Optimizing red blood cell transfusion practices in the intensive care unit: a multi-phased health technology reassessment.

BACKGROUND: Health technology reassessment (HTR) is a process to manage existing health technologies to ensure ongoing optimal use. A model to guide HTR was developed; however, there is limited practical experience. This paper addresses this knowledge gap through the completion of a multi-phase HTR of red blood cell (RBC) transfusion practices in the intensive care unit (ICU). OBJECTIVE: The HTR consisted of three phases and here we report on the final phase: the development, implementation, and evaluation of behavior change interventions aimed at addressing inappropriate RBC transfusions in an ICU. METHODS: The interventions, comprised of group education and audit and feedback, were co-designed and implemented with clinical leaders. The intervention was evaluated through a controlled before-and-after pilot feasibility study. The primary outcome was the proportion of potentially inappropriate RBC transfusions (i.e., with a pre-transfusion hemoglobin of 70 g/L or more). RESULTS: There was marked variability in the monthly proportion of potentially inappropriate RBC transfusions. Relative to the pre-intervention phase, there was no significant difference in the proportion of potentially inappropriate RBC transfusions post-intervention. Lessons from this work include the importance of early and meaningful engagement of clinical leaders; tailoring the intervention modalities; and, efficient access to data through an electronic clinical information system. CONCLUSIONS: It was feasible to design, implement, and evaluate a tailored, multi-modal behavior change intervention in this small-scale pilot study. However, early evaluation of the intervention revealed no change in technology use leading to reflection on the important question of how the HTR model needs to be improved.

Exploratory Evaluation of the Relationship Between iNKT Cells and Systemic Cytokine Profiles of Critically Ill Patients with Neurological Injury.

BACKGROUND: Neurological injury can alter the systemic immune system, modifying the functional capacity of immune cells and causing a dysfunctional balance of cytokines, although mechanisms remain incompletely understood. The objective of this study was to assess the temporal relationship between changes in the activation status of circulating invariant natural killer T (iNKT) cells and the balance of plasma cytokines among critically ill patients with neurological injury. METHODS: We conducted an exploratory prospective observational study of adult (18 years or older) intensive care unit (ICU) patients with acute neurological injury (n = 20) compared with ICU patients without neurological injury (n = 22) and healthy controls (n = 10). Blood samples were collected on days 1, 2, 4, 7, 14, and 28 following ICU admission to analyze the activation status of circulating iNKT cells by flow cytometry and the plasma concentration of inflammation-relevant immune mediators, including T helper 1 (TH1) and T helper 2 (TH2) cytokines, by multiplex bead-based assay. RESULTS: Invariant natural killer T cells were activated in both ICU patient groups compared with healthy controls. Neurological patients had decreased levels of multiple immune mediators, including TH1 cytokines (interferon-γ, tumor necrosis factor-α, and interleukin-12p70), indicative of immunosuppression. This led to a greater than twofold increase in the ratio of TH2/TH1 cytokines early after injury (days 1 - 2) compared with healthy controls, a shift that was also observed for ICU controls. Systemic TH2/TH1 cytokine ratios were positively associated with iNKT cell activation in the neurological patients and negatively associated in ICU controls. These relationships were strongest for the CD4+ iNKT cell subset compared with the CD4- iNKT cell subset. The relationships to individual cytokines similarly differed between patient groups. Forty percent of the neurological patients developed an infection; however, differences for the infection subgroup were not identified. CONCLUSIONS: Critically ill patients with neurological injury demonstrated altered systemic immune profiles early after injury, with an association between activated peripheral iNKT cells and elevated systemic TH2/TH1 cytokine ratios. This work provides further support for a brain-immune axis and the ability of neurological injury to have far-reaching effects on the body's immune system.

Effect of age of transfused red blood cells on neurologic outcome following traumatic brain injury (ABLE-tbi Study): a nested study of the Age of Blood Evaluation (ABLE) trial.

