Home Print this page Email this page Small font size Default font size Increase font size
Users Online: 522
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Contacts Login 

 Table of Contents  
Year : 2016  |  Volume : 5  |  Issue : 2  |  Page : 94-100

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

1 Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Intensive Care Unit, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

Date of Web Publication1-Apr-2016

Correspondence Address:
Hossein Khalili
Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2279-042X.179569

Rights and Permissions

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

How to cite this article:
Zabet MH, Mohammadi M, Ramezani M, Khalili H. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock. J Res Pharm Pract 2016;5:94-100

How to cite this URL:
Zabet MH, Mohammadi M, Ramezani M, Khalili H. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock. J Res Pharm Pract [serial online] 2016 [cited 2021 Sep 17];5:94-100. Available from: https://www.jrpp.net/text.asp?2016/5/2/94/179569

  Introduction Top

Sepsis is a life-threatening systemic inflammatory response that can result in multi-organ dysfunction and intractable hypotension. [1] In critically ill patients, severe sepsis and septic shock are known as the main causes of mortality. [2] Adequate fluid resuscitation, infection control, cardiovascular and respiratory supports are recommended for the management of severe sepsis and septic shock. [3] Septic shock usually does not response to intravenous fluid resuscitation and most patients need a vasopressor drug administration. [1],[4],[5] Concomitant vasodilatation and reduced vascular response to the vasopressors have been detected in septic shock. [6],[7] Several mechanisms such as adrenal insufficiency, endothelial damage, oxidative stress, and depletion of catecholamine storage are proposed for vascular hyporesponsiveness to vasopressors in critically ill patients with septic shock. [8],[9],[10],[11]

Ascorbic acid (Vitamin C) is an essential nutrient with potent antioxidant properties. [12],[13] Ascorbic acid deficiency defined as serum ascorbic acid level <23 μmol/L has been reported in critically ill patients with acute respiratory infections and sepsis. [14],[15],[16] High-dose ascorbic acid improved edema and respiratory function in critically ill patients with severe burn injury and decreased organ failure and duration of Intensive Care Unit (ICU) stay in patients after major surgery. [17],[18]

Effects of ascorbic acid on hemodynamic parameters were evaluated in nonsurgical critically ill patients in limited previous studies. High-dose ascorbic acid in patients with burn injury decreased fluid and vasopressors' requirements. Also, in patients with severe sepsis, high-dose intravenous ascorbic acid improved hemodynamic parameters. [15],[17],[19],[20] Potential benefit of ascorbic acid in surgical critically ill patients with diagnosis of severe sepsis or septic shock has not yet been evaluated. In this study, the effects of high-dose ascorbic acid on vasopressor requirement were evaluated in surgical critically ill patients with septic shock.

  Methods Top

This double-blinded randomized clinical trial was conducted in an ICU of Imam Khomeini Hospital, a referral general hospital affiliated to Tehran University of Medical Sciences, Tehran, Iran. This ICU has 18 beds and most of the beds are usually allocated for postoperative patients. The researchers, ICU nurses, and physicians were blinded regarding the intervention and the product (ascorbic acid or placebo) was prepared by Hospital Pharmacy Department. During the study period, from September 2014 to January 2016, 28 adult (18-65-year-old) surgical critically ill patients with diagnosis of septic shock who needed a vasopressor drug to maintain mean arterial pressure (MAP) >65 mmHg despite adequate fluid resuscitation were recruited. The sample size of the study was considered based on the ICU patients' turn-over and number of patients who were hospitalized with a diagnosis of septic shock during the same period in previous years.

Septic shock was defined based on the Surviving Sepsis Campaign and patients with the following criteria: (1) Presence of a systemic inflammatory response: (fever: T >38°C or hypothermia: T <36°C, heart rate >90 beats/min, leukocytosis or leukopenia (white blood cell >12,000/μL and <4000/μL, respectively, or >10% band forms), (2) suspected or proven infection, (3) presence of sepsis-induced organ dysfunction (arterial hypoxemia [PaO 2 /FiO 2 <300], systolic blood pressure [SBP] <90 mmHg, or SBP decrease >40 mmHg unexplained by other causes), urine output <0.5 ml/kg/h for >6 h despite fluid resuscitation, platelet count <100,000/μL, acutely developing coagulopathy (international normalized ratio >1.5), serum bilirubin concentration >2 mg/dL were considered for enrollment [3] Concomitant use of other antioxidants (such as Vitamin E, selenium, and N-acetylcysteine), corticosteroids administration, any contraindication for high-dose ascorbic acid including bilateral ureteric obstruction, chronic hemodialysis, iron overload, oxalate stone formers, [21] hemochromatosis, and glucose-6-phosphate dehydrogenase deficiency [22] were defined as exclusions.

Ethical Committee of the hospital approved the study protocol and the patients or one of their first-degree family members signed the study's informed consent form.

Treatment of septic shock in the ICU was based on the Surviving Sepsis Campaign recommendations. [3] Fluid resuscitation strategy was the administration of a crystalloid solution (0.9% saline) to maintain central venous pressure >12 mmHg. In patients who had MAP <65 mmHg despite adequate fluid administration for 6 h, a vasopressor drug (norepinephrine) was started. Norepinephrine was started with a dose of 5 mcg/min and was titrated based on the patient's hemodynamic status, up to 30 mcg/min. Antibiotic regimens were guided based on the hospital recommendations. Stress ulcer prophylaxis (pantoprazole 40 mg daily as intravenous injection) and deep venous thrombosis prophylaxis (heparin 5000 IU every 8 h as subcutaneous injection) were considered for all patients. Analgosedation (fentanyl as continuous intravenous infusion) was the sedation protocol in our center.

The patients were included in ascorbic acid or placebo group according to the permuted block randomization. The randomization scheme consisted of seven blocks and each block contained four patients in random order. Patients in the ascorbic acid group received 25 mg/kg intravenous ascorbic acid every 6 h for 72 h. The dose and duration of intervention were selected based on the literature review. [15],[17],[19],[20] Each dose of ascorbic acid was diluted in 50 ml of dextrose 5% solution and was administered as intravenous infusion over 30 min. Patients in the placebo group received 50 ml of dextrose 5% solution as intravenous infusion over 30 min.

The patients' demographic data (including age, sex, baseline diseases, and causes of ICU admission) were extracted from their medical charts, and the patients' clinical characteristics (such as vital signs and hemodynamic parameters) were monitored as daily interval. Laboratory data such as serum electrolyte concentrations, blood urea nitrogen (BUN), and serum creatinine levels were extracted from the patients' medical charts. The patients' Acute Physiology and Chronic Health Evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were calculated at the time of recruitment.

Change in the hemodynamic parameters (MAP and pulse rate), oxygenation status (respiratory rate, oxygen saturation, duration of mechanical ventilation, pH, and PaO 2 /FiO 2 ratio), fluid intake, renal function (BUN, serum creatinine, and urine output), and serum electrolytes during the study period were compared between the groups.

Vasopressor dose and duration were evaluated on a daily basis for 3 days and were considered as the primary outcomes. Duration of ICU stay and 28-day mortality has been defined as secondary outcomes.

During the study period, patients were followed for any ascorbic acid-related adverse effects including nausea, vomiting, abdominal pain, hematuria, flushing, and significant arterial blood pressure change.

