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Background: Hypovitamin B1 occurs frequently during critical illness but is challenging to predict or rapidly diagnose. The aim of this study was to evaluate whether plasma phosphate concentrations predict hypovitamin B1, enteral nutrition prevents hypovitamin B1 and intravenous thiamine supplementation achieves supraphysiological concentrations in critically ill patients. Methods: Thirty‐two enterally fed critically ill patients, with a plasma phosphate concentration ≤0.65 mmol/L, formed a nested cohort within a larger randomised clinical trial. Patients were assigned to receive intravenous thiamine (200 mg) twice daily, and controls were not administered intravenous thiamine. Thiamine pyrophosphate concentrations were measured at four time points (pre‐ and post‐infusion and 4‐ and 6‐h post‐infusion) on days 1 and 3 in those allocated to thiamine and once in the control group. Results: Baseline thiamine pyrophosphate concentrations were similar (intervention 88 [67, 93] vs. control 89 [62, 110] nmol/L, p = 0.49). Eight (25%) patients had hypovitamin B1 (intervention 3 vs. control 5), with two patients in the control group remaining insufficient at day 3. There was no association between baseline phosphate and thiamine pyrophosphate concentrations. Intravenous thiamine achieved supraphysiological concentrations 6 h post first infusion, with concentrations increasing to day 3. In the control group, thiamine pyrophosphate concentrations were not statistically different between baseline and day 3 (mean change: 8.6 [−6.0, 23.1] nmol/L, p = 0.25). Conclusions: Phosphate concentrations did not predict hypovitamin B1, which was observed in 25% of the participants. Enteral nutrition alone prevented the development of new hypovitamin B1. Administration of a single 200‐mg dose of intravenous thiamine achieved supraphysiological concentrations of thiamine pyrophosphate, with repeated dosing sustaining this effect. Key points: Hypovitamin B1 appears prevalent in critically ill patients.Serum phosphate concentrations did not predict hypovitamin B1.Administration of a 200‐mg dose of intravenous thiamine achieved supraphysiological concentrations of thiamine pyrophosphate. [ABSTRACT FROM AUTHOR]

Objective: The application of rapid, non‐operator‐dependent, non‐invasive cardiac output monitoring (COM) may provide early physiological information in ED patients with haemodynamic instability (HI). Our primary objective was to assess the feasibility of measuring pre‐intervention (baseline) cardiac index (CI) and associated haemodynamic parameters. Methods: We performed a prospective observational study of adults shortly after presentation to the ED of a large university hospital with tachycardia or hypotension or both. We applied non‐invasive COM for 5 min and recorded CI, mean arterial pressure (MAP), stroke volume index (SVI) and systemic vascular resistance index (SVRI). We assessed for differences between those presenting with hypotension or hypotension and tachycardia with tachycardia alone and between those with or without suspected infection. Results: We obtained haemodynamic parameters in 46 of 49 patients. In patients with hypotension or hypotension and tachycardia (n = 15) rather than tachycardia alone (n = 31), we observed a lower MAP (60.8 vs 87.7, P < 0.0001), CI (2.8 vs 3.9, P = 0.0167) and heart rate (85.5 vs 115.4, P < 0.0001). There was no difference in SVI (33.7 vs 33.4, P = 0.93) or SVRI (1970 vs 2088, P = 0.67). Patients with suspected infection had similar haemodynamic values except for a lower SVRI (1706 vs 2237, P = 0.011). Conclusions: Rapid, non‐operator‐dependent, non‐invasive COM was possible in >90% of ED patients presenting with HI. Compared with tachycardia alone, patients with hypotension had lower CI, MAP and heart rate, while those with suspected infection had a lower SVRI. This technology provides novel insights into the early state of the circulation in ED patients with HI. [ABSTRACT FROM AUTHOR]

Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P <.05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients. [ABSTRACT FROM AUTHOR]

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30‐day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6‐ and 24‐h post‐enrolment, time to antimicrobial administration, intensive care admission, organ support and in‐hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre‐enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in‐hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy. [ABSTRACT FROM AUTHOR]

