Background: The telemedicine intensive care unit (Tele-ICU) is defined as a system in which intensive care professionals remotely provide care to critically ill patients and support the on-site staff in the intensive care unit (ICU) using secured audio–video and electronic links. Although the Tele-ICU is expected to resolve the shortage of intensivists and reduce the regional disparities in intensive care resources, the efficacy has not yet been evaluated in Japan because of a lack of clinically available system. Methods: This was a single-center, historical comparison study in which the impact of the Tele-ICU on ICU performance and changes in workload of the on-site staff were evaluated. The Tele-ICU system developed in the United States was used. Data for 893 adult ICU patients before the Tele-ICU implementation and for all adult patients registered in the Tele-ICU system from April 2018 to March 2020 were abstracted and included. We investigated ICU and hospital mortality and length of stay and ventilation duration after the Tele-ICU implementation in each ICU, and compared between pre and post implementation and changes over time. We also assessed physician workload as defined by the frequency and duration of access to the electronic medical record (EMR) of the targeted ICU patients. Results: After the Tele-ICU implementation 5438 patients were included. In unadjusted data pre/post study showed significant decreases in ICU (8.5–3.8%) and hospital (12.4–7.7%) mortality and ICU length of stay (p < 0.001), and those values were maintained for 2 years. In data stratified by predicted hospital mortality, ICU and hospital actual mortality in high and medium risk patients decreased significantly after the implementation. Ventilation duration was shortened (p < 0.007). Access frequency of the on-site physicians decreased by 25%, and the decrease occurred in the daytime shift and in the physicians with 3–15 years of work experience. Conclusions: Our study showed the Tele-ICU implementation was associated with lower mortality, especially in medium and high risk patients, and decreased EMR-related tasks of on-site physicians. These results suggest that the Tele-ICU could be a solution of the shortage of intensivists and regional disparities for intensive care.

Mechanical ventilation can initiate ventilator-associated lung injury (VALI) and contribute to the development of multiple organ dysfunction. Although a lung protective strategy limiting both tidal volume and plateau pressure reduces VALI, uneven intrapulmonary gas distribution is still capable of increasing regional stress and strain, especially in non-homogeneous lungs, such as during acute respiratory distress syndrome. Real-time monitoring of regional ventilation may prevent inhomogeneous ventilation, leading to a reduction in VALI. Electrical impedance tomography (EIT) is a technique performed at the patient’s bedside. It is noninvasive and radiation-free and provides dynamic tidal images of gas distribution. Studies have reported that EIT provides useful information both in animal and clinical studies during mechanical ventilation. EIT has been shown to be useful during lung recruitment, titration of positive end-expiratory pressure, lung volume estimation, and evaluation of homogeneity of gas distribution in a single EIT measure or in combination with multiple EIT measures. EIT-guided mechanical ventilation preserved the alveolar architecture and maintained oxygenation and lung mechanics better than low-tidal volume ventilation in animal models. However, careful assessment is required for data analysis owing to the limited understanding of the results of EIT interpretation. Previous studies indicate monitoring regional ventilation by EIT is feasible in the intensive care setting and has potential to lead to lung protective ventilation. Further clinical studies are warranted to evaluate whether monitoring of regional ventilation using EIT can shorten the duration of ventilation or improve mortality in patients with acute respiratory distress syndrome.

This is a prospective multicenter cohort study aiming to investigate the association between early mobilization (EM), defined as a rehabilitation level of sitting at the edge of the bed or higher within 72 h of ICU admission, and psychiatric outcome. Consecutive patients, admitted to the ICU for more than 48 h, were enrolled. The primary outcome was the incidence of psychiatric symptoms at 3 months after hospital discharge defined as the presence of any of three symptoms: depression, anxiety, or post-traumatic stress disorder (PTSD). Risk ratio (RR) and multiple logistic regression analysis were used. As a sensitivity analysis, two methods for inverse probability of treatment weighting statistics were performed. Of the 192 discharged patients, 99 (52%) were assessed. The patients who achieved EM had a lower incidence of psychiatric symptoms compared to those who did not (25% vs. 51%, p-value 0.008, odds ratio (OR) 0.27, adjusted p = 0.032). The RR for psychiatric symptoms in the EM group was 0.49 [95% Confidence Interval, 0.29–0.83]. Sensitivity analysis accounting for the influence of death, loss to follow-up (OR 0.28, adjusted p = 0.008), or potential confounders (OR 0.49, adjusted p = 0.046) consistently showed a lower incidence of psychiatric symptoms in the EM group. EM was consistently associated with fewer psychiatric symptoms.

Hyperinflammation plays an important role in severe and critical COVID-19. Using inconsistent criteria, many researchers define hyperinflammation as a form of very severe inflammation with cytokine storm. Therefore, COVID-19 patients are treated with anti-inflammatory drugs. These drugs appear to be less efficacious than expected and are sometimes accompanied by serious adverse effects. SARS-CoV-2 promotes cellular ATP release. Increased levels of extracellular ATP activate the purinergic receptors of the immune cells initiating the physiologic pro-inflammatory immune response. Persisting viral infection drives the ATP release even further leading to the activation of the P2X7 purinergic receptors (P2X7Rs) and a severe yet physiologic inflammation. Disease progression promotes prolonged vigorous activation of the P2X7R causing cell death and uncontrolled ATP release leading to cytokine storm and desensitisation of all other purinergic receptors of the immune cells. This results in immune paralysis with co-infections or secondary infections. We refer to this pathologic condition as hyperinflammation. The readily available and affordable P2X7R antagonist lidocaine can abrogate hyperinflammation and restore the normal immune function. The issue is that the half-maximal effective concentration for P2X7R inhibition of lidocaine is much higher than the maximal tolerable plasma concentration where adverse effects start to develop. To overcome this, we selectively inhibit the P2X7Rs of the immune cells of the lymphatic system inducing clonal expansion of Tregs in local lymph nodes. Subsequently, these Tregs migrate throughout the body exerting anti-inflammatory activities suppressing systemic and (distant) local hyperinflammation. We illustrate this with six critically ill COVID-19 patients treated with lidocaine.

Purpose: Gait independence is one of the most important factors related to returning home from the hospital for patients treated in the intensive care unit (ICU), but the factors affecting gait independence have not been clarified. This study aimed to determine the factors affecting gait independence at hospital discharge using a standardized early mobilization protocol that was shared by participating hospitals. Materials and methods: Patients who entered the ICU from January 2017 to March 2018 were screened. The exclusion criteria were mechanical ventilation < 48 hours, age < 18, loss of gait independence before hospitalization, being treated for neurological issues, unrecoverable disease, unavailability of continuous data, and death during ICU stay. Basic attributes, such as age, ICU length of stay, information on early mobilization while in the ICU, Medical Research Council (MRC) sum-score at ICU discharge, incidence of ICU-acquired weakness (ICU-AW) and delirium, and the degree of gait independence at hospital discharge, were collected. Gait independence was determined using a mobility scale of the Barthel Index, and the factors that impaired gait independence at hospital discharge were investigated using a Cox proportional hazard regression analysis. Results: One hundred thirty-two patients were analyzed. In the univariate analysis, age, APACHE II score, duration of mechanical ventilation, ICU length of stay, incidence of delirium, and MRC sum-score at ICU discharge were extracted as significant. In the multivariate analysis, age (p = 0.014), MRC sum-score < 48 (p = 0.021), and delirium at discharge from ICU (p < 0.0001) were extracted as significant variables. Conclusions: We found that age and incidence of ICU-AW and delirium were significantly related to impaired gait independence at hospital discharge.

Stretching the alveolar epithelial type I (AT I) cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP) (purinergic signaling). Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases. When extracellular ATP reaches levels >100 μM, the ATP receptors of the AT II cells become desensitized and surfactant impairment is initiated. The resulting alteration in viscoelastic properties and in alveolar opening and collapse time-constants leads to alveolar collapse and the redistribution of inspired air from the alveoli to the alveolar ducts, which become pathologically dilated. The collapsed alveoli connected to these dilated alveolar ducts are subject to a massive strain, exacerbating the ATP release. After reaching concentrations >300 μM extracellular ATP acts as a danger-associated molecular pattern, causing capillary leakage, alveolar space edema, and further deactivation of surfactant by serum proteins. Decreasing the tidal volume to 6 mL/kg or less at this stage cannot prevent further lung injury.