Prehospital Tranexamic Acid for Severe Trauma.

BACKGROUND: Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain. METHODS: We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 ("upper good recovery" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 ("lower moderate disability") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury. RESULTS: A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups. CONCLUSIONS: Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).

Transforming research to improve therapies for trauma in the twenty-first century.

Improvements have been made in optimizing initial care of trauma patients, both in prehospital systems as well as in the emergency department, and these have also favorably affected longer term outcomes. However, as specific treatments for bleeding are largely lacking, many patients continue to die from hemorrhage. Also, major knowledge gaps remain on the impact of tissue injury on the host immune and coagulation response, which hampers the development of interventions to treat or prevent organ failure, thrombosis, infections or other complications of trauma. Thereby, trauma remains a challenge for intensivists. This review describes the most pressing research questions in trauma, as well as new approaches to trauma research, with the aim to bring improved therapies to the bedside within the twenty-first century.

Patient blood management guideline for adults with critical bleeding.

INTRODUCTION: The management of patients with critical bleeding requires a multidisciplinary approach to achieve haemostasis, optimise physiology, and guide blood component use. The 2011 Patient blood management guidelines: module 1 - critical bleeding/massive transfusion were updated and published. Systematic reviews were conducted for pre-specified research questions, and recommendations were based on meta-analyses of included studies. MAIN RECOMMENDATIONS: The critical bleeding/massive transfusion guideline includes seven recommendations and 11 good practice statements addressing: major haemorrhage protocols (MHPs) facilitating a multidisciplinary approach to haemorrhage control, correction of coagulopathy and normalisation of physiological derangement; measurement of physiological, biochemical and metabolic parameters in critical bleeding/massive transfusion; the optimal ratio of red blood cells to other blood components; the use of tranexamic acid; viscoelastic haemostatic assays; and cell salvage. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINE: The new guideline recommends MHPs be established as standard of care in all institutions managing patients with critical bleeding. In addition to routine physiological markers, the new guideline recommends temperature, biochemistry and coagulation profiles be measured early and frequently, providing parameters that define critical derangements. Ratio-based MHPs should include no fewer than four units of fresh frozen plasma and one adult unit of platelets for every eight units of red blood cells. In the setting of trauma and obstetric haemorrhage, administration of tranexamic acid within three hours of bleeding onset is recommended. The use of recombinant activated factor VII (rFVIIa) is not recommended. There was insufficient evidence to make recommendations on the use of viscoelastic haemostatic assays or cell salvage as part of MHPs.

Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III).

Rationale: The SPICE III (Sedation Practice in Intensive Care Evaluation) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation. Objectives: To quantify the association of different infusion rates of dexmedetomidine and propofol, given in combination, with mortality and to determine if this is modified by age. Methods: We included 1,177 patients randomized in SPICE III to receive dexmedetomidine and given supplemental propofol, stratified by age (>65 or ⩽65 yr). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality. Measurements and Main Results: Younger patients (598 of 1,177 [50.8%]) received significantly higher doses of both sedatives compared with older patients to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 µg/kg/h) was associated with reduced adjusted mortality in younger but not older patients. This was consistent with multivariable regression modeling (hazard ratio, 0.59; 95% confidence interval, 0.43-0.78; P < 0.0001) adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients, using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality (hazard ratio, 1.30; 95% confidence interval, 1.03-1.65; P = 0.029). Conclusions: In patients ⩽65 years of age sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registered with www.clinicaltrials.gov (NCT01728558).

Natural language processing diagnosed behavioural disturbance phenotypes in the intensive care unit: characteristics, prevalence, trajectory, treatment, and outcomes.

