ascorbic-acid and Multiple-Organ-Failure

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with a high morbidity and mortality rate. Exogenous vitamin C supplementation is a potential therapeutic option for the treatment of multi-organ dysfunction in sepsis due to the significantly lower levels of vitamin C in the circulating blood of sepsis patients compared to healthy subjects and the importance of vitamin C in many of the physiological processes of sepsis. Vitamin C may influence the function of numerous organs and systems, including the heart, lungs, kidneys, brain, and immune defences, by reducing oxidative stress, inhibiting inflammatory factor surges, regulating the synthesis of various mediators and hormones, and enhancing immune cell function. With the development of multiple clinical randomized controlled trials, the outcomes of vitamin C treatment for critically ill patients have been discussed anew. This review's objectives are to provide an overview of how vitamin C affects various organ functions in sepsis and to illustrate how it affects each organ. Understanding the pharmacological mechanism of vitamin C and the organ damage caused by sepsis may help to clarify the conditions and clinical applications of vitamin C.

Topics: Ascorbic Acid; Heart; Humans; Multiple Organ Failure; Oxidative Stress; Randomized Controlled Trials as Topic; Sepsis

Sepsis induced by bacteria or viruses can result in multiorgan dysfunction, which is a major cause of death in intensive care units. Current treatments are only supportive, and there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so it is a rational treatment for sepsis. Here, we summarise data that support the use of megadose vitamin C as a treatment for sepsis and COVID-19. Megadose intravenous sodium ascorbate (150 g per 40 kg over 7 h) dramatically improved the clinical state and cardiovascular, pulmonary, hepatic and renal function and decreased body temperature, in a clinically relevant ovine model of Gram-negative bacteria-induced sepsis. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. These findings suggest that megadose vitamin C should be trialled as a treatment for sepsis and COVID-19.

Topics: Animals; Ascorbic Acid; COVID-19; Humans; Multiple Organ Failure; SARS-CoV-2; Sepsis; Sheep

COVID-19 is a severe pandemic which has caused a devastating amount of loss in lives around the world, and yet we still don't know how to appropriately treat this disease. We know very little about the pathogenesis of SARS-CoV-2, the virus which induces the COVID-19. However, COVID-19 does share many similar symptoms with SARS and influenza. Previous scientific discoveries learned from lab animal models and clinical practices shed light on possible pathogenic mechanisms in COVID-19. In the past decades, accumulated scientific findings confirmed the pathogenic role of free radicals damage in respiratory virus infection. Astonishingly very few medical professionals mention the crucial role of free radical damage in COVID-19. This hypothesis aims to summarize the crucial pathogenic role of free radical damage in respiratory virus induced pneumonia and suggest an antioxidative therapeutic strategy for COVID-19.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Azithromycin; Betacoronavirus; Clinical Trials as Topic; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Drug Therapy, Combination; Free Radicals; Glutathione; Humans; Hydroxychloroquine; Mice; Multiple Organ Failure; NF-E2-Related Factor 2; Nitric Oxide; Orthomyxoviridae Infections; Oxidative Stress; Pandemics; Pneumonia, Viral; Reactive Oxygen Species; SARS-CoV-2; Severe Acute Respiratory Syndrome

The pleiotropic biochemical and antioxidant functions of vitamin C have sparked recent interest in its application in intensive care. Vitamin C protects important organ systems (cardiovascular, neurologic and renal systems) during inflammation and oxidative stress. It also influences coagulation and inflammation; its application might prevent organ damage. The current evidence of vitamin C's effect on pathophysiological reactions during various acute stress events (such as sepsis, shock, trauma, burn and ischemia-reperfusion injury) questions whether the application of vitamin C might be especially beneficial for cardiac surgery patients who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of vitamin C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between vitamin C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence on the administration of vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage, and appropriate application strategy.

