Frailty trajectories in ICU survivors: A comparison between the clinical frailty scale and the Tilburg frailty Indicator and association with 1 year mortality.

PURPOSE: To test the agreement of the Clinical Frailty Scale (CFS) and the Tilburg Frailty Indicator (TFI), their association with 3, 6 months and 1-year mortality and the trajectory of frailty in a mixed population of ICU survivors. MATERIAL AND METHODS: This is a prospective, multicenter, longitudinal study on ICU survivors ≥18 years old with an ICU stay >72 h. For each patient, sociodemographic and clinical data were collected. Frailty was assessed during ICU stay and at 3, 6, 12 months after ICU discharge, through both CFS and TFI. RESULTS: 124 patients with a mean age of 66 years old were enrolled. The baseline prevalence of frailty was 15.3% by CFS and 44.4% by TFI. Baseline CFS and TFI correlated but showed low agreement (Cohen's K = 0.23, p < 0.001). Baseline CFS score, but not TFI, was significantly associated to 1 year mortality. Moreover, CFS score during the follow-up was independently associated 1-year mortality (OR = 1.43; 95% CI: 1.18-1.73). CONCLUSIONS: CFS and TFI identify different populations of frail ICU survivors. Frail patients before ICU according to CFS have a significantly higher mortality after ICU discharge. The CFS during follow-up is an independent negative prognostic factor of long-term mortality in the ICU population.

Relationship between Muscle Mass, Bone Density and Vascular Calcifications in Elderly People with SARS-CoV-2 Pneumonia.

BACKGROUND: Little is known about the changes in organs and tissues that may make elder patients more vulnerable to acute stressors such as SARS-CoV-2 infection. METHODS: In 80 consecutive elderly patients with SARS-CoV-2 infection, we evaluated the association between the descending thoracic aorta calcium score, L1 bone density and T12 skeletal muscle density measured on the same scan by high-resolution computed tomography. RESULTS: At median regression, the ln-transformed DTA calcium score was inversely associated with L1 bone density (-0.02, 95%CI -0.04 to -0.01 ln-Agatston units for an increase of 1 HU) and with T12 muscle density (-0.03, -0.06 to -0.001 ln-Agatston units for an increase of 1 HU). At penalized logistic regression, an increase of 1 ln-Agatston unit of DTA calcium score was associated with an OR of death of 1.480 (1.022 to 2.145), one of 1 HU of bone density with an OR of 0.981 (0.966 to 0.996) and one of 1 HU of muscle density with an OR of 0.973 (0.948 to 0.999). These relationships disappeared after correction for age and age was the stronger predictor of body composition and death. CONCLUSIONS: Age has a big effect on the relationship between vascular calcifications, L1 bone density and T12 muscle density and on their relationship with the odds of dying.

Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study.

BACKGROUND: Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. METHODS: This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. RESULTS: Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). CONCLUSIONS: DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).

Clinical implications of microvascular CT scan signs in COVID-19 patients requiring invasive mechanical ventilation.

PURPOSE: COVID-19-related acute respiratory distress syndrome (ARDS) is characterized by the presence of signs of microvascular involvement at the CT scan, such as the vascular tree in bud (TIB) and the vascular enlargement pattern (VEP). Recent evidence suggests that TIB could be associated with an increased duration of invasive mechanical ventilation (IMV) and intensive care unit (ICU) stay. The primary objective of this study was to evaluate whether microvascular involvement signs could have a prognostic significance concerning liberation from IMV. MATERIAL AND METHODS: All the COVID-19 patients requiring IMV admitted to 16 Italian ICUs and having a lung CT scan recorded within 3 days from intubation were enrolled in this secondary analysis. Radiologic, clinical and biochemical data were collected. RESULTS: A total of 139 patients affected by COVID-19 related ARDS were enrolled. After grouping based on TIB or VEP detection, we found no differences in terms of duration of IMV and mortality. Extension of VEP and TIB was significantly correlated with ground-glass opacities (GGOs) and crazy paving pattern extension. A parenchymal extent over 50% of GGO and crazy paving pattern was more frequently observed among non-survivors, while a VEP and TIB extent involving 3 or more lobes was significantly more frequent in non-responders to prone positioning. CONCLUSIONS: The presence of early CT scan signs of microvascular involvement in COVID-19 patients does not appear to be associated with differences in duration of IMV and mortality. However, patients with a high extension of VEP and TIB may have a reduced oxygenation response to prone positioning. TRIAL REGISTRATION: NCT04411459.

Bacterial infections in critically ill patients with SARS-2-COVID-19 infection: results of a prospective observational multicenter study.

PURPOSE: To investigate the prevalence, incidence and characteristics of bacterial infections and their impact on outcome in critically ill patients infected with COVID-19. METHODS: We conducted a prospective observational study in eight Italian ICUs from February to May 2020; data were collected through an interactive electronic database. Kaplan-Meier analysis (limit product method) was used to identify the occurrence of infections and risk of acquisition. RESULTS: During the study period 248 patients were recruited in the eight participating ICUs. Ninety (36.3%) patients developed at least one episode of secondary infection. An ICU length of stay between 7 and 14 days was characterized by a higher occurrence of infectious complications, with ventilator-associated pneumonia being the most frequent. At least one course of antibiotic therapy was given to 161 (64.9%) patients. Overall ICU and hospital mortality were 33.9% and 42.9%, respectively. Patients developing bacteremia had a higher risk of ICU mortality [45.9% vs. 31.6%, odds ratio 1.8 (95% CI 0.9-3.7), p = 0.069] and hospital mortality [56.8% vs. 40.3%, odds ratio 1.9 (95% CI 1.1-3.9), p = 0.04]. CONCLUSION: In critically ill patients infected with COVID-19 the incidence of bacterial infections is high and associated with worse outcomes. Regular microbiological surveillance and strict infection control measures are mandated.

Health-related quality of life profiles, trajectories, persistent symptoms and pulmonary function one year after ICU discharge in invasively ventilated COVID-19 patients, a prospective follow-up study.

BACKGROUND: Health-related quality of life (HRQoL) impairment is often reported among COVID-19 ICU survivors, and little is known about their long-term outcomes. We evaluated the HRQoL trajectories between 3 months and 1 year after ICU discharge, the factors influencing these trajectories and the presence of clusters of HRQoL profiles in a population of COVID-19 patients who underwent invasive mechanical ventilation (IMV). Moreover, pathophysiological correlations of residual dyspnea were tested. METHODS: We followed up 178 survivors from 16 Italian ICUs up to one year after ICU discharge. HRQoL was investigated through the 15D instrument. Available pulmonary function tests (PFTs) and chest CT scans at 1 year were also collected. A linear mixed-effects model was adopted to identify factors associated with different HRQoL trajectories and a two-step cluster analysis was performed to identify HRQoL clusters. RESULTS: We found that HRQoL increased during the study period, especially for the significant increase of the physical dimensions, while the mental dimensions and dyspnea remained substantially unchanged. Four main 15D profiles were identified: full recovery (47.2%), bad recovery (5.1%) and two partial recovery clusters with mostly physical (9.6%) or mental (38.2%) dimensions affected. Gender, duration of IMV and number of comorbidities significantly influenced HRQoL trajectories. Persistent dyspnea was reported in 58.4% of patients, and weakly, but significantly, correlated with both DLCO and length of IMV. CONCLUSIONS: HRQoL impairment is frequent 1 year after ICU discharge, and the lowest recovery is found in the mental dimensions. Persistent dyspnea is often reported and weakly correlated with PFTs alterations. TRIAL REGISTRATION: NCT04411459.

Quality of life of COVID-19 critically ill survivors after ICU discharge: 90 days follow-up.

PURPOSE: The onset of the coronavirus disease 19 (COVID-19) pandemic in Italy induced a dramatic increase in the need for intensive care unit (ICU) beds for a large proportion of patients affected by COVID-19-related acute respiratory distress syndrome (ARDS). The aim of the present study was to describe the health-related quality of life (HRQoL) at 90 days after ICU discharge in a cohort of COVID-19 patients undergoing invasive mechanical ventilation and to compare it with an age and sex-matched sample from the general Italian and Finnish populations. Moreover, the possible associations between clinical, demographic, social factors, and HRQoL were investigated. METHODS: COVID-19 ARDS survivors from 16 participating ICUs were followed up until 90 days after ICU discharge and the HRQoL was evaluated with the 15D instrument. A parallel cohort of age and sex-matched Italian population from the same geographic areas was interviewed and a third group of matched Finnish population was extracted from the Finnish 2011 National Health survey. A linear regression analysis was performed to evaluate potential associations between the evaluated factors and HRQoL. RESULTS: 205 patients answered to the questionnaire. HRQoL of the COVID-19 ARDS patients was significantly lower than the matched populations in both physical and mental dimensions. Age, sex, number of comorbidities, ARDS class, duration of invasive mechanical ventilation, and occupational status were found to be significant determinants of the 90 days HRQoL. Clinical severity at ICU admission was poorly correlated to HRQoL. CONCLUSION: COVID-19-related ARDS survivors at 90 days after ICU discharge present a significant reduction both on physical and psychological dimensions of HRQoL measured with the 15D instrument. TRIAL REGISTRATION: NCT04411459.

Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID-19 patients: a cohort study.

