End-tidal carbon dioxide monitoring using a naso-buccal sensor is not appropriate to monitor capnia during non-invasive ventilation.

BACKGROUND: In acute respiratory failure, arterial blood gas analysis (ABG) is used to diagnose hypercapnia. Once non-invasive ventilation (NIV) is initiated, ABG should at least be repeated within 1 h to assess PaCO2 response to treatment in order to help detect NIV failure. The main aim of this study was to assess whether measuring end-tidal CO2 (EtCO2) with a dedicated naso-buccal sensor during NIV could predict PaCO2 variation and/or PaCO2 absolute values. The additional aim was to assess whether active or passive prolonged expiratory maneuvers could improve the agreement between expiratory CO2 and PaCO2. METHODS: This is a prospective study in adult patients suffering from acute hypercapnic respiratory failure (PaCO2 ≥ 45 mmHg) treated with NIV. EtCO2 and expiratory CO2 values during active and passive expiratory maneuvers were measured using a dedicated naso-buccal sensor and compared to concomitant PaCO2 values. The agreement between two consecutive values of EtCO2 (delta EtCO2) and two consecutive values of PaCO2 (delta PaCO2) and between PaCO2 and concomitant expiratory CO2 values was assessed using the Bland and Altman method adjusted for the effects of repeated measurements. RESULTS: Fifty-four datasets from a population of 11 patients (8 COPD and 3 non-COPD patients), were included in the analysis. PaCO2 values ranged from 39 to 80 mmHg, and EtCO2 from 12 to 68 mmHg. In the observed agreement between delta EtCO2 and deltaPaCO2, bias was -0.3 mmHg, and limits of agreement were -17.8 and 17.2 mmHg. In agreement between PaCO2 and EtCO2, bias was 14.7 mmHg, and limits of agreement were -6.6 and 36.1 mmHg. Adding active and passive expiration maneuvers did not improve PaCO2 prediction. CONCLUSIONS: During NIV delivered for acute hypercapnic respiratory failure, measuring EtCO2 using a dedicating naso-buccal sensor was inaccurate to predict both PaCO2 and PaCO2 variations over time. Active and passive expiration maneuvers did not improve PaCO2 prediction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01489150

A diaphragmatic electrical activity-based optimization strategy during pressure support ventilation improves synchronization but does not impact work of breathing.

Poor patient-ventilator synchronization is often observed during pressure support ventilation (PSV) and has been associated with prolonged duration of mechanical ventilation and poor outcome. Diaphragmatic electrical activity (Eadi) recorded using specialized nasogastric tubes is a surrogate of respiratory brain stem output. This study aimed at testing whether adapting ventilator settings during PSV using a protocolized Eadi-based optimization strategy, or Eadi-triggered and -cycled assisted pressure ventilation (or PSVN) could (1) improve patient-ventilator interaction and (2) reduce or normalize patient respiratory effort as estimated by the work of breathing (WOB) and the pressure time product (PTP). This was a prospective cross-over study. Patients with a known chronic pulmonary obstructive or restrictive disease, asynchronies or suspected intrinsic positive end-expiratory pressure (PEEP) who were ventilated using PSV were enrolled in the study. Four different ventilator settings were sequentially applied for 15 minutes (step 1: baseline PSV as set by the clinician, step 2: Eadi-optimized PSV to adjust PS level, inspiratory trigger, and cycling settings, step 3: step 2 + PEEP adjustment, step 4: PSVN). The same settings as step 3 were applied again after step 4 to rule out a potential effect of time. Breathing pattern, trigger delay (Td), inspiratory time in excess (Tiex), pressure-time product (PTP), and work of breathing (WOB) were measured at the end of each step. Eleven patients were enrolled in the study. Eadi-optimized PSV reduced Td without altering Tiex in comparison with baseline PSV. PSVN reduced Td and Tiex in comparison with baseline and Eadi-optimized PSV. Respiratory pattern did not change during the four steps. The improvement in patient-ventilator interaction did not lead to changes in WOB or PTP. Eadi-optimized PSV allows improving patient ventilator interaction but does not alter patient effort in patients with mild asynchrony. Clinicaltrials.gov identifier: NCT 02067403 . Registered 7 February 2014

Simple equations to predict the effects of veno-venous ECMO in decompensated Eisenmenger syndrome.

Adult patients with uncorrected congenital heart diseases and chronic intracardiac shunt may develop Eisenmenger syndrome (ES) due to progressive increase of pulmonary vascular resistance, with significant morbidity and mortality. Acute decompensation of ES in conditions promoting a further increase of pulmonary vascular resistance, such as pulmonary embolism or pneumonia, can precipitate major arterial hypoxia and death. In such conditions, increasing systemic oxygenation with veno-venous extracorporeal membrane oxygenation (VV-ECMO) could be life-saving, serving as a bridge to treat a potential reversible cause for the decompensation, or to urgent lung transplantation. Anticipating the effects of VV-ECMO in this setting could ease the clinical decision to initiate such therapeutic strategy. Here, we present a series of equations to accurately predict the effects of VV-ECMO on arterial oxygenation in ES and illustrate this point by a case of ES decompensation with refractory hypoxaemia consecutive to an acute respiratory failure due to viral pneumonia

Information conveyed by electrical diaphragmatic activity during unstressed, stressed and assisted spontaneous breathing: a physiological study.

The electrical activity of the crural diaphragm (Eadi), a surrogate of respiratory drive, can now be measured at the bedside in mechanically ventilated patients with a specific catheter. The expected range of Eadi values under stressed or assisted spontaneous breathing is unknown. This study explored Eadi values in healthy subjects during unstressed (baseline), stressed (with a resistance) and assisted spontaneous breathing. The relation between Eadi and inspiratory effort was analyzed. Thirteen healthy male volunteers were included in this randomized crossover study. Eadi and esophageal pressure (Peso) were recorded during unstressed and stressed spontaneous breathing and under assisted ventilation delivered in pressure support (PS) at low and high assist levels and in neurally adjusted ventilatory assist (NAVA). Overall eight different situations were assessed in each participant (randomized order). Peak, mean and integral of Eadi, breathing pattern, esophageal pressure-time product (PTPeso) and work of breathing (WOB) were calculated offline. Median [interquartile range] peak Eadi at baseline was 17 [13-22] μV and was above 10 μV in 92% of the cases. Eadi <sub>max</sub> defined as Eadi measured at maximal inspiratory capacity reached 90 [63 to 99] μV. Median peak Eadi/Eadi <sub>max</sub> ratio was 16.8 [15.6-27.9]%. Compared to baseline, respiratory rate and minute ventilation were decreased during stressed non-assisted breathing, whereas peak Eadi and PTPeso were increased. During unstressed assisted breathing, peak Eadi decreased during high-level PS compared to unstressed non-assisted breathing and to NAVA (p = 0.047). During stressed breathing, peak Eadi was lower during all assisted ventilation modalities compared to stressed non-assisted breathing. During assisted ventilation, across the different conditions, peak Eadi changed significantly, whereas PTPeso and WOB/min were not significantly modified. Finally, Eadi signal was still present even when Peso signal was suppressed due to high assist levels. Eadi analysis provides complementary information compared to respiratory pattern and to Peso monitoring, particularly in the presence of high assist levels. Trial registration The study was registered as NCT01818219 in clinicaltrial.gov. Registered 28 February 2013

Circulating calprotectin levels four months after severe and non-severe COVID-19.

