ascorbic-acid and Shock

Septic and vasoplegic shock are common types of vasodilatory shock (VS) with high mortality. After fluid resuscitation and the use of catecholamine-mediated vasopressors (CMV), vasopressin, angiotensin II, methylene blue (MB), and hydroxocobalamin can be added to maintain blood pressure.. VS treatment utilizes a phased approach with secondary vasopressors added to vasopressor agents to maintain an acceptable mean arterial pressure (MAP). This review covers additional vasopressors and adjunctive therapies used when fluid and catecholamine-mediated vasopressors fail to maintain target MAP.. Evidence supporting additional vasopressor agents in catecholamine-resistant VS is limited to case reports, series, and a few randomized control trials (RCTs) to guide recommendations. Vasopressin is the most common agent added next when MAPs are not adequately supported with CMV. VS patients failing fluids and vasopressors with cardiomyopathy may have cardiotonic agents such as dobutamine or milrinone added before or after vasopressin. Angiotensin II, another class of vasopressor, is used in VS to maintain adequate MAP. MB and/or hydroxocobalamin, vitamin C, thiamine, and corticosteroids are adjunctive therapies used in refractory VS. More RCTs are needed to confirm the utility of these drugs, at what doses, which combinations and in what order they should be given.

Topics: Angiotensin II; Ascorbic Acid; Cardiotonic Agents; Catecholamines; Cytomegalovirus Infections; Dobutamine; Humans; Hydroxocobalamin; Methylene Blue; Milrinone; Shock; Shock, Septic; Thiamine; Vasoconstrictor Agents; Vasopressins

The neurobiological functions of ascorbate have both intra- and extracellular sites of action. Intracellularly, it participates predominantly in enzymic and transport reactions for neurotransmitter and hormone biosynthesis. Ascorbate is the cofactor for the dopamine beta-hydroxylase and peptidylglycine alpha-amidating monooxygenase systems, which catalyze the synthesis of norepinephrine and a variety of alpha-amidated peptides, respectively. The localization of these enzymes within the neurotransmitter- or hormone-containing storage vesicle requires a system for the constant regeneration of ascorbate to the reduced form. In fact, ascorbate participates in its own regeneration as a component of the vesicular electron-transport system. In addition to the roles of ascorbate in messenger synthesis, it is secreted from cells from different subcellular compartments. The extracellular role(s) of ascorbate are still unknown, although its interaction with and modification of plasma membrane proteins suggests some modulatory function.

Topics: Adrenal Medulla; Animals; Ascorbic Acid; Biological Transport; Chromaffin System; Dehydroascorbic Acid; Dopamine beta-Hydroxylase; Humans; Hypoglycemia; Mixed Function Oxygenases; Multienzyme Complexes; Oxidation-Reduction; Shock

In sepsis and burns, ascorbic acid (AA) is hypothesized advantageous during volume resuscitation. There is uncertainty regarding its safety and dosing. This study evaluated high dose AA (HDAA: 66 mg/kg/h for 24 hours) versus low dose AA (LDAA: 3.5 g/days) administration during the first 24 hours in severely burned adults. We conducted a retrospective study comparing fluid administration before and after switching from low dose to HDAA in severely burned adults. A total of 38 adults with burns >20% TBSA, who received either HDAA or LDAA were included in this retrospective study. AA serum concentrations were quantified at 0, 24, and 72 hours postburn. HDAA impact on hemodynamics, acid-base homeostasis, acute kidney injury, vasopressor use, resuscitation fluid requirement, urinary output, and the incidence of adverse effects was evaluated; secondary clinical outcomes were analyzed. AA plasma levels were 10-fold elevated in the LDAA and 150-fold elevated in the HDAA group at 24 hours and decreased in both groups afterwards. HDAA was not associated with a significantly increased risk of any complications. A significant reduction in colloid fluid requirements was noted (LDAA: 947 ± 1722 ml/24 hours vs HDAA: 278 ± 667 ml/24 hours, P = 0.029). Other hemodynamic and resuscitation measures, as well as secondary clinical outcomes were comparable between groups. HDAA was associated with higher AA levels and lower volumes of colloids in adults with severe burns. The rate of adverse events was not significantly higher in patients treated with HDAA. Future studies should consider prolonged administration of AA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Burns; Colloids; Creatinine; Dose-Response Relationship, Drug; Female; Fluid Therapy; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Renal Replacement Therapy; Resuscitation; Retrospective Studies; Shock; Urine; Vasoconstrictor Agents; Young Adult

