A time-sensitive solution to a common problem
- Many cancer therapies, especially biotherapies, can result in potentially fatal I.V. infusion reactions.
- Nurses at this hospital lacked the authority to immediately apply pharmacologic interventions in the event of a hypersensitivity reaction.
- A nurse-driven protocol allows for autonomy in practice and better medication administration response times.
Before the implementation of a nurse-driven protocol at our multicampus hospital, nurses practicing in oncology settings gained general knowledge of emergency management of hypersensitivity infusion reactions through didactic instruction, but they couldn’t apply immediate pharmacologic interventions. This situation resulted from an absence of standing orders for emergency medicine in these high-risk situations. To address this issue and foster autonomy, a team of oncology educators and pharmacists worked to develop a hypersensitivity reaction protocol to improve patient safety and foster efficient care delivery.
Infusion therapy: A model for safe practice in the home setting
Cancer treatments and adverse effects
Both traditional and recently developed chemotherapies, biotherapies, and immunotherapies work to extend the lives of patients with cancer. Chemotherapy includes a group of hazardous drugs designed to kill cancer cells. It works by preventing the growth, division, and creation of more cells. Biotherapy stimulates or restores the ability of the immune system to fight infection and disease. It includes any form of treatment that uses the body’s natural abilities to fight infection and disease or to protect it from some of the side effects of treatment. Immunotherapy represents a newer type of biological therapy, but little information exists about long-term effects. For this reason, immunotherapies are treated as hazardous.
Many cancer therapies, especially biotherapies, can result in I.V. infusion reactions. They occur unexpectedly and frequently with severe or even fatal results. These reactions (including fever, nausea, vomiting, flushing, back pain, angioedema, maculopapular rash, dyspnea, bronchospasm, feelings of impending doom, and alterations in heart rate and blood pressure) interfere with the completion of first-line therapy, which leads to treatment interruption. The decision to discontinue current therapy or re-challenge a patient after a reaction depends on many clinical factors, including the reaction severity and the efficacy of alternative therapies.
The Oncology Nursing Society’s recommendations for managing acute infusion reactions caused by hypersensitivity, anaphylaxis, and cytokine-release syndrome include immediately stopping the infusion, notifying the physician and activating emergency response, and conducting ongoing observation and monitoring. Emergency pharmacologic management also might require administering epinephrine, diphenhydramine, cimetidine, and corticosteroids as ordered by the physician or according to standing protocols.
Protocol development process
After reviewing the literature, a group of clinical oncology education specialists and pharmacists formed an oncology committee and developed the Adult Hypersensitivity Reaction and Anaphylaxis to Chemotherapy and Biotherapy Protocol. After approval of the protocol by hospital management and before implementation, the committee provided standardized education (including its application in various case scenarios) throughout the hospital system. Initiation of the nurse-driven protocol included allowing nurses to administer epinephrine based on their clinical judgment and established guidelines for Grade 3 reactions.
Symptom severity determines reaction grading. A Grade 3 reaction requires immediate cessation of the infusion and administration of supportive medications, such as epinephrine. For ease of use, the protocol recommends an epinephrine pen (EpiPen). The dose may be repeated every 5 minutes for up to 15 minutes for a total of four doses for persistent symptoms.
Initially, a written order set put this protocol into effect. The protocol became part of the Chemotherapy/Biotherapy/Orders Treatment Plan, which nurses implemented as needed unless contrary documentation existed. The oncology committee placed a copy of the protocol on the front of every chart containing orders for chemotherapy or biotherapy and within the patient’s electronic health record (EHR).
Protocol adjustments
Initially, the committee didn’t include Grade 1 and 2 reactions in the protocol. A Grade 1 reaction, the most benign, requires only further observation. However, Grade 2 reactions include fever, rash, arthralgia, noisy breathing without respiratory distress, shortness of breath with minimal exertion, intense itching, or moderate disorientation.
Based on the overwhelming positive response from the staff using the nurse-driven protocol for Grade 3 reactions, the committee enhanced it to include pharmacologic intervention for Grade 2 reactions. Previously, the pharmacologic treatment of Grade 2 reactions required calling the provider to receive intervention orders. This step caused delays in treatment. In addition, data gathered by the committee indicated that most reported reactions were classified as Grade 2, which created a significant impact on patients due to delays. The committee agreed to move forward to enhance the guidelines.
