Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial.

BACKGROUND: Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock. METHODS: APROCCHSS was a randomised controlled trial that investigated the effects of hydrocortisone plus fludrocortisone, drotrecogin-alfa (activated), or both on mortality in septic shock in a two-by-two factorial design; after drotrecogin-alfa was withdrawn on October 2011, from the market, the trial continued on two parallel groups. It was conducted in 34 centres in France. In this subgroup study, patients with CAP were a preselected subgroup for an exploratory secondary analysis of the APROCCHSS trial of hydrocortisone plus fludrocortisone in septic shock. Adults with septic shock were randomised 1:1 to receive, in a double-blind manner, a 7-day treatment with daily administration of intravenous hydrocortisone 50 mg bolus every 6h and a tablet of 50 µg of fludrocortisone via the nasogastric tube, or their placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included all-cause mortality at intensive care unit (ICU) and hospital discharge, 28-day and 180-day mortality, the number of days alive and free of vasopressors, mechanical ventilation, or organ failure, and ICU and hospital free-days to 90-days. Analysis was done in the intention-to-treat population. The trial was registered at ClinicalTrials.gov (NCT00625209). FINDINGS: Of 1241 patients included in the APROCCHSS trial, CAP could not be ruled in or out in 31 patients, 562 had a diagnosis of CAP (279 in the placebo group and 283 in the corticosteroid group), and 648 patients did not have CAP (329 in the placebo group and 319 in the corticosteroid group). In patients with CAP, there were 109 (39%) deaths of 283 patients at day 90 with hydrocortisone plus fludrocortisone and 143 (51%) of 279 patients receiving placebo (odds ratio [OR] 0·60, 95% CI 0·43-0·83). In patients without CAP, there were 148 (46%) deaths of 319 patients at day 90 in the hydrocortisone and fludrocortisone group and 157 (48%) of 329 patients in the placebo group (OR 0·95, 95% CI 0·70-1·29). There was significant heterogeneity in corticosteroid effects on 90-day mortality across subgroups with CAP and without CAP (p=0·046 for both multiplicative and additive interaction tests; moderate credibility). Of 1241 patients included in the APROCCHSS trial, 648 (52%) had ARDS (328 in the placebo group and 320 in the corticosteroid group). There were 155 (48%) deaths of 320 patients at day 90 in the corticosteroid group and 186 (57%) of 328 patients in the placebo group. The OR for death at day 90 was 0·72 (95% CI 0·53-0·98) in patients with ARDS and 0·85 (0·61-1·20) in patients without ARDS (p=0·45 for multiplicative interaction and p=0·42 for additive interaction). The OR for observing at least one serious adverse event (corticosteroid group vs placebo) within 180 days post randomisation was 0·64 (95% CI 0·46-0·89) in the CAP subgroup and 1·02 (0·75-1·39) in the non-CAP subgroup (p=0·044 for multiplicative interaction and p=0·042 for additive interaction). INTERPRETATION: In a pre-specified subgroup analysis of the APROCCHSS trial of patients with CAP and septic shock, hydrocortisone plus fludrocortisone reduced mortality as compared with placebo. Although a large proportion of patients with CAP also met criteria for ARDS, the subgroup analysis was underpowered to fully discriminate between ARDS and CAP modifying effects on mortality reduction with corticosteroids. There was no evidence of a significant treatment effect of corticosteroids in the non-CAP subgroup. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health, by Programme d'Investissements d'Avenir, France 2030, and IAHU-ANR-0004.

Determination of energy requirements after minor burns using indirect calorimetry: A descriptive cohort study.

