Nurse-Led Grading of Antineoplastic Infusion-Related Reactions: A Call to Action

Abstract

Infusion-related reactions (IRRs) are unpredictable oncologic emergencies that occur during or after administration of antineoplastic therapies or other infusion medications (e.g., iron). IRRs are complex, ranging from mild to severe in symptom severity grading, including life-threatening anaphylaxis. Oncology nurses can readily assess symptom severity using a standardized and objective symptom severity grading scale to recognize them, intervene, and manage patient care effectively. This article reviews the Brown grading system, an adult-specific IRR grading tool for antineoplastic agents and iron products.

AT A GLANCE

• ■ A delay in the identification of anaphylaxis requiring immediate treatment with epinephrine places the patient at high risk for preventable morbidity and mortality.

• ■ A standardized reaction severity grading scale can guide accurate and efficient interprofessional communication, resulting in timely and potentially lifesaving treatment.

• ■ Implementing nurse-led grading is a novel concept that empowers nurses as first responders to immediately identify reaction severity and initiate associated treatment.

An infusion-related reaction (IRR) is an adverse event experienced during or after administration of antineoplastic therapies or other infusion medications (e.g., iron). IRRs typically occur with the first or second medication administration. However, they are unpredictable and may occur anytime during a patient’s treatment trajectory. IRRs present as mild, moderate, or severe in symptom severity, including life-threatening anaphylaxis. Typically, IRRs are mild or moderate and can be effectively managed by interprofessional teams using a rapid and standardized rescue response. In addition, IRRs are low-volume, high-risk events and are difficult to predict, despite known intrinsic and extrinsic risk factors and preventive measures (Corbett & Nesbitt, 2025; Olsen et al., 2023).

Determining the incidence of IRRs is challenging given the initial identification, terminology, and severity grading. Many are underreported. Antineoplastic therapies and monoclonal antibodies most associated with IRRs include alemtuzumab, asparaginase, bleomycin, cetuximab, cytarabine, etoposide, ixabepilone, pegylated liposomal doxorubicin, platinums, procarbazine, rituximab (both IV and subcutaneous), taxanes, and trastuzumab (Castells et al., 2023; LaCasce et al., 2025). Although aware of known risks, oncology nurses in adult ambulatory infusion settings administer numerous lifesaving antineoplastic medications and other infusion therapies (e.g., iron) to patients daily. In the United States, within drug-induced anaphylaxis, chemotherapy is identified as the third leading cause of mortality (Pagani et al., 2022), thus requiring oncology clinicians to ensure and demonstrate clinical competency in emergency management of IRRs.

Many oncology nurses are aware of IRR risk and often worry about which patients may experience an IRR and when. When IRRs disrupt a patient’s treatment regimen, the goal is to resume the full dose of first-line therapy as tolerated to ensure the best anticancer response and patient outcome. Variability in IRR rescue response practices have potential known and inherent patient safety risks. Nurses can mitigate these short- and long-term risks by immediate identification and management of the IRR using a standardized, evidence-based, best-practice approach (i.e., IRR algorithm to direct care delivery), inclusive of a severity grading scale (Corbett & Nesbitt, 2025; Olsen et al., 2023).

Severity Grading Scales

Numerous allergic reaction scoring systems or severity grading scales are available when assessing patients having an IRR (Shah et al., 2023). The Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (National Cancer Institute Cancer Therapy Evaluation Program, 2017), may be familiar to oncology nurses because clinicians use it in oncology clinical trial documentation to categorize the severity of various symptoms and associated adverse events. Some teams have built the CTCAE into electronic health record systems and embedded it within established oncology literature. Three CTCAE scales are available to retrospectively document allergic reactions, anaphylaxis, and cytokine release syndrome. The criteria in these scales are not always helpful to clinicians during the acute phase of an IRR (i.e., real time). Symptoms listed in the CTCAE scales are often unknown (e.g., which scale to use, allergic versus nonallergic versus cytokine release) during the immediate, acute IRR response and treatment period. The CTCAE may be more helpful when retrospectively assessing and documenting a patient’s IRR and implications for treatment.

Introduced in 2004, the Brown grading system for generalized hypersensitivity reactions (see Table 1) has been utilized during acute reactions; in response to symptoms, interventions, ongoing care, and research; and in diagnosing and determining etiology, risk factors, and treatment. This adult-specific scale is not allergen specific and applies a three-tier approach of grade 1 (mild), grade 2 (moderate), or grade 3 (severe). This simple and clinically relevant grading system links patient symptoms to a specific severity grade number, guiding nurses to administer the appropriate rescue and/or symptom management medications or other interventions within the IRR algorithm based on the grade (i.e., patient symptoms) of the reaction. The Oncology Nursing Society’s infusion-related toxicity algorithm includes the Brown grading system, as does relevant antineoplastic IRR literature (Corbett & Nesbitt, 2025; Lynch et al., 2023; Olsen et al., 2023; Pagani et al., 2022).

