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Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

ABSTRACT: The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.

SUBMITTER: Ichim TE

PROVIDER: S-EPMC3061919 | biostudies-other | 2011 Mar

REPOSITORIES: biostudies-other

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Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

Ichim Thomas E TE Minev Boris B Braciak Todd T Luna Brandon B Hunninghake Ron R Mikirova Nina A NA Jackson James A JA Gonzalez Michael J MJ Miranda-Massari Jorge R JR Alexandrescu Doru T DT Dasanu Constantin A CA Bogin Vladimir V Ancans Janis J Stevens R Brian RB Markosian Boris B Koropatnick James J Chen Chien-Shing CS Riordan Neil H NH

Journal of translational medicine 20110304

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop s ...[more]

PMID: 21375761

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Project description:Fluid responsiveness is proposed as a physiology-based method to titrate fluid therapy based on preload dependence. The objectives of this study were to determine if a fluid responsiveness protocol would decrease progression of organ dysfunction, and a fluid responsiveness protocol would facilitate a more aggressive resuscitation.Prospective, 10-center, randomized interventional trial.suspected sepsis and lactate 2.0 to 4.0?mmol/L. Exclusion criteria (abbreviated): systolic blood pressure more than 90?mmHg, and contraindication to aggressive fluid resuscitation.fluid responsiveness protocol using Non-Invasive Cardiac Output Monitor (NICOM) to assess for fluid responsiveness (>10% increase in stroke volume in response to 5?mL/kg fluid bolus) with balance of a liter given in responsive patients.standard clinical care.primary-change in Sepsis-related Organ Failure Assessment (SOFA) score at least 1 over 72?h; secondary-fluids administered. Trial was initially powered at 600 patients, but stopped early due to a change in sponsor's funding priorities.Sixty-four patients were enrolled with 32 in the treatment arm. There were no significant differences between arms in age, comorbidities, baseline vital signs, or SOFA scores (P?>?0.05 for all). Comparing treatment versus Standard of Care-there was no difference in proportion of increase in SOFA score of at least 1 point (30% vs. 33%) (note bene underpowered, P?=?1.0) or mean preprotocol fluids 1,050?mL (95% confidence interval [CI]: 786-1,314) vs. 1,031?mL (95% CI: 741-1,325) (P?=?0.93); however, treatment patients received more fluids during the protocol (2,633?mL [95% CI: 2,264-3,001] vs. 1,002?mL [95% CI: 707-1,298]) (P?<?0.001).In this study of a "preshock" population, there was no change in progression of organ dysfunction with a fluid responsiveness protocol. A noninvasive fluid responsiveness protocol did facilitate delivery of an increased volume of fluid. Additional properly powered and enrolled outcomes studies are needed.

Project description:AbstractBackground: Acute kidney injury (AKI) occurs frequently in septic patients and correlates with increased mortality. Because clinical studies investigating hydrocortisone, ascorbic acid, and thiamine (HAT) have demonstrated discordant results, studies were performed using mortality stratification for therapy to identify candidates for therapy and determine mechanisms of organ injury. Methods: Sepsis was induced using the cecal ligation and puncture (CLP) model of sepsis with fluid and antibiotic support. Heart rate (HR) measurements obtained 6 hours after CLP stratified mice into live predicted (P-Live) or die predicted (P-Die). Stratified mice were then randomized for treatment with HAT or vehicle given 7 hours after CLP. Physiologic measurements were taken again at 24 hours, and mice were killed to collect blood and organs. Results: The following five groups were created: (1) P-Live vehicle, (2) P-Live HAT, (3) P-Die vehicle, (4) P-Die HAT, and (5) naive mice. Comparisons were made to test the hypotheses that (1) P-Die vehicle mice will have significant deterioration compared with P-Live mice targeting the kidney and (2) HAT will correct these deleterious changes in P-Die mice. Compared with P-Live, P-Die mice had a significant decline in all measured physiologic parameters (HR, cardiac output, breath rate, and temperature), which were corrected with HAT therapy (P < 0.05 for all parameters). The P-Die mice had declines in the ascorbic acid within the blood, peritoneal lavage, and kidney homogenate compared with P-Live mice indicating consumption, and the decline was corrected with HAT. Elevated IL-6, KC, Macrophage Inflammatory Protein-2, and IL-1RA were found in P-Die mice and decreased with HAT. Markers of endothelial cell injury (glypican 1 and glypican 4) were elevated in the P-Die mice, and these values were decreased with HAT therapy. Low oxygen levels with subsequent oxidative stress (OS) in the kidney were visualized in histologic sections using hypoxyprobe and also with carbonyl proteins and 8-iso-prostaglandin F2α in kidney homogenates. The P-Die mice had significant elevations of renal OSs, which was ameliorated with HAT. Kidney injury was evident in the P-Die mice compared with P-Live mice with elevations in blood urea nitrogen and cystatin C, which were significantly reduced with HAT. There was no evidence of global hypoxia or organ injury because hepatic parameters remained normal. Conclusions: Our data show that in CLP-induced sepsis, P-Die mice have increased inflammation, OS, and kidney injury. Hydrocortisone, ascorbic acid, and thiamine therapy decreased renal OS and injury in the P-Die group when given after the onset of sepsis-induced physiologic changes.

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Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

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Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

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