PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma: A case report.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT): A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome.

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H2O (ΔCollapse24-6). Patients were classified as low, medium, or high recruiters on the basis of tertiles of ΔCollapse24-6. Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H2O for low versus medium versus high recruitability (P < 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H2O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension. Clinical trial registered with www.clinicaltrials.gov (NCT04460859).

Ineffective Effort in Patients With Acute Brain Injury Undergoing Invasive Mechanical Ventilation.

BACKGROUND: Ineffective effort (IE) is a frequent patient-ventilator asynchrony in invasive mechanical ventilation. This study aimed to investigate the incidence of IE and to explore its relationship with respiratory drive in subjects with acute brain injury undergoing invasive mechanical ventilation. METHODS: We retrospectively analyzed a clinical database that assessed patient-ventilator asynchrony in subjects with acute brain injury. IE was identified based on airway pressure, flow, and esophageal pressure waveforms collected at 15-min intervals 4 times daily. At the end of each data set recording, airway-occlusion pressure (P0.1) was determined by the airway occlusion test. IE index was calculated to indicate the severity of IE. The incidence of IE in different types of brain injuries as well as its relationship with P0.1 was determined. RESULTS: We analyzed 852 data sets of 71 subjects with P0.1 measured and undergoing mechanical ventilation for at least 3 d after enrollment. IE was detected in 688 (80.8%) data sets, with a median index of 2.2% (interquartile range 0.4-13.1). Severe IE (IE index ≥ 10%) was detected in 246 (28.9%) data sets. The post craniotomy for brain tumor and the stroke groups had higher median IE index and lower P0.1 compared with the traumatic brain injury group (2.6% [0.7-9.7] vs 2.7% [0.3-21] vs 1.2% [0.1-8.5], P = .002; 1.4 [1-2] cm H2O vs 1.5 [1-2.2] cm H2O vs 1.8 [1.1-2.8] cm H2O, P = .001). Low respiratory drive (P0.1 < 1.14 cm H2O) was independently associated with severe IE in the expiratory phase (IEE) even after adjusting for confounding factors by logistic regression analysis (odds ratio 5.18 [95% CI 2.69-10], P < .001). CONCLUSIONS: IE was very common in subjects with acute brain injury. Low respiratory drive was independently associated with severe IEE.

Incidence, Risk Factors and Outcomes of Sepsis in Critically Ill Post-craniotomy Patients: A Single-Center Prospective Cohort Study.

Background: Data concerning the epidemiology of sepsis in critically ill post-craniotomy patients are scarce. This study aimed to assess the incidence, risk factors, and outcomes of sepsis in this population. Methods: This was a single-center prospective cohort study. Post-craniotomy patients admitted to the intensive care unit (ICU) were screened daily for the presence of infection and sepsis. Results: Of the 900 included patients, 300 developed sepsis. The cumulative incidence of sepsis was 33.3% [95% confidence interval (CI), 30.2-36.4%]. Advanced age, male, hypertension, trauma, postoperative intracranial complications, and lower Glasgow Coma Scale (GCS) on the first postoperative day were independent risk factors of sepsis. Septic patients had higher hospital mortality (13.7 vs. 8.3%, P = 0.012), longer ICU length of stay (LOS) (14 vs. 4 days, P < 0.001), longer hospital LOS (31 vs. 19 days, P < 0.001), and higher total medical cost (CNY 138,394 vs. 75,918, P < 0.001) than patients without sepsis. Conclusion: Sepsis is a frequent complication in critically ill post-craniotomy patients. Advanced age, male, hypertension, trauma, postoperative intracranial complications, and lower GCS on the first postoperative day were independent risk factors of sepsis.

Partition of respiratory mechanics in patients with acute respiratory distress syndrome and association with outcome: a multicentre clinical study.

PURPOSE: In acute respiratory distress syndrome (ARDS), physiological parameters associated with outcome may help defining targets for mechanical ventilation. This study aimed to address whether transpulmonary pressures (PL), including transpulmonary driving pressure (DPL), elastance-derived plateau PL, and directly-measured end-expiratory PL, are better associated with 60-day outcome than airway driving pressure (DPaw). We also tested the combination of oxygenation and stretch index [PaO2/(FiO2*DPaw)]. METHODS: Prospective, observational, multicentre registry of ARDS patients. Respiratory mechanics were measured early after intubation at 6 kg/ml tidal volume. We compared the predictive power of the parameters for mortality at day-60 through receiver operating characteristic (ROC) and assessed their association with 60-day mortality through unadjusted and adjusted Cox regressions. Finally, each parameter was dichotomized, and Kaplan-Meier survival curves were compared. RESULTS: 385 patients were enrolled 2 [1-4] days from intubation (esophageal pressure and arterial blood gases in 302 and 318 patients). As continuous variables, DPaw, DPL, and oxygenation stretch index were associated with 60-day mortality after adjustment for age and Sequential Organ Failure Assessment, whereas elastance-derived plateau PL was not. DPaw and DPL performed equally in ROC analysis (P = 0.0835). DPaw had the best-fit Cox regression model. When dichotomizing the variables, DPaw ≥ 15, DPL ≥ 12, plateau PL ≥ 24, and oxygenation stretch index < 10 exhibited lower 60-day survival probability. Directly measured end-expiratory PL ≥ 0 was associated with better outcome in obese patients. CONCLUSION: DPL was equivalent predictor of outcome than DPaw. Our study supports the soundness of limiting lung and airway driving pressure and maintaining positive end-expiratory PL in obese patients.

A U-shaped association of tracheostomy timing with all-cause mortality in mechanically ventilated patients admitted to the intensive care unit: A retrospective cohort study.

Objectives: To evaluate the association of tracheostomy timing with all-cause mortality in patients with mechanical ventilation (MV). Method: It's a retrospective cohort study. Adult patients undergoing invasive MV who received tracheostomy during the same hospitalization based on the Medical Information Mart for Intensive Care-III (MIMIC-III) database, were selected. The primary outcome was the relationship between tracheostomy timing and 90-day all-cause mortality. A restricted cubic spline was used to analyze the potential non-linear correlation between tracheostomy timing and 90-day all-cause mortality. The secondary outcomes included free days of MV, incidence of ventilator-associated pneumonia (VAP), free days of analgesia/sedation in the intensive care unit (ICU), length of stay (LOS) in the ICU, LOS in hospital, in-ICU mortality, and 30-day all-cause mortality. Results: A total of 1,209 patients were included in this study, of these, 163 (13.5%) patients underwent tracheostomy within 4 days after intubation, while 647 (53.5%) patients underwent tracheostomy more than 11 days after intubation. The tracheotomy timing showed a U-shaped relationship with all-cause mortality, patients who underwent tracheostomy between 5 and 10 days had the lowest 90-day mortality rate compared with patients who underwent tracheostomy within 4 days and after 11 days [84 (21.1%) vs. 40 (24.5%) and 206 (31.8%), P < 0.001]. Conclusion: The tracheotomy timing showed a U-shaped relationship with all-cause mortality, and the risk of mortality was lowest on day 8, but a causal relationship has not been demonstrated.

Development of an early prediction model for postoperative delirium in neurosurgical patients admitted to the ICU after elective craniotomy (E-PREPOD-NS): A secondary analysis of a prospective cohort study.

Postoperative delirium (POD) is a significant clinical problem in neurosurgical patients after intracranial surgery. Identification of high-risk patients may optimize perioperative management, but an adequate risk model for use at early phase after operation has not been developed. In the secondary analysis of a prospective cohort study, 800 adult patients admitted to the ICU after elective intracranial surgeries were included. The POD was diagnosed as Confusion Assessment Method for the ICU positive on postoperative day 1 to 3. Multivariate logistic regression analysis was used to develop early prediction model (E-PREPOD-NS) and the final model was validated with 200 bootstrap samples. The incidence of POD in this cohort was19.6%. We identified nine variables independently associated with POD in the final model: advanced age (OR 3.336, CI 1.765-6.305, 1 point), low education level (OR 2.528, 1.446-4.419, 1), smoking history (OR 2.582, 1.611-4.140, 1), diabetes (OR 2.541, 1.201-5.377, 1), supra-tentorial lesions (OR 3.424, 2.021-5.802, 1), anesthesia duration > 360 min (OR 1.686, 1.062-2.674, 0.5), GCS < 9 at ICU admission (OR 6.059, 3.789-9.690, 1.5), metabolic acidosis (OR 13.903, 6.248-30.938, 2.5), and neurosurgical drainage tube (OR 1.924, 1.132-3.269, 0.5). The area under the receiver operator curve (AUROC) of the risk score for prediction of POD was 0.865 (95% CI 0.835-0.895). The AUROC was 0.851 after internal validation (95% CI 0.791-0.912). The model showed good calibration. The E-PREPOD-NS model can predict POD in patients admitted to the ICU after elective intracranial surgery with good accuracy. External validation is needed in the future.

