03518nam a2200313   4500001000800000005001700008007000300025008004100028040000800069041000800077100003700085245006900122300002300191520249600214650003802710650003002748650004302778650003402821650002402855700002702879700003202906700002902938700003002967700002502997700002503022773010903047942003103156999001703187ESSALUD20260821114519.0ta      t        pe ||||| |||| 00| 0 spa d  aBMG  aeng  aConnolly, Bronwen eAutor954233  aCarbocisteine or hypertonic saline for acute respiratory failure  apáginas: 739-752  aBackground: Mucoactive agents are widely used in patients with acute respiratory failure despite limited evidence of their effectiveness or safety. Methods: We conducted a multicenter, open-label, randomized trial with a 2-by-2 factorial design that involved critically ill, mechanically ventilated participants 16 years of age or older with acute respiratory failure and difficult-to-clear secretions. All participants received usual care along with carbocisteine (750 mg three times daily enterally), 6% or 7% nebulized hypertonic saline (HTS) (4 ml four times daily), both interventions, or usual care alone for up to 28 days. The primary outcome was duration of mechanical ventilation (from randomization to first successful unassisted breathing). The primary comparisons were between any carbocisteine and no carbocisteine and between any HTS and no HTS, with each comparison comprising two treatment groups. Results: A total of 1956 participants underwent randomization: 486 were assigned to carbocisteine, 485 to HTS, 492 to both treatments, and 493 to usual care alone (472, 474, 479, and 478, respectively, were included in the primary analysis). No evidence of treatment interaction was found (hazard ratio, 1.01, 95% confidence interval [CI], 0.83 to 1.22; P=0.91). The median duration of mechanical ventilation was 186.1 hours (95% CI, 168.3 to 196.6) with carbocisteine and 172.7 hours (95% CI, 165.2 to 190.4) with no carbocisteine (adjusted hazard ratio, 0.96; 95% CI, 0.87 to 1.05; P=0.34) and 184.5 hours (95% CI, 165.6 to 194.1) with HTS and 174.3 hours (95% CI, 166.9 to 192.7) with no HTS (adjusted hazard ratio, 1.00; 95% CI, 0.91 to 1.10; P=0.98). Clinically important upper gastrointestinal bleeding occurred significantly more often with carbocisteine than with no carbocisteine (13 of 965 [1.4%] vs. 2 of 966 [0.2%]; risk ratio, 6.51; 95% CI, 1.47 to 28.76; P=0.01). Bronchoconstriction leading to bronchodilator use occurred significantly more often with HTS than with no HTS (23 of 967 [2.4%] vs. 4 of 964 [0.4%]; risk ratio, 5.73; 95% CI, 1.99 to 16.52; P=0.001), as did hypoxemia during nebulization (40 of 967 [4.1%] vs. 3 of 964 [0.3%]; risk ratio, 13.29; 95% CI, 4.12 to 42.83; P<0.001). One serious adverse reaction was reported in the combination group. Conclusions: Among critically ill patients with acute respiratory failure, neither carbocisteine nor HTS significantly reduced the duration of mechanical ventilation, and each was associated with harm.

  aMEDICINA CLÍNICA GENERAL953666  aCUIDADOS INTENSIVOS95208  aMEDICINA CLÍNICA HOSPITALARIA953754  aVENTILACIÓN MECANICA937360  aNEUMOLOGÍA925628  aDickson, Naomi 954234  aCampbell, Christina 954235  aBradley, Judy M. 954236  aO’Neill, Brenda 954237  aAgus, Ashley 954238  aBarker, Mike 9542390 022717922650dMassachusetts NEJM GroupoNEJM12tThe New England Journal of Medicine wESSALUDx0028-4793  cARTICULOSe2026-08-21zsqb  c22850d22850