Utility of paired plasma and drainage fluid mNGS in diagnosing acute intra-abdominal infections with sepsis.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has been increasingly applied in sepsis. We aimed to evaluate the diagnostic and therapeutic utility of mNGS of paired plasma and peritoneal drainage (PD) fluid samples in comparison to culture-based microbiological tests (CMTs) among critically ill patients with suspected acute intra-abdominal infections (IAIs). METHODS: We conducted a prospective study from October 2021 to December 2022 enrolling septic patients with suspected IAIs (n = 111). Pairwise CMTs and mNGS of plasma and PD fluid were sent for pathogen detection. The mNGS group underwent therapeutic regimen adjustment based on mNGS results for better treatment. The microbial community structure, clinical features, antibiotic use and prognoses of the patients were analyzed. RESULTS: Higher positivity rates were observed with mNGS versus CMTs for both PD fluid (90.0% vs. 48.3%, p < 0.005) and plasma (76.7% vs. 1.6%, p < 0.005). 90% of enrolled patients had clues of suspected pathogens combining mNGS and CMT methods. Gram-negative pathogens consist of most intra-abdominal pathogens, including a great variety of anaerobes represented by Bacteroides and Clostridium. Patients with matched plasma- and PD-mNGS results had higher mortality and sepsis severity. Reduced usage of carbapenem (30.0% vs. 49.4%, p < 0.05) and duration of anti-MRSA treatment (5.1 ± 3.3 vs. 7.0 ± 8.4 days, p < 0.05) was shown in the mNGS group in our study. CONCLUSIONS: Pairwise plasma and PD fluid mNGS improves microbiological diagnosis compared to CMTs for acute IAI. Combining plasma and PD mNGS could predict poor prognosis. mNGS may enable optimize empirical antibiotic use.

The effects of UCP2 on autophagy through the AMPK signaling pathway in septic cardiomyopathy and the underlying mechanism.

BACKGROUND: Mitochondrial dysfunction plays an important role in the development of septic cardiomyopathy. This study aimed to reveal the protective role of uncoupling protein 2 (UCP2) in mitochondria through AMP-activated protein kinase (AMPK) on autophagy during septic cardiomyopathy. METHODS: UCP2 knockout mice via a cecal ligation and puncture (CLP) model and the H9C2 cardiomyocyte cell line in response to lipopolysaccharide (LPS) in vitro were used to study the effect. The myocardial morphological alterations, indicators of mitochondrial injury and levels of autophagy-associated proteins (pAMPK, pmTOR, pULK1, pTSC2, Beclin-1, and LC3-I/II) were assessed. In addition, the mechanism of the interaction between UCP2 and AMPK was further studied through gain- and loss-of-function studies. RESULTS: Compared with the wild-type mice, the UCP2 knockout mice exhibited more severe cardiomyocyte injury after CLP, and the AMPK agonist AICAR protected against such injury. Consistent with this result, silencing UCP2 augmented the LPS-induced pathological damage and mitochondrial injury in the H9C2 cells, limited the upregulation of autophagy proteins and reduced AMPK phosphorylation. AICAR protected the cells from morphological changes and mitochondrial membrane potential loss and promoted autophagy. The silencing and overexpression of UCP2 led to correlated changes in the AMPK upstream kinases pLKB1 and CAMKK2. CONCLUSIONS: UCP2 exerts cardioprotective effects on mitochondrial dysfunction during sepsis via the action of AMPK on autophagy.

Plasma mitochondrial DNA levels are associated with acute lung injury and mortality in septic patients.

BACKGROUND: Mitochondrial DNA (mtDNA) is a critical activator of inflammation. Circulating mtDNA released causes lung injury in experimental models. We hypothesized that elevated plasma mtDNA levels are associated with acute lung injury (ALI) in septic patients. METHODS: We enrolled 66 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between January 2019 and October 2019. Respiratory, hemodynamic and bedside echocardiographic parameters were recorded. Plasma mtDNA, procalcitonin, interleukin 6, and interleukin 8 levels were examined. RESULTS: Plasma mtDNA levels within 24 h after admission were significantly increased in the group of septic patients with ALI [5.01 (3.38-6.64) vs 4.13 (3.20-5.07) log copies/µL, p 0.0172]. mtDNA levels were independently associated with mortality (hazard ratio, 3.2052; 95% CI 1.1608-8.8500; p 0.0253) and ALI risk (odds ratio 2.7506; 95% CI 1.1647-6.4959; p 0.0210). Patients with high mtDNA levels had worse outcomes, and post hoc tests showed significant differences in 28-day survival rates. Increased mtDNA levels were seen in patients with abdominal infection. CONCLUSIONS: Increased plasma mtDNA levels within 24 h after admission were significantly associated with ALI incidence and mortality in septic patients.

Fluctuations of driving pressure during mechanical ventilation indicates elevated central venous pressure and poor outcomes.

Inappropriate mechanical ventilation may induce hemodynamic alterations through cardiopulmonary interactions. The aim of this study was to explore the relationship between airway pressure and central venous pressure during the first 72 h of mechanical ventilation and its relevance to patient outcomes. We conducted a retrospective study of the Department of Critical Care Medicine of Peking Union Medical College Hospital and a secondary analysis of the MIMIC-III clinical database. The relationship between the ranges of driving pressure and central venous pressure during the first 72 h and their associations with prognosis were investigated. Data from 2790 patients were analyzed. Wide range of driving airway pressure (odds ratio, 1.0681; 95% CI, 1.0415-1.0953; p < 0.0001) were independently associated with mortality, ventilator-free time, intensive care unit and hospital length of stay. Furthermore, wide range of driving pressure and elevated central venous pressure exhibited a close correlation. The area under receiver operating characteristic demonstrated that range of driving pressure and central venous pressure were measured at 0.689 (95% CI, 0.670-0.707) and 0.681 (95% CI, 0.662-0.699), respectively. Patients with high ranges of driving pressure and elevated central venous pressure had worse outcomes. Post hoc tests showed significant differences in 28-day survival rates (log-rank (Mantel-Cox), 184.7; p < 0.001). In conclusion, during the first 72 h of mechanical ventilation, patients with hypoxia with fluctuating driving airway pressure have elevated central venous pressure and worse outcomes.

Pulmonary hypertension with adult respiratory distress syndrome: prevalence, clinical impact, and association with central venous pressure.

Pulmonary hypertension (PH) occurs in patients with acute respiratory distress syndrome (ARDS); the most severe form comprises acute cor pulmonale (ACP). Here, we investigated the prevalence of PH in patients with ARDS to evaluate its correlation with ACP risk, ARDS severity and central venous pressure (CVP). We conducted a secondary analysis using data from the MIMIC-III open-source clinical database. The prevalence of PH associated with new-onset ARDS during the first 72 h after intensive care unit admission was investigated; moreover, the association between ACP risk score and PH was validated. We also evaluated the association between elevated CVP (mean CVP > 10 mmHg) and PH and other clinical outcomes. Among 2434 patients who met the ARDS Berlin criteria and underwent echocardiography or pulmonary artery catheterization evaluation, a total of 583 (24.0%) patients were diagnosed with moderate or severe PH, of which 418 had low and 165 had high ACP risk. After adjustment for disease/ARDS severity, ACP risk score, and other demographic variables, elevated CVP was independently associated with the occurrence of PH (odds ratio, 2.239 (1.674, 2.993), p < 0.005). Among patients with PH, higher mean CVP was associated with prolonged hospital stay (13.4 vs. 15.2 days, p = 0.041) and duration of ventilation (116.5 vs. 150.5 h, p = 0.023). Incidence of PH was 24.0% in patients with new-onset ARDS in this retrospective study. Elevated CVP is relevant with higher incidence of PH and worse clinical outcome; these highlighted the importance of hemodynamic monitoring in the management of ARDS.

Central venous pressure value can assist in adjusting norepinephrine dosage after the initial resuscitation of septic shock.

