Twenty percent human albumin solution fluid bolus administration therapy in patients after cardiac surgery-II: a multicentre randomised controlled trial.

PURPOSE: After cardiac surgery, fluid bolus therapy (FBT) with 20% human albumin may facilitate less fluid and vasopressor administration than FBT with crystalloids. We aimed to determine whether, after cardiac surgery, FBT with 20% albumin reduces the duration of vasopressor therapy compared with crystalloid FBT. METHODS: We conducted a multicentre, parallel-group, open-label, randomised clinical trial in six intensive care units (ICUs) involving cardiac surgery patients deemed to require FBT. We randomised 240 patients to receive up to 400 mL of 20% albumin/day as FBT, followed by 4% albumin for any subsequent FBT on that day, or to crystalloid FBT for at least the first 1000 mL, with use of crystalloid or 4% albumin FBT thereafter. The primary outcome was the cumulative duration of vasopressor therapy. Secondary outcomes included fluid balance. RESULTS: Of 480 randomised patients, 466 provided consent and contributed to the primary outcome (mean age 65 years; median EuroSCORE II 1.4). The cumulative median duration of vasopressor therapy was 7 (interquartile range [IQR] 0-19.6) hours with 20% albumin and 10.8 (IQR 0-22.8) hours with crystalloids (difference - 3.8 h, 95% confidence interval [CI] - 8 to 0.4; P = 0.08). Day one fluid balance was less with 20% albumin FBT (mean difference - 701 mL, 95% CI - 872 to - 530). CONCLUSIONS: In patients after cardiac surgery, when compared to a crystalloid-based FBT, 20% albumin FBT was associated with a reduced positive fluid balance but did not significantly reduce the duration of vasopressor therapy.

Impact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.

RATIONALE: Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high dose early active mobilization. OBJECTIVES: To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial. METHODS: All TEAM trial patients were included. The primary outcome was days alive and out of hospital at day 180. Secondary outcomes included 180-day mortality and long-term functional outcomes at day 180. Logistic and median regression models were used to explore the effect of high dose early mobilization on outcomes by diabetes status. MEASUREMENTS AND MAIN RESULTS: All 741 patients from the original trial were included. Of these, 159 patients (21.4%) had diabetes. Patients with diabetes had a lower number of days alive and out of hospital at day 180 (124 [0-153] vs. 147 [82-164], p = 0.013), and higher 180-day mortality (30% vs. 18%, p = 0.044). In patients receiving high dose early mobilization, days alive and out of hospital at day 180 was 73.0 (0.0 - 144.5) in patients with diabetes and 146.5 (95.8 - 163.0) in patients without diabetes (p for interaction = 0.108). However, in patients with diabetes, high dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio 3.47; 95% confidence interval [CI], 1.67-7.61, p value for interaction, 0.001). CONCLUSIONS: In this secondary analysis of the TEAM trial, in patients with diabetes, a high dose early mobilization strategy did not significantly decrease the number of days alive and out of hospital at day 180 but it increased 180-day mortality.

Magnitude and time to peak oxygenation effect of prone positioning in ventilated adults with COVID-19 related acute hypoxemic respiratory failure.

BACKGROUND: Prone positioning may improve oxygenation in acute hypoxemic respiratory failure and was widely adopted in COVID-19 patients. However, the magnitude and timing of its peak oxygenation effect remain uncertain with the optimum dosage unknown. Therefore, we aimed to investigate the magnitude of the peak effect of prone positioning on the PaO2 :FiO2 ratio during prone and secondly, the time to peak oxygenation. METHODS: Multi-centre, observational study of invasively ventilated adults with acute hypoxemic respiratory failure secondary to COVID-19 treated with prone positioning. Baseline characteristics, prone positioning and patient outcome data were collected. All arterial blood gas (ABG) data during supine, prone and after return to supine position were analysed. The magnitude of peak PaO2 :FiO2 ratio effect and time to peak PaO2 :FIO2 ratio effect was measured. RESULTS: We studied 220 patients (mean age 54 years) and 548 prone episodes. Prone positioning was applied for a mean (±SD) 3 (±2) times and 16 (±3) hours per episode. Pre-proning PaO2 :FIO2 ratio was 137 (±49) for all prone episodes. During the first episode. the mean PaO2 :FIO2 ratio increased from 125 to a peak of 196 (p < .001). Peak effect was achieved during the first episode, after 9 (±5) hours in prone position and maintained until return to supine position. CONCLUSIONS: In ventilated adults with COVID-19 acute hypoxemic respiratory failure, peak PaO2 :FIO2 ratio effect occurred during the first prone positioning episode and after 9 h. Subsequent episodes also improved oxygenation but with diminished effect on PaO2 :FIO2 ratio. This information can help guide the number and duration of prone positioning episodes.

