Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study / 中华胃肠外科杂志

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.

Neural control of pressure support ventilation improved patient-ventilator synchrony in patients with different respiratory system mechanical properties: a prospective, crossover trial / 中华医学杂志(英文版)

BACKGROUND@#Conventional pressure support ventilation (PSP) is triggered and cycled off by pneumatic signals such as flow. Patient-ventilator asynchrony is common during pressure support ventilation, thereby contributing to an increased inspiratory effort. Using diaphragm electrical activity, neurally controlled pressure support (PSN) could hypothetically eliminate the asynchrony and reduce inspiratory effort. The purpose of this study was to compare the differences between PSN and PSP in terms of patient-ventilator synchrony, inspiratory effort, and breathing pattern.@*METHODS@#Eight post-operative patients without respiratory system comorbidity, eight patients with acute respiratory distress syndrome (ARDS) and obvious restrictive acute respiratory failure (ARF), and eight patients with chronic obstructive pulmonary disease (COPD) and mixed restrictive and obstructive ARF were enrolled. Patient-ventilator interactions were analyzed with macro asynchronies (ineffective, double, and auto triggering), micro asynchronies (inspiratory trigger delay, premature, and late cycling), and the total asynchrony index (AI). Inspiratory efforts for triggering and total inspiration were analyzed.@*RESULTS@#Total AI of PSN was consistently lower than that of PSP in COPD (3% vs. 93%, P = 0.012 for 100% support level; 8% vs. 104%, P = 0.012 for 150% support level), ARDS (8% vs. 29%, P = 0.012 for 100% support level; 16% vs. 41%, P = 0.017 for 150% support level), and post-operative patients (21% vs. 35%, P = 0.012 for 100% support level; 15% vs. 50%, P = 0.017 for 150% support level). Improved support levels from 100% to 150% statistically increased total AI during PSP but not during PSN in patients with COPD or ARDS. Patients' inspiratory efforts for triggering and total inspiration were significantly lower during PSN than during PSP in patients with COPD or ARDS under both support levels (P < 0.05). There was no difference in breathing patterns between PSN and PSP.@*CONCLUSIONS@#PSN improves patient-ventilator synchrony and generates a respiratory pattern similar to PSP independently of any level of support in patients with different respiratory system mechanical properties. PSN, which reduces the trigger and total patient's inspiratory effort in patients with COPD or ARDS, might be an alternative mode for PSP.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/record/NCT01979627.

Role of immunodeficiency in Acinetobacter baumannii associated pneumonia in mice / 中华医学杂志(英文版)

BACKGROUND@#Acinetobacter baumannii (A. baumannii) has become one of the most important opportunistic pathogens inducing nosocomial pneumonia and increasing mortality in critically ill patients recently. The interaction between A. baumannii infection and immune response can influence the prognosis of A. baumannii related pneumonia. The target of the present study was to investigate the role of immunodeficiency in A. baumannii induced pneumonia.@*METHODS@#Male BALB/c mice were randomly divided into the normal immunity control (NIC) group, normal immunity infection (NIA) group, immune compromised control (CIC) group, and immune compromised infection (CIA) group (n = 15 for each group). Intraperitoneal injection of cyclophosphamide and intranasal instillation of A. baumannii solution were used to induce compromised immunity and murine pneumonia, respectively. The mice were sacrificed at 6 and 24 h later and the specimens were collected for further tests. Seven-day mortality of mice was also assessed.@*RESULTS@#After A. baumannii stimulation, the recruitment of neutrophils in mice with normal immunity increased sharply (P = 0.030 at 6 h), while there was no significant raise of neutrophil counts in mice with compromised immune condition (P = 0.092 at 6 h, P = 0.772 at 24 h). The Th cell polarization presented with pulmonary interleukin (IL)-4 and interferon (IFN)-γ level in response to the A. baumannii in CIA group were significantly depressed in comparison with in NIA group (IFN-γ: P = 0.003 at 6 h; P = 0.001 at 24 h; IL-4: P < 0.001 at 6 h; P < 0.001 at 24 h). The pulmonary conventional dendritic cell accumulation was even found to be inhibited after A. baumannii infection in immunocompromised mice (P = 0.033). Correspondingly, A. baumannii associated pneumonia in mice with compromised immunity caused more early stage death, more severe histopathological impairment in lung.@*CONCLUSION@#A. baumannii could frustrate the immune response in immunocompromised conditions, and this reduced immune response is related to more severe lung injury and worse outcome in A. baumannii induced pneumonia.