BACKGROUND: Anemia is common in critically ill patients with traumatic brain injury, and often requires red blood cell transfusion. Studies suggest that prolonged storage causes lesions of the red blood cells, including a decreased ability to carry oxygen. Considering the susceptibility of the brain to hypoxemia, victims of traumatic brain injury may thus be more vulnerable to exposure to older red blood cells. METHODS: Our study aimed to ascertain whether the administration of fresh red blood cells (seven days or less) results in a better neurologic outcome compared with standard red blood cells in critically ill patients with traumatic brain injury requiring transfusion. The Age of Blood Evaluation in traumatic brain injury (ABLE-tbi) study was a nested study within the ABLE study (ISRCTN44878718). Our primary outcome was the extended Glasgow Outcome Scale (GOSe) at six months. RESULTS: In the ABLE study, 217 subjects suffered a traumatic brain injury: 110 in the fresh group, and 107 in the standard group. In the fresh group, 68 (73.1%) of the patients had an unfavourable neurologic outcome (GOSe ≤ 4) compared with 60 (64.5%) in the standard group (P = 0.21). Using a sliding dichotomy approach, we observed no overall effect of fresh red blood cells on neurologic outcome (odds ratio [OR], 1.34; 95% confidence interval [CI], 0.72 to 2.50; P = 0.35) but observed differences across prognostic bands with a decreased odds of unfavourable outcome in patients with the best prognosis at baseline (OR, 0.33; 95% CI, 0.11 to 0.96; P = 0.04) but an increased odds in those with intermediate and worst baseline prognosis (OR, 5.88; 95% CI,1.66 to 20.81; P = 0.006; and OR, 1.67; 95% CI, 0.53 to 5.30; P = 0.38, respectively). CONCLUSION: Overall, transfusion of fresh red blood cells was not associated with a better neurologic outcome at six months in critically ill patients with traumatic brain injury. Nevertheless, we cannot exclude a differential effect according to the patient baseline prognosis. TRIAL REGISTRATION: ABLE study (ISRCTN44878718); registered 22 August, 2008.

Continuous Assessment of "Optimal" Cerebral Perfusion Pressure in Traumatic Brain Injury: A Cohort Study of Feasibility, Reliability, and Relation to Outcome.

BACKGROUND: Guidelines recommend maintaining cerebral perfusion pressure (CPP) between 60 and 70 mmHg in patients with severe traumatic brain injury (TBI), but acknowledge that optimal CPP may vary depending on cerebral blood flow autoregulation. Previous retrospective studies suggest that targeting CPP where the pressure reactivity index (PRx) is optimized (CPPopt) may be associated with improved recovery. METHODS: We performed a retrospective cohort study involving TBI patients who underwent PRx monitoring to assess issues of feasibility relevant to future interventional studies: (1) the proportion of time that CPPopt could be detected; (2) inter-observer variability in CPPopt determination; and (3) agreement between manual and automated CPPopt estimates. CPPopt was determined for consecutive 6-h epochs during the first week following TBI. Sixty PRx-CPP tracings were randomly selected and independently reviewed by six critical care professionals. We also assessed whether greater deviation between actual CPP and CPPopt (ΔCPP) was associated with poor outcomes using multivariable models. RESULTS: In 71 patients, CPPopt could be manually determined in 985 of 1173 (84%) epochs. Inter-observer agreement for detectability was moderate (kappa 0.46, 0.23-0.68). In cases where there was consensus that it could be determined, agreement for the specific CPPopt value was excellent (weighted kappa 0.96, 0.91-1.00). Automated CPPopt was within 5 mmHg of manually determined CPPopt in 93% of epochs. Lower PRx was predictive of better recovery, but there was no association between ΔCPP and outcome. Percentage time spent below CPPopt increased over time among patients with poor outcomes (p = 0.03). This effect was magnified in patients with impaired autoregulation (defined as PRx > 0.2; p = 0.003). CONCLUSION: Prospective interventional clinical trials with regular determination of CPPopt and corresponding adjustment of CPP goals are feasible, but measures to maximize consistency in CPPopt determination are necessary. Although we could not confirm a clear association between ΔCPP and outcome, time spent below CPPopt may be particularly harmful, especially when autoregulation is impaired.

Challenges and potential solutions to the evaluation, monitoring, and regulation of surgical innovations.

