What is the recommended dosing regimen of atracurium for skeletal‑muscle paralysis, including intubating dose and maintenance infusion, and how should the dose be adjusted for elderly, frail or debilitated patients, renal or hepatic impairment, and relevant contraindications?

Atracurium Dosing for Skeletal Muscle Paralysis

Intubating Dose

The recommended initial dose of atracurium for intubation is 0.4 to 0.5 mg/kg IV bolus, which produces good to excellent intubation conditions within 2 to 2.5 minutes and maximum neuromuscular block within 3 to 5 minutes. 1

• This dose represents 1.7 to 2.2 times the ED95 (0.23 mg/kg) 1
• Clinically required neuromuscular block lasts 20 to 35 minutes under balanced anesthesia 1
• Recovery to 25% of control occurs at approximately 35 to 45 minutes, with 95% recovery at 60 to 70 minutes 1

Reduced Initial Dosing for High-Risk Patients

For patients with significant cardiovascular disease, history of severe anaphylactoid reactions, asthma, or following succinylcholine use, reduce the initial dose to 0.3 to 0.4 mg/kg given slowly or in divided doses over one minute. 1

• This reduced dose minimizes histamine release and cardiovascular instability 1
• Dosage reductions must also be considered in patients with neuromuscular disease, severe electrolyte disorders, or carcinomatosis 1

Maintenance Dosing

Intermittent Bolus Technique

Maintenance doses of 0.08 to 0.10 mg/kg are recommended during prolonged surgical procedures, typically required at 15 to 25 minute intervals under balanced anesthesia. 1

• The first maintenance dose is generally required 20 to 45 minutes after the initial injection 1
• Higher doses (up to 0.2 mg/kg) permit maintenance dosing at longer intervals 1
• Atracurium lacks cumulative effects, allowing maintenance doses at relatively regular intervals with predictable results 1

Continuous Infusion Technique

After an initial bolus of 0.3 to 0.5 mg/kg, begin continuous infusion at 9 to 10 mcg/kg/min to rapidly counteract spontaneous recovery, then reduce to 5 to 9 mcg/kg/min for maintenance. 1

• Initiate infusion only after early evidence of spontaneous recovery from the bolus dose 1
• Occasional patients may require rates as low as 2 mcg/kg/min or as high as 15 mcg/kg/min 1
• Use a precision infusion device and adjust according to train-of-four (TOF) monitoring 1
• Target TOF count of 1-2 twitches out of 4 for adequate paralysis 2, 3

Dose Adjustments for Inhalational Anesthetics

Reduce the initial atracurium dose by approximately one-third (to 0.25 to 0.35 mg/kg) when administered under steady-state isoflurane or enflurane anesthesia. 1

• Isoflurane and enflurane increase atracurium potency by approximately 35% and prolong neuromuscular block 1
• With halothane, which has only a marginal 20% potentiating effect, smaller dosage reductions may be considered 1
• Reduce infusion rates by approximately one-third for patients receiving inhalation anesthesia 1

Special Populations

Elderly, Frail, or Debilitated Patients

No dose adjustment is required for elderly patients, as clinical duration and recovery from neuromuscular block show no significant difference compared to younger patients. 1

• Elderly patients may have slightly decreased total plasma clearance offset by increased volume of distribution, resulting in no net clinical effect 1

Renal Impairment

No dose adjustment is required for patients with renal disease, including severe renal impairment (GFR <15 mL/min), as atracurium's duration of neuromuscular block does not correlate with renal function. 1, 4

• Atracurium is eliminated via organ-independent pathways: Hofmann elimination and ester hydrolysis 3, 5, 1
• Recovery to TOF ratio >0.7 occurs within 34-85 minutes after discontinuation, independent of renal function 3, 5
• Critical caveat: Laudanosine, a breakdown product, can accumulate in renal impairment, particularly with prolonged infusions (>72 hours) 3, 6
• In patients with renal impairment receiving prolonged infusions, laudanosine concentrations may exceed 10 mcg/mL 6

Hepatic Impairment

No modification of the initial dose is required for patients with hepatic failure, as atracurium has similar pharmacokinetic and pharmacodynamic profiles regardless of liver function. 3

• Atracurium's organ-independent elimination ensures predictable duration of action in liver failure 3
• Important caveat: Laudanosine is metabolized by the liver and can accumulate in hepatic failure 3
• For grade V liver injury, continuous infusion is preferred over intermittent bolus dosing to maintain stable neuromuscular blockade while minimizing total drug exposure 3

Morbidly Obese Patients

Dose atracurium based on ideal body weight (0.5 mg/kg IBW), not total body weight, in morbidly obese patients. 7

• Dosing on ideal body weight results in predictable muscle relaxation with adequate intubation conditions and recovery within 60 minutes without need for reversal 7
• Dosing on total body weight causes dose-dependent prolongation of action with 70% of patients requiring neostigmine reversal 7
• This recommendation applies to patients with body weights ranging from 112 to 260 kg 7

Pediatric Patients

No dose adjustment is required for children aged 2 years or older; use standard adult dosing. 1

• For infants (1 month to 2 years) under halothane anesthesia, use 0.3 to 0.4 mg/kg as the initial dose 1
• Maintenance doses may be required with slightly greater frequency in infants and children than in adults 1

Mandatory Monitoring Requirements

Use a peripheral nerve stimulator with quantitative train-of-four (TOF) monitoring throughout atracurium administration to optimize dosing, minimize overdose risk, and evaluate recovery. 8, 2, 1

• TOF monitoring is mandatory for all patients receiving neuromuscular blockade 2, 3, 5
• Continue monitoring after reversal until TOF ratio ≥0.9 is achieved 8, 2
• Recovery is defined as TOF ratio >0.7 3, 5

Reversal of Neuromuscular Block

Reversal can be attempted approximately 20 to 35 minutes after an initial dose of 0.4 to 0.5 mg/kg, or 10 to 30 minutes after a maintenance dose, when recovery of muscle twitch has started. 1

• Use neostigmine 0.04 mg/kg (40 mcg/kg) with atropine 0.02 mg/kg (20 mcg/kg) for reversal 8, 2
• Complete reversal is usually attained within 8 to 10 minutes of administering reversing agents 1
• Critical pitfall: Reversal should only be attempted when TOF count shows reappearance of at least 2-4 twitches 8
• Attempting reversal at deep levels of block or using inadequate doses increases the risk of residual neuromuscular block 1

Safety Considerations and Contraindications

Prolonged Use Precautions

Implement daily drug holidays (stopping atracurium until clinical condition necessitates restart) to decrease the incidence of acquired quadriplegic myopathy syndrome (AQMS), particularly in patients receiving corticosteroids. 2, 3, 5

• Both atracurium and cisatracurium carry risk of prolonged weakness when combined with corticosteroids 2
• Discontinue neuromuscular blockade as soon as clinically feasible 2, 3, 5

Administration Precautions

Do not administer atracurium by intramuscular injection, as this may result in tissue irritation. 1

• Atracurium should not be administered before unconsciousness has been induced 1
• Do not mix atracurium in the same syringe or administer simultaneously through the same needle with alkaline solutions (e.g., barbiturate solutions) 1

Histamine Release

Histamine release is minimal with initial doses up to 0.5 mg/kg, but atracurium is a less potent histamine releaser than d-tubocurarine or metocurine. 1

• For patients at higher risk of histamine-related reactions, use the reduced initial dose of 0.3 to 0.4 mg/kg given slowly 1