Venovenous extra-corporeal membrane oxygenation for severe acute respiratory distress syndrome: a matched cohort study / 中华医学杂志(英文版)

Background@#Although the use of extra-corporeal membrane oxygenation (ECMO) has been rapidly increasing, the benefit of ECMO in patients with acute respiratory distress syndrome (ARDS) remains unclear. Our objective was to investigate the effect of venovenous ECMO (VV-ECMO) on adult patients with severe ARDS.@*Methods@#We conducted a multi-center, retrospective, cohort study in the intensive care units (ICUs) of six teaching hospitals between January 2013 and December 2018. Patients with severe ARDS who received VV-ECMO support were included. The detailed demographic data and physiologic data were used to match ARDS patients without ECMO. The primary endpoint was the 28-day mortality.@*Results@#Ninety-nine patients with severe ARDS supported by VV-ECMO and 72 patients without ECMO were included in this study. The acute physiology and chronic health evaluation II score was 23.1 ± 6.3 in the ECMO group and 24.8 ± 8.5 in the control group (P = 0.1195). The sequential organ failure assessment score was 12.8 ± 3.4 in the ECMO group and 13.7 ± 3.5 in the control group (P = 0.0848). The 28-day mortality of patients with ECMO support was 39.4%, and that of the control group was 55.6%. The survival analysis curve showed that the 28-day mortality in the ECMO group was significantly lower than that in the control group (P = 0.0097). Multivariate Cox regression analysis showed that the independent predictors of the 28-day mortality were the requirement of vasopressors before ECMO (hazard ratio [HR]: 1.006; 95% confidence interval [CI]: 1.001–1.013; P = 0.030) and duration of mechanical ventilation before ECMO (HR: 3.299; 95% CI: 1.264–8.609; P = 0.034).@*Conclusions@#This study showed that ECMO improved the survival of patients with severe ARDS. The duration of mechanical ventilation and the requirement of vasopressors before ECMO might be associated with an increased risk of death.

Venovenous extra-corporeal membrane oxygenation for severe acute respiratory distress syndrome: a matched cohort study / 中华医学杂志(英文版)

BACKGROUND@#Although the use of extra-corporeal membrane oxygenation (ECMO) has been rapidly increasing, the benefit of ECMO in patients with acute respiratory distress syndrome (ARDS) remains unclear. Our objective was to investigate the effect of venovenous ECMO (VV-ECMO) on adult patients with severe ARDS.@*METHODS@#We conducted a multi-center, retrospective, cohort study in the intensive care units (ICUs) of six teaching hospitals between January 2013 and December 2018. Patients with severe ARDS who received VV-ECMO support were included. The detailed demographic data and physiologic data were used to match ARDS patients without ECMO. The primary endpoint was the 28-day mortality.@*RESULTS@#Ninety-nine patients with severe ARDS supported by VV-ECMO and 72 patients without ECMO were included in this study. The acute physiology and chronic health evaluation II score was 23.1 ± 6.3 in the ECMO group and 24.8 ± 8.5 in the control group (P = 0.1195). The sequential organ failure assessment score was 12.8 ± 3.4 in the ECMO group and 13.7 ± 3.5 in the control group (P = 0.0848). The 28-day mortality of patients with ECMO support was 39.4%, and that of the control group was 55.6%. The survival analysis curve showed that the 28-day mortality in the ECMO group was significantly lower than that in the control group (P = 0.0097). Multivariate Cox regression analysis showed that the independent predictors of the 28-day mortality were the requirement of vasopressors before ECMO (hazard ratio [HR]: 1.006; 95% confidence interval [CI]: 1.001-1.013; P = 0.030) and duration of mechanical ventilation before ECMO (HR: 3.299; 95% CI: 1.264-8.609; P = 0.034).@*CONCLUSIONS@#This study showed that ECMO improved the survival of patients with severe ARDS. The duration of mechanical ventilation and the requirement of vasopressors before ECMO might be associated with an increased risk of death.

Acute Respiratory Distress Syndrome: Challenge for Diagnosis and Therapy / 中华医学杂志(英文版)

<p><b>Objective</b>Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome whose diagnosis and therapy are still in question. The aim of this review was to discuss the current challenge for the diagnosis and treatment of ARDS.</p><p><b>Data Sources</b>Data sources were the published articles in English through December 2017 in PubMed using the following key words: "acute respiratory distress syndrome," "definition", "diagnosis," "therapy," "lung protective strategy," "right ventricular dysfunction," and "molecular mechanism."</p><p><b>Study Selection</b>The selection of studies focused on both preclinical studies and clinical studies of therapy of ARDS.</p><p><b>Results</b>The incidence of ARDS is still high, and ARDS causes high intensive care units admissions and high mortality. The Berlin Definition proposed in 2012 is still controversial owing to lack of sensitivity and specificity. ARDS is still under recognition and it is associated with high mortality. Lung protective strategies with low tidal volume (VT) and lung recruitment should consider the physiology of ARDS because ARDS presents lung inhomogeneity; the same low VT might increase local stress and strain in some patients with low compliance, and lung recruitment could injure lungs in ARDS patients with low recruitability and hemodynamic instability. Acute cor pulmonale is common in severe ARDS. ARDS itself and some treatments could worsen acute cor pulmonale. Molecular understanding of the pathogenic contributors to ARDS has improved, but the molecular-associated treatments are still under development.</p><p><b>Conclusions</b>ARDS is a devastating clinical syndrome whose incidence and mortality has remained high over the past 50 years. Its definition and treatments are still confronted with challenges, and early recognition and intervention are crucial for improving the outcomes of ARDS. More clinical studies are needed to improve early diagnosis and appropriate therapy.</p>

