What is the dosage and administration of Atracurium (non-depolarizing neuromuscular blocking agent) for a typical adult patient with potential renal or hepatic impairment undergoing surgery?

Atracurium: Comprehensive Clinical Overview

Mechanism of Action and Pharmacokinetics

Atracurium is a benzylisoquinolinium non-depolarizing neuromuscular blocking agent that competitively binds to cholinergic receptors at the motor end plate, with the unique advantage of organ-independent elimination through ester hydrolysis and Hofmann elimination. 1

• This dual elimination pathway means renal or hepatic dysfunction does not affect the duration of blockade, making atracurium particularly valuable in patients with organ failure 1
• Laudanosine, a breakdown product of Hofmann elimination, is metabolized by the liver and has been associated with CNS excitation at extremely high doses, though clinical seizures are exceedingly rare (only one reported case in surgical patients) 1
• In hepatic failure, laudanosine can accumulate, but even after infusions up to 72 hours, concentrations do not reach levels causing adverse effects 1

Dosing and Administration

Standard Adult Dosing

For intubation and initial paralysis, administer atracurium 0.4-0.5 mg/kg IV, which produces maximum neuromuscular block within 3-5 minutes and clinically required block lasting 20-35 minutes under balanced anesthesia. 2

• An alternative initial dose of 0.3-0.4 mg/kg given slowly or in divided doses over one minute is recommended for patients with significant cardiovascular disease or history suggesting greater risk of histamine release 2
• Maintenance doses of 0.08-0.10 mg/kg are required 20-45 minutes after initial injection, with subsequent doses administered at approximately 15-25 minute intervals under balanced anesthesia 2
• Recovery to 25% of control occurs approximately 35-45 minutes after injection, with 95% recovery at approximately 60 minutes 2

Continuous Infusion Protocol

After an initial bolus of 0.3-0.5 mg/kg, initiate continuous infusion at 9-10 mcg/kg/min to counteract spontaneous recovery, then reduce to 5-9 mcg/kg/min for maintenance (range 2-15 mcg/kg/min based on individual response). 2

• In the ICU setting, infusion rates of 11-13 mcg/kg/min (range 4.5-29.5 mcg/kg/min) provide adequate neuromuscular block in adults 2
• Continuous infusion provides readily controllable blockade for prolonged procedures (128-233 minutes studied), with full spontaneous recovery in mean time of 42.2 minutes after discontinuation 3
• Train-of-four (TOF) monitoring is mandatory to optimize dosing and minimize overdose risk 1, 4

Pediatric Dosing

No dosage adjustments are required for children ≥2 years of age; use standard adult doses of 0.4-0.5 mg/kg. 2

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

Special Populations

Renal and Hepatic Impairment

Atracurium is the preferred neuromuscular blocking agent in renal or hepatic failure due to its organ-independent elimination, and no initial dose adjustment is required. 1, 4

• The pharmacokinetic and pharmacodynamic profiles are similar in patients with and without kidney and liver failure 1
• Do not modify the initial dose in renal/hepatic failure patients to ensure effective concentrations during intubation 1
• Atracurium has a strong recommendation (GRADE 2+) over other muscle relaxants in this population 1

Following Succinylcholine

After succinylcholine for intubation, reduce the initial atracurium dose to 0.3-0.4 mg/kg under balanced anesthesia, and permit the patient to recover from succinylcholine effects before atracurium administration. 2

• Further reductions may be necessary with potent inhalation anesthetics 2

Interaction with Inhalation Anesthetics

Atracurium is potentiated by isoflurane and enflurane; reduce the initial dose by approximately one-third (to 0.25-0.35 mg/kg) if administered under steady-state of these agents. 2

• With halothane, which has only marginal (approximately 20%) potentiating effect, smaller dosage reductions may be considered 2
• During continuous infusion, reduce the rate by approximately one-third in the presence of steady-state enflurane or isoflurane; smaller reductions with halothane 2

Monitoring Requirements

Use peripheral nerve stimulator with train-of-four (TOF) monitoring continuously to optimize dosing, minimize overdose, and evaluate recovery. 1, 4

• TOF monitoring is the most reliable method for evaluating degree of neuromuscular blockade 4
• Target TOF count of 1-2 twitches out of 4 for adequate paralysis 4
• Recovery is defined as TOF ratio >0.7, typically occurring within 34-85 minutes after discontinuation, independent of organ function 1, 4

Reversal

Reversal with neostigmine is prompt and adequate; administer neostigmine 40 mcg/kg with atropine 20 mcg/kg when spontaneous recovery begins. 5, 6

• Induced reversal with neostigmine shortens recovery time to mean of 16.4 minutes compared to 42.2 minutes for spontaneous recovery 3
• Continue quantitative TOF monitoring after neostigmine administration until TOF ratio ≥0.9 is achieved 5

Cardiovascular Effects and Histamine Release

Atracurium has minimal cardiovascular adverse effects at standard doses but is associated with histamine release at higher doses, which can cause hemodynamic instability. 1, 7

• No evidence of important changes in heart rate or arterial pressure using simple clinical means at recommended doses 6
• For patients with cardiovascular disease or asthma history, use reduced initial dose of 0.3-0.4 mg/kg given slowly over one minute 2

Critical Safety Considerations for Prolonged Use

Implement daily drug holidays (stopping NMBAs until clinical condition necessitates restart) to decrease the incidence of acquired quadriplegic myopathy syndrome (AQMS), particularly in patients receiving corticosteroids. 4

• Discontinue neuromuscular blockade as soon as clinically feasible to minimize complications 4
• For patients receiving both NMBAs and corticosteroids, make every effort to discontinue as soon as possible due to increased risk of prolonged weakness and myopathy 4
• Prolonged weakness has been reported following atracurium use 1

Comparison with Cisatracurium

Cisatracurium, an isomer of atracurium, is increasingly preferred for prolonged use because it produces significantly less histamine release and generates lower laudanosine concentrations (peak 16-21 ng/mL vs higher with atracurium). 1, 4

• Cisatracurium has few, if any, cardiovascular effects and lesser tendency for mast cell degranulation 1
• Both agents have similar recovery times (34-85 minutes to TOF ratio >0.7) 1
• No mandatory waiting period is required when switching from atracurium to cisatracurium; transition can occur once TOF monitoring shows reappearance of twitches 5

Lack of Cumulative Effects

Atracurium demonstrates no cumulative effects with repeated administration, allowing maintenance doses at relatively regular intervals. 2, 8

• Incremental doses of 0.2 mg/kg provide relaxation for approximately 30 minutes without evidence of cumulation 6
• This consistent response pattern distinguishes atracurium from other competitive blocking agents 9