Table 1.
Summary of studies examining the effect of NAC in acute viral respiratory infections humans.
| Author | Country | WHO Region (see WHO tab) | Design (eg Cohort, cross-sectional) | Study duration | Study Population / Disease or Condition | Administration of NAC | Dose | Duration of Treatment | Control or Placebo | Total Number of Subjects | N in intervetion and placebo | Measure of Outcome | Outcome | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bernard, et al. [3] | USA, Canada | The Region of the Americas | DBPC RCT | March 17, 1992 to Feb 26, 1993 | ICU, diagnosed with ARDS and needing ventilation | IV solution of 10 % NAC diluted with 5% dextrose in water | 70 mg (0.4 mol)/kg body weight; OTZ, 63 mg (0.4 mol)/kg of body weight | 30 min., every 8 h for a total of 30 doses during a 10-day treatment period | Placebo (5%dextrose in water) | n = 48 | NAC: n = 14 OTZ: n = 17 Placebo: n = 15 | RBC glutathione levels | NAC: increased from baseline 47 % (p < .05) OTZ: not significant Placebo: not significant |
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| Mortality | No difference | |||||||||||||||||||||||||||||
| Organ-failure free days | No difference | |||||||||||||||||||||||||||||
| Domenighetti, et al. [4] | Switzerland | European | PC RCT | 16-month period | ICU patients diagnosed with ARDS | IV solution | 190 mg/kg/day of NAC or placebo | Continuous infusion over the first 3 days | Placebo (saline) | n = 42 | NAC: n = 22; Placebo: n = 20 | Incidence of ventilatory support | No difference | |||||||||||||||||
| PaO2/FIO2 | No difference | |||||||||||||||||||||||||||||
| Lung Injury Score | NAC: 1.53 (SD 0.21) Placebo: 2.15 (SD 0.19) (p < .04) |
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| Chest radiograph | No difference | |||||||||||||||||||||||||||||
| Howe, et al. [5] | America USA | The Region of the Americas | DBPC RCT | ICU patients requiring mechanical ventilation | Enterally administered antioxidant supplementation via a bolus | Group 1: 5 mL dose of placebo; Group 2: 5 mL dose of vitamin E (100IU) and 5 mL dose of placebo; Group 3: rml dose of vitamin C (1000 mg), 5 mL dose of vitamin E (1000IU) and 5 mL dose of NAC (400 mg) | Bolus given every 8 h for 28 days or until they were weaned from mechanical ventilation (whichever was shorter) | Placebo | n = 72 | C + E+NAC: n = 23; Placebo: n = 22; C + E n = 27 | All-cause mortality | No difference | ||||||||||||||||||
| Days in ICU | No difference | |||||||||||||||||||||||||||||
| Days in hospital | No difference | |||||||||||||||||||||||||||||
| Number of days on mechanical ventilation | C + E group: Mean, 10 days C + E+NAC: Mean, 12 days Placebo: Mean, 19 days (p = .02) |
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| Jepsen, et al. [6] | Denmark and Sweden | European | DBPC RCT | ICU patients diagnosed with ARDS | IV solution | NAC 150 mg/kg as a loading dose and then 20 mg/kg/hr | Initial dose was given for 30 min. on day one. Then continuous for the next 6 days | Placebo | n = 66 | NAC: n = 32; Placebo: n = 34 | Adverse events | NAC: a rash was observed in one patient after the loading dose. | ||||||||||||||||||
| Oxygenation | No difference | |||||||||||||||||||||||||||||
| Administration of corticosteriods, prostaglandin E1 or NSAIDs | No difference | |||||||||||||||||||||||||||||
| Time taken to recover from ARDS | No difference | |||||||||||||||||||||||||||||
| Chest radiographs | No difference | |||||||||||||||||||||||||||||
| Lai, et al. [1] | Hong Kong | South East Asia | Case report | Not applicable | One patient diagnosed with novel H1N1 influenza pneumonia, septic shock, type 1 respiratory failure | IV solution | NAC 100 mg/kg continuous IV infusion for 3 days. | Intial treatment with norepinephrine infusion, hdyrozortisone for septic shock. Oral oseltamivir 75 mg twice daily, IV antibiotics next day. Next day, oseltamivir 150 mg BD, IV NAC daily for 3 days. | None | n = 1 | n = 1 | Patient improved rapidly after high dose NAC therapy plus antiviral medications. CRP concentrations were also seen to decrease with the introduction of NAC high dose. |
