Skin mottling score assesses peripheral tissue hypoperfusion in critically ill patients following cardiac surgery.

BACKGROUND: Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. METHODS: Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. RESULTS: Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling. CONCLUSION: In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion.

Furosemide Responsiveness Predicts Acute Kidney Injury Progression After Cardiac Surgery.

BACKGROUND: As patients with acute kidney injury (AKI) progress to a higher stage, the risk for poor outcomes dramatically rises. Early identification of patients at high risk for AKI progression remains a major challenge. This study aimed to evaluate the value of furosemide responsiveness (FR) for predicting AKI progression in patients with initial mild and moderate AKI after cardiac surgery. METHODS: We performed 2 separate exploratory analyses. The Zhongshan cohort was a single-center, prospective, observational cohort, whereas the Beth Israel Deaconess Medical Center cohort was a single-center, retrospective cohort. We calculated 2 FR parameters for each patient, namely the FR index and modified FR index, defined as 2-hour urine output divided by furosemide dose (FR index, mL/mg/2 h) and by furosemide dose and body weight (modified FR index, mL/[mg·kg]/2 h), respectively. The primary outcome was AKI progression within 7 days. RESULTS: AKI progression occurred in 80 (16.0%) and 359 (11.3%) patients in the Zhongshan and Beth Israel Deaconess Medical Center cohorts, respectively. All FR parameters (considered continuously or in quartiles) were inversely associated with risk of AKI progression in both cohorts (all adjusted P < .01). The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models involving C-index, net reclassification improvement, and integrated discrimination improvement index in both cohorts (all P < .01). CONCLUSIONS: FR parameters were inversely associated with risk of AKI progression in patients with mild and moderate AKI after cardiac surgery. The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models.

Extracellular vesicles derived from CD4+ T cells carry DGKK to promote sepsis-induced lung injury by regulating oxidative stress and inflammation.

BACKGROUND: Sepsis is an abnormal immune response after infection, wherein the lung is the most susceptible organ to fail, leading to acute lung injury. To overcome the limitations of current therapeutic strategies and develop more specific treatment, the inflammatory process, in which T cell-derived extracellular vesicles (EVs) play a central role, should be explored deeply. METHODS: Liquid chromatography-tandem mass spectrometry was performed for serum EV protein profiling. The serum diacylglycerol kinase kappa (DGKK) and endotoxin contents of patients with sepsis-induced lung injury were measured. Apoptosis, oxidative stress, and inflammation in A549 cells, bronchoalveolar lavage fluid, and lung tissues of mice were measured by flow cytometry, biochemical analysis, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and western blot. RESULTS: DGKK, the key regulator of the diacylglycerol (DAG)/protein kinase C (PKC) pathway, exhibited elevated expression in serum EVs of patients with sepsis-induced lung injury and showed strong correlation with sepsis severity and disease progression. DGKK was expressed in CD4+ T cells under regulation of the NF-κB pathway and delivered by EVs to target cells, including alveolar epithelial cells. EVs produced by CD4+ T lymphocytes exerted toxic effects on A549 cells to induce apoptotic cell death, oxidative cell damage, and inflammation. In mice with sepsis induced by cecal ligation and puncture, EVs derived from CD4+ T cells also promoted tissue damage, oxidative stress, and inflammation in the lungs. These toxic effects of T cell-derived EVs were attenuated by the inhibition of PKC and NOX4, the downstream effectors of DGKK and DAG. CONCLUSIONS: This approach established the mechanism that T-cell-derived EVs carrying DGKK triggered alveolar epithelial cell apoptosis, oxidative stress, inflammation, and tissue damage in sepsis-induced lung injury through the DAG/PKC/NOX4 pathway. Thus, T-cell-derived EVs and the elevated distribution of DGKK should be further investigated to develop therapeutic strategies for sepsis-induced lung injury.

Early prediction of noninvasive ventilation failure after extubation: development and validation of a machine-learning model.