Effects of Propofol on Respiratory Drive and Patient-ventilator Synchrony during Pressure Support Ventilation in Postoperative Patients: A Prospective Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Propofol is increasingly used during partial support mechanical ventilation such as pressure support ventilation (PSV) in postoperative patients. However, breathing pattern, respiratory drive, and patient-ventilator synchrony are affected by the sedative used and the sedation depth. The present study aimed to evaluate the physiologic effects of varying depths of propofol sedation on respiratory drive and patient-ventilator synchrony during PSV in postoperative patients.</p><p><b>METHODS</b>Eight postoperative patients receiving PSV for <24 h were enrolled. Propofol was administered to achieve and maintain a Ramsay score of 4, and the inspiratory pressure support was titrated to obtain a tidal volume (VT) of 6-8 ml/kg. Then, the propofol dose was reduced to achieve and maintain a Ramsay score of 3 and then 2. At each Ramsay level, the patient underwent 30-min trials of PSV. We measured the electrical activity of the diaphragm, flow, airway pressure, neuro-ventilatory efficiency (NVE), and patient-ventilator synchrony.</p><p><b>RESULTS</b>Increasing the depth of sedation reduced the peak and mean electrical activity of the diaphragm, which suggested a decrease in respiratory drive, while VT remained unchanged. The NVE increased with an increase in the depth of sedation. Minute ventilation and inspiratory duty cycle decreased with an increase in the depth of sedation, but this only achieved statistical significance between Ramsay 2 and both Ramsay 4 and 3 (P < 0.05). The ineffective triggering index increased with increasing sedation depth (9.5 ± 4.0%, 6.7 ± 2.0%, and 4.2 ± 2.1% for Ramsay 4, 3, and 2, respectively) and achieved statistical significance between each pair of depth of sedation (P < 0.05). The depth of sedation did not affect gas exchange.</p><p><b>CONCLUSIONS</b>Propofol inhibits respiratory drive and deteriorates patient-ventilator synchrony to the extent that varies with the depth of sedation. Propofol has less effect on breathing pattern and has no effect on VT and gas exchange in postoperative patients with PSV.</p>

Epidemiological Study of Sepsis in China: Protocol of a Cross-sectional Survey / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sepsis is the leading cause of death among critically ill patients. Herein, we conducted a national survey to provide data on epidemiology and treatment of sepsis in the clinical practice in China, which has no detailed epidemiological data available on sepsis.</p><p><b>METHODS</b>This was a prospective cross-sectional survey from December 1, 2015 to January 31, 2016 in all provinces/municipalities of the mainland of China. The primary outcome of this study was the incidence of sepsis, and the secondary outcome was its etiology in China. Patients with sepsis admitted to the Intensive Care Units were included in this study. The demographic, physiological, bacteriological, and therapeutic data of these patients were recorded. The incidence of sepsis was estimated using the data from the sixth census in China, reported by the Chinese National Health and Family Planning Commission and the National Bureau of Statistics as the standard population. The independent risk factors for increased mortality from sepsis were calculated.</p><p><b>CONCLUSIONS</b>This study indicated the incidence and outcome of sepsis in China. It also showed the most common etiology of different sites and types of infection, which could guide empiric antibiotic therapy. Moreover, it provided information on the independent risk factors for increased mortality due to sepsis. The findings provide evidence to guide clinical management and may help improve the outcome in septic patients.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov, NCT02448472; https://clinicaltrials.gov/show/NCT02448472.</p>

Physiological Correlation of Airway Pressure and Transpulmonary Pressure Stress Index on Respiratory Mechanics in Acute Respiratory Failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Stress index at post-recruitment maneuvers could be a method of positive end-expiratory pressure (PEEP) titration in acute respiratory distress syndrome (ARDS) patients. However, airway pressure (Paw) stress index may not reflect lung mechanics in the patients with high chest wall elastance. This study was to evaluate the Pawstress index on lung mechanics and the correlation between Pawstress index and transpulmonary pressure (PL) stress index in acute respiratory failure (ARF) patients.</p><p><b>METHODS</b>Twenty-four ARF patients with mechanical ventilation (MV) were consecutively recruited from July 2011 to April 2013 in Zhongda Hospital, Nanjing, China and Ospedale S. Giovanni Battista-Molinette Hospital, Turin, Italy. All patients underwent MV with volume control (tidal volume 6 ml/kg) for 20 min. PEEP was set according to the ARDSnet study protocol. The patients were divided into two groups according to the chest wall elastance/respiratory system elastance ratio. The high elastance group (H group, n = 14) had a ratio ≥30%, and the low elastance group (L group, n = 10) had a ratio <30%. Respiratory elastance, gas-exchange, Pawstress index, and PLstress index were measured. Student's t-test, regression analysis, and Bland-Altman analysis were used for statistical analysis.</p><p><b>RESULTS</b>Pneumonia was the major cause of respiratory failure (71.0%). Compared with the L group, PEEP was lower in the H group (5.7 ± 1.7 cmH2O vs. 9.0 ± 2.3 cmH2O, P < 0.01). Compared with the H group, lung elastance was higher (20.0 ± 7.8 cmH2O/L vs. 11.6 ± 3.6 cmH2O/L, P < 0.01), and stress was higher in the L group (7.0 ± 1.9 vs. 4.9 ± 1.9, P = 0.02). A linear relationship was observed between the Pawstress index and the PLstress index in H group (R2 = 0.56, P < 0.01) and L group (R2 = 0.85, P < 0.01).</p><p><b>CONCLUSION</b>In the ARF patients with MV, Pawstress index can substitute for PLto guide ventilator settings.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov NCT02196870 (https://clinicaltrials.gov/ct2/show/NCT02196870).</p>