High dose ascorbic acid (HDAA) has been touted to ameliorate inflammation and reduce fluid requirements during burn shock resuscitation (BSR). Whether this leads to improved outcomes is not known. The authors' aim for this study was to compare ventilator days, ventilator-associated pneumonia, and mortality between patients who did and did not receive HDAA during BSR.The authors performed a retrospective case control study from 2012 to 2015. They identified 38 patients (HDAA) who received HDAA during BSR. Using age and %TBSA, the authors identified and matched 42 control patients (CTL) who did not receive HDAA for BSR during that same time period. The authors collected data for age, %TBSA, hospital days (LOS), ventilator days (VENT), inhalation injury (INH), ventilator-associated pneumonia (VAP), and mortality (MORT).There were no differences in age and %TBSA or %TBSA of third-degree burn injury between groups. There was no significant difference in the incidence of INH (HDAA-52% vs CTL-36%, P = .17) and the groups had similar LOS and VENT. Additionally, there was no significant difference in VAP incidence (HDAA-29% vs CTL-14%, P = .13) or mortality (HDAA-26% vs CTL-23%, P = .8). HDAA patients had a numerically higher incidence of acute renal failure requiring dialysis (23 vs 7%, P = .06) which was confirmed in a multivariate analysis (odds ratio 5.4; 95% confidence interval 1.1-26). HDAA, while potentially reducing inflammation and fluid requirements during BSR, may not improve any meaningful outcomes such as ventilator requirements, ventilator-associated pneumonia, and mortality.

Topics: Adult; Age Factors; Antioxidants; Ascorbic Acid; Burns; Female; Fluid Therapy; Humans; Incidence; Length of Stay; Male; Middle Aged; Pneumonia, Ventilator-Associated; Respiration, Artificial; Resuscitation; Retrospective Studies; Shock; Survival Rate; Treatment Outcome; Young Adult

Quantitative monitoring of the redox status is the foundation for redox-related treatment. The purpose of this study was to evaluate the reliability of a new depolarization curve method for plasma redox potential (ORP) monitoring.. Using the new method, we performed redox determinations for the first time under different sample-handling conditions, including redox titration experiments using KMnO4 and vitamin C and dynamic redox monitoring in burn patients. The relative ORP value (ΔORP) method (improved traditional method) was used as the reference.. The new method's better reliability, electrochemical specificity and practicability, and known group validity, which are closely associated with the redox-related pathological processes of severe burns, were confirmed. Furthermore, bidirectional change in the redox status in severe burn patients was also observed for the first time.. This simple, stable new method could be a better practical tool for making the dynamic monitoring of the redox status feasible and for providing useful quantitative information for the judgment of redox-related pathological process, thus improving corresponding individualized treatments that rely on quantitative adjustments to the redox status.