BACKGROUND: Noninvasive ventilation (NIV) has been widely used in critically ill patients after extubation. However, NIV failure is associated with poor outcomes. This study aimed to determine early predictors of NIV failure and to construct an accurate machine-learning model to identify patients at risks of NIV failure after extubation in intensive care units (ICUs). METHODS: Patients who underwent NIV after extubation in the eICU Collaborative Research Database (eICU-CRD) were included. NIV failure was defined as need for invasive ventilatory support (reintubation or tracheotomy) or death after NIV initiation. A total of 93 clinical and laboratory variables were assessed, and the recursive feature elimination algorithm was used to select key features. Hyperparameter optimization was conducted with an automated machine-learning toolkit called Neural Network Intelligence. A machine-learning model called Categorical Boosting (CatBoost) was developed and compared with nine other models. The model was then prospectively validated among patients enrolled in the Cardiac Surgical ICU of Zhongshan Hospital, Fudan University. RESULTS: Of 929 patients included in the eICU-CRD cohort, 248 (26.7%) had NIV failure. The time from extubation to NIV, age, Glasgow Coma Scale (GCS) score, heart rate, respiratory rate, mean blood pressure (MBP), saturation of pulse oxygen (SpO2), temperature, glucose, pH, pressure of oxygen in blood (PaO2), urine output, input volume, ventilation duration, and mean airway pressure were selected. After hyperparameter optimization, our model showed the greatest accuracy in predicting NIV failure (AUROC: 0.872 [95% CI 0.82-0.92]) among all predictive methods in an internal validation. In the prospective validation cohort, our model was also superior (AUROC: 0.846 [95% CI 0.80-0.89]). The sensitivity and specificity in the prediction group is 89% and 75%, while in the validation group they are 90% and 70%. MV duration and respiratory rate were the most important features. Additionally, we developed a web-based tool to help clinicians use our model. CONCLUSIONS: This study developed and prospectively validated the CatBoost model, which can be used to identify patients who are at risk of NIV failure. Thus, those patients might benefit from early triage and more intensive monitoring. TRIAL REGISTRATION: NCT03704324. Registered 1 September 2018, https://register. CLINICALTRIALS: gov .

Recombinant human brain natriuretic peptide ameliorates venous return function in congestive heart failure.

AIMS: Recombinant human brain natriuretic peptide (rh-BNP) is commonly used as a decongestive therapy. This study aimed to investigate the instant effects of rh-BNP on cardiac output and venous return function in post-cardiotomy patients with congestive heart failure (CHF). METHODS AND RESULTS: Twenty-four post-cardiotomy heart failure patients were enrolled and received a standard loading dose of rh-BNP. Haemodynamic monitoring was performed via a pulmonary artery catheter before and after the administration of rh-BNP. The cardiac output and venous return functions were estimated by depicting Frank-Starling and Guyton curves. After rh-BNP infusion, variables reflecting cardiac congestion and venous return function, such as pulmonary artery wedge pressure, mean systemic filling pressure (Pmsf) and venous return resistance index (VRRI), reduced from 15 ± 3 to 13 ± 3 mmHg, from 32 ± 7 to 28 ± 7 mmHg and from 6.7 ± 2.6 to 5.7 ± 1.8 mmHg min m2 /L, respectively. Meanwhile, cardiac index, stroke volume index, and the cardiac output function curve remained unchanged per se. The decline in Pmsf [-13% (-22% to -8%)] and VRRI [-12% (-25% to -5%)] was much greater than that in the systemic vascular resistance index [-7% (-14% to 0%)]. In the subgroup analysis of reduced ejection fraction (<40%) patients, the aforementioned changes were more significant. CONCLUSIONS: rh-BNP might ameliorate venous return rather than cardiac output function in post-cardiotomy CHF patients.

Remifentanil versus Dexmedetomidine in Cardiac Surgery Patients with Noninvasive Ventilation Intolerance: Protocol for the REDNIVI Trial.

BACKGROUND: Respiratory failure is one of the most common complications following cardiac surgery. Although noninvasive ventilation (NIV) has been an effective treatment, it has a high rate of intolerance. Both remifentanil and dexmedetomidine are used as sedatives in cardiac surgery (CS) patients with NIV intolerance. However, no randomized controlled trials have compared the effects of these drugs in relieving the intolerance. METHODS: REDNIVI will be a multicenter, prospective, single-blind, randomized controlled trial carried out in six clinical sites in China. Subjects with NIV intolerance will be randomized to receive remifentanil or dexmedetomidine in a ratio of 1:1. Primary outcomes of intolerance remission rate at different timings (15 minutes, 1, 3, 6, 12, 24, 36, 48, 60, 72 hours after initiation of treatment) and 72 h average remission rate will be determined. In addition, secondary outcomes such as mortality, duration of intensive care unit (ICU) stay, duration of mechanical ventilation (MV), the need for endotracheal intubation, hemodynamic changes, and delirium incidence will also be determined. CONCLUSIONS: This trial will provide evidence to determine the effects of remifentanil and dexmedetomidine in patients with NIV intolerance after cardiac surgery. CLINICAL TRIAL REGISTRATION: This study has been registered on ClinicalTrials.gov (NCT04734418).

