Identification of risk factors for iatrogenic hypophosphatemia: A retrospective case-control study.

BACKGROUND AND OBJECTIVES: To investigate the iatrogenic risk factors for hypophosphatemia in intensive care unit (ICU) patients. METHODS AND STUDY DESIGN: A total of 120 patients were enrolled and further divided into 4 groups, namely normal, mild, moderate or severe, according to the degree of hypophosphatemia. A number of related factors were analyzed and compared among the 4 groups, including the treatment method and outcomes. Univariate and multivariate regression analyses were employed to identify and confirm the risk factors associated with the occurrence of hypophosphatemia. RESULTS: The results revealed that the acute physiology and chronic health evaluation II (APACHEII), Sequential Organ Failure Assessment (SOFA), modified NUTrition Risk in Critically ill (NUTRIC) scores as well as the length of patient stays in ICUs exhibited a gradually increasing trend of aggravation of hypophosphatemia. Univariate regression analysis identified the use of dehydrating drugs to be closely associated with the occurrence of hypophosphatemia, which was further confirmed by a multivariate regression analysis. CONCLUSIONS: The use of dehydrating drugs led to hypophosphatemia; therefore blood phosphorus concentrations should be closely monitored during treatment of ICU patients.

Risk factors and predictors of QTc prolongation in critically ill Chinese patients.

BACKGROUND: To recognize and validate the predictor of risk factors for ICU patients with QTc intervals ≥500 ms. METHODS: We retrospectively reviewed 160 ICU patients with their medical electronic records including all demographic data, diagnosis measurements, ECGs and medication from March 1, 2018 to December 1, 2018. All information of patients' baseline, comorbidities, electrolytes and Long QT syndrome (LQTS)-inducing medications of patients with QT interval corrected (QTc) ≥ 500 ms (n = 80) and <500 ms (n = 80) were collected and analyzed using univariate and multivariate analyses to find predictors. RESULTS: Comparing to patients with QTc < 500 ms, patients with QTc ≥ 500 ms had increased SOFA (P = 0.010) and APACHE II scores (P = 0.002), longer lengths of ICU stays (P < 0.001), greater incidence of congestive heart failure (P = 0.005) and more preset risk factors (P < 0.001). The frequency of administration of mosapride (P = 0.015), amiodarone (P = 0.027) and number of combined LQTS-inducing medications (P = 0.012) were greater in patients with QTc ≥ 500 ms than in those with QTc < 500 ms. But after multivariate analysis, we found that risk factors related to a QTc ≥ 500 ms were only congestive heart failure (OR: 5.28), number of combined LQTS-inducing medications (OR: 1.60) and APACHE II score (OR: 1.08). CONCLUSIONS: For critically ill patients, congestive heart failure, number of combined LQTS-inducing medications and APACHE II score are proved as risk factors associated with QTc > 500 ms.

Effects of nurse-led sedation protocols on mechanically ventilated intensive care adults: A systematic review and meta-analysis.

OBJECTIVES: The objective of the study was to compare nurse-led sedation protocols with physician-led usual care in intensive care units (ICUs) in treating mechanically ventilated adult patients. REVIEW METHOD USED: This is a systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library, EMBASE, CINAHL, China National Knowledge Infrastructure, and China Wanfang databases were interrogated for articles published before May 2020. REVIEW METHOD: As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, eight randomised controlled trials (RCTs) and six preintervention and postintervention studies published in English and Chinese met the inclusion criteria for the meta-analysis. Two reviewers independently extracted data into a tabular format using predefined data fields. Disagreements were resolved by consensus. The quality of the included RCTs and preintervention and postintervention studies was assessed using the Cochrane Quality Assessment Tool and Risk Of Bias In Non-randomised Studies of Interventions assessment tool. RESULTS: Eight RCTs were of intermediate methodological quality, and six preintervention and postintervention studies exhibited a low to moderate risk of bias. Compared with usual care, nurse-led sedation protocols resulted in significantly decreased durations of mechanical ventilation (days) (standardised mean difference = -1.765; 95% confidence interval [CI] = -2.461, -1.068); P < 0.001; I2 = 97.7%); decreased length of ICU stay (days) (standardised mean difference = -1.463; 95% CI = -2.181, -0.745; P < 0.001; I2 = 97.3%); reduced ICU mortality (relative risk [RR] = 0.854; 95% CI = 0.747, 0.983; P = 0.027), I2 = 0%); and decreased incidence of ventilator-associated pneumonia (RR = 0.438; 95% CI = 0.292, 0.657; P < 0.001; I2 = 41.4%), delirium (RR = 0.522; 95% CI = 0.338, 0.807; P = 0.003; I2 = 26.6%), and extubation failure (RR = 0.498; 95% CI = 0.266, 0.932; P = 0.029; I2 = 45.1%). CONCLUSIONS: Although pre-post intervention study design cannot establish causality, the present findings raise the considerable possibility that a sedation protocol can be safely implemented by nurses to reduce mortality in ICUs and sedation-related adverse events in patients on mechanical ventilation compared with physician-led usual care.

