Interventions Relieving Dyspnea in Intubated Patients Show Responsiveness of the Mechanical Ventilation-Respiratory Distress Observation Scale.

Rationale: Breathing difficulties are highly stressful. In critically ill patients, they are associated with an increased risk of posttraumatic manifestations. Dyspnea, the corresponding symptom, cannot be directly assessed in noncommunicative patients. This difficulty can be circumvented using observation scales such as the mechanical ventilation-respiratory distress observation scale (MV-RDOS). Objective: To investigate the performance and responsiveness of the MV-RDOS to infer dyspnea in noncommunicative intubated patients. Methods: Communicative and noncommunicative patients exhibiting breathing difficulties under mechanical ventilation were prospectively included and assessed using a dyspnea visual analog scale, MV-RDOS, EMG activity of alae nasi and parasternal intercostals, and EEG signatures of respiratory-related cortical activation (preinspiratory potentials). Inspiratory-muscle EMG and preinspiratory cortical activities are surrogates of dyspnea. Assessments were conducted at baseline, after adjustment of ventilator settings, and, in some cases, after morphine administration. Measurements and Main Results: Fifty patients (age, 67 [(interquartile interval [IQR]), 61-76] yr; Simplified Acute Physiology Score II, 52 [IQR, 35-62]) were included, 25 of whom were noncommunicative. Relief occurred in 25 (50%) patients after ventilator adjustments and in 21 additional patients after morphine administration. In noncommunicative patients, MV-RDOS score decreased from 5.5 (IQR, 4.2-6.6) at baseline to 4.2 (IQR, 2.1-4.7; P < 0.001) after ventilator adjustments and 2.5 (IQR, 2.1-4.2; P = 0.024) after morphine administration. MV-RDOS and alae nasi/parasternal EMG activities were positively correlated (ρ = 0.41 and 0.37, respectively). MV-RDOS scores were higher in patients with EEG preinspiratory potentials (4.9 [IQR, 4.2-6.3] vs. 4.0 [IQR, 2.1-4.9]; P = 0.002). Conclusions: The MV-RDOS seems able to detect and monitor respiratory symptoms reasonably well in noncommunicative intubated patients. Clinical trial registered with www.clinicaltrials.gov (NCT02801838).

Heterogeneity in defining multiple trauma: a systematic review of randomized controlled trials.

INTRODUCTION: While numerous randomized controlled trials (RCTs) have been conducted in the field of trauma, a substantial portion of them are yielding negative results. One potential contributing factor to this trend could be the lack of agreement regarding the chosen definitions across different trials. The primary objective was to identify the terminology and definitions utilized for the characterization of multiple trauma patients within randomized controlled trials (RCTs). METHODS: A systematic review of the literature was performed in MEDLINE, EMBASE and clinicaltrials.gov between January 1, 2002, and July 31, 2022. RCTs or RTCs protocols were eligible if they included multiple trauma patients. The terms employed to characterize patient populations were identified, and the corresponding definitions for these terms were extracted. The subsequent impact on the population recruited was then documented to expose clinical heterogeneity. RESULTS: Fifty RCTs were included, and 12 different terms identified. Among these terms, the most frequently used were "multiple trauma" (n = 21, 42%), "severe trauma" (n = 8, 16%), "major trauma" (n = 4, 8%), and trauma with hemorrhagic shock" (n = 4, 8%). Only 62% of RCTs (n = 31) provided a definition for the terms used, resulting a total of 21 different definitions. These definitions primarily relied on the injury severity score (ISS) (n = 15, 30%), displaying an important underlying heterogeneity. The choice of the terms had an impact on the study population, affecting both the ISS and in-hospital mortality. Eleven protocols were included, featuring five different terms, with "severe trauma" being the most frequent, occurring six times (55%). CONCLUSION: This systematic review uncovers an important heterogeneity both in the terms and in the definitions employed to recruit trauma patients within RCTs. These findings underscore the imperative of promoting the use of a unique and consistent definition.

Thromboelastometry-guided haemostatic resuscitation in severely injured patients: a propensity score-matched study.

