Effect Of Intravenous Vitamin Research Articles

Effect of Intravenous Vitamin C on Serum Level and Urinary Excretion of Methadone in Patients with Methadone Poisoning: A Randomized Single-Blind Clinical Trial

Background: Methadone poisoning intentionally or accidentally leads to a high rate of treatment burden and cost and deaths. The evaluation of the factors affecting the severity of poisoning can reduce recovery time, costs, and potential risks. Objectives: This study aimed to investigate the effect of intravenous vitamin C (ascorbic acid) administration on serum level and urinary excretion of methadone. Patients and Methods: In this single-blind study, 54 patients who were diagnosed with methadone poisoning were divided into three groups. The two intervention groups received different doses of vitamin C, including 12 and 24 g, and the control group received normal saline. The serum methadone level and urine pH were measured at the time of arrival and 24 hours after admission. The data were analyzed using repeated measure analysis of variance (ANOVA) in STATA version 12. Results: In this study, 18 patients were placed in each group. The three groups were not significantly different in basic variables, such as age, gender, and methadone dosage. Between and within-group comparison showed a significant decrease in the serum methadone levels over time after adjusting age, gender and methadone dosage (P < 0.05). Post-hoc analyses revealed a significant difference in methadone reduction between 12 g of vitamin C and control groups (P = 0.04), and there was no significant difference between the control and 24 g of vitamin C groups (P > 0.05). However, between and within-group comparisons showed no significant difference between the three groups in terms of urine pH (P > 0.05). In addition, interaction was observed between intervention and time on serum methadone levels (P < 0.001) and urine pH (P = 0.04) variables. Conclusions: Consuming 12 g of vitamin C further reduced the serum methadone level in patients with methadone poisoning. There was no effect on methadone urinary excretion in patients.

The effect of intravenous Vitamin C, thiamine and hydrocortisone on the outcome of septic patients

The effect of intravenous Vitamin C, thiamine and hydrocortisone on the outcome of septic patients

An investigation into the Effects of Intravenous Vitamin C on Pulmonary CT Findings and Clinical Outcomes of Patients with COVID 19 Pneumonia A Randomized Clinical Trial.

In late December 2019, a series of unexplained cases of pneumonia were reported in Wuhan, China. On January 12, 2020, the World Health Organization temporarily named the virus responsible for the emerging cases of pneumonia as the 2019 coronavirus. Acute respiratory distress syndrome (ARDS) due to Covid-19 has rapidly spread around the world, and while no specific treatment or vaccine has been reported, mortality rates remain high. One of the suggested treatments for cellular damage in the pathogenesis of ARDS caused by the coronavirus is the administration of high doses of intravenous vitamin C. Considering the paucity of literature on the therapeutic effects of high doses of intravenous vitamin C in patients with ARDS resulting from the coronavirus, this study was conducted to assess this therapeutic supplement in these patients. This study was performed as a single-center clinical trial in patients with a documented diagnosis of COVID-19 pneumonia. 54 eligible patients with moderate to severe COVID-19 symptoms, based on specific inclusion and exclusion criteria, were included in the investigation and randomly divided into two groups. The control group consisted of 26 patients who received standard treatment, whereas the treatment group was comprised of 18 patients administered intravenous vitamin C at a dose of 2 g every 6 hours for 5 days in addition to standard treatment. Demographic characteristics, underlying diseases, length of hospital stay, and mortality rates were reviewed and collected. Oxygen saturation, respiratory rates, serum C Reactive Protein (CRP) levels, lymphopenia and lung parenchymal involvement on CT were investigated at the time of admission and on the sixth day after hospitalization. Finally, all variables were analyzed with IBM SPSS Statistics 23 software and a significant statistical difference was defined for all variables, P <0.05. Of these variables, the amount of oxygen saturation in the vitamin C group increased significantly from 86±5% on the first day of hospitalization to 90±3% on the sixth day of hospitalization (P value=0.02). Also, the respiratory rate in the vitamin C group decreased significantly from 27±3 on the first day of hospitalization to 24±3 on the sixth day of hospitalization (P value=0.03). Lung CT scans of patients in the two groups reported by two radiologists were also compared. Based on the report of the radiologists, the rate of lung involvement in the vitamin C group was significantly lower than in the control group at the end of treatment (P value=0.02). Due to the effectiveness of high doses of intravenous vitamin C on reducing lung involvement and improving clinical symptoms, further studies with a larger sample size are recommended to demonstrate the effects of this drug supplement.

Effect of intravenous vitamin C on arterial blood gas analyser and Accu-Chek point-of-care glucose monitoring in critically ill patients

Background: Intravenous vitamin C is known to interfere with some point-of-care blood glucose meters. We aimed to determine the concentrations at which ascorbate interferes with glucose concentrations measured using a point-of-care blood glucose meter. We also compared the point-of-care meter and an arterial blood gas (ABG) analyser in the intensive care unit with laboratory glucose monitoring in septic patients receiving intravenous vitamin C infusions. Methods: Blood samples containing normal, depleted and supplemented glucose and increasing concentrations of ascorbate (0.1-1.0 mmol/L) were tested using an Accu-Chek Inform II (Roche Diagnostics, USA) glucometer. For the in vivo study, 41 individual blood samples were drawn daily from septic patients (n = 16) receiving infusions of 25 mg/kg of vitamin C every 6 hours. The glucose values of matched blood samples were assessed using Accu-Chek, ABG and laboratory glucose methods. Results: For every 1 mmol/L of ascorbate added, the glucose concentration measured by the point-of-care monitor increased by 1.4 mmol/L (95% CI, 1.0-1.8; P < 0.001). Analysis of matched blood samples collected following intravenous vitamin C infusion indicated that 98% of the ABG and 83% of the Accu-Chek values met the International Organization for Standardization (ISO) 15197:2013 accuracy criteria. One patient had severe renal impairment, which contributed to elevated plasma vitamin C concentrations (median, 0.95 mmol/L; range, 0.64-1.10 mmol/L), resulting in elevated Accu-Chek readings and presenting a moderate clinical risk for the highest value. Conclusions: Vitamin C concentrations < 0.8 mmol/L do not interfere with point-of-care glucose monitoring. Intravenous vitamin C infusion of 25 mg/kg every 6 hours does not interfere with point-of-care glucose monitoring unless the patient has renal impairment, in which case laboratory glucose tests should be used.

The Effects of Intravenous Vitamin C on Stress Response Severity in Abdominal Hysterectomy Following Prolonged Fasting Time.

BackgroundInevitable prolonged fasting time before surgery leads to inflammatory reactions, surgery-related stress response, and consequently unfavorable outcomes; thus, developing strategies to mitigate these consequences is crucial.ObjectivesIn this study, we evaluated the effect of ascorbic acid on stress response reduction in abdominal hysterectomy following prolonged fasting time.MethodsEligible women candidates for abdominal hysterectomy following prolonged fasting time were enrolled in the study and divided into 2 groups of vitamin C [group C; 1 g intravenously (IV) before surgery] and placebo (group P). Before induction of anesthesia, C-reactive protein (CRP), mean arterial pressure (MAP), heart rate (HR), and blood sugar (BS) were measured and compared between the 2 groups at 4-point times, 24 and 48 hours immediately after extubation.ResultsFinally, the data of 80 patients were included for the final analysis. A statistically significant difference was observed between the 2 groups in terms of CRP and BS values in T1 CRP serum levels; at the end of the study, CRP values were 0.5 ± 0.55 and 0.92 ± 0.69 in groups C and P, respectively (P = 0.012), and BS levels were 124.12 ± 18.11 and 152.0 ± 17.36 in groups C and P, respectively (P = 0.0001). However, this significant difference was not observed at T2 regarding CRP (P = 0.145) and BS (P = 0.135), as well as at T3 regarding CRP (P = 0.282) and BS (P = 0.213). However, according to both CRP and BS values, the trend of changes from T0 to T3 was significant in the 2 groups (P < 0.0001). Hemodynamic parameters were not significantly different between the 2 groups. No adverse event was reported in the 2 groups.ConclusionsWe found that ascorbic acid could induce short-term positive effects in abdominal hysterectomy following prolonged fasting time. Obviously, the optimal dosage, timing, and specific cases that benefit the most from this intervention should be investigated.

Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial

BackgroundHigh-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients.MethodsThis is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations.DiscussionVitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest.Trial registrationClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL

Vitamin C Therapy for Routine Care in Septic Shock (ViCTOR) Trial: Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone Administration on Inpatient Mortality among Patients with Septic Shock.

BackgroundSepsis remains a leading cause of death worldwide despite advances in management strategies. Preclinical and observational studies have found mortality benefit with high-dose vitamin C in sepsis. Our study aims to prospectively evaluate the effect of intravenous hydrocortisone, vitamin C [ascorbic acid (AA)], and thiamine (HAT) administration in reducing inpatient all-cause mortality among patients with septic shock.Materials and methodsOur single-center, prospective, open-label, randomized controlled trial recruited patients with admitting diagnosis of septic shock and assigned eligible patients (1:1) into either intervention (HAT) or control group (routine). The HAT group received intravenous combination of vitamin C (1.5 g every 6 hours), thiamine (200 mg every 12 hours), and hydrocortisone (50 mg every 6 hours) within 6 hours of onset of septic shock admission. The treatment was continued for at least 4 days, in addition to the routine standard of care provided to the control group. Thiamine and hydrocortisone use in control arm was not restricted. Vitamin C levels were estimated at baseline and at the end of the 4 days of treatment for both groups. The primary outcome evaluated was mortality during inpatient stay.ResultsAmong 90 patients enrolled, 88 patients completed the study protocol. The baseline characteristics between the HAT (n = 45) and the routine (n = 43) groups were comparable. The all-cause mortality in the HAT cohort was 57% (26/45) compared to 53% (23/43) in the routine care group (p = 0.4, OR 1.19, 95% CI 0.51–2.76). The time to reversal of septic shock was significantly lower in the HAT (34.58 ± 22.63 hours) in comparison to the routine care (45.42 ± 24.4 hours) (p = 0.03, mean difference −10.84, 95% CI −20.8 to −0.87). No significant difference was observed between the HAT and the routine care with respect to changes in sequential organ failure assessment (SOFA) scores at 72 hours (2.23 ± 2.4 vs 1.38 ± 3.1), the use of mechanical ventilation (48% vs 46%), and mean Vasoactive Inotropic Score (7.77 ± 12.12 vs 8.86 ± 12.5).ConclusionIntravenous administration of vitamin C, thiamine, and hydrocortisone did not significantly improve the inpatient all-cause mortality among patients with septic shock.Clinical significanceHAT protocol does not reduce hospital mortality but decreases time to shock reversal in septic shock.How to cite this articleMohamed ZU, Prasannan P, Moni M, Edathadathil F, Prasanna P, Menon A, et al. Vitamin C Therapy for Routine Care in Septic Shock (ViCTOR) Trial: Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone Administration on Inpatient Mortality among Patients with Septic Shock. Indian J Crit Care Med 2020;24(8):653–661.

Effect of Intravenous Injection of Vitamin C on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery: A Double-Blind, Randomized Trial.

PurposeIn this study, the effect of intravenous vitamin C during surgery on the incidence of postoperative pulmonary complications (PPCs) in patients undergoing cardiopulmonary bypass and cardiac surgery was observed, and its protective effect on the lungs was evaluated to provide a reference for clinical medication.Patients and MethodsPatients undergoing cardiac surgery under cardiopulmonary bypass (CPB) were selected. The patients were divided into group A and group C by random sequence. Patients in group A received intravenous vitamin C 1 g 10 minutes after induction of anesthesia, 10 minutes before cardiac reanimation and at the moment of sternal closure. Patients in group C were intravenously injected with the same volume of saline at the same time. The primary outcome was the postoperative pulmonary complication severity score. Other outcomes were the incidence of PPCs, awakening time, extubation time, length of ICU stay, length of hospital stay, adverse events, oxygenation index (PaO2/FiO2), alveolar arterial oxygen partial pressure difference (A-aDO2), dynamic lung compliance (Cd) and static lung compliance (Cs).ResultsSeventy patients completed the study. Compared to group C, the postoperative pulmonary complication score [2(2–3) vs 2(1–2); P=0.009] and the incidence of postoperative pulmonary complications (32.43% vs 12.12%; P =0.043) were lower in group A. There were no significant differences in awakening time, extubation time, length of ICU stay, length of hospital stay, adverse events, PaO2/FiO2, A-aDO2, Cs, and Cd between the two groups (P>0.05).ConclusionIn summary, this small randomized trial including low-risk cardiac surgery patients shows that intravenous vitamin C may safely be administered and may be helpful to prevent PPCs after cardiac surgery.

The Effect of Intravenous Vitamin C on Urine Neutrophil Gelatinase-Associated Lipocalin Among Septic Patients

Background&#x0D; The role of vitamin C to decrease organ dysfunction in sepsis was still controversial. This study aimed to explore the effect of intravenous (IV) vitamin C on urine NGAL (uNGAL) levels among septic patients in ICU.&#x0D; Methods&#x0D; This study was a randomized clinical trial held in Cipto Mangunkusumo Hospital from April to July 2019 with consecutive sampling method. Patients aged &gt; 18 years with sepsis based on the criteria of sepsis-3 who were admitted to the ICU were included in this study. Exclusion criteria were those with chronic kidney problems, with kidney stones, undergo renal replacement therapy in the ICU. All subjects were divided into: Group A was treated with combination of vitamin C and thiamine while Group B was given thiamine only. The uNGAL level was measured at baseline, 24, 48 and 72 h after treatment. Anova for repeated measurement using General Linear Model for Repeated Measurement was used with level of significant at p-value &lt;0.05.&#x0D; Results&#x0D; Total of 33 subjects were included. In Group A we found uNGAL (ng/ mL) were 74.5 (13.3-102.9), 77.3 (15.2-98.4), 67.2 (22.6-100.6), 77.2 (17.0-100.5) for baseline, 24 h, 48 h, and 72 h respectively. While in Group B uNGAL were 57.7 (11.5-94.5), 57.1 (6.4-97.7), 53.7 (13.3-99.6), 47.6 (4.5-100.9). No significant difference in terms of uNGAL between two groups at each hour was found.&#x0D; Conclusions&#x0D; This study showed that intravenous vitamin C administration had no effect on uNGAL among septic patients. Need more study to investigate approaches to improve kidney and inflammatory biomarker among septic patients.

Effect of Intravenous Vitamin C on SOFA Score Among Septic Patients

Effect of Intravenous Vitamin C on SOFA Score Among Septic Patients

Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone (The Metabolic Resuscitation Protocol) on Early Weaning from Vasopressors in Patients with Septic Shock. A Descriptive Case Series Study

Objectives: The aim of this study was to assess the efficacy of intravenous vitamin C, hydrocortisone, and thiamine in early weaning (within 48 hours) from vasopressor support in patients with septic shock. We also aimed to assess mortality and intensive care unit (ICU) stay.Study Design: We conducted a descriptive case series study of 50 patients with septic shock who were admitted in the ICU of the Combined Military Hospital Rawalpindi in Pakistan from August 2017 until April 2018.Materials and Methods: The study included men and women (16 to 80 years of age) who were admitted to the ICU with septic shock. Data were analysed using the IBM Statistical Package for Social Sciences (SPSS), version 18.0 (IBM Corp., Armonk, NY, USA). Inferential analysis was done with the help of simple and multivariate binary logistic regression that generated unadjusted and adjusted odds ratios (OR), respectively.Results: Of the 50 patients, 56% (N = 28) were male with a mean age of the respondents being 46.7 ± 18.4. Eighty-four percent were successfully weaned off vasopressors within 48 hours. Median days in the ICU were reported as 8.3 (interquartile range (IQR) = 5). Primary bacteremia (34%) was the most reported cause of ICU admission. The most common vasopressor was norepinephrine and its mean dose was 21.6 ± 10.7 microgram/min. The ICU mortality was observed at 52% (N = 26). Unadjusted OR showed a dose of norepinephrine, Sequential Organ Failure Assessment (SOFA) score, plasma procalcitonin, and plasma lactate to be significant predictors (p-value < 0.05), while the adjusted odds ratio (AOR) showed only a dose of norepinephrine to be a statistically significant predictor (AOR = 0.804, 95% CI = 0.674 - 0.960; p-value = 0.016).Conclusion: The administration of intravenous vitamin C, hydrocortisone, and thiamine to patients with septic shock was successful in early weaning from vasopressors. There was also a reduction in procalcitonin and lactate levels, as well as the SOFA score. Further trials are needed to determine whether the metabolic resuscitation protocol can become part of the treatment for septic shock.

