Search

The article presents a study which tested the hypothesis that the hyperinflammatory subphenotype is associated with worse acute brain dysfunction in patients who are in mechanically ventilated intensive care units (ICUs). Topics include baseline characteristics of the overall cohort and by subphenotype, associations between hyperinflammatory subphenotype and acute brain dysfunction and death, and strengths of the study.

Despite prior publications of clinical practice guidelines related to ventilator liberation, some questions remain unanswered. Many of these questions relate to the details of bedside implementation. We, therefore, formed a guidelines committee of individuals with experience and knowledge of ventilator liberation as well as a medical librarian. Using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we make the following recommendations: (1) We suggest that calculation of a rapid shallow breathing index is not needed to determine readiness for a spontaneous breathing trial (SBT) (conditional recommendation; moderate certainty); (2) We suggest that SBTs can be conducted with or without pressure support ventilation (conditional recommendation, moderate certainty); (3) We suggest a standardized approach to assessment and, if appropriate, completion of an SBT before noon each day (conditional recommendation, very low certainty); and (4) We suggest that FIO2 should not be increased during an SBT (conditional recommendation, very low certainty). These recommendations are intended to assist bedside clinicians to liberate adult critically ill patients more rapidly from mechanical ventilation. [ABSTRACT FROM AUTHOR]

Acute Respiratory Distress Syndrome (ARDS) is one of the most demanding conditions in an Intensive Care Unit (ICU). Management of analgesia and sedation in ARDS is particularly challenging. An expert panel was convened to produce a 'state-of-the-art' article to support clinicians in the optimal management of analgesia/sedation in mechanically ventilated adults with ARDS, including those with COVID-19. Current ICU analgesia/sedation guidelines promote analgesia first and minimization of sedation, wakefulness, delirium prevention and early rehabilitation to facilitate ventilator and ICU liberation. However, these strategies cannot always be applied to patients with ARDS who sometimes require deep sedation and/or paralysis. Patients with severe ARDS may be under-represented in analgesia/sedation studies and currently recommended strategies may not be feasible. With lightened sedation, distress-related symptoms (e.g., pain and discomfort, anxiety, dyspnea) and patient-ventilator asynchrony should be systematically assessed and managed through interprofessional collaboration, prioritizing analgesia and anxiolysis. Adaptation of ventilator settings (e.g., use of a pressure-set mode, spontaneous breathing, sensitive inspiratory trigger) should be systematically considered before additional medications are administered. Managing the mechanical ventilator is of paramount importance to avoid the unnecessary use of deep sedation and/or paralysis. Therefore, applying an 'ABCDEF-R' bundle (R = Respiratory-drive-control) may be beneficial in ARDS patients. Further studies are needed, especially regarding the use and long-term effects of fast-offset drugs (e.g., remifentanil, volatile anesthetics) and the electrophysiological assessment of analgesia/sedation (e.g., electroencephalogram devices, heart-rate variability, and video pupillometry). This review is particularly relevant during the COVID-19 pandemic given drug shortages and limited ICU-bed capacity., Author(s): Gerald Chanques [sup.1] [sup.2], Jean-Michel Constantin [sup.3], John W. Devlin [sup.4] [sup.5], E. Wesley Ely [sup.6] [sup.7] [sup.8], Gilles L. Fraser [sup.9], Céline Gélinas [sup.10], Timothy D. Girard [sup.11], [...]