BACKGROUND: Minor burns could be associated with moderate hypermetabolism. In this study, the primary outcome was measured energy expenditure (mEE) determined by indirect calorimetry in patients with minor burns. We also compared mEE with predictive values and actual energy intakes. METHODS: Adults with minor burns exclusively treated on an outpatient basis were included. During the week following injury, a dietitian performed indirect calorimetry (Q-NRG in canopy mode), calculated the estimated energy expenditure (eEE) based on the Harris-Benedict (HB) and Henry formulas, and evaluated daily energy intakes using a food anamnesis. RESULTS: Forty-nine patients (59.2% male; median age: 35 [interquartile range: 29-46.5] years; body mass index [BMI]: 26.2 [22.3-29.6] kg/m2; burn surface area [BSA]: 1.5% [1%-2%]) were included 4 (2-6) days after injury. The mEE was 1863 (1568-2199) kcal or 25 (22.4-28.5) kcal/kg and 1838 (1686-2026) kcal or 26.1 (23.7-27.7) kcal/kg in patients who were respectively fasting for >10 h or not (P = 0.991 or P = 0.805). The total mEE was 104% (95%-116%) and 108% (99%-122%) of the total eEE using the HB and Henry formulas, respectively, with diet-induced thermogenesis and physical activity level. Hypermetabolism (ie, oxygen consumption at rest ≥3.5 ml/kg/min) was observed in 21/49 (42.9%) patients. Energy intakes corresponded to 71% (60%-86%) of the total mEE. CONCLUSION: Performing indirect calorimetry in adults with minor burns revealed that ≥40% of the tested adults presented a hypermetabolism and that their mEE was not covered by their energy intakes.

Perceived Quality of Life in Intensive Care Medicine Physicians: A French National Survey.

Purpose: There is a growing interest in the quality of work life (QWL) of healthcare professionals and staff well-being. We decided to measure the perceived QWL of ICU physicians and the factors that could influence their perception. Methods: We performed a survey coordinated and executed by the French Trade Union of Intensive Care Physicians (SMR). QWL was assessed using the French version of the Work-Related Quality of Life (WRQoL) scale, perceived stress using the French version of 10 item-Perceived Stress Scale (PSS-10) and group functioning using the French version of the Reflexivity Scale, the Social Support at Work Questionnaire (QSSP-P). Results: 308 French-speaking ICU physicians participated. 40% perceived low WRQoL, mainly due to low general well-being, low satisfaction with working conditions and low possibility of managing the articulation between their private and professional lives. Decreased QWL was associated with being a woman (p = .002), having children (p = .022) and enduring many monthly shifts (p = .022). Conclusions: This work highlights the fact that ICU physicians feel a significant imbalance between the demands of their profession and the resources at their disposal. Communication and exchanges within a team and quality of social support appear to be positive elements to maintain and/or develop within our structures.

Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients.

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).

Sniffing out safety: canine detection and identification of SARS-CoV-2 infection from armpit sweat.

Detection dogs were trained to detect SARS-CoV-2 infection based on armpit sweat odor. Sweat samples were collected using cotton pads under the armpits of negative and positive human patients, confirmed by qPCR, for periods of 15-30 min. Multiple hospitals and organizations throughout Belgium participated in this study. The sweat samples were stored at -20°C prior to being used for training purposes. Six dogs were trained under controlled atmosphere conditions for 2-3 months. After training, a 7-day validation period was conducted to assess the dogs' performances. The detection dogs exhibited an overall sensitivity of 81%, specificity of 98%, and an accuracy of 95%. After validation, training continued for 3 months, during which the dogs' performances remained the same. Gas chromatography/mass spectrometry (GC/MS) analysis revealed a unique sweat scent associated with SARS-CoV-2 positive sweat samples. This scent consisted of a wide variety of volatiles, including breakdown compounds of antiviral fatty acids, skin proteins and neurotransmitters/hormones. An acceptability survey conducted in Belgium demonstrated an overall high acceptability and enthusiasm toward the use of detection dogs for SARS-CoV-2 detection. Compared to qPCR and previous canine studies, the detection dogs have good performances in detecting SARS-CoV-2 infection in humans, using frozen sweat samples from the armpits. As a result, they can be used as an accurate pre-screening tool in various field settings alongside the PCR test.

Mid-Term Evolution of the Serum Acylcarnitine Profile in Critically Ill Survivors: A Metabolic Insight into Survivorship.