BACKGROUND: As it may be argued that many surgical interventions provide obvious patient benefits, formal, staged assessment of the efficacy and safety of surgical procedures has historically been and remains uncommon. The majority of innovative surgical procedures have therefore often been developed based on anatomical and pathophysiological principles in an attempt to better manage clinical problems. MAIN BODY: In this manuscript, we sought to review and contrast the models for pharmaceutical and surgical innovation in North America, including their stages of development and methods of evaluation, monitoring, and regulation. We also aimed to review the present structure of academic surgery, the role of methodological experts and funding in conducting surgical research, and the current system of regulation of innovative surgical procedures. Finally, we highlight the influence that evidence and surgical history, education, training, and culture have on elective and emergency surgical decision-making. The above discussion is used to support the argument that the model used for assessment of innovative pharmaceuticals cannot be applied to that for evaluating surgical innovations. It is also used to support our position that although the evaluation and monitoring of innovative surgical procedures requires a rigorous, fit-for-purpose, and formal system of assessment to protect patient safety and prevent unexpected adverse health outcomes, it will only succeed if it is supported and championed by surgical practice leaders and respects surgical history, education, training, and culture. CONCLUSION: We conclude the above debate by providing a recommended approach to the evaluation, monitoring, and regulation of surgical innovations, which we hope may be used as a guide for all stakeholders involved in interpreting and/or conducting future surgical research.

The high cost of critical care unit over-utilization for patients with NSTE ACS.

BACKGROUND: There is substantial variability among hospitals in critical care unit (CCU) utilization for patients admitted with non-ST-Segment Elevation Acute Coronary Syndromes (NSTE ACS). We estimated the potential cost saving if all hospitals adopted low CCU utilization practices for patients with NSTE ACS. METHODS: National hospital claims data were used to identify all patients with a primary diagnosis of NSTE ACS initially admitted to an acute care hospital between 2007 and 2013. Hospital CCU utilization was classified as low (<30%), medium (30-70%), or high (>70%). RESULTS: Among the 270,564 NSTE ACS hospitalizations (71.6% non-ST-segment elevation myocardial infarction; 28.4% unstable angina) admitted to 261 hospitals, 41.9% (inter-hospital range 0.3%-95.1%) were admitted to a CCU. The proportion of patients admitted to a CCU in low, medium and high utilization hospitals was 16.3%, 49.5%, and high 81.1%, respectively. No differences in adjusted inpatient mortality were observed by hospital CCU utilization. The overall inpatient costs of caring for NSTE ACS were $1.1 billion. CCU care accounted for 45.2% of all hospitalization costs including 22.6%, 49.9%, and 69.0% (P < .001) of costs in low, medium and high utilization centers. The national potential direct cost savings of medium and high CCU utilization centers adopting low NSTE ACS CCU utilization practices was $113.4 million over the study period. CONCLUSIONS: In a population-based contemporary cohort, CCU utilization for patients with NSTE ACS varied widely and in-hospital mortality was similar between low, medium and high utilization centers. CCU care accounted for 45% of hospitalization costs; thus, implementing policies and admission practices to align hospital resources with patient care needs have the potential to reduce overall health care costs.

Indicators of intensive care unit capacity strain: a systematic review.

BACKGROUND: Strained intensive care unit (ICU) capacity represents a fundamental supply-demand mismatch in ICU resources. Strain is likely to be influenced by a range of factors; however, there has been no systematic evaluation of the spectrum of measures that may indicate strain on ICU capacity. METHODS: We performed a systematic review to identify indicators of strained capacity. A comprehensive peer-reviewed search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and Web of Science Core Collection was performed along with selected grey literature sources. We included studies published in English after 1990. We included studies that: (1) focused on ICU settings; (2) included description of a quality or performance measure; and (3) described strained capacity. Retrieved studies were screened, selected and extracted in duplicate. Quality was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Analysis was descriptive. RESULTS: Of 5297 studies identified in our search; 51 fulfilled eligibility. Most were cohort studies (n = 39; 76.5%), five (9.8%) were case-control, three (5.8%) were cross-sectional, two (3.9%) were modeling studies, one (2%) was a correlational study, and one (2%) was a quality improvement project. Most observational studies were high quality. Sixteen measures designed to indicate strain were identified 110 times, and classified as structure (n = 4, 25%), process (n = 7, 44%) and outcome (n = 5, 31%) indicators, respectively. The most commonly identified indicators of strain were ICU acuity (n = 21; 19.1% [process]), ICU readmission (n = 18; 16.4% [outcome]), after-hours discharge (n = 15; 13.6% [process]) and ICU census (n = 13; 11.8% [structure]). There was substantial heterogeneity in the operational definitions used to define strain indicators across studies. CONCLUSIONS: We identified and characterized 16 indicators of strained ICU capacity across the spectrum of healthcare quality domains. Future work should aim to evaluate their implementation into practice and assess their value for evaluating strategies to mitigate strain. SYSTEMATIC REVIEW REGISTRATION: This systematic review was registered at PROSPERO (March 27, 2015; CRD42015017931 ).

