Search

Importance: Although most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice., Objective: To describe practice variation in IMV discontinuation internationally, associations between initial discontinuation events and outcomes, and factors associated with the use of select discontinuation strategies and failed initial spontaneous breathing trials (SBTs)., Design, Setting, and Participants: Prospective, multinational, observational study of critically ill adults who received IMV for at least 24 hours from 142 intensive care units (ICUs) in 19 countries within 6 regions (27 in Canada, 23 in India, 22 in the UK, 26 in Europe, 21 in Australia/New Zealand, and 23 in the US)., Exposures: Receiving IMV., Main Outcomes and Measures: Primary analyses characterized types of initial IMV discontinuation events (extubation, SBT, or tracheostomy) and associations with clinical outcomes (including duration of ventilation, ICU and hospital mortality, and ICU and hospital length of stay). Secondary analyses examined the associations between SBT outcome and SBT timing and clinical outcomes., Results: Among 1868 patients (median [interquartile range] age, 61.8 [48.9-73.1] years; 1173 [62.8%] men) 424 (22.7%) underwent direct extubation, 930 (49.8%) had an initial SBT (761 [81.8%] successful), 150 (8.0%) underwent direct tracheostomy, and 364 (19.5%) died before a weaning attempt. Across regions, there was variation in the use of written directives to guide care, daily screening, SBT techniques, ventilator modes, and the roles played by clinicians involved in weaning. Compared with initial direct extubation, patients who had an initial SBT had higher ICU mortality (20 [4.7%] vs 96 [10.3%]; absolute difference, 5.6% [95% CI, 2.6%-8.6%]), longer duration of ventilation (median of 2.9 vs 4.1 days; absolute difference, 1.2 days [95% CI, 0.7-1.6]), and longer ICU stay (median of 6.7 vs 8.1 days; absolute difference, 1.4 days [95% CI, 0.8-2.4]). Patients whose initial SBT failed (vs passed) had higher ICU mortality (29 [17.2%] vs 67 [8.8%]; absolute difference, 8.4% [95% CI, 2.0%-14.7%]), longer duration of ventilation (median of 6.1 vs 3.5 days; absolute difference, 2.6 days [95% CI, 1.6-3.6]), and longer ICU stay (median of 10.6 vs 7.7 days; absolute difference, 2.8 days [95% CI, 1.1-5.2]). Compared with patients who underwent early initial SBTs, patients who underwent late initial SBTs (>2.3 days after intubation) had longer duration of ventilation (median of 2.1 vs 6.1 days; absolute difference, 4.0 days [95% CI, 3.7-4.5]), longer ICU stay (median of 5.9 vs 10.8 days; absolute difference, 4.9 days [95% CI, 4.0-6.3]), and longer hospital stay (median of 14.3 vs 22.8 days; absolute difference, 8.5 days [95% CI, 6.0-11.0])., Conclusions and Relevance: In this observational study of invasive mechanical ventilation discontinuation in 142 ICUs in Canada, India, the UK, Europe, Australia/New Zealand, and the US from 2013 to 2016, weaning practices varied internationally., Trial Registration: ClinicalTrials.gov Identifier: NCT03955874.

Background: Identifying critically ill patients who have unmet needs for palliative care is the first step in integrating the palliative approach for patients and their families into intensive care units., Objective: To explore how palliative care is addressed in an intensive care unit and to develop and test a screening tool for unmet needs that may be met through the palliative approach., Methods: A mixed-methods study was conducted in the intensive care unit of a tertiary care hospital to explore the palliative approach. Focus groups and a survey were used to identify items for the screening tool. After pilot testing of the tool, interviews were conducted to refine the content., Results: The first focus group (14 participants) revealed participants' frustration with unclear communication and a desire for better collaboration among health care team members regarding patients with serious life-limiting illnesses and their families. The survey (response rate: 20%; 30 of 150) showed clinicians' preference for items that identify specific needs rather than diagnoses. The second focus group (8 participants) yielded strategies to operationalize the tool for all patients in the intensive care unit. After 2 separate pilot testing cycles, bedside nurses noted that use of the screening tool prompted earlier discussions and broader assessments of what is meaningful to patients and their families., Conclusion: Development of a screening tool for unmet palliative care needs among intensive care unit patients is feasible and acceptable and may help to systematically integrate the palliative approach into routine care for critically ill patients., (Copyright© 2020 American Association of Critical-Care Nurses.)

Rationale: In critically ill patients receiving invasive mechanical ventilation (MV), research supports the use of daily screening to identify patients who are ready to undergo a spontaneous breathing trial (SBT) followed by conduct of an SBT. However, once daily (OD) screening is poorly aligned with the continuous care provided in most intensive care units (ICUs) and the best SBT technique for clinicians to use remains controversial., Objectives: To identify the optimal screening frequency and SBT technique to wean critically ill adults in the ICU., Methods: We aim to conduct a multicenter, factorial design randomized controlled trial with concealed allocation, comparing the effect of both screening frequency (once versus at least twice daily [ALTD]) and SBT technique (Pressure Support [PS] + Positive End-Expiratory Pressure [PEEP] vs T-piece) on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American ICUs. In the OD arm, respiratory therapists (RTs) will screen study patients between 06:00 and 08:00 h. In the ALTD arm, patients will be screened at least twice daily between 06:00 and 08:00 h and between 13:00 and 15:00 h with additional screens permitted at the clinician's discretion. When the SBT screen is passed, an SBT will be conducted using the assigned technique (PS + PEEP or T-piece). We will follow patients until successful extubation, death, ICU discharge, or until day 60 after randomization. We will contact patients or their surrogates six months after randomization to assess health-related quality of life and functional status., Relevance: The around-the-clock availability of RTs in North American ICUs presents an important opportunity to identify the optimal SBT screening frequency and SBT technique to minimize patients' exposure to invasive ventilation and ventilator-related complications., Trial Registration: Clinical Trials.gov, NCT02399267 . Registered on Nov 21, 2016 first registered.

Introduction: Research supports the use of specific strategies to discontinue mechanical ventilation (MV) in critically ill patients. Little is known about how clinicians actually wean and discontinue MV in practice or the association between different discontinuation strategies and outcomes. The primary objective of this study is to describe international practices in the use of (1) daily screening for readiness to discontinue MV, (2) modes of MV used before initial discontinuation attempts, (3) weaning and spontaneous breathing trial (SBT) protocols, (4) SBT techniques and (5) sedation and mobilisation practices to facilitate weaning and discontinuation. The secondary objectives are to identify patient characteristics and time-dependent factors associated with use of selected strategies, investigate associations between SBT outcome (failure vs success) and outcomes, explore differences between patients who undergo an SBT early versus later in their intensive care unit (ICU) stay, and investigate the associations between different SBT techniques and humidification strategies on outcomes., Methods and Analysis: We will conduct an international, prospective, observational study of MV discontinuation practices among critically ill adults who receive invasive MV for at least 24 hours at approximately 150 ICUs in six geographic regions (Canada, USA, UK, Europe, India and Australia/New Zealand). Research personnel at participating ICUs will collect demographic data, data to characterise the initial strategy or event that facilitated discontinuation of MV (direct extubation, direct tracheostomy, initial successful SBT, initial failed SBT or death before any attempt could be made), clinical outcomes and site information. We aim to collect data on at least 10 non-death discontinuation events in each ICU (at least 1500 non-death discontinuation events)., Ethics and Dissemination: This study received Research Ethics Approval from St. Michael's Hospital (11-024) Research ethics approval will be sought from all participating sites. The results will be disseminated through publications in peer-reviewed journals., Trial Registration Number: NCT03955874., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: It is unknown whether more frequent screening of invasively ventilated patients, identifies patients earlier for a spontaneous breathing trial, and shortens the duration of ventilation. We assessed the feasibility of conducting a large trial to evaluate screening frequency in critically ill adults in the North American context., Design: We conducted two contemporaneous, multicenter, pilot, randomized controlled trials (the LibeRation from MEchanicaL VEntilAtion and ScrEening Frequency [RELEASE] and Screening Elderly PatieNts For InclusiOn in a Weaning [SENIOR] trials) to address concerns regarding the potential for higher enrollment, fewer adverse events, and better outcomes in younger patients., Setting: Ten and 11 ICUs in Canada, respectively., Patients: Parallel trials of younger (RELEASE < 65 yr) and older (SENIOR ≥ 65 yr) critically ill adults invasively ventilated for at least 24 hours., Interventions: Each trial compared once daily screening to "at least twice daily" screening led by respiratory therapists., Measurements and Main Results: In both trials, we evaluated recruitment (aim: 1-2 patients/month/ICU) and consent rates, reasons for trial exclusion, protocol adherence (target: ≥ 80%), crossovers (aim: ≤ 10%), and the effect of the alternative screening frequencies on adverse events and clinical outcomes. We included 155 patients (53 patients [23 once daily, 30 at least twice daily] in RELEASE and 102 patients [54 once daily, 48 at least twice daily] in SENIOR). Between trials, we found similar recruitment rates (1.32 and 1.26 patients/month/ICU) and reasons for trial exclusion, high consent and protocol adherence rates (> 92%), infrequent crossovers, and few adverse events. Although underpowered, at least twice daily screening was associated with a nonsignificantly faster time to successful extubation and more successful extubations but significantly increased use of noninvasive ventilation in both trials combined., Conclusions: Similar recruitment and consent rates, few adverse events, and comparable outcomes in younger and older patients support conduct of a single large trial in North American ICUs assessing the net clinical benefits associated with more frequent screening.