TABLE 1.

BROWN GRADING SYSTEM FOR GENERALIZED HYPERSENSITIVITY REACTIONS

GRADE	BROAD CLINICAL FEATURES OR SYSTEMS INVOLVED	DEFINING SIGNS AND SYMPTOMS
1: mild	Skin and subcutaneous tissues only	Generalized erythema, urticaria, periorbital edema, angioedema
2: moderate	Features suggesting respiratory, cardiovascular, or gastrointestinal involvement	Dyspnea, stridor, wheeze, nausea, vomiting, dizziness, (presyncope), diaphoresis, chest or throat tightness, abdominal pain
3: severe	Hypoxia, hypotension, neurologic compromise	Cyanosis, or blood oxygen saturation ≤ 92% at any stage of hypotension; systolic blood pressure < 90 mmHg in adults; confusion; collapse; loss of consciousness; incontinence

Note. Mild reactions can be further subclassified into those with and without angioedema.

Note. Based on information from Brown, 2004.

Note. From Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (2nd ed., p. 390), by M. Olsen, K.B. LeFebvre, S.L. Walker, & E. Prechtel Dunphy (Eds.), 2023, Oncology Nursing Society. Copyright 2023 by Oncology Nursing Society. Reprinted with permission.

When applying the Brown grading system, healthcare professionals consider grade 1 reactions (nonanaphylaxis) to be mild, involving skin and subcutaneous tissues only. Grade 2 reactions (nonanaphylaxis) are moderate, with respiratory, cardiovascular, or gastrointestinal involvement. Grade 3 reactions are severe, including hypoxia, hypotension, or neurologic compromise with vital sign changes. Grade 3 reactions are considered anaphylaxis, consistent with the included definition (Brown, 2004).

In addition, the Oncology Nursing Society infusion-related toxicity algorithm guides emergency response clinicians to assess for grade 3 (anaphylaxis) first, knowing immediate recognition and treatment with epinephrine administration can be lifesaving (Olsen et al., 2023). Infusion reaction severity is unpredictable, and the delay of epinephrine during anaphylaxis can lead to fatalities (0.25%–0.33%), which are often underdiagnosed (Bock, 2024). Early diagnosis and treatment are most responsive and may prevent fatalities (Bock, 2024; Campbell & Kelso, 2024, 2025; Olsen et al., 2023; Shaker et al., 2020). Prince et al. (2018) describe barriers to administering epinephrine in the setting of anaphylaxis because of the complexity of making this diagnosis. Using a standardized severity grading system provides objectivity and supports infusion nurses in associating patient symptoms with a reaction grade, thus expediting appropriate and potentially lifesaving treatment guided by the patient’s clinical presentation (Corbett & Nesbitt, 2025).

Nurse-Led Grading of IRRs

Nurse-led symptom-based grading of IRRs is defined and enhanced by the concept of infusion nurses as first responders. Although not typically considered first responders by traditional definition (e.g., police, fire, emergency medical service), infusion nurses are most often the first clinicians to respond to IRR emergencies in adult ambulatory oncology settings. Accepting this role identity empowers nurses to assess patient symptoms rapidly, associate these symptoms with a severity grade defined within the Brown grading system, and intervene immediately (Corbett & Nesbitt, 2025).

As summarized by Shah et al. (2023), most severity grading scales use a symptom-based approach. Typically, nurses identify an IRR, perform a patient assessment to identify IRR symptoms, and then subjectively describe these symptoms without standardized terminology. Nurse-led severity grading allows nurses, as first responders, to immediately grade the IRR based on patient symptoms using standard terminology. As soon as the nurse determines the reaction grade, the nurse can administer rescue and/or symptom management medications (see Table 2) as recommended for each severity grade by following an IRR algorithm (Corbett & Nesbitt, 2025).

TABLE 2.

