1.Important step of weaning from mechanical ventilation: accurate assessment of respiratory muscle strength
Chinese Critical Care Medicine 2024;36(4):337-339
Mechanical ventilation (MV) is a powerful mean to rescue patients with respiratory failure. In view of the different etiology and basic respiratory function of patients with respiratory failure, weaning failure often occurs. Prolonged MV time is often accompanied by many complications. Thus, deeply understanding the pathophysiological changes of respiratory failure and strengthen monitoring of respiratory mechanics are helpful to optimize MV parameter settings, reduce ventilator-induced lung injury and wean from MV as early as possible. A successful weaning from MV depends on many factors, the most important factors are respiratory muscle strength, respiratory load and respiratory drive. Spontaneous breathing trial (SBT) is an important part of weaning process. The main purpose of implementing SBT is to screen patients and opportunities to weaning from MV, and find reversible reasons for not passing SBT. Because the accuracy of SBT in assessing weaning prognosis is about 85%, it is not adequate for difficult weaning patients. Standardized measurement of weaning indicators for patients with difficulty weaning is conducive to accurate assessment of respiratory muscle strength and improve the success rate of weaning from MV.
2.How to implement prone position and prone ventilation accurately
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(4):396-400
Prone position and position ventilation(PPV)are effective methods to save patients with refractory hypoxemia,and prone position has become the standard treatment for acute respiratory distress syndrome(ARDS).Successful clinical implementation requires understanding the mechanisms improving oxygenation and hemodynamic effects.In the use of prone position combined with PPV,the common factors affecting ventilation or oxygenation should be given extra an attention,such as the changes in respiratory mechanics,intra-abdominal pressure(IAP)and hemodynamics.However,consensus is lacking on optimal proning protocols and patient selection criteria.The causes of acute hypoxia and respiratory failure are complex,and should be assessed accurately.The success rate of rescuing critically ill patients can be improved by applying multiple effective treatments and standardized implementing prone position and PPV to improve oxygenation at the same time.
3.Application and challenges of chest CT peritumoral radiomics in the precision diagnosis and treatment of non-small cell lung cancer
Ting WU ; Linyu WU ; Chen GAO ; Xinjing LOU ; Jiawei CHEN ; Jun WU ; Maosheng XU
Chinese Journal of Radiological Medicine and Protection 2024;44(5):443-449
By extracting quantitative radiomic features from regions of interest in medical images and correlating them with the biological features and heterogeneity of tumors, radiomics can provide critical information and a basis for personalized precision diagnosis and treatment. Peritumoral regions contain a wealth of microbiological information. Therefore, chest CT peritumoral radiomics, which can provide quantitative non-invasive assessment for patients with non-small cell lung cancer (NSCLC) by mining the deep heterogeneity of peritumoral regions, has broad prospects for future clinical applications. Given the rapid progress in computer and medical big data techniques, as well as the in-depth efforts in multi-center, high-quality, and large-sample data in the future, it is reasonably believed that radiomics research will be gradually normalized and reproducible. This is conducive to the translation and application of radiomics research to clinical practice, thus laying a foundation for personalized and accurate diagnosis, treatment, and follow-up for lung cancer patients.
4.The value of maximal rate of left ventricular pressure in evaluating cardiac function in patients with sepsis-induced cardiomyopathy.
Junyi WANG ; Zhengzhong HE ; Xinjing GAO ; Zhiyong WANG ; Chengfen YIN ; Tong LI
Chinese Critical Care Medicine 2023;35(6):620-626
OBJECTIVE:
To investigate the value of maximal rate of left ventricular pressure (dp/dtmax) in evaluating the changes of cardiac function before and after heart rate reduction in patients with sepsis-induced cardiomyopathy (SIC).
