airway if necessary.
	+ airway: look specifically at lips, tongue and throat for swelling; if appropriate, ask individual to say his/her name to assess glottic/peri-glottic swelling
- 3. Place individual on his/her back (supine) and elevate lower extremities. The vaccinee should remain in this position. Fatality can occur within seconds if the vaccinee stands or sits suddenly, due to empty vena cava/empty ventricle syndrome. Exceptions to the supine position:
	+ if in respiratory distress, place in a position of comfort (elevate head and chest)
	+ if vomiting or unconscious, place lying on his/her side
	+ if pregnant, place lying on their left side
- 4. Inject EPINEPHrine:
	+ Dose: 0.01 mg/kg body weight of 1:1000 (1 mg/mL) solution, MAX 0.5 mg (see  for dosage by age or weight)
	+ Route: INTRAMUSCULAR (IM) in mid-anterolateral thigh (*vastus lateralis- muscle)
	+ Repeat every 5 minutes if symptoms persist (most patients improve in 1-2 doses)
	+ Record the time of each dose
	+ Stabilize and monitor patient (see steps  & )
Weight is the preferred basis for dosage but if unknown, use age as a guide.
 autoinjector dose
 or
 1 mg/mL
Adapted from: Australian Immunisation Handbook (ATAGI, confirmed June 2018). . 
Adapted from: TREKK. Dec 2018. Pediatric anaphylaxis algorithm. Version 1.1. Accessed June 28, 2020 from: \_Anaphylaxis\_algorithm\_v\_1.1.pdf?1545083235
Cheng A; Canadian Paediatric Society, Acute Care Committee. Emergency treatment of anaphylaxis in infants and children. Paediatr Child Health 2011; 16(1):35-40.
Jensen J, Ryu J, Clifton H, Brown J. Impact of Pre-Arrival epinephrine in Emergency Department or Urgent Care pediatric anaphylaxis patients weighing < 15 kg, Poster P010, Ann Allergy Asthma Immunol 2018; 121: S22S62.
As of October 2020, three EPINEPHrine autoinjectors were on the Canadian market: EpiPen,  Allerject and EMERADETM.
In infants, it is recommended that EPINEPHrine be administered via a syringe rather than by an autoinjector. Needle lengths that are too long have a risk of intraosseous administration (due to the need to apply pressure in order to deploy the autoinjector). The depth of the needle is better controlled with the syringe administration rather than autoinjector.
Sicherer SH and FER Simons, Pediatrics 2007; 199:638-646.
- 5. Stabilize vaccinee: perform cardiopulmonary resuscitation if necessary, give oxygen and establish intravenous access if available
	+ give supplemental oxygen (6 to 8 L/minute) by face mask or oropharyngeal airway (if available) to people with cyanosis, dyspnea or any other severe reaction requiring repeated doses of EPINEPHrine
	+ if hypotensive, consider giving IV normal saline, 20 mL/kg if IV access established and if available.
- 6. Monitor vaccinee's blood pressure, cardiac rate and function, and respiratory status.
- 7. Transfer to hospital for observation. All vaccinees receiving emergency EPINEPHrine must be transported to hospital immediately for evaluation and observation. The symptoms of an anaphylactic reaction can reoccur after the initial reaction (biphasic anaphylaxis) in up to 23% of patients with anaphylaxis.

## EPINEPHrine treatment - additional information
Prompt intramuscular administration of EPINEPHrine is the priority and should not be delayed. EPINEPHrine is the treatment of choice for management of anaphylaxis in community and healthcare settings as it prevents and relieves upper airway swelling, hypotension and shock. In addition, it causes increased heart rate, increased force of cardiac contractions, increased bronchodilation, and decreased release of histamine and other mediators of inflammation. EPINEPHrine reaches peak plasma and tissue concentrations rapidly.
Failure to administer EPINEPHrine promptly may result in greater risk to the vaccinee with anaphylaxis than using EPINEPHrine improperly.
If uncertain, err on the side of treatment; there are no contraindications to the use of EPINEPHrine. If time is lost early in the treatment of an acute anaphylactic episode, subsequent management can become more difficult.
EPINEPHrine 0.01 mg/kg body weight of 1:1000 (1 mg/mL) solution (max 0.5 mg) should be administered into the mid-anterolateral aspect of the thigh (*vastus lateralis- muscle); the deltoid muscle of the arm should not be used as it is not as effective as the thigh in absorbing EPINEPHrine. Scissors may be needed to cut clothing to establish access. If scissors are not readily available, EPINEPHrine may be administered through clothing. Although there is a slightly increased risk of infection, timely administration of EPINEPHrine is the priority. The risk of infection can be addressed once the person has stabilized. For infants weighing less than 5 kg, the dose of EPINEPHrine should be determined by weight, if possible. For example, an infant weighing 4 kg (8.8 lb) should receive 0.04 mg of EPINEPHrine, which is 0.04 mL of a 1 mg/mL solution. However, if a vial is not available at the time of anaphylaxis, the 0.15 mg EPINEPHrine autoinjector device can be safely used. (Refer to  for EPINEPHrine dosing guidelines). Mild and transient effects such as pallor, tremor, anxiety, palpitations, headache and dizziness occur within minutes after injection of a recommended dose of EPINEPHrine. These effects confirm that a therapeutic dose has been given.

# Antihistamines
Antihistamines (first generation and second generation) have no role in preventing or treating respiratory or cardiovascular symptoms of anaphylaxis in a community setting and should never be used in place of EPINEPHrine.
Swelling and urticarial rash at the injection site
Swelling and urticarial rash (i.e., hives) at the injection site can occur and may be the first indication of an evolving anaphylaxis. For this reason, while such reactions are not always caused by an allergic reaction, the individual should be observed for at least 30 minutes in order to ensure that the swelling or hives remain localized. Ice can be applied to the injection site for comfort. If the hives or swelling disappears and there is no evidence of any progression to other parts of the body and there are no other symptoms within the 30-minute observation period, no further observation is necessary. However, if any other symptoms arise, even if considered mild (e.g., sneezing, nasal congestion, tearing, coughing, facial flushing), or if there is evidence of any progression of the hives or swelling to other parts of the body during the 30-minute observation period, EPINEPHrine should be given (refer to the ). 
A mild local reaction resolving by itself within a few minutes is not indicative of an allergic reaction and does not require special observation or specialized assessment prior to subsequent vaccination.