Role of Early Enteral Nutrition in Mechanically Ventilated COVID-19 Patients.

Current guidance recommends initiation of early enteral nutrition (early EN) within 24-36 hours of ICU admission in critically ill COVID-19 patients. Despite this recommendation, there is quite limited evidence describing the effect of early EN on outcomes in COVID-19 patients. The association between early EN (within 3 d post intubation) and clinical outcomes in adult COVID-19 patients requiring mechanical ventilation (within 2 d post ICU admission) was evaluated. DESIGN: We performed a nationwide observational cohort study using a nationwide administrative-financial database (Premier) in United States. SETTING: Information pertaining to all COVID-19 patients admitted to ICU from 75 hospitals between April and December 2020 was analyzed. PATIENTS: A total of 861 COVID-19 patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical outcomes were assessed via regression models to control for patient and hospital characteristics. We identified 513 COVID-19 ICU patients (59.2%) requiring mechanical ventilation who received early EN and had similar baseline characteristics to late EN group. Compared with late EN group, the early EN group had shorter ICU (hazard ratio [HR], 1.39; 95% CI, 1.15-1.68) and hospital length of stays (LOS) (HR, 1.53; 95% CI, 1.23-1.91), fewer mechanical ventilation days (HR, 1.25; 95% CI, 1.01-1.54), and lower cost (-$22,443; 95% CI, -$32,342 to -$12,534). All comparisons were statistically significant (p < 0.05). CONCLUSIONS: In patients with COVID-19 requiring mechanical ventilation, early EN is associated with earlier liberation from mechanical ventilation, shorter ICU and hospital LOS, and decreased cost. Our results are among the first to support guideline recommendations for initiation of early EN in COVID-19 ICU patients. Further, our data show nearly 40% of critically ill COVID-19 patients fail to have early EN initiated, even at 3 d post initiation of mechanical ventilation. These results emphasize the need for targeted strategies promoting initiation of early EN, as this may lead to improved clinical and economic outcomes in severe COVID-19 patients.

Code blue pit crew model: A novel approach to in-hospital cardiac arrest resuscitation.

BACKGROUND: Mortality from in-hospital cardiac arrests remains a large problem world-wide. In an effort to improve in-hospital cardiac arrest mortality, there is a renewed focus on team training and operations. Here, we describe the implementation of a "pit crew" model to provide in-hospital resuscitation care. METHODS: In order to improve our institution's code team organization, we implemented a pit crew resuscitation model. The model was introduced through computer-based modules and lectures and was reemphasized at our institution-based ACLS training and mock code events. To assess the effect of our model, we reviewed pre- and post-pit crew implementation data from five sources: defibrillator downloads, a centralized hospital database, mock codes, expert-led debriefings, and confidential surveys. Data with continuous variables and normal distribution were analyzed using a standard two-sample t-test. For yes/no categorical data either a Z-test for difference between proportions or Chi-square test was used. RESULTS: There were statistically significant improvements in compression rates post-intervention (mean rate 133.5 pre vs. 127.9 post, two-tailed, p = 0.02) and in adequate team communication (33% pre vs. 100% post; p = 0.05). There were also trends toward a reduction in the number of shockable rhythms that were not defibrillated (32.7% pre vs. 18.4% post), average time to shock (mean 1.96 min pre vs. 1.69 min post), and overall survival to discharge (31% pre vs. 37% post), though these did not reach statistical significance. CONCLUSION: Implementation of an in-hospital, pit crew resuscitation model is feasible and can improve both code team communication as well as key ACLS metrics.

Perioperative issues and sleep-disordered breathing.

Sleep-disordered breathing in the perioperative setting poses an increase in both perceived and demonstrated challenges for health care providers. Some of these challenges relate to identifying patients at high risk for obstructive sleep apnea prior to surgery. Other management challenges include identifying the proper monitoring techniques, using the correct mix of pharmacologic and nonpharmacologic strategies to manage these patients, and identifying the proper and safe disposition strategy after surgery. Additional populations, such as pediatrics and the morbidly obese, are also highlighted, which may help address questions in populations that are frequently managed in the critical care setting postoperatively.

Microvesicular caspase-1 mediates lymphocyte apoptosis in sepsis.

OBJECTIVE: Immune dysregulation during sepsis is poorly understood, however, lymphocyte apoptosis has been shown to correlate with poor outcomes in septic patients. The inflammasome, a molecular complex which includes caspase-1, is essential to the innate immune response to infection and also important in sepsis induced apoptosis. Our group has recently demonstrated that endotoxin-stimulated monocytes release microvesicles (MVs) containing caspase-1 that are capable of inducing apoptosis. We sought to determine if MVs containing caspase-1 are being released into the blood during human sepsis and induce apoptosis.. DESIGN: Single-center cohort study. MEASUREMENTS: 50 critically ill patients were screened within 24 hours of admission to the intensive care unit and classified as either a septic or a critically ill control. Circulatory MVs were isolated and analyzed for the presence of caspase-1 and the ability to induce lymphocyte apoptosis. Patients remaining in the ICU for 48 hours had repeated measurement of caspase-1 activity on ICU day 3. MAIN RESULTS: Septic patients had higher microvesicular caspase-1 activity 0.05 (0.04, 0.07) AFU versus 0.0 AFU (0, 0.02) (p<0.001) on day 1 and this persisted on day 3, 0.12 (0.1, 0.2) versus 0.02 (0, 0.1) (p<0.001). MVs isolated from septic patients on day 1 were able to induce apoptosis in healthy donor lymphocytes compared with critically ill control patients (17.8±9.2% versus 4.3±2.6% apoptotic cells, p<0.001) and depletion of MVs greatly diminished this apoptotic signal. Inhibition of caspase-1 or the disruption of MV integrity abolished the ability to induce apoptosis. CONCLUSION: These findings suggest that microvesicular caspase-1 is important in the host response to sepsis, at least in part, via its ability to induce lymphocyte apoptosis. The ability of microvesicles to induce apoptosis requires active caspase-1 and intact microvesicles.