BACKGROUND: Natural language processing (NLP) may help evaluate the characteristics, prevalence, trajectory, treatment, and outcomes of behavioural disturbance phenotypes in critically ill patients. METHODS: We obtained electronic clinical notes, demographic information, outcomes, and treatment data from three medical-surgical ICUs. Using NLP, we screened for behavioural disturbance phenotypes based on words suggestive of an agitated state, a non-agitated state, or a combination of both. RESULTS: We studied 2931 patients. Of these, 225 (7.7%) were NLP-Dx-BD positive for the agitated phenotype, 544 (18.6%) for the non-agitated phenotype and 667 (22.7%) for the combined phenotype. Patients with these phenotypes carried multiple clinical baseline differences. On time-dependent multivariable analysis to compensate for immortal time bias and after adjustment for key outcome predictors, agitated phenotype patients were more likely to receive antipsychotic medications (odds ratio [OR] 1.84, 1.35-2.51, p < 0.001) compared to non-agitated phenotype patients but not compared to combined phenotype patients (OR 1.27, 0.86-1.89, p = 0.229). Moreover, agitated phenotype patients were more likely to die than other phenotypes patients (OR 1.57, 1.10-2.25, p = 0.012 vs non-agitated phenotype; OR 4.61, 2.14-9.90, p < 0.001 vs. combined phenotype). This association was strongest in patients receiving mechanical ventilation when compared with the combined phenotype (OR 7.03, 2.07-23.79, p = 0.002). A similar increased risk was also seen for patients with the non-agitated phenotype compared with the combined phenotype (OR 6.10, 1.80-20.64, p = 0.004). CONCLUSIONS: NLP-Dx-BD screening enabled identification of three behavioural disturbance phenotypes with different characteristics, prevalence, trajectory, treatment, and outcome. Such phenotype identification appears relevant to prognostication and trial design.

The Australian Delirium Clinical Care Standard: not just another brick in the wall.

Delivering delirium care is challenging. Systems may not be set up to facilitate good delirium practice and staff may have low baseline understanding of how to spot, stop and treat delirium. In this context, delirium guidelines are especially important. In this article, we review the 2021 Australian Delirium Clinical Care Standards. The care standards are different to guidelines insofar as they focus on main presentations and represent eight quality statements describing the best evidence-based care patients with delirium should be offered. The standards speak to three different audiences: consumer, clinician and healthcare organisations. As such, they provide some system-level solutions to practice-level problems. They incorporate latest evidence and reflect the sway away from prescribing to treat delirium, stating that antipsychotics should be avoided. Furthermore, they promote inclusivity of families and carers in delirium care processes as an important medium to engender good practice. Limitations include the fact that they extend to delirium in multiple settings where different approaches may be necessary. They also lack the granularity of being able to provide recommendations on a greater range of drugs that might be used and assume settings are ready to introduce best delirium practice. In sum, they represent an important step forward for delirium knowledge translation and are particularly relevant for patients in the geriatric setting. The guidelines though are constrained as to what they can advocate due to research gaps especially into treatment of delirium.

Early Sedation with Dexmedetomidine in Critically Ill Patients.

BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied. METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days. RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group. CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.).

A pilot randomized clinical trial of cryopreserved versus liquid-stored platelet transfusion for bleeding in cardiac surgery: The cryopreserved versus liquid platelet-New Zealand pilot trial.

BACKGROUND AND OBJECTIVES: Platelets for transfusion have a shelf-life of 7 days, limiting availability and leading to wastage. Cryopreservation at -80°C extends shelf-life to at least 1 year, but safety and effectiveness are uncertain. MATERIALS AND METHODS: This single centre blinded pilot trial enrolled adult cardiac surgery patients who were at high risk of platelet transfusion. If treating clinicians determined platelet transfusion was required, up to three units of either cryopreserved or liquid-stored platelets intraoperatively or during intensive care unit admission were administered. The primary outcome was protocol safety and feasibility. RESULTS: Over 13 months, 89 patients were randomized, 23 (25.8%) of whom received a platelet transfusion. There were no differences in median blood loss up to 48 h between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 103 /µl vs. 157 × 103 /µl, median difference 39.5 ×103 /µl, p = 0.03). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24-h blood loss, red cell transfusion or a composite bleeding outcome. CONCLUSION: This pilot randomized controlled trial demonstrated the feasibility of the protocol and adds to accumulating data supporting the safety of this intervention. Given the clear advantage of prolonged shelf-life, particularly for regional hospitals in New Zealand, a definitive non-inferiority phase III trial is warranted.

Perspective: the top 11 priorities to improve trauma outcomes, from system to patient level.