Features of CT and EUS in mesenteric plexiform neurofibroma with Neurofibromatosis type I: A case report.

Plexiform neurofibroma(PNF) is a rare benign tumor of the peripheral nerve, belonging to a subtype of neurofibroma. PNF is common in the head, neck and trunk. It is uncommonly observed in the mesentery. We report a case of mesenteric PNF in a 64-year-old man history of neurofibromatosis type I(NF1), which caused abdomen pain. In addition, the computer tomography(CT) and endoscopic ultrasonography(EUS) manifestations of mesenteric PNF were analyzed. The imaging appearance of a mesenteric plexiform neurofibroma is that many low-density (CT) /mixed echo (EUS) soft tissue masses surrounding the superior mesenteric artery, but not surrounding the superior mesenteric vein. Our case adds to the limited literature regarding NF1 presenting with mesenteric PNF. The computer tomography and endoscopic ultrasonography may facilitate confirma diagnosis of mesenteric PNF.

Role of a successful spontaneous breathing trial in ventilator liberation in brain-injured patients.

BACKGROUND: Spontaneous breathing trials (SBTs) have been shown to improve outcomes in critically ill patients. However, in patients with brain injury, indications for intubation and mechanical ventilation are different from those of non-neurological patients, and the role of an SBT in patients with brain injury is less established. The aim of the present study was to compare key respiratory variables acquired during a successful SBT between patients with successful ventilator liberation versus failed ventilator liberation. METHODS: In this prospective study, patients with brain injury (≥18 years of age), who completed a 30-min SBT, were enrolled. Airway pressure, flow, esophageal pressure, and diaphragm electrical activity (ΔEAdi) were recorded before (baseline) and during the SBT. Respiratory rate (RR), tidal volume, inspiratory muscle pressure (ΔPmus), ΔEAdi, and neuromechanical efficiency (ΔPmus/ΔEAdi) of the diaphragm were calculated breath by breath and compared between the liberation success and failure groups. Failed liberation was defined as the need for invasive ventilator assistance within 48 h after the SBT. RESULTS: In total, 46 patients (51.9±13.2 years, 67.4% male) completed the SBT. Seventeen (37%) patients failed ventilator liberation within 48 h. Another 11 patients required invasive ventilation within 7 days after completing the SBT. There were no differences in baseline characteristics between the success and failed groups. In-depth analysis showed similar changes in patterns and values of respiratory physiological parameters between the groups. CONCLUSIONS: In patients with brain injury, ventilator liberation failure was common after successful SBT. In-depth physiological analysis during the SBT did not provide data to predict successful liberation in these patients. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (No. NCT02863237).

Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients.

BACKGROUND: In patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity. METHODS: Prospective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering. RESULTS: Seventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0-50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering. CONCLUSION: Low levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity. Trial Registration ClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.

The impact of tracheostomy timing on clinical outcomes and adverse events in intubated patients with infratentorial lesions: early versus late tracheostomy.

We evaluated the association between the timing of tracheostomy and clinical outcomes in patients with infratentorial lesions. We performed a retrospective observational cohort study in a neurosurgical intensive care unit (ICU) at a tertiary academic medical center from January 2014 to December 2018. Consecutive adult patients admitted to the ICU who underwent resection of infratentorial lesions as well as tracheostomy were included for analysis. Early tracheostomy was defined as performed on postoperative days 1-10 and late tracheostomy on days 10-20 after operation. Univariate and multivariate analyses were used to compare the characteristics and outcomes between both cohorts. A total of 143 patients were identified, and 96 patients received early tracheostomy. Multivariable analysis identified early tracheostomy as an independent variable associated with lower occurrence of pneumonia (odds ratio, 0.25; 95% CI, 0.09-0.73; p = 0.011), shorter stays in ICUs (hazard ratio, 0.4; 95% CI, 0.3-0.6; p = 0.03), and earlier decannulation (hazard ratio, 0.5; 95% CI, 0.4-0.8; p = 0.003). However, no significant differences were observed between the early and late tracheostomy groups regarding hospital mortality (p > 0.999) and the modified Rankin scale after 6 months (p = 0.543). We also identified postoperative brainstem deficits, including cough, swallowing attempts, and extended tongue as well as GCS < 8 at ICU admission as the risk factors independently associated with patients underwent tracheostomy. There is a significant association between early tracheostomy and beneficial clinical outcomes or reduced adverse event occurrence in patients with infratentorial lesions.