Early Net Ultrafiltration during Continuous Renal Replacement Therapy: Impact of Admission Diagnosis and Association with Mortality.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is common in the intensive care unit (ICU) but a high net ultrafiltration rate (UFNET) calculated with daily data may increase mortality. We aimed to study early UFNET practice using minute-by-minute CRRT machine recordings and to assess its association with admission diagnosis and mortality. METHODS: We studied CRRT treatments in three adult ICUs over 7 years. We calculated early UFNET rates minute-by-minute and categorized UFNET into tertiles of mean UFNET in the first 72 h and admission diagnosis. We applied Cox-proportional hazards modelling with censoring of patients who died within 72 h. RESULTS: We studied 1,218 patients, 154,712 h, and 9,282,729 min of CRRT (5,702 circuits). Mean early UFNET was 1.52 (1.46-1.57) mL/kg/h. Early UFNET tertiles were similar to, but somewhat higher than, previously reported values at 0.00-1.20 mL/kg/h, 1.21-1.93 mL/kg/h, and >1.93 mL/kg/h. UFNET values were similar whether evaluated at 24 or 72 h or for the entire duration of CRRT. There was, however, significant variation in UFNET practice by admission diagnosis: higher in respiratory diseases (pneumonia p = 0.01, other p < 0.0001) and cardiovascular disease (p = 0.005) but lower in cardiothoracic surgery (p = 0.04), renal (p = 0.0003) and toxicology-associated diagnoses (p = 0.01). Higher UFNET was associated with an increased hazard of death, HR 1.24 (1.13-1.37), independent of admission diagnosis, weight, age, sex, presence of end-stage kidney disease, and severity of illness. CONCLUSION: Early UFNET practice varies significantly by admission diagnosis. Higher early UFNET is independently associated with mortality. Impacts of UFNET on mortality may vary by admission diagnosis. Further work is required to elucidate the nature and mechanisms responsible for this association.

Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.

PURPOSE: Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. METHODS: Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. RESULTS: We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). CONCLUSION: During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.

Study protocol for TARGET protein: The effect of augmented administration of enteral protein to critically ill adults on clinical outcomes: A cluster randomised, cross-sectional, double cross-over, clinical trial.

Background: It is unknown whether increasing dietary protein to 1.2-2.0 g/kg/day as recommended in international guidelines compared to current practice improves outcomes in intensive care unit (ICU) patients. The TARGET Protein trial will evaluate this. Objective: To describe the study protocol for the TARGET Protein trial. Design setting and participants: TARGET Protein is a cluster randomised, cross-sectional, double cross-over, pragmatic clinical trial undertaken in eight ICUs in Australia and New Zealand. Each ICU will be randomised to use one of two trial enteral formulae for three months before crossing over to the other formula, which is then repeated, with enrolment continuing at each ICU for 12 months. All patients aged ≥16 years in their index ICU admission commencing enteral nutrition will be eligible for inclusion. Eligible patients will receive the trial enteral formula to which their ICU is allocated. The two trial enteral formulae are isocaloric with a difference in protein dose: intervention 100g/1000 ml and comparator 63g/1000 ml. Staggered recruitment commenced in May 2022. Main outcomes measures: The primary outcome is days free of the index hospital and alive at day 90. Secondary outcomes include days free of the index hospital at day 90 in survivors, alive at day 90, duration of invasive ventilation, ICU and hospital length of stay, incidence of tracheostomy insertion, renal replacement therapy, and discharge destination. Conclusion: TARGET Protein aims to determine whether augmented enteral protein delivery reduces days free of the index hospital and alive at day 90. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12621001484831).

