Search

Delirium is a common condition in the ICU, and while non-pharmacological interventions are recommended, pharmacological treatment with haloperidol is often used despite recommendations against it. Two recent trials, the MIND-USA Study and the AID-ICU trial, examined the effectiveness and safety of haloperidol for delirium treatment in ICU patients. Both trials found no significant difference in their primary outcomes, but the AID-ICU trial did find lower mortality rates in the haloperidol group. The trials were well-designed and had low bias, but the difference in mortality outcomes is surprising and requires further investigation. Table 1 in the document provides detailed information on the trials' characteristics, interventions, and outcomes. While there were some differences in definitions and participant characteristics, subgroup analyses found no evidence of treatment effect heterogeneity. Differences in exposure to open-label antipsychotics may explain some of the differences in mortality outcomes. The AID-ICU trial showed potential benefits of haloperidol for days alive and out of the hospital, days alive without delirium or coma, and mortality. However, there is still uncertainty about the effects of haloperidol in delirious ICU patients, and more research is needed to understand its mechanisms of action and long-term outcomes. [Extracted from the article]

Editorials Critical Care Medicine www.ccmjournal.org 377 I n this issue of Critical Care Medicine, Vallet et al (1) present a high-quality systematic review of 129 epidemiologic studies published since 2000 that examined mortality after critical illness among people greater than or equal to 75 years old. Finally, research strongly suggests that social determinants of health and health behaviors account for ~60% of health outcomes (13). Editorials Critical Care Medicine www.ccmjournal.org 375 ability to predict impending death may be improved by novel technological tools (e.g., biomarker screening from small blood samples and noninvasive microchip monitoring of vitals). However, such a characterization would be a major contribution that would help patients make decisions about their own care preferences, help health systems design high-quality critical care delivery services, and help critical care providers better advocate for upstream and downstream resources to improve patients' outcomes. [Extracted from the article]

Objectives: Little is known about frailty that develops following critical illness. We sought to describe the prevalence of newly acquired frailty, its clinical course, and the co-occurrence of frailty with disability and cognitive impairment in survivors of critical illness.Design: Longitudinal prospective cohort study.Setting: Medical and surgical ICUs at five U.S. centers.Patients: Adult patients treated for respiratory failure and/or shock.Measurements and Main Results: We measured frailty with the Clinical Frailty Scale at baseline (i.e., study enrollment) and at 3 and 12 months postdischarge. We constructed alluvial diagrams to describe the course of frailty and Venn diagrams to describe the overlap of frailty with disability in activities of daily living and cognitive impairment. We included 567 participants a median (interquartile range) of 61 years old (51-70 yr old) with a high severity of illness (Acute Physiology and Chronic Health Evaluation II of 23). Frailty (Clinical Frailty Scale scores ≥ 5) was present in 135 of 567 (24%) at baseline, 239 of 530 (45%) at 3 months, and 163 of 445 (37%) at 12 months. Of those with frailty at 3- or 12-month follow-up, 61% were not frail at baseline. Transition to a worse frailty state occurred in 242 of 530 of patients (46%) between baseline and 3 months and in 179 of 445 of patients (40%) between baseline and 12 months. There were 376 patients with frailty, disability, or cognitive impairment at 3-month follow-up. Of these, 53 (14%) had frailty alone. At 12 months, 276 patients had frailty, disability, or cognitive impairment, 37 (13%) of whom had frailty alone.Conclusions: Frailty is common among survivors of critical illness. In the majority, frailty is newly acquired. Roughly one in seven had frailty without co-occurring disability or cognitive impairment. Studies to understand outcomes of frailty that develops as the result of a critical illness and to identify modifiable risk factors for this potentially reversible syndrome are needed. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest older patients hospitalized for community-acquired pneumonia are at risk for new-onset cognitive impairment. The characteristics of long-term cognitive impairment after pneumonia, however, have not been elucidated.Objective: To characterize long-term cognitive impairment among adults of all ages hospitalized for community-acquired pneumonia.Design: Prospective cohort study.Participants: Adults without severe preexisting cognitive impairment who were hospitalized with community-acquired pneumonia.Main Measures: At enrollment, we estimated baseline cognitive function with the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). At 2- and 12-month follow-up, we assessed cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and tests of executive function, diagnosing cognitive impairment when results were ≥ 1.5 standard deviations below published age-adjusted means for the general population. We also identified subtypes of mild cognitive impairment using standard definitions.Key Results: We assessed 58 (73%) of 80 patients who survived to 2-month follow-up and 57 (77%) of 74 who survived to 12-month follow-up. The median [range] age of survivors tested was 57 [19-97] years. Only 8 (12%) had evidence of mild cognitive impairment at baseline according to the Short IQCODE, but 21 (38%) at 2 months and 17 (30%) at 12 months had mild cognitive impairment per the RBANS. Moderate-to-severe cognitive impairment was common among adults ≥ 65 years [4/13 (31%) and 5/13 (38%) at 2 and 12 months, respectively] but also affected many of those < 65 years [10/43 (23%) and 8/43 (19%) at 2 and 12 months, respectively]. Deficits were most often noted in visuospatial function, attention, and memory.Conclusions: A year after hospitalization for community-acquired pneumonia, moderate-to-severe impairment in multiple cognitive domains affected one-third of patients ≥ 65 years old and 20% of younger patients, and another third of survivors had mild cognitive impairment. [ABSTRACT FROM AUTHOR]

