Noninvasive respiratory support for COVID-19 patients: when, for whom, and how?

The significant mortality rate and prolonged ventilator days associated with invasive mechanical ventilation (IMV) in patients with severe COVID-19 have incited a debate surrounding the use of noninvasive respiratory support (NIRS) (i.e., HFNC, CPAP, NIV) as a potential treatment strategy. Central to this debate is the role of NIRS in preventing intubation in patients with mild respiratory disease and the potential beneficial effects on both patient outcome and resource utilization. However, there remains valid concern that use of NIRS may prolong time to intubation and lung protective ventilation in patients with more advanced disease, thereby worsening respiratory mechanics via self-inflicted lung injury. In addition, the risk of aerosolization with the use of NIRS has the potential to increase healthcare worker (HCW) exposure to the virus. We review the existing literature with a focus on rationale, patient selection and outcomes associated with the use of NIRS in COVID-19 and prior pandemics, as well as in patients with acute respiratory failure due to different etiologies (i.e., COPD, cardiogenic pulmonary edema, etc.) to understand the potential role of NIRS in COVID-19 patients. Based on this analysis we suggest an algorithm for NIRS in COVID-19 patients which includes indications and contraindications for use, monitoring recommendations, systems-based practices to reduce HCW exposure, and predictors of NIRS failure. We also discuss future research priorities for addressing unanswered questions regarding NIRS use in COVID-19 with the goal of improving patient outcomes.

Association between the plasma-to-red blood cell ratio and survival in geriatric and non-geriatric trauma patients undergoing massive transfusion: a retrospective cohort study

Background The benefits of a high plasma-to-red blood cell (RBC) ratio on the survival of injured patients who receive massive transfusions remain unclear, especially in older patients. We aimed to investigate the interaction of age with the plasma-to-RBC ratio and clinical outcomes of trauma patients. Methods In this retrospective study conducted from 2013 to 2016, trauma patients who received massive transfusions were included. Using a generalized additive model (GAM),we assessed how the plasma-to-RBC ratio and age affected the in-hospital mortality rates. The association of the plasma-to-RBC ratio [low (< 0.5), medium (0.5–1.0), and high (≥ 1.0)] with in-hospital mortality and the incidence of adverse events were assessed for the overall cohort and for patients stratified into non-geriatric (16–64 years) and geriatric (≥ 65 years) groups using logistic regression analyses. Results In total, 13,894 patients were included. The GAM plot of the plasma-to-RBC ratio for in-hospital mortality demonstrated a downward convex unimodal curve for the entire cohort. The low-transfusion ratio group was associated with increased odds of in-hospital mortality in the non-geriatric cohort [odds ratio 1.38, 95% confidence interval (CI) 1.22–1.56]; no association was observed in the geriatric group (odds ratio 0.84, 95% CI 0.62–1.12). An increase in the transfusion ratio was associated with a higher incidence of adverse events in the non-geriatric and geriatric groups. Conclusion The association of the non-geriatric age category and plasma-to-RBC ratio for in-hospital mortality was clearly demonstrated. However, the relationship between the plasma-to-RBC ratio with mortality among geriatric patients remains inconclusive.

Esmolol response in septic shock patients in relation to vascular waterfall phenomenon measured by critical closure pressure and mean systemic filling pressure: a prospective observational study

Background Bedside measurements of critical closure pressure (Pcc) and mean systemic circulation filling pressure (Pmsf) were utilized to evaluate the response to esmolol in septic shock patients, in relation to the vascular waterfall phenomenon and body oxygen supply and demand. Methods This prospective observational self-controlled study included patients with septic shock, newly admitted to the intensive care unit, between August 2019 and January 2021. Pcc and Pmsf, along with the heart rate and other hemodynamic indicators were observed and compared before and 1 h after esmolol IV infusion. Results After 24 h of initial hemodynamic optimization, 56 patients were finally enrolled. After start of esmolol infusion, patients had a significant decrease in cardiac index (CI) (4.0 vs. 3.3 L/min/m2, P < 0.001), a significant increase in stroke index (SI) (34.1 vs. 36.6 mL/m2, P < 0.01), and a significant decrease in heart rate (HR) (116.8 vs. 90.6 beats/min, P < 0.001). After 1 h of treatment with esmolol, patients had a significant increase in Pcc (31.4 vs. 36.7 mmHg, P < 0.01). The difference between Pcc and Pmsf before and after treatment was statistically different (4.0 vs. 10.0 mmHg, P < 0.01). After heart rate control with esmolol, the patients had a significant increase in the body circulation vascular resistance indices (RIs) (15.14 vs. 18.25 mmHg/min/m2/L, P < 0.001). There was an increase in ScvO2 in patients after treatment with esmolol, but the difference was not statistically significant (68.4% vs. 69.8%, P > 0.05), while Pcv-aCO2 was significantly lower (6.3 vs. 4.9 mmHg, P < 0.001) and patients had a significant decrease in blood lactate levels (4.0 vs. 3.6 mmol/L, P < 0.05). Conclusion Patients with septic shock whose heart rate is greater than 95 beats/min after hemodynamic optimization were treated with esmolol, which could effectively control heart rate and reduce CI, as well as improve Pcc and increase the difference between Pcc and Pmsf (known as “vascular waterfall” phenomenon), without affecting MAP, CVP, Pmsf and arteriovenous vascular resistance, and improve the balance of oxygen supply and demand in the body.

Blood purification could tackle COVID-19?

Coronavirus disease 2019 (COVID-19) threatened human lives worldwide since first reported. The current challenge for global intensivists is to establish an effective treatment for severe COVID-19. Blood purification has been applied to the treatment of various critical illnesses. Theoretically, its technique also has an enormous possibility of treating severe COVID-19 in managing inflammatory cytokines and coagulopathy. Recent clinical studies have revealed the positive clinical effect of therapeutic plasma exchange. Other studies have also indicated the considerable potential of other blood purification techniques, such as Cytosorb, AN69 surface-treated membrane, and polymyxin b hemoperfusion. Further research is needed to elucidate the actual effects of these applications.

Prolonged enhancement of cytotoxic T lymphocytes in the post-recovery state of severe COVID-19

We evaluated the peripheral blood immune responses of lymphocytes in severe Coronavirus disease 2019 (COVID-19) patients in different stages of recovery using single-cell mass cytometry. The patients with prolonged hospitalization did not show recovery of B lymphocyte counts and CD4-positive T lymphocyte counts but did show abundant CD8-positive T lymphocytes. CD4 and CD8 T cells expressing high levels of T-bet and Granzyme B were more abundant in post-recovery patients. This study showed that cytotoxic Th1 and CD8 T cells are recruited to the peripheral blood long after recovery from COVID-19.

Ultrafiltration in Japanese critically ill patients with acute kidney injury on renal replacement therapy

A recent worldwide survey indicates an international diversity in net ultrafiltration (UFNET) practices for the treatment of fluid overload in critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT). The sub-analysis of the survey has demonstrated that maximum doses of furosemide used before determination of diuretic resistance are lower in Japan than those prescribed worldwide and UFNET is lower but is initiated earlier. In contrast, the interval during which practitioners evaluate fluid balance is longer. The characterization of RRT in critically ill patients in Japan should unveil more appropriate approaches to the successful treatment of AKI.

Hydrocortisone, ascorbic acid, and thiamine (HAT) for sepsis and septic shock: a meta-analysis with sequential trial analysis

Background Sepsis is a primary global health threat and costs a lot, requiring effective and affordable treatments. We performed this meta-analysis to explore the treatment of hydrocortisone, ascorbic acid, and thiamine (HAT) in sepsis and septic shock. Methods We searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to August 14, 2021. We included randomized controlled trials (RCTs) that evaluated the HAT treatments in sepsis and septic shock. The primary outcome was the change in SOFA score over the 72 h. The second outcomes were the hospital, and 28-/30-day mortality, the duration of vasopressors, PCT clearance, hospital length of stay (LOS), and ICU LOS. We performed a subgroup analysis and a trial sequential analysis (TSA). The Der Simonian–Laird random-effects models were used to report the pooled risk ratios (RR) or mean difference (MD) with confidence intervals (CI). Results Nine RCTs, enrolling 1427 patients of sepsis and septic shock treated with HAT (717) or only standard care (710), were included. There was a significant difference between the two groups in the change in SOFA score over the first 72 h (MD 0.65, 95% CI 0.30 to 1.00), the duration of vasopressors (MD − 18.16, 95% CI − 25.65 to − 10.68) and the PCT clearance (MD 14.54, 95% CI 0.64 to 28.43). In addition, there was no significant difference in the hospital mortality (RR 1.07, 95% CI 0.85 to 1.34), the 28-/30-day mortality (RR 0.96, 95% CI 0.80 to 1.15), the hospital LOS (MD 0.78, 95% CI − 0.30 to 1.86), and ICU LOS (MD 0.12, 95% CI − 0.53 to 0.78). Conclusions The HAT combination improves the SOFA score in the first 72 h and reduces the duration of vasopressors in patients with sepsis. Given the minor mean difference of the change in SOFA score, the mortality benefit has not been observed. Trial registration PROSPERO, CRD42020203166.

Letter the editor: serious methodological concerns about a recently published meta-analysis on oxygen therapy

In a recent paper, Chen et al. report the findings of a systematic review with meta-analysis concerning conservative versus conventional oxygen therapy for critically ill patients. We wish to commend the authors for their interest in the matter. However, the authors appear to misquote findings, fail to report results for all specified analyses, do not identify all relevant trials, have post hoc changed the eligibility criteria, and have seemingly switched directions of effects in analyses of secondary outcomes. These issues have led to incorrect conclusions concerning the effects of targeted oxygen therapy in critically ill patients.

Automated alert and activation of medical emergency team using early warning score

Background Timely recognition of warning signs from deteriorating patients and proper treatment are important in improving patient safety. In comparison to the traditional medical emergency team (MET) activation triggered by phone calls, automated activation of MET may minimize activation delays. However, limited data are available on the effects of automated activation systems on the time from derangement to MET activation and on clinical outcomes. The objective of this study was to determine the impact of an automated alert and activation system for MET on clinical outcomes in unselected hospitalized patients. Methods This is an observational study using prospectively collected data from consecutive patients managed by the MET at a university-affiliated, tertiary hospital from March 2013 to December 2019. The automated alert system automatically calculates the Modified Early Warning Score (MEWS) and subsequently activates MET when the MEWS score is 7 or higher, which was implemented since August 2016. The outcome measures of interest including hospital mortality in patients with MEWS of 7 or higher were compared between pre-implementation and post-implementation groups of the automated alert and activation system in the primary analysis. The association between the implementation of the system and hospital mortality was evaluated with logistic regression analysis. Results Of the 7678 patients who were managed by MET during the study period, 639 patients during the pre-implementation period and 957 patients during the post-implementation period were included in the primary analysis. MET calls due to abnormal physiological variables were more common during the pre-implementation period, while MET calls due to medical staff’s worries or concern about the patient’s condition were more common during the post-implementation period. The median time from deterioration to MET activation was significantly shortened in the post-implementation period compared to the pre-implementation period (34 min vs. 60 min, P < 0.001). In addition, unplanned ICU admission rates (41.2% vs. 71.8%, P < 0.001) was reduced during the post-implementation period. Hospital mortality was decreased after implementation of the automated alert system (27.2% vs. 38.5%, P < 0.001). The implementation of the automated alert and activation system was associated with decreased risk of death in the multivariable analysis (adjusted OR 0.73, 95% CI 0.56–0.90). Conclusions After implementing an automated alert and activation system, the time from deterioration to MET activation was shortened and clinical outcomes were improved in hospitalized patients.

Intensive care unit versus high-dependency care unit for patients with acute heart failure: a nationwide propensity score-matched cohort study

Background A structure and staffing model similar to that in general intensive care unit (ICUs) is applied to cardiac intensive care unit (CICUs) for patients with acute heart failure. However, there is limited evidence on the structure and staffing model of CICUs. The present study aimed to assess whether critical care for patients with acute heart failure in the ICUs is associated with improved outcomes than care in the high-dependency care units (HDUs), the hospital units in which patient care levels and costs are between the levels found in the ICU and general ward. Methods This nationwide, propensity score-matched, retrospective cohort study was performed using a national administrative inpatient database in Japan. We identified all patients who were hospitalized for acute heart failure and admitted to the ICU or HDU on the day of hospital admission from April 2014 to March 2019. Propensity score-matching analysis was performed to compare the in-hospital mortality between acute heart failure patients treated in the ICU and HDU on the day of hospital admission. Results Of 202,866 eligible patients, 78,646 (39%) and 124,220 (61%) were admitted to the ICU and HDU, respectively, on the day of admission. After propensity score matching, there was no statistically significant difference in in-hospital mortality between patients who were admitted to the ICU and HDU on the day of admission (10.7% vs. 11.4%; difference, − 0.6%; 95% confidence interval, − 1.5% to 0.2%). In the subgroup analyses, there was a statistically significant difference in in-hospital mortality between the ICU and HDU groups among patients receiving noninvasive ventilation (9.4% vs. 10.5%; difference, − 1.0%; 95% confidence interval, − 1.9% to − 0.1%) and patients receiving intubation (32.5% vs. 40.6%; difference, − 8.0%; 95% confidence interval, − 14.5% to − 1.5%). There were no statistically significant differences in other subgroup analyses. Conclusions Critical care in ICUs was not associated with lower in-hospital mortality than critical care in HDUs among patients with acute heart failure. However, critical care in ICUs was associated with lower in-hospital mortality than critical care in HDUs among patients receiving noninvasive ventilation and intubation.