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| Laurent, et al. [7] | Switzerland | European | DB PC RCT | ICU patients diagnosed with severe ARDS | IV solution | 190 mg/kg/day of NAC | Continuous infusion over the first 3 days | Placebo (isotonic saline solution) | n = 16 | NAC n = 8; Placebo n = 8 | Unstimulated oxygen radical production | No difference | ||||||||||||||||||
| Granulocyte GSH | Significantly higher in the NAC group compared to placebo (p < 0.01). Difference was abolished by day 5 (all treatment stopped on day 3). | |||||||||||||||||||||||||||||
| Elastase release | No difference | |||||||||||||||||||||||||||||
| Moradi, et al. [8] | Iran | Eastern Mediterranean | SB PC RCT | July 2005 and April 2006 | Ventilated ICU patients with ALI/ARDS | IV solution | 150 mg/kg at first day, followed by 50 mg/kg for 3 days | Initial dose was given for day one, then followed by continuous infusions for 3 days | Placebo (5%dextrose in water) | n = 30 | NAC: n = 14; Placebo: n = 13 | Mortality rate | NAC: 35.7 %; Placebo: 76.9 % (p = .03) | |||||||||||||||||
| Duration of mechanical ventilation | No difference | |||||||||||||||||||||||||||||
| Length of ICU stay | No difference | |||||||||||||||||||||||||||||
| PaO2/FiO2 (Day 2) | NAC: 227.3 (SD 23.9); Placebo: 155.0 (SD 15.5) (p = .02) | |||||||||||||||||||||||||||||
| PaO2/FiO2 (Day 3) | NAC: 344.0 (SD 38.3); Placebo: 166.5 (SD 119.0) (p < .001) | |||||||||||||||||||||||||||||
| PaO2/FiO2 (Day 4) | NAC: 440.9 (SD 47.5); Placebo: 151.2 (SD 24.6) (p < .001) | |||||||||||||||||||||||||||||
| Ortolani, et al. [11] | Italy | European | RCT | May 1995 to October 1997 | ICU patients, diagnosed early ARDS requiring ventilation | IV solution of 5% NAC diluted with 5% dextrose in water alone or combined with Rutin 0.5 % | NAC 50 mg/kg OR NAC 50 mg/kg + Rutin 5 mg/kg every 8 h | 9 days (trial length) then as long as artificial ventilation was needed | Control 250 mL 5% dextrose in water | n = 36 | NAC: n = 12; NAC + Rutin: n = 12; Control: n = 12; | Oxidised and total glutathione in epithelial lining fluid (ELF) | No difference | |||||||||||||||||
| Oxygenation | NAC: Improved | |||||||||||||||||||||||||||||
| Lipid peroxidation (ethane expiration) | [Day 9] NAC: reduced 43 % NAC + Rutin: reduced 46 % Placebo: reduced 15 % (p < .01) |
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| Polymorphonuclear (PMN) cell count in ELF | NAC: Reduced 50 % NAC + Rutin: Reduced 30 % Placebo: No change (p < .05) |
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| Mortality [day 9 and day 30] | No difference | |||||||||||||||||||||||||||||
| Sharafkhah, et al. [9] | Iran | Eastern Mediterranean | DBPC RDT | March 2014 to June 2016 | Adult ICU admitted patients undergoing endotracheal intu-bation and mechanical ventilation | NAC (600 mg; water-soluble tablets) through nasogastric tube | Twice daily | Administered within the first 12 h of mechanical ventilation after hospital admission, and continued until performing extubation, tracheostomy, discharge, or death. | Placebo (water-soluble vitamin tablets) | n = 60 | NAC: n = 30; Placebo: n = 30 | Incidence of ventilator-associated pneumonia | NAC: 26.6 % Placebo: 46.6 % (p = .032) |
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| Time to recovery | Patients who survived in the treatment group showed a more rapid recovery compared with the control group. | |||||||||||||||||||||||||||||
| Incidence of ventilator associated pneumonia (VAP) | Patients treated with NAC were significantly less likely to develop clinically confirmed VAP compared with patients treated with placebo. | |||||||||||||||||||||||||||||
| Time to VAP (days) | NAC: 6.42 (SD 1.9) Placebo: 3.46 (SD 2.53) (p = .002) |
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| Duration of mechanical ventilation (days) | No difference | |||||||||||||||||||||||||||||
| ICU stay (days) | NAC: 14.36 (SD 4.69) Placebo: 17.81 (SD 6.37) (p = .028) |
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| Hospital stay (days) | NAC: 19.23 (SD 5.54 Placebo: 24.61 (SD 6.81) (p = .030) |
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| Recovery rate of VAP |
Complete - NAC: 56.6%; Placebo: 30% (p = .006) Modest – no difference Lack – NAC: 10.0%; Placebo: 26.6% (p = .040) Death: no difference |
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| Adverse events | No adverse events related to NAC were identified. | |||||||||||||||||||||||||||||
| Soltan-Sharifi, et al. [2] | Iran | Eastern Mediterranean | Controlled clinical trial | 24 July 2005 and 30 April 2006 | ICU patients with Illness known to be associated with ALI/ARDS who required mechanical ventilation | "Infused" NAC (150 mg/kg) diluted in 5% dextrose and and 50 mg/kg/day diluted in 5% dextrose | NAC (150 mg/kg) infused for 20 min the first day and then 50 mg/kg/day for three days. | 3 days | None | n = 24 | NAC: n = 14; Control: n = 10 | Acute Physiology and Chronic Health Evaluation(APACHE II) score | NAC: Increased Placebo: Decreased (p < .01) |
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| Intracellular glutathione (GSH) (48 h) | NAC: Increased 59 % Placebo: Decreased 23 % (p < .001) |
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| GSH/GSSG ratio | NAC: Increased (22 vs 64.2) Placebo: No change (p < .01) |
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| Total antioxidant power (TAP) (mmol/L) (72 h) | NAC: 3.6 (SD 0.38) Placebo: 1.8 (SD 0.25) (p = .013) |
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| Suter, et al. [10] | Switzerland | European | DBPC RDT | 12- month period | Patients with risk factors for ARDS, and presenting with mild-to-moderate acute lung injury | Continuous IV infusion | NAC 40 mg/kg/day | 3 days | Placebo | n = 61 | NAC: n = 32; Placebo: n = 29 | Incidence of ventilatory support | NAC: Reduced (69 % vs 17 %) Placebo: Reduced (76 % vs 48 %) (p = .01) |
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| FiO2 administered | NAC: Reduced (0.29 vs 0.48) Placebo: No difference (0.35 vs 0.48) (p < .05) |
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| PaO2/FiO2 | No difference | |||||||||||||||||||||||||||||
| Lung injury score | NAC: Decreased (1.39 vs 0.67) Placebo: No difference (p < .01) |
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| Chest radiograph score | NAC: No change at day 3; Decreased at discharge (1.8 vs 1.1) Placebo: Increased at day 3 (p < .05) |
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| van Meenen, et al. [12] | Netherlands | European | RCT | June 22, 2014, to November 24, 2016 | ICU patients receiving invasive ventilation | Nebulized 5 mL solution (300 mg acetylcysteine) administered alone or in combination with 5 mL solutions containing salbutamol (2.5 mg) | On demand nebulization group: 5 ml solutions containing acetylcysteine (300 mg) OR 5 ml solutions containing salbutamol (2.5 mg) dependent on patient presentation. Routine nebulization group: acetylcysteine (300 mg) with salbutamol (2.5 mg) four times daily | Maximum 28 days. On demand group were reassessed daily. Routine group - from start to end of invasive ventilation and, in the case of ventilation through a tracheostomy tube, until ventilator support was discontinued for longer than 24 h. | None | n = 842 | On-demand group: n = 389; Routine group: n = 453 | Number of ventilator-free days | No difference | |||||||||||||||||
| Mortality | No difference | |||||||||||||||||||||||||||||
| ICU and hospital length of stay | No difference | |||||||||||||||||||||||||||||
| Adverse events |
Total On demand: 13.8 % Routine: 29.3 % (p < .001) Tachyarrhythmia On demand: 12.5 % Routine: 25.9 % (p < .001) Agitation On demand: 0.2 % Routine: 4.3 % (p < .001) |
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| Zhang, et al. [13] | China | Western Pacific Region | RCT | August 2016 and March 2017 | All patients admitted to the hospital with community acquired pneumonia | Oral 600 mg tablet | NAC 1200 mg (600 mg tablet twice daily) | 10 days | Standard care | n = 39 | NAC: n = 21; Standard care: n = 18 | Malondialdehyde (7 days) | NAC: +1.34 (SD 1.35) Non-NAC: +0.43 (SD 1.28) (p = .004) |
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| Tumour-necrosis factor-α | NAC: +9.5 (SD 3.62) Non-NAC: 6.25 (SD 3.98) (p < .001) |
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| Total antioxidant capacity | NAC: +4.16 (SD 2.95) Non-NAC: +1.78 (SD 3.21) (p = .005) |
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| Superoxide dismutase | No difference | |||||||||||||||||||||||||||||
| CT Image comparison | No difference | |||||||||||||||||||||||||||||