Association between afterhours admission to the intensive care unit, strained capacity, and mortality: a retrospective cohort study.

BACKGROUND: Admission to the intensive care unit (ICU) outside daytime hours has been shown to be variably associated with increased morbidity and mortality. We aimed to describe the characteristics and outcomes of patients admitted to the ICU afterhours (22:00-06:59 h) in a large Canadian health region. We further hypothesized that the association between afterhours admission and mortality would be modified by indicators of strained ICU capacity. METHODS: This is a population-based cohort study of 12,265 adults admitted to nine ICUs in Alberta from June 2012 to December 2014. We used a path-analysis modeling strategy and mixed-effects multivariate regression analysis to evaluate direct and integrated associations (mediated through Acute Physiology and Chronic Health Evaluation (APACHE) II score) between afterhours admission (22:00-06:59 h) and ICU mortality. Further analysis examined the effects of strained ICU capacity and varied definitions of afterhours and weekend admissions. ICU occupancy ≥ 90% or clustering of admissions (≥ 0.15, defined as number of admissions 2 h before or after the index admission, divided by the number of ICU beds) were used as indicators of strained capacity. RESULTS: Of 12,265 admissions, 34.7% (n = 4251) occurred afterhours. The proportion of afterhours admissions varied amongst ICUs (range 26.7-37.8%). Patients admitted afterhours were younger (median (IQR) 58 (44-70) vs 60 (47-70) years, p < 0.0001), more likely to have a medical diagnosis (75.9% vs 72.1%, p < 0.0001), and had higher APACHE II scores (20.9 (8.6) vs 19.9 (8.3), p < 0.0001). Crude ICU mortality was greater for those admitted afterhours (15.9% vs 14.1%, p = 0.007), but following multivariate adjustment there was no direct or integrated effect on ICU mortality (odds ratio (OR) 1.024; 95% confidence interval (CI) 0.923-1.135, p = 0.658). Furthermore, direct and integrated analysis showed no association of afterhours admission and hospital mortality (p = 0.90) or hospital length of stay (LOS) (p = 0.27), although ICU LOS was shorter (p = 0.049). Early-morning admission (00:00-06:59 h) with ICU occupancy ≥ 90% was associated with short-term (≤ 7 days) and all-cause ICU mortality. CONCLUSIONS: One-third of critically ill patients are admitted to the ICU afterhours. Afterhours ICU admission was not associated with greater mortality risk in most circumstances but was sensitive to strained ICU capacity.

Intensity of care and withdrawal of life-sustaining therapies in severe traumatic brain injury patients: a post-hoc analysis of a multicentre retrospective cohort study.

PURPOSE: The intensity of care provided to critically ill patients has been shown to be associated with mortality. In patients with traumatic brain injury (TBI), specialized neurocritical care is often required, but whether it affects clinically significant outcomes is unknown. We aimed to determine the association of the intensity of care on mortality and the incidence of withdrawal of life-sustaining therapies in critically ill patients with severe TBI. METHODS: We conducted a post hoc analysis of a multicentre retrospective cohort study of critically ill adult patients with severe TBI. We defined the intensity of care as a daily cumulative sum of interventions during the intensive care unit stay. Our outcome measures were all-cause hospital mortality and the incidence of withdrawal of life-sustaining therapies. RESULTS: Seven hundred sixteen severe TBI patients were included in our study. Most were male (77%) with a mean (standard deviation) age of 42 (20.5) yr and a median [interquartile range] Glasgow Coma Scale score of 3 [3-6]. Our results showed an association between the intensity of care and mortality (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.63 to 0.74) and the incidence of withdrawal of life-sustaining therapy (HR, 0.73; 95% CI, 0.67 to 0.79). CONCLUSION: In general, more intense care was associated with fewer deaths and a lower incidence of withdrawal of life-sustaining therapies in critically ill patients with severe TBI.

History of the Innovation of Damage Control for Management of Trauma Patients: 1902-2016.