Objectives: Acute kidney injury frequently complicates critical illness and is associated with high morbidity and mortality. Frailty is common in critical illness survivors, but little is known about the impact of acute kidney injury. We examined the association of acute kidney injury and frailty within a year of hospital discharge in survivors of critical illness.Design: Secondary analysis of a prospective cohort study.Setting: Medical/surgical ICU of a U.S. tertiary care medical center.Patients: Three hundred seventeen participants with respiratory failure and/or shock.Interventions: None.Measurements and Main Results: Acute kidney injury was determined using Kidney Disease Improving Global Outcomes stages. Clinical frailty status was determined using the Clinical Frailty Scale at 3 and 12 months following discharge. Covariates included mean ICU Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score as well as baseline comorbidity (i.e., Charlson Comorbidity Index), kidney function, and Clinical Frailty Scale score. Of 317 patients, 243 (77%) had acute kidney injury and one in four patients with acute kidney injury was frail at baseline. In adjusted models, acute kidney injury stages 1, 2, and 3 were associated with higher frailty scores at 3 months (odds ratio, 1.92; 95% CI, 1.14-3.24; odds ratio, 2.40; 95% CI, 1.31-4.42; and odds ratio, 4.41; 95% CI, 2.20-8.82, respectively). At 12 months, a similar association of acute kidney injury stages 1, 2, and 3 and higher Clinical Frailty Scale score was noted (odds ratio, 1.87; 95% CI, 1.11-3.14; odds ratio, 1.81; 95% CI, 0.94-3.48; and odds ratio, 2.76; 95% CI, 1.34-5.66, respectively). In supplemental and sensitivity analyses, analogous patterns of association were observed.Conclusions: Acute kidney injury in survivors of critical illness predicted worse frailty status 3 and 12 months postdischarge. These findings have important implications on clinical decision making among acute kidney injury survivors and underscore the need to understand the drivers of frailty to improve patient-centered outcomes. [ABSTRACT FROM AUTHOR]

Background: This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society (ATS) and the American College of Chest Physicians (CHEST).Methods: A multidisciplinary panel posed six clinical questions in a population, intervention, comparator, outcomes (PICO) format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, confidence in the evidence, certainty about how much the public values the main outcomes, magnitude and balance of desirable and undesirable outcomes, resources and costs associated with the intervention, impact on health disparities, and acceptability and feasibility of the intervention.Results: Evidence-based recommendations were formulated and graded initially by subcommittees and then modified following full panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation.Conclusions: The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and CHEST. [ABSTRACT FROM AUTHOR]

A growing body of literature has shown that survivors of critical illness often struggle with cognitive impairment that persists months to years after hospital discharge. We describe the epidemiology of this form of cognitive impairment-which we refer to as critical illness brain injury-and review the history and maturation of the investigation of this previously unrecognized, yet common problem. We then review the characteristics of critical illness brain injury, which can vary in severity and typically affects multiple domains of cognition. Finally, we examine known risk factors for critical illness brain injury and, based on these data, suggest approaches to patient management. [ABSTRACT FROM AUTHOR]

The effect of statins on functional status in older patients is unclear. Statins might carry a deleterious effect on muscle function leading to myopathy and therefore affecting functional recovery. We evaluated the relationship between statin exposure at in-hospital rehabilitation admission and functional outcome at discharge. This was a retrospective cohort study of older patients 70 years and older consecutively admitted to an in-hospital rehabilitation after an acute hospitalization. Statin exposure was measured at the time of rehabilitation admission. Functional status was defined with the Barthel Index (BI) score at the time of discharge. A multi-variable linear regression model was used to evaluate the association between statin exposure and functional status at discharge adjusting for potential confounders through a propensity score for statin exposure. A total of 2435 patients were included. The cohort had a mean age of 81.1 years. Of these 9% ( n=220) were on statins at the time of admission. In the multi-variable analysis, the use of statins at the time of admission was independently associated with an improved functional status at discharge (point estimate 5.2; 95% confidence interval 1.5-8.9; p<0.01) after adjusting for relevant confounders. Patients who were receiving statins at the time of admission had a BI score 5 points higher compared to those who were not receiving statins. The use of statins was overall safe in a group of co-morbid older patients undergoing rehabilitation training after an acute hospitalization. Additionally, a possible benefit was found given the positive association between statin use and higher functional status at discharge. [ABSTRACT FROM AUTHOR]