Objective: To describe the development, implementation and initial evaluation of an initiative to improve glucose control in critically ill patients., Design: Glucose control in critically ill patients was chosen by critical care leaders as a target for improvement. This was an observational study to document changes in processes and measures of glucose control in each intensive care unit (ICU). ICU nurse educators were interviewed to document relevant changes between April 2012 and April 2016., Setting: 16 ICUs in British Columbia, Canada., Participants: ICU leaders., Intervention(s): A community of practice (CoP) was formed, guidelines were adopted, two learning sessions were held, and an electronic system to collect data was created. Then, each ICU introduced their own educational and process interventions., Main Outcome Measure(s): Average hyperglycemic index (area under the curve of serum glucose concentration versus time above the upper limit (10 mmol/l) divided by time on insulin infusion), number of hypoglycemic events (<3.5 mmol/l) divided by time on insulin infusion and standardized mortality rate (actual/predicted hospital mortality) for each 3-month period., Results: Although there were some isolated points and short trends that indicated special cause variation, there were no major trends over time and no obvious association with any of the process changes for each hospital. However, the average hyperglycemic index was higher in some of the smaller hospitals than in the larger hospitals., Conclusions: In this, 4-year observation of glucose control in ICUs within a CoP, the lack of sustained improvement suggests the need for more active and durable interventions., (© The Author(s) 2018. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Very elderly (over 80 yr of age) critically ill patients admitted to medical-surgical intensive care units (ICUs) have a high incidence of mortality, prolonged hospital length of stay, and dependent living conditions should they survive. The primary purpose of this study is to describe the outcomes and differences in outcomes between very elderly medical patients and their surgical counterparts admitted to Canadian ICUs, thereby informing decision-making for clinicians and substitute decision-makers., Methods: This was a prospective multicentre cohort study of very elderly medical and surgical patients admitted to 22 Canadian academic and non-academic ICUs. Outcome measures included ICU length of stay and mortality, hospital length of stay and mortality, and disposition following hospital discharge., Results: There were 1,671 patients evaluated in this study. Patient demographics included a mean age of 84.5 yr, baseline Acute Physiology and Chronic Health Evaluation (APACHE) II score of 22.4, baseline Sequential Organ Failure Assessment (SOFA) score of 5.3, overall ICU mortality of 21.8%, and overall hospital mortality of 35.0%. Medical patient median ICU length of stay was 4.1 days, hospital length of stay was 16.2 days, ICU mortality was 26.5%, and hospital mortality was 41.5%. Surgical patient median ICU length of stay was 3.8 days, hospital length of stay was 20.1 days, ICU mortality was 18.7%, and hospital mortality was 31.6%. Only 45.0% of medical patients and 41.6% of surgical emergency patients were able to return home to live., Conclusions: In this large sample of critically ill medical and surgical patients, the admission SOFA score and hospital lengths of stay were not different between the two groups, but medical patients had longer ICU lengths of stay and higher ICU and hospital mortality than surgical patients.

Background: Very elderly (80 years of age and above) critically ill patients admitted to medical intensive care units (ICUs) have a high incidence of mortality, prolonged hospital length of stay, and living in a dependent state should they survive., Objective: The objective was to develop a clinical prediction tool for hospital mortality to improve future end-of-life decision making for very elderly patients who are admitted to Canadian ICUs., Design: This was a prospective, multicenter cohort study., Setting: Data from 1033 very elderly medical patients admitted to 22 Canadian academic and nonacademic ICUs were analyzed., Interventions: A univariate analysis of selected predictors to ascertain prognostic power was performed, followed by multivariable logistic regression to derive the final prediction tool., Main Results: We included 1033 elderly patients in the analyses. Mean age was 84.6±3.5 years, 55% were male, mean Acute Physiology and Chronic Health Evaluation II score was 23.1±7.9, Sequential Organ Failure Assessment score was 5.3±3.4, median ICU length of stay was 4.1 (interquartile range, 6.2) days, median hospital length of stay was 16.2 (interquartile range, 25.0) days, and ICU mortality and all-cause hospital mortality were 27% and 41%, respectively. Important predictors of hospital mortality at the time of ICU admission include age (85-90 years of age had an odds ratio of hospital mortality of 1.63 [1.04-2.56]; >90 years of age had an odds ratio of hospital mortality of 2.64 [1.27-5.48]), serum creatinine (120-300 had an odds ratio of hospital mortality of 1.57 [1.01-2.44]; >300 had an odds ratio of hospital mortality of 5.29 [2.43-11.51]), Glasgow Coma Scale (13-14 had an odds ratio of hospital mortality of 2.09 [1.09-3.98]; 8-12 had an odds ratio of hospital mortality of 2.31 [1.34-3.97]; 4-7 had an odds ratio of hospital mortality of 5.75 [3.02-10.95]; 3 had an odds ratio of hospital mortality of 8.97 [3.70-21.74]), and serum pH (<7.15 had an odds ratio of hospital mortality of 2.44 [1.07-5.60])., Conclusion: We identified high-risk characteristics for hospital mortality in the elderly population and developed a Risk Scale that may be used to inform discussions regarding goals of care in the future. Further study is warranted to validate the Risk Scale in other settings and evaluate its impact on clinical decision making., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: We sought to develop and internally validate a clinical prediction model to estimate the outcome of very elderly patients 12 months after being admitted to the ICU., Design: Prospective, longitudinal cohort study., Setting: Twenty-two Canadian ICUs., Patients: We recruited 527 patients 80 years or older who had a medical or urgent surgical diagnosis and were admitted to an ICU for at least 24 hours., Measurements and Main Results: At baseline, we completed a comprehensive geriatric assessment of enrolled patients; survival and functional status was determined 12 months later. We defined recovery from critical illness as Palliative Performance Scale score of greater than or equal to 60. We used logistic regression analysis to examine factors associated with this outcome. Of the 434 patients (82%) whose Palliative Performance Scale was known at 12 months, 50% had died and 29% (126/434) had a score of greater than or equal to 60. In the multivariable model, we found that being married, having a primary diagnosis of emergency coronary artery bypass grafting or valve replacement, and higher baseline Palliative Performance Scale were independently predictive of a 12-month Palliative Performance Scale score of greater than or equal to 60. Male sex, primary diagnosis of stroke, and higher Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity index, or clinical frailty scale were independently predictive of Palliative Performance Scale score of less than 60., Conclusion: Approximately one-quarter of very old ICU patients achieve a reasonable level of function 1 year after admission. This prediction model applied to individual patients may be helpful in decision making about the utility of life support for very elderly patients who are admitted to the ICU.

