Effect of a pre-emptive 2-hour session of high-flow nasal oxygen on postoperative oxygenation after major gynaecologic surgery: a randomised clinical trial.

BACKGROUND: We aimed at determining whether a 2-h session of high-flow nasal oxygen (HFNO) immediately after extubation improves oxygen exchange after major gynaecological surgery in the Trendelenburg position in adult female patients. METHODS: In this single-centre, open-label, randomised trial, patients who underwent major gynaecological surgery were randomised to HFNO or conventional oxygen treatment with a Venturi mask. The primary outcome was the Pao2/FiO2 ratio after 2 h of treatment. Secondary outcomes included lung ultrasound score, diaphragm thickening fraction, dyspnoea, ventilatory frequency, Paco2, the percentage of patients with impaired gas exchange (Pao2/FiO2 ≤40 kPa) after 2 h of treatment, and postoperative pulmonary complications at 30 days. RESULTS: A total of 83 patients were included (42 in the HFNO group and 41 in the conventional treatment group). After 2 h of treatment, median (inter-quartile range) Pao2/FiO2 was 52.9 (47.9-65.2) kPa in the HFNO group and 45.7 (36.4 -55.9) kPa in the conventional treatment group (mean difference 8.7 kPa [95% CI: 3.4 to 13.9], P=0.003). The lung ultrasound score was lower in the HFNO group than in the conventional treatment group (9 [6-10] vs 12 [10-14], P<0.001), mostly because of the difference of the score in dorsal areas (7 [6-8] vs 10 [9-10], P<0.001). The percentage of patients with impaired gas exchange was lower in the HFNO group than in the conventional treatment group (5% vs 37%, P<0.001). All other secondary outcomes were not different between groups. CONCLUSIONS: In patients who underwent major gynaecological surgery, a pre-emptive 2-h session of HFNO after extubation improved postoperative oxygen exchange and reduced atelectasis compared with a conventional oxygen treatment strategy. CLINICAL TRIAL REGISTRATION: NCT04566419.

Advantages and drawbacks of helmet noninvasive support in acute respiratory failure.

INTRODUCTION: Non-invasive ventilation (NIV) represents an effective strategy for managing acute respiratory failure. Facemask NIV is strongly recommended in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with hypercapnia and acute cardiogenic pulmonary edema (ACPE). Its role in managing acute hypoxemic respiratory failure (AHRF) remains a debated issue. NIV and continuous positive airway pressure (CPAP) delivered through the helmet are recently receiving growing interest for AHRF management. AREAS COVERED: In this narrative review, we discuss the clinical applications of helmet support compared to the other available noninvasive strategies in the different phenotypes of acute respiratory failure. EXPERT OPINION: Helmets enable the use of high positive end-expiratory pressure, which may protect from self-inflicted lung injury: in AHRF, the possible superiority of helmet support over other noninvasive strategies in terms of clinical outcome has been hypothesized in a network metanalysis and a randomized trial, but has not been confirmed by other investigations and warrants confirmation. In AECOPD patients, helmet efficacy may be inferior to that of face masks, and its use prompts caution due to the risk of CO2 rebreathing. Helmet support can be safely applied in hypoxemic patients with ACPE, with no advantages over facemasks.

Usefulness of differential time to positivity between catheter and peripheral blood cultures for diagnosing catheter-related bloodstream infection: Data analysis from routine clinical practice in the intensive care unit.

PURPOSE: To assess the accuracy of differential time to positivity (DTP) method for the diagnosis of catheter-related bloodstream infections (CRBSI) in the routine practice of our intensive care unit (ICU). MATERIALS AND METHODS: Over a five-year study period, ICU patients with a central venous catheter in place for ≥48 h and undergoing DTP test with catheter tip culture were analyzed. We investigated: the accuracy of DTP test with the usual threshold of 120 min in confirming the clinical suspicion of CRBSI; the most accurate threshold value of DTP to detect CRBSI; the diagnostic accuracy of the ratio (rather than the difference) between times to positivity. RESULTS: Among 278 episodes of paired blood cultures, 13% were CRBSIs. DTP value ≥120 min used for the diagnosis of CRBSI yielded 41% sensitivity and 74% specificity. Performance of DTP values in predicting CRBSI was low (AUC = 0.60 [95%CI: 0.48-0.72]). Cutoff value of the ratio between times to positivity was 0.80, with 46% sensitivity and 79% specificity. CONCLUSIONS: The routine use of the DTP method at any cutoff point has inadequate accuracy in detecting CRBSI in the real every day clinical practice. Not even the ratio between times to positivity seems to be clinically useful.