Exosome-Derived From Sepsis Patients' Blood Promoted Pyroptosis of Cardiomyocytes by Regulating miR-885-5p/HMBOX1.

Background: Septic myocardial depression has been associated with increased morbidity and mortality. miR-885-5p has been shown to regulate cell growth, senescence, and/or apoptosis. Published studies demonstrated that Homeobox-containing protein 1 (HMBOX1) inhibits inflammatory response, regulates cell autophagy, and apoptosis. However, the role of miR-885-5p/HMBOX1 in sepsis and septic myocardial depression and the underlying mechanism is not fully understood. Materials and Methods: Exosomes (exos) derived from sepsis patients (sepsis-exos) were isolated using ultracentrifugation. Rats were subjected to cecal ligation and puncture surgery and treated with sepsis-exos. HMBOX1 was knocked down or overexpressed in AC16 cells using lentiviral plasmids carrying short interfering RNAs targeting human HMBOX1 or carrying HMBOX1 cDNA. Cell pyroptosis was measured by flow cytometry. The secretion of IL-1ß and IL-18 was examined by ELISA kits. Quantitative polymerase chain reaction (PCR) or western blot was used for gene expression. Results: Sepsis-exos increased the level of miR-885-5p, decreased HMBOX1, elevated IL-1ß and IL-18, and promoted pyroptosis in AC16 cells. Septic rats treated with sepsis-exos increased the serum inflammatory cytokines is associated with increased pyroptosis-related proteins of hearts. MiR-885-5p bound to the three prime untranslated regions of HMBOX1 to negatively regulate its expression. Overexpressing HMBOX1 reversed miR-885-5p-induced elevation of inflammatory cytokines and upregulation of NLRP3, caspase-1, and GSDMD-N in AC16 cells. The mechanistic study indicated that the effect of HMBOX1 was NF-κB dependent. Conclusion: Sepsis-exos promoted the pyroptosis of AC16 cells through miR-885-5p via HMBOX1. The results show the significance of the miR-885-5p/HMBOX1 axis in myocardial cell pyroptosis and provide new directions for the treatment of septic myocardial depression.

Change in left ventricular velocity time integral during Trendelenburg maneuver predicts fluid responsiveness in cardiac surgical patients in the operating room.

BACKGROUND: Fluid responsiveness is an important topic for clinicians. We investigated whether changes in left ventricular outflow tract (LVOT) velocity time integral (VTI) during a Trendelenburg position (TP) maneuver can predict fluid responsiveness as a non-invasive marker in coronary artery bypass graft (CABG) surgery patients in the operating room. METHODS: This prospective, single-center observational study, performed in the operating room, enrolled 65 elective CABG patients. Hemodynamic data coupled with transesophageal echocardiography monitoring of the LVOT VTI and the peak velocity were collected at each step [baseline 1, TP, baseline 2 and fluid challenge (FC)]. Patients whose VTI increased ≥15% after FC (500 mL of Gelofusine infusion within 30 min) were considered responders. RESULTS: Twenty-eight (43.1%) patients were responders to fluid administration. VTI changes during the TP maneuver predicted fluid responsiveness with an area under the receiver operating characteristic curve (AUC) of 0.90 (95% CI, 0.79-0.96), with a sensitivity of 100%, and a specificity of 70% at a threshold of 10% (gray zone, 8-15%). The increase in VTI during the TP was correlated with the VTI changes induced by FC (r=0.61, P<0.0001). Changes in peak velocity and pulse pressure during the TP were poorly predictive of fluid responsiveness, with an AUC of 0.72 (95% CI: 0.60-0.82) and 0.66 (95% CI: 0.53-0.77), respectively. CONCLUSIONS: An increase in VTI induced by the TP could predict fluid responsiveness in CABG patients in the operating room. However, changes in peak velocity and pulse pressure stimulated by the TP could not reliably predict fluid responsiveness.

Inhaled nitric oxide reduces the intrapulmonary shunt to ameliorate severe hypoxemia after acute type A aortic dissection surgery.

