Infusion reaction, anaphylaxis and hypersensitivity management

Revised: August 21, 2023

Critical Notes!
Pediatric outpatient and hospital-based outpatients, refer to the Anaphylaxis and Allergy
Management Protocol in the EHR.
Adults refer to Hypersensitivity/Anaphylaxis Treatment After Receiving Chemotherapy,
Monoclonal Antibody or Targeted Therapy Protocol in the EHR.

Introduction

Chemotherapeutic agents administered IV can cause infusion reactions involving the immune
system. Anaphylaxis—a type 1 hypersensitivity reaction—occurs suddenly when the body releases
immunoglobulin (Ig) E in response to a foreign protein in an administered agent. Other
hypersensitivity reactions—types 2 to 4—can also occur; however, these reactions are less severe
than a type 1 reaction because they're mediated by IgM or IgG. 1 Most reactions to
chemotherapeutic agents are type 1 hypersensitivities. These reactions usually occur immediately,
within 5 to 30 minutes of the start of an infusion, but delayed reactions may occur 10 to 12 hours
after exposure. 1 2

Medications associated with hypersensitivity reactions include L-asparaginase, PACLitaxel,

DOCEtaxel, CISplatin, CARBOplatin, oxaliplatin, etoposide, procarbazine, and teniposide. 2 The
administration route and rate, dosage form, and use of concomitant medications all affect the risk of
developing an infusion reaction. Administering a test dose of the agent may help predict whether a
reaction will occur. 1

Premedication administration can help prevent or minimize an infusion reaction but doesn't usually
prevent anaphylaxis. 3 If a reaction occurs, prompt recognition and treatment help ensure a
positive patient outcome.

Equipment

Emergency equipment (code cart with emergency medications, handheld resuscitation bag
with mask, defibrillator, and intubation equipment)
Oxygen delivery equipment
Oxygen source
Powder-free chemotherapy gloves
Prescribed chemotherapeutic agent
Prescribed IV fluid
Prescribed premedications
Pulse oximeter and probe
Vital signs monitoring equipment
Optional: facility-approved infusion reaction grading system; National Institute for
Occupational Safety and Health (NIOSH)–approved respirator mask (if aerosolization is likely);
nonlinting, nonabsorbent disposable gown; other personal protective equipment

Preparation of Equipment

Inspect all equipment and supplies. If a product is expired, is defective, or has compromised
integrity, remove it from patient use, label it as expired or defective, and report the expiration or
defect as directed by your facility.
Make sure that emergency equipment is functioning properly and readily available.
Implementation

Preventing an infusion reaction

Familiarize yourself with the prescribed chemotherapeutic agent to determine the patient's risk
of developing an infusion reaction because certain medications pose an increased risk of
infusion reaction. 1 3
Review the patient's medical record for factors that increase the risk of an infusion reaction,
such as higher-than-standard drug doses, assigned female at birth, treatment naïveté, older
age, preexisting cardiac or pulmonary disease, seasonal allergies, iodine or seafood allergy,
autoimmune disease, beta-adrenergic blocker use, previous exposure to the medication, and
previous immediate reaction to a medication. 1
Gather and prepare the necessary equipment and supplies.
Perform hand hygiene. 4 5 6 7 8 9

Confirm the patient's identity using at least two patient identifiers. 10

Provide privacy. 11 12 13 14

Explain the procedure to the patient and family (if appropriate) according to their individual
communication and learning needs to increase their understanding, allay their fears, and
enhance cooperation. 15
Raise the bed to waist level before providing care to prevent caregiver back strain. 16
Perform hand hygiene. 4 5 6 7 8 9

Obtain the patient's vital signs to serve as baselines for comparison. 2

Administer ordered premedications, such as antihistamines, corticosteroids, and
acetaminophen, following safe medication administration practices. 2 3 17 18 19 20

If written standing orders for managing infusion reactions aren't present, obtain an order for
emergency treatment before beginning the infusion. 2
Review specific signs and symptoms of potential complications, such as hypersensitivity and
anaphylaxis, with the patient and family (if appropriate) that they should monitor for during
administration of high-risk agents. Instruct the patient and family to report signs and
symptoms of an infusion reaction immediately. 2
Perform hand hygiene. 4 5 6 7 8 9

Put on powder-free chemotherapy gloves to comply with standard precautions. If needed, put
on other personal protective equipment, such as a nonlinting, nonabsorbent disposable gown;
eye and face protection (face shield and goggles or a combination of goggles, mask and face
shield) if splashing is likely; and a NIOSH–approved respirator mask if aerosolization is
likely. 2 21 22 23
Administer the chemotherapeutic agent following safe medication administration
practices. 17 18 19 20 (See the "Chemotherapy administration, intravascular (IV)" and
"Immunotherapy administration" procedures.) If ordered, increase the administration rate
incrementally to lower the risk of future infusion reactions. 24
Monitor the patient closely for signs and symptoms of an infusion reaction. (See Recognizing
an infusion reaction.)

