Effect of high-flow nasal cannula oxygen versus standard oxygen on mortality in patients with acute hypoxaemic respiratory failure: protocol for a multicentre, randomised controlled trial (SOHO).

INTRODUCTION: First-line oxygenation strategy in patients with acute hypoxaemic respiratory failure consists in standard oxygen or high-flow nasal oxygen therapy. Clinical practice guidelines suggest the use of high-flow nasal oxygen rather than standard oxygen. However, findings remain contradictory with a low level of certainty. We hypothesise that compared with standard oxygen, high-flow nasal oxygen may reduce mortality in patients with acute hypoxaemic respiratory failure. METHOD AND ANALYSIS: The Standard Oxygen versus High-flow nasal Oxygen-trial is an investigator-initiated, multicentre, open-label, randomised controlled trial comparing high-flow nasal oxygen versus standard oxygen in patients admitted to an intensive care unit (ICU) for acute respiratory failure with moderate-to-severe hypoxaemia. 1110 patients will be randomly assigned to one of the two groups with a ratio of 1:1. The primary outcome is the number of patients who died 28 days after randomisation. Secondary outcomes include comfort, dyspnoea and oxygenation 1 hour after treatment initiation, the number of patients intubated at day 28, mortality in ICU, in hospital and until day 90, and complications during ICU stay. ETHICS AND DISSEMINATION: The study has been approved by the central Ethics Committee 'Sud Méditerranée III' (2020-07-05) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04468126.

Oxygen therapy and noninvasive respiratory supports in acute hypoxemic respiratory failure: a narrative review.

BACKGROUND: This narrative review was written by an expert panel to the members of the jury to help in the development of clinical practice guidelines on oxygen therapy. RESULTS: According to the expert panel, acute hypoxemic respiratory failure was defined as PaO2 < 60 mm Hg or SpO2 < 90% on room air, or PaO2/FiO2 ≤ 300 mm Hg. Supplemental oxygen should be administered according to the monitoring of SpO2, with the aim at maintaining SpO2 above 92% and below 98%. Noninvasive respiratory supports are generally reserved for the most hypoxemic patients with the aim of relieving dyspnea. High-flow nasal cannula oxygen (HFNC) seems superior to conventional oxygen therapy (COT) as a means of avoiding intubation and may therefore be should probably be used as a first-line noninvasive respiratory support in patients requiring more than 6 L/min of oxygen or PaO2/FiO2 ≤ 200 mm Hg and a respiratory rate above 25 breaths/minute or clinical signs of respiratory distress, but with no benefits on mortality. Continuous positive airway pressure (CPAP) cannot currently be recommended as a first-line noninvasive respiratory support, since its beneficial effects on intubation remain uncertain. Despite older studies favoring noninvasive ventilation (NIV) over COT, recent clinical trials fail to show beneficial effects with NIV compared to HFNC. Therefore, there is no evidence to support the use of NIV or CPAP as first-line treatment if HFNC is available. Clinical trials do not support the hypothesis that noninvasive respiratory supports may lead to late intubation. The potential benefits of awake prone positioning on the risk of intubation in patients with COVID-19 cannot be extrapolated to patients with another etiology. CONCLUSIONS: Whereas oxygen supplementation should be initiated for patients with acute hypoxemic respiratory failure defined as PaO2 below 60 mm Hg or SpO2 < 90% on room air, HFNC should be the first-line noninvasive respiratory support in patients with PaO2/FiO2 ≤ 200 mm Hg with increased respiratory rate. Further studies are needed to assess the potential benefits of CPAP, NIV through a helmet and awake prone position in patients with acute hypoxemic respiratory failure not related to COVID-19.

Pressure control plus spontaneous ventilation versus volume assist-control ventilation in acute respiratory distress syndrome. A randomised clinical trial.

