Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.

End-Expiratory Lung Volumes During Spontaneous Breathing Trials in Tracheostomized Subjects on Prolonged Mechanical Ventilation.

BACKGROUND: The role of end-expiratory lung volume (EELV) during a spontaneous breathing trial (SBT) in patients who were tracheostomized and on prolonged mechanical ventilation is unclear. This study aimed to assess EELV during a 60-min SBT and its correlation with weaning success. METHODS: Enrolled subjects admitted to a weaning unit were measured for EELV and relevant parameters before and after the SBT. RESULTS: Of the 44 enrolled subjects, 29 (66%) were successfully liberated, defined as not needing mechanical ventilation for 5 d. The success group had fewer subjects with chronic kidney disease (41% vs 73%, P = .044), stronger mean ± SD maximum inspiratory pressure (41.6 ± 10.4 vs 34.1 ± 7.1 cm H2O; P = .02) and mean ± SD maximum expiratory pressure (46.9 ± 11.7 vs 35.3 ± 16.9 cm H2O; P = .01) versus the failure group. Toward the end of the SBT, the success group had a significant increase in the mean ± SD EELV (before vs after: 1,278 ± 744 vs 1,493 ± 867 mL; P = .040) and a decrease in the mean ± SD rapid shallow breathing index (83.8 ± 39.4 vs 66.3 ± 29.4; P = .02), whereas there were no significant changes in these 2 parameters in the failure group. The Cox regression analysis showed that, at the beginning of SBT, a greater difference between EELV with a PEEP of 0 cm H2O and with a PEEP of 5 cm H2O was significantly correlated to a higher likelihood of weaning success. Toward the end of the SBT, a greater EELV level at a PEEP of 0 cm H2O was also correlated with weaning success. Also, the greater difference of EELV at a PEEP of 0 cm H2O between the beginning and the end of the SBT was also correlated with a shorter duration to weaning success. CONCLUSIONS: The change in EELV during a 60-min SBT may be of prognostic value for liberation from prolonged mechanical ventilation in patients who had a tracheostomy. Our findings suggest a model to understand the underlying mechanism of failure of liberation from mechanical ventilation in these patients.

Kinetics of oxygen uptake during unassisted breathing trials in prolonged mechanical ventilation: a prospective pilot study.

Few studies have investigated the measurement of oxygen uptake ([Formula: see text]O2) in tracheostomized patients undergoing unassisted breathing trials (UBTs) for liberation from mechanical ventilation (MV). Using an open-circuit, breath-to-breath method, we continuously measured [Formula: see text]O2 and relevant parameters during 120-min UBTs via a T-tube in 49 tracheostomized patients with prolonged MV, and calculated mean values in the first and last 5-min periods. Forty-one (84%) patients successfully completed the UBTs. The median [Formula: see text]O2 increased significantly (from 235.8 to 298.2 ml/min; P = 0.025) in the failure group, but there was no significant change in the success group (from 223.1 to 221.6 ml/min; P = 0.505). In multivariate logistic regression analysis, an increase in [Formula: see text]O2 > 17% from the beginning period (odds ratio [OR] 0.084; 95% confidence interval [CI] 0.012-0.600; P = 0.014) and a peak inspiratory pressure greater than - 30 cmH2O (OR 11.083; 95% CI 1.117-109.944; P = 0.04) were significantly associated with the success of 120-min UBT. A refined prediction model combining heart rate, energy expenditure, end-tidal CO2 and oxygen equivalent showed a modest increase in the area under the receiver operating characteristic curve of 0.788 (P = 0.578) and lower Akaike information criterion score of 41.83 compared to the traditional prediction model including heart rate and respiratory rate for achieving 48 h of unassisted breathing. Our findings show the potential of monitoring [Formula: see text]O2 in the final phase of weaning in tracheostomized patients with prolonged MV.

Improving patient safety during intrahospital transportation of mechanically ventilated patients with critical illness.

AIM: Intrahospital transportation (IHT) of patients under mechanical ventilation (MV) significantly increases the risk of patient harm. A structured process performed by a well-prepared team with adequate communication among team members plays a vital role in enhancing patient safety during transportation. DESIGN AND IMPLEMENTATION: We conducted this quality improvement programme at the intensive care units of a university-affiliated medical centre, focusing on the care of patients under MV who received IHT for CT or MRI examinations. With the interventions based on the analysis finding of the IHT process by healthcare failure mode and effects analysis, we developed and implemented strategies to improve this process, including standardisation of the transportation process, enhancing equipment maintenance and strengthening the teamwork among the transportation teammates. In a subsequent cycle, we developed and implemented a new process with the practice of reminder-assisted briefing. The reminders were printed on cards with mnemonics including 'VITAL' (Vital signs, Infusions, Tubes, Alarms and Leave) attached to the transportation monitors for the intensive care unit nurses, 'STOP' (Secretions, Tubes, Oxygen and Power) attached to the transportation ventilators for the respiratory therapists and 'STOP' (Speak-out, Tubes, Others and Position) attached to the examination equipment for the radiology technicians. We compared the incidence of adverse events and completeness and correctness of the tasks deemed to be essential for effective teamwork before and after implementing the programme. RESULTS: The implementation of the programme significantly reduced the number and incidence of adverse events (1.08% vs 0.23%, p=0.01). Audits also showed improved teamwork during transportation as the team members showed increased completeness and correctness of the essential IHT tasks (80.8% vs 96.5%, p<0.001). CONCLUSION: The implementation of reminder-assisted briefings significantly enhanced patient safety and teamwork behaviours during the IHT of mechanically ventilated patients with critical illness.

Significant Clinical Factors Associated with Long-term Mortality in Critical Cancer Patients Requiring Prolonged Mechanical Ventilation.

Studies about prognostic assessment in cancer patients requiring prolonged mechanical ventilation (PMV) for post-intensive care are scarce. We retrospectively enrolled 112 cancer patients requiring PMV support who were admitted to the respiratory care center (RCC), a specialized post-intensive care weaning facility, from November 2009 through September 2013. The weaning success rate was 44.6%, and mortality rates at hospital discharge and after 1 year were 43.8% and 76.9%, respectively. Multivariate logistic regression showed that weaning failure, in addition to underlying cancer status, was significantly associated with an increased 1-year mortality (odds ratio, 6.269; 95% confidence interval, 1.800-21.834; P = 0.004). Patients who had controlled non-hematologic cancers and successful weaning had the longest median survival, while those with other cancers who failed weaning had the worst. Patients with low maximal inspiratory pressure, anemia, and poor oxygenation at RCC admission had an increased risk of weaning failure. In conclusion, cancer status and weaning outcome were the most important determinants associated with long-term mortality in cancer patients requiring PMV. We suggest palliative care for those patients with clinical features associated with worse outcomes. It is unknown whether survival in this specific patient population could be improved by modifying the risk of weaning failure.