EMERGENCY DRUGS FOR USE WITH HYPERSENSITIVITY OR ANAPHYLACTIC REACTIONS

INDICATION	DRUG	DOSE	COMMENTS
Bronchial constriction (e.g., dyspnea, wheezing, stridor)	■ Epinephrine	■ 0.1–0.5 mg IM into thigh (0.1–0.5 ml of 1:1,000 solution or EpiPen® 0.3 mg automatic device) ■ IV administration is indicated for patients with profound hypotension or signs or symptoms of impending shock who have not responded to IM dose.	■ IM administration is preferred over IV to minimize adverse cardiac effects. ■ Anterolateral upper thigh is preferable to deltoid (may also be administered by inhalation or subcutaneously). ■ Repeat every 5–10 minutes if needed.
Patients who do not respond after at least 2 doses of epinephrine and take a beta-blocker	■ Glucagon	■ 1 mg/50 ml IV over at least 5 minutes ■ Dose may be repeated up to 5 times for a total of 5 mg. ■ A continuous infusion may be indicated. ■ Consider a higher level of care if not responding.	■ The drug is given preferably via IV pump at a controlled rate to minimize adverse effects of severe nausea and vomiting. If nausea and vomiting continue or occur even with a pump-controlled rate of administration, stop the drug. ■ Glucagon counteracts the systemic effects of anaphylaxis, as glucagon acts independently of alpha and beta receptors.
Shortness of breath, tachypnea (rate > 20 breaths per minute), or decreased oxygen saturation	■ Oxygen	■ 2–6 L per minute via a nasal cannula; 15 L via nonrebreather, if needed	■ Patients who are hemodynamically unstable may also benefit from oxygen.
	■ Albuterol	■ 2.5 mg/3 ml of 0.083% inhalation solution by nebulizer or 180 mcg (2 puffs) by metered-dose inhaler	■ Hold if heart rate is > 110 beats per minute.
Hypotension (> 30% decrease in systolic blood pressure from baseline)	■ Epinephrine	■ Recommended dose is 0.01 mg/kg (maximum dose: 0.5 mg) IM into the anterolateral thigh. ■ The dose should be drawn up using a 1 ml syringe using the 1 mg/ml formulation of epinephrine. ■ A single-dose vial is preferred. ■ The use of an autoinjector EpiPen (0.3 mg) is preferred for speed, reliability, and ease of use.	■ IM administration is preferred over IV to minimize adverse cardiac effects, except in the presence of cardiovascular collapse. Cardiac monitoring is recommended.
	■ Normal saline IV	■ 500 ml fluid bolus	■ Administer over 10 minutes once and then as ordered. ■ Multiple fluid boluses may be required if the patient remains hypotensive despite epinephrine. ■ Massive fluid shifts can occur.
Hives, itching, flushing, swollen lips or tongue	■ Diphenhydramine ■ Famotidine ■ Ranitidine	■ 25–50 mg IVP ■ 25–50 mg IVP ■ 50 mg IVP	■ To counteract the multiple effects of histamine release, both H1 and H2 antagonists should be administered.
Wheezing, cough, hives, or flushing	■ Montelukast	■ 10 mg by mouth	■ The drug has an off-label use for infusion-related reactions. It may be given as premedication.
Pain	■ Ketorolac	■ 15 mg IVP	■ The drug is for the short-term management of moderately severe acute pain.
To prevent biphasic (delayed) reaction or for use with cytokine release reaction/cytokine release syndrome	■ Methylprednisolone ■ Hydrocortisone ■ Dexamethasone	■ 40 mg IV (80 mg for > 120 kg) ■ 100–500 mg IV ■ 10–20 mg IV	■ A systematic review failed to find significant benefit in the initial prevention of anaphylaxis or as a delayed/biphasic reaction.

IM—intramuscular; IVP—IV push

Note. Additional emergency medications for advanced cardiovascular life support and emergency supplies (e.g., oxygen, suction machine with catheters, bag valve mask) should be available in a medical emergency.

Note. Based on information from Campbell & Kelso, 2021; Castells et al., 2022; Commins, 2017; Galvão et al., 2017; Wilkes & Barton-Burke, 2020.

Note. From Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (2nd ed., pp. 388–389), by M. Olsen, K.B. LeFebvre, S.L. Walker, & E. Prechtel Dunphy (Eds.), 2023, Oncology Nursing Society. Copyright 2023 by Oncology Nursing Society. Reprinted with permission.

The Brown grading system is easy to use, given its clear symptom descriptions and simple three-point classification system. A severity grading scale allows clinicians to speak a common clinical language. When a team member identifies a particular reaction grade, other team members readily understand the patient’s symptoms and the clinical care indicated or provided. For example, when clinicians treat a patient with a grade 2 reaction who is not responding to treatment, the team can efficiently recognize and communicate if the patient has impending anaphylaxis (transitioning to a grade 3) and consider the immediate use of epinephrine. Team communication, efficiency, and accuracy are foundational during an acute emergency such as an IRR. A severity grading scale can also support informed resumption (i.e., rechallenge) of the causative medication critical to the cancer treatment plan. Typically, grade 1 or 2 reactions may be considered safe to resume at a slower rate and with possible premedication modifications, although a grade 3 is never rechallenged. The clinical care team members make these decisions in accordance with established policies, procedures, guidelines, and the IRR algorithm (Corbett & Nesbitt, 2025). See Figure 1 for two case study scenarios.

FIGURE 1.

