Determinants of Depressive Symptoms at 1 Year Following ICU Discharge in Survivors of ≥ 7 Days of Mechanical Ventilation: Results From the RECOVER Program, a Secondary Analysis of a Prospective Multicenter Cohort Study.

BACKGROUND: Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver factors associated with the development of these symptoms. METHODS: This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II [BDI-II]), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay [LOS]), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months. RESULTS: BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale [P = .28] and Center for Epidemiologic Studies Depression Scale [P = .74]). CONCLUSIONS: Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders.

Patient safety, cost-effectiveness, and quality of life: reduction of delirium risk and postoperative cognitive dysfunction after elective procedures in older adults-study protocol for a stepped-wedge cluster randomized trial (PAWEL Study).

BACKGROUND: Postoperative delirium is a common disorder in older adults that is associated with higher morbidity and mortality, prolonged cognitive impairment, development of dementia, higher institutionalization rates, and rising healthcare costs. The probability of delirium after surgery increases with patients' age, with pre-existing cognitive impairment, and with comorbidities, and its diagnosis and treatment is dependent on the knowledge of diagnostic criteria, risk factors, and treatment options of the medical staff. In this study, we will investigate whether a cross-sectoral and multimodal intervention for preventing delirium can reduce the prevalence of delirium and postoperative cognitive decline (POCD) in patients older than 70 years undergoing elective surgery. Additionally, we will analyze whether the intervention is cost-effective. METHODS: The study will be conducted at five medical centers (with two or three surgical departments each) in the southwest of Germany. The study employs a stepped-wedge design with cluster randomization of the medical centers. Measurements are performed at six consecutive points: preadmission, preoperative, and postoperative with daily delirium screening up to day 7 and POCD evaluations at 2, 6, and 12 months after surgery. Recruitment goals are to enroll 1500 patients older than 70 years undergoing elective operative procedures (cardiac, thoracic, vascular, proximal big joints and spine, genitourinary, gastrointestinal, and general elective surgery procedures). DISCUSSION: Results of the trial should form the basis of future standards for preventing delirium and POCD in surgical wards. Key aims are the improvement of patient safety and quality of life, as well as the reduction of the long-term risk of conversion to dementia. Furthermore, from an economic perspective, we expect benefits and decreased costs for hospitals, patients, and healthcare insurances. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00013311 . Registered on 10 November 2017.

Delirium assessment in neuro-critically ill patients: A validation study.

BACKGROUND: Delirium is underinvestigated in the neuro-critically ill, although the harmful effect of delirium is well established in patients in medical and surgical intensive care units (ICU).To detect delirium, a valid tool is needed. We hypothesized that delirium screening would be feasible in patients with acute brain injury and we aimed to validate and compare the Confusion Assessment Method for the ICU and the Intensive Care Delirium Screening Checklist against clinical International Classification of Diseases-10 criteria as reference. METHODS: Nurses assessed delirium using the Confusion Assessment Method for the ICU and Intensive Care Delirium Screening Checklist in adult patients with acute brain injury admitted to the Neurointensive care unit (Neuro-ICU), Copenhagen University Hospital, if their Richmond agitation-sedation scale score was -2 or above. As the reference, a team of psychiatrist assessed patients using the International Classification of Diseases-10 criteria. RESULTS: We enrolled 74 patients, of whom 25 (34%) were deemed unable to assess by the psychiatrists, leaving 49 (66%) for final analysis. Sensitivity and specificity for the Confusion Assessment Method for the ICU was 59% (95% CI: 41-75) and 56% (95% CI: 32-78), respectively, and 85% (95% CI: 70-94) and 75% (95% CI: 51-92), respectively, for the Intensive Care Delirium Screening Checklist. CONCLUSIONS: Our findings suggest that the Intensive Care Delirium Screening Checklist may be a valid tool and the Confusion Assessment Method for the ICU is less suitable for delirium detection for patients in the Neuro-ICU. In the neuro-critically ill, delirium screening is challenged by limited feasibility.

Delirium Assessment Tools for Use in Critically Ill Adults: A Psychometric Analysis and Systematic Review.

BACKGROUND: Delirium is highly prevalent in critically ill patients. Its detection with valid tools is crucial. OBJECTIVE: To analyze the development and psychometric properties of delirium assessment tools for critically ill adults. METHODS: Databases were searched to identify relevant studies. Inclusion criteria were English language, publication before January 2015, 30 or more patients, and patient population of critically ill adults (>18 years old). Search terms were delirium, scales, critically ill patients, adult, validity, and reliability. Thirty-six manuscripts were identified, encompassing 5 delirium assessment tools (Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Cognitive Test for Delirium, Delirium Detection Score, Intensive Care Delirium Screening Checklist (ICDSC), and Nursing Delirium Screening Scale). Two independent reviewers analyzed the psychometric properties of these tools by using a standardized scoring system (range, 0-20) to assess the tool development process, reliability, validity, feasibility, and implementation of each tool. RESULTS: Psychometric properties were very good for the CAM-ICU (19.6) and the ICDSC (19.2), moderate for the Nursing Delirium Screening Scale (13.6), low for the Delirium Detection Score (11.2), and very low for the Cognitive Test for Delirium (8.2). CONCLUSIONS: The results indicate that the CAM-ICU and the ICDSC are the most valid and reliable delirium assessment tools for critically ill adults. Additional studies are needed to further validate these tools in critically ill patients with neurological disorders and those at various levels of sedation or consciousness.

Workplace Blame and Related Concepts: An Analysis of Three Case Studies.

Blame has been thought to affect quality by decreasing error reporting. Very little is known about the incidence, characteristics, or consequences of the distress caused by being blamed. Blame-related distress (B-RD) may be related to moral distress, but may also be a factor in burnout, compassion fatigue, lateral violence, and second-victim syndrome. The purpose of this article is to explore these related concepts through a literature review applied to three index critical care clinician cases.

Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. METHODS/DESIGN: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. DISCUSSION: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.

Cost-effectiveness of dalteparin vs unfractionated heparin for the prevention of venous thromboembolism in critically ill patients.

IMPORTANCE: Venous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin. OBJECTIVE: To evaluate the comparative cost-effectiveness of LMWH vs UFH for prophylaxis against VTE in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Prospective economic evaluation concurrent with the Prophylaxis for Thromboembolism in Critical Care Randomized Trial (May 2006 to June 2010). The economic evaluation adopted a health care payer perspective and in-hospital time horizon; derived baseline characteristics and probabilities of intensive care unit and in-hospital events; and measured costs among 2344 patients in 23 centers in 5 countries and applied these costs to measured resource use and effects of all enrolled patients. MAIN OUTCOMES AND MEASURES: Costs, effects, incremental cost-effectiveness of LMWH vs UFH during the period of hospitalization, and sensitivity analyses across cost ranges. RESULTS: Hospital costs per patient were $39,508 (interquartile range [IQR], $24,676 to $71,431) for 1862 patients who received LMWH compared with $40,805 (IQR, $24,393 to $76,139) for 1862 patients who received UFH (incremental cost, -$1297 [IQR, -$4398 to $1404]; P = .41). In 78% of simulations, a strategy using LMWH was most effective and least costly. In sensitivity analyses, a strategy using LMWH remained least costly unless the drug acquisition cost of dalteparin increased from $8 to $179 per dose and was consistent among higher- and lower-spending health care systems. There was no threshold at which lowering the acquisition cost of UFH favored prophylaxis with UFH. CONCLUSIONS AND RELEVANCE: From a health care payer perspective, the use of the LMWH dalteparin for VTE prophylaxis among critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH. These findings were driven by lower rates of pulmonary embolus and heparin-induced thrombocytopenia and corresponding lower overall use of resources with LMWH.

I-SAVE study: impact of sedation, analgesia, and delirium protocols evaluated in the intensive care unit: an economic evaluation.

BACKGROUND: Intensive care units (ICUs) account for considerable health care costs. Adequate pain and sedation management is important to clinical care. OBJECTIVE: To determine whether implementing a protocol for management of analgesia, sedation, and delirium in the ICU would save costs. METHODS: With data from the I-SAVE (Impact of Sedation, Analgesia and Delirium Protocols Evaluated in the Intensive Care Unit: an Economic Evaluation) study, a prospective pre- and postprotocol design was used. Between the 2 periods, protocols for systematic management of sedation, analgesia, and delirium were implemented. Cost-effectiveness was calculated by associating the variation of cost and effectiveness measures (proportion of patients within targeted pain, sedation, and delirium goals). Total costs (in 2004 Canadian dollars), by patient, consisted of the sum of sedation, analgesia, and delirium drug acquisition costs during the ICU stay and the cost of the ICU stay. RESULTS: A total of 1214 patients, 604 in the preprotocol group and 610 in the postprotocol group, were included. The mean (SD) ICU length of stay and the duration of mechanical ventilation were shorter among patients of the postprotocol group compared with those of the preprotocol group (5.43 [6.43] and 6.39 [8.05] days, respectively; p = 0.004 and 5.95 [6.80] and 7.27 [9.09] days, respectively; p < 0.009). The incidence of delirium remained the same. The proportion of patients with Richmond Agitation and Sedation (RASS) scores between -1 and +1 increased from 57.0% to 66.2% (p = 0.001), whereas the proportion of patients with a numeric rating scale (NRS) score of 1 or less increased from 56.3% to 66.6% (p < 0.001). The mean total cost of ICU hospitalization decreased from $6212.64 (7846.86) in the preprotocol group to $5279.90 (6263.91) in the postprotocol group (p = 0.022). The cost analyses for pain and agitation management improved; the proportion of patients with RASS scores between -1 and +1 or NRS scores of 1 or less increased significantly in the postprotocol group while costing, on average, $932.74 less per hospitalization. CONCLUSIONS: Establishing protocols for patient-driven management of sedation, analgesia, and delirium is a cost-effective practice and allows savings of nearly $1000 per hospitalization.

Assessment of delirium in the intensive care unit: nursing practices and perceptions.

BACKGROUND: Despite practice guidelines promoting delirium assessment in intensive care, few data exist regarding current delirium assessment practices among nurses and how these practices compare with those for sedation assessment. OBJECTIVES: To identify current practices and perceptions of intensive care nurses regarding delirium assessment and to compare practices for assessing delirium with practices for assessing sedation. METHODS: A paper/Web-based survey was administered to 601 staff nurses working in 16 intensive care units at 5 acute care hospitals with sedation guidelines specifying delirium assessment in the Boston, Massachusetts area. RESULTS: Overall, 331 nurses (55%) responded. Only 3% ranked delirium as the most important condition to evaluate, compared with altered level of consciousness (44%), presence of pain (23%), or improper placement of an invasive device (21%). Delirium assessment was less common than sedation assessment (47% vs 98%, P < .001) and was more common among nurses who worked in medical intensive care units (55% vs 40%, P = .03) and at academic centers (53% vs 13%, P < .001). Preferred methods for assessing delirium included assessing ability to follow commands (78%), checking for agitation-related events (71%), the Confusion Assessment Method for the Intensive Care Unit (36%), the Intensive Care Delirium Screening Checklist (11%), and psychiatric consultation (9%). Barriers to assessment included intubation (38%), complexity of the tool for assessing delirium (34%), and sedation level (13%). CONCLUSIONS: Practice and perceptions of delirium assessment vary widely among critical care nurses despite the presence of institutional sedation guidelines that promote delirium assessment.

Prophylaxis against deep vein thrombosis in critically ill patients with severe renal insufficiency with the low-molecular-weight heparin dalteparin: an assessment of safety and pharmacodynamics: the DIRECT study.

BACKGROUND: Use of low-molecular-weight heparins is avoided in patients with renal insufficiency because of concerns about an excessive anticoagulant effect and increased bleeding risk. To challenge this premise, we evaluated if deep vein thrombosis (DVT) prophylaxis with dalteparin sodium confers an excessive anticoagulant effect in critically ill patients with severe renal insufficiency. METHODS: We conducted a multicenter, single-arm clinical trial of DVT prophylaxis with dalteparin sodium, 5000 IU once daily in critically ill patients with a creatinine clearance lower than 30 mL/min (to convert to milliliters per second, multiply by 0.0167). Bioaccumulation was defined by a trough anti-Xa level higher than 0.40 IU/mL, measured twice weekly. The pharmacodynamic properties of dalteparin were assessed by serial anti-Xa levels measured on days 3, 10, and 17. RESULTS: We enrolled 156 patients with a mean (SD) creatinine clearance of 18.9 (6.5) mL/min; 18 were excluded because they died or were discharged before testing (n = 3) or had prevalent DVT (n = 15). Of 138 patients included, the median (interquartile range [IQR]) duration of dalteparin exposure was 7 (4-12) days. In 120 patients who had at least 1 trough anti-Xa level (427 total measurements), no patient had bioaccumulation (0%; 95% confidence interval [CI]: 0%-3.0%); the median (IQR) trough anti-Xa level was undetectable (<0.10 IU/mL [<0.10 to <0.10 IU/mL]). Based on serial measurements, peak anti-Xa levels were 0.29 to 0.34 IU/mL and trough levels were lower than 0.06 IU/mL. Deep vein thrombosis occurred in 7 of 138 patients (5.1%; 95% CI, 2.5%-10.1%); major bleeding occurred in 10 patients (7.2%; 95% CI, 4.0%-12.8%), all with trough anti-Xa levels of 0.18 IU/mL or lower. CONCLUSION: In critically ill patients with severe renal insufficiency, DVT prophylaxis with dalteparin sodium, 5000 IU once daily, is not associated with an excessive anticoagulant effect due to drug bioaccumulation and is unlikely to contribute to bleeding. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00138099.