A Multicenter Trial of Vena Cava Filters in Severely Injured Patients.

BACKGROUND: Whether early placement of an inferior vena cava filter reduces the risk of pulmonary embolism or death in severely injured patients who have a contraindication to prophylactic anticoagulation is not known. METHODS: In this multicenter, randomized, controlled trial, we assigned 240 severely injured patients (Injury Severity Score >15 [scores range from 0 to 75, with higher scores indicating more severe injury]) who had a contraindication to anticoagulant agents to have a vena cava filter placed within the first 72 hours after admission for the injury or to have no filter placed. The primary end point was a composite of symptomatic pulmonary embolism or death from any cause at 90 days after enrollment; a secondary end point was symptomatic pulmonary embolism between day 8 and day 90 in the subgroup of patients who survived at least 7 days and did not receive prophylactic anticoagulation within 7 days after injury. All patients underwent ultrasonography of the legs at 2 weeks; patients also underwent mandatory computed tomographic pulmonary angiography when prespecified criteria were met. RESULTS: The median age of the patients was 39 years, and the median Injury Severity Score was 27. Early placement of a vena cava filter did not result in a significantly lower incidence of symptomatic pulmonary embolism or death than no placement of a filter (13.9% in the vena cava filter group and 14.4% in the control group; hazard ratio, 0.99; 95% confidence interval [CI], 0.51 to 1.94; P = 0.98). Among the 46 patients in the vena cava filter group and the 34 patients in the control group who did not receive prophylactic anticoagulation within 7 days after injury, pulmonary embolism developed in none of those in the vena cava filter group and in 5 (14.7%) in the control group, including 1 patient who died (relative risk of pulmonary embolism, 0; 95% CI, 0.00 to 0.55). An entrapped thrombus was found in the filter in 6 patients. CONCLUSIONS: Early prophylactic placement of a vena cava filter after major trauma did not result in a lower incidence of symptomatic pulmonary embolism or death at 90 days than no placement of a filter. (Funded by the Medical Research Foundation of Royal Perth Hospital and others; Australian New Zealand Clinical Trials Registry number, ACTRN12614000963628.).

Intensive care doctors and nurses personal preferences for Intensive Care, as compared to the general population: a discrete choice experiment.

BACKGROUND: To test the hypothesis that Intensive Care Unit (ICU) doctors and nurses differ in their personal preferences for treatment from the general population, and whether doctors and nurses make different choices when thinking about themselves, as compared to when they are treating a patient. METHODS: Cross sectional, observational study conducted in 13 ICUs in Australia in 2017 using a discrete choice experiment survey. Respondents completed a series of choice sets, based on hypothetical situations which varied in the severity or likelihood of: death, cognitive impairment, need for prolonged treatment, need for assistance with care or requiring residential care. RESULTS: A total of 980 ICU staff (233 doctors and 747 nurses) participated in the study. ICU staff place the highest value on avoiding ending up in a dependent state. The ICU staff were more likely to choose to discontinue therapy when the prognosis was worse, compared with the general population. There was consensus between ICU staff personal views and the treatment pathway likely to be followed in 69% of the choices considered by nurses and 70% of those faced by doctors. In 27% (1614/5945 responses) of the nurses and 23% of the doctors (435/1870 responses), they felt that aggressive treatment would be continued for the hypothetical patient but they would not want that for themselves. CONCLUSION: The likelihood of returning to independence (or not requiring care assistance) was reported as the most important factor for ICU staff (and the general population) in deciding whether to receive ongoing treatments. Goals of care discussions should focus on this, over likelihood of survival.

The needs of patients with post-intensive care syndrome: A prospective, observational study.