Hepatic Perfusion Alterations in Septic Shock Patients: Impact of Early Goal-directed Therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Early goal-directed therapy (EGDT) has become an important therapeutic management in early salvage stage of septic shock. However, splenic organs possibly remained hypoperfused and hypoxic despite fluid resuscitation. This study aimed to evaluate the effect of EGDT on hepatic perfusion in septic shock patients.</p><p><b>METHODS</b>A prospective observational study was carried out in early septic shock patients who were admitted to Intensive Care Unit within 24 h after onset and who met all four elements of the EGDT criteria after treatment with the standard EGDT procedure within 6 h between December 1, 2012 and November 30, 2013. The hemodynamic data were recorded, and oxygen metabolism and hepatic functions were monitored. An indocyanine green clearance test was applied to detect the hepatic perfusion. The patients' characteristics were compared before treatment (T0), immediately after EGDT (T1), and 24 h after EGDT (T2). This study is registered at ClinicalTrials.org, NCT02060773.</p><p><b>RESULTS</b>Twenty-one patients were included in the study; however, the hepatic perfusion data were not included in the analysis for two patients; therefore, 19 patients were eligible for the study. Hemodynamics data, as monitored by pulse-indicator continuous cardiac output, were obtained from 16 patients. There were no significant differences in indocyanine green plasma disappearance rate (ICG-PDR) and 15-min retention rate (R15) at T0 (11.9 ± 5.0%/min and 20.0 ± 13.2%), T1 (11.4 ± 5.1%/min and 23.6 ± 14.9%), and T2 (11.0 ± 4.5%/min and 23.7 ± 15.3%) (all P > 0.05). Both of the alterations of ICG-PDR and R15 showed no differences at T0, T1, and T2 in the patients of different subgroups that achieved different resuscitation goal numbers when elected (P > 0.05).</p><p><b>CONCLUSION</b>There were no hepatic perfusion improvements after EGDT in the early phase of patients with septic shock.</p><p><b>TRIAL REGISTRATION</b>Clinicaltrials.gov NCT02060773 (https://clinicaltrials.gov/ct2/show/NCT02060773).</p>

Effect of early goal directed therapy on tissue perfusion in patients with septic shock / 世界急诊医学杂志（英文）

@#BACKGROUND: This study aimed to observe the effect of early goal directed therapy (EGDT) on tissue perfusion, microcirculation and tissue oxygenation in patients with septic shock. METHODS: Patients with early septic shock (<24 hours) who had been admitted to the ICU of Zhongda Hospital Affiliated to Southeast University from September 2009 through May 2011 were enrolled (research time: 12 months), and they didn't meet the criteria of EGDT. Patients who had one of the following were excluded: stroke, brain injury, other types of shock, severe heart failure, acute myocardial infarction, age below 18 years, pregnancy, end-stage disease, cardiac arrest, extensive burns, oral bleeding, difficulty in opening the mouth, and the onset of septic shock beyond 24 hours. Patients treated with the standard protocol of EGDT were included. Transcutaneous pressure of oxygen and carbon dioxide (PtcO2, PtcCO2) were monitored and hemodynamic measurements were obtained. Side-stream dark field (SDF) imaging device was applied to obtain sublingual microcirculation. Hemodynamics, tissue oxygen, and sublingual microcirculation were compared before and after EGDT. If the variable meets the normal distribution, Student's t test was applied. Otherwise, Wilcoxon's rank-sum test was used. Correlation between variables was analyzed with Pearson's product-moment correlation coefficient method. RESULTS: Twenty patients were involved, but one patient wasn't analyzed because he didn't meet the EGDT criteria. PtcO2 and PtcCO2 were monitored in 19 patients, of whom sublingual microcirculation was obtained. After EGDT, PtcO2 increased from 62.7±24.0 mmHg to 78.0±30.9 mmHg (P<0.05) and tissue oxygenation index (PtcO2/FiO2) was 110.7±60.4 mmHg before EGDT and 141.6±78.2 mmHg after EGDT (P<0.05). The difference between PtcCO2 and PCO2 decreased significantly after EGDT (P<0.05). The density of perfused small vessels (PPV) and microcirculatory flow index of small vessels (MFI) tended to increase, but there were no significant differences between them (P>0.05). PtcO2, PtcO2/FiO2, and PtcCO2 were not linearly related to central venous saturation, lactate, oxygen delivery, and oxygen consumption (P>0.05). CONCLUSION: Peripheral perfusion was improved after EGDT in patients with septic shock, and it was not exactly reflected by the index of systemic perfusion.