It is unknown if the abnormal acylcarnitine (AC) profile observed early after discharge of a prolonged stay in an intensive care unit (ICU) would persist over time. This prospective observational study aimed to describe the mid-term AC profile evolution in survivors of a prolonged ICU stay (≥7 days). Adults enrolled in our post-ICU follow-up program and who attended the consultation 3 months (M3) after discharge were included. Serum AC concentrations were assessed within 7 days following ICU discharge (T0) and at M3. A total of 64 survivors were analyzed after an ICU stay of 15 (9-24) days. Free carnitine (C0) concentration decreased from 45.89 (35.80-127.5) to 28.73 (20.31-38.93) µmol/L (p < 0.001). C0 deficiency was not observed at T0 but in 7/64 (11%) survivors at M3. The total AC/C0 ratio (normal ≤ 0.4) was 0.33 (0.24-0.39) at T0 and reached 0.39 (0.30-0.56) at M3 (p = 0.001). A ratio >0.4 was observed in 16/64 (25%) at T0 and in 32/64 (50%) at M3 (p = 0.006). The short-chain ACs decreased from 1.310 (0.927-1.829) at T0 to 0.945 (0.709-1.127) µmol/L at M3 (p < 0.001). In parallel, the urea/creatinine ratio and the Sarcopenic Index, respectively, decreased and increased between T0 and M3. This AC profile is suspected to signal a mitochondrial dysfunction and was, especially for short-chain ACs, a marker of protein catabolism.

Quadriceps handheld dynamometry during the post-ICU trajectory: using strictly the same body position is mandatory for repeated measures.

BACKGROUND: The level of quadriceps strength (QS) generated in the supine or seated position is not similar. For QS follow-up from intensive care unit (ICU) stay to recovery, getting comparable measures is essential. This study aimed to develop and validate new equations for estimating QS in a given position based on the measurement taken in another one. METHODS AND RESULTS: Isometric QS was measured using a handheld dynamometer and a standardized protocol in a supine and in a seated position. In a first cohort of 77 healthy adults, two QS conversion equations were developed using a multivariate model integrating independent parameters such as age, sex, body mass index (BMI) and baseline QS. These equations were tested in two cohorts for external validation, using the interclass correlation coefficient (ICC) and Bland-Altman graphical method. Only one was validated in the second cohort (62 different healthy adults): the ICC was 0.87 (95% CI 0.59-0.94) and the bias was - 0.49 N/Kg (limits of agreement: - 1.76-0.78 N/kg). However, this equation did not perform well in the third cohort (50 ICU survivors): the ICC was 0.60 (95% CI 0.24-0.78), and the bias was - 0.53 N/Kg (limits of agreement: - 1.01-2.07 N/kg). CONCLUSIONS: As no conversion equation has been validated in the present study, repeated QS measurements should be performed strictly in the same standardized and documented position.

Construction of reference criteria to admit patients to intermediate care units in France: a Delphi survey of intensivists, anaesthesiologists and emergency medicine practitioners (first part of the UNISURC project).

OBJECTIVES: No consensus criteria describe the medical eligibility of the patients to intermediate care units (IMCUs). In this first part of the UNISURC project, we aimed to develop criteria based on a consensus of physicians from the main specialties involved in IMCU admission decisions. DESIGN: We selected criteria from IMCU literature, scoring systems and intensive care unit nursing workload. We submitted these criteria to a panel of experts in a Delphi survey. We used a two-round Delphi survey procedure to assess the validity and feasibility of each criterion. SETTING: Medical practitioners in either public or private French institutions and proposed by the national scientific societies of anaesthesiology, emergency medicine and intensive care. The Delphi rounds took place in 2015-2016. OUTCOME MEASURES: Validity and feasibility of the proposed criteria; uniformity of the judgement across the primary specialty and the hospital category of the responders. RESULTS: The criteria submitted to vote were classified as one of: chronic factor (CF); acute factor (AF); specific pathway (SP); nursing activity (NA) and hospital environment (HE). Of 189 experts invited, 81 (41%) responded to the first round and 62 of them (76%) responded to the second round. A definite selection of 63 items was made, distributed across 6 CF, 18 AF, 31 SP, 3 NA and 5 HE. Validity and feasibility were influenced by the specialty or the public/private status of the institution of the responders for a few items. CONCLUSION: We created a set of 63 consensus criteria with acceptable validity and feasibility to assess the medical eligibility of the patients to IMCUs. The second part of the UNISURC project will assess the distribution of each criterion in a prospective multicentre national cohort. TRIAL REGISTRATION NUMBER: NCT02590172.