Topics: Antioxidants; Ascorbic Acid; Cardiac Surgical Procedures; Cardiovascular System; Critical Care; Humans; Kidney; Multiple Organ Failure; Nervous System; Oxidative Stress; Postoperative Complications; Vitamins

This narrative review summarizes the role of vitamin C in mitigating oxidative injury-induced microcirculatory impairment and associated organ failure in ischemia/reperfusion or sepsis. Preclinical studies show that high-dose vitamin C can prevent or restore microcirculatory flow impairment by inhibiting activation of nicotinamide adenine dinucleotide phosphate-oxidase and inducible nitric oxide synthase, augmenting tetrahydrobiopterin, preventing uncoupling of oxidative phosphorylation, and decreasing the formation of superoxide and peroxynitrite, and by directly scavenging superoxide. Vitamin C can additionally restore vascular responsiveness to vasoconstrictors, preserve endothelial barrier by maintaining cyclic guanylate phosphatase and occludin phosphorylation and preventing apoptosis. Finally, high-dose vitamin C can augment antibacterial defense. These protective effects against overwhelming oxidative stress due to ischemia/reperfusion, sepsis or burn seems to mitigate organ injury and dysfunction, and promote recovery after cardiac revascularization and in critically ill patients, in the latter partially in combination with other antioxidants. Of note, several questions remain to be solved, including optimal dose, timing and combination of vitamin C with other antioxidants. The combination obviously offers a synergistic effect and seems reasonable during sustained critical illness. High-dose vitamin C, however, provides a cheap, strong and multifaceted antioxidant, especially robust for resuscitation of the circulation. Vitamin C given as early as possible after the injurious event, or before if feasible, seems most effective. The latter could be considered at the start of cardiac surgery, organ transplant or major gastrointestinal surgery. Preoperative supplementation should consider the inhibiting effect of vitamin C on ischemic preconditioning. In critically ill patients, future research should focus on the use of short-term high-dose intravenous vitamin C as a resuscitation drug, to intervene as early as possible in the oxidant cascade in order to optimize macrocirculation and microcirculation and limit cellular injury.

Topics: Animals; Antioxidants; Ascorbic Acid; Capillary Permeability; Critical Care; Endothelium, Vascular; Heart; Humans; Microcirculation; Multiple Organ Failure; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Sepsis; Vitamins

This review presents the rationale for the therapeutic use of antioxidants in treating critically ill patients; it is not a systematic review of the clinical evidence that has been assessed recently by others. Clinical and nonclinical evidence is presented to support the notion that natural antioxidants are of therapeutic value in treating cardiovascular shock. Oxidative stress is a major promoter and mediator of the systemic inflammatory response. The microcirculation is particularly susceptible to oxidative stress that causes hemodynamic instability, leading to multiple organ failure due to systemic inflammatory response syndrome. Vitamin C is the antioxidant used experimentally to demonstrate oxidative stress as a key pathophysiologic factor in septic shock. Pharmacologic studies reveal that vitamin C (as ascorbate), at supraphysiologic doses, significantly affects the bioavailability of nitric oxide during acute inflammation, including inhibiting nitric oxide synthetase induction. Parenteral high-dose vitamin C inhibits endotoxin-induced endothelial dysfunction and vasohyporeactivity in humans and reverses sepsis-induced suppression of microcirculatory control in rodents. In severe burn injury, in both animals and patients, parenteral high-dose vitamin C significantly reduces resuscitation fluid volumes. Therefore, a significant body of pharmacologic evidence and sound preliminary clinical evidence supports the biological feasibility of using the exemplary antioxidant, vitamin C, in the treatment of the critically ill.

Topics: Animals; Antioxidants; Ascorbic Acid; Critical Illness; Dose-Response Relationship, Drug; Endothelium, Vascular; Humans; Microcirculation; Multiple Organ Failure; Oxidative Stress; Shock, Septic; Systemic Inflammatory Response Syndrome; Vasodilation; Vitamins; Wounds and Injuries

The systemic inflammatory response syndrome results from an uncontrolled, overexpression of the normal host inflammatory response, leading to destruction of host tissue and subsequent organ failure. Oxidant stress has been implicated in this process both as a mechanism for direct cellular injury, as well as activation of intracellular signaling cascades within inflammatory cells resulting in progression of the inflammatory response. Vitamin E is an inexpensive, nontoxic, chain-breaking antioxidant that has therapeutic potential in regulating this process. This review seeks to evaluate the current literature regarding the use of Vitamin E in controlling the excessive inflammation seen in systemic inflammatory response syndrome and argues for further study of its therapeutic potential for these critically ill patients.