Purpose: Increasingly, very old patients are admitted to Intensive Care Units (ICUs). The objective of this study was to describe 12-month outcomes of these patients and determine which characteristics are associated with a return to baseline physical function 1 year later., Methods: In this prospective cohort study in 22 Canadian hospitals, we recruited 610 patients aged 80 years or older who were admitted to ICU for at least 24 h. At baseline, we completed a comprehensive geriatric assessment and followed patients to determine 12-month survival and physical function. Our primary outcome was physical recovery from critical illness at 12 months, defined as being alive with Short Form-36 physical function score of at least 10 points, and not 10 or more points below baseline. We used regression analysis to examine factors associated with physical recovery., Results: Patients were on average 84 years old (range 80-99). Mortality was 14% in ICU, 26% in hospital and 44% at 12 months after admission. Of 505 patients evaluable at 12 months, 26% achieved physical recovery. In the multivariable model, physical recovery was significantly associated with younger age, lower APACHE II score, lower Charlson comorbidity score, lower frailty index, lower baseline physical function score, and specific admission diagnoses., Conclusions: One-quarter of patients aged 80 years or older who are admitted to ICU survived and returned to baseline levels of physical function at 1 year. Routine assessment of baseline physical function and frailty status could aid in prognostication and informed decision-making for very old critically ill patients. (ClinicalTrials.gov number NCT01293708).

Purpose: To compare the effect of intensive versus conventional blood glucose control in patients with traumatic brain injury., Methods: In a large international randomized trial patients were randomly assigned to a target blood glucose (BG) range of either 4.5-6.0 mmol/L (intensive control) or <10 mmol/L (conventional control). Patients with traumatic brain injury (TBI) were identified at randomization and data were collected to examine the extended Glasgow outcome score (includes mortality) at 24 months., Results: Of the 6104 randomized patients, 391 satisfied diagnostic criteria for TBI; 203 (51.9%) were assigned to intensive and 188 (48.1%) to conventional control; the primary outcome was available for 166 (81.8%) and 149 (79.3%) patients, respectively. The two groups had similar baseline characteristics. At 2 years 98 (58.7%) patients in the intensive group and 79 (53.0%) in the conventional group had a favorable neurological outcome (odds ratio [OR] 1.26, 95% CI 0.81-1.97; P = 0.3); 35 patients (20.9%) in the intensive group and 34 (22.8%) in the conventional group had died (OR 0.90, 95% CI 0.53-1.53; P = 0.7); moderate hypoglycemia (BG 2.3-3.9 mmol/L; 41-70 mg/dL) occurred in 160/202 (79.2%) and 17/188 (9.0%), respectively (OR 38.3, 95% CI 21.0-70.1; P < 0.0001); severe hypoglycemia (BG ≤ 2.2 mmol/L; ≤40 mg/dL) in 10 (4.9%) and 0 (0.0%), respectively (OR 20.5 95% CI 1.2-351.6, P = 0.003)., Conclusion: Although patients with traumatic brain injury randomly assigned to intensive compared to conventional glucose control experienced moderate and severe hypoglycemia more frequently, we found no significant difference in clinically important outcomes.

Objectives: To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU., Design: Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial., Setting: Sixty-seven medical-surgical ICUs in six countries., Patients: Three thousand seven hundred forty-six medical-surgical critically ill patients., Interventions: All patients received anticoagulant thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin at standard doses., Measurements and Main Results: Independent predictors for venous thromboembolism, proximal leg deep vein thrombosis, and pulmonary embolism developing during critical illness were assessed. A total of 289 patients (7.7%) developed venous thromboembolism. Predictors of thromboprophylaxis failure as measured by development of venous thromboembolism included a personal or family history of venous thromboembolism (hazard ratio, 1.64; 95% CI, 1.03-2.59; p = 0.04) and body mass index (hazard ratio, 1.18 per 10-point increase; 95% CI, 1.04-1.35; p = 0.01). Increasing body mass index was also a predictor for developing proximal leg deep vein thrombosis (hazard ratio, 1.25; 95% CI, 1.06-1.46; p = 0.007), which occurred in 182 patients (4.9%). Pulmonary embolism occurred in 47 patients (1.3%) and was associated with body mass index (hazard ratio, 1.37; 95% CI, 1.02-1.83; p = 0.035) and vasopressor use (hazard ratio, 1.84; 95% CI, 1.01-3.35; p = 0.046). Low-molecular-weight heparin (in comparison to unfractionated heparin) thromboprophylaxis lowered pulmonary embolism risk (hazard ratio, 0.51; 95% CI, 0.27-0.95; p = 0.034) while statin use in the preceding week lowered the risk of proximal leg deep vein thrombosis (hazard ratio, 0.46; 95% CI, 0.27-0.77; p = 0.004)., Conclusions: Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparin is more likely in ICU patients with elevated body mass index, those with a personal or family history of venous thromboembolism, and those receiving vasopressors. Alternate management or incremental risk reduction strategies may be needed in such 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.

Background: Thrombocytopenia occurs in 20% to 45% of critically ill medical-surgical patients. The 4Ts heparin-induced thrombocytopenia (HIT) score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason[s] for thrombocytopenia) might reliably identify patients at low risk for HIT. Interobserver agreement on 4Ts scoring is uncertain in this setting., Objective: To evaluate whether a published clinical prediction rule (the "4Ts score") reliably rules out HIT in "low-risk" intensive care unit (ICU) patients as assessed by research coordinators (who prospectively scored) and 2 adjudicators (who scored retrospectively) during an international heparin thromboprophylaxis trial (PROTECT, NCT00182143)., Methods: Of 3746 medical-surgical ICU patients in PROTECT, 794 met the enrollment criteria for this HIT substudy. Enrollment was predicated on one of the following occurring in ICU: platelets less than 50×10(9)/L, platelets decreased to 50% of ICU admission value (if admission value<100×10(9)/L), any venous thrombosis, or if HIT was otherwise clinically suspected. Independently, 4Ts scores were completed in real time by research coordinators blinded to study drug and laboratory HIT results, and retrospectively by 2 adjudicators blinded to study drug, laboratory HIT results, and research coordinators' scores; the adjudicators arrived at consensus in all cases. Of the 763 patients, 474 had a central or local laboratory HIT test performed and had 4Ts scoring by adjudicators; 432 were scored by trained research coordinators. Heparin-induced thrombocytopenia was defined by a centrally performed positive serotonin release assay (SRA)., Results: Of the 474 patients with central adjudication, 407 (85.9%) had a 4Ts score of 3 or lower, conferring a low pretest probability (PTP) of HIT; of these, 6 (1.5% [95% confidence interval, 0.7%-3.2%) had a positive SRA. Fifty-nine (12.4%) had a moderate PTP (4Ts score of 4-5); of these, 4 (6.8%) had a positive SRA. Eight patients had a high PTP (4Ts score of ≥6); of these, 1 (12.5%) had a positive SRA. Raw agreement between research coordinators and central adjudication on each domain of the 4Ts score and low, intermediate, and high PTP was good. However, chance-corrected agreement was variable between adjudicators (weighted κ values of 0.31-0.93) and between the adjudicator consensus and research coordinators (weighted κ values of 0.13 and 0.78). Post hoc review of the 6 SRA-positive cases with an adjudicated low PTP demonstrated that their scores would have been increased if the adjudicators had had additional information on heparin exposure prior to ICU admission. In general, the fourth domain of 4Ts (oTher causes of thrombocytopenia) generated the most disagreement., Conclusions: Real-time 4Ts scoring by research coordinators at the time of testing for HIT was not consistent with 4Ts scores obtained by central adjudicators. The results of this comprehensive HIT testing highlight the need for further research to improve the assessment of PTP scoring of HIT for critically ill patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Importance: Critically ill patients are at risk of venous thrombosis, and therefore guidelines recommend daily thromboprophylaxis. Deep vein thrombosis (DVT) commonly occurs in the lower extremities but can occur in other sites including the head and neck, trunk, and upper extremities. The risk of nonleg deep venous thromboses (NLDVTs), predisposing factors, and the association between NLDVTs and pulmonary embolism (PE) or death are unclear., Objective: To describe the frequency, anatomical location, risk factors, management, and consequences of NLDVTs in a large cohort of medical-surgical critically ill adults., Design, Setting, and Participants: A nested prospective cohort study in the setting of secondary and tertiary care intensive care units (ICUs). The study population comprised 3746 patients, who were expected to remain in the ICU for at least 3 days and were enrolled in a randomized clinical trial of dalteparin vs standard heparin for thromboprophylaxis., Main Outcomes and Measures: The proportion of patients who had NLDVTs, the mean number per patient, and the anatomical location. We characterized NLDVTs as prevalent or incident (identified within 72 hours of ICU admission or thereafter) and whether they were catheter related or not. We used multivariable regression models to evaluate risk factors for NLDVT and to examine subsequent anticoagulant therapy, associated PE, and death. RESULTS Of 3746 trial patients, 84 (2.2%) developed 1 or more non-leg vein thromboses (superficial or deep, proximal or distal). Thromboses were more commonly incident (n = 75 [2.0%]) than prevalent (n = 9 [0.2%]) (P < .001) and more often deep (n = 67 [1.8%]) than superficial (n = 31 [0.8%]) (P < .001). Cancer was the only independent predictor of incident NLDVT (hazard ratio [HR], 2.22; 95% CI, 1.06-4.65). After adjusting for Acute Physiology and Chronic Health Evaluation (APACHE) II scores, personal or family history of venous thromboembolism, body mass index, vasopressor use, type of thromboprophylaxis, and presence of leg DVT, NLDVTs were associated with an increased risk of PE (HR, 11.83; 95% CI, 4.80-29.18). Nonleg DVTs were not associated with ICU mortality (HR, 1.09; 95% CI, 0.62-1.92) in a model adjusting for age, APACHE II, vasopressor use, mechanical ventilation, renal replacement therapy, and platelet count below 50 × 10(9)/L. CONCLUSIONS AND RELEVANCE Despite universal heparin thromboprophylaxis, nonleg thromboses are found in 2.2% of medical-surgical critically ill patients, primarily in deep veins and proximal veins. Patients who have a malignant condition may have a significantly higher risk of developing NLDVT, and patients with NLDVT, compared with those without, appeared to be at higher risk of PE but not higher risk of death., Trial Registration: clinicaltrials.gov Identifier: NCT00182143.