PURPOSE: The aim of this study was to compare the effect of a pressure-controlled strategy allowing non-synchronised unassisted spontaneous ventilation (PC-SV) to a conventional volume assist-control strategy (ACV) on the outcome of patients with acute respiratory distress syndrome (ARDS). METHODS: Open-label randomised clinical trial in 22 intensive care units (ICU) in France. Seven hundred adults with moderate or severe ARDS (PaO2/FiO2 < 200 mmHg) were enrolled from February 2013 to October 2018. Patients were randomly assigned to PC-SV (n = 348) or ACV (n = 352) with similar objectives of tidal volume (6 mL/kg predicted body weight) and positive end-expiratory pressure (PEEP). Paralysis was stopped after 24 h and sedation adapted to favour patients' spontaneous ventilation. The primary endpoint was in-hospital death from any cause at day 60. RESULTS: Hospital mortality [34.6% vs 33.5%, p = 0.77, risk ratio (RR) = 1.03 (95% confidence interval [CI] 0.84-1.27)], 28-day mortality, as well as the number of ventilator-free days and organ failure-free days at day 28 did not differ between PC-SV and ACV groups. Patients in the PC-SV group received significantly less sedation and neuro-muscular blocking agents than in the ACV group. A lower proportion of patients required adjunctive therapy of hypoxemia (including prone positioning) in the PC-SV group than in the ACV group [33.1% vs 41.3%, p = 0.03, RR = 0.80 (95% CI 0.66-0.98)]. The incidences of pneumothorax and refractory hypoxemia did not differ between the groups. CONCLUSIONS: A strategy based on PC-SV mode that favours spontaneous ventilation reduced the need for sedation and adjunctive therapies of hypoxemia but did not significantly reduce mortality compared to ACV with similar tidal volume and PEEP levels.

End-tidal carbon dioxide during spontaneous breathing trial to predict extubation failure: A prospective observational study.

Despite advances in weaning protocols, extubation failure (EF) is associated with poor outcomes. Many predictors of EF have been proposed, including hypercapnia at the end of the spontaneous breathing test (SBT). However, performing arterial blood gases at the end of SBT is not routinely recommended, whereas end-tidal carbon dioxide (EtCO2) can be routinely monitored during SBT. We aimed to evaluate the clinical utility of EtCO2 to predict EF. Patients undergoing planned extubation were eligible. Non-inclusion criteria were tracheostomy and patients extubated after successful T-tube SBT. We recorded clinical data and EtCO2 in 189 patients during a successful one-hour low pressure support SBT. EtCO2 measured before successful SBT was lower in patients with EF compared to those with successful extubation (27 [24-29] vs 30 [27-47] mmHg, p = 0.02), while EtCO2 measured at five minutes and at the end of the SBT was not different between the two groups (26 [22-28] vs. 29 [28-49] mmHg, p = 0.06 and 26 [26-29] vs. 29 [27-49] mmHg, p = 0.09, respectively). Variables identified by multivariable analysis as independently associated with EF were acute respiratory failure as the cause of intubation and ineffective cough. Our study suggests that recording EtCO2 during successful SBT appears to have limited predictive value for EF.

Performance and impact of rapid multiplex PCR on diagnosis and treatment of ventilated hospital-acquired pneumonia in patients with extended-spectrum ß-lactamase-producing Enterobacterales rectal carriage.

BACKGROUND: Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene. METHODS: This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP. RESULTS: Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1-35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6-22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5-22.1), p = 0.01). CONCLUSION: mPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted.

Dyspnea is severe and associated with a higher intubation rate in de novo acute hypoxemic respiratory failure.