Topics: Acute Disease; alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Dietary Supplements; Humans; Infant, Newborn; Inflammation; Models, Biological; Models, Chemical; Multiple Organ Failure; Respiratory Distress Syndrome, Newborn; Systemic Inflammatory Response Syndrome; Vitamin E

The Lessening Organ Dysfunction with Vitamin C trial showed a harmful effect of vitamin C on 28-day death or persistent organ dysfunction. To maximize interpretation, we present a post hoc Bayesian reanalysis.. Bayesian reanalysis of a randomized placebo-controlled trial.. Thirty-five ICUs.. Adults with proven or suspected infection, vasopressor support, and no more than 24 hours of ICU admission.. Patients were allocated to receive either vitamin C (50 mg/kg of body weight) or placebo every 6 hours for up to 96 hours.. The primary outcome was the composite of death or persistent organ dysfunction (i.e., vasopressor use, invasive mechanical ventilation, or new renal replacement therapy) at 28 days. We used Bayesian log-binomial models with random effects for hospital site and varying informative prior beliefs for the effect of vitamin C to estimate risk ratios (RRs) with 95% credible intervals (Crls) in the intention to treat population (vitamin C, 435 patients; placebo, 437 patients). Using weakly neutral priors, patients allocated to vitamin C had a higher risk of death or persistent organ dysfunction at 28 days (RR, 1.20; 95% Crl, 1.04-1.39; probability of harm, 99%). This effect was consistent when using optimistic (RR, 1.14; 95% Crl, 1.00-1.31; probability of harm, 98%) and empiric (RR, 1.09; 95% Crl, 0.97-1.22; probability of harm, 92%) priors. Patients allocated to vitamin C also had a higher risk of death at 28 days under weakly neutral (RR, 1.17; 95% Crl, 0.98-1.40; probability of harm, 96%), optimistic (RR, 1.10; 95% Crl, 0.94-1.30; probability of harm, 88%), and empiric (RR, 1.05; 95% Crl, 0.92-1.19; probability of harm, 76%) priors.. The use of vitamin C in adult patients with proven or suspected infection and vasopressor support is associated with high probability of harm.

Topics: Adult; Ascorbic Acid; Bayes Theorem; Humans; Multiple Organ Failure; Sepsis; Vitamins

Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction.. In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28.. A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event.. In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

Topics: Adult; Ascorbic Acid; Humans; Hypoglycemic Agents; Intensive Care Units; Multiple Organ Failure; Quality of Life; Sepsis; Vasoconstrictor Agents; Vitamins

Sepsis is a health problem of global importance; treatments focus on controlling infection and supporting failing organs. Recent clinical research suggests that intravenous vitamin C may decrease mortality in sepsis. We have designed a randomized controlled trial (RCT) to ascertain the effect of vitamin C on the composite endpoint of death or persistent organ dysfunction at 28 days in patients with sepsis.. LOVIT (Lessening Organ dysfunction with VITamin C) is a multicenter, parallel-group, blinded (participants, clinicians, study personnel, Steering Committee members, data analysts), superiority RCT (minimum n = 800). Eligible patients have sepsis as the diagnosis for admission to the intensive care unit (ICU) and are receiving vasopressors. Those admitted to the ICU for more than 24 h are excluded. Eligible patients are randomized to high-dose intravenous vitamin C (50 mg/kg every 6 h for 96 h) or placebo. The primary outcome is a composite of death or persistent organ dysfunction (need for vasopressors, invasive mechanical ventilation, or new and persisting renal replacement therapy) at day 28. Secondary outcomes include persistent organ dysfunction-free days to day 28, mortality and health-related quality of life at 6 months, biomarkers of dysoxia, inflammation, infection, endothelial function, and adverse effects (hemolysis, acute kidney injury, and hypoglycemia). Six subgroup analyses are planned.. This RCT will provide evidence of the effect of high-dose intravenous vitamin C on patient-important outcomes in patients with sepsis.. clinicaltrials.gov, NCT03680274, first posted 21 September 2018.

Topics: Acute Kidney Injury; Administration, Intravenous; Adult; Antioxidants; Ascorbic Acid; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hemolysis; Hospital Mortality; Humans; Hypoglycemia; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Quality of Life; Sepsis; Treatment Outcome; Vasoconstrictor Agents

The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock.. To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock.. Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019.. Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102).. The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses.. Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively).. In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock.. ClinicalTrials.gov Identifier: NCT03389555.

Topics: Adrenal Cortex Hormones; Adult; Aged; Ascorbic Acid; Cross Infection; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypernatremia; Male; Middle Aged; Multiple Organ Failure; Organ Dysfunction Scores; Proportional Hazards Models; Shock, Septic; Thiamine; Treatment Failure

Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS).. To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS.. The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018.. Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours.. The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours.. Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours.. In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS.. ClinicalTrials.gov Identifier: NCT02106975.

Topics: Adult; Aged; Ascorbic Acid; Biomarkers; C-Reactive Protein; Double-Blind Method; Female; Humans; Infusions, Intravenous; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Organ Dysfunction Scores; Respiratory Distress Syndrome; Sepsis; Thrombomodulin; Vitamins

Early high-dose IV vitamin C is being investigated as adjuvant therapy in patients who are critically ill, but the optimal dose and infusion method are unclear. The primary aim of this study was to describe the dose-plasma concentration relationship and safety of four different dosing regimens.. This was a four-group randomized pharmacokinetic trial. Patients who were critically ill with multiple organ dysfunction were randomized to receive 2 or 10 g/d vitamin C as a twice daily bolus infusion or continuous infusion for 48 h. End points were plasma vitamin C concentrations during 96 h, 12-h urine excretion of vitamin C, and oxalate excretion and base excess. A population pharmacokinetic model was developed using NONMEM.. Twenty patients were included. A two-compartment pharmacokinetic model with creatinine clearance and weight as independent covariates described all four regimens best. With 2 g/d bolus, plasma vitamin C concentrations at 1 h were 29 to 50 mg/L and trough concentrations were 5.6 to 16 mg/L. With 2 g/d continuous, steady-state concentrations were 7 to 37 mg/L at 48 h. With 10 g/d bolus, 1-h concentrations were 186 to 244 mg/L and trough concentrations were 14 to 55 mg/L. With 10 g/d continuous, steady-state concentrations were 40 to 295 mg/L at 48 h. Oxalate excretion and base excess were increased in the 10 g/d dose. Forty-eight hours after discontinuation, plasma concentrations declined to hypovitaminosis levels in 15% of patients.. The 2 g/d dose was associated with normal plasma concentrations, and the 10 g/d dose was associated with supranormal plasma concentrations, increased oxalate excretion, and metabolic alkalosis. Sustained therapy is needed to prevent hypovitaminosis.. ClinicalTrials.gov; No.: NCT02455180; URL: www.clinicaltrials.gov.

Topics: Aged; Ascorbic Acid; Biomarkers; Critical Illness; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Male; Middle Aged; Multiple Organ Failure; Retrospective Studies; Vitamins

Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis.. Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored.. Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury.. Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury.. ClinicalTrials.gov identifier NCT01434121.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Demography; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Multiple Organ Failure; Placebos; Protein Precursors; Sepsis; Thrombomodulin

Enteral diets enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants have previously been shown to improve outcomes in patients with acute respiratory distress syndrome. Several studies using animal models of sepsis demonstrate that enteral nutrition enriched with omega-3 fatty acids reduces mortality rate. This study investigated whether an enteral diet enriched with EPA, GLA, and antioxidant vitamins can improve outcomes and reduce 28-day all-cause mortality in patients with severe sepsis or septic shock requiring mechanical ventilation.. Prospective, double-blind, placebo-controlled, randomized trial.. Three different intensive care units of a tertiary hospital in Brazil.. The study enrolled 165 patients.. Patients were randomized to be continuously tube-fed with either a diet enriched with EPA, GLA, and elevated antioxidants or an isonitrogenous and isocaloric control diet, delivered at a constant rate to achieve a minimum of 75% of basal energy expenditure x 1.3 during a minimum of 4 days.. Patients were monitored for 28 days. Patients who were fed with the study diet experienced a significant reduction in mortality rate compared with patients fed with the control diet, the absolute mortality reduction amounting to 19.4% (p = .037). The group who received the study diet also experienced significant improvements in oxygenation status, more ventilator-free days (13.4 +/- 1.2 vs. 5.8 +/- 1.0, p < .001), more intensive care unit (ICU)-free days (10.8 +/- 1.1 vs. 4.6 +/- 0.9, p < .001), and a lesser development of new organ dysfunctions (p < .001).. In patients with severe sepsis or septic shock and requiring mechanical ventilation and tolerating enteral nutrition, a diet enriched with EPA, GLA, and elevated antioxidants contributed to better ICU and hospital outcomes and was associated with lower mortality rates.

Topics: Aged; Antioxidants; Ascorbic Acid; Brazil; Double-Blind Method; Eicosapentaenoic Acid; Enteral Nutrition; Female; gamma-Linolenic Acid; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Distress Syndrome; Sepsis; Shock, Septic; Vitamin E

A decrease in ascorbic acid (AA) plasma concentration is well known during the postoperative period and postulated to be caused by increased radical scavenging activity in response to surgical trauma. This often affects postoperative patients and is associated with multiple organ failure. Therefore, substitution of AA could potentially decrease the risk of postoperative complications. This study examines the effect of preoperative oral administration of 1,000 mg AA on the postoperative AA plasma concentration.. 54 patients were randomly split into two groups; patients in group 1 received no AA preoperatively while group 2 received oral AA (1,000 mg). Plasma samples were obtained preoperatively and on the first postoperative day for AA analysis (HPLC).. In both groups the AA concentration was normal preoperatively and reduced postoperatively.. A preoperative substitution of 1,000 mg AA is not sufficient to prevent postoperative lowered plasma concentration.

Topics: Administration, Oral; Aged; Antioxidants; Ascorbic Acid; Humans; Middle Aged; Multiple Organ Failure; Postoperative Complications; Postoperative Period; Preoperative Care; Surgical Procedures, Operative

To determine the effectiveness of early, routine antioxidant supplementation using alpha-tocopherol and ascorbic acid in reducing the rate of pulmonary morbidity and organ dysfunction in critically ill surgical patients.. Oxidative stress has been associated with the development of the acute respiratory distress syndrome (ARDS) and organ failure through direct tissue injury and activation of genes integral to the inflammatory response. In addition, depletion of endogenous antioxidants has been associated with an increased risk of nosocomial infections. The authors postulated that antioxidant supplementation in critically ill surgical patients may reduce the incidence of ARDS, pneumonia, and organ dysfunction.. This randomized, prospective study was conducted to compare outcomes in patients receiving antioxidant supplementation (alpha-tocopherol and ascorbate) versus those receiving standard care. The primary endpoint for analysis was pulmonary morbidity (a composite measure of ARDS and nosocomial pneumonia). Secondary endpoints included the development of multiple organ failure, duration of mechanical ventilation, length of ICU stay, and mortality.. Five hundred ninety-five patients were enrolled and analyzed, 91% of whom were victims of trauma. The relative risk of pulmonary morbidity was 0.81 (95% confidence interval 0.60-1.1) in patients receiving antioxidant supplementation. Multiple organ failure was significantly less likely to occur in patients receiving antioxidants than in patients receiving standard care, with a relative risk of 0.43 (95% confidence interval 0.19-0.96). Patients randomized to antioxidant supplementation also had a shorter duration of mechanical ventilation and length of ICU stay.. The early administration of antioxidant supplementation using alpha-tocopherol and ascorbic acid reduces the incidence of organ failure and shortens ICU length of stay in this cohort of critically ill surgical patients.