BACKGROUND: The Haemorrhage, Airway, Breathing, Circulation, Disability, Exposure/Environmental control approach to individual patient management in trauma is well established and embedded in numerous training courses worldwide. Further improvements in trauma outcomes are likely to result from a combination of system-level interventions in prevention and quality improvement, and from a sophisticated approach to clinical innovation. TOP ELEVEN TRAUMA PRIORITIES: Based on a narrative review of remaining preventable mortality and morbidity in trauma, the top eleven priorities for those working throughout the spectrum of trauma care, from policy-makers to clinicians, should be: (1) investment in effective trauma prevention (likely to be the most cost-effective intervention); (2) prioritisation of resources, quality improvement and innovation in prehospital care (where the most preventable mortality remains); (3) building a high-performance trauma team; (4) applying evidence-based clinical interventions that stop bleeding, open & protect the airway, and optimise breathing most effectively; (5) maintaining enough circulating blood volume and ensuring adequate cardiac function; (6) recognising the role of the intensive care unit in modern damage control surgery; (7) prioritising good intensive care unit intercurrent care, especially prophylaxis for thromboembolic disease; (8) conducting a thorough tertiary survey, noting that on average the intensive care unit is where approximately 15% of injuries are detected; (9) facilitating early extubation; (10) investing in formal quantitative and qualitative quality assurance and improvement; and (11) improving clinical trial design. CONCLUSION: Dramatic reductions in population trauma mortality and injury case fatality rate over recent decades have demonstrated the value of a comprehensive approach to trauma quality and process improvement. Continued attention to these principles, targeting areas with highest remaining preventable mortality while also prioritising functional outcomes, should remain the focus of both clinician and policy-makers.

Stress response during early sedation with dexmedetomidine compared with usual-care in ventilated critically ill patients.

BACKGROUND: Sedative agents may variably impact the stress response. Dexmedetomidine is a sympatholytic alpha2-adrenergic agonist mainly used as a second-line sedative agent in mechanically ventilated patients. We hypothesised that early sedation with dexmedetomidine as the primary agent would result in a reduced stress response compared to usual sedatives in critically ill ventilated adults. METHODS: This was a prospective sub-study nested within a multi-centre randomised controlled trial of early sedation with dexmedetomidine versus usual care. The primary outcome was the mean group differences in plasma levels of stress response biomarkers measured over 5 days following randomisation. Other hormonal, biological and physiological parameters were collected. Subgroup analyses were planned for patients with proven or suspected sepsis. RESULTS: One hundred and three patients were included in the final analysis. Baseline illness severity (APACHE II score), the proportion of patients receiving propofol and the median dose of propofol received were comparable between groups. More of the usual-care patients received midazolam (57.7% vs 33.3%; p = 0.01) and at higher dose (median (95% interquartile range) 0.46 [0.20-0.93] vs 0.14 [0.08-0.38] mg/kg/day; p < 0.01). The geometric mean (95% CI) plasma level of the stress hormones, adrenaline (0.32 [0.26-0.4] vs 0.38 [0.31-0.48]), noradrenaline (4.27 [3.12-5.85] vs 6.2 [4.6-8.5]), adrenocorticotropic hormone (17.1 [15.1-19.5] vs 18.1 [15.9-20.5]) and cortisol (515 [409-648] vs 618 [491-776)] did not differ between dexmedetomidine and usual-care groups, respectively. There were no significant differences in any other assayed biomarkers or physiological parameters Sensitivity analyses showed no effect of age or sepsis. CONCLUSIONS: Early sedation with dexmedetomidine as the primary sedative agent in mechanically ventilated critically ill adults resulted in comparable changes in physiological and blood-borne parameters associated with the stress-response as with usual-care sedation.

Dexmedetomidine for Facilitating Mechanical Ventilation Extubation in Difficult-to-Wean ICU Patients: Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Agitation and delirium are common in mechanically ventilated adult intensive care unit (ICU) patients and may contribute to delayed extubation times. Difficult-to-wean ICU patients have been associated with an increased risk of longer ICU length of stays and mortality. The purpose of this systematic review and meta-analysis is to evaluate the evidence of dexmedetomidine facilitating successful mechanical ventilation extubation in difficult-to-wean ICU patients and clinical outcomes. METHODS: A literature search was conducted using MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Global Health, Cochrane Central Register of Controlled Trials, Clinical Trial Registries, and the Health Technology Assessment Database from inception to December 5, 2019. Randomized controlled trials evaluating dexmedetomidine with the intended purpose to facilitate mechanical ventilation liberation in adult ICU patients (≥18 years) experiencing extubation failure were included. The primary outcome of time to extubation was evaluated using the weighted mean difference (WMD), with a random effects model. Secondary analyses included hospital and ICU length of stay, in-hospital mortality, hypotension, and bradycardia. RESULTS: A total of 6 trials (n = 306 patients) were included. Dexmedetomidine significantly reduced the time to extubation (WMD: -11.61 hours, 95% CI: -16.5 to -6.7, P = .005) and ICU length of stay (WMD: -3.04 days; 95% CI: -4.66 to -1.43). Hypotension risk was increased with dexmedetomidine (risk ratio [RR]: 1.62, 95% CI: 1.05-2.51), but there was no difference in bradycardia risk (RR: 3.98, 95% CI: 0.70-22.78). No differences were observed in mortality rates (RR: 1.30, 95% CI: 0.45-3.75) or hospital length of stay (WMD: -2.67 days; 95% CI: -7.73 to 2.39). CONCLUSIONS: Dexmedetomidine was associated with a significant reduction in the time to extubation and shorter ICU stay in difficult-to-wean ICU patients. Although hypotension risk was increased with dexmedetomidine, no differences in other clinical outcomes were observed.

An observational study of hypoactive delirium in the post-anesthesia recovery unit of a pediatric hospital.

BACKGROUND: Hypoactive delirium is present when an awake child is unaware of his or her surroundings, is unable to focus attention, and appears quiet and withdrawn. This condition has been well-described in the intensive care setting but has not been extensively studied in the immediate post-anesthetic period. AIM: To determine if hypoactive emergence delirium occurs in the recovery unit of a pediatric hospital, and if so, what proportion of emergence delirium is hypoactive in nature. METHODS: We conducted an observational study using the Cornell Assessment of Pediatric Delirium in a cohort of 4424 children recovered at a tertiary pediatric hospital. The incidence of emergence delirium detected using the Pediatric Anesthetic Emergence Delirium (PAED) scale was also recorded for comparison. RESULTS: There were 74 cases of emergence delirium detected during the study period using the Cornell Assessment of Pediatric Delirium (1.7%). Only 57 cases were detected using the Pediatric Anesthetic Emergence Delirium scale. The additional 17 cases detected using the Cornell Assessment of Pediatric Dlirium represent cases of hypoactive delirium. In this cohort of pediatric patients, 23% of all cases of emergence delirium were hypoactive in nature. CONCLUSION: The significance of hypoactive delirium in this population is unknown; however, previous studies have shown that emergence delirium can result in post-operative behavior changes and may affect compliance with future episodes of care. However, hypoactive delirium is often missed without active screening. The prevalence detected in this study therefore suggests hypoactive delirium warrants further investigation.

Fibrinogen in traumatic haemorrhage.

PURPOSE OF REVIEW: Recent advances in the understanding of the pathophysiological processes associated with traumatic haemorrhage and trauma-induced coagulopathy (TIC) have resulted in improved outcomes for seriously injured trauma patients. However, a significant number of trauma patients still die from haemorrhage. This article reviews the role of fibrinogen in normal haemostasis, the effect of trauma and TIC on fibrinogen levels and current evidence for fibrinogen replacement in the management of traumatic haemorrhage. RECENT FINDINGS: Fibrinogen is usually the first factor to reach critically low levels in traumatic haemorrhage and hypofibrinogenaemia after severe trauma is associated with increased risk of massive transfusion and death. It is postulated that the early replacement of fibrinogen in severely injured trauma patients can improve outcomes. There is, however, a paucity of evidence to support this, and in addition, there is little evidence to support or refute the effects of cryoprecipitate or fibrinogen concentrate for fibrinogen replacement. SUMMARY: The important role fibrinogen plays in haemostasis and effective clot formation is clear. A number of pilot trials have investigated different strategies for fibrinogen replacement in severe trauma. These trials have formed the basis of several large-scale phase III trials, which, cumulatively will provide a firm evidence base to harmonise worldwide clinical management of severely injured trauma patients with major haemorrhage.

Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.

BACKGROUND: After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. METHODS: We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. RESULTS: We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. CONCLUSIONS: In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158 .).

Characteristics and Outcomes of Critically Ill Trauma Patients in Australia and New Zealand (2005-2017).

OBJECTIVES: To compare the characteristics of adults admitted to the ICU in Australia and New Zealand after trauma with nonelective, nontrauma admissions. To describe trends in hospital mortality and rates of discharge home among these two groups. DESIGN: Retrospective review (2005-2017) of the Australia and New Zealand Intensive Care Society's Center for Outcome and Resource Evaluation Adult Patient Database. SETTING: Adult ICUs in Australia and New Zealand. PATIENTS: Adult (≥17 yr), nonelective, ICU admissions. INTERVENTION: Observational study. MEASUREMENTS AND MAIN RESULTS: We compared 77,002 trauma with 741,829 nonelective, nontrauma patients. Trauma patients were younger (49.0 ± 21.6 vs 60.6 ± 18.7 yr; p < 0.0001), predominantly male (73.1% vs 53.9%; p < 0.0001), and more frequently treated in tertiary hospitals (74.7% vs 45.8%; p < 0.0001). The mean age of trauma patients increased over time but was virtually static for nonelective, nontrauma patients (0.72 ± 0.02 yr/yr vs 0.03 ± 0.01 yr/yr; p < 0.0001). Illness severity increased for trauma but fell for nonelective, nontrauma patients (mean Australia and New Zealand risk of death: 0.10% ± 0.02%/yr vs -0.21% ± 0.01%/yr; p < 0.0001). Trauma patients had a lower hospital mortality than nonelective, nontrauma patients (10.0% vs 15.8%; p < 0.0001). Both groups showed an annual decline in the illness severity adjusted odds ratio (odds ratio) of hospital mortality, but this was slower among trauma patients (trauma: odds ratio 0.976/yr [0.968-0.984/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 0.957/yr [0.955-0.959/yr; p < 0.0001]; interaction p < 0.0001). Trauma patients had lower rates of discharge home than nonelective, nontrauma patients (56.7% vs 64.6%; p < 0.0001). There was an annual decline in illness severity adjusted odds ratio of discharge home among trauma patients, whereas nonelective, nontrauma patients displayed an annual increase (trauma: odds ratio 0.986/yr [0.981-0.990/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 1.014/yr [1.012-1.016/yr; p < 0.0001]; interaction: p < 0.0001). CONCLUSIONS: The age and illness severity of adult ICU trauma patients in Australia and New Zealand has increased over time. Hospital mortality is lower for trauma than other nonelective ICU patients but has fallen more slowly. Trauma patients have become less likely to be discharged home than other nonelective ICU patients.

Preoperative identification of cardiac surgery patients at risk of receiving a platelet transfusion: The Australian Cardiac Surgery Platelet Transfusion (ACSePT) risk prediction tool.

Platelet (PLT) transfusions are limited and costly resources. Accurately predicting clinical demand while limiting product wastage remains difficult. A PLT transfusion prediction score was developed for use in cardiac surgery patients who commonly require PLT transfusions. STUDY DESIGN AND METHODS: Using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database, significant predictors for PLT transfusion were identified by multivariate logistic regression. Using a development data set containing 2005 to 2016 data, the Australian Cardiac Surgery Platelet Transfusion (ACSePT) risk prediction tool was developed by assigning weights to each significant predictor that corresponded to a probability of PLT transfusion. The predicted probability for each score was compared to actual PLT transfusion occurrence in a validation (2017) data set. RESULTS: The development data set contained 38 independent variables and 91 521 observations. The validation data set contained 12 529 observations. The optimal model contained 23 variables significant at P < .001 and an area under the receiver operating characteristic (ROC) curve of 0.69 (95% confidence interval [CI], 0.68-0.69). ACSePT contained nine variables and had an area under the ROC curve of 0.66 (95% CI, 0.65-0.66) and overall predicted probability of PLT transfusion of 19.8% for the validation data set compared to an observed risk of 20.3%. CONCLUSION: The ACSePT risk prediction tool is the first scoring system to predict a cardiac surgery patient's risk of receiving a PLT transfusion. It can be used to identify patients at higher risk of receiving PLT transfusions for inclusion in clinical trials and by PLT inventory managers to predict PLT demand.