BACKGROUND: Dyspnea is a key symptom of de novo acute hypoxemic respiratory failure. This study explores dyspnea and its association with intubation and mortality in this population. METHODS: This was a secondary analysis of a multicenter, randomized, controlled trial. Dyspnea was quantified by a visual analog scale (dyspnea-VAS) from zero to 100 mm. Dyspnea was measured in 259 of the 310 patients included. Factors associated with intubation were assessed with a competing risks model taking into account ICU discharge. The Cox model was used to evaluate factors associated with 90-day mortality. RESULTS: At baseline (randomization in the parent trial), median dyspnea-VAS was 46 (interquartile range, 16-65) mm and was ≥ 40 mm in 146 patients (56%). The intubation rate was 45%. Baseline variables independently associated with intubation were moderate (dyspnea-VAS 40-64 mm) and severe (dyspnea-VAS ≥ 65 mm) dyspnea at baseline (sHR 1.96 and 2.61, p = 0.023), systolic arterial pressure (sHR 2.56, p < 0.001), heart rate (sHR 1.94, p = 0.02) and PaO2/FiO2 (sHR 0.34, p = 0.028). 90-day mortality was 20%. The cumulative probability of survival was lower in patients with baseline dyspnea-VAS ≥ 40 mm (logrank test, p = 0.049). Variables independently associated with mortality were SAPS 2 ≥ 25 (p < 0.001), moderate-to-severe dyspnea at baseline (p = 0.073), PaO2/FiO2 (p = 0.118), and treatment arm (p = 0.046). CONCLUSIONS: In patients admitted to the ICU for de novo acute hypoxemic respiratory failure, dyspnea is associated with a higher risk of intubation and with a higher mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier # NCT01320384.

Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome.

OBJECTIVE: Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. DESIGN: Prospective before-after study. SETTINGS: Intensive-care unit of a French teaching hospital and sickle cell disease referral center. PATIENTS: Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. INTERVENTIONS: Patients were treated with intermittent administration during the first period (April 2016 -April 2018) and with continuous infusion during the second period (May 2018 -August 2019). MEASUREMENTS AND MAIN RESULTS: We included 60 episodes of acute chest syndrome in 58 patients (29 [25-34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48-88] vs. 61 [57-64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4-13.3] vs. 0 [0-0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. CONCLUSION: As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.

Accuracy of tidal volume delivery by paediatric intensive care ventilators: A bench-model study.

BACKGROUND: Tidal volume (Vt) delivery during mechanical ventilation is influenced by gas compression, humidity, and temperature. OBJECTIVES: This bench study aimed at assessing the accuracy of Vt delivery by paediatric intensive care ventilators according to the humidification system. Secondary objectives were to assess the following: (i) the accuracy of Vt delivery in ventilators with an integrated Y-piece pneumotachograph and (ii) the ability of ventilators to deliver and maintain a preset positive end-expiratory pressure. METHODS: Six latest-generation intensive care ventilators equipped with a paediatric mode were tested on the ASL5000 test lung in four simulated paediatric bench models (full-term neonate, infant, preschool-age chile, and school-age child), under volume-controlled mode with a heated humidifier (HH) or a heat moisture exchanger, with various loading conditions. Three ventilators equipped with a Y-piece pneumotachograph were tested with or without the pneumotachograph in the neonatal and infant models. "Accurate Vt" delivery was defined as a volume error (percentage of the preset Vt under body temperature and pressure and saturated water vapour conditions) being ≤10 % of the absolute preset value. RESULTS: Vt accuracy varied significantly across ventilators but was acceptable in almost all the ventilators and all the models, except the neonatal model. The humidification system had an impact on Vt delivery in the majority of the tested conditions (p < 0.05). The use of an HH was associated with a better Vt accuracy in four ventilators (V500, V800, R860, and ServoU) and allowed to achieve an acceptable level of volume error in the neonatal model as compared to the use of heat moisture exchanger. The use of an integrated pneumotachograph was associated with lower volume error in only one ventilator (p < 0.01). All the tested ventilators were able to maintain adequate positive end-expiratory pressure levels. CONCLUSION: The humidification system affects Vt accuracy of paediatric intensive care ventilators, especially in the youngest patients for whom the HH should be preferred.

Geo-economic Influence on the Effect of Fluid Volume for Sepsis Resuscitation: A Meta-Analysis.

Rationale: Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. Objectives: To explore the influence of country income group on risk-benefit balance of fluid management strategies in sepsis. Methods: We searched e-databases for all randomized controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. The effect of fluid strategies (higher versus lower volumes) on mortality was analyzed per income group (i.e., low- and middle-income countries [LMICs] or high-income countries [HICs]). Measurements and Main Results: Twenty-nine studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in studies of LMICs as compared with those of HICs: median, 37% (interquartile range [IQR]: 26-41) versus 29% (IQR: 17-38; P = 0.06). Income group significantly interacted with the effect of fluid volume on mortality: Higher fluid volume was associated with higher mortality in LMICs but not in HICs: odds ratio (OR), 1.47; 95% confidence interval (95% CI): 1.14-1.90 versus 1.00 (95% CI: 0.87-1.16), P = 0.01 for subgroup differences. Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR, 1.24 [95% CI: 1.08-1.43]) but not in HICs (OR, 1.02 [95% CI: 0.80-1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45 [95% CI: 1.09-1.93] vs. 1.09 [95% CI: 0.93-1.28], P = 0.02 for subgroup differences). Conclusions: In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher volume of fluid resuscitation associated with increased mortality in LMICs and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.

Influence of different noninvasive oxygenation support devices on tidal volume.

BACKGROUND: Multiple devices are available for noninvasive oxygenation support, including non-rebreather oxygen mask (O2-mask), high-flow oxygen through nasal cannula (HFNC), continuous positive airway pressure (CPAP), mask noninvasive ventilation (Mask-NIV) and helmet NIV (Helmet-NIV). As tidal volume is a key determinant of efficacy and safety during ventilatory support, we assessed whether it was influenced by the type of noninvasive oxygenation device. METHODS: A bench study using a manikin with a realistic face connected to a lung simulator was performed. Six conditions were assessed: no device, O2-mask, HFNC, CPAP, Mask-NIV and Helmet-NIV. Three respiratory mechanics were simulated (normal, obstructive, restrictive), at three simulated efforts (low, moderate, respiratory distress). Flow was recorded at the lung simulator inlet and mouth pressure into the manikin mouth. The same devices were evaluated on healthy volunteers with tidal volume assessed by electrical impedance tomography (EIT). RESULTS: Tidal volume was significantly influenced by oxygenation devices in bench model. As compared to O2-mask, HFNC and CPAP delivered significantly lower tidal volumes (440 ± 352 mL, 414 ± 333 mL and 377 ± 297 mL, respectively), while Mask-NIV or Helmet-NIV were associated with significantly higher tidal volumes (690 ± 321 mL and 652 ± 366 mL, respectively). Tidal volume was strongly correlated with the specific effect of each device on mouth pressure during inspiration: HFNC and CPAP were characterized by a negative PTPmouth (- 0.3 [- 0.8 to - 0.2] and - 0.7 [- 2.2 to - 0.5] cmH2O.sec/cycle, respectively), while Helmet-NIV and Mask-NIV were associated with a positive PTPmouth (4.5 [4.1-4.6] and 6.1 [5.9-7.1] cmH2O.sec/cycle, respectively). Tidal volume was also significantly influenced by oxygenation devices in healthy volunteers, with similar tidal volumes between O2-mask and CPAP (644 [571-764] and 648 [586-770] mL) but higher with HFNC, Mask-NIV and Helmet-NIV (819 [609-918], 1110 [661-1305] and 1086 [833-1243] mL). CONCLUSIONS: Tidal volume is significantly influenced by noninvasive oxygenation support devices, with a strong correlation with the pressure variation generated into the mouth during inspiration. NIV was associated with the highest tidal volumes and CPAP with the lowest ones. Clinical studies are needed to clarify the clinical implications of these effects.

A new reservoir-based CPAP with low oxygen consumption: the Bag-CPAP.

BACKGROUND: Several noninvasive ventilatory supports rely in their design on high oxygen consumption which may precipitate oxygen shortage, as experienced during the COVID-19 pandemic. In this bench-to-bedside study, we assessed the performance of a new continuous positive airway pressure (CPAP) device integrating a large reservoir ("Bag-CPAP") designed to minimize oxygen consumption, and compared it with other CPAP devices. METHODS: First, a bench study compared the performances of Bag-CPAP and four CPAP devices with an intensive care unit ventilator. Two FiO2 targets (40-60% and 80-100%) at a predefined positive end expiratory pressure (PEEP) level between 5 and 10 cm H2O were tested and fraction of inspired oxygen (FiO2) and oxygen consumption were measured. Device-imposed work of breathing (WOB) was also evaluated. Second, an observational clinical study evaluated the new CPAP in 20 adult patients with acute respiratory failure in two hospitals in France. Actual FiO2, PEEP, peripheral oxygen saturation, respiratory rate, and dyspnea score were assessed. RESULTS: All six systems tested in the bench study reached the minimal FiO2 target of 40% and four reached at least 80% FiO2 while maintaining PEEP in the predefined range. Device-delivered FiO2/consumed oxygen ratio was the highest with the new reservoir-based CPAP irrespective of FiO2 target. WOB induced by the device was higher with Bag-CPAP. In the clinical study, Bag-CPAP was well tolerated and could reach high (> 90%) and moderate (> 50%) FiO2 with an oxygen flow rate of 15 [15-16] and 8 [7-9] L/min, respectively. Dyspnea score improved significantly after introduction of Bag-CPAP, and SpO2 increased. CONCLUSIONS: In vitro, Bag-CPAP exhibited the highest oxygen saving properties albeit had increased WOB. It was well accepted clinically and reduced dyspnea. Bag-CPAP may be useful to treat patients with acute respiratory failure in the field, especially when facing constraints in oxygen delivery.

A novel method for assessment of airway opening pressure without the need for low-flow insufflation.

BACKGROUND: Airway opening pressure (AOP) detection and measurement are essential for assessing respiratory mechanics and adapting ventilation. We propose a novel approach for AOP assessment during volume assist control ventilation at a usual constant-flow rate of 60 L/min. OBJECTIVES: To validate the conductive pressure (Pcond) method, which compare the Pcond-defined on the airway pressure waveform as the difference between the airway pressure level at which an abrupt change in slope occurs at the beginning of insufflation and PEEP-to resistive pressure for AOP detection and measurement, and to compare its respiratory and hemodynamic tolerance to the standard low-flow insufflation method. METHODS: The proof-of-concept of the Pcond method was assessed on mechanical (lung simulator) and physiological (cadavers) bench models. Its diagnostic performance was evaluated in 213 patients, using the standard low-flow insufflation method as a reference. In 45 patients, the respiratory and hemodynamic tolerance of the Pcond method was compared with the standard low-flow method. MEASUREMENTS AND MAIN RESULTS: Bench assessments validated the Pcond method proof-of-concept. Sensitivity and specificity of the Pcond method for AOP detection were 93% and 91%, respectively. AOP obtained by Pcond and standard low-flow methods strongly correlated (r = 0.84, p < 0.001). Changes in SpO2 were significantly lower during Pcond than during standard method (p < 0.001). CONCLUSION: Determination of Pcond during constant-flow assist control ventilation may permit to easily and safely detect and measure AOP.

Dual titration of minute ventilation and sweep gas flow to control carbon dioxide variations in patients on venovenous extracorporeal membrane oxygenation.

BACKGROUND: The implantation of venovenous extracorporeal membrane oxygenation (VV-ECMO) support to manage severe acute respiratory distress syndrome generates large variations in carbon dioxide partial pressure (PaCO2) that are associated with intracranial bleeding. We assessed the feasibility and efficacy of a pragmatic protocol for progressive dual titration of sweep gas flow and minute ventilation after VV-ECMO implantation in order to limit significant PaCO2 variations. PATIENTS AND METHODS: A protocol for dual titration of sweep gas flow and minute ventilation following VV-ECMO implantation was implemented in our unit in September 2020. In this single-centre retrospective before-after study, we included patients who required VV-ECMO from March, 2020 to May, 2021, which corresponds to two time periods: from March to August, 2020 (control group) and from September, 2020 to May, 2021 (protocol group). The primary endpoint was the mean absolute change in PaCO2 in consecutive arterial blood gases samples drawn over the first 12 h following VV-ECMO implantation. Secondary endpoints included large (> 25 mmHg) initial variations in PaCO2, intracranial bleedings and mortality in both groups. RESULTS: Fifty-one patients required VV-ECMO in our unit during the study period, including 24 in the control group and 27 in the protocol group. The protocol was proved feasible. The 12-h mean absolute change in PaCO2 was significantly lower in patients of the protocol group as compared with their counterparts (7 mmHg [6-12] vs. 12 mmHg [6-24], p = 0.007). Patients of the protocol group experienced less large initial variations in PaCO2 immediately after ECMO implantation (7% vs. 29%, p = 0.04) and less intracranial bleeding (4% vs. 25%, p = 0.04). Mortality was similar in both groups (35% vs. 46%, p = 0.42). CONCLUSION: Implementation of our protocol for dual titration of minute ventilation and sweep gas flow was feasible and associated with less initial PaCO2 variation than usual care. It was also associated with less intracranial bleeding.

Impact of cardiac output and alveolar ventilation in estimating ventilation/perfusion mismatch in ARDS using electrical impedance tomography.

INTRODUCTION: Electrical impedance tomography (EIT) can be used to assess ventilation/perfusion (V/Q) mismatch within the lungs. Several methods have been proposed, some of them neglecting the absolute value of alveolar ventilation (VA) and cardiac output (QC). Whether this omission results in acceptable bias is unknown. METHODS: Pixel-level V/Q maps of 25 ARDS patients were computed once considering (absolute V/Q map) and once neglecting (relative V/Q map) the value of QC and VA. Previously published indices of V/Q mismatch were computed using absolute V/Q maps and relative V/Q maps. Indices computed with relative V/Q maps were compared to their counterparts computed using absolute V/Q maps. RESULTS: Among 21 patients with ratio of alveolar ventilation to cardiac output (VA/QC) > 1, relative shunt fraction was significantly higher than absolute shunt fraction [37% (24-66) vs 19% (11-46), respectively, p < 0.001], while relative dead space fraction was significantly lower than absolute dead space fraction [40% (22-49) vs 58% (46-84), respectively, p < 0.001]. Relative wasted ventilation was significantly lower than the absolute wasted ventilation [16% (11-27) vs 29% (19-35), respectively, p < 0.001], while relative wasted perfusion was significantly higher than absolute wasted perfusion [18% (11-23) vs 11% (7-19), respectively, p < 0.001]. The opposite findings were retrieved in the four patients with VA/QC < 1. CONCLUSION: Neglecting cardiac output and alveolar ventilation when assessing V/Q mismatch indices using EIT in ARDS patients results in significant bias, whose direction depends on the VA/QC ratio value.

Study protocol for a randomized controlled trial of Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: the PROMIZING study.

BACKGROUND: Proportional assist ventilation with load-adjustable gain factors (PAV+) is a mechanical ventilation mode that delivers assistance to breathe in proportion to the patient's effort. The proportional assistance, called the gain, can be adjusted by the clinician to maintain the patient's respiratory effort or workload within a normal range. Short-term and physiological benefits of this mode compared to pressure support ventilation (PSV) include better patient-ventilator synchrony and a more physiological response to changes in ventilatory demand. METHODS: The objective of this multi-centre randomized controlled trial (RCT) is to determine if, for patients with acute respiratory failure, ventilation with PAV+ will result in a shorter time to successful extubation than with PSV. This multi-centre open-label clinical trial plans to involve approximately 20 sites in several continents. Once eligibility is determined, patients must tolerate a short-term PSV trial and either (1) not meet general weaning criteria or (2) fail a 2-min Zero Continuous Positive Airway Pressure (CPAP) Trial using the rapid shallow breathing index, or (3) fail a spontaneous breathing trial (SBT), in this sequence. Then, participants in this study will be randomized to either PSV or PAV+ in a 1:1 ratio. PAV+ will be set according to a target of muscular pressure. The weaning process will be identical in the two arms. Time to liberation will be the primary outcome; ventilator-free days and other outcomes will be measured. DISCUSSION: Meta-analyses comparing PAV+ to PSV suggest PAV+ may benefit patients and decrease healthcare costs but no powered study to date has targeted the difficult to wean patient population most likely to benefit from the intervention, or used consistent timing for the implementation of PAV+. Our enrolment strategy, primary outcome measure, and liberation approaches may be useful for studying mechanical ventilation and weaning and can offer important results for patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02447692 . Prospectively registered on May 19, 2015.

