Research progress of metabolomics in acute kidney injury / 中华危重病急救医学

Acute kidney injury (AKI) is caused by a variety of diseases, which leads to acute renal function decline, azotemia, water and electrolyte disorders and acid-base balance disorders. Metabolomics is a research method that can quantitatively analyze all metabolites in an organism and find the relative relationship between metabolites and physiological and pathological changes. In recent years, several metabolites screened based on metabolomics have been proposed as potential biomarkers to assess the early development and prognosis of AKI and for the discovery of unknown potential therapeutic targets. Based on metabolomics, this paper reviews the risk prediction, early diagnosis, disease monitoring, prognosis assessment and the application of corresponding drugs for AKI, so as to provide reference for precision medicine.

Systematic review of ultrasound-guided fluid resuscitation vs. early goal-directed therapy in patients with septic shock / 中华危重病急救医学

Objective:To systematically review the efficacy of ultrasound-guided fluid resuscitation and early goal-directed therapy (EGDT) in patients with septic shock.Methods:Multiple databases including Wanfang, CNKI, SinoMed, VIP, PubMed, Embase, Cochrane Library and Web of Science were searched from initial to August 2019 for randomized controlled trial (RCT) studies about the comparison of ultrasound-guided fluid resuscitation and EGDT on resuscitation effect in patients with septic shock. Language, country and region were unlimited. Data extraction and quality evaluation were carried out by means of independent review and cross check results by two researchers.Results:Finally, only two English RCT studies were enrolled. In the two RCT studies, the ultrasound groups used inferior vena cava collapse index (VCCI) and ultrasound score to guide fluid resuscitation, which resulted in clinical heterogeneity. Because the results could not be pooled, only systematic review, not meta-analysis, could be done. There were measurement bias and selection bias in the two RCT studies, and the literature quality level was B and C respectively. System review results showed that using ultrasound would reduce 7-day mortality (15.0% vs. 35.0%, P = 0.039) and prescribe less of 24-hour intravenous fluids (mL: 900 vs. 1 850, P < 0.01) for patients with septic shock as compared with EGDT. Ultrasound was easy to assess the reactive capacity and cardiac function of patients with septic shock, so as to decrease the incidence of pulmonary edema, which was significantly lower than EGDT (15.0% vs. 37.5%, P = 0.022). However, there was no statistically significant difference in 28-day mortality, duration of mechanical ventilation or length of intensive care unit (ICU) stay between the two groups. Conclusion:The ultrasound-guided fluid resuscitation may be useful and practical for septic shock patients within 7 days after admission as compared with EGDT, but it cannot reduce the 28-day mortality, duration of mechanical ventilation or length of ICU stay.

Clinical value of non-coding RNA molecular markers for sepsis / 中华危重病急救医学

Sepsis and septic shock are important clinical problems in critically ill patients, accounting for the first cause of death in intensive care unit (ICU). Therefore, early diagnosis and treatment are particularly important. Recently, genome-wide expression analysis of non-coding RNA in septic patients showed that more than 80% were differentially expressed compared with healthy individuals. These molecules play important roles in biological processes, including innate immunity, mitochondrial function and apoptosis. Therefore, a class of non-coding RNAs such as microRNA (miRNA), long-chain non-coding RNA (lncRNA) and circular non-coding RNA (circRNA) are increasingly recognized as a regulator of various signaling pathways. The potential of regulatory non-coding RNA target to treat sepsis was discussed by studying non-coding RNAs that might serve as molecular markers of sepsis, and its clinical value was evaluated.

Effectiveness of Xuebijing in treatment of multiple organ dysfunction syndrome: a Meta analysis / 中华危重病急救医学

Objective To systematical evaluate the effect of Xuebijing injection in the treatment of multiple organ dysfunction syndrome (MODS).Methods With the keywords including Xuebijing, multiple organ dysfunction syndrome, multiple organ dysfunction and multiple organ failure, PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP and Wanfang Data from the database start until March 4th, 2018 were searched for relevant randomized controlled trials (RCTs) related to Xuebijing injection combined conventional treatment versus conventional treatment alone for MODS. The control group received conventional western medicine treatment, including etiological treatment, antibiotics, mechanical ventilation, nutritional support, and comprehensive treatment to maintain fluid, electrolyte, acid and alkali balance. The experimental group was given traditional western medicine combined with Xuebijing injection. The observation parameters included 7-day and 28-day mortality, acute physiology and chronic health evaluationⅡ (APACHEⅡ) and Marshall score, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), the number of platelets, activated partial thromboplastin time (APTT) and prothrombin time (PT). According to the inclusion and exclusion criteria, two evaluators independently screened the literature, extracted data and evaluated the methodological quality of the included studies. RevMan 5.3 software was used for Meta analysis. Funnel plot was used to analyze publication bias.Results A total of 35 RCTs and 2131 patients were enrolled, including 1076 in the experimental group and 1055 in the control group. The results of Meta analysis showed that compared with control group, Xuebijing combined conventional treatment was in favor to decrease the mortality of patients with MODS [7-day mortality: odds ratio (OR) = 0.42, 99％ confidence interval (99％CI) = 0.26-0.69,P < 0.00001; 28-day mortality:OR= 0.31, 99％CI= 0.21-0.45,P < 0.00001], also could obviously reduce critical condition degree of APACHE Ⅱ score and the organ function of Marshall score [APACHEⅡ: mean difference (MD) =3.24, 99％CI = 2.00-4.49,P < 0.00001; Marshall score:MD = 1.95, 99％CI = 0.50-3.40,P = 0.0005]. Meanwhile, the results of conventional western medicine combined with Xuebijing in the removal of IL-6 and TNF-α, platelets increase and improvement of PT were better than those of conventional western medicine (IL-6:MD = 5.56, 99％CI = 1.44-9.68, P = 0.0005; TNF-α:MD = 4.97, 99％CI = 3.44-6.50,P < 0.00001; platelets:MD = -50.79, 99％CI = -74.84 to -26.74, P < 0.0001; PT:MD = 4.55, 99％CI = 3.96-5.14,P < 0.00001), however, there was no obvious advantage in improving APTT (MD = 0.96, 99％CI = -5.08-7.00,P = 0.68). The analysis of funnel map showed that the effect points of various studies were mainly centered on the amount of combined effect, and the "inverted funnel" type was generally symmetrical distribution. However, because the number of the included studies was less, the literature bias could not be completely eliminated.Conclusion Xuebijing injection may through its strong cytokines clearance, platelet increase and blood coagulation improvement to protect the organ function in patients with MODS, so as to reduce the mortality and improve the prognosis.

Study of prevention and control of delirium in ventilated patients by simulating blockage of circadian rhythm with sedative in intensive care unit / 中华危重病急救医学

Objective To explore the effect of giving sedatives according to the circadian rhythm in prevention of occurrence of delirium and the prognosis of patients undergoing mechanical ventilation in intensive care unit (ICU). Methods A prospective double-blinded randomized controlled trial (RCT) was conducted. The patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University from July 2014 to February 2015, undergoing invasive mechanical ventilation over 12 hours were enrolled. All the patients were given fentanyl for analgesia, and they were randomly divided into simulated circadian clock group (study group, n = 35) and non-simulated circadian clock group (control group, n = 35). The patients in each group were subdivided into three subgroups according to the kinds of sedative drugs, namely dexmedetomidine group (n = 8), propofol group (n = 14), and dexmedetomidine combined with propofol group (combination group, n = 13). Visual analogue scale (VAS) standard and Richmond agitation-sedation scale (RASS) were used to control the analgesic and to quantify the depth of sedation by titrating the dose of sedative drugs, the simulated circadian clock was set to control the RASS score at 0-1 during the day, and -1 to -2 at night in study group. The RASS score in the control group was set at -1 to -2 day and night. The urine 6-hydroxy acid melatonin (aMT6s) levels at different time points in the first diurnal rhythm (06:00, 12:00, 18:00, 24:00) were determined by enzyme linked immunosorbent assay (ELISA). The incidence of delirium, severe hypotension, severe bradycardia and other adverse reactions, duration of mechanical ventilation and the time of extubation, length of ICU stay, amount of sedative and analgesic drugs used were recorded. The correlation between delirium and other indexes was analyzed by using Spearman correlation analysis. Results ① There were no significant differences in gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score among groups. ② Urine aMT6s levels did not show circadian rhythm in both groups, aMT6s level at 06:00 in study group showed an increasing tendency as compared with the control group, but the difference was not statistically significant. ③ Compared with the control group, the incidence of delirium was significantly lowered in the study group (14.3% vs. 37.1%, P = 0.029), but no significant differences were found in the incidence of severe hypotension or severe bradycardia (20.0% vs. 25.7%, 11.4% vs. 20.0%, both P > 0.05). In simulated circadian clock group, the incidence of delirium in dexmedetomidine group was significantly lower than that of the propofol group (6.3% vs. 32.1%, P 0.05). Conclusions Administration of sedatives according to simulating circadian time could decrease the duration of mechanical ventilation, extubation time, and the length of ICU stay, decrease the dosage of sedative drugs, and reduce the incidence of delirium. Dexmedetomidine could reduce the incidence of delirium, and improve the prognosis of patients. Trial registration Registration of clinical trials in China, ChiCTR-IPR-15006644.

A study of using dexmedetomidine in ventilator bundle treatment in an ICU / 中华危重病急救医学

ObjectiveTo compare the sedative effect and safety of dexmedetomidine and midazolam in the intensive care unit (ICU) patients undergoing ventilator bundle treatment.MethodsA prospective single-blind randomized controlled trial (RCT) was conducted. Ninety patients receiving ICU ventilator-assisted therapy and ventilator bundle treatments for more than 3 days in the First Department of Critical Care Medicine of the Second Hospital of Lanzhou University from January 2013 to December 2014 were enrolled. The patients were randomly divided into two groups for sedative treatment. The patients in dexmedetomidine group (n = 42) were given dexmedetomidine 0.2-0.7μg·kg-1·h-1 to achieve a goal of satisfactory sedation [Richmond agitation-sedation scale (RASS) score 0 to - 2 during the day, and -1 to -3 at night). The patients in midazolam group (n = 48) were given midazolam 2-3 mg intravenously first, and then 0.05 mg·kg-1·h-1 for maintenance. The drug dose was adjusted according to RASS every 4 hours to maintain the appropriate sedation depth. The patients in both groups received continuous intravenous infusion of fentanyl for analgesia. Ventilator bundle treatments included the head of a bed up 30°to 45°, awaken and extubation appraisal, daily use of proton pump inhibitors for peptic ulcer prevention, prevention of deep vein thrombosis (DVT), chlorhexidine mouth nursing, and removal of sputum by suction from subglottic area. When the patients in both groups obtained satisfactory target sedation, daily awakening was conducted, and spontaneous breathing test (SBT) was carried out to determine optional weaning time. When the condition was optimal, weaning was conducted, otherwise ventilator bundle treatments were continued. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), respiratory frequency (RR) were monitored before and 15, 30, 60, 120, 180 minutes after the treatment, and at the moment of extubation and 30 minutes after extubation. The duration of mechanical ventilation, extubation time, length of ICU stay, and the incidence of adverse events were also recorded. Results Both dexmedetomidine and midazolam could give rise to sedation with same score of analgesia in patients in both groups, and similar effect of sedation and analgesia could be achieved. Compared with midazolam, dexmedetomidine could significantly reduce the duration of mechanical ventilation (hours: 108.33±21.96 vs. 119.85±20.29,t = -2.586, P = 0.011), earlier extubation time (hours: 112.95±22.20 vs. 128.58±26.18,t = -3.031,P = 0.003), length of ICU stay (hours: 149.21±20.47 vs. 163.88±33.59,t = -2.457,P = 0.016), the incidence of delirium [9.5% (4/42) vs. 31.2% (15/48),χ2 = 6.349,P = 0.012], but it would elevate the incidence of severe hypotension [28.6% (12/42) vs. 8.3% (4/48),χ2 = 6.277,P = 0.012] and severe bradycardia [19.0% (8/42) vs. 8.3% (4/48),χ2 = 2.225,P = 0.136]. Both drugs could lower SBP, DBP, MAP, and HR, and the effect in dexmedetomidine group was more significant from 60 minutes after treatment [SBP (mmHg, 1 mmHg = 0.133 kPa): 113.12±14.42 vs. 124.40±15.79, DBP (mmHg): 69.02±9.62 vs. 76.94±10.41, MAP (mmHg): 83.76±10.50 vs. 92.77±11.87, HR (bpm): 79.19±12.28 vs. 87.42±17.77,P< 0.05 orP< 0.01]. Both sedatives could significantly lower the rate of spontaneous breathing, and the effect of midazolam group was more significant from 60 minutes after treatment compared with dexmedetomidine group (times/min: 18.27±4.29 vs. 20.07±4.11,P< 0.05).Conclusions The sedative effects of dexmedetomidine in the ICU patients treated with ventilator bundle treatment are satisfactory, and it can shorten the duration of mechanical ventilation, extubation time and length of ICU stay, reduce the incidence of delirium. However, monitoring should be strengthened in order to prevent and control the adverse effects such as severe hypotension and severe bradycardia.

A systematic review of clinical application of Percu Twist tracheostomy in intensive care unit / 中华危重病急救医学

Objective To evaluate the effectiveness of Percu Twist (PT) tracheostomy comparing with that of operative tracheostomy(OT)in intensive care unit(ICU). Methods Related data were retrieved from CBM,CNKI,Wanfang Data,VIP,PubMed,EMBASE,CENTRAL,and Web of Science from the time of their establishment to May 15th 2014,and the data of randomized controlled trials(RCTs)concerning PT and OT were selected. The risk of bias assessment and data extraction were performed by two independent reviewers. Meta analysis was conducted using RevMan 5.2 software. Results A total of 12 RCTs were identified,and 893 patients in ICU were involved. The results of Meta-analysis showed that PT could significantly shorten the operation time〔mean difference (MD)=-15.11,95% confidence interval(95%CI)=-17.14 to -13.07,P<0.000 01〕,reduce the volume of blood loss(MD=-17.59,95%CI=-21.90 to-13.28,P<0.000 01),reduce the size of incision(MD=-2.20, 95%CI=-2.57 to -1.82,P<0.000 01),shor ten the time of healing(MD=-3.60,95%CI=-4.15 to -3.05, P<0.000 01),and reduce complications such as infection of the wound〔odds ratio(OR)=0.20,95%CI=0.10-0.44,P<0.000 1〕and cutaneous emphysema/mediastinal emphysema(OR=0.22,95%CI=0.10-0.47,P<0.000 1)compared with OT group. The funnel plot suggested that publication bias might be found among 12 researches. Conclusions PT was shown to be more effective than OT in ICU with lower incidence of complications. As number of RCT cases is still small with unsatis factory quality,further clinical use is warranted for a better assessment.