Data were analyzed using  SPSS software version 17 (SPSS Inc., Chicago, USA). The Kolmogorov-Smirnov test was used to assess the normal distribution of continuous variables. Normally distributed continuous data were expressed as mean ± standard deviation. Categorical variables were reported as percentages. Chi-square or Fisher's exact test was used for comparing the categorical variables between the groups. Continuous variables were compared by the independent t-test. Mortality rate was compared between the groups using Chi-square test. Changes in the hemodynamic, oxygenation, and electrolyte parameters during the study period were assessed using one-way analysis of variance with repeated measure. P < 0.05 was defined as statistically significant.

  Results Top

During the study period, 28 patients (14 in each group) were recruited. No patient was excluded during 3-day intervention. Demographic and clinical characteristics of the recruited patients are shown in [Table 1]. From the participants, 71.42% and 78.57% in the ascorbic acid and control groups were male, respectively. Included subjects were admitted to the ICU following gastrointestinal surgeries. No statistically significant difference was detected between the groups in terms of demographic data and clinical characteristics. Severity of illnesses based on the SOFA and APACHE II scores was comparable between the groups at the time of enrollment.
Table 1: Demographic data of the patients

Click here to view

Hemodynamic parameters and laboratory tests did not differ significantly between the groups. In addition, changes in these parameters during the study period were not statistically significant. Data regarding these parameters are shown in [Table 2] and [Table 3].
Table 2: Hemodynamic parameters and oxygenation status of the patients

Click here to view
Table 3: Laboratory parameters of the patients

Click here to view

Mean dose of vasopressor (norepinephrine) during the study period (7.44 ± 3.65 vs. 13.79 ± 6.48 mcg/min, P = 0.004), mean dose of norepinephrine in the first 24 h of enrollment (6.51 ± 3.53 vs. 12.58 ± 5.99 mcg/min, P = 0.003), total dose of norepinephrine in the first 24 h (156.42 ± 84.81 vs. 302.14 ± 143.85 mcg, P = 0.003), and duration of receiving norepinephrine (49.64 ± 25.67 vs. 71.57 ± 1.60 h, P = 0.007) were significantly lower in the ascorbic acid than the placebo group [Table 4].
Table 4: Primary and secondary outcomes of the study in ascorbic and placebo groups

Click here to view

No statistically significant difference was detected between the groups regarding the length of ICU stay. However, the 28-day mortality was significantly lower in the ascorbic acid than the placebo group (14.28% vs. 64.28%, respectively; P = 0.009).

No ascorbic acid-related adverse events were identified in the treatment group during the study.

  Discussion Top

In this study, administration of high-dose ascorbic acid significantly decreased the requirement for vasopressor's dose and duration in surgical critically ill patients with septic shock. Several mechanisms including anti-oxidant, anti-inflammatory, nitric oxide (NO) synthase inhibitory, reversing vascular hyporesponsiveness to vasopressors, increasing catecholamines and cortisol synthesis in adrenal medulla, and improving vascular endothelium integrity properties may justified the role of ascorbic acid in septic shock. [8],[9],[10],[11],[15],[18],[23],[24]

Severe ascorbic acid deficiency (serum ascorbate level <27 μmol/L) was reported in critically ill patients. [15],[16],[25],[26],[27] Up to 3000 mg/day, ascorbic acid was needed to normalize the plasma level of ascorbic acid (68 μmol/L) in these patients. [28] Ascorbic acid deficiency was not prevented by the use of parenteral nutrition containing ascorbic acid in critically ill patients and most patients required high dose of this nutrient. [29],[30],[31],[32]

Catecholamines (dopamine, norepinephrine, and epinephrine) are produced by sympathetic nervous system and adrenal medulla. [33] Brain and adrenal glands have the highest levels of ascorbic acid in the body. [34] In catecholamine synthesis pathway, ascorbic acid is an essential cofactor for the copper-containing enzyme; dopamine β-hydroxylase. [35],[36] This enzyme has a critical role in norepinephrine synthesis from dopamine. Ascorbic acid deficiency was associated with decreased level of norepinephrine, especially in the adrenal glands. [37],[38],[39] Insufficiency in adrenal hormone synthesis has also been observed in critically ill patients. [40],[41]

Vasopressin is a peptide hormone that is synthesized form a preprohormone in the hypothalamus and stored in the posterior pituitary gland. [42] It is secreted following blood volume and arterial pressure dropping or plasma osmolality raising, attaches to vascular smooth muscle cells (AVPR 1a ), and kidney-collecting ducts (AVPR 2 ), receptors, and consequently induces vasoconstriction and water retention. [43] A significant increase in the vasopressin level was detected during the initial phase of septic shock. However, in the later phase, it decreased dramatically. [6],[44] The decrease in circulating vasopressin level is due to the depletion of pituitary storage and its synthesis. [7] Peptidylglycine α-amidating monooxygenase, a copper-containing enzyme with ascorbic acid cofactor, is essential for endogenous synthesis of vasopressin. [45] Decreasing activity of this enzyme during sepsis period may limit vasopressin synthesis. [7],[44],[46] Correlation between ascorbic acid deficiency and vasopressin insufficiency has been reported in critically ill patients. [26] Administration of ascorbic acid enhanced the circulating level of vasopressin. [47]

Septic shock is characterized by decreased peripheral vascular resistance and impaired blood and oxygen supply to the body's vital organs. A combination of vasodilatation and pronounced decrease in vascular response to vasopressor including high-dose norepinephrine often results in resistant hypotension. [6],[46] Overproduction of NO appears to be an important mechanism in septic shock, and inhibition of NO synthase might provide a novel therapeutic approach. In 1991, Petros et al. [8] assessed the effects of NO synthase inhibitors in two patients with life-threatening and unresponsive septic shock. NG monomethyl-L-arginine (L-NMMA) caused dose-dependent increase in blood pressure and systemic vascular resistance in both patients, and a similar effect was observed in the second patient after treatment with NG-nitro-L-arginine methyl ester. In another study, L-NMMA increased vascular tone and raised blood pressure in 12 patients with septic shock. [9] Furthermore, methylene blue as a guanylate cyclase and NO synthase inhibitor increased arterial blood pressure and improved cardiac function in septic patients. [10],[11]

Intravenous ascorbic acid improved cardiovascular functioning and decreased requirement for catecholamine administration in a patient with septic shock. [25] In another case with typical symptoms of scurvy and fluid-resistant severe orthostatic hypotension, intravenous ascorbic acid improved the patients' hemodynamic status within 24 h after its administration.

Inflammatory cascades and release of inflammatory cytokines are from known pathways in the pathogenesis of sepsis. [26] Administration of high-dose intravenous ascorbic acid to severely affected patients with burn injury decreased the fluid and vasopressors requirements. [17],[48] In a recent phase I, randomized controlled trial in 24 patients with severe sepsis, intravenous infusions of high-dose ascorbic acid (200 mg/kg/24 h) caused rapid reduction in SOFA score and improvement in hemodynamic parameters. Vascular endothelial repair following reduction in the proinflammatory biomarkers including C-reactive protein and procalcitonin as well as reduction of thrombomodulin level was suggested for ascorbic acid. [15],[49]

Anti-oxidant property may be responsible for some beneficial effects of ascorbic acid in severe sepsis and septic shock. Early administration of antioxidants; α-tocopherol, 1000 IU every 8 h and ascorbic acid 1000 mg intravenously in 100 ml D5W every 8 h for a short duration, reduced the incidence of organ failure and ICU length of stay in critically ill surgical patients. [18] Administration of Vitamin C augmented the inotropic response to dobutamine in human subjects who were selected for elective diagnostic heart catheterization. Redox-regulated pathways of adrenergic system and ventricular contractility may be responsible for this effect of ascorbic acid. [23]