To ensure immediate management of these predominant incidents, the committee worked with the oncology clinical pharmacist to create an enhanced nurse-driven protocol that includes evidenced-based therapies. After final approval of the updated protocol, the committee implemented simulation and educational processes across the hospital system to demonstrate how to conduct first-line management of hypersensitivity, how to identify high-risk patients, and how to differentiate among the grades and response of hypersensitivity and anaphylaxis. (See The protocol.)
The protocol
The Adult Hypersensitivity Reaction and Anaphylaxis to Chemotherapy and Biotherapy Protocol includes the following:
Grade 1 reaction
Closely monitor patients upon signs/symptoms of a Grade 1 reaction, including transient flushing or rash, mild itching, anxiety, or mild disorientation. Do not interrupt the infusion. Monitor the patient until symptoms resolve.
Grade 2 reaction
Immediately stop infusion upon signs/symptoms of a Grade 2 reaction, including fever, rash, arthralgia, noisy breathing without respiratory distress, dyspnea with minimal exertion, intense itching, or moderate disorientation. Fully disconnect the line to avoid any infusion of the drug, maintain I.V. access, and initiate the following Grade 2 orders:
- Administer diphenhydramine 50 mg I.V. push once.
- Administer famotidine 20 mg I.V. piggyback once.
- Administer methylprednisolone 125 mg I.V. push once.
- If the patient has noisy breathing or dyspnea, administer albuterol 2.5mg/3mL via nebulizer once.
- Monitor vital signs every 15 minutes until all indications of a reaction have subsided. After the reaction resolves and the provider has been notified and given an order to continue therapy, restart the infusion at 50% of the initial rate. If tolerated after 30 minutes, reinitiate the full infusion rate.
Grade 3 or 4 reaction
Stop the infusion immediately upon signs/symptoms of a Grade 3 reaction, including severe arthralgia, extensive rash, symptomatic bronchospasm with or without urticaria, hypotension, angioedema, dyspnea with stridor, decrease in oxygen saturation and respiratory distress at rest, rash covering 30% of the body with widespread itching, severe disorientation, or hallucinations.
For a Grade 4 reaction, stop the infusion immediately upon signs and symptoms, including severe cardiac or respiratory compromise requiring urgent intervention such as ventilator support, tracheostomy, or intubation. Fully disconnect the line to avoid any infusion of the drug. Call a Rapid Response or Code Blue if necessary (or 911 in noncontagious outpatient facilities).
Initiate Grade 3 or 4 orders:
- Administer epinephrine auto injector 0.3mg IM STAT.
- Administer 1 L of normal saline wide open as ordered.
- Administer 100% oxygen via non-rebreather mask.
- Begin continuous oxygen saturation monitoring.
- Administer supportive medications as listed in Grade 2 reaction response above.
- Repeat epinephrine injection every 5 minutes for up to 15 minutes (four doses total) for persistent symptoms.
The committee also worked to make the protocol available on the health system intranet, as well as in EHR documentation. Those who served on the review committee worked to ensure inclusion of the protocol and appropriate medication orders in every applicable patient treatment plan.
The release of the revised protocol eliminated the need for nurses to call the physician for orders when a patient experiences Grade 2 reactions. The new practice now includes a nurse-driven order set to administer pharmacologic management as needed, including diphenhydramine, famotidine, methylprednisolone, and albuterol. For Grade 3 reactions, the practice of using the EpiPen continues. The protocol also provides guidance about the rate for restarting infusion therapy. In addition, updated policies (included as part of the patient’s treatment plan in the EHR) reflect the new practice for managing infusion reactions.
To reinforce this practice change, the committee developed new simulation scenarios for inclusion in annual competency sessions for all oncology nurses. The scenarios provide education about the updates in the protocol and require immediate verbal feedback to ascertain the nurse’s understanding of the grading criteria and system-based interventions.
Nurse feedback
The Adult Hypersensitivity Reaction and Anaphylaxis to Chemotherapy and Biotherapy Protocol was successfully put into practice in the oncology settings across all five hospital campuses. Each year, nurses receive education as part of systemwide oncology competencies to ensure consistency in performance and review of critical skills.
