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.

Physiological effects of adding ECCO2R to invasive mechanical ventilation for COPD exacerbations.

BACKGROUND: Extracorporeal CO2 removal (ECCO2R) could be a valuable additional modality for invasive mechanical ventilation (IMV) in COPD patients suffering from severe acute exacerbation (AE). We aimed to evaluate in such patients the effects of a low-to-middle extracorporeal blood flow device on both gas exchanges and dynamic hyperinflation, as well as on work of breathing (WOB) during the IMV weaning process. STUDY DESIGN AND METHODS: Open prospective interventional study in 12 deeply sedated IMV AE-COPD patients studied before and after ECCO2R initiation. Gas exchange and dynamic hyperinflation were compared after stabilization without and with ECCO2R (Hemolung, Alung, Pittsburgh, USA) combined with a specific adjustment algorithm of the respiratory rate (RR) designed to improve arterial pH. When possible, WOB with and without ECCO2R was measured at the end of the weaning process. Due to study size, results are expressed as median (IQR) and a non-parametric approach was adopted. RESULTS: An improvement in PaCO2, from 68 (63; 76) to 49 (46; 55) mmHg, p = 0.0005, and in pH, from 7.25 (7.23; 7.29) to 7.35 (7.32; 7.40), p = 0.0005, was observed after ECCO2R initiation and adjustment of respiratory rate, while intrinsic PEEP and Functional Residual Capacity remained unchanged, from 9.0 (7.0; 10.0) to 8.0 (5.0; 9.0) cmH2O and from 3604 (2631; 4850) to 3338 (2633; 4848) mL, p = 0.1191 and p = 0.3013, respectively. WOB measurements were possible in 5 patients, indicating near-significant higher values after stopping ECCO2R: 11.7 (7.5; 15.0) versus 22.6 (13.9; 34.7) Joules/min., p = 0.0625 and 1.1 (0.8; 1.4) versus 1.5 (0.9; 2.8) Joules/L, p = 0.0625. Three patients died in-ICU. Other patients were successfully hospital-discharged. CONCLUSIONS: Using a formalized protocol of RR adjustment, ECCO2R permitted to effectively improve pH and diminish PaCO2 at the early phase of IMV in 12 AE-COPD patients, but not to diminish dynamic hyperinflation in the whole group. A trend toward a decrease in WOB was also observed during the weaning process. Trial registration ClinicalTrials.gov: Identifier: NCT02586948.

[Use of the IntelliVent-ASV mode for maintaining the target EtCO2 range in patients with severe TBI]. / Ispol'zovanie rezhima IntelliVent-ASV dlia podderzhaniia tselevogo diapazona EtCO2 u patsientov s tiazheloi ChMT.

PURPOSE: the study purpose was to evaluate the efficacy of the IntelliVent-ASV mode in maintaining the target range of PaCO2 in patients with severe TBI. MATERIAL AND METHODS: The study included 12 severe TBI patients with the wakefulness level scored 4-9 (GCS). This was a crossover design study. Two ventilation modes were consecutively used: IntelliVent-ASV and P-CMV, for 12 h each. When using the P-CMV mode, the ventilation parameters were set to maintain PaCO2 in a range of 35-38 mm Hg. The IntelliVent-ASV mode involved the Brain Injury ventilation algorithm. The target range of EtCO2 was set in accordance with the delta PaCO2-EtCO2 to maintain PaCO2 in a range of 35-38. At the beginning of each ventilation period and every 3 hours, the arterial blood gas composition was analyzed. When PaCO2 occurred out of the 35-38 range, appropriate adjustments were made to the ventilation parameters. In the P-CMV mode, the Pinsp and RR parameters were adjusted to achieve the target PaCO2 range. In IntelliVent mode, a shift of the target EtCO2 range was adjusted in accordance with a changed PaCO2-EtCO2 difference. In all patients, ICP, blood pressure, and EtCO2 were monitored; the arterial blood gas composition was analyzed every 3 h; the frequency of manual settings of ventilation parameters was recorded. RESULTS: The EtCO2 and PaCO2 parameters were found not to be significantly different in the P-CMV and IntelliVent modes, but the spread in these parameters was significantly lower in the IntelliVent ventilation mode. The PaCO2 parameter occurred out of the target range significantly less often in the IntelliVent mode than in the P-CMV mode. The mean frequency of manual respirator settings needed to maintain the target EtCO2 range was significantly lower in the IntelliVent-ASV mode than in the P-CMV mode. CONCLUSION: The IntelliVent-ASV mode provides more efficient maintenance of PaCO2 in the target range compared to traditional artificial ventilation using fewer manual settings of the ventilation parameters.

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 (VT), transpulmonary pressure (PTP), 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 -10 cmH2O at rates of 20 and 30 breaths/min were simulated. Ventilator settings were high pressure 30 cmH2O, positive end-expiratory pressure (PEEP) 15 cmH2O, frequency 15 breaths/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 VT and PTP 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 VT and a high variability with APRV. CONCLUSION: Despite identical ventilator settings, the different PPV modes lead to substantial differences in VT, PTP, and breathing variability in the presence spontaneous efforts. Clinicians should be aware of the possible harmful effects of i-synchronization especially when high VT is undesirable.