What is the sequence of administration for intramuscular (IM) 1:1000 0.5 ml Epinephrine (adrenaline), intramuscular (IM) chlorpheniramine 10mg, intramuscular (IM) ranitidine 50mg, and intramuscular (IM) hydrocortisone in the management of anaphylaxis in adults?

Sequence of Drug Administration in Adult Anaphylaxis

Administer intramuscular epinephrine (adrenaline) 1:1000 0.5 ml FIRST and IMMEDIATELY—this is the only life-saving medication and must never be delayed for any other drug. 1

Primary Treatment Sequence

1. Epinephrine (Adrenaline) - FIRST LINE

• Give 0.5 ml of 1:1000 solution (0.5 mg) intramuscularly into the anterolateral thigh (vastus lateralis) immediately 1, 2
• Repeat every 5 minutes as necessary to control symptoms and blood pressure 1
• This is the ONLY medication with life-saving pharmacologic effects across multiple organ systems 2
• Common pitfall: Delaying epinephrine to give antihistamines or steroids first—this contributes to anaphylaxis fatalities 2, 3

2. Secondary Medications (ONLY AFTER Epinephrine)

The following medications are second-line therapy and should be given AFTER epinephrine, not instead of it 1:

Antihistamines (can be given simultaneously):

• Chlorpheniramine 10 mg IM or IV slowly 1
• Ranitidine 50 mg IV (diluted in 5% dextrose to 20 mL, given over 5 minutes) 1
• The combination of H1-antihistamine (chlorpheniramine) plus H2-antagonist (ranitidine) is superior to H1-antihistamine alone 1
• These have much slower onset than epinephrine and should never be used alone 1

Corticosteroids (given AFTER antihistamines):

• Hydrocortisone 200 mg IM or IV 1
• Glucocorticosteroids are not helpful acutely but may prevent biphasic or protracted anaphylaxis 1
• Should be given every 6 hours at dosage equivalent to 1.0-2.0 mg/kg/day if severe or prolonged anaphylaxis 1

Algorithmic Sequence Summary

1. Epinephrine 0.5 ml of 1:1000 IM (anterolateral thigh) - IMMEDIATE 1, 2
2. Chlorpheniramine 10 mg IM/IV + Ranitidine 50 mg IV (can give together after epinephrine) 1
3. Hydrocortisone 200 mg IM/IV (after antihistamines) 1

Critical Management Points

Supportive Measures (Concurrent with Epinephrine):

• Position patient recumbent with legs elevated 1
• Establish IV access with normal saline for volume replacement (may need 1-2 L rapidly in adults at 5-10 mL/kg in first 5 minutes) 1
• Administer 100% oxygen at 6-8 L/min 1
• Maintain airway—intubate if necessary 1

When to Repeat or Escalate Epinephrine:

• Repeat IM epinephrine every 5 minutes if symptoms persist or blood pressure remains low 1
• Consider epinephrine infusion if multiple doses required 1
• IV epinephrine should only be used in cardiac arrest or profoundly hypotensive patients who fail to respond to IM epinephrine and IV fluids—risk of lethal arrhythmias 1

Common Pitfalls to Avoid:

• Never delay epinephrine to give antihistamines or steroids first 1, 2
• Never use antihistamines or steroids alone without epinephrine 1
• Never give IV epinephrine as first-line unless in cardiac arrest—use IM route 1
• Injecting epinephrine subcutaneously instead of intramuscularly delays onset of action 2

Observation Period:

• Monitor for biphasic reactions for 4-12 hours depending on severity and risk factors 1, 4, 5
• Risk factors for biphasic reactions include severe initial presentation and need for repeated epinephrine doses 5