Understanding Atracurium and Its Mechanism
Atracurium is a non-depolarizing neuromuscular blocking agent (NMBA) used in medical settings to cause muscle relaxation, often to facilitate endotracheal intubation and mechanical ventilation [1.7.1]. It functions by competing with acetylcholine at the neuromuscular junction, preventing muscle contraction [1.7.1].
One of its defining characteristics is its unique metabolism. Atracurium is primarily broken down in the plasma through two processes: ester hydrolysis by non-specific enzymes and a chemical process called Hofmann elimination [1.4.1]. This degradation is dependent on the body's pH and temperature rather than organ function, making atracurium a preferred agent in critically ill patients who may have renal or hepatic dysfunction [1.4.1, 1.4.5]. However, this metabolism is not without consequence, as it produces metabolites like laudanosine [1.4.1].
The Primary Prolonged Effect: Muscle Weakness and Myopathy
The most significant prolonged effect associated with atracurium infusion is profound and lasting muscle weakness [1.3.2, 1.3.3]. While atracurium was initially thought to have a lower risk of this complication compared to other NMBAs like pancuronium and vecuronium, numerous reports have confirmed its occurrence [1.2.1, 1.2.2].
ICU-Acquired Weakness (ICUAW)
Prolonged immobility from neuromuscular blockade is a major risk factor for ICU-acquired weakness (ICUAW) [1.2.6]. This broad term encompasses several conditions:
- Critical Illness Myopathy (CIM): An acute necrotizing myopathy that causes weakness [1.3.6]. The combination of atracurium with corticosteroids has been strongly associated with the development of CIM [1.2.1, 1.3.6].
- Critical Illness Polyneuropathy (CIP): This condition affects the peripheral nerves, leading to weakness, with distal muscles often more affected than proximal ones [1.7.5].
- Critical Illness Neuromyopathy (CINM): A combination of both myopathy and neuropathy [1.2.6].
These conditions can significantly complicate a patient's recovery, prolonging the need for mechanical ventilation and extending the length of their hospital stay [1.7.6]. The risk of developing prolonged weakness is estimated to be 5–10% if NMBAs are used for more than 24 hours [1.3.4].
Residual Paralysis
Even after short-term use, residual paralysis—also known as postoperative residual curarization (PORC)—is a documented problem [1.8.2, 1.8.3]. This is a state where muscle function has not fully returned to baseline before tracheal extubation, increasing the risk of adverse pulmonary events, upper airway obstruction, and pneumonia [1.2.6, 1.8.3]. Studies have shown a high incidence of PORC, with one report finding 65% of patients having a train-of-four (TOF) ratio of ≤0.7 at extubation [1.8.2]. Shorter surgical duration was identified as a key predictor for PORC, possibly due to work pressures leading to inappropriately early extubation [1.8.2].
The Role of Metabolites: Laudanosine
A primary metabolite from the Hofmann elimination of atracurium is laudanosine [1.4.1]. Unlike atracurium, laudanosine is eliminated by the liver and kidneys and has a much longer half-life (approximately 197 minutes vs. 20 minutes for atracurium) [1.4.1, 1.4.3]. During prolonged infusions, laudanosine can accumulate, particularly in patients with hepatic or renal failure [1.4.3].
Laudanosine can cross the blood-brain barrier and act as a central nervous system stimulant [1.4.1, 1.4.3]. While rare, high plasma concentrations have been linked to seizures in animal studies and are a theoretical risk in ICU patients receiving long-term infusions, especially those with pre-existing conditions like head trauma or uremia [1.2.5].
Atracurium vs. Other NMBAs
| Feature | Atracurium | Cisatracurium | Vecuronium |
|---|---|---|---|
| Metabolism | Hofmann elimination & ester hydrolysis; organ-independent [1.4.1]. | Primarily Hofmann elimination; organ-independent [1.4.7]. | Primarily hepatic; has active metabolites [1.3.7]. |
| Prolonged Weakness | Documented, especially with corticosteroids [1.2.1, 1.3.4]. | Lower risk of prolonged weakness reported [1.7.2]. | Higher association with prolonged weakness [1.3.7, 1.5.1]. |
| Laudanosine Production | Produces laudanosine [1.4.1]. | Produces less laudanosine than atracurium [1.7.2]. | Does not produce laudanosine [1.3.7]. |
| Histamine Release | Can cause histamine release, especially at high doses [1.2.5, 1.4.3]. | Minimal histamine release, better cardiovascular stability [1.5.6, 1.7.2]. | No significant histamine release [1.5.4]. |
| Clinical Outcome (ARDS) | Not specified. | Associated with fewer ventilator and ICU days compared to vecuronium in some studies [1.5.1]. | Not specified. |
Minimizing Prolonged Effects: Monitoring and Management
To mitigate the risk of prolonged effects, careful monitoring is essential. The use of a peripheral nerve stimulator to assess the depth of neuromuscular blockade via a train-of-four (TOF) stimulation pattern is the standard of care [1.6.2, 1.6.3]. This quantitative monitoring is recommended over relying on clinical signs alone, which are not accurate determinants of recovery [1.6.2, 1.6.4]. Guidelines recommend confirming a TOF ratio of ≥0.9 before extubation to avoid residual paralysis [1.6.4]. Continuous assessment of respiratory status, blood pressure, and heart rate is also crucial [1.6.1].
Conclusion
While atracurium offers the advantage of organ-independent metabolism, its prolonged use is not without risk. The primary concerns are prolonged muscle weakness, the development of ICU-acquired weakness (especially when combined with corticosteroids), and postoperative residual paralysis [1.2.1, 1.8.2]. Furthermore, the accumulation of its metabolite, laudanosine, presents a theoretical risk of CNS stimulation and seizures [1.2.5]. These potential complications underscore the critical importance of continuous neuromuscular monitoring and individualized dosing to ensure patient safety and facilitate a timely recovery.
