N-Acetylcysteine Enhances Recovery From Acute Lung Injury in Man – Methods

Multiple trauma included patients with multiple major fractures (two or more major long bones or unstable pelvic fracture) associated with trauma to another region of the body such as craniocerebral or abdominal, requiring surgical intervention.
Aspiration was defined as recent (during the previous 6 h) inhalation of gastric contents, documented by suctioning of gastric material from the bronchial tree or by fiberoptic bronchoscopy showing typical mucosal lesions.
Necrotizing pancreatitis was seen as severe abdominal pain, vomiting, increased serum amylase levels, circulatory shock, and a Ranson score of 3 or above.
Hemorrhagic shock was defined as requiring administration of more than 20 U of blood within 24 h.
Near drowning was defined as an immersion accident requiring endotracheal intubation.
Patients younger than 16 years, pregnant women, immunocompromised patients, and those with a severe lung injury (LIS > 2.S) or cardiogenic pulmonary edema were excluded from this trial.
Data were collected at admission to the ICU (baseline), on the first 3 days after admission, and on the day of discharge from the unit. Severity of illness was assessed by the simplified acute physiological score (SAPS).2®
Respiratory dysfunction was assessed daily by the requirement for mechanical ventilatory support, the FIo2 administered, and the evolution of the lung injury score using its first three components (chest radiograph, PaOj/FIOj ratio, and respiratory system compliance). The FIo2 was controlled during mechanical ventilation using the built-in oxygen cell of the ventilator. In extubated and spontaneously breathing patients, FIo2 was regulated by using a Ventimask or a similar device. The FIo2 obtained was checked regularly with a paramagnetic oxygen sensor (Oxydig, Dr&ger, Ltibeck, Germany).
Mechanical ventilation was initiated and maintained at the discretion of the physician in charge of the patient. The standards for mechanical ventilatory support, oxygen therapy, weaning criteria, and other treatment modalities are applied quite uniformly in the four ICUs participating in the trial. Clinical and biochemical assessment was done regularly. Cardiovascular state, central nervous system, kidney, and liver function were monitored closely.
The patients were randomized to receive either NAC, 40 mg/kg/ d, or placebo, administered as a continuous intravenous infusion over the first 3 days after admission to the ICU. This dose and duration of treatment were chosen according to previous work on NAC in ARDS and in other abnormalities. A dose of 40 mg/kg is one order of magnitude higher than what is normally applied in regimens of chronic respiratory disease and yet one order lower than the dose for paracetamol intoxication. We believed that this dose could offer sufficient efficacy as a preventive therapy in ARDS without exposing to drug toxicity. N-acetylcysteine and placebo were packed in similar numbered vials allowing randomization and double-blind administration.
Informed consent was obtained from the patient or, if this was not possible because of the clinical condition, from the next of kin. The protocol was submitted to and approved by the committees for ethics in human research of the university hospital of Basel, Geneva, and Lausanne.

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