BACKGROUND: The needs of critical illness survivors and how best to address these are unclear. OBJECTIVES: The objective of this study was to identify critical illness survivors who had developed post-intensive care syndrome and to explore their use of community healthcare resources, the socioeconomic impact of their illness, and their self-reported unmet healthcare needs. METHODS: Patients from two intensive care units (ICUs) in Western Australia who were mechanically ventilated for 5 days or more and/or had a prolonged ICU admission were included in this prospective, observational study. Questionnaires were used to assess participants' baseline health and function before admission, which were then repeated at 1 and 3 months after ICU discharge. RESULTS: Fifty participants were enrolled. Mean Functional Activities Questionnaire scores increased from 1.8 out of 30 at baseline (95% confidence interval [CI]: 0-3.5) to 8.9 at 1 month after ICU discharge (95% CI: 6.5-11.4; P = <0.001) and 7.0 at 3 months after ICU discharge (95% CI: 4.9-9.1; P = < 0.001). Scores indicating functional dependence increased from 8% at baseline to 54% and 33% at 1 and 3 months after ICU discharge, respectively. Statistically significant declines in health-related quality of life were identified in the domains of Mobility, Personal Care, Usual Activities, and Pain/Discomfort at 1 month after ICU discharge and in Mobility, Personal Care, Usual Activities, and Anxiety/Depression at 3 months after ICU discharge. An increase in healthcare service use was identified after ICU discharge. Participants primarily identified mental health services as the service that they felt they would benefit from but were not accessing. Very low rates of return to work were observed, with 35% of respondents at 3 months, indicating they were experiencing financial difficulty as a result of their critical illness. CONCLUSIONS: Study participants developed impairments consistent with post-intensive care syndrome, with associated negative socioeconomic ramifications, and identified mental health as an area they need more support in.

Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: a multicenter, randomized, placebo controlled trial (the MIDAS trial).

BACKGROUND: Patients admitted to intensive care units (ICU) are often treated with intravenous (IV) vasopressors. Persistent hypotension and dependence on IV vasopressors in otherwise resuscitated patients lead to delay in discharge from ICU. Midodrine is an oral alpha-1 adrenergic agonist approved for treatment of symptomatic orthostatic hypotension. This trial aims to evaluate whether oral administration of midodrine is an effective adjunct to standard therapy to reduce the duration of IV vasopressor treatment, and allow earlier discharge from ICU and hospital. METHODS: The MIDAS trial is an international, multicenter, randomized, double-blind, placebo-controlled clinical trial being conducted in the USA and Australia. We are targeting 120 patients. Adult patients admitted to the ICU who are resuscitated and otherwise stable on low dose IV vasopressors for at least 24 h will be considered for recruitment. Participants will be randomized to receive midodrine (20 mg) or placebo three times a day, in addition to standard care. The primary outcome is time (hours) from initiation of midodrine or placebo to discontinuation of IV vasopressors. Secondary outcomes include time (hours) from ICU admission to discharge readiness, ICU length of stay (LOS) (days), hospital LOS (days), rates of ICU readmission, and rates of adverse events related to midodrine administration. DISCUSSION: Midodrine is approved by the Food and Drug Administration (FDA) for the treatment of symptomatic orthostatic hypotension. In August 2010, FDA proposed to withdraw approval of midodrine because of lack of studies that verify the clinical benefit of the drug. We obtained Investigational New Drug (IND 113,330) approval to study its effects in critically ill patients who require IV vasopressors but are otherwise ready for discharge from the ICU. A pilot observational study in a cohort of surgical ICU patients showed that the rate of decline in vasopressor requirements increased after initiation of midodrine treatment. We hypothesize that midodrine administration is effective to wean IV vasopressors and shorten ICU and hospital LOS. This trial may have significant implications on lowering costs of hospital care and obtaining FDA approval for new indications for midodrine. TRIAL REGISTRATION: This study has been registered at clinicaltrials.gov on 02/09/2012 (NCT01531959).

Intravenous vitamin C for vasoplegia: A double-blinded randomised clinical trial (VALENCIA trial).