Topics: Abbreviated Injury Scale; Adult; Ascorbic Acid; Blood Chemical Analysis; Burns; Electrochemistry; Electrodes; Female; Humans; Male; Methemoglobin; Middle Aged; Monitoring, Physiologic; Oxidation-Reduction; Oxidative Stress; Potassium Permanganate; Reperfusion Injury; Reproducibility of Results; Sensitivity and Specificity; Sepsis; Shock; Uric Acid

Thermal injuries with more than 20% of burned body surface area (BSA) lead to systemic shock with generalised oedema in addition to local tissue destruction. This condition, known as burn injury, is caused by immunmodulative mediators whose individual significance is not known in detail. We present an experimental model where plasma of burned animals (burn plasma) is transmitted to healthy animals, to trigger burn iniury without performing direct burn trauma.. The systemic oedema is measured by extravasation of fluorescent albumin in mesenterial venules of Wistar rats. In addition, leukocyte-endothelial interactions ("leukocyte rolling and sticking") is examined.. The systemic capillary leak is induced by both direct thermal trauma as well as by infusion of burn plasma. This is evident even after plasma dilution (1% in Ringer's lactate) of the burn plasma. In addition, topical therapy for burned animals (donors) with cerium nitrate led to a significant reduction of plasma extravasation in receiver animals. In addition, systemic antioxidant therapy with high-dose vitamin C of receiver animals, led to a significant reduction of the capillary leak. Leukocyte-endothelial interactions are not significantly affected in either case.. In summary, for the first time a reliable model of burn injury has been established, which eliminates mediator-independent effects. In addition, our studies show that antioxidant therapy with high doses of vitamin C and topical treatment with cerium nitrate both reduce the systemic capillary leak in receiver animals. Their positive influence could therefore soon be integrated in clinical treatment algorithms.

Topics: Animals; Anti-Infective Agents, Local; Antioxidants; Ascorbic Acid; Blood Flow Velocity; Burns; Capillary Leak Syndrome; Cell Adhesion; Cerium; Cytokines; Disease Models, Animal; Edema; Extravasation of Diagnostic and Therapeutic Materials; Leukocytes; Male; Mesenteric Veins; Microcirculation; Plasma; Rats; Rats, Wistar; Shock; Venules

To investigate the effect of vitamin C (VC) on visceral lipid oxidative injury during oral fluid resuscitation of burn shock.. Twelve male Beagle dogs were surgically prepared for arterial and venous cannulation, and 24 hours later they were subjected to a 50% TBSA full-thickness flame injury. In the first 24 hours after burn dogs were resuscitated with gastric infusion of either glucose-electrolyte solution (GES group, n = 6) or GES containing 250 mg/kg of VC (GES/VC group, n = 6). The delivery rate and volume of GES was in accordance with that of Parkland formula (4 ml x kg(-1) x 1% TBSA(-1) in the first 24 hours). In the second 24 hours all animals received delayed i.v. fluid resuscitation. At end of 72 hours after injury, animals were sacrificed, and specimens of heart, lung, liver, kidney and jejunum were harvested for evaluation of xanthine oxidase (XOD), malondialdehyde (MDA) and assessment of the tissue water content (ratio of dry to wet weight) of organs. The plasma levels of alanine aminotransferase (ALT), creatinine (Cr), MB isoenzyme of creatine kinase (CK-MB) and diamine oxidase (DAO) were determined at same time.. At 72 hours after burn it was showed significant higher activities of XOD in GES/CAR than GES group in heart, kidney and jejunum, and lower contents of MDA in heart, lung, liver, kidney and jejunum (P all < 0.01). Tissue water contents were significantly lower in GES/CAR than GES group in heart [(75.4 +/-1.1)% vs (78.5 +/- 0.8)%], lung [(68.1 +/- 0.9)% vs (73.9 +/- 1.0)%], liver [ (75.2 +/- 0.8)% vs (78.3 +/- 1.2)%], kidney [(73.8 +/- 1.1)% vs (78.1 +/- 0.8)%] and jejunum [(76.3 +/- 0.8)% vs ( 80.4 +/- 0.6)] respectively, all P < 0.01. The levels of ALT, CK-MB, Cr and DAO in GES/CAR group were (46.6 +/- 2.49) U/L, (43.4 +/- 7.05) mol/L, (7156 +/- 596) U/L and (1.86 +/- 0.45) U/L respectively, all significantly lower than those of the GES group [(86.9 +/- 7.89) U/L, (95.2 +/- 1.23) mol/L, (8023 +/- 384) U/L and (2.68 +/- 0.61) U/L respectively, all P < 0.05].. The results indicated that vitamin C alleviated visceral tissue edema and organ injury by inhibiting free radical production during oral fluid resuscitation of burn shock.