Background: Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU)., Objective: To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients., Methods: In a randomized trial of thromboprophylaxis, patients with suspected PE were adjudicated as possible, probable or definite PE. Data were then retrospectively abstracted for the Geneva Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic scores. The chance-corrected agreement between adjudicated categories and each score was calculated. ANOVA was used to compare values across the three adjudicated PE categories., Results: Among 70 patients with suspected PE, agreement was poor between adjudicated categories and Geneva pretest probabilities (kappa=0.01 [95% CI -0.0643 to 0.0941]) or Wells pretest probabilities (kappa=-0.03 [95% CI -0.1462 to 0.0914]). Among four possible, 16 probable and 50 definite PEs, there were no significant differences in Geneva scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30)., Conclusions: Pretest probability scores developed outside the ICU do not correlate with adjudicated PE categories in critically ill patients. Research is needed to develop prediction scores for this population.

Purpose: Bleeding frequently complicates critical illness and may have serious consequences. Our objectives are to describe the predictors of major bleeding and the association between bleeding and mortality in medical-surgical critically ill patients receiving heparin thromboprophylaxis., Methods: We prospectively studied patients from 67 intensive care units and six countries enrolled in a thromboprophylaxis trial (NCT00182143) comparing dalteparin with unfractionated heparin. Patients with trauma, orthopedic surgery or neurosurgery were excluded. Trained research coordinators used a validated tool to document bleeding, which underwent duplicate independent blinded adjudication. Major bleeding was defined as hypovolemic shock, bleeding into critical sites, requiring an invasive intervention or transfusion of at least two units of red blood cells, or associated with hypotension or tachycardia in the absence of other causes. Adjusted Cox proportional hazard regression analysis was used to identify major bleeding predictors and the association between bleeding and mortality., Results: Among 3,746 patients, bleeding occurred in 208 [5.6 %, 95 % confidence interval (CI) 4.9-6.3 %]. Time-dependent predictors were prolonged activated partial thromboplastin time [hazard ratio (HR) 1.10, 1.05-1.14 per 10 s increase], lower platelet count (HR 1.16, 1.09-1.24 per 50 × 10(9)/L decrease), therapeutic heparin (HR 3.26, 1.72-6.17), antiplatelet agents (HR 1.38, 1.02-1.88), renal replacement therapy (HR 1.75, 1.20-2.56), and recent surgery (HR 1.64, 1.01-2.65). Type of pharmacologic thromboprophylaxis was not associated with bleeding. Patients with bleeding had a higher risk of in-hospital death (HR 2.09, 1.69-2.57)., Conclusions: As major bleeding has modifiable risk factors and is associated with in-hospital mortality, strategies to mitigate these factors should be evaluated in critically ill patients.

Background: Ventilator-associated conditions (VACs) and infection-related ventilator-associated complications (iVACs) are the Centers for Disease Control and Prevention's new surveillance paradigms for patients who are mechanically ventilated. Little is known regarding the clinical impact and preventability of VACs and iVACs and their relationship to ventilator-associated pneumonia (VAP). We evaluated these using data from a large, multicenter, quality-improvement initiative., Methods: We retrospectively applied definitions for VAC and iVAC to data from a prospective time series study in which VAP clinical practice guidelines were implemented in 11 North American ICUs. Each ICU enrolled 30 consecutive patients mechanically ventilated &gt; 48 h during each of four study periods. Data on clinical outcomes and concordance with prevention recommendations were collected. VAC, iVAC, and VAP rates over time, the agreement (κ statistic) between definitions, associated morbidity/mortality, and independent risk factors for each were determined., Results: Of 1,320 patients, 139 (10.5%) developed a VAC, 65 (4.9%) developed an iVAC, and 148 (11.2%) developed VAP. The agreement between VAP and VAC was 0.18, and between VAP and iVAC it was 0.19. Patients who developed a VAC or iVAC had significantly more ventilator days, hospital days, and antibiotic days and higher hospital mortality than patients who had neither of these conditions. Increased concordance with VAP prevention guidelines during the study was associated with decreased VAP and VAC rates but no change in iVAC rates., Conclusions: VACs and iVACs are associated with significant morbidity and mortality. Although the agreement between VAC, iVAC, and VAP is poor, a higher adoption of measures to prevent VAP was associated with lower VAP and VAC rates.

Objective: We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care., Data Sources: We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews., Study Selection: Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies., Data Extraction: Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care., Data Synthesis: From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized mean difference [95% CI]: 0.26 [0.1, 0.42]; p = 0.001 and four observational studies and one randomized controlled trial; 0.83 [0.37, 1.29]; p = 0.0004, respectively). Heterogeneity among studies within topics ranged from low to extreme. The exclusion of randomized controlled trials did not change our results. Single-intervention and lower-quality studies had higher standardized mean differences compared to multiple-intervention and higher-quality studies (p = 0.013 and 0.016, respectively). There were no associated improvements in clinical outcomes., Conclusions: Knowledge translation interventions in the ICU that include protocols with or without education are associated with the greatest improvements in processes of critical care.

Objective: Operations research is the application of mathematical modeling, statistical analysis, and mathematical optimization to understand and improve processes in organizations. The objective of this study was to illustrate how the methods of operations research can be used to identify opportunities to reduce the absolute value and variability of interfacility transport intervals for critically ill patients., Methods: After linking data from two patient transport organizations in British Columbia, Canada, for all critical care transports during the calendar year 2006, the steps for transfer of critically ill patients were tabulated into a series of time intervals. Statistical modeling, root-cause analysis, Monte Carlo simulation, and sensitivity analysis were used to test the effect of changes in component intervals on overall duration and variation of transport times. Based on quality improvement principles, we focused on reducing the 75th percentile and standard deviation of these intervals., Results: We analyzed a total of 3808 ground and air transports. Constraining time spent by transport personnel at sending and receiving hospitals was projected to reduce the total time taken by 33 minutes with as much as a 20% reduction in standard deviation of these transport intervals in 75% of ground transfers. Enforcing a policy of requiring acceptance of patients who have life- or limb-threatening conditions or organ failure was projected to reduce the standard deviation of air transport time by 63 minutes and the standard deviation of ground transport time by 68 minutes., Conclusions: Based on findings from our analyses, we developed recommendations for technology renovation, personnel training, system improvement, and policy enforcement. Use of the tools of operations research identifies opportunities for improvement in a complex system of critical care transport.

