High Airway Occlusion Pressure Is Associated with Dyspnea and Increased Mortality in Critically Ill Mechanically Ventilated Patients.

RATIONALE: 100 ms airway occlusion pressure (P0.1) reflects central respiratory drive. We aimed to assess factors associated with P0.1 and whether an abnormally low or high P0.1 value is associated with higher mortality and longer duration of mechanical ventilation (MV). METHODS: Secondary analysis of a prospective cohort study conducted in 10 intensive care units in France to evaluate dyspnea in communicative MV patients. In patients intubated for more than 24 hours, P0.1 was measured with dyspnea as soon as patients could communicate and the following day. RESULTS: 260 patients were assessed after a median time of ventilation of 4 days. P0.1 was 1.9 (1 - 3.5) cmH2O on enrollment, 24% had a P0.1 >3.5 cmH2O, 37% had a P0.1 between 1.5 and 3.5 cmH2O, and 39% had a P0.1 <1.5 cmH2O. In multivariable linear regression, independent factors associated with P0.1 level were presence of dyspnea (p=0.037), respiratory rate (p<0.001), and PaO2 (p=0.008). 90-day mortality was 33% in patients with P0.1 >3.5 cmH2O vs. 19% in those with a P0.1 between 1.5 and 3.5 cmH2O and 17% in patients with P0.1 <1.5 cmH2O (p=0.046). After adjustment for the main risk factors, P0.1 was associated with 90-day mortality (per cmH2O of P0.1, Hazard ratio 1.19, 95% Confidence interval 1.04 - 1.37, p=0.011). P0.1 was also independently associated with a longer duration of MV (per cmH2O of P0.1, Hazard ratio 1.10, 95% Confidence interval 1.02-1.19, p=0.016). CONCLUSIONS: In patients receiving invasive mechanical ventilation, abnormally high P0.1 values may suggest dyspnea and is associated with higher mortality and prolonged duration of MV.

Balanced Solution versus Normal Saline in Predicted Severe Acute Pancreatitis: A Stepped Wedge Cluster Randomized Trial.

OBJECTIVE: To compare the effect of balanced multielectrolyte solutions(BMES) versus normal saline(NS) for intravenous fluid on chloride levels and clinical outcomes.in patients with predicted severe acute pancreatitis (pSAP). SUMMARY BACKGROUND DATA: Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown. METHODS: In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (APACHE II score ≥8 and C-reactive protein >150 mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase(Sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day3. Secondary endpoints included a composite of clinical and laboratory measures. RESULTS: Overall, 259 patients were enrolled from eleven sites to receive NS(n=147) or BMES(n=112). On trial day3, the mean chloride level was significantly lower in patients who received BMES(101.8 mmol/L(SD4.8) versus 105.8 mmol/L(SD5.9), difference -4.3 mmol/L [95%CI -5.6 to -3.0 mmol/L];P<0.001). For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome(19/112,17.0% versus 43/147,29.3%, P=0.024) and increased organ failure-free days (3.9 d(SD2.7) versus 3.5days(SD2.7), P<0.001) by trial day7. They also spent more time alive and out of ICU(26.4 d(SD5.2) versus 25.0days(SD6.4), P=0.009) and hospital(19.8 d(SD6.1) versus16.3days(SD7.2), P<0.001) by trial day30. CONCLUSIONS: Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits(Trial registration number: ChiCTR2100044432).

Diaphragm Neurostimulation Assisted Ventilation in Critically Ill Patients.

Diaphragm neurostimulation consists of placing electrodes directly on or in proximity to the phrenic nerve(s) to elicit diaphragmatic contractions. Since its initial description in the 18th century, indications have shifted from cardiopulmonary resuscitation to long-term ventilatory support. Recently, the technical development of devices for temporary diaphragm neurostimulation has opened up the possibility of a new era for the management of mechanically ventilated patients. Combining positive pressure ventilation with diaphragm neurostimulation offers a potentially promising new approach to the delivery of mechanical ventilation which may benefit multiple organ systems. Maintaining diaphragm contractions during ventilation may attenuate diaphragm atrophy and accelerate weaning from mechanical ventilation. Preventing atelectasis and preserving lung volume can reduce lung stress and strain and improve homogeneity of ventilation, potentially mitigating ventilator-induced lung injury. Furthermore, restoring the thoracoabdominal pressure gradient generated by diaphragm contractions may attenuate the drop in cardiac output induced by positive pressure ventilation. Experimental evidence suggests diaphragm neurostimulation may prevent neuroinflammation associated with mechanical ventilation. This review describes the historical development and evolving approaches to diaphragm neurostimulation during mechanical ventilation and surveys the potential mechanisms of benefit. The review proposes a research agenda and offers perspectives for the future of diaphragm neurostimulation assisted mechanical ventilation for critically ill patients.

Occurrences of post-traumatic stress disorder, anxiety, depression, and burnout syndrome in ICU staff workers after two-year of the COVID-19 pandemic: the international PSY-CO in ICU study.

PURPOSE: The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. MATERIALS AND METHODS: An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. RESULTS: PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. CONCLUSION: The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.

A three-step support strategy for relatives of patients dying in the intensive care unit: a cluster randomised trial.

BACKGROUND: In relatives of patients dying in intensive care units (ICUs), inadequate team support can increase the prevalence of prolonged grief and other psychological harm. We aimed to evaluate whether a proactive communication and support intervention would improve relatives' outcomes. METHODS: We undertook a prospective, multicentre, cluster randomised controlled trial in 34 ICUs in France, to compare standard care with a physician-driven, nurse-aided, three-step support strategy for families throughout the dying process, following a decision to withdraw or withhold life support. Inclusion criteria were relatives of patients older than 18 years with an ICU length of stay 2 days or longer. Participating ICUs were randomly assigned (1:1 ratio) into an intervention cluster and a control cluster. The randomisation scheme was generated centrally by a statistician not otherwise involved in the study, using permutation blocks of non-released size. In the intervention group, three meetings were held with relatives: a family conference to prepare the relatives for the imminent death, an ICU-room visit to provide active support, and a meeting after the patient's death to offer condolences and closure. ICUs randomly assigned to the control group applied their best standard of care in terms of support and communication with relatives of dying patients. The primary endpoint was the proportion of relatives with prolonged grief (measured with PG-13, score ≥30) 6 months after the death. Analysis was by intention to treat, with the bereaved relatives as the unit of observation. The study is registered with ClinicalTrials.gov, NCT02955992. FINDINGS: Between Feb 23, 2017, and Oct 8, 2019, we enrolled 484 relatives of ICU patients to the intervention group and 391 to the control group. 379 (78%) relatives in the intervention group and 309 (79%) in the control group completed the 6-month interview to measure the primary endpoint. The intervention significantly reduced the number of relatives with prolonged grief symptoms (66 [21%] vs 57 [15%]; p=0·035) and the median PG-13 score was significantly lower in the intervention group than in the control group (19 [IQR 14-26] vs 21 [15-29], mean difference 2·5, 95% CI 1·04-3·95). INTERPRETATION: Among relatives of patients dying in the ICU, a physician-driven, nurse-aided, three-step support strategy significantly reduced prolonged grief symptoms. FUNDING: French Ministry of Health.

Long-Term Outcome of Severe Metabolic Acidemia in ICU Patients, a BICAR-ICU Trial Post Hoc Analysis.

OBJECTIVES: Long-term prognosis of ICU survivors is a major issue. Severe acidemia upon ICU admission is associated with very high short-term mortality. Since the long-term prognosis of these patients is unknown, we aimed to determine the long-term health-related quality of life and survival of these patients. DESIGN: Post hoc analysis of a multicenter, randomized, controlled trial. SETTING: Twenty-six French ICUs. PATIENTS: Day 28 critically ill survivors admitted with severe acidemia and enrolled in the BICAR-ICU trial. INTERVENTION: Sodium bicarbonate versus no sodium bicarbonate infusion according to the randomization group. MEASUREMENTS AND MAIN RESULTS: The primary outcome was health-related quality of life (HRQoL) measured with the 36-item Short Form Health Survey and the EuroQol 5-D questionnaires. Secondary outcomes were mortality, end-stage renal disease treated with renal replacement therapy or renal transplantation, place of residence, professional status, and ICU readmission. HRQoL was reduced with no significant difference between the two groups. HRQoL was reduced particularly in the role-physical health domain (64/100 ± 41 in the control group and 49/100 ± 43 in the bicarbonate group, p = 0.28), but it was conserved in the emotional domains (96/100 ± 19 in the control group and 86/100 ± 34 in the bicarbonate group, p = 0.44). Forty percent of the survivors described moderate to severe problems walking, and half of the survivors described moderate to severe problems dealing with usual activities. Moderate to severe anxiety or depression symptoms were present in one third of the survivors. Compared with the French general population, HRQoL was decreased in the survivors mostly in the physical domains. The 5-year overall survival rate was 30% with no significant difference between groups. CONCLUSIONS: Long-term HRQoL was decreased in both the control and the sodium bicarbonate groups of the BICAR-ICU trial and was lower than the general population, especially in the physical domains.

Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study.

BACKGROUND: Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort. METHODS: The 'French-Speaking ICU Nutritional Survey' (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses. RESULTS: During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23-2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00-1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01-1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98-1.11). CONCLUSIONS: In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk. Trial registration ClinicalTrials.gov Identifier: NCT02599948. Retrospectively registered on November 5th 2015.

Thoracic epidural analgesia in intensive care unit patients with acute pancreatitis: the EPIPAN multicenter randomized controlled trial.

BACKGROUND: Findings from preclinical studies and one pilot clinical trial suggest potential benefits of epidural analgesia in acute pancreatitis. We aimed to assess the efficacy of thoracic epidural analgesia, in addition to usual care, in improving clinical outcomes of intensive care unit patients with acute pancreatitis. METHODS: A multicenter, open-label, randomized, controlled trial including adult patients with a clinical diagnosis of acute pancreatitis upon admission to the intensive care unit. Participants were randomly assigned (1:1) to a strategy combining thoracic epidural analgesia and usual care (intervention group) or a strategy of usual care alone (control group). The primary outcome was the number of ventilator-free days from randomization until day 30. RESULTS: Between June 2014 and January 2019, 148 patients were enrolled, and 135 patients were included in the intention-to-treat analysis, with 65 patients randomly assigned to the intervention group and 70 to the control group. The number of ventilator-free days did not differ significantly between the intervention and control groups (median [interquartile range], 30 days [15-30] and 30 days [18-30], respectively; median absolute difference of - 0.0 days, 95% CI - 3.3 to 3.3; p = 0.59). Epidural analgesia was significantly associated with longer duration of invasive ventilation (median [interquartile range], 14 days [5-28] versus 6 days [2-13], p = 0.02). CONCLUSIONS: In a population of intensive care unit adults with acute pancreatitis and low requirement for intubation, this first multicenter randomized trial did not show the hypothesized benefit of epidural analgesia in addition to usual care. Safety of epidural analgesia in this setting requires further investigation. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02126332 , April 30, 2014.

Prevalence, Intensity, and Clinical Impact of Dyspnea in Critically Ill Patients Receiving Invasive Ventilation.

Rationale: Dyspnea is a traumatic experience. Only limited information is available on dyspnea in intubated critically ill patients. Objectives: Our objectives were 1) to quantify the prevalence and severity of dyspnea; and 2) to evaluate the impact of dyspnea on ICU length of stay and post-traumatic stress disorder (PTSD) 90 days after ICU discharge. Methods: This was a prospective cohort study in 10 ICUs in France. In patients intubated for more than 24 hours, dyspnea was quantified with a visual analog scale (from 0 to 10) as soon as they were able to communicate, the following day, and before spontaneous breathing trials. PTSD was defined by an Impact of Event Scale-Revised score of at least 22. Measurements and Main Results: Among the 612 patients assessed, 34% reported dyspnea, with a median dyspnea rating of 5 (interquartile range, 4-7). ICU length of stay was not significantly different between patients with versus without dyspnea (6 [3-12] and 6 [3-13] days, respectively; P = 0.781). Mortality was not different between groups. Of the 153 patients interviewed on Day 90, a higher proportion of individuals with probable PTSD was observed among patients who were dyspneic on enrollment (29% vs. 13%; P = 0.017). The density of dyspnea (number of dyspneic episodes divided by time from enrollment to extubation) was independently associated with PTSD (odds ratio, 1.07; 95% confidence interval, 1.01-1.13; P = 0.031). Conclusions: Dyspnea was frequent and intense in intubated critically ill patients. ICU length of stay was not significantly different among patients reporting dyspnea, but PTSD was more frequent at Day 90. Clinical trial registered with www.clinicaltrials.gov (NCT02336464).

Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients.

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

High-Flow Versus VenturiMask Oxygen Therapy to Prevent Reintubation in Hypoxemic Patients after Extubation: A Multicenter Randomized Clinical Trial.

Rationale: When compared with VenturiMask after extubation, high-flow nasal oxygen provides physiological advantages. Objectives: To establish whether high-flow oxygen prevents endotracheal reintubation in hypoxemic patients after extubation, compared with VenturiMask. Methods: In this multicenter randomized trial, 494 patients exhibiting PaO2:FiO2 ratio ⩽ 300 mm Hg after extubation were randomly assigned to receive high-flow or VenturiMask oxygen, with the possibility to apply rescue noninvasive ventilation before reintubation. High-flow use in the VenturiMask group was not permitted. Measurements and Main Results: The primary outcome was the rate of reintubation within 72 hours according to predefined criteria, which were validated a posteriori by an independent adjudication committee. Main secondary outcomes included reintubation rate at 28 days and the need for rescue noninvasive ventilation according to predefined criteria. After intubation criteria validation (n = 492 patients), 32 patients (13%) in the high-flow group and 27 patients (11%) in the VenturiMask group required reintubation at 72 hours (unadjusted odds ratio, 1.26 [95% confidence interval (CI), 0.70-2.26]; P = 0.49). At 28 days, the rate of reintubation was 21% in the high-flow group and 23% in the VenturiMask group (adjusted hazard ratio, 0.89 [95% CI, 0.60-1.31]; P = 0.55). The need for rescue noninvasive ventilation was significantly lower in the high-flow group than in the VenturiMask group: at 72 hours, 8% versus 17% (adjusted hazard ratio, 0.39 [95% CI, 0.22-0.71]; P = 0.002) and at 28 days, 12% versus 21% (adjusted hazard ratio, 0.52 [95% CI, 0.32-0.83]; P = 0.007). Conclusions: Reintubation rate did not significantly differ between patients treated with VenturiMask or high-flow oxygen after extubation. High-flow oxygen yielded less frequent use of rescue noninvasive ventilation. Clinical trial registered with www.clinicaltrials.gov (NCT02107183).

A randomized controlled trial of the intraoperative use of noninvasive ventilation versus supplemental oxygen by face mask for procedural sedation in an electrophysiology laboratory.

PURPOSE: The efficacy of noninvasive ventilation (NIV) during procedures that require sedation and analgesia has not been established. We evaluated whether NIV reduces the incidence of respiratory events. METHODS: In this randomized controlled trial, we included 195 patients with an American Society of Anesthesiologists Physical Status of III or IV during electrophysiology laboratory procedures. We compared NIV with face mask oxygen therapy for patients under sedation. The primary outcome was the incidence of respiratory events determined by a computer-driven blinded analysis and defined by hypoxemia (peripheral oxygen saturation < 90%) or apnea/hypopnea (absence of breathing for 20 sec on capnography). Secondary outcomes included hemodynamic variables, sedation, patient safety (composite scores of major or minor adverse events), and adverse outcomes at day 7. RESULTS: A respiratory event occurred in 89/98 (95%) patients in the NIV group and in 69/97 (73%) patients with face masks (risk ratio [RR], 1.29; 95% confidence interval [CI], 1.13 to 1.47; P < 0.001). Hypoxemia occurred in 40 (42%) patients in the NIV group and in 33 (34%) patients with face masks (RR, 1.21; 95% CI, 0.84 to 1.74; P = 0.30). Apnea/hypopnea occurred in 83 patients (92%) in the NIV group vs 65 patients (70%) with face masks (RR, 1.32; 95% CI, 1.14 to 1.53; P < 0.001). Hemodynamic variables, sedation, major or minor safety events, and patient outcomes were not different between the groups. CONCLUSIONS: Respiratory events were more frequent among patients receiving NIV without any safety or outcome impairment. These results do not support the routine use of NIV intraoperatively. STUDY REGISTRATION: ClinicalTrials.gov (NCT02779998); registered 4 November 2015.

RéSUMé: OBJECTIF: L'efficacité de la ventilation non invasive (VNI) pendant les interventions nécessitant une sédation et une analgésie n'a pas été établie. Nous avons évalué si la VNI réduisait l'incidence des complications respiratoires. MéTHODE: Dans cette étude randomisée contrôlée, nous avons inclus 195 patient·es de statut physique III ou IV selon l'American Society of Anesthesiologists pendant des interventions en laboratoire d'électrophysiologie. Nous avons comparé la VNI à l'oxygénothérapie par masque facial pour les patient·es sous sédation. Le critère d'évaluation principal était l'incidence des complications respiratoires déterminée par une analyse en aveugle assistée par ordinateur et définie par une hypoxémie (saturation périphérique en oxygène < 90 %) ou une apnée/hypopnée (absence de respiration pendant 20 secondes à la capnographie). Les critères d'évaluation secondaires comprenaient les variables hémodynamiques, la sédation, la sécurité des patient·es (scores composites des événements indésirables majeurs ou mineurs) et les issues indésirables au jour 7. RéSULTATS: Un événement respiratoire est survenu chez 89/98 (95 %) patient·es du groupe VNI et chez 69/97 (73 %) patient·es ayant un masque facial (risque relatif [RR], 1,29; intervalle de confiance [IC] à 95 %, 1,13 à 1,47; P < 0,001). Une hypoxémie est survenue chez 40 (42 %) patient·es du groupe VNI et chez 33 (34 %) patient·es ayant un masque facial (RR, 1,21 ; IC à 95 %, 0,84 à 1,74; P = 0,30). Une hypoxémie est survenue chez 40 (42 %) patient·es du groupe VNI et chez 33 (34 %) patient·es ayant un masque facial (RR, 1,21; IC 95 %, 0,84 à 1,74; P = 0,30). Les variables hémodynamiques, la sédation, les événements de sécurité majeurs ou mineurs et les issues pour les patient·es n'étaient pas différents entre les groupes. CONCLUSION: Les complications respiratoires étaient plus fréquentes chez les patient·es recevant une VNI sans aucun impact sur la sécurité ou les issues. Ces résultats n'appuient pas l'utilisation systématique de la VNI en peropératoire. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02779998); enregistrée le 4 novembre 2015.

Discomfort improvement for critically ill patients using electronic relaxation devices: results of the cross-over randomized controlled trial E-CHOISIR (Electronic-CHOIce of a System for Intensive care Relaxation).

PURPOSE: To assess the impact of different electronic relaxation devices on common stressful patient symptoms experienced in intensive care unit (ICU). METHODS: Sixty critically ill patients were enrolled in four relaxation sessions using a randomized cross-over design: standard relaxation (TV/radio), music therapy (MUSIC-CARE©), and two virtual reality systems using either real motion pictures (DEEPSEN©) or synthetic motion pictures (HEALTHY-MIND©). The goal was to determine which device was the best to reduce overall patient discomfort intensity (0-10 Numeric Rating Scale (NRS); primary endpoint). Secondary endpoints were specific stressful symptoms (pain, anxiety, dyspnea, thirst, and lack of rest feeling) and stress response measured by Analgesia/Nociception Index (ANI). Multivariate mixed-effect analysis was used, taking into account patient characteristics and multiple measurements. RESULTS: Fifty patients followed the full research protocol, and ten patients did at least one research planned session of relaxation. HEALTHY-MIND© was associated with a significant decrease in overall discomfort, the primary endpoint (median NRS = 4[2-6] vs. 2[0-5]; p = 0.01, mixed-effect model), accompanied by a significant decrease in stress response (increase in ANI, secondary endpoint; p < 0.01). Regarding other secondary endpoints, each of the two virtual reality systems was associated with a decrease in anxiety (p < 0.01), while HEALTHY-MIND© was associated also with a decrease in pain (p = 0.001) and DEEPSEN© with a decrease in lack of rest (p = 0.01). Three incidents (claustrophobia/dyspnea/agitation) were reported among 109 virtual reality sessions. Cybersickness was rare (NRS = 0[0-0]). CONCLUSION: Electronic relaxation therapy is a promising, safe, and effective non-pharmacological solution that can be used to improve overall discomfort in alert and non-delirious ICU patients. Its effectiveness depends on technical characteristics (virtual reality using a synthetic imagined world versus a real world or music therapy alone without virtual reality), as well as the type of symptoms.

Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center.

BACKGROUND: Molecular Adsorbent Recirculating System (MARS®) is a non-biological artificial liver device. The benefit risk ratio between uncertain clinical effects and potential adverse events remains difficult to assess. We sought to describe adverse events related to MARS® therapy as well as biological and clinical effects. METHODS: All intensive care unit (ICU) admissions to whom MARS® therapy was prescribed from March 2005 to August 2021 were consecutively and prospectively included. The main endpoint was the incidence of adverse events related to MARS® therapy. Secondary endpoints were the biological and clinical effects of MARS® therapy. RESULTS: We reported 180 admissions treated with MARS® therapy. Among the 180 admissions, 56 (31.1%) were for acute-on-chronic liver failure, 32 (17.8%) for acute liver failure, 28 (15.5%) for post-surgery liver failure, 52 (28.9%) for pruritus and 12 (6.7%) for drug intoxication. At least one adverse event occurred in 95 (52.8%) admissions. Thrombocytopenia was the most frequent adverse event which was recorded in 55 admissions (30.6%). Overall, platelets count was 131 (± 95) × 109/L before and 106 (± 72) × 109/L after MARS® therapy (p < .001). After MARS® therapy, total bilirubin was significantly decreased in all groups (p < 0.05). Hepatic encephalopathy significantly improved in both the acute-on-chronic and in the acute liver failure group (p = 0.01). In the pruritus group, pruritus intensity score was significantly decreased after MARS® therapy (p < 0.01). CONCLUSION: In this large cohort of patients treated with MARS® therapy we report frequent adverse events. Thrombocytopenia was the most frequent adverse event. In all applications significant clinical and biological improvements were shown with MARS® therapy.

Association between in-ICU red blood cells transfusion and 1-year mortality in ICU survivors.

BACKGROUND: Impact of in-ICU transfusion on long-term outcomes remains unknown. The purpose of this study was to assess in critical-care survivors the association between in-ICU red blood cells transfusion and 1-year mortality. METHODS: FROG-ICU, a multicenter European study enrolling all-comers critical care patients was analyzed (n = 1551). Association between red blood cells transfusion administered in intensive care unit and 1-year mortality in critical care survivors was analyzed using an augmented inverse probability of treatment weighting-augmented inverse probability of censoring weighting method to control confounders. RESULTS: Among the 1551 ICU-survivors, 42% received at least one unit of red blood cells while in intensive care unit. Patients in the transfusion group had greater severity scores than those in the no-transfusion group. According to unweighted analysis, 1-year post-critical care mortality was greater in the transfusion group compared to the no-transfusion group (hazard ratio (HR) 1.78, 95% CI 1.45-2.16). Weighted analyses including 40 confounders, showed that transfusion remained associated with a higher risk of long-term mortality (HR 1.21, 95% CI 1.06-1.46). CONCLUSIONS: Our results suggest a high incidence of in-ICU RBC transfusion and that in-ICU transfusion is associated with a higher 1-year mortality among in-ICU survivors. Trial registration ( NCT01367093 ; Registered 6 June 2011).

Videolaryngoscopy as a first-intention technique for tracheal intubation in unselected surgical patients: a before and after observational study.

BACKGROUND: Using a Macintosh-style videolaryngoscope as a first-intention device for tracheal intubation of unselected patients in the operating room has not often been studied. We hypothesised that using a Macintosh-style videolaryngoscope as a first-intention device is associated with an increased proportion of easy tracheal intubation. METHODS: In a quality improvement project for airway management aimed at implementing a Macintosh-style videolaryngoscope as a first-intention device, we included all consecutive tracheal intubations in adults from March, 2017 to September, 2020 in two French teaching hospitals. We divided the cohort into three temporal cohorts: the pre-intervention, implementation, and post-intervention periods. The primary outcome was the proportion of easy airway management. The secondary outcomes were the rescue technique, Cormack-Lehane III or IV view, and operator-reported difficulty of intubation. Data from one hospital compliant with the quality improvement project were compared with data from a non-compliant hospital. RESULTS: A total of 26 692 tracheal intubations were performed. Among 11 938 intubations included in the compliant hospital, 5487 were included in the pre-intervention, 1845 in the implementation, and 4606 in the post-intervention periods. In comparison to the pre-intervention period, the proportions of easy tracheal intubation increased from 94.3% (5177 of 5487) to 98.7% (4547 of 4606)) in the post-intervention period (+4.4% [95% confidence interval 3.7-5.1%], P<0.001). In comparison to the pre-intervention period, all secondary outcome proportions were significantly lower in the post-intervention period. No significant changes were noted in the non-compliant hospital between the pre- and post-intervention periods. CONCLUSIONS: Using a Macintosh-style videolaryngoscope as a first-intention device for tracheal intubation in the operating room was associated with a significant increase in the proportion of easy tracheal intubation, compared with use of the standard Macintosh laryngoscope.

Hydroxyethyl Starch for Fluid Management in Patients Undergoing Major Abdominal Surgery: A Systematic Review With Meta-analysis and Trial Sequential Analysis.

BACKGROUND: In critically ill patients, warnings about a risk of death and acute kidney injury (AKI) with hydroxyethyl starch (HES) solutions have been raised. However, HES solutions may yet have a role to play in major abdominal surgery. This meta-analysis and trial sequential analysis (TSA) aimed to investigate the effect of HES intravascular volume replacement on the risk of AKI, intraoperative blood transfusion, and postoperative intra-abdominal complications compared to crystalloid intravascular volume replacement. METHODS: In this meta-analysis and TSA, we searched for randomized controlled trials (RCTs) comparing intraoperative HES intravascular volume replacement to crystalloid intravascular volume replacement in adult patients undergoing major abdominal surgery. Primary outcome was 30-day AKI, defined as a binary outcome according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, combining stages 1, 2, and 3 into an AKI category versus no AKI category (stage 0). Secondary outcomes included rates of intraoperative blood transfusion and postoperative intra-abdominal complications. We used random effects models to calculate summary estimates. We used relative risk (RR) as summary measure for dichotomous outcomes, with corresponding 95% confidence intervals (CIs) for the primary outcome (P value <.05 was considered statistically significant) and 99% CI after Bonferroni correction for the secondary outcomes (P value <.01 was considered statistically significant). RESULTS: Seven RCTs including 2398 patients were included. HES intravascular volume replacement was not associated with an increased risk of 30-day AKI (RR = 1.22, 95% CI, 0.94-1.59; P = .13), when compared to crystalloid intravascular volume replacement. According to TSA, this analysis was underpowered. HES intravascular volume replacement was associated with higher rates of blood transfusion (RR = 1.57 99% CI, 1.10-2.25; P = .001), and similar rates of postoperative intra-abdominal complications (RR = 0.76 99% CI, 0.57-1.02; P = .02). CONCLUSIONS: In this meta-analysis to focus on HES intravascular volume replacement in major abdominal surgery, HES intravascular volume replacement was not associated with a higher risk of 30-day AKI when compared to crystalloid intravascular volume replacement. However, CI and TSA do not exclude harmful effects of HES intravascular volume replacement on the renal function.

Renal Replacement Therapy for Acute Kidney Injury in French Intensive Care Units: A Nationwide Survey of Practices.