Topics: Adolescent; Adult; Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Confidence Intervals; Critical Illness; Dietary Supplements; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Postoperative Period; Probability; Prospective Studies; Reference Values; Respiratory Distress Syndrome; Surgical Procedures, Operative; Survival Analysis; Treatment Outcome; Wounds and Injuries

Reactive oxygen species have been implicated in the etiology of multiorgan dysfunction syndrome and infectious complications in trauma patients by either direct cellular toxicity and/or the activation of intracellular signaling pathways. Studies have shown that the antioxidant defenses of the body are decreased in trauma patients; these include glutathione, for which N-acetylcysteine is a precursor, and selenium, which is a cofactor for glutathione. Eighteen trauma patients were prospectively randomized to a control or antioxidant group where they received N-acetylcysteine, selenium, and vitamins C and E for 7 days. As compared with the controls, the antioxidant group showed fewer infectious complications (8 versus 18) and fewer organs dysfunctioning (0 versus 9). There were no deaths in either group. We conclude that these preliminary data may support a role for the use of this antioxidant mixture to decrease the incidence of multiorgan dysfunction syndrome and infectious complications in the severely injured patient. This remains to be confirmed in larger trials.

Topics: Acetylcysteine; Antioxidants; Ascorbic Acid; Humans; Infections; Injury Severity Score; Multiple Organ Failure; Prospective Studies; Selenium; Treatment Outcome; Vitamin E; Wounds and Injuries

Fluoroacetamide poisoning is the acute and severe disease of human, which leads to nervous, digestive, and cardiovascular system damage or even death in a short period of time.. We report a case of a 65-year-old woman with loss of consciousness, nausea, and vomiting who was sent to the hospital by passers-by.. She was diagnosed with severe fluoroacetamide poisoning with combined multiple organ dysfunction syndrome.. When the diagnosis was unclear, we gave gastric lavage, support and symptomatic treatment, and closely with the vital sign. When the diagnosis was clear, based on the evidence of retrieved, muscle injection of acetamide, calcium gluconate, and vitamin C. Traditional Chinese medicine aspect, oral administration of mung bean soup of glycyrrhizae and Da-Cheng-Qi decoction enema.. By setting reasonable treatment for patients, she had no special discomfort and complications after treatment. Besides, through 1-month follow-up, it was confirmed that the treatments were effective.. Evidence-based integrated Chinese and Western medicines can effectively improve the therapeutic effects in severe fluoroacetamide-poisoned patients with combined MODS.

Topics: Acetamides; Aged; Antidotes; Ascorbic Acid; Calcium Gluconate; Diagnosis, Differential; Drugs, Chinese Herbal; Evidence-Based Medicine; Female; Fluoroacetates; Gastric Lavage; Humans; Medicine, Chinese Traditional; Multiple Organ Failure

One of the major causes of mortality in the world is represented by multiple traumas. Thoracic trauma is commonly associated with polytraumas. A series of physiopathological complications follow polytraumas, leading to a significant decrease in the survival rate. As a result of injuries, significant quantities of free radicals (FR) are produced, responsible for oxidative stress (OS). To minimize the effects of OS, we recommend the administration of antioxidant substances. In this study we want to highlight statistically significant correlations between antioxidant therapy and a series of clinical variables.. This retrospective study included 132 polytrauma patients admitted to the ICU-CA between January 2013 and December 2014. The selection criteria were: injury severity score (ISS) ≥ 16, ≥ 18 years, presence of thoracic trauma (abbreviated injury scale, AIS ≥ 3). Eligible patients (n = 82) were divided into two groups: Group 1 (n = 32, antioxidant free, patients from 2013) and Group 2 (n = 50 antioxidant therapy, patients from 2014). Antioxidant therapy consisted in the administration of vitamin C (i.v.), vitamin B1 (i.v.), and N-acetylcysteine (i.v.). Clinical and biological tests were repeated until discharge from ICU-CA or death.. Between Group 1 and Group 2 statistically significant differences were highlighted regarding the ISS score (p = 0.0030). 66% of patients from Group 2 were admitted at more than 24 hours after the trauma, in contrast to the patients from Group 1, where 62.5% were directly admitted to the ICU (p = 0.0114). Compared with the patients from Group 1, patients who received antioxidant therapy show improved parameters: leukocytes (p < 0.0001), platelets (p = 0.0489), urea (p = 0.0199), total bilirubin (p = 0.0111), alanine transaminase (p = 0.0010), lactat dehydrogenase (p < 0.0001). Between the two groups there were no statistically significant differences regarding the length of stay in the ICU-CA (p = 0.4697) and mortality (p = 0.1865).. Following the study, we can affirm that due to the administration of antioxidant substances, posttraumatic complications are greatly reduced. Moreover, the administration of high dose of antioxidants remarkably improves the clinical status of the critical patient.

