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Efficacy of enteral glutamine supplementation in patients with severe and predicted severe acute pancreatitis— A randomized controlled trial

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Abstract

Background

In severe acute pancreatitis (AP), intravenous glutamine has been shown to reduce the rate of complications, hospital stay, and mortality. In the present randomized trial, we aimed to evaluate the effect of enteral glutamine supplementation on clinical outcomes, gut permeability, systemic inflammation, oxidative stress, and plasma glutamine levels in patients with severe and predicted severe AP.

Methods

Patients with AP admitted within 72 h of onset of symptoms were included. The primary outcome measure was development of infected pancreatic and peri-pancreatic necrosis and in-hospital mortality. High-sensitivity C-reactive protein (HS-CRP) and interleukin-6 (IL-6) were evaluated as markers of inflammation; plasma thiobarbituric acid reactive substances (TBARS) and activities of serum superoxide dismutase and glutathione peroxidase were determined to evaluate oxidative stress; serum polyethylene glycol (PEG) was tested for intestinal permeability; subjective global assessment (SGA) was used for nutritional assessment, and an improvement in organ function was measured by the Modified Marshall score. Intention-to-treat analysis was used. A p-value of < 0.05 was considered statistically significant.

Results

After power calculation, we enrolled 18 patients in the glutamine and 22 in the control arm. There was no significant improvement in the development of infected necrosis and in-hospital mortality between the groups. Improvement in Modified Marshall score was observed in a higher proportion of patients receiving glutamine (15 [83.3%] vs. 12 [54.5%]; p = 0.05). Plasma glutamine levels improved more in glutamine-treated group (432.72 ± 307.83 vs. 618.06 ± 543.29 μM/L; p = 0.004), while it was lower in controls (576.90 ± 477.97 vs. 528.20 ± 410.45 μM/L; p = 0.003). PEG level was lower after glutamine supplementation (39.91 ± 11.97 vs. 32.30 ± 7.39 ng/mL; p = 0.02). Statistically significant reduction in IL-6 concentration was observed in the glutamine group at the end of treatment (87.44 ± 7.1 vs. 63.42 ± 33.7 μM/L; p = 0.02).

Conclusions

Despite absence of improvement in infected necrosis and in-hospital mortality, enteral glutamine supplementation showed improvement in gut permeability, oxidative stress, and a trend towards improvement in organ function as depicted by improvement in the Modified Marshall score.

Trial registration: NCT01503320

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Acknowledgments

Dr. M. Sasikala and late Dr. C. Subramanyam for guiding with biochemical evaluation and providing valuable advice; Ms. Merlin Annie Raj for clinical monitoring of patients; Mr. Balakumar Reddy, Mr. Venu, and Mr. Sadik for assisting in laboratory work.

Author information

Authors and Affiliations

  1. Department of Clinical Nutrition, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India

    Madhulika Arutla

  2. Department of Endocrinology and Metabolism, National Institute of Nutrition, Near Tarnaka, Jamai-Osmania, Hyderabad, 500 007, India

    M. Raghunath

  3. Department of Biochemistry, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India

    G. Deepika

  4. Wellcome DBT Labs., Institute of Translational Research, Asian Healthcare Foundation, Hyderabad, 500 082, India

    Aparna Jakkampudi

  5. Department of Biostatistics, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India

    H. V. V. Murthy

  6. Department of Surgical Gastroenterology, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India

    G. V. Rao

  7. Department of Medical Gastroenterology, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India

    D. Nageshwar Reddy & Rupjyoti Talukdar

  8. Pancreas Clinic, Pancreas Research Group, Asian Healthcare Foundation, Asian Institute of Gastroenterology, 6-3-661 Somajiguda, Hyderabad, 500 082, India

    Rupjyoti Talukdar

Authors
  1. Madhulika Arutla
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  2. M. Raghunath
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  3. G. Deepika
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  7. D. Nageshwar Reddy
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  8. Rupjyoti Talukdar
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Contributions

• Madhulika Arutla recruited and monitored patients, collected data, conducted nutritional and biochemical evaluations, and drafted the manuscript.

• M. Raghunath provided intellectual inputs and mentoring.

• Deepika G supervised biochemical assays.

• Aparna Jakkampudi performed FACS for cytokine assay.

• H.V.V. Murthy performed statistical analyses.

• G. V. Rao recruited patients and provided intellectual inputs.

• D. Nageshwar Reddy recruited patients and provided intellectual inputs.

Corresponding author

Correspondence to Rupjyoti Talukdar.

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Conflict of interest

MA, MR, CD, AJ, HVVM, GVR, DNR, and RT declare that they have no conflict of interest.

Ethics statement

The authors declare that the study was performed in a manner conforming to the Helsinki declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights, and the authors followed the policy concerning informed consent as shown on Springer.com.

Prior approval was obtained from the Institutional Review Board (IRBno. AIG/GI/2011/05) of the Asian Institute of Gastroenterology, Hyderabad. Written informed consent was obtained from all the patients before being enrolled in the study.

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Arutla, M., Raghunath, M., Deepika, G. et al. Efficacy of enteral glutamine supplementation in patients with severe and predicted severe acute pancreatitis— A randomized controlled trial. Indian J Gastroenterol 38, 338–347 (2019). https://doi.org/10.1007/s12664-019-00962-7

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  • DOI: https://doi.org/10.1007/s12664-019-00962-7

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