Delirium is a common condition in intensive care unit (ICU) patients and is associated with negative outcomes. While non-pharmacologic treatments have shown some success in reducing delirium, there is currently no recommended pharmacologic treatment. Haloperidol, a commonly used medication, has not been found to be more effective than a placebo in reducing delirium. However, a recent study found that haloperidol may have a positive effect on long-term mortality in ICU patients. Further research is needed to determine the optimal dose of haloperidol and to explore other factors that may influence long-term outcomes. ICU clinicians should not increase their use of haloperidol until more research is conducted. [Extracted from the article]

Objectives: Many patients, due to a combination of illness and sedatives, spend a considerable amount of time in a comatose state that can include time in burst suppression. We sought to determine if burst suppression measured by processed electroencephalography during coma in sedative-exposed patients is a predictor of post-coma delirium during critical illness. Design: Observational convenience sample cohort. Setting: Medical and surgical ICUs in a tertiary care medical center. Patients: Cohort of 1 24 mechanically ventilated ICU patients. Interventions: None. Measurements and Main Results: Depth of sedation was monitored twice daily using the Richmond Agitation-Sedation Scale and continuously monitored by processed electroencephalography. When noncomatose, patients were assessed for delirium twice daily using Confusion Assessment Method for the ICU. Multiple logistic regression and Cox proportional hazards regression were used to assess associations between time in burst suppression and both prevalence and time to resolution of delirium, respectively, adjusting for time in deep sedation and a principal component score consisting of Acute Physiology and Chronic Health Evaluation II score and cumulative doses of sedatives while comatose. Of the 1 24 patients enrolled and monitored, 55 patients either never had coma or never emerged from coma, yielding 69 patients for whom we performed these analyses; 42 of these 69 (61%) had post-coma delirium. Most patients had burst suppression during coma, although often short-lived (median [interquartile range] time in burst suppression, 6.4 [1 -58] min). After adjusting for covariates, even this short time in burst suppression independently predicted a higher prevalence of post-coma delirium (odds ratio, 4.16; 95% Cl, 1.27-13.62; p = 0.02) and a lower likelihood (delayed) resolution of delirium (hazard ratio, 0.78; 95% Cl, 0.53-0.98; p = 0.04). Conclusions: Time in burst suppression during coma, as measured by processed electroencephalography, was an independent predictor of prevalence and time to resolution of postcoma/ post-deep sedation delirium. These findings of this single-center investigation support lighter sedation strategies. [ABSTRACT FROM AUTHOR]

Objective: The updated clinical practice guidelines for the management of pain, agitation, and delirium recommend either daily sedation interruption or maintaining light levels of sedation as methods to improve outcomes for patients who are sedated in the ICU. We review the evidence supporting both methods and discuss whether one method is preferable or if they should be used concurrently. Data Source: Original research articles identified using the electronic PubMed database. Study Selection and Data Extraction: Randomized controlled trials and large prospective cohort studies of mechanically ventilated ICU patients requiring sedation were selected. Data Synthesis: The methods of daily sedation interruption and targeting light sedation levels (including avoidance of deep sedation) are safe in critically ill patients with no increase, and a potential decrease, in long-term psychiatric disturbances. Randomized trials comparing these methods with standard care, which has traditionally involved moderate to heavy sedation, found that both methods reduced duration of mechanical ventilation and ICU length of stay. Additionally, one trial noted that daily sedation interruption paired with spontaneous breathing trials improved 1-year survival, whereas a large observational study found that deep sedation was associated with decreased 180-day survival. Two common characteristics of these interventions in trials showing benefits were avoidance of deep levels of sedation and significant reductions in sedative doses, especially benzodiazepines. Thus, combining targeted light sedation with daily sedation interruption may be more beneficial than either method alone if sedative doses are reduced and arousal and mobility are facilitated during the ICU stay. Conclusion: Daily sedation interruption and targeting light sedation levels are safe and proven to improve outcomes for sedated CU patients when these approaches result in reduced sedative exposure and facilitate arousal. It remains unclear as to whether one approach is superior, and further studies are needed to evaluate which patients benefit most from either or both techniques. [ABSTRACT FROM AUTHOR]

Current research indicates that the majority of survivors of critical illness develop post-intensive care syndrome (PICS), which includes new or worsening cognitive or psychiatric disorders that persist for months to years after critical illness. These cognitive impairments and psychiatric disorders are profound and long-lasting, adversely affecting survivors' daily functioning, ability to return to work, and quality of life, as well as altering the lives of their family members. The medical effects of cognitive and psychiatric disability after critical illness translate directly into a large economic burden. A large and growing body of intensive care unit (ICU) survivors with cognitive and psychiatric morbidities presents challenges for research and identification of best practices and interventions, both during and after the ICU, including rehabilitation to prevent or remediate long-term neurological outcomes. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the association between duration of delirium in the intensive care unit and long-term cognitive impairment after critical illness requiring mechanical ventilation. The setting of the prospective cohort study was a medical intensive care unit in a large U.S. community hospital. The patients involved in the study underwent comprehensive cognitive assessments months after discharge.

The article presents a placebo-controlled trial of antipsychotics for patients in the intensive care unit (ICU) suffering from delirium and a test if antipsychotics improve days alive for patients without delirium. The study involved 101 ICU patients who received haloperidol or zipradone, or placebo. The study found the feasibility of a randomized, placebo-controlled trial of antipsychotics for delirium in ICU patients and suggests the need to examine the appropriateness of using antipsychotics.

The article presents a study on the application of time-varying Cox regression for observational cohort studies. It aims to assess the bias introduced by using the method time-fix in analyzing the effect of a time-varying exposure in the intensive care unit (ICU). It concludes that using a time-fixed analytic approach in learning the relationship of exposure and clinical outcomes can result in considerable bias.

The authors discuss the findings of their study to determine the effectiveness of a protocol pairing spontaneous awakening trials (SATs or sedative interruption) with spontaneous breathing trials (SBTs) for the removal of sedation and mechanical ventilation from critically ill patients. Patients on mechanical ventilation in intensive care units were randomly assigned to daily SAT followed by SBT, or sedation per usual care plus daily SBT (controls). The authors found that this protocol offers improved outcomes and suggest it should become routine practice.

The article focuses the mechanical ventilation (MV) in acute respiratory distress syndrome (ARDS), a sudden, life-threatening lung failure. Mechanical ventilation is an indispensable component of the care of patients with ARDS, and a large number of randomized controlled trials have been conducted evaluating the efficacy and safety of various methods of MV for the treatment of ARDS. The article reviews these trials and makes recommendations regarding the use of mechanical ventilation.

This Viewpoint discusses the possibility that survivors of severe COVID-19 will experience persistent symptoms similar to those of post-sepsis syndrome and reviews best practices for promoting recovery from intensive care illness, including referral to physical and occupational therapy, medication optimization, and structured exercise. [ABSTRACT FROM AUTHOR]

The connection between biomarkers measured early during critical illness and subsequent delirium severity is novel and suggests that an early blood-based assessment may have prognostic utility among ICU patients with delirium. Although well-validated delirium assessment tools are widely used, their sensitivity varies in different settings ([14], [15]) and specificity of delirium as a predictor of long-term outcomes is limited. Yet, with this work, the evidence implicating neuroinflammation and astrocyte injury as mechanisms of delirium during critical illness grows, and the field takes a step toward a delirium assay. [Extracted from the article]

Prominent among the numerous events that contribute to the enhanced susceptibility of elderly patients to infection is the decline of immune function that accompanies aging. Elderly patients experience a marked decline in cell-mediated immune function and reduced humoral immune function. Age-dependent defects in T and B cell function are readily demonstrable in elderly patients, yet the essential elements of innate immunity are remarkably well preserved. The cytokine and chemokine signaling networks are altered in elderly patients and tends to favor a type 2 cytokine response over type 1 cytokine responses. The induction of proinflammatory cytokines after septic stimuli is not adequately controlled by anti-inflammatory mechanisms in elderly persons. This immune dysregulation is accompanied by a more pronounced procoagulant state in older patients. These molecular events function in concert to render elderly patients at excess risk for mortality from severe sepsis and septic shock. [ABSTRACT FROM AUTHOR]

Up to 60% of patients who develop severe sepsis in the United States are &ges;65 years of age, and the incidence of sepsis in this population is steadily increasing. Elderly individuals have an increased risk of developing sepsis, compared with younger patients, because of frequent comorbidities, institutionalization, declining performance status, and altered immune function. The clinical presentation of older patients with sepsis is often atypical, leading to a difficult and delayed diagnosis. Although increasing age appears to confer a high risk of death due to severe sepsis, recent evidence shows that many older patients respond well to selected interventions when the interventions are initiated in a timely fashion. Newly published clinical practice guidelines outline key recommendations regarding the treatment of patients with severe sepsis. Clinicians must be aware of the level of evidence in support of various interventions and must keenly screen older survivors for ongoing deficits that will limit their functional recovery. [ABSTRACT FROM AUTHOR]

