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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.

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 124 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 124 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% CI, 1.27-13.62; p = 0.02) and a lower likelihood (delayed) resolution of delirium (hazard ratio, 0.78; 95% CI, 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.

Objective: Since statins have pleiotropic effects on inflammation and coagulation that may interrupt delirium pathogenesis, we tested the hypotheses that statin exposure is associated with reduced delirium during critical illness, whereas discontinuation of statin therapy is associated with increased delirium., Design: Multicenter, prospective cohort study., Setting: Medical and surgical ICUs in two large tertiary care hospitals in the United States., Patients: Patients with acute respiratory failure or shock., Interventions: None., Measurements and Main Results: We measured statin exposure prior to hospitalization and daily during the ICU stay, and we assessed patients for delirium twice daily using the Confusion Assessment Method for the ICU. Of 763 patients included, whose median (interquartile range) age was 61 years (51-70 yr) and Acute Physiology and Chronic Health Evaluation II was 25 (19-31), 257 (34%) were prehospital statin users and 197 (26%) were ICU statin users. Overall, delirium developed in 588 patients (77%). After adjusting for covariates, ICU statin use was associated with reduced delirium (p < 0.01). This association was modified by sepsis and study day; for example, statin use was associated with reduced delirium among patients with sepsis on study day 1 (odds ratio, 0.22; 95% CI, 0.10-0.49) but not among patients without sepsis on day 1 (odds ratio, 0.92; 95% CI, 0.46-1.84) or among those with sepsis later, for example, on day 13 (odds ratio, 0.70; 95% CI, 0.35-1.41). Prehospital statin use was not associated with delirium (odds ratio, 0.86; 95% CI, 0.44-1.66; p = 0.18), yet the longer a prehospital statin user's statin was held in the ICU, the higher the odds of delirium (overall p < 0.001 with the odds ratio depending on sepsis status and study day due to significant interactions)., Conclusions: In critically ill patients, ICU statin use was associated with reduced delirium, especially early during sepsis; discontinuation of a previously used statin was associated with increased delirium.

Background: Critical illness is associated with cognitive impairment, but mental health and functional disabilities in survivors of intensive care are inadequately characterised. We aimed to assess associations of age and duration of delirium with mental health and functional disabilities in this group., Methods: In this prospective, multicentre cohort study, we enrolled patients with respiratory failure or shock who were undergoing treatment in medical or surgical ICUs in Nashville, TN, USA. We obtained data for baseline demographics and in-hospital variables, and assessed survivors at 3 months and 12 months with measures of depression (Beck Depression Inventory II), post-traumatic stress disorder (PTSD, Post-Traumatic Stress Disorder Checklist-Event Specific Version), and functional disability (activities of daily living scales, Pfeffer Functional Activities Questionnaire, and Katz Activities of Daily Living Scale). We used linear and proportional odds logistic regression to assess the independent associations between age and duration of delirium with mental health and functional disabilities. This study is registered with ClinicalTrials.gov, number NCT00392795., Findings: We enrolled 821 patients with a median age of 61 years (IQR 51-71), assessing 448 patients at 3 months and 382 patients at 12 months after discharge. At 3 months, 149 (37%) of 406 patients with available data reported at least mild depression, as did 116 (33%) of 347 patients at 12 months; this depression was mainly due to somatic rather than cognitive-affective symptoms. Depressive symptoms were common even among individuals without a history of depression (as reported by a proxy), occurring in 76 (30%) of 255 patients with data at 3 months and 62 (29%) of 217 individuals at 12 months. Only 7% of patients (27 of 415 at 3 months and 24 of 361 at 12 months) had symptoms consistent with post-traumatic distress disorder. Disabilities in basic activities of daily living (ADL) were present in 139 (32%) of 428 patients at 3 months and 102 (27%) of 374 at 12 months, as were disabilities in instrumental ADL in 108 (26%) of 422 individuals at 3 months and 87 (23%) of 372 at 12 months. Mental health and functional difficulties were prevalent in patients of all ages. Although old age was frequently associated with mental health problems and functional disabilities, we observed no consistent association between the presence of delirium and these outcomes., Interpretation: Poor mental health and functional disability is common in patients treated in intensive-care units. Depression is five times more common than is post-traumatic distress disorder after critical illness and is driven by somatic symptoms, suggesting approaches targeting physical rather than cognitive causes could benefit patients leaving critical care., Funding: National Institutes of Health AG027472 and the Geriatric Research, Education and Clinical Center (GRECC), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness., Methods: We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%)., Results: Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% (92-100%) of study days beginning 1.0 (1.0-1.0) day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients, and 42/43 (98%) of cognitive plus physical therapy patients on 17% (10-26%), 67% (46-87%), and 75% (59-88%) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up., Conclusions: This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.

