High vs Low PEEP in Patients With ARDS Exhibiting Intense Inspiratory Effort During Assisted Ventilation: A Randomized Crossover Trial.

BACKGROUND: Positive end-expiratory pressure (PEEP) can potentially modulate inspiratory effort (ΔPes), which is the major determinant of self-inflicted lung injury. RESEARCH QUESTION: Does high PEEP reduce ΔPes in patients with moderate-to-severe ARDS on assisted ventilation? STUDY DESIGN AND METHODS: Sixteen patients with Pao2/Fio2 ≤ 200 mm Hg and ΔPes ≥ 10 cm H2O underwent a randomized sequence of four ventilator settings: PEEP = 5 cm H2O or PEEP = 15 cm H2O + synchronous (pressure support ventilation [PSV]) or asynchronous (pressure-controlled intermittent mandatory ventilation [PC-IMV]) inspiratory assistance. ΔPes and respiratory system, lung, and chest wall mechanics were assessed with esophageal manometry and occlusions. PEEP-induced alveolar recruitment and overinflation, lung dynamic strain, and tidal volume distribution were assessed with electrical impedance tomography. RESULTS: ΔPes was not systematically different at high vs low PEEP (pressure support ventilation: median, 20 cm H2O; interquartile range (IQR), 15-24 cm H2O vs median, 15 cm H2O; IQR, 13-23 cm H2O; P = .24; pressure-controlled intermittent mandatory ventilation: median, 20; IQR, 18-23 vs median, 19; IQR, 17-25; P = .67, respectively). Similarly, respiratory system and transpulmonary driving pressures, tidal volume, lung/chest wall mechanics, and pendelluft extent were not different between study phases. High PEEP resulted in lower or higher ΔPes, respiratory system driving pressure, and transpulmonary driving pressure according to whether this increased or decreased respiratory system compliance (r = -0.85, P < .001; r = -0.75, P < .001; r = -0.80, P < .001, respectively). PEEP-induced changes in respiratory system compliance were driven by its lung component and were dependent on the extent of PEEP-induced alveolar overinflation (r = -0.66, P = .006). High PEEP caused variable recruitment and systematic redistribution of tidal volume toward dorsal lung regions, thereby reducing dynamic strain in ventral areas (pressure support ventilation: median, 0.49; IQR, 0.37-0.83 vs median, 0.96; IQR, 0.62-1.56; P = .003; pressure-controlled intermittent mandatory ventilation: median, 0.65; IQR, 0.42-1.31 vs median, 1.14; IQR, 0.79-1.52; P = .002). All results were consistent during synchronous and asynchronous inspiratory assistance. INTERPRETATION: The impact of high PEEP on ΔPes and lung stress is interindividually variable according to different effects on the respiratory system and lung compliance resulting from alveolar overinflation. High PEEP may help mitigate the risk of self-inflicted lung injury solely if it increases lung/respiratory system compliance. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04241874; URL: www. CLINICALTRIALS: gov.

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.

Physiological effects of awake prone position in acute hypoxemic respiratory failure.

