An international RAND/UCLA expert panel to determine the optimal diagnosis and management of burn inhalation injury.

BACKGROUND: Burn inhalation injury (BII) is a major cause of burn-related mortality and morbidity. Despite published practice guidelines, no consensus exists for the best strategies regarding diagnosis and management of BII. A modified DELPHI study using the RAND/UCLA (University of California, Los Angeles) Appropriateness Method (RAM) systematically analysed the opinions of an expert panel. Expert opinion was combined with available evidence to determine what constitutes appropriate and inappropriate judgement in the diagnosis and management of BII. METHODS: A 15-person multidisciplinary panel comprised anaesthetists, intensivists and plastic surgeons involved in the clinical management of major burn patients adopted a modified Delphi approach using the RAM method. They rated the appropriateness of statements describing diagnostic and management options for BII on a Likert scale. A modified final survey comprising 140 statements was completed, subdivided into history and physical examination (20), investigations (39), airway management (5), systemic toxicity (23), invasive mechanical ventilation (29) and pharmacotherapy (24). Median appropriateness ratings and the disagreement index (DI) were calculated to classify statements as appropriate, uncertain, or inappropriate. RESULTS: Of 140 statements, 74 were rated as appropriate, 40 as uncertain and 26 as inappropriate. Initial intubation with ≥ 8.0 mm endotracheal tubes, lung protective ventilatory strategies, initial bronchoscopic lavage, serial bronchoscopic lavage for severe BII, nebulised heparin and salbutamol administration for moderate-severe BII and N-acetylcysteine for moderate BII were rated appropriate. Non-protective ventilatory strategies, high-frequency oscillatory ventilation, high-frequency percussive ventilation, prophylactic systemic antibiotics and corticosteroids were rated inappropriate. Experts disagreed (DI ≥ 1) on six statements, classified uncertain: the use of flexible fiberoptic bronchoscopy to guide fluid requirements (DI = 1.52), intubation with endotracheal tubes of internal diameter < 8.0 mm (DI = 1.19), use of airway pressure release ventilation modality (DI = 1.19) and nebulised 5000IU heparin, N-acetylcysteine and salbutamol for mild BII (DI = 1.52, 1.70, 1.36, respectively). CONCLUSIONS: Burns experts mostly agreed on appropriate and inappropriate diagnostic and management criteria of BII as in published guidance. Uncertainty exists as to the optimal diagnosis and management of differing grades of severity of BII. Future research should investigate the accuracy of bronchoscopic grading of BII, the value of bronchial lavage in differing severity groups and the effectiveness of nebulised therapies in different severities of BII.

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.).

Immediate Cooling and Early Decompression for the Treatment of Cervical Spinal Cord Injury: A Safety and Feasibility Study.

Cervical spinal cord injury (SCI) usually results in severe, long-term disability. Early therapeutic hypothermia (33-34°C) has been used to improve outcomes in preclinical studies, but previous clinical studies have commenced cooling after arrival at hospital. The objective of the study is to determine the feasibility and safety of early therapeutic hypothermia initiated by paramedics and maintained for up to 24 hours in hospital in patients with SCI. This is a pilot clinical study. The study was undertaken at Ambulance Victoria and The Alfred Hospital, Victoria, Australia. A total of 17 consecutive patients with suspected acute traumatic cervical SCI were enrolled. Patients with suspected cervical SCI were administered a bolus (up to 20 mL/kg) intravenous (IV) cold (4°C) normal saline in the prehospital phase of care. After hospital admission and spinal imaging, further cooling used IV catheter temperature control or surface cooling. Major complications and long-term outcomes were compared with historical controls admitted to the same center before the study. A decrease in core temperature of 1.1°C was achieved during prehospital care and the target temperature was achieved in 6 hours with mechanical temperature management devices in the hospital. There were no major safety concerns. Patients with motor complete SCI who underwent early decompressive surgery had a favorable rate of partial spinal cord recovery compared with historical controls. Therapeutic hypothermia induced using bolus, large-volume, ice-cold saline prehospital and maintained for 24 hours using mechanical devices appears to be feasible and safe in patients with SCI. Larger trials need to be undertaken to determine whether prehospital cooling combined with early decompressive surgery improves outcomes in patients with complete cervical SCI. Australian and New Zealand Clinical Trials Registry (ACTRN12616001086459).

