For rapid‑sequence intubation in adults and children, especially those with hepatic or renal impairment, what is the recommended atracurium dose, onset time, duration of paralysis, contraindications, and reversal strategy?

Atracurium for Rapid-Sequence Intubation and Neuromuscular Blockade

Atracurium is an intermediate-acting neuromuscular blocker that is particularly advantageous in patients with hepatic or renal impairment because it undergoes organ-independent elimination via Hofmann degradation and ester hydrolysis, making dose adjustments unnecessary regardless of organ function. 1

Recommended Dosing

Initial Intubating Dose

• Standard dose: 0.4–0.5 mg/kg IV produces maximum neuromuscular block within 3–5 minutes, with good to excellent intubation conditions achieved within 2–2.5 minutes in most patients 2, 3
• The ED95 (dose producing 95% twitch suppression) is 0.2–0.23 mg/kg; intubating doses are typically 2× ED95 2, 3
• Do not modify the initial dose in renal or hepatic failure patients—the usual dose ensures effective concentrations during intubation 1

Maintenance Dosing

• 0.08–0.10 mg/kg IV for maintenance, typically required 20–45 minutes after the initial dose 2
• Subsequent maintenance doses are usually needed at approximately 15–25 minute intervals 2
• No cumulative effect occurs with repeated dosing if recovery is allowed to begin prior to repeat administration 1, 2, 3

Continuous Infusion (ICU Setting)

• Not typically used for rapid-sequence intubation, but for sustained paralysis in critically ill patients 1
• Fixed infusion rates of 1 mg/kg/hr have been studied in ARDS patients 4

Onset and Duration

Onset Time

• 3–5 minutes to maximum block after 0.4–0.5 mg/kg 2
• 2–2.5 minutes for intubation conditions in most patients 2
• Onset is slower than succinylcholine or rocuronium, making atracurium not ideal for true rapid-sequence intubation when compared to these alternatives 5

Duration of Paralysis

• Recovery begins at 20–35 minutes after initial dose under balanced anesthesia 2
• Recovery to 25% of control: 35–45 minutes 2
• 95% recovery: 60–70 minutes after injection 2
• Duration is approximately one-third to one-half that of pancuronium or d-tubocurarine 2
• Recovery proceeds more rapidly than with long-acting agents once it begins 2

Special Populations

Renal and Hepatic Impairment

• Atracurium is the optimal choice for patients with renal or hepatic failure because approximately 50% is eliminated by organ-independent Hofmann elimination and ester hydrolysis 1, 6
• Pharmacokinetics and pharmacodynamics remain similar in patients with and without kidney or liver failure 1, 7
• No dose adjustment required even in anephric patients 1, 7
• No evidence of cumulation even with repeated doses over 2.5 hours in patients with no renal function 7

Laudanosine Accumulation Concerns

• Laudanosine, a breakdown product of Hofmann elimination, accumulates in renal failure but does not reach concentrations causing adverse effects even after infusions up to 72 hours 1
• Only one case report exists of a surgical patient having a seizure while receiving atracurium 1
• In patients with renal impairment receiving prolonged infusions, laudanosine concentrations can exceed 10 mcg/mL, though no seizures were recorded in studies 4
• Exercise caution with extremely high doses or prolonged infusions in hepatic failure, as laudanosine is metabolized by the liver 1

Elderly Patients

• Slightly altered pharmacokinetics with decreased total plasma clearance offset by increased volume of distribution 2
• No significant difference in clinical duration or recovery compared to younger patients—no dose adjustment needed 2

Obese Patients

• Dose based on total body weight, not ideal body weight 8
• Higher median effective concentrations in obese patients (470 ng/mL vs 312 ng/mL in non-obese), but recovery time remains similar 8

Contraindications and Precautions

Absolute Contraindications

• Known hypersensitivity to atracurium or benzylisoquinolinium compounds 2

Relative Contraindications and Cautions

• Histamine release at higher doses (≥0.5 mg/kg): can cause arterial pressure decrease (13–20%) and heart rate increase (5–8%) 2, 3
• Minimal histamine release at doses up to 0.4 mg/kg 1, 2
• Less histamine release than d-tubocurarine or metocurine, but more than cisatracurium 1
• Avoid in patients with severe asthma or bronchospasm risk due to potential mast cell degranulation 1

Drug Interactions

• Potent inhalation anesthetics enhance neuromuscular blockade: isoflurane and enflurane increase potency by ~35%; halothane by ~20% 2
• Consider dose reduction (approximately 30–35%) when using volatile anesthetics 2

Reversal Strategy

Timing of Reversal

• Reversal can usually be attempted 20–35 minutes after initial dose of 0.4–0.5 mg/kg under balanced anesthesia 2
• 10–30 minutes after maintenance dose of 0.08–0.10 mg/kg, when recovery of muscle twitch has started 2
• Do not attempt reversal at deep levels of block—this increases risk of residual neuromuscular blockade 2

Reversal Agents

• Anticholinesterase agents: neostigmine, edrophonium, or pyridostigmine 1, 2
• Must be combined with anticholinergic agent: atropine or glycopyrrolate 1, 2
• Complete reversal usually attained within 8–10 minutes of administering reversing agents 2
• Sugammadex is NOT effective for atracurium reversal—it only reverses steroidal neuromuscular blockers (rocuronium, vecuronium) 1, 6

Monitoring

• Train-of-four (TOF) monitoring is essential to assess degree of muscle relaxation and guide reversal timing 1, 2
• Rare instances of breathing difficulties related to incomplete reversal have been reported 2
• Inadequate doses of reversal agents increase risk of residual block 2

Clinical Algorithm for Atracurium Use

For Rapid-Sequence Intubation

1. Consider alternatives first: Succinylcholine or rocuronium provide faster onset for true rapid-sequence scenarios 5
2. If atracurium is chosen (e.g., renal/hepatic failure):
   • Administer 0.4–0.5 mg/kg IV bolus 2
   • Expect intubation conditions in 2–2.5 minutes 2
   • No dose adjustment for organ dysfunction 1

For Elective Intubation with Renal/Hepatic Impairment

1. Atracurium is the preferred agent 1, 6
2. Administer 0.4–0.5 mg/kg IV 2
3. Monitor with TOF stimulation 1, 2
4. Maintenance: 0.08–0.10 mg/kg every 15–25 minutes as needed 2

For Prolonged Paralysis (ICU)

1. Consider cisatracurium instead—more potent with less laudanosine generation 1
2. If using atracurium: bolus 0.4–0.5 mg/kg, then maintenance doses 1
3. Monitor TOF continuously 1
4. Be aware of laudanosine accumulation in renal impairment with prolonged use 4

Common Pitfalls to Avoid

• Do not use atracurium for true rapid-sequence intubation when succinylcholine or rocuronium are available and not contraindicated—onset is too slow 5
• Do not reduce initial dose in renal/hepatic failure—this compromises intubation conditions 1
• Do not attempt reversal too early—wait for spontaneous recovery to begin 2
• Do not use sugammadex to reverse atracurium—it is ineffective for benzylisoquinolinium compounds 1, 6
• Monitor for histamine release at doses ≥0.5 mg/kg, especially in patients with cardiovascular instability 2, 3
• Reduce dose by 30–35% when using potent volatile anesthetics 2