Effect of intravenous vitamin C on postoperative pain in uvulopalatopharyngoplasty with tonsillectomy.

Postoperative pain is a common problem in hospitals. Adults undergoing uvulopalatopharyngoplasty (UPPP) with tonsillectomy experience an unacceptable level of intense postoperative pain, especially during the first 24 h after surgery. This study investigated the analgesic effects of vitamin C in patients undergoing UPPP and tonsillectomy. This study was done on forty patients that were evaluated in a randomised double-blinded clinical trial. Patients included in the study were within the age range of 25-50 years with BMI<35, physical status I,II according to the American Society of Anesthesia (ASA) and who underwent uvulopalatopharyngoplasty and tonsillectomy. Patients with epilepsy, BMI>35, any neuropsychiatric disorders, a history of chronic pain, liver and/or renal disease, drug allergy, and drug abuse were excluded from the study. All patients underwent the same method of anaesthesia and surgical procedure. During the first 30 min after the beginning of the surgery, group C (vitamin C) received infusion of 3 g vitamin C in 500 mL of Ringer and group P received 6 mL normal saline in 500 mL of Ringer. Measurements of systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and heart rate were recorded before and during anaesthesia and at intervals of 0,15,30 and 60 min after extubation. Pain severity was recorded according to VAS score at intervals of 0 (recovery room), 6, 12 and 24 h after the procedure, request for analgesic drugs (iv paracetamol or pethedine) according to total number of times of analgesic request and time of the first dose of analgesic use and dose of pethidine were also recorded by questionnaire. There was a significant difference in evaluations for mean pain severity between the two groups at recovery room, 6, 12 and 24 h after surgery (P-value = 0.001). There was a significant difference in mean times that patient requested an analgesic, time of first dose of analgesic and pethidine dose between the two groups (P-value< 0.05). There was no significant differences in measurements of systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and heart rate in different times between the two groups (P-value> 0.05). Blood loss was similar in the two groups (P-value> 0.05). According to this study, administration of vitamin C 3 g IV intraoperative reduced postoperative pain without increased side-effects in patients undergoing UPPP and tonsillectomy.

The effects of intravenous vitamin C on point-of-care glucose monitoring.

Ascorbic acid (vitamin C) decreases systemic inflammation and lowers fluid requirements after thermal injury; therefore it has been adopted in many burn centers as an adjunct to resuscitation. However, recent concerns have been expressed over clinically significant hypoglycemic events caused by vitamin C interference with the point-of-care (POC) glucose measurements. This case series presents a direct comparison of POC and laboratory reference glucose values in the patients receiving vitamin C infusion. Vitamin C was administered at 66 mg/kg/hour in seven patients with burns >30% TBSA. The baseline characteristics and burn characteristics were recorded. POC glucose measurements were made with a commonly used hand-held device, and the laboratory values were obtained using standard spectrophotometric methods. POC and laboratory glucose values drawn within the same hour were compared. Hemoglobin, which is known to cause interference in POC testing, was also recorded. All the patients demonstrated falsely elevated POC glucose values during and/or immediately after the infusion period, with discrepancies ranging from 10 to 200 mg/dl. These findings were irregular, unpredictable and unrelated to hemoglobin levels. The findings suggest an idiosyncratic reaction that cannot be easily corrected at the bedside using mathematical equations. POC glucose monitoring should be avoided during and after vitamin C therapy.

The Effect of Intravenous Vitamin C on Cancer- and Chemotherapy-Related Fatigue and Quality of Life

Cancer patients commonly experience a number of symptoms of disease progression and the side-effects of radiation therapy and adjuvant chemotherapy, which adversely impact on their quality of life (QOL). Fatigue is one of the most common and debilitating symptom reported by cancer patients and can affect QOL more than pain. Several recent studies have indicated that intravenous (IV) vitamin C alleviates a number of cancer- and chemotherapy-related symptoms, such as fatigue, insomnia, loss of appetite, nausea, and pain. Improvements in physical, role, cognitive, emotional, and social functioning, as well as an improvement in overall health, were also observed. In this mini review, we briefly cover the methods commonly used to assess health-related QOL in cancer patients, and describe the few recent studies examining the effects of IV vitamin C on cancer- and chemotherapy-related QOL. We discuss potential mechanisms that might explain an improvement in QOL and also considerations for future studies.

The Effect of Intravenous Vitamin C Infusion on Periprocedural Myocardial Injury for Patients Undergoing Elective Percutaneous Coronary Intervention

BackgroundThis small study has determined the effect of vitamin C on myocardial reperfusion in patients undergoing elective percutaneous coronary intervention (PCI). This study was to explore whether antioxidant vitamin C infusion before the procedure is able to affect the incidence of periprocedural myocardial injury (PMI) in patients undergoing PCI. MethodsIn this prospective single-centre randomized study, 532 patients were randomized into 2 groups: the vitamin C group, which received a 3-g vitamin C infusion within 6 hours before PCI, and a control group, which received normal saline. The primary end point was the troponin I–defined PMI, and the second end point was the creatine kinase (CK)-MB–defined PMI. Separate analyses using both end points were performed. PMI was defined as an elevation of cardiac biomarker values (CK-MB or troponin I) > 5 times the upper limit of normal (ULN), alone or associated with chest pain or ST-segment or T-wave changes. ResultsAfter PCI, the incidence of PMI was reduced, whether defined by troponin or by CK-MB, compared with the control group (troponin I, 10.9% vs 18.4%; P = 0.016; CK-MB, 4.2% vs 8.6%; P = 0.035). Logistic multivariate analysis showed that preprocedure use of vitamin C is an independent predictor of PMI either defined by troponin I (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.33-0.97; P = 0.037) or by CK-MB (OR, 0.37; 95% CI, 0.14-0.99; P = 0.048). ConclusionsIn patients undergoing elective PCI, preprocedure intravenous treatment with vitamin C is associated with less myocardial injury.

Effect of intravenous vitamin C on cytokine activation and oxidative stress in end-stage renal disease patients receiving intravenous iron sucrose

Reticuloendothelial blockade in hemodialysis patients prevents optimal intravenous (IV) iron utilization. Vitamin C has emerged as a potential therapy to improve anemia treatment by enhancing iron mobilization. However, Vitamin C can act as a pro-oxidant in the presence of iron. This was a prospective, open-label, crossover study. Thirteen patients with end-stage renal disease on hemodialysis and four healthy controls were assigned to receive 100mg of IV iron sucrose (IS) or 100mg of IV IS co-administered with 300mg of IV Vitamin C (IS+C) in random sequence. Serum samples for IL-1, IL-6, TNF-α and IL-10 and non-transferrin bound iron were obtained at baseline, 45min and 105min post study medication administration. Peripheral blood mononuclear cells were isolated at the same time points and stained with fluorescent probes to identify intracellular reactive oxygen species and mitochondrial membrane potential (Δψm) by flow cytometry. Lipid peroxidation was assessed by plasma F2-isoprosatane concentration. Both IS and IS+C were associated with increased plasma F2-isoprostanes concentrations post-infusion. Maximal plasma F2-isoprostane concentrations after IS+C were significantly elevated from baseline (234±0.04 vs. 0.198±0.028ng/mL, p=0.02). After IS+C, IL-1, IL-6, IL-10, and TNF-alpha were significantly elevated compared to baseline. After IS alone only IL-6 was noted to be elevated. Intracellular production of H(2)O(2) and loss of mitochondrial membrane potential (Δψm) was observed after IS while IS+C was associated with increased O (2) (·-) production. Both IS and IS+C induced serum cytokine activation accompanied by lipid peroxidation, however, IS+C induced higher plasma concentrations of F2-isoprostanes, IL-1, IL-10, and TNF-α post-infusion. Long-term safety studies of IV iron co-administered with Vitamin C are warranted.

