Atracurium 

1. Overview

Atracurium is a non-depolarizing neuromuscular blocking agent (NDNMBA) of the benzylisoquinolinium class

• Intermediate-acting
• Organ-independent metabolism  (major advantage in ICU)
• Causes histamine release 

2. Mechanism of Action

• Competitive antagonist at nicotinic acetylcholine receptors (Nm) at NMJ
• Prevents ACh binding → no depolarization → flaccid paralysis

Sequence of paralysis:

1. Small muscles (eyes, face)
2. Limbs
3. Intercostals
4. Diaphragm (last)

Recovery occurs in reverse order.

 3. Pharmacokinetics 

Unique metabolism:

1. Hofmann elimination (non-enzymatic, temp & pH dependent)
2. Ester hydrolysis (non-specific esterases)

No dependence on:

• Liver 
• Kidney 

➡️ Drug of choice in organ failure ICU patients

 4. Hofmann Elimination 

• Occurs at physiological pH and temperature
• Produces:
• Laudanosine (CNS stimulant )

Clinical implications:

• Hypothermia ↓ metabolism → prolonged block
• Acidosis ↓ metabolism → prolonged block

 5. Dosing in ICU

 Intubation dose:

• 0.4–0.5 mg/kg IV

Maintenance bolus:

• 0.1–0.2 mg/kg

Continuous infusion:

• 5–10 mcg/kg/min

 Titrate using TOF monitoring (goal: 1–2 twitches)

6. Neuromuscular Monitoring (TOF)

4

7. Adverse Effects 

1. Histamine release (dose-related)

• Hypotension
• Tachycardia
• Bronchospasm

 Avoid rapid bolus

2. Laudanosine toxicity

• Crosses BBB
• Can cause:
• Seizures (rare in ICU dosing)

 More concern with:

• Prolonged infusion
• Hepatic failure (accumulation)

3. Prolonged paralysis

• Hypothermia
• Acidosis
• Drug interactions

4. ICU-acquired weakness (with prolonged use)

 8. Drug Interactions

Potentiation of block:

• Aminoglycosides (e.g., amikacin)
• Magnesium sulfate
• Calcium channel blockers
• Volatile anesthetics

Resistance:

• Chronic anticonvulsants
• Burns (>48 hrs)
• Critical illness (variable)

 9. Reversal

Options:

1. Neostigmine + Glycopyrrolate
2. Spontaneous recovery (due to Hofmann elimination)

 Sugammadex  NOT effective (works only for aminosteroids like rocuronium)

 10. Atracurium vs Cisatracurium

Cisatracurium = stereoisomer → cleaner drug