Aggression, violence and threatening behaviour during critical illness.

Objective: This article aims to quantify prevalence of patient aggression or threatened/actual violence during critical illness. Design: This is a retrospective cohort study. Setting: This study was conducted in single adult trauma intensive care unit (ICU). Participants: Patients aged 18 years or over, admitted between January 2015 and December 2020, who triggered a "Code Grey" response due to aggression or threatened/actual violence. Main outcome measure: The primary outcome was prevalence of Code Grey events. Secondary outcomes included unadjusted and adjusted (logistic mixed model) effects of patient demographics, diagnoses and severity of illness on Code Grey events. Results: There were 16175 ICU admissions relating to 14085 patients and 807 Code Grey events involving 379 (2.7%) patients. The observed count of events increased progressively from 2015 (n = 77) to 2020 (n = 204). For patients with a Code Grey, the median count of events was 3 (range 1-33). Independent predictors of at least one ICU Code Grey event included male sex (OR 2.5; 95% CI 1.8 to 3.4), young age (most elevated odds ratio in patients 20-30 years), admission from the emergency department (OR 2.8, 95% CI 2.1 to 3.6) and a trauma diagnosis (OR 1.4, 95% CI 1.1 to 1.9). Code Grey patients had longer admissions with a reduced risk of death. Conclusions: The prevalence of Code Grey events in ICU appears to be increasing. Patients may have repeated events. Younger male patients admitted to ICU via the emergency department with a trauma or medical diagnosis are at greatest risk of a Code Grey event.

A Clinical Score for Quantifying Edema in Mechanically Ventilated Children With Congenital Heart Disease in Intensive Care.

Standardized clinical measurements of edema do not exist. OBJECTIVES: To describe a 19-point clinical edema score (CES), investigate its interobserver agreement, and compare changes between such CES and body weight. DESIGN SETTING AND PARTICIPANTS: Prospective observational study in a tertiary PICU of mechanically ventilated children with congenital heart disease. MAIN OUTCOMES AND MEASURES: Differences in the median CES between observer groups. RESULTS: We studied 61 children, with a median age of 8.0 days (interquartile range, 1.0-14.0 d). A total of 539 CES were performed by three observer groups (medical 1 [reference], medical 2, and bedside nurse) at 0, 24, and 48 hours from enrollment. Overall, there was close agreement between observer groups in mean, median, and upper quartile of CES scores, with least agreement observed in the lower quartile of scores. Across all quartiles of CES, after adjusting for baseline weight, cardiac surgical risk, duration of cardiopulmonary bypass, or peritoneal dialysis during the study, observer groups returned similar mean scores (medical 2: 25th centile +0.1 [95% CI, -0.2 to 0.5], median +0.6 [95% CI, -0.4 to 1.5], 75th centile +0.1 [95% CI, -1.1 to 1.4] and nurse: 25th centile +0.5 [95% CI, 0.0-0.9], median +0.7 [95% CI, 0.0-1.5], 75th centile -0.2 [95% CI, -1.3 to 1.0]) Within a multivariable mixed-effects linear regression model, including adjustment for baseline CES, each 1 point increase in CES was associated with a 12.1 grams (95% CI, 3.2-21 grams) increase in body weight. CONCLUSIONS AND RELEVANCE: In mechanically ventilated children with congenital heart disease, three groups of observers tended to agree when assessing overall edema using an ordinal clinical score assessed in six body regions, with agreement least at low edema scores. An increase in CES was associated with an increase in body weight, suggesting some validity for quantifying edema. Further exploration of the CES as a rapid clinical tool is indicated.

Beta-hydroxy-beta-methylbutyrate supplementation and functional outcomes in multitrauma patients: A pilot randomized controlled trial.