PURPOSE: To determine whether intravenous vitamin C compared with placebo, reduces vasopressor requirements in patients with vasoplegic shock. METHODS: Double-blinded, randomised clinical trial (RCT) conducted in two intensive care units in Perth, Australia. Vasopressor requirements at enrolment needed to be >10 µg/min noradrenaline after hypovolaemia was clinically excluded. Patients received either intravenous 1.5 g sodium ascorbate in 100 ml normal saline every 6 h for 5 days, or placebo (100 ml normal saline). The primary outcome was duration of vasopressor usage in hours. Secondary outcomes were ICU and hospital length of stay, and 28-day, ICU and hospital mortality. RESULTS: Of the 71 patients randomised (35 vitamin C, 36 placebo group), the median vasopressor duration was 44 h [95% CI, 37-54 h] and 55 h [95% CI, 33-66 h]) in the vitamin C and placebo groups (p = 0.057). ICU and hospital length of stay, mortality outcomes were similar between groups. CONCLUSIONS: In this RCT of patients with vasoplegic shock of at least moderate severity, the use of IV vitamin C compared with placebo did not significantly reduce the duration of vasopressors. TRIAL REGISTRATION: Prospective registration - trial number ACTRN12617001392358.

Oral midodrine does not expedite liberation from protracted vasopressor infusions: A case-control study.

Vasopressor dependence is a common problem affecting patients in the recovery phase of critical illness, often necessitating intensive care unit (ICU) admission and other interventions which carry associated risks. Midodrine is an orally administered vasopressor which is commonly used off-label to expedite weaning from vasopressor infusions and facilitate discharge from ICU. We performed a single-centre, case-control study to assess whether midodrine accelerated liberation from vasopressor infusions in patients who were vasopressor dependent. Cases were identified at the discretion of treating intensivists and received 20 mg oral midodrine every eight h from enrolment. Controls received placebo. Data on duration and dose of vasopressor infusion, haemodynamics and adverse events were collected. Between 2012 and 2019, 42 controls and 19 cases were recruited. Cases had received vasopressor infusions for a median of 94 h versus 29.3 h for controls, indicating prolonged vasopressor dependence amongst cases. Midodrine use in cases was not associated with faster weaning of intravenous (IV) vasopressors (26 h versus 24 h for controls, P = 0.51), ICU or hospital length of stay after adjustment for confounders. Midodrine did not affect mean heart rate but was associated with bradycardia. This case-control study demonstrates that midodrine has limited efficacy in expediting weaning from vasopressor infusions in patients who have already received relatively prolonged courses of these infusions.

Integrating the Choosing Wisely 5 Questions into Family Meetings in the Intensive Care Unit: A Randomized Controlled Trial Investigating the Effect on Family Perceived Involvement in Decision-Making.

Family members often act as surrogate decision makers for patients in the intensive care unit (ICU). The use of printed prompts may assist with families feeling empowered to fulfill this role. Prospective, randomized controlled trial in 3 ICUs in Western Australia. In the intervention arm, families received the Choosing Wisely 5 questions as printed prompts prior to a family meeting, and the control arm did not receive prompts. The primary outcome was family perceived involvement in decision-making. Outcomes were measured using a survey. Sixty families participated in the study. The majority of families (87.1% control, 79.3% intervention; P = .334) reported feeling "very included" in decision-making. There was no difference in secondary outcomes, including minimal uptake of the questions by the intervention arm. This has been the first randomized trial evaluating the use of a decision-making tool for families in the ICU. Despite ceiling effects in outcome measures, these results suggest room for future study of the Choosing Wisely 5 questions in the ICU.

A Prospective Evaluation of Grip Strength Comparing a Low-Tech Method to Dynanometry in Preoperative Surgical Patients and Weak Intensive Care Patients.

