What is the role of cisatracurium in the management of Acute Respiratory Distress Syndrome (ARDS)?

Role of Cisatracurium in the Management of ARDS

Cisatracurium should be administered as a continuous IV infusion early in the course of ARDS for patients with a PaO2/FiO2 ratio less than 150 mmHg, particularly during the first 48 hours of mechanical ventilation. 1

Indications and Benefits

• Cisatracurium is indicated as an adjunct to facilitate mechanical ventilation in ICU patients with ARDS 2
• Early administration of cisatracurium (within the first 48 hours) in moderate-to-severe ARDS (PaO2/FiO2 < 150 mmHg) may reduce mortality compared to no neuromuscular blockade 1
• A 48-hour continuous infusion of cisatracurium has been shown to reduce 28-day mortality, hospital mortality, and barotrauma without increasing ICU-acquired weakness 1
• The number needed to treat with a 48-hour cisatracurium infusion to save one additional life is approximately eight patients, assuming a baseline mortality rate of 45% for ARDS patients 1

Mechanism of Action and Benefits

• Cisatracurium prevents ventilator asynchrony, which may decrease airway pressures and lung stress 1
• By maintaining expiratory transpulmonary pressure, cisatracurium can prevent expiratory efforts causing derecruitment 1
• Cisatracurium may have anti-inflammatory properties by blocking the nicotinic acetylcholine receptor 1
• Compared to other neuromuscular blocking agents, cisatracurium has minimal cardiovascular effects and does not cause clinically significant tachycardia 1

Dosing and Administration

• Cisatracurium should be administered as a continuous IV infusion for 48 hours in the early phase of ARDS 1
• Train-of-four (TOF) titration may be more effective than fixed dosing, resulting in improved oxygenation while using approximately 60% less medication 3
• Consider administering additional boluses when plateau airway pressures exceed 32 cmH2O 1

Patient Selection

• Most appropriate for patients with moderate-to-severe ARDS (PaO2/FiO2 < 150 mmHg) 1
• Particularly beneficial in patients with the most severe hypoxemia (PaO2/FiO2 < 120 mmHg) 4
• Should be considered when patients require deep sedation to facilitate lung-protective ventilation or prone positioning 1
• May be especially useful when plateau airway pressures exceed 30-35 cmH2O despite optimal ventilator settings 1

Recent Evidence and Controversies

• While earlier studies showed mortality benefit, the most recent large RCT (ROSE trial) comparing cisatracurium versus light sedation showed no mortality difference 1
• Current evidence suggests that neuromuscular blockade may be more beneficial when compared with deep sedation strategies rather than light sedation strategies 1
• The 2024 American Thoracic Society clinical practice guideline suggests using neuromuscular blockade in patients with early severe ARDS (conditional recommendation, low certainty) 1
• The 2020 ICM Rapid Practice Guideline does not support early routine use of NMBA infusion in ARDS of any severity but considers it a reasonable option for patients requiring deep sedation to facilitate lung-protective ventilation or prone positioning 1

Comparison with Other Neuromuscular Blocking Agents

• Most clinical trials showing mortality benefit have used cisatracurium specifically 1
• Observational data comparing cisatracurium to vecuronium found no difference in mortality but showed that cisatracurium was associated with fewer ventilator days and ICU days 5
• A small study comparing cisatracurium to atracurium found no significant differences in oxygenation improvement, ventilator-free days, ICU length of stay, or mortality 6
• Cisatracurium has favorable pharmacological properties compared to other agents, including minimal cardiovascular effects and no histamine release 7

Potential Adverse Effects and Monitoring

• Neuromuscular blockade requires sustained deep sedation, which may have its own adverse effects 1
• Prolonged use may be associated with ICU-acquired weakness, particularly when used with corticosteroids or in patients with hyperglycemia 4
• Current evidence suggests that a 48-hour infusion of cisatracurium does not increase the risk of ICU-acquired weakness compared to no neuromuscular blockade 1
• Regular monitoring of neuromuscular function is recommended, with TOF monitoring being preferred over fixed dosing 3

Implementation in Clinical Practice

• Cisatracurium should be used as part of a comprehensive ARDS management strategy that includes lung-protective ventilation (4-8 ml/kg PBW tidal volumes, plateau pressure <30 cmH2O) 8
• Consider as an adjunct to other evidence-based strategies such as higher PEEP and prone positioning in severe ARDS 8
• Sedation should be reduced and partial ventilator support can be used once gas exchange, respiratory mechanics, and hemodynamic status have improved 1