OBJECTIVE: To review the history of the innovation of damage control (DC) for management of trauma patients. BACKGROUND: DC is an important development in trauma care that provides a valuable case study in surgical innovation. METHODS: We searched bibliographic databases (1950-2015), conference abstracts (2009-2013), Web sites, textbooks, and bibliographies for articles relating to trauma DC. The innovation of DC was then classified according to the Innovation, Development, Exploration, Assessment, and Long-term study model of surgical innovation. RESULTS: The "innovation" of DC originated from the use of therapeutic liver packing, a practice that had previously been abandoned after World War II because of adverse events. It then "developed" into abbreviated laparotomy using "rapid conservative operative techniques." Subsequent "exploration" resulted in the application of DC to increasingly complex abdominal injuries and thoracic, peripheral vascular, and orthopedic injuries. Increasing use of DC laparotomy was followed by growing reports of postinjury abdominal compartment syndrome and prophylactic use of the open abdomen to prevent intra-abdominal hypertension after DC laparotomy. By the year 2000, DC surgery had been widely adopted and was recommended for use in surgical journals, textbooks, and teaching courses ("assessment" stage of innovation). "Long-term study" of DC is raising questions about whether the procedure should be used more selectively in the context of improving resuscitation practices. CONCLUSIONS: The history of the innovation of DC illustrates how a previously abandoned surgical technique was adapted and readopted in response to an increased understanding of trauma patient physiology and changing injury patterns and trauma resuscitation practices.

Human Albumin Use in Adults in U.S. Academic Medical Centers.

OBJECTIVE: To determine rates and predictors of albumin administration, and estimated costs in hospitalized adults in the United States. DESIGN: Cohort study of adult patients from the University HealthSystem Consortium database from 2009 to 2013. SETTING: One hundred twenty academic medical centers and 299 affiliated hospitals. PATIENTS: A total of 12,366,264 hospitalization records. INTERVENTIONS: Analysis of rates and predictors of albumin administration, and estimated costs. MEASUREMENTS AND MAIN RESULTS: Overall the proportion of admissions during which albumin was administered increased from 6.2% in 2009 to 7.5% in 2013; absolute difference 1.3% (95% CI, 1.30-1.40%; p < 0.0001). The increase was greater in surgical patients from 11.7% in 2009 to 15.1% in 2013; absolute difference 3.4% (95% CI, 3.26-3.46%; p < 0.0001). Albumin use varied geographically being lowest with no increase in hospitals in the North Eastern United States (4.9% in 2009 and 5.3% in 2013) and was more common in bigger (> 750 beds; 5.2% in 2009 and 7.3% in 2013) compared to smaller hospitals (< 250 beds; 4.4% in 2009 to 6.2% in 2013). Factors independently associated with albumin use were appropriate indication for albumin use (odds ratio, 65.220; 95% CI, 62.459-68.103); surgical admission (odds ratio, 7.942; 95% CI, 7.889-7.995); and high severity of illness (odds ratio, 8.933; 95% CI, 8.825-9.042). Total estimated albumin cost significantly increased from $325 million in 2009 to $468 million in 2013; (absolute increase of $233 million), p value less than 0.0001. CONCLUSIONS: The proportion of hospitalized adults in the United States receiving albumin has increased, with marked, and currently unexplained, geographic variability and variability by hospital size.

Healthcare Provider Perceptions of Causes and Consequences of ICU Capacity Strain in a Large Publicly Funded Integrated Health Region: A Qualitative Study.

OBJECTIVES: Discrepancy in the supply-demand relationship for critical care services precipitates a strain on ICU capacity. Strain can lead to suboptimal quality of care and burnout among providers and contribute to inefficient health resource utilization. We engaged interprofessional healthcare providers to explore their perceptions of the sources, impact, and strategies to manage capacity strain. DESIGN: Qualitative study using a conventional thematic analysis. SETTING: Nine ICUs across Alberta, Canada. SUBJECTS: Nineteen focus groups (n = 122 participants). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants' perspectives on strain on ICU capacity and its perceived impact on providers, families, and patient care were explored. Participants defined "capacity strain" as a discrepancy between the availability of ICU beds, providers, and ICU resources (supply) and the need to admit and provide care for critically ill patients (demand). Four interrelated themes of contributors to strain were characterized (each with subthemes): patient/family related, provider related, resource related, and health system related. Patient/family-related subthemes were "increasing patient complexity/acuity," along with patient-provider communication issues ("paucity of advance care planning and goals-of-care designation," "mismatches between patient/family and provider expectations," and "timeliness of end-of-life care planning"). Provider-related factor subthemes were nursing workforce related ("nurse attrition," "inexperienced workforce," "limited mentoring opportunities," and "high patient-to-nurse ratios") and physician related ("frequent turnover/handover" and "variations in care plan"). Resource-related subthemes were "reduced service capability after hours" and "physical bed shortages." Health system-related subthemes were "variable ICU utilization," "preferential "bed" priority for other services," and "high ward bed occupancy." Participants perceived that strain had negative implications for patients ("reduced quality and safety of care" and "disrupted opportunities for patient- and family-centered care"), providers ("increased workload," "moral distress," and "burnout"), and the health system ("unnecessary, excessive, and inefficient resource utilization"). CONCLUSIONS: Engagement with frontline critical care providers is essential for understanding their experiences and perspectives regarding strained capacity and for the development of sustainable strategies for improvement.

Indications for Use of Damage Control Surgery in Civilian Trauma Patients: A Content Analysis and Expert Appropriateness Rating Study.

OBJECTIVES: To characterize and evaluate indications for use of damage control (DC) surgery in civilian trauma patients. BACKGROUND: Although DC surgery may improve survival in select, severely injured patients, the procedure is associated with significant morbidity, suggesting that it should be used only when appropriately indicated. METHODS: Two investigators used an abbreviated grounded theory method to synthesize indications for DC surgery reported in peer-reviewed articles between 1983 and 2014 into a reduced number of named, content-characteristic codes representing unique indications. An international panel of trauma surgery experts (n = 9) then rated the appropriateness (expected benefit-to-harm ratio) of the coded indications for use in surgical practice. RESULTS: The 1107 indications identified in the literature were synthesized into 123 unique pre- (n = 36) and intraoperative (n = 87) indications. The panel assessed 101 (82.1%) of these indications to be appropriate. The indications most commonly reported and assessed to be appropriate included pre- and intraoperative hypothermia (median temperature <34°C), acidosis (median pH <7.2), and/or coagulopathy. Others included 5 different injury patterns, inability to control bleeding by conventional methods, administration of a large volume of packed red blood cells (median >10 units), inability to close the abdominal wall without tension, development of abdominal compartment syndrome during attempted abdominal wall closure, and need to reassess extent of bowel viability. CONCLUSIONS: This study identified a comprehensive list of candidate indications for use of DC surgery. These indications provide a practical foundation to guide surgical practice while studies are conducted to evaluate their impact on patient care and outcomes.

Decompressive Craniectomy in Patients with Traumatic Brain Injury: Are the Usual Indications Congruent with Those Evaluated in Clinical Trials?

BACKGROUND: In patients with traumatic brain injury (TBI), multicenter randomized controlled trials have assessed decompressive craniectomy (DC) exclusively as treatment for refractory elevation of intracranial pressure (ICP). DC reliably lowers ICP but does not necessarily improve outcomes. However, some patients undergo DC as treatment for impending or established transtentorial herniation, irrespective of ICP. METHODS: We performed a population-based cohort study assessing consecutive patients with moderate-severe TBI. Indications for DC were compared with enrollment criteria for the DECRA and RESCUE-ICP trials. RESULTS: Of 644 consecutive patients, 51 (8 %) were treated with DC. All patients undergoing DC had compressed basal cisterns, 82 % had at least temporary preoperative loss of ≥1 pupillary light reflex (PLR), and 80 % had >5 mm of midline shift. Most DC procedures (67 %) were "primary," having been performed concomitantly with evacuation of a space-occupying lesion. ICP measurements influenced the decision to perform DC in 18 % of patients. Only 10 and 16 % of patients, respectively, would have been eligible for the DECRA and RESCUE-ICP trials. DC improved basal cistern compression in 76 %, and midline shift in 94 % of patients. Among patients with ≥1 absent PLR at admission, DC was associated with lower mortality (46 vs. 68 %, p = 0.03), especially when the admission Marshall CT score was 3-4 (p = 0.0005). No patients treated with DC progressed to brain death. Variables predictive of poor outcome following DC included loss of PLR(s), poor motor score, midline shift ≥11 mm, and development of perioperative cerebral infarcts. CONCLUSIONS: DC is most often performed for clinical and radiographic evidence of herniation, rather than for refractory ICP elevation. Results of previously completed randomized trials do not directly apply to a large proportion of patients undergoing DC in practice.

Evidence-based design in an intensive care unit: end-user perceptions.

BACKGROUND: The objective of this study was to describe end-user impressions and experiences in a new intensive care unit built using evidence-based design. METHODS: This qualitative study was comprised of early (2-3 months after opening) and late (12-15 months after opening) phase individual interviews with end-users (healthcare providers, support staff, and patient family members) of the newly constructed Foothills Medical Centre intensive care unit in Calgary, Canada. The study unit was the recipient of the Society of Critical Care Medicine Design Citation award in 2012. RESULTS: We conducted interviews with thirty-nine ICU end-users, twenty-four in the early phase and fifteen in the late phase. We identified four themes (eleven sub-themes): atmosphere (abundant natural light and low noise levels), physical spaces (single occupancy rooms, rooms clustered into clinical pods, medication rooms, and tradeoffs of larger spaces), family participation in care (family support areas and social networks), and equipment (usability, storage, and providers connectivity). Abundant natural light was the design feature most frequently associated with a pleasant atmosphere. Participants emphasized the tradeoffs of size and space, and reported that the benefits of additional space (e.g., fewer interruptions due to less noise) out-weighed the disadvantages (e.g., greater distances between patients, families and providers). End-users advised that local patient care policies (e.g., number of visitors allowed at a time) and staffing needed to be updated to reflect the characteristics of the new facility design. CONCLUSIONS: End-users identified design elements for creating a pleasant atmosphere, attention to the tradeoffs of space and size, designing family support areas to encourage family participation in care, and updating patient care policies and staffing to reflect the new physical space as important aspects to consider when building intensive care units. Evidence-based design may optimize ICU structure for patients, patient families and providers.

Association Between Nighttime Discharge from the Intensive Care Unit and Hospital Mortality: A Multi-Center Retrospective Cohort Study.

BACKGROUND: We aimed to determine the impact of nighttime discharge from the intensive care unit (ICU) to the ward on hospital mortality and readmission rates in consecutive critically ill patients admitted to five Canadian ICUs. We hypothesized that hospital mortality and readmission rates would be higher for patients discharged after hours compared with discharge during the day. METHODS: A multi-center retrospective cohort study was carried out at five hospitals in Edmonton, Canada, between July 2002 and December 2009. Nighttime discharge was defined as discharge from the ICU occurring between 07:00 pm and 07:59 am. Logistic regression analysis was used to explore the associations between nighttime discharge and outcomes. RESULTS: Of 19,622 patients discharged alive from the ICU, 3,505 (17.9%) discharges occurred during nighttime. Nighttime discharge occurred more commonly among medical than surgical patients (19.9% vs. 13.8%, P < 0.001) and among those with more comorbid conditions, compared with daytime discharged patients. Crude hospital mortality (11.8% versus 8.8%, P < 0.001) was greater for nighttime discharged as compared to daytime discharged patients. In a multivariable analysis, after adjustment for comorbidities, diagnosis and source of admission, nighttime discharge remains associated with higher mortality (odds ratio [OR] 1.29; 95% CI, 1.14 to 1.46, P < 0.001). This finding was robust in two sensitivity analyses examining discharges occurring between 00:00 am and 04:59 am (OR 1.28; 1.12-1.47; P < 0.001) and for those who died within 48 h of ICU discharge without readmission (OR 1.24; 1.07-1.42, P = 0.002). There was no difference in ICU readmission for nighttime compared with daytime discharges (7.4% vs. 6.9 %, p = 0.26). However, rates were higher for nighttime discharges in community compared with tertiary hospitals (7.7% vs. 5.7%, P = 0.023). CONCLUSIONS: In a large integrated health region, 1 in 5 ICU patients are discharged at nighttime, a factor with increasing occurrence during our study and shown to be independently associated with higher hospital mortality.

Pharmacokinetics and Pharmacodynamics of Tissue Plasminogen Activator Administered Through an External Ventricular Drain.

BACKGROUND: Intraventricular hemorrhage (IVH) frequently complicates spontaneous intracerebral or subarachnoid hemorrhage (SAH). Administration of intraventricular tissue plasminogen activator (TPA) accelerates blood clearance, but optimal dosing has not been clarified. Using a standardized TPA dose, we assessed peak cerebrospinal fluid (CSF) TPA concentrations, the rate at which TPA clears, and the relationship between TPA concentration and biological activity. METHODS: Twelve patients with aneurysmal SAH and IVH, treated with endovascular coiling and ventricular drainage, were randomized to receive either 2 mg intraventricular TPA or placebo every 12 h (five doses). CT scans were performed 12, 48, and 72 h after initial administration, and blood was quantified using the SAH Sum and IVH Scores. CSF TPA and fibrin degradation product (D-dimer) concentrations were measured at baseline and 1, 6, and 12 h after the first dose using ELISA assays. RESULTS: Median CSF TPA concentrations in seven TPA-treated patients were 525 (IQR 352-2129), 323 (233-413), and 47 (29-283) ng/ml, respectively, at 1, 6, and 12 h after drug administration. Peak concentrations varied markedly (401-8398 ng/ml). Two patients still had slightly elevated levels (283-285 ng/ml) when the second dose was due after 12 h. There was no significant correlation between the magnitude of CSF TPA elevation and the rate of blood clearance or degree of D-dimer elevation. D-dimer peaked at 6 h, had declined by 12 h, and correlated strongly with radiographic IVH clearance (r = 0.82, p = 0.02). CONCLUSIONS: The pharmacokinetics of intraventricular TPA administration varies between individual patients. TPA dose does not need to exceed 2 mg. The optimal administration interval is every 8-12 h.

Multi-modality neuro-monitoring: conventional clinical trial design.

Multi-modal monitoring has become an integral part of neurointensive care. However, our approach is at this time neither standardized nor backed by data from randomized controlled trials. The goal of the second Neurocritical Care Research Conference was to discuss research priorities in multi-modal monitoring, what research tools are available, as well as the latest advances in clinical trial design. This section of the meeting was focused on how such a trial should be designed so as to maximize yield and avoid mistakes of the past.

Neurocritical care: why does it make a difference?

PURPOSE OF REVIEW: The care of critically ill brain-injured patients is complex and requires careful balancing of cerebral and systemic treatment priorities. A growing number of studies have reported improved outcomes when patients are admitted to dedicated neurocritical care units (NCCUs). The reasons for this observation have not been definitively clarified. RECENT FINDINGS: When recently published articles are combined with older literature, there have been more than 40 000 patients assessed in observational studies that compare neurological and general ICUs. Although results are heterogeneous, admission to NCCUs is associated with lower mortality and a greater chance of favorable recovery. These findings are remarkable considering that there are few interventions in neurocritical care that have been demonstrated to be efficacious in randomized trials. Whether the relationship is causal is still being elucidated but potential explanations include higher patient volume and, in turn, greater clinician experience; more emphasis on and adherence to protocols to avoid secondary brain injury; practice differences related to prognostication and withdrawal of life-sustaining interventions; and differences in the use and interpretation of neuroimaging and neuromonitoring data. SUMMARY: Neurocritical care is an evolving field that is associated with improvements in outcomes over the past decade. Further research is required to determine how monitoring and treatment protocols can be optimized.

A meta-analysis to derive literature-based benchmarks for readmission and hospital mortality after patient discharge from intensive care.

INTRODUCTION: We sought to derive literature-based summary estimates of readmission to the ICU and hospital mortality among patients discharged alive from the ICU. METHODS: We searched MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials from inception to March 2013, as well as the reference lists in the publications of the included studies. We selected cohort studies of ICU discharge prognostic factors that in which readmission to the ICU or hospital mortality among patients discharged alive from the ICU was reported. Two reviewers independently abstracted the number of patients readmitted to the ICU and hospital deaths among patients discharged alive from the ICU. Fixed effects and random effects models were used to estimate the pooled cumulative incidence of ICU readmission and the pooled cumulative incidence of hospital mortality. RESULTS: The analysis included 58 studies (n = 2,073,170 patients). The majority of studies followed patients until hospital discharge (n = 46 studies) and reported readmission to the ICU (n = 46 studies) or hospital mortality (n = 49 studies). The cumulative incidence of ICU readmission was 4.0 readmissions (95% confidence interval (CI), 3.9 to 4.0) per 100 patient discharges using fixed effects pooling and 6.3 readmissions (95% CI, 5.6 to 6.9) per 100 patient discharges using random effects pooling. The cumulative incidence of hospital mortality was 3.3 deaths (95% CI, 3.3 to 3.3) per 100 patient discharges using fixed effects pooling and 6.8 deaths (95% CI, 6.1 to 7.6) per 100 patient discharges using random effects pooling. There was significant heterogeneity for the pooled estimates, which was partially explained by patient, institution and study methodological characteristics. CONCLUSIONS: Using current literature estimates, for every 100 patients discharged alive from the ICU, between 4 and 6 patients on average will be readmitted to the ICU and between 3 and 7 patients on average will die prior to hospital discharge. These estimates can inform the selection of benchmarks for quality metrics of transitions of patient care between the ICU and the hospital ward.