BACKGROUND: To accelerate the diagnosis and treatment of trauma-induced coagulopathy (TIC), viscoelastic haemostatic assays (VHA) are increasingly used worldwide, although their value is still debated, with a recent randomised trial showing no improvement in outcome. The objective of this retrospective study was to compare 2 cohorts of injured patients in which TIC was managed with either a VHA-based algorithm or a conventional coagulation test (CCT)-based algorithm. METHODS: Data were retrieved from 2 registries and patients were included in the study if they received at least 1 unit of red blood cell in the first 24 h after admission. A propensity score, including sex, age, blunt vs. penetrating, systolic blood pressure, GCS, ISS and head AIS, admission lactate and PTratio, tranexamic acid administration, was then constructed. Primary outcome was the proportion of subjects who were alive and free of massive transfusion (MT) at 24 h after injury. We also compared the cost for blood products and coagulation factors. RESULTS: From 2012 to 2019, 7250 patients were admitted in the 2 trauma centres, and among these 624 were included in the study (CCT group: 380; VHA group: 244). After propensity score matching, 215 patients remained in each study group without any significant difference in demographics, vital signs, injury severity, or laboratory analysis. At 24 h, more patients were alive and free of MT in the VHA group (162 patients, 75%) as compared to the CCT group (112 patients, 52%; p < 0.01) and fewer patients received MT (32 patients, 15% vs. 91 patients, 42%, p < 0.01). However, no significant difference was observed for mortality at 24 h (odds ratio 0.94, 95% CI 0.59-1.51) or survival at day 28 (odds ratio 0.87, 95% CI 0.58-1.29). Overall cost of blood products and coagulation factors was dramatically reduced in the VHA group as compared to the CCT group (median [interquartile range]: 2357 euros [1108-5020] vs. 4092 euros [2510-5916], p < 0.001). CONCLUSIONS: A VHA-based strategy was associated with an increase of the number of patients alive and free of MT at 24 h together with an important reduction of blood product use and associated costs. However, that did not translate into an improvement in mortality.

In-hospital mortality of older patients with COVID-19 throughout the epidemic waves in the great Paris area: a multicenter cohort study.

BACKGROUND: Mortality is high in older patients hospitalized with COVID-19. Previous studies observed lower mortality during the Omicron wave, yet no data is available on older patients. The objective was to compare in-hospital mortality between the Omicron and previous waves in older patients hospitalized with COVID-19. METHODS: This retrospective observational multicenter cohort study used the Greater Paris University Hospitals Group's data warehouse (38 hospitals). Patients aged ≥ 75 years with a confirmed COVID-19 diagnosis and hospitalized from March 2020 to January 2022 were included. The study period was divided into five waves. The fifth wave (January 1st to 31st 2022) was considered as the Omicron wave as it was the predominant variant (≥ 50%), and was compared with waves 1 (March-July 2020), 2 (August-December 2020), 3 (January-June 2021) and 4 (July-December 2021). Primary outcome was in-hospital mortality. Secondary outcome was occurrence of ICU admission or in-hospital death. Multivariate logistic regression was performed, with a sensitivity analysis according to variant type. RESULTS: Of the 195,084 patients hospitalized with COVID-19, 19,909 patients aged ≥ 75 years were included (median age 85 [IQR 79-90] years, 53% women). Overall in-hospital mortality was 4,337 (22%), reaching 345 (17%) during wave 5. Waves 1 and 3 were significantly associated with increased in-hospital mortality in comparison with wave 5 (adjusted Odds Ratios aOR 1.42 [95%CI 1.21-1.66] and 1.56 [95%CI 1.33-1.83] respectively). Waves 1 to 3 were associated with an increased risk of occurrence of ICU admission or in-hospital death in comparison with wave 5: aOR 1.29 [95% CI 1.12 to 1.49] for wave 1, aOR 1.25 [95% CI 1.08 to 1.45] for wave 2 and aOR 1.56 [95% CI 1.36 to 1.79] for wave 3. Sensitivity analysis found that Omicron variant was associated with decreased mortality, in comparison with previous variants. CONCLUSIONS: Mortality was lower during the 5th Omicron wave in the older population, but remained high, implying that this variant could be considered as "milder" but not "mild". This persistently high mortality during the 5th Omicron wave highlights the importance of including older patients in clinical trials to confirm the benefit/risk balance of COVID-19 treatments in this fragile population.

Important Issues to Severe Trauma Survivors: A Qualitative Study.

OBJECTIVE: Identify issues that are important to severe trauma survivors up to 3 years after the trauma. BACKGROUND: Severe trauma is the first cause of disability-adjusted life years worldwide, yet most attention has focused on acute care and the impact on long-term health is poorly evaluated. METHOD: We conducted a large-scale qualitative study based on semi-structured phone interviews. Qualitative research methods involve the systematic collection, organization, and interpretation of conversations or textual data with patients to explore the meaning of a phenomenon experienced by individuals themselves. We randomly selected severe trauma survivors (abbreviated injury score ≥3 in at least 1 body region) who were receiving care in 6 urban academic level-I trauma centers in France between March 2015 and March 2018. We conducted double independent thematic analysis. Issues reported by patients were grouped into overarching domains by a panel of 5 experts in trauma care. Point of data saturation was estimated with a mathematical model. RESULTS: We included 340 participants from 3 months to 3 years after the trauma [median age: 41 years (Q1-Q3 24-54), median injury severity score: 17 (Q1-Q3 11-22)]. We identified 97 common issues that we grouped into 5 overarching domains: body and neurological issues (29 issues elicited by 277 participants), biographical disruption (23 issues, 210 participants), psychological and personality issues (21 issues, 147 participants), burden of treatment (14 issues, 145 participants), and altered relationships (10 issues, 87 participants). Time elapsed because the trauma, injury location, or in-hospital trauma severity did not affect the distribution of these domains across participants' answers. CONCLUSIONS: This qualitative study explored trauma survivors' experiences of the long-term effect of their injury and allowed for identifying a set of issues that they consider important, including dimensions that seem overlooked in trauma research. Our findings confirm that trauma is a chronic medical condition that demands new approaches to post-discharge and long-term care.

Brain Biopsy for Neurological Diseases of Unknown Etiology in Critically Ill Patients: Feasibility, Safety, and Diagnostic Yield.

OBJECTIVES: Brain biopsy is a useful surgical procedure in the management of patients with suspected neoplastic lesions. Its role in neurologic diseases of unknown etiology remains controversial, especially in ICU patients. This study was undertaken to determine the feasibility, safety, and the diagnostic yield of brain biopsy in critically ill patients with neurologic diseases of unknown etiology. We also aimed to compare these endpoints to those of non-ICU patients who underwent a brain biopsy in the same clinical context. DESIGN: Monocenter, retrospective, observational cohort study. SETTING: A French tertiary center. PATIENTS: All adult patients with neurologic diseases of unknown etiology under mechanical ventilation undergoing in-ICU brain biopsy between January 2008 and October 2020 were compared with a cohort of non-ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 2,207 brain-biopsied patients during the study period, 234 biopsies were performed for neurologic diseases of unknown etiology, including 29 who were mechanically ventilated and 205 who were not ICU patients. Specific histological diagnosis and final diagnosis rates were 62.1% and 75.9%, respectively, leading to therapeutic management modification in 62.1% of cases. Meningitis on prebiopsy cerebrospinal fluid analysis was the sole predictor of obtaining a final diagnosis (2.3 [1.4-3.8]; p = 0.02). ICU patients who experienced therapeutic management modification after the biopsy had longer survival (p = 0.03). The grade 1 to 4 (mild to severe) complication rates were: 24.1%, 3.5%, 0%, and 6.9%, respectively. Biopsy-related mortality was significantly higher in ICU patients compared with non-ICU patients (6.9% vs 0%; p = 0.02). Hematological malignancy was associated with biopsy-related mortality (1.5 [1.01-2.6]; p = 0.04). CONCLUSIONS: Brain biopsy in critically ill patients with neurologic disease of unknown etiology is associated with high diagnostic yield, therapeutic modifications and postbiopsy survival advantage. Safety profile seems acceptable in most patients. The benefit/risk ratio of brain biopsy in this population should be carefully weighted.

Learning from terrorist mass casualty incidents: a global survey.

BACKGROUND: Reports published directly after terrorist mass casualty incidents frequently fail to capture difficulties that may have been encountered. An anonymised consensus-based platform may enable discussion and collaboration on the challenges faced. Our aim was to identify where to focus improvement for future responses. METHODS: We conducted a mixed methods study by email of clinicians' experiences of leading during terrorist mass casualty incidents. An initial survey identified features that worked well, or failed to, during terrorist mass casualty incidents plus ongoing challenges and changes that were implemented as a result. A follow-up, quantitative survey measured agreement between responses within each of the themes using a Likert scale. RESULTS: Thirty-three participants responded from 22 hospitals that had received casualties from a terrorist incident, representing 17 cities in low-middle, middle and high income countries. The first survey identified themes of sufficient (sometimes abundant) human resource, although coordination of staff was a challenge. Difficulties highlighted were communication, security, and management of blast injuries. The most frequently implemented changes were education on specific injuries, revising future plans and preparatory exercises. Persisting challenges were lack of time allocated to training and psychological well-being. The follow-up survey recorded highest agreement amongst correspondents on the need for re-triage at hospital (90% agreement), coordination roles (85% agreement), flexibility (100% agreement), and large-scale exercises (95% agreement). CONCLUSION: This survey collates international experience gained from clinicians managing terrorist mass casualty incidents. The organisation of human response, rather than consumption of physical supplies, emerged as the main finding. NHSH Clinical Effectiveness Unit project registration number: 2020/21-036.

