Table 1

Characteristics of included studies

Author and yearNo of participantsAge (years, mean±SD)Population
(ventilation as described in paper)
Mucoactive agent intervention and doseControlDuration to last follow-up (days)Outcomes measured relevant for this r eview
Bandeshe38 2016*214Placebo: 59
Usual care: 62
Intervention: 57
(reported as medians)
Mixed
(invasive mechanical ventilation)
Heparin
(Nebulised; 2 mL 5000 units every 6 hours)
Placebo (0.9%) NaCl
Usual care
Not reportedMortality, ICU stay, hospital stay, duration of mechanical ventilation and adverse events.
Bernard33 199746Control: 47±4
Intervention: 43±6
ARDS
(mechanically ventilated)
NAC
(Intravenous; 70 mg/kg, every 8 hours, for 10 days)
Placebo
(5% dextrose in water)
30Mortality, ventilator free days at day 30 and adverse events.
Dixon40 201050Control: 55.5±17.0
Intervention: 56.0±16.5
Mixed
(invasive mechanical ventilation)
Heparin
(Nebulised; 25 000 U/5 mL every 4 or 6 hours)
Placebo
(0.9% NaCl)
60Mortality, ventilator free days at day 28, ICU stay, hospital stay and adverse events.
Domenighetti31 199742Control: 52.4±17
Intervention: 52.1±17.8
ARDS
(invasive and non-invasive ventilation)
N-acetylcysteine
(Intravenous; 190 mg/kg/day, for 2 days)
Placebo
(not defined in paper)
ICU discharge
(not reported)
Mortality, ICU stay, duration of ventilation and adverse events.
Jepsen35 199266Control: 51.5
Intervention: 50.5
ARDS
(tracheal intubation)
N-acetylcysteine
(Intravenous; 150 mg/kg then 20 mg/kg/hour for 6 days)
Placebo
(not defined in paper)
60Mortality.
Masoompour30 201540Control: 50.6±21
Intervention: 59.7±22
Mixed
(invasive ventilation)
N-acetylcysteine
(Nebulised; 2 mL of 20%, 3 times per day)
Control
(isotonic saline)
1Mortality.
Moradi37 200927Control: 49.2±4.5
Intervention: 48.4±5.5
ARDS/ALI
(mechanically ventilated)
N-acetylcysteine
Intravenous; 150 mg/kg diluted in 5% dextrose day 1 then 50 mg/kg/day for 3 consecutive days)
Placebo
(5% dextrose)
Not reportedMortality, ICU stay and duration of mechanical ventilation.
Ortolani36 200036Control: 55±13
Intervention: 57±14
ARDS
(artificial ventilation)
N-acetylcysteine
(Intravenous; 50 mg/kg in 5% dextrose, every 8 hours for 9 days)
Placebo
(5% dextrose in water)
30Mortality and ICU stay.
Saleh39 201780Control: 34.8±14.8
Intervention: 34.3±14.6
ARDS
(mechanical ventilation)
Heparin
(Nebulised; 5000 IU heparin mixed with 3 mL of normal
Saline every 4 hours)
Standard Care
(Conventional management of ARDS: Mechanical ventilation with open lung protective strategy, conservative fluid management, solumedrol at a dose of 1 mg/kg/day, antimicrobials and bronchodilators if needed)
End of ICU stayMortality, ICU stay and duration of mechanical ventilation.
Suter32 199461Control: 48.1±21.9
Intervention: 46.6±19.7
ALI
(invasive ventilation)
N-acetylcysteine
(Intravenous; 40 mg/kg/day for 3 days)
Placebo
(not defined in paper)
ICU discharge
(not reported)
Mortality, ICU stay and adverse effects.
Van Meenen26
(NEBULAE) 2018†
922 Control: 66
 Intervention: 65
 (median values reported)
Mixed
(invasive)
On demand N-acetylcysteine
(Nebulised; 300 mg with 2.5 mg salbutamol)
Routine N-acetylcysteine
(300 mg with 2.5 mg salbutamol, 4 times daily for upto 28 days)
90Mortality, duration of ventilation, ventilator free days at day 28, ICU stay, hospital length of stay and adverse events.
Yong-Jun34 201468Control: 57±8
Intervention: 58±12
ARDS
(invasive and non-invasive ventilation)
Ambroxol
(Intravenous; 1005 mg/day, for 7 days)
Placebo
(0.9% isotonic saline)
Not reportedDuration of ventilation, ICU stay and hospital stay.
Dahruog 20172960Control: 41.87±16.44
intervention: 41.30±14.13
ARDS
(invasive ventilation)
Hypertonic saline
(nebulised; 3%, 4 mL once daily, for 7 days)
Control
(not defined in paper)
30Mortality, duration of mechanical ventilation, ICU stay and adverse events.
  • *Standard care and placebo were combined as one group using methodology from the Cochrane Handbook Table 7.7, as this was a three arm trial comparing placebo, mucoactive and standard care.

  • †The control group (routine nebulisation) was regarded as mucoactive group in the analyses and the on-demand group was regarded as the control/standard care. The analyses compared the routine nebulisation group to a subset of patients from the on-demand group that received no nebulisations (n=268). This excluded patients that received NAC and salbutamol treatment in the control group.

  • ALI, acute lung injury; ARDS, acute respiratory distress syndrome; ICU, intensive care unit; NAC, N-acetylcysteine.