General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 72

5. Preventing and Managing Adverse Reactions

Updates

Major changes to the best practice guidance include 1) more descriptive characterization 

of anaphylactic allergy and 2) incorporation of protocols for managing adverse reactions.

 

Benefit and Risk Communication

Parents, guardians, legal representatives, and adolescent and adult patients should be 

informed about the benefits of and risks from vaccines in language that is culturally 

sensitive and at an appropriate educational level. Opportunity for questions should be 

provided before each vaccination. Discussion of the benefits of and risks from vaccination 

is sound medical practice and is required by law.

The National Childhood Vaccine Injury Act of 1986 (1) requires that vaccine information 

materials be developed for each vaccine covered by the Act (uscode.house.gov). These 

materials, known as vaccine information statements (VISs), must be provided by all public 

and private vaccination providers each time a vaccine is administered. Copies of VISs are 

available from state health authorities responsible for vaccination and from CDC 

(www.cdc.gov/vaccines/hcp/vis/index.html). Translations of VISs into languages other 

than English are available from certain state vaccination programs and from the 

Immunization Action Coalition website (http://www.immunize.org). The act does not 

require that a signature be obtained; however, documentation of consent might be 

recommended or required by certain state or local health authorities or school authorities.

Some parents or patients question the need for or safety of vaccinations and want to 

discuss the risks from and benefits of certain vaccines. Some refuse certain vaccines or 

reject all vaccinations for personal or religious reasons. Having a basic understanding of 

how patients and parents of patients view vaccine risk and developing effective 

approaches to address vaccine safety concerns are imperative for vaccination providers.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 73

Each person understands and reacts to vaccine information on the basis of different 

factors, including previous experience, education, personal values, method of data 

presentation, perceptions of the risk for disease and perceived ability to control these 

risks, and risk tolerance. In some circumstances, decisions about vaccination are based on 

inaccurate information about risk provided by the media and certain websites. Websites 

and other sources of vaccine information may be inaccurate or incomplete. Health care 

providers can be a pivotal source of science-based credible information by discussing with 

parents and patients the risks from and benefits of vaccines, which helps patients make 

informed decisions.

When a parent or patient initiates a discussion about a perceived vaccine adverse reaction, 

the health care provider should discuss the specific concerns and provide factual 

information, using appropriate language. Effective, empathetic vaccine risk 

communication is essential in responding to misinformation and concerns, with health 

care providers recognizing that risk assessment and decision-making can be difficult and 

confusing. Certain vaccines might be acceptable to a parent who is resistant to other 

vaccines. This partial acceptance can be used to facilitate additional communication. Their 

concerns can be addressed using the VIS and offering other resource materials (e.g., 

vaccination information from CDC: www.cdc.gov/vaccines/hcp/vis/index.html).

The American Academy of Pediatrics (AAP) does not recommend that providers exclude 

from their practice patients whose parents or guardians question or refuse vaccination. 

However, an effective public health strategy is to identify common ground and discuss 

measures that need to be followed if the decision is to defer vaccination (2). Health care 

providers should reinforce key points about each vaccine, including safety, and emphasize 

risks for disease among unvaccinated children. Parents should be advised of state laws 

regarding entry to schools or child-care facilities, which might require that unvaccinated 

children be excluded from the facility during outbreaks (www.cdc.gov/vaccines/imzmanagers/coverage/schoolvaxview/requirements/index.html). These discussions should 

be documented in the patient’s medical record, including the refusal to receive certain 

vaccines (i.e., informed refusal). When a vaccine is refused when first offered the provider 

should take the opportunity to offer the vaccine again at the next visit.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 74

Preventing Adverse Reactions

Vaccines are intended to produce active immunity to specific antigens. An adverse 

reaction is an undesirable side effect that occurs after a vaccination. Vaccine adverse 

reactions are classified as 1) local, 2) systemic, or 3) allergic (additional information is 

available at 

https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm09383

3.htm. Local reactions (e.g., redness) are usually the least severe and most frequent. 

Systemic reactions (e.g., fever) occur less frequently than local reactions, and severe 

allergic reactions (e.g., anaphylaxis) are the least frequent reactions. Severe adverse 

reactions are rare (3).

