Physical and Cognitive Impairment in Acute Respiratory Failure.

Recent research has brought renewed attention to the multifaceted physical and cognitive dysfunction that accompanies acute respiratory failure (ARF). This state-of-the-art review provides an overview of the evidence landscape encompassing ARF-associated neuromuscular and neurocognitive impairments. Risk factors, mechanisms, assessment tools, rehabilitation strategies, approaches to ventilator liberation, and interventions to minimize post-intensive care syndrome are emphasized. The complex interrelationship between physical disability, cognitive dysfunction, and long-term patient-centered outcomes is explored. This review highlights the need for comprehensive, multidisciplinary approaches to mitigate morbidity and accelerate recovery.

Advancing specificity in delirium: The delirium subtyping initiative.

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.

Protocol for a systematic review and meta-analysis assessing conservative versus liberal intravenous fluid administration in patients with sepsis or septic shock at risk of fluid overload.

INTRODUCTION: Intravenous crystalloid fluid resuscitation forms a crucial part of the early intervention bundle for sepsis and septic shock, with the Surviving Sepsis Campaign guidelines recommending a 30 mL/kg fluid bolus within the first hour. Compliance with this suggested target varies in patients with comorbidities such as congestive heart failure, chronic kidney disease and cirrhosis due to concerns regarding iatrogenic fluid overload. However, it remains unclear whether resuscitation with higher fluid volumes puts them at greater risk of adverse outcomes. Thus, this systematic review will synthesise evidence from existing studies to assess the effects of a conservative as compared with a liberal approach to fluid resuscitation in patients at greater perceived risk of fluid overload due to comorbid conditions. METHODS AND ANALYSIS: This protocol was registered on PROSPERO and has been drafted following the checklist of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search MEDLINE, MEDLINE Epub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations, Embase, Embase Classic, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, CINAHL Complete and ClinicalTrials.gov. A preliminary search of these databases was performed from their inception to 30 August 2022. The risk of bias and random errors will be assessed using the revised Cochrane risk-of-bias tool for randomised clinical trials and the Newcastle-Ottawa Scale for case-control and cohort studies. If a sufficient number of comparable studies are identified, we will perform a meta-analysis applying random effects model. We will investigate heterogeneity using a combination of visual inspection of the funnel plot as well as the Egger's test. ETHICS AND DISSEMINATION: No ethics approval is required for this study since no original data will be collected. The findings will be disseminated through peer-reviewed publication and conference presentation. PROSPERO REGISTRATION NUMBER: CRD42022348181.

Sleep Fragmentation and Cognitive Trajectories After Critical Illness.

BACKGROUND: ICU survivors can experience both cognitive dysfunction and persistent sleep disturbances after hospitalization. Sleep disturbances have been linked with cognitive impairment in various patient populations, and the apolipoprotein E (APOE) genotype has been linked to sleep-related impairments in cognition. RESEARCH QUESTION: Is there an association between sleep, long-term cognition, and APOE status in ICU survivors? STUDY DESIGN AND METHODS: We enrolled 150 patients from five centers who had been mechanically ventilated for at least 3 days; 102 patients survived to ICU discharge. Actigraphy and cognitive testing were undertaken at 7 days, 6 months, and 12 months after ICU discharge, and sleep duration, quality, and timing were estimated by actigraphy. APOE single nucleotide polymorphisms were assessed for each patient. RESULTS: Actigraphy-estimated sleep fragmentation, but not total sleep time or interdaily stability (estimate of circadian rhythmicity), was associated with worse cognitive impairment at 7 days of ICU discharge. No actigraphy-estimated variable of sleep estimation at 7 days post-ICU discharge predicted cognitive impairment or persistent sleep abnormalities at 6 and 12 months of follow-up in subsequently assessed survivors. Possessing the APOE ε4 allele was not significantly associated with sleep disturbances and its presence did not modify the risk of sleep-related cognitive impairment at follow-up. INTERPRETATION: Sleep fragmentation estimated by actigraphy was associated with worse cognitive performance in hospital, but not at later time intervals. Further research is needed to better delineate the relationship between persistent sleep disturbances and cognition in larger numbers of ICU survivors. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02086877; URL: www.clinicaltrials.gov.

Optimal VAsopressor TitraTION in patients 65 years and older (OVATION-65): protocol and statistical analysis plan for a randomised clinical trial.