Abstract Introduction Benzodiazepines and α2 adrenoceptor agonists exert opposing effects on innate immunity and mortality in animal models of infection. We hypothesized that sedation with dexmedetomidine (an α2 adrenoceptor agonist), as compared with lorazepam (a benzodiazepine), would provide greater improvements in clinical outcomes among septic patients than among non-septic patients. Methods In this a priori-determined subgroup analysis of septic vs non-septic patients from the MENDS double-blind randomized controlled trial, adult medical/surgical mechanically ventilated patients were randomized to receive dexmedetomidine-based or lorazepam-based sedation for up to 5 days. Delirium and other clinical outcomes were analyzed comparing sedation groups, adjusting for clinically relevant covariates as well as assessing interactions between sedation group and sepsis. Results Of the 103 patients randomized, 63 (31 dexmedetomidine; 32 lorazepam) were admitted with sepsis and 40 (21 dexmedetomidine; 19 lorazepam) without sepsis. Baseline characteristics were similar between treatment groups for both septic and non-septic patients. Compared with septic patients who received lorazepam, the dexmedetomidine septic patients had 3.2 more delirium/coma-free days (DCFD) on average (95% CI for difference, 1.1 to 4.9), 1.5 (-0.1, 2.8) more delirium-free days (DFD) and 6 (0.3, 11.1) more ventilator-free days (VFD). The beneficial effects of dexmedetomidine were more pronounced in septic patients than in non-septic patients for both DCFDs and VFDs (P-value for interaction = 0.09 and 0.02 respectively). Additionally, sedation with dexmedetomidine, compared with lorazepam, reduced the daily risk of delirium [OR, CI 0.3 (0.1, 0.7)] in both septic and non-septic patients (P-value for interaction = 0.94). Risk of dying at 28 days was reduced by 70% [hazard ratio 0.3 (0.1, 0.9)] in dexmedetomidine patients with sepsis as compared to the lorazepam patients; this reduction in death was not seen in non-septic patients (P-value for interaction = 0.11). Conclusions In this subgroup analysis, septic patients receiving dexmedetomidine had more days free of brain dysfunction and mechanical ventilation and were less likely to die than those that received a lorazepam-based sedation regimen. These results were more pronounced in septic patients than in non-septic patients. Prospective clinical studies and further preclinical mechanistic studies are needed to confirm these results. Trial Registration NCT00095251.

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long‐term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium‐spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. Highlights: Delirium features must be clearly defined, standardized, and operationalized.Large datasets incorporating both clinical and biomarker variables should be analyzed together.Delirium screening should incorporate communication and reasoning. [ABSTRACT FROM AUTHOR]

The article discusses ventilator-associated brain injury (VABI) as a potential complication of mechanical ventilation, presenting evidence from preclinical studies and observational data. It defines VABI as brain injury resulting directly from positive pressure mechanical ventilation, independent of other factors like sedation. It highlights the need for further research to understand the mechanisms of VABI and evaluate potential therapeutic strategies.

Background: 7T MRI allows implementation of high‐resolution quantitative susceptibility mapping (QSM) which can be used to assess the cerebral microvascular/hypoperfusion pathogenic hypothesis in Alzheimer's disease (AD) and in the post‐SARS‐CoV2 setting to explore if there may be similarities in brain changes in these two conditions. The magnetic susceptibility (reflective of tissue iron) of hippocampal subfields was assessed in patients with 1) CSF‐Amyloidß‐status AD; 2) mild COVID‐19 over 6 months previously (Cv); 3) severe COVID‐19 with ICU admission >6 months previously (ICU‐Cv); and 4) age‐matched healthy controls (HC). Methods: 33 participants (10 HC, 14 Cv, 9 ICU‐Cv) for the COVID study and 24 participants (14 AD, 11HC) from AD patients with confirmed CSF‐Amyloidß levels, aged 42‐79, were scanned on a 7T scanner with the following protocol T2* GRE for the AD groups (0.7×0.7×0.7mm3,TE/TR = 20/31ms) and T2* multi‐echo GRE for the Cv groups (0.38×0.38×0.75mm3,TE1/TE2/TR = 8.2/18.4/24ms). Data were processed using QSMbox1 to produce susceptibility maps. PSIR (0.55×0.55×0.55mm3,TE/TR = 3.1/6.9ms) and T2‐weighted FSE (0.38×0.39×1.5mm3, TE/TR = 117/5900ms) images were used to segment the hippocampal subfields (Figure 1)2. One‐way analyses were used in SPSS for comparison between the HC group and each of the Cv, ICU‐Cv, and AD groups. Results: There was no change in susceptibility for the whole hippocampus between AD and HC, but there was a significant difference for the DG subfield (p = 0.045), Figure 2. For COVID patients, there was a significant difference between the susceptibility of the whole hippocampus in the ICU‐Cv group (p = 0.035), but not in the Cv group (p = 0.788), Figure 3, compared to HC. In subfield analyses there was a trend towards decreased susceptibility in the subiculum, an area known to be affected by Alzheimer pathology, in the ICU‐Cv group (p = 0.032) compared to HC. Conclusion: The lower susceptibility within the hippocampal structures observed in AD and ICU‐Cv patients may reflect less iron either from cerebral hypoperfusion or vascular injuries in AD or additionally result from sequelae of hypoxaemia in ICU‐Cv. The study provides preliminary evidence of detectable in vivo microstructural changes in hippocampal subfields in both AD and post‐COVID settings. Funding: Medical Research Council, UK (MR/T005580/1); National Institute of Health, USA (1R56AG074467‐01) References: 1. https://doi.org/10.1016/j.neuroimage.2018.07.065 2. https://doi.org/10.1002/hbm.22627 [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has disproportionately affected ethno‐racial minority populations and people with greater social deprivation. It is unknown whether such disparities influence research participation for investigations of long‐term neuro‐cognitive effects of SARS‐CoV‐2 infection. Method: Across 3 US and 1 UK sites, we are enrolling a multi‐racial cohort of SARS‐CoV‐2 infected individuals and age, sex, race‐matched non‐infected controls. Utilizing harmonized protocols for cognitive assessments and 7‐Tesla MRI, we aim to provide ultra‐high‐field data on natural history of COVID‐19 driven microstructural and microvascular cerebral changes and associated cognitive trajectories. We will also compare the imaging markers to those observed in an existing cohort of early onset Alzheimer's Disease and Related Dementias (ADRD). We analyzed screening and enrollment data to determine potential age, sex, race, ethnicity, and social deprivation disparities in research participation. We derived address‐based Area Deprivation Index (ADI) (scale 1 ‐10), with higher ADI indicating greater deprivation. Logistic regression models were fit to evaluate associates of non‐response and refusal. Odds Ratios (OR) and 95% confidence intervals (CI) are reported. Result: Over a 11‐month period, at a single US site, a total of 1,046 SARS‐CoV‐2 infected people and their controls were contacted, and 379 (36.2%) responded. In univariable analyses, non‐response was associated with younger age, male sex, non‐White race, and higher ADI (Table 1). In the fully adjusted model, non‐White race was independently associated with higher likelihood of non‐response [OR (CI) for Black vs. White: 1.49 (1.04, 2.12) and for Asian vs. White: 1.88 (1.28, 2.76)]., Independent of race, higher ADI was also associated with likelihood of non‐response (Table 2 and Figure 1). Among the responders, 228 (60.2%) refused. Although, no socio‐demographic factors were significantly associated with likelihood of refusal, the point estimates in the fully adjusted model suggest potential racial disparities in providing consent (Tables 1 and 2). Aggregated data from all sites will be presented. Conclusion: It is imperative to recognize and mitigate persistent disparities in the COVID‐19 pandemic, particularly pertaining to participation in long‐COVID research. Mechanisms of such persistent disparities need to be studied in context of cultures, beliefs, access, and clinical factors. [ABSTRACT FROM AUTHOR]

Background: Patients with acute respiratory failure have multiple risk factors for disability following their intensive care unit stay. Interventions to facilitate independence at hospital discharge may be more effective if personalized for patient subtypes. Objectives: To identify subtypes of patients with acute respiratory failure requiring mechanical ventilation and compare post–intensive care functional disability and intensive care unit mobility level among subtypes. Methods: Latent class analysis was conducted in a cohort of adult medical intensive care unit patients with acute respiratory failure receiving mechanical ventilation who survived to hospital discharge. Demographic and clinical medical record data were collected early in the stay. Clinical characteristics and outcomes were compared among subtypes by using Kruskal-Wallis tests and χ2 tests of independence. Results: In a cohort of 934 patients, the 6-class model provided the optimal fit. Patients in class 4 (obesity and kidney impairment) had worse functional impairment at hospital discharge than patients in classes 1 through 3. Patients in class 3 (alert patients) had the lowest magnitude of functional impairment (P <.001) and achieved the earliest out-of-bed mobility and highest mobility level of all subtypes (P <.001). Conclusions: Acute respiratory failure survivor subtypes identified from clinical data available early in the intensive care unit stay differ in post–intensive care functional disability. Future research should target high-risk patients in early rehabilitation trials in the intensive care unit. Additional investigation of contextual factors and mechanisms of disability is critical to improving quality of life in acute respiratory failure survivors. [ABSTRACT FROM AUTHOR]