Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock

Mohadeseh Hosseini Zabet, Mostafa Mohammadi, Masoud Ramezani, Hossein Khalili, Mohadeseh Hosseini Zabet, Mostafa Mohammadi, Masoud Ramezani, Hossein Khalili

Abstract

Objective: Effects of ascorbic acid on hemodynamic parameters of septic shock were evaluated in nonsurgical critically ill patients in limited previous studies. In this study, the effect of high-dose ascorbic acid on vasopressor drug requirement was evaluated in surgical critically ill patients with septic shock.

Methods: Patients with septic shock who required a vasopressor drug to maintain mean arterial pressure >65 mmHg were assigned to receive either 25 mg/kg intravenous ascorbic acid every 6 h or matching placebo for 72 h. Vasopressor dose and duration were considered as the primary outcomes. Duration of Intensive Care Unit (ICU) stay and 28-day mortality has been defined as secondary outcomes.

Findings: During the study period, 28 patients (14 in each group) completed the trial. Mean dose of norepinephrine during the study period (7.44 ± 3.65 vs. 13.79 ± 6.48 mcg/min, P = 0.004) and duration of norepinephrine administration (49.64 ± 25.67 vs. 71.57 ± 1.60 h, P = 0.007) were significantly lower in the ascorbic acid than the placebo group. No statistically significant difference was detected between the groups regarding the length of ICU stay. However, 28-day mortality was significantly lower in the ascorbic acid than the placebo group (14.28% vs. 64.28%, respectively; P = 0.009).

Conclusion: High-dose ascorbic acid may be considered as an effective and safe adjuvant therapy in surgical critically ill patients with septic shock. The most effective dose of ascorbic acid and the best time for its administration should be determined in future studies.

Keywords: Ascorbic acid; norepinephrine; sepsis; shock; vasopressor.