Objective: Survivors of critical illness are frequently left with long-lasting disability. The association between delirium and disability in critically ill patients has not been described. We hypothesized that the duration of delirium in the ICU would be associated with subsequent disability and worse physical health status following a critical illness., Design: Prospective cohort study nested within a randomized controlled trial of a paired sedation and ventilator weaning strategy., Setting: A single-center tertiary-care hospital., Patients: One hundred twenty-six survivors of a critical illness., Measurements and Main Results: Confusion Assessment Method for the ICU, Katz activities of daily living, Functional Activities Questionnaire (measuring instrumental activities of daily living), Medical Outcomes Study 36-item Short Form General Health Survey Physical Components Score, and Awareness Questionnaire were used. Associations between delirium duration and outcomes were determined via proportional odds logistic regression with generalized estimating equations (for Katz activities of daily living and Functional Activities Questionnaire scores) or via generalized least squares regression (for Medical Outcomes Study 36-item Short Form General Health Survey Physical Components Score and Awareness Questionnaire scores). Excluding patients who died prior to follow-up but including those who withdrew or were lost to follow-up, we assessed 80 of 99 patients (81%) at 3 months and 63 of 87 patients (72%) at 12 months. After adjusting for covariates, delirium duration was associated with worse activities of daily living scores (p = 0.002) over the course of the 12-month study period but was not associated with worse instrumental activities of daily living scores (p = 0.15) or worse Medical Outcomes Study 36-item Short Form General Health Survey Physical Components Score (p = 0.58). Duration of delirium was also associated with lower Awareness Questionnaire Motor/Sensory Factors scores (p 0.02)., Conclusion: In the setting of critical illness, longer delirium duration is independently associated with increased odds of disability in activities of daily living and worse motor-sensory function in the following year. These data point to a need for further study into the determinants of functional outcomes in ICU survivors.

Objective: Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sought to characterize the organizational structure, processes of care, use of protocols, and standardized outcomes in a large sample of U.S. ICUs., Design: We surveyed 69 ICUs about organization, size, volume, staffing, processes of care, use of protocols, and annual ICU mortality., Setting: ICUs participating in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study., Subjects: Sixty-nine intensivists completed the survey., Measurements and Main Results: We characterized structure and process variables across ICUs, investigated relationships between these variables and annual ICU mortality, and adjusted for illness severity using Acute Physiology and Chronic Health Evaluation II. Ninety-four ICU directors were invited to participate in the study and 69 ICUs (73%) were enrolled, of which 25 (36%) were medical, 24 (35%) were surgical, and 20 (29%) were of mixed type, and 64 (93%) were located in teaching hospitals with a median number of five trainees per ICU. Average annual ICU mortality was 10.8%, average Acute Physiology and Chronic Health Evaluation II score was 19.3, 58% were closed units, and 41% had a 24-hour in-house intensivist. In multivariable linear regression adjusted for Acute Physiology and Chronic Health Evaluation II and multiple ICU structure and process factors, annual ICU mortality was lower in surgical ICUs than in medical ICUs (5.6% lower [95% CI, 2.4-8.8%]) or mixed ICUs (4.5% lower [95% CI, 0.4-8.7%]). We also found a lower annual ICU mortality among ICUs that had a daily plan of care review (5.8% lower [95% CI, 1.6-10.0%]) and a lower bed-to-nurse ratio (1.8% lower when the ratio decreased from 2:1 to 1.5:1 [95% CI, 0.25-3.4%]). In contrast, 24-hour intensivist coverage (p = 0.89) and closed ICU status (p = 0.16) were not associated with a lower annual ICU mortality., Conclusions: In a sample of 69 ICUs, a daily plan of care review and a lower bed-to-nurse ratio were both associated with a lower annual ICU mortality. In contrast to 24-hour intensivist staffing, improvement in team communication is a low-cost, process-targeted intervention strategy that may improve clinical outcomes in ICU patients.

Background: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized., Methods: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders., Results: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months., Conclusions: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

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 ICU 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.

Objectives: To determine types of potentially (PIMs) and actually inappropriate medications (AIMs), which PIMs are most likely to be considered AIMs, and risk factors for PIMs and AIMs at hospital discharge in elderly intensive care unit (ICU) survivors., Design: Prospective cohort study., Setting: Tertiary care, academic medical center., Participants: One hundred twenty individuals aged 60 and older who survived an ICU hospitalization., Measurements: Potentially inappropriate medications were defined according to published criteria; a multidisciplinary panel adjudicated AIMs. Medications from before admission, ward admission, ICU admission, ICU discharge, and hospital discharge were abstracted. Poisson regression was used to examine independent risk factors for hospital discharge PIMs and AIMs., Results: Of 250 PIMs prescribed at discharge, the most common were opioids (28%), anticholinergics (24%), antidepressants (12%), and drugs causing orthostasis (8%). The three most common AIMs were anticholinergics (37%), nonbenzodiazepine hypnotics (14%), and opioids (12%). Overall, 36% of discharge PIMs were classified as AIMs, but the percentage varied according to drug type. Whereas only 16% of opioids, 23% of antidepressants, and 10% of drugs causing orthostasis were classified as AIMs, 55% of anticholinergics, 71% of atypical antipyschotics, 67% of nonbenzodiazepine hypnotics and benzodiazepines, and 100% of muscle relaxants were deemed AIMs. The majority of PIMs and AIMs were first prescribed in the ICU. Preadmission PIMs, discharge to somewhere other than home, and discharge from a surgical service predicted number of discharge PIMs, but none of the factors predicted AIMs at discharge., Conclusion: Certain types of PIMs, which are commonly initiated in the ICU, are more frequently considered inappropriate upon clinical review. Efforts to reduce AIMs in elderly ICU survivors should target these specific classes of medications., (© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.)