BACKGROUND: To assess the relationship between the intrapulmonary shunt and PaO2/FiO2 in severe hypoxemic patients after acute type A aortic dissection (ATAAD) surgery and to evaluate the effect of inhaled nitric oxide (iNO) on intrapulmonary shunt. METHODS: Postoperative ATAAD patients with PaO2/FiO2 ≤ 150 mmHg were enrolled. Intrapulmonary shunt was calculated from oxygen content of different sites (artery [CaO2], mixed venous [CvO2], and alveolar capillary [CcO2]) using the Fick equation, where intrapulmonary shunt = (CcO2-CaO2)/(CcO2-CvO2). Related variables were measured at baseline (positive end expiratory pressure [PEEP] 5 cm H2O), 30 min after increasing PEEP (PEEP 10 cm H2O), 30 min after 5 ppm iNO therapy (PEEP 10 cm H2O + iNO), and 30 min after decreasing PEEP (PEEP 5 cm H2O + iNO). RESULTS: A total of 20 patients were enrolled between April 2019 and December 2019. Intrapulmonary shunt and PaO2/FiO2 were correlated in severe hypoxemic, postoperative ATAAD patients (adjusted R2 = 0.467, p < 0.001). A mixed model for repeated measures revealed that iNO, rather than increasing PEEP, significantly decreased the intrapulmonary shunt (by 15% at a PEEP of 5 cm H2O and 16% at a PEEP of 10 cm H2O, p < 0.001 each) and increased PaO2/FiO2 (by 63% at a PEEP of 5 cm H2O and 65% at a PEEP of 10 cm H2O, p < 0.001 each). After iNO therapy, the decrement of intrapulmonary shunt and the increment of PaO2/FiO2 were also correlated (adjusted R2 = 0.375, p < 0.001). CONCLUSIONS: This study showed that intrapulmonary shunt and PaO2/FiO2 were correlated in severe hypoxemic, postoperative ATAAD patients. Furthermore, iNO, rather than increasing PEEP, significantly decreased the intrapulmonary shunt to improve severe hypoxemic conditions.

Trendelenburg maneuver predicts fluid responsiveness in patients on veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Evaluation of fluid responsiveness during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support is crucial. The aim of this study was to investigate whether changes in left ventricular outflow tract velocity-time integral (ΔVTI), induced by a Trendelenburg maneuver, could predict fluid responsiveness during VA-ECMO. METHODS: This prospective study was conducted in patients with VA-ECMO support. The protocol included four sequential steps: (1) baseline-1, a supine position with a 15° upward bed angulation; (2) Trendelenburg maneuver, 15° downward bed angulation; (3) baseline-2, the same position as baseline-1, and (4) fluid challenge, administration of 500 mL gelatin over 15 min without postural change. Hemodynamic parameters were recorded at each step. Fluid responsiveness was defined as ΔVTI of 15% or more, after volume expansion. RESULTS: From June 2018 to December 2019, 22 patients with VA-ECMO were included, and a total of 39 measurements were performed. Of these, 22 measurements (56%) met fluid responsiveness. The R2 of the linear regression was 0.76, between ΔVTIs induced by Trendelenburg maneuver and the fluid challenge. The area under the receiver operating characteristic curve of ΔVTI induced by Trendelenburg maneuver to predict fluid responsiveness was 0.93 [95% confidence interval (CI) 0.81-0.98], with a sensitivity of 82% (95% CI 60-95%), and specificity of 88% (95% CI 64-99%), at a best threshold of 10% (95% CI 6-12%). CONCLUSIONS: Changes in VTI induced by the Trendelenburg maneuver could effectively predict fluid responsiveness in VA-ECMO patients. Trial registration ClinicalTrials.gov, NCT03553459 (the TEMPLE study). Registered on May 30, 2018.

Remifentanil versus dexmedetomidine for treatment of cardiac surgery patients with moderate to severe noninvasive ventilation intolerance (REDNIVIN): a prospective, cohort study.