A Pilot Study on Oxidative Stress during the Recovery Phase in Critical COVID-19 Patients in a Rehabilitation Facility: Potential Utility of the PAOT® Technology for Assessing Total Anti-Oxidative Capacity.

BACKGROUND: Oxidative stress (OS) could cause various COVID-19 complications. Recently, we have developed the Pouvoir AntiOxydant Total (PAOT®) technology for reflecting the total antioxidant capacity (TAC) of biological samples. We aimed to investigate systemic oxidative stress status (OSS) and to evaluate the utility of PAOT® for assessing TAC during the recovery phase in critical COVID-19 patients in a rehabilitation facility. MATERIALS AND METHODS: In a total of 12 critical COVID-19 patients in rehabilitation, 19 plasma OSS biomarkers were measured: antioxidants, TAC, trace elements, oxidative damage to lipids, and inflammatory biomarkers. TAC level was measured in plasma, saliva, skin, and urine, using PAOT and expressed as PAOT-Plasma, -Saliva, -Skin, and -Urine scores, respectively. Plasma OSS biomarker levels were compared with levels from previous studies on hospitalized COVID-19 patients and with the reference population. Correlations between four PAOT scores and plasma OSS biomarker levels were analyzed. RESULTS: During the recovery phase, plasma levels in antioxidants (γ-tocopherol, ß-carotene, total glutathione, vitamin C and thiol proteins) were significantly lower than reference intervals, whereas total hydroperoxides and myeloperoxidase (a marker of inflammation) were significantly higher. Copper negatively correlated with total hydroperoxides (r = 0.95, p = 0.001). A similar, deeply modified OSS was already observed in COVID-19 patients hospitalized in an intensive care unit. TAC evaluated in saliva, urine, and skin correlated negatively with copper and with plasma total hydroperoxides. To conclude, the systemic OSS, determined using a large number of biomarkers, was always significantly increased in cured COVID-19 patients during their recovery phase. The less costly evaluation of TAC using an electrochemical method could potentially represent a good alternative to the individual analysis of biomarkers linked to pro-oxidants.

Serum Acylcarnitines Profile in Critically Ill Survivors According to Illness Severity and ICU Length of Stay: An Observational Study.

The acylcarnitine (AC) profile has been shown to be altered in survivors of a prolonged stay in intensive care unit (ICU), with higher short-chain derivates compared to reference ranges. The present study aimed at describing the AC profile of patients surviving a short ICU stay versus patients surviving a >7-day multiple organ dysfunction. Patients discharged from ICU after an elective and non-complicated cardiac surgery (CS) were recruited. For each CS, one to two adults, matched for gender and age, were recruited among patients enrolled in our post-ICU follow-up program after an ICU stay ≥7 days (PS). In both groups, the AC profile was determined during the week following ICU discharge. A total of 50 CS patients (SAPS II 23 (18-27)) survived an ICU stay of 2 (2-3) days and were matched to 85 PS patients (SAPS II 36 (28-51), p < 0.001) who survived an ICU stay of 11 (8-15.5) days. No carnitine deficiency was observed in either group. Their total AC/C0 ratio was similar: 0.355 (0.268-0.415) and 0.358 (0.289-0.417), respectively (p = 0.391). A ratio >0.4 representing a disturbed mitochondrial metabolism was observed in 26/85 (30.6%) PS patients and in 15/50 (30%) CS patients (p > 0.999). The long-chain ACs were elevated in both groups, with a greater increase in the CS group. The short-chain ACs were higher in the PS group: 1.520 (1.178-1.974) vs. 1.185 (0.932-1.895) µmol/L (p < 0.001). The role of the AC profile as potential marker of catabolism and/or mitochondrial dysfunction during the critical illness trajectory should be further investigated.

Systematic Review of the Key Factors Influencing the Indoor Airborne Spread of SARS-CoV-2.