METHODS:
A single-center, prospective randomized controlled study was conducted. Adult patients with sepsis/septic shock admitted to the department of intensive care unit (ICU) of Tianjin Third Central Hospital from April 1, 2020 to February 28, 2022 were enrolled. Speckle tracking echocardiography (STE) and pulse indication continuous cardiac output (PiCCO) monitoring were performed immediately after the completion of the 1 h-Bundle therapy. The patients with heart rate over 100 beats/minutes were selected and randomly divided into esmolol group and regular treatment group, 55 cases in each group. All patients underwent STE and PiCCO monitoring at 6, 24 and 48 hours after admission in ICU and calculated acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA). Primary outcome measure: change in dp/dtmax after reducing heart rate by esmolol. Secondary outcome measures: correlation between dp/dtmax and global longitudinal strain (GLS); changes of vasoactive drug dosage, oxygen delivery (DO2), oxygen consumption (VO2) and stroke volume (SV) after the administration of esmolol; proportion of heart rate reaching the target after the administration of esmolol; 28-day and 90-day mortality in two groups.
RESULTS:
Baseline data on age, gender, body mass index, SOFA score, APACHE II score, heart rate, mean arterial pressure, lactic acid, 24-hour fluid balance, sepsis etiology and prior comorbidities were similar between esmolol group and regular treatment group, there were no significant differences between the two groups. All SIC patients achieved the target heart rate after 24 hours of esmolol treatment. Compared with regular treatment group, parameters reflecting myocardial contraction such as GLS, global ejection fraction (GEF) and dp/dtmax were significantly increased in esmolol group [GLS: (-12.55±4.61)% vs. (-10.73±4.82)%, GEF: (27.33±4.62)% vs. (24.18±5.35)%, dp/dtmax (mmHg/s): 1 312.1±312.4 vs. 1 140.9±301.0, all P < 0.05], and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased [μg/L: 1 364.52 (754.18, 2 389.17) vs. 3 508.85 (1 433.21, 6 988.12), P < 0.05], DO2 and SV were significantly increased [DO2 (mL×min-1×m-2): 647.69±100.89 vs. 610.31±78.56, SV (mL): 49.97±14.71 vs. 42.79±15.77, both P < 0.05]. The system vascular resistance index (SVRI) in esmolol group was significantly higher than that in regular treatment group (kPa×s×L-1: 287.71±66.32 vs. 251.17±78.21, P < 0.05), even when the dosage of norepinephrine was similar between the two groups. Pearson correlation analysis showed that dp/dtmax was negatively correlated with GLS in SIC patients at 24 hours and 48 hours after ICU admission (r values were -0.916 and -0.935, respectively, both P < 0.05). Although there was no significant difference in 28-day mortality between esmolol group and regular treatment group [30.9% (17/55) vs. 49.1% (27/55), χ2 = 3.788, P = 0.052], the rate of esmolol use in patients who died within 28 days was lower than that in patients who survived [38.6% (17/44) vs. 57.6% (38/66), χ2 = 3.788, P = 0.040]. In addition, esmolol has no effect on the 90-day mortality of patients. Logistic regression analysis showed that after adjusting for SOFA score and DO2 factors, patients who used esmolol had a significantly lower risk of 28-day mortality compared with patients who did not use esmolol [odds ratio (OR) = 2.700, 95% confidence interval (95%CI) was 1.038-7.023, P = 0.042].
CONCLUSIONS
dp/dtmax in PiCCO parameter can be used as a bedside indicator to evaluate cardiac function in SIC patients due to its simplicity and ease of operation. Esmolol control of heart rate in SIC patients can improve cardiac function and reduce short-term mortality.
Adult
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Humans
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Prospective Studies
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Ventricular Pressure
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Sepsis/complications*
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Shock, Septic/drug therapy*
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Cardiomyopathies/etiology*
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Prognosis
5.Volume dynamics and volume management in intensive care unit patients
Yingzhi QIN ; Yuning HE ; Quansheng FENG ; Zhibo LI ; Zhiyong WANG ; Yaxuan WU ; Jing ZHAO ; Xinjing GAO
Chinese Critical Care Medicine 2022;34(7):673-675
Volume dynamics is a two-compartment dynamical model using hemoglobin (Hb) derived plasma diluted level as input data and urine output as input variable through consecutive repeated measurements of Hb concentration in the blood during infusion. It could be applied to evaluate and guide crystalloid fluid rehydration for patients with dehydration or hypovolemia and during anesthesia or surgery. Volume dynamics could be also used to quantificate of strains, hypovolume, and the change of fluid distribution and elimination caused by anesthesia or surgery. The factors which influence the volume resuscitation are complex, including gender, age, hemodynamic state [mean arterial pressure (MAP)], health and stress state, renal function, consciousness, surgical or anesthesia state and so on, which may affect the half-life, distribution, and volume of the fluid. This article summarizes and analyzes the pathophysiological changes of crystalloids fluid in vivo, in order to provide reference for volume management in critically ill patients.