Background: Delirium is common in hospitalised patients but its epidemiology remains poorly characterised. Aims: To test the hypothesis that patient demographics, clinical phenotype, management and outcomes of patient with delirium in hospital ward patients differ from intensive care unit (ICU) patients. Methods: Retrospective cohort of patients admitted to an Australian university‐affiliated hospital between March 2013 and April 2017 and coded for delirium at discharge using the International Classification of Diseases System, 10th revision, criteria. Results: Among 61 032 hospitalised patients, 2864 (4.7%) were coded for delirium. From these, we studied a random sample of 100 ward patients and 100 ICU patients. Ward patients were older (median age: 84 vs 65 years; P < 0.0001), more likely to have dementia (38% vs 2% for ICU patients; P < 0.0001) and less likely to have had surgery (24% vs 62%; P < 0.0001). Of ward patients, 74% had hypoactive delirium, while 64% of ICU patients had agitated delirium (P < 0.0001). Persistent delirium at hospital discharge was more common among ward patients (66% vs 17%, P < 0.0001). On multivariable analysis, age and dementia predicted persistent delirium, while surgery predicted recovery. Conclusions: Delirium in ward patients is profoundly different from delirium in ICU patients. It has a dominant hypoactive clinical phenotype, is preceded by dementia and is less likely to recover at hospital discharge. Therefore, delirium prevention, detection and goals of care should be adapted to the environment in which it occurs. [ABSTRACT FROM AUTHOR]

Objective: There is uncertainty about the optimal i.v. fluid volume and timing of vasopressor commencement in the resuscitation of patients with sepsis and hypotension. We aim to study current resuscitation practices in EDs in Australia and New Zealand (the Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis [ARISE FLUIDS] observational study). Methods: ARISE FLUIDS is a prospective, multicentre observational study in 71 hospitals in Australia and New Zealand. It will include adult patients presenting to the ED during a 30 day period with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation. We will obtain data on baseline demographics, clinical and laboratory variables, all i.v. fluid given in the first 24 h, vasopressor use, time to antimicrobial administration, admission to intensive care, organ failure and in‐hospital mortality. We will specifically describe (i) the volume of fluid administered at the following time points: when meeting eligibility criteria, in the first 6 h, at 24 h and prior to vasopressor commencement and (ii) the frequency and timing of vasopressor use in the first 6 h and at 24 h. Screening logs will provide reliable estimates of the proportion of ED patients meeting eligibility criteria for a subsequent randomised controlled trial. Discussion: This multicentre, observational study will provide insight into current haemodynamic resuscitation practices in patients with sepsis and hypotension as well as estimates of practice variation and patient outcomes. The results will inform the design and feasibility of a multicentre phase III trial of early haemodynamic resuscitation in patients presenting to ED with sepsis and hypotension. [ABSTRACT FROM AUTHOR]