Determinants of Adherence to Best Practice in Severe Traumatic Brain Injury: A Qualitative Study.

BACKGROUND: Management of patients with severe traumatic brain injury (sTBI) is highly variable and inconsistently aligned with evidence derived from high-quality trials, including those examining intravenous fluid resuscitation and use of decompressive craniectomy surgery. This study explored the barriers and facilitators of general and specific evidence-based practices in sTBI from the perspectives of stakeholder clinicians. METHODS: This was a qualitative study of semistructured interviews conducted with specialist clinicians responsible for acute care of patients with sTBI. Interview analysis was guided by the Theoretical domains framework (TDF), and key themes were mapped to relevant TDF behavioral domains. RESULTS: Ten neurosurgeons, 12 intensive care specialists, and three trauma physicians from six high-income countries participated between May 2020 and May 2021. Key TDF domains were environmental context and resources, social influences, and beliefs about consequences. Evidence-aligned management of patients with sTBI is perceived to be facilitated by admission to academic research-oriented hospitals, development of local practice protocols, and interdisciplinary collaboration. Determinants of specific practices varied and included health policy change for fluid resuscitation and development of patient-centered goals for surgical decision-making. CONCLUSIONS: In choosing interventions for patients with sTBI, clinicians integrate local environmental, social, professional, and emotional influences with evidence and associated clinical practice guideline recommendations. This study highlights determinants of evidence-based practice that may inform implementation efforts and thereby improve outcomes for patients with sTBI.

Decompressive Craniectomy Practice following Traumatic Brain Injury in Comparison with Randomized Trials: Harmonized, Multi-Center Cohort Studies in Europe, the United Kingdom, and Australia.

High quality evidence shows decompressive craniectomy (DC) following traumatic brain injury (TBI) may improve survival but increase the number of severely disabled survivors. Contemporary international practice is unknown. We sought to describe international use of DC, and the alignment with evidence and clinical practice guidelines, by analyzing the harmonized Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and Australia-Europe NeuroTrauma Effectiveness Research in Traumatic Brain Injury (OzENTER-TBI) core study datasets, which include patients admitted to intensive care units (ICUs) in Europe, the United Kingdom, and Australia between 2015 and 2017. Outcomes of interest were treatment with DC relative to clinical trial evidence and the Brain Trauma Foundation guidelines. Of 2336 people admitted to ICUs following TBI, DC was performed in 320 (13.7%): in 64/1422 (4.5%) patients with diffuse TBI and 195/640 (30.5%) patients with traumatic mass lesions. Secondary DC (for treatment of intracranial hypertension) was used infrequently in patients who met enrollment criteria of the two randomized clinical trials informing the guidelines-specifically, in 11/124 (8.9%) of those matching Decompressive Craniectomy in Diffuse Traumatic Brain Injury trial (DECRA) enrollment, and in 30/224 (13.4%) of those matching Randomised Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp). Of patients who underwent DC, 258/320 (80.6%) were ineligible for either trial: 149/320 (46.6%) underwent primary DC, 62/320 (19.4%) were outside the trials' age criteria, and 126/320 (39.4%) did not develop intracranial hypertension refractory to non-operative therapies prior to DC. Secondary DC was used infrequently in patients in whom it had been shown to increase survival with severe disability, indicating alignment between contemporaneous evidence and practice. However, most patients who underwent DC were ineligible for the key trials; whether they benefited from DC remains unknown.

Use of a sensitive multisugar test for measuring segmental intestinal permeability in critically ill, mechanically ventilated adults: A pilot study.