Corticosteroids have an important position in preventing beta adrenergic receptors' down-regulation and maintaining vasopressors' responsiveness of the vascular bed in septic shock. [11] Cortisol-sparing effect of ascorbic acid has been reported. Vitamin C significantly prevented etomidate-induced adrenal insufficiency and serum cortisol depletion. [24]

Ascorbic acid is a safe anti-oxidant nutrient and no any considerable adverse event has been reported yet, even after high-dose administration. In Nathens et al. study, critically ill surgical patients tolerated ascorbic acid, 1 g every 8 h for 28 days, without any adverse effect. [18] In addition, no adverse event was detected in critically ill patients with burn injury who received ascorbic acid with a dose of 66 mg/kg/h for 24 h. [17] Aggressive repletion of plasma ascorbic acid level was safe in patients with severe sepsis. No patient with the low (50 mg/kg/24 h) or high (200 mg/kg/24 h) dose of ascorbic acid experienced any identifiable ascorbic acid-related adverse event. [15] Similar to previous studies, we did not detect any ascorbic acid-related adverse events in the included patients.

Fluid resuscitation, vasopressor therapy, and ventilation supports are cornerstones of severe sepsis and septic shock management. Although oxygenation status, duration of mechanical ventilation, and hemodynamic parameters were comparable between the two groups in our study, for targeting these points, patients in the placebo group needed higher dose and longer duration of vasopressor therapy.

Although the results of our study are promising, the study suffers from some limitations. Small sample size, short period of intervention, and no assessment of the patients' serum ascorbate baseline level are the major limitations of our study. Further randomized controlled trials with sufficient sample size and assessment of baseline serum ascorbate level, serum antioxidant capacity, and proinflammatory cytokines may be considered in future studies.

Our results suggested that high-dose of ascorbic acid (25 mg/kg intravenously every 6 h for 72 h) with its probable anti-oxidant, anti-inflammatory, cortisol sparing, NO synthase inhibitory and increasing catecholamines synthesis in the brain, and adrenal medulla properties may be considered as an effective and safe adjuvant therapy in critically ill surgical patients with septic shock. However, as limited evidences are now available, the most effective dose of ascorbic acid and the best time for its administration should be determined in future studies.

  Authors' Contribution Top

MH: Data gathering and primary drafting of the manuscript, MM: Clinical evaluation of the patients, MR: Controlling of the patients' medications and hemodynamic assessment, HK: Designing of the study and editing the manuscript.


This study was the result of a Pharm.D student thesis. The authors expressed sincere gratitude to all the nursing staff of general ICU of Imam Khomeini Hospital for their kind support.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Remick DG. Pathophysiology of sepsis. Am J Pathol 2007;170:1435-44.  Back to cited text no. 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.  Back to cited text no. 2
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.  Back to cited text no. 3
Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369:840-51.  Back to cited text no. 4
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.  Back to cited text no. 5
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.  Back to cited text no. 6
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.  Back to cited text no. 7
Petros A, Bennett D, Vallance P. Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 1991;338:1557-8.  Back to cited text no. 8
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.  Back to cited text no. 9
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.  Back to cited text no. 10
O'Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet 2002;359:1209-10.  Back to cited text no. 11
Carr A, Frei B. Does Vitamin C act as a pro-oxidant under physiological conditions? FASEB J 1999;13:1007-24.  Back to cited text no. 12
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.  Back to cited text no. 13
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.  Back to cited text no. 14
Fowler AA 3 rd , 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.  Back to cited text no. 15
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.  Back to cited text no. 16
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.  Back to cited text no. 17
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.  Back to cited text no. 18
Wilson JX. Evaluation of Vitamin C for adjuvant sepsis therapy. Antioxid Redox Signal 2013;19:2129-40.  Back to cited text no. 19
Oudemans-van Straaten HM, Spoelstra-de Man A, de Waard MC. Vitamin C revisited. Crit Care Med 2014;18:460.  Back to cited text no. 20
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.  Back to cited text no. 21
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.  Back to cited text no. 22
Mak S, Newton GE. Vitamin C augments the inotropic response to dobutamine in humans with normal left ventricular function. Circulation 2001;103:826-30.  Back to cited text no. 23
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.  Back to cited text no. 24
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.  Back to cited text no. 25
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.  Back to cited text no. 26
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.  Back to cited text no. 27
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.  Back to cited text no. 28
29 Fukushima R, Yamazaki E. Vitamin C requirement in surgical patients. Curr Opin Clin Nutr Metab Care 2010;13:669-76.  Back to cited text no. 29
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.  Back to cited text no. 30
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.  Back to cited text no. 31
Lowry SF, Goodgame JT Jr., Maher MM, Brennan MF. Parenteral Vitamin requirements during intravenous feeding. Am J Clin Nutr 1978;31:2149-58.  Back to cited text no. 32
De Backer D, Scolletta S. Clinical management of the cardiovascular failure in sepsis. Curr Vasc Pharmacol 2013;11:222-42.  Back to cited text no. 33
Hornig D. Distribution of ascorbic acid, metabolites and analogues in man and animals. Ann N Y Acad Sci 1975;258:103-18.  Back to cited text no. 34
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.  Back to cited text no. 35
Levine M. Ascorbic acid specifically enhances dopamine beta-monooxygenase activity in resting and stimulated chromaffin cells. J Biol Chem 1986;261:7347-56.  Back to cited text no. 36
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.  Back to cited text no. 37
Hoehn SK, Kanfer JN. Effects of chronic ascorbic acid deficiency on guinea pig lysosomal hydrolase activities. J Nutr 1980;110:2085-94.  Back to cited text no. 38
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.  Back to cited text no. 39
Duggan M, Browne I, Flynn C. Adrenal failure in the critically ill. Br J Anaesth 1998;81:468-70.  Back to cited text no. 40
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.  Back to cited text no. 41
Treschan TA, Peters J. The vasopressin system: Physiology and clinical strategies. Anesthesiology 2006;105:599-612.  Back to cited text no. 42
Russell JA. Bench-to-bedside review: Vasopressin in the management of septic shock. Crit Care Med 2011;15:226.  Back to cited text no. 43
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.  Back to cited text no. 44
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.  Back to cited text no. 45
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.  Back to cited text no. 46
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.  Back to cited text no. 47
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.  Back to cited text no. 48
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.  Back to cited text no. 49


  [Table 1], [Table 2], [Table 3], [Table 4]