BACKGROUND: The use of sedation to noninvasive ventilation (NIV) patients remains controversial, however, for intolerant patients who are uncooperative, administration of analgesics and sedatives may be beneficial before resorting to intubation. The aim of this study was to evaluate the efficacy of remifentanil (REM) versus dexmedetomidine (DEX) for treatment of cardiac surgery (CS) patients with moderate to severe NIV intolerance. METHODS: This prospective cohort study of CS patients with moderate to severe NIV intolerance was conducted between January 2018 and March 2019. Patients were treated with either REM or DEX, decided by the bedside intensivist. Depending on the treatment regimen, the patients were allocated to one of two groups: the REM group or DEX group. RESULTS: A total of 90 patients were enrolled in this study (52 in the REM group and 38 in the DEX group). The mitigation rate, defined as the percentage of patients who were relieved from the initial moderate to severe intolerant status, was greater in the REM group than DEX group at 15 min and 3 h (15 min: 83% vs. 61%, P=0.029; 3 h: 92% vs. 74%, P=0.016), although the mean mitigation rate (81% vs. 85%, P=0.800) was comparable between the two groups. NIV failure, defined as reintubation or death over the course of study, was comparable between the two groups (19.2% vs. 21.1%, respectively, P=0.831). There were no significant differences between the two groups in other clinical outcomes, including tracheostomy (15.4% vs. 15.8%, P=0.958), in-hospital mortality (11.5% vs. 10.5%, P=0.880), ICU length of stay (LOS) (7 vs. 7 days, P=0.802), and in-hospital LOS (17 vs. 19 days, P=0.589). CONCLUSIONS: REM was as effective as DEX in CS patients with moderate to severe NIV intolerance. Although the effect of REM was better than that of DEX over the first 3 h, the cumulative effect was similar between the two treatments.

Comparison of the proximal and distal approaches for axillary vein catheterization under ultrasound guidance (PANDA) in cardiac surgery patients susceptible to bleeding: a randomized controlled trial.

BACKGROUND: The present study aimed at comparing the success rate and safety of proximal versus distal approach for ultrasound (US)-guided axillary vein catheterization (AVC) in cardiac surgery patients susceptible to bleeding. METHODS: In this single-center randomized controlled trial, cardiac surgery patients susceptible to bleeding and requiring AVC were randomized to either the proximal or distal approach group for US-guided AVC. Patients susceptible to bleeding were defined as those who received oral antiplatelet drugs or anticoagulants for at least 3 days. Success rate, catheterization time, number of attempts, and mechanical complications within 24 h were recorded for each procedure. RESULTS: A total of 198 patients underwent randomization: 99 patients each to the proximal and distal groups. The proximal group had the higher first puncture success rate (75.8% vs. 51.5%, p < 0.001) and site success rate (93.9% vs. 83.8%, p = 0.04) than the distal group. However, the overall success rates between the two groups were similar (99.0% vs. 99.0%; p = 1.00). Moreover, the proximal group had fewer average number of attempts (p < 0.01), less access time (p < 0.001), and less successful cannulation time (p < 0.001). There was no significant difference in complications between the two groups, such as major bleeding, minor bleeding, arterial puncture, pneumothorax, nerve injuries, and catheter misplacements. CONCLUSIONS: For cardiac surgery patients susceptible to bleeding, both proximal and distal approaches for US-guided AVC can be considered as feasible and safe methods of central venous cannulation. In terms of the first puncture success rate and cannulation time, the proximal approach is superior to the distal approach. Trial registration Clinicaltrials.gov, NCT03395691. Registered January 10, 2018, https://clinicaltrials.gov/ct2/show/NCT03395691?cond=NCT03395691&draw=1&rank=1 .

Evaluation of radial artery pulse pressure effects on detection of stroke volume changes after volume loading maneuvers in cardiac surgical patients.

BACKGROUND: Fluid responsiveness is defined as an increase in cardiac output (CO) or stroke volume (SV) of >10-15% after fluid challenge (FC). However, CO or SV monitoring is often not available in clinical practice. The aim of this study was to evaluate whether changes in radial artery pulse pressure (rPP) induced by FC or passive leg raising (PLR) correlates with changes in SV in patients after cardiac surgery. METHODS: This prospective observational study included 102 patients undergoing cardiac surgery, in which rPP and SV were recorded before and immediately after a PLR test and FC with 250 mL of Gelofusine for 10 min. SV was measured using pulse contour analysis. Patients were divided into responders (≥15% increase in SV after FC) and non-responders. The hemodynamic variables between responders and non-responders were analyzed to assess the ability of rPP to track SV changes. RESULTS: A total of 52% patients were fluid responders in this study. An rPP increase induced by FC was significantly correlated with SV changes after a FC (ΔSV-FC, r=0.62, P<0.01). A fluid-induced increase in rPP (ΔrPP-FC) of >16% detected a fluid-induced increase in SV of >15%, with a sensitivity of 91% and a specificity of 73%. The area under the receiver operating characteristic curve (AUROC) for the fluid-induced changes in rPP identified fluid responsiveness was 0.881 (95% CI: 0.802-0.937). A grey zone of 16-34% included 30% of patients for ΔrPP-FC. The ΔrPP-PLR was weakly correlated with ΔSV-FC (r=0.30, P<0.01). An increase in rPP induced by PLR (ΔrPP-PLR) predicted fluid responsiveness with an AUROC of 0.734 (95% CI: 0.637-0.816). A grey zone of 10-23% included 52% of patients for ΔrPP-PLR. CONCLUSIONS: Changes in rPP might be used to detect changes in SV via FC in mechanically ventilated patients after cardiac surgery. In contrast, changes in rPP induced by PLR are unreliable predictors of fluid responsiveness.