Purpose: The pathophysiology of delirium in critical illness is unclear. 25-OH vitamin D (25-OHD) has neuroprotective properties but a relationship between serum 25-OHD and delirium has not been examined. We tested the hypothesis that low serum 25-OHD is associated with delirium during critical illness., Materials and Methods: In a prospective cohort of 120 medical intensive care unit (ICU) patients, blood was collected within 24 hours of ICU admission for measurement of 25-OHD. Delirium was identified once daily using the Confusion Assessment Method for the ICU. Multivariable logistic regression was used to analyze the association between 25-OHD and delirium assessed the same day and the subsequent day after 25-OHD measurement, with adjustments for age and severity of illness., Results: Median age was 52 years (interquartile range, 40-62), and Acute Physiology and Chronic Health Evaluation II was 23 (interquartile range, 17-30). Thirty-seven patients (41%) were delirious on the day of 25-OHD measurement. 25-OHD levels were not associated with delirium on the day of 25-OHD measurement (odds ratio, 1.01; 95% confidence interval, 0.98-1.02) or on the day after measurement (odds ratio, 1.01; 95% confidence interval, 0.99-1.03)., Conclusions: This pilot study suggests that 25-OHD levels measured early during critical illness are not important determinants of delirium risk. Since 25-OHD levels can fluctuate during critical illness, a study of daily serial measurements of 25-OHD levels and their relationship to delirium during the duration of critical illness may yield different results., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.

Intensive care medical training, whether as a primary specialty or as secondary add-on training, should include key competences to ensure a uniform standard of care, and the number of intensive care physicians needs to increase to keep pace with the growing and anticipated need. The organisation of intensive care in multiple specialty or central units is heterogeneous and evolving, but appropriate early treatment and access to a trained intensivist should be assured at all times, and intensivists should play a pivotal role in ensuring communication and high-quality care across hospital departments. Structures now exist to support clinical research in intensive care medicine, which should become part of routine patient management. However, more translational research is urgently needed to identify areas that show clinical promise and to apply research principles to the real-life clinical setting. Likewise, electronic networks can be used to share expertise and support research. Individuals, physicians and policy makers need to allow for individual choices and priorities in the management of critically ill patients while remaining within the limits of economic reality. Professional scientific societies play a pivotal role in supporting the establishment of a defined minimum level of intensive health care and in ensuring standardised levels of training and patient care by promoting interaction between physicians and policy makers. The perception of intensive care medicine among the general public could be improved by concerted efforts to increase awareness of the services provided and of the successes achieved., (Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.)

Delirium in the intensive care unit (ICU) is exceedingly common, and risk factors for delirium among the critically ill are nearly ubiquitous. Addressing modifiable risk factors including sedation management, deliriogenic medications, immobility, and sleep disruption can help to prevent and reduce the duration of this deadly syndrome. The ABCDE approach to critical care is a bundled approach that clinicians can implement for many patients treated in their ICUs to prevent the adverse outcomes associated with delirium and critical illness., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To assess the associations between a priori-selected markers of inflammation and coagulation and delirium during critical illness., Methods: In this prospective cohort study, we collected blood from mechanically ventilated medical intensive care unit (ICU) patients and measured nine plasma markers of inflammation and coagulation. We assessed patients daily for delirium using the Confusion Assessment Method for the ICU and used multivariable regression to analyze the associations between plasma markers and subsequent delirium, after adjusting for age, severity of illness, and sepsis., Results: Among the 138 patients studied, with median age of 66 years and median Acute Physiology and Chronic Health Evaluation (APACHE) II of 27, 107 (78 %) were delirious at some point during the study. Two markers of inflammation and one of coagulation were significantly associated with delirium. After adjusting for covariates, lower plasma concentrations of matrix metalloproteinase-9 (MMP-9) and protein C were associated with increased probability of delirium (p = 0.04 and 0.01, respectively), and higher concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1) were associated with increased probability of delirium (p < 0.01). Concentrations of C-reactive protein (p = 0.82), myeloperoxidase (p = 0.11), neutrophil gelatinase-associated lipocalin (p = 0.70), D-dimer (p = 0.83), plasminogen activator inhibitor type 1 (p = 0.98), and Von Willebrand factor antigen (p = 0.65) were not associated with delirium., Conclusions: In this study, MMP-9, protein C, and sTNFR1 were independently associated with subsequent ICU delirium. These results suggest that specific aspects of inflammation and coagulation may play a role in the evolution of delirium during critical illness and that these markers should be examined in larger studies of ICU patients.