Analysis of human bronchial epithelial cell proinflammatory response to Burkholderia cenocepacia infection: inability to secrete il-1ß.

Burkholderia cenocepacia, the causative agent of cepacia syndrome, primarily affects cystic fibrosis patients, often leading to death. In the lung, epithelial cells serve as the initial barrier to airway infections, yet their responses to B. cenocepacia have not been fully investigated. Here, we examined the molecular responses of human airway epithelial cells to B. cenocepacia infection. Infection led to early signaling events such as activation of Erk, Akt, and NF-κB. Further, TNFα, IL-6, IL-8, and IL-1ß were all significantly induced upon infection, but no IL-1ß was detected in the supernatants. Because caspase-1 is required for IL-1ß processing and release, we examined its expression in airway epithelial cells. Interestingly, little to no caspase-1 was detectable in airway epithelial cells. Transfection of caspase-1 into airway epithelial cells restored their ability to secrete IL-1ß following B. cenocepacia infection, suggesting that a deficiency in caspase-1 is responsible, at least in part, for the attenuated IL-1ß secretion.

MiR-155 induction by microbes/microbial ligands requires NF-κB-dependent de novo protein synthesis.

MiR-155 regulates numerous aspects of innate and adaptive immune function. This miR is induced in response to Toll-like receptor ligands, cytokines, and microbial infection. We have previously shown that miR-155 is induced in monocytes/macrophages infected with Francisella tularensis and suppresses expression of the inositol phosphatase SHIP to enhance activation of the PI3K/Akt pathway, which in turn promotes favorable responses for the host. Here we examined how miR-155 expression is regulated during infection. First, our data demonstrate that miR-155 can be induced through soluble factors of bacterial origin and not the host. Second, miR-155 induction is not a direct effect of infection and it requires NF-κB signaling to up-regulate fos/jun transcription factors. Finally, we demonstrate that the requirement for NF-κB-dependent de novo protein synthesis is globally shared by microbial ligands and live bacteria. This study provides new insight into the complex regulation of miR-155 during microbial infection.

A comparison of zinc metabolism, inflammation, and disease severity in critically ill infected and noninfected adults early after intensive care unit admission.

BACKGROUND: Zinc deficiency is a cause of immune dysfunction and infection. Previous human studies have shown that the activation of the acute phase response alters zinc metabolism. Whether the alteration in zinc metabolism is predictive of disease severity in the setting of critical illness is unclear. OBJECTIVE: We sought to determine whether differences occur in zinc metabolism at the onset of critical illness between infected (septic) and noninfected subjects. DESIGN: We conducted this prospective study in an adult medical intensive care unit (MICU) at a tertiary care hospital. Subjects were enrolled within 24 h of intensive care unit admission. Subjects who did not meet sepsis criteria were considered for the critically ill control (CIC) arm. After patient consent, blood was immediately collected to measure plasma zinc and cytokine concentrations and zinc transporter gene expression in peripheral blood monocytes. Clinical data during the MICU stay were also recorded. RESULTS: A total of 56 patients were evaluated (22 septic, 22 CIC, and 12 healthy subjects). Plasma zinc concentrations were below normal in CIC patients and further reduced in the septic cohort (57.2 ± 18.2 compared with 45.5 ± 18.1 µg/dL). Cytokine concentrations increased with decreasing plasma zinc concentrations (P = 0.05). SLC39A8 gene expression was highest in patients with the lowest plasma zinc concentrations and the highest severity of illness. CONCLUSIONS: The alteration of zinc metabolism was more pronounced in septic patients than in noninfected critically ill patients. Specifically, sepsis was associated with lower plasma zinc concentrations and higher SLC39A8 mRNA expression, which correlated with an increased severity of illness, including cardiovascular dysfunction.

Inflammasome mRNA expression in human monocytes during early septic shock.

RATIONALE: Monocytes are central to the initiation of the inflammatory response in sepsis, with caspase-1 activation playing a key role. Monocyte deactivation during sepsis has been linked to poor outcomes. OBJECTIVES: Given the importance of caspase-1 in the immune response, we investigated whether monocytes from patients early in septic shock demonstrate alterations in mRNAs for caspase-1-related molecules. METHODS: Patients with septic shock (n = 26; age >18 years), critically ill intensive care unit patients (n = 20), and healthy volunteers (n = 22) were enrolled in a prospective cohort study in a university intensive care unit. Demographic, biological, physiologic, and plasma cytokine measurements were obtained. Monocytes were assayed for ex vivo tumor necrosis factor-alpha production, and fresh monocyte mRNA was analyzed by quantitative reverse-transcription polymerase chain reaction for Toll-like receptors, NOD-LRR proteins, cytokines, and nuclear factor-kappaB-related genes. MEASUREMENTS AND MAIN RESULTS: Relative copy numbers for the inflammasome mRNAs for ASC, caspase-1, NALP1, and Pypaf-7 were significantly lower in patients with septic shock compared with critically ill control subjects. NALP1 mRNA levels were linked to survival in patients with sepsis (P = 0.0068) and correlated with SAPS II scores (r = -0.63). CONCLUSIONS: These data suggest that monocyte deactivation occurs during the earliest stages of the systemic inflammatory response and that changes in inflammasome mRNA expression are part of this process.