Some of the systemic reactions may be complicated by the onset of syncope. Syncope 

(vasovagal or vasodepressor reaction) can occur after vaccination and is most common 

among adolescents and young adults. In 2005, the Vaccine Adverse Event Reporting 

System (VAERS) began detecting a trend of increasing syncope reports that coincided with 

the licensure of 3 vaccines for adolescents: human papillomavirus (HPV), MenACWY, and 

Tdap (4). Of particular concern among adolescents has been the risk for serious secondary 

injuries, including skull fracture and cerebral hemorrhage. Of 463 VAERS reports of 

syncope during January 1, 2005, to July 31, 2007, a total of 41 listed syncope with 

secondary injury with information on the timing after vaccination, and the majority of 

these syncope reports (76%) occurred among adolescents. Among all age groups, 80% of 

reported syncope episodes occur within 15 minutes of vaccine administration (additional 

information is available at www.cdc.gov/vaccinesafety/concerns/fainting.html). Providers 

should take appropriate measures to prevent injuries if a patient becomes weak or dizzy or 

loses consciousness. Adolescents and adults should be seated or lying down during 

vaccination.Vaccine providers, particularly when vaccinating adolescents, should consider 

observing patients (with patients seated or lying down) for 15 minutes after vaccination to 

decrease the risk for injury should they faint (4). If syncope develops, patients should be 

observed until the symptoms resolve.

Although allergic reactions are a common concern for vaccine providers, these reactions 

are uncommon and anaphylaxis following vaccines is rare, occurring at a rate of 

approximately one per million doses for many vaccines (5). 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 75

Epinephrine and equipment for managing an airway should be available for immediate 

use (6). The best practice to prevent allergic reactions is to identify individuals at 

increased risk by obtaining a history of allergy to previous vaccinations and vaccine 

components that might indicate an underlying hypersensitivity. Acute allergic reactions 

following vaccinations might be caused by the vaccine antigen, residual animal protein, 

antimicrobial agents, preservatives, stabilizers, or other vaccine components (7). 

Components of each vaccine are listed in the respective package insert. An extensive list of 

vaccine components and their use, as well as the vaccines that contain each component, 

has been published (8) and also is available from CDC 

(www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/b/excipient-table- 2.pdf). 

Additional information and tables of potential allergens in different vaccines are available 

at (http://www.vaccinesafety.edu/components-Allergens.htm). The allergens identified in 

the history can be cross-checked against the allergens identified in package inserts.

 

Managing Acute Vaccine Reactions

Vaccine providers should be familiar with identifying immediate-type allergic reactions, 

including anaphylaxis, and be competent in treating these events at the time of vaccine 

administration. Providers should also have a plan in place to contact emergency medical 

services immediately in the event of a severe acute vaccine reaction.

Allergic reactions can include: local or generalized urticaria (hives) or angioedema; 

respiratory compromise due to wheezing or swelling of the throat; hypotension; and 

shock. Immediate-immunoglobulin E (IgE)–mediated (type 1) immune reactions, such as 

anaphylaxis, usually occur within minutes of parenteral administration and involve 

specific IgE interactions with discrete antigens (9,10). Rapid recognition and initiation of 

treatment are required to prevent possible progression to respiratory failure or 

cardiovascular collapse. It is important to note that urticaria may not be present in all 

cases of anaphylaxis. For respiratory or cardiovascular symptoms, or other signs or 

symptoms of anaphylaxis, immediate intramuscular epinephrine is the treatment of 

choice (11,12). Additional doses of epinephrine as well as other drugs also might be 

indicated (Tables 5-1 and 5-2) (12). Considering the availability of emergency services, 

providers should plan for the availability of at least 3 doses of epinephrine (in dosing 

formulations appropriate to each and every age/group served by the provider) for a 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 76

hypothetical emergency situation. If hypotension is present, the patient should be placed 

in a recumbent position with the legs elevated. Maintenance of the airway, oxygen 

administration, and intravenous normal saline might be necessary. 