BACKGROUND: Beta-hydroxy-beta-methylbutyrate (HMB) is a nutrition supplement that may attenuate muscle wasting from critical illness. This trial aimed to determine feasibility of administering a blinded nutrition supplement in the intensive care unit (ICU) and continuing it after ICU discharge. METHODS: Single-center, parallel-group, blinded, placebo-controlled, randomized feasibility trial. After traumatic injury necessitating admission to ICU, participants were randomized to receive an enteral study supplement of 3 g of HMB (intervention) or placebo daily for 28 days or until hospital discharge. Primary outcome was feasibility of administering the study supplement, quantified as protocol adherence. Secondary outcomes included change in quadriceps muscle thickness, measured weekly until day 28 or hospital discharge by using ultrasound and analyzed by using a linear mixed model. RESULTS: Fifty randomized participants (intervention, n = 26; placebo, n = 24) showed comparable baseline characteristics. Participants received 862 (84.3%) of the 1022 prescribed supplements during hospitalization with 543 (62.8%) delivered via an enteral feeding tube. The median (IQR) number of study supplements successfully administered per participant was 19.5 (13.0-24.0) in the intervention group and 16.5 (8.5-23.5) in the placebo group. Marked loss of quadriceps muscle thickness occurred in both groups, with the point estimate favoring attenuated muscle loss with the intervention, albeit with wide CIs (mean intervention difference after 28 days, 0.26 cm [95% CI, -0.13 to 0.64]). CONCLUSION: A blinded, placebo-controlled, randomized clinical trial of daily enteral HMB supplementation for up to 28 days in hospital is feasible. Any effect of HMB supplementation to attenuate muscle wasting after traumatic injury remains uncertain.

Continuous Renal Replacement Therapy during Extracorporeal Membrane Oxygenation: Circuit Haemodynamics and Circuit Failure.

INTRODUCTION: Treatment with continuous renal replacement therapy (CRRT) is common during extracorporeal membrane oxygenation (ECMO). Such ECMO-CRRT has specific technical characteristics, which may affect circuit life. Accordingly, we studied CRRT haemodynamics and circuit life during ECMO. METHODS: ECMO and non-ECMO-CRRT treatments in two adult intensive care units were compared using data collected over a 3-year period. A potential predictor of circuit survival identified in a 60% training data subset as a time-varying covariate within a Cox proportional hazard model was subsequently assessed in the complementary remaining data (40%). RESULTS: Median [interquartile range] CRRT circuit life was greater when associated with ECMO (28.8 [14.0-65.2] vs. 20.2 [9.8-40.2] h, p < 0.0001). Access, return, prefilter, and effluent pressures were also greater during ECMO. Higher ECMO flows were associated with higher access and return pressures. Classification and regression tree analysis identified an association between high access pressures and accelerated circuit failure, while both first access pressures ≥190 mm Hg (HR 1.58 [1.09-2.30]) and patient weight (HR 1.85 [1.15-2.97] third tertile vs. first tertile) were independently associated with circuit failure in a multivariable Cox model. Access dysfunction was associated with a stepwise increase in transfilter pressure, suggesting a potential mechanism of membrane injury. CONCLUSION: CRRT circuits used in conjunction with ECMO have a longer circuit life than usual CRRT despite exposure to higher circuit pressures. Markedly elevated access pressures, however, may predict early CRRT circuit failure during ECMO, possibly via progressive membrane thrombosis as evidenced by increased transfilter pressure gradients.

A pilot study of agreement between noninvasive thermometers and the core temperature of postoperative cardiothoracic surgical patients.

OBJECTIVE: Reliable and accurate temperature assessment is fundamental for clinical monitoring; noninvasive thermometers of various designs are widely used in intensive care units, sometimes without a specific assessment of their suitability and interchangeability. This study evaluated agreement of four noninvasive thermometers with a pulmonary artery catheter temperature. METHODS: This prospective method comparison study was conducted in an Australian adult intensive care unit. One hundred postoperative adult cardiothoracic surgery patients who had a pulmonary artery catheter (Edwards Lifescience) in situ were identified. The temperature reading from the pulmonary artery catheter was compared to contemporaneous measurements returned by four different thermometers-temporal Artery (TA, Technimed), Per Axilla (Axilla, Welch Allyn), Tympanic (Tymp, Covidien), and the NexTemp® (NEXT, Medical Indicators [used per axilla]). The time required to obtain each noninvasive temperature measurement was recorded. RESULTS: Agreements between each noninvasive temperature and the pulmonary artery catheter standard were assessed using summary statistics and the Bland-Altman method comparison approach. A clinically acceptable maximum difference from the standard was defined as ±0.5 °C. Temperature agreement with the pulmonary artery standard (mean difference °C [95% limits of agreement °C]) was greatest for Tymp (-0.20 [-0.92 to 0.52]), intermediate for AXILLA (-0.37 [-1.3 to 0.59]) and NEXT (-0.71 [-1.7 to 0.27]), and least for TA (-0.60 [-2.0 to 0.81]). The proportion of measurements within ±0.5 °C of the standard were TYMP (81%), AXILLA (63%), TA (45%), and NEXT (30%). The time to obtain measurements varied, with the Tymp and TA estimates immediate, the AXILLA a mean of 40 s (standard deviation = 11 s), while NEXT results were at the manufacturer-recommended 3-min point. CONCLUSIONS: Tympanic thermometers showed closest agreement with the pulmonary artery standard. Deviations by more than 0.5 °C from that standard were relatively common with all noninvasive devices.

Early Active Mobilization during Mechanical Ventilation in the ICU.

BACKGROUND: Intensive care unit (ICU)-acquired weakness often develops in patients who are undergoing invasive mechanical ventilation. Early active mobilization may mitigate ICU-acquired weakness, increase survival, and reduce disability. METHODS: We randomly assigned 750 adult patients in the ICU who were undergoing invasive mechanical ventilation to receive increased early mobilization (sedation minimization and daily physiotherapy) or usual care (the level of mobilization that was normally provided in each ICU). The primary outcome was the number of days that the patients were alive and out of the hospital at 180 days after randomization. RESULTS: The median number of days that patients were alive and out of the hospital was 143 (interquartile range, 21 to 161) in the early-mobilization group and 145 days (interquartile range, 51 to 164) in the usual-care group (absolute difference, -2.0 days; 95% confidence interval [CI], -10 to 6; P = 0.62). The mean (±SD) daily duration of active mobilization was 20.8±14.6 minutes and 8.8±9.0 minutes in the two groups, respectively (difference, 12.0 minutes per day; 95% CI, 10.4 to 13.6). A total of 77% of the patients in both groups were able to stand by a median interval of 3 days and 5 days, respectively (difference, -2 days; 95% CI, -3.4 to -0.6). By day 180, death had occurred in 22.5% of the patients in the early-mobilization group and in 19.5% of those in the usual-care group (odds ratio, 1.15; 95% CI, 0.81 to 1.65). Among survivors, quality of life, activities of daily living, disability, cognitive function, and psychological function were similar in the two groups. Serious adverse events were reported in 7 patients in the early-mobilization group and in 1 patient in the usual-care group. Adverse events that were potentially due to mobilization (arrhythmias, altered blood pressure, and desaturation) were reported in 34 of 371 patients (9.2%) in the early-mobilization group and in 15 of 370 patients (4.1%) in the usual-care group (P = 0.005). CONCLUSIONS: Among adults undergoing mechanical ventilation in the ICU, an increase in early active mobilization did not result in a significantly greater number of days that patients were alive and out of the hospital than did the usual level of mobilization in the ICU. The intervention was associated with increased adverse events. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; TEAM ClinicalTrials.gov number, NCT03133377.).

Circuit haemodynamics during non-citrate and regional citrate continuous renal replacement, and impact of blood flow on filter life.

BACKGROUND: During continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA), blood flow (Qb) might affect vascular access dysfunction (AD) and, thereby, circuit life. METHODS: Circuit life and circuit haemodynamics were studied in three intensive care units (ICUs) by analysing hemofilter device data (Prismaflex®, Baxter, Chicago, IL). The three sites shared similar RCA protocols but differed in Qb (120-130 vs 150-200 mL/h). Non-RCA circuits were compared with RCA circuits in which the impact of Qb was also assessed. RESULTS: About 3,981,906 min of circuit pressures were analysed in 2568 circuits in 567 patients. High-Qb RCA was associated with more extreme pressures, and greater AD (IRR 3.7 (1.93-7.08) as well as reduced filter life 21.1 (10.2-42.6) vs 27.0 (14.8-41.6) h). AD in high-Qb RCA circuits was associated with a 49% reduction in filter life, versus 24% reduction in low-Qb RCA, associated with a rise in the rate of increase in transfilter pressure. CONCLUSIONS: High-Qb RCA-CRRT was associated with greater access dysfunction, earlier filter loss and increased haemodynamic impacts of access dysfunction, suggesting low-Qb RCA-CRRT may improve circuit mechanics, function and longevity.