Objective: Grip strength testing offers a mechanism to identify patients in whom frailty might be present, discriminate between robust elderly and vulnerable younger patients, and can be used as a tool to track changes in muscle bulk over the course of an inpatient stay. We compared gold-standard quantitative grip strength measurement to a low-tech alternative, a manual bedside sphygmomanometer. Design: Under supervision, subjects performed hand-grip strength testing with each instrument. A mean score is calculated from three measurements on the dominant and nondominant hand. Setting. Testing was performed in a tertiary centre in Perth, Western Australia, in both outpatient clinics and intensive care units. Participants. 51 adult pre-operative surgical outpatients were assessed, alongside 20 intensive care inpatients identified as being weak. Main outcome measures. A statistical correlation between the two measures was evaluated. Feasibility, safety, and convenience were also assessed in outpatient and bedside settings. Results: Highly correlated results in both tertiary surgical outpatients (r s = 0.895, p ≤ 0.001, N = 102; r (100) = 0.899, p ≤ 0.001) and weak intensive care patients (r s = 0.933, p ≤ 0.001, N = 39 r (37) = 0.935, p ≤ 0.001). Conclusions: Modifying a manual bedside sphygmomanometer to measure grip strength is feasible and correlates well with a formal dynamometer in preadmission surgical patients and weak patients in the intensive care unit. The use of an existing, safe, and available device removes barriers to the measurement of weakness in patients and may encourage uptake of objective measurement in multiple settings.

Incidence and determinants of malpositioning tracheostomy tubes in critically ill adult patients.

Tracheostomy tubes are chosen primarily based on their internal diameter; however, the length of the tube may also be important. We performed a prospective clinical audit of 30 critically ill patients following tracheostomy to identify the type of tracheostomy tube inserted, the incidence of malpositioning and the factors associated with the need to change the tracheostomy tube subsequently. Anthropometric neck measurements, distance between the skin and tracheal rings and the position of the tracheostomy cuff relative to the tracheal stoma were recorded and analysed. Malpositioning of the tracheostomy tube was noted in 20%, with a high riding cuff being the most common cause of malpositioning, resulting in an audible leak and a need to change the tracheostomy tube subsequently. A high riding cuff was more common when a small tracheostomy tube (e.g. Portex (Smiths Medical Australasia, Macquarie Park, NSW) ≤8.0 mm internal diameter with length <7.5 cm) was used, with risk further increased when the patient's skin to trachea depth was greater than 0.8 cm. Identifying a high riding cuff relative to the tracheal stoma confirmed by a translaryngeal bronchoscopy strongly predicted the risk of air leak and the need to change the tracheostomy tube subsequently. Our study suggests that when a small (and short) tracheostomy tube is planned for use, intraoperative translaryngeal bronchoscopy is warranted to exclude malpositioning of the tracheostomy tube with a high riding cuff.

Muscle Growth and Anabolism in Intensive Care Survivors (GAINS) trial: a pilot randomised controlled trial.

BACKGROUND: To explore the feasibility, safety, and potential benefits of administration of the anabolic steroid nandrolone to patients in the recovery phase from critical illness weakness. METHODS: In this phase II, double blind, randomized, controlled trial, adult critically ill patients admitted to one of two tertiary Intensive Care Units in Western Australia for longer than 7 days with significant weakness were enrolled. Patients received nandrolone (200 mg males, 100 mg females) intramuscularly or placebo weekly for up to 3 weeks in addition to standard care. The primary outcome measures were improvement in grip strength, Medical Research Council muscle strength sum score, and functional activity level (Chelsea critical care assessment tool [CPAx]). RESULTS: A total of 22 patients was enrolled between September 2017 and May 2019. No significant adverse events were detected. Median grip strength change was non-significantly greater in the nandrolone group (8.5 vs. 13.0, P=0.185), while hospital length of stay (36 vs. 26 days, P=0.023) and duration of mechanical ventilation (377 vs. 168, P=0.032) were lower. The discharge CPAx and intensive care unit mobility scores were higher in the nandrolone group, although there was no difference in the change in CPAx score (17.0 vs. 17.7, P=0.865). There were no changes in ultrasound-detected muscle thickness between the two groups. CONCLUSIONS: In patients with prolonged critical illness, nandrolone appears to be safe. However, a larger study, potentially combined with resistance exercise, is needed to definitively address the potential benefits of nandrolone.