Objectives: The Family Satisfaction in the Intensive Care Unit 24 (FS-ICU 24) survey consists of two domains (overall care and medical decision-making) and was validated only for family members of adult patients in the ICU. The purpose of this study was to evaluate the internal consistency and construct validity of the FS-ICU 24 survey modified for parents/caregivers of pediatric patients (Pediatric Family Satisfaction in the Intensive Care Unit 24 [pFS-ICU 24]) by comparing it to McPherson's PICU satisfaction survey, in a similar racial/ethnic population as the original Family Satisfaction in the Intensive Care Unit validation studies (English-speaking Caucasian adults). We hypothesized that the pFS-ICU 24 would be psychometrically sound to assess satisfaction of parents/caregivers with critically ill children., Design: A prospective survey examination of the pFS-ICU 24 was performed (1/2011-12/2011). Participants completed the pFS-ICU 24 and McPherson's survey with the order of administration alternated with each consecutive participant to control for order effects (nonrandomized). Cronbach's alphas (α) were calculated to examine internal consistency reliability, and Pearson correlations were calculated to examine construct validity., Setting: University-affiliated, children's hospital, cardiothoracic ICU., Subjects: English-speaking Caucasian parents/caregivers of children less than 18 years old admitted to the ICU (on hospital day 3 or 4) were approached to participate if they were at the bedside for greater than or equal to 2 days., Measurements and Main Results: Fifty parents/caregivers completed the surveys (mean age ± SD = 36.2±9.6 yr; 56% mothers). The α for the pFS-ICU 24 was 0.95 and 0.92 for McPherson's survey. Overall, responses for the pFS-ICU 24 and McPherson's survey were significantly correlated (r = 0.73; p < 0.01). The average overall pFS-ICU 24 satisfaction score was 92.6 ± 8.3. The average pFS-ICU 24 satisfaction with care domain and medical decision-making domain scores were 93.3 ± 8.8 and 91.2 ± 8.9, respectively., Conclusions: The pFS-ICU 24 is a psychometrically sound measure of satisfaction with care and medical decision-making of parents/caregivers with children in the ICU.

Context: Protocolized sedation and daily sedation interruption are 2 strategies to minimize sedation and reduce the duration of mechanical ventilation and intensive care unit (ICU) stay. We hypothesized that combining these strategies would augment the benefits., Objective: To compare protocolized sedation with protocolized sedation plus daily sedation interruption in critically ill patients., Design, Setting, and Patients: Randomized controlled trial of 430 critically ill, mechanically ventilated adults conducted in 16 tertiary care medical and surgical ICUs in Canada and the United States between January 2008 and July 2011., Intervention: Continuous opioid and/or benzodiazepine infusions and random allocation to protocolized sedation (n = 209) (control) or to protocolized sedation plus daily sedation interruption (n = 214). Using validated scales, nurses titrated infusions to achieve light sedation. For patients receiving daily interruption, nurses resumed infusions, if indicated, at half of previous doses. Patients were assessed for delirium and for readiness for unassisted breathing., Main Outcome Measure: Time to successful extubation. Secondary outcomes included duration of stay, doses of sedatives and opioids, unintentional device removal, delirium, and nurse and respiratory therapist clinical workload (on a 10-point visual analog scale [VAS])., Results: Median time to successful extubation was 7 days in both the interruption and control groups (median [IQR], 7 [4-13] vs 7 [3-12]; interruption group hazard ratio, 1.08; 95% CI, 0.86-1.35; P = .52). Duration of ICU stay (median [IQR], 10 [5-17] days vs 10 [6-20] days; P = .36) and hospital stay (median [IQR], 20 [10-36] days vs 20 [10-48] days; P = .42) did not differ between the daily interruption and control groups, respectively. Daily interruption was associated with higher mean daily doses of midazolam (102 mg/d vs 82 mg/d; P = .04) and fentanyl (median [IQR], 550 [50-1850] vs 260 [0-1400]; P < .001) and more daily boluses of benzodiazepines (mean, 0.253 vs 0.177; P = .007) and opiates (mean, 2.18 vs 1.79; P < .001). Unintentional endotracheal tube removal occurred in 10 of 214 (4.7%) vs 12 of 207 patients (5.8%) in the interruption and control groups, respectively (relative risk, 0.82; 95% CI, 0.36-1.84; P = .64). Rates of delirium were not significantly different between groups (53.3% vs 54.1%; relative risk, 0.98; 95% CI, 0.82-1.17; P = .83). Nurse workload was greater in the interruption group (VAS score, 4.22 vs 3.80; mean difference, 0.41; 95% CI, 0.17-0.66; P = .001)., Conclusion: For mechanically ventilated adults managed with protocolized sedation, the addition of daily sedation interruption did not reduce the duration of mechanical ventilation or ICU stay., Trial Registration: clinicaltrials.gov Identifier: NCT00675363.

Background: Whether hypoglycemia leads to death in critically ill patients is unclear., Methods: We examined the associations between moderate and severe hypoglycemia (blood glucose, 41 to 70 mg per deciliter [2.3 to 3.9 mmol per liter] and ≤40 mg per deciliter [2.2 mmol per liter], respectively) and death among 6026 critically ill patients in intensive care units (ICUs). Patients were randomly assigned to intensive or conventional glucose control. We used Cox regression analysis with adjustment for treatment assignment and for baseline and postrandomization covariates., Results: Follow-up data were available for 6026 patients: 2714 (45.0%) had moderate hypoglycemia, 2237 of whom (82.4%) were in the intensive-control group (i.e., 74.2% of the 3013 patients in the group), and 223 patients (3.7%) had severe hypoglycemia, 208 of whom (93.3%) were in the intensive-control group (i.e., 6.9% of the patients in this group). Of the 3089 patients who did not have hypoglycemia, 726 (23.5%) died, as compared with 774 of the 2714 with moderate hypoglycemia (28.5%) and 79 of the 223 with severe hypoglycemia (35.4%). The adjusted hazard ratios for death among patients with moderate or severe hypoglycemia, as compared with those without hypoglycemia, were 1.41 (95% confidence interval [CI], 1.21 to 1.62; P<0.001) and 2.10 (95% CI, 1.59 to 2.77; P<0.001), respectively. The association with death was increased among patients who had moderate hypoglycemia on more than 1 day (>1 day vs. 1 day, P=0.01), those who died from distributive (vasodilated) shock (P<0.001), and those who had severe hypoglycemia in the absence of insulin treatment (hazard ratio, 3.84; 95% CI, 2.37 to 6.23; P<0.001)., Conclusions: In critically ill patients, intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death. The association exhibits a dose-response relationship and is strongest for death from distributive shock. However, these data cannot prove a causal relationship. (Funded by the Australian National Health and Medical Research Council and others; NICE-SUGAR ClinicalTrials.gov number, NCT00220987.).

