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Canadian Immunization Guide

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Part 2
Vaccine Safety

Early vaccine reactions including anaphylaxis

This chapter is intended as a guide for the initial management of vaccine recipients who develop vaccine reactions within a two hour period following immunization in a non-hospital setting (e.g., public health clinic, medical office). For a vaccine recipient with severe, life-threatening anaphylaxis, establishment of intravenous (IV) access for drug and fluid administration will be necessary, and endotracheal intubation and other manoeuvres may be required. These interventions are generally best performed by ambulance personnel or in a hospital’s emergency department.

Since the publication of the 2006 Canadian Immunization Guide:

  • The intramuscular route has been preferentially recommended for injection of epinephrine for anaphylaxis management.
  • The recommended steps for basic management of anaphylaxis in a non-hospital setting have been updated according to the World Allergy Organization Guidelines for the assessment and management of anaphylaxis published in 2011 and updated in 2012.
  • Recommendations for adjunctive treatment of anaphylaxis have been revised.
  • The dosing guidelines for epinephrine have been revised, and there is now more information regarding the use of auto-injectors. 
  • When a vaccine has been given subcutaneously an additional dose of epinephrine is no longer recommended at the injection site, as this is not part of the WAO guidelines and there is no evidence to support it.
  • The recommended items in an anaphylaxis management kit have been revised.

Fainting, anxiety or breath-holding

Fainting (vasovagal syncope), anxiety and breath-holding episodes are benign reactions to vaccination which occur more commonly than anaphylaxis.

Fainting

During fainting, the individual suddenly becomes pale, loses consciousness and collapses to the ground. Fainting is sometimes accompanied by brief clonic seizure activity (i.e., rhythmic jerking of the limbs) which generally requires no specific treatment or investigation. Fainting is managed by placing the vaccinee in a recumbent position. Recovery of consciousness occurs within a minute or two, but the person may remain pale, diaphoretic and mildly hypotensive for several minutes.

The likelihood of fainting is reduced by measures that lower stress in those awaiting immunization, such as short waiting times, comfortable room temperature, preparation of vaccines out of view of recipients, and privacy during the procedure. To reduce injuries due to fainting, people should be immunized while seated. For those at risk of fainting, consider a recumbent position. Foster a safe environment and educate vaccinees on avoiding unsafe activities, such as stair climbing or driving immediately after immunization. For example, school immunization programs may wish to institute a pairing policy (two students remain together) so vaccinees are not alone for the first 10 to 15 minutes after leaving the immediate clinic location, in case they faint and fall or begin to experience symptoms of anaphylaxis.

Anxiety

People experiencing anxiety may appear fearful, pale and diaphoretic and complain of lightheadedness, dizziness and numbness, as well as tingling of the face and extremities. Hyperventilation is usually evident. Treatment consists of reassurance and rebreathing using a paper bag until symptoms subside.

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.

Swelling and urticarial rash at the injection site

Swelling and urticarial rash (i.e., hives) at the injection site can occur but are not always caused by an allergic reaction. The swelling or hives should be observed for at least 30 minutes in order to ensure that the reaction remains localized, and if so, the vaccinee may leave after this observation period. Ice can be applied to the injection site for comfort. If the hives or swelling disappear 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, further observation is not 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 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.

Anaphylaxis

Anaphylaxis is a serious, potentially life-threatening allergic reaction to foreign antigens; it has been proven to be associated with vaccines. Anaphylaxis is rare with an estimated range of occurrence of 1-10 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 of the vaccine(s) being considered 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 having vaccinees remain within a short distance of the vaccinator (e.g., within the school when immunization is carried out in that setting) and return immediately for assessment if they feel unwell. As noted above, a pairing policy is recommended in school settings.

