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).

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.

Potential for Lung Recruitment Estimated by the Recruitment-to-Inflation Ratio in Acute Respiratory Distress Syndrome. A Clinical Trial.

Rationale: Response to positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome depends on recruitability. We propose a bedside approach to estimate recruitability accounting for the presence of complete airway closure.Objectives: To validate a single-breath method for measuring recruited volume and test whether it differentiates patients with different responses to PEEP.Methods: Patients with acute respiratory distress syndrome were ventilated at 15 and 5 cm H2O of PEEP. Multiple pressure-volume curves were compared with a single-breath technique. Abruptly releasing PEEP (from 15 to 5 cm H2O) increases expired volume: the difference between this volume and the volume predicted by compliance at low PEEP (or above airway opening pressure) estimated the recruited volume by PEEP. This recruited volume divided by the effective pressure change gave the compliance of the recruited lung; the ratio of this compliance to the compliance at low PEEP gave the recruitment-to-inflation ratio. Response to PEEP was compared between high and low recruiters based on this ratio.Measurements and Main Results: Forty-five patients were enrolled. Four patients had airway closure higher than high PEEP, and thus recruitment could not be assessed. In others, recruited volume measured by the experimental and the reference methods were strongly correlated (R2 = 0.798; P < 0.0001) with small bias (-21 ml). The recruitment-to-inflation ratio (median, 0.5; range, 0-2.0) correlated with both oxygenation at low PEEP and the oxygenation response; at PEEP 15, high recruiters had better oxygenation (P = 0.004), whereas low recruiters experienced lower systolic arterial pressure (P = 0.008).Conclusions: A single-breath method quantifies recruited volume. The recruitment-to-inflation ratio might help to characterize lung recruitability at the bedside.Clinical trial registered with www.clinicaltrials.gov (NCT02457741).

Patient self-inflicted lung injury and positive end-expiratory pressure for safe spontaneous breathing.

PURPOSE OF REVIEW: The potential risks of spontaneous effort and their prevention during mechanical ventilation is an important concept for clinicians and patients. The effort-dependent lung injury has been termed 'patient self-inflicted lung injury (P-SILI)' in 2017. As one of the potential strategies to render spontaneous effort less injurious in severe acute respiratory distress syndrome (ARDS), the role of positive end-expiratory pressure (PEEP) is now discussed. RECENT FINDINGS: Experimental and clinical data indicate that vigorous spontaneous effort may worsen lung injury, whereas, at the same time, the intensity of spontaneous effort seems difficult to control when lung injury is severe. Experimental studies found that higher PEEP strategy can be effective to reduce lung injury from spontaneous effort while maintaining some muscle activity. The recent clinical trial to reevaluate systemic early neuromuscular blockade in moderate-severe ARDS (i.e., reevaluation of systemic early neuromuscular blockade (ROSE) trial) support that a higher PEEP strategy can facilitate 'safe' spontaneous breathing under the light sedation targets (i.e., no increase in barotrauma nor 90 days mortality versus early muscle paralysis). SUMMARY: To prevent P-SILI in ARDS, it seems feasible to facilitate 'safe' spontaneous breathing in patients using a higher PEEP strategy in severe ARDS.

Intrathoracic Airway Closure Impacts CO2 Signal and Delivered Ventilation during Cardiopulmonary Resuscitation.

RATIONALE: End-tidal CO2 (EtCO2) is used to monitor cardiopulmonary resuscitation (CPR), but it can be affected by intrathoracic airway closure. Chest compressions induce oscillations in expired CO2, and this could reflect variable degrees of airway patency. OBJECTIVES: To understand the impact of airway closure during CPR, and the relationship between the capnogram shape, airway closure, and delivered ventilation. METHODS: This study had three parts: 1) a clinical study analyzing capnograms after intubation in patients with out-of-hospital cardiac arrest receiving continuous chest compressions, 2) a bench model, and 3) experiments with human cadavers. For 2 and 3, a constant CO2 flow was added in the lung to simulate CO2 production. Capnograms similar to clinical recordings were obtained and different ventilator settings tested. EtCO2 was compared with alveolar CO2 (bench). An airway opening index was used to quantify chest compression-induced expired CO2 oscillations in all three clinical and experimental settings. MEASUREMENTS AND MAIN RESULTS: A total of 89 patients were analyzed (mean age, 69 ± 15 yr; 23% female; 12% of hospital admission survival): capnograms exhibited various degrees of oscillations, quantified by the opening index. CO2 value varied considerably across oscillations related to consecutive chest compressions. In bench and cadavers, similar capnograms were reproduced with different degrees of airway closure. Differences in airway patency were associated with huge changes in delivered ventilation. The opening index and delivered ventilation increased with positive end-expiratory pressure, without affecting intrathoracic pressure. Maximal EtCO2 recorded between ventilator breaths reflected alveolar CO2 (bench). CONCLUSIONS: During chest compressions, intrathoracic airway patency greatly affects the delivered ventilation. The expired CO2 signal can reflect CPR effectiveness but is also dependent on airway patency. The maximal EtCO2 recorded between consecutive ventilator breaths best reflects alveolar CO2.

New physiological insights in ventilation during cardiopulmonary resuscitation.

PURPOSE OF REVIEW: In the setting of cardiopulmonary resuscitation (CPR), classical physiological concept about ventilation become challenging. Ventilation may exert detrimental hemodynamic effects that must be balanced with its expected benefits. The risks of hyperventilation have been thoroughly addressed, even questioning the need for ventilation, emphasizing the need to prioritize chest compression quality. However, ventilation is mandatory for adequate gas exchange as soon as CPR is prolonged. Factors affecting the capability of chest compressions to produce alveolar ventilation are poorly understood. In this review, we discuss the conventional interpretation of interactions between ventilation and circulation, from the perspective of novel physiological observations. RECENT FINDINGS: Many patients with cardiac arrest exhibit 'intrathoracic airway closure.' This phenomenon is associated with lung volume reduction, impedes chest compressions to generate ventilation and overall limits the delivered ventilation. This phenomenon can be reversed by the application of small levels of positive end-expiratory pressure. Also, a novel interpretation of the capnogram can rate the magnitude of this phenomenon, contributing to clarify the physiological meaning of exhaled CO2 and may help assess the real amount of delivered ventilation. SUMMARY: Recent advances in the understanding of ventilatory physiology during CPR shows that capnogram analysis not only provides information on the quality of resuscitation but also on the amount of ventilation produced by chest compressions and on the total amount of ventilation.

Should we use driving pressure to set tidal volume?

PURPOSE OF REVIEW: Ventilator-induced lung injury (VILI) can occur despite use of tidal volume (VT) limited to 6 ml/kg of predicted body weight, especially in patients with a smaller aerated compartment (i.e. the baby lung) in which, indeed, tidal ventilation takes place. Because respiratory system static compliance (CRS) is mostly affected by the volume of the baby lung, the ratio VT/CRS (i.e. the driving pressure, ΔP) may potentially help tailoring interventions on VT setting. RECENT FINDINGS: Driving pressure is the ventilatory variable most strongly associated with changes in survival and has been shown to be the key mediator of the effects of mechanical ventilation on outcome in the acute respiratory distress syndrome. Observational data suggest an increased risk of death for patients with ΔP more than 14 cmH2O, but a well tolerated threshold for this parameter has yet to be identified. Prone position along with simple ventilatory adjustments to facilitate CO2 clearance may help reduce ΔP in isocapnic conditions. The safety and feasibility of low-flow extracorporeal CO2 removal in enhancing further reduction in VT and ΔP are currently being investigated. SUMMARY: Driving pressure is a bedside available parameter that may help identify patients prone to develop VILI and at increased risk of death. No study had prospectively evaluated whether interventions on ΔP may provide a relevant clinical benefit, but it appears physiologically sound to try titrating VT to minimize ΔP, especially when it is higher than 14 cmH2O and when it has minimal costs in terms of CO2 clearance.

Recruitment-to-inflation ratio reflects the impact of peep on dynamic lung strain in a highly recruitable model of ARDS.

BACKGROUND: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. METHODS: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). RESULTS: Between high (median [interquartile range] 20 cmH2O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74]). CONCLUSIONS: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain.

Recruitment-to-inflation ratio for bedside PEEP selection in acute respiratory distress syndrome.

In acute respiratory distress syndrome, the role of positive end-expiratory pressure (PEEP) to prevent ventilator-induced lung injury is controversial. Randomized trials comparing higher versus lower PEEP strategies failed to demonstrate a clinical benefit. This may depend on the inter-individually variable potential for lung recruitment (i.e. recruitability), which would warrant PEEP individualization to balance alveolar recruitment and the unavoidable baby lung overinflation produced by high pressure. Many techniques have been used to assess recruitability, including lung imaging, multiple pressure-volume curves and lung volume measurement. The Recruitment-to-Inflation ratio (R/I) has been recently proposed to bedside assess recruitability without additional equipment. R/I assessment is a simplified technique based on the multiple pressure-volume curve concept: it is measured by monitoring respiratory mechanics and exhaled tidal volume during a 10-cmH2O one-breath derecruitment maneuver after a short high-PEEP test. R/I scales recruited volume to respiratory system compliance, and normalizes recruitment to a proxy of actual lung size. With modest R/I (<0.3-0.4), setting low PEEP (5-8 cmH2O) may be advisable; with R/I>0.6-0.7, high PEEP (≥15 cmH2O) can be considered, provided that airway and/or transpulmonary plateau pressure do not exceed safety limits. In case of intermediate R/I (≈0.5), a more granular assessment of recruitability may be needed. This could be accomplished with advanced monitoring tools, like sequential lung volume measurement with granular R/I assessment or electrical impedance tomography monitoring during a decremental PEEP trial. In this review, we discuss R/I rationale, applications and limits, providing insights on its clinical use for PEEP selection in moderate-to-severe acute respiratory distress syndrome.

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.

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.