A multicentre observational study of the use of antiseizure medication in patients with aneurysmal subarachnoid haemorrhage in the PROMOTE-SAH study.

Our objective was to describe antiseizure medication (ASM) prescription patterns, and associations between ASM use and death and disability outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to ICU. This was a multi-centre prospective observational study. The study took place in eleven ICUs across Australia and New Zealand. Data was collected from 1 April 2017 to 1 October 2018. Three hundred and fifty-seven adult patients with aSAH were enrolled. The primary outcome was to describe patterns of ASM prescription. The secondary outcome of interest was death or disability (modified Rankin Scale (mRS) score ≥ 4) at six months, and its association with ASM therapy, and relevant clinical subgroups. Forty percent of patients received an ASM and the most commonly used agent was levetiracetam. The median length of ASM administration was eight days (IQR 4.5-12.5). A number of patients with prehospital seizures did not receive ASM therapy (14/55, 2725%). There was a tendency towards ASM prescription with both higher radiological and clinical grade aSAH. There was no significant association between death or disability at six month (mRS ≥ 4) and ASM vs No ASM prescription. Testing for an interaction effect between ASM administration and WFNS grade suggested inferior outcomes with ASM use in lower aSAH grades (p = 0.04). In conclusion, the prescription of ASM for aSAH in Australia is variable across and within sites, with the majority of patients not receiving ASM chemoprophylaxis. We demonstrated no significant association between death or disability at six months and the use of ASM. There may be an association with poorer outcomes in patients with lower grade aSAH. This finding requires further exploration.

Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial.

PURPOSE: Delirium is common in the critically ill, highly distressing to patients and families and associated with increased morbidity and mortality. Results of studies on preventative use of melatonin in various patient groups have produced mixed results. The aim of this study was to determine whether administration of melatonin decreases the prevalence of delirium in critically ill patients. METHODS: Multicentre, randomized, placebo-controlled, double-blind trial across 12 Australian ICUs recruiting patients from July 2016 to September 2019. Patients of at least 18 years requiring ICU admission with an expected length of stay (LOS) greater than 72 h; enrolled within 48 h of ICU admission. Indistinguishable liquid melatonin (4 mg; n = 419) or placebo (n = 422) was administered enterally at 21:00 h for 14 consecutive nights or until ICU discharge. The primary outcome was the proportion of delirium-free assessments, as a marker of delirium prevalence, within 14 days or before ICU discharge. Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU) score. Secondary outcomes included sleep quality and quantity, hospital and ICU LOS, and hospital and 90-day mortality. RESULTS: A total of 847 patients were randomized into the study with 841 included in data analysis. Baseline characteristics of the participants were similar. There was no significant difference in the average proportion of delirium-free assessments per patient between the melatonin and placebo groups (79.2 vs 80% respectively, p = 0.547). There was no significant difference in any secondary outcomes including ICU LOS (median: 5 vs 5 days, p = 0.135), hospital LOS (median: 14 vs 12 days, p = 0816), mortality at any time point including at 90 days (15.5 vs 15.6% p = 0.948), nor in the quantity or quality of sleep. There were no serious adverse events reported in either group. CONCLUSION: Enteral melatonin initiated within 48 h of ICU admission did not reduce the prevalence of delirium compared to placebo. These findings do not support the routine early use of melatonin in the critically ill.

Associations Between Nutrition Markers and Muscle Mass on Bioimpedance Analysis in Patients Receiving Parenteral Nutrition.