BACKGROUND Calprotectin is an inflammatory marker mainly released by activated neutrophils that is increased in acute severe COVID-19. After initial recovery, some patients have persistent respiratory impairment with reduced diffusion capacity of the lungs for carbon monoxide (DLCO) months after infection. Underlying causes of this persistent impairment are unclear. We aimed to investigate the correlation between circulating calprotectin, persistent lung functional impairment and intensive care unit (ICU) stay after COVID-19 in two university hospital centres in Switzerland. METHODS Calprotectin levels were measured in serum from 124 patients (50% male) from the Bern cohort (post-ICU and non-ICU patients) and 68 (76% male) from the Lausanne cohort (only post-ICU patients) four months after COVID-19. Calprotectin was correlated with clinical parameters. Multivariate linear regression (MLR) was performed to evaluate the independent association of calprotectin in different models. RESULTS Overall, we found that post-ICU patients, compared to non-ICU, were significantly older (age 59.4 ± 13.6 (Bern), 60.5 ± 12.0 (Lausanne) vs. 48.8 ± 13.4 years) and more obese (BMI 28.6 ± 4.5 and 29.1 ± 5.3 vs. 25.2 ± 6.0 kg/m2, respectively). 48% of patients from Lausanne and 44% of the post-ICU Bern cohort had arterial hypertension as a pre-existing comorbidity vs. only 10% in non-ICU patients. Four months after COVID-19 infection, DLCO was lower in post-ICU patients (75.96 ± 19.05% predicted Bern, 71.11 ± 18.50% Lausanne) compared to non-ICU (97.79 ± 21.70% predicted, p < 0.01). The post-ICU cohort in Lausanne had similar calprotectin levels when compared to the cohort in Bern (Bern 2.74 ± 1.15 µg/ml, Lausanne 2.49 ± 1.13 µg/ml vs. non-ICU 1.86 ± 1.02 µg/ml; p-value < 0.01). Calprotectin correlated negatively with DLCO (r= -0.290, p < 0.001) and the forced vital capacity (FVC) (r= -0.311, p < 0.001). CONCLUSIONS Serum calprotectin is elevated in post-ICU patients in two independent cohorts and higher compared to non-ICU patients four months after COVID-19. In addition, there is a negative correlation between calprotectin levels and DLCO or FVC. The relationship between inflammation and lung functional impairment needs further investigations. TRIAL REGISTRATION NCT04581135

Accuracy of P0.1 measurements performed by ICU ventilators: a bench study.

