Prospective multi-center evaluation of the incidence of unplanned extubation and its outcomes in French intensive care units. The Safe-ICU study.

BACKGROUND: We aimed to determine the epidemiology and outcomes of unplanned extubation (UE), both accidental and self-extubation, in ICU. METHODS: A multicentre prospective cohort study was conducted in 47 French ICUs. The number of mechanical ventilation (MV) days, and planned and unplanned extubation were recorded in each center over a minimum period of three consecutive months to evaluate UE incidence. Patient characteristics, UE environmental factors, and outcomes were compared based on the UE mechanism (accidental or self-extubation). Self-extubation outcomes were compared with planned extubation using a propensity-matched population. Finally, risk factors for extubation failure (re-intubation before day 7) were determined following self-extubation. RESULTS: During the 12-month inclusion period, we found a pooled UE incidence of 1.0 per 100 MV days. UE accounted for 9% of all endotracheal removals. Of the 605 UE, 88% were self-extubation and 12% were accidental-extubations. The latter had a worse prognosis than self-extubation (34%vs. 8% ICU-mortality, p < 0.001). Self-extubation did not increase mortality compared with planned extubation (8 vs. 11%, p = 0.075). Regardless of the type of extubation, planned or unplanned, extubation failure was independently associated with a poor outcome. Cancer, higher respiratory rate, lower PaO2/FiO2 at the time of extubation, weaning process not-ongoing, and immediate post-extubation respiratory failure were independent predictors of failed self-extubation. CONCLUSION: Unplanned extubation, mostly represented by self-extubation, is common in ICU and accounts for 9% of all endotracheal extubations. While accidental extubations are a serious and infrequent adverse event, self-extubation does not increase mortality compared to planned extubation.

French practice of emergency resuscitative thoracotomy. A study based on the Traumabase Registry.

AIM OF THE STUDY: Emergency resuscitative thoracotomy (ERT) has been described as a potentially life-saving procedure for trauma patients who have been admitted in refractory shock or with recent loss of sign of life (SOL). This nationwide registry analysis aimed to describe the French practice of ERT. PATIENTS AND METHODS: From 2015 to 2021, all severe trauma patients who underwent ERT were extracted from the TraumaBase→ registry. Demographic data, prehospital management and in-hospital outcomes were recorded to evaluate predictors of success-to rescue after ERT at 24-hour and 28-day. RESULTS: Only 10/26 Trauma centers have an effective practice of ERT, three of them perform more than 1 ERT/year. Sixty-six patients (74% male, 49/66) with a median age of 37 y/o [26-51], mostly with blunt trauma (52%, 35/66) were managed with ERT. The median pre-hospital time was 64mins [45-89]. At admission, the median injury severity score was 35 [25-48], and 51% (16/30) of patients have lost SOL. ERT was associated with a massive transfusion protocol including 8 RBCs [6-13], 6 FFPs [4-10], and 0 PCs [0-1] in the first 6h. The overall success-to-rescue after ERT at 24-h and 28-d were 27% and 15%, respectively. In case of refractory shock after penetrating trauma, survival was 64% at 24-hours and 47% at 28-days. CONCLUSIONS: ERT integrated into the trauma protocol remains a life-saving procedure that appears to be underutilized in France, despite significant success-to-rescue observed by trained teams for selected patients.

Prognosis of major trauma in patients older than 85 years admitted to the ICU, a registry-based study.

BACKGROUND: The aging population in France and Western Europe is on the rise, particularly among individuals aged 65 years and older. Although older adults are susceptible to traumatic injuries, they constitute a minority of trauma center admissions especially those aged 85 and above. The aim of our study was to investigate the prognostic factors for mortality among the older old population (aged 85 years and above) managed in ICU of Traumabase group trauma centers. METHODS: This retrospective observational cohort study, conducted from 2013 to 2022, analyzed all severely injured older patients (aged ≥ 85 years) managed in 14 ICU trauma centers enrolled in the Traumabase registry. The study examined sociodemographic, clinical, and outcome variables. Frailty was assessed using the Clinical Frailty Scale. RESULTS: Among the 365 older trauma patients, 190 (52.1%) were classified as non-frail (CFS 1-3), 80 (21.9%) as pre-frail (CFS 4,5), and 95 (26%) as frail (CFS 6-9). Falls were the most common mechanism of injury. High mortality rates were observed, with 43.5% ICU mortality and 45.5% mortality at day 30. Factors most associated with ICU mortality included traumatic brain injury (CGS < 13), pre-hospital micromethod hemoglobin < 13 and severity of injury (ISS > 16). CONCLUSION: Factors such as traumatic brain injury and severe hemorrhage (micromethod hemoglobin < 13) and ISS > 16 are associated with ICU mortality in in patients older than 85 years trauma patient. Early geriatric intervention is crucial for optimizing outcomes in this vulnerable population.

A locally optimised machine learning approach to early prognostication of long-term neurological outcomes after out-of-hospital cardiac arrest.

Background: Out-of-hospital cardiac arrest (OHCA) represents a major burden for society and health care, with an average incidence in adults of 67 to 170 cases per 100,000 person-years in Europe and in-hospital survival rates of less than 10%. Patients and practitioners would benefit from a prognostication tool for long-term good neurological outcomes. Objective: We aim to develop a machine learning (ML) pipeline on a local database to classify patients according to their neurological outcomes and identify prognostic features. Methods: We collected clinical and biological data consecutively from 595 patients who presented OHCA and were routed to a single regional cardiac arrest centre in the south of France. We applied recursive feature elimination and ML analyses to identify the main features associated with a good neurological outcome, defined as a Cerebral Performance Category score less than or equal to 2 at six months post-OHCA. Results: We identified 12 variables 24 h after admission, capable of predicting a six-month good neurological outcome. The best model (extreme gradient boosting) achieved an AUC of 0.96 and an accuracy of 0.92 in the test cohort. Conclusion: We demonstrated that it is possible to build accurate, locally optimised prediction and prognostication scores using datasets of limited size and breadth. We proposed and shared a generic machine-learning pipeline which allows external teams to replicate the approach locally.

Postoperative outcomes after total sevoflurane inhalation sedation using a disposable delivery system (Sedaconda-ACD) in cardiac surgery.

Introduction: The COVID-19 pandemic prompted our team to develop new solutions for performing cardiac surgery without intravenous anesthetics due to a shortage of these drugs. We utilized an anesthetic conserving device (Sedaconda-ACD) to administer total inhaled anesthesia because specific vaporizers were unavailable for administering inhaled agents during cardiopulmonary bypass (CPB) in our center. We documented our experience and postoperative cardiovascular outcomes. The primary outcome was the peak level of troponin, with secondary outcomes encompassing other cardiovascular complications. Material and methods: A single-center retrospective study was conducted. We performed a multivariate analysis with a propensity score. This investigation took place at a large university referral center. Participants: Adult patients (age ≥ 18) who underwent elective cardiac surgery with CPB between June 2020 to March 2021. Intervention: During the inclusion period, two anesthesia protocols for the maintenance of anesthesia coexisted-total inhaled anesthesia with Sedaconda-ACD and our classic protocol with intravenous drugs during and after CPB. Primary endpoint: Troponin peak level recorded after surgery (highest level recorded within 48 h following the surgery). Results: Out of the 654 included patients, 454 were analyzed after matching (intravenous group = 297 and inhaled group = 157). No significant difference was found between the groups in postoperative troponin peak levels (723 ng/l vs. 993 ng/l-p = 0.2). Total inhaled anesthesia was associated with a decreased requirement for inotropic medications (OR = 0.53, 95% CI 0.29-0.99, p = 0.04). Conclusion: In our cohort, the Sedaconda-ACD device enabled us to achieve anesthesia without intravenous agents, and we did not observe any increase in postoperative complications. Total inhaled anesthesia with sevoflurane was not associated with a lower incidence of myocardial injury assessed by the postoperative troponin peak level. However, in our cohort, the use of inotropic drugs was lower.

Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma.