Effect of Sequential Noninvasive Ventilation on Early Extubation After Acute Type A Aortic Dissection.

BACKGROUND: Acute type A aortic dissection (aTAAD) is associated with a high incidence of prolonged postoperative invasive mechanical ventilation. We aimed to assess whether sequential noninvasive ventilation (NIV) could facilitate early extubation postoperatively after a spontaneous breathing trial (SBT) failure among aTAAD patients. METHODS: Beginning in December 2016, we transitioned our weaning strategy from repeated SBT until success (phase 1) to extubation concomitant with sequential NIV (phase 2) for subjects who failed their first SBT. The primary outcomes were re-intubation rate, duration of invasive ventilation, and total duration of ventilation. RESULTS: During the study period, 78 subjects with aTAAD failed their first postoperative SBT (38 subjects in phase 1 and 40 subjects in phase 2). Subjects extubated with sequential NIV had shorter median (interquartile range [IQR]) duration of invasive ventilation of 39.5 (30.8-57.8) h vs 89.5 (64-112) h (P < .001) and median (IQR) length of ICU stay of 6 (4.0-7.8) d vs 7.5 (5.8-9.0) d (P = .030). There were no significant differences between the 2 phases with regard to rates of re-intubation (7.5% vs 7.89%, P = .95), tracheostomy (2.5% vs 5.26%, P = .53), and in-hospital mortality (2.5% vs 2.63%, P = .97). CONCLUSIONS: Early extubation followed by sequential NIV significantly reduced duration of invasive ventilation and length of ICU stay without increasing re-intubation rate in postoperative subjects with aTAAD who failed their first SBT.

Serum N-terminal Pro-B-type Natriuretic Peptide Predicts Mortality in Cardiac Surgery Patients Receiving Renal Replacement Therapy.

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful cardiac biomarker that is associated with acute kidney injury (AKI) and mortality after cardiac surgery. However, its prognostic value in cardiac surgical patients receiving renal replacement therapy (RRT) remains unclear. Objectives: Our study aimed to assess the prognostic value of NT-proBNP in patients with established AKI receiving RRT after cardiac surgery. Methods: A total of 163 cardiac surgical patients with AKI requiring RRT were enrolled in this study. Baseline characteristics, hemodynamic variables at RRT initiation, and NT-proBNP level before surgery, at RRT initiation, and on the first day after RRT were collected. The primary outcome was 28-day mortality after RRT initiation. Results: Serum NT-proBNP levels in non-survivors was markedly higher than survivors before surgery (median: 4,096 [IQR, 962.0-9583.8] vs. 1,339 [IQR, 446-5,173] pg/mL; P < 0.01), at RRT initiation (median: 10,366 [IQR, 5,668-20,646] vs. 3,779 [IQR, 1,799-11,256] pg/mL; P < 0.001), and on the first day after RRT (median: 9,055.0 [IQR, 4,392-24,348] vs. 5,255 [IQR, 2,134-9,175] pg/mL; P < 0.001). The area under the receiver operating characteristic curve of NT-proBNP before surgery, at RRT initiation, and on the first day after RRT for predicting 28-day mortality was 0.64 (95% CI, 0.55-0.73), 0.71 (95% CI, 0.63-0.79), and 0.68 (95% CI, 0.60-0.76), respectively. Consistently, Cox regression revealed that NT-proBNP levels before surgery (HR: 1.27, 95% CI, 1.06-1.52), at RRT initiation (HR: 1.11, 95% CI, 1.06-1.17), and on the first day after RRT (HR: 1.17, 95% CI, 1.11-1.23) were independently associated with 28-day mortality. Conclusions: Serum NT-proBNP was an independent predictor of 28-day mortality in cardiac surgical patients with AKI requiring RRT. The prognostic role of NT-proBNP needs to be confirmed in the future.