Topics: Abbreviated Injury Scale; Acetylcysteine; Adult; Aged; Antioxidants; Ascorbic Acid; Critical Illness; Female; Humans; Incidence; Inflammation; Injury Severity Score; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Oxidation-Reduction; Oxidative Stress; Respiration, Artificial; Retrospective Studies; Sepsis; Thiamine; Thoracic Injuries

Multiple organ dysfunction syndrome (MODS) is the principal cause of death in patients with sepsis. Recent work supports the notion that parenteral vitamin C (VitC) is protective in sepsis through pleiotropic mechanisms. Whether suboptimal levels of circulating VitC increase susceptibility to sepsis-induced MODS is unknown.. Unlike mice, humans lack the ability to synthesize VitC because of loss of L-gulono-γ-lactone oxidase (Gulo), the final enzyme in the biosynthesis of VitC. To examine whether physiological levels of VitC are required for defense against a catastrophic infection, we induced sepsis in VitC sufficient and VitC deficient Gulo(-/-) mice by intraperitoneal infusion of a fecal stem solution (FIP). Some VitC deficient Gulo(-/-) mice received a parenteral infusion of ascorbic acid (AscA, 200 mg/kg) 30 minutes after induction of FIP. We used molecular, histological, and biochemical analyses to assess for MODS as well as abnormalities in the coagulation system and circulating blood cells.. FIP produced injury to lungs, kidneys and liver (MODS) in VitC deficient Gulo(-/-) mice. MODS was not evident in FIP-exposed VitC sufficient Gulo(-/-) mice and attenuated in VitC deficient Gulo(-/-) mice infused with AscA. Septic VitC deficient Gulo(-/-) mice developed significant abnormalities in the coagulation system and circulating blood cells. These were attenuated by VitC sufficiency/infusion in septic Gulo(-/-) mice.. VitC deficient Gulo(-/-) mice were more susceptible to sepsis-induced MODS. VitC sufficiency or parenteral infusion of VitC, following induction of sepsis, normalized physiological functions that attenuated the development of MODS in sepsis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Cells; Blood Coagulation; Infusions, Parenteral; Kidney; L-Gulonolactone Oxidase; Liver; Lung; Mice, Knockout; Multiple Organ Failure; Sepsis; Vitamins

Vitamin C (VitC) has recently been shown to exert beneficial effects, including protecting organ function and inhibiting inflammation, in various critical care conditions, but the specific mechanism remains unclear. Induction of heme oxygenase (HO)-1, a heat shock protein, has been shown to prevent organ injuries in hemorrhagic shock (HS) but the relationship between VitC and HO-1 are still ill-defined so far. Here we conducted a systemic in vivo study to investigate if VitC promoted HO-1 expression in multiple organs, and then tested if the HO-1 induction property of VitC was related to its organ protection and anti-inflammatory effect.. Firstly, to determine the HO-1 induction property of VitC, the HO-1 level were measured in tissues including kidney, liver and lung of the normal and HS model of Sprague-Dawley (SD) rats after VitC treatment (100 mg/kg body weight). Secondly, to testify if VitC prevented HS related organ injuries via inducing HO-1, the HS model of rats were separately pre- and post-treated with VitC, and some of them also received Zinc protoporphyrin (Znpp), a specific HO-1 inhibitor. The HO-1 activity in tissues was tested; the organ injuries (as judged by histological changes in tissues and the biochemical indicators level in serum) and inflammatory response in tissues (as judged by the level of pro-inflammatory cytokines Tumor necrosis factor-α and Interleukin-6 ) were analyzed.. The HO-1 mRNA and protein level in kidney, liver, and lung were highly induced by VitC treatement under normal and HS conditions. The HO-1 activity in tissues was enhanced by both VitC pre- and post-treatment, which was shown to improve the organ injuries and inhibit the inflammatory response in the HS model of rats. Of note, the beneficial effects of VitC were abolished after HO-1 activity was blocked by Znpp.. VitC led to a profound induction of HO-1 in multiple organs including the kidney, liver and lung, and this property might be responsible for the organ protection and inflammation inhibitory effects of both pre- and post-treatment with VitC in HS.

Topics: Animals; Ascorbic Acid; Enzyme Inhibitors; Heme Oxygenase-1; Inflammation; Interleukin-6; Kidney; Liver; Lung; Multiple Organ Failure; Protoporphyrins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Shock, Hemorrhagic; Tumor Necrosis Factor-alpha; Vitamins

Sepsis/multiple organ dysfunction syndrome (MODS) is a major cause of high mortality in the intensive care unit. We have recently reported that 100% oxygen treatment is beneficial to mice with zymosan-induced sterile inflammation by increasing antioxidant enzymatic activities. Yet, the use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. It is believed that systemic inflammation and overproduction of reactive oxygen species (ROS) contribute to the mechanism underlying sepsis/MODS. A ROS scavenger has been proven to protect against sepsis/MODS in some animal models. Therefore, we hypothesized that ROS scavenger pretreatment might enhance the protective action of 100% oxygen treatment against zymosan-induced sterile inflammation in mice. In the present study, we showed that 100% oxygen treatment prevented the abnormal changes in serum biochemical parameters, tissue oxygenation, and organ histopathology, and improved the 14-day survival rate in zymosan-stimulated mice, indicating that 100% oxygen treatment had a protective action on sterile inflammation. We found that pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea) abolished this protective action of 100% oxygen treatment. We also showed that 100% oxygen treatment decreased the levels of serum proinflammatory cytokines (TNF-alpha, IL-6, and high-mobility group box 1), increased the level of serum anti-inflammatory cytokine (IL-10), and upregulated the activities of serum and tissue antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in zymosan-stimulated mice, which were reversed by the pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea). We thus conclude that ROS scavenger pretreatment partly abolishes the protective effects of 100% oxygen treatment on sterile inflammation in mice by regulating inflammatory cytokines as well as antioxidant enzymes.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Cytokines; Free Radical Scavengers; Heart; Inflammation; Kidney; Liver; Lung; Male; Mice; Multiple Organ Failure; Myocardium; Oxygen; Reactive Oxygen Species; Sepsis; Thiourea; Zymosan

The aim of this study was to determine the effects of enrofloxacin (ENR), flunixin meglumine (FM) and dexamethasone (DEX) on antioxidant status and organ damage markers in experimentally-induced endotoxemia. Rats were divided into three groups. To induce endotoxemia, lipopolysaccharide (LPS) was injected into all groups, including the positive control. The two other groups received the following drugs (simultaneously with LPS): ENR + FM + low-dose DEX and ENR + FM + high-dose DEX. After the treatments, blood samples were collected at 0, 1, 2, 4, 6, 8, 12, 24 and 48 h. Oxidative stress parameters were determined by ELISA, while serum organ damage markers were measured by autoanalyser. LSP increased (p < 0.05) malondialdehyde, 13,14-dihydro-15-keto-prostaglandin F(2 alpha) and nitric oxide, while LPS reduced vitamin C. These changes were especially inhibited (p < 0.05) by ENR + FM + high-dose DEX. LPS increased organ damages markers. Cardiac and hepatic damage was not completely inhibited by any treatment, whereas renal damage was inhibited by two treatments. This study suggested that ENR + FM + high-dose DEX is most effective in the LPS-caused oxidative stress and organ damages.

Topics: Animals; Ascorbic Acid; Autoanalysis; Biomarkers; Clonixin; Dexamethasone; Dinoprost; Disease Models, Animal; Drug Therapy, Combination; Enrofloxacin; Enzyme-Linked Immunosorbent Assay; Female; Fluoroquinolones; Heart Diseases; Kidney Diseases; Lipopolysaccharides; Liver Diseases; Male; Malondialdehyde; Multiple Organ Failure; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Shock, Septic; Superoxide Dismutase; Time Factors

Topics: Aged; Ascorbic Acid; Diagnosis, Differential; Hemodynamics; Humans; Male; Multiple Organ Failure; Scurvy