Reevaluation Of Systemic Early Neuromuscular Blockade
Condition: Acute Respiratory Distress Syndrome
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
Intervention: Cisatracurium Besylate
Intervention description: Patients randomized to the early neuromuscular blockade arm will receive a cisatracurium besylate bolus of 15 mg, followed by a continuous infusion of 37.5 mg/hour for 48 hours. Patients randomized to the control arm will receive no protocol specified neuromuscular blockade.
Intervention MeSH terms: Cisatracurium
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1008.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ARDS; neuromuscular blocker; cisatracurium

Summary:

      This study evaluates whether giving a neuromuscular blocker (skeletal muscle relaxant) to a
      patient with acute respiratory distress syndrome will improve survival. Half of the patients
      will receive a neuromuscular blocker for two days and in the other half the use of
      neuromuscular blockers will be discouraged.
    

Eligibility criteria:

        Inclusion Criteria

          1. Age > 18 years

          2. Presence of all of the following conditions for < 48 hours:

             i. PaO2/FiO2 < 150 with PEEP >/= 8 cm H2O OR, if ABG not available, SaO2/FiO2 ratio
             that is equivalent to a PaO2/FiO2 < 150 with PEEP >/= 8 cm H2O , and a confirmatory
             SaO2/FiO2 ratio that is again equivalent 1-6 hours later

        ii. Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules.

        iii. Respiratory failure not fully explained by cardiac failure or fluid overload; need
        objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk
        factor present.

        Patients must be enrolled within 48 hours of meeting inclusion criteria.

        Exclusion Criteria:

          1. Lack of informed consent

          2. Continuous neuromuscular blockade at enrollment

          3. Known pregnancy

          4. Currently receiving ECMO therapy

          5. Chronic respiratory failure defined as PaCO2 > 60 mm Hg in the outpatient setting

          6. Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for
             CPAP/BIPAP used solely for sleep-disordered breathing

          7. Actual body weight exceeding 1 kg per centimeter of height

          8. Severe chronic liver disease defined as a Child-Pugh score of 12-15 (Appendix A2)

          9. Bone marrow transplantation within the last 1 year

         10. Expected duration of mechanical ventilation of < 48 hours

         11. Decision to withhold life-sustaining treatment; except in those patients committed to
             full support except cardiopulmonary resuscitation if an actual cardiac arrest occurs

         12. Moribund patient not expected to survive 24 hours; if CPR provided, assess for
             moribund status greater than 6 from CPR conclusion

         13. Diffuse alveolar hemorrhage from vasculitis

         14. Burns > 70% total body surface

         15. Unwillingness to utilize the ARDS Network 6 ml/kg IBW ventilation protocol

         16. Previous hypersensitivity or anaphylactic reaction to cisatracurium

         17. Neuromuscular conditions that may potentiate neuromuscular blockade and/or impair
             spontaneous ventilation (Appendix A2)

         18. Neurologic conditions undergoing treatment for intracranial hypertension

         19. Enrollment in an interventional ARDS trial with direct impact on neuromuscular
             blockade and PEEP

         20. >120 hours of mechanical ventilation

         21. P/F < 200 mmHg at the time of randomization (if available)