BACKGROUND: Prone positioning (PP) has been used to improve oxygenation in patients affected by the SARS-CoV-2 disease (COVID-19). Several mechanisms, including lung recruitment and better lung ventilation/perfusion matching, make a relevant rational for using PP. However, not all patients maintain the oxygenation improvement after returning to supine position. Nevertheless, no evidence exists that a sustained oxygenation response after PP is associated to outcome in mechanically ventilated COVID-19 patients. We analyzed data from 191 patients affected by COVID-19-related acute respiratory distress syndrome undergoing PP for clinical reasons. Clinical history, severity scores and respiratory mechanics were analyzed. Patients were classified as responders (≥ median PaO2/FiO2 variation) or non-responders (< median PaO2/FiO2 variation) based on the PaO2/FiO2 percentage change between pre-proning and 1 to 3 h after re-supination in the first prone positioning session. Differences among the groups in physiological variables, complication rates and outcome were evaluated. A competing risk regression analysis was conducted to evaluate if PaO2/FiO2 response after the first pronation cycle was associated to liberation from mechanical ventilation. RESULTS: The median PaO2/FiO2 variation after the first PP cycle was 49 [19-100%] and no differences were found in demographics, comorbidities, ventilatory treatment and PaO2/FiO2 before PP between responders (96/191) and non-responders (95/191). Despite no differences in ICU length of stay, non-responders had a higher rate of tracheostomy (70.5% vs 47.9, P = 0.008) and mortality (53.7% vs 33.3%, P = 0.006), as compared to responders. Moreover, oxygenation response after the first PP was independently associated to liberation from mechanical ventilation at 28 days and was increasingly higher being higher the oxygenation response to PP. CONCLUSIONS: Sustained oxygenation improvement after first PP session is independently associated to improved survival and reduced duration of mechanical ventilation in critically ill COVID-19 patients.

Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study.

BACKGROUND: The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU). METHODS: This was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Of the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3-8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP (p = 0.003), PCT (p = 0.025) and CRP (p = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75). CONCLUSIONS: While the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically ill patients developing nosocomial sepsis. Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1 .

A possible future for anaesthesia in breast surgery: thoracic paravertebral block and awake surgery. A prospective observational study.

INTRODUCTION: Quadrantectomy is a surgical procedure traditionally performed under general anaesthesia with intraoperative and postoperative opioid-based analgesia. The use of locoregional anaesthesia techniques in breast surgery has become widespread and allows excellent management of intraoperative and postoperative pain with reduced opioid consumption. We chose thoracic paravertebral block as regional anaesthesia technique in breast surgery to investigate the possibility of carrying out this surgery with the patient awake. METHODS: A prospective observational study on 50 patients was designed. The primary outcome for this study was the possibility to carry out the surgery with only the paravertebral block associated with mild sedation without general anaesthesia. Forty minutes before the start of the surgery, an ultrasound-guided thoracic paravertebral block was performed at two thoracic levels, and for each level, 7 mL of ropivacaine 0.7% was injected. Sedation was obtained with target-controlled infusion of propofol. RESULTS: Forty-nine patients underwent the operation awake; in one case, we had to place an I-gel and perform general anaesthesia. No patient needed intraoperative or postoperative opioids. The numeric rating scale, recorded at 0, 2, 6, 12, 24, and 36 hours, was greater than 3 in only five patients. CONCLUSIONS: We believe that if in the future we try to make quadrantectomy an intervention in which the anaesthesia is exclusively regional, therefore with a patient awake and collaborating, it will not be possible to ignore the use of thoracic paravertebral block.

Factors influencing liberation from mechanical ventilation in coronavirus disease 2019: multicenter observational study in fifteen Italian ICUs.

BACKGROUND: A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation.The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality. METHODS: This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk. RESULTS: Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO2/FiO2 ratio during the first 5 days of MV, respiratory system compliance (CRS) lower than 40 mL/cmH2O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications.ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable. CONCLUSIONS: Age, SOFA score at ICU admission, CRS, PaO2/FiO2, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19. TRIAL REGISTRATION: NCT04411459.

Bronchial blocker positioning: learning curve and confidence in its use.

BACKGROUND: Despite being simple and safe to use and cheap, EZ blocker (EZB) remains underused probably because it requires particular skills in recognizing airway and in using fiber-bronchoscopy to check the exact position of their cuffs. Thus, we planned an education training program on the use of EZB for novices in anesthesia and evaluated the number of procedures required for the acquisition of the skills of this technique. METHODS: The educational training program included three different phases as follows. The first phase included a lecture on the utility of one-lung ventilation in thoracic surgery, on the use of the fiber- bronchoscopy and on the characteristics of EZB. The second phase consisted in a practical teaching course performed on a manikin model to acquire the skills in EZB. The third phase was a clinical training where each participant performed a defined number in patients scheduled for thoracic surgery procedures. The acquisition of dexterity and satisfaction were then statistically valuated. RESULTS: The dexterity in placing EZB significantly increased after six attempts (P<0.1). Participants acquired skills in correcting position EZB after 15 attempts. Participants increased their level of confidence with EZB (score 5.7±1.3) and were highly satisfied with the training received (score 5.8±1.6). CONCLUSIONS: EZB is a valid strategy for obtaining one lung ventilation. Thus, it should be included in the armamentarium of all anesthetists interested in the field of thoracic surgery. Our teaching course seems to be a valuable method to instill easily and speedily in training novices in anesthesia the skills in placing EZB.