This article has been cited by
1 Vitamin C, Quo Vadis?*
L. Nelson Sanchez-Pinto,Eric L. Wald
Pediatric Critical Care Medicine. 2021; 22(6): 588
[Pubmed] | [DOI]
2 Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial
Sander Rozemeijer,Harm-Jan de Grooth,Paul W. G. Elbers,Armand R. J. Girbes,Corstiaan A. den Uil,Eric A. Dubois,Evert-Jan Wils,Thijs C. D. Rettig,Arthur R. H. van Zanten,Roel Vink,Bas van den Bogaard,Rob J. Bosman,Heleen M. Oudemans-van Straaten,Angélique M. E. de Man
Trials. 2021; 22(1)
[Pubmed] | [DOI]
3 Vitamina C, tiamina e hidrocortisona en choque séptico (protocolo VITHA): estudio de cohortes
Claudia Patricia Cardona Campo,José Fernando Gómez González,Germán Alberto Moreno Gómez,Andrés Mauricio García Cuevas,Carlos Mario Sánchez Cadavid,Edgardo Quiñones Quiñones
Acta Colombiana de Cuidado Intensivo. 2021;
[Pubmed] | [DOI]
4 Adjunctive treatments for the management of septic shock – a narrative review of the current evidence
K. Donovan,A. Shah,J. Day,S. R. McKechnie
Anaesthesia. 2021;
[Pubmed] | [DOI]
5 Rapid screening of critically ill patients for low plasma vitamin C concentrations using a point-of-care oxidation–reduction potential measurement
Sander Rozemeijer,Bob Smit,Paul W. G. Elbers,Armand R. J. Girbes,Heleen M. Oudemans-van Straaten,Angelique M. E. de Man
Intensive Care Medicine Experimental. 2021; 9(1)
[Pubmed] | [DOI]
6 SARS-CoV-2 Mediated Endothelial Dysfunction: The Potential Role of Chronic Oxidative Stress
Ryan Chang,Abrar Mamun,Abishai Dominic,Nhat-Tu Le
Frontiers in Physiology. 2021; 11
[Pubmed] | [DOI]
7 Micronutrients in Sepsis and COVID-19: A Narrative Review on What We Have Learned and What We Want to Know in Future Trials
Matteo Rossetti,Gennaro Martucci,Christina Starchl,Karin Amrein
Medicina. 2021; 57(5): 419
[Pubmed] | [DOI]
8 Vitamin C-Induced Oxalate Nephropathy in a Septic Patient
Tasheen Wissanji,Marie-Eve Dupuis,Virginie Royal,Vincent Pichette,Han Ting Wang
Critical Care Explorations. 2021; 3(4): e0389
[Pubmed] | [DOI]
9 The effect of vitamin C on pulmonary oedema in patients with severe preeclampsia: A single-centre, randomised, placebo-controlled, double-blind trial
Monika Korenc,Laurent Zieleskiewicz,Tatjana Stopar Pintaric,Iva Blajic,Jana Ambrozic,Miha Lucovnik
Anaesthesia Critical Care & Pain Medicine. 2021; 40(1): 100800
[Pubmed] | [DOI]
10 Mortality in septic patients treated with vitamin C: a systematic meta-analysis
Sean S. Scholz,Rainer Borgstedt,Nicole Ebeling,Leoni C. Menzel,Gerrit Jansen,Sebastian Rehberg
Critical Care. 2021; 25(1)
[Pubmed] | [DOI]
11 Ascorbic acid as an adjunctive therapy in critically ill patients with COVID-19: a propensity score matched study
Khalid Al Sulaiman,Ohoud Aljuhani,Khalid Bin Saleh,Hisham A. Badreldin,Abdullah Al Harthi,Mohammed Alenazi,Aisha Alharbi,Rahmah Algarni,Shmeylan Al Harbi,Abdullah M. Alhammad,Ramesh Vishwakarma,Sarah Aldekhyl
Scientific Reports. 2021; 11(1)
[Pubmed] | [DOI]
12 A pilot study on the melatonin treatment in patients with early septic shock: results of a single-center randomized controlled trial
Abbas Taher,Farnaz Shokoohmand,Elham Abdoli,Younes Mohammadi,Maryam Mehrpooya
Irish Journal of Medical Science (1971 -). 2021;
[Pubmed] | [DOI]
13 Combined hydrocortisone, ascorbic acid, and thiamine therapy for septic shock with complicated intraabdominal infection: before and after cohort study
Yong Oh Kim,Kee Sang Yoo,Kyoung Won Yoon,Hyo Jung Park,Chi-Min Park
Annals of Surgical Treatment and Research. 2021; 100(6): 356
[Pubmed] | [DOI]
14 Analysis of the Effect of Vitamin C at IC50 on RAW264.7 and K562 Cells Based on 1H NMR Metabonomics
Hui Li,Yang Lu,Yue Geng
ACS Food Science & Technology. 2021;
[Pubmed] | [DOI]
15 Effect of Vitamin C on mortality of critically ill patients with severe pneumonia in intensive care unit: a preliminary study
Ata Mahmoodpoor,Kamran Shadvar,Sarvin Sanaie,Mir Reza Hadipoor,Mohammad Ata Pourmoghaddam,Seied Hadi Saghaleini
BMC Infectious Diseases. 2021; 21(1)
[Pubmed] | [DOI]
16 Ex Vivo Evaluation of the Sepsis Triple Therapy High-Dose Vitamin C in Combination with Vitamin B1 and Hydrocortisone in a Human Peripheral Blood Mononuclear Cells (PBMCs) Model
Annie Lauer,Markus Burkard,Heike Niessner,Christian Leischner,Olga Renner,Claudia Vollbracht,Holger Michels,Christian Busch,Tobias Sinnberg,Sascha Venturelli
Nutrients. 2021; 13(7): 2366
[Pubmed] | [DOI]
17 Vitamin therapy in sepsis
Eric L. Wald,Colleen M. Badke,Lauren K. Hintz,Michael Spewak,L. Nelson Sanchez-Pinto
Pediatric Research. 2021;
[Pubmed] | [DOI]
18 Steroid, ascorbic acid, and thiamine in adults with sepsis and septic shock: a systematic review and component network meta-analysis
Ka Man Fong,Shek Yin Au,George Wing Yiu Ng
Scientific Reports. 2021; 11(1)
[Pubmed] | [DOI]
19 Novel insights into peptide amidation and amidating activity in the human circulation
Paul Kaufmann,Andreas Bergmann,Olle Melander
Scientific Reports. 2021; 11(1)
[Pubmed] | [DOI]
20 Measuring vitamin C in critically ill patients: clinical importance and practical difficulties—Is it time for a surrogate marker?
Sander Rozemeijer,Frans A. L. van der Horst,Angélique M. E. de Man
Critical Care. 2021; 25(1)
[Pubmed] | [DOI]
21 Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice
Connie P. C. Ow,Anton Trask-Marino,Ashenafi H. Betrie,Roger G. Evans,Clive N. May,Yugeesh R. Lankadeva
Journal of Clinical Medicine. 2021; 10(17): 3798
[Pubmed] | [DOI]
22 Vitamin C – neue Therapiemöglichkeit bei Sepsis?
Stefan Müller,Thomas Wiesmann,Hinnerk Wulf,Christian Arndt
AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie. 2021; 56(05): 374
[Pubmed] | [DOI]
23 Vitamin C and corticosteroids in viral pneumonia
Matthew Harry Anstey,Jacky Luu,Erina Myers,Robert N Palmer,Bradley Wibrow,Kwok M Ho
