Safety and efficacy of adding intravenous N-acetylcysteine to parenteral L-alanyl-L-glutamine in hospitalized patients undergoing surgery of the colon: a randomized controlled trial.

Abstract

ABSTRACTBACKGROUND: Colon surgery can cause systemic inflammatory response syndrome (SIRS). There is a recent trend towards the use of antioxidant agents in the prevention or alleviation of the severity of postoperative SIRS, but its use is controversial as studies have shown conflicting results.OBJECTIVES: Investigate the efficacy and tolerability of perioperative intravenous administration of N-acetylcysteine (NAC) as an antioxidant and anti-inflammatory agent in patients undergoing colon surgery.DESIGN: Randomized, double-blinded, and controlled clinical trial.SETTING: Surgical critical care unit in Egypt.PATIENTS AND METHODS: Sixty patients who required admission to the ICU following colon surgery were enrolled in the study between July 2015 and October 2016. Eligibility included the need for parenteral nutrition for at least 5 days due to failure of or contraindication to enteral nutrition. Patients were randomly allocated using a computer-generated list to a loading dose of NAC followed by continuous infusion started one hour prior to induction, and continued over 48 hours, or to the control group, who received the same volume of dextrose 5%. Allocation was concealed using opaque, sealed envelopes under pharmacy control. The researcher, the anesthesiologist, the surgeon, and patients were blinded to the treatment allocation.MAIN OUTCOME MEASURES: Clinical and laboratory evaluation for manifestations of SIRS, serum levels of tumor necrosis factor alpha and malondialdehyde, and occurrence of side effects in the study group.SAMPLE SIZE: 60 patients with mean (SD) ages of 56 (15.1) years in the study group (n=30) and 57.7 (12.3) years in the control group (n=30).RESULTS: There was a significant difference in the mean serum level of ALT (22.6 (9.9) U/L in the study group vs. 31.1 (17.8) U/L in the control group, P=.028) after treatment with NAC, but differences between the groups in the serum level of tumor necrosis factor alpha and malondialdehyde after treatment were not significant. Serum levels of malondialdehyde increased in both groups after treatment P<.001. There was no statistically significant difference from baseline or between the groups after treatment in other clinical data and laboratory parameters following NAC administration, and only 6.6% of the patients in the study group experienced mild side effects.CONCLUSIONS: Preoperative administration of NAC is safe, but its efficacy as an antioxidant and anti-inflammatory agent was not statistically significant and requires further investigation in a larger sample.LIMITATIONS: Single-center study, small sample size, and short duration of NAC administration.CLINICAL TRIALS REGISTRY: NCT03589495.CONFLICT OF INTEREST: None.