Purpose: To use the World Health Organisation's International Classification of Functioning to measure disability following critical illness using patient-reported outcomes.Methods: A prospective, multicentre cohort study conducted in five metropolitan intensive care units (ICU). Participants were adults who had been admitted to the ICU, received more than 24 h of mechanical ventilation and survived to hospital discharge. The primary outcome was measurement of disability using the World Health Organisation's Disability Assessment Schedule 2.0. The secondary outcomes included the limitation of activities and changes to health-related quality of life comparing survivors with and without disability at 6 months after ICU.Results: We followed 262 patients to 6 months, with a mean age of 59 ± 16 years, and of whom 175 (67%) were men. Moderate or severe disability was reported in 65 of 262 (25%). Predictors of disability included a history of anxiety/depression [odds ratio (OR) 1.65 (95% confidence interval (CI) 1.22, 2.23), P = 0.001]; being separated or divorced [OR 2.87 (CI 1.35, 6.08), P = 0.006]; increased duration of mechanical ventilation [OR 1.04 (CI 1.01, 1.08), P = 0.03 per day]; and not being discharged to home from the acute hospital [OR 1.96 (CI 1.01, 3.70) P = 0.04]. Moderate or severe disability at 6 months was associated with limitation in activities, e.g. not returning to work or studies due to health (P < 0.002), and reduced health-related quality of life (P < 0.001).Conclusion: Disability measured using patient-reported outcomes was prevalent at 6 months after critical illness in survivors and was associated with reduced health-related quality of life. Predictors of moderate or severe disability included a prior history of anxiety or depression, separation or divorce and a longer duration of mechanical ventilation.Trial Registration: NCT02225938. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the prevalence, risk factors, prophylactic treatment and impact on mortality for venous thromboembolism (VTE) in patients with moderate to severe traumatic brain injury (TBI) treated in the intensive care unit.Methods: A post hoc analysis of the erythropoietin in traumatic brain injury (EPO-TBI) trial that included twice-weekly lower limb ultrasound screening. Venous thrombotic events were defined as ultrasound-proven proximal deep venous thrombosis (DVT) or clinically detected pulmonary embolism (PE). Results are reported as events, percentages or medians and interquartile range (IQR). Cox regression analysis was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to VTE and death.Results: Of 603 patients, 119 (19.7%) developed VTE, mostly comprising DVT (102 patients, 16.9%) with a smaller number of PE events (24 patients, 4.0%). Median time to DVT diagnosis was 6 days (IQR 2-11) and to PE diagnosis 6.5 days (IQR 2-16.5). Mechanical prophylaxis (MP) was used in 91% of patients on day 1, 97% of patients on day 3 and 98% of patients on day 7. Pharmacological prophylaxis was given in 5% of patients on day 1, 30% of patients on day 3 and 57% of patients on day 7. Factors associated with time to VTE were age (HR per year 1.02, 95% CI 1.01-1.03), patient weight (HR per kg 1.01, 95% CI 1-1.02) and TBI severity according to the International Mission for Prognosis and Analysis of Clinical Trials risk of poor outcome (HR per 10% increase 1.12, 95% CI 1.01-1.25). The development of VTE was not associated with mortality (HR 0.92, 95% CI 0.51-1.65).Conclusions: Despite mechanical and pharmacological prophylaxis, VTE occurs in one out of every five patients with TBI treated in the ICU. Higher age, greater weight and greater severity of TBI increase the risk. The development of VTE was not associated with excess mortality. [ABSTRACT FROM AUTHOR]

Objective The aim of the present paper is to study the indications for fluid bolus therapy (FBT) and its associated physiological changes in ED patients. Methods Prospective observational study of FBT in a tertiary ED, we recorded indications, number, types and volumes, resuscitation goals and perceived success rates of FBT. Moreover, we studied key physiological variables before, 10 min, 1 h and 2 h after FBT. Results We studied 500 FBT episodes (750 [500-1250] mL). Median age was 59 (36-76) years and 57% were male. Shock was deemed present in 135 (27%) patients, septic shock in 80 (16%), and cardiogenic shock in 30 (6%). Overall, 0.9% saline (84%) was the most common fluid and hypotension the most common indication (70%). 'Avoidance of hospital/ICU admission' was the goal perceived to have the greatest success rate (85%). However, although mean arterial pressure (MAP) increased ( P < 0.01) and heart rate (HR) decreased ( P = 0.04) at 10 min ( P = 0.01), both returned to baseline at 1 and 2 h. In contrast, respiratory rate (RR) increased at 1 ( P < 0.01) and 2 h ( P = 0.03) and temperature decreased at 1 and 2 h (both P < 0.001). In patients with shock, 1 h after FBT, there was a median 3 mmHg increase in MAP ( P = 0.01) but no change in HR ( P = 0.44), while RR increased ( P < 0.01) and temperature decreased ( P = 0.01). Conclusions In ED, FBT is used mostly in patients without shock. However, after an immediate haemodynamic effect, FBT is associated with absent or limited physiological changes at 1 or 2 h. Even in shocked patients, the changes in MAP at 1 or 2 h after FBT are small. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the characteristics and outcomes of critically ill patients with severe acute kidney injury (AKI) treated and not treated with renal replacement therapy (RRT). Methods: Secondary analysis of a multi-centre cohort study. Primary exposure was RRT. Primary outcome was propensity and multi-variable adjusted-hospital mortality. Results: We studied 1250 patients (71.3%) who received and 502 (28.7%) who did not receive RRT. Reasons for not starting RRT (not mutually exclusive) were limitations of support (33.6%, n=169), adequate urine output (46.2%; n=232), plan to observe (56.4%; n=283), and advanced age (12.6%; n=63). Mortality was higher in those not receiving RRT due to limitations and advanced age but lower for adequate urine output and plan to observe. Propensity and multi-variable adjusted analysis showed no statistical difference in hospital mortality (adj-OR 1.47; 95% CI, 0.93-2.24) in patients receiving RRT. Results were similar in a sensitivity analysis restricted to patients fulfilling risk, injury, failure, loss, end-stage kidney disease-FAILURE criteria (37.0%; n= 446) (adj-OR 1.36; 95% CI, 0.70-2.66). Conclusion: In this cohort, reasons for not starting RRT included limitations of support and perception of impending renal recovery. Despite similar risk of mortality after adjusting for selection bias and confounders, RRT-treated patients were fundamentally different from non-treated patients across a spectrum of variables that precludes valid comparison in observational data. [ABSTRACT FROM AUTHOR]