Acute and Critical Care. 2021; 36(2): 169
[Pubmed] | [DOI]
24 Effect of high-dose intravenous vitamin c on point-of-care blood glucose level in septic patients: a retrospective, single-center, observational case series
Juan He,Guanhao Zheng,Xian Qian,Huiqiu Sheng,Bing Chen,Bing Zhao,Erzhen Chen,Enqiang Mao,Xiaolan Bian
Current Medical Research and Opinion. 2021; : 1
[Pubmed] | [DOI]
25 A prospective, randomised clinical study comparing triple therapy regimen to hydrocortisone monotherapy in reducing mortality in septic shock patients
Abdelrhman A. Hussein,Nirmeen A. Sabry,Maged S. Abdalla,Samar F. Farid
International Journal of Clinical Practice. 2021;
[Pubmed] | [DOI]
26 Therapeutic potential of megadose vitamin C to reverse organ dysfunction in sepsis and COVID-19
Clive N. May,Rinaldo Bellomo,Yugeesh R. Lankadeva
British Journal of Pharmacology. 2021;
[Pubmed] | [DOI]
27 The relationship between vitamin C or thiamine levels and outcomes for severe sepsis patients admitted to the ICU
Nandan Prasad,Anne V. Grossestreuer,Nuala J. Meyer,Sarah M. Perman,Mark E. Mikkelsen,Judd Hollander,David F. Gaieski
Scientific Reports. 2021; 11(1)
[Pubmed] | [DOI]
28 Vitamin C and COVID-19
Harri Hemilä,Angelique M. E. de Man
Frontiers in Medicine. 2021; 7
[Pubmed] | [DOI]
29 Lack of Benefit of High-Dose Vitamin C, Thiamine, and Hydrocortisone Combination for Patients With Sepsis
Andre C. Kalil
JAMA. 2020;
[Pubmed] | [DOI]
30 Vitamin C levels amongst initial survivors of out of hospital cardiac arrest
Ryan Gardner,Xiaowen Liu,Yanbo Wang,Andrew Cole,Stanley Heydrick,Michael W. Donnino,Ari Moskowitz
Resuscitation. 2020; 156: 190
[Pubmed] | [DOI]
31 General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections
Gianfranco Umberto Meduri,George P. Chrousos
Frontiers in Endocrinology. 2020; 11
[Pubmed] | [DOI]
32 Sepsis-Induced Myocardial Dysfunction (SIMD): the Pathophysiological Mechanisms and Therapeutic Strategies Targeting Mitochondria
Yao Lin,Yinchuan Xu,Zhaocai Zhang
Inflammation. 2020;
[Pubmed] | [DOI]
33 Vitamin C, Thiamine, and Steroids in the Sepsis Conquest: Replete to Defeat
Erenie Guirguis,Yasmin Grace,Harm Maarsingh,Thi Ca Tran,Elena Tkachuk
Journal of Pharmacy Practice. 2020; 33(5): 682
[Pubmed] | [DOI]
34 The Effect of the Vitamin Protocol for Treating Sepsis or Septic Shock in Pediatric Intensive Care Unit
Hyun Jung Ko,Min Jae Jung,Jae Song Kim,Eun Sun Son,Yun Mi Yu
Korean Journal of Clinical Pharmacy. 2020; 30(3): 161
[Pubmed] | [DOI]
35 Ascorbic Acid, Thiamine, and Steroids in Septic Shock: Propensity Matched Analysis
Farid Sadaka,Justin Grady,Nikhil Organti,Bhargavi Donepudi,Matthew Korobey,David Tannehill,Jacklyn O’Brien
Journal of Intensive Care Medicine. 2020; 35(11): 1302
[Pubmed] | [DOI]
36 A Possible Application of High Dose Vitamin C in the Prevention and Therapy for Coronavirus Infections
Ba X. Hoang,D. Graeme Shaw,William Fang,Bo Han
Journal of Global Antimicrobial Resistance. 2020;
[Pubmed] | [DOI]
37 Vitamin C measurement in critical illness: challenges, methodologies and quality improvements
Jake T.B. Collie,Ronda F. Greaves,Oliver A.H. Jones,Glenn Eastwood,Rinaldo Bellomo
Clinical Chemistry and Laboratory Medicine (CCLM). 2020; 58(4): 460
[Pubmed] | [DOI]
38 Vitamin C and thiamine are associated with lower mortality in sepsis
Saskya Byerly,Joshua P. Parreco,Hahn Soe-Lin,Jonathan J. Parks,Eugenia E. Lee,Ilya Shnaydman,Alejandro Mantero,D. Dante Yeh,Nicholas Namias,Rishi Rattan
Journal of Trauma and Acute Care Surgery. 2020; 89(1): 111
[Pubmed] | [DOI]
39 The critical care literature 2019
Michael E. Winters,Kami Hu,Joseph P. Martinez,Haney Mallemat,William J. Brady
The American Journal of Emergency Medicine. 2020;
[Pubmed] | [DOI]
40 Reanalysis of the Effect of Vitamin C on Mortality in the CITRIS-ALI Trial: Important Findings Dismissed in the Trial Report
Harri Hemilä,Elizabeth Chalker
Frontiers in Medicine. 2020; 7
[Pubmed] | [DOI]
41 The Emerging Role of Vitamin C as a Treatment for Sepsis
Markos G. Kashiouris,Michael L’Heureux,Casey A. Cable,Bernard J. Fisher,Stefan W. Leichtle,Alpha A. Fowler
Nutrients. 2020; 12(2): 292
[Pubmed] | [DOI]
42 Dosing vitamin C in critically ill patients with special attention to renal replacement therapy: a narrative review
Patrick M. Honore,Herbert D. Spapen,Paul Marik,Willem Boer,Heleen Oudemans-van Straaten
Annals of Intensive Care. 2020; 10(1)
[Pubmed] | [DOI]
43 Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children
Scott L. Weiss,Mark J. Peters,Waleed Alhazzani,Michael S. D. Agus,Heidi R. Flori,David P. Inwald,Simon Nadel,Luregn J. Schlapbach,Robert C. Tasker,Andrew C. Argent,Joe Brierley,Joseph Carcillo,Enitan D. Carrol,Christopher L. Carroll,Ira M. Cheifetz,Karen Choong,Jeffry J. Cies,Andrea T. Cruz,Daniele De Luca,Akash Deep,Saul N. Faust,Claudio Flauzino De Oliveira,Mark W. Hall,Paul Ishimine,Etienne Javouhey,Koen F. M. Joosten,Poonam Joshi,Oliver Karam,Martin C. J. Kneyber,Joris Lemson,Graeme MacLaren,Nilesh M. Mehta,Morten Hylander Møller,Christopher J. L. Newth,Trung C. Nguyen,Akira Nishisaki,Mark E. Nunnally,Margaret M. Parker,Raina M. Paul,Adrienne G. Randolph,Suchitra Ranjit,Lewis H. Romer,Halden F. Scott,Lyvonne N. Tume,Judy T. Verger,Eric A. Williams,Joshua Wolf,Hector R. Wong,Jerry J. Zimmerman,Niranjan Kissoon,Pierre Tissieres
Pediatric Critical Care Medicine. 2020; 21(2): e52
[Pubmed] | [DOI]
44 Overview of the possible role of vitamin C in management of COVID-19
Anis Abobaker,Aboubaker Alzwi,Alsalheen Hamed A. Alraied
Pharmacological Reports. 2020;
[Pubmed] | [DOI]
45 The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19
Giuseppe Cerullo,Massimo Negro,Mauro Parimbelli,Michela Pecoraro,Simone Perna,Giorgio Liguori,Mariangela Rondanelli,Hellas Cena,Giuseppe D’Antona