Computer-driven automated weaning reduces weaning duration in difficult-to-wean patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Weaning difficulties occur in 31% of total intubated patients, and result in prolonged weaning duration. A computer-driven automated weaning system can perform a spontaneous breathing trial (SBT) automatically and display a message when the trial is successfully passed. Such a system might have a beneficial effect on difficult-to-wean patients. The aim of this study was to examine whether the computer-driven automated weaning system can accelerate discontinuation of mechanical ventilation and improve outcomes in difficult-to-wean patients.</p><p><b>METHODS</b>This randomized controlled study included 39 difficult-to-wean patients who failed their first spontaneous breathing trial. Before initiating weaning, eligible patients were randomly allocated to wean by computer-driven automated weaning system (CDW group, n = 19) or a physician-controlled local protocol (PW group, n = 20). Weaning duration, defined as the time from inclusion until first extubation, was the primary endpoint. Secondary endpoints were total duration of mechanical ventilation, the length of intensive care unit (ICU) stay, the number of reintubations, the mortality rate in the ICU, the number of noninvasive ventilations, the number of complications in the ICU, and the number of ventilator-associated pneumonia cases.</p><p><b>RESULTS</b>The weaning duration was reduced with the computer-driven weaning as compared with the usual protocol (median 29.0 hours vs. 45.5 hours, P = 0.044). Total duration of mechanical ventilation and duration of the ICU stay did not differ between the CDW and PW groups. There was no difference in the number of reintubations between the CDW and PW groups (3 and 4 patients, P = 0.732). The study groups showed comparable numbers of tracheostomy, self-extubations, ventilator-associated pneumonia, and non-invasive ventilation. Mortality in the ICU was similar in the CDW and the PW groups (21.1% vs. 20.0%, P = 0.935).</p><p><b>CONCLUSION</b>The computer-driven automated weaning system can reduce weaning duration in difficult-to-wean patients as compared with a physician-controlled weaning protocol.</p>

Changes in arterial blood pressure induced by passive leg raising predict hypotension during the induction of sedation in critically ill patients without severe cardiac dysfunction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypotension due to the induction of sedation with dexmedetomidine infusion may be harmful in critically ill patients. Changes in pulse pressure induced by the passive leg raising test (PLR-ΔPP) as marker of fluid responsiveness, assessed prior to sedation, may predict hemodynamic changes. The present study was to investigate the power of the PLR test in critically ill patients in predicting hypotension induced by the induction of dexmedetomidine sedation.</p><p><b>METHODS</b>Fluid responsiveness was estimated by a passive leg raising (PLR) test before dexmedetomidine sedation. Patients were assigned to either the "Nonresponders" or "Responders" group according to their hemodynamic responses to the PLR test ("Nonresponders", PLR-ΔPP < 10.3%; "Responders", PLR-ΔPP ≥ 10.3%). Sedation was performed with a dexmedetomidine infusion (0.5 µg/kg over a 10-minute loading period, then 0.2 - 0.7 µg×kg(-1)×h(-1)) and titrated to maintain the target Richmond agitation sedation scale (RASS) score in the range of -2 to -1 and the bispectral index value in the range of 60 to 75. Radial artery pulse pressure, heart rate (HR), and central venous pressure (CVP) were measured at each phase of the study procedure. Hemodynamic fluctuations during the use of dexmedetomidine sedation were recorded and compared between the two groups.</p><p><b>RESULTS</b>Fifty patients had a median (25% - 75% interquartile range) of 71 (61 - 78) years old were studied. At baseline, 39 of the 50 patients were "Nonresponders" and 11 were "Responders". Following dexmedetomidine sedation, patients classified as "Responders" had a significantly greater systolic blood pressure decrease during the induction of dexmedetomidine sedation than the "Nonresponders" ((-26.3 ± 6.8)% vs. -11.8 ± 8.5)%, P < 0.001). In addition, the "Responders" group required significantly more fluid boluses (8 vs. 3; P < 0.001) and vasopressors (2 vs. 0; P < 0.05) than the "Nonresponders" group to restore blood pressure. Finally, PLR-ΔPP was positively correlated with changes in systolic blood pressure (PLR-ΔSBP) (r(2) = 0.576; P < 0.001) and significantly correlated with dexmedetomidine infusion-induced changes in SBP (r(2) = 0.202; P < 0.05). AUC for PLR-ΔPP was 0.84 (95%CI 0.71 - 0.93). PLR-ΔPP predicted hypotension with a sensitivity of 73% and a specificity of 92%.</p><p><b>CONCLUSIONS</b>The fluid responsiveness assessment pre-sedation was found to predict blood pressure fluctuation during the induction of dexmedetomidine sedation. The PLR test conducted prior to sedation may be a useful tool to identify patients with a high risk of hemodynamic events and may be used to indicate the need for prophylactic treatment.</p>

Positive end expiratory pressure titrated by transpulmonary pressure improved oxygenation and respiratory mechanics in acute respiratory distress syndrome patients with intra-abdominal hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intra-abdominal hypertension (IAH) is common in acute respiratory distress syndrome (ARDS) patients and when resulting in decrease of chest wall compliance will weaken the effect of positive end expiratory pressure (PEEP). We investigated the effect of PEEP titrated by transpulmonary pressure (Ptp) on oxygenation and respiratory mechanics in ARDS patients with IAH compared with PEEP titrated by ARDSnet protocol.</p><p><b>METHODS</b>ARDS patients admitted to the intensive care unit (ICU) of the Zhongda Hospital were enrolled. Patients were ventilated with volume control mode with tidal volume of 6 ml/kg under two different PEEP levels titrated by Ptp method and ARDSnet protocol. Respiratory mechanics, gas exchange and haemodynamics were measured after 30 minutes of ventilation in each round. IAH was defined as intra-abdominal pressure of 12 mmHg or more.</p><p><b>RESULTS</b>Seven ARDS patients with IAH and 8 ARDS patients without IAH were enrolled. PEEP titrated by Ptp were significant higher than PEEP titrated by ARDSnet protocol in both ARDS patients with IAH ((17.3 ± 2.6) cmH2O vs. (6.3 ± 1.6) cmH2O and without IAH ((9.5 ± 2.1) cmH2O vs. (7.8 ± 1.9) cmH2O). Arterial pressure of O2/fraction of inspired oxygen (PaO2/FiO2) was much higher under PEEP titrated by Ptp when compared with PEEP titrated by ARDSnet protocol in ARDS patients with IAH ((27.2 ± 4.0) cmHg vs. (20.9 ± 5.0) cmHg. But no significant difference of PaO2/FiO2 between the two methods was found in ARDS patients without IAH. In ARDS patients with IAH, static compliance of lung and respiratory system were higher under PEEP titrated by Ptp than by ARDSnet protocol. In ARDS patients with IAH, central venous pressure (CVP) was higher during PEEP titrated by Ptp than by ARDSnet protocol.</p><p><b>CONCLUSION</b>Positive end expiratory pressure titrated by transpulmonary pressure was higher than PEEP titrated by ARDSnet protocol and improved oxygenation and respiratory mechanics in ARDS patients with IAH.</p>

Assessment of central venous-to-arterial CO(2) difference during early goal-directed therapy in patients with septic shock / 中华外科杂志

<p><b>OBJECTIVE</b>To detect the changes of central venous-to-arterial carbon dioxide difference (P(cv-a)CO(2)) during early goal-directed therapy (EGDT) in patients with septic shock and evaluate its' value in predicting adequate resuscitation and prognosis.</p><p><b>METHODS</b>From April 2009 to October 2010, 26 septic shock patients were enrolled in the study. EGDT was performed in all the patients immediately after enrollment. According to the whether they achieved early goal with in the 6 hour or not, patients were separated to EGDT achievement and un-achievement groups. At the onset and after the 6 hours EGDT, mean arterial pressure (MAP), cardiac index (CI), central venous oxygen saturation (ScvO(2)), oxygen delivery (DO(2)), oxygen consumption (VO(2)), oxygen extraction ratio (O(2) ext), lactate, P(cv-a)CO(2) were recorded. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and 28 day mortality were compared between 2 groups.</p><p><b>RESULTS</b>There were no significant difference of age and sex between the 15 patients who achieved early goals and 11 patients who did not. EGDT un-achievement patients had higher APACHE II score (21 ± 5) and 28 day mortality (9/11) when compared with EGDT achievement patients (t = 2.985, χ(2) = 4.547, P < 0.05). In EGDT un-achievement group, MAP, CI, DO(2), VO(2), O(2)ext, ScvO(2), Lac, P(cv-a)CO(2) were comparable between the onset and 6 hours after EGDT. However, in EGDT achievement group, MAP ((90 ± 9) mmHg (1 mmHg = 0.133 kPa)), CI ((4.0 ± 1.8) L×min(-1)×m(-2)), DO(2) ((596 ± 274) ml×min(-1)×m(-2)), ScvO(2) (76.9% ± 4.1%) increased, and P(cv-a)CO(2) ((4.2 ± 2.7) mmHg) decreased significantly after 6 hours of EGDT (t values were -3.393, -2.985, -2.103 and -3.195 respectively, all P < 0.05). The changes of P(cv-a)CO(2) between the onset and 6 hours after EGDT, demonstrated high value for predictability of outcome, according to the area under the ROC curve (AUC) was 0.839 (P = 0.004). As a predictor for death, increasing of P(cv-a)CO(2) after 6 hours of EGDT has a sensibility of 100% and specificity of 60%.</p><p><b>CONCLUSIONS</b>Increasing of P(cv-a)CO(2) after EGDT purports inadequate tissue perfusion in patients with septic shock. Changes of P(cv-a)CO(2) during EGDT demonstrated a useful tool to evaluate adequate resuscitation and prognosis.</p>

