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).

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.

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.

Blockage of interleukin-1ß with canakinumab in patients with Covid-19.

There is the urgent need to study the effects of immunomodulating agents as therapy for Covid-19. An observational, cohort, prospective study with 30 days of observation was carried out to assess clinical outcomes in 88 patients hospitalized for Covid-19 pneumonia and treated with canakinumab (300 mg sc). Median time from diagnosis of Covid-19 by viral swab to administration of canakinumab was 7.5 days (range 0-30, IQR 4-11). Median PaO2/FiO2 increased from 160 (range 53-409, IQR 122-210) at baseline to 237 (range 72-533, IQR 158-331) at day 7 after treatment with canakinumab (p < 0.0001). Improvement of oxygen support category was observed in 61.4% of cases. Median duration of hospitalization following administration of canakinumab was 6 days (range 0-30, IQR 4-11). At 7 days, 58% of patients had been discharged and 12 (13.6%) had died. Significant differences between baseline and 7 days were observed for absolute lymphocyte counts (mean 0.60 vs 1.11 × 109/L, respectively, p < 0.0001) and C-reactive protein (mean 31.5 vs 5.8 mg/L, respectively, p < 0.0001).Overall survival at 1 month was 79.5% (95% CI 68.7-90.3). Oxygen-support requirements improved and overall mortality was 13.6%. Confirmation of the efficacy of canakinumab for Covid-19 warrants further study in randomized controlled trials.

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.

Single shot ultrasound-guided thoracic paravertebral block for opioid-free radical mastectomy: a prospective observational study.

BACKGROUND: General anesthesia (GA) is the most commonly used anesthesiological technique for radical mastectomy operations and can be associated with loco-regional anesthesia techniques. The aim of our study, carried out on 51 patients, was to assess the effectiveness of thoracic paravertebral block (TPVB) associated with GA, or as a sole anesthesiological technique for postoperative pain control and for the reduction of intra and postoperative opioids consumption. MATERIALS AND METHODS: Fifty-one patients with neoplastic breast disease and elected as candidates for radical mastectomy were included in the study. The primary outcomes for this study were intra and postoperative opioid consumption and postoperative pain intensity. In 37 patients, TPVB was associated with GA while in 14 patients it was used as the sole anesthesiological technique. Data are reported as mean with standard deviation median with interquartile range, number, and percentage, depending on the underlying distribution. RESULTS: We did not use intra or postoperative opioids for any patient and the Numeric Rate Scale, assessed at time 0, at the end of the surgery, and 2, 6, 12, and 24 hrs after surgery, was >3 in seven patients only. CONCLUSIONS: This study aims to show how TPVB can be used to carry out radical mastectomy procedures so that intra and postoperative opioids use can be avoided. In our study, TPVB was used in total mastectomy procedures in association with GA or as the sole anesthesiological technique, without the intra and postoperative use of opioids and with a significant reduction of local anesthetic dosages compared to those reported in the existing literature.

Successful use of targeted temperature management in pregnancy after out-of-hospital cardiac arrest.

Targeted temperature management (TTM) may be considered on an individual basis after cardiac arrest in a comatose pregnant patient. The only 3 cases published so far describing the use of TTM in this setting have conflicting results in terms of fetal outcome.

Succinylcholine activation of human horizontal eye muscles.

PURPOSE: Succinylcholine (Sch) can induce contracture in slow, multiply innervated muscle fibres of the extraocular muscles in animals of different species. Slow muscle fibres also exist in human eye muscle but their physiological properties have not been studied. METHODS: Isometric tension development was recorded in the lateral and medial rectus muscles in 12 patients operated under general anaesthesia. A strain gauge probe was attached with 5-0 silk sutures to the muscle tendon. Recordings were made in 12 eye muscles with the tendon attached to the globe and in four muscles detached from the globe. Muscle activation was produced by i.v. injection of Sch at a dose of 0.2-0.3 mg/kg bodyweight. RESULTS: A single injection of Sch induced slow contractures lasting for several minutes. In the muscles attached to the globe, mean maximal isometric tension was 12.2 g in the lateral rectus and 12.8 g in the medial rectus. Similar tension was shown in the muscles detached from the globe. CONCLUSIONS: The contracture of eye muscles in response to Sch showed characteristics typical of slow muscle fibre activation in amphibian and avian muscle and confirmed the participation of slow fibre systems in ocular motor control.

Assessment of the risk of bleeding in patients undergoing surgery or invasive procedures: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET).

SYNOPSIS OF RECOMMENDATIONS: The Italian Society for Thrombosis and Haemostasis (SISET: Società Italiana per lo Studio dell' Emostasi e della Trombosi) promoted the development of a series of guidelines which would adopt evidence-based medicine methodology on clinically relevant problems in the field of haemostasis and thrombosis. The objective of the present guidelines is to provide recommendations for the pre-operative and pre-procedural assessment of the bleeding risk with the aim of reducing the incidence of preventable bleeding complications and limiting laboratory tests to the those necessary. The predictive value of haemostatic tests for bleeding complications after surgery or invasive procedures has been evaluated in prospective or retrospective cohort studies only. All retrieved studies were of low methodological quality with a high potential for bias because none conducted a blinded outcome assessment. In addition, different criteria for the severity of bleeding events and different reference values of the laboratory tests were adopted. The low methodological quality limits the validity of the results of these studies. Some of the clinical queries proposed by the working group were not addressed by the studies available in the literature. The areas with evidence, although of low quality, are the following: general surgery in adults (for history, PT, APTT, platelet count and bleeding time), neurosurgery in adults (for history, PT, APTT, platelet count), adenotonsillectomy in children (for history, PT, APTT, platelet count and bleeding time), invasive procedures in adults (for PT, APTT, platelet count), dental extractions (for the bleeding time only), cataract extraction (for platelet count). No studies are available in children for major surgery other than adenotonsillectomy, neurosurgery and invasive procedures.