Rationale: Venous thromboembolism is difficult to diagnose in critically ill patients and may increase morbidity and mortality., Objectives: To evaluate the cost-effectiveness of strategies to reduce morbidity from venous thromboembolism in critically ill patients., Methods: A Markov decision analytic model to compare weekly compression ultrasound screening (screening) plus investigation for clinically suspected deep vein thrombosis (DVT) (case finding) versus case finding alone; and a hypothetical program to increase adherence to DVT prevention. Probabilities were derived from a systematic review of venous thromboembolism in medical-surgical intensive care unit patients. Costs (in 2010 $US) were obtained from hospitals in Canada, Australia, and the United States, and the medical literature. Analyses were conducted from a societal perspective over a lifetime horizon. Outcomes included costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios., Measurements and Main Results: In the base case, the rate of proximal DVT was 85 per 1,000 patients. Screening resulted in three fewer pulmonary emboli than case-finding alone but also two additional bleeding episodes, and cost $223,801 per QALY gained. In sensitivity analyses, screening cost less than $50,000 per QALY only if the probability of proximal DVT increased from a baseline of 8.5-16%. By comparison, increasing adherence to appropriate pharmacologic thromboprophylaxis by 10% resulted in 16 fewer DVTs, one fewer pulmonary emboli, and one additional heparin-induced thrombocytopenia and bleeding event, and cost $27,953 per QALY gained. Programs achieving increased adherence to best-practice venous thromboembolism prevention were cost-effective over a wide range of program costs and were robust in probabilistic sensitivity analyses., Conclusions: Appropriate prophylaxis provides better value in terms of costs and health gains than routine screening for DVT. Resources should be targeted at optimizing thromboprophylaxis.

Rationale: Nurses in the intensive care unit (ICU) commonly work frequent 12 h shifts, potentially leading to fatigue and reduced vigilance. The authors hypothesised that rates of hypoglycaemia in patients receiving an insulin infusion would be associated with the intensity of work of the bedside nurse in the preceding 72 h., Methods: The authors identified ICU patients who had hypoglycaemia (glucose ≤3.5 mmol/l, 63 mg/dl) between October 2006 and June 2007. The number of shifts worked in the previous 72 h was calculated for the nurse caring for the patient when the event occurred (case shift). For each case shift, the authors identified up to three control shifts (24, 48 and 72 h before the event in the same patient) and calculated the number of shifts worked by nurses on these shifts in the previous 72 h. Conditional logistic regression was used to determine whether the number of shifts worked was associated with hypoglycaemia., Results: There were 41 events (32 patients). Each additional shift worked in the previous 72 h was associated with a significantly increased risk of hypoglycaemia (OR = 1.65/shift, 95% CI 1.01 to 2.68, p = 0.04) after controlling for nurse age and experience. The association was greater for the 23 events associated with an error in management according to the insulin protocol (OR = 2.93/shift, 1.15 to 7.44, p = 0.02) compared with events not associated with an error (OR = 1.34/shift, 0.73 to 2.45, p = 0.34)., Conclusions: Intensive nursing work schedules are associated with hypoglycaemic events in ICU patients.

Rationale: One in three Americans under 65 years of age does not have health insurance during some portion of each year. Patients who are critically ill and lack health insurance may be at particularly high risk of morbidity and mortality due to the high cost of intensive care., Objectives: To systematically review the medical and nonmedical literature to determine whether differences in critical care access, delivery, and outcomes are associated with health insurance status., Methods: Nine electronic databases (inception to 11 April 2008) were independently screened and abstracted in duplicate., Measurements and Main Results: From 5,508 citations, 29 observational studies met eligibility criteria. Among the general U.S. population, patients who were uninsured were less likely to receive critical care services than those with insurance (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.55-0.56). Once admitted to the intensive care unit, patients who were uninsured had 8.5% (95% CI, 6.0-11.1) fewer procedures, were more likely to experience hospital discharge delays (OR 4.51; 95% CI, 1.46-13.93), and were more likely to have life support withdrawn (OR 2.80; 95% CI, 1.12-7.02). Lack of insurance may confer an independent risk of death for patients who are critically ill (OR 1.16; 95% CI, 1.01-1.33). Patients in managed care systems had 14.3% (95% CI, 11.5-17.2) fewer procedures in intensive care, but were also less likely to receive "potentially ineffective" care. Differences in unmeasured confounding factors may contribute to these findings., Conclusions: Patients in the United States who are critically ill and do not have health insurance receive fewer critical care services and may experience worse clinical outcomes. Improving preexisting health care coverage, as opposed to solely delivering more critical care services, may be one mechanism to reduce such disparities.

Data from the British Columbia Linked Health Database were analyzed to determine if size of hospital is associated with in-hospital death of critically ill adults whose admitting diagnosis is congestive heart failure (CHF). Patients who were <19 years of age, transferred from or to other hospitals, or who developed CHF as a complication were excluded. In unadjusted logistic regression analysis of 2616 patients, the odds ratio (OR) for in-hospital death associated with a doubling of the number of hospital beds was 1.12 (95% confidence interval [CI] = 1.03-1.23; P = .01). After adjustment for age, sex, CHF-specific comorbidity index, number of cardiac and noncardiac procedures, number of hospital admissions for CHF in the preceding year, and socioeconomic variables, the OR was 1.08 (95% CI = 0.96-1.20; P = .21). The conclusion is that the adjusted rate of in-hospital deaths for this patient group does not differ significantly based solely on the number of acute hospital beds.

Background: The optimal target range for blood glucose in critically ill patients remains unclear., Methods: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization., Results: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39)., Conclusions: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.), (2009 Massachusetts Medical Society)

Purpose: The aim of this study was to determine the association between transport intervals (including time from call to arrival of transport team at the sending hospital, time spent by the transport team in the sending hospital, and transport time between the sending and receiving hospital) and intensive care unit (ICU) and hospital length of stay and hospital mortality at the receiving hospital., Materials and Methods: This was a retrospective, stratified cohort study involving all patients 15 years and older who were transferred from one hospital to another of equal or larger size in British Columbia, Canada, and who spent at least 1 day in an ICU or coronary care unit (CCU) at the receiving hospital during 1999 (n = 1930). Data were obtained from 6 administrative databases and linked using generalized software., Results: After adjustment for age, sex, comorbidity, and diagnostic group, longer time from call to arrival of paramedics at the sending hospital was associated with a shorter length of ICU/CCU stay (rate ratio [RR], 0.91; 95% confidence interval [CI], 0.86-0.97) for survivors and a longer length of hospital (RR, 1.12; 95% CI, 1.05-1.21) and ICU/CCU (RR, 1.14; 95% CI, 1.04-1.25) stay for nonsurvivors in the higher-priority air transport group, and with a slightly shorter length of hospital stay (RR, 0.97; 95% CI, 0.95-0.99) for all patients in the lower-priority air transport group. Longer time spent by paramedics at the sending hospital was associated with a shorter length of hospital stay (RR, 0.79; 95% CI, 0.65-0.96) for survivors in the higher-priority air transport group. Longer time for transport between the sending and receiving hospitals was associated with a longer length of ICU/CCU stay (RR, 1.69; 95% CI, 1.26-2.27) for survivors in the higher-priority air transport group but a slightly shorter length of ICU/CCU stay (RR, 0.97; 95% CI, 0.95-0.99) for all patients in the ground transport group. There were no associations between transport times and hospital mortality., Conclusions: Transport intervals are independently associated with ICU/CCU and hospital lengths of stay at the receiving hospital for critically ill adults transferred to referral centers.

Background: To improve communication and decision making related to cardiopulmonary resuscitation (CPR), a greater understanding of the perspectives of hospitalized patients with advanced diseases and their family members are needed., Methods: In five Canadian hospitals, we administered a face-to-face questionnaire to older inpatients with end-stage cancer and advanced medical diseases and, where possible, to one of their family members, regarding information needs, the deliberation process, and their preferred decisional role., Findings: A total of 440 of 569 patients (78%) and 160 of 176 available caregivers (91%) agreed to participate. Most patients (61%) had thought about what treatment they wanted if their heart stopped, few patients (11.3%) could describe more than two components of CPR, and only 2.7% of patients thought that the success rate of CPR was < 10%. A minority of patients (34%) had discussed CPR with their physician; 37% did not want to discuss their preferences with their doctor. Patients who felt that end-of-life issues were relevant to them were 5.5 times more likely to want a discussion with the physician regarding resuscitation (odds ratio, 5.5; 95% confidence interval, 2.5 to 12.0). The preferred role in decision making was variable, but most patients (59.7%) and family members (81.6%) preferred some degree of shared decision making that included the family member. There were no significant differences between cancer and medical patients in their preferred decisional role., Interpretation: Seriously ill hospitalized patients have poor knowledge about CPR, and variable preferences for deliberation and their role in the decision-making process regarding their treatment. Strategies that improve understanding of CPR and foster discussions that involve patients, family members, and physicians in the decision-making process may improve the quantity and quality of communication and decision making about CPR.

