Meta-analysis of efficacy and safety of sedative therapy with midazolam and dexmedetomidine/propofol in critically ill patients undergoing mechanical ventilation / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of midazolam and dexmedetomidine/propofol for the sedation of critically ill patients undergoing mechanical ventilation， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， Embase， Web of Science， Cochrane Library， Clinical trials. gov， China Journal Full Text Database， Chinese Science and Technology Journal Database， Wanfang database and China Biomedical Literature Database， the data on the efficacy and safety of midazolam and dexmetomidine/propofol for the sedation of critically ill patients undergoing mechanical ventilation were collected from the establishment of the database to March 31， 2023. After extracting data from clinical studies that met the inclusion criteria， the meta-analysis was conducted by using the RevMan 5.3 statistical software. RESULTS A total of 31 literature were included， with a total of 2 765 patients. Results of meta-analysis showed that the mechanical ventilation time [MD＝14.13， 95%CI （13.75， 14.52）， P＜0.000 01] and the length of hospitalization in the intensive care unit [MD＝0.92， 95%CI （0.54， 1.30）， P＜0.000 01] of patients in the midazolam group was longer than dexmedetomidine/ propofol group. The incidence of bradycardia in midazolam group was lower dexmedetomidine/propofol group [OR＝0.60， 95%CI （0.41， 0.90）， P＝0.01]， but there was no statistically significant difference in the incidence of hypotension between the two groups [OR＝0.69， 95%CI （0.47， 1.01）， P＝0.06]. The incidence of delirium [OR＝3.88， 95%CI （2.74， 5.49）， P＜0.000 01]， ventilator- associated pneumonia [OR＝2.32， 95%CI （1.19， 4.51）， P＝0.01]， and respiratory depression [OR＝5.70， 95%CI （3.09， 10.52）， P＜0.000 01] in midazolam group were higher than dexmedetomidine/propofol group. CONCLUSIONS Compared with dexmedetomidine/propofol， midazolam increases patients’ mechanical ventilation time and the length of hospitalization in the intensive care unit in terms of efficacy， and increases the risk of delirium and pulmonary complications in terms of safety， but has a smaller cardiovascular impact.

Enzyme production mechanism of anaerobic fungus Orpinomyces sp. YF3 in yak rumen induced by different carbon source / 生物工程学报

In order to investigate the enzyme production mechanism of yak rumen-derived anaerobic fungus Orpinomyces sp. YF3 under the induction of different carbon sources, anaerobic culture tubes were used for in vitro fermentation. 8 g/L of glucose (Glu), filter paper (Flp) and avicel (Avi) were respectively added to 10 mL of basic culture medium as the sole carbon source. The activity of fiber-degrading enzyme and the concentration of volatile fatty acid in the fermentation liquid were detected, and the enzyme producing mechanism of Orpinomyces sp. YF3 was explored by transcriptomics. It was found that, in glucose-induced fermentation solution, the activities of carboxymethyl cellulase, microcrystalline cellulase, filter paper enzyme, xylanase and the proportion of acetate were significantly increased (P < 0.05), the proportion of propionate, butyrate, isobutyrate were significantly decreased (P < 0.05). The results of transcriptome analysis showed that there were 5 949 differentially expressed genes (DEGs) between the Glu group and the Flp group, 10 970 DEGs between the Glu group and the Avi group, and 6 057 DEGs between the Flp group and the Avi group. It was found that the DEGs associated with fiber degrading enzymes were significantly up-regulated in the Glu group. Gene ontology (GO) function enrichment analysis identified that DEGs were mainly associated with the xylan catabolic process, hemicellulose metabolic process, β-glucan metabolic process, cellulase activity, endo-1,4-β-xylanase activity, cell wall polysaccharide metabolic process, carbohydrate catabolic process, glucan catabolic process and carbohydrate metabolic process. Moreover, the differentially expressed pathways associated with fiber degrading enzymes enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were mainly starch and sucrose metabolic pathways and other glycan degradation pathways. In conclusion, Orpinomyces sp. YF3 with glucose as carbon source substrate significantly increased the activity of cellulose degrading enzyme and the proportion of acetate, decreased the proportion of propionate, butyrate and isobutyrate. Furthermore, the degradation ability and energy utilization efficiency of fungus in the presence of glucose were improved by means of regulating the expression of cellulose degrading enzyme gene and participating in starch and sucrose metabolism pathway, and other glycan degradation pathways, which provides a theoretical basis for the application of Orpinomyces sp. YF3 in practical production and facilitates the application of Orpinomyces sp. YF3 in the future.