Protective effect of nimesulide on acute lung injury in mice with severe acute pancreatitis.

The study was designed to investigate the effect of Nimesulide (NIM) on acute lung injury (ALI) in mice with severe acute pancreatitis (SAP). In our study, caerulein and LPS were employed to establish the ALI mice model induced by SAP. All animals were divided into four groups randomly: control, model (SAP), NIM low and high dosages groups. Following treatment with NIM, histopathology observation of pancreatic tissues and lung tissues were detected by hematoxylin and eosin (H&E) staining. The levels of serum amylase, lipase, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and IL-6 were measured by ELISA. The ratio of wet lung to dry lung (W/D) was calculated. In addition, the expression levels of TNF-α, IL-1ß and IL-6 were measured by Western blotting. Moreover, the expression of cyclooxygenase-2 (COX-2) was detected using Immunohistochemistry analysis. The results revealed that NIM markedly improved pancreatic histological injury and decreased the levels of serum amylase, lipase, TNF-α, IL-1ß and IL-6 in a dose-dependent after NIM treatment. For ALI induced by SAP, pulmonary edema were significantly alleviated compared with the mice in SAP group. In addition, the decreased ratio of W/D were observed after NIM intervene. The expression levels of TNF-α, IL-1ß and IL-6 proteins were downregulated following NIM treatment. More, NIM inhibited the expression of COX2 in lung tissues. Taken together, our study demonstrated that NIM was able to protect against ALI induced by SAP via inhibiting inflammation, which will be of novel therapeutic strategies for the clinical treatment of ALI.

A multi-center cross-sectional study on blood purification among adult patients in intensive care unit in China: a study protocol.

BACKGROUND: Blood purification (BP) is one of the most important rescue measures for patients with critical illness in the intensive care unit (ICU), especially for those with acute kidney injury. The purpose of this nationwide survey was to reveal the real world of current BP practice in different ICUs all over China. This study was designed to be a multi-center cross-sectional study. METHODS: All adult patients (over 18 years of age), who were admitted to ICU and required BP in 35 sub-centers across China were included during 30-day survey period in 2018. Demographic characteristics and clinical data were recorded including the timing of treatment initiation, indications, modality, relative contraindication, establishment of vascular access, selection of filter/membrane, settings, anti-coagulation, executive department, complication, intake, and output. DISCUSSION: This nationwide survey may contribute to reveal the real world of current BP practice in different ICUs all over China. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-EOC-17013119; http://www.chictr.org.cn/showproj.aspx?proj=22487.

Dexmedetomidine protects against lipopolysaccharide-induced sepsis-associated acute kidney injury via an α7 nAChR-dependent pathway.