Patient-ventilator asynchrony in acute brain-injured patients: a prospective observational study.

BACKGROUND: Patient-ventilator asynchrony is common in mechanically ventilated patients and may be related to adverse outcomes. Few studies have reported the occurrence of asynchrony in brain-injured patients. We aimed to investigate the prevalence, type and severity of patient-ventilator asynchrony in mechanically ventilated patients with brain injury. METHODS: This prospective observational study enrolled acute brain-injured patients undergoing mechanical ventilation. Esophageal pressure monitoring was established after enrollment. Flow, airway pressure, and esophageal pressure-time waveforms were recorded for a 15-min interval, four times daily for 3 days, for visually detecting asynchrony by offline analysis. At the end of each dataset recording, the respiratory drive was determined by the airway occlusion maneuver. The asynchrony index was calculated to represent the severity. The relationship between the prevalence and the severity of asynchrony with ventilatory modes and settings, respiratory drive, and analgesia and sedation were determined. Association of severe patient-ventilator asynchrony, which was defined as an asynchrony index ≥ 10%, with clinical outcomes was analyzed. RESULTS: In 100 enrolled patients, a total of 1076 15-min waveform datasets covering 330,292 breaths were collected, in which 70,156 (38%) asynchronous breaths were detected. Asynchrony occurred in 96% of patients with the median (interquartile range) asynchrony index of 12.4% (4.3%-26.4%). The most prevalent type was ineffective triggering. No significant difference was found in either prevalence or asynchrony index among different classifications of brain injury (p > 0.05). The prevalence of asynchrony was significantly lower during pressure control/assist ventilation than during other ventilatory modes (p < 0.05). Compared to the datasets without asynchrony, the airway occlusion pressure was significantly lower in datasets with ineffective triggering (p < 0.001). The asynchrony index was significantly higher during the combined use of opioids and sedatives (p < 0.001). Significantly longer duration of ventilation and hospital length of stay after the inclusion were found in patients with severe ineffective triggering (p < 0.05). CONCLUSIONS: Patient-ventilator asynchrony is common in brain-injured patients. The most prevalent type is ineffective triggering and its severity is likely related to a long duration of ventilation and hospital stay. Prevalence and severity of asynchrony are associated with ventilatory modes, respiratory drive and analgesia/sedation strategy, suggesting treatment adjustment in this particular population. Trial registration The study has been registered on 4 July 2017 in ClinicalTrials.gov (NCT03212482) ( https://clinicaltrials.gov/ct2/show/NCT03212482 ).

Derecruitment volume assessment derived from pressure-impedance curves with electrical impedance tomography in experimental acute lung injury.

OBJECTIVE: To investigate the accuracy of derecruitment volume (VDER) assessed by pressure-impedance (P-I) curves derived from electrical impedance tomography (EIT). METHODS: Six pigs with acute lung injury received decremental positive end-expiratory pressure (PEEP) from 15 to 0 in steps of 5 cmH2O. At the end of each PEEP level, the pressure-volume (P-V) curves were plotted using the low constant flow method and release maneuvers to calculate the VDER between the PEEP of setting levels and 0 cmH2O (VDER-PV). The VDER derived from P-I curves that were recorded simultaneously using EIT was the difference in impedance at the same pressure multiplied by the ratio of tidal volume and corresponding tidal impedance (VDER-PI). The regional P-I curves obtained by EIT were used to estimate VDER in the dependent and nondependent lung. RESULTS: The global lung VDER-PV and VDER-PI showed close correlations (r = 0.948, P<0.001); the mean difference was 48 mL with limits of agreement of -133 to 229 mL. Lung derecruitment extended into the whole process of decremental PEEP levels but was unevenly distributed in different lung regions. CONCLUSIONS: P-I curves derived from EIT can assess VDER and provide a promising method to estimate regional lung derecruitment at the bedside.