ß-Hydroxy-ß-methylbutyrate (HMB) supplementation and functional outcomes in multi-trauma patients: a study protocol for a pilot randomised clinical trial (BOOST trial).

BACKGROUND: There are no therapies proven to diminish the muscle wasting that occurs in patients after major trauma who are admitted to the intensive care unit (ICU). ß-Hydroxy-ß-methylbutyrate (HMB) is a nutrition intervention that may attenuate muscle loss and, thereby, improve recovery. The primary aim of this study is to determine the feasibility of a blinded randomised clinical trial of HMB supplementation to patients after major trauma who are admitted to the ICU. Secondary aims are to establish estimates for the impact of HMB when compared to placebo on muscle mass and nutrition-related patient outcomes. METHODS: This prospective, single-centre, blinded, randomised, placebo-controlled, parallel-group, feasibility trial with allocation concealment will recruit 50 participants over 18 months. After informed consent, participants will be randomised [1:1] to receive either the intervention (three grams of HMB dissolved in either 150 ml of orange juice for those allowed oral intake or 150 ml of water for those being enterally fed) or placebo (150 ml of orange juice for those allowed oral intake or 150 ml of water for those being enterally fed). The intervention will be commenced in ICU, continued after ICU discharge and ceased at hospital discharge or day 28 post randomisation, whichever occurs first. The primary outcome is the feasibility of administering the intervention. Secondary outcomes include change in muscle thickness using ultrasound and other nutritional and patient-centred outcomes. DISCUSSION: This study aims to determine the feasibility of administering HMB to critically ill multi-trauma patients throughout ICU admission until hospital discharge. Results will inform design of a larger randomised clinical trial. TRIAL REGISTRATION: The protocol is registered with Australian New Zealand Clinical Trials Registry (ANZCTR) ANZCTR: 12620001305910 . UTN: U1111-1259-5534.

Communication with bereaved family members after death in the ICU: the CATHARTIC randomised clinical trial.

Objective: It is uncertain whether psychological distress in the family members of patients who die during an intensive care unit (ICU) admission may be improved by bereavement interventions. In this trial, relatives' symptoms of anxiety and depression after 6 months were measured when allocated to three commonly used bereavement follow-up strategies. Design: Single-centre, randomised, three parallel-group trial. Setting: A tertiary ICU in Australia. Participants: Relatives of patients who died in the ICU. Interventions: Relatives received bereavement follow-up 4 weeks after the death using a condolence letter, short telephone call or no contact. Main outcome measures: The primary outcome was the total Hospital Anxiety and Depression Scale (HADS-T) score. Secondary outcomes estimated anxiety, depression, complicated grief, post-traumatic stress, and satisfaction with ICU care. Results: Seventy-one relatives participated (24 had no contact, 19 were contacted by letter and 28 by telephone 4 weeks after the death). The mean HADS-T score for no contact was 16.1 (95% CI, 12.4-19.8). Receipt of a letter was associated with a mean HADS-T increase of 1.4 (4.0 decrease to 6.8 increase), and a condolence call was accompanied by a mean decrease of 1.6 (6.6 decrease to 3.4 increase; P > 0.5). Non-significant differences were observed for all secondary outcomes. Conclusions: Anxiety and depression at 6 months in the relatives of patients who died in the ICU was not meaningfully alleviated by receipt of either a condolence letter or telephone call. Trial registration: Australia New Zealand Clinical Trials Registry (ACTRN12619000917134).

The relationship between commencement of continuous renal replacement therapy and urine output, fluid balance, mean arterial pressure and vasopressor dose.