Signs and symptoms of anaphylaxis

In anaphylaxis, signs and symptoms develop over several minutes and by definition involve at least two body systems (e.g. the skin, respiratory, gastrointestinal or circulatory systems). The cardinal features of anaphylaxis are:

  • itchy, urticarial rash
  • progressive, painless swelling (angioedema) about the face and mouth, which may be preceded by itchiness, tearing, nasal congestion or facial flushing
  • respiratory symptoms, including sneezing, coughing, wheezing, laboured breathing and upper airway swelling (indicated by hoarseness and/or difficulty swallowing) possibly causing airway obstruction
  • gastrointestinal symptoms, including crampy abdominal pain and vomiting
  • sudden reduced blood pressure or symptoms of end-organ dysfunction (e.g., hypotonia and incontinence). In infants, symptoms may also include fussiness, irritability, drowsiness or lethargy

Skin and mucosal symptoms are reported to occur in 80% to 90% of anaphylaxis cases and respiratory symptoms occur in up to 70%. Cardiovascular system symptoms such as chest pain, palpitations, or tachycardia occur in up to 45% and central nervous system symptoms of uneasiness, altered mental status, dizziness, or confusion occur in up to 15%. Gastrointestinal symptoms like nausea, vomiting and diarrhea may occur in up to 45% of anaphylaxis cases. Features of severe anaphylaxis include obstructive swelling of the upper airway, marked bronchospasm and hypotension. Hypotension can progress to cause shock and collapse. Unconsciousness is rarely the sole manifestation of anaphylaxis; it occurs only as a late event in severe cases.

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. Symptoms vary from one person to another and only a few symptoms may be present. Death can occur within minutes.

Risk factors for severe anaphylaxis

Anaphylaxis is a rare complication of immunization. Risk factors for increased severity of anaphylaxis include very young or old age; pregnancy; asthma; cardiovascular disease; and concurrent use of certain medications (i.e., angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARB] or beta-blockers). Even in these populations, however, anaphylaxis is rare.

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 auto-injector or in a vial may be used to treat anaphylaxis; however, vials of epinephrine must be available for treatment of infants weighing less than 15 kg (refer to Epinephrine for additional information). Epinephrine solutions for injection (vials or auto-injectors) have a short shelf-life (generally 12 to 18 months) and past this time, will start to break down to inactive substances. Epinephrine and other emergency supplies should be checked on a regular basis and replaced when outdated. Refer to the list of essential items in an anaphylaxis management kit. 

List of recommended items in an anaphylaxis management kit
Essential Items
  • A clear, concise summary of the anaphylaxis emergency management protocol
  • Laminated table of dosage recommendations for epinephrine and diphenhydramine hydrochloride (e.g. Benadryl) by weight and by ageFootnote *
  • Two vials of aqueous epinephrine 1:1000
  • A range of autoinjectors of epinephrine labelled by age and weight (optional)
  • One vial of injectable diphenhydramine hydrochloride
  • Two – 1 cc syringes with attached needles (1 – 25 gauge,1 inch needle; 1 – 25 gauge, 5/8 inch needle)
  • One – 25 gauge, 5/8 inch needle (extra)
  • Two– 25 gauge, 1 inch and 1.5 inch needles (extra for larger adults)
  • Scissors
  • Alcohol swabs
  • One nasopharyngeal airway and one oropharyngeal airway for each age range anticipated in the clinic
  • Pocket mask
  • Stethoscope and sphygmomanometer
  • Tongue depressors
  • Flashlight
  • Wristwatch with second hand to measure pulse
  • Cell phone if no easy access to onsite phone
Additional Items
  • IV lines and fluids, and related equipment (e.g., tourniquet)
  • Oxygen and related equipment
Footnote *
Refer to Table 1 and Table 2 for recommended dosing information.
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.

Protocols

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. Refer to Steps for basic management of anaphylaxis for a summary of the basic management of anaphylaxis in a non-hospital setting.

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

(Steps 1, 2, 3 should be done promptly and simultaneously)

  1. Assess circulation, airway, breathing, mental status, skin, and body weight (mass). Secure an oral airway if necessary. Direct someone to call 911(where available) or emergency medical services.
  2. Position the vaccine recipient on their back or in a position of comfort if there is respiratory distress; elevate the lower extremities. Place the vaccinee on their side if vomiting or unconscious. Pregnant anaphylactic vaccinees should be placed semi-recumbent on their left side with their legs elevated.
  3. Inject epinephrine intramuscularly in the mid-anterolateral aspect of the thigh: 0.01 mg/kg body weight of 1:1000 (1 mg/mL) solution
    • ADOLESCENT or ADULT: maximum - 0.5 mg
    • CHILD: maximum - 0.3 mg

      Record the time of the dose.