The COVID-19 pandemic due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been plaguing the world since late 2019/early 2020 and has changed the way we function as a society, halting both economic and social activities worldwide. Classrooms, offices, restaurants, public transport, and other enclosed spaces that typically gather large groups of people indoors, and are considered focal points for the spread of the virus. For society to be able to go "back to normal", it is crucial to keep these places open and functioning. An understanding of the transmission modes occurring in these contexts is essential to set up effective infection control strategies. This understanding was made using a systematic review, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA) 2020 guidelines. We analyze the different parameters influencing airborne transmission indoors, the mathematical models proposed to understand it, and discuss how we can act on these parameters. Methods to judge infection risks through the analysis of the indoor air quality are described. Various mitigation measures are listed, and their efficiency, feasibility, and acceptability are ranked by a panel of experts in the field. Thus, effective ventilation procedures controlled by CO2-monitoring, continued mask wearing, and a strategic control of room occupancy, among other measures, are put forth to enable a safe return to these essential places.

Incidence of near-death experiences in patients surviving a prolonged critical illness and their long-term impact: a prospective observational study.

BACKGROUND: So far, the few prospective studies on near-death experience (NDE) were carried out only in intensive care unit (ICU) patients with homogeneous aetiologies, such as cardiac arrest or trauma survivors. The aims of this 1-year prospective and monocentric study were to investigate the incidence of NDE in ICU survivors (all aetiologies) as well as factors that may affect its frequency, and to assess quality of life up to 1 year after enrolment. METHODS: We enrolled adults with a prolonged ICU stay (> 7 days). During the first 7 days after discharge, all eligible patients were assessed in a face-to-face interview for NDE using the Greyson NDE scale, dissociative experiences using the Dissociative Experience Scale, and spirituality beliefs using the WHOQOL-SRPB. Medical parameters were prospectively collected. At 1-year after inclusion, patients were contacted by phone to measure quality of life using the EuroQol five-dimensional questionnaire. RESULTS: Out of the 126 included patients, 19 patients (15%) reported having experienced a NDE as identified by the Greyson NDE scale (i.e. cut-off score ≥ 7/32). In univariate analyses, mechanical ventilation, sedation, analgesia, reason for admission, primary organ dysfunction, dissociative and spiritual propensities were associated with the emergence of NDE. In multivariate logistic regression analysis, only the dissociative and spiritual propensity strongly predicted the emergence of NDE. One year later (n = 61), the NDE was not significantly associated with quality of life. CONCLUSIONS: The recall of NDE is not so rare in the ICU. In our cohort, cognitive and spiritual factors outweighed medical parameters as predictors of the emergence of NDE. Trial registration This trial was registered in Clinicaltrials.gov in February 2020 ( NCT04279171 ).

Characteristics of Mid-Term Post-Intensive Care Syndrome in Patients Attending a Follow-Up Clinic: A Prospective Comparison Between COVID-19 and Non-COVID-19 Survivors.

At present, it is not clear if critically ill COVID-19 survivors have different needs in terms of follow-up compared with other critically ill survivors, and thus if duplicated post-ICU trajectories are mandatory. OBJECTIVES: To compare the post-intensive care syndrome (PICS) of COVID-19 acute respiratory distress syndrome and non-COVID-19 (NC) survivors referred to a follow-up clinic at 3 months (M3) after ICU discharge. DESIGN SETTING AND PARTICIPANTS: Adults who survived an ICU stay greater than or equal to 7 days and attended the M3 consultation were included in this observational study performed in a post-ICU follow-up clinic of a single tertiary hospital. MAIN OUTCOMES AND MEASURES: Patients underwent a standardized assessment, addressing health-related quality of life (3-level version of EQ-5D), sleep disorders (Pittsburgh Sleep Quality Index [PSQI]), physical status (Barthel index, handgrip and quadriceps strengths), mental health disorders (Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised [IES-R]), and cognitive impairment (Montreal Cognitive Assessment [MoCA]). RESULTS: A total of 143 survivors (86 COVID and 57 NC) attended the M3 consultation. Their median age and severity scores were similar. NC patients had a shorter ICU stay (10 d [8-17.2 d]) compared with COVID group (18 d [10.8-30 d]) (p = 0.001). M3 outcomes were similar in the two groups, except for a higher PSQI (p = 0.038) in the COVID group (6 [3-9.5]) versus NC group (4 [2-7]), and a slightly lower Barthel index in the NC group (100 [100-100]) than in the COVID group (100 [85-100]) (p = 0.026). However, the proportion of patients with abnormal values at each score was similar in the two groups. Health-related quality of life was similar in the two groups. The three MoCA (≥ 26), IES-R (<33), and Barthel (=100) were normal in 58 of 143 patients (40.6%). In contrast, 68.5% (98/143) had not returned to their baseline level of daily activities. CONCLUSIONS AND RELEVANCE: In our follow-up clinic at 3 months after discharge, the proportion of patients presenting alterations in the main PICS domains was similar whether they survived a COVID-19 or another critical illness, despite longer ICU stay in COVID group. Cognition and sleep were the two most affected PICS domains.