• On days with delirium, stroke patients had more generalized EEG abnormalities, even when excluding those with anesthetic use. • Delirious stroke patients had fewer focal EEG abnormalities, though these differences were not significant. • These findings may reinforce the diffuse nature of delirium, even in patients with structural brain lesions. Delirium is an acute cognitive disorder associated with multiple electroencephalographic (EEG) abnormalities in non-neurological patients, though specific EEG characteristics in patients with stroke remain unclear. We aimed to compare the prevalence of EEG abnormalities in stroke patients during delirium episodes with periods that did not correspond to delirium. We retrospectively analyzed clinical EEG reports for stroke patients who received daily delirium assessments as part of a prospective study. We compared the prevalence of EEG features corresponding to patient-days with vs. without delirium, including focal and generalized slowing, and focal and generalized epileptiform abnormalities (EAs). Among 58 patients who received EEGs, there were 192 days of both EEG and delirium monitoring (88% [n = 169] corresponding to delirium). Generalized slowing was significantly more prevalent on days with vs. without delirium (96% vs. 57%, p = 0.03), as were bilateral or generalized EAs (38% vs. 13%, p = 0.03). In contrast, focal slowing (53% vs. 74%, p = 0.11) and focal EAs were less prevalent on days with delirium (38% vs. 48%, p = 0.37), though these differences were not statistically significant. We found a higher prevalence of generalized but not focal EEG abnormalities in stroke patients with delirium. These findings may reinforce the diffuse nature of delirium-associated encephalopathy, even in patients with discrete structural lesions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine associations between markers of inflammation and endogenous anticoagulant activity with delirium and coma during critical illness. Methods: In this prospective cohort study, we enrolled adults with respiratory failure and/or shock treated in medical or surgical intensive care units (ICUs) at 5 centers. Twice per day in the ICU, and daily thereafter, we assessed mental status using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). We collected blood samples on study days 1, 3, and 5, measuring levels of C-reactive protein (CRP), interferon gamma (IFN-γ), interleukin (IL)-1 beta (IL-1β), IL-6, IL-8, IL-10, IL-12, matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 1 (TNFR1), and protein C using validated protocols. We used multinomial logistic regression to analyze associations between biomarkers and the odds of delirium or coma versus normal mental status the following day, adjusting for age, sepsis, Sequential Organ Failure Assessment (SOFA), study day, corticosteroids, and sedatives. Results: Among 991 participants with a median age (interquartile range, IQR) of 62 [53–72] years and enrollment SOFA of 9 [7–11], higher concentrations of IL-6 (odds ratio [OR] [95% CI]: 1.8 [1.4–2.3]), IL-8 (1.3 [1.1–1.5]), IL-10 (1.5 [1.2–1.8]), TNF-α (1.2 [1.0–1.4]), and TNFR1 (1.3 [1.1–1.6]) and lower concentrations of protein C (0.7 [0.6–0.8])) were associated with delirium the following day. Higher concentrations of CRP (1.4 [1.1–1.7]), IFN-γ (1.3 [1.1–1.5]), IL-6 (2.3 [1.8–3.0]), IL-8 (1.8 [1.4–2.3]), and IL-10 (1.5 [1.2–2.0]) and lower concentrations of protein C (0.6 [0.5–0.8]) were associated with coma the following day. IL-1β, IL-12, and MMP-9 were not associated with mental status. Conclusion: Markers of inflammation and possibly endogenous anticoagulant activity are associated with delirium and coma during critical illness. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Mild Cognitive Impairment and Risk of Critical Illness" by Teeters et al.

The authors comment on a study on post-extubation respiratory support in the pediatric intensive care unit (PICU). They note the differences between high flow nasal cannula (HFNC) and continuous positive airway pressure (CPAP) as first-line support for assistance in breathing in children. They identify potential limitations of the study including non-adherence of respiratory support switch events to study procedures and differences in patient inclusion criteria in the HFNC and CPAP cohorts.

The authors comment on a study of the incidence of and risk factors for acute lung injury and acute respiratory distress syndrome (ALI/ARDS) published by R. E. Hoesch and colleagues within the issue. The study involved patients who were mechanically ventilated for >48 hours in the intensive care unit (ICU). Among the risk factors for ALI/ARDS assessed in the study were pneumonia and loss of cough. They cite the link between mechanical ventilation and high ALI/ARDS incidence.