Respective Effects of Helmet Pressure Support, Continuous Positive Airway Pressure, and Nasal High-Flow in Hypoxemic Respiratory Failure: A Randomized Crossover Clinical Trial.

Rationale: The respective effects of positive end-expiratory pressure (PEEP) and pressure support delivered through the helmet interface in patients with hypoxemia need to be better understood. Objectives: To assess the respective effects of helmet pressure support (noninvasive ventilation [NIV]) and continuous positive airway pressure (CPAP) compared with high-flow nasal oxygen (HFNO) on effort to breathe, lung inflation, and gas exchange in patients with hypoxemia (PaO2/FiO2 ⩽ 200). Methods: Fifteen patients underwent 1-hour phases (constant FiO2) of HFNO (60 L/min), helmet NIV (PEEP = 14 cm H2O, pressure support = 12 cm H2O), and CPAP (PEEP = 14 cm H2O) in randomized sequence. Measurements and Main Results: Inspiratory esophageal (ΔPES) and transpulmonary pressure (ΔPL) swings were used as surrogates for inspiratory effort and lung distension, respectively. Tidal Volume (Vt) and end-expiratory lung volume were assessed with electrical impedance tomography. ΔPES was lower during NIV versus CPAP and HFNO (median [interquartile range], 5 [3-9] cm H2O vs. 13 [10-19] cm H2O vs. 10 [8-13] cm H2O; P = 0.001 and P = 0.01). ΔPL was not statistically different between treatments. PaO2/FiO2 ratio was significantly higher during NIV and CPAP versus HFNO (166 [136-215] and 175 [158-281] vs. 120 [107-149]; P = 0.002 and P = 0.001). NIV and CPAP similarly increased Vt versus HFNO (mean change, 70% [95% confidence interval (CI), 17-122%], P = 0.02; 93% [95% CI, 30-155%], P = 0.002) and end-expiratory lung volume (mean change, 198% [95% CI, 67-330%], P = 0.001; 263% [95% CI, 121-407%], P = 0.001), mostly due to increased aeration/ventilation in dorsal lung regions. During HFNO, 14 of 15 patients had pendelluft involving >10% of Vt; pendelluft was mitigated by CPAP and further by NIV. Conclusions: Compared with HFNO, helmet NIV, but not CPAP, reduced ΔPES. CPAP and NIV similarly increased oxygenation, end-expiratory lung volume, and Vt, without affecting ΔPL. NIV, and to a lesser extent CPAP, mitigated pendelluft. Clinical trial registered with clinicaltrials.gov (NCT04241861).

Vitamin D Status and Potential Therapeutic Options in Critically Ill Patients: A Narrative Review of the Clinical Evidence.

Vitamin D covers roles of paramount importance in the regulation of multiple physiological pathways of the organism. The metabolism of vitamin D involves kidney-liver crosstalk and requires an adequate function of these organs, where vitamin D is progressively turned into active forms. Vitamin D deficiency has been widely reported in patients living in the community, being prevalent among the most vulnerable subjects. It has been also documented in many critically ill patients upon admission to the intensive care unit. In this context, vitamin D deficiency may represent a risk factor for the development of life-threatening clinical conditions (e.g., infection and sepsis) and worse clinical outcomes. Several researchers have investigated the impact of vitamin D supplementation showing its feasibility, safety, and effectiveness, although conflicting results have put into question its real benefit in critically ill patients. The existing studies included heterogeneous critically ill populations and used slightly different protocols of vitamin D supplementation. For these reasons, pooling up the results is difficult and not conclusive. In this narrative review, we described vitamin D physiology and the pathophysiology of vitamin D depletion with a specific focus on critically ill patients with liver dysfunction, acute kidney injury, acute respiratory failure, and sepsis.

Partition of respiratory mechanics in patients with acute respiratory distress syndrome and association with outcome: a multicentre clinical study.

PURPOSE: In acute respiratory distress syndrome (ARDS), physiological parameters associated with outcome may help defining targets for mechanical ventilation. This study aimed to address whether transpulmonary pressures (PL), including transpulmonary driving pressure (DPL), elastance-derived plateau PL, and directly-measured end-expiratory PL, are better associated with 60-day outcome than airway driving pressure (DPaw). We also tested the combination of oxygenation and stretch index [PaO2/(FiO2*DPaw)]. METHODS: Prospective, observational, multicentre registry of ARDS patients. Respiratory mechanics were measured early after intubation at 6 kg/ml tidal volume. We compared the predictive power of the parameters for mortality at day-60 through receiver operating characteristic (ROC) and assessed their association with 60-day mortality through unadjusted and adjusted Cox regressions. Finally, each parameter was dichotomized, and Kaplan-Meier survival curves were compared. RESULTS: 385 patients were enrolled 2 [1-4] days from intubation (esophageal pressure and arterial blood gases in 302 and 318 patients). As continuous variables, DPaw, DPL, and oxygenation stretch index were associated with 60-day mortality after adjustment for age and Sequential Organ Failure Assessment, whereas elastance-derived plateau PL was not. DPaw and DPL performed equally in ROC analysis (P = 0.0835). DPaw had the best-fit Cox regression model. When dichotomizing the variables, DPaw ≥ 15, DPL ≥ 12, plateau PL ≥ 24, and oxygenation stretch index < 10 exhibited lower 60-day survival probability. Directly measured end-expiratory PL ≥ 0 was associated with better outcome in obese patients. CONCLUSION: DPL was equivalent predictor of outcome than DPaw. Our study supports the soundness of limiting lung and airway driving pressure and maintaining positive end-expiratory PL in obese patients.

Compassionate use of anti-IL6 receptor antibodies in critically ill patients with acute respiratory distress syndrome due to SARS-CoV-2.

BACKGROUND: COVID-19 patients developing the acute respiratory distress syndrome (ARDS) show increased production of pro-inflammatory cytokines, including interleukin-6 (IL-6). The use of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) may represent a potential treatment strategy. We analyzed the effects of compassionate use of tocilizumab and sarilumab on clinical outcome of patients affected by ARDS due COVID-19. METHODS: This single-center, observational, exploratory study was performed during the acute phase of COVID-19 outbreak, between March 7th and April 21st, 2020 in a University Hospital in Rome, Italy. All consecutive adult patients admitted to the intensive care unit with laboratory-confirmed COVID-19 and fulfilling ARDS criteria were enrolled. Patients who were treated with anti-IL-6R therapy were compared to those who were not, as per clinical decision. Inverse probability weights were applied to weight individual's contribution to survival curves and in the multivariate regression model. RESULTS: Among 105 ARDS patients, 65 received compassionate treatment with anti-IL-6R therapy (43 [66%] Tocilizumab [Hoffmann-La Roche, Basel, Switzerland] and 22 [34%] Sarilumab, respectively], with oxygenation improvement. In the multivariable Cox proportional regression hazards model with propensity score inverse probability weighting, patients who received anti-IL-6R treatment had lower risk of death compared to those who did not, with a hazard ration of 0.34 [95% confidence interval 0.17-0.74], P=0.001. CONCLUSIONS: Our data suggested that immune modulator therapy based on anti-human IL-6 receptor monoclonal antibodies might lead to improved outcome in patients with ARDS due to COVID-19. These data support the need for confirmatory randomized trials to assess the effect of immune modulator therapies on mortality.