Clinical analysis of 56 cases of neonatal osteomyelitis / 中国新生儿科杂志

Objective:To study the clinical characteristics, pathogens, treatments and prognosis of neonatal osteomyelitis.Methods:From May 2015 to October 2019, infants admitted to our hospital and diagnosed with neonatal osteomyelitis were retrospectively studied. Clinical characteristics, laboratory examinations, treatments and prognosis were analyzed.Results:A total of 56 cases with neonatal osteomyelitis were included, including 39 males and 17 females. The time of onset was 1~28 d after birth, with 66.1% during 14~28 d. 62.5% (35/56) patients were hospitalized because of limited limb movement and crying during passive motion. Femur was involved in 57.1% (32/56) patients and 76.8% (43/56) had two or more bones involvement. All patients had local symptoms, including local swelling (94.6%), local tenderness (94.6%) and increased skin temperature (83.9%). 40 patients (71.4%) had increased white blood cell count (WBC) and 28 (50.0%) showed increased C-reactive protein (CRP). Staphylococcus aureus was the most common pathogen in blood cultures (25.0%) and in local pus cultures (40.9%). Klebsiella pneumoniae was the most common pathogen in bone marrow cultures (33.3%).11 patients (19.6%) were treated conservatively using antibiotics and 45 patients (80.4%) required surgical treatments. 48 patients were followed up. 45 had good prognosis, 1 patient had malposition, 1 patient had disparity of the legs(the affected side was longer) and 1 patient had genu valgum.Conclusions:The early manifestations of neonatal osteomyelitis are nonspecific. For neonates with suspected osteomyelitis, early laboratory and imaging examinations are recommended. Early diagnosis and timely treatment may help reduce sequelae.

Advance of early supplementation of vitamin AD improve the prognosis of preterm infants / 国际儿科学杂志

Vitamin AD is an essential nutrient in human, which can maintain the normal function of vision, immune system, respiratory tract, gastrointestinal epithelium and nervous system.Preterm infants are prone to vitamin AD deficiency due to low prenatal storage, low food intake, high energy metabolism, et al.Studies have shown that early supplementation of vitamin AD can promote the growth and development of preterm infants.This paper summarizes recent advances of vitamin AD supplementation in the improvement of retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, brain injury and metabolic bone diseases of prematurity.The result has showed that vitamin AD supplementation within 1 week after birth could improve the occurrence of complications in preterm infants, which could provide new ideas and methods for reducing the major complications of preterm infants.

Accuracy of color Doppler in predicting acute kidney injury / 中华麻醉学杂志

Objective To evaluate the accuracy of color Doppler in predicting acute kidney injury ( AKI) . Methods Patients of both sexes with AKI risk factors not diagnosed with AKI, aged ≥18 yr, were enrolled in this study. Within 1 h after inclusion, the renal blood flow ( RBF) grade was monitored u-sing color Doppler, and renal resistive index ( RRI) value of renal interlobar artery was monitored at the level of renal interlobar or arcuate arteries, and corrected RRI value was calculated. The development of AKI was recorded within 24 h through measuring serum creatinine and urine volume, and the receiver oper-ating characteristic curve was plotted. Results Thirty-eight patients were included in non-AKI group and 40 ones in AKI group. Compared with non-AKI group, RBF grade was significantly decreased, RRI value was increased ( P<0. 05) , and no significant change was found in the corrected RRI value in AKI group ( P>0. 05) . The area under the curve of RBF grade and RRI value in predicting AKI occurred within 24 h and 95％ confidence interval were 0. 659 ( 0. 561-0. 747) and 0. 669 ( 0. 572-0. 756) , respectively. Con-clusion Color Doppler has a certain value in predicting AKI within 24 h.

Effect of continuous renal replacement therapy on the plasma concentration of imipenem in severe infection patients with acute renal injury / 中华危重病急救医学