BACKGROUND: The frequency of acute kidney injury (AKI) can be as high as 50% in the intensive care unit (ICU). Despite the publication of national guidelines in France in 2015 for the use of RRT, there are no data describing the implementation of these recommendations in real-life. METHODS: We performed a nationwide survey of practices from November 15, 2019, to January 24, 2020, in France. An electronic questionnaire based on the items recommended in the national guidelines was sent using an online survey platform, to the chiefs of all ICUs in France. The questionnaire comprised a section for the Department Chief about local organization and facilities, and a second section destined for individual physicians about their personal practices. RESULTS: We contacted the Department Chief in 356 eligible ICUs, of whom 88 (24.7%) responded regarding their ICU organization. From these 88 ICUs, 232/285 physicians (82%) completed the questionnaire regarding individual practices. The practices reported by respondent physicians were as follows: intermittent RRT was first-line choice in >75% in a patient with single organ (kidney) failure at the acute phase, whereas continuous RRT was predominant (>75%) in patients with septic shock or multi-organ failure. Blood and dialysate flow for intermittent RRT were 200-300 mL/min and 400-600 mL/min, respectively. The dose of dialysis for continuous RRT was 25-35 mL/kg/h (65%). Insertion of the dialysis catheter was mainly performed by the resident under echographic guidance, in the right internal jugular vein. The most commonly used catheter lock was citrate (53%). The most frequently cited criterion for weaning from RRT was diuresis, followed by a drop in urinary markers (urea and creatinine). CONCLUSION: This study shows a satisfactory level of reported compliance with French guidelines and recent scientific evidence among ICU physicians regarding initiation of RRT for AKI in the ICU.

Shear Wave Elastography, a New Tool for Diaphragmatic Qualitative Assessment: A Translational Study.

Rationale: Prolonged mechanical ventilation is often associated with either a decrease (known atrophy) or an increase (supposed injury) in diaphragmatic thickness. Shear wave elastography is a noninvasive technique that measures shear modulus, a surrogate of tissue stiffness and mechanical properties. Objectives: To describe changes in shear modulus (SM) during the ICU stay and the relationship with alterations in muscle thickness. To perform a comprehensive ultrasound-based characterization of histological and force production changes occurring in the diaphragm. Methods: Translational study using critically ill patients and mechanically ventilated piglets. Serial ultrasound examination of the diaphragm collecting thickness and SM was performed in both patients and piglets. Transdiaphragmatic pressure and diaphragmatic biopsies were collected in piglets. Measurements and Main Results: We enrolled 102 patients, 88 of whom were invasively mechanically ventilated. At baseline, SM was 14.3 ± 4.3 kPa and diaphragm end-expiratory thickness was 2.0 ± 0.5 mm. Decrease or increase by more than 10% from baseline was reported in 86% of the patients for thickness and in 92% of the patients for SM. An increase in diaphragmatic thickness during the stay was associated with a decrease in SM (ß = -9.34 ± 4.41; P = 0.03) after multivariable analysis. In the piglet sample, a decrease in SM over 3 days of mechanical ventilation was associated with loss of force production, slow and fast fiber atrophy, and increased lipid droplets accumulation. Conclusions: Increases in diaphragm thickness during critical illness is associated with decreased tissue stiffness as demonstrated by shear wave ultrasound elastography, consistent with the development of muscle injury and weakness. Clinical trial registered with www.clinicaltrials.gov (NCT03550222).

Characteristics and outcomes of patients undergoing anesthesia while SARS-CoV-2 infected or suspected: a multicenter register of consecutive patients.

BACKGROUND: There are limited data to detail the perioperative anesthetic management and the incidence of postoperative respiratory complications among patients requiring an anesthetic procedure while being SARS-CoV-2 positive or suspected. METHODS: An observational multicenter cohort study was performed including consecutive patients who were SARS-CoV-2 confirmed or suspected and who underwent scheduled and emergency anesthesia between March 17 and May 26, 2020. RESULTS: A total of 187 patients underwent anesthesia with SARS-CoV-2 confirmed or suspected, with ultimately 135 (72.2%) patients positive and 52 (27.8%) negative. The median SOFA score was 2 [0; 5], and the median ARISCAT score was 49 [36; 67]. The major respiratory complications rate was 48.7% (n = 91) with 40.4% (n = 21) and 51.9% (n = 70) in the SARS-CoV-2-negative and -positive groups, respectively (p = 0.21). Among both positive and negative groups, patients with a high ARISCAT risk score (> 44) had a higher risk of presenting major respiratory complications (p < 0.01 and p = 0.1, respectively). DISCUSSION: When comparing SARS-COV-2-positive and -negative patients, no significant difference was found regarding the rate of postoperative complications, while baseline characteristics strongly impact these outcomes. This finding suggests that patients should be scheduled for anesthetic procedures based on their overall risk of postoperative complication, and not just based on their SARS-CoV-2 status.