After the patient is stabilized, arrangements should be made for immediate transfer to an 

emergency facility for additional evaluation and treatment. Because anaphylaxis may 

recur after patients begin to recover, monitoring in a medical facility for several hours is 

advised, even after complete resolution of symptoms and signs. Additional information on 

management of patients with anaphylaxis has been published (9).

Persons Who Have Had an Allergic Reaction Following a 

Previous Immunization

For an individual patient who has experienced an immediate reaction to immunization, it 

is important to identify the type of reaction that occurred, obtain a history of prior allergic 

reactions, and try to identify the particular agent responsible. An algorithm approach to 

these patients has been published (13) and additional advice is available for allergists on 

the evaluation of these adverse events (10). In general, a history of a severe allergic 

reaction to a vaccine should be considered a contraindication to additional doses of the 

same vaccine (13). Referral of the individual to an allergist for evaluation is usually 

indicated to possibly determine the component responsible, before making decisions 

regarding administration of the additional doses of the same vaccine or other vaccines that 

have the same components. Patients who have not had a severe allergic reaction following 

a vaccine, but who have a history of possible allergy to a vaccine component can often be 

vaccinated safely after careful evaluation (6).

Influenza Vaccination of Persons with a History of Egg 

Allergy

Severe allergic and anaphylactic reactions can occur in response to a number of influenza 

vaccine components, but such reactions are rare (6). All but the recombinant inactivated 

influenza vaccine may have come into contact with egg protein. The use of influenza 

vaccines for persons with a history of egg allergy has been reviewed recently by ACIP (14). 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 77

VAERS data mining did not identify a higher than expected proportion of serious allergic 

events after influenza vaccination during the 2011-2012 season, relative to all other 

reported vaccines and adverse events in the database. Persons with a history of egg allergy 

should receive recombinant inactivated vaccine (if 18 years or older), or IIV.

Other measures, such as dividing and administering the vaccine by a 2-step approach and 

skin testing with vaccine, are not recommended (10).

All vaccines should be administered in settings in which personnel and equipment for 

rapid recognition and treatment of anaphylaxis are available. ACIP recommends that all 

vaccination providers be certified in cardiopulmonary resuscitation (CPR), have an office 

emergency plan, and ensure that all staff are familiar with the plan (6). Some persons who 

report allergy to egg might not be egg-allergic. Those who are able to eat lightly cooked egg 

(e.g., scrambled egg) without reaction are unlikely to be allergic.

Egg-allergic persons might tolerate egg in baked products (e.g., bread or cake). Tolerance 

to egg-containing foods does not exclude the possibility of egg allergy (15). Egg allergy can 

be confirmed by a consistent medical history of adverse reactions to eggs and eggcontaining foods, plus skin and/or blood testing for IgE antibodies to egg proteins.

A previous severe allergic reaction to influenza vaccine, regardless of the component 

suspected to be responsible for the reaction, is a contraindication to future receipt of the 

vaccine (14).

Yellow Fever Vaccination of Persons with a History of Egg 

Allergy

Yellow fever vaccine contains egg protein. There have been insufficient studies to 

determine which patients with egg allergy may be able to receive yellow fever vaccine, but 

there are reports of patients with true egg allergy safely receiving yellow fever vaccine after 

evaluation by specialists with expertise in the management of allergic reactions (16,17). 

According to the manufacturer, persons who are able to eat eggs or egg products may 

receive the vaccine (18). However, potential hypersensitivity reactions might occur in 

persons with a history of minor reactions to eggs. 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 78

For egg-sensitive persons, a scratch test or intradermal test can be performed before 

administering the vaccine to check for reactivity. 

If a person has a severe egg-sensitivity or has a positive skin test to the vaccine, but the 

vaccination is recommended because of their travel destination-specific risk, 

desensitization can be performed under direct supervision of a physician experienced in 

the management of anaphylaxis. 

The desensitization procedure is detailed in the product insert (see yellow fever 

recommendations at 

https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm09407

4.htm). 

