Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP) in patients with acute exacerbation of COPD: From the French OUTCOMEREA cohort.

BACKGROUND: Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a nosocomial pneumonia that is not related to invasive mechanical ventilation (IMV), has been less studied than ventilator-associated pneumonia, and never in the context of patients in an ICU for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This study aimed to determine the factors associated with NV-ICU-AP occurrence and assess the association between NV-ICU-AP and the outcomes of these patients. METHODS: Data were extracted from the French ICU database, OutcomeRea™. Using survival analyses with competing risk management, we sought the factors associated with the occurrence of NV-ICU-AP. Then we assessed the association between NV-ICU-AP and mortality, intubation rates, and length of stay in the ICU. RESULTS: Of the 844 COPD exacerbations managed in ICUs without immediate IMV, NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per 1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness (sHR, 0.35 [0.16; 0.76]; p < 0.01) were associated with a lower risk of NV-ICU-AP. After adjusting for confounders, NV-ICU-AP was associated with increased 28-day mortality (HR = 3.03 [1.36; 6.73]; p < 0.01), an increased risk of intubation (csHR, 5.00 [2.54; 9.85]; p < 0.01) and with a 10-day increase in ICU length of stay (p < 0.01). CONCLUSION: We found that NV-ICU-AP incidence reached 10.8/1000 patient-days and was associated with increased risks of intubation, 28-day mortality, and longer stay for patients admitted with AECOPD.

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. MATERIALS AND METHODS: The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. RESULTS: Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13-9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23-11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07-33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76-10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01-4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42-1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. CONCLUSION: PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

Bench Study of a Spontaneous Breathing Trial with Different Modalities.

BACKGROUND: The spontaneous breathing trial (SBT) is the final step of weaning from invasive mechanical ventilation. An SBT is aimed at predicting work of breathing (WOB) after extubation and, most importantly, a patient's eligibility for extubation. The optimal SBT modality remains debated. A high-flow oxygen (HFO) has been tested during SBT in clinical study only, which is why no definite conclusion can be drawn on its physiologic effects on the endotracheal tube. Our objective was to assess, on a bench, inspiratory tidal volume (VT), total PEEP, and WOB across 3 different SBT modalities: T-piece, 40 L/min HFO, and 60 L/min HFO. METHODS: A test lung model was set with 3 conditions of resistance and linear compliance, 3 inspiratory efforts (low, normal, and high), each at 2 breathing frequencies (low and high for 20 and 30 breaths/min, respectively). Pairwise comparisons and a quasi-Poisson generalized linear model that compared SBT modalities were performed. RESULTS: Inspiratory VT, total PEEP, and WOB differed from one SBT modality to another. Inspiratory VT remained higher with the T-piece than in the HFO independent of the mechanical condition, effort intensity, and breathing frequency (P < .001 in each comparison). WOB adjusted by the inspiratory VT was significantly lower during SBT performed with an HFO than when performed with the T-piece (P < .001 in each comparison). The total PEEP was significantly higher in the HFO at 60 L/min than in the other modalities (P < .001). The end points were significantly influenced by breathing frequency, effort intensity, and mechanical condition. CONCLUSIONS: With the same effort intensity and breathing frequency, inspiratory VT was higher in the T-piece than in the other modalities. Compared with the T-piece, WOB was significantly lower in the HFO condition and higher flow was a benefit. Based on the results of the present study, the HFO as an SBT modality would seem to require clinical testing.

Corticosteroids for severe acute exacerbations of chronic obstructive pulmonary disease in intensive care: From the French OUTCOMEREA cohort.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a frequent cause of intensive care unit (ICU) admission. However, data are scarce and conflicting regarding the impact of systemic corticosteroid treatment in critically ill patients with acute exacerbation of COPD. The aim of the study was to assess the impact of systemic corticosteroids on the occurrence of death or need for continuous invasive mechanical ventilation at day 28 after ICU admission. METHODS: In the OutcomeReaTM prospective French national ICU database, we assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of prednisone or equivalent during the first 24 hours ICU stay) on a composite outcome (death or invasive mechanical ventilation) using an inverse probability treatment weighting. RESULTS: Between January 1, 1997 and December 31, 2018, 391 out of 1,247 patients with acute exacerbations of COPDs received corticosteroids at ICU admission. Corticosteroids improved the main composite endpoint (OR = 0.70 [0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients, this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no significant impact of corticosteroids on rates of non-invasive ventilation failure, length of ICU or hospital stay, mortality or on the duration of mechanical ventilation. Patients on corticosteroids had the same prevalence of nosocomial infections as those without corticosteroids, but more glycaemic disorders. CONCLUSION: Using systemic corticosteroids for acute exacerbation of COPD at ICU admission had a positive effect on a composite outcome defined by death or need for invasive mechanical ventilation at day 28.

Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease in the ICU: An Observational Study From the OUTCOMEREA Database, 1997-2018.

OBJECTIVES: Our aim was to describe changes in the management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) by ICUs and patient outcomes. DESIGN: We extracted data from the OutcomeRea database concerning patients admitted for AECOPD between 1997 and 2018. We analyzed trends in the use of ventilatory support, corticosteroid therapy, antibiotic therapy, and patient survival. SETTING: ICUs at 32 French sites. PATIENTS: One thousand eight hundred sixteen patients in the database had a diagnosis of AECOPD. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over time, there was a reduction in the prescription of corticosteroids and antibiotics. In a time-series analysis, these changes in practice were not linked with ICU mortality. The proportion of patients treated with invasive mechanical ventilation (IMV) also gradually declined (from 51% between 1997 and 2002 to 35% between 2013 and 2018) with an association between decrease in IMV use and reduction in ICU mortality in a time series analysis. Rates of noninvasive ventilation (NIV) failure decreased with an increase in NIV use to support weaning from IMV. There was a reduction in the median ICU length of stay (from 8 d in 1997-2002 to 4 d in 2013-2018) and in the median total duration of hospitalization (from 23 d in 1997-2002 to 14 d in 2013-2018). We observed an improvement in prognosis, with decreases in overall hospital mortality (from 24% between 1997 and 2002 to 15% between 2013 and 2018), ICU mortality (from 14% between 1997 and 2002 to 10% between 2013 and 2018), and 90-day mortality (from 41% between 1997 and 2002 to 22% between 2013 and 2018). CONCLUSIONS: The length of stay and mortality of patients with AECOPD admitted to ICUs has decreased over the last 20 years, with a wider use of NIV and a reduction in antibiotic and corticosteroid prescriptions.

Quality of life of patients with solid malignancies at 3 months after unplanned admission in the intensive care unit: A prospective case-control study.

BACKGROUND: Although short- and long-term survival in critically ill patients with cancer has been described, data on their quality of life (QoL) after an intensive care unit (ICU) stay are scarce. This study aimed to determine the impact of an ICU stay on QoL assessed at 3 months in patients with solid malignancies. METHODS: A prospective case-control study was conducted in three French ICUs between February 2020 and February 2021. Adult patients with lung, colorectal, or head and neck cancer who were admitted in the ICU were matched in a 1:2 ratio with patients who were not admitted in the ICU regarding their type of cancer, curative or palliative anticancer treatment, and treatment line. The primary endpoint was the QoL assessed at 3 months from inclusion using the mental and physical components of the Short Form 36 (SF-36) Health Survey. The use of anticancer therapies at 3 months was also evaluated. RESULTS: In total, 23 surviving ICU cancer patients were matched with 46 non-ICU cancer patients. Four patients in the ICU group did not respond to the questionnaire. The mental component score of the SF-36 was higher in ICU patients than in non-ICU patients: median of 54 (interquartile range: 42-57) vs. 47 (37-52), respectively (p = 0.01). The physical component score of the SF-36 did not differ between groups: 35 (31-47) vs. 42 (34-47) (p = 0.24). In multivariate analysis, no association was found between patient QoL and an ICU stay. A good performance status and a non-metastatic cancer at baseline were independently associated with a higher physical component score. The use of anticancer therapies at 3 months was comparable between the two groups. CONCLUSION: In patients with solid malignancies, an ICU stay had no negative impact on QoL at 3 months after discharge when compared with matched non-ICU patients.