BACKGROUND: The effects of awake prone position on the breathing pattern of hypoxemic patients need to be better understood. We conducted a crossover trial to assess the physiological effects of awake prone position in patients with acute hypoxemic respiratory failure. METHODS: Fifteen patients with acute hypoxemic respiratory failure and PaO2/FiO2 < 200 mmHg underwent high-flow nasal oxygen for 1 h in supine position and 2 h in prone position, followed by a final 1-h supine phase. At the end of each study phase, the following parameters were measured: arterial blood gases, inspiratory effort (ΔPES), transpulmonary driving pressure (ΔPL), respiratory rate and esophageal pressure simplified pressure-time product per minute (sPTPES) by esophageal manometry, tidal volume (VT), end-expiratory lung impedance (EELI), lung compliance, airway resistance, time constant, dynamic strain (VT/EELI) and pendelluft extent through electrical impedance tomography. RESULTS: Compared to supine position, prone position increased PaO2/FiO2 (median [Interquartile range] 104 mmHg [76-129] vs. 74 [69-93], p < 0.001), reduced respiratory rate (24 breaths/min [22-26] vs. 27 [26-30], p = 0.05) and increased ΔPES (12 cmH2O [11-13] vs. 9 [8-12], p = 0.04) with similar sPTPES (131 [75-154] cmH2O s min-1 vs. 105 [81-129], p > 0.99) and ΔPL (9 [7-11] cmH2O vs. 8 [5-9], p = 0.17). Airway resistance and time constant were higher in prone vs. supine position (9 cmH2O s arbitrary units-3 [4-11] vs. 6 [4-9], p = 0.05; 0.53 s [0.32-61] vs. 0.40 [0.37-0.44], p = 0.03). Prone position increased EELI (3887 arbitrary units [3414-8547] vs. 1456 [959-2420], p = 0.002) and promoted VT distribution towards dorsal lung regions without affecting VT size and lung compliance: this generated lower dynamic strain (0.21 [0.16-0.24] vs. 0.38 [0.30-0.49], p = 0.004). The magnitude of pendelluft phenomenon was not different between study phases (55% [7-57] of VT in prone vs. 31% [14-55] in supine position, p > 0.99). CONCLUSIONS: Prone position improves oxygenation, increases EELI and promotes VT distribution towards dependent lung regions without affecting VT size, ΔPL, lung compliance and pendelluft magnitude. Prone position reduces respiratory rate and increases ΔPES because of positional increases in airway resistance and prolonged expiratory time. Because high ΔPES is the main mechanistic determinant of self-inflicted lung injury, caution may be needed in using awake prone position in patients exhibiting intense ΔPES. Clinical trail registeration: The study was registered on clinicaltrials.gov (NCT03095300) on March 29, 2017.

Recruitment-to-inflation Ratio Assessed through Sequential End-expiratory Lung Volume Measurement in Acute Respiratory Distress Syndrome.

BACKGROUND: Positive end-expiratory pressure (PEEP) benefits in acute respiratory distress syndrome are driven by lung dynamic strain reduction. This depends on the variable extent of alveolar recruitment. The recruitment-to-inflation ratio estimates recruitability across a 10-cm H2O PEEP range through a simplified maneuver. Whether recruitability is uniform or not across this range is unknown. The hypotheses of this study are that the recruitment-to-inflation ratio represents an accurate estimate of PEEP-induced changes in dynamic strain, but may show nonuniform behavior across the conventionally tested PEEP range (15 to 5 cm H2O). METHODS: Twenty patients with moderate-to-severe COVID-19 acute respiratory distress syndrome underwent a decremental PEEP trial (PEEP 15 to 13 to 10 to 8 to 5 cm H2O). Respiratory mechanics and end-expiratory lung volume by nitrogen dilution were measured the end of each step. Gas exchange, recruited volume, recruitment-to-inflation ratio, and changes in dynamic, static, and total strain were computed between 15 and 5 cm H2O (global recruitment-to-inflation ratio) and within narrower PEEP ranges (granular recruitment-to-inflation ratio). RESULTS: Between 15 and 5 cm H2O, median [interquartile range] global recruitment-to-inflation ratio was 1.27 [0.40 to 1.69] and displayed a linear correlation with PEEP-induced dynamic strain reduction (r = -0.94; P < 0.001). Intraindividual recruitment-to-inflation ratio variability within the narrower ranges was high (85% [70 to 109]). The relationship between granular recruitment-to-inflation ratio and PEEP was mathematically described by a nonlinear, quadratic equation (R2 = 0.96). Granular recruitment-to-inflation ratio across the narrower PEEP ranges itself had a linear correlation with PEEP-induced reduction in dynamic strain (r = -0.89; P < 0.001). CONCLUSIONS: Both global and granular recruitment-to-inflation ratio accurately estimate PEEP-induced changes in lung dynamic strain. However, the effect of 10 cm H2O of PEEP on lung strain may be nonuniform. Granular recruitment-to-inflation ratio assessment within narrower PEEP ranges guided by end-expiratory lung volume measurement may aid more precise PEEP selection, especially when the recruitment-to-inflation ratio obtained with the simplified maneuver between PEEP 15 and 5 cm H2O yields intermediate values that are difficult to interpret for a proper choice between a high and low PEEP strategy.

Personalized Respiratory Support in ARDS: A Physiology-to-Bedside Review.

Acute respiratory distress syndrome (ARDS) is a leading cause of disability and mortality worldwide, and while no specific etiologic interventions have been shown to improve outcomes, noninvasive and invasive respiratory support strategies are life-saving interventions that allow time for lung recovery. However, the inappropriate management of these strategies, which neglects the unique features of respiratory, lung, and chest wall mechanics may result in disease progression, such as patient self-inflicted lung injury during spontaneous breathing or by ventilator-induced lung injury during invasive mechanical ventilation. ARDS characteristics are highly heterogeneous; therefore, a physiology-based approach is strongly advocated to titrate the delivery and management of respiratory support strategies to match patient characteristics and needs to limit ARDS progression. Several tools have been implemented in clinical practice to aid the clinician in identifying the ARDS sub-phenotypes based on physiological peculiarities (inspiratory effort, respiratory mechanics, and recruitability), thus allowing for the appropriate application of personalized supportive care. In this narrative review, we provide an overview of noninvasive and invasive respiratory support strategies, as well as discuss how identifying ARDS sub-phenotypes in daily practice can help clinicians to deliver personalized respiratory support and potentially improve patient outcomes.

Long-term outcome of COVID-19 patients treated with helmet noninvasive ventilation vs. high-flow nasal oxygen: a randomized trial.

BACKGROUND: Long-term outcomes of patients treated with helmet noninvasive ventilation (NIV) are unknown: safety concerns regarding the risk of patient self-inflicted lung injury and delayed intubation exist when NIV is applied in hypoxemic patients. We assessed the 6-month outcome of patients who received helmet NIV or high-flow nasal oxygen for COVID-19 hypoxemic respiratory failure. METHODS: In this prespecified analysis of a randomized trial of helmet NIV versus high-flow nasal oxygen (HENIVOT), clinical status, physical performance (6-min-walking-test and 30-s chair stand test), respiratory function and quality of life (EuroQoL five dimensions five levels questionnaire, EuroQoL VAS, SF36 and Post-Traumatic Stress Disorder Checklist for the DSM) were evaluated 6 months after the enrollment. RESULTS: Among 80 patients who were alive, 71 (89%) completed the follow-up: 35 had received helmet NIV, 36 high-flow oxygen. There was no inter-group difference in any item concerning vital signs (N = 4), physical performance (N = 18), respiratory function (N = 27), quality of life (N = 21) and laboratory tests (N = 15). Arthralgia was significantly lower in the helmet group (16% vs. 55%, p = 0.002). Fifty-two percent of patients in helmet group vs. 63% of patients in high-flow group had diffusing capacity of the lungs for carbon monoxide < 80% of predicted (p = 0.44); 13% vs. 22% had forced vital capacity < 80% of predicted (p = 0.51). Both groups reported similar degree of pain (p = 0.81) and anxiety (p = 0.81) at the EQ-5D-5L test; the EQ-VAS score was similar in the two groups (p = 0.27). Compared to patients who successfully avoided invasive mechanical ventilation (54/71, 76%), intubated patients (17/71, 24%) had significantly worse pulmonary function (median diffusing capacity of the lungs for carbon monoxide 66% [Interquartile range: 47-77] of predicted vs. 80% [71-88], p = 0.005) and decreased quality of life (EQ-VAS: 70 [53-70] vs. 80 [70-83], p = 0.01). CONCLUSIONS: In patients with COVID-19 hypoxemic respiratory failure, treatment with helmet NIV or high-flow oxygen yielded similar quality of life and functional outcome at 6 months. The need for invasive mechanical ventilation was associated with worse outcomes. These data indicate that helmet NIV, as applied in the HENIVOT trial, can be safely used in hypoxemic patients. Trial registration Registered on clinicaltrials.gov NCT04502576 on August 6, 2020.

Non-invasive ventilation for acute hypoxemic respiratory failure, including COVID-19.

Optimal initial non-invasive management of acute hypoxemic respiratory failure (AHRF), of both coronavirus disease 2019 (COVID-19) and non-COVID-19 etiologies, has been the subject of significant discussion. Avoidance of endotracheal intubation reduces related complications, but maintenance of spontaneous breathing with intense respiratory effort may increase risks of patients' self-inflicted lung injury, leading to delayed intubation and worse clinical outcomes. High-flow nasal oxygen is currently recommended as the optimal strategy for AHRF management for its simplicity and beneficial physiological effects. Non-invasive ventilation (NIV), delivered as either pressure support or continuous positive airway pressure via interfaces like face masks and helmets, can improve oxygenation and may be associated with reduced endotracheal intubation rates. However, treatment failure is common and associated with poor outcomes. Expertise and knowledge of the specific features of each interface are necessary to fully exploit their potential benefits and minimize risks. Strict clinical and physiological monitoring is necessary during any treatment to avoid delays in endotracheal intubation and protective ventilation. In this narrative review, we analyze the physiological benefits and risks of spontaneous breathing in AHRF, and the characteristics of tools for delivering NIV. The goal herein is to provide a contemporary, evidence-based overview of this highly relevant topic.

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).

Lung-protective ventilation during Trendelenburg pneumoperitoneum surgery: A randomized clinical trial.

Study objective To assess the effects of a protective ventilation strategy during Trendelenburg pneumoperitoneum surgery on postoperative oxygenation. DESIGNS: Parallel-group, randomized trial. SETTING: Operating room of a university hospital, Italy. PATIENTS: Morbidly obese patients undergoing Trendelenburg pneumoperitoneum gynaecological surgery. INTERVENTIONS: Participants were randomized to standard (SV: tidal volume = 10 ml/kg of predicted body weight, PEEP = 5 cmH2O) or protective (PV: tidal volume = 6 ml/kg of predicted body weight, PEEP = 10 cmH2O, recruitment maneuvers) ventilation during anesthesia. MEASUREMENTS: Primary outcome was PaO2/FiO2 one hour after extubation. Secondary outcomes included day-1 PaO2/FiO2, day-2 respiratory function and intraoperative respiratory/lung mechanics, assessed through esophageal manometry, end-expiratory lung volume (EELV) measurement and pressure-volume curves. MAIN RESULTS: Sixty patients were analyzed (31 in SV group, 29 in PV group). Median [IqR] tidal volume was 350 ml [300-360] in PV group and 525 [500-575] in SV group. Median PaO2/FiO2 one hour after extubation was 280 mmHg [246-364] in PV group vs. 298 [250-343] in SV group (p = 0.64). Day-1 PaO2/FiO2, day-2 forced vital capacity, FEV-1 and Tiffenau Index were not different between groups (all p > 0.10). Intraoperatively, 59% of patients showed complete airway closure during pneumoperitoneum, without difference between groups: median airway opening pressure was 17 cmH2O. In PV group, airway and transpulmonary driving pressure were lower (12 ± 5 cmH2O vs. 17 ± 7, p < 0.001; 9 ± 4 vs. 13 ± 7, p < 0.001), PaCO2 and respiratory rate were higher (48 ± 8 mmHg vs. 42 ± 12, p < 0.001; 23 ± 5 breaths/min vs. 16 ± 4, p < 0.001). Intraoperative EELV was similar between PV and SV group (1193 ± 258 ml vs. 1207 ± 368, p = 0.80); ratio of tidal volume to EELV was lower in PV group (0.45 ± 0.12 vs. 0.32 ± 0.09, p < 0.001). CONCLUSIONS: In obese patients undergoing Trendelenburg pneumoperitoneum surgery, PV did not improve postoperative oxygenation nor day-2 respiratory function. PV was associated with intraoperative respiratory mechanics indicating less injurious ventilation. The high prevalence of complete airway closure may have affected study results. TRIAL REGISTRATION: Prospectively registered on http://clinicaltrials.govNCT03157479 on May 17th, 2017.

Personalized Noninvasive Respiratory Support in the Perioperative Setting: State of the Art and Future Perspectives.

Background: Noninvasive respiratory support (NRS), including high-flow nasal oxygen therapy (HFNOT), noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP), are routinely used in the perioperative period. Objectives: This narrative review provides an overview on the perioperative use of NRS. Preoperative, intraoperative, and postoperative respiratory support is discussed, along with potential future areas of research. Results: During induction of anesthesia, in selected patients at high risk of difficult intubation, NIV is associated with improved gas exchange and reduced risk of postoperative respiratory complications. HFNOT demonstrated an improvement in oxygenation. Evidence on the intraoperative use of NRS is limited. Compared with conventional oxygenation, HFNOT is associated with a reduced risk of hypoxemia during procedural sedation, and recent data indicate a possible role for HFNOT for intraoperative apneic oxygenation in specific surgical contexts. After extubation, "preemptive" NIV and HFNOT in unselected cohorts do not affect clinical outcome. Postoperative "curative" NIV in high-risk patients and among those exhibiting signs of respiratory failure can reduce reintubation rate, especially after abdominal surgery. Data on postoperative "curative" HFNOT are limited. Conclusions: There is increasing evidence on the perioperative use of NRS. Use of NRS should be tailored based on the patient's specific characteristics and type of surgery, aimed at a personalized cost-effective approach.

Helmet noninvasive support for acute hypoxemic respiratory failure: rationale, mechanism of action and bedside application.

INTRODUCTION: Helmet noninvasive support may provide advantages over other noninvasive oxygenation strategies in the management of acute hypoxemic respiratory failure. In this narrative review based on a systematic search of the literature, we summarize the rationale, mechanism of action and technicalities for helmet support in hypoxemic patients. MAIN RESULTS: In hypoxemic patients, helmet can facilitate noninvasive application of continuous positive-airway pressure or pressure-support ventilation via a hood interface that seals at the neck and is secured by straps under the arms. Helmet use requires specific settings. Continuous positive-airway pressure is delivered through a high-flow generator or a Venturi system connected to the inspiratory port of the interface, and a positive end-expiratory pressure valve place at the expiratory port of the helmet;  alternatively, pressure-support ventilation is delivered by connecting the helmet to a mechanical ventilator through a bi-tube circuit. The helmet interface allows continuous treatments with high positive end-expiratory pressure with good patient comfort. Preliminary data suggest that helmet noninvasive ventilation (NIV) may provide physiological benefits compared to other noninvasive oxygenation strategies (conventional oxygen, facemask NIV, high-flow nasal oxygen) in non-hypercapnic patients with moderate-to-severe hypoxemia (PaO2/FiO2 ≤ 200 mmHg), possibly because higher positive end-expiratory pressure (10-15 cmH2O) can be applied for prolonged periods with good tolerability. This improves oxygenation, limits ventilator inhomogeneities, and may attenuate the potential harm of lung and diaphragm injury caused by vigorous inspiratory effort. The potential superiority of helmet support for reducing the risk of intubation has been hypothesized in small, pilot randomized trials and in a network metanalysis. CONCLUSIONS: Helmet noninvasive support represents a promising tool for the initial management of patients with severe hypoxemic respiratory failure. Currently, the lack of confidence with this and technique and the absence of conclusive data regarding its efficacy render helmet use limited to specific settings, with expert and trained personnel. As per other noninvasive oxygenation strategies, careful clinical and physiological monitoring during the treatment is essential to early identify treatment failure and avoid delays in intubation.

Remdesivir plus Dexamethasone in COVID-19: A cohort study of severe patients requiring high flow oxygen therapy or non-invasive ventilation.

INTRODUCTION: Remdesivir and Dexamethasone represent the cornerstone of therapy for critically ill patients with acute hypoxemic respiratory failure caused by Coronavirus Disease 2019 (COVID-19). However, clinical efficacy and safety of concomitant administration of Remdesivir and Dexamethasone (Rem-Dexa) in severe COVID-19 patients on high flow oxygen therapy (HFOT) or non-invasive ventilation (NIV) remains unknown. MATERIALS AND METHODS: Prospective cohort study that was performed in two medical Intensive Care Units (ICUs) of a tertiary university hospital. The clinical impact of Rem-Dexa administration in hypoxemic patients with COVID-19, who required NIV or HFOT and selected on the simplified acute physiology score II, the sequential organ failure assessment score and the Charlson Comorbidity Index score, was investigated. The primary outcome was 28-day intubation rate; secondary outcomes were end-of-treatment clinical improvement and PaO2/FiO2 ratio, laboratory abnormalities and clinical complications, ICU and hospital length of stay, 28-day and 90-day mortality. RESULTS: We included 132 patients and found that 28-day intubation rate was significantly lower among Rem-Dexa group (19.7% vs 48.5%, p<0.01). Although the end-of-treatment clinical improvement was larger among Rem-Dexa group (69.7% vs 51.5%, p = 0.05), the 28-day and 90-day mortalities were similar (4.5% and 10.6% vs. 15.2% and 16.7%; p = 0.08 and p = 0.45, respectively). The logistic regression and Cox-regression models showed that concomitant Rem-Dexa therapy was associated with a reduction of 28-day intubation rate (OR 0.22, CI95% 0.05-0.94, p = 0.04), in absence of laboratory abnormalities and clinical complications (p = ns). CONCLUSIONS: In COVID-19 critically ill patients receiving HFO or NIV, 28-day intubation rate was lower in patients who received Rem-Dexa and this finding corresponded to lower end-of-treatment clinical improvement. The individual contribution of either Remdesevir or Dexamethasone to the observed clinical effect should be further investigated.

Viral Encephalitis in Adults: A Narrative Review.

Viral infections of the central nervous system cause frequent hospitalization. The pathogenesis of viral encephalitis involves both the direct action of invading pathogens and the damage generated by the inflammatory reaction they trigger. The type of signs and symptoms presented by the patient depends on the severity and location of the ongoing inflammatory process. Most of the viral encephalitides are characterized by an acute development, fever, variable alterations in consciousness (confusion, lethargy, even coma), seizures (focal and generalized) and focal neurologic signs. The specific diagnosis of encephalitis is usually based on lumbar puncture. Cerebrospinal fluid examination should be performed in all patients unless absolutely contraindicated. Also, electroencephalogram and neuroimaging play a prominent role in diagnosis. Airway protection, ventilatory support, the management of raised intracranial pressure and correction of electrolyte disorders must be immediately considered in a patient with altered mental status. The only therapy strictly recommended is acyclovir in HSV encephalitis. The use of adjunctive glucocorticoids has poor-quality evidence in HSV, EBV, or VZV encephalitis. The role of antiviral therapy in other types of viral encephalitis is not well defined.

Dyspnoea and clinical outcome in critically ill patients receiving noninvasive support for COVID-19 respiratory failure: post hoc analysis of a randomised clinical trial.

In #COVID19 patients, presence of moderate-to-severe dyspnoea is a marker of disease severity correlated to clinical outcomes https://bit.ly/3Bp2G1b.

Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial.

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19. Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone. Design, Setting, and Participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200). Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55). Main Outcomes and Measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay. Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99). Conclusions and Relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation. Trial Registration: ClinicalTrials.gov Identifier: NCT04502576.