Frontiers in Immunology. 2020; 11
[Pubmed] | [DOI]
46 Role of vitamin C in critically ill patients with COVID-19: is it effective?
Siddique Mohyud Din Chaudhary,Robert Matthew Wright,Gabriel Patarroyo-Aponte
Acute and Critical Care. 2020; 35(4): 307
[Pubmed] | [DOI]
47 Adjunctive therapy with vitamin c and thiamine in patients treated with steroids for refractory septic shock: A propensity matched before-after, case-control study
Coloretti Irene,Biagioni Emanuela,Venturelli Sophie,Munari Elena,Martina Tosi,Roat Erika,Brugioni Lucio,Gelmini Roberta,Venturelli Claudia,Girardis Massimo
Journal of Critical Care. 2020;
[Pubmed] | [DOI]
48 Sepsis-Induced Cardiomyopathy: a Comprehensive Review
Michael L’Heureux,Michael Sternberg,Lisa Brath,Jeremy Turlington,Markos G. Kashiouris
Current Cardiology Reports. 2020; 22(5)
[Pubmed] | [DOI]
49 Metabolic Resuscitation Using Hydrocortisone, Ascorbic Acid, and Thiamine: Do Individual Components Influence Reversal of Shock Independently?
Paidi Ramakrishna Reddy,Sangeeta Yelle,Boggu Rajyalakshmi
Indian Journal of Critical Care Medicine. 2020; 24(8): 649
[Pubmed] | [DOI]
50 Lessening Organ dysfunction with VITamin C (LOVIT): protocol for a randomized controlled trial
Marie-Hélène Masse,Julie Ménard,Sheila Sprague,Marie-Claude Battista,Deborah J. Cook,Gordon H. Guyatt,Daren K. Heyland,Salmaan Kanji,Ruxandra Pinto,Andrew G. Day,Dian Cohen,Djillali Annane,Shay McGuinness,Rachael Parke,Anitra Carr,Yaseen Arabi,Bharath Kumar Tirupakuzhi Vijayaraghavan,Frédérick D’Aragon,Élaine Carbonneau,David Maslove,Miranda Hunt,Bram Rochwerg,Tina Millen,Michaël Chassé,Martine Lebrasseur,Patrick Archambault,Estel Deblois,Christine Drouin,François Lellouche,Patricia Lizotte,Irene Watpool,Rebecca Porteous,France Clarke,Nicole Marinoff,Émilie Belley-Côté,Brigitte Bolduc,Scott Walker,John Iazzetta,Neill K. J. Adhikari,François Lamontagne
Trials. 2020; 21(1)
[Pubmed] | [DOI]
51 Surgical Infection Society Research Priorities: A Narrative Review of Fourteen Years of Progress
Tina S. Mele,Haytham M.A. Kaafarani,Christopher A. Guidry,Michele M. Loor,David Machado-Aranda,April E. Mendoza,Gareth Morris-Stiff,Rishi Rattan,Sebastian D. Schubl,Philip S. Barie
Surgical Infections. 2020;
[Pubmed] | [DOI]
52 Hydrocortisone–Ascorbic Acid–Thiamine Use Associated with Lower Mortality in Pediatric Septic Shock
Eric L. Wald,L. Nelson Sanchez-Pinto,Craig M. Smith,Thomas Moran,Colleen M. Badke,Matthew F. Barhight,Marcelo R. Malakooti
American Journal of Respiratory and Critical Care Medicine. 2020; 201(7): 863
[Pubmed] | [DOI]
53 Hydrocortisone, ascorbic acid and thiamine for sepsis: Is the jury out?
Paul Ellis Marik,Joseph Varon,Salim Surani
World Journal of Diabetes. 2020; 11(4): 90
[Pubmed] | [DOI]
54 The Potential Influence of Vitamin A, C, and D and Zinc Supplements on the Severity of COVID-19 Symptoms and Clinical Outcomes: An Updated Review of Literature
Abeer Salman Alzaben
Current Research in Nutrition and Food Science Journal. 2020; 8(3): 703
[Pubmed] | [DOI]
55 Glucocorticoids in Sepsis: To Be or Not to Be
Jolien Vandewalle,Claude Libert
Frontiers in Immunology. 2020; 11
[Pubmed] | [DOI]
56 Vitamin C in health and disease: A companion animal focus
D.S. Gordon,A.J. Rudinsky,J. Guillaumin,V.J. Parker,K.J. Creighton
Topics in Companion Animal Medicine. 2020; : 100432
[Pubmed] | [DOI]
57 Effects of thiamine on vasopressor requirements in patients with septic shock: a prospective randomized controlled trial
Suttasinee Petsakul,Sunthiti Morakul,Viratch Tangsujaritvijit,Parinya Kunawut,Pongsasit Singhatas,Pitsucha Sanguanwit
BMC Anesthesiology. 2020; 20(1)
[Pubmed] | [DOI]
58 Impact of Vitamin C and Thiamine Administration on Delirium-Free Days in Patients with Septic Shock
Jong Eun Park,Tae Gun Shin,Ik Joon Jo,Kyeongman Jeon,Gee Young Suh,Minsu Park,Hojeong Won,Chi Ryang Chung,Sung Yeon Hwang
Journal of Clinical Medicine. 2020; 9(1): 193
[Pubmed] | [DOI]
59 Treating sepsis with vitamin C, thiamine, and hydrocortisone: Exploring the quest for the magic elixir
J. Obi,S.M. Pastores,L.V. Ramanathan,J. Yang,N.A. Halpern
Journal of Critical Care. 2020;
[Pubmed] | [DOI]
60 Reversal of Vasodilatory Shock
Jonathan H. Chow,Ezeldeen Abuelkasem,Susan Sankova,Reney A. Henderson,Michael A. Mazzeffi,Kenichi A. Tanaka
Anesthesia & Analgesia. 2020; 130(1): 15
[Pubmed] | [DOI]
61 Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19
Patrick Holford,Anitra C. Carr,Thomas H. Jovic,Stephen R. Ali,Iain S. Whitaker,Paul E. Marik,A. David Smith
Nutrients. 2020; 12(12): 3760
[Pubmed] | [DOI]
62 Safety, Pharmacodynamics, and Efficacy of High- Versus Low-Dose Ascorbic Acid in Severely Burned Adults
Sarah Sophie Nagel,Christian Andreas Radu,Thomas Kremer,David Meess,Johannes Horter,Benjamin Ziegler,Christoph Hirche,Volker Juergen Schmidt,Ulrich Kneser,Gabriel Hundeshagen
Journal of Burn Care & Research. 2020;
[Pubmed] | [DOI]
63 In Vitro and In Silico Analysis of Ascorbic Acid Towards Lanosterol 14-a-Demethylase Enzyme of Fluconazole-Resistant Candida albicans
Arumugam Ganeshkumar,Suvaiyarasan Suvaithenamudhan,Rajendran Rajaram
Current Microbiology. 2020;
[Pubmed] | [DOI]
64 Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis
Harri Hemilä,Elizabeth Chalker
Journal of Intensive Care. 2020; 8(1)
[Pubmed] | [DOI]
65 Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children