Vaccines with MMR or Varicella Components and Persons 

with a History of Egg Allergy

Varicella vaccine is grown in human diploid cell cultures and can safely be administered to 

persons with a severe allergy to eggs or egg proteins (19). Measles and mumps vaccine 

viruses are grown in chick embryo fibroblast tissue culture. However, persons with a 

severe egg allergy can receive measles- or mumps-containing vaccines in the usual manner 

because the content of these proteins is extremely low (20). The rare severe allergic 

reactions after measles- or mumps-containing vaccines or varicella are thought to be 

caused by other components of the vaccine (e.g., gelatin) (21-24). MMR, MMRV, varicella 

and other vaccines contain hydrolyzed gelatin as a stabilizer.

Vaccines and Persons with a History of Allergy to 

Substances Other than Eggs

Persons who have had an anaphylactic reaction to gelatin or gelatin-containing products 

should be evaluated by an allergist prior to receiving gelatin-containing vaccines (6).

Certain vaccines contain trace amounts of antimicrobial agents or other preservatives 

(e.g., neomycin or thimerosal), although allergies to these are rare. No licensed vaccine 

contains penicillin or penicillin derivatives.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 79

Most often, neomycin hypersensitivity manifests as contact dermatitis, a delayed-type 

(cell-mediated) immune response rather than immediate-hypersensitivity (IgE-mediated 

allergy)–type response (25,26). A history of delayed-type reactions to neomycin is not a 

contraindication for administration of neomycin-containing vaccines. There has only been 

1 reported case of immediate hypersensitivity reaction following a neomycin-containing 

vaccine (27). Persons who have had anaphylactic reactions to neomycin should be 

evaluated by an allergist prior to receiving vaccines containing neomycin (6).

Thimerosal, an organic mercurial compound in use since the 1930s, is added to certain 

immunobiologics as a preservative. Since mid-2001, vaccines routinely recommended for 

infants younger than 6 months of age have been manufactured without thimerosal as a 

preservative (14). Live, attenuated vaccines have never contained thimerosal. Thimerosalfree formulations of inactivated influenza vaccine are available. Inactivated influenza 

vaccine also is available in formulations with only trace amounts of thimerosal, which 

remains as a manufacturing residual but is not added at the higher concentration that 

would be necessary for it to function as a preservative. Thimerosal at a preservative 

concentration is present in certain other vaccines that can be administered to children 

(e.g., Td and DT). Information about the thimerosal content of vaccines is available from 

FDA at 

https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096

22 8. 

Reactions to thimerosal have been described as local delayed-type hypersensitivity 

reactions with only rare reports of immediate reactions (28-31). Thimerosal elicits positive 

delayed-type hypersensitivity patch tests in 1%-18% of persons tested; however, these tests 

have no relevance to acute allergic reactions that might occur within minutes or hours 

after immunization (32,33). The majority of persons do not experience reactions to 

thimerosal administered as a component of vaccines even when patch or intradermal tests 

for thimerosal indicate hypersensitivity (31). A local or delayed-type hypersensitivity 

reaction to thimerosal is not a contraindication to receipt of a vaccine that contains 

thimerosal (34). 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 80

Latex is sap from the rubber tree. Latex contains naturally occurring plant proteins that 

can be responsible for immediate-type allergic reactions. Latex is processed to form either 

natural rubber latex products such as gloves or dry, natural rubber products such as 

syringe plunger tips and vial stoppers. Synthetic rubber is also used in gloves, syringe 

plungers, and vial stoppers but does not contain the latex proteins linked to immediatetype allergic reactions. Natural rubber latex or dry, natural rubber used in vaccine 

packaging generally is noted in the manufacturers’ package inserts.

Immediate-type allergic reactions due to latex allergy have been described after 

vaccination, but such reactions are rare (35).

If a person reports a severe anaphylactic allergy to latex, vaccines supplied in vials or 

syringes that contain natural rubber latex should be avoided if possible (6). If not, if the 

decision is made to vaccinate, providers should be prepared to treat immediate allergic 

reactions due to latex, including anaphylaxis. The most common type of latex 

hypersensitivity is a delayed-type (type 4, cell-mediated) allergic contact dermatitis (36). 

For patients with a history of contact allergy to latex, vaccines supplied in vials or syringes 

that contain dry natural rubber or natural rubber latex may be administered.

Reporting Adverse Events After Vaccination

Modern vaccines are safe and effective; however, adverse events have been reported after 

administration of all vaccines (3). More complete information about adverse reactions to a 

specific vaccine is available in the package insert for each vaccine and from CDC at 

www.cdc.gov/vaccines/vac-gen/side-effects.htm. An adverse event is an untoward event 

that occurs after a vaccination that might be caused by the vaccine product or vaccination 

process. These events range from common, minor, local reactions to rare, severe, allergic 

reactions (e.g., anaphylaxis). Reporting to VAERS helps establish trends, identify clusters 

of adverse events, or generate hypotheses. However, establishing evidence for cause and 

effect on the basis of case reports and case series alone is usually not possible, because 

health problems that have a temporal association with vaccination do not necessarily 

indicate causality.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 81

Many adverse events require more detailed epidemiologic studies to compare the 

incidence of the event among vaccinees with the incidence among unvaccinated persons. 

Potential causal associations between reported adverse events after vaccination can be 

assessed through epidemiologic or clinical studies.

The National Childhood Vaccine Injury Act of 1986 (1) requires health care personnel and 

vaccine manufacturers to report to VAERS specific adverse events that occur after 

vaccination. The reporting requirements are different for manufacturers and health care 

personnel. Manufacturers are required to report all adverse events that occur after 

vaccination to VAERS, whereas health-care providers are required to report events that 

appear in the reportable events table on the VAERS website at 

https://vaers.hhs.gov/docs/VAERS_Table_of_Reportable_Events_Following_Vaccinat

ion.pdf. 

In addition to the mandated reporting of events listed on the reportable events table, 

health care personnel should report to VAERS all events listed in product inserts as 

contraindications, as well as all clinically significant adverse events, even if they are 

uncertain that the adverse event is related causally to vaccination (6). Persons other than 

health care personnel also can report adverse events to VAERS.

General information on VAERS is available at https://vaers.hhs.gov/index.html. Specific 

information for healthcare providers is available 

at https://vaers.hhs.gov/resources/infoproviders.html. Reporting to VAERS is fully 

electronic and can be done using an online reporting tool or a writable PDF; instructions 

are available at https://vaers.hhs.gov/reportevent.html. Further assistance on VAERS 

reporting is available through email at info@VAERS.org and the VAERS toll free number 

1-800-822-7967.

National Vaccine Injury Compensation Program

The National Vaccine Injury Compensation Program, established by the National 

Childhood Vaccine Injury Act of 1986 (1), is a no-fault system in which persons thought to 

have experienced an injury or to have died as a result of administration of a covered 

vaccine can seek compensation. 
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 82

The program became operational on October 1, 1988, and is intended as an alternative to 

civil litigation under the traditional tort system in that negligence need not be proven. 

Claims arising from covered vaccines must first be adjudicated through the program 

before civil litigation can be pursued.

The program relies on the Vaccine Injury Table, which lists the vaccines covered by the 

program and the injuries (including death), disabilities, illnesses, and conditions for which 

compensation might be awarded. The table defines the time during which the first 

symptom or substantial aggravation of an injury must appear after vaccination to be 

eligible. Successful claimants receive a legal presumption of causation if a condition listed 

in the table is proven, thus avoiding the need to prove actual causation in an individual 

case. Claimants also can prevail for conditions not listed in the reportable events table if 

they prove causation for covered vaccines. 

Additional information is available from the Health Resources and Services 

Administration (HRSA at https://www.hrsa.gov/vaccine-compensation/index.html or by 

telephone at 800-338- 2382). Persons who would like to file a claim for vaccine injury 

should contact the U.S. Court of Federal Claims (717 Madison Place, N.W., Washington, 

DC 20005; telephone: 202-357-6400).
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 83

TABLE 5-1: Rapid overview: Emergent management of anaphylaxis in 

infants and children(a)

Diagnosis is 

made 

clinically:

The most common signs and symptoms are cutaneous (e.g., sudden onset of generalized 

urticaria, angioedema, flushing, pruritus). However, 10 to 20% of patients have no skin 

findings.

