A survey of Australian public opinion on using comorbidity to triage intensive care patients in a pandemic.

ObjectivesThis study aimed to determine which method to triage intensive care patients using chronic comorbidity in a pandemic was perceived to be the fairest by the general public. Secondary objectives were to determine whether the public perceived it fair to provide preferential intensive care triage to vulnerable or disadvantaged people, and frontline healthcare workers.MethodsA postal survey of 2000 registered voters randomly selected from the Australian Electoral Commission electoral roll was performed. The main outcome measures were respondents' fairness rating of four hypothetical intensive care triage methods that assess comorbidity (chronic medical conditions, long-term survival, function and frailty); and respondents' fairness rating of providing preferential triage to vulnerable or disadvantaged people, and frontline healthcare workers.ResultsThe proportion of respondents who considered it fair to triage based on chronic medical conditions, long-term survival, function and frailty, was 52.1, 56.1, 65.0 and 62.4%, respectively. The proportion of respondents who considered it unfair to triage based on these four comorbidities was 31.9, 30.9, 23.8 and 23.2%, respectively. More respondents considered it unfair to preferentially triage vulnerable or disadvantaged people, than fair (41.8% versus 21.2%). More respondents considered it fair to preferentially triage frontline healthcare workers, than unfair (44.2% versus 30.0%).ConclusionRespondents in this survey perceived all four hypothetical methods to triage intensive care patients based on comorbidity in a pandemic disaster to be fair. However, the sizable minority who consider this to be unfair indicates that these triage methods could encounter significant opposition if they were to be enacted in health policy.

Selective digestive tract decontamination in critically ill adults with acute brain injuries: a post hoc analysis of a randomized clinical trial.

PURPOSE: The aim of this study was to determine whether selective decontamination of the digestive tract (SDD) reduces in-hospital mortality in mechanically ventilated critically ill adults admitted to the intensive care unit (ICU) with acute brain injuries or conditions. METHODS: We carried out a post hoc analysis from a crossover, cluster randomized clinical trial. ICUs were randomly assigned to adopt or not to adopt a SDD strategy for two alternating 12-month periods, separated by a 3-month inter-period gap. Patients in the SDD group (n = 2791; 968 admitted to the ICU with an acute brain injury) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191; 1093 admitted to the ICU with an acute brain injury) received standard care. The primary outcome was in-hospital mortality within 90 days. There were four secondary clinical outcomes: death in ICU, ventilator-, ICU- and hospital-free days to day 90. RESULTS: Of 2061 patients with acute brain injuries (mean age, 55.8 years; 36.4% women), all completed the trial. In patients with acute brain injuries, there were 313/968 (32.3%) and 415/1093 (38%) in-hospital deaths in the SDD and standard care groups (unadjusted odds ratio [OR], 0.76, 95% confidence interval [CI] 0.63-0.92; p = 0.004). The use of SDD was associated with statistically significant improvements in the four clinical secondary outcomes compared to standard care. There was no significant heterogeneity of treatment effect between patients with and without acute brain injuries (interaction p = 0.22). CONCLUSIONS: In this post hoc analysis of a randomized clinical trial in critically ill patients with acute brain injuries receiving mechanical ventilation, the use of SDD significantly reduced in-hospital mortality in patients compared to standard care without SDD. These findings require confirmation.

Protocol summary and statistical analysis plan for the low oxygen intervention for cardiac arrest injury limitation (LOGICAL) trial.