Scott L. Weiss,Mark J. Peters,Waleed Alhazzani,Michael S. D. Agus,Heidi R. Flori,David P. Inwald,Simon Nadel,Luregn J. Schlapbach,Robert C. Tasker,Andrew C. Argent,Joe Brierley,Joseph Carcillo,Enitan D. Carrol,Christopher L. Carroll,Ira M. Cheifetz,Karen Choong,Jeffry J. Cies,Andrea T. Cruz,Daniele De Luca,Akash Deep,Saul N. Faust,Claudio Flauzino De Oliveira,Mark W. Hall,Paul Ishimine,Etienne Javouhey,Koen F. M. Joosten,Poonam Joshi,Oliver Karam,Martin C. J. Kneyber,Joris Lemson,Graeme MacLaren,Nilesh M. Mehta,Morten Hylander Møller,Christopher J. L. Newth,Trung C. Nguyen,Akira Nishisaki,Mark E. Nunnally,Margaret M. Parker,Raina M. Paul,Adrienne G. Randolph,Suchitra Ranjit,Lewis H. Romer,Halden F. Scott,Lyvonne N. Tume,Judy T. Verger,Eric A. Williams,Joshua Wolf,Hector R. Wong,Jerry J. Zimmerman,Niranjan Kissoon,Pierre Tissieres
Intensive Care Medicine. 2020; 46(S1): 10
[Pubmed] | [DOI]
66 Pharmacologic Agents for the Treatment of Vasodilatory Shock
Hans Knotzer,Bernhard Poidinger,Axel Kleinsasser
Current Pharmaceutical Design. 2019; 25(19): 2133
[Pubmed] | [DOI]
67 Reporting of Organ Support Outcomes in Septic Shock Randomized Controlled Trials
Simon Bourcier,Patrick Hindlet,Bertrand Guidet,Agnès Dechartres
Critical Care Medicine. 2019; 47(7): 984
[Pubmed] | [DOI]
68 Combination therapy of vitamin C and thiamine for septic shock in a multicentre, double-blind, randomized, controlled study (ATESS): study protocol for a randomized controlled trial
Sung Yeon Hwang,Jong Eun Park,Ik Joon Jo,Seonwoo Kim,Sung Phil Chung,Taeyoung Kong,Jonghwan Shin,Hui Jai Lee,Kyoung Min You,You Hwan Jo,Doyun Kim,Gil Joon Suh,Taegyun Kim,Won Young Kim,Youn-Jung Kim,Seung Mok Ryoo,Sung-Hyuk Choi,Tae Gun Shin
Trials. 2019; 20(1)
[Pubmed] | [DOI]
69 Early Vitamin C and Thiamine Administration to Patients with Septic Shock in Emergency Departments: Propensity Score-Based Analysis of a Before-and-After Cohort Study
Tae Gun Shin,Youn-Jung Kim,Seung Mok Ryoo,Sung Yeon Hwang,Ik Joon Jo,Sung Phil Chung,Sung-Hyuk Choi,Gil Joon Suh,Won Young Kim
Journal of Clinical Medicine. 2019; 8(1): 102
[Pubmed] | [DOI]
70 Lactated Ringer’s Versus 4% Albumin on Lactated Ringer’s in Early Sepsis Therapy in Cancer Patients
Clarice Hyesuk Lee Park,Juliano Pinheiro de Almeida,Gisele Queiroz de Oliveira,Stéphanie Itala Rizk,Julia Tizue Fukushima,Rosana Ely Nakamura,Matheus Moraes Mourão,Filomena Regina Barbosa Gomes Galas,Edson Abdala,Maristela Pinheiro Freire,Roberto Kalil Filho,Jose Otavio Costa Auler,Pasquale Nardelli,Greg S. Martin,Giovanni Landoni,Ludhmila Abrahao Hajjar
Critical Care Medicine. 2019; 47(10): e798
[Pubmed] | [DOI]
71 Vitamin C in surgical sepsis
Tanya Anand,Lauren K. Roller,Gregory J. Jurkovich
Current Opinion in Critical Care. 2019; 25(6): 712
[Pubmed] | [DOI]
72 Effects of different ascorbic acid doses on the mortality of critically ill patients: a meta-analysis
Ying Wang,Huan Lin,Bing-wen Lin,Jian-dong Lin
Annals of Intensive Care. 2019; 9(1)
[Pubmed] | [DOI]
73 The Effect of Vitamin C on Clinical Outcome in Critically Ill Patients
Alessandro Putzu,Anne-Marie Daems,Juan Carlos Lopez-Delgado,Vito Federico Giordano,Giovanni Landoni
Critical Care Medicine. 2019; 47(6): 774
[Pubmed] | [DOI]
74 Understanding Vitamin C in Critical Illness
Michael H. Hooper,David N. Hager
Critical Care Medicine. 2019; 47(6): 867
[Pubmed] | [DOI]
75 Adjunctive Therapies in the Management of Septic Shock
Raj Parikh,Samuel H. Belok,Lakshmana Swamy,Christine C. Reardon
American Journal of Respiratory and Critical Care Medicine. 2019; 200(3): 381
[Pubmed] | [DOI]
76 Reduced plasma ascorbic acid levels in recipients of myeloablative conditioning and hematopoietic cell transplantation
Mahmood Rasheed,Gary Simmons,Bernard Fisher,Kevin Leslie,Jason Reed,Catherine Roberts,Ramesh Natarajan,Alpha Fowler,Amir Toor
European Journal of Haematology. 2019;
[Pubmed] | [DOI]
77 Different doses of vitamin C supplementation enhances the Th1 immune response to early Plasmodium yoelii 17XL infection in BALB/c mice
Xiaosong Qin,Jianhua Liu,Yunting Du,Ying Li,Li Zheng,Guang Chen,Yaming Cao
International Immunopharmacology. 2019; 70: 387
[Pubmed] | [DOI]
78 Sepsis - What's new in 2019?
Mark E. Nunnally,Arpit Patel
Current Opinion in Anaesthesiology. 2019; 32(2): 163
[Pubmed] | [DOI]
79 Vitamin C Can Shorten the Length of Stay in the ICU: A Meta-Analysis
Harri Hemilä,Elizabeth Chalker
Nutrients. 2019; 11(4): 708
[Pubmed] | [DOI]
80 Challenges in the management of septic shock: a narrative review
Daniel De Backer,Maurizio Cecconi,Jeffrey Lipman,Flavia Machado,Sheila Nainan Myatra,Marlies Ostermann,Anders Perner,Jean-Louis Teboul,Jean-Louis Vincent,Keith R. Walley
Intensive Care Medicine. 2019;
[Pubmed] | [DOI]
81 Perioperative Vitamin C and E levels in Cardiac Surgery Patients and Their Clinical Significance
Aileen Hill,Christina Borgs,Christina Fitzner,Christian Stoppe
Nutrients. 2019; 11(9): 2157
[Pubmed] | [DOI]
82 Safety of vitamin C in sepsis
Niloofar Khoshnam-Rad,Hossein Khalili
Current Opinion in Critical Care. 2019; 25(4): 329
[Pubmed] | [DOI]
83 Sepsis 2019: What Surgeons Need to Know
Vanessa P. Ho,Haytham Kaafarani,Rishi Rattan,Nicholas Namias,Heather Evans,Tanya L. Zakrison
Surgical Infections. 2019;
[Pubmed] | [DOI]
84 Efficacy of vitamin C in patients with sepsis: A updated meta-analysis
Xue-biao Wei,Zhong-hua Wang,Xiao-long Liao,Wei-xin Guo,Jian-Yi Wen,Tie-he Qin,Shou-hong Wang
European Journal of Pharmacology. 2019; : 172889
[Pubmed] | [DOI]
85 Revisiting the Role of Vitamin C in Sepsis. Is it a Forlorn Hope or is there Still Dearth of data?
Salim Surani,Munish Sharma
The Open Respiratory Medicine Journal. 2019; 13(1): 55
[Pubmed] | [DOI]
86 The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial
David N. Hager,Michael H. Hooper,Gordon R. Bernard,Laurence W. Busse,E. Wesley Ely,Alpha A. Fowler,David F. Gaieski,Alex Hall,Jeremiah S. Hinson,James C. Jackson,Gabor D. Kelen,Mark Levine,Christopher J. Lindsell,Richard E. Malone,Anna McGlothlin,Richard E. Rothman,Kert Viele,David W. Wright,Jonathan E. Sevransky,Greg S. Martin