Acute kidney injury (AKI) is a clinical syndrome that results in severe tubular damage with high morbidity and mortality. However, there is a lack of effective therapy strategies. Therefore, it is critical to develop effective drugs for AKI. Dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist, has neuroprotective, anti-inflammatory and sympatholytic properties. The present study aimed to investigate the effect DEX on attenuating the inflammatory reaction and apoptosis in the kidney tissues of septic mice and to explore its underlying mechanisms. Sepsis-induced AKI mice models were generated via intraperitoneal injection of lipopolysaccaride (LPS). DEX reduced LPS-induced local inflammation and tubular apoptosis, which was aggravated in the pathogenesis of renal dysfunction. Reverse transcription-quantitative polymerase chain reaction and western blot analysis results revealed that the expression of pro-apoptotic genes and inflammatory factors were markedly reduced by DEX pretreatment. Furthermore, the protective role of DEX was markedly inhibited by the α7 nicotinic acetylcholine receptor (nAChR) antagonist α-bungarotoxin. These findings provided novel evidence for the anti-apoptotic and anti-inflammatory effects of DEX in LPS-induced AKI mice through an α7 nAChR-dependent signaling pathway.

GTS-21 attenuates LPS-induced renal injury via the cholinergic anti-inflammatory pathway in mice.

This study aimed to investigate the role of GTS-21 in cholinergic anti-inflammatory pathway-mediated protection of LPS-induced septic renal injury in mice. C57BL/6 mice were used to construct septic injury models. The optimal duration of lipopolysaccharide (LPS) treatment was determined using HE staining and TUNEL assay. Mice injected with saline were used as blank control and with LPS (10 mg/kg) as model, which were further treated with α-bungarotoxin (BT-LPS), GTS-21 (GTS-21-LPS) and BT and GTS-21 (BT-GTS-21-LPS). The pathological examinations were performed on HE stained renal tissues, apoptosis was determined using TUNEL assay, mRNA expression of NF-kB p65, Caspase-3, Caspase-8, Bcl-2, Bax, p53 and a7nACh was quantified using qRT-PCR, protein levels of IL-6, IL-1ß, TNF-α and phosphorylated STAT3 (p-STAT3) were analyzed using Western blots. HE staining and TUNEL assays showed that the optimal LPS treatment time for renal injury induction was 16 h. Compared with the blank control, mice in LPS group had significantly higher levels of NF-Kb p65, Caspase-3, Caspase-8, Bax, p53, IL-6, IL-1ß, TNF-α and p-STAT3, while α7nAChR and Bcl-2 levels were decreased significantly (P < 0.01); GTS-21 and BT significantly increased the expression of NF-Kb p65, Caspase-3, Caspase-8, Bax, p53, IL-6, IL-1ß, TNF-α and p-STAT3, while α7nAChR and Bcl-2 levels were decreased significantly (P < 0.01). It is concluded that GTS-21 can effective alleviate the renal injury, while α7nAChR-specific blocker BT is antagonistic against the anti-inflammatory effect of GTS-21 on sepsis in mice.

Procalcitionin as a diagnostic marker to distinguish upper and lower gastrointestinal perforation.

AIM: To assess the accuracy of serum procalcitionin (PCT) as a diagnostic marker in verifying upper and lower gastrointestinal perforation (GIP). METHODS: This retrospective study included 46 patients from the surgical intensive care unit (ICU) of the Second Affiliated Hospital of Harbin Medical University who were confirmed to have GIP between June 2013 and December 2016. Demographic and clinical patient data were recorded on admission to ICU. Patients were divided into upper (n = 19) and lower (n = 27) GIP groups according to the perforation site (above or below Treitz ligament). PCT and WBC count was obtained before laparotomy and then compared between groups. Meanwhile, the diagnostic accuracy of PCT was analyzed. RESULTS: Patients with lower GIP exhibited significantly higher APACHE II score, SOFA score and serum PCT level than patients with upper GIP (P = 0.017, 0.004, and 0.001, respectively). There was a significant positive correlation between serum PCT level and APACHE II score or SOFA score (r = 0.715 and r = 0.611, respectively), while there was a significant negative correlation between serum PCT level and prognosis (r = -0.414). WBC count was not significantly different between the two groups, and WBC count showed no significant correlation with serum PCT level, APACHE II score, SOFA score or prognosis. The area under the receiver operating characteristic curve of PCT level to distinguish upper or lower GIP was 0.778. Patients with a serum PCT level above 17.94 ng/dL had a high likelihood of lower GIP, with a sensitivity of 100% and a specificity of 42.1%. CONCLUSION: Serum PCT level is a reliable and accurate diagnostic marker in identifying upper or lower GIP before laparotomy.