Background and objectives: The effect of initiating continuous renal replacement therapy (CRRT) on urine output, fluid balance and mean arterial pressure (MAP) in adult intensive care unit (ICU) patients is unclear. We aimed to evaluate the impact of CRRT on urine output, MAP, vasopressor requirements and fluid balance, and to identify factors affecting urine output during CRRT. Design: Retrospective cohort study using data from existing databases and CRRT machines. Setting: Medical and surgical ICUs at a single university-associated centre. Participants: Patients undergoing CRRT between 2015 and 2018. Main outcome measures: Hourly urine output, fluid balance, MAP and vasopressor dose 24 hours before and after CRRT commencement. Missing values were estimated via Kaplan smoothing univariate time-series imputation. Mixed linear modelling was performed with noradrenaline equivalent dose and urine output as outcomes. Results: In 215 patients, CRRT initiation was associated with a reduction in urine output. Multivariate analysis confirmed an immediate urine output decrease (-0.092 mL/kg/h; 95% confidence interval [CI], -0.150 to -0.034 mL/kg/h) and subsequent progressive urine output decline (effect estimate, -0.01 mL/kg/h; 95% CI, -0.02 to -0.01 mL/kg/h). Age and greater vasopressor dose were associated with lower post-CRRT urine output. Higher MAP and lower rates of net ultrafiltration were associated with higher post-CRRT urine output. With MAP unchanged, vasopressor dose increased in the 24 hours before CRRT, then plateaued and declined in the 24 hours thereafter (effect estimate, -0.004 µg/kg/ min per hour; 95% CI, -0.005 to -0.004 µg/kg/min per hour). Fluid balance remained positive but declined towards neutrality following CRRT implementation. Conclusions: CRRT was associated with decreased urine output despite a gradual decline in vasopressor and a positive fluid balance. The mechanisms behind the reduction in urine output associated with commencement of CRRT requires further investigation.

Common microbial isolates in an adult intensive care unit before and after its relocation and expansion.

Objective: To describe the prevalence of common and clinically relevant microbial isolates before and after the migration of a 24-bed, open plan, adult intensive care unit (ICU) to a new extended design of 32 single rooms, supporting an expanded clinical oncology casemix while continuing all existing clinical services. Design: Retrospective, observational descriptive analysis covering the period 5 May 2014 to 4 May 2018 - the 2 years before and after the ICU relocation on 5 May 2016. Setting: A university-associated, tertiary teaching hospital and state trauma centre in Victoria, Australia. Patients: Adult ICU patients. Main outcome measures: Bacterial isolate frequency and incident rate ratios (IRRs) during the study period. Results: When compared with the old ICU, the incidence rates per 1000 occupied bed-days in the new ICU were lower for bacterial isolates overall (IRR, 0.88; 95% CI, 0.83-0.93), for coagulase-negative staphylococci (IRR, 0.64; 95% CI, 0.55-0.75) and for vancomycin-resistant enterococci (IRR, 0.50; 95% CI, 0.32-0.80). The incidence rates per 1000 occupied bed-days between ICU locations were unchanged for Staphylococcus aureus (IRR, 1.1; 95% CI, 0.91-1.3), extended-spectrum beta-lactamase-producing organisms (IRR, 1.4; 95% CI, 0.78-2.6) and carbapenemase-producing Enterobacterales (IRR, 0.85; 95% CI, 0.11-6.4). Conclusion: Within the limits of a before-after design and clinically directed sampling, relocation to a new ICU with single rooms and a growing oncological patient casemix was accompanied by no overall change in the apparent prevalence of the nosocomial pathogens S. aureus, extended-spectrum beta-lactamase-producing organisms or carbapenemase-producing Enterobacterales. These finding suggest that advanced physical infrastructure, including patient accommodation in single rooms, may play a role in overall safe delivery of critical care.

Study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-ll (HAS FLAIR-II) trial.

Background: Fluid bolus therapy with 20% albumin may shorten the duration of vasopressor therapy in patients after cardiac surgery. Objective: To describe the study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-II (HAS FLAIR-II) trial. Design, setting, participants and intervention: HAS FLAIR-II is a phase 2b, multicentre, parallel group, openlabel, randomised controlled trial that will be conducted at six Australian intensive care units. Patients requiring fluid bolus therapy after cardiac surgery will be randomly assigned in a 1:1 ratio to the intervention of fluid bolus therapy with 20% albumin or a comparator of fluid bolus therapy with a crystalloid solution. Main outcome measures: The primary outcome measure is the cumulative duration of vasopressor therapy. Secondary outcomes include vasopressor use, service utilisation, and mortality. All analyses will be conducted on an intention-to-treat basis. Results and conclusion: The study protocol and statistical analysis plan will guide the conduct and analysis of the HAS FLAIR-II trial, such that analytical and reporting biases are minimised. Trial registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN No. 12620000137998).