Multidisciplinary quality improvement programme for older patients admitted to a vascular surgery ward.

BACKGROUND: Older vascular surgical patients are at high risk of hospital-associated complications and prolonged stays. AIMS: To implement a multidisciplinary co-management model for older vascular patients and evaluate impact on length of stay (LOS), delirium incidence, functional decline, medical complications and discharge destination. METHODS: Prospective pre-post evaluation of a quality improvement intervention, enrolling pre-intervention (August 2012-January 2013) and post-intervention cohort (September 2013-March 2014). Participants were consenting patients aged 65 years and over admitted to the vascular surgical ward of a metropolitan teaching hospital for at least 3 days. Intervention was physician-led co-management plus a multidisciplinary improvement programme targeting delirium and functional decline. Primary outcomes were LOS, delirium and functional decline. Secondary outcomes were medical complications and discharge destination. Process measures included documented consultation patterns. Administrative data were also compared for all patients aged 65 and older for 12 months pre- and post-intervention. RESULTS: We enrolled 112 participants pre-intervention and 123 participants post-intervention. LOS was reduced post-intervention (geometric mean 7.6 days vs 9.3 days; ratio of geometric means 0.82 (95% confidence interval CI0.68-1.00), P = 0.04). There was a trend to less delirium (18 (14.6%) vs 24 (21.4%), P = 0.17) and functional decline (18 (14.6%) vs 27 (24.3%), P = 0.06), with greatest reductions in the urgently admitted subgroup. Administrative data showed reduced median LOS (5.2 days vs 6 days, P = 0.03) and greater discharge home (72% vs 50%, P < 0.01). CONCLUSIONS: Physician-led co-management plus a multidisciplinary improvement programme may reduce LOS and improve functional outcomes in older vascular surgical patients.

Short- and long-term outcomes of neutropenic cancer patients in intensive care according to requirement for invasive ventilation.

BACKGROUND: Neutropenic fever is a frequently encountered complication when caring for cancer patients and can lead to intensive care admission, with high mortality rates in those patients who require invasive mechanical ventilation (IMV). Although hospital survival in this population has improved, long-term outcomes of critically ill neutropenic cancer patients have not been well defined. AIMS: To evaluate short- and long-term outcomes of neutropenic cancer patients admitted to intensive care, according to requirement for invasive ventilation. Additionally, we aimed to determine predictors of poor clinical outcomes in this group. METHODS: A retrospective cohort study of neutropenic cancer patients admitted to our intensive care unit (ICU) from 2008 to 2016. RESULTS: We included 192 cancer patients of whom 100 (52.1%) required IMV. Overall ICU mortality was 29.7% and 12-month post-ICU mortality was 61.5%. Patients requiring IMV had significantly higher short- and long-term mortality (P < 0.001). Multivariate analysis determined three variables to be predictors of mortality at ICU discharge in the whole cohort: IMV (OR 13.52), renal replacement therapy (RRT, OR 2.37) and higher APACHE II scores (OR 1.1 for each unit increase). These variables were identical in the subgroup requiring invasive ventilation, with RRT (OR 2.76) and APACHE II scores (OR 1.1 for each unit increase) predicting short-term mortality. CONCLUSION: Neutropenic cancer patients admitted to ICU have lower short-term mortality than previously reported in cohort studies, however their mortality rises significantly following discharge from ICU. Those patients who require IMV are at significantly increased risk of both short- and long-term mortality.

A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP-I trial (Editorial, p. 2759).

BACKGROUND: Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval. STUDY DESIGN AND METHODS: The Cryopreserved vs. Liquid Platelet (CLIP) study was a double-blind, pilot, multicenter RCT involving high-risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid-stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought. RESULTS: A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid-stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, -343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid-stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid-stored PLTs (difference between groups, 1 unit [95% CI, -3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh-frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, -0.03 to 2.0 units]; p = 0.012). There were no between-group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group. CONCLUSION: In this pilot RCT, compared to liquid-stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted.

Resuscitation Fluid Choices to Preserve the Endothelial Glycocalyx.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .