Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Characteristics and outcome of ill critical patients with influenza A infection

Introduction: To describe all patients admitted to Tunisian intensive care unit with a diagnosis of influenza A/H1N1 virus infection after the 2009 influenza pandemic and to analyse their characteristics, predictors of complications and outcome. Methods: All patients with influenza &gt; 18-yearsold hospitalized to the ICU department of Tunisian University hospital of Sousse, between December 1, 2009 and March 31, 2016, with a positive influenza A/H1N1/09 reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal specimen were included, were included. Results: 40 cases were admitted to intensive care units. During the reporting period, 22 deaths in intensive care units (55%) were reported, the median age was 53 years (IQR 37-61), 24 (61%) were male, The median scores SAPS II and SOFA were respectively 29 (IQR 23-36) and 6 (IQR 3-10), 27% had chronic obstructive pulmonary disease (COPD), 33.3% diabetic and no patients were vaccinated against influenza A. The cause of admission was in 72.5% of the cases was hypoxemic pneumonae. By using a logistic regression, we found after adjustment to age, that acute respiratory distress syndrome (ARDS) (OR = 27; 95%CI: 3.62-203.78) was the only factor significantly associated with severe outcomes of the cases. Conclusion: Patients in the first post pandemic season were significantly older and more frequently had underlying medical conditions. Multivariate analysis showed that older male patients with chronic lung disease were at increased risk for a severe clinical outcome

Interference with zinc homeostasis and oxidative stress induction as probable mechanisms for cadmium-induced embryo-toxicity in zebrafish

International audienceThe present study was conducted to provide new insights into the mechanisms that may be responsible for cadmium (Cd)-induced toxicity in zebrafish larvae as well as the role of the trace element zinc (Zn) in reversing Cd harmful effects. For this purpose, zebrafish eggs were exposed to Cd or/and Zn for 96 h. The effects on morphological aspect; mortality rate; Cd, Zn, and metallothionein (MT) levels; oxidative stress biomarkers; as well as molecular expression of some genes involved in Zn metabolism (Zn-MT, ZIP10, and ZnT1) and in antioxidant defense system (Cu/Zn-SOD, CAT and GPx) were examined. Our results showed that Cd toxicity was exerted, initially, by an interference with Zn metabolism. Thus, Cd was able to modify the expression of the corresponding genes so as to ensure its intracellular accumulation at the expense of Zn, causing its depletion. An oxidative stress was then generated, representing the second mode of Cd action which resulted in developmental anomalies and subsequently mortality. Interestingly, significant corrections have been noted following Zn supplementation based, essentially, on its ability to interact with the toxic metal. The increases of Zn bioavailability, the improvement of the oxidative status, as well as changes in Zn transporter expression profile are part of the protection mechanisms. The decrease of Cd-induced MTs after Zn supplement, both at the protein and the mRNA level, suggests that the protection provided by Zn is ensured through mechanisms not involving MT expression but which rather depend on the oxidative status

Melatonin counteracts cadmium‐induced rat testicular toxicity via the mechanistic target rapamycin (mTOR) pathway

The protective action of melatonin (MLT) against the harmful effects of cadmium (Cd) on testicular activity in rats has been documented previously; however, the involved molecular mechanisms have yet to be elucidated. Herein, we investigate the involvement of the mammalian target of rapamycin (mTOR) on the ability of MLT to counteract the damage induced by Cd on the rat testicular activity. Our study confirmed that Cd has harmful effects on the testes of rats and the protective action exerted by MLT. We reported, for the first time, that the addition of rapamycin (Rapa), a specific mTOR inhibitor, to animals co-treated with Cd and MLT completely abolished the beneficial effects exerted by MLT, indicating that the mTOR pathway partially modulates its helpful effects on Cd testicular toxicity. Interestingly, Rapa-alone treatment, provoking mTOR inhibition, produced altered morphological parameters, increased autophagy of germ and somatic cells, and reduced serum testosterone concentration. In addition, mTOR inhibition also reduced protein levels of markers of steroidogenesis (3β-Hydroxysteroid dehydrogenase) and blood–testis barrier integrity (occludin and connexin 43). Finally, Rapa altered sperm parameters as well as the ability of mature spermatozoa to perform a proper acrosome reaction. Although further investigation is needed to better clarify the molecular pathway involved in MLT action, we confirm that MLT alleviating Cd effects can be used as a supplement to enhance testicular function and improve male gamete quality

Immunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database

Background: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p &lt; 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p &lt; 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p &lt; 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p &lt; 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p &lt; 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease