Anaphylaxis and other acute reactions following vaccination: Canadian Immunization Guide

For health professionals

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 Table 1 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.

Table 1 lists clinical features that differentiate fainting due to vasovagal syncope from anaphylaxis.

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.

Table 1: Key distinguishing features of anaphylaxis and vasovagal syncope.

Clinical features	Anaphylaxis	Vasovagal syncope
Onset from time of immunization	Within minutes up to 4 hours after injection; most within 2 hours	During or within minutes of injection
Skin	Urticaria, angioedema, pruritus, erythema	Generalized pallor, cold clammy skin
Respiratory	Cough, wheeze, stridor, respiratory distress, rhinorrhea, sneezing	Normal respiration – may be shallow but not laboured
Cardiac	Tachycardia	Bradycardia
Neurologic	Sense of severe anxiety and distress; loss of consciousness – no improvement once supine or in head down position	Sense of light-headedness; loss of consciousness – improves once supine or in head down position; may be transient jerking of the limbs and eye-rolling

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 Table 2.

For techniques to decrease anxiety and fainting, refer to Vaccine Administration Practices 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.

Refer to Vaccine Administration Practices in Part 1 for a pre-vaccination administration checklist.

Refer to Contents of Immunizing Agents Available in Canada in Part 1 for a list of potential allergens in immunizing agents.

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.

Refer to Vaccine Administration Practices in Part 1 for more information on post-vaccination counselling and observation.

For information about reporting AEFI such as anaphylaxis, refer to Adverse Events Following Immunization (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.

Table 2: Signs and symptoms of anaphylaxis

System	Signs and symptoms
General/CNS	Fussiness, irritability, drowsiness, lethargy, reduced level of consciousness, somnolence
Skin	Urticaria, pruritus, angioedema, flushing
Upper airway	Stridor, hoarseness, oropharyngeal or laryngeal edema, uvular edema, swollen lips/tongue, sneezing, rhinorrhea, upper airway obstruction
Lower airway	Coughing, dyspnea, bronchospasm, tachypnea, respiratory arrest
Cardiovascular	Tachycardia, hypotension, dizziness, syncope, arrhythmias, diaphoresis, pallor, cyanosis, cardiac arrest
Gastrointestinal	Nausea, vomiting, diarrhea, abdominal pain
CNS Central nervous system

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.

Download the printable poster for the diagnosis and management of anaphylaxis following vaccination in community settings.

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 [ACE] 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 treatment - additional information). EPINEPHrine and other emergency supplies should be checked on a regular basis and replaced when outdated.

Table 3: Anaphylaxis management kits: recommended items ^{Footnote 1}

Items	Essential	Optional
Laminated documents	Clear, concise summary of emergency management protocol EPINEPHrine dosage by weight and age	N/A
Drugs	EPINEPHrineFootnote 2: three vials - 1:1000 (1 mg/mL) solution for IM injectionFootnote 3	N/A
Injection suppliesFootnote 4	Two 1 cc syringes with attached 25 gauge needle (one - 1 inch; one 5/8 inch) Three extra 25 gauge needles of each different size: 5/8 inch, 1 or 1.25 inch, 1.5 inch	EPINEPHrineFootnote 2 autoinjectors labelled by age and weight
Other	Scissors Alcohol swabs Tongue depressors Pocket mask Wristwatch with second hand (for heart rate) Ready access to a phone to call emergency services Flashlight	1 nasopharyngeal, 1 oropharyngeal airway for each age range anticipated in the clinic Oxygen and related equipment IV lines, fluids and related equipment Stethoscope Sphygmomanometer
Footnote 1 All immunization sites should have the essential items. Optional items reflect variations in immunization sites some of which are equipped for advanced care. Return to footnote 1 referrer Footnote 2 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. Return to footnote 2 referrer Footnote 3 Refer to Table 4 for recommended EPINEPHrine dosing information. Return to footnote 3 referrer Footnote 4 Refer to Vaccine Administration Practices in Part 1 for information on intramuscular injections and needle selection guidelines. Return to footnote 4 referrer

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 Table 4 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 5 & 6)

Table 4: Dosage of intramuscular EPINEPHrine 1:1000 (1 mg/mL) solution, by age or weight^{Footnote 1}

Weight is the preferred basis for dosage but if unknown, use age as a guide.

