Intergroup comparability is of paramount importance in clinical research since it is impossible to draw conclusions on a treatment if populations with different characteristics are compared. While an adequate randomization process in randomized controlled trials (RCTs) ensures a balanced distribution of subjects between groups, the distribution in observational prospective and retrospective studies may be influenced by many confounders. Propensity score (PS) is a statistical technique that was developed more than 30 years ago with the purpose of estimating the probability to be assigned to a group. Once evaluated, the PS could be used to adjust and balance the groups using different methods such as matching, stratification, covariate adjustment, and weighting. The validity of PS is strictly related to the confounders used in the model, and confounders that are either not identified or not available will produce biases in the results. RCTs will therefore continue to provide the highest quality of evidence, but PS allows fine adjustments on otherwise unbalanced groups, which will increase the strength and quality of observational studies.
Weaning failure has been defined as failure to discontinue mechanical ventilation, as assessed by the spontaneous breathing trial, or need for re-intubation after extubation, so-called extubation failure. Both events represent major clinical and economic burdens, and are associated with high morbidity and mortality. The most important mechanism leading to discontinuation failure is an unfavourable balance between respiratory muscle capacity and the load they must face. Beyond specific diseases leading to loss of muscle force-generating capacity, other factors may impair respiratory muscle function, including prolonged mechanical ventilation, sedation, and ICU-acquired neuromuscular dysfunction, potentially consequent to multiple factors. The load depends on the mechanical properties of the respiratory system. An increased load is consequent to any condition leading to increased resistance, reduced compliance, and/or occurrence of intrinsic positive-end-expiratory pressure. Noteworthy, the load can significantly increase throughout the spontaneous breathing trial. Cardiac, cerebral, and neuropsychiatric disorders are also causes of discontinuation failure. Extubation failure may depend, on the one hand, on a deteriorated force-load balance occurring after removal of the endotracheal tube and, on the other hand, on specific problems. Careful patient evaluation, avoidance and treatment of all the potential determinants of failure are crucial to achieve successful discontinuation and extubation.
Abstract Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
Rationale: Prone positioning reduces mortality in patients with severe acute respiratory distress syndrome (ARDS). To date, no evidence supports the use of prone positioning (PP) during venovenous extracorporeal oxygenation (ECMO).Objectives: The aim of the study was to assess the feasibility, safety, and effect on oxygenation and lung mechanics of PP during ECMO. As a secondary exploratory aim, we assessed the association between PP and hospital mortality.Methods: We performed a multicenter retrospective cohort study in six Italian ECMO centers, including patients managed with PP during ECMO support (prone group; four centers) and patients managed in the supine position (control group; two centers). Physiological variables were analyzed at four time points (supine before PP, start of PP, end of PP, and supine after PP). The association between PP and hospital mortality was assessed by multivariate analysis and propensity score-matching.Results: A total of 240 patients were included, with 107 in the prone group and 133 in the supine group. The median duration of the 326 pronation cycles was 15 (12-18) hours. Minor reversible complications were reported in 6% of PP maneuvers. PP improved oxygenation and reduced intrapulmonary shunt. Unadjusted hospital mortality was lower in the prone group (34 vs. 50%; P = 0.017). After adjusting for covariates, PP remained significantly associated with a reduction of hospital mortality (odds ratio, 0.50; 95% confidence interval, 0.29-0.87). Sixty-six propensity score-matched patients were identified in each group. In this matched sample, patients who underwent pronation had higher ECMO duration (16 vs. 10 d; P = 0.0344) but lower hospital mortality (30% vs. 53%; P = 0.0241).Conclusions: PP during ECMO improved oxygenation and was associated with a reduction of hospital mortality.
