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

Manal El Hamamsy, Rasha Bondok, Sara Shaheen, Ghada Hussein Eladly, Manal El Hamamsy, Rasha Bondok, Sara Shaheen, Ghada Hussein Eladly

Abstract

Background: 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.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Patient flow chart.
Figure 2.
Figure 2.
Estimation plot of differences in means for in alanine aminotransferase (ALT) in control and study groups after treatment with intravenous N-acetylcysteine and parenteral L-alanyl-L-glutamine.
Figure 3.
Figure 3.
Serum levels of malondialdehyde (A) and tumor necrosis factor alpha (B) before and after treatment with N-acetylcysteine in the control and study groups (comparison of before and after within the two groups statistically significant for malondialdehyde [P<.001 for both groups; comparisons between the control and study groups statistically nonsignificant].

References

    1. Scardapane A, Brindicci D, Fracella M, Angelelli G. Post colon surgery complications: Imaging findings. Eur J Radiol. 2005; 53: 397–409.
    1. Weinstein S, Osei Bonsu S, Aslam R, Yee F. Multidetector CT of the postoperative colon: review of normal appearances and common complications. Radio Graphics. 2013; 33: 515–32.
    1. Deniz M, Borman H, Seyhan T, Haberal M. An effective antioxidant drug on prevention of the necrosis of zone of stasis: N-acetylcysteine. Burns. 2012; 39(2): 320–25.
    1. Mokhtari V, Afsharian P, Shahhoseini M, Kalanta S, Moini A. A Review on Various Uses of N-acetylcysteine. Cell J. 2017; 19(1) 11–17.
    1. Heyland DK, Dhaliwal R, Day AG, Muscedere J, Drover J, Suchner U, et al. Reducing deaths due to oxidative stress (the REDOXS study): rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients. Proc Nutr Soc. 2006; 65: 250–263.
    1. Van Stijn MFM, Ligthart Melis GC, Boelens PG, Scheffer PG, Teerlink T, Twisk JWR, et al. Antioxidant enriched enteral nutrition and oxidative stress after major gastrointestinal tract surgery. World J Gastroenterol. 2008; 14(45): 6960–69.
    1. Ziegler F, Seddiki L, Marion letellier R. Effects of L glutamine supplementation alone or with antioxidants on hydrogen peroxide induced injury in human intestinal epithelial cells. E SPEN, the European e Journal of Clinical Nutrition and Metabolism. 2011; 6: 211–16.
    1. Molnar Z., Szakmany T, Marton S. Lack of Effect of Prophylactic N acetylcysteine on postoperative organ dysfunction following major abdominal tumor surgery: A randomized, placebo controlled, double blinded clinical trial. Anaesth Intensive Care. 2003; 31(3): 267–71.
    1. Santiago FM, Bueno P, Olmedo C, Muffak Granero K, Comino A, Serradilla M, et al. Effect of N-acetylcysteine administration on intraoperative plasma levels of interleukin -4 and Interleukin-10 in liver transplant recipients. Transplantation Proc. 2008; 40(9): 2978–80. 10.1016/j.transproceed.2008.08.103
    1. Ozaydin M, Icli A, Yucel H, Akcay S, Peker O, Erdogan D, et al. Metoprolol vs. carvedilol or carvedilol plus N-acetylcysteine on postoperative atrial fibrillation: a randomized, double-blind, placebo-controlled study. Eur Heart J. 2013, 34: 597–604.
    1. Beyaz S, Yelken B, Kanbak G. The effects of N-acetylcysteine on hepatic function during isoflurane anesthesia for laparoscopic surgery patients. Indian J Anesth. 2011; 55(6): 567–72.
    1. Ibrahim Eand Sharawy A. Effectiveness of intravenous infusion of N-acetylcysteine in cirrhotic patients undergoing major abdominal surgeries. Saudi J Anaesth. 2015; 9(3): 272–78
    1. Kuyumcu A, Akyol A, Buyuktuncer Z, Ozmen M, Besler H. Improved oxidative status in major abdominal surgery patients after N-acetylcysteine supplementation. Nutr J. 2015; 14(4): 1–9. 10.1186/1475-2891-14-4
    1. Machin D, Campbell M, Fayers P, Pinol A. Sample size tables for clinical studies. 2nd Edition Malden MA: Blackwell Science; 1997.
    1. Liu XH, Xu CY, Fan GH. Efficacy of N-acetylcysteine in preventing atrial fibrilla-tion after cardiac surgery: a meta-analysis of published randomized controlled trials. BMC Cardiovasc Disord. 2014; 14(52): 1–8.
    1. Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. Drug evaluation N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin. Biol. Ther. 2008; 8(12): 1955–62.
    1. El hamamsy I, Stevens L, Carrier M, Pellerin M, Demers P, Cartier R, et al. Effect of intravenous N-acetylcysteine on outcomes after coronary artery bypass surgery: A randomized, double-blind, placebo controlled clinical trial. J Thorac Cardiovasc Surg. 2007; 133: 7–12.
    1. Pastor A, Collado P, Almar M, Gonzalez JG. Antioxidant enzyme status in biliary obstructed rats: effects of N acetylcysteine. J Hepatol. 1997; 27: 363–70.
    1. Sadowska AM, Keenoy B, De Backer WA. Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: Discordant in vitro and in vivo dose effects: A review. Pulm Pharmacol Ther. 2007; 20(1): 9–22.
    1. Mahmoud KM and Ammar AS. Effect of N-acetylcysteine on cardiac injury and oxidative stress after abdominal aortic aneurysm repair: A randomized controlled trial. Acta Anaesthesiol Scand. 2011; 55: 1015–1021.
    1. Engel J, Menges T, Martens F, Kwapisz M, Hempelmann G, Pitz S, et al. Role of glutamine administration on T-cell derived inflammatory response after cardiopulmonary bypass. Clin Nutr. 2009; 28:15–20.
    1. Ho J, Tumkaya T, Aryal S, Choi H, Claridge-Chang A. Moving beyond P values: Everyday data analysis with estimation plots. bioRxiv [Internet]. 2018. [cited 2019 Feb 11];377978 Available from:

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa