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.

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.

Driving pressure-guided ventilation decreases the mechanical power compared to predicted body weight-guided ventilation in the Acute Respiratory Distress Syndrome.

BACKGROUND: Whether targeting the driving pressure (∆P) when adjusting the tidal volume in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS) may decrease the risk of ventilator-induced lung injury remains a matter of research. In this study, we assessed the effect of a ∆P-guided ventilation on the mechanical power. METHODS: We prospectively included adult patients with moderate-to-severe ARDS. Positive end expiratory pressure was set by the attending physician and kept constant during the study. Tidal volume was first adjusted to target 6 ml/kg of predicted body weight (PBW-guided ventilation) and subsequently modified within a range from 4 to 10 ml/kg PBW to target a ∆P between 12 and 14 cm H2O. The respiratory rate was then re-adjusted within a range from 12 to 40 breaths/min until EtCO2 returned to its baseline value (∆P-guided ventilation). Mechanical power was computed at each step. RESULTS: Fifty-one patients were included between December 2019 and May 2021. ∆P-guided ventilation was feasible in all but one patient. The ∆P during PBW-guided ventilation was already within the target range of ∆P-guided ventilation in five (10%) patients, above in nine (18%) and below in 36 (72%). The change from PBW- to ∆P-guided ventilation was thus accompanied by an overall increase in tidal volume from 6.1 mL/kg PBW [5.9-6.2] to 7.7 ml/kg PBW [6.2-8.7], while respiratory rate was decreased from 29 breaths/min [26-32] to 21 breaths/min [16-28] (p < 0.001 for all comparisons). ∆P-guided ventilation was accompanied by a significant decrease in mechanical power from 31.5 J/min [28-35.7] to 28.8 J/min [24.6-32.6] (p < 0.001), representing a relative decrease of 7% [0-16]. With ∆P-guided ventilation, the PaO2/FiO2 ratio increased and the ventilatory ratio decreased. CONCLUSION: As compared to a conventional PBW-guided ventilation, a ∆P-guided ventilation strategy targeting a ∆P between 12 and 14 cm H2O required to change the tidal volume in 90% of the patients. Such ∆P-guided ventilation significantly reduced the mechanical power. Whether this physiological observation could be associated with clinical benefit should be assessed in clinical trials.

Electrical impedance tomography to titrate positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome.

RATIONALE: Patients with coronavirus disease-19-related acute respiratory distress syndrome (C-ARDS) could have a specific physiological phenotype as compared with those affected by ARDS from other causes (NC-ARDS). OBJECTIVES: To describe the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics in C-ARDS patients in supine and prone position, and as compared to NC-ARDS. The primary endpoint was the best PEEP defined as the smallest sum of hyperdistension and collapse. METHODS: Seventeen patients with moderate-to-severe C-ARDS were monitored by electrical impedance tomography (EIT) and evaluated during PEEP titration in supine (n = 17) and prone (n = 14) position and compared with 13 NC-ARDS patients investigated by EIT in our department before the COVID-19 pandemic. RESULTS: As compared with NC-ARDS, C-ARDS exhibited a higher median best PEEP (defined using EIT as the smallest sum of hyperdistension and collapse, 12 [9, 12] vs. 9 [6, 9] cmH2O, p < 0.01), more collapse at low PEEP, and less hyperdistension at high PEEP. The median value of the best PEEP was similar in C-ARDS in supine and prone position: 12 [9, 12] vs. 12 [10, 15] cmH2O, p = 0.59. The response to PEEP was also similar in C-ARDS patients with higher vs. lower respiratory system compliance. CONCLUSION: An intermediate PEEP level seems appropriate in half of our C-ARDS patients. There is no solid evidence that compliance at low PEEP could predict the response to PEEP.

Antimicrobial strategy for severe community-acquired legionnaires' disease: a multicentre retrospective observational study.

Background: Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases. Objectives: To evaluate the effect of antimicrobial strategy on ICU mortality. Methods: Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used. Results: Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P = 0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P = 0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P = 0.02]. Conclusions: Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates.

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.

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.

Patient-Self Inflicted Lung Injury: A Practical Review.

Patients with severe lung injury usually have a high respiratory drive, resulting in intense inspiratory effort that may even worsen lung damage by several mechanisms gathered under the name "patient-self inflicted lung injury" (P-SILI). Even though no clinical study has yet demonstrated that a ventilatory strategy to limit the risk of P-SILI can improve the outcome, the concept of P-SILI relies on sound physiological reasoning, an accumulation of clinical observations and some consistent experimental data. In this review, we detail the main pathophysiological mechanisms by which the patient's respiratory effort could become deleterious: excessive transpulmonary pressure resulting in over-distension; inhomogeneous distribution of transpulmonary pressure variations across the lung leading to cyclic opening/closing of nondependent regions and pendelluft phenomenon; increase in the transvascular pressure favoring the aggravation of pulmonary edema. We also describe potentially harmful patient-ventilator interactions. Finally, we discuss in a practical way how to detect in the clinical setting situations at risk for P-SILI and to what extent this recognition can help personalize the treatment strategy.

Refractory ineffective triggering during pressure support ventilation: effect of proportional assist ventilation with load-adjustable gain factors.