AgeFootnote 1, Footnote 2 Use weight if available	WeightFootnote 2 (kg)	EPINEPHrine dose (1 mg/mL) ampoule/vial		EPINEPHrine autoinjector doseFootnote 5 Use only if measured dose by weight is unavailable
		mg or mg/kg/dose	Volume 1 mg/mL (mL)
Birth to less 5 kg	Less than 5 kg	0.01 mg/kg/doseFootnote 3 or 0.1 mg Footnote 3, Footnote 4	0.01 mL/kg/dose or 0.1 mL Footnote 3, Footnote 4	N/A
Greater than 5 kg and less than 2 years	5 - 10	0.1 mg	0.1 mL	0.15 mgFootnote 4, Footnote 6
2 to less than 4 years	11 - 15	0.15 mg	0.15 mL
4 to less than 7 years	16 - 20	0.2 mg	0.2 mL
	21 - 25	0.25 mg	0.25 mL	0.3 mg Footnote 2, Footnote 7
7 to less than 10 years	26 - 30	0.3 mg	0.3 mL
	31 - 35	0.35 mg	0.35 mL
10 to 12 years	36 - 40	0.4 mg	0.4 mL
	41 - 45	0.45 mg	0.45 mL
Older than 12 years	46 and above	0.5 mg	0.5 mL	0.5 mg
Footnote t4-1 Adapted from: Australian Immunisation Handbook (ATAGI, confirmed June 2018). https://immunisationhandbook.health.gov.au/resources/handbook-tables/doses-of-intramuscular-11000-adrenaline-for-anaphylaxis. [Accessed June 1, 2020] Return to footnote 1 referrer Footnote t4-2 Adapted from: TREKK. Dec 2018. Pediatric anaphylaxis algorithm. Version 1.1. Accessed June 28, 2020 from: https://trekk.ca/system/assets/assets/attachments/339/original/2018-12-10_Anaphylaxis_algorithm_v_1.1.pdf?1545083235 Return to footnote 2 referrer Footnote t4-3 Cheng A; Canadian Paediatric Society, Acute Care Committee. Emergency treatment of anaphylaxis in infants and children. Paediatr Child Health 2011; 16(1):35-40. Return to footnote 3 referrer Footnote t4-4 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: S22−S62. Return to footnote 4 referrer Footnote t4-5 As of October 2020, three EPINEPHrine autoinjectors were on the Canadian market: EpiPen®,  Allerject® and EMERADE™. Return to footnote 5 referrer Footnote t4-6 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. Return to footnote 6 referrer Footnote t4-7 Sicherer SH and FER Simons, Pediatrics 2007; 199:638-646. Return to footnote 7 referrer

• 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 Table 4 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.

Download the printable table on epinephrine dosage for the management of anaphylaxis following immunization in a community setting.

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 Steps for basic management of anaphylaxis in a non-hospital setting).

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.

Selected references

• Alqurashi W, Ellis AK. Do Corticosteroids Prevent Biphasic Anaphylaxis? J allergy Clin Immunol Pract. 2017;5(5):1194-1205. doi:10.1016/j.jaip.2017.05.022
• Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook, Australian Government Department of Health, Canberra, 2018, immunisationhandbook.health.gov.au.
• Cheng A. Canadian Paediatric Society. Emergency treatment of anaphylaxis in infants and children. Paediatr Child Health 2011;16(1):35-40. Reaffirmed February 2018. https://www.cps.ca/en/documents/position/emergency-treatment-anaphylaxis
• Greenhawt M, Gupta RC, Meadows A, Pistiner M, Spergel JM, Camargo CA, Simons ER, Lieberman PL. Guiding Principles for the Recognition, Diagnosis, and Management of Infants with Anaphylaxis: An Expert Panel Consensus. J Allergy Clin Immunol Pract 2019;7 (4):1148-56.
• Halbrich M, Mack DP, Carr S, Watson W, Kim H. CSACI position statement: epinephrine autoinjectors and children less than 15 kg. Allergy, Asthma & Clinical Immunology (2015) 11:20.
• 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: S22−S62.
• Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. 2005;115:S483-523.
• Kaleo, Inc. Product Monograph - Allerject^®. November 2019.
• McNeil MM, Weintraub ES, Duffy J, et al. Risk of anaphylaxis after vaccination in children and adults. The Journal of allergy and clinical immunology. 2016;137(3):868-878. doi:10.1016/j.jaci.2015.07.048.
• Mylan Specialty Dey Pharma L.P. Product Monograph - EpiPen^®and EpiPen^®Jr. May 2017.
• Nilsson L, Brocknow K, Alm J et al. Vaccination and allergy: EAACI position paper, practical aspects. Pediatr Allergy Immunol. 2017;28:628-640.
• Sicherer SH, Simons FE and the Section on Allergy and Immunology. Self-injectable epinephrine for first-aid management of anaphylaxis. Pediatrics 2007; 199:638-646.
• Simons FE, Arudusso LR, Bilo MB et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. J Allergy Clin Immunol 2011;127(3):593e1-22.
• Simons FE, Ebisawa M, Sanchez-Borges M, et al. 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines. World Allergy Organization Journal (2015) 8:32.
• Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: Intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 2001; 108:5: 871- 873.
• Simons FE, Sampson HA. Anaphylaxis: Unique aspects of clinical diagnosis and management in infants (birth to age 2 years). J Allergy Clin Immunol, 2015; 135:1125-31.
• Translating Emergency Knowledge for Kids (TREKK). Bottom Line Recommendations: Anaphylaxis. December 2018, Version 1.2. Accessed July 9, 2019 from: https://trekk.ca/system/assets/assets/attachments/338/original/2018-12-14_Anaphylaxis_BLR_version_1.2.pdf?1545083199
• Translating Emergency Knowledge for Kids (TREKK). Pediatric anaphylaxis algorithm. Dec 2018. Version 1.1. Accessed June 28, 2020 from: https://trekk.ca/system/assets/assets/attachments/339/original/2018-12-10_Anaphylaxis_algorithm_v_1.1.pdf?1545083235