High Failure Rate of Noninvasive Oxygenation Strategies in Critically Ill Subjects With Acute Hypoxemic Respiratory Failure Due to COVID-19.

BACKGROUND: The efficacy of noninvasive oxygenation strategies (NIOS) in treating COVID-19 disease is unknown. We conducted a prospective observational study to assess the rate of NIOS failure in subjects treated in the ICU for hypoxemic respiratory failure due to COVID-19. METHODS: Patients receiving first-line treatment NIOS for hypoxemic respiratory failure due to COVID-19 in the ICU of a university hospital were included in this study; laboratory data were collected upon arrival, and 28-d outcome was recorded. After propensity score matching based on Simplified Acute Physiology (SAPS) II score, age, [Formula: see text] and [Formula: see text] at arrival, the NIOS failure rate in subjects with COVID-19 was compared to a previously published cohort who received NIOS during hypoxemic respiratory failure due to other causes. RESULTS: A total of 85 subjects received first-line treatment with NIOS. The most frequently used methods were helmet noninvasive ventilation and high-flow nasal cannula; of these, 52 subjects (61%) required endotracheal intubation. Independent factors associated with NIOS failure were SAPS II score (P = .009) and serum lactate dehydrogenase at enrollment (P = .02); the combination of SAPS II score ≥ 33 with serum lactate dehydrogenase ≥ 405 units/L at ICU admission had 91% specificity in predicting the need for endotracheal intubation. In the propensity-matched cohorts (54 pairs), subjects with COVID-19 showed higher risk of NIOS failure than those with other causes of hypoxemic respiratory failure (59% vs 35%, P = .02), with an adjusted hazard ratio of 2 (95% CI 1.1-3.6, P = .01). CONCLUSIONS: As compared to hypoxemic respiratory failure due to other etiologies, subjects with COVID-19 who were treated with NIOS in the ICU were burdened by a 2-fold higher risk of failure. Subjects with a SAPS II score ≥ 33 and serum lactate dehydrogenase ≥ 405 units/L represent the population with the greatest risk.

Clinical Management of Infectious Diarrhea.

BACKGROUND: Infectious diarrhea is the most common cause of diarrhea worldwide and is responsible for more deaths than other gastrointestinal tract diseases such as gastrointestinal cancers, peptic ulcer disease or inflammatory bowel disease. Diarrheal disease still represents the 8th leading cause of death worldwide, with more than 1,6 million attributed fatalities in 2016 alone. The majority of cases can be divided into three principal clinical presentations: acute watery diarrhea lasting 5-10 days and normally self-limiting, bloody diarrhea (dysentery), and persistent diarrhea with or without intestinal malabsorption. METHODS: We performed an electronic search on PUBMED of the scientific literature concerning infectious diarrhea and its clinical management. AIM: In this review article, we analyze the most important causes of infectious diarrhea and their constellation of signs and symptoms, providing an update on the diagnostic tools available in today's practice and on the different treatment options. CONCLUSION: Even though the majority of intestinal infections are self-limiting in immunocompetent individuals, specific diagnosis and identification of the causative agent remain crucial from public health and epidemiological perspectives. Specific diagnostic investigation can be reserved for patients with severe dehydration, more severe illness, persistent fever, bloody stools, immunosuppression, and for cases of suspected nosocomial infection or outbreak and it includes complete blood count, creatinine and electrolytes evaluation, determination of leukocytes and lactoferrin presence in the stools, stool culture, together with C. difficile testing, PCR, ova and parasites' search, endoscopy and abdominal imaging. Since acute diarrhea is most often self-limited and caused by viruses, routine antibiotic use is not recommended for most adults with mild, watery diarrhea. However, when used appropriately, antibiotics are effective against shigellosis, campylobacteriosis, C. difficile colitis, traveler's diarrhea, and protozoal infections. Furthermore, antibiotics use should be considered in patients who are older than 65 years, immunocompromised, severely ill, or septic.