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.

Depacked patients who underwent a shortened perihepatic packing for severe blunt liver trauma have a high survival rate: 20 years of experience in a level I trauma center.

INTRODUCTION: Non-operative management is currently the preferred approach in blunt liver trauma, including high grade liver lesions. However, hemodynamic instability imposes the need for an emergency laparotomy, with a perihepatic packing (PHP) to control liver bleeding in most cases. Our retrospective study aimed to assess the outcomes of liver trauma patients who underwent a shortened PHP. METHODS: All consecutive patients who underwent PHP for blunt liver trauma from 1998 to 2019 in our Level I trauma center were included in the study. Unstable patients with severe liver trauma were transferred to the operating room without any delay, and a collective decision was made to perform abbreviated laparotomy to pack the liver. Demographics, perioperative data, postoperative outcomes, and mortality were retrospectively collected, and survivors and deceased patients were compared with a paired t-test. RESULTS: Fifty-nine patients of 206 patients admitted with severe liver injuries were treated with shortened PHP. Thirty-four (57.6%) patients died, including 26 (76.5%) within the first 24 h. Twelve (20.3%) patients had a selective hepatic embolization and eight (13.6%) had an extrahepatic embolization. Forty-eight patients had an extra abdominal associated injury. This was not a predictive factor of mortality. The removal of packing was performed in 24 patients within 72 h after laparotomy, with an 80% survival rate in these patients. CONCLUSION: Shortened PHP is an effective strategy for controlling liver bleeding in severe hepatic trauma. The mortality rate of these patients is high, but after the removal of packing, the survival is good.

Post-operative opioid-related adverse events with intravenous oxycodone compared to morphine: A randomized controlled trial.

BACKGROUND: The value of intravenous oxycodone compared to morphine remains controversial. The purpose of this trial was to compare opioid-related adverse events (ORAES) of intravenous oxycodone and morphine after total hip arthroplasty. METHODS: Patients scheduled for total hip arthroplasty were enrolled in this study of post-operative pain treatment with intravenous oxycodone or intravenous morphine (ratio 1:1). After surgery, patients received similar drug regimens for titration in the post-operative care unit followed by intravenous patient-controlled analgesia (PCA). The primary outcome was the number of patients with ≥1 ORAEs within the first 24 hours defined as either nausea, vomiting, respiratory depression, pruritus, urinary retention requiring evacuation, allergy, hallucinations. Secondary outcomes included pain scores and opioid consumption. RESULTS: The analysis included 238 patients with similar characteristics. There were 55 patients with at least one ORAEs in the oxycodone group vs 46 in the morphine group: 48% vs 40%, P = .19; relative risk = 1.22 (0.91:1.63). Intravenous oxycodone vs intravenous morphine requirements were respectively (median, IQR): 6 (0-11) vs 8 (0-12) mg (P = .06) for titration, 15 (8-26) vs 8 (5-16) mg (P = .001) for PCA, and 22 (12-37) mg vs 19 (11-28) mg for cumulated intravenous consumption (P = .048). During the first 24 hours, there was no difference in secondary outcomes (oxycodone vs morphine, respectively, in %): nausea (15 vs 13), vomiting (5 vs 5), urinary retention (20 vs 12) or pain scores. CONCLUSION: This study demonstrates that IV oxycodone did not significantly reduce ORAEs within the first 24 hours compared to similar ratio of IV morphine.

Impact of Sleep Deprivation on Respiratory Motor Output and Endurance. A Physiological Study.