Topics: Animals; Ascorbic Acid; Burns; Dogs; Fluid Therapy; Male; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Shock

To investigate the effect of vitamin C (VC) on alleviating peroxidative damage in gut of dogs during enteral fluid resuscitation of severe burn shock.. Eighteen male Beagle dogs were subjected to 50% total body surface area (TBSA) full-thickness burn 24 hours after duodenostomy and cannulation of cervical artery and vein. The dogs were divided into no resuscitation (NR) group (no treatment after burn), enteral resuscitation (ER) group, and ER+VC group according to the random number table, with 6 dogs in each group. Dogs in ER and ER+VC groups were respectively infused with glucose-electrolyte solution (GES) and GES containing 250 mg/kg VC through duodenostomy tube 30 minutes after burn. The infusion rate and volume of GES were in accordance with Parkland formula. Venous blood of dogs was drawn before (0) and at 2, 4, 6, and 8 post burn hours (PBH) to determine the activity of diamine oxidase (DAO) in plasma. Dogs were sacrificed at PBH 8 to collect specimens of jejunum tissue for determining the content of malondialdehyde (MDA), and activity of myeloperoxidase (MPO), xanthine oxidase (XOD) and superoxide dismutase (SOD), and assessment of the water ratio of intestinal tissue by dry-wet weight method.. 50% TBSA burn injury resulted in significant elevation of DAO in every group. The activity of DAO in ER group was obviously higher than that in NR group at PBH 6 and 8 (P < 0.05), but DAO activity in ER+VC group was significantly lower than those in the other two groups after PBH 2 (P < 0.05 or P < 0.01). MDA content, MPO and XOD activity and the water ratio of intestinal tissue [(5.74 +/- 0.51) nmol/mg, (2.08 +/- 0.46) U/g, (58.4 +/- 3.8) U/mg, (81.5 +/- 1.8)%] in ER group at PBH 8 was respectively significantly higher than that in NR group [(5.43 +/- 0.25) nmol/mg, (1.55 +/- 0.21) U/g, (50.1 +/- 2.8) U/mg, (78.3 +/- 1.5)%, P < 0.05 or P < 0.01]. While the activity of SOD in ER group (72 +/- 12) U/mg was lower than that in NR group (97 +/- 20) U/mg. MDA content, MPO and XOD activity and water ratio of intestinal tissue in ER+VC group was respectively lower than that in ER group, with activity of SOD in the former group higher than that in the latter group (P < 0.01).. Vitamin C can alleviate peroxidative damage and tissue edema in gut induced by ischemia and reperfusion, and intestinal complications during oral rehydration during burn shock can be reduced.

Topics: Animals; Ascorbic Acid; Burns; Dogs; Fluid Therapy; Intestine, Small; Male; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Shock

The concept of shock and its close relationship with that of stress dates back to the experiments of Hans Selye initiated in 1936 at McGill University in Montreal, with whom I collaborated between 1939 and 1942. It was demonstrated that the General Adaptation Syndrome begins with an Alarm Reaction, which consists of a Stage of Shock and one of Counter-Shock, followed by a Stage of Adaptation and finally a Stage of Exhaustion. My Ph.D. thesis concluded that shock was due to an adrenal insufficiency postulating that active metabolic processes drain the body of certain essential compounds the lack of which causes shock. My interest in the role of the glucose metabolism in shock led me to work with Bernardo Houssay in 1942 at the Institute of Physiology of the University of Buenos Aires and in 1944 with C.N.H. Long at Yale University. There I developed a method for the induction of hemorrhagic shock in the guinea pig with 94% lethality; curiously, the administration of 200 mg of ascorbic acid prevented death. Upon my return to Buenos Aires, these results were confirmed and moreover, it was demonstrated that the administration of cortisone led to 40% survival of the animals while desoxycorticosterone had no effect. At the time, no explanation was available but to-day, half a century later, this Symposium should be able to explain the mechanisms leading to death by hemorrhagic shock.

Topics: Animals; Ascorbic Acid; History, 20th Century; Humans; Nitric Oxide; Rats; Shock; Shock, Hemorrhagic

To ascertain whether surgery causes ischaemia-reperfusion (I-R) related injury, if this injury is augmented by preoperative shock, and reduced with low dose allopurinol.. Randomised blind placebo controlled trial.. Surgical laboratory.. 22 pigs were randomly allocated to four groups; OP = operation/placebo, OA = operation/ allopurinol, SOP = shock + operation/placebo, SOA = shock + operation/allopurinol. An aortic tube prosthesis was inserted in all. In groups SOP and SOA preoperative shock was induced by exsanguination. Allopurinol was administered in group OA on the preoperative day and peroperatively, in group SOA during shock and peroperatively.. Perioperative blood concentrations of thiobarbituric acid reactive species (TBARS), ascorbic acid (AA), albumin, 99mTc-albumin and creatine phosphokinase (CPK) as indicators of oxidative membrane damage, antioxidant activity, microvascular permeability changes and muscular cell damage respectively.. In the OP and OA groups TBARS gradually increased, while AA, 99mTc-albumin and CPK remained unchanged and albumin decreased. No effect of allopurinol was observed in these groups. In the SOP group TBARS and AA were not significantly different from groups OP and OA. Yet, albumin, 99mTc-albumin and CPK decreased significantly more in the SOP group. Compared with the SOP group, allopurinol treatment (SOA) produced lower TBARS and higher AA levels, and reduced the effect of shock on albumin, 99mTc-albumin and CPK concentrations.. Aortic surgery causes no I-R related damage. Pre-operative shock produces I-R related damage, which is reduced by allopurinol.

Topics: Allopurinol; Animals; Antioxidants; Aorta, Abdominal; Ascorbic Acid; Blood Vessel Prosthesis; Capillary Permeability; Creatine Kinase; Female; Granulocytes; Ischemia; Muscle, Skeletal; Oxidation-Reduction; Placebos; Random Allocation; Reperfusion Injury; Serum Albumin; Shock; Single-Blind Method; Swine; Technetium; Thiobarbituric Acid Reactive Substances

The ascorbic acid content of Drosophila melanogaster was found to be high in the absence of a dietary source. The amount of ascorbic acid per fly declined with aging in both the Oregon R and Swedish C strains. The median life span at 25 degrees C was 45 days for Swedish C and 59 days for Oregon R. The amount of ascorbic acid in Swedish C flies (0.078 micrograms/fly) was higher than that for Oregon R (0.058 micrograms/fly) for newly emerged flies but the rate of decline with aging was greater for Swedish C than Oregon R. The decline in ascorbic acid content with aging was 70.4% for Swedish C versus 19.9% for Oregon R. A brief cold shock was found to significantly increase the amount of ascorbic acid in Oregon R flies. Feeding the precursor of ascorbic acid synthesis, L-gulonolactone, did not improve the life span. Life-time feeding of ascorbic acid did not improve the life span of either Swedish C or Oregon R flies.

Topics: Aging; Animals; Ascorbic Acid; Chromatography, High Pressure Liquid; Cold Temperature; Diet; Drosophila; Drug Stability; Prodrugs; Shock

Topics: Adult; Ascorbic Acid; Female; Humans; Male; Orthomolecular Therapy; Physical Exertion; Shock; Stress, Physiological

Topics: Ascorbic Acid; Fructose; Glucose; Humans; Magnesium; Parenteral Nutrition; Phosphates; Postoperative Complications; Potassium; Shock; Sodium; Sorbitol; Vitamin A; Vitamin B Complex; Vitamin D; Vitamin K; Vitamins; Xylitol; Zinc

Topics: Alcoholic Intoxication; Aluminum; Aminopyrine; Anti-Inflammatory Agents; Ascorbic Acid; Benzyl Compounds; Child; Child, Preschool; Cosmetics; Female; Hallucinations; Humans; Hyperkinesis; Male; Methylamines; Nalidixic Acid; Perfume; Phenethylamines; Piperidines; Poisoning; Pyrazoles; Rutin; Shock; Speech Disorders

Topics: Adrenal Glands; Animals; Ascorbic Acid; Body Weight; Cold Temperature; Formaldehyde; Liver; Male; Organ Size; Rats; Shock; Stilbenes; Stress, Physiological; Testis

Topics: Animals; Ascorbic Acid; Blood Group Incompatibility; Blood Pressure; Blood Volume; Cardiac Output; Dogs; Extracorporeal Circulation; Hematocrit; Hemoglobinometry; Hydrocortisone; Phenoxybenzamine; Shock; Vascular Resistance

Topics: Animals; Ascorbic Acid; Dogs; Humans; Infusions, Parenteral; Shock; Shock, Surgical; Shock, Traumatic; Vitamin B Complex

Topics: Adolescent; Ascorbic Acid; Bandages; Baths; Blood Transfusion; Burns; Child; Classification; Contracture; Debridement; Drug Therapy; Gluconates; Humans; Infant; Mortality; Penicillins; Potassium; Psychotherapy; Regeneration; Shock; Silver Nitrate; Skin; Skin Transplantation; Sodium Chloride; Streptomycin; Toxicology; Wound Infection

Topics: Animals; Ascorbic Acid; Blood Cells; Blood Chemical Analysis; Blood Transfusion; Dogs; Plasma; Research; Shock; Shock, Hemorrhagic

Topics: Adrenal Cortex; Adrenal Glands; Animals; Ascorbic Acid; Biochemical Phenomena; Biochemistry; Blood Transfusion; Dogs; Research; Shock; Shock, Hemorrhagic

Topics: Ascorbic Acid; Cholinesterases; Hydrocortisone; Hydroxylamines; Pyridines; Shock

Topics: Acetylcholinesterase; Ascorbic Acid; Prednisolone; Prognosis; Shock; Surgical Procedures, Operative; Vitamins

Topics: Ascorbic Acid; Humans; Methylene Blue; Shock; Shock, Hemorrhagic; Vitamins

Topics: Adrenal Glands; Animals; Ascorbic Acid; Asphyxia; Carbohydrate Metabolism; Rats; Shock

Topics: Ascorbic Acid; Biomedical Research; Hospitals; Shock; Surgical Procedures, Operative; Vitamins

Topics: Ascorbic Acid; Shock; Shock, Surgical; Surgical Procedures, Operative

Topics: Ascorbic Acid; Shock; Vitamins

Topics: Ascorbic Acid; Brain; Capillary Permeability; Cardiovascular System; Flavonoids; Humans; Shock; Vitamin K; Vitamins

Topics: Animals; Ascorbic Acid; Body Fluids; Caproates; Carbohydrate Metabolism; Cold Temperature; Rats; Shock; Temperature

Topics: Adrenocorticotropic Hormone; Ascorbic Acid; Confusion; Convulsive Therapy; Shock; Stupor; Vitamins

Topics: Ascorbic Acid; Dehydroascorbic Acid; Ergocalciferols; Humans; Shock; Urine; Vitamin A; Vitamin D; Vitamin K; Vitamins

Topics: Ascorbic Acid; Guinea Pigs; Hemorrhage; Shock; Shock, Hemorrhagic