The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood. Inflammation is potentially an important but still undervalued factor. Here, we present a first-in-human prospective study using the 18-kDa translocator protein (TSPO) radioligand 18F-DPA714 for PET imaging to allow in vivo neuroimmune activation quantification in patients with coma (n = 17) following either anoxia or traumatic brain injuries in comparison with age- and sex-matched controls. Our findings yielded novel evidence of an early inflammatory component predominantly located within key cortical and subcortical brain structures that are putatively implicated in consciousness emergence and maintenance after severe brain injury (i.e. mesocircuit and frontoparietal networks). We observed that traumatic and anoxic patients with coma have distinct neuroimmune activation profiles, both in terms of intensity and spatial distribution. Finally, we demonstrated that both the total amount and specific distribution of PET-measurable neuroinflammation within the brain mesocircuit were associated with the patient's recovery potential. We suggest that our results can be developed for use both as a new neuroprognostication tool and as a promising biometric to guide future clinical trials targeting glial activity very early after severe brain injury.

Comparing COVID-19 and influenza: Epidemiology, clinical characteristics, outcomes and mortality in the ICU.

RATIONALE: Several authors have compared COVID-19 infection with influenza in the ICU. OBJECTIVE: This study aimed to compare the baseline clinical profiles, care procedures, and mortality outcomes of patients admitted to the intensive care unit, categorized by infection status (Influenza vs. COVID-19). METHODS: Retrospective observational study. Data were extracted from the Toulouse University Hospital from March 2014 to March 2021. To compare survival curves, we plotted the survival at Day-90 using the Kaplan-Meier curve and conducted a log-rank test. Additionally, we performed propensity score matching to adjust for confounding factors between the COVID-19 and influenza groups. Furthermore, we use the CART model for multivariate analysis. RESULTS: The study included 363 patients admitted to the ICU due to severe viral pneumonia: 152 patients (41.9 %) with influenza and 211 patients (58.1 %) with COVID-19. COVID-19 patients exhibited a higher prevalence of cardiovascular risk factors, whereas influenza patients had significantly higher severity scores (SOFA: 10 [6-12] vs. 6 [3-9], p<0.01 and SAPS II: 51 [35-67] vs. 37 [29-50], p<0.001). Overall mortality rates were comparable between the two groups (27.6 % (n = 42) in the influenza group vs. 21.8 % (n = 46) in the COVID-19 group, p=NS). Mechanical ventilation was more commonly employed in the influenza group (76.3 % (n = 116) vs. 59.7 % (n = 126), p<0.001); however, COVID-19 patients required longer durations of mechanical ventilation (18 [9-29] days vs. 13 [5-24] days, p<0.006) and longer hospital stays (23 [13-34] days vs. 18.5 [9-34.5] days, p = 0.009). The CART analysis revealed that the use of extra renal replacement therapy was the most influential prognostic factor in the influenza group, while the PaO2/FiO2-PEEP ratio played a significant role in the COVID-19 group. CONCLUSIONS: Despite differences in clinical presentation and prognostic factors, the mortality rates at 90 days, after adjusting for confounding factors, were similar between COVID-19 and influenza patients.

SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant.

Introduction: In November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating the COVID-19 pandemic over the world. Omicron displays a number of mutations, particularly in the spike protein, leading to specific characteristics including a higher potential for transmission. Although Omicron has caused a significant number of deaths worldwide, it generally induces less severe clinical signs compared to earlier variants. As its impact on blood platelets remains unknown, we investigated platelet behavior in severe patients infected with Omicron in comparison to Delta. Methods: Clinical and biological characteristics of severe COVID-19 patients infected with the Omicron (n=9) or Delta (n=11) variants were analyzed. Using complementary methods such as flow cytometry, confocal imaging and electron microscopy, we examined platelet activation, responsiveness and phenotype, presence of virus in platelets and induction of selective autophagy. We also explored the direct effect of spike proteins from the Omicron or Delta variants on healthy platelet signaling. Results: Severe Omicron variant infection resulted in platelet activation and partial desensitization, presence of the virus in platelets and selective autophagy response. The intraplatelet processing of Omicron viral cargo was different from Delta as evidenced by the distribution of spike protein-positive structures near the plasma membrane and the colocalization of spike and Rab7. Moreover, spike proteins from the Omicron or Delta variants alone activated signaling pathways in healthy platelets including phosphorylation of AKT, p38MAPK, LIMK and SPL76 with different kinetics. Discussion: Although SARS-CoV-2 Omicron has different biological characteristics compared to prior variants, it leads to platelet activation and desensitization as previously observed with the Delta variant. Omicron is also found in platelets from severe patients where it induces selective autophagy, but the mechanisms of intraplatelet processing of Omicron cargo, as part of the innate response, differs from Delta, suggesting that mutations on spike protein modify virus to platelet interactions.