BACKGROUND: Increased intestinal permeability (IP) is associated with sepsis in the intensive care unit (ICU). This study aimed to pilot a sensitive multisugar test to measure IP in the nonfasted state. METHODS: Critically ill, mechanically ventilated adults were recruited from 2 ICUs in Australia. Measurements were completed within 3 days of admission using a multisugar test measuring gastroduodenal (sucrose recovery), small-bowel (lactulose-rhamnose [L-R] and lactulose-mannitol [L-M] ratios), and whole-gut permeability (sucralose-erythritol ratio) in 24-hour urine samples. Urinary sugar concentrations were compared at baseline and after sugar ingestion, and IP sugar recoveries and ratios were explored in relation to known confounders, including renal function. RESULTS: Twenty-one critically ill patients (12 males; median, 57 years) participated. Group median concentrations of all sugars were higher following sugar administration; however, sucrose and mannitol increases were not statistically significant. Within individual patients, sucrose and mannitol concentrations were higher in baseline than after sugar ingestion in 9 (43%) and 4 (19%) patients, respectively. Patients with impaired (n = 9) vs normal (n = 12) renal function had a higher L-R ratio (median, 0.130 vs 0.047; P = .003), lower rhamnose recovery (median, 15% vs 24%; P = .007), and no difference in lactulose recovery. CONCLUSION: Small-bowel and whole-gut permeability measurements are possible to complete in the nonfasted state, whereas gastroduodenal permeability could not be measured reliably. For small-bowel IP measurements, the L-R ratio is preferred over the L-M ratio. Alterations in renal function may reduce the reliability of the multisugar IP test, warranting further exploration.

Characteristics, management and outcomes of patients with severe traumatic brain injury in Victoria, Australia compared to United Kingdom and Europe: A comparison between two harmonised prospective cohort studies.

OBJECTIVE: The aim of this manuscript is to compare characteristics, management, and outcomes of patients with severe Traumatic Brain Injury (TBI) between Australia, the United Kingdom (UK) and Europe. METHODS: We enrolled patients with severe TBI in Victoria, Australia (OzENTER-TBI), in the UK and Europe (CENTER-TBI) from 2015 to 2017. Main outcome measures were mortality and unfavourable outcome (Glasgow Outcome Scale Extended <5) 6 months after injury. Expected outcomes were compared according to the IMPACT-CT prognostic model, with observed to expected (O/E) ratios and 95% confidence intervals. RESULTS: We included 107 patients from Australia, 171 from UK, and 596 from Europe. Compared to the UK and Europe, patients in Australia were younger (median 32 vs 44 vs 44 years), a larger proportion had secondary brain insults including hypotension (30% vs 17% vs 21%) and a larger proportion received ICP monitoring (75% vs 74% vs 58%). Hospital length of stay was shorter in Australia than in the UK (median: 17 vs 23 vs 16 days), and a higher proportion of patients were discharged to a rehabilitation unit in Australia than in the UK and Europe (64% vs 26% vs 28%). Mortality overall was lower than expected (27% vs 35%, O/E ratio 0.77 [95% CI: 0.64 - 0.87]. O/E ratios were comparable between regions for mortality in Australia 0.86 [95% CI: 0.49-1.23] vs UK 0.82 [0.51-1.15] vs Europe 0.76 [0.60-0.87]). Unfavourable outcome rates overall were in line with historic expectations (O/E ratio 1.32 [0.96-1.68] vs 1.13 [0.84-1.42] vs 0.96 [0.85-1.09]). CONCLUSIONS: There are major differences in case-mix between Australia, UK, and Europe; Australian patients are younger and have a higher rate of secondary brain insults. Despite some differences in management and discharge policies, mortality was less than expected overall, and did not differ between regions. Functional outcomes were similar between regions, but worse than expected, emphasizing the need to improve treatment for patients with severe TBI.

Protocol for a multicentre prehospital randomised controlled trial investigating tranexamic acid in severe trauma: the PATCH-Trauma trial.