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 noncomatose 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.

Background: Although enteral nutrition (EN) is provided to most mechanically ventilated patients, the effect of specific feeding strategies on circulating markers of coagulation and inflammation is unknown., Methods: Markers of inflammation (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, interferon [IFN]-γ, IL-6, IL-8, IL-10, IL-12) and coagulation (tissue factor [TF], plasminogen activator inhibitor-1) were measured at baseline (n = 185) and 6 days (n = 103) in mechanically ventilated intensive care unit patients enrolled in a randomized controlled study of trophic vs full-energy feeds to test the hypothesis that trophic enteral feeds would be associated with decreases in markers of inflammation and coagulation compared to full-energy feeds., Results: There were no differences in any of the biomarkers measured at day 6 between patients who were randomized to receive trophic feeds compared to full-energy feeds. However, TF levels decreased modestly in patients from baseline to day 6 in the trophic feeding group (343.3 vs 247.8 pg/mL, P = .061) but increased slightly in the full-calorie group (314.3 vs 331.8 pg/mL). Lower levels of TF at day 6 were associated with a lower mortality, and patients who died had increasing TF levels between days 0 and 6 (median increase of 39.7) compared to decreasing TF levels in patients who lived (median decrease of 95.0, P = .033)., Conclusions: EN strategy in critically ill patients with acute respiratory failure does not significantly modify inflammation and coagulation by day 6, but trophic feeds may have some modest effects in attenuating inflammation and coagulation.

Delirium is a prevalent organ dysfunction in critically ill patients associated with significant morbidity and mortality, requiring advancements in the clinical and research realms to improve patient outcomes. Increased clinical recognition and utilisation of delirium assessment tools, along with clarification of specific risk factors and presentations in varying patient populations, will be necessary in the future. To improve predictive models for outcomes, the continued development and implementation of delirium assessment tools and severity scoring systems will be required. The interplay between the pathophysiological pathways implicated in delirium and resulting clinical presentations and outcomes will need to guide the development of appropriate prevention and treatment protocols. Multicentre randomised controlled trials of interventional therapies will then need to be performed to test their ability to improve clinical outcomes. Physical and cognitive rehabilitation measures need to be further examined as additional means of improving outcomes from delirium in the hospital setting., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Critically ill patients frequently experience acute brain dysfunction in the form of coma or delirium, both of which are common during acute and chronic critical illness (CCI). These manifestations of brain dysfunction are associated with numerous adverse outcomes during acute critical illness, including prolonged hospitalization, increased healthcare costs, and increased mortality. The prognosis of CCI patients with coma or delirium has not yet been thoroughly studied, but preliminary studies suggest this population is at high risk for detrimental outcomes associated with acute brain dysfunction. Additionally, a high percentage of patients who survive acute or CCI suffer from long-term brain dysfunction, which manifests primarily as memory deficits and executive dysfunction and is predicted by brain dysfunction in the ICU. Interventions directed at reducing the burden of brain dysfunction during critical illness have shown promise in studies of patients with acute critical illness, but these therapies have yet to be studied during CCI. Thus, multicenter randomized trials are needed to determine which interventions are most effective for such patients. Until these data are available, management strategies that have been proven beneficial during acute critical illness-such as reduction of sedative exposure, especially to benzodiazepines, and early use of physical and occupational therapy-should be employed during the treatment of patients with CCI., (2012 Daedalus Enterprises)

The use of sedation has long been integrated into critical care. Because pain, discomfort, anxiety, and agitation are commonly experienced by critically ill patients, the use of medications to alleviate and control these symptoms will continue; however, data showing that prolonged use of sedating medications imparts harm to patients obligate physicians to use agents and methods of sedation that minimize these negative side effects. Numerous observational studies and clinical trials have proven that decisions in sedation management play a crucial role in determining outcomes for mechanically ventilated ICU patients, and recent evidence supports the use of protocols that streamline efforts to discontinue sedation and mechanical ventilation in a safe and parallel fashion. Regardless of choice of sedating agent, and even when patient-targeted sedation protocols are used to minimize oversedation, the use of spontaneous awakening trials dramatically improves patient outcomes for critically ill patients. Intensive care physicians must continue to study the delivery of sedation in efforts to maximize patient comfort while minimizing patient harm., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: To describe the reliability and sustainability of delirium and sedation measurements of bedside intensive care unit (ICU) nurses., Design: Prospective cohort study., Setting: A tertiary care academic medical center., Participants: Five hundred ten ICU patients from 2007 to 2010; 627 bedside nurses., Measurements: Bedside nurses and well-trained reference-rater research nurses independently measured delirium and sedation levels in routine care. Bedside nurses were instructed to use the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) every 12 hours to measure delirium and the Richmond Agitation-Sedation Scale (RASS) every 4 hours to measure sedation. CAM-ICU and RASS assessment agreement were computed using weighted kappa statistics across the entire population and subgroups (e.g., ICU type). Sensitivity and specificity of bedside nurse identification of delirium were calculated to understand sources of discordance., Results: Six thousand one hundred ninety-eight CAM-ICU and 6,880 RASS measurement pairs obtained on 3,846 patient-days. For CAM-ICU measurements, agreement between bedside and research nurses was substantial (weighted kappa = 0.67, 95% confidence interval (CI) = 0.66-0.70) and stable over 3 years of data collection. RASS measures also demonstrated substantial agreement (weighted kappa = 0.66, 95% CI = 0.64-0.68), which was stable across all years of data collection. The sensitivity of delirium nurse assessments was 0.81 (95% CI = 0.78-0.83), and the specificity was 0.81 (95% CI = 0.78-0.85)., Conclusion: Bedside nurse measurements of delirium and sedation are sustainable and reliable sources of information. These measures can be used for clinical decision-making, quality improvement, and quality measurement activities., (© 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.)

Purpose of Review: Critically ill patients are prescribed sedatives and analgesics to decrease pain and anxiety, improve patient-ventilator dyssynchrony and ensure patient safety. These medications may themselves lead to delirium and ICU-acquired weakness, which are associated with worse clinical outcomes. This review will focus on the epidemiology of these two disease processes and discuss strategies aimed at reducing these devastating complications of critical illness., Recent Findings: Delirium and ICU-acquired weakness are associated with longer hospital stay, increased cost and decreased quality of life after discharge from the ICU. Delirium has also shown to be associated with increased mortality. Strategies aimed at reducing sedative exposure through protocols and coordination of daily sedation and ventilator cessation trials, avoiding benzodiazepines in favor of alternative sedative regimens and early mobilization of patients have all shown to significantly improve patient outcomes., Summary: Delirium and ICU-acquired weakness are complications of critical illness associated with worse clinical outcomes and functional decline in survivors. An evidence-based approach based on the following tenets - minimization of sedative medication, particularly benzodiazepines, delirium monitoring and management and early mobilization may mitigate these complications.

Introduction: Non-intensive care unit (ICU) cohorts have shown an association between inflammatory disturbances and delirium, though these relationships have not been studied in critically ill patients. This study sought to investigate the relationship between two inflammatory biomarkers, procalcitonin and C-reactive protein (CRP), and duration of acute brain dysfunction in ventilated patients., Methods: Patients enrolled in the Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) trial were assessed daily for delirium using the Confusion Assessment Method-ICU. Plasma levels of procalcitonin and CRP were obtained within 24 hours of enrollment. Proportional odds logistic regression was used to examine the association between procalcitonin and CRP separately with delirium/coma-free days, adjusting for age, acute physiology score (APS) of the Acute Physiology And Chronic Health Evaluation (APACHE) II, sedation group (dexmedetomidine vs. lorazepam), and sepsis. Secondary analyses examined the association of these markers with other organ dysfunctions and 28-day survival., Results: Eighty-seven patients were included in this analysis. The median age of the patients was 60 years with APACHE II scores of 28; 68% had sepsis within 48 hours of admission. Higher levels of procalcitonin were associated with fewer delirium/coma-free days [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3 to 1.0; P = 0.04], whereas higher CRP levels showed trends towards fewer delirium/coma-free days (OR, 0.6; 95% CI, 0.3 to 1.1; P = 0.08). Similar relationships were found regardless of the presence of sepsis. No associations were found between procalcitonin or CRP with 28-day survival (P = 0.40 and 0.16, respectively)., Conclusions: In our pilot study, high baseline inflammatory biomarkers predicted prolonged periods of acute brain dysfunction, implicating inflammation as an important mechanism in the pathophysiology of delirium and coma during critical illness, irrespective of whether patients had sepsis or not.

Heavy sedation in the ICU is associated with coma, delirium, and prolonged stays, but links between sedatives and non-brain organ failure have rarely been described. In a post hoc analysis, Strøm and colleagues explored associations between sedation and acute kidney injury among ICU patients randomly assigned to one of two sedation strategies. The 'no sedation' protocol was associated with less kidney injury, but methodologic limitations preclude firm conclusions regarding mechanisms underlying this association. This hypothesis-generating study warns that sedation may harm organs other than the brain during critical illness, a possibility that warrants careful study in the future.

We face a profound and emerging public health problem in the form of acute and chronic brain dysfunction. This affects both young and elderly intensive care unit survivors and is altering the landscape of society. Two-thirds of intensive care unit patients develop delirium, and this is associated with longer stays, increased costs, and excess mortality. In addition, over half of intensive care unit survivors suffer a dementia-like illness that impacts their physical and cognitive functional abilities and which appears to be related to the duration of their intensive care unit delirium. A new paradigm of how intensivists handle the brain is required. We propose a three-step approach to address this emerging epidemic, which includes Screening, Prevention, and Restoration of brain function (SPR). Screening combines risk factor identification and delirium assessment using validated instruments. Prevention of acute and chronic brain dysfunction requires implementation of a core model of care that combines evidence-based practices: awakening and breathing, coordination with target-based sedation, delirium monitoring, and exercise/early mobility (ABCDE). Restoration introduces strategies of ongoing screening and treatment for intensive care unit survivors at high risk of ongoing brain dysfunction. This practical system applying many evidence-based concepts incorporates personalized medicine, systems-based practice, and continuing research and development toward improving acute and chronic cognitive outcomes.

Background: Communication with family members of patients in intensive care units is challenging and fraught with dissatisfaction., Objectives: We hypothesized that family attendance at structured interdisciplinary family rounds would enhance communication and facilitate end-of-life planning (when appropriate)., Methods: The study was conducted in the 26-bed medical intensive care unit of a tertiary care, academic medical center from April through October 2006. Starting in July 2006, families were invited to attend daily interdisciplinary rounds where the medical team discussed the plan for care. Family members were surveyed at least 1 month after the patient's stay in the unit, completing the validated "Family Satisfaction in the ICU" tool before and after implementation of family rounds., Results: Of 227 patients enrolled, 187 patients survived and 40 died. Among families of survivors, participation in family rounds was associated with higher family satisfaction regarding frequency of communication with physicians (P = .004) and support during decision making (P = .005). Participation decreased satisfaction regarding time for decision making (P = .02). Overall satisfaction scores did not differ between families who attended rounds and families who did not. For families of patients who died, participation in family rounds did not significantly change satisfaction., Conclusions: In the context of this pilot study of family rounds, certain elements of satisfaction were improved, but not overall satisfaction. The findings indicate that structured interdisciplinary family rounds can improve some families' satisfaction, whereas some families feel rushed to make decisions. More work is needed to optimize communication between staff in the intensive care unit and patients' families, families' comprehension, and the effects on staff workload.

Objective: To test the hypothesis that duration of delirium in the intensive care unit is an independent predictor of long-term cognitive impairment after critical illness requiring mechanical ventilation., Design: Prospective cohort study., Setting: Medical intensive care unit in a large community hospital in the United States., Patients: Mechanically ventilated medical intensive care unit patients who were assessed daily for delirium while in the intensive care unit and who underwent comprehensive cognitive assessments 3 and 12 mos after discharge., Measurements and Main Results: Of 126 eligible patients, 99 survived>or=3 months after critical illness; long-term cognitive outcomes were obtained for 77 (78%) patients. Median age was 61 yrs, 51% were admitted with sepsis/acute respiratory distress syndrome, and median duration of delirium was 2 days. At 3-mo and 12-mo follow-up, 79% and 71% of survivors had cognitive impairment, respectively (with 62% and 36% being severely impaired). After adjusting for age, education, preexisting cognitive function, severity of illness, severe sepsis, and exposure to sedative medications in the intensive care unit, increasing duration of delirium was an independent predictor of worse cognitive performance-determined by averaging age-adjusted and education-adjusted T-scores from nine tests measuring seven domains of cognition-at 3-mo (p=.02) and 12-mo follow-up (p=.03). Duration of mechanical ventilation, alternatively, was not associated with long-term cognitive impairment (p=.20 and .58)., Conclusions: In this study of mechanically ventilated medical intensive care unit patients, duration of delirium (which is potentially modifiable) was independently associated with long-term cognitive impairment, a common public health problem among intensive care unit survivors.

Introduction: Benzodiazepines and alpha2 adrenoceptor agonists exert opposing effects on innate immunity and mortality in animal models of infection. We hypothesized that sedation with dexmedetomidine (an alpha2 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.

Objectives: To examine the bias introduced by using time-fixed methodology to analyze the effects of a time-varying exposure incurred in the intensive care unit., Design: Prospective cohort and Monte Carlo simulation studies., Setting: Medical and coronary intensive care units in a university hospital., Patients: A total of 224 mechanically ventilated patients., Methods: Part I was a case study analyzing the association between delirium in the intensive care unit (exposure variable) and outcomes (intensive care unit length of stay and 6-mo mortality) in a prospective cohort study. Part II was a Monte Carlo simulation generating 16,000 data sets wherein the true associations between delirium and outcomes were known before analysis. In both parts, we assessed associations between delirium in the intensive care unit and outcomes (intensive care unit length of stay and mortality), using time-fixed vs. time-varying Cox regression methodology., Measurements and Main Results: In the case study, delirium analyzed as a time-fixed variable was associated with a delayed intensive care unit discharge (adjusted hazard ratio = 1.9, 95% confidence interval, 1.3-2.7, p < .001), but no association was noted using a time-varying method (adjusted hazard ratio = 1.1, 95% confidence interval = 0.7-1.6, p = .70). Alternatively, delirium analyzed as a time-fixed variable was not associated with 6-mo mortality (adjusted hazard ratio = 2.9, 95% confidence interval, 0.9-5.0, p = .09), whereas delirium analyzed as a time-varying variable was associated with increased mortality (adjusted hazard ratio = 3.2, 95% confidence interval, 1.4-7.7, p = .008). In the simulation study, time-fixed methods produced erroneous results in 97.1% of the data sets with no true association; time-varying methods produced erroneous results in only 3.7%. Similarly, time-fixed methods produced biased results when a true association was present, whereas time-varying methods produced accurate results., Conclusions: Studies using a time-fixed analytic approach to understand relationships between exposures and clinical outcomes can result in considerable bias when the variables overlap temporally in occurrence. Those conducting such studies, and clinicians reading them, should ensure that time-varying exposures are correctly analyzed to avoid biased conclusions.

Aim: The pathophysiology of delirium remains elusive though neurotransmitters and their precursor large neutral amino acids (LNAAs) may play a role. This pilot study investigated whether alterations of tryptophan (Trp), phenylalanine (Phe), and tyrosine (Tyr) plasma levels were associated with a higher risk of transitioning to delirium in critically ill patients., Methods: Plasma LNAA concentrations were determined on days 1 and 3 in mechanically ventilated (MV) patients from the MENDS randomized controlled trial (dexmedetomidine vs. lorazepam sedation). Three independent variables were calculated by dividing plasma concentrations of Trp, Phe, and Tyr by the sum of all other LNAA concentrations. Delirium was assessed daily using the confusion assessment method for the intensive care unit (CAM-ICU). Markov regression models were used to analyze independent associations between plasma LNAA ratios and transition to delirium after adjusting for covariates., Results: The 97 patients included in the analysis had a high severity of illness (median APACHE II, 28; IQR, 24-32). After adjusting for confounders, only high or very low tryptophan/LNAA ratios (p = 0.0003), and tyrosine/LNAA ratios (p = 0.02) were associated with increased risk of transitioning to delirium, while phenylalanine levels were not (p = 0.27). Older age, higher APACHE II scores and increasing fentanyl exposure were also associated with higher probabilities of transitioning to delirium., Conclusions: In this pilot study, plasma tryptophan/LNAA and tyrosine/LNAA ratios were associated with transition to delirium in MV patients, suggesting that alterations of amino acids may be important in the pathogenesis of ICU delirium. Future studies evaluating the role of amino acid precursors of neurotransmitters are warranted in critically ill patients.

Liberation from mechanical ventilation is a vital treatment goal in the management of critically ill patients. The duration of mechanical ventilation is affected by strategies for ventilator weaning and sedation. The authors review literature on weaning from mechanical ventilation and delivery of sedation in critically ill patients, including current guidelines recommending the use of spontaneous breathing trials and spontaneous awakening trials. Implementation of these strategies in a wake-up-and-breathe protocol has demonstrated benefit over the use of spontaneous breathing trials alone.

Objective: A 2001 survey found that most healthcare professionals considered intensive care unit (ICU) delirium as a serious problem, but only 16% used a validated delirium screening tool. Our objective was to assess beliefs and practices regarding ICU delirium and sedation management., Design and Setting: Between October 2006 and May 2007, a survey was distributed to ICU practitioners in 41 North American hospitals, seven international critical care meetings and courses, and the American Thoracic Society e-mail database., Study Participants: A convenience sample of 1384 healthcare professionals including 970 physicians, 322 nurses, 23 respiratory care practitioners, 26 pharmacists, 18 nurse practitioners and physicians' assistants, and 25 others., Results: A majority [59% (766 of 1300)] estimated that more than one in four adult mechanically ventilated patients experience delirium. More than half [59% (774 of 1302)] screen for delirium, with 33% of those respondents (258 of 774) using a specific screening tool. A majority of respondents use a sedation protocol, but 29% (396 of 1355) still do not. A majority (76%, 990 of 1309) has a written policy on spontaneous awakening trials (SATs), but the minority of respondents (44%, 446 of 1019) practice spontaneous awakening trials on more than half of ICU days., Conclusions: Delirium is considered a serious problem by a majority of healthcare professionals, and the percent of practitioners using a specific screening tool has increased since the last published survey data. Although most respondents have adopted specific sedation protocols and have an approved approach to stopping sedation daily, few report even modest compliance with daily cessation of sedation.

Though seminal clinical trials have identified efficacious methods of liberating patients from mechanical ventilation (ie, weaning), this knowledge is not applied often by physicians in routine practice. Weaning protocols are a strategies by which research results can be translated effectively and efficiently into clinical practice, but results of clinical trials evaluating weaning protocols have not been uniform, and controversy continues to surround this important area in critical care medicine. This article reviews the rationale for and against the routine use of weaning protocols and highlights informative details of many clinical trials that have evaluated such protocols.

