A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients

Heyland, Daren K.; Muscedere, John; Wischmeyer, Paul E.; Cook, Deborah J.; Jones, Gwynne; Albert, Martin; Elke, Gunnar; Berger, Mette M.; Day, Andrew G.

doi:10.1097/01.sa.0000441043.83064.4c

Cited by 58 publications

(70 citation statements)

References 19 publications

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“…Oral administration of ascorbate (1500 mg/day) in combination with other antioxidants (vitamin E, beta carotene, zinc, and selenium) failed to decrease mortality in critically ill adults who had multiorgan failure, but it is not known if plasma ascorbate concentration was restored to normal by the enteral ascorbate administration (27). Parenteral ascorbate administration can normalize plasma ascorbate (21,35), but little is known about the clinical outcomes of this intervention.…”

Section: Mortality and Morbiditymentioning

confidence: 99%

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

Wilson

2013

Antioxidants & Redox Signaling

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Significance: Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. Recent Advances: Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is available. The characteristics of severe sepsis include ascorbate (reduced vitamin C) depletion, excessive protein nitration in microvascular endothelial cells, and microvascular dysfunction composed of refractive vasodilation, endothelial barrier dysfunction, and disseminated intravascular coagulation. Parenteral administration of ascorbate prevents or even reverses these pathological changes and thereby decreases hypotension, edema, multiorgan failure, and death in animal models of sepsis. Critical Issues: Dehydroascorbic acid appears to be as effective as ascorbate for protection against microvascular dysfunction, organ failure, and death when injected in sepsis models, but information about pharmacodynamics and safety in human subjects is only available for ascorbate. Although the plasma ascorbate concentration in critically ill and septic patients is normalized by repletion protocols that use high doses of parenteral ascorbate, and such doses are tolerated well by most healthy subjects, whether such large amounts of the vitamin trigger adverse effects in patients is uncertain. Future Directions: Further study of sepsis models may determine if high concentrations of ascorbate in interstitial fluid have pro-oxidant and bacteriostatic actions that also modify disease progression. However, the ascorbate depletion observed in septic patients receiving standard care and the therapeutic mechanisms established in models are sufficient evidence to support clinical trials of parenteral ascorbate as an adjuvant therapy for sepsis.

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Section: Mortality and Morbiditymentioning

confidence: 99%

Evaluation of Vitamin C for Adjuvant Sepsis Therapy

Wilson

2013

Antioxidants & Redox Signaling

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“…Severe inflammatory stimulation may stimulate proliferation of immune cells and increase glutamine requirement. Supplemented glutamine may also increase glutamine degradation by increasing lymphocyte proliferation and cytokine production (44)(45)(46) In their study published in 2013, Heyland et al (47) and colleagues reported that glutamine significantly increased 28-day mortality. Then, glutamine supplementation for intensive care patients was criticized, especially in liver and kidney dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Neuromuscular Dysfunction in Experimental Sepsis and Glutamine

et al. 2016

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Background: Electrophysiological studies show that critical illness polyneuromyopathy appears in the early stage of sepsis before the manifestation of clinical findings. The metabolic response observed during sepsis causes glutamine to become a relative essential amino acid. Aims: We aimed to assess the changes in neuromuscular transmission in the early stage of sepsis after glutamine supplementation. Study Design: Animal experimentation. Methods: Twenty male Sprague-Dawley rats were randomized into two groups. Rats in both groups were given normal feeding for one week. In the study group, 1 g/kg/day glutamine was added to normal feeding by feeding tube for one week. Cecal ligation and perforation (CLP) surgery was performed at the end of one week. Before and 24 hours after CLP, compound muscle action potentials were recorded from the gastrocnemius muscle. Results: Latency measurements before and 24 hours after CLP were 0.68±0.05 ms and 0.80±0.09 ms in the control group and 0.69±0.07 ms and 0.73±0.07 ms in the study group (p<0.05). Conclusion: Since enteral glutamine prevented compound muscle action potentials (CMAP) latency prolongation in the early phase of sepsis, it was concluded that enteral glutamine replacement might be promising in the prevention of neuromuscular dysfunction in sepsis; however, further studies are required.

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“…In relation to a higher mortality being associated with a high dose of glutamine, we suppose that Ozcelik and colleagues are referring to the REDOXS study [4]. In the REDOXS we found a lot of potentially confusing factors (extremely high doses, normal basal levels of glutamine, combination of routes of administration, renal failure…).…”

Section: Dear Editormentioning

confidence: 99%