Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative ...in patients with hypoxemia.
We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28.
A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval CI, 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006).
In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).
Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited.
We conducted a monocenter retrospective study ...comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS).
We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning sub-hazard ratio = 1.72 (1.14-2.52), p < 0.01. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS 2 (2%) vs. 12 (15%), p = 0.003, but there was no difference in Aspergillus colonization.
In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group.
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 (PaO
2
/FiO
2
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 PaO
2
/FiO
2
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.
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).
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.
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.
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 cmH
O, 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 cmH
O, p = 0.59. The response to PEEP was also similar in C-ARDS patients with higher vs. lower respiratory system compliance.
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.
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.
Prospective before-after study.
Intensive-care unit of a French teaching hospital and sickle cell disease referral center.
Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease.
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).
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.
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.
Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a ...clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes.
Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR
monocytes and CD8
PD-1
lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls.
Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p < 0.0001). ARDS patients with shock had lower BAL fluid-to-serum ratio of IL-1Ra (p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8
lymphocytes PD-1 expression and hospital mortality.
IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.
Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for ...acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015-2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval 95% CI, 13.3%-19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio aOR, 0.98; 95% CI 0.95-0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05-1.14; p < 0.0001), higher haemoglobin level (aOR, 1.22; 95% CI 1.01-1.48; p = 0.038), impaired creatinine clearance at ICU admission (aOR, 0.98; 95% CI 0.97-0.98; p < 0.0001), and red blood cell exchange before ICU admission (aOR, 5.16; 95% CI 1.16-22.94; p = 0.031). Patients with SCD have a substantial risk of adverse outcomes if they require ICU admission. Early ICU admission should be encouraged in patients who develop abnormal physiological parameters.
Abstract
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 H
2
O. The respiratory rate was then re-adjusted within a range from 12 to 40 breaths/min until EtCO
2
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 PaO
2
/FiO
2
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 H
2
O 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.
Interleukin 6 (IL-6) is a predictive factor of poor prognosis in patients with acute respiratory distress syndrome (ARDS). However, its acute pulmonary hemodynamic effects and role in lung injury ...have not been investigated in a clinically relevant murine model of ARDS.
We used adult C57Bl6 wild-type (WT) and IL-6 knock-out (IL-6KO) mice. The animals received intravenous recombinant human IL-6 (rHuIL-6) or vehicle followed by intratracheal lipopolysaccharide (LPS) or saline before undergoing low tidal volume mechanical ventilation (MV) for 5 h. Before sacrifice, right ventricular systolic pressure and cardiac output were measured and total pulmonary resistance was calculated. After sacrifice, lung inflammation, edema and injury were assessed with bronchoalveolar lavage (BAL) and histology. In other experiments, right ventricular systolic pressure was recorded during hypoxic challenges in uninjured WT mice pretreated with rHuIL-6 or rHuIL-6 + non-selective nitric oxide synthase inhibitor L-NAME or vehicle.
IL-6KO
mice showed a faster deterioration of lung elastic properties and more severe bronchoalveolar cellular inflammation as compared to WT
. Treatment with rHuIL-6 partially prevented this lung deterioration. Total pulmonary resistance was higher in IL-6KO
mice and this increase was abolished in rHuIL-6-treated IL-6KO mice. Finally, rHuIL-6 reduced hypoxic pulmonary vasoconstriction in uninjured WT mice, an effect that was abolished by co-treatment with L-NAME.
In a double-hit murine model of ARDS, IL-6 deficient mice experienced more severe bronchoalveolar cellular inflammation as compared to wild-type littermates. Furthermore, IL-6 deficiency caused marked acute pulmonary hypertension, which may be, at least partially, due to vasoactive mechanisms. A dysregulation of nitric oxide synthase may account for this observation, a hypothesis that will need to be investigated in future studies.
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