What is the nutritional status of patients with prolonged disorders of consciousness? A retrospective cross-sectional study.

BACKGROUND: Nutritional status of patients with disorders of consciousness (DoC) is poorly studied. OBJECTIVES: To evaluate the relationship between nutritional status (body mass index, daily calories intake) and clinical variables (level of consciousness, time since injury, diagnosis, etiology and spastic muscle overactivity; SMO,) in patients with prolonged DoCor emerging. Our main hypotheses are i) patients with lower level of consciousness (UWS) have worse nutritional status compared to patients in minimally conscious state (MCS) and ii) SMO could influence nutritional status. METHODS AND RESULTS: Among the 80 patients included in the study (19 UWS, 47 MCS, 14 emerging MCS; 43 ± 15 yo; 3 ± 4 years post-injury, 35 traumatic etiology, 34 females), 9% were at risk to be undernourished, with no differences between UWS and MCS. Patients without SMO had a higher BMI compared to patients with severe SMO. Compared to the recommended daily calories intake, patients with the highest BMI received less calories and patients with the lowest BMI received more calories. We observed a negative correlation between SMO (in lower limbs) and BMI. CONCLUSION: Our study shows that most patients are well nourished, independently from the level of consciousness. SMO may require additional calories in patients' daily needs; however, longitudinal studies are needed to explore the causal relationship between these variables.

Diaphragm function in patients with sepsis and septic shock: A longitudinal ultrasound study.

BACKGROUND: Previous literature on the determinants of diaphragm dysfunction in septic patients is limited. The goal of this study is to assess diaphragm dysfunction in terms of its prevalence and its potential associated factors in septic intensive care unit (ICU) patients. METHODS: This prospective and observational study was conducted between June 2015 and July 2019. Ultrasound measures of diaphragm thickness were performed daily on septic patients. The primary outcome was the prevalence of diaphragm dysfunction at baseline and during the ICU stay. The secondary outcome was the diaphragm thickness. Possible associated factors were prospectively recorded. RESULTS: Fifty patients were enrolled in the study. The prevalence of diaphragm dysfunction was 58%. No diaphragm atrophy was found during the ICU stay. Diaphragm dysfunction was associated with the alteration of consciousness, intra-abdominal sepsis, hypnotics and opioids, and mechanical ventilation. Administration of hypnotics, opioids, and steroids was associated with a decreased diaphragm thickening fraction. Diaphragm dysfunction had no impact on patient outcomes. CONCLUSIONS: Our data reveal a high prevalence of diaphragm dysfunction in septic patients at the onset of sepsis. Administration of hypnotics, opioids, and steroids was associated with the alteration of diaphragm function as well as intra-abdominal sepsis.

Increased KL-6 levels in moderate to severe COVID-19 infection.

