What is the appropriate dosing and preparation of an atracurium infusion for an adult ICU patient with acute respiratory failure requiring neuromuscular blockade?

Atracurium Infusion Dosing and Preparation for Acute Respiratory Failure in ICU

For ICU patients with acute respiratory failure requiring neuromuscular blockade, current evidence does not support routine early use of continuous atracurium infusion; however, if deep sedation is required to facilitate lung-protective ventilation or prone positioning, atracurium can be administered as a 0.4-0.5 mg/kg IV bolus followed by continuous infusion at 0.6 mg/kg/hr (10 μg/kg/min), titrated to train-of-four (TOF) monitoring with a target of 1-2 twitches. 1, 2

Current Guideline Recommendations for ARDS

The 2020 Intensive Care Medicine guidelines fundamentally changed practice after the ROSE trial (n=1006 patients):

• Routine continuous NMBA infusions are NOT recommended for adults with ARDS of any severity 1
• Avoid continuous NMBA infusion in patients managed with lighter sedation strategies 1
• For patients requiring deep sedation to facilitate lung-protective ventilation or prone positioning who need neuromuscular blockade, a 48-hour NMBA infusion is a reasonable option 1

This represents a significant shift from older 2002 guidelines that suggested more liberal use of NMBAs in ARDS 1

Atracurium Dosing Protocol

Initial Bolus Dose

• Standard dose: 0.4-0.5 mg/kg IV bolus produces intubation conditions in 2-2.5 minutes with maximum block at 3-5 minutes 2
• For cardiovascular instability or histamine concerns: 0.3-0.4 mg/kg given slowly over 1 minute or in divided doses 2
• Do NOT administer before unconsciousness is induced 2

Continuous Infusion Dosing

• Standard infusion rate: 0.6 mg/kg/hr (10 μg/kg/min) 3
• Alternative dosing from research: 1 mg/kg/hr provided effective paralysis in ARDS patients over 72 hours 4, 5
• Titrate to TOF response: Target 1-2 twitches out of 4 3
• Infusion range: 0.4-0.8 mg/kg/hr based on TOF monitoring 1

Preparation Instructions

1. Atracurium comes as 10 mg/mL solution 2
2. Example preparation for 70 kg patient:
   • Bolus: 28-35 mg (2.8-3.5 mL) IV push
   • Infusion: 42 mg/hr = Mix 420 mg (42 mL) in 100 mL NS = run at 10 mL/hr
3. Do NOT mix with alkaline solutions (e.g., barbiturates) in same syringe 2
4. Administer via dedicated IV line when possible 2

Mandatory Monitoring Requirements

TOF monitoring with peripheral nerve stimulator is absolutely essential to optimize dosing and prevent overdose 1, 3, 2:

• Monitor continuously throughout infusion 3, 6
• Target: 1-2 twitches out of 4 for adequate paralysis 3
• Recovery defined as TOF ratio >0.7 (typically 34-85 minutes after discontinuation) 3, 7
• After reversal, continue monitoring until TOF ratio ≥0.9 3

Special Populations in Respiratory Failure

Renal Impairment

• Atracurium is preferred due to organ-independent elimination via Hofmann degradation and ester hydrolysis 3, 6
• No dose adjustment required for renal failure 6
• Caution: Laudanosine (metabolite) can accumulate with renal impairment, potentially reaching >10 μg/mL with prolonged infusions 4
• Consider switching to cisatracurium (produces less laudanosine: 16-21 ng/mL vs higher with atracurium) for prolonged use in renal failure 3

Hepatic Failure

• Atracurium is the agent of choice as metabolism is independent of liver function 3
• No dose modification required 3
• Laudanosine is metabolized by liver and may accumulate, but clinical seizures are rare 1, 3

Critical Safety Considerations

Duration of Therapy

• Limit infusion to 48 hours when possible based on ARDS guideline recommendations 1
• Implement daily drug holidays: Stop NMBA until clinical condition necessitates restart to decrease risk of ICU-acquired weakness 3, 6
• Discontinue as soon as clinically feasible 3, 6

Concurrent Corticosteroid Use

• High risk of prolonged weakness and myopathy when NMBAs combined with corticosteroids 3, 6
• Make every effort to discontinue NMBAs as soon as possible in this population 3, 6

Resistance and Tachyphylaxis

• Progressively increasing requirements may indicate resistance (documented cases requiring up to 3.57 mg/kg/hr) 8
• Cross-resistance can occur between atracurium and vecuronium 8
• Consider switching to alternative agent (doxacurium) if tachyphylaxis develops 1

Recovery and Reversal

Expected Recovery Time

• Spontaneous recovery: 31-96 minutes (median 45 minutes) after stopping 72-hour infusion 4
• Recovery to 25% control: 35-45 minutes 2
• 95% recovery: approximately 60 minutes 2

Reversal Protocol

• Neostigmine 0.04 mg/kg + atropine 0.02 mg/kg 3
• Only attempt reversal when TOF shows at least 2-4 twitches present 3
• Continue TOF monitoring until ratio ≥0.9 3

Common Pitfalls to Avoid

1. Starting continuous infusion without clear indication: Use only when deep sedation required for lung-protective ventilation or prone positioning 1
2. Failure to use TOF monitoring: This is mandatory, not optional 1, 3, 2
3. Prolonged use beyond 48 hours without reassessment: Increases myopathy risk 1, 3
4. Mixing with alkaline solutions: Causes drug incompatibility 2
5. Inadequate sedation before administration: Always induce unconsciousness first 2