Staff feedback remains positive as a result of accelerated response times during adverse reactions. The staff in the outpatient ambulatory infusion suite, for example, can’t rely on quick access to some of the highly trained individuals (such as rapid response teams) that inpatient nurses can call on. Previously, patients were transferred to the hospital by ambulance for supplemental evaluation and treatment. With the new protocol, nurses in this setting can provide the required intervention.
To further assist in mitigating the stress associated with these scenarios, the nurses developed an Emergency Plan Proposal. Working together, they enhanced the efficiency of their efforts during these events by pre-assigning a unique role to specific members of the response team. For instance, the primary nurse alerts the triage nurse to the need for the emergency cart. The nurse working directly with the patient releases and scans the emergency medications. The triage nurse assists with this process while also maintaining clear communication with the rest of the team. The assistant nurse manager then gathers any additional supplies and calls 911 if a transfer to the emergency department is required.
By dividing their roles and limiting the number of people involved, they care for the patient quickly and unobtrusively without causing concern for other individuals within close proximity. Most importantly, they’ve improved the patient experience and outcome. (See Emergency plan proposal.)
Emergency plan proposal
Staff working in the outpatient ambulatory infusion site developed the following emergency plan in the event of an infusion reaction:
- Purpose. Ensure a safe and calm flow of treatment/course of action for patients, a less-frightening experience for family members, proper documentation, and clear communication/role division among team members.
- Plan. In the event of a hypersensitivity reaction/emergency situation, assigned team members include the primary nurse, nurse stationed directly next to the primary nurse (secondary nurse), the triage nurse, and the assistant nurse manager (if available) or charge nurse. Each team member performs a specific role to ensure proper communication and flow of care.
- Primary nurse. Alert the triage nurse about the need for the emergency cart. Provide a quick briefing to the emergency team about what occurred, along with the patient’s baseline status. Administer any necessary medications/oxygen and take vital signs. Remain with the patient at all times to promote comfort and ensure safe patient care. Provide a report to the emergency medical technician (EMT)/emergency department (ED) RN if necessary.
- Secondary nurse. Release emergency medications as they’re obtained for administration, scan all administered medications, call the physician to notify them of the situation, and obtain any new orders. Document the situation and all actions in the Notes section of the electronic health record, including physician notification, whether a report was given to anyone (such as the ED RN), and patient outcome (for example, infusion restarted, patient transferred to the ED). This ensures all medication documentation occurs at the time it’s administered and relieves the primary RN from documenting later.
- Triage nurse. Obtain the emergency cart (or backboard if needed). Remain the only team member in the cart obtaining medications and preparing them for administration. State out loud what time and what medication is being obtained to maintain clear communication with the team. This will ensure proper documentation and patient safety. When the emergency resolves, work with the assistant nurse manager or charge RN to inform the pharmacy that the emergency cart must be restocked and locked.
- Assistant nurse manager or charge RN. Gather any additional supplies (for example, oxygen tubing), and ensure proper implementation of the emergency plan. If required, call 911 for patient transfer to the ED. Take notes of the sequence and times of the situation (for example, when vital signs are taken and 911 is called). If needed, give a report to the EMT.
Improve care
Each year during protocol review, staff members report examples of how it’s improved care for their patients by either eliminating symptoms of distress or the need to interrupt treatment. In fact, it has proven so critical to patient care that the same in-person education was provided during the pandemic at a time when most learning took place virtually.
The ability to offer annual educational reinforcement and competency assessment across five hospital campuses to more than 150 nurses is no easy task. It takes a team of dedicated individuals and the right amount of creativity to maintain the interest of the staff while also increasing their knowledge. However, these efforts have led to a greater understanding of the necessity for timely intervention during infusion reactions, as well as an opportunity to demonstrate their responses in real time during simulation with immediate feedback.
Lisa Chichelo is a BMT/leukemia clinical coordinator at Hackensack Meridian Jersey Shore University Medical Center at Hope Tower in Neptune, New Jersey. Kathy Colopoulos is a retired oncology clinical nurse specialist who worked at Jersey Shore University Medical Center in Neptune, New Jersey.
American Nurse Journal. 2025; 20(1). Doi: 10.51256/ANJ012522
References
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Key words: hypersensitivity reaction, cancer treatment, chemotherapy, biotherapy, immunotherapy