Delirium, an acute and fluctuating disturbance of consciousness and cognition, is a common manifestation of acute brain dysfunction in critically ill patients, occurring in up to 80% of the sickest intensive care unit (ICU) populations. Critically ill patients are subject to numerous risk factors for delirium. Some of these, such as exposure to sedative and analgesic medications, may be modified to reduce risk. Although dysfunction of other organ systems continues to receive more clinical attention, delirium is now recognized to be a significant contributor to morbidity and mortality in the ICU, and it is recommended that all ICU patients be monitored using a validated delirium assessment instrument. Patients with delirium have longer hospital stays and lower 6-month survival than do patients without delirium, and preliminary research suggests that delirium may be associated with cognitive impairment that persists months to years after discharge. Little evidence exists regarding the prevention and treatment of delirium in the ICU, but multicomponent interventions reduce the incidence of delirium in non-ICU studies. Strategies for the prevention and treatment of ICU delirium are the subjects of multiple ongoing investigations.

Context: Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction., Objective: To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam., Design, Setting, Patients, and Intervention: Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU)., Main Outcome Measures: Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal., Results: Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P = .01) and a lower prevalence of coma (63% vs 92%; P < .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P = .04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group (P = .18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P = .61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group (P = .48)., Conclusion: In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion., Trial Registration: clinicaltrials.gov Identifier: NCT00095251.

Background: It is unclear how best to measure sedative/analgesic drug exposure in the clinical care of critically ill patients. Large doses and prolonged use of sedatives and analgesics in the intensive care unit (ICU) may lead to oversedation and adverse effects, including delirium and long-term cognitive impairment. These issues are of particular concern in elderly patients (aged > or =65 years), who account for at least half of all ICU admissions and nearly two thirds of ICU days., Objective: This pilot study explored the relationships between clinical sedation scores, sedative/analgesic drug doses, and plasma drug concentrations in critically ill patients, the majority of whom were elderly., Methods: This was a prospective, observational study conducted in a 500-bed, tertiary care community hospital. Study patients included a cohort of mechanically ventilated, medical ICU patients who were admitted to the hospital between April and June 2004 who required use of fentanyl, lorazepam, or propofol. Sedative/analgesic medications were administered according to clinical guidelines. Patients' sedation levels were measured twice daily using the Richmond Agitation-Sedation Scale (RASS). Dosing of fentanyl, lorazepam, and propofol was recorded. Blood was sampled twice daily for up to 5 days to analyze plasma drug concentrations. To specifically evaluate the effects of acute, extended (rather than chronic) sedative and analgesic exposure, the study focused on an ICU population receiving these agents for at least 48 hours but <2 weeks., Results: Eighteen medical ICU patients (11 females, 7 males; mean [SD] age, 66.1 [18.1] years) on mechanical ventilation comprised the study cohort. Fifteen patients were aged >62 years, and 11 of those were aged > or =71 years. Plasma drug concentrations (median and interquartile range) were as follows: fentanyl--2.1 ng/mL, 0.9-3.4 ng/mL; lorazepam--266 ng/mL, 112-412 ng/mL; and propofol--845 ng/mL, 334-1342 ng/mL. Maximum concentrations were 3- to 12-fold higher than medians (fentanyl, 7.3 ng/mL; lorazepam, 3108 ng/mL; propofol, 10,000 ng/mL). Medication doses were only moderately correlated with RASS scores (Spearman rho): fentanyl--rho = -0.39, P = 0.002; lorazepam--rho = -0.28, P = 0.001; and propofol--rho = -0.46, P < 0.001. Plasma drug concentrations of fentanyl and lorazepam demonstrated moderate correlations with sedation scores (fentanyl--rho = -0.46, P = 0.002; lorazepam: rho = -0.49, P < 0.001), while propofol concentrations correlated poorly with sedation scores (rho = -0.18, P = 0.07). Associations between interval drug doses and plasma concentrations were as follows: fentanyl, rho = 0.84; lorazepam, rho = 0.76; and propofol, rho = 0.61 (all, P < 0.001). Instructive examples of discrepant dose versus plasma concentration profiles and drug interactions are provided, including 3 cases with patients aged > or =64 years., Conclusions: Elderly patients are commonly encountered in the ICU setting. Only moderate correlations existed between clinical sedation levels and dose or plasma concentration of sedative/analgesic medications in this study population. Further work is needed to understand appropriate and feasible measures of exposure to sedatives/analgesics relating to clinical outcomes.

Bacteremia and sepsis are common complications of infection in older patients. Comorbidities, institutionalization, instrumentation, and immunosenescence place older persons at high risk for bacteremia and sepsis, and clinicians must have a heightened suspicion for these infectious disorders in older patients because nonspecific clinical manifestations of infection are common in this vulnerable population. Although increasing age is associated with a high risk of death due to bacteremia and sepsis, recent evidence suggests that many older patients respond well to treatments of proven efficacy. This article discusses the epidemiology, pathophysiology, diagnosis, and prognosis of bacteremia and sepsis in older patients and provides evidence-based recommendations regarding the treatment of these infectious disorders in older persons.