Respiratory multiplex PCR and procalcitonin to reduce antibiotic exposure in severe SARS-CoV-2 pneumonia: a multicentre randomized controlled trial.

OBJECTIVES: We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia. METHODS: This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28. RESULTS: Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, -2.0, (95% CI, -10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups. DISCUSSION: In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice.

Long-term variations of arterial stiffness in patients with obesity and obstructive sleep apnea treated with continuous positive airway pressure.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cardiovascular co-morbidities and mortality. Arterial stiffness is an independent predictor of cardiovascular risk and mortality, and is influenced by the presence of OSA and related comorbidities. There is a paucity of data regarding long-term evolution of arterial stiffness in CPAP-treated OSA patients. We aimed to prospectively study long term PWV variations and determinants of PWV deterioration. METHODS: In a prospective obese OSA cohort, at time of diagnosis and after several years of follow-up we collected arterial stiffness measured by carotid-femoral pulse wave velocity (PWV), clinical and metabolic parameters, and CPAP adherence. Univariate and multivariate analyses were performed in order to determine contributing factors. RESULTS: Seventy two OSA patients (men: 52.8%, median age: 55.8 years and median BMI of 38.5 kg/m2) with a prevalence of hypertension: 58.3%, type 2 diabetes: 20.8%, hypercholesterolemia: 33.3%, current or past smoking: 59.7%, were evaluated after a median follow-up of 7.4 [5.8; 8.3] years. Over the period of follow-up, the median increase in PWV was 1.34 [0.10; 2.37] m/s. In multivariate analysis, the increase in PWV was associated with older age (10 extra years was associated with a 5.24 [1.35; 9.12] % increase in PWV) and hypertension (a significant increase in PWV of 8.24 [1.02; 15.57] %). No impact of CPAP adherence on PWV evolution was found. CONCLUSION: PWV progression in CPAP-treated OSA patients is mainly related to pre-existing cardio-metabolic comorbidities and not influenced by CPAP adherence. In this high cardiovascular risk population, it is crucial to associated weight management and exercise with CPAP treatment.

The Somatotropic Axis in the Sleep Apnea-Obesity Comorbid Duo.

Background: Growth hormone (GH) stimulates the production of insulin-like growth factor 1 (IGF-1) in most tissues and together GH and IGF-1 profoundly impact adipose tissue deposition, glucose metabolism and cardiovascular function. A low serum IGF-I level has been reported as being associated with obstructive sleep apnea (OSA) and might be one of the mechanisms underlying cardio-metabolic risk in OSA patients. Methods: In a multicenter national study, 817 patients consulting for suspicion of OSA (OSA confirmed for 567 patients) underwent serum IGF-1 measurements. We analyzed the association between an IGF-1 level below the median value of the population and variables related to cardio-metabolic risk: body mass index (BMI) and waist circumference, apnea hypopnea index (AHI), cholesterol and triglycerides (expressed as median and divided into quartiles for continuous variables). Results: After adjustment for age and gender, low IGF-1 levels were associated with increased BMI and AHI (Odds ratios (OR) = 2.83; p < 0.0001 and OR = 3.03, p < 0.0001 for Quartile 4 vs. Quartile1, respectively), with elevated cholesterol levels (OR = 1.36, p = 0.0444), and elevated triglyceride levels (OR = 1.36; p = 0.0008). Conclusions: Both adiposity and sleep apnea synergistically predict low levels of IGF-1 and thus could together contribute toward cardio-metabolic risk. Further work are needed to confirm whether IGF-1 levels allow grading severity and predicting response to treatments to aim at a personalized medicine for patients suffering from OSA.

A Comprehensive Bench Assessment of Automatic Tube Compensation in ICU Ventilators for Better Clinical Management.