Aminoglycoside use and intensive care unit-acquired weakness: A systematic review and meta-analysis.

BACKGROUND: The relationship between aminoglycoside use and intensive care unit (ICU)-acquired weakness remains controversial. In the present study, we performed a systematic review and meta-analysis to examine the relationship between aminoglycoside use and ICU-acquired weakness in critically ill patients. METHODS: The PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Cumulative Index of Nursing and Allied Health Literature databases were searched from the earliest available date to July 10, 2019. Randomized controlled trials and prospective cohort studies examining the relationship between aminoglycosides and ICU-acquired weakness in adult ICU patients were included. Two authors independently screened titles/abstracts, reviewed full text and extracted data from the included studies. We performed the Meta-analysis using Stata version 15.0 and used the DerSimonian-Laird random effects model for data analyses. Heterogeneity was evaluated using the χ2 statistic and I2 statistic. Publication bias was evaluated with funnel plots qualitatively, the Begg's test and Egger's test quantitatively. RESULTS: Ten prospective cohort studies were included and analysed in this review. The overall effect sizes of the studies revealed a statistically significant relationship between aminoglycoside use and ICU-acquired weakness (OR, 2.06; 95%CI, 1.33-3.21; I2 = 56%). Subgroup and sensitivity analyses suggested a significant association between aminoglycoside use and studies limited to patients with clinical weakness (OR, 2.74; 95%CI, 1.83-4.10; I2 = 0%), and not to studies limited to patients with abnormal electrophysiology (OR, 1.78; 95%CI, 0.94-3.39; I2 = 59%), a large sample size (OR, 1.81; 95%CI, 0.97-3.39; I2 = 75%), or low risk of bias (OR, 1.59; 95%CI, 0.97-2.60; I2 = 56%); however, statistical heterogeneity was obvious. There were no significant publication biases found in the review. CONCLUSIONS: The review revealed a significant relationship between aminoglycoside use and ICU-acquired weakness.

Adenomyoma of the distal common bile duct demonstrated by endoscopic ultrasound: A case report and review of the literature.

BACKGROUND: Adenomyomatous hyperplasia of the distal common bile duct (CBD) is very rare, with only scarce case reports in the literature. Diagnosis is usually based on imaging findings, and endoscopic biopsy is very difficult before operation. It is believed that adenomyomatous hyperplasia has little or no risk of malignant transformation. CASE SUMMARY: A 68-year-old woman with abdominal pain in the right upper quadrant was referred to our hospital. Abdominal ultrasonography in the emergency ward revealed acute cholecystitis and dilated CBD. Laboratory findings showed elevated levels of transaminases, phosphatase, and γ-glutamyltranspeptidase. Pharmaceutical treatment for 3 d did not relieve the symptoms. Magnetic resonance cholangiopancreatography (MRCP) and computed tomography (CT) showed proximal bile duct dilatation but could not identify the cause. Endoscopic ultrasonography (EUS) demonstrated a mixed echogenic mass in the distal CBD. During surgery, a firm mass was found in the distal CBD and the Whipple procedure was performed with the initial concern of malignancy. Histology showed diffuse adenomyomatous hyperplasia. CONCLUSION: EUS may be a useful choice to diagnose adenomyoma of the distal CBD before operation, especially in patients with ambiguous MRCP/CT findings.

Additional Expiratory Resistance Elevates Airway Pressure and Lung Volume during High-Flow Tracheal Oxygen via Tracheostomy.

The standard high-flow tracheal (HFT) interface was modified by adding a 5-cm H2O/L/s resistor to the expiratory port. First, in a test lung simulating spontaneous breathing, we found that the modified HFT caused an elevation in airway pressure as a power function of flow. Then, three tracheal oxygen treatments (T-piece oxygen at 10 L/min, HFT and modified HFT at 40 L/min) were delivered in a random crossover fashion to six tracheostomized pigs before and after the induction of lung injury. The modified HFT induced a significantly higher airway pressure compared with that in either T-piece or HFT (p < 0.001). Expiratory resistance significantly increased during modified HFT (p < 0.05) to a mean value of 4.9 to 6.7 cm H2O/L/s. The modified HFT induced significant augmentation in end-expiratory lung volume (p < 0.05) and improved oxygenation for lung injury model (p = 0.038) compared with the HFT and T-piece. There was no significant difference in esophageal pressure swings, transpulmonary driving pressure or pressure time product among the three treatments (p > 0.05). In conclusion, the modified HFT with additional expiratory resistance generated a clinically relevant elevation in airway pressure and lung volume. Although expiratory resistance increased, inspiratory effort, lung stress and work of breathing remained within an acceptable range.