Background: The effect of conservative vs. liberal oxygen therapy on outcomes of intensive care unit (ICU) patients with hypoxic ischaemic encephalopathy (HIE) is uncertain and will be evaluated in the Low Oxygen Intervention for Cardiac Arrest injury Limitation (LOGICAL) trial. Objective: The objective of this study was to summarise the protocol and statistical analysis plans for the LOGICAL trial. Design setting and participants: LOGICAL is a randomised clinical trial in adults in the ICU who are comatose with suspected HIE (i.e., those who have not obeyed commands following return of spontaneous circulation after a cardiac arrest where there is clinical concern about possible brain damage). The LOGICAL trial will include 1400 participants and is being conducted as a substudy of the Mega Randomised registry trial comparing conservative vs. liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU (Mega-ROX). Main outcome measures: The primary outcome is survival with favourable neurological function at 180 days after randomisation as measured with the Extended Glasgow Outcome Scale (GOS-E). A favourable neurological outcome will be defined as a GOS-E score of lower moderate disability or better (i.e. a GOS-E score of 5-8). Secondary outcomes include survival time, day 180 mortality, duration of invasive mechanical ventilation, ICU length of stay, hospital length of stay, the proportion of patients discharged home, quality of life assessed at day 180 using the EQ-5D-5L, and cognitive function assessed at day 180 using the Montreal Cognitive Assessment (MoCA-blind). Conclusions: The LOGICAL trial will provide reliable data on the impact of conservative vs. liberal oxygen therapy in ICU patients with suspected HIE following resuscitation from a cardiac arrest. Prepublication of the LOGICAL protocol and statistical analysis plan prior to trial conclusion will reduce the potential for outcome-reporting or analysis bias. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12621000518864).

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

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

Remi-fent 1-A pragmatic randomised controlled study to evaluate the feasibility of using remifentanil or fentanyl as sedation adjuncts in mechanically ventilated patients.

Objective: To evaluate the feasibility of conducting a prospective randomised controlled trial (pRCT) comparing remifentanil and fentanyl as adjuncts to sedate mechanically ventilated patients. Design: Single-center, open-labelled, pRCT with blinded analysis. Setting: Australian tertiary intensive care unit (ICU). Participants: Consecutive adults between June 2020 and August 2021 expected to receive invasive ventilation beyond the next day and requiring opioid infusion were included. Exclusion criteria were pregnant/lactating women, intubation >12 h, or study-drug hypersensitivity. Interventions: Open-label fentanyl and remifentanil infusions per existing ICU protocols. Outcomes: Primary outcomes were feasibility of recruiting ≥1 patient/week and >90 % compliance, namely no other opioid infusion used during the study period. Secondary outcomes included complications, ICU-, ventilator- and hospital-free days, and mortality (ICU, hospital). Blinded intention-to-treat analysis was performed concealing the allocation group. Results: 208 patients were enrolled (mean 3.7 patients/week). Compliance was 80.6 %. More patients developed complications with fentanyl than remifentanil: bradycardia (n = 44 versus n = 21; p < 0.001); hypotension (n = 78 versus n = 53; p < 0.01); delirium (n = 28 versus n = 15; p = 0.001). No differences were seen in ICU (24.3 % versus 27.6 %,p = 0.60) and hospital mortalities (26.2 % versus 30.5 %; p = 0.50). Ventilator-free days were higher with remifentanil (p = 0.01). Conclusions: We demonstrated the feasibility of enrolling patients for a pRCT comparing remifentanil and fentanyl as sedation adjuncts in mechanically ventilated patients. We failed to attain the study-opioid compliance target, likely because of patients with complex sedative/analgesic requirements. Secondary outcomes suggest that remifentanil may reduce mechanical ventilation duration and decrease the incidence of complications. An adequately powered multicentric phase 2 study is required to evaluate these results.

Association Between Selective Decontamination of the Digestive Tract and In-Hospital Mortality in Intensive Care Unit Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis.

Importance: The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain. Objective: To determine whether SDD is associated with reduced risk of death in adults receiving mechanical ventilation in intensive care units (ICUs) compared with standard care. Data Sources: The primary search was conducted using MEDLINE, EMBASE, and CENTRAL databases until September 2022. Study Selection: Randomized clinical trials including adults receiving mechanical ventilation in the ICU comparing SDD vs standard care or placebo. Data Extraction and Synthesis: Data extraction and risk of bias assessments were performed in duplicate. The primary analysis was conducted using a bayesian framework. Main Outcomes and Measures: The primary outcome was hospital mortality. Subgroups included SDD with an intravenous agent compared with SDD without an intravenous agent. There were 8 secondary outcomes including the incidence of ventilator-associated pneumonia, ICU-acquired bacteremia, and the incidence of positive cultures of antimicrobial-resistant organisms. Results: There were 32 randomized clinical trials including 24 389 participants in the analysis. The median age of participants in the included studies was 54 years (IQR, 44-60), and the median proportion of female trial participants was 33% (IQR, 25%-38%). Data from 30 trials including 24 034 participants contributed to the primary outcome. The pooled estimated risk ratio (RR) for mortality for SDD compared with standard care was 0.91 (95% credible interval [CrI], 0.82-0.99; I2 = 33.9%; moderate certainty) with a 99.3% posterior probability that SDD reduced hospital mortality. The beneficial association of SDD was evident in trials with an intravenous agent (RR, 0.84 [95% CrI, 0.74-0.94]), but not in trials without an intravenous agent (RR, 1.01 [95% CrI, 0.91-1.11]) (P value for the interaction between subgroups = .02). SDD was associated with reduced risk of ventilator-associated pneumonia (RR, 0.44 [95% CrI, 0.36-0.54]) and ICU-acquired bacteremia (RR, 0.68 [95% CrI, 0.57-0.81]). Available data regarding the incidence of positive cultures of antimicrobial-resistant organisms were not amenable to pooling and were of very low certainty. Conclusions and Relevance: Among adults in the ICU treated with mechanical ventilation, the use of SDD compared with standard care or placebo was associated with lower hospital mortality. Evidence regarding the effect of SDD on antimicrobial resistance was of very low certainty.

Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Whether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain. Objective: To determine whether SDD reduces in-hospital mortality in critically ill adults. Design, Setting, and Participants: A cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021. Interventions: ICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a 3-month interperiod gap. Patients in the SDD group (n = 2791) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191) received standard care. Main Outcomes and Measures: The primary outcome was in-hospital mortality within 90 days. There were 8 secondary outcomes, including the proportion of patients with new positive blood cultures, antibiotic-resistant organisms (AROs), and Clostridioides difficile infections. For the ecological assessment, a noninferiority margin of 2% was prespecified for 3 outcomes including new cultures of AROs. Results: Of 5982 patients (mean age, 58.3 years; 36.8% women) enrolled from 19 ICUs, all patients completed the trial. There were 753/2791 (27.0%) and 928/3191 (29.1%) in-hospital deaths in the SDD and standard care groups, respectively (mean difference, -1.7% [95% CI, -4.8% to 1.3%]; odds ratio, 0.91 [95% CI, 0.82-1.02]; P = .12). Of 8 prespecified secondary outcomes, 6 showed no significant differences. In the SDD vs standard care groups, 23.1% vs 34.6% had new ARO cultures (absolute difference, -11.0%; 95% CI, -14.7% to -7.3%), 5.6% vs 8.1% had new positive blood cultures (absolute difference, -1.95%; 95% CI, -3.5% to -0.4%), and 0.5% vs 0.9% had new C difficile infections (absolute difference, -0.24%; 95% CI, -0.6% to 0.1%). In 8599 patients enrolled in the ecological assessment, use of SDD was not shown to be noninferior with regard to the change in the proportion of patients who developed new AROs (-3.3% vs -1.59%; mean difference, -1.71% [1-sided 97.5% CI, -∞ to 4.31%] and 0.88% vs 0.55%; mean difference, -0.32% [1-sided 97.5% CI, -∞ to 5.47%]) in the first and second periods, respectively. Conclusions and Relevance: Among critically ill patients receiving mechanical ventilation, SDD, compared with standard care without SDD, did not significantly reduce in-hospital mortality. However, the confidence interval around the effect estimate includes a clinically important benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT02389036.

Pain assessment and analgesic management in patients admitted to intensive care: an Australian and New Zealand point prevalence study.