RECOGNIZING AN INFUSION REACTION

This table presents the clinical findings associated with an infusion reaction to a chemotherapeutic
agent. Familiarize yourself with these findings, which are organized according to body system, to
quickly identify and respond to an infusion reaction. 1 2

Body system Associated clinical findings

Cardiovascular Chest pain

Palpitations

Hypotension or hypertension

Tachycardia or bradycardia

Arrhythmias

Edema

Cardiac ischemia or infarction

Cardiac arrest

Respiratory Dyspnea

Cough

Nasal congestion or rhinitis

Sneezing

Tachypnea

Wheezing

Chest tightness

Hypoxemia

Bronchospasm

Stridor

Cyanosis

Acute respiratory distress syndrome

Reduced expiratory flow

Oropharyngeal or laryngeal edema

Neurologic Fever

Throbbing headache

Dizziness
 Confusion

Anxiety or a sense of impending doom

Restlessness

Loss of consciousness

Rigors

Tunnel vision 2

GI Nausea

Vomiting

Abdominal cramps and bloating

Diarrhea

Genitourinary Urinary incontinence

Uterine cramps or pelvic pain

Renal impairment

Integumentary Diaphoresis

Rash

Pruritus

Urticaria

Flushing

Angioedema

Musculoskeletal Back, chest, or pelvic pain

Arthralgia or myalgia

Fatigue

Tumor pain

Hypotonia

Responding to an infusion reaction

Stop the infusion immediately and call for assistance from other staff members if you note
signs and symptoms of an infusion reaction. Have someone notify the health care team and
practitioner. Alert the emergency response team if needed. 1 2 24
 Assess the patient's circulation, airway, and breathing. Intervene as needed to secure the
patient's airway and maintain breathing and circulation. 1 2
Keep the patient's vascular access device patent by infusing normal saline solution or another
appropriate IV solution. 1 2
Obtain the patient's vital signs and oxygen saturation level using pulse oximetry. Monitor them
every 2 to 5 minutes until the patient's condition stabilizes. 1 2 If the patient is hypotensive,
place the patient in a recumbent position with the lower extremities elevated. 1 2 If shortness
of breath or vomiting occurs, place the patient in an upright position. 2
Administer supplemental oxygen as needed and ordered.
Administer emergency medications as indicated by the patient's condition following safe
medication administration practices. (See Emergency medications.) 1 2 17 18 19 20 24

EMERGENCY MEDICATIONS

The practitioner should individualize treatment for an infusion reaction according to the patient's
condition. 1 2 The severity of the patient's signs and symptoms indicates the medication needed
to treat the reaction. 2

Medication and indications Special considerations

EPINEPHrine—wheezing, bronchospasm, stridor, Administer IM in the anterolateral thigh

hypotension to minimize adverse cardiac effects. 2

Give repeat doses every 5 to 10 minutes

if needed. 2

Administer IV if the patient has profound

hypotension and impending shock and is
unresponsive to IM administration. 2

Alternatively, administer by inhalation or

subcutaneous injection.

DOPamine—hypotension unresponsive to Administer via IV infusion and titrate

EPINEPHrine 1 according to the patient's blood
pressure.

Glucagon—reversal of complicating effects in Administer IV over 5 minutes. 1

patients taking beta-adrenergic blockers 25

Albuterol—shortness of breath, tachypnea, Administer by inhalation.

bronchospasm
Hold the drug if the patient's heart rate
exceeds 110 beats/minute. 2

Famotidine—hives, pruritus, flushing, Administer with diphenhydrAMINE if

angioedema tachycardia and cutaneous signs and
symptoms are present. 1
 Administer IV. 2

DiphenhydrAMINE—hives, pruritus, flushing, Administer IV. 2

angioedema
Consider PO for a mild reaction. 1

MethylPREDNISolone, hydrocortisone, or Administer IV. 2

dexamethasone—reduction of the duration of
the reaction or prevention of recurrence Consider administering PO for a mild
reaction. 1

After the patient's condition stabilizes, assess vital signs every 5 minutes for 30 minutes and
then every 15 minutes. 1 2
Assess the patient for symptom recurrence, especially if the chemotherapeutic agent's half-life
is longer than the emergency medication's half-life. Patients with a severe reaction may
require close monitoring for 24 hours; 2 those with reactive airway disease may require
monitoring for a longer period.
Grade the patient's reaction using a facility-approved grading system (if indicated) to help the
prescribing practitioner decide whether administration of the agent is safe. (See Grading the
infusion reaction.) 1

SCROLL

GRADING THE INFUSION REACTION

Use a grading tool such as the Common Terminology Criteria for Adverse Events tool to grade the severity of a patient's
infusion reaction.