INTRODUCTION: Haemorrhage causes most preventable prehospital trauma deaths and about a third of in-hospital trauma deaths. Tranexamic acid (TXA), administered soon after hospital arrival in certain trauma systems, is an effective therapy in preventing or managing acute traumatic coagulopathy. However, delayed administration of TXA appears to be ineffective or harmful. The effectiveness of prehospital TXA, incidence of thrombotic complications, benefit versus risk in advanced trauma systems and the mechanism of benefit remain uncertain. METHODS AND ANALYSIS: The Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) is comparing TXA, initiated prehospital and continued in hospital over 8 hours, with placebo in patients with severe trauma at risk of acute traumatic coagulopathy. We present the trial protocol and an overview of the statistical analysis plan. There will be 1316 patients recruited by prehospital clinicians in Australia, New Zealand and Germany. The primary outcome will be the eight-level Glasgow Outcome Scale Extended (GOSE) at 6 months after injury, dichotomised to favourable (GOSE 5-8) and unfavourable (GOSE 1-4) outcomes, analysed using an intention-to-treat (ITT) approach. Secondary outcomes will include mortality at hospital discharge and at 6 months, blood product usage, quality of life and the incidence of predefined adverse events. ETHICS AND DISSEMINATION: The study was approved by The Alfred Hospital Research and Ethics Committee in Victoria and also approved in New South Wales, Queensland, South Australia, Tasmania and the Northern Territory. In New Zealand, Northern A Health and Disability Ethics Committee provided approval. In Germany, Witten/Herdecke University has provided ethics approval. The PATCH-Trauma study aims to provide definitive evidence of the effectiveness of prehospital TXA, when used in conjunction with current advanced trauma care, in improving outcomes after severe injury. TRIAL REGISTRATION NUMBER: NCT02187120.

Adherence to Guidelines in Adult Patients with Traumatic Brain Injury: A Living Systematic Review.

Guidelines aim to improve the quality of medical care and reduce treatment variation. The extent to which guidelines are adhered to in the field of traumatic brain injury (TBI) is unknown. The objectives of this systematic review were to (1) quantify adherence to guidelines in adult patients with TBI, (2) examine factors influencing adherence, and (3) study associations of adherence to clinical guidelines and outcome. We searched EMBASE, MEDLINE, Cochrane Central, PubMed, Web of Science, PsycINFO, SCOPUS, CINAHL, and grey literature in October 2014. We included studies of evidence-based (inter)national guidelines that examined the acute treatment of adult patients with TBI. Methodological quality was assessed using the Research Triangle Institute item bank and Quality in Prognostic Studies Risk of Bias Assessment Instrument. Twenty-two retrospective and prospective observational cohort studies, reported in 25 publications, were included, describing adherence to 13 guideline recommendations. Guideline adherence varied considerably between studies (range 18-100%) and was higher in guideline recommendations based on strong evidence compared with those based on lower evidence, and lower in recommendations of relatively more invasive procedures such as craniotomy. A number of patient-related factors, including age, Glasgow Coma Scale, and intracranial pathology, were associated with greater guideline adherence. Guideline adherence to Brain Trauma Foundation guidelines seemed to be associated with lower mortality. Guideline adherence in TBI is suboptimal, and wide variation exists between studies. Guideline adherence may be improved through the development of strong evidence for guidelines. Further research specifying hospital and management characteristics that explain variation in guideline adherence is warranted.

Spinal Surgery in Patients Aged 80 Years and Older: Risk Stratification Using the Modified Frailty Index.

STUDY DESIGN: This was an ambispective clinical quality registry study. OBJECTIVE: To evaluate utility of 11-variable modified Frailty Index (mFI) in predicting postoperative outcomes among patients ≥80 years undergoing spinal surgery. METHODS: Consecutive patients ≥80 years who underwent spinal surgery between January 1, 2013, and June 30, 2018, were included. Primary outcome measure was rate of major complication. Secondary outcome measures were (1) overall complication rate, (2) surgical site infection, and (3) 6-month mortality. RESULTS: A total of 121 operations were performed. Demographic metrics were (1) age (mean ± SD) = 83.1 ± 2.8 years and (2) mFI (mean ± SD) = 2.1 ± 1.4 variables. As mFI increased from 0 to ≥4 variables, risk of major complication increased from 18.2% to 40.0% (P = .014); overall complication increased from 45.5% to 70.0% (P = .032); surgical site infection increased from 0.0% to 25.0% (P = .007). There were no significant changes in risk of 6-month mortality across mFIs (P = .115). Multivariate analysis showed that a higher mFI score of ≥3 variables was associated with a significantly higher risk of (1) major complication (P = .025); (2) overall complication (P = .015); (3) surgical site infection (P = .007); and (4) mortality (P = .044). CONCLUSIONS: mFI scores of ≥3/11 variables were associated with a higher risk of postoperative morbidity in patients aged ≥80 years undergoing spinal surgery. The mFI-associated risk stratification provides a valuable adjunct in surgical decision making for this rapidly growing subpopulation of patients.