ObjectiveTo investigate the extracorporeal clearance rate of imipenem in severe infection patients in the mode of continuous vena-venous hemofiltration (CVVH) during continuous renal replacement therapy (CRRT), in order to approach if the concentration of imipenem in plasma could achieve effective levels of anti-infection, and to explore the effect of time and anticoagulation measure on imipenem clearance during CRRT treatment.Methods A prospective observational study was conducted. All adult severe infection patients complicating acute kidney injury (AKI) in the Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University from March 2013 to September 2014, who were prescribed imipenem as part of their required medical care, and CRRT for treatment of AKI were enrolled. 0.5 g doses of imipenem was administered intravenously every 6 hours or 8 hours according to random number table, and infused over 0.5 hour. The unfractionated heparin was used for anticoagulation in the patients without contraindications, and no anticoagulation strategy was used in the patients with high risk of bleeding. At 24 hours after first time of administration, postfilter venous blood and ultrafiltrate samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 5, 6, and 8 hours after imipenem administration. The concentration of imipenem in above samples was determined with liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS).Results A total of 25 patients were enrolled. Thirteen patients received imipenem intravenously every 6 hours, and 12 patients, every 8 hours. The anticoagulation was conducted with heparin in 13 cases, and 12 cases without anticoagulation. The intra-day precision, inter-day precision, matrix effect, and recovery rate in low, medium, and high concentration of plasma and ultrafiltrate, and the stability of samples under different conditions showed a good result, the error of accuracy was controlled in the range of±15%. With the application of Prismaflex blood filtration system and AN69-M100 filter, under the mode with CVVH, the total clearance rate of imipenem was (8.874±2.828) L/h when the actual dose of replacement fluid was (31.63±1.48) mL·kg-1·h-1, the total CRRT clearance rate of imipenem in vitro was (2.211±0.539) L/h, which accounting for (30.1±15.7)% of the total drug clearance. In 6 hours interval dosage regimen, the percentages of the time> 4×minimum inhibitory concentration (MIC) at specific 4×MIC of 2, 4, 6, and 8μg/mL of imipenem were more than 40% of the dosing interval. But in the 8 hours interval dosage regimen, when the level was above the 4×MIC of 4μg/mL, maintaining time would drop below 40% of the dosing interval, with significant differences compared with that in 6 hours interval dosage regimen [4×MIC = 2μg/mL: (60.84±20.25)%vs. (94.01±12.46)%,t = 4.977,P = 0.001; 4×MIC = 4μg/mL: (39.85±15.88)% vs. (68.74±9.57)%,t = 5.562, P = 0.000; 4×MIC = 6μg/mL: (27.58±13.70)% vs. (53.97±8.36)%,t = 5.867,P = 0.000; 4×MIC = 8μg/mL:(18.87±12.43)% vs. (43.48±7.83)%,t = 5.976,P = 0.000]. No significant change in sieving coefficient of imipenem was found within a short time (6 hours), which indicated that there was no effect of anticoagulation on clearance of imipenem by AN69-M100 filter, and no statistical significance was found with repeated measure analysis (F = 0.186, P> 0.05).ConclusionsThe clearance rate of imipenem is increased significantly in vitro under the mode of CVVH with the actual dose of replacement fluid was (31.63±1.48) mL·kg-1·h-1 in severe infective patients with severe sepsis complicating AKI, affecting the level of plasma drug concentration, need to adjust the dosage regimen. When the time of the dosing interval was shortened, the concentration of imipenem in patients' plasma could be increased significantly. In a short period of time, the sieving coefficient of imipenem through AN69 filter is not affected by anticoagulation measures and time cleaning efficiency will not decline.

The effect of AN69 ST membrane on filter lifetime in continuous renal replacement therapy without anticoagulation in patients with high risk of bleeding / 中华危重病急救医学

ObjectiveTo evaluate whether AN69 ST membrane would prolong filter lifetime in continuous renal replacement therapy (CRRT) without anticoagulation in patients with high risk of bleeding.Methods A single-center, prospective, randomized, double-blind control trial with crossover design was conducted. From March 1st to December 31st in 2013, patients who were admitted to Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University meeting CRRT treatment indications, but could not receive systemic anticoagulation because of high risk of bleeding were studied. The selected patients were randomly divided into two groups according to a random number table, and four filters consisting of two AN69 ST100 membrane filters (A) and two traditional AN69 M100 membrane filters (B) were used for them. GroupⅠ with the filter order of A-B-A-B, and groupⅡ with the order of B-A-B-A. The clinical data of patients was recorded in detail, and conventional AN69 ST and AN69 membrane filter lifetime, their influence on coagulability, and the incidence of bleeding complications were compared.Results Seventeen patients were enrolled, with 10 in groupⅠ, and 7 in groupⅡ. The basic medical characteristics including gender, age, acute physiology and chronic health evaluationⅡ (APAECHⅡ) score, sequential organ failure score (SOFA), Acute Renal Injury Network (AKIN) stage, activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), platelet count (PLT), and use of mechanical ventilation were not significantly different between two groups. But the use of vasoactive drug was more frequent in groupⅡcompared with that of groupⅠ[100.0% (7/7) vs. 30.0% (3/10),χ2 = 8.330,P = 0.010]. AN69 ST filter lifetime (n =34) was (15.92±2.10) hours, there was no statistically significant difference compared with that of AN69 membrane (t = 0.088,P = 0.942), filter lifetime of which (n = 34) was (16.12±1.38) hours. It was also found by Kaplan-Meier survival analysis that there was no significant difference between the two membrane filter lifetime (χ2=1.589,P =0.208). Logistic regression analysis showed that the life of the first filter was not correlated with coagulation indicators, including APTT, PT, INR, and PLT [APTT: odds ratio (OR) = 0.977, 95% confidence interval (95%CI) = 0.892-1.071, P = 0.623; PT:OR = 1.001, 95%CI = 0.901-1.109,P = 0.988; INR:OR = 1.078, 95%CI = 0.348-3.340,P = 0.896;PLT:OR = 0.996, 95%CI = 0.974-1.019,P = 0.735]. The application rate of vasoactive drugs, which was different between two groups for basic medical indications showed no effect on filter life time (OR = 2.541, 95%CI = 0.239-26.955,P = 0.439). Reasons of clotting in filters were also analyzed, and it was found that blood coagulation in the filter ranked the top (88.2%), and the other reasons were catheter-related problems, death, and unscheduled transport. No difference in blood coagulation function was found in both groups after treatment for 12 hours, and there was no bleeding complication.ConclusionDuring the CRRT without systemic anticoagulant, both surface-treatment with polyethyleneimine AN69 and AN69 ST membrane cannot prolong filter lifetime.