BACKGROUND: Automatic tube compensation (ATC) unloads endotracheal tube (ETT) resistance. We conducted a bench assessment of ATC functionality in ICU ventilators to improve clinical management. METHODS: This study had 2 phases. First, we performed an international survey on the use of ATC in clinical practice, hypothesizing a rate of ATC use of 25%. Second, we tested 7 modern ICU ventilators in a lung model mimicking a normal subject (Normal), a subject with ARDS, and a subject with COPD. Inspiratory effort consisted of esophageal pressure over 30 consecutive breaths obtained in a real patient under weaning. A brand new 8-mm inner diameter ETT was attached to the lung model, and ATC was set at 100% compensation for the ETT. The 30 breaths were first run with ATC off and no ETT (ie, reference period), and then with ATC on and ETT (ie, active period). The primary end point was the difference in tidal volume (VT) between reference and active periods. We hypothesized that the VT difference should be equal to 0 in an ideally functioning ATC. VT difference was compared across ventilators and respiratory mechanics conditions using a linear mixed-effects model. RESULTS: The clinical use of ATC was 64% according to 644 individuals who responded to the international survey. The VT difference varied significantly across ventilators in all respiratory mechanics configurations. The divergence between VT difference and 0 was small but significant: the extreme median (interquartile range) values were -0.013 L (-0.019 to -0.002) in the COPD model and 0.056 L (0.051-0.06) in the Normal model. VT difference for all ventilators was 0.015 L (95% CI 0.013-0.018) in the ARDS model, which was significantly different from 0.021 L (95% CI 0.018-0.024) in the Normal model (P < .001) and 0.010 L (0.007-0.012) in the COPD model (P = .003). CONCLUSIONS: ATC is used more frequently in clinical practice than expected. In addition, VT delivery by ATC differed slightly though significantly between ventilators.

Lung and chest wall mechanics in patients with acute respiratory distress syndrome, expiratory flow limitation, and airway closure.

Tidal expiratory flow limitation (EFL), which may herald airway closure (AC), is a mechanism of loss of aeration in ARDS. In this prospective, short-term, two-center study, we measured static and dynamic chest wall (Est,cw and Edyn,cw) and lung (Est,L and Edyn,L) elastance with esophageal pressure, EFL, and AC at 5 cmH2O positive end-expiratory pressure (PEEP) in intubated, sedated, and paralyzed ARDS patients. For EFL determination, we used the atmospheric method and a new device allowing comparison of tidal flow during expiration to PEEP and to atmosphere. AC was validated when airway opening pressure (AOP) assessed from volume-pressure curve was found greater than PEEP by at least 1 cmH2O. EFL was defined whenever flow did not increase between exhalation to PEEP and to atmosphere over all or part of expiration. Elastance values were expressed as percentage of normal predicted values (%N). Among the 25 patients included, eight had EFL (32%) and 13 AOP (52%). Between patients with and without EFL Edyn,cw [median (1st to 3rd quartiles)] was 70 (16-127) and 102 (70-142) %N (P = 0.32) and Edyn,L338 (332-763) and 224 (160-275) %N (P < 0.001). The corresponding values for Est,cw and Est,L were 70 (56-88) and 85 (64-103) %N (P = 0.35) and 248 (206-348) and 170 (144-195) (P = 0.02), respectively. Dynamic EL had an area receiver operating characteristic curve of 0.88 [95% confidence intervals 0.83-0.92] for EFL and 0.74[0.68-0.79] for AOP. Higher Edyn,L was accurate to predict EFL in ARDS patients; AC can occur independently of EFL, and both should be assessed concurrently in ARDS patients.NEW & NOTEWORTHY Expiratory flow limitation (EFL) and airway closure (AC) were observed in 32% and 52%, respectively, of 25 patients with ARDS investigated during mechanical ventilation in supine position with a positive end-expiratory pressure of 5 cmH2O. The performance of dynamic lung elastance to detect expiratory flow limitation was good and better than that to detect airway closure. The vast majority of patients with EFL also had AC; however, AC can occur in the absence of EFL.

Impact of obstructive sleep apnea on the obesity paradox in critically ill patients.