Management of Australian Patients with Severe Traumatic Brain Injury: Are Potentially Harmful Treatments Still Used?

Clinical trials have shown that intravenous albumin and decompressive craniectomy to treat early refractory intracranial hypertension can cause harm in patients with severe traumatic brain injury (TBI). The extent to which these treatments remain in use is unknown. We conducted a multi-center retrospective cohort study of adult patients with severe TBI admitted to five neurotrauma centers across Australia between April 2013 and March 2015. Patients were identified from local trauma and intensive care unit (ICU) registries and followed until hospital discharge. Main outcome measures were the administration of intravenous albumin, and decompressive craniectomy for intracranial hypertension. Analyses were predominantly descriptive. There were 303 patients with severe TBI, of whom a minority received albumin (6.9%) or underwent early decompressive craniectomy for treatment of refractory intracranial hypertension complicating diffuse TBI (2.3%). The median (intequartile range [IQR]) age was 35 (24, 58), and most injuries were caused by road traffic accidents (57.4%) or falls (25.1%). Overall, 34.3% of patients died while in the hospital and the remainder were discharged to rehabilitation (44.6%), other health care facilities (4.6%), or home (16.5%). There were no patient characteristics significantly associated with use of albumin or craniectomy. Intravenous albumin and craniectomy for treatment of intracranial hypertension were used infrequently in Australian neurotrauma centers, indicating alignment between best available evidence and practice.

The Utility of the Modified Frailty Index in Outcome Prediction for Elderly Patients with Acute Traumatic Subdural Hematoma.

This study aimed to evaluate the utility of the 11-variable modified Frailty Index (mFI) in prognosticating elderly patients with traumatic acute subdural hematomas (aSDHs). A state-service level 1 trauma center registry was interrogated to investigate consecutive patients ≥65 years of age presenting with traumatic aSDH, with or without major extracranial injury, between January 2013 and December 2017. mFI on admission, demographics, and admission details, including Glasgow Coma Scale (GCS) and pupillary status and radiological findings, were retrospectively retrieved from institutional records. Clinical outcome data were retrieved from medical records and the Victorian State Trauma Registry (VSTR). Outcome measures were 1) 30-day mortality and 2) 6-month unfavorable outcome, defined by the Extended Glasgow Outcome Scale (GOS-E). Five hundred twenty-nine consecutive cases were identified from the registry. Demographic data included: 1) age (median; interquartile range) = 80.46; 74.17-85.89; 2) mFI (mean ± standard deviation) = 1.96 ± 1.42 of 11 variables. Four hundred sixteen cases (79%) had complete outcome data. As mFI increased from 0/11 variables to ≥5/11 variables (≥0.45), 30-day mortality risk increased from 17.72% to 39.29% (p = 0.023) and 6-month unfavorable outcome risk increased from 40.51% to 96.43% (p < 0.001). Multi-variate analysis showed that greater mFI score of ≥3/11 variables (≥0.27) suggested a significantly higher risk of 30-day mortality (p = 0.009) and unfavorable outcome (p < 0.001). We conclude that increasing frailty, as measured by the mFI, was associated with significantly higher risk of 30-day mortality and 6-month unfavorable outcome in elderly patients presenting with aSDH to a level 1 neurotrauma center. Assessment of mFI in elderly patients with aSDH may be a useful determinant of outcome for this rapidly growing population.

Nutrition therapy in critical illness: a review of the literature for clinicians.