Postoperative delirium is a risk factor of institutionalization after hip fracture: an observational cohort study.

Introduction: Hip fracture is a common clinical problem in geriatric patients often associated with poor postoperative outcomes. Postoperative delirium (POD) and postoperative neurocognitive disorders (NCDs) are particularly frequent. The consequences of these disorders on postoperative recovery and autonomy are not fully described. The aim of this study was to determine the role of POD and NCDs on the need for institutionalization at 3 months after hip fracture surgery. Method: A population-based prospective cohort study was conducted on hip fracture patients between March 2016 and March 2018. The baseline interview, which included a Mini-Mental State Examination (MMSE), was conducted in the hospital after admission for hip fracture. NCDs were appreciated by MMSE scoring evolution (difference between preoperative MMSE and MMSE at day 5 >2 points). POD was evaluated using the Confusion Assessment Method. The primary endpoint was the rate of new institutionalization at 3 months. We used a multivariate analysis to assess the risk of new institutionalization. Results: A total of 63 patients were included. Thirteen patients (20.6%) were newly institutionalized at 3 months. Two factors were significantly associated with the risk of postoperative institutionalization at 3 months: POD (OR = 5.23; 95% CI 1.1-27.04; p = 0.04) and IADL evolution (OR = 1.8; 95% CI 1.23-2.74; p = 0.003). Conclusion: Only POD but not NCDs was associated with the risk of dependency and institutionalization after hip fracture surgery. The prevention of POD appears to be essential for improving patient outcomes and optimizing the potential for returning home.

Influence of arterial blood gases on the renal arterial resistive index in intensive care unit.

BACKGROUND: Renal artery Doppler sonography with resistive index (RI) determination is a noninvasive, fast, and reliable diagnostic tool increasingly used in the intensive care unit (ICU) to predict and assess the reversibility of acute kidney injury (AKI). However, interpreting the RI can be challenging due to numerous influencing factors. While some studies have explored various confounding factors, arterial blood gases have received limited attention. Therefore, our study aims to evaluate the impact of arterial blood gases on the RI in the ICU setting. METHODS: This prospective observational study enrolled ICU patients who required blood gas analysis and had not experienced significant hemodynamic changes recently. The RI was measured using standardized Doppler ultrasound within an hour of the arterial blood gases sampling and analysis. RESULTS: A total of sixty-four patients were included in the analysis. Univariate analysis revealed a correlation between the RI and several variables, including PaCO2 (R = 0.270, p = 0.03), age (R = 0.574, p < 0.0001), diastolic arterial pressure (DAP) (R = - 0.368, p = 0.0028), and SaO2 (R = - 0.284, p = 0.0231). Multivariate analysis confirmed that age > 58 years and PaCO2 were significant factors influencing the RI, with respective odds ratios of 18.67 (p = 0.0003) and 1.132 (p = 0.0267). CONCLUSION: The interpretation of renal arterial RI should take into account thresholds for PaCO2, age, and diastolic arterial pressure. Further studies are needed to develop a comprehensive scoring system that incorporates all these cofactors for a reliable analysis of RI levels. Trial registration This observational study, registered under number 70-0914, received approval from local Ethical Committee of Toulouse University Hospital.

Immunohistologic Features of Cerebral Venous Thrombosis Due to Vaccine-Induced Immune Thrombotic Thrombocytopenia.