Rationale: Sleep deprivation can alter endurance of skeletal muscles, but its impact on respiratory command is unknown.Objectives: We aimed to assess the effect of sleep deprivation on respiratory motor output and inspiratory endurance.Methods: Inspiratory endurance was investigated twice in random order, following a normal sleep night and a sleepless night. Healthy participants were asked to breathe as long as possible until task failure against a moderate inspiratory threshold constraint. Transdiaphragmatic pressure and diaphragm electrical activity were measured throughout the trial to assess pressure output of the diaphragm and overall respiratory motor output. Cortical contribution to respiratory motor output was assessed by measurement of preinspiratory motor potential amplitude and by cervical magnetic simulation.Measurements and Main Results: Twenty healthy male participants were studied. Time to task failure was significantly shorter after sleep deprivation than after normal sleep: (30 min [interquartile range [IQR], 17-41] vs. 60 min [IQR, 45-60], P = 0.002). At the beginning of the trial, preinspiratory motor potential amplitude was significantly lower in the sleep-deprivation condition (4.5 µV [IQR, 2.5-6.4] vs. 7.3 µV [IQR, 4.3-10.4], P = 0.02) and correlated significantly with the duration of the endurance trial. In the sleep-deprivation condition, preinspiratory motor potential amplitude, electrical activity of the diaphragm, pressure output of the diaphragm, and Vt decreased and the respiratory rate increased significantly from the beginning to the end of the trial. Such decreases did not occur in the normal-sleep condition.Conclusions: One night of sleep deprivation reduces respiratory motor output by altering its cortical component with subsequent reduction of inspiratory endurance by half. These results suggest that altered sleep triggers severe brain dysfunctions that could precipitate respiratory failure.

Management of the injured bowel: preserving bowel continuity as a gold standard.

BACKGROUND: Management of bowel traumatic injuries is a challenge. Although anastomotic or suture leak remains a feared complication, preserving bowel continuity is increasingly the preferred strategy. The aim of this study was to evaluate the outcomes of such a strategy. METHODS: All included patients underwent surgery for bowel traumatic injuries at a high volume trauma center between 2007 and 2017. Postoperative course was analyzed for abdominal complications, morbidity and mortality. RESULTS: Among 133 patients, 78% had small bowel injuries and 47% had colon injuries. 87% of small bowel injuries and 81% of colon injuries were treated with primary repair or anastomosis, with no difference in treatment according to injury site (p = 0.381). Mortality was 8%. Severe overall morbidity was 32%, and abdominal complications occurred in 32% of patients. Risk factors for severe overall morbidity were stoma creation (p = 0.036), heavy vascular expansion (p = 0.005) and a long delay before surgery (p = 0.023). Fistula rate was 2.2%; all leaks occurred after repairing small bowel wounds. CONCLUSION: Primary repair of bowel injuries should be the preferred option in trauma patient, regardless of the site-small bowel or colon-of the injury. Stoma creation is an important factor for postoperative morbidity, which should be weighed against the risk of an intestinal suture or anastomosis.

Retrospective Observational Study of Brain MRI Findings in Patients with Acute SARS-CoV-2 Infection and Neurologic Manifestations.

Background This study provides a detailed imaging assessment in a large series of patients infected with coronavirus disease 2019 (COVID-19) and presenting with neurologic manifestations. Purpose To review the MRI findings associated with acute neurologic manifestations in patients with COVID-19. Materials and Methods This was a cross-sectional study conducted between March 23 and May 7, 2020, at the Pitié-Salpêtrière Hospital, a reference center for COVID-19 in the Paris area. Adult patients were included if they had a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and referral for brain MRI. Patients with a prior history of neurologic disease were excluded. The characteristics and frequency of different MRI features were investigated. The findings were analyzed separately in patients in intensive care units (ICUs) and other departments (non-ICU). Results During the inclusion period, 1176 patients suspected of having COVID-19 were hospitalized. Of 308 patients with acute neurologic symptoms, 73 met the inclusion criteria and were included (23.7%): thirty-five patients were in the ICU (47.9%) and 38 were not (52.1%). The mean age was 58.5 years ± 15.6 [standard deviation], with a male predominance (65.8% vs 34.2%). Forty-three patients had abnormal MRI findings 2-4 weeks after symptom onset (58.9%), including 17 with acute ischemic infarct (23.3%), one with a deep venous thrombosis (1.4%), eight with multiple microhemorrhages (11.3%), 22 with perfusion abnormalities (47.7%), and three with restricted diffusion foci within the corpus callosum consistent with cytotoxic lesions of the corpus callosum (4.1%). Multifocal white matter-enhancing lesions were seen in four patients in the ICU (5%). Basal ganglia abnormalities were seen in four other patients (5%). Cerebrospinal fluid analyses were negative for SARS-CoV-2 in all patients tested (n = 39). Conclusion In addition to cerebrovascular lesions, perfusion abnormalities, cytotoxic lesions of the corpus callosum, and intensive care unit-related complications, we identified two patterns including white matter-enhancing lesions and basal ganglia abnormalities that could be related to severe acute respiratory syndrome coronavirus 2 infection. © RSNA, 2020 Online supplemental material is available for this article.