BACKGROUND: Parenteral nutrition (PN) is used for malnourished patients and those intolerant of enteral nutrition. This pilot study assessed repeatability of bioimpedance analysis (BIA) in critically ill patients and association with nutrition markers and patients' length of hospital stay. METHODS: Twenty-two patients receiving PN, after major surgery or during critical illness, were enrolled and underwent serial BIA and Subjective Global Assessment (SGA) by a dietitian. Repeatability of BIA was assessed by repeating BIA measurements within 10 minutes in 18 of the 22 study patients (82%). RESULTS: All BIA parameters were repeatable with strong intraclass correlation coefficients (>0.78). Phase angle (PhA), reflective of muscle mass, was significantly associated with serum albumin (R2 = 0.198, P < .001), total lymphocyte count (R2 = 0.083, P = .018), and body mass index (R2 = 0.084, P = .015). Of the 48 SGAs performed, 4 were considered severely malnourished, and all were associated with low PhA (<5°) compared with only 53% and 33% for those considered to be moderately malnourished and well nourished, respectively (χ2 test: P = .042). Low PhA was significantly associated with an increased length of hospital stay compared with those without low PhA (median 36 vs 16 days, respectively; P < .001). CONCLUSION: BIA is repeatable in critically ill patients receiving PN. Low PhA was prevalent for those judged as severely malnourished and was associated with reduced total lymphocyte count and serum albumin and prolonged length of hospital stay compared with those with a higher PhA.

Airway pressure release ventilation in mechanically ventilated patients with COVID-19: a multicenter observational study.

BACKGROUND: Evidence prior to the coronavirus disease 2019 (COVID-19) pandemic suggested that, compared with conventional ventilation strategies, airway pressure release ventilation (APRV) can improve oxygenation and reduce mortality in patients with acute respiratory distress syndrome. We aimed to assess the association between APRV use and clinical outcomes among adult patients receiving mechanical ventilation for COVID-19 and hypothesized that APRV use would be associated with improved survival compared with conventional ventilation. METHODS: A total of 25 patients with COVID-19 pneumonitis was admitted to intensive care units (ICUs) for invasive ventilation in Perth, Western Australia, between February and May 2020. Eleven of these patients received APRV. The primary outcome was survival to day 90. Secondary outcomes were ventilation-free survival days to day 90, mechanical complications from ventilation, and number of days ventilated. RESULTS: Patients who received APRV had a lower probability of survival than did those on other forms of ventilation (hazard ratio, 0.17; 95% confidence interval, 0.03-0.89; P=0.036). This finding was independent of indices of severity of illness to predict the use of APRV. Patients who received APRV also had fewer ventilator-free survival days up to 90 days after initiation of ventilation compared to patients who did not receive APRV, and survivors who received APRV had fewer ventilator-free days than survivors who received other forms of ventilation. There were no differences in mechanical complications according to mode of ventilation. CONCLUSIONS: Based on the findings of this study, we urge caution with the use of APRV in COVID-19.

Statistical analysis plan for the Prophylactic Melatonin for Delirium in Intensive Care (ProMEDIC): a randomised controlled trial.

RATIONALE: Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium. METHODS AND DESIGN: The 'Prophylactic Melatonin for Delirium in Intensive Care' study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium. RESULTS: This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications. DISCUSSION: The SAP details the analyses that will be done to avoid bias coming from knowledge of the results in advance. This trial will determine whether prophylactic melatonin administered to intensive care unit patients helps decrease the rate and the severity of delirium. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry (ANZCTR) ACTRN1261600043647 , registration date: 06 April 2016. WHO Trial Number - U1111-1175-1814.

Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: the randomised, placebo-controlled, restoration of gut microflora in critical illness trial (ROCIT).