BACKGROUND: Ineffective triggering is frequent during pressure support ventilation (PSV) and may persist despite ventilator adjustment, leading to refractory asynchrony. We aimed to assess the effect of proportional assist ventilation with load-adjustable gain factors (PAV+) on the occurrence of refractory ineffective triggering. DESIGN: Observational assessment followed by prospective cross-over physiological study. SETTING: Academic medical ICU. PATIENTS: Ineffective triggering was detected during PSV by a twice-daily inspection of the ventilator's screen. The impact of pressure support level (PSL) adjustments on the occurrence of asynchrony was recorded. Patients experiencing refractory ineffective triggering, defined as persisting asynchrony at the lowest tolerated PSL, were included in the physiological study. INTERVENTIONS: Physiological study: Flow, airway, and esophageal pressures were continuously recorded during 10 min under PSV with the lowest tolerated PSL, and then under PAV+ with the gain adjusted to target a muscle pressure between 5 and 10 cmH2O. MEASUREMENTS: Primary endpoint was the comparison of asynchrony index between PSV and PAV+ after PSL and gain adjustments. RESULTS: Among 36 patients identified having ineffective triggering under PSV, 21 (58%) exhibited refractory ineffective triggering. The lowest tolerated PSL was higher in patients with refractory asynchrony as compared to patients with non-refractory ineffective triggering. Twelve out of the 21 patients with refractory ineffective triggering were included in the physiological study. The median lowest tolerated PSL was 17 cmH2O [12-18] with a PEEP of 7 cmH2O [5-8] and FiO2 of 40% [39-42]. The median gain during PAV+ was 73% [65-80]. The asynchrony index was significantly lower during PAV+ than PSV (2.7% [1.0-5.4] vs. 22.7% [10.3-40.1], p < 0.001) and consistently decreased in every patient with PAV+. Esophageal pressure-time product (PTPes) did not significantly differ between the two modes (107 cmH2O/s/min [79-131] under PSV vs. 149 cmH2O/s/min [129-170] under PAV+, p = 0.092), but the proportion of PTPes lost in ineffective triggering was significantly lower with PAV+ (2 cmH2O/s/min [1-6] vs. 8 cmH2O/s/min [3-30], p = 0.012). CONCLUSIONS: Among patients with ineffective triggering under PSV, PSL adjustment failed to eliminate asynchrony in 58% of them (21 of 36 patients). In these patients with refractory ineffective triggering, switching from PSV to PAV+ significantly reduced or even suppressed the incidence of asynchrony.

Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside.

BACKGROUND: We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter ("Filter Frugal CPAP", FF-CPAP) in and out the ICU. METHODS: (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak. RESULTS: Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient's work of breathing (6-34%) needed to sustain the tidal volume, depending on the filter's resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO2. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p < 0.001 by log-rank test). CONCLUSION: Adding a filter to the Boussignac valve does not affect the delivered pressure but may variably increase the resistive load depending on the filter used. Clinical assessment suggests that FF-CPAP is a frugal solution to provide a ventilatory support and improve oxygenation to numerous patients suffering from AHRF in the context of a massive outbreak.

Rescue therapy with inhaled nitric oxide and almitrine in COVID-19 patients with severe acute respiratory distress syndrome.

BACKGROUND: In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for VA/Q mismatch, as hypoxic vasoconstriction alteration. This study aimed to evaluate the capacity of inhaled nitric oxide (iNO)-almitrine combination to restore oxygenation in severe COVID-19 ARDS (C-ARDS) patients. METHODS: We conducted a monocentric preliminary pilot study in intubated patients with severe C-ARDS. Respiratory mechanics was assessed after a prone session. Then, patients received iNO (10 ppm) alone and in association with almitrine (10 µg/kg/min) during 30 min in each step. Echocardiographic and blood gases measurements were performed at baseline, during iNO alone, and iNO-almitrine combination. The primary endpoint was the variation of oxygenation (PaO2/FiO2 ratio). RESULTS: Ten severe C-ARDS patients were assessed (7 males and 3 females), with a median age of 60 [52-72] years. Combination of iNO and almitrine outperformed iNO alone for oxygenation improvement. The median of PaO2/FiO2 ratio varied from 102 [89-134] mmHg at baseline, to 124 [108-146] mmHg after iNO (p = 0.13) and 180 [132-206] mmHg after iNO and almitrine (p < 0.01). We found no correlation between the increase in oxygenation caused by iNO-almitrine combination and that caused by proning. CONCLUSION: In this pilot study of severe C-ARDS patients, iNO-almitrine combination was associated with rapid and significant improvement of oxygenation. These findings highlight the role of pulmonary vascular function in COVID-19 pathophysiology.

Prone positioning in acute respiratory distress syndrome after abdominal surgery: a multicenter retrospective study : SAPRONADONF (Study of Ards and PRONe position After abDOmiNal surgery in France).

BACKGROUND: The recent demonstration of prone position's strong benefit on patient survival has rendered proning a major therapeutic intervention in severe ARDS. Uncertainties remain as to whether or not ARDS patients in the postoperative period of abdominal surgery should be turned prone because of the risk of abdominal complications. Our aim was to investigate the prevalence of surgical complications between patients with and without prone position after abdominal surgery. METHODS: This study was a multicenter retrospective cohort of patients with ARDS in a context of recent abdominal surgery. Primary outcome was the number of patients who had at least one surgical complication that could be induced or worsened by prone position. Secondary outcomes included effects of prone position on oxygenation. Data from the prone group were compared with those from the supine group (not having undergone at least a prone position session). RESULTS: Among 98 patients included, 36 (37%) had at least one prone position session. The rate of surgical complications induced or worsened by prone position did not differ between prone and supine groups [respectively, 14 (39%) vs 27 (44%); p = 0.65]. After propensity score application, there was no significant difference between the two groups (OR 0.72 [0.26-2.02], p = 0.54). Revision surgery did not differ between the groups. The first prone session significantly increased PaO2/FiO2 ratio from 95 ± 47 to 189 ± 92 mmHg, p < 0.0001. CONCLUSION: Prone position of ARDS patients after abdominal surgery was not associated with an increased rate of surgical complication. Intensivists should not refrain from proning these patients.