[Effect of airway humidification on lung injury induced by mechanical ventilation].

OBJECTIVE: To explore the effect of airway humidification on lung injury as a result of mechanical ventilation with different tidal volume (VT). METHODS: Twenty-four male Japanese white rabbits were randomly divided into four groups: low VT with airway humidification group, high VT with airway humidification group, low VT and high VT group without humidification, with 6 rabbits in each group. Mechanical ventilation was started after intubation and lasted for 6 hours. Low VT denoted 8 mL/kg, while high VT was 16 mL/kg, fraction of inspired oxygen (FiO2) denoted 0.40, positive end-expiratory pressure (PEEP) was 0. Temperature at Y piece of circuit in airway humidification groups was monitored and controlled at 40 centigrade. Arterial blood gas analysis, including pH value, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), lung mechanics indexes, including peak airway pressure (P(peak)) and airway resistance (Raw), and lung compliance was measured at 0, 2, 4, 6 hours of mechanical ventilation. The levels of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in plasma and bronchoalveolar lavage fluid (BALF) were determined by enzyme linked immunosorbent assay (ELISA). The animals were sacrificed at the end of mechanical ventilation. The wet to dry (W/D) ratio of lung tissues was calculated. Histopathologic changes in the lung tissueies were observed with microscope, and lung injury score was calculated. Scanning and transmission electron microscopies were used to examine the integrity of the airway cilia and the tracheal epithelium. RESULTS: Compared with low V(T) group, pH value in high V(T) group was significantly increased, PaCO2was significantly lowered, and no difference in PaO2was found. P(peak), Raw, and lung compliance were significantly increased during mechanical ventilation. There were no significant differences in blood gas analysis and lung mechanics indexes between low V(T) with airway humidification group and low V(T) group. Compared with high V(T) group, PaCO2in high V(T) with airway humidification group was significantly decreased, Ppeak raised obviously, and no difference in pH value, PaO2, Raw and pulmonary compliance was found. Compared with low V(T) with airway humidification group, no difference in blood gas analysis (PaCO2, mmHg, 1 mmHg=0.133 kPa) was found, but Ppeak (cmH2O, 1 cmH2O=0.098 kPa), Raw (cmH2O), and lung compliance (mL/cmH2O) were increased significantly in high V(T) with airway humidification group (PaCO2at 2 hours: 27.96 ± 4.64 vs. 36.08 ± 2.11, 4 hours: 28.62 ± 2.93 vs. 34.55 ± 5.50, 6 hours: 29.33 ± 2.14 vs. 35.01 ± 5.53; Ppeak at 0 hour: 14.34 ± 1.97 vs. 8.84 ± 1.32, 2 hours: 17.33 ± 0.52 vs. 11.17 ± 2.14, 4 hours: 17.83 ± 0.98 vs. 12.67 ± 2.06, 6 hours: 18.67 ± 1.22 vs. 13.50 ± 2.16; Raw at 0 hour: 37.36 ± 5.14 vs. 27.0 5 ± 2.93, 2 hours: 43.94 ± 6.58 vs. 31.95 ± 3.56, 4 hours: 48.04 ± 6.07 vs. 35.24 ± 3.50, 6 hours: 50.33 ± 6.34 vs. 36.66 ± 3.64; pulmonary compliance at 6 hours: 2.28 ± 0.18 vs. 1.86 ± 0.37, all P<0.05). The lung W/D ratio in high VT group was significantly higher than that of the low V(T) group (6.17 ± 2.14 vs. 3.50 ± 1.52, P<0.05). W/D in high V(T) with airway humidification group was higher than that of low V(T) with airway humidification group but without statistically significant difference (5.17 ± 2.14 vs. 3.00 ± 1.10, P>0.05). Microscopic observation showed that cilia were partially detached, adhered and sparse in low V(T) group, while cilia in high V(T) group showed serious detachment and lodging. Remaining cilia were sparse, with lodging, and cellular structure was damaged. Lung tissue pathological injury score in the high V(T) group was significantly higher than that of low V(T) group (6.17 ± 2.14 vs. 3.50 ± 1.52, P<0.05). Cilia density and cellularity were normal in low V(T) with airway humidification group, and no difference in lung tissue pathological injury score was found compared with low V(T) group (3.00 ± 1.10 vs. 3.50 ± 1.52, P>0.05). Cilia were severely detached, adhered and lodging, and cellularity were not obvious in high V(T) with airway humidification group, and lung tissue pathological injury score was elevated significantly than that of the low V(T) with airway humidification group but without statistically significant difference (5.17 ± 2.14 vs. 3.00 ± 1.10, P>0.05). TNF-α and IL-8 concentrations showed no change in plasma and BALF in all groups during ventilation, and no significant difference was found among the groups. CONCLUSIONS: Airway humidification can alleviate pathological lung injury, damage of cilia and cellular structure in trachea caused by mechanical ventilation with low and high V(T). High V(T) with humidification can result in serious pulmonary edema.