Trials. 2019; 20(1)
[Pubmed] | [DOI]
87 Vitamin C: The next step in sepsis management?
J. Teng,A. Pourmand,M. Mazer-Amirshahi
Journal of Critical Care. 2018; 43: 230
[Pubmed] | [DOI]
88 Making sense of early high-dose intravenous vitamin C in ischemia/reperfusion injury
Angelique M. E. Spoelstra-de Man,Paul W. G. Elbers,Heleen M. Oudemans-van Straaten
Critical Care. 2018; 22(1)
[Pubmed] | [DOI]
89 Bet 2: Does intravenous vitamin C improve mortality in patients with severe sepsis?
Mohammed Sheikh,Daniel Horner
Emergency Medicine Journal. 2018; 35(4): 272
[Pubmed] | [DOI]
90 Vitamin C for the treatment of sepsis: The scientific rationale
Paul E. Marik
Pharmacology & Therapeutics. 2018;
[Pubmed] | [DOI]
91 Vitamin therapy in critically ill patients: focus on thiamine, vitamin C, and vitamin D
Karin Amrein,Heleen M. Oudemans-van Straaten,Mette M. Berger
Intensive Care Medicine. 2018;
[Pubmed] | [DOI]
92 Recognition and Management of Sepsis in the Obstetric Patient
Sheryl E. Parfitt,Sandra L. Hering
AACN Advanced Critical Care. 2018; 29(3): 303
[Pubmed] | [DOI]
93 The Use of Intravenous Vitamin C as a Supportive Therapy for a Patient with Glioblastoma Multiforme
Nicola Baillie,Anitra Carr,Selene Peng
Antioxidants. 2018; 7(9): 115
[Pubmed] | [DOI]
94 Refractory septic shock: our pragmatic approach
Prashanth Nandhabalan,Nicholas Ioannou,Christopher Meadows,Duncan Wyncoll
Critical Care. 2018; 22(1)
[Pubmed] | [DOI]
95 Evidence is stronger than you think: a meta-analysis of vitamin C use in patients with sepsis
Jing Li
Critical Care. 2018; 22(1)
[Pubmed] | [DOI]
96 Vitamin C in burns, sepsis, and trauma
Tanya Anand,Ruby Skinner
Journal of Trauma and Acute Care Surgery. 2018; 85(4): 782
[Pubmed] | [DOI]
97 A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D
Justin B. Belsky,Charles R. Wira,Vinitha Jacob,John E. Sather,Patty J. Lee
Nutrition Research Reviews. 2018; : 1
[Pubmed] | [DOI]
98 Involvement of Aromatic Metabolites in the Pathogenesis of Septic Shock
Natalia V. Beloborodova,Yulia N. Sarshor,Aleksandra Yu. Bedova,Ekaterina A. Chernevskaya,Alisa K. Pautova
SHOCK. 2018; 50(3): 273
[Pubmed] | [DOI]
99 A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality
Chiara Sartini,Vladimir Lomivorotov,Marina Pieri,Juan Carlos Lopez Delgado,Martina Baiardo Redaelli,Ludhmila Hajjar,Antonio Pisano,Valery Likhvantsev,Evgeny Fominskiy,Nikola Bradic,Luca Cabrini,Maxim Novikov,Daniele Avancini,Hynek Riha,Rosalba Lembo,Gordana Gazivoda,Gianluca Paternoster,Chengbin Wang,Simona Tamà,Gabriele Alvaro,Chew Yin Wang,Agostino Roasio,Laura Ruggeri,Chow-Yen Yong,Daniela Pasero,Luca Severi,Laura Pasin,Giuseppe Mancino,Paolo Mura,Mario Musu,Savino Spadaro,Massimiliano Conte,Rosetta Lobreglio,Simona Silvetti,Carmine Domenico Votta,Alessandro Belletti,Diana Di Fraja,Francesco Corradi,Claudia Brusasco,Emanuela Saporito,Alessandro DæAmico,Salvatore Sardo,Alessandro Ortalda,Claudio Riefolo,Monaco Fabrizio,Alberto Zangrillo,Rinaldo Bellomo,Giovanni Landoni
Journal of Cardiothoracic and Vascular Anesthesia. 2018;
[Pubmed] | [DOI]
100 Metabolic resuscitation strategies to prevent organ dysfunction in sepsis
Vera Reitsema,Bastiaan Star,Vincent de Jager,Matijs van Meurs,Robert H Henning,Hjalmar Bouma
Antioxidants & Redox Signaling. 2018;
[Pubmed] | [DOI]
101 Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation
Ari Moskowitz,Lars W. Andersen,David T. Huang,Katherine M. Berg,Anne V. Grossestreuer,Paul E. Marik,Robert L. Sherwin,Peter C. Hou,Lance B. Becker,Michael N. Cocchi,Pratik Doshi,Jonathan Gong,Ayan Sen,Michael W. Donnino
Critical Care. 2018; 22(1)
[Pubmed] | [DOI]
102 Vitamin C in the critically ill - indications and controversies
Christoph S Nabzdyk,Edward A Bittner
World Journal of Critical Care Medicine. 2018; 7(5): 52
[Pubmed] | [DOI]
103 Vitamin C for the critically ills: is the evidence strong enough?
Pascal L. Langlois,François Lamontage
Nutrition. 2018;
[Pubmed] | [DOI]
104 Vitamin C and Helicobacter pylori Infection: Current Knowledge and Future Prospects
Haixin Mei,Hongbin Tu
Frontiers in Physiology. 2018; 9
[Pubmed] | [DOI]
105 Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients—Review and Pragmatic Approach
Aileen Hill,Sebastian Wendt,Carina Benstoem,Christina Neubauer,Patrick Meybohm,Pascal Langlois,Neill Adhikari,Daren Heyland,Christian Stoppe
Nutrients. 2018; 10(8): 974
[Pubmed] | [DOI]
106 Vitamin C
Angélique M.E. Spoelstra-de Man,Paul W.G. Elbers,Heleen M. Oudemans-Van Straaten
Current Opinion in Critical Care. 2018; : 1
[Pubmed] | [DOI]
107 Combined vitamin C, hydrocortisone, and thiamine therapy for patients with severe pneumonia who were admitted to the intensive care unit: Propensity score-based analysis of a before-after cohort study
Won-Young Kim,Eun-Jung Jo,Jung Seop Eom,Jeongha Mok,Mi-Hyun Kim,Ki Uk Kim,Hye-Kyung Park,Min Ki Lee,Kwangha Lee
Journal of Critical Care. 2018; 47: 211
[Pubmed] | [DOI]
108 Recent advances in nanomedicine for sepsis treatment
Simseok A Yuk,Diego A Sanchez-Rodriguez,Michael D Tsifansky,Yoon Yeo
Therapeutic Delivery. 2018; 9(6): 435
[Pubmed] | [DOI]
109 Vitamin C Supplementation in the Critically Ill: A Systematic Review and Meta-Analysis
Pascal L. Langlois,William Manzanares,Neill K. J. Adhikari,François Lamontagne,Christian Stoppe,Aileen Hill,Daren K. Heyland
Journal of Parenteral and Enteral Nutrition. 2018;
[Pubmed] | [DOI]
110 Vitamin C in sepsis
Sven-Olaf Kuhn,Konrad Meissner,Lena M. Mayes,Karsten Bartels
Current Opinion in Anaesthesiology. 2017; : 1
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Authors' Contrib...
Article Tables

 Article Access Statistics
    PDF Downloaded2491    
    Comments [Add]    
    Cited by others 110    

Recommend this journal