Nutrition therapy during critical illness has been a focus of recent research, with a rapid increase in publications accompanied by two updated international clinical guidelines. However, the translation of evidence into practice is challenging due to the continually evolving, often conflicting trial findings and guideline recommendations. This narrative review aims to provide a comprehensive synthesis and interpretation of the adult critical care nutrition literature, with a particular focus on continuing practice gaps and areas with new data, to assist clinicians in making practical, yet evidence-based decisions regarding nutrition management during the different stages of critical illness.

Lactate, bicarbonate and anion gap for evaluation of patients presenting with sepsis to the emergency department: A prospective cohort study.

OBJECTIVE: A serum lactate level >2 mmol/L has been chosen as the preferred cut-off value for screening of patients with suspected sepsis. In patients with suspected sepsis presenting to the ED, we aimed to determine the outcomes of patients with initial lactate levels ≤2 mmoL/L, but abnormal bicarbonate or anion gaps (AGs). METHODS: This prospective cohort study enrolled patients from an adult tertiary referral hospital who presented with suspected sepsis. The predictive value of lactate, bicarbonate and the AG for intensive care unit (ICU) admission and death at hospital discharge were evaluated using area under the receiver operating characteristic curves (AUROC). RESULTS: There were 441 patients with suspected sepsis enrolled from February 2016 to June 2017. There were 96 (22.0%) patients who were admitted to the ICU and at hospital discharge, 42 (9.6%) patients had died. There was no statistically significant difference between the AUROCs of lactate or bicarbonate level or AG to predict ICU admission (P = 0.17). There was no statistically significant difference between the AUROCs of lactate or bicarbonate level or AG to predict mortality at hospital discharge (P = 0.44). Among the 73 patients with normal lactate levels, but abnormal bicarbonate or AG, there were seven (9.6%) deaths. CONCLUSIONS: A normal lactate level alone should not be used to exclude life-threatening sepsis. Patients with metabolic acidosis characterised by low bicarbonate or high AG levels, but with normal lactate levels, have high rates of ICU requirement and mortality and should also be considered for early, aggressive therapy.

Fresh Red Cells for Transfusion in Critically Ill Adults: An Economic Evaluation of the Standard Issue Transfusion Versus Fresher Red-Cell Use in Intensive Care (TRANSFUSE) Clinical Trial.

OBJECTIVES: Trials comparing the effects of transfusing RBC units of different storage durations have considered mortality or morbidity as outcomes. We perform the first economic evaluation alongside a full age of blood clinical trial with a large population assessing the impact of RBC storage duration on quality-of-life and costs in critically ill adults. DESIGN: Quality-of-life was measured at 6 months post randomization using the EuroQol 5-dimension 3-level instrument. The economic evaluation considers quality-adjusted life year and cost implications from randomization to 6 months. A generalized linear model was used to estimate incremental costs (2016 U.S. dollars) and quality-adjusted life years, respectively while adjusting for baseline characteristics. SETTING: Fifty-nine ICUs in five countries. PATIENTS: Adults with an anticipated ICU stay of at least 24 hours when the decision had been made to transfuse at least one RBC unit. INTERVENTIONS: Patients were randomized to receive either the freshest or oldest available compatible RBC units (standard practice) in the hospital transfusion service. MEASUREMENTS AND MAIN RESULTS: EuroQol 5-dimension 3-level utility scores were similar at 6 months-0.65 in the short-term and 0.63 in the long-term storage group (difference, 0.02; 95% CI, -0.00 to 0.04; p = 0.10). There were no significant differences in resource use between the two groups apart from 3.0 fewer hospital readmission days (95% CI, -5.3 to -0.8; p = 0.01) during follow-up in the short-term storage group. There were no significant differences in adjusted total costs or quality-adjusted life years between the short- and long-term storage groups (incremental costs, -$2,358; 95% CI, -$5,586 to $711) and incremental quality-adjusted life years: 0.003 quality-adjusted life years (95% CI, -0.003 to 0.008). CONCLUSIONS: Without considering the additional supply cost of implementing a freshest available RBC strategy for critical care patients, there is no evidence to suggest that the policy improves quality-of-life or reduces other costs compared with standard transfusion practice.