Effects of pulmonary stretch reflex on lung injury in rabbits with acute respiratory distress syndrome / 世界急诊医学杂志（英文）

BACKGROUND: Pulmonary stretch reflex plays an important role in regulation of respiratory movement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury in rabbits with acute respiratory distress syndrome (ARDS). METHODS: ARDS rabbits were given intratracheal infusion of hydrochloric acid and ventilated with neurally adjusted ventilatory assistance (NAVA) with a tidal volume (VT) of 6 mL/kg and the electrical activity of diaphragm (EAdi)-determined positive end expiratory pressure. After isolation of the bilateral vagusnerve trunk, the rabbits were randomized into two groups: sham operation (SHAM) group (n=5) and bilateral vagotomy (VAG) group (n=5). Gas exchange and respiratory mechanics were detected at baseline, after lung injury and 1, 2, and 3 hours after ventilation respectively. Pulmonary permeability index, pathological changes and inflammatory response were also measured. RESULTS: Compared with the SHAM group, PaO2/FiO2 in the VAG group decreased significantly 2 and 3 hours after ventilation (P<0.05). There was no significant difference in PaCO2 between the SHAM and VAG groups (P>0.05), and the VAG group had a high VT, peak pressure (Ppeak), and mean pressure (Pm) compared with the SHAM group 1, 2, 3 hours after ventilation (P<0.05). Compared to the SHAM group, dead space fraction (VD/VT) and respiratory system elastance (Ers) in the VAG group increased (P<0.05) and static pulmonary compliance (Cst) decreased markedly (P<0.05) after ventilation for 3 hours. Lung wet/dry weight ratio (W/D) (8.4±1.2 vs. 6.6±1.0), lung injury score (6.3±1.8 vs. 3.8±1.3), tumor necrosis factor-α (TNF-α) (779±372 pg/mL vs. 355±130 pg/mL) and interleukin-8 (IL-8) (169±21 pg/mL vs. 118±17 pg/mL) increased significantly in the VAG group compared with the SHAM group (P<0.05). CONCLUSION: Lung injury is aggravated after bilateral vagotomy, demonstrating that pulmonary stretch reflex may have protective effect on the lung.

Effect of post recruitment maneuver ventilation by different tidal volume on lung vascular endothelial diastole function in rats with acute lung injury / 世界急诊医学杂志（英文）

@#BACKGROUND: This study aimed to observe the effect of recruitment maneuver (RM) and post-RM ventilation at different tidal volume on lung vascular diastole endothelial function in rats with acute lung injury (ALI). METHODS: A ALI rat model was produced by intravenous infusion of lipopolysaccharide (6 mg/kg). Twenty-five rats were randomly divided into five groups: control group (n=5), ALI group (n=5), low tidal volume group (LV group, VT 6 mL/kg, n=5), sustained inflation (SI) with low tidal volume group (SI+LV group, VT 6 mL/kg, n=5), and SI with moderate tidal volume group (SI+MV group, VT 12 mL/kg, n=5). RM was performed with SI, airway pressure 30 cmH2O for 30 seconds, and positive end-expiratory pressure (PEEP) was set to 5 cmH2O. Lung tissue was taken after 5 hours of mechanical ventilation. Mean arterial blood pressure (MAP) was monitored during the experiment. Endothelin-1 (ET-1), endothelial nitricoxide synthase (eNOS), Ach-induced endothelium-dependent relaxation response of isolated pulmonary artery rings were determined at 5 hours. RESULTS: LPS increased ET-1 level, decreased the expression of eNOS in lung tissue, impaired the Ach-induced endothelium-dependent relaxation response in the pulmonary artery, without obvious effect on systemic hemodynamics. SI+LV significantly reduced LPS-induced elevation of ET-1 level, increased the expression of eNOS, significantly improved endothelial dysfunction, and improved the dysfunction of endothelium-dependent relaxation in the pulmonary artery. CONCLUSIONS: RM with a high or low tidal volume ventilation could improve the lung vascular endothelial function of rats with acute lung injury, and RM with low tidal volume ventilation could lower significantly the injury of lung vascular endothelial diastole function in rats with acute lung injury.

Passive leg raising predicts volume responsiveness in patients with septic shock / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the hemodynamic response to passive leg raising (PLR) indicates fluid responsiveness in patients with septic shock.</p><p><b>METHODS</b>Twenty patients with septic shock, considered for fluid challenge (FC), were enrolled in the study from June 2009 to May 2010. Hemodynamic changes were determined by pulse-contour derived cardiac index at baseline, before and after PLR, return to baseline for 10 min, before and after fluid challenge (250 ml saline for 10 min). An increase of SV after fluid challenge (FC-ΔSV) ≥ 10% were defined responders.</p><p><b>RESULTS</b>Twenty patients with septic shock were included in the study. PLR and fluid challenge were performed 46 instances, among which 15 instances were defined as response group. SV and pulse pressure induced by PLR (PLR-ΔSV and PLR-ΔPP) were increased significantly in response group [(76 ± 19) ml vs. (65 ± 18) ml, (73 ± 20) mmHg vs. (62 ± 20) mmHg (1 mmHg = 0.133 kPa), P < 0.05], while in nonresponse group there were no significant change. PLR-ΔSV and PLR-ΔPP were correlated with FC-ΔSV (r = 0.51, P = 0.001; r = 0.45, P = 0.006), central venous pressure (CVP) were unrelated with FC-ΔSV. Area under curve (AUC) for PLR-ΔSV, PLR-ΔPP and stroke volume variation (SVV) were 0.846, 0.791 and 0.708. PLR-ΔSV ≥ 12.5% predicted fluid responsiveness with sensitivity of 80% and specificity of 93.5%. PLR-ΔPP ≥ 9.5% predicted fluid responsiveness with sensitivity of 73.3% and specificity of 83.9%.</p><p><b>CONCLUSIONS</b>PLR-ΔSV and PLR-ΔPP can predict fluid responsiveness in patients with septic shock. PLR-ΔSV and PLR-ΔPP have a greater ability in predicting volume responsiveness than CVP and SVV.</p>

Effects of different reference point on intra-abdominal pressure measurement in critically ill patients: a clinical trial / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of different reference point on intra-abdominal pressure (IAP) measurement.</p><p><b>METHODS</b>Nine critically ill patients with risk of intra-abdominal hypertension (IAH) were studied from July 2008 to June 2010, all of the patients were equipped with abdominal cavity drain and urinary drainage tube. By which IAP was measured using direct and indirect methods respectively. The symphysis pubis, phlebostatic axis and the midaxillary line at the level of the iliac crest were defined as reference points. According to the different reference point, three sets of IAP measurements were obtained in the supine position with each method and kept as IAP(S), IAP(P), IAP(I). Bland-Altman method analysis and Pearson's correlation were performed to evaluate the relationships between results from different reference points with direct and indirect methods. Paired t-test was performed to evaluate the differences among different reference points.</p><p><b>RESULTS</b>Sixty measurements of IAP(S), IAP(P) and IAP(I) were obtained. In direct measurement through abdominal cavity drain, IAP(I) (13.8 ± 3.9) mmHg (1 mmHg = 0.133 kPa) was significantly higher than IAP(P) (12.8 ± 3.6) mmHg and IAP(S) (9.1 ± 3.6) mmHg, P < 0.05; while in indirect measurement through urinary drainage tube, IAP(I) (12.7 ± 3.2) mmHg was significantly higher than IAP(P) (11.7 ± 2.9) mmHg and IAP(S) (7.9 ± 3.0) mmHg too, P < 0.05. In either direct or indirect method, IAP(P) was higher than IAP(S), P < 0.05. And good correlations were found among IAP(S), IAP(P) and IAP(I).</p><p><b>CONCLUSIONS</b>In the supine position, pressure obtained via the bladder could reflect authentic IAP. But selection of reference point has great impact on IAP measurement.</p>

Timing of tracheotomy on the prognosis of patients with prolonged mechanical ventilation: a meta-analysis of randomized controlled trials / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of timing of tracheotomy on the prognosis of prolonged mechanically ventilated patients.</p><p><b>METHODS</b>Randomized controlled trials (RCTs) that studied the effect of timing of tracheotomy on the prognosis of prolonged mechanically ventilated patients were searched from Pubmed, Embase, The Cochrane Library, CBM during January 1990 to June 2010. The quality of the RCTs was evaluated. Meta-analysis of timing of tracheotomy on the prognosis of prolonged mechanically ventilated patients were conducted using the methods recommended by the Cochrane Collaboration. Definition of early tracheotomy was the patients performed tracheotomy during 10 days after admission to hospital or ICU, mechanical ventilation or intubation. Late tracheotomy was defined tracheotomy performed beyond 10 days of admission to hospital or ICU, mechanical ventilation or intubation; or those mechanically ventilated through intubation all the time.</p><p><b>RESULTS</b>Eight hundred and twenty eight patients, 411 in early tracheotomy group and 417 in late tracheotomy group, from 6 RCTs were included in the analysis of data. The meta-analysis showed that early tracheotomy could reduce mortality of patients (RR: 0.81, 95%CI: 0.66 - 0.99, P = 0.04); but it didn't significantly alter the incidence of pneumonia (RR:0.89, 95%CI: 0.68 - 1.17, P = 0.41), mechanical ventilation days (mean difference: -2.19, 95%CI: -9.86 - 5.49, P = 0.58) and length of ICU stay (mean difference: -5.65, 95%CI: -17.11 - 5.81, P = 0.33).</p><p><b>CONCLUSIONS</b>In critically ill adult patients who require prolonged mechanical ventilation, early tracheotomy performed at an earlier stage reduces the mortality, but doesn't reduce the incidence of pneumonia and shorten the mechanical ventilation days and ICU length of stay. But more high quality RCTs are required to confirm it.</p>