OBJECTIVE: Patients admitted to an intensive care unit (ICU) frequently suffer from multiple chronic diseases, including obstructive sleep apnea (OSA). Until recently OSA was not considered as a key determinant in an ICU patient's prognosis. The objective of this study was to document the impact of OSA on the prognosis of ICU patients. METHODS: Data were retrospectively collected concerning adult patients admitted to ICU at two university hospitals. In a nested study OSA status was checked using the hospital electronic medical records to identify exposed and unexposed cases. The following outcomes were considered: length of stay in the ICU, ICU mortality, in-hospital mortality, ventilator-associated pneumonia (VAP). RESULTS: Out of 5146 patients included in the study, 289 had OSA at ICU admission (5.6%). After matching, the overall impact of OSA on length of ICU stay was not significant (p = .24). In a predefined subgroup analysis, there was a significant impact of OSA on the length of ICU stay for patients with BMI over 40 kg/m2 (IRR: 1.56 [1.05; 2.32], p = .03). OSA status had no impact on ICU or hospital mortality and VAP. CONCLUSION: In general, known OSA did not increase the ICU stay except for patients with both OSA and morbid obesity.

Contribution of obstructive sleep apnoea to arterial stiffness: a meta-analysis using individual patient data.

BACKGROUND: Arterial stiffness, measured by pulse wave velocity (PWV), is a strong independent predictor of late cardiovascular events and mortality. It is recognised that obstructive sleep apnoea (OSA) is associated with cardiovascular comorbidities and mortality. Although previous meta-analyses concluded that PWV is elevated in OSA, we feel that an individual patient data analysis from nine relatively homogeneous studies could help answer: to what extent does OSA drive arterial stiffness? METHODS: Individual data from well-characterised patients referred for suspicion of OSA, included in nine studies in which carotid-femoral PWV was measured using a Complior device, were merged for an individual patient data meta-analysis. RESULTS: 893 subjects were included (age: 56±11 (mean±SD), 72% men, 84% with confirmed OSA). Body Mass Index varied from 15 to 81 kg/m2 (30±7 kg/m2). PWV ranged from 5.3 to 20.5 m/s (10.4±2.3 m/s). In univariate analysis, log(PWV) was strongly related to age, gender, systolic blood pressure, presence of type 2 diabetes (all p<0.01) as well as to dyslipidaemia (p=0.03) and an Epworth Sleepiness Scale score ≥9 (p=0.04), whereas it was not related to obesity (p=0.54), a severe Apnoea-Hypopnoea Index (p=0.14), mean nocturnal saturation (p=0.33) or sleep time with oxygen saturation below 90% (p=0.47). In multivariable analysis, PWV was independently associated with age, systolic blood pressure and diabetes (all p<0.01), whereas severe OSA was not significantly associated with PWV. CONCLUSION: Our individual patient meta-analysis showed that elevated arterial stiffness in patients with OSA is driven by conventional cardiovascular risk factors rather than apnoea parameters.

[Pathophysiology of obstructive sleep apnea syndrome and its cardiometabolic consequences]. / Physiopathologie du syndrome d'apnées-hypopnées obstructives du sommeil et de ses conséquences cardio-métaboliques.

Obstructive sleep apnoea syndrome (OSAS) is characterized by recurrent partial or complete pharyngeal collapses during sleep. The pathophysiology of OSAS is complex and multifactorial. Factors influencing upper airway patency include a reduction in upper airway dimensions that can result from both anatomical and functional alterations (obesity, fluid shift or maxillo-facial structural changes), and increased pharyngeal collapsibility owing to reduced neuromuscular compensation and lack of the pharyngeal protective reflex during sleep. Severe OSAS is associated with a high cardiometabolic risk. Obstructive apnoeic events incorporate a range of stressors that activate mechanisms contributing to the initiation and progression of cardiac, vascular and metabolic diseases. Obstructed breathing induces markedly negative intrathoracic pressure and also provokes hypoxia and hypercapnia. The hypoxaemic stress is further amplified by the subsequent reoxygenation (intermittent hypoxia), resulting in the generation of reactive oxygen species (ROS), sympathetic activation and inflammation. OSAS is able to increase the number of fatal and non-fatal cardiovascular events, including arrhythmias, myocardial infarction and stroke. OSAS is associated with dyslipidemia, type 2 diabetes, its poor control and non-alcoholic fatty liver disease. Screening, diagnosis and integrated care of OSAS should be included in an aggressive management of risk reduction in chronic cardiovascular and metabolic diseases.