Danger signs: Rapid progression of symptoms, evidence of respiratory distress (e.g., stridor, 

wheezing, dyspnea, increased work of breathing, retractions, persistent cough, cyanosis), signs 

of poor perfusion, abdominal pain, vomiting, dysrhythmia, hypotension, collapse.

Acute 

management:

The first and most important therapy in anaphylaxis is epinephrine. There are NO absolute 

contraindications to epinephrine in the setting of anaphylaxis.

Airway: Immediate intubation if evidence of impending airway obstruction from angioedema. 

Delay may lead to complete obstruction. Intubation can be difficult and should be performed 

by the most experienced clinician available. Cricothyrotomy may be necessary.

IM epinephrine (1 mg/mL preparation): Epinephrine 0.01 mg/kg should be injected 

intramuscularly in the mid-outer thigh. For large children (>50 kg), the maximum is 0.5 mg 

per dose. If there is no response or the response is inadequate, the injection can be repeated in 

5 to 15 minutes (or more frequently). If epinephrine is injected promptly IM, patients respond 

to one, two, or at most, three injections. If signs of poor perfusion are present or symptoms are 

not responding to epinephrine injections, prepare IV epinephrine for infusion (see below).

Place patient in recumbent position, if tolerated, and elevate lower extremities.

Oxygen: Give 8 to 10 L/minute via facemask or up to 100% oxygen, as needed.

Normal saline rapid bolus: Treat poor perfusion with rapid infusion of 20 mL/kg. Reevaluate 

and repeat fluid boluses (20 mL/kg), as needed. Massive fluid shifts with severe loss of 

intravascular volume can occur. Monitor urine output.

Albuterol: For bronchospasm resistant to IM epinephrine, give albuterol 0.15 mg/kg 

(minimum dose: 2.5 mg) in 3 mL saline inhaled via nebulizer. Repeat, as needed.

H1 antihistamine: Consider giving diphenhydramine 1 mg/kg (max 50 mg) IV given over 5 

minutes, or cetirizine (children age 6 months to 5 years can receive 2.5 mg IV, those 6 to 11 years 

of age can receive 5 or 10 mg IV, over 2 minutes).

H2 antihistamine: Consider giving famotidine 0.25 mg/kg (max 20 mg) IV, over at least 2 

minutes.

Glucocorticoid: Consider giving methylprednisolone 1 mg/kg (max 125 mg) IV.

Monitoring: Continuous noninvasive hemodynamic monitoring and pulse oximetry monitoring 

should be performed. Urine output should be monitored in patients receiving IV fluid 

resuscitation for severe hypotension or shock.

Treatment of 

refractory 

symptoms:

Epinephrine infusion:(b) In patients with inadequate response to IM epinephrine and IV saline, 

give epinephrine continuous infusion at 0.1 to 1 mcg/kg/minute, titrated to effect.

Vasopressors:(b) Patients may require large amounts of IV crystalloid to maintain blood 

pressure. Some patients may require a second vasopressor (in addition to epinephrine). All 

vasopressors should be given by infusion pump, with the doses titrated continuously according

to blood pressure and cardiac rate/function monitored continuously and oxygenation 

monitored by pulse oximetry

IM: intramuscular; IV: intravenous.

(a) A child is defined as a prepubertal patient weighing less than 40 kg.

(b) All patients receiving an infusion of epinephrine and/or another vasopressor require continuous noninvasive 

monitoring of blood pressure, heart rate and function, and oxygen saturation. We suggest that pediatric centers 

provide instructions for preparation of standard concentrations and also provide charts for established infusion 

rate for epinephrine and other vasopressors in infants and children.

Source: Campbell RL, Kelso JM. Anaphylaxis: Emergency treatment. In: UpToDate, 

Post TW (Ed), UpToDate, Waltham, MA. (Accessed on December 9, 2021) 

Source: (37).
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 84

Table 5-2: Rapid overview: Emergency management of anaphylaxis in 

adults

Diagnosis is made clinically: The most common signs and symptoms are cutaneous 

(e.g., sudden onset of generalized urticaria, 

angioedema, flushing, pruritus). However, 10 to 20% of 

patients have no skin findings.