Grade 1—Mild transient reaction; infusion interruption and intervention not indicated

Grade 2—Reaction that requires therapy or infusion interruption but responds promptly to symptomatic treatments
with such agents as antihistamines, nonsteroidal anti-inflammatory agents, opioids, and IV fluids; preventive
medications indicated for 24 hours or less

Grade 3—Prolonged reaction that doesn't rapidly respond to symptomatic treatment, infusion interruption, or both;
symptoms recur after initial improvement; hospitalization indicated for clinical sequelae

Grade 4—Life-threatening consequences; urgent intervention indicated

Grade 5—Death

Adapted from: U.S. Department of Health and Human Services, et al. (2017). Common terminology criteria for adverse
events (CTCAE) (version 5.0). Retrieved July 2023
from https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf

Completing the procedure

Return the bed to the lowest position to prevent falls and maintain the patient's safety. 26
Discard used supplies in appropriate receptacles. 23
Remove and discard your gloves and, if worn, other personal protective equipment. 22 23

Perform hand hygiene. 4 5 6 7 8 9

 Document the procedure. 27 28 29 30

Special Considerations

Skin testing is most valuable for patients who will receive platinum-containing chemotherapy
drugs; it should be performed only by allergists or immunology specialists with the appropriate
training. 2
Unlike most hypersensitivity reactions, CARBOplatin reactions generally occur after the sixth
cycle of treatment. Oxaliplatin reactions also usually occur after the patient has received
multiple cycles of the drug. Because of these variations, always be alert for a possible infusion
reaction when administering these and other high-risk drugs. 2 24

Complications
Complications associated with anaphylaxis and hypersensitivity infusion reaction may include:

airway compromise
shortness of breath
wheezing
respiratory arrest
tachycardia
hypotension
myocardial infarction
cardiac arrest
confusion
agitation
loss of consciousness
erythema
urticaria
periorbital or facial edema. 2

Documentation

Documentation associated with anaphylaxis and hypersensitivity infusion reaction includes:

documentation on a chemotherapy flow sheet (according to your facility's documentation

system)
any premedications administered
administration of the test dose (if ordered)
administration of the scheduled dose
any adverse reactions
assessment findings
interventions performed
response to those interventions
grading and recording of the reaction using a facility-approved grading system (if
indicated)
name of the practitioner notified
date and time the practitioner was notified
 any additional prescribed interventions
teaching provided to the patient and family (if applicable)
understanding of that teaching
follow-up teaching needed.
Related Procedures
Anaphylaxis emergency patient care, ambulatory care
Anaphylaxis emergency patient care, home care
Anaphylaxis management (Advanced practice)
Assessment, patient taking neuroleptic medications
Cardiovascular toxicity management, oncology
Cutaneous toxicity management, oncology
Diarrhea management, oncology
Extrapyramidal symptom assessment
Infiltration and extravasation management, home care
Infusion reaction, cytokine-release syndrome management
Insulin pump use, home care
IV infusion administration, home care
IV infusion pump use, home care
IV pump use
IV syringe pump use
IV syringe pump use, home care
IV time tape use
Ocular toxicity management, oncology
Oral mucositis management, oncology
Pulmonary toxicity management, oncology

References
(Rating System for the Hierarchy of Evidence for Intervention/Treatment Questions)
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Abstract | Complete Reference | Full Text
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Rating System for the Hierarchy of Evidence for Intervention/Treatment Questions

The following leveling system is from Evidence-Based Practice in Nursing and Healthcare: A
Guide to Best Practice (2nd ed.) by Bernadette Mazurek Melnyk and Ellen Fineout-Overholt.
Level I: Evidence from a systematic review or meta-analysis of all relevant randomized
controlled trials (RCTs)
Level II: Evidence obtained from well-designed RCTs
Level III: Evidence obtained from well-designed controlled trials without randomization
Level IV: Evidence from well-designed case-control and cohort studies
Level V: Evidence from systematic reviews of descriptive and qualitative studies
Level VI: Evidence from single descriptive or qualitative studies
Level VII: Evidence from the opinion of authorities and/or reports of expert committees
Modified from Guyatt, G. & Rennie, D. (2002). Users' Guides to the Medical Literature. Chicago, IL: American
Medical Association; Harris, R.P., Hefland, M., Woolf, S.H., Lohr, K.N., Mulrow, C.D., Teutsch, S.M., et al.
(2001). Current Methods of the U.S. Preventive Services Task Force: A Review of the Process. American
Journal of Preventive Medicine, 20, 21-35.