Changes in Stroke Volume Variation Induced by Passive Leg Raising to Predict Fluid Responsiveness in Cardiac Surgical Patients With Protective Ventilation.

OBJECTIVES: Stroke volume variation (SVV) has been used to predict fluid responsiveness. The authors hypothesized the changes in SVV induced by passive leg raising (PLR) might be an indicator of fluid responsiveness in patients with protective ventilation after cardiac surgery. DESIGN: A prospective single-center observational study. SETTING: A single cardiac surgery intensive care unit at a tertiary hospital. PARTICIPANTS: A total of 123 patients undergoing cardiac surgery with hemodynamic instability. Tidal volume was set between 6 and 8 mL/kg of ideal body weight. INTERVENTIONS: PLR maneuver, fluid challenge. MEASUREMENTS AND MAIN RESULTS: SVV was continuously recorded using pulse contour analysis before and immediately after a PLR test and after fluid challenge (500 mL of colloid given over 30 min). Sixty-three (51.22%) patients responded to fluid challenge, in which PLR and fluid challenge significantly increased the SV and decreased the SVV. The decrease in SVV induced by PLR was correlated with the SV changes induced by fluid challenge. A 4% decrease in the SVV induced by PLR-discriminated responders to fluid challenge with an area under the curve of 0.90. The gray zone identified a range of SVV changes induced by PLR (between -3.94% and -2.91%) for which fluid responsiveness could not be predicted reliably. The gray zone included 15.45% of the patients. The SVV at baseline predicted fluid responsiveness with an area under the curve of 0.72. CONCLUSIONS: Changes in the SVV induced by PLR predicted fluid responsiveness in cardiac surgical patients with protective ventilation.

CXCL16/CXCR6 is involved in LPS-induced acute lung injury via P38 signalling.

Although several chemokines play key roles in the pathogenesis of acute lung injury (ALI), the roles of chemokine (C-X-C motif) ligand 16 (CXCL16) and its receptor C-X-C chemokine receptor type 6 (CXCR6) in ALI pathogenesis remain to be elucidated. The mRNA and protein expression of CXCL16 and CXCR6 was detected after lipopolysaccharide (LPS) stimulation with or without treatment with the nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC). Lung injury induced by LPS was evaluated in CXCR6 knockout mice. CXCL16 level was elevated in the serum of ALI patients (n = 20) compared with healthy controls (n = 30). CXCL16 treatment (50, 100, and 200 ng/mL) in 16HBE cells significantly decreased the epithelial barrier integrity and E-cadherin expression, and increased CXCR6 expression, reactive oxygen species (ROS) production, and p38 phosphorylation. Knockdown of CXCR6 or treatment with the p38 inhibitor SB203580 abolished the effects of CXCL16. Moreover, treatment of 16HBE cells with LPS (5, 10, 20 and 50 µg/mL) significantly increased CXCL16 release as well as the mRNA and protein levels of CXCL16 and CXCR6. The effects of LPS treatment (20 µg/mL) were abolished by treatment with PDTC. The results of the luciferase assay further demonstrated that PDTC treatment markedly inhibited the activity of the CXCL16 promoter. In conclusion, CXCL16, whose transcription was enhanced by LPS, may be involved in ROS production, epithelial barrier dysfunction and E-cadherin down-regulation via p38 signalling, thus contributing to the pathogenesis of ALI. Importantly, CXCR6 knockout or inhibition of p38 signalling may protect mice from LPS-induced lung injury by decreasing E-cadherin expression.

Reliability of three-dimensional color flow Doppler and two-dimensional pulse wave Doppler transthoracic echocardiography for estimating cardiac output after cardiac surgery.

