1.Effect of vitamin D3 on the severity and prognosis of patients with sepsis: a prospective randomized double-blind placebo study
Fulai DING ; Bin ZANG ; Jiahong FU ; Kaiqiang JI
Chinese Critical Care Medicine 2017;29(2):106-110
Objective To observe the relationship between vitamin D3 and the severity as well as prognosis in patients with sepsis, and to explore whether exogenous vitamin D3 can improve the prognosis in patients with sepsis.Methods A prospective randomized double-blind placebo study was conducted. Fifty-seven patients with sepsis admitted to intensive care unit (ICU) of Shengjing Hospital Affiliated to China Medical University from March to November in 2015 were enrolled. Twenty patients with systemic inflammatory response syndrome (SIRS) and 20 healthy volunteers with normal physical examination as control were enrolled during the same time. Patients with sepsis were divided into general sepsis group and severe sepsis group (including septic shock) according to the criteria for the diagnosis of severe sepsis and septic shock in 2012. According to the diagnostic criteria established by the American Endocrine Society, and on the basis of 25-hydroxy vitamin D3 [25(OH)D3], the sepsis patients with deficiency [25(OH)D320-30μg/L] or insufficiency [25(OH)D3 < 20μg/L] of vitamin D were divided into D3 treatment group (supplemented 300 kU vitamin D3) and placebo group (injected 1 mL physiological saline). 28th day was set as the end point, and the patients with sepsis were divided into survival group and death group. The levels of serum 25(OH)D3 in each group were measured by electrochemical luminescence method, and the difference in 25(OH)D3 levels among patients with different severity, gender, and age were recorded. Procalcitonin (PCT), C-reactive protein (CRP), blood routine, liver and kidney function, electrolytes and arterial blood gas analysis, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure score (SOFA), duration of mechanical ventilation, and length of ICU stay of patients with sepsis were observed. Multivariate Cox proportional hazard regression analysis was used to analyze the risk factors of prognosis in patients with sepsis.Results ① In 57 patients with sepsis, there were 15 patients in general sepsis group, and 42 in severe sepsis group; 29 in D3 treatment group, and 28 in the placebo group; 8 patients died within 28 days with mortality rate of 14.04%. ② The levels of serum 25(OH)D3 in sepsis group and SIRS group were significantly lower than those in healthy control group [μg/L: 3.92 (< 3.00, 11.22), 6.99 (3.51, 9.77) vs. 17.25 (13.48, 22.50), both P < 0.01], but there was no significant difference in the serum 25(OH)D3 level between sepsis group and SIRS group as well as patients with different degrees of sepsis. The serum 25(OH)D3 level in female patients with sepsis (n = 24) was significantly lower than that in male (n = 33), and the difference was statistically significant [μg/L: <3.00 (<3.00, 3.87) vs. 11.96 (5.14, 17.29),Z = -4.020,P = 0.000]. There was no significant difference in serum 25(OH)D3 level between the young (age <60 years old,n = 30) and the old (age ≥ 60 years old,n = 27) patients with sepsis [μg/L: 4.54 (<3.00, 9.88) vs. 3.00 (<3.00, 15.08),Z = -0.601,P = 0.548]. ③ In patients with sepsis, there was no significant difference in the duration of mechanical ventilation [hours: 41.00 (7.50, 82.50) vs. 67.00 (4.75, 127.75)], length of ICU stay (days: 5.48±4.08 vs. 6.68±4.87) and 28-day mortality (10.34% vs. 17.86%) between D3 treatment group and placebo group (allP > 0.05). It was shown by Kaplan-Meier survival curve analysis that there was no significance in 28-day accumulated survived rate between the two groups [log-rank test: χ2 = 0.222,P = 0.638]. It was shown by multivariate Cox regression analysis that APACHE Ⅱ score [relative risk (RR) = 8.487, 95% confidence interval (95%CI) = 1.506-47.835, P = 0.015] and 25(OH)D3 < 20μg/L (RR = 0.088, 95%CI = 0.013-0.592,P = 0.012) were the risk factors of prognosis in patients with sepsis.Conclusions The serum 25(OH)D3 level in ICU patients with sepsis was lower than that in healthy people, but there was no significant difference between patients with sepsis and SIRS. The serum 25(OH)D3 level in sepsis patients was related with gender, and the level of the female was lower than that of the male, but was not related with age. Exogenous vitamin D3 supplementation cannot improve the prognosis of ICU patients with sepsis. APACHE Ⅱ score and 25(OH)D3 < 20μg/L were risk factors for the prognosis in ICU patients with sepsis.
2.Analysis of occurrence and risk factors of chronic kidney disease in the ICU patients
Yuhong ZHAO ; Kaiqiang JI ; Bin ZANG ; Detian LI
Chinese Journal of Nephrology 2013;29(9):660-664
Objective To analyze the occurrence and clinical features of chronic kidney disease (CKD) in the ICU patients and identify the possible risk factors.Methods A retrospective study was performed in 2281 ICU patients enrolled from Shengjing hospital between January 2007 and December 2010,in which 1860 cases had complete data and were followed-up,the other 421 cases were excluded for the reasons of dying,suffering from CKD originally,lacking complete data and missing.The cases were divided into CKD and non-CKD groups according to SCODRED and CKD diagnosis standards.Assessment was performed to screen risk factors of CKD.Results There were obvious differences between CKD and non-CKD groups at age,pregnancy,AKI and liver function (P <0.05).The CKD's annual morbidity rate of ICU patients was 20%-30%,and the incidence showed an increasing trend with time.Age,pregnancy,AKI,APACHE-Ⅱ score,invasive diagnosis and treatment,mechanical ventilation,organ failure and kidney-hurt drugs were risk factors for CKD in the ICU patients.Conclusions The morbidity rate of CKD in the ICU patients is high,and the number of CKD patients show an increasing trend with time.Age,APACHE-Ⅱ score > 15,the number of failed organs ≥2,the variety of kidney-hurt drug≥2,pregnancy,AKI,the number of invasive diagnosis and treatment≥3,mechanical ventilation are independent risk factors of CKD in the ICU patients.
3.The effects of preconditioning and postconditioning with isoflurane on focal cerebral ischemi/reperfusion injury in rats
Guofu LI ; Jia JIA ; Jiahong FU ; Haiyuan WANG ; Kaiqiang JI ; Bin ZANG
Chinese Critical Care Medicine 2014;26(6):431-435
Objective To investigate the effects of preconditioning and postconditioning with isoflurane on pro-inflammatory cytokines and lipid peroxidation in focal cerebral ischemic/reperfusion (I/R) injury in rats.Methods Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups:control group,model group,isoflurane preconditioning group and isoflurane postconditioning group,with 8 rats in each group.Rats in control group did not receive any challenge.In rats of model group right middle cerebral artery occlusion (MCAO) was conducted for 90 minutes.Rats in isoflurane preconditioning group received 2% isoflurane exposure for 30 minutes 24 hours before MCAO for 90 minutes.Rats in isoflurane postconditioning group were given 60-minute 2% isoflurane exposure after reperfusion of right MCAO.Twenty-four hours after the procedure,all rats were anesthetized with isoflurane,and blood sample taken from the heart was centrifuged,and the pro-inflammatory cytokines,including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α),and lipid peroxidation products such as malonaldehyde (MDA) and superoxide dismutase (SOD) were determined.The mRNA and protein expression levels of matrix metalloproteinase (MMP-2,MMP-9),tight junction protein Calaudin-5 and Occludin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.Results Compared with control group,serum levels of IL-1 β (ng/L),TNF-α (ng/L) and MDA (μmol/L) were elevated and activity of SOD (U/L) decreased in rats of model group (IL-1β:76.81 ± 11.14 vs.52.43 ± 8.86,TNF-α:64.93 ± 10.81 vs.33.64 ± 7.94,MDA:8.63 ± 1.42 vs.4.14 ± 0.98,SOD:0.95 ± 0.21 vs.2.36 ± 0.80,all P<0.05).After isoflurane preconditioning and postconditioning,compared with model group,the levels of IL-1 β,TNF-α and MDA were lowered,while activity of SOD was increased (IL-1 β:54.37 ± 9.06,56.82 ± 8.67 vs.76.81 ± 1 1.14,TNF-α:43.72 ± 6.16,39.49 ± 9.34 vs.64.93 ± 10.81,MDA:5.65 ± 0.83,5.82 ± 0.78 vs.8.63 ± 1.42,SOD:1.64 ± 0.47,1.71 ± 0.52 vs.0.95 ± 0.21,all P<0.05).Focal cerebral I/R injury could lead to an increased expression of MMP accompanied with a decreased expression of tight junction protein.Compared with model group,after isoflurane preconditioning and postconditioning,it was found that there were decreased mRNA and protein expression of MMP-2 and MMP-9 (MMP-2 mRNA:1.25 ± 0.08,1.32 ± 0.12 vs.2.48 ± 0.26,MMP-2 protein:1.56 ± 0.09,1.50 ± 0.08 vs.2.12 ± 0.11 ; MMP-9 mRNA:1.26 ± 0.13,1.20 ± 0.12 vs.2.74 ± 0.28,MMP-9 protein:1.53 ± 0.04,1.51 ± 0.05 vs.2.23 ± 0.09,all P<0.05) and increased levels of Calaudin-5 and Occludin (Claudin-5 mRNA:0.40 ± 0.08,0.38 ± 0.06 vs.0.28 ± 0.03,Claudin-5 protein:0.80 ± 0.06,0.81 ± 0.07 vs.0.39 ± 0.02; Occludin mRNA:0.54 ± 0.07,0.50 ± 0.08 vs.0.26 ± 0.06,Occludin protein:0.64 ± 0.06,0.69 ± 0.05 vs.0.49 ± 0.02,all P<0.05).Conclusion Preconditioning and postconditioning with isoflurane can lower the levels of pro-inflammatory cytokines and the degree of lipid peroxidation,and lower the hydrolytic activity of MMP to the tight junction protein in cerebral tissue,thereby decrease the loss of tight junction protein and alleviate I/R injury.