6.Analysis of the causes of arrhythmia induced by citrate anticoagulation in continuous renal replacement therapy
Xinjing GAO ; Quansheng FENG ; Lei XU
Chinese Critical Care Medicine 2021;33(6):748-751
Objective:To analyze the possible causes of arrhythmia in patients receiving continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA).Methods:A retrospective cohort study was conducted. All patients underwent RCA-CRRT treatment from January 1, 2020 to October 31, 2020 in the intensive care unit (ICU) of Tianjin Third Central Hospital were enrolled. The patients were divided into arrhythmia group and non-arrhythmia group according to whether arrhythmia occurred. The gender, age, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, catheterization site, underlying diseases, electrocardiogram (ECG), electrolytes [total calcium, serum free calcium (iCa 2+), phosphorus, magnesium, potassium] and blood gas analysis (pH value, HCO 3-) of patients in the two groups were recorded. The changes of ECG were observed, the differences in electrolyte and blood gas analysis indexes between the two groups of patients at different time points (before CRRT, 24, 48, 72 hours after CRRT, and when arrhythmia occurred) were compared. Results:A total of 86 RCA-CRRT patients were enrolled, of which 12 cases (13.95%) had arrhythmia, and the remaining 74 cases (86.05%) had no arrhythmia. The average time for the occurrence of arrhythmia in the 12 patients was (44.00±16.82) hours. There was no significant ST-segment change in the ECG when the arrhythmia occurred compared with that before CRRT, the total calcium level was significantly higher than that before CRRT (mmol/L: 2.48±0.40 vs. 2.13±0.35, P < 0.05), the blood magnesium level was significantly lower than that before CRRT (mmol/L: 0.73±0.20 vs. 0.95±0.25, P < 0.05). There was no significant difference in iCa 2+, blood phosphorus, blood potassium, pH value and HCO 3- between before CRRT and when arrhythmia occurred. Over time, the total calcium levels in the two groups increased, and there was a statistical difference between the 48 hours after CRRT and before CRRT (mmol/L: 2.48±0.33 vs. 2.13±0.35 in the arrhythmia group, and 2.30±0.22 vs. 2.15±0.48 in non-arrhythmia group, both P < 0.05). The linear change trend of iCa 2+, pH value and HCO 3- was not obvious in the two groups. The blood phosphorus and blood magnesium levels in the two groups decreased. The blood potassium in the arrhythmia group decreased, however, the blood potassium level in non-arrhythmia group did not change significantly. The total calcium level in the arrhythmia group was significantly higher than that in the non-arrhythmia group at 72 hours after CRRT (mmol/L: 2.69±0.35 vs. 2.45±0.23, P < 0.05); however, there was no significant difference in serum iCa 2+, phosphorus, magnesium, potassium, pH value and HCO 3- between the two groups. Conclusion:Patients receiving RCA-CRRT were less likely to develop arrhythmia, the causes may be related to the accumulation of citric acid and electrolyte disturbances such as calcium, phosphorus, and magnesium.