      Repeat every 5 to 15 minutes as needed, for a maximum of three doses.
  4. Stabilize vaccinee; perform cardiopulmonary resuscitation if necessary, give oxygen and establish intravenous access if available and give adjunctive treatment (i.e. diphenhydramine hydrochloride or Benadryl®) if indicated.
  5. Monitor vaccinee’s blood pressure, cardiac rate and function, and respiratory status.
  6. Transfer to hospital for observation.

Adapted from 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.

Rapid assessment and positioning

Rapid intervention is of paramount importance. Assess airway, breathing and circulation; establish an airway if needed. When assessing the airway, look specifically at the lips, tongue and throat for signs of swelling. Position the person flat on the back, unless he/she is vomiting or unconscious (then place on the side) or in respiratory distress (may need to elevate head and chest for comfort). Legs should be elevated to help maintain blood pressure. Direct someone to call 911 or emergency medical services for transportation to hospital.

Epinephrine

Prompt administration of epinephrine is the priority and should not be delayed. Epinephrine is the treatment of choice for management of anaphylaxis in community and health care 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 risks to the anaphylactic vaccinee 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 a 1:1000 (1 mg/mL) solution should be administered into the mid-anterolateral aspect of the thigh; the deltoid muscle of the arm 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. Refer to Table 1 for epinephrine dosing guidelines. For infants less than 7 months of age, 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 in 0.04 mL of 1:1000 (1 mg/mL) solution.

Table 1: Dose of epinephrine (1:1000, 1 mg/mL solution), by age or weight
Age WeightTable 1 - Footnote 1 Dose by injection Dose by autoinjector
Adapted from Immunization Action Coalition. Medical Management of Vaccine Reactions in Children and Teens (PDF document)External Link. Accessed June 2012.
Table 1 - Footnote 1
Rounded weight at the 50th percentile for each age range
Table 1 - Footnote 2
Maximum dose for children 12 years of age and younger
Table 1 - Footnote 3
Maximum dose for adolescents
0 – 6 months Up to 9 kg (20 pounds) 0.01 mg/kg body weight Not applicable
7 - 36 months 9 - 14.5 kg (20 - 32 lb) 0.1 - 0.2 mg Not applicable
37 - 59 months 15 - 17.5 kg (33 – 39 lb) 0.15 -  0.3 mgTable 1 - Footnote 2 Junior dose of 0.15 mg
5 - 7 years 18 - 25.5 kg (40 – 56 lb) 0.2 - 0.3 mgTable 1 - Footnote 2 Junior dose of 0.15 mg
8 - 12 years 26 - 45 kg (57 – 99 lb) 0.3 mgTable 1 - Footnote 2 If , less than 30 kg (66 lbs) give Junior dose
If 30 kg or more: Give standard dose
13 years and older 46 + kg (100 + lb) 0.5 mgTable 1 - Footnote 3 Give standard dose of 0.3mg

An epinephrine auto-injector (Allerject™, Anapen®, EpiPen® or Twinject®) may be used if the person who administers it is knowledgeable about proper use and the correct dose of epinephrine for age or body weight is available in the auto-injector. The junior dose is intended for children who weigh 15-30 kg. The “junior” or pediatric preparations contain 0.15 mg (0.3 mL) of epinephrine 1:2000 per dose (EpiPen® Jr.; Anapen Jr. 150) or 0.15 mg (0.15 mL) of epinephrine 1:1000 per dose (Twinject® 0.15 mg). The standard dose is intended for children and adults weighing 30 kg or more. The standard preparations contain 0.3 mg (0.3 mL) of epinephrine 1:1000 per dose.

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.

Ensure the person lies down. Fatality can occur within seconds if the vaccinee stands or sits suddenly after epinephrine. People should remain in a recumbent position following receipt of an epinephrine injection and be monitored closely.