Intensive care unit trainee perception of end-of-life care provided during medical emergency team activation events.

BACKGROUND: Hospital medical emergency team (MET) activation events involving end-of-life care (EOLC) are common. The issues faced by medical staff attending these events are incompletely described. AIMS: The purpose of this study was to measure the perceptions of Victorian hospital medical staff, training in the speciality of intensive care, about multiple aspects of EOLC MET calls. We sought to determine the overall extent of formal training in MET and EOLC and assess the domains of self-perceived confidence, barriers to communication, frequency of clinician agreement and trainee distress. METHODS: We conducted an anonymous, voluntary, Internet-based survey of registered trainees of the College of Intensive Care Medicine of Australia and New Zealand in May 2019. The participants eligible were those trainees working in an adult intensive care unit in Victoria, Australia, during the study period. The main outcome measures were self-reported levels of confidence, barriers to communication, frequency of conflict and distress, senior support, supervision and access to training. RESULTS: Of 124 trainees surveyed, 75 (60%) responded. Overall, 78% of respondents felt confident to manage EOLC MET calls, but the frequently reported barriers to effective patient/next of kin communication included: (i) lack of private meeting rooms; (ii) resource and time constraints; and (iii) lack of patient and family availability during a MET call to discuss medical treatment limitations. Two-thirds of respondents reported emotional distress at least occasionally, this being frequent in one in five. Most (68%) trainees experienced conflict with other medical teams at least occasionally. Factors associated with experiencing distress at least occasionally include greater trainee age, patients' being unable to participate in discussion due to illness, resource and time constraints and negative encounters with other medical teams. CONCLUSIONS: Victorian intensive care trainees were confident managing EOLC MET activation events. However, distress was reported commonly and strategies are required to address the areas of concern.

Low Blood Flow Continuous Veno-Venous Haemodialysis Compared with Higher Blood Flow Continuous Veno-Venous Haemodiafiltration: Effect on Alarm Rates, Filter Life, and Azotaemic Control.

TITLE: Low blood flow continuous veno-venous haemodialysis (CVVHD) compared with higher blood flow continuous veno-venous haemodiafiltration (CVVHDF): effect on alarm rates, filter life, and azotaemic control. INTRODUCTION: Continuous renal replacement therapy (CRRT) can be delivered via convective, diffusive, or mixed approaches. Higher blood flows have been advocated for convective clearance efficiency and promotion of filter life. It is unclear whether a lower blood flow predominantly diffusive approach may benefit filter life and alarm rates. MATERIALS AND METHODS: Sequential cohort study of 284 patients undergoing 874 CRRT circuits from January 2015 to August 2018 in a single university-associated tertiary referral hospital in Australia. Patients underwent a protocol of either CVVHDF at blood flow 200-250 mL/min or CVVHD at blood flow 100-130 mL/min. Machine and patient data were analysed. Outcomes of azotaemic control, filter life, and warning alarm rates were log transformed and analysed with mixed linear modelling with patient as a random effect. RESULTS: Both groups had similar azotaemic control (effect estimate on log creatinine CVVHD vs. CVVHDF 1.04 [0.87-1.25], p = 0.68) and median filter life (CVVHDF 16.8 [8.4-90.5] h and CVVHD 16.4 [9.4-82.3] h, p = 0.97). However, circuit pressures were less extreme with a narrower distribution during CVVHD. Multivariate analysis showed CVVHD had a reduced risk of warning alarms (incidence risk ratio [IRR] 0.51 [0.38-0.70]) and femoral access placement also had a reduced risk of alarms (IRR 0.55 [0.41-0.73]). CONCLUSION: Low blood flow CVVHD and femoral vascular access reduce alarms while maintaining azotaemic control and circuit patency thus minimizing bedside clinician workload.