Postural preinspiratory cortical activity, genioglossus activity and fluid shift in awake obstructive sleep apnoea patients.

NEW FINDING: What is the central question of this study? Transition to supine posture induces an inspiratory load associated with cortical activation in awake healthy subjects. Some obstructive sleep apnoea patients exhibit this cortical activity in the sitting position contributing to the arousal-dependent compensation of their upper airway abnormalities. Does a transition to the supine posture in awake obstructive sleep apnoea patients increase this cortical activity? What is the main finding and its importance? The transition to supine posture induces a reduction in the cortical activity despite evidence of an increase in genioglossus activity, suggesting that genioglossus activation is not driven by cortical activity. ABSTRACT: The anatomy and mechanical properties of the upper airway (UA) depend on posture. Lying in a supine position causes cephalad fluid shift to the neck, thus narrowing the UA and predisposing the individual to obstructive sleep apnoea (OSA). Increased UA dilator muscle activity during wakefulness prevents the UA collapse but the underlying mechanism has not yet been elucidated. In the sitting position during wakefulness, some OSA patients exhibit preinspiratory cortical activity (preinspiratory potential, PIP) probably related to UA abnormalities. The aim of this study was to investigate changes in the preinspiratory cortical activity and UA dilator muscle in OSA patients during postural challenge. An electroencephalogram was used to detect PIP, and the genioglossus electromyographic activity and ventilation were analysed in 17 awake, male OSA patients while they were sitting, just after lying down, and then in response to leg positive pressure to enhance cephalad fluid shift. The prevalence of PIP decreased from 53% (sitting) to 12% (supine) (P = 0.002) in association with increased genioglossus activity (tonic from median (25th, 75th centiles) 2.3 (1.8, 2.8)% to 3.6 (1.7, 5.0)% of voluntary deglutition, P = 0.019; phasic from 2.3 (1.9, 2.8)% to 3.7 (2.0, 6.1)%, P = 0.024), and with increased transcutaneous carbon dioxide pressure (from 43.0 (42.4, 44.2) to 44.6 (43.5, 45.2) mmHg). No change was observed during leg-positive-pressure application. Moving from the sitting position to the supine position reduces respiratory-related premotor cortical activity in awake OSA patients. The concomitant increase in genioglossus activity, therefore, is not driven by cortical respiratory activity.

Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry.

BACKGROUND: Hyperoxemia has been associated with increased mortality in critically ill patients, but little is known about its effect in trauma patients. The objective of this study was to assess the association between early hyperoxemia and in-hospital mortality after severe trauma. We hypothesized that a PaO2 ≥ 150 mmHg on admission was associated with increased in-hospital mortality. METHODS: Using data issued from a multicenter prospective trauma registry in France, we included trauma patients managed by the emergency medical services between May 2016 and March 2019 and admitted to a level I trauma center. Early hyperoxemia was defined as an arterial oxygen tension (PaO2) above 150 mmHg measured on hospital admission. In-hospital mortality was compared between normoxemic (150 > PaO2 ≥ 60 mmHg) and hyperoxemic patients using a propensity-score model with predetermined variables (gender, age, prehospital heart rate and systolic blood pressure, temperature, hemoglobin and arterial lactate, use of mechanical ventilation, presence of traumatic brain injury (TBI), initial Glasgow Coma Scale score, Injury Severity Score (ISS), American Society of Anesthesiologists physical health class > I, and presence of hemorrhagic shock). RESULTS: A total of 5912 patients were analyzed. The median age was 39 [26-55] years and 78% were male. More than half (53%) of the patients had an ISS above 15, and 32% had traumatic brain injury. On univariate analysis, the in-hospital mortality was higher in hyperoxemic patients compared to normoxemic patients (12% versus 9%, p < 0.0001). However, after propensity score matching, we found a significantly lower in-hospital mortality in hyperoxemic patients compared to normoxemic patients (OR 0.59 [0.50-0.70], p < 0.0001). CONCLUSION: In this large observational study, early hyperoxemia in trauma patients was associated with reduced adjusted in-hospital mortality. This result contrasts the unadjusted in-hospital mortality as well as numerous other findings reported in acutely and critically ill patients. The study calls for a randomized clinical trial to further investigate this association.

Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. METHODS: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. RESULTS: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. CONCLUSION: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.

Postural respiratory-related cortical activation and rostral fluid shift in awake healthy humans.

NEW FINDINGS: What is the central question of this study? Moving to supine induces upper airway modifications and a fluid shift to the neck, which represent inspiratory load that predisposes to upper airway collapse. Is there cortical participation in the response to the load induced by transition to a supine posture in awake healthy subjects? What is the main finding and its importance? Moving to supine induces transient cortical activation in awake healthy subjects, with greater fluid shift, supporting possible cortical participation in the response to upper airway load induced by transition to a supine posture. Our findings open new perspectives in the understanding of the pathogenesis of obstructive sleep apnoea. ABSTRACT: Moving from sitting upright to lying supine causes anatomical modifications and a fluid shift to the neck, which represent inspiratory loads that predispose to upper airway collapse. The pre-inspiratory potential (PIP) corresponds to the cortical activity observed during inspiratory load. In the sitting position during wakefulness, some obstructive sleep apnoea patients exhibit PIP, probably in relationship to upper airway abnormalities. The aim of this study was to investigate whether moving to the supine position induces respiratory-related cortical activation (PIP) in awake healthy subjects. The ECG was analysed to detect PIP, and EMG activity of the genioglossus muscle and ventilation were measured in the sitting position, immediately after moving to the supine position, and during application of leg positive pressure in the supine position to promote fluid shift, which was measured by bioelectrical impedance. Twenty-four subjects were included. From sitting to lying, PIP prevalence increased from 1/24 to 11/24 (P = 0.002), and ventilation decreased with no change in genioglossus activity. The fluid shift from sitting to supine was higher in the subjects exhibiting PIP while supine compared with the subjects without PIP [median (25th; 75th centiles) 440 (430; 520) versus 320 (275; 385) ml, P = 0.018], without any other differences. From before to during leg positive pressure, PIP disappeared (P = 0.006). These results indicate that moving from sitting to lying induces transient respiratory-related cortical activity in awake healthy subjects with greater fluid shift, supporting possible cortical participation in the response to upper airway loading induced by moving from sitting upright to lying supine. This study offers new perspectives in the understanding of obstructive sleep apnoea pathogenesis.

Importance of Early Diagnosis and Care in Knee Dislocations Associated with Vascular Injuries.

BACKGROUND: Arterial injury secondary to acute knee dislocation (KD) is a rare but devastative complication. The aim of this study is to evaluate functional sequelae and factors of poor prognosis. METHODS: A retrospective monocentric series of consecutive KD with acute ischemia by popliteal artery injury was analyzed between 2005 and 2017. The main outcome was the amputation rate. RESULTS: Sixteen dislocations were included. Nine (56%) were due to public road accidents, 5 (31%) were due to falls from height, and 2 (13%) were due to sports injuries. Dislocation had occurred in the posterior location in 8 (50%) cases. Regarding arterial injury, there were 7 (44%) ruptures, 7 (44%) dissections, and 2 (13%) isolated thromboses. Eleven (69%) KDs with vascular trauma were associated with signs of acute ischemia. Revascularization was achieved by anatomical venous bypass in 14 (88%), resection and direct anastomosis in one (6%), and isolated thrombectomy in one (6%). Median time to surgery (time between trauma and vascular repair) was 7 hours (3.25-60.92 hours). Primary revascularization was performed in 12 (75%) cases. In three cases (19%), orthopedic reduction and stabilization were performed first. In one case, (6%) three-step management with vascular shunt at first, then with knee stabilization, and finally vascular bypass was carried out. Stabilization was achieved by using an external fixator in 13 (82%) cases, by open reduction and internal fixation in one case (6%), by ligamentoplasty in one (6%), and by using a long leg cast in one (6%). Fasciotomy was required in 12 (75%) cases. Two patients had early vascular complications, and 2 had early systemic complications. Three secondary transfemoral amputations were performed. Median follow-up duration was 23 months. No secondary amputation was recorded. At the end of follow-up, functional outcomes were evaluated using the Oxford Knee Score (OKS). The median OKS was 30 versus the pretrauma median OKS of 47 (P < 0.00028). No risk factor associated with limb amputation has been highlighted. CONCLUSIONS: Analysis of these results provided indications for therapeutic management of this condition. This study shows poor functional outcomes because of severity of vascular lesion in patients with orthopedic trauma but with healthy arteries.