Adjunctive treatment

As an optional adjunct to epinephrine, a dose of diphenhydramine hydrochloride (e.g., Benadryl®) may be given to relieve itching, flushing, urticaria, and nasal and eye symptoms. Generally the injectable format is used although oral tablets or liquid elixir may also be used; in all formats the dosing is the same. Refer to Table 2 for diphenhydramine hydrochloride dosing guidelines. Diphenhydramine is generally not recommended for infants under 12 months of age, and should be used with caution between 12-23 months because it may cause drowsiness or paradoxical excitement. When given to children, dosage should be determined by weight (1mg/kg).

Table 2: Dose of diphenhydramine hydrochloride, by age
Age Weight (pounds) Dose of diphenhydramine hydrochloride
Table 2 - Footnote 1
Use with caution in children 12 - 23 months due to risk of sedation or paradoxical excitement.
12-23 monthsTable 2 - Footnote 1 7-12 kg (15-25 lbs) 6.25 - 12.5 mg
2 to 4 years 12-25 kg (25-55 lbs) 12.5 - 25 mg
5 to 11 years 25-45 kg (55-99 lbs) 25 - 50 mg
12 years and older 45 kg + (99 lbs or more) 50 mg

When indicated, give high-flow 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.

People on beta-blockers may be more resistant to epinephrine.

Transfer to hospital

All vaccinees receiving emergency epinephrine must be transported to hospital immediately for evaluation and observation. Since the symptoms of an anaphylactic reaction can reoccur after the initial reaction (biphasic anaphylaxis) in up to 23% of adults and up to 11% of children, hospitalization is recommended for monitoring. Generally, patients are hospitalized overnight or monitored for at least 12 hours. A biphasic course of anaphylaxis is more likely to occur if the administration of epinephrine is delayed.

Selected references

Campbell RL, Hagan JB, Manivannan V et al. Evaluation of the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria for the diagnosis of anaphylaxis in emergency department patients. J Allergy Clin Immunol 2012;129:748-52.

Centers for Disease Control and Prevention. General Recommendations on Immunization Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2011;60(2):1-61.

Dey Pharma L.P. Product Monograph – EpiPen® and EpiPen® Jr. March 2012.

Immunization Action Coalition. Medical Management of Vaccine Reactions in Children and Teens (PDF document)External Link. Accessed June 2012.

Immunization Action Coalition. Medical Management of Vaccine Reactions in Adult Patients (PDF document)External Link. Accessed June 2012.

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.

Kim H, Fischer D. Anaphylaxis. Allergy Asthma Clin Immuno 2011;7(Suppl 1):S6.

Lincoln Medical Ltd. Summary of Product Characteristics – Anapen 150. 2006.

Lincoln Medical Ltd. Summary of Product Characteristics – Anapen 300. 2006.

Simons FE. Anaphylaxis pathogenesis and treatment. Allergy 2011;66(Suppl.96):31-34.

Simons FE, Arudusso LR, Bilo MB et al. 2012 Update: World Allergy Organization Guidelines for the assessment and management of anaphylaxis. Curr Opin Allergy Clin Immunology 2012;12:389-99.

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 KJ, Simons FE. Epinephrine and its use in anaphylaxis: current issues. Curr Opin Allergy Clin Immunol 2010;10:354-361.

Soar J, Pumphrey R, Cant A et al. Emergency treatment of anaphylactic reactions – guidelines for healthcare providers. Resuscitation 2008;77:157-169.

Verus Pharmaceuticals, Inc. Prescribing Information - Twinject® 0.3 mg Auto-Injector and Twinject® 0.15 mg Auto-Injector. August 2006.

Waserman S, Chad Z, Francoeur, MJ et al. Management of anaphylaxis in primary care: Canadian expert consensus recommendations. Allergy 2010;65:1082-92.

Winodradow J, Geppert G, Reinhard W et al. Tako-tsubo cardiomyopathy after administration of intravenous epinephrine during an anaplylactic reaction. Int J Cardiol 2011;147:309-11.

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