Effect Of High-dose Vitamin C In Sepsis

ObjectiveTo evaluate the efficacy of high-dose vitamin c in sepsis.MethodsThis prospective randomized clinical trial was designed to evaluate the efficacy of high-dose vitamin c in sepsis.There were 122 septic patients enrolled in the intensive care unit(ICU)of the First Affiliated Hospital of Dalian Medical University from June2016 to January 2019,and they were randomly assigned to three groups[Placebo group(n=42),Low-dose group(n=41)and High-dose group(n=39)],and different dose of vitamin c was intravenously pumped within 96 hours[Low-dose group:50 mg/(kg·d),High-dose group:150mg/(kg·d),and Placebo group:0.9%saline].The following treatments were based on the latest guidelines of Surviving Sepsis Campaign(SSC).28-day mortality was considered as the primary outcome.Secondary outcomes contains duration of ICU stay,duration of hospital stay,duration of ventilation,illness severity[Acute Physiology and Chronic Health Evaluation(APACHE)Ⅱscore,Sequential Organ Failure Assessment(SOFA)score and Multiple Organ Dysfunction Syndrome(MODS)score],indicators of inflammation and immunity[procalcitonin,c-reactive protein,interleukin-6,interleukin-10,T lymphocyte subsets(CD4~+,CD8~+,CD4~+/CD8~+),expression of CD14~+monocytic HLA-DR(mHLA-DR)],hemodynamic parameters[fluid intake,urine output,mean arterial pressure,arterial lactate,norepinephrine dose and duration],and indicators of organ functions[alanine aminotransferase,total bilirubin,serum creatinine,uric acid],and safety evaluation(vitamin c plasma concentration and adverse reactions of intravenous vitamin c).Results1.A total of 122 septic patients were recruited in this trail(42 in Placebo group,41in Low-dose group and 39 in High-dose group),whose mean age was(69.50±15.86)years,including 88 males(72.13%),36 patients with septic shock(29.51%),the primary cause of sepsis was pulmonary infection(86.07%).No statistically significant difference was detected between three groups in terms of baseline characteristics(baseline diseases,vital signs,severity of illness,biomarkers of inflammation and organ functions)(all P>0.05).2.The plasma concentration of vitamin c in 122 septic patients was(3.61±2.62)μmol/L.After 24 hours of enrollment,the plasma levels of vitamin c in patients were significantly different between three groups,High-dose group was significantly higher than Low-dose group and Low-dose group was significantly higher than Placebo group,all the difference was statistically significant(all P<0.05).The adverse reaction of intravenous vitamin c was not detected in all patients who received vitamin c within 96hours.3.There was a statistically significant difference in 28-day mortality between three groups[Placebo group(33.33%)vs.Low-dose group(24.39%)vs.High-dose group(10.26%),P=0.046)],and 28-day mortality in High-dose group was significantly lower than that in Placebo group[Placebo group(33.33%)vs.High-dose group(10.26%),P=0.013).No significant difference was detected between three groups regarding the length of ICU stay,total hospital stay,and duration of ventilation[length of ICU stay:Placebo group(19.74±14.93 days)vs.Low-dose group(19.46±11.57 days)vs.High-dose group(19.11±14.42 days),P=0.979,total hospital stay:Placebo group(22.62±16.41 days)vs.Low-dose group(23.17±15.24 days)vs.High-dose group(22.76±16.20 days),P=0.987,duration of ventilation:Placebo group(12.81±13.95 days)vs.Low-dose group(12.54±12.09 days)vs.High-dose group(13.15±13.92 days),P=0.979)].4.The decrease rate of APACHE II score,SOFA score and MODS score in High-dose group was significantly faster than Placebo group and Low-dose group during the study period[APACHE II score:Placebo group(-0.03±0.29)vs.Low-dose group(-0.14±0.28)vs.High-dose group(-0.27±0.15),P<0.001;SOFA score:Placebo group(-0.03±0.38)vs.Low-dose group(-0.14±0.29)vs.High-dose group(-0.34±0.25),P<0.001;MODS score:Placebo group(-0.03±0.43)vs.Low-dose group(-0.11±0.37)vs.High-dose group(-0.33±0.25),P=0.001].5.The decline rate of procalcitonin and c-reactive protein in High-dose group was significantly faster than that in Placebo group and Low-dose group during the study period{procalcitonin(represented by median and quartile,respectively,the same as below):Placebo group[-0.61(-0.83,0.21)]vs.Low-dose group[-0.66(-0.87,-0.26)]vs.High-dose group[-0.81(-0.91,-0.58)],P=0.017;c-reactive protein:Placebo group[-0.35(-0.67,-0.02)]vs.Low-dose group[-0.37(-0.73,-0.04)]vs.High-dose group[-0.69(-0.79,-0.49)],P=0.006]}.The decline rate of interleukin-6 in High-dose group was significantly faster than that in Placebo group during study period{Placebo group[0.00(-0.36,0.50)]vs.High-dose group[-0.43(-0.82,-0.01)],P=0.015},The decline rate of expression of CD14~+mHLA-DR in High-dose group was significantly faster than Placebo group[Placebo group(0.05±0.38)vs.High-dose group(0.60±1.28),P=0.010],while there were no significant differences between three groups in terms of interleukin-10,lymphocyte subsets(CD4~+,CD8~+,CD4~+/CD8~+)(all P>0.05).6.Subgroup analysis of septic patients requiring norepinephrine indicated that the decline rate of norepinephrine dose in High-dose group was significantly faster than that in Placebo group during the study period{Placebo group[0.33(-0.31,1.32)]vs.High-dose group[-0.73(-1.00,0.67)],P=0.016}.No significant differences between three groups regarding fluid intake,urine output,mean arterial pressure,arterial lactate and duration of receiving norepinephrine(all P>0.05).7.High-dose group can effectively improve kidney function compared with Placebo group[the rate of 96h change of creatinine:Placebo group(0.05±0.59)vs.High-dose group(-0.20±0.21),P=0.004;the rate of 96h change of uric acid:Placebo group(-0.15±0.42)vs.High-dose group(-0.35±0.33),P=0.030].While there were no significant differences between three groups regarding alanine aminotransferase and total bilirubin(all P>0.05).ConclusionsThe deficiency of vitamin c is common in sepsis.Intravenously infusion of high-dose vitamin c is safe and effective,which can effectively inhibit inflammatory response,improve immunity and kidney function,reduce norepinephrine consumption,reduce the scores of illness severity and the 28-day mortality of septic patients.