Prevalence and risk factors for acute kidney injury among trauma patients: a multicenter cohort study.

BACKGROUND: Organ failure, including acute kidney injury (AKI), is the third leading cause of death after bleeding and brain injury in trauma patients. We sought to assess the prevalence, the risk factors and the impact of AKI on outcome after trauma. METHODS: We performed a retrospective analysis of prospectively collected data from a multicenter trauma registry. AKI was defined according to the risk, injury, failure, loss of kidney function and end-stage kidney disease (RIFLE) classification from serum creatinine only. Prehospital and early hospital risk factors for AKI were identified using logistic regression analysis. The predictive models were internally validated using bootstrapping resampling technique. RESULTS: We included 3111 patients in the analysis. The incidence of AKI was 13% including 7% stage R, 3.7% stage I and 2.3% stage F. AKI incidence rose to 42.5% in patients presenting with hemorrhagic shock; 96% of AKI occurred within the 5 first days after trauma. In multivariate analysis, prehospital variables including minimum prehospital mean arterial pressure, maximum prehospital heart rate, secondary transfer to the trauma center and data early collected after hospital admission including injury severity score, renal trauma, blood lactate and hemorrhagic shock were independent risk factors in the models predicting AKI. The model had good discrimination with area under the receiver operating characteristic curve of 0.85 (0.82-0.88) to predict AKI stage I or F and 0.80 (0.77-0.83) to predict AKI of all stages. Rhabdomyolysis severity, assessed by the creatine kinase peak, was an additional independent risk factor for AKI when it was forced into the model (OR 1.041 (1.015-1.069) per step of 1000 U/mL, p < 0.001). AKI was independently associated with a twofold increase in ICU mortality. CONCLUSIONS: AKI has an early onset and is independently associated with mortality in trauma patients. Its prevalence varies by a factor 3 according to the severity of injuries and hemorrhage. Prehospital and early hospital risk factors can provide good performance for early prediction of AKI after trauma. Hence, studies aiming to prevent AKI should target patients at high risk of AKI and investigate therapies early in the course of trauma care.

Development and validation of a pre-hospital "Red Flag" alert for activation of intra-hospital haemorrhage control response in blunt trauma.

BACKGROUND: Haemorrhagic shock is the leading cause of early preventable death in severe trauma. Delayed treatment is a recognized prognostic factor that can be prevented by efficient organization of care. This study aimed to develop and validate Red Flag, a binary alert identifying blunt trauma patients with high risk of severe haemorrhage (SH), to be used by the pre-hospital trauma team in order to trigger an adequate intra-hospital standardized haemorrhage control response: massive transfusion protocol and/or immediate haemostatic procedures. METHODS: A multicentre retrospective study of prospectively collected data from a trauma registry (Traumabase®) was performed. SH was defined as: packed red blood cell (RBC) transfusion in the trauma room, or transfusion ≥ 4 RBC in the first 6 h, or lactate ≥ 5 mmol/L, or immediate haemostatic surgery, or interventional radiology and/or death of haemorrhagic shock. Pre-hospital characteristics were selected using a multiple logistic regression model in a derivation cohort to develop a Red Flag binary alert whose performances were confirmed in a validation cohort. RESULTS: Among the 3675 patients of the derivation cohort, 672 (18%) had SH. The final prediction model included five pre-hospital variables: Shock Index ≥ 1, mean arterial blood pressure ≤ 70 mmHg, point of care haemoglobin ≤ 13 g/dl, unstable pelvis and pre-hospital intubation. The Red Flag alert was triggered by the presence of any combination of at least two criteria. Its predictive performances were sensitivity 75% (72-79%), specificity 79% (77-80%) and area under the receiver operating characteristic curve 0.83 (0.81-0.84) in the derivation cohort, and were not significantly different in the independent validation cohort of 2999 patients. CONCLUSION: The Red Flag alert developed and validated in this study has high performance to accurately predict or exclude SH.