The author reflects on a study concerning the psychological risk of having post-traumatic stress disorder (PTSD) among intensive care unit (ICU) patients. He features the assessment conducted by Dr. Treggiari and colleagues wherein they examined the possible psychological outcomes among patients given lighter sedation and those given with heavy sedation. According to the examination's outcome, light sedation does not contribute to the risk of having mental illness on ICU patients.

A response to a letter to the editor by the authors of the article "Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial" from a previous issue is presented.

The author reflects on a study related to biomarkers of cardiac injury in patients with the acute respiratory distress syndrome (ARDS). Such biomarkers have proved useful in the assessment of the cardiac effects of critical illness. The findings add to a growing body of evidence suggesting that cardiac injury may play an important role in determining the outcome of patients with ARDS.

Objectives: To describe the frequency of co-occurring newly acquired cognitive impairment, disability in activities of daily livings, and depression among survivors of a critical illness and to evaluate predictors of being free of post-intensive care syndrome problems.Design: Prospective cohort study.Setting: Medical and surgical ICUs from five U.S. centers.Patients: Patients with respiratory failure or shock, excluding those with preexisting cognitive impairment or disability in activities of daily livings.Interventions: None.Measurements and Main Results: At 3 and 12 months after hospital discharge, we assessed patients for cognitive impairment, disability, and depression. We categorized patients into eight groups reflecting combinations of cognitive, disability, and mental health problems. Using multivariable logistic regression, we modeled the association between age, education, frailty, durations of mechanical ventilation, delirium, and severe sepsis with the odds of being post-intensive care syndrome free. We analyzed 406 patients with a median age of 61 years and an Acute Physiology and Chronic Health Evaluation II of 23. At 3 and 12 months, one or more post-intensive care syndrome problems were present in 64% and 56%, respectively. Nevertheless, co-occurring post-intensive care syndrome problems (i.e., in two or more domains) were present in 25% at 3 months and 21% at 12 months. Post-intensive care syndrome problems in all three domains were present in only 6% at 3 months and 4% at 12 months. More years of education was associated with greater odds of being post-intensive care syndrome free (p < 0.001 at 3 and 12 mo). More severe frailty was associated with lower odds of being post-intensive care syndrome free (p = 0.005 at 3 mo and p = 0.048 at 12 mo).Conclusions: In this multicenter cohort study, one or more post-intensive care syndrome problems were present in the majority of survivors, but co-occurring problems were present in only one out of four. Education was protective from post-intensive care syndrome problems and frailty predictive of the development of post-intensive care syndrome problems. Future studies are needed to understand better the heterogeneous subtypes of post-intensive care syndrome and to identify modifiable risk factors. [ABSTRACT FROM AUTHOR]

Background: An update of evidence-based guidelines concerning liberation from mechanical ventilation is needed as new evidence has become available. The American College of Chest Physicians (CHEST) and the American Thoracic Society (ATS) have collaborated to provide recommendations to clinicians concerning liberation from the ventilator.Methods: Comprehensive evidence syntheses, including meta-analyses, were performed to summarize all available evidence relevant to the guideline panel's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, and the results were summarized in evidence profiles. The evidence syntheses were discussed and recommendations developed and approved by a multidisciplinary committee of experts in mechanical ventilation.Results: Recommendations for three population, intervention, comparator, outcome (PICO) questions concerning ventilator liberation are presented in this document. The guideline panel considered the balance of desirable (benefits) and undesirable (burdens, adverse effects, costs) consequences, quality of evidence, feasibility, and acceptability of various interventions with respect to the selected questions. Conditional (weak) recommendations were made to use inspiratory pressure augmentation in the initial spontaneous breathing trial (SBT) and to use protocols to minimize sedation for patients ventilated for more than 24 h. A strong recommendation was made to use preventive noninvasive ventilation (NIV) for high-risk patients ventilated for more than 24 h immediately after extubation to improve selected outcomes. The recommendations were limited by the quality of the available evidence.Conclusions: The guideline panel provided recommendations for inspiratory pressure augmentation during an initial SBT, protocols minimizing sedation, and preventative NIV, in relation to ventilator liberation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the editorial on the impact immortal time bias in critical care research in the previous issue.

A response by the authors to a letter to the editor about their article "Effect of Sedation With Dexmedetomidine vs Lorazepam on Acute Brain Dysfunction in Mechanically Ventilated Patients" from the December 12, 2007 issue is presented.