The importance of drug-induced sedation endoscopy (D.I.S.E.) techniques in surgical decision making: conventional versus target controlled infusion techniques-a prospective randomized controlled study and a retrospective surgical outcomes analysis.

Drug-Induced Sedation Endoscopy (DISE) consists of the direct observation of the upper airways during sedative-induced sleep, allowing the identification of the sites of pharyngeal collapse, which is the main pathological event in Obstructive Sleep Apnea (OSA). The Authors have compared Target Controlled Infusion (TCI) sedation endoscopy (TCI-DISE) technique to conventional DISE (CDISE), performed by a manual bolus injection of sedative agent, to recreate accurately and safely snoring and apnea patterns comparable to natural sleep. The authors conducted a prospective, randomized, long-term study and a retrospective analysis of surgical outcomes. The apnea-event observation and its correlation with pharyngeal collapse patterns is the primary endpoint; secondary endpoints are defined as stability and safety of sedation plan of DISE-TCI technique. From January 2009 to January 2011, OSA patients were included in the study and randomly allocated into two groups: the bolus injection conventional DISE group and the TCI-DISE group. Third endpoint is to compare the surgical outcomes enrolling OSA patients from January 2009 to June 2015. We recorded the complete apnea-event at oropharynx and hypopharynx levels in 15/50 pts in conventional DISE group (30%) and in 99/123 pts in TCI-DISE group (81%) (p < 0.0001). Four pts needed oxygen in conventional DISE group because a severe desaturation occurred during the first bolus of propofol (1 mg/kg) (p = 0.4872 ns). We recorded instability of the sedation plan in 13 patients of conventional DISE group (65%) and 1 patient of the TCI-DISE group (5%) (p = 0.0001). In 37 TCI-DISE group surgical patients we reported a significant reduction of postoperative AHI (from 42.7 ± 20.2 to 11.4 ± 10.3) in comparison with postoperative AHI in 15 C-DISE group surgical patients (from 41.3 ± 23.4 to 20.4 ± 15.5) (p = 0.05). Our results suggest the DISE-TCI technique as first choice in performing sleep-endoscopy because of its increased accuracy, stability and safety. However, it is mandatory an accurate assessment of PSG/PM, which allows us to differentiate OSA patients in whom UA anatomical abnormalities are predominant in comparison with not-anatomical pathophysiologic factors, achieving good surgical patient's selection and outcomes as a consequence.

Expiratory Flow Limitation as a Risk Factor for Pulmonary Complications After Major Abdominal Surgery.

BACKGROUND: Postoperative pulmonary complications are major causes of postoperative morbidity and mortality. Although several risk factors have been associated with postoperative pulmonary complications, they are not consistent between studies and, even in those studies in which these factors were identified, the predictive power is low. We hypothesized that postoperative pulmonary complications would correlate with the presence of intraoperative expiratory flow limitation. METHODS: Candidates for this prospective observational study were patients undergoing general anesthesia for major abdominal surgery. Preoperative data collection included age, body mass index, American Society of Anesthesiologists class, smoking and dyspnea history, and room air PO2. Expiratory flow limitation was assessed intraoperatively using the positive end-expiratory pressure test. Postoperative data collection included the incidence of postoperative pulmonary complications. RESULTS: Of the 330 patients we enrolled, 31% exhibited expiratory flow limitation. On univariate analysis, patients with expiratory flow limitation were more likely to have postoperative pneumonia (5% vs 0%, P < .001) and acute respiratory failure (11% vs 1%, P < .001) and a longer length of hospital stay (7 vs 9 days, P < .01). Multivariate analysis identified that expiratory flow limitation increased the risk of developing postoperative pulmonary complications by >50% (risk ratio, 2.7; 95% confidence interval, 1.7-4.2). Age and Medical Research Council dyspnea score were also significant multivariate risk factors for pulmonary complications. CONCLUSIONS: Our results show that intraoperative expiratory flow limitation correlates with that of postoperative pulmonary complication after major abdominal surgery. Further work is needed to better understand the relevance of expiratory flow limitation on postoperative pulmonary outcomes.