Purpose: The aim of the study was to determine whether the use of specialist transport personnel improves patient outcome at the receiving hospital for critically ill patients transferred to higher centers., Materials and Methods: A search of 6 electronic databases, 15 relevant journals, and the reference lists of all retrieved articles was conducted for studies comparing outcome at the receiving hospital for critically ill adult or pediatric patients transported by dedicated transport crews or tertiary-based specialists with other forms of transport personnel including referring house staff. All potentially relevant articles were retrieved in full and reviewed independently by 2 reviewers to determine eligibility for inclusion. Data were tabulated and results were summarized., Results: Six cohort studies (n = 4534) were included. When patients of equal severity were assessed, only 1 study demonstrated an improvement in outcome at the receiving hospital (survival to 6 hours) when specialist personnel transported the patients. Methodological limitations and interstudy differences in participants and transport personnel precluded pooling of results., Conclusions: Current data are insufficient. The study designs used create opportunity for significant bias, preventing any useful inferences to be drawn. Further study is warranted.

Purpose: Most deaths in intensive care units (ICUs) follow a withdrawal of life support (LS). Evaluation of this process including the related perspectives of grieving family members is integral to improvement of palliation in the ICU., Methods: A prospective, multicentre, cohort study in six Canadian university-affiliated ICUs included 206 ICU patients (length of stay >or=48 hr) who received mechanical ventilation (MV) before LS withdrawal. We recorded modes, sequence and time course of LS withdrawal and drug usage (4 hr before; 4-8 hr and 8-12 hr before death). We asked a specified family member to assess patient comfort and key aspects of end-of life care., Results: MV was withdrawn from 155/206 (75.2%) patients; 97/155 (62.6%) died after extubation and 58/155 (37.4%) died with an airway in place. The most frequently used drugs and the cumulative doses [median (range)] in the four hours before death were: morphine 119/206, 24 mg, (2-450 mg); midazolam 45/206, 24 mg, (2-380 mg); and lorazepam 35/206, 4 mg, (1-80 mg). These doses did not differ among the three time periods before death. Of 196 responses from family members most indicated that patients were perceived to be either totally (73, 37.2%), very (48, 24.5%), or mostly comfortable (58, 29.6%). Times to death, morphine use and family members' perceptions of comfort were similar for each type of change to MV., Conclusions: Most patients were perceived by family members to die in comfort during a withdrawal of LS. Perceptions of patient comfort and drug use in the hours before death were not associated with the mode or sequence of withdrawal of LS, or the time to death.

Objective: Predicting outcomes for critically ill patients is an important aspect of discussions with families in the intensive care unit. Our objective was to evaluate clinical intensive care unit survival predictions and their consequences for mechanically ventilated patients., Design: Prospective cohort study., Setting: Fifteen tertiary care centers., Patients: Consecutive mechanically ventilated patients > or = 18 yrs of age with expected intensive care unit stay > or = 72 hrs., Interventions: We recorded baseline characteristics at intensive care unit admission. Daily we measured multiple organ dysfunction score (MODS), use of advanced life support, patient preferences for life support, and intensivist and bedside intensive care unit nurse estimated probability of intensive care unit survival., Measurements and Main Results: The 851 patients were aged 61.2 (+/- 17.6, mean + SD) yrs with an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 21.7 (+/- 8.6). Three hundred and four patients (35.7%) died in the intensive care unit, and 341 (40.1%) were assessed by a physician at least once to have a < 10% intensive care unit survival probability. Independent predictors of intensive care unit mortality were baseline APACHE II score (hazard ratio, 1.16; 95% confidence interval, 1.08-1.24, for a 5-point increase) and daily factors such as MODS (hazard ratio, 2.50; 95% confidence interval, 2.06-3.04, for a 5-point increase), use of inotropes or vasopressors (hazard ratio, 2.14; 95% confidence interval, 1.66-2.77), dialysis (hazard ratio, 0.51; 95% confidence interval, 0.35-0.75), patient preference to limit life support (hazard ratio, 10.22; 95% confidence interval, 7.38-14.16), and physician but not nurse prediction of < 10% survival. The impact of physician estimates of < 10% intensive care unit survival was greater for patients without vs. those with preferences to limit life support (p < .001) and for patients with less vs. more severe organ dysfunction (p < .001). Mechanical ventilation, inotropes or vasopressors, and dialysis were withdrawn more often when physicians predicted < 10% probability of intensive care unit survival (all ps < .001)., Conclusions: Physician estimates of intensive care unit survival < 10% are associated with subsequent life support limitation and more powerfully predict intensive care unit mortality than illness severity, evolving or resolving organ dysfunction, and use of inotropes or vasopressors.

Objective: This study was conducted to develop evidence-based clinical practice guidelines for nutrition support (ie, enteral and parenteral nutrition) in mechanically ventilated critically ill adults., Options: The following interventions were systematically reviewed for inclusion in the guidelines: enteral nutrition (EN) versus parenteral nutrition (PN), early versus late EN, dose of EN, composition of EN (protein, carbohydrates, lipids, immune-enhancing additives), strategies to optimize delivery of EN and minimize risks (ie, rate of advancement, checking residuals, use of bedside algorithms, motility agents, small bowel versus gastric feedings, elevation of the head of the bed, closed delivery systems, probiotics, bolus administration), enteral nutrition in combination with supplemental PN, use of PN versus standard care in patients with an intact gastrointestinal tract, dose of PN and composition of PN (protein, carbohydrates, IV lipids, additives, vitamins, trace elements, immune enhancing substances), and the use of intensive insulin therapy., Outcomes: The outcomes considered were mortality (intensive care unit [ICU], hospital, and long-term), length of stay (ICU and hospital), quality of life, and specific complications., Evidence: We systematically searched MEDLINE and CINAHL (cumulative index to nursing and allied health), EMBASE, and the Cochrane Library for randomized controlled trials and meta-analyses of randomized controlled trials that evaluated any form of nutrition support in critically ill adults. We also searched reference lists and personal files, considering all articles published or unpublished available by August 2002. Each included study was critically appraised in duplicate using a standard scoring system., Values: For each intervention, we considered the validity of the randomized trials or meta-analyses, the effect size and its associated confidence intervals, the homogeneity of trial results, safety, feasibility, and the economic consequences. The context for discussion was mechanically ventilated patients in Canadian ICUs., Benefits, Harms, and Costs: The major potential benefit from implementing these guidelines is improved clinical outcomes of critically ill patients (reduced mortality and ICU stay). Potential harms of implementing these guidelines include increased complications and costs related to the suggested interventions. SUMMARIES OF EVIDENCE AND RECOMMENDATIONS: When considering nutrition support in critically ill patients, we strongly recommend that EN be used in preference to PN. We recommend the use of a standard, polymeric enteral formula that is initiated within 24 to 48 hours after admission to ICU, that patients be cared for in the semirecumbent position, and that arginine-containing enteral products not be used. Strategies to optimize delivery of EN (starting at the target rate, use of a feeding protocol using a higher threshold of gastric residuals volumes, use of motility agents, and use of small bowel feeding) and minimize the risks of EN (elevation of the head of the bed) should be considered. Use of products with fish oils, borage oils, and antioxidants should be considered for patients with acute respiratory distress syndrome. A glutamine-enriched formula should be considered for patients with severe burns and trauma. When initiating EN, we strongly recommend that PN not be used in combination with EN. When PN is used, we recommend that it be supplemented with glutamine, where available. Strategies that maximize the benefit and minimize the risks of PN (hypocaloric dose, withholding lipids, and the use of intensive insulin therapy to achieve tight glycemic control) should be considered. There are insufficient data to generate recommendations in the following areas: use of indirect calorimetry; optimal pH of EN; supplementation with trace elements, antioxidants, or fiber; optimal mix of fats and carbohydrates; use of closed feeding systems; continuous versus bolus feedings; use of probiotics; type of lipids; and mode of lipid delivery., Validation: This guideline was peer-reviewed and endorsed by official representatives of the Canadian Critical Care Society, Canadian Critical Care Trials Group, Dietitians of Canada, Canadian Association of Critical Care Nurses, and the Canadian Society for Clinical Nutrition., Sponsors: This guideline is a joint venture of the Canadian Critical Care Society, the Canadian Critical Trials Group, the Canadian Society for Clinical Nutrition, and Dietitians of Canada. The Canadian Critical Care Society and the Institute of Nutrition, Metabolism, and Diabetes of the Canadian Institutes of Health Research provided funding for development of this guideline.

Study Objective: To identify independent risk markers for thrombocytopenia in critically ill patients., Design: Prospective, observational study., Setting: Eleven-bed intensive care unit-coronary care unit (ICU-CCU) in a community hospital., Patients: Three hundred sixty-two consecutive patients meeting inclusion criteria during 1 year., Intervention: Potential risk marker data were collected on admission to the ICU-CCU and for the period before development of thrombocytopenia (defined as two or more consecutive platelet counts < 150 x 10(3)/mm3 obtained at least 12 hours apart), or for the duration of ICU-CCU stay if thrombocytopenia did not develop., Measurements and Main Results: Thrombocytopenia developed in 68 patients (18.8%). Multivariate logistic regression analyses identified patients at risk on admission, but the predictive, potential of the regression model improved when all risk marker exposures during the ICU-CCU stay were considered. Independent risk markers included fresh frozen plasma administration, sepsis, musculoskeletal diagnosis, pulmonary artery catheter insertion, gastrointestinal diagnosis, packed red blood cell administration, and nonsurgical respiratory diagnosis. Higher admission platelet count and aspirin administration were associated with a lower risk of thrombocytopenia. Heparin administration was not identified as a risk marker, and no patient developed heparin-induced thrombocytopenia with thrombosis. Patients with thrombocytopenia had longer ICU-CCU and hospital stays, and higher ICU-CCU and hospital mortality than those without thrombocytopenia., Conclusions: Development of thrombocytopenia in critically ill patients is associated with specific diagnoses, packed red cell and fresh frozen plasma transfusions, pulmonary artery catheter insertion, and admission platelet count.

The article discusses a study conducted to describe perspectives of family members about care provided to patients who were aged 80 years or over in Intensive Care Units (ICUs) across Canada. Topics discussed include study procedure, statistical analysis of the study and results of the study, which reveal incongruity between family values and preferences for end-of-life care and actual care received for very elderly patients.

The article presents the author's comments on the study titled "Benefits and Risks of Tight Glucose Control in Critically Ill Adults," by researcher Renda Soylemez Wiener and colleagues. It informs that the meta-analysis showed that tight glucose control and usual care did not differ for short-term mortality or new need for dialysis. It states that tight glucose control reduced risk for septicemia but increased risk for hypoglycemia more than usual care.

Objectives: To examine adverse events and associated factors and outcomes during transition from ICU to hospital ward (after ICU discharge).Design: Multicenter cohort study.Setting: Ten adult medical-surgical Canadian ICUs.Patients: Patients were those admitted to one of the 10 ICUs from July 2014 to January 2016.Interventions: None.Measurements and Main Results: Two ICU physicians independently reviewed progress and consultation notes documented in the medical record within 7 days of patient's ICU discharge date to identify and classify adverse events. The adverse event data were linked to patient characteristics and ICU and ward physician surveys collected during the larger prospective cohort study. Analyses were conducted using multivariable logistic regression. Of the 451 patients included in the study, 84 (19%) experienced an adverse event, the majority (62%) within 3 days of transfer from ICU to hospital ward. Most adverse events resulted only in symptoms (77%) and 36% were judged to be preventable. Patients with adverse events were more likely to be readmitted to the ICU (odds ratio, 5.5; 95% CI, 2.4-13.0), have a longer hospital stay (mean difference, 16.1 d; 95% CI, 8.4-23.7) or die in hospital (odds ratio, 4.6; 95% CI, 1.8-11.8) than those without an adverse event. ICU and ward physician predictions at the time of ICU discharge had low sensitivity and specificity for predicting adverse events, ICU readmissions, and hospital death.Conclusions: Adverse events are common after ICU discharge to hospital ward and are associated with ICU readmission, increased hospital length of stay and death and are not predicted by ICU or ward physicians. [ABSTRACT FROM AUTHOR]

Objective: Very elderly persons admitted to ICUs are at high risk of death. To document life-sustaining interventions (mechanical ventilation, vasopressors, renal replacement therapy) provided in the ICU and outcomes of care. Design: Multicenter, prospective cohort study. Setting: ICUs of 24 Canadian hospitals. Participants/Setting: Patients 80 years old or older admitted to the ICU. Interventions: None. Measurements and Main Results: One thousand six hundred seventy- one patients were included. The average age of the cohort was 85 years (range, 80-100 yr). Median total length of stay in ICU was 4 days (interquartile range, 2-8 d) and in hospital was 17 days (interquartile range, 8-33 d). Of all patients included, 502 (30%) stayed in ICU for 7 days or more and 344 (21%) received some form of life-sustaining treatment for at least 7 days. ICU and hospital mortality were 22% and 35%, respectively. For nonsurvivors, the median time from ICU admission to death was 10 days (interquartile range, 3-20 d). Of those who died (n = 5 85), 289 (49%) died while receiving mechanical ventilation, vasopressors, or dialysis. The presence of frailty or advance directives had little impact on limiting use of life-sustaining treatments or shortening the time from admission to death. Conclusions: In this multicenter study, one third of very elderly ICU patients died in hospital, many after a prolonged ICU stay while continuing to receive aggressive life-sustaining interventions. These findings raise questions about the use of critical care at the end of life for the very elderly. [ABSTRACT FROM AUTHOR]

Objective: Delirium is common during critical illness and associated with adverse outcomes. We compared characteristics and outcomes of delirious and nondelirious patients enrolled in a multicenter trial comparing protocolized sedation with protocolized sedation plus daily sedation interruption. Design: Randomized trial. Setting: Sixteen North American medical and surgical ICUs. Patients: Four hundred thirty critically ill, mechanically ventilated adults. Interventions: All patients had hourly titration of opioid and benzodiazepine infusions using a validated sedation scale. For patients in the interruption group, infusions were resumed, if indicated, at half of previous doses. Delirium screening occurred daily; positive screening was defined as an Intensive Care Delirium Screening Checklist score of 4 or more at any time. Measurements and Main Results: Delirium was diagnosed in 226 of 420 assessed patients (53.8%). Coma was identified in 32.7% of delirious compared with 22.7% of nondelirious patients (p = 0.03). The median time to onset of delirium was 3.5 days (interquartile range, 2–7), and the median duration of delirium was 2 days (interquartile range, 1–4). Delirious patients were more likely to be male (61.1% vs 46.6%; p = 0.005), have a surgical/trauma diagnosis (21.2% vs 11.0%; p = 0.030), and history of tobacco (31.5% vs 16.2%; p = 0.002) or alcohol use (34.6% vs 20.9%; p = 0.009). Patients with positive delirium screening had longer duration of ventilation (13 vs 7 d; p < 0.001), ICU stay (12 vs 8 d; p < 0.0001), and hospital stay (24 vs 15 d; p < 0.0001). Delirious patients were more likely to be physically restrained (86.3% vs 76.7%; p = 0.014) and undergo tracheostomy (34.6% vs 15.5%; p < 0.0001). Antecedent factors independently associated with delirium onset were restraint use (hazard ratio, 1.87; 95% CI, 1.33–2.63; p = 0.0003), antipsychotic administration (hazard ratio, 1.67; 95% CI, 1.005–2.767; p = 0.047), and midazolam dose (hazard ratio, 0.998; 95% CI, 0.997–1.0; p = 0.049). There was no difference in delirium prevalence or duration between the interruption and control groups. Conclusion: In mechanically ventilated adults, delirium was common and associated with longer duration of ventilation and hospitalization. Physical restraint was most strongly associated with delirium. [ABSTRACT FROM AUTHOR]