What is the appropriate management for a patient who develops chills as a manifestation of a hypersensitivity reaction?

Management of Hypersensitivity Reaction-Induced Chills

For chills occurring as part of a hypersensitivity reaction, immediately assess whether this represents true anaphylaxis versus a milder cytokine-release syndrome, then treat accordingly with either intramuscular epinephrine (for anaphylaxis) or slowing/stopping the infusion with H1/H2 antihistamines and corticosteroids (for non-anaphylactic reactions). 1

Initial Assessment: Distinguish Anaphylaxis from Cytokine-Release Syndrome

The critical first step is determining whether chills are part of anaphylaxis or a milder hypersensitivity reaction:

• Stop the infusion immediately and assess the patient's airway, breathing, circulation, and level of consciousness 1
• Look for signs of anaphylaxis: hypotension, bronchospasm, angioedema, cardiovascular collapse, or bradycardia—these require immediate epinephrine 1
• If only chills with flushing, mild fever, or urticaria without life-threatening features, this likely represents cytokine-release syndrome or a Grade 1-2 hypersensitivity reaction 1

Management Algorithm Based on Severity

If Anaphylaxis is Suspected (Life-Threatening Features Present)

Epinephrine is the only first-line treatment and must never be delayed:

• Administer epinephrine 0.2-0.5 mg (1 mg/mL) intramuscularly into the lateral thigh (vastus lateralis), repeating every 5-15 minutes if symptoms persist 1, 2, 3
• Position the patient supine with lower extremities elevated if hypotensive; sitting up if respiratory distress; recovery position if unconscious 1, 2
• Initiate aggressive IV fluid resuscitation with normal saline 1-2 L at 5-10 mL/kg in the first 5 minutes for adults; crystalloids or colloids in 20 mL/kg boluses for children 1, 2
• Administer supplemental oxygen at 6-8 L/min for respiratory symptoms 2, 4

After epinephrine administration, give adjunctive medications:

• H1/H2 antagonists: diphenhydramine 50 mg IV plus ranitidine 50 mg IV (or famotidine 20 mg IV) 1, 3
• Corticosteroids: methylprednisolone 1-2 mg/kg IV every 6 hours (equivalent dose) 1
• For persistent bronchospasm: albuterol nebulizer or IV salbutamol infusion 1, 4
• For refractory hypotension: dopamine 400 mg in 500 mL at 2-20 μg/kg/min or vasopressin 25 U in 250 mL (0.1 U/mL) at 0.01-0.04 U/min 1
• For patients on beta-blockers with refractory symptoms: glucagon 1-5 mg IV over 5 minutes 1, 4

If Cytokine-Release/Non-Anaphylactic HSR is Suspected (No Life-Threatening Features)

Grade 1 (mild symptoms including chills, flushing, fever <38°C):

• Slow the rate of infusion 1
• Monitor vital signs closely for progression 1

Grade 2 (moderate symptoms requiring intervention):

• Slow or temporarily stop the infusion 1
• Administer H1/H2 antagonists: diphenhydramine 50 mg IV plus ranitidine 50 mg IV 1
• Give corticosteroids: methylprednisolone 1-2 mg/kg IV every 6 hours 1
• Restart infusion at 50% rate and titrate to tolerance once symptoms improve 1

Grade 3/4 (severe but not anaphylaxis):

• Stop the infusion permanently 1
• Administer H1/H2 antagonists and corticosteroids as above 1
• Rechallenge is discouraged in severe reactions 1

Critical Pitfalls to Avoid

Common errors that increase morbidity and mortality:

• Never substitute antihistamines or corticosteroids for epinephrine in true anaphylaxis—this is the most dangerous error and contributes to fatalities 2, 3, 4
• Do not delay epinephrine while giving other medications first; delay is directly associated with increased mortality and biphasic reactions 2, 3, 4
• Do not allow patients to stand or walk during a reaction, as this can precipitate cardiovascular collapse 4
• Do not discharge prematurely—observe for minimum 4-6 hours after complete symptom resolution, as biphasic reactions can occur up to 72 hours later 2, 4
• Do not rely on corticosteroids to prevent biphasic reactions—multiple studies show no clear evidence they prevent recurrence 3, 4

Post-Reaction Management

After stabilization, ensure appropriate follow-up:

• Monitor vital signs continuously until complete resolution 1
• Observe for 24 hours if severe reaction; minimum 4-6 hours for all patients 1, 2, 4
• Prescribe two epinephrine auto-injectors with hands-on training 2, 4
• Refer to allergist for evaluation, skin testing, and development of emergency action plan 2, 4
• Provide written anaphylaxis emergency action plan with education on trigger avoidance and biphasic reaction risk 2, 4

Special Considerations

Recognize that chills alone may be an early warning sign:

• Patients may feel "odd" or uncomfortable before developing full anaphylaxis—take these symptoms seriously and measure blood pressure and pulse rate 1
• Some patients express a need to urinate or defecate before anaphylaxis develops—this warrants immediate evaluation 1
• Chills with rigors during infusion may represent cytokine release rather than true IgE-mediated anaphylaxis, but both require immediate intervention 1

The key distinction is whether life-threatening features (hypotension, bronchospasm, angioedema, cardiovascular collapse) are present—if yes, treat as anaphylaxis with immediate epinephrine; if no, manage as cytokine-release syndrome with infusion modification and adjunctive medications. 1