Purpose: Oxygen (O2) is the most common therapy in mechanically ventilated patients, but targets and dose are poorly understood. We aimed to describe current O2 administration and titration in such patients in an academic intensive care unit. Materials and Methods: In consecutive ventilated (>48 hours) patients we prospectively obtained fraction of inspired O2 (FIO2), pulse oximetry O2 saturation (SpO2) and arterial O2 tension (PaO2) every 6 hours. We calculated the amount of excess O2 delivery and the intensivists' response to hyperoxemia (SpO2 >98%). Results: During 358 mechanical ventilation days in 51 critically ill patients, median calculated excess O2 delivery was 3472 L per patient. Patients spent most of their time with their SpO2 >98% (59% [29- 83]) and PaO2 between 80 and 120 mm Hg (59% [38-72]). In addition, 50% of all observations showed hyperoxemia and 4% severe hyperoxemia (PaO2 >202.5 mm Hg). Moreover, 71% of the calculated total excess 263,841 L of O2 was delivered when the FIO2 was 0.3 to 0.5. When hyperoxemia occurred with an FIO2 between 0.3 and 0.4, for 88% of episodes, no FIO2 adjustments were made. Conclusions: Excess O2 delivery and liberal O2 therapy were common in mechanically ventilated patients. Current O2 therapy practice may be suboptimal and further investigations are warranted. [ABSTRACT FROM AUTHOR]

Purpose: It is unclear if blood pressure targets for patients with shock should be adjusted to pre-morbid levels. We aimed to investigate mean deficit between the achieved mean perfusion pressure (MPP) in vasopressor-treated patients and their estimated basal (resting) MPP, and assess whether MPP deficit has any association with subsequent acute kidney injury (AKI). Materials and Methods: Fifty-one consecutive, non-trauma patients, aged ⩾40 years, with ⩾2 organ dysfunction and requiring vasopressor ⩾4 hours were observed at an academic intensive care unit. Mean MPP deficit [=%(basal MPP - achieved MPP)/basal MPP] and % time spent with >20% MPP deficit were assessed during initial 72 vasopressor hours (T0-T72) for each patient. Results: Achieved MPP was unrelated to basal MPP (P = .99). Mean MPP deficit was 18%(95%CI 15-21). Patients spent 48% (95% CI 39-57) time with >20% MPP deficit. Despite similar risk scores at T0, subsequent AKI (⩾2 RIFLE class increase from T0) occurred more frequently in patients with higher (Nmedian) MPP deficit compared to patients with lower MPP deficit (56% vs 28%; P = .045). Incidence of subsequent AKI was also higher among patients who spent greater % time with >20% MPP deficit (P = .04). Conclusions: Achieved blood pressure during vasopressor therapy had no relationship to the pre-morbid basal level. This resulted in significant and varying degree of relative hypotension (MPP deficit), which could be a modifiable risk factor for AKI in patients with shock. [ABSTRACT FROM AUTHOR]