Effect of Intravenous Calcitriol on Cardiac Systolic and Diastolic Function in Patients on Hemodialysis

The systolic and diastolic function of the heart of hemodialysis (HD) patients and the effect of intravenous vitamin D therapy on cardiac function was studied by Doppler and digitized M-mode echocardiography in 10 HD patients before and after 3–4.5 months of calcitriol therapy. Calcitriol was administered intravenously 1–3 times a week at a dose of 1–2 µg after the dialysis sessions. Ten age- and sex-matched healthy controls were also examined echocardiographically. Before calcitriol therapy cardiac wall thicknesses (interventricular septum, posterior wall) and left ventricle (LV) dimensions (end diastolic, end systolic) were greater, and LV diastolic (peak late diastolic velocity, peak early diastolic velocity/peak late diastolic velocity ratio, isovolumic relaxation time) and systolic (fractional shortening) function was impaired in HD patients as compared to controls. The LV posterior wall thickness was related to plasma parathyroid hormone (PTH; r = 0.70, p = 0.01) in the patients. Calcitriol therapy raised serum ionized Ca from 1.23±0.04 to 1.33 ± 0.04 mmol/l and reduced PTH from 41.1±10.7 to 34.2±11.7 pmol/l (29±11%). Calcitriol therapy did not cause any significant changes in cardiac function in the whole patient group. However, in a subgroup of 5 patients with severe but controllable hyperparathyroidism (PTH >3 times upper normal margin) the LV dimensions and systolic function improved (LV end systolic dimension from 39.0 ± 4.0 to 31.3 ± 2.9 mm, p = 0.03; LV end diastolic dimension from 57.7 ± 3.1 to 53.4 ± 3.0 mm, p = 0.06; fractional shortening from 33 ± 4 to 42 ± 3%, p = 0.03). The diastolic indices improved also, but not significantly. In conclusion, left ventricle hypertrophy and systolic and diastolic dysfunction was observed in HD patients. Intravenous calcitriol therapy improved cardiac function in patients with severe secondary hyperparathyroidism.

The effect of intravenous vitamin E and menadiol sodium diphosphate on vitamin K dependent clotting factors

During a Phase I study of intravenous vitamin E-free alcohol (all-rac-a-tocopherol or Ephynal®) in patients with neuroblastoma, we noticed a bleeding diathesis in two patients receiving 2300 mg/m 2 daily for four or more days in succession. Both blood prothrombin time and acclerated partial thromboplastin times were prolonged. These spontaneously returned to normal levels three days after interrupting vitamin E infusions. It was also noted that factors VII, IX and X were decreased, which corresponded with the prolonged PT and APTT. It was found that by infusing menadiol sodium diphosphate just prior to the vitamin E, these inhibiting effects on procoagulant factors could be abrogated and high dosages of vitamin E-free alcohol safely given.

Effects of intravenous vitamin D on bone and phosphate metabolism in osteomalacia.

The effect of a 1 mg dose of intravenous Vitamin D3 (40,000 i.u.) on bone histology and phosphate metabolism was investigated in 19 patients with normal bone histology and 28 patients with histological evidence of osteomalacia. No significant changes occurred in the control patients after Vitamin D but the patients with osteomalacia showed a marked increase, within seven days, in the proportion of osteoid having a calcification front. This was accompanied by a progressive rise in the serum phosphate, which was associated with an increase in the renal tubular reabsorption of phosphate to normal.