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center. METHODS: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination. RESULTS: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall. DISCUSSION: Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process.

Prevalence and risk factors of significant persistent pain symptoms after critical care illness: a prospective multicentric study.

BACKGROUND: Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. METHODS: We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. RESULTS: Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4-12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1-5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1-2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3-4]), prone positioning (OR 3 95% CI [1.4-6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7-3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1-6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. CONCLUSIONS: Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. TRIAL REGISTRATION: NCT04817696. Registered March 26, 2021.

Comprehensive analysis of coagulation factor delivery strategies in a cohort of trauma patients.

PURPOSE: The 5th edition of The European recommendations for the management of major bleeding and coagulopathy following trauma leaves room for various coagulation factor administration strategies. The present study examines these strategies reporting prevalence and timing of administration, quantity dispensed, and transfusion ratios in French trauma centers and their compliance with recommendations alongside associated mortality data. METHODS: All adult patients, admitted directly to participating centers between 2011 and 2019, were extracted from a trauma registry. Two subpopulations were studied: severe hemorrhage (SH) and massive transfusion (MT) groups. RESULTS: A total of 19,396 patients were included, among whom 8.4% (1630) experienced SH and 3% (579) received MT. Within the first 24 hours, 10% received fresh frozen plasma (FFP), rising to 93% and 99% in the subgroups of patients experiencing SH and MT respectively. Only, 8% received fibrinogen concentrate (FC), increasing to 75% and 92% in subgroups SH and MT respectively. Co-administration of FFP and FC became the dominant strategy with 68% of patients at 6 h and 72% at 24 h in SH subgroup. In unadjusted data, mortality was systematically lower in groups that complied with recommendations, a lower mortality than expected was mostly observed in contrast to non-compliant subgroups. The per-patient compliance to studied recommendations was 21% and 22% in SH and MT subgroups. CONCLUSION: The main hemostatic strategy for major bleeding combined the administration of both FFP and FC, favoring an early additional supply of fibrinogen. Compliance with the recommendations was low in SH and MT subgroups.

Externalized Reusable Permanent Pacemaker for Prolonged Temporary Cardiac Pacing in Critical Cardiac Care Units: An Observational Monocentric Retrospective Study.

INTRODUCTION: The use of temporary cardiac pacing is frequent in critical care units for severe bradycardia or electrical storm, but may be associated with frequent and potentially severe complications, especially when indwelling for several days. In some cases, transient indication or ongoing contraindication for a permanent pacemaker justifies prolonged temporary pacing. In that case, the implantation of an active-fixation lead connected to an externalized pacemaker represents a valuable option to increase safety and patient comfort. Yet, evidence remains scarce. We aimed to describe the population receiving prolonged temporary cardiac pacing (PTCP) and their outcomes. METHODS: We retrospectively included all consecutive patients, admitted to our hospital from 2016 to 2021, who underwent PTCP. We collected in-hospital and six-month outcomes. RESULTS: Forty-six patients (median age of 73, 63% male) were included, and twenty-nine (63%) had prior heart disease. Indications for PTCP were found: seventeen (37%) potentially reversible high-grade conduction disorders, fourteen (30%) indications for permanent pacemaker but ongoing infection, seven (15%) cardiac implantable electronic device infections requiring extraction in pacing-dependent patients, seven (15%) severe vagal hyperreactivity in prolonged critical care hospitalizations, and one (2%) recurrent sustained ventricular tachycardia requiring overdrive pacing. The median PTCP duration was nine (5-13) days. Ten (22%) patients exhibited at least one complication during hospitalization. Twenty-six (56.5%) patients required definite device implantation (twenty-five pacemakers and one cardioverter-defibrillator) and twenty (43.5%) did not (fifteen PTCP device removal for recovery and five deaths under PTCP). At six months, two (5%) deaths and two (5%) new infections of a definite implanted device occurred, all in patients with initial active infection. CONCLUSION: The use of prolonged temporary cardiac pacing, with an active -fixation lead connected to an externalized pacemaker, is possible and reasonable; this would allow for the possible recovery or resolution of contraindication for definite device implantation.