Technical Innovation in Critical Care in a World of Constraints: Lessons from the COVID-19 Pandemic.

The COVID-19 crisis was characterized by a massive need for respiratory support, which has unfortunately not been met globally. This situation mimicked those which gave rise to critical care in the past. Since the polio epidemic in the 50's, the technological evolution of respiratory support has enabled health professionals to save the lives of critically-ill patients worldwide every year. However, much of the current innovation work has turned around developing sophisticated, complex, and high-cost standards and approaches whose resilience is still questionable upon facing constrained environments or contexts, as seen in resuscitation work outside intensive care units, during pandemics, or in low-income countries. Ventilatory support is an essential life-saving tool for patients with respiratory distress. It requires an oxygen source combined to a ventilatory assistance device, an adequate monitoring system, and properly trained caregivers to operate it. Each of these elements can be subject to critical constraints, which we can no longer ignore. The innovation process should incorporate them as a prima materia, whilst focusing on the core need of the field using the concept of frugal innovation. Having a universal access to oxygen and respiratory support, irrespective of the context and constraints, necessitates: i) developing cost-effective, energy-efficient, and maintenance-free oxygen generation devices; ii) improving the design of non-invasive respiratory devices (for example, with oxygen saving properties); iii) conceiving fully frugal ventilators and universal monitoring systems; iv) broadening ventilation expertise by developing end-user training programs in ventilator assistance. The frugal innovation approach may give rise to a more resilient and inclusive critical care system. This paradigm shift is essential for the current and future challenges.

Spontaneous pneumomediastinum: a surrogate of P-SILI in critically ill COVID-19 patients.

Spontaneous pneumomediastinum (SP) has been described early during the COVID-19 pandemic in large series of patients with severe pneumonia, but most patients were receiving invasive mechanical ventilation (IMV) at the time of SP diagnosis. In this retrospective multicenter observational study, we aimed at describing the prevalence and outcomes of SP during severe COVID-19 with pneumonia before any IMV, to rule out mechanisms induced by IMV in the development of pneumomediastinum.Among 549 patients, 21 patients (4%) developed a SP while receiving non-invasive respiratory support, after a median of 6 days [4-12] from ICU admission. The proportion of patients requiring IMV was similar. However, the time to tracheal intubation was longer in patients with SP (6 days [5-13] vs. 2 days [1-4]; P = 0.00002), with a higher first-line use of non-invasive ventilation (n = 11; 52% vs. n = 150; 28%; P = 0.02). The 21 patients who developed a SP had persisting signs of severe lung disease and respiratory failure with lower ROX index between ICU admission and occurrence of SP (3.94 [3.15-5.55] at admission vs. 3.25 [2.73-4.02] the day preceding SP; P = 0.1), which may underline potential indirect signals of Patient-self inflicted lung injury (P-SILI).In this series of critically ill COVID-19 patients, the prevalence of SP without IMV was not uncommon, affecting 4% of patients. They received more often vasopressors and had a longer ICU length of stay, as compared with their counterparts. One pathophysiological mechanism may potentially be carried out by P-SILI related to a prolonged respiratory failure, as underlined by a delayed use of IMV and the evolution of the ROX index between ICU admission and the day preceding SP.