The large and growing population of patients currently struggling with postacute sequelae of COVID-19 ([1]), also known as long COVID, has focused a spotlight on a fact long recognized by survivors of critical illness - short-term recovery from a seemingly acute illness is often just the beginning of a much longer journey. If depression and anxiety were underdiagnosed in the setting of cognitive impairment, which was more common in older critical illness survivors with socioeconomic disadvantage, the signal between socioeconomic disadvantage and post-critical illness mental health symptoms would have been diminished. Among the millions of patients who survive an acute life-threatening illness or injury each year, new or worsening deficits in physical ([2]), cognitive ([3]), and psychiatric function ([4]) are collectively known as post-intensive care syndrome (PICS), a disorder that affects up to 60% of patients whose acute illness required life-support measures (such as mechanical ventilation) ([5]). [Extracted from the article]

Importance: Agitation is common in mechanically ventilated ICU patients, but little is known about physician attitudes regarding agitation in this setting. Objectives: To characterize physician attitudes regarding agitation in mechanically ventilated ICU patients. Design, Setting, and Participants: We surveyed critical care physicians within a multicenter health system in Western Pennsylvania, assessing attitudes regarding agitation during mechanical ventilation and use of and confidence in agitation management options. We used quantitative clinical vignettes to determine whether agitation influences confidence regarding readiness for extubation. We sent our survey to 332 critical care physicians, of whom 80 (24%) responded and 69 were eligible (had cared for a mechanically ventilated patient in the preceding three months). Main Outcomes and Measures: Respondent confidence in patient readiness for extubation (0–100%, continuous) and frequency of use and confidence in management options (1–5, Likert). Results: Of 69 eligible responders, 61 (88%) agreed agitation is common and 49 (71%) agreed agitation is a barrier to extubation, but only 27 (39%) agreed their approach to agitation is evidence-based. Attitudes regarding agitation did not differ much by practice setting or physician demographics, though respondents working in medical ICUs were more likely (P =.04) and respondents trained in surgery or emergency medicine were less likely (P =.03) than others to indicate that agitation is an extubation barrier. Fifty-three (77%) respondents reported they frequently use non-pharmacologic measures to treat agitation, and 42 (70%) of those who reported they used non-pharmacologic measures during the prior 3 months indicated confidence in their effectiveness. In responses to clinical vignettes, confidence in patient's readiness for extubation was significantly lower if the patient was agitated (P <.001) or tachypneic (P <.001), but the presence of both agitation and tachypnea did not reduce confidence compared with tachypnea alone (P =.24). Conclusions and Relevance: Most critical care physicians consider agitation during mechanical ventilation a common problem and agreed that agitation is a barrier to extubation. Treatment practice varies widely. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU). Methods: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web‑based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities. Results: The ICM‑RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia". Conclusion: This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities. [ABSTRACT FROM AUTHOR]

A substantial proportion of critically ill patients require ventilator support with the majority requiring invasive mechanical ventilation. Timely and safe liberation from invasive mechanical ventilation is a critical aspect of patient care in the intensive care unit (ICU) and is a top research priority for patients and clinicians. In this article, we discuss how to (1) identify candidates for liberation from mechanical ventilation, (2) conduct spontaneous breathing trials (SBTs), and (3) optimize patients for liberation from mechanical ventilation. We also discuss the roles for (4) extubation to noninvasive ventilation and (5) newer modes of mechanical ventilation during liberation from mechanical ventilation. We conclude that, though substantial progress has been made in identifying patients who are likely to be liberated (e.g., through the use of SBTs) and management strategies that speed liberation from the ventilator (e.g., protocolized SBTs, lighter sedation, and early mobilization), many important questions regarding liberation from mechanical ventilation in clinical practice remain unanswered. [ABSTRACT FROM AUTHOR]

Background: Several studies have previously reported the presence of altered cerebral perfusion during sepsis. However, the role of non-invasive neuromonitoring, and the impact of altered cerebral perfusion, in sepsis patients with delirium remains unclear. Methods: We performed a systematic review of studies that used near-infrared spectroscopy (NIRS) and/or transcranial Doppler (TCD) to assess adults (-18 years) with sepsis and delirium. From study inception to July 28, 2020, we searched the following databases: Ovid MedLine, Embase, Cochrane Library, and Web of Science. Results: Of 1546 articles identified, 10 met our inclusion criteria. Although NIRS-derived regional cerebral oxygenation was consistently lower, this difference was only statistically significant in one study. TCD-derived cerebral blood flow velocity was inconsistent across studies. Importantly, both impaired cerebral autoregulation during sepsis and increased cerebrovascular resistance were associated with delirium during sepsis. However, the heterogeneity in NIRS and TCD devices, duration of recording (from 10 seconds to 72 hours), and delirium assessment methods (e.g., electronic medical records, confusion assessment method for the intensive care unit), precluded meta-analysis. Conclusion: The available literature demonstrates that cerebral perfusion disturbances may be associated with delirium in sepsis. However, future investigations will require consistent definitions of delirium, delirium assessment training, harmonized NIRS and TCD assessments (e.g., consistent measurement site and length of recording), as well as the quantification of secondary and tertiary variables (i.e., Cox, Mxa, MAPOPT), in order to fully assess the relationship between cerebral perfusion and delirium in patients with sepsis. [ABSTRACT FROM AUTHOR]