PURPOSE: In adults requiring treatment in an intensive care unit, probiotic therapy using Lactobacillus plantarum 299v may reduce nosocomial infection. The aim of this study was to determine whether early and sustained L. plantarum 299v therapy administered to adult ICU patients increased days alive and at home. METHODS: A multicentre, parallel group, placebo-controlled, randomised clinical trial was conducted. Adult patients within 48 h of intensive care admission and expected to require intensive care beyond the day after recruitment were eligible to participate. L plantarum 299v or placebo were administered immediately after enrolment and continued for 60 days. The primary outcome was days alive and out of hospital to Day 60 (DAOH60). Secondary outcomes included nosocomial infections. RESULTS: The median [interquartile range (IQR)] number of DAOH60 in the probiotic (n = 110) and placebo group (n = 108) was 49.5 (IQR 37.0-53.0) and 49.0 (IQR 43.8-53.0) respectively, between-group difference of 0.0 [95% confidence interval (CI) - 6.10 to 7.1, P = 0.55]. Nosocomial infection occurred in 8 (7.3%) and 5 (4.6%) of the probiotic and placebo group participants, respectively, odds ratio 1.62 (95% CI 0.51-5.10), P = 0.57. There were no serious, or probiotic-associated adverse events. CONCLUSION: Early and sustained untargeted administration of probiotic therapy with Lactobacillus plantarum 299v to adult patients admitted to the ICU is safe, but not associated with improved patient outcomes.

Clinically Significant Pleural Effusion in Intensive Care: A Prospective Multicenter Cohort Study.

OBJECTIVES: The prevalence and optimal management of clinically significant pleural effusion, confirmed by thoracic ultrasound, in the critically ill is unknown. This study aimed to determine: 1) the prevalence, characteristics, and outcomes of patients treated in intensive care with clinically significant effusion and 2) the comparative efficacy and safety of pleural drainage or expectant medical management. DESIGN: A prospective multicenter cohort study. SETTING: ICUs in four teaching hospitals in Western Australia. PATIENTS: Consecutive patients with clinically significant pleural effusions (depth ≥ 2 cm on thoracic ultrasound with clinician-determined adverse effects on patient progress). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was the change in Pao2:Fio2 (mm Hg) ratio from baseline to 24 hours. Changes in diagnosis and treatment based on pleural fluid analysis and pleural effusion related serious adverse events between those who underwent either drainage within 24 hours or expectant management were compared. Of the 7,342 patients screened, 226 patients (3.1%) with 300 pleural effusions were enrolled. Early drainage of pleural effusion occurred in 76 patients (34%) and significantly improved oxygenation (Pao2:Fio2 ratio 203 at baseline vs 263 at 24 hr, +29.6% increment; p < 0.01). This was not observed in the other 150 patients who had expectant management (Pao2:Fio2 ratio 250 at baseline vs 268 at 24 hr, +7.2% increment; p = 0.44). The improvement in oxygenation after early drainage remained unchanged after adjustment for a propensity score on the decision to initiate early drainage. Pleural effusion related serious adverse events were not different between the two groups (early drainage 10.5% vs no early drainage 16.0%; p = 0.32). Improvements in diagnosis were noted in 91 initial (nonrepetitive) drainages (76.5% out of 119); treatment strategy was optimized after 80 drainage episodes (59.7% out of 134). CONCLUSIONS: Early drainage of clinically significant pleural effusion was associated with improved oxygenation and diagnostic accuracy without increased complications.

The Healthy Heart-Mind Trial: Randomized Controlled Trial of Melatonin for Prevention of Delirium.

OBJECTIVES: Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery. DESIGN: Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design). SETTING: The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia. PARTICIPANTS: We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery. INTERVENTION: Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery. MEASUREMENTS: The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery. RESULTS: The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] = .78; 95% confidence interval [CI] = .35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = -1.03; P = .304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ2 = .93; P = .334; adjusted OR = 1.98; 95% CI = .40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance. CONCLUSION: The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery. J Am Geriatr Soc 68:112-119, 2019.

Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial.

PURPOSE: ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α1-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement. METHODS: In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates. RESULTS: Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02). CONCLUSION: Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.