The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study.

BACKGROUND: Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. METHODS: The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. CONCLUSIONS: The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

High-stress surgery in severely frail patients: a case report of personalized and multidisciplinary shared decision-making.

We report the case of a 65-year-old severely disabled man diagnosed with advanced renal neoplasm who was scheduled for major urologic surgery. Through a multidisciplinary approach, a shared decision-making process and mutual listening of all the health professionals involved, it was decided not to have major surgery due to the high risk of worsening the patient's health and quality of life.

Assessment of Inspiratory Effort in Spontaneously Breathing COVID-19 ARDS Patients Undergoing Helmet CPAP: A Comparison between Esophageal, Transdiaphragmatic and Central Venous Pressure Swing.

INTRODUCTION: The clinical features of COVID-19 are highly variable. It has been speculated that the progression across COVID-19 may be triggered by excessive inspiratory drive activation. The aim of the present study was to assess whether the tidal swing in central venous pressure (ΔCVP) is a reliable estimate of inspiratory effort. METHODS: Thirty critically ill patients with COVID-19 ARDS underwent a PEEP trial (0-5-10 cmH2O) during helmet CPAP. Esophageal (ΔPes) and transdiaphragmatic (ΔPdi) pressure swings were measured as indices of inspiratory effort. ΔCVP was assessed via a standard venous catheter. A low and a high inspiratory effort were defined as ΔPes ≤ 10 and >15 cmH2O, respectively. RESULTS: During the PEEP trial, no significant changes in ΔPes (11 [6-16] vs. 11 [7-15] vs. 12 [8-16] cmH2O, p = 0.652) and in ΔCVP (12 [7-17] vs. 11.5 [7-16] vs. 11.5 [8-15] cmH2O, p = 0.918) were detected. ΔCVP was significantly associated with ΔPes (marginal R2 0.87, p < 0.001). ΔCVP recognized both low (AUC-ROC curve 0.89 [0.84-0.96]) and high inspiratory efforts (AUC-ROC curve 0.98 [0.96-1]). CONCLUSIONS: ΔCVP is an easily available a reliable surrogate of ΔPes and can detect a low or a high inspiratory effort. This study provides a useful bedside tool to monitor the inspiratory effort of spontaneously breathing COVID-19 patients.

Incidence, Risk Factors, and Consequences of Post-Traumatic Stress Disorder Symptoms in Survivors of COVID-19-Related ARDS.

Purpose: To assess the prevalence of symptoms of Post-Traumatic Stress Disorder (PTSD) in survivors of COVID-19 Acute Respiratory Distress Syndrome that needed ICU care; to investigate risk factors and their impact on the Health-Related Quality of life (HR-QoL). Materials and Methods: This multicenter, prospective, observational study included all patients who were discharged from the ICU. Patients were administered the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) questionnaire, the Short-Form Health Survey 36Version 2 (SF-36v2), a socioeconomic question set and the Impact of Event Scale-Revised (IES-R) to assess PTSD. Results: The multivariate logistic regression model found that an International Standard Classification of Education Score (ISCED) higher than 2 (OR 3.42 (95% CI 1.28-9.85)), monthly income less than EUR 1500 (OR 0.36 (95% CI 0.13-0.97)), and more than two comorbidities (OR 4.62 (95% CI 1.33-16.88)) are risk factors for developing PTSD symptoms. Patients with PTSD symptoms are more likely to present a worsening in their quality of life as assessed by EQ-5D-5L and SF-36 scales. Conclusion: The main factors associated with the development of PTSD-related symptoms were a higher education level, a lower monthly income, and more than two comorbidities. Patients who developed symptoms of PTSD reported a significantly lower Health-Related Quality of life as compared to patients without PTSD. Future research areas should be oriented toward recognizing potential psychosocial and psychopathological variables capable of influencing the quality of life of patients discharged from the intensive care unit to better recognize the prognosis and longtime effects of diseases.

The Effects of Positive End Expiratory Pressure and Lung Volume on Diaphragm Thickness and Thickening.