Danger signs: Rapid progression of symptoms, 

respiratory distress (e.g., stridor, wheezing, dyspnea, 

increased work of breathing, persistent cough, 

cyanosis), vomiting, abdominal pain, hypotension, 

dysrhythmia, chest pain, collapse.

Acute management: The first and most important treatment in anaphylaxis 

is epinephrine. There are NO absolute contraindications 

to epinephrine in the setting of anaphylaxis.

Airway: Immediate intubation if evidence of impending 

airway obstruction from angioedema. Delay may lead to 

complete obstruction. Intubation can be difficult and 

should be performed by the most experienced clinician 

available. Cricothyrotomy may be necessary.

Promptly and simultaneously, give: IM epinephrine (1 mg/mL preparation): Give 

epinephrine 0.3 to 0.5 mg intramuscularly, preferably 

in the mid-outer thigh. Can repeat every 5 to 15 

minutes (or more frequently), as needed. If 

epinephrine is injected promptly IM, most patients 

respond to one, two, or at most, three doses. If 

symptoms are not responding to epinephrine 

injections, prepare IV epinephrine for infusion.

Place patient in recumbent position, if tolerated, and 

elevate lower extremities.

Oxygen: Give 8 to 10 L/minute via facemask or up to 

100% oxygen, as needed.

Normal saline rapid bolus: Treat hypotension with 

rapid infusion of 1 to 2 liters IV. Repeat, as needed. 

Massive fluid shifts with severe loss of intravascular 

volume can occur.

Albuterol (salbutamol): For bronchospasm resistant to 

IM epinephrine, give 2.5 to 5 mg in 3 mL saline via 

nebulizer. Repeat, as needed.

Adjunctive therapies: H1 antihistamine:(a) Consider giving cetirizine 10 mg 

IV (given over 2 minutes) diphenhydramine 25 to 50 

mg IV (given over 5 minutes) (for relief of urticaria 

and itching only)

H2 antihistamine:(a) Consider giving famotidine 20 

mg IV (given over 2 minutes).

Glucocorticoid:(a) Consider giving methylprednisolone 

125 mg IV.

Monitoring: Continuous noninvasive hemodynamic 

monitoring and pulse oximetry monitoring should be 

performed. Urine output should be monitored in 

patients receiving IV fluid resuscitation for severe 

hypotension or shock.

Treatment of refractory symptoms: Epinephrine infusion(b),: For patients with inadequate 

response to IM epinephrine and IV saline, give

epinephrine continuous infusion, beginning at 0.1 

mcg/kg/minute by infusion pump(c) . Titrate the dose 

continuously according to blood pressure, cardiac rate 

and function, and oxygenation.

Vasopressors(b: Some patients may require a second 

vasopressor (in addition to epinephrine). All 

vasopressors should be given by infusion pump, with 

the doses titrated continuously according to blood 

pressure and cardiac rate/function and oxygenation 

monitored by pulse oximetry.
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 85

Glucagon: Patients on beta blockers may not respondto 

epinephrine and can be given glucagon 1 to 5 mg IV 

over 5 minutes, followed by infusion of 5 to 15 

mcg/minute. Rapid administration of glucagon can 

cause vomiting.

Instructions on how to prepare and administer epinephrine for IV continuous infusions are available as 

separate tables in UpToDate.

IM: intramuscular; IV: intravenous.

(a) These medications should not be used as initial or sole treatment.

(b) All patients receiving an infusion of epinephrine and another vasopressor require continuous noninvasive 

monitoring of blood pressure, heart rate and function, and oxygen saturation.

(c) For example, the initial infusion rate for a 70 kg patient would be 7 mcg/minute. This is consistent with the 

recommended range for non–weight-based dosing for adults, which is 2 to 10 mcg/minute. Non–weight-based 

dosing can be used if the patient's weight is not known and cannot be estimated.

Source: Campbell RL, Kelso JM. Anaphylaxis: Emergency treatment. In: UpToDate, Post 

TW (Ed), UpToDate, Waltham, MA. (Accessed on December 9, 2021)

Source: (37).
General Best Practice Guidelines for Immunization: Preventing and Managing Adverse Reactions 86

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