BACKGROUND: New definitions for sepsis and septic shock (Sepsis-3) were published, but the strategy to adjust vasopressors after the initial guidelines is still unclear. We conducted a retrospective observational study to explore dosing strategy of norepinephrine (NE). METHODS: A retrospective observational study in the 15-bed mixed intensive care unit of a tertiary care university hospital. The study was performed on septic shock patients after 30 mL/kg fluid resuscitation and mean arterial pressure (MAP) levels reached >65 mmHg requiring NE. We divided patients into NE dosage increase and decrease groups, and collected hemodynamic and tissue perfusion parameters before (T1) and after (T2) adjusting NE dosage. RESULTS: In both NE increase and decrease groups, central venous pressure (CVP) and pressure difference between usual MAP and MAP (dMAP) at the T1 time point were associated with lactate clearance. In groups LC HM (CVP <10 mmHg, dMAP > 0 mmHg) and HC HM (CVP ≥ 10 mmHg, dMAP > 0 mmHg), decrease in NE dosage decreased lactate level, while in group HC LM (CVP ≥ 10 mmHg, dMAP ≤ 0 mmHg), both increase and decrease in NE dosage led to increase lactate level. CONCLUSIONS: After patients with septic shock (Sepsis-3) resuscitated to reach the initial recovery target goals, combination of CVP and MAP refer to usual levels can help doctors make the next decision to make the correct choice of increase NE dosage or decrease NE dosage.

Association between elevated central venous pressure and outcomes in critically ill patients.

BACKGROUND: Some prior studies have shown that elevated mean central venous pressure in certain patient populations and disease processes may lead to poor prognosis. However, these studies failed to generalize the concept of elevated central venous pressure (ECVP) load to all patients in critical care settings because of the limited cases and exclusive cohorts. The aim of the study was to investigate the association between elevated central venous pressure and outcomes in critical care. METHODS: We performed a retrospective analysis on a single-center public database (MIMIC) of more than 9000 patients and more than 500,000 records of central venous pressure measurement. We evaluated the association between mean central venous pressure level and 28-day mortality after intensive care unit admission. The secondary outcomes were duration of mechanical ventilation, vasoactive drug use, laboratory results related to organ dysfunction and length of intensive care unit hospitalization. Accordingly, we proposed the concept of ECVP10 (the time sum of CVP above 10 mmHg) and investigated its association with outcome. RESULTS: There were 1645 deaths at 28 days after admission. Compared with the lowest quartile of mean central venous pressure [mean (SD) 7.4 (1.9) mmHg], the highest quartile [17.4 (4.1) mmHg] was associated with a 33.6% (95% CI 1.117-1.599) higher adjusted risk of death. Poor secondary outcomes were also associated with higher quartiles of elevated mean central venous pressure. After stratification by mean central venous pressure, elevated duration of central venous pressure above 10 mmHg was significantly higher in the non-survival group than in the survival group. CONCLUSIONS: Elevated central venous pressure level correlated with poor outcomes and prolonged treatment in critical care settings. Level and duration of elevated central venous pressure should be both evaluated to establish its cause and apply appropriate treatment.

Use of Lung Ultrasound to Assess the Efficacy of an Alveolar Recruitment Maneuver in Rabbits With Acute Respiratory Distress Syndrome.

OBJECTIVES: To investigate the application of lung ultrasound (US) in the evaluation and implementation of alveolar recruitment maneuvers in acute respiratory distress syndrome (ARDS). METHODS: Twelve rabbits with saline lavage-induced lung injury were randomly divided into 2 groups: one with alveolar recruitment guided by lung US and the other with alveolar recruitment guided by maximal oxygenation. Recruitment maneuvers were applied according to a stepwise incremental positive end-expiratory pressure method in both groups. In the oxygenation group, a sum of the partial pressures of oxygen and carbon dioxide exceeding 400 mm Hg was used to define adequate recruitment. In the lung US group, a new protocol for reaeration in US-guided lung recruitment was used to guide treatment. Evaluation by lung US, respiratory mechanical parameters, the Smith pathologic score (Crit Care Med 1997; 25:1888-1897), and wet-to-dry ratio were compared between the groups. RESULTS: Opening pressure was significantly higher in the lung US group (mean ± SD, 23.4 ± 3.4 cm H2O) than the oxygenation group (18.7 ± 2.1 cm H2O; P < .05). The reaeration score in the lung US group significantly increased during alveolar recruitment (6.5 ± 1.6 points at baseline versus 13.8 ± 3.0 points after completion; P < .05). Lung compliance, dead space shunts, the Smith pathologic score, and tissue wet-to-dry ratio, however, were not significantly different between the groups. CONCLUSIONS: Lung US is an effective means of evaluating and guiding alveolar recruitment in ARDS. Compared with the maximal oxygenation-guided method, the protocol for reaeration in US-guided lung recruitment achieved a higher opening pressure, resulted in greater improvements in lung aeration, and substantially reduced lung heterogeneity in ARDS.