BACKGROUND: Three-dimensional color flow Doppler (3DCF) is a new convenient technique for cardiac output (CO) measurement. However, to date, no one has evaluated the accuracy of 3DCF echocardiography for CO measurement after cardiac surgery. Therefore, this single-center, prospective study was designed to evaluate the reliability of three-dimensional color flow and two-dimensional pulse wave Doppler (2D-PWD) transthoracic echocardiography for estimating cardiac output after cardiac surgery. METHODS: Post-cardiac surgical patients with a good acoustic window and a low dose or no dose of vasoactive drugs (norepinephrine < 0.05 µg/kg/min) were enrolled for CO estimation. Three different methods (third generation FloTrac/Vigileo™ [FT/V] system as the reference method, 3DCF, and 2D-PWD) were used to estimate CO before and after interventions (baseline, after volume expansion, and after a dobutamine test). RESULTS: A total of 20 patients were enrolled in this study, and 59 pairs of CO measurements were collected (one pair was not included because of increasing drainage after the dobutamine test). Pearson's coefficients were 0.260 between the CO-FT/V and CO-PWD measurements and 0.729 between the CO-FT/V and CO-3DCF measurements. Bland-Altman analysis showed the bias between the absolute values of CO-FT/V and CO-PWD measurements was - 0.6 L/min with limits of agreement between - 3.3 L/min and 2.2 L/min, with a percentage error (PE) of 61.3%. The bias between CO-FT/V and CO-3DCF was - 0.14 L/min with limits of agreement between - 1.42 L /min and 1.14 L/min, with a PE of 29.9%. Four-quadrant plot analysis showed the concordance rate between ΔCO-PWD and ΔCO-3FT/V was 93.3%. CONCLUSIONS: In a comparison with the FT/V system, 3DCF transthoracic echocardiography could accurately estimate CO in post-cardiac surgical patients, and the two methods could be considered interchangeable. Although 2D-PWD echocardiography was not as accurate as the 3D technique, its ability to track directional changes was reliable.

Initial clinical impact of inhaled nitric oxide therapy for refractory hypoxemia following type A acute aortic dissection surgery.

BACKGROUND: To evaluate the effect of inhaled nitric oxide (iNO) therapy on oxygenation and clinical outcomes in patients with refractory hypoxemia after surgical reconstruction for acute type A aortic dissection (TAAD). METHODS: A before-and-after interventional study was conducted in patients with refractory hypoxemia after surgical reconstruction for TAAD. Postoperative refractory hypoxemia was defined as a persistent PaO2/FiO2 ratio ≤100 mmHg despite conventional therapy. From January to November 2016, conventional treatment was carried out for refractory hypoxemia. From December 2016 to October 2017, on the basis of conventional therapy, we explored the use of iNO to treat refractory hypoxemia. RESULTS: Fifty-three TAAD patients with refractory hypoxemia were enrolled in this study. Twenty-seven patients received conventional treatment (conventional group), while the remaining 26 patients received iNO therapy. The PaO2/FiO2 ratio was significantly higher in the iNO group after treatment than in the conventional group when analyzed over the entire 72 hours. The duration of invasive mechanical ventilation was significantly reduced in the iNO group (69.19 vs. 104.56 hours; P=0.003). Other outcomes, such as mortality (3.85% vs. 7.41%, P=1.000), intensive care unit (ICU) duration (9.88 vs. 12.36 days, P=0.059) and hospital stay (16.88 vs. 20.76 days, P=0.060), were not significantly different between the two groups. CONCLUSIONS: iNO therapy might play an ameliorative role in patients with refractory hypoxemia after surgical reconstruction for TAAD. This therapy may lead to sustained improvement in oxygenation and reduce the duration of invasive mechanical ventilation.

Internal jugular vein variability predicts fluid responsiveness in cardiac surgical patients with mechanical ventilation.

BACKGROUND: To evaluate the efficacy of using internal jugular vein variability (IJVV) as an index of fluid responsiveness in mechanically ventilated patients after cardiac surgery. METHODS: Seventy patients were assessed after cardiac surgery. Hemodynamic data coupled with ultrasound evaluation of IJVV and inferior vena cava variability (IVCV) were collected and calculated at baseline, after a passive leg raising (PLR) test and after a 500-ml fluid challenge. Patients were divided into volume responders (increase in stroke volume ≥ 15%) and non-responders (increase in stroke volume < 15%). We compared the differences in measured variables between responders and non-responders and tested the ability of the indices to predict fluid responsiveness. RESULTS: Thirty-five (50%) patients were fluid responders. Responders presented higher IJVV, IVCV and stroke volume variation (SVV) compared with non-responders at baseline (P < 0.05). The relationship between IJVV and SVV was moderately correlated (r = 0.51, P < 0.01). The areas under the receiver operating characteristic (ROC) curves for predicting fluid responsiveness were 0.88 (CI 0.78-0.94) for IJVV compared with 0.83 (CI 0.72-0.91), 0.97 (CI 0.89-0.99), 0.91 (CI 0.82-0.97) for IVCV, SVV, and the increase in stroke volume in response to a PLR test, respectively. CONCLUSIONS: Ultrasound-derived IJVV is an accurate, easily acquired noninvasive parameter of fluid responsiveness in mechanically ventilated postoperative cardiac surgery patients, with a performance similar to that of IVCV.