Influence of N-Acetylcysteine on Morbidity, Oxygenation and Cytokine Levels in Partial or Total Esophagectomy for Cancer
Condition: Pulmonary Morbidity
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate the effect of high-dose n-acetylcysteine on
      inflammatory reaction, pulmonary morbidity, oxygenation and quality of life in patients
      undergoing transthoracic, partial or total resection of the esophagus for cancer.
    

Detailed description: 
      Cancer of the esophagus has a poor long term prognosis as well as high perioperative
      morbidity. Pulmonary complications play thereby a major role. The standard procedure is
      either a combined transabdominal/transthoracic approach, which allows better visualisation of
      the tumor and more radical surgery (which may increase R0 resections and consequently overall
      survival) or a blunt transhiatal technique. In Zurich, Basel and Lucerne, the combined
      technique is the standard procedure. The combined surgical approach, pre-existing pulmonary
      disorders, poor nutritional status and the release of pro-inflammatory cytokines may be
      important contributing factors to pulmonary complications such as pneumonia, atelectasis,
      pleural effusions and the Acute Respiratory Distress Syndrome (ARDS). N-Acetylcysteine (NAC)
      has been shown to have direct and indirect oxygen scavenging abilities. In severe sepsis and
      acute respiratory distress syndrome, positive effects of NAC on morbidity and mortality were
      discovered. Aim of this study is to assess the influence of NAC on morbidity, oxygenation
      parameters and cytokine levels.

      According to power analysis, 90 patients have to be included in the trial. A multicenter
      approach was chosen to finish the study within 3 years. Respective to the average number of
      operations per institution and year, the following distribution is planned: Triemli Hospital
      40, University Hospital Basel 30, Kantonsspital Lucerne 20. Inclusion criteria for this trial
      are patients undergoing thoraco-abdomino-cervical or abdomino-thoracic esophagectomy for
      cancer between 20 and 90 years and given informed consent. Exclusion criteria are known
      allergy or hypersensitivity to NAC and pregnancy. Patients are randomised to receive either
      high dose N-Acetylcysteine administered perioperatively and postoperatively for three days
      (150mg/kg perioperatively and 50mg/kg days 1-3) or placebo (glucose 5%).

      Pre-, peri- and postoperatively cytokines (IL-1, IL-1ra, IL-6, IL-8, IL-10, TNF-α), are
      quantified by enzyme-linked immuno assay (ELISA) from blood, broncho-alveolar lavage and
      lavage of pleural space. Leucocytes, C-reactive protein, Procalcitonin and oxygenation
      parameters (arterial blood gas analyses = ABGA) are regularly measured. Morbidity and
      mortality is assessed. Furthermore, all patients are asked to complete a quality of life
      questionnaire (EORTC QLQ-OES18 and 30, SF-36) before and after the operation (12, 24, 36
      months post-op).
    

Intervention name(s): n-acetylcysteine; 250mL glucose 5%
Intervention type(s): Drug; Drug
Intervention description(s): 150mg/kg N-Acetylcysteine in 250mL Glucose 5% at time of induction of anaesthesia 50mg/kg N-Acetylcysteine in 250mL Glucose 5% on post-op days 1-3; placebo (250mL glucose 5%) at time of induction of anaesthesia placebo (250mL glucose 5%) on post-op days 1-3
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: n-acetylcysteine; esophagectomy; inflammatory reaction; pulmonary morbidity