INTRODUCTION: Vasodilatory hypotension is common among intensive care unit (ICU) patients; vasopressors are considered standard of care. However, optimal mean arterial pressure (MAP) targets for vasopressor titration are unknown. The objective of the Optimal VAsopressor TitraTION in patients 65 years and older (OVATION-65) trial is to ascertain the effect of permissive hypotension (vasopressor titration to achieve MAP 60-65 mm Hg) versus usual care on biomarkers of organ injury in hypotensive patients aged ≥65 years. METHODS AND ANALYSIS: OVATION-65 is an allocation-concealed randomised trial in 7 Canadian hospitals. Eligible patients are ≥65 years of age, in an ICU with vasodilatory hypotension, receiving vasopressors for ≤12 hours to maintain MAP ≥65 mm Hg during or after adequate fluid resuscitation, and expected to receive vasopressors for ≥6 additional hours. Patients are excluded for any of the following: active treatment for spinal cord or acute brain injury; vasopressors given solely for bleeding, ventricular failure or postcardiopulmonary bypass vasoplegia; withdrawal of life-sustaining treatments expected within 48 hours; death perceived as imminent; previous enrolment in OVATION-65; organ transplant within the last year; receiving extracorporeal life support or lack of physician equipoise. Patients are randomised to permissive hypotension versus usual care for up to 28 days. The primary outcome is high-sensitivity troponin T, a biomarker of cardiac injury, on day 3. Secondary outcomes include biomarkers of injury to other organs (brain, liver, intestine, skeletal muscle); lactate (a biomarker of global tissue dysoxia); resource utilisation; adverse events; mortality (90 days and 6 months) and cognitive function (6 months). Assessors of biomarkers, mortality and cognitive function are blinded to allocation. ETHICS AND DISSEMINATION: This protocol has been approved at all sites. Consent is obtained from the eligible patient, the substitute decision-maker if the patient is incapable, or in a deferred fashion where permitted. End-of-grant dissemination plans include presentations, publications and social media platforms and discussion forums. TRIAL REGISTRATION NUMBER: NCT03431181.

Sleep and Circadian Rhythm in Critical Illness.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Sleep on the ward in intensive care unit survivors: a case series of polysomnography.

BACKGROUND: Few studies have investigated sleep in patients after intensive care despite the possibility that inadequate sleep might further complicate an acute illness impeding recovery. AIMS: To assess the quality and quantity of a patient's sleep on the ward by polysomnography (PSG) within a week of intensive care unit (ICU) discharge and to explore the prevalence of key in-ICU risk factors for persistent sleep fragmentation. METHODS: We enrolled 20 patients after they have been mechanically ventilated for at least 3 days and survived to ICU discharge. We included all patients over the age of 16 years and excluded patients with advanced cognitive impairment or who were unable to follow simple commands before their acute illness, primary admission diagnosis of neurological injury, uncontrolled psychiatric illness or not fluent in English. RESULTS: Twenty patients underwent an overnight PSG recording on day 7 after ICU discharge (SD, 1 day). ICU survivors provided 292.8 h of PSG recording time with median recording times of 16.8 h (Interquartile range (IQR), 15.0-17.2 h). The median total sleep time per patient was 5.3 h (IQR, 2.6-6.3 h). In a multivariable regression model, postoperative admission diagnosis (P = 0.04) and patient report of poor ICU sleep (P = 0.001) were associated with less slow-wave (restorative) sleep on the wards after ICU discharge. CONCLUSIONS: Patients reported poor sleep while in the ICU, and a postoperative admission diagnosis may identify a high-risk subgroup of patients who may derive greater benefit from interventions to improve sleep hygiene.

Oral neutrophils are an independent marker of the systemic inflammatory response after cardiac bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) is an immuno-reactive state where neutrophils are activated and accumulate in different tissues. Edema and tissue necrosis are the most common sequelae observed, predominantly in the lungs, kidneys, and heart, heralding significant risk for postoperative complications. No method exists to noninvasively assess in vivo neutrophil activity. The objective of this study was to determine if neutrophil recruitment to the oral cavity would correlate with specific biomarkers after coronary bypass surgery (CPB). METHODS: We conducted a single site prospective observational study including non-consecutive adult patients undergoing elective, on-pump CPB. Blood and either oral cavity rinses or swabs were collected pre- and post-CPB. Absolute neutrophil counts from oral samples and serum biomarkers were measured. The association between neutrophil recruitment to the oral cavity, biomarkers and outcomes after CPB were analyzed. RESULTS: CPB was associated with statistically significant increases in oral and blood neutrophil counts, as well as an increase in certain biomarkers over preoperative baseline. Peripheral blood neutrophil count were increased at all time points however statistically significant differences in median oral neutrophil counts were observed only at the time point immediately postoperative, and in what seems to be two unique patient populations (p < 0.001; group 1, median: 1.6×10(5), Interquartile range [IQR], 1.1×10(5) - 4.8×10(5), and group 2, median: 1.9×10(6), IQR, 8.7×10(5) - 4.0×10(6)). CONCLUSIONS: CPB is associated with a transient increase in oral neutrophils that may correlate with the systemic inflammatory response; oral neutrophils may have the ability to discriminate and identify unique patient populations based on their tissue migration.