Prognosis of Acute Subdural Hematoma in the Elderly: A Systematic Review.

Acute subdural hematoma (aSDH) is among the most common injury types encountered by neurosurgeons, and carries a poor prognosis, particularly in the elderly. As the incidence of aSDH in the elderly population rises, identifying those patients who may benefit from operative intervention is crucial. This systematic review aimed to identify data on prognostic factors or indices, such as the modified frailty index, that may help predict outcome, and hence guide management. A comprehensive search of online databases was conducted by two independent authors, and data on prognostic factors and outcomes were extracted. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Of 769 studies identified in the initial search, 7 satisfied inclusion and exclusion criteria. Mortality and morbidity varied considerably among studies. Initial Glasgow Coma Scale (GCS) of 3-8 was the most consistently reported negative prognostic feature. Several studies evaluated the impact of medical comorbidities and premorbid frailty, but were limited by small sample size. A previous history of pneumonia was shown to increase the risk of Glasgow Outcome Score (GOS) 1-3 (odds ratio [OR] 6.4 [95% CI 1.6-25.2], p = 0.04) in a single study, which also reported a greater increase in GOS at 3 months in those with fewer than five comorbidities (56% vs. 19%, p < 0.01). There are limited data describing prognostic factors or the use of frailty indices within the specific group of elderly patients with aSDH. Prospective research is needed to evaluate the utility of accurate and validated assessments of frailty to enhance the neurosurgeon's ability to appropriately manage this complex and expanding patient group.

Effect of Early Sustained Prophylactic Hypothermia on Neurologic Outcomes Among Patients With Severe Traumatic Brain Injury: The POLAR Randomized Clinical Trial.

Importance: After severe traumatic brain injury, induction of prophylactic hypothermia has been suggested to be neuroprotective and improve long-term neurologic outcomes. Objective: To determine the effectiveness of early prophylactic hypothermia compared with normothermic management of patients after severe traumatic brain injury. Design, Setting, and Participants: The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury-Randomized Clinical Trial (POLAR-RCT) was a multicenter randomized trial in 6 countries that recruited 511 patients both out-of-hospital and in emergency departments after severe traumatic brain injury. The first patient was enrolled on December 5, 2010, and the last on November 10, 2017. The final date of follow-up was May 15, 2018. Interventions: There were 266 patients randomized to the prophylactic hypothermia group and 245 to normothermic management. Prophylactic hypothermia targeted the early induction of hypothermia (33°C-35°C) for at least 72 hours and up to 7 days if intracranial pressures were elevated, followed by gradual rewarming. Normothermia targeted 37°C, using surface-cooling wraps when required. Temperature was managed in both groups for 7 days. All other care was at the discretion of the treating physician. Main Outcomes and Measures: The primary outcome was favorable neurologic outcomes or independent living (Glasgow Outcome Scale-Extended score, 5-8 [scale range, 1-8]) obtained by blinded assessors 6 months after injury. Results: Among 511 patients who were randomized, 500 provided ongoing consent (mean age, 34.5 years [SD, 13.4]; 402 men [80.2%]) and 466 completed the primary outcome evaluation. Hypothermia was initiated rapidly after injury (median, 1.8 hours [IQR, 1.0-2.7 hours]) and rewarming occurred slowly (median, 22.5 hours [IQR, 16-27 hours]). Favorable outcomes (Glasgow Outcome Scale-Extended score, 5-8) at 6 months occurred in 117 patients (48.8%) in the hypothermia group and 111 (49.1%) in the normothermia group (risk difference, 0.4% [95% CI, -9.4% to 8.7%]; relative risk with hypothermia, 0.99 [95% CI, 0.82-1.19]; P = .94). In the hypothermia and normothermia groups, the rates of pneumonia were 55.0% vs 51.3%, respectively, and rates of increased intracranial bleeding were 18.1% vs 15.4%, respectively. Conclusions and Relevance: Among patients with severe traumatic brain injury, early prophylactic hypothermia compared with normothermia did not improve neurologic outcomes at 6 months. These findings do not support the use of early prophylactic hypothermia for patients with severe traumatic brain injury. Trial Registration: clinicaltrials.gov Identifier: NCT00987688; Anzctr.org.au Identifier: ACTRN12609000764235.

Statistical analysis plan for the POLAR-RCT: The Prophylactic hypOthermia trial to Lessen trAumatic bRain injury-Randomised Controlled Trial.

BACKGROUND: The Prophylactic hypOthermia to Lessen trAumatic bRain injury-Randomised Controlled Trial (POLAR-RCT) will evaluate whether early and sustained prophylactic hypothermia delivered to patients with severe traumatic brain injury improves patient-centred outcomes. METHODS: The POLAR-RCT is a multicentre, randomised, parallel group, phase III trial of early, prophylactic cooling in critically ill patients with severe traumatic brain injury, conducted in Australia, New Zealand, France, Switzerland, Saudi Arabia and Qatar. A total of 511 patients aged 18-60 years have been enrolled with severe acute traumatic brain injury. The trial intervention of early and sustained prophylactic hypothermia to 33 °C for 72 h will be compared to standard normothermia maintained at a core temperature of 37 °C. The primary outcome is the proportion of favourable neurological outcomes, comprising good recovery or moderate disability, observed at six months following randomisation utilising a midpoint dichotomisation of the Extended Glasgow Outcome Scale (GOSE). Secondary outcomes, also assessed at six months following randomisation, include the probability of an equal or greater GOSE level, mortality, the proportions of patients with haemorrhage or infection, as well as assessment of quality of life and health economic outcomes. The planned sample size will allow 80% power to detect a 30% relative risk increase from 50% to 65% (equivalent to a 15% absolute risk increase) in favourable neurological outcome at a two-sided alpha of 0.05. DISCUSSION: Consistent with international guidelines, a detailed and prospective analysis plan has been developed for the POLAR-RCT. This plan specifies the statistical models for evaluation of primary and secondary outcomes, as well as defining covariates for adjusted analyses and methods for exploratory analyses. Application of this statistical analysis plan to the forthcoming POLAR-RCT trial will facilitate unbiased analyses of these important clinical data. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00987688 (first posted 1 October 2009); Australian New Zealand Clinical Trials Registry, ACTRN12609000764235 . Registered on 3 September 2009.

Erythropoietin to Reduce Mortality in Traumatic Brain Injury: A Post-hoc Dose-effect Analysis.

OBJECTIVE: We aimed to assess whether the dosing regimen of erythropoietin shows a relationship to mortality in critically ill patients with traumatic brain injury (TBI). BACKGROUND: Erythropoietin may decrease mortality in patients with TBI; however, the optimal dosing regimen remains uncertain. METHODS: We conducted a post-hoc analysis of a multicenter, randomized trial of weekly erythropoietin versus placebo in patients with moderate and severe TBI admitted to intensive care. We assessed whether the cumulative dosage of erythropoietin was differentially associated with all-cause patient mortality evaluated at 6 months after injury. RESULTS: There was a nonlinear relationship between dose and mortality (P = 0.008) that remained after adjustment for site and severity of illness (P = 0.01). Six-month mortality was lower in randomized patients who received 1 [adjusted hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.33-1.01; P = 0.06] or 2 doses of erythropoietin (HR 0.31, 95% CI 0.12-0.80; P = 0.02) compared with those who received no doses. No benefit was seen with 3 doses (HR 1.55, 95% CI 0.66-3.62; P = 0.33). There was no differential effect of dose on functional neurological outcomes. Results across subgroups and secondary intention to treat analyses were consistent with primary findings. CONCLUSIONS: This post-hoc, hypothesis-generating analysis found potential reductions in mortality following 1 or 2 weekly doses of 40,000 IU of erythropoietin in intensive care unit patients with moderate or severe TBI, but not with 3 doses. These findings will inform the design of future trials of erythropoietin in critically ill patients with TBI and trauma.