Introduction: Diaphragm dysfunction is common in patients undergoing mechanical ventilation. The application of positive end-expiratory pressure (PEEP) and the varying end-expiratory lung volume cause changes in diaphragm geometry. We aimed to assess the impact of the level of PEEP and lung inflation on diaphragm thickness, thickening fraction and displacement. Methods: An observational study in a mixed medical and surgical ICU was conducted. The patients underwent a PEEP-titration trial with the application of three random levels of PEEP: 0 cmH2O (PEEP0), 8 cmH2O (PEEP8) and 15 cmH2O (PEEP15). At each step, the indices of respiratory effort were assessed, together with arterial blood and diaphragm ultrasound; end-expiratory lung volume was measured. Results: 14 patients were enrolled. The tidal volume, diaphragm displacement and thickening fraction were significantly lower with higher levels of PEEP, while both the expiratory and inspiratory thickness increased with higher PEEP levels. The inspiratory effort, as evaluated by the esophageal pressure swing, was unchanged. Both the diaphragm thickening fraction and displacement were significantly correlated with inspiratory effort in the whole dataset. For both measurements, the correlation was stronger at lower levels of PEEP. The difference in the diaphragm thickening fraction during tidal breathing between PEEP 15 and PEEP 0 was negatively related to the change in the functional residual capacity and the change in alveolar dead space. Conclusions: Different levels of PEEP significantly modified the diaphragmatic thickness and thickening fraction, showing a PEEP-induced decrease in the diaphragm contractile efficiency. When using ultrasound to assess diaphragm size and function, the potential effect of lung inflation should be taken into account.

Quality of Life in COVID-Related ARDS Patients One Year after Intensive Care Discharge (Odissea Study): A Multicenter Observational Study.

BACKGROUND: Investigating the health-related quality of life (HRQoL) after intensive care unit (ICU) discharge is necessary to identify possible modifiable risk factors. The primary aim of this study was to investigate the HRQoL in COVID-19 critically ill patients one year after ICU discharge. METHODS: In this multicenter prospective observational study, COVID-19 patients admitted to nine ICUs from 1 March 2020 to 28 February 2021 in Italy were enrolled. One year after ICU discharge, patients were required to fill in short-form health survey 36 (SF-36) and impact of event-revised (IES-R) questionnaire. A multivariate linear or logistic regression analysis to search for factors associated with a lower HRQoL and post-traumatic stress disorded (PTSD) were carried out, respectively. RESULTS: Among 1003 patients screened, 343 (median age 63 years [57-70]) were enrolled. Mechanical ventilation lasted for a median of 10 days [2-20]. Physical functioning (PF 85 [60-95]), physical role (PR 75 [0-100]), emotional role (RE 100 [33-100]), bodily pain (BP 77.5 [45-100]), social functioning (SF 75 [50-100]), general health (GH 55 [35-72]), vitality (VT 55 [40-70]), mental health (MH 68 [52-84]) and health change (HC 50 [25-75]) describe the SF-36 items. A median physical component summary (PCS) and mental component summary (MCS) scores were 45.9 (36.5-53.5) and 51.7 (48.8-54.3), respectively, considering 50 as the normal value of the healthy general population. In all, 109 patients (31.8%) tested positive for post-traumatic stress disorder, also reporting a significantly worse HRQoL in all SF-36 domains. The female gender, history of cardiovascular disease, liver disease and length of hospital stay negatively affected the HRQoL. Weight at follow-up was a risk factor for PTSD (OR 1.02, p = 0.03). CONCLUSIONS: The HRQoL in COVID-19 ARDS (C-ARDS) patients was reduced regarding the PCS, while the median MCS value was slightly above normal. Some risk factors for a lower HRQoL have been identified, the presence of PTSD is one of them. Further research is warranted to better identify the possible factors affecting the HRQoL in C-ARDS.

Chest wall loading during supine and prone position in patients with COVID-19 ARDS: effects on respiratory mechanics and gas exchange.

BACKGROUND: Recent reports of patients with severe, late-stage COVID-19 ARDS with reduced respiratory system compliance described paradoxical decreases in plateau pressure and increases in respiratory system compliance in response to anterior chest wall loading. We aimed to assess the effect of chest wall loading during supine and prone position in ill patients with COVID-19-related ARDS and to investigate the effect of a low or normal baseline respiratory system compliance on the findings. METHODS: This is a single-center, prospective, cohort study in the intensive care unit of a COVID-19 referral center. Consecutive mechanically ventilated, critically ill patients with COVID-19-related ARDS were enrolled and classified as higher (≥ 40 ml/cmH2O) or lower respiratory system compliance (< 40 ml/cmH2O). The study included four steps, each lasting 6 h: Step 1, supine position, Step 2, 10-kg continuous chest wall compression (supine + weight), Step 3, prone position, Step 4, 10-kg continuous chest wall compression (prone + weight). The mechanical properties of the respiratory system, gas exchange and alveolar dead space were measured at the end of each step. RESULTS: Totally, 40 patients were enrolled. In the whole cohort, neither oxygenation nor respiratory system compliance changed between supine and supine + weight; both increased during prone positioning and were unaffected by chest wall loading in the prone position. Alveolar dead space was unchanged during all the steps. In 16 patients with reduced compliance, PaO2/FiO2 significantly increased from supine to supine + weight and further with prone and prone + weight (107 ± 15.4 vs. 120 ± 18.5 vs. 146 ± 27.0 vs. 159 ± 30.4, respectively; p < 0.001); alveolar dead space decreased from both supine and prone position after chest wall loading, and respiratory system compliance significantly increased from supine to supine + weight and from prone to prone + weight (23.9 ± 3.5 vs. 30.9 ± 5.7 and 31.1 ± 5.7 vs. 37.8 ± 8.7 ml/cmH2O, p < 0.001). The improvement was higher the lower the baseline compliance. CONCLUSIONS: Unlike prone positioning, chest wall loading had no effects on respiratory system compliance, gas exchange or alveolar dead space in an unselected cohort of critically ill patients with C-ARDS. Only patients with a low respiratory system compliance experienced an improvement, with a higher response the lower the baseline compliance.

Central venous pressure swing outperforms diaphragm ultrasound as a measure of inspiratory effort during pressure support ventilation in COVID-19 patients.

PURPOSE: The COVID-19-related shortage of ICU beds magnified the need of tools to properly titrate the ventilator assistance. We investigated whether bedside-available indices such as the ultrasonographic changes in diaphragm thickening ratio (TR) and the tidal swing in central venous pressure (ΔCVP) are reliable estimates of inspiratory effort, assessed as the tidal swing in esophageal pressure (ΔPes). METHODS: Prospective, observational clinical investigation in the intensive care unit of a tertiary care Hospital. Fourteen critically-ill patients were enrolled (age 64 ± 7 years, BMI 29 ± 4 kg/m2), after 6 [3; 9] days from onset of assisted ventilation. A three-level pressure support trial was performed, at 10 (PS10), 5 (PS5) and 0 cmH2O (PS0). In each step, the esophageal and central venous pressure tidal swing were recorded, as well as diaphragm ultrasound. RESULTS: The reduction of pressure support was associated with an increased respiratory rate and a reduced tidal volume, while minute ventilation was unchanged. ΔPes significantly increased with reducing support (5 [3; 8] vs. 8 [14; 13] vs. 12 [6; 16] cmH2O, p < 0.0001), as did the diaphragm TR (9.2 ± 6.1 vs. 17.6 ± 7.2 vs. 28.0 ± 10.0%, p < 0.0001) and the ΔCVP (4 [3; 7] vs. 8 [5; 9] vs. 10 [7; 11] cmH2O, p < 0.0001). ΔCVP was significantly associated with ΔPes (R2 = 0.810, p < 0.001), as was diaphragm TR, albeit with a lower coefficient of determination (R2 = 0.399, p < 0.001). CONCLUSIONS: In patients with COVID-19-associated respiratory failure undergoing assisted mechanical ventilation, ΔCVP is a better estimate of inspiratory effort than diaphragm ultrasound.

High rates of impaired quality of life and social and economic problems at 6 months after COVID-19-related ARDS.