Background: Acute brain dysfunction (delirium and coma) during critical illness is prevalent and costly, but the pathophysiology remains unclear. The relationship of acute brain dysfunction with endothelial function, which is impaired in critical illness and may contribute to alterations in cerebral blood flow and blood-brain barrier permeability, has not been studied. This study sought to determine whether systemic endothelial dysfunction is associated with acute brain dysfunction during critical illness.Methods: In this prospective cohort study, adult medical/surgical intensive care unit patients in shock and/or respiratory failure were enrolled. Endothelial function was assessed at enrollment using peripheral artery tonometry to calculate the reactive hyperemia index, with lower reactive hyperemia index indicative of worse endothelial function. Patients were assessed for coma and delirium with the Richmond Agitation-Sedation Scale and Confusion Assessment Method for the Intensive Care Unit. Multivariable linear regression was used to analyze the association between reactive hyperemia index and (1) delirium/coma-free days among all patients and (2) delirium duration among survivors, both over a 14-day period.Results: One hundred forty-seven patients with median age of 57 yr and median Acute Physiology and Chronic Health Evaluation II score of 26 were enrolled. After adjusting for age, severity of illness, severe sepsis, preexisting cognitive function, medical versus surgical intensive care unit admission, and prehospital statin use, lower reactive hyperemia index (worse systemic endothelial function) was associated with fewer delirium/coma-free days (P = 0.02) and more delirium days (P = 0.05).Conclusions: In this study, critically ill patients with lower vascular reactivity indicative of worse systemic endothelial function had increased duration of acute brain dysfunction. [ABSTRACT FROM AUTHOR]

Background. In the coming years, the number of survivors of critical illness is expected to increase. These survivors frequently develop newly acquired physical and cognitive impairments. Long-term cognitive impairment is common following critical illness and has dramatic effects on patients' abilities to function autonomously. Neuromuscular weakness affects similar proportions of patients and leads to equally profound life alterations. As knowledge of these short-term and long-term consequences of critical illness has come to light, interventions to prevent and rehabilitate these devastating consequences have been sought. Physical rehabilitation has been shown to improve functional outcomes in people who are critically ill, but subsequent studies of physical rehabilitation after hospital discharge have not. Post-hospital discharge cognitive rehabilitation is feasible in survivors of critical illness and is commonly used in people with other forms of acquired brain injury. The feasibility of early cognitive therapy in people who are critically ill remains unknown. Objective. The purpose of this novel protocol trial will be to determine the feasibility of early and sustained cognitive rehabilitation paired with physical rehabilitation in patients who are critically ill from medical and surgical intensive care units. Design. This is a randomized controlled trial. Setting. The setting for this trial will be medical and surgical intensive care units of a large tertiary care referral center. Patients. The participants will be patients who are critically ill with respiratory failure or shock. Intervention. Patients will be randomized to groups receiving usual care, physical rehabilitation, or cognitive rehabilitation plus physical rehabilitation. Twice-daily cognitive rehabilitation sessions will be performed with patients who are non-comatose and will consist of orientation, memory, and attention exercises (eg, forward and reverse digit spans, matrix puzzles, letter-number sequences, pattern recognition). Daily physical rehabilitation sessions will advance patients from passive range of motion exercises through ambulation. Patients with cognitive or physical impairment at discharge will undergo a 12-week, in-home cognitive rehabilitation program. Measurements. A battery of neurocognitive and functional outcomes will be measured 3 and 12 months after hospital discharge.Conclusions. If feasible, these interventions will lay the groundwork for a larger, multicenter trial to determine their efficacy. [ABSTRACT FROM AUTHOR]

The authors reflect on the need to prescribe benzodiazepines to mechanically ventilated patients in intensive care units (ICUs). They note that the use of the said drug as sedative to patients in the ICU is dangerous because they can be at risks of brain dysfunction. They state that there are several studies which show that sedation in the ICU should be reduced.

The article presents a study which investigated the association between kynurenine pathway activity as determined by plasma kynurenine concentrations and kynurenine/tryptophan rations and presence or absence of acute brain dysfunction in intensive care unit (ICU) patients. It tested the hypothesis that elevations of both plasma kynurenine and kynurenine/tryptophan ratio would be associated with neurologic injury and thus fewer days from acute brain dysfunction in the critically ill.