Remifentanil vs. dexmedetomidine for cardiac surgery patients with noninvasive ventilation intolerance: a multicenter randomized controlled trial.

BACKGROUND: The optimal sedative regime for noninvasive ventilation (NIV) intolerance remains uncertain. The present study aimed to assess the efficacy and safety of remifentanil (REM) compared to dexmedetomidine (DEX) in cardiac surgery patients with moderate-to-severe intolerance to NIV. METHODS: In this multicenter, prospective, single-blind, randomized controlled study, adult cardiac surgery patients with moderate-to-severe intolerance to NIV were enrolled and randomly assigned to be treated with either REM or DEX for sedation. The status of NIV intolerance was evaluated using a four-point NIV intolerance score at different timepoints within a 72-h period. The primary outcome was the mitigation rate of NIV intolerance following sedation. RESULTS: A total of 179 patients were enrolled, with 89 assigned to the REM group and 90 to the DEX group. Baseline characteristics were comparable between the two groups, including NIV intolerance score [3, interquartile range (IQR) 3-3 vs. 3, IQR 3-4, p = 0.180]. The chi-squared test showed that mitigation rate, defined as the proportion of patients who were relieved from their initial intolerance status, was not significant at most timepoints, except for the 15-min timepoint (42% vs. 20%, p = 0.002). However, after considering the time factor, generalized estimating equations showed that the difference was statistically significant, and REM outperformed DEX (odds ratio = 3.31, 95% confidence interval: 1.35-8.12, p = 0.009). Adverse effects, which were not reported in the REM group, were encountered by nine patients in the DEX group, with three instances of bradycardia and six cases of severe hypotension. Secondary outcomes, including NIV failure (5.6% vs. 7.8%, p = 0.564), tracheostomy (1.12% vs. 0%, p = 0.313), ICU LOS (7.7 days, IQR 5.8-12 days vs. 7.0 days, IQR 5-10.6 days, p = 0.219), and in-hospital mortality (1.12% vs. 2.22%, p = 0.567), demonstrated comparability between the two groups. CONCLUSIONS: In summary, our study demonstrated no significant difference between REM and DEX in the percentage of patients who achieved mitigation among cardiac surgery patients with moderate-to-severe NIV intolerance. However, after considering the time factor, REM was significantly superior to DEX. Trial registration ClinicalTrials.gov (NCT04734418), registered on January 22, 2021. URL of the trial registry record: https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000AM4S&selectaction=Edit&uid=U00038YX&ts=3&cx=eqn1z0 .

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.

Postoperative glucocorticoids in patients with acute type A aortic dissection (GLAD): study protocol for a prospective, single-center, randomized controlled trial.

BACKGROUND: Patients receiving surgical treatment of acute type A Aortic Dissection (aTAAD) are common to suffer organ dysfunction in the intensive care unit due to overwhelming inflammation. Previous studies have revealed that glucocorticoids may reduce complications in certain patient groups, but evidence between postoperative glucocorticoids administration and improvement in organ dysfunction after aTAAD surgery are lacking. METHODS: This study will be an investigator-initiated, prospective, single-blind, randomized, single-center study. Subjects with confirmed diagnosis of aTAAD undergoing surgical treatment will be enrolled and 1:1 randomly assigned to receive either glucocorticoids or normal treatment. All patients in the glucocorticoids group will be given methylprednisolone intravenously for 3 days after enrollment. The primary endpoint will be the amplitude of variation of Sequential Organ Failure Assessment score on post-operative day 4 compared to baseline. DISCUSSION: The trial will explore the rationale for postoperative application of glucocorticoids in patients after aTAAD surgery. TRIAL REGISTRATION: This study has been registered on ClinicalTrials.gov (NCT04734418).

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.

Weaning from venous-arterial extracorporeal membrane oxygenation: The hemodynamic and clinical aspects of flow challenge test.

The cardiac function reserve is crucial for the successful weaning of V-A ECMO. During the V-A ECMO weaning phase, the gradual reduction in pump flow converts the blood flow originally driven by the pump to native cardiac output and also transforms afterload (caused by retrograde flow) into ventricular preload, thus introducing a "flow challenge" to the native heart. In this perspective, we propose to use this flow challenge as a test to simulate the preload-to-afterload conversion to assess cardiac functional reserve quantitatively. With this short article we offer the hemodynamic and clinical aspects regarding the flow challenge test.

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.

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.

Veno-Arterial Extracorporeal Membrane Oxygenation for Patients Undergoing Acute Type A Aortic Dissection Surgery: A Six-Year Experience.

Objectives: Acute type A aortic dissection (aTAAD) is usually lethal without emergency surgery. Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in patients with cardiogenic shock following cardiac surgery, VA-ECMO support following aTAAD surgery has not been well-described. Based on our 6-year experience, we aimed to retrospectively analyze risk factors, application and timing of VA-ECMO, and outcomes in aTAAD patients. Methods: In this retrospective, single-center study, we enrolled adult patients who underwent aTAAD surgery from January 2014 to December 2019 and were supported with VA-ECMO. Patients were divided into two groups according to whether or not they were successfully weaned from VA-ECMO. Preoperative, intraoperative and postoperative variables were assessed and analyzed. Outcomes of the patients were followed up until discharge. Results: Twenty-seven patients who received aTAAD surgery with VA-ECMO support were included in the study. Nine patients (33.3%) were successfully weaned from VA-ECMO. The median VA-ECMO support time and length of hospital stay in the successfully weaned group were significantly longer than in the group could not be successfully weaned (192 [111-327] vs. 55 [23-95] h, p < 0.01; 29 [18-40] vs. 4 [3-8] days, p < 0.01). Overall in-hospital mortality was 81.5%. The main causes of death were bleeding (37%), neurological complications (15%), and multiple organ dysfunction syndrome (15%). Preoperative levels of creatine kinase-MB (CK-MB) were lower in patients who were successfully weaned from VA-ECMO than in the failed group (14 [6-30] vs. 55 [28-138] U/L, p < 0.01). Postoperative peak levels of CK-MB, cardiac troponin T, lactate dehydrogenase, and lactate were significantly lower in the successful group than in the failed group. Conclusion: Postoperative VA-ECMO support was rarely used in aTAAD patients. Our study showed that VA-ECMO can be considered as a salvage treatment in aTAAD patients, despite the high rate of complications and mortality.

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.

Veno-Arterial Extracorporeal Membrane Oxygenation for Patients Undergoing Heart Transplantation: A 7-Year Experience.

Objective: Primary graft dysfunction (PGD) is the leading cause of early death after heart transplantation. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide temporary mechanical circulatory support and time for functional recovery of the transplanted heart. The purpose of this study was to analyze the timing and prognoses of VA-ECMO in patients with severe PGD after heart transplantation. Methods: A total of 130 patients underwent heart transplantation at the Zhongshan Hospital Affiliated with Fudan University between January 2014 and December 2020. All patients received basiliximab immunoinduction and a classic double vena cava anastomosis orthotopic heart transplantation. Among them, 29 patients (22.3%) developed severe PGD in the early postoperative period. VA-ECMO was performed in patients with difficulty weaning from cardiopulmonary bypass (CPB) or postoperative refractory cardiogenic shock. Patients were divided into two groups according to whether or not they were successfully weaned from VA-ECMO (patients who survived for 48 h after weaning and did not need VA-ECMO assistance again). The perioperative clinical data were recorded, and all patients were followed up until discharge. Early outcomes were compared between groups. Results: A total of 29 patients with VA-ECMO support after heart transplantation were included in this study. The proportion of patients receiving VA-ECMO was 22.3% (29/130). Nineteen patients (65.5%) needed VA-ECMO due to difficulty with weaning from CPB, and 10 patients required VA-ECMO for postoperative cardiogenic shock. Nineteen patients (65.5%) were successfully weaned from VA-ECMO. Overall, in-hospital mortality of VA-ECMO support patients was 55.2%. The main causes of death were ventricular fibrillation (four cases), major bleeding (three cases), infection (four cases), and graft failure (five cases). Conclusion: Despite advances in heart transplantation, severe PGD remains a lethal complication after heart transplantation. At present, the treatment for severe PGD after heart transplantation is a challenge. VA-ECMO provides an effective treatment for severe PGD after heart transplantation, which can promote graft function recovery.

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.

End-expiratory occlusion test predicts fluid responsiveness in cardiac surgical patients in the operating theatre.

BACKGROUND: The aim of this study was to evaluate whether a 20-second end-expiratory occlusion (EEO) test can predict fluid responsiveness in cardiac surgery patients in the operating theatre. METHODS: This prospective study enrolled 75 mechanically ventilated patients undergoing elective coronary artery bypass grafting surgery. Hemodynamic data coupled with transesophageal echocardiography monitoring of the velocity time integral (VTI) and the peak velocity (Vmax) at the left ventricular outflow tract were collected at each step (baseline 1, EEO, baseline 2 and fluid challenge). Patients were divided into fluid responders (increase in VTI ≥15%) and non-responders (increase in VTI <15%) after a fluid challenge (6 mL 0.9% saline per kg, given in 10 minutes). RESULTS: Fluid challenge significantly increased the VTI by more than 15% in 36 (48%) patients (responders). An increase in VTI greater than 5% during the EEO test predicted fluid responsiveness with a sensitivity of 81% and a specificity of 93%. The area under the receiver-operating characteristic curve (AUROC) of ΔVTI-EEO was 0.90 [95% confidence interval (CI): 0.83-0.97]. ΔVmax-EEO was poorly predictive of fluid responsiveness, with an AUC of 0.75 (95% CI: 0.63-0.86). CONCLUSIONS: Changes in VTI induced by a 20-second EEO can reliably predict fluid responsiveness in cardiac surgical patients in the operating theatre, whereas the changes in Vmax cannot.

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.