References

    1. Remick DG. Pathophysiology of sepsis. Am J Pathol. 2007;170:1435–44.
    1. Dombrovskiy VY, Martin AA, Sunderram J, Paz HL. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: A trend analysis from 1993 to 2003. Crit Care Med. 2007;35:1244–50.
    1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165–228.
    1. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369:840–51.
    1. Vasu TS, Cavallazzi R, Hirani A, Kaplan G, Leiby B, Marik PE. Norepinephrine or dopamine for septic shock: Systematic review of randomized clinical trials. J Intensive Care Med. 2012;27:172–8.
    1. Landry DW, Levin HR, Gallant EM, Seo S, D’Alessandro D, Oz MC, et al. Vasopressin pressor hypersensitivity in vasodilatory septic shock. Crit Care Med. 1997;25:1279–82.
    1. Sharshar T, Carlier R, Blanchard A, Feydy A, Gray F, Paillard M, et al. Depletion of neurohypophyseal content of vasopressin in septic shock. Crit Care Med. 2002;30:497–500.
    1. Petros A, Bennett D, Vallance P. Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet. 1991;338:1557–8.
    1. Petros A, Lamb G, Leone A, Moncada S, Bennett D, Vallance P. Effects of a nitric oxide synthase inhibitor in humans with septic shock. Cardiovasc Res. 1994;28:34–9.
    1. Preiser JC, Lejeune P, Roman A, Carlier E, De Backer D, Leeman M, et al. Methylene blue administration in septic shock: A clinical trial. Crit Care Med. 1995;23:259–64.
    1. O’Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet. 2002;359:1209–10.
    1. Carr A, Frei B. Does Vitamin C act as a pro-oxidant under physiological conditions? FASEB J. 1999;13:1007–24.
    1. Carr AC, Frei B. Toward a new recommended dietary allowance for Vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr. 1999;69:1086–107.
    1. Hunt C, Chakravorty NK, Annan G, Habibzadeh N, Schorah CJ. The clinical effects of Vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res. 1994;64:212–9.
    1. Fowler AA, 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014;12:32.
    1. Schorah CJ, Downing C, Piripitsi A, Gallivan L, Al-Hazaa AH, Sanderson MJ, et al. Total Vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients. Am J Clin Nutr. 1996;63:760–5.
    1. Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: A randomized, prospective study. Arch Surg. 2000;135:326–31.
    1. Nathens AB, Neff MJ, Jurkovich GJ, Klotz P, Farver K, Ruzinski JT, et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg. 2002;236:814–22.
    1. Wilson JX. Evaluation of Vitamin C for adjuvant sepsis therapy. Antioxid Redox Signal. 2013;19:2129–40.
    1. Oudemans-van Straaten HM, Spoelstra-de Man A, de Waard MC. Vitamin C revisited. Crit Care Med. 2014;18:460.
    1. Riordan HD, Hunninghake RB, Riordan NH, Jackson JJ, Meng X, Taylor P, et al. Intravenous ascorbic acid: Protocol for its application and use. P R Health Sci J. 2003;22:287–90.
    1. Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, et al. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol. 2008;19:1969–74.
    1. Mak S, Newton GE. Vitamin C augments the inotropic response to dobutamine in humans with normal left ventricular function. Circulation. 2001;103:826–30.
    1. Nooraee N, Fathi M, Edalat L, Behnaz F, Mohajerani SA, Dabbagh A. Effect of Vitamin C on serum cortisol reduction after etomidate induction of anesthesia. J Cell Mol Anesth. 2015;1:28–33.
    1. Kieffer P, Thannberger P, Wilhelm JM, Kieffer C, Schneider F. Multiple organ dysfunction dramatically improving with the infusion of Vitamin C: More support for the persistence of scurvy in our “welfare” society. Intensive Care Med. 2001;27:448.
    1. Zipursky JS, Alhashemi A, Juurlink D. A rare presentation of an ancient disease: Scurvy presenting as orthostatic hypotension. BMJ Case Rep 2014. 2014:pii: Bcr2013201982.
    1. Holley AD, Osland E, Barnes J, Krishnan A, Fraser JF. Scurvy: Historically a plague of the sailor that remains a consideration in the modern intensive care unit. Intern Med J. 2011;41:283–5.
    1. Long CL, Maull KI, Krishnan RS, Laws HL, Geiger JW, Borghesi L, et al. Ascorbic acid dynamics in the seriously ill and injured. J Surg Res. 2003;109:144–8.
    1. Fukushima R, Yamazaki E. Vitamin C requirement in surgical patients. Curr Opin Clin Nutr Metab Care. 2010;13:669–76.
    1. Crandon JH, Landau B, Mikal S, Balmanno J, Jefferson M, Mahoney N. Ascorbic acid economy in surgical patients as indicated by blood ascorbic acid levels. N Engl J Med. 1958;258:105–13.
    1. Kirkemo AK, Burt ME, Brennan MF. Serum Vitamin level maintenance in cancer patients on total parenteral nutrition. Am J Clin Nutr. 1982;35:1003–9.
    1. Lowry SF, Goodgame JT, Jr, Maher MM, Brennan MF. Parenteral Vitamin requirements during intravenous feeding. Am J Clin Nutr. 1978;31:2149–58.
    1. De Backer D, Scolletta S. Clinical management of the cardiovascular failure in sepsis. Curr Vasc Pharmacol. 2013;11:222–42.
    1. Hornig D. Distribution of ascorbic acid, metabolites and analogues in man and animals. Ann N Y Acad Sci. 1975;258:103–18.
    1. May JM, Qu ZC, Nazarewicz R, Dikalov S. Ascorbic acid efficiently enhances neuronal synthesis of norepinephrine from dopamine. Brain Res Bull. 2013;90:35–42.
    1. Levine M. Ascorbic acid specifically enhances dopamine beta-monooxygenase activity in resting and stimulated chromaffin cells. J Biol Chem. 1986;261:7347–56.
    1. Deana R, Bharaj BS, Verjee ZH, Galzigna L. Changes relevant to catecholamine metabolism in liver and brain of ascorbic acid deficient guinea-pigs. Int J Vitam Nutr Res. 1975;45:175–82.
    1. Hoehn SK, Kanfer JN. Effects of chronic ascorbic acid deficiency on guinea pig lysosomal hydrolase activities. J Nutr. 1980;110:2085–94.
    1. Bornstein SR, Yoshida-Hiroi M, Sotiriou S, Levine M, Hartwig HG, Nussbaum RL, et al. Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2) FASEB J. 2003;17:1928–30.
    1. Duggan M, Browne I, Flynn C. Adrenal failure in the critically ill. Br J Anaesth. 1998;81:468–70.
    1. Nieboer P, van der Werf TS, Beentjes JA, Tulleken JE, Zijlstra JG, Ligtenberg JJ. Catecholamine dependency in a polytrauma patient: Relative adrenal insufficiency? Intensive Care Med. 2000;26:125–7.
    1. Treschan TA, Peters J. The vasopressin system: Physiology and clinical strategies. Anesthesiology. 2006;105:599–612.
    1. Russell JA. Bench-to-bedside review: Vasopressin in the management of septic shock. Crit Care Med. 2011;15:226.
    1. Sharshar T, Blanchard A, Paillard M, Raphael JC, Gajdos P, Annane D. Circulating vasopressin levels in septic shock. Crit Care Med. 2003;31:1752–8.
    1. Prigge ST, Mains RE, Eipper BA, Amzel LM. New insights into copper monooxygenases and peptide amidation: Structure, mechanism and function. Cell Mol Life Sci. 2000;57:1236–59.
    1. Landry DW, Levin HR, Gallant EM, Ashton Rc, Jr, Seo S, D’Alessandro D, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation. 1997;95:1122–5.
    1. Giusti-Paiva A, Domingues VG. Centrally administered ascorbic acid induces antidiuresis, natriuresis and neurohypophyseal hormone release in rats. Neuro Endocrinol Lett. 2010;31:87–91.
    1. Kahn SA, Beers RJ, Lentz CW. Resuscitation after severe burn injury using high-dose ascorbic acid: A retrospective review. J Burn Care Res. 2011;32:110–7.
    1. Morelli A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Laderchi A, et al. Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: A randomized, controlled trial. Crit Care Med. 2008;12:R143.

Source: PubMed

3
Tilaa