Objective: To document current management of blood glucose in Australian and New Zealand intensive care units (ICUs) and to investigate the association between insulin administration, blood glucose concentration and hospital outcome.Design and Setting: Practice survey and inception cohort study in closed multi-disciplinary ICUs in Australia and New Zealand.Patients: Twenty-nine ICU directors and 939 consecutive admissions to 29 ICUs during a 2-week period.Measurement and Results: Data collected included unit approaches to blood glucose management, patient characteristics, blood glucose concentrations, insulin administration and patient outcomes. Ten percent of the ICU directors reported using an intensive insulin regimen in all their patients. In 861 patients (91.7%) blood glucose concentration was greater than 6.1[Symbol: see text]mmol/l, 287 (31.1%) received insulin, and the median blood glucose concentration triggering insulin administration was 11.5 (IQR 9.4-14) mmol/l. Univariate analysis demonstrated that non-survivors had a higher maximum daily blood glucose concentration (12 mmol/l, 9.4-14.8, vs. 9.5, 7.6-12.2) and were more likely to receive insulin (47% vs. 28%). Multiple logistic regression analysis showed age (OR per 5-year decrease 0.93, 95% CI 0.87-1.00) and APACHE II (OR per point decrease 0.87, 95% CI 0.84-0.90) to be independently associated with hospital mortality. After controlling for age and APACHE II both daily highest blood glucose (OR 0.95, 95% CI 0.90-1.00) and administration of insulin (OR 0.62, 95% CI 0.39-1.00) were independently associated when added to the model alone; neither was independently associated when they were simultaneously included in the model.Conclusion: Few Australian and New Zealand ICUs have adopted intensive insulin therapy. In this study, insulin administration and highest daily blood glucose concentration could not be separated in their association with hospital mortality. [ABSTRACT FROM AUTHOR]

Background: Optimal cerebral oxygenation is considered fundamental to cerebral protection in cardiac arrest (CA) patients. Hypercapnia increases cerebral blood flow and may also improve cerebral oxygenation. It is uncertain, however, whether this effect occurs in mechanically ventilated early survivors of CA.Methods: We enrolled mechanically ventilated resuscitated patients within 36h of their cardiac arrest. We performed a prospective double cross-over physiological study comparing the impact of normocapnia (PaCO2 35-45mmHg) vs. mild hypercapnia (PaCO2 45-55mmHg) on regional cerebral tissue oxygen saturation (SctO2) assessed by near infrared spectroscopy (NIRS).Results: We studied seven adult CA patients with a median time to return of spontaneous circulation of 28min at a median of 26h and 30min after CA. During normocapnia (median EtCO2 of 32mmHg [30-41mmHg] and PaCO2 of 37mmHg [32-45mmHg]) the median NIRS-derived left frontal SctO2 was 61% [52-65%] and the right frontal SctO2 was 61% [54-68%]. However, during mild hypercapnia (median EtCO2 of 49mmHg [40-57mmHg] and PaCO2 of 52mmHg [43-55mmHg) the median left frontal SctO2 increased to 69% [59-78%] and the right frontal SctO2 increased to 73% [61-76%])(p=0.001, for all comparisons).Conclusion: During the early post-resuscitation period, in mechanically ventilated CA patients, mild hypercapnia increases cerebral oxygenation as assessed by NIRS. Further investigations of the effect of prolonged mild hypercapnia on cerebral oxygenation and patient outcomes appear justified. [ABSTRACT FROM AUTHOR]

Aim: A new definition of sepsis released by an international task-force has introduced the concept of quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA). This study aimed to measure the proportion of patients who fulfilled qSOFA criteria during a Rapid Response Team (RRT) review and to assess their associated outcomes.Methods: We conducted a prospective study of adult RRT reviews over a one month period between 6th June and 10th July 2016 in a large tertiary hospital in Melbourne Australia RESULTS: Over a one-month period, there were 282 RRT reviews, 258 of which were included. One hundred out of 258 (38.8%) RRT review patients fulfilled qSOFA criteria. qSOFA positive patients were more likely to be admitted to the intensive care unit (29% vs 18%, P=0.04), to have repeat RRT reviews (27% vs 13%; p=0.007) and die in hospital (31% vs 10%, P<0.001). qSOFA positive patients with suspected infection were more likely to be admitted to the intensive care unit compared to patients with infection alone (37% vs 15%, P=0.002). Eleven of 42 patients (26%) who had infection and qSOFA died whilst in hospital, compared to 8/55 (15%) of patients with infection alone (P=0.2).Conclusion: Adult patients who are qSOFA positive at the time of their RRT review are at increased risk of in-hospital mortality. The assessment of qSOFA may be a useful triage tool during a RRT review. [ABSTRACT FROM AUTHOR]