PURPOSE: Assess long-term quality of life (HR-QoL) and socio-economic impact in COVID-19-related ARDS (C-ARDS) survivors. METHODS: C-ARDS survivors were followed up at 6 months in this prospective, cohort study. HR-QoL was assessed using SF-36 and EQ-5D-5L, and the socio-economic burden of COVID-19 was evaluated with a dedicated questionnaire. Clinical data were prospectively recorded. RESULTS: Seventy-nine survivors, age 63 [57-71], 84% male, were enrolled. The frequency of EQ-5D-5L reported problems was significantly higher among survivors compared to normal, in mobility, usual activities, and self-care; anxiety and depression and pain were not different. SF-36 scores were lower than the reference population, and physical and mental summary scores were below normal in 52% and 33% of the subjects, respectively. In the multivariable analysis, prolonged hospital length of stay (OR 1.45; p 0.02) and two or more comorbidities on admission (OR 7.42; p 0.002) were significant predictors of impaired "physical" and "mental" HR-QoL, respectively. A total of 38% subjects worsened social relations, 42% changed their employment status, and 23% required personal care support. CONCLUSIONS: C-ARDS survivors have long-term impairment in HR-QoL and socio-economic problems. Prolonged hospital stay and previous comorbidities are risk factors for developing health-related issues.

Carotid vs. aortic velocity time integral and peak velocity to predict fluid responsiveness in mechanically ventilated patients. A comparative study.

BACKGROUND: The carotid artery velocity-time integral (CVTI) and the carotid Doppler peak velocity (cDPV), as well as measures of their variation induced by the respiratory cycle, have been proposed as fast and easy to obtain ultrasound measures for assessing fluid responsiveness in intensive care unit patients. To investigate this possibility, we conducted a prospective observational study in hemodynamically unstable patients under mechanical ventilation. METHODS: From May 1 to December 31, 2019, we conducted a prospective observational study involving 50 hemodynamically unstable patients under mechanical ventilation. We obtained a total of 800 Doppler ultrasound measurements from the left common carotid artery and at the level of the aortic annulus in the apical five-chamber view. The two measurements were performed before and after a 7 mL/kg fluid challenge and within the first hour of the onset of hemodynamic instability. The maximum Doppler peak velocity, the minimum Doppler peak velocity, and the maximum and minimum VTI at both the aortic and carotid level were acquired. RESULTS: Twenty-eight (56%) patients showed a ≥15% increase in AoVTI after the fluid challenge, and were therefore identified as "fluid responders". All Doppler measurements were always significantly greater (P<0.0001) in fluid responders in relation to both carotid and aortic parameters. Good agreement between the above-mentioned measurements was found: Cohen's kappa coefficient between the carotid and aortic ΔDPV was 0.76 (95% CI 0.58-0.94); and between the Carotid and Aortic ΔVTI it was 0.84 (95% CI 0.68-0.99). CONCLUSIONS: CDPV was found to predict fluid responsiveness in unstable mechanically ventilated patients.

Conscious sedation in critically ill patients is associated with stressors perception lower than assessed by caregivers.

BACKGROUND: In ICU, the stay is frequently a stressful experience. Caregivers may help to understand patients' perceptions; however, their reliability is uncertain. Despite the recent recommendations of lighter sedation targets, little is known about the impact of "conscious sedation" on ICU patients memories. Purpose of this prospective, observational study is to analyze the stress perception in consciously-sedated ICU-patients, comparing it to caregivers and staff members. METHODS: Twenty-nine high-risk ICU-patients treated with awake/cooperative sedation were enrolled. Before discharge, patients received a validated questionnaire for ICU stressors evaluation, also administered to their main caregiver (N.=29), to caregivers of other ICU patients not enrolled in the study (N.=33) and to staff members (ICU nurses, attending physicians, residents, medical students, N.=56). RESULTS: Total stress score was: patients 141±41, patient relatives 210±63, other relatives: 202±73, ICU staff: 232±44, P<0.001. Among patients, older age (P=0.031), longer ICU-stay (P=0.018) and awake-sedation (P=0.022) were associated with lower stress; sex and illness severity had no effect; mechanical ventilation length (P=0.021) and agitation (P=0.029) were associated with higher stress. Nurses tended to overestimate stressors more than attending physicians and trainees. Within staff members, age (P=0.021) and years of experience (P=0.069) were positively associated with overestimation. CONCLUSIONS: Conscious sedation is associated with stress perception lower than stress assessed by caregivers: relatives and staff members tend to overestimate ICU patient stress, more so with increasing age or expertise. A number of stressors underestimated by staff and families could be target of specific interventions to ameliorate quality of life during ICU stay.