Abstract Background: ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1 st day of controlled mechanical ventilation (CMV) are associated with intensive care unit (ICU) mortality in COVID-19 acute respiratory distress syndrome (ARDS). Methods: observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28 th -April 28 th , 2020), who received CMV, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1 st day of CMV were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. Results: 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: i) Crs was not linearly associated with ICU mortality (p-value for non-linearity=0.01), with a greater risk of death for values <48 ml/cmH 2 O; ii) the association between DP and ICU mortality was linear (p-value for non-linearity=0.68), and increasing DP from 10 to 14 cmH 2 O caused significant higher odds of in-ICU death (OR 1.45, 95%CI 1.06-1.99); iii) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95%CI 0.55-1.52). Multivariable analysis confirmed these findings. Conclusions: Crs <48 ml/cmH 2 O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.
Background: Bleeding incidents during percutaneous dilatational tracheostomy are concerning, and most cases occur in patients with unrecognized and unanticipated anatomical variations in the vascular anatomy. However, the extent of this variation remains unclear. To address this knowledge gap, our study aimed to comprehensively map laryngeal vascular anatomy in a cohort of adult patients.Methods: Ultrasound assessments of the soft tissue in the neck were performed, spanning from the thyroid cartilage to the third tracheal ring and extending 2 cm laterally on both sidesperformed. We subdivided this area into 12 zones comprising four medial and eight lateral sections. A pre-planned form was used to document the presence of arteries or veins in each zone. The results are reported as odds ratios, 95% CIs, and corresponding P values.Results: Five-hundred patients were enrolled from August 14, 2023, to November 13, 2023, at the University Hospital of Padua. Arteries and veins were identified in all investigated zones (varying from a minimum of 1.0%–46.4%). The presence of invessels progressively increased from the cricothyroid membrane to the third tracheal ring and from the midline to the paramedian laryngeal area.Conclusions: Given the prevalence of arteries and veins, particularly in areas where tracheostomies are commonly performed, we strongly advocate for routine ultrasound assessments before such procedures are performed.
Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes.A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups.1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates.VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.
Abstract Introduction The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the Intensive Care Unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: 1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and 2) assessing whether the length of NIV application affects patient survival. Methods This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. Results Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06 - 4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04 - 1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. Conclusions In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.
AbstractBackground:Non-invasive ventilation (NIV) is commonly used in clinical practice to reduce intubation times and enhance patient comfort. However, patient-ventilator interaction (PVI) during NIV, particularly with helmet interfaces, can be challenging due to factors such as dead space and compliance. Neurally adjusted ventilatory assist (NAVA) has shown promise in improving PVI during helmet-NIV, but limitations remain. A new mode, Neural Pressure Support (NPS), aims to address these limitations by providing synchronized and steep pressurization. This study aims to assess whether NPS per se improves PVI during helmet-NIV compared to standard pressure support ventilation (PSV).Methods:The study included adult patients requiring NIV with a helmet. Patients were randomized into two arms: one starting with NPS and the other with PSV. Physiological parameters and arterial blood gas analysis were collected during ventilation trials. Expert adjustments to ventilator settings were recorded in order to investigate the impact of the expertise of the clinician as confounding variable.Results:Twenty-four patients were enrolled, with no study interruptions due to safety concerns. NPS demonstrated significantly longer Timesync (0.64 ± 0.03 s vs. 0.37 ± 0.03 s, p < 0.001) and shorter Inspiratory Delay (0.15 ± 0.01 s vs. 0.35 ± 0.01 s, p < 0.001) compared to PSV. NPS also showed better Neural-Ventilator Coupling - Inspiratory (78 ± 2% vs. 45 ± 2%, p < 0.001). Ventilator parameters were not significantly different between NPS and PSV, except for minor adjustments by the expert clinician.Conclusions:NPS improves PVI during helmet-NIV, as evidenced by longer Timesync and better coupling compared to PSV. Expert adjustments to ventilator settings had minimal impact on PVI. These findings support the use of NPS in enhancing patient-ventilator synchronization and warrant further investigation into its clinical outcomes and applicability across different patient populations and interfaces.Trial Registration:This study was registered on www.clinicaltrials.gov NCT06004206 Registry URL: https://clinicaltrials.gov/study/NCT06004206 on September 08, 2023.
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
