Pulmonary Disorders I

was not exclusively conducted in ARDS patients, subgroup analysis in ARDS was planned a priori.

In the ARDS subgroup, no differences in mortality, mechanical ventilation duration, or ICU length

of stay were observed between treatment arms. However, it must be noted that the sample size of

ARDS patients in the intervention (n=19) and standard of care (n=11) study groups was very small,

which may limit clinical interpretation for this patient population.

NMBAs

against routine use of NMBAs, the 2024 ATS guidelines do recommend NMBAs in severe ARDS

(P/F ratio less than 100 mm Hg) within 48 hours of ARDS onset with no recommendation for later

Early administration (within 48 hours of ARDS onset) of cisatracurium over 48 hours has consistently

improved oxygenation without increasing the risk of neuromuscular weakness.

The ACURASYS trial showed decreased 90-day adjusted mortality with cisatracurium compared

with placebo (HR 0.68; 95% CI, 0.48–0.98; p=0.04). Subgroup analysis suggested the greatest

mortality benefit in patients with ARDS having a Pao2/Fio2 less than 120 mm Hg. Cisatracurium was

also associated with significantly more ventilator-free days (up to 28 and 90 days) and organ failure–

free days (up to 28 days). Cisatracurium did not significantly increase the risk of ICU-acquired

(42.5%) and placebo (42.8%) (between-group difference -0.3 percentage points; 95% CI, -6.4 to

5.9; p=0.93). No differences between study groups were found for secondary end points at day 28,

including in-hospital mortality, days free of MV, and days not in the ICU or hospital (N Engl J Med

2019;380:1997-2008).

The optimal strategy for NMBA dosing and monitoring in ARDS remains debatable. The

ACURASYS and ROSE trials had similar dosing strategies of a cisatracurium 15-mg bolus followed

by continuous infusion at 37.5 mg/hour over 48 hours without titration or train-of-four monitoring.

Additional boluses were allowed in patients with elevated plateau pressures (i.e., greater than 30

cm H2O), given concerns for increased risk of ventilator-induced lung injury. However, differing

sedation practices with non-paralyzed patients and lack of proning in the ROSE trial may account

for the differing results.

The ESICM 2023 clinical practice guidelines recommend against routine use of NMBAs in ARDS

CVP

(Recommended)

Pulmonary Artery Occlu-

sion Pressure (optional)

MAP ≥ 60 mm Hg AND No Vasoactive Support ≥ 12 Hr

Urinary Output < 0.5 mL/

kg/hr

Urinary Output ≥ 0.5 mL/

kg/hr

> 8

> 12

Administer furosemide and

reevaluate in 1 hr

Administer furosemide and

reevaluate in 4 hr

4–8

8–12

Administer fluid bolus and

reevaluate in 1 hr

Administer furosemide and

reevaluate in 4 hr

< 4

< 8

Administer fluid bolus and

reevaluate in 1 hr

Monitor and reevaluate in 4

hr

aInitial recommended furosemide dosing = 20-mg bolus or 3-mg/hr infusion. Recommended 2-fold incremental increase in subsequent furosemide doses up to a

maximum of 160-mg bolus/24-mg/hr infusion rate or until goal CVP/pulmonary artery occlusion pressure achieved. See clinical trial publication for further details.

CVP = central venous pressure; MAP = mean arterial pressure.