Occlusion pressure at 100 ms (P0.1), defined as the negative pressure measured 100 ms after the initiation of an inspiratory effort performed against a closed respiratory circuit, has been shown to be well correlated with central respiratory drive and respiratory effort. Automated P0.1 measurement is available on modern ventilators. However, the reliability of this measurement has never been studied. This bench study aimed at assessing the accuracy of P0.1 measurements automatically performed by different ICU ventilators. Five ventilators set in pressure support mode were tested using a two-chamber test lung model simulating spontaneous breathing. P0.1 automatically displayed on the ventilator screen (P0.1 &lt;sub&gt;vent&lt;/sub&gt; ) was recorded at three levels of simulated inspiratory effort corresponding to P0.1 of 2.5, 5 and 10 cm H &lt;sub&gt;2&lt;/sub&gt; O measured directly at the test lung and considered as the reference values of P0.1 (P0.1 &lt;sub&gt;ref&lt;/sub&gt; ). The pressure drop after 100 ms was measured offline on the airway pressure-time curves recorded during the automated P0.1 measurements (P0.1 &lt;sub&gt;aw&lt;/sub&gt; ). P0.1 &lt;sub&gt;vent&lt;/sub&gt; was compared to P0.1 &lt;sub&gt;ref&lt;/sub&gt; and to P0.1 &lt;sub&gt;aw&lt;/sub&gt; . To assess the potential impact of the circuit length, P0.1 were also measured with circuits of different lengths (P0.1 &lt;sub&gt;circuit&lt;/sub&gt; ). Variations of P0.1 &lt;sub&gt;vent&lt;/sub&gt; correlated well with variations of P0.1 &lt;sub&gt;ref&lt;/sub&gt; . Overall, P0.1 &lt;sub&gt;vent&lt;/sub&gt; underestimated P0.1 &lt;sub&gt;ref&lt;/sub&gt; except for the Löwenstein &lt;sup&gt;®&lt;/sup&gt; ventilator at P0.1 &lt;sub&gt;ref&lt;/sub&gt; 2.5 cm H &lt;sub&gt;2&lt;/sub&gt; O and for the Getinge group &lt;sup&gt;®&lt;/sup&gt; ventilator at P0.1 &lt;sub&gt;ref&lt;/sub&gt; 10 cm H &lt;sub&gt;2&lt;/sub&gt; O. The agreement between P0.1 &lt;sub&gt;vent&lt;/sub&gt; and P0.1 &lt;sub&gt;ref&lt;/sub&gt; assessed with the Bland-Altman method gave a mean bias of - 1.3 cm H &lt;sub&gt;2&lt;/sub&gt; O (limits of agreement: 1 and - 3.7 cm H &lt;sub&gt;2&lt;/sub&gt; O). Analysis of airway pressure-time and flow-time curves showed that all the tested ventilators except the Getinge group &lt;sup&gt;®&lt;/sup&gt; ventilator performed an occlusion of at least 100 ms to measure P0.1. The agreement between P0.1 &lt;sub&gt;vent&lt;/sub&gt; and P0.1 &lt;sub&gt;aw&lt;/sub&gt; assessed with the Bland-Altman method gave a mean bias of 0.5 cm H &lt;sub&gt;2&lt;/sub&gt; O (limits of agreement: 2.4 and - 1.4 cm H &lt;sub&gt;2&lt;/sub&gt; O). The circuit's length impacted P0.1 measurements' values. A longer circuit was associated with lower P0.1 &lt;sub&gt;circuit&lt;/sub&gt; values. P0.1 &lt;sub&gt;vent&lt;/sub&gt; relative changes are well correlated to P0.1 &lt;sub&gt;ref&lt;/sub&gt; changes in all the tested ventilators. Accuracy of absolute values of P0.1 &lt;sub&gt;vent&lt;/sub&gt; varies according to the ventilator model. Overall, P0.1 &lt;sub&gt;vent&lt;/sub&gt; underestimates P0.1 &lt;sub&gt;ref&lt;/sub&gt; . The length of the circuit may partially explain P0.1 &lt;sub&gt;vent&lt;/sub&gt; underestimation

Potentially harmful effects of inspiratory synchronization during pressure preset ventilation

Purpose: Pressure preset ventilation (PPV) modes with set inspiratory time can be classified according to their ability to synchronize pressure delivery with patient's inspiratory efforts (i-synchronization). Non-i-synchronized (like airway pressure release ventilation, APRV), partially i-synchronized (like biphasic airway pressure), and fully i-synchronized modes (like assist-pressure control) can be distinguished. Under identical ventilatory settings across PPV modes, the degree of i-synchronization may affect tidal volume (V T), transpulmonary pressure (P TP), and their variability. We performed bench and clinical studies. Methods: In the bench study, all the PPV modes of five ventilators were tested with an active lung simulator. Spontaneous efforts of −10cmH2O at rates of 20 and 30breaths/min were simulated. Ventilator settings were high pressure 30cmH2O, positive end-expiratory pressure (PEEP) 15cmH2O, frequency 15breaths/min, and inspiratory to expiratory ratios (I:E) 1:3 and 3:1. In the clinical studies, data from eight intubated patients suffering from acute respiratory distress syndrome (ARDS) and ventilated with APRV were compared to the bench tests. In four additional ARDS patients, each of the PPV modes was compared. Results: As the degree of i-synchronization among the different PPV modes increased, mean V T and P TP swings markedly increased while breathing variability decreased. This was consistent with clinical comparison in four ARDS patients. Observational results in eight ARDS patients show low V T and a high variability with APRV. Conclusion: Despite identical ventilator settings, the different PPV modes lead to substantial differences in V T, P TP, and breathing variability in the presence spontaneous efforts. Clinicians should be aware of the possible harmful effects of i-synchronization especially when high V T is undesirabl