SEVERITY GRADING CASE SCENARIOS

IRR—infusion-related reaction; SOB—shortness of breath; SpO₂—oxygen saturation

Of note, patient symptoms may lessen or worsen during an IRR (i.e., a reaction can transition up from grade 1 to grade 2 or grade 3, or down from grade 2 to grade 1 until complete resolution of symptoms). As a result, nurses perform ongoing symptom assessments with regrading because further treatment may be indicated. In addition, nurse documentation needs to reflect severity grading in relationship to treatment interventions and subsequent patient outcome/response to treatment. This enhances care consistency when considering ongoing (i.e., future) administration of the causative medication.

Implementation of Nurse-Led Severity Grading

A collaborative interprofessional team, including oncology nurses, providers, pharmacists, and allergists, can implement a standardized severity grading scale for IRRs and the practice of nurse-led grading. Although the Brown grading system is one option, modification may be warranted. The involvement of an allergist helps ensure the scale’s validity and determines appropriate severity grade and defining signs and symptoms, which guide the rescue and symptom management medications and interventions provided. This interprofessional support and team collaboration promotes adoption of use and prioritizes patient safety. Organizations can embed the severity grading scale into the IRR algorithm, policies, guidelines, treatment plans, procedures, and electronic health record documentation.

An implementation plan and includes mandatory comprehensive education for all clinical teams on how the severity grading scale influences associated treatments and interventions. Initial and ongoing education maintains competency and ensures consistent application (i.e., inter-rater reliability) of the severity grading scale and IRR algorithm adherence. This ensures all clinicians assess (i.e., grade) reactions the same way, based on patient symptoms, and prioritize the assessment of anaphylaxis first (Olsen et al., 2023; Prince et al., 2018). The IRR algorithm should include specific clinical criteria for anaphylaxis and warrants a specific grade within the grading scale, typically associated with a higher-grade reaction (i.e., grade 3). Implementing postevent evaluation or facilitated debriefing practices is recommended to allow for team support, feedback, and ongoing quality improvement (Corbett, 2025; Corbett & Nesbitt, 2025).

Implications for Practice and Conclusion

Oncology nurses in ambulatory infusion settings are often the first responders to an IRR via early recognition and management. To ensure optimal outcomes and enhance patient safety, nurses must intervene immediately. This can occur when the interprofessional team defines a standardized approach to prevention, recognition, nurse-led severity grading, and emergency treatment. Using a standardized nurse-led severity grading scale during the acute IRR facilitates the enhanced quality of team communication to mobilize the needed resources. A severity grading scale also standardizes communication, leading to consensus on interventions.

In addition, nurse-led severity grading enhances continuity of care for patients who may need to continue to receive the causative medication to treat their cancer despite experiencing an IRR. Nurse-led severity grading facilitates accurate and often chronologic patient assessments, which provide a comprehensive overview of the patient experience, symptom severity, and response to interventions. Allergist consultation may be considered post-IRR, and patient assessment and documentation provided by the nurse support the allergist’s or treating physician’s medical record review for determining a patient’s course of action, which may include desensitization or adjustments to the treatment plan. Integrating the severity grading scale into an electronic health record system supports use. Integration eases the documentation burden and supports nurses in having accurate, timely, comprehensive, and clear communication to promote continuity of care among interprofessional care team members.

For patients who experience an IRR, nurse-led severity grading is a proactive intervention, enhancing patient safety through immediate symptom recognition and treatment interventions. This concept invites a shift in organizational culture, recognizing nurses as first responders, and requires dedicated implementation time with administrative-level support and engagement. An organizational culture that prioritizes nurse autonomy, empowerment, and operational efficiency can optimize patient outcomes through nurse-led severity grading for IRR response. Continuous quality improvement requires ongoing monitoring, including adherence audits, data analysis, transparent reporting, and competency-based and interprofessional education to maintain algorithm adherence and inter-rater reliability of the nurse-led severity grading scale (Corbett et al., 2023). In addition, critical incident debriefing following IRRs is an evidence-based best practice to facilitate event discussion, foster communication, and perhaps enhance critical thinking, patient safety, and quality of care (Corbett, 2025; Joyce & Itano, 2024). Ultimately, these combined efforts can empower nurses, transform IRR management, and create an adaptive system for continuous improvement.

TEST YOUR KNOWLEDGE.

During a carboplatin infusion, a patient is experiencing abdominal pain and urticaria. The patient is alert with stable vital signs. According to the Brown severity grading system, what grade is the reaction?

• ■ Grade 1

• ■ Grade 2

• ■ Grade 3

• ■ Grade 4

The correct answer is grade 2.

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Essentials updates readers about the foundation of clinical oncology practice. If you are interested in writing for this department, contact Associate Editor John Bourgeois, DNP, MMHC, RN, OCN^®, CCRP, NEA-BC, at john.bourgeois@emoryhealthcare.org.