Use of the Bispectral Index to Predict Recovery of Consciousness in Patients with Spontaneous Intracerebral Hemorrhage After Surgical Hematoma Evacuation: A Prospective Cohort Study.

BACKGROUND Our study aimed to test the predictive value of the bispectral index (BIS) for the post-operational consciousness recovery in patients undergone hematoma evacuation due to spontaneous intracerebral hemorrhage (ICH). MATERIAL AND METHODS In this prospective cohort study, we enrolled adult spontaneous ICH patients after surgical hematoma evacuation who did not recover consciousness on the first postoperative day. After patient enrollment, the BIS was continuously monitored for 12 hours, and the motor response on the Glasgow Coma Scale (GCS-M) was evaluated. The patients were followed up for 30 days and divided into a consciousness recovery group and a nonrecovery group. Receiver operating characteristic curve analysis was performed to investigate the predictive values of the BIS, GCS-M and ICH score on the consciousness recovery. The area under the curve (AUC) and 95% confidence interval (95%CI) were calculated. During the 12-hour monitoring period, the peak BIS value after GCS-M stimulation was used for ROC analysis. RESULTS Of the 55 enrolled patients, 19 patients recovered consciousness, and 36 patients did not. The BIS value of the consciousness recovery group was significantly higher than that of the nonrecovery group (P<0.001). For consciousness recovery prediction, the AUC (95%CI) of the BIS values after external stimulation was 0.97 (0.91-1.00), which was superior to the GCS-M (0.75 [0.59-0.91]) and ICH score (0.57 [0.41-0.73]). CONCLUSIONS Our study demonstrates that BIS might be a potential tool for predicting the consciousness recovery in ICH patients undergone surgical hematoma evacuation.

Stress Index Can Be Accurately and Reliably Assessed by Visually Inspecting Ventilator Waveforms.

BACKGROUND: Stress index provides a noninvasive approach to detect injurious ventilation patterns and to personalize ventilator settings. Obtaining the stress index (SI), however, requires quantitatively analyzing the shape of pressure-time curve with dedicated instruments or a specific ventilator, which may encumber its clinical implementation. We hypothesized that the SI could be qualitatively determined through a visual inspection of ventilator waveforms. METHODS: Thirty-six adult subjects undergoing volume controlled ventilation without spontaneous breathing were enrolled. For each subject, 2 trained clinicians visually inspected the pressure-time curve directly from the ventilator screen. They then qualitatively categorized the shape of pressure-time curve as linear, a downward concavity, or an upward concavity at the bedside. We simultaneously recorded airway pressure and flow signals using a dedicated instrument. A quantitative off-line analysis was performed to calculate the SI using specific research software. This quantitative analysis of the SI served as the reference method for classifying the shape of the pressure-time curve (ie, linear, a downward concavity, or an upward concavity). We compared the SI categorized by visual inspection with that by the reference. RESULTS: We obtained 200 SI assessments of pressure-time curves, among which 125 (63%) were linear, 55 (27%) were a downward concavity, and 20 (10%) were an upward concavity as determined by the reference method. The overall accuracy of visual inspection and weighted kappa statistic (95% CI) was 93% (88-96%) and 0.88 (0.82-0.94), respectively. The sensitivity and specificity to distinguish a downward concavity from a linear shape were 91% and 98%, respectively. The respective sensitivity and specificity to distinguish an upward concavity from a linear shape were 95% and 95%. CONCLUSIONS: Visual inspection of the pressure-time curve on the ventilator screen is a simple and reliable approach to assess SI at the bedside. This simplification may facilitate the implementation of SI in clinical practice to personalize mechanical ventilation. (ClinicalTrials.gov registration NCT03096106.).