7.A clinical study on the wean effect of setting parameters of proportional pressure support on acute exacerbation of chronic obstructive pulmonary disease patients with difficult weaning
Chengfen YIN ; Lei XU ; Xinjing GAO ; Zhiyong WANG ; Quansheng FENG ; Yongle ZHI ; Tong LI
Chinese Critical Care Medicine 2021;33(9):1074-1079
Objective:To investigate the clinical effect of setting proportional pressure support (PPS) parameters by target tidal volume (VT) method.Methods:The study was conducted retrospectively on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients admitted to Tianjin Third Central Hospital from January 2016 to December 2020. According to the PPS parameter setting method, the patients were divided into the airway blocking group and target VT group. The baseline characteristics, initial setting values of flow assist (FA) and volume assist (VA), respiratory system parameters, and clinical outcomes were collected and compared between the two groups.Results:Fifty-nine patients were enrolled, 29 patients in the airway blocking group, and 30 in the target VT group. There was no statistically significant difference in baseline characteristics, compliance, resistance, and initial settings of FA and VA between the two groups. Compared with the target VT group, the respiratory rate (RR), mean arterial pressure (MAP), VT, and arterial partial pressure of oxygen (PaO 2) recorded 1 hour after the initial setting of the PPS parameters in the airway block method group were significantly reduced [RR (times/minute): 21.0 (18.5, 22.5) vs. 23.0 (21.0, 25.0), MAP (mmHg, 1 mmHg = 0.133 kPa): 84.0 (79.0, 90.5) vs. 90.0 (87.0, 96.2), VT (mL): 305.24±41.07 vs. 330.87±46.84, PaO 2 (mmHg): 68.0 (66.0, 73.5) vs. 74.0 (69.8, 82.5), all P < 0.05], while arterial partial pressure of carbon dioxide (PaCO 2) and oral closure pressure (P0.1) were both increased significantly [PaCO 2 (mmHg): 41.0 (39.0, 46.0) vs. 37.5 (35.0, 42.2), P0.1 (cmH 2O, 1 cmH 2O = 0.098 kPa): 1.42±0.78 vs. 0.90±0.67, both P < 0.05]. Compared with airway blocking group, the duration of weaning, ICU stay, and hospital stay in the target VT group were significantly shorter [duration of weaning (hours): 42.0 (24.0, 70.5) vs. 64.0 (30.5, 97.5), ICU stay: 10.00±3.38 to 13.28±5.41, hospital stay (days): 12.07±3.40 vs. 15.41±5.60, all P < 0.05]. There was no statistically significant difference in the invasive mechanical ventilation time, weaning failure rate, ICU mortality and in-hospital mortality between the two groups. Conclusion:This study suggested that the target TV method has the advantages of practicality, safety, convenience, and rapid to set PPS parameters than the airway block method, which shortens the duration of weaning and ICU stay, and has a good clinical prospect.
8.Preliminary establishment of weaning prediction model
Lian LIU ; Chengfen YIN ; Yongle ZHI ; Xinjing GAO ; Lei XU
Chinese Critical Care Medicine 2020;32(2):171-176
Objective:To establish a model that can predict weaning failure from ventilation through hemodynamic and fluid balance parameters.Methods:A retrospective analysis was conducted. The patients who underwent invasive mechanical ventilation for more than 24 hours and having spontaneous breathing test admitted to intensive care unit (ICU) of Tianjin Third Central Hospital from January 1st, 2017 to December 31st, 2018 were enrolled. The information was collected, which included the baseline data, hemodynamic parameters by pulse indicator continuous cardiac output (PiCCO) monitoring, B-type natriuretic peptide (BNP), urinary output, fluid balance in first 24 hours when patients admitted to ICU, and hemodynamic parameters by PiCCO monitoring, BNP, urinary output, fluid balance, diuretic usage, noradrenalin usage within 24 hours before weaning as well as usage of continuous renal replacement therapy (CRRT) during mechanical ventilation. According to weaning success or failure, the patients were divided into weaning success group and weaning failure group, and the statistical differences between the two groups were calculated. Variables with statistical significance within 24 hours before weaning were included in the multivariate Logistic regression analysis to establish weaning failure prediction model and find out the possible risk factors of weaning failure.Results:A total of 159 patients were included in this study, which included 138 patients in the weaning success group and 21 patients in the weaning failure group. There were no statistical differences in all hemodynamic parameters by PiCCO monitoring, BNP, urinary output, fluid balance within 24 hours into ICU between two groups. There were statistical differences in BNP ( χ2 = 9.262, P = 0.026), central venous pressure (CVP; χ2 = 7.948, P = 0.047), maximum rate of the increase in pressure (dPmx; χ2 = 10.486, P = 0.015), urinary output ( χ2 = 8.921, P = 0.030), fluid balance ( χ2 = 9.172, P = 0.027) within 24 hours before weaning between two groups. In addition, variable about cardiac index (CI; χ2 = 7.789, P = 0.051) was included into multivariate Logistic regression model to improve the prediction model and enhance the accuracy of model. Finally, variables included in the multivariate Logistic regression model were BNP, CVP, CI, dPmx, urinary output, fluid balance volume, and the accuracy of the weaning failure prediction model was 92.9%, the sensitivity was 100%, and the specificity was 76.8%. When the model was adjusted by variables of age and noradrenalin usage, the accuracy of model to predict failure of weaning was 94.2%, the sensitivity was 100%, the specificity was 81.2%. Conclusion:Weaning failure prediction model based on hemodynamic parameters by PiCCO monitoring and variables about liquid balance has high accuracy and can guide clinical weaning.