Calculating the burden of disease of avian-origin H7N9 infections in China.

OBJECTIVE: A total of 131 cases of avian-originated H7N9 infection have been confirmed in China mainland from February 2013 to May 2013. We calculated the overall burden of H7N9 cases in China as of 31 May 2013 to provide an example of comprehensive burden of disease in the 21st century from an acute animal-borne emerging infectious disease. DESIGN: We present an accurate and operable method for estimating the burden of H7N9 cases in China. The main drivers of economic loss were identified. Costs were broken down into direct (outpatient and inpatient examination and treatment) and indirect costs (cost of disability-adjusted life years (DALYs) and losses in the poultry industry), which were estimated based on field surveys and China statistical year book. SETTING: Models were applied to estimate the overall burden of H7N9 cases in China. PARTICIPANTS: 131 laboratory-confirmed H7N9 cases by 31 May 2013. OUTCOME MEASURE: Burden of H7N9 cases including direct and indirect losses. RESULTS: The total direct medical cost was ¥16 422 535 (US$2 627 606). The mean cost for each patient was ¥10 117 (US$1619) for mild patients, ¥139 323 (US$22 292) for severe cases without death and ¥205 976 (US$32 956) for severe cases with death. The total cost of DALYs was ¥17 356 561 (US$2 777 050). The poultry industry losses amounted to ¥7.75 billion (US$1.24 billion) in 10 affected provinces and ¥3.68 billion (USD$0.59 billion) in eight non-affected adjacent provinces. CONCLUSIONS: The huge poultry industry losses followed live poultry markets closing down and poultry slaughtering in some areas. Though the proportion of direct medical losses and DALYs losses in the estimate of H7N9 burden was small, the medical costs per case were extremely high (particularly for addressing the use of modern medical devices). A cost-effectiveness assessment for the intervention should be conducted in a future study.

[Apoptosis of cultured cortical neurons of rat's brain induced by heroin].

OBJECTIVE: To investigate whether heroin can directly induce apoptosis in primary cultured cortical neurons of rat's brain. METHODS: Cultured primary neurons cultures were obtained from cerebral cortex of embryo rats. After 7 days, the cells were incubated with different concentrations of heroin (purity-80%) for 24 hours. The neuronal survival was assessed by cell viability counting with fluorescent diacetate (FDA) staining. The morphological and biochemical changes were observed with Hoechst 33258 fluorescent staining and then analyzed by agarose gel electrophoresis, respectively. RESULTS: After treatment with different concentrations of heroin, the neurons showed a decreased survival rate in a dose dependent manner, and there was a significant difference in the survival rate between the heroin group and the control group (P < 0.05). When exposed to different concentrations of heroin, neurons exhibited the morphological and biochemical features of apoptosis, including cell shrinkage, neurite degeneration, network disappearance, condensation and aggregation of nuclear chromatin, and the formation of DNA ladders. With the increase of heroin concentration of rat's brain more apoptotic bodies were seen. CONCLUSION: Heroin can directly induce apoptosis in primary cultured cortical neurons in rat's brain.