Meta-analysis Of The Effects Of Ascorbic Acid Over Critical Illnesses: Focusing On The Courses And The Doses

Background:Low plasma concentration of ascorbic acid has been found in critically ill patients.Pre-clinical studies have shown promising outcomes upon ascorbic acid administration,including scavenging reactive oxygen species and reducing oxidative stress response.However,the effects of ascorbic acid on mortality over critically ill patients remains controversial.This meta-analysis is performed to evaluate the effects of ascorbic acid on the mortality over critically ill patients,focusing on the course and doses.Methods:Critically ill patients treated with intravenous ascorbic acid were included when searching the database,with the predefined primary endpoint being all-cause mortality at final follow-up.Outcomes:The included 24 trials enrolled a total of 4522 patients.Intravenous ascorbic acid doses of 3-10 g/d and>10 g/d reduced the mortality of critically ill patients(OR=0.82;95%CI(0.67-0.89);P=0.044;I~2=46.8%vs OR=0.66;95%CI(0.50-0.87);P=0.003;I~2=0.0%),while low(<3 g/d)had no effect(OR=1.83;95%CI(0.88-3.79);P=0.104;I~2=0.0%).The long treatment course(≥3d)was associated with a decreased mortality compared with the short one(<3d)(OR=0.66;95%CI(0.50-0.85);P=0.002;I~2=49.9%vs OR=0.81;95%CI(0.64-1.03);P=0.087;I~2=38.8%).The administration of ascorbic acid alone lower the mortality rates,whereas in combination with other antioxidant agents did not have the effects(OR=0.71;95%CI(0.56-0.91);P=0.007;I~2=35.6%vs OR=0.85;95%CI(0.69-1.04);P=0.116;I~2=45.6%).In the condition of sepsis and burn,ascorbic acid could decrease the mortality rates(OR=0.79;95%CI(0.65-0.96);P=0.020;I~2=46.4%vs OR=0.71;95%CI(0.52-0.97);P=0.030;I~2=3.3%).Furthermore,ascorbic acid was associated with a decreased duration of vasopressor support(SMD=-1.1;95%CI(-1.65--0.37);P=0.002;I~2=80.5%),a shorten time of mechanical ventilation(SMD=-0.74;95%CI(-1.25--0.24);P=0.004;I~2=0.0%)and an increased urine output during the first 24 h of admission(SMD=0.35;95%CI(0.11-0.60);P=0.004;I~2=43.4%).However,ascorbic acid had no influence on the fluid requirement during the first 24 h of admission(SMD=-0.47;95%CI(-1.07-0.13);P=0.124;I~2=83.6%),and could not decreased the length of both the intensive care units stay(SMD=0.34;95%CI(-0.50-1.19);P=0.424;I~2=87.7%)and the hospital stay(SMD=-0.03;95%CI(-0.28-0.22);P=0.191;I~2=36.6%).No differences were observed in the number of patients suffering from acute kidney injury(OR=1.13;95%CI(0.69-1.85);P=0.622;I2=0.0%)and renal replacement therapy(OR=0.96;95%CI(0.70-1.33);P=0.815;I~2=45.3%).Conclusion:Intravenously administration of ascorbic acid was associated with a lower mortality rates over critically ill patients,especially for patients suffering from sepsis and burn.Administrating ascorbic acid without antioxidant agents mentioned,in a dose more than 3 g/d or at a course longer than 3 days could decrease the mortality rates.In view of the limitations of the primary literature,further studies are required to fully elaborate the effectiveness of ascorbic acid during the management of the critically ill patients.