BACKGROUND: The global coronavirus disease 2019 (COVID-19) has presented significant challenges and created concerns worldwide. Besides, patients who have experienced a SARS-CoV-2 infection could present post-viral complications that can ultimately lead to pulmonary fibrosis. Serum levels of Krebs von den Lungen 6 (KL-6), high molecular weight human MUC1 mucin, are increased in the most patients with various interstitial lung damage. Since its production is raised during epithelial damages, KL-6 could be a helpful non-invasive marker to monitor COVID-19 infection and predict post-infection sequelae. METHODS: We retrospectively evaluated KL-6 levels of 222 COVID-19 infected patients and 70 healthy control. Serum KL-6, fibrinogen, lactate dehydrogenase (LDH), platelet-lymphocytes ratio (PLR) levels and other biological parameters were analyzed. This retrospective study also characterized the relationships between serum KL-6 levels and pulmonary function variables. RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects (470 U/ml vs 254 U/ml, P <0.00001). ROC curve analysis enabled us to identify that KL-6 > 453.5 U/ml was associated with COVID-19 (AUC = 0.8415, P < 0.0001). KL-6 level was positively correlated with other indicators of disease severity such as fibrinogen level (r = 0.1475, P = 0.0287), LDH level (r = 0,31, P = 0,004) and PLR level (r = 0.23, P = 0.0005). However, KL-6 levels were not correlated with pulmonary function tests (r = 0.04, P = 0.69). CONCLUSIONS: KL-6 expression was correlated with several disease severity indicators. However, the association between mortality and long-term follow-up outcomes needs further investigation. More extensive trials are required to prove that KL-6 could be a marker of disease severity in COVID-19 infection.

Measured Energy Expenditure Using Indirect Calorimetry in Post-Intensive Care Unit Hospitalized Survivors: A Comparison with Predictive Equations.

Actual energy needs after a stay in intensive care units (ICUs) are unknown. The aims of this observational study were to measure the energy expenditure (mEE) of ICU survivors during their post-ICU hospitalization period, and to compare this to the estimations of predictive equations (eEE). Survivors of an ICU stay ≥ 7 days were enrolled in the general ward during the first 7 days after ICU discharge. EE was measured using the Q-NRG calorimeter in canopy mode. This measure was compared to the estimated EE using the Harris−Benedict (HB) equation multiplied by a 1.3 stress factor, the Penn−State (PS) equation or the 30 kcal weight-based (WB) equation. A total of 55 adults were included (67.3% male, age 60 (52−67) y, body mass index 26.1 (22.2−29.7) kg/m2). Indirect calorimetry was performed 4 (3−6) d after an ICU stay of 12 (7−16) d. The mEE was 1682 (1328−1975) kcal/d, corresponding to 22.9 (19.1−24.2) kcal/kg/day. The eEE values derived using HB and WB equations were significantly higher than mEE: 3048 (1805−3332) and 2220 (1890−2640) kcal/d, respectively (both p < 0.001). There was no significant difference between mEE and eEE using the PS equation: 1589 (1443−1809) kcal/d (p = 0.145). The PS equation tended to underestimate mEE with a bias of −61.88 kcal and a wide 95% limit of agreement (−717.8 to 594 kcal). Using the PS equation, agreement within 15% of the mEE was found in 32/55 (58.2%) of the patients. In the present cohort of patients who survived a prolonged ICU stay, mEE was around 22−23 kcal/kg/day. In this post-ICU hospitalization context, none of the tested equations were accurate in predicting the EE measured by indirect calorimetry.

One-Year Functional Decline in COVID-19 and Non-COVID-19 Critically Ill Survivors: A Prospective Study Incorporating a Pre-ICU Status Assessment.

We aimed to describe the one-year (1-y) functional status of survivors of COVID-19 critical illness, compared to non-COVID-19 survivors, and compared to their pre-ICU status. Adults who survived a COVID-19 critical illness (COVID group) during the first two waves in 2 hospitals were contacted by phone 1-y after discharge. They were compared to non-COVID-19 ICU survivors. A standardized assessment focused on quality of life (EQ-5D-3L), autonomy for activities of daily living (Barthel Index), and physical activity quantification (IPAQ-SF). Patients rated their 1-y and pre-ICU status. We included 220 survivors (132 COVID and 88 NC). Their age and severity scores were similar. ICU stay was shorter in NC group (3 [3−6] d) than in COVID group (8 [4.2−16.7] d) (p = 0.001). Proportions of organ supports were similar in the two groups. At 1-y, a significant reduction in EQ-5D-3L total score, in Barthel Index and in physical activity was observed in both groups, compared to the respective baseline values. Dependency (Barthel < 100) was observed in at least 35% of survivors at 1-y. Independently of the critical illness, HRQoL, autonomy and physical activities at 1-y were still significantly inferior to the pre-ICU values.