9.Dynamic measurement of volume of atelectasis area in the evaluation of the prognosis of patients with moderate-to-severe acute respiratory distress syndrome
Xing LU ; Yuxin HAN ; Xinjing GAO ; Fengmei WANG ; Lei XU
Chinese Critical Care Medicine 2020;32(9):1056-1060
Objective:To assess the impact of not inflated lung tissue (NILT) volume on the prognosis of patients with moderate-to-severe acute respiratory distress syndrome (ARDS).Methods:The clinical data of 131 patients with moderate-to-severe ARDS admitted to the intensive care unit (ICU) of Tianjin Third Central Hospital from March 2016 to June 2019 were collected. The basic data of patients, including gender, age, body mass index (BMI), causes of ARDS, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score and oxygenation index (PaO 2/FiO 2), were collected. The CT imaging data of patients on the 1st and 7th day in the ICU were collected. According to the CT value, they were divided into hyperventilated areas (-1 000 to -900 HU), normal ventilation areas (-899 to -500 HU), poorly ventilated areas (-499 to -100 HU), and atelectasis area (-99 to 100 HU). The total lung volume and the percentage of NILT to the total lung volume (NILT%) were calculate. At the same time, duration of mechanical ventilation, length of ICU stay, total length of hospital stay were collected. According to the 28-day follow-up, they were divided into survival group and death group. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in ARDS patients. The receiver operating characteristic (ROC) curve was drawn, the area under ROC curve (AUC) and 95% confidence interval (95% CI) were calculated to determine the accuracy of NILT% in predicting the 28-day prognosis of ARDS patients, and the NILT% threshold was used for subgroup analysis of patients. Results:Among the 131 patients with moderate-to-severe ARDS, patients were excluded for more than 48 hours after ARDS diagnosis, repeated admission to ICU due to ARDS, the ICU duration less than 7 days, death within 72 hours of admission, chronic interstitial lung disease or congestive heart failure, no chest CT examination within 7 days of admission to ICU, and no specimen collection within 2 hours of admission to ICU. Finally, a total of 53 patients were enrolled in the analysis. Of the 53 patients, 31 patients survived and 22 patients died. The 28-day mortality was 41.5%. Compared with the survival group, patients in the death group were older (years old: 65.32±11.29 vs. 55.77±14.23), and had a higher SOFA score (11.68±3.82 vs. 8.39±2.23) with significant differences (both P < 0.05), while there were no significant differences in gender, BMI, ARDS cause, APACHE Ⅱ score and PaO 2/FiO 2 between the two groups. There was no significant difference in CT value, total lung volume and NILT% between the two groups at 1st day after admission to ICU; NILT% on day 7 after admission to ICU in the death group was significantly higher than that in the survival group [(28.95±8.40)% vs. (20.35±5.91)%, P < 0.01], but there was no significant difference in CT value and total lung volume between the two groups. Multivariate Logistic regression analysis showed that the 28-day prognosis of ARDS was related to age, SOFA score and NILT% independently [age: odds ratio ( OR) = 0.892, 95% CI was 0.808-0.984, P = 0.023; SOFA score: OR = 0.574, 95% CI was 0.387-0.852, P = 0.006; NILT%: OR = 0.841, 95% CI was 0.730-0.968, P = 0.016]. ROC curve analysis showed that 7-day NILT% could predict the 28-day prognosis of patients with moderate-to-severe ARDS, and AUC was 0.810 (95% CI was 0.678-0.952, P < 0.01). The NILT% threshold was 15.50%, sensitivity was 95.5%, specificity was 80.6%, positive predictive value was 85.7%, and negative predictive value was 74.6%. According to the 7-day NILT% threshold, a subgroup analysis of patients was performed, and 7-day NILT% > 15.50% was defined as a high-risk clinical prognosis, and ≤ 15.50% was a low-risk. Compared with low-risk patients ( n = 7), the duration of mechanical ventilation, the length of ICU stay and total length of hospital stay in high-risk patients ( n = 46) were significantly prolonged [duration of mechanical ventilation (days): 9.37±6.14 vs. 4.43±1.72, length of ICU stay (days): 12.11±5.85 vs. 7.57±1.13, total length of hospital stay (days): 18.39±5.87 vs. 11.29±2.22, all P < 0.05]. Conclusion:The 7-day NILT% > 15.50% of patients with moderate-to-severe ARDS after ICU admission is related to poor prognosis.
10.Continuous contrast-enhanced ultrasound applied to acute kidney injury caused by sepsis: a diagnostic clinical study
Junyi WANG ; Xinjing GAO ; Dong WANG ; Zhiyong WANG ; Zhibo LI ; Dong LIU ; Lei XU
Chinese Critical Care Medicine 2018;30(2):160-164
Objective To evaluate the diagnostic value of contrast-enhanced ultrasound in acute kidney injury (AKI) caused by sepsis. Methods The sepsis patients admitted to intensive care unit of Tianjin Third Central Hospital from January 2015 to June 2017 were enrolled. All of the patients were completed the 6-hour Bundle treatment and the bilateral renal contrast-enhanced ultrasound within 24 hours, and the peak signal intensity (PSI), peak intensity time (PIT), wash internal rate (WIR) and renal function parameters were measured at the same time. The patients were divided into AKI 24 hours group and non-AKI 24 hours group according to Kidney Disease: Improving Global Outcomes (KDIGO)-AKI diagnostic criteria, and the parameters differences were compared between the two groups. The receiver operating characteristic (ROC) curve were used to analyze the diagnostic value of the parameters. Renal function of the non-AKI group patients was measured again 7 days after hospital admission, and patients were divided into AKI 7 days group and non-AKI 7 days group, and the related parameters of the two groups measured within 24 hours were compared. Results ① Ninety-six patients were enrolled, with 39 cases of AKI occurred within 24 hours after admission, and with an incidence of 40.6%. Contrast-enhanced ultrasound showed that the time-intensity curve (TIC) of non-AKI patients manifested as a slow down after rapid rise to the peak, but the AKI patients showed as slow rise to the peak and more slow decrease. Compared with non-AKI 24 hours group, AKI 24 hours group performance as PSI weakened, PIT extended and WIR decreased [PSI (dB): 114.41±19.38 vs. 141.24±24.65, PIT (s): 22.86±4.29 vs. 17.39±3.68, WIR (dB/s): 5.53±4.17 vs. 7.85±1.84, all 1 < 0.01]. ROC curve analysis showed that area under the ROC curve (AUC) of WIR, PIT, PSI was 0.85, 0.84, 0.82 respectively (all 1 < 0.01), the cut-off value of WIR was 7.18 dB/S, the sensitivity, specificity and accuracy were 82.05%, 80.70% and 81.25% respectively; the cut-off value of PIT was 18.45 s, the sensitivity, specificity and accuracy were 74.35%, 73.68% and 73.95% respectively;the cut-off values of PSI was 121.21 dB, the sensitivity, specificity and accuracy were 71.79%, 87.72% and 81.25% respectively. ② The incidence of AKI within 7 days in non-AKI patients was 26.3% (15/57). There were significant differences in PIT, WIR and PSI between AKI 7 days group and non-AKI 7 days group [PSI (dB): 124.97±26.64 vs. 147.02±21.51, PIT (s): 20.61±3.27 vs. 16.24±3.13, WIR (dB/s): 6.81±1.76 vs. 8.22±1.75, all 1 < 0.05]. However, there was no significant difference in serum creatinine (SCr), blood urea nitrogen (BUN) and creatinine clearance rate (CCr). Conclusion Compared to SCr and BUN, contrast-enhanced ultrasound parameters can early response to renal dysfunction, and contribute to early diagnosis of sepsis induced AKI.

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