Objective: To describe pain assessment and analgesic management practices in patients in intensive care units (ICUs) in Australia and New Zealand. Design, setting and participants: Prospective, observational, multicentre, single-day point prevalence study conducted in Australian and New Zealand ICUs. Observational data were recorded for all adult patients admitted to an ICU without a neurological, neurosurgical or postoperative cardiac diagnosis. Demographic characteristics and data on pain assessment and analgesic management for a 24-hour period were collected. Main outcome measures: Types of pain assessment tools used and frequency of their use, use of opioid analgesia, use of adjuvant analgesia, and differences in pain assessment and analgesic management between postoperative and non-operative patients. Results: From the 499 patients enrolled from 45 ICUs, pain assessment was performed at least every 4 hours in 56% of patients (277/499), most commonly with a numerical rating scale. Overall, 286 patients (57%) received an opioid on the study day. Of the 181 mechanically ventilated patients, 135 (75%) received an intravenous opioid, with the predominant opioid infusion being fentanyl. The median dose of opioid infusion for ventilated patients was 140 mg oral morphine equivalents. Of the 318 non-ventilated patients, 41 (13%) received patient-controlled analgesia and 76 (24%) received an oral opioid, with the predominant opioid being oxycodone. Paracetamol was administered to 63 ventilated patients (35%) and 164 non-ventilated patients (52%), while 2% of all patients (11/499) received a non-steroidal anti-inflammatory drug. Ketamine infusion and regional analgesia were used in 15 patients (3%) and 17 patients (3%), respectively. Antineuropathic agents (predominantly gabapentinoids) were used in 53 patients (11%). Conclusions: Although a majority of ICU patients were frequently assessed for pain with a validated pain assessment tool, cumulative daily doses of opioids were high, and the use of multimodal adjuvant analgesia was low. Our data on current pain assessment and analgesic management practices may inform further research in this area.

Determinants of long-term unplanned readmission and mortality following self-inflicted and non-self-inflicted major injury: a retrospective cohort study.

PURPOSE: To describe the characteristics of major injury and identify determinants of long-term unplanned readmission and mortality after self-inflicted and non-self-inflicted injury to inform potential readmission screening. METHOD: A retrospective cohort study of 11,269 individuals aged ≥ 15 years hospitalised for a major injury during 2013-2017 in New South Wales, Australia. Unplanned readmission and mortality up to 27-month post-injury were examined. Logistic regression was used to examine predictors of unplanned readmission. RESULTS: During the 27-month follow-up, 2700 (24.8%) individuals with non-self-inflicted and 98 (26.1%) with self-inflicted injuries had an unplanned readmission. Individuals with an anxiety-related disorder and a non-self-inflicted injury who were discharged home were three times more likely (OR: 3.27; 95%CI 2.28-4.69) or if they were discharged to a psychiatric facility were four times more likely (OR: 4.11; 95%CI 1.07-15.80) to be readmitted. Compared to individuals aged 15-24 years, individuals aged ≥ 65 years were 3 times more likely to be readmitted (OR 3.12; 95%CI 2.62-3.70). Individuals with one (OR 1.60; 95%CI 1.39-1.84) or ≥ 2 (OR 1.88; 95%CI 1.52-2.32) comorbidities, or who had a drug-related dependence (OR 1.88; 95%CI 1.52-2.31) were more likely to be readmitted. The post-discharge age-adjusted mortality rate following a self-inflicted injury (35.6%; 95%CI 29.9-41.8) was higher than for individuals with a non-self-inflicted injury (11.0%; 95%CI 10.4-11.8). CONCLUSIONS: Unplanned readmission after injury is associated with injury intent, age, and comorbid health. Screening for anxiety and drug-related dependence after major injury, accompanied by service referrals and post-discharge follow-up, has potential to prevent readmission.

Third generation cephalosporins and piperacillin/tazobactam have distinct impacts on the microbiota of critically ill patients.

Effective implementation of antibiotic stewardship, especially in critical care, is limited by a lack of direct comparative investigations on how different antibiotics impact the microbiota and antibiotic resistance rates. We investigated the impact of two commonly used antibiotics, third-generation cephalosporins (3GC) and piperacillin/tazobactam (TZP) on the endotracheal, perineal and faecal microbiota of intensive care patients in Australia. Patients exposed to either 3GC, TZP, or no ß-lactams (control group) were sampled over time and 16S rRNA amplicon sequencing was performed to examine microbiota diversity and composition. While neither treatment significantly affected diversity, numerous changes to microbiota composition were associated with each treatment. The shifts in microbiota composition associated with 3GC exposure differed from those observed with TZP, consistent with previous reports in animal models. This included a significant increase in Enterobacteriaceae and Enterococcaceae abundance in endotracheal and perineal microbiota for those administered 3GC compared to the control group. Culture-based analyses did not identify any significant changes in the prevalence of specific pathogenic or antibiotic-resistant bacteria. Exposure to clinical antibiotics has previously been linked to reduced microbiota diversity and increased antimicrobial resistance, but our results indicate that these effects may not be immediately apparent after short-term real-world exposures.

Early sedation with dexmedetomidine in ventilated critically ill patients and heterogeneity of treatment effect in the SPICE III randomised controlled trial.

PURPOSE: To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. METHODS: Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. RESULTS: HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. CONCLUSION: In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.

Protocol summary and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) crossover, cluster randomised controlled trial.

Background: It is unclear whether the use of selective decontamination of the digestive tract (SDD) improves outcomes in ventilated patients in intensive care units (ICUs) and whether SDD is associated with the development of antibiotic resistance. Objective: To describe the study protocol and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) trial. Design, setting, participants and intervention: SuDDICU is an international, crossover, cluster randomised controlled trial of mechanically ventilated patients in ICUs using two 12-month trial periods. For each period, participating ICUs will implement SDD plus standard care or standard care alone. The SuDDICU drug intervention is an oral paste and gastric suspension of three antibiotics combined with a 4-day course of intravenous antibiotics. Observational ecological assessments will be conducted during five surveillance periods. The trial will be conducted in 19 ICUs in Australia and ten ICUs in Canada and the United Kingdom, and will recruit 15 000-17 000 patients. Recruitment commenced in Australia in 2017. Main outcome measures: The primary outcome is all-cause hospital mortality. Secondary outcomes include: duration of ventilation, ICU stay and hospital stay; incidence of new antibiotic-resistant organisms during the index ICU admission; changes in antibiotic-resistant organism rates; incidence of new Clostridioides difficile infections; and total use of antibiotics. Results and conclusions: SuDDICU will determine whether the use of SDD plus standard care is associated with a reduction in hospital mortality in ventilated ICU patients compared with standard care alone. It will also quantify the impact of the use of SDD on the development of antibiotic resistance. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12615000411549) and ClinicalTrials.gov (NCT02389036).

Patient Outcomes at Twelve Months after Early Decompressive Craniectomy for Diffuse Traumatic Brain Injury in the Randomized DECRA Clinical Trial.

Functional outcomes at 12 months were a secondary outcome of the randomized DECRA trial of early decompressive craniectomy for severe diffuse traumatic brain injury (TBI) and refractory intracranial hypertension. In the DECRA trial, patients were randomly allocated 1:1 to either early decompressive craniectomy or intensive medical therapies (standard care). We conducted planned secondary analyses of the DECRA trial outcomes at 6 and 12 months, including all 155 patients. We measured functional outcome using the Glasgow Outcome Scale-Extended (GOS-E). We used ordered logistic regression, and dichotomized the GOS-E using logistic regression, to assess outcomes in patients overall and in survivors. We adjusted analyses for injury severity using the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. At 12 months, the odds ratio (OR) for worse functional outcomes in the craniectomy group (OR 1.68; 95% confidence interval [CI]: 0.96-2.93; p = 0.07) was no longer significant. Unfavorable functional outcomes after craniectomy were 11% higher (59% compared with 48%), but were not significantly different from standard care (OR 1.58; 95% CI: 0.84-2.99; p = 0.16). Among survivors after craniectomy, there were fewer good (OR 0.33; 95% CI: 0.12-0.91; p = 0.03) and more vegetative (OR 5.12; 95% CI: 1.04-25.2; p = 0.04) outcomes. Similar outcomes in survivors were found at 6 months after injury. Vegetative (OR 5.85; 95% CI: 1.21-28.30; p = 0.03) and severely disabled outcomes (OR 2.49; 95% CI: 1.21-5.11; p = 0.01) were increased. Twelve months after severe diffuse TBI and early refractory intracranial hypertension, decompressive craniectomy did not improve outcomes and increased vegetative survivors.

Early Sedation with Dexmedetomidine in Critically Ill Patients.

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

The prevalence of perceptions of mismatch between treatment intensity and achievable goals of care in the intensive care unit: a cross-sectional study.

PURPOSE: To describe the prevalence of perceptions of patients receiving a mismatch in treatment intensity, as perceived by intensive care unit (ICU) healthcare providers, and to assess the congruence of perceptions between providers. METHODS: In this cross-sectional, observational study conducted in 21 ICUs in Australia and New Zealand, patient prevalence data was linked to an ICU staff survey to describe the extent to which patient treatment intensity was matched to the perceived prognosis and patient wishes. RESULTS: Of the 307 study patients, 62 (20.2%) were reported to be receiving a mismatch in treatment intensity by at least one ICU healthcare professional. For reported mismatch, there was consensus amongst staff members for 52/62 (84%) of patients. Patients were significantly more likely to receive mismatched treatments if they were more severely unwell (APACHE II score > 20 vs. ≤ 20), odds ratio OR 2.35, 95% confidence interval (CI) 1.63-3.37, p < 0.0001, if they were an emergency admission (OR 3.05, CI 1.18-7.89, p = 0.0212) or if they had an advance care directive (OR 3.68, 95% CI 1.66-8.16, p = 0.0013). CONCLUSIONS: Being more severely unwell, being an emergency admission or having an advance care directive made patients more likely to be perceived as having a mismatch between the intensity of treatments provided and either the achievable goals of care, expected prognosis or patient's wishes.

Survival and predictors of outcome among patients with decompensated liver disease in a non-liver transplant intensive care unit. Pessimism is historical and unjustified.

BACKGROUND: Recent literature emanating from the United Kingdom and United States has reported decreasing mortality rates in patients with decompensated cirrhosis and organ failures presenting to the intensive care unit (ICU). AIM: To determine if there were comparable outcomes in a single-centre non-transplant unit in Australia. METHODS: A retrospective observational study was conducted in a tertiary, non-liver transplant unit in Sydney, Australia. Admission data and mortality outcomes were collected from patients with cirrhosis non-electively admitted to ICU between 2013 and 2017. Liver-specific and general intensive care scoring tools were also assessed for their discriminative ability to predict short-term prognostic outcomes. RESULTS: Sixty-three patients were admitted with decompensated liver disease who fulfilled the inclusion criteria. The overall hospital mortality was 37% (95% CI: 0.26-0.49). There was no difference in survival based on aetiology of liver disease (P = 0.96) but a significant difference was found based on the presenting diagnosis, with greater survival among patients diagnosed with hepatic encephalopathy on ICU admission (P = 0.02). There was 4% mortality in patients with no organ failure and 52% mortality in those with ≥3 organs in failure (P < 0.001). The ICU prognostic Sequential Organ Failure Assessment score was the better discriminative tool in predicting short-term outcomes when compared to liver prognostic scores. CONCLUSION: The outcomes of this single-centre Australian study align with current overseas literature. These results reinforce and expand on limited local evidence, corroborating the former universal prognostic pessimism towards cirrhotic patients with organ failure as unwarranted.

Post-partum catastrophic antiphospholipid syndrome presenting with shock and digital ischaemia - A diagnostic and management challenge.

Catastrophic antiphospholipid syndrome is a rare multisystem autoimmune condition characterised by rapid development of widespread thrombotic disease and subsequent multi-organ failure. It is the most severe complication of antiphospholipid syndrome, carrying significant morbidity and mortality. We report a patient with post-partum catastrophic antiphospholipid syndrome with cardiac, hepatic, renal and cutaneous manifestations. The diagnostic challenges in establishing a definitive diagnosis in catastrophic antiphospholipid syndrome is discussed, along with the difficulties in managing these patients in the intensive care unit.

Communication with Families Regarding Organ and Tissue Donation after Death in Intensive Care (COMFORT): a multicentre before-and-after study.

OBJECTIVE: To implement a best-practice intervention offering deceased organ donation, testing whether it increased family consent rates. DESIGN: A multicentre before-and-after study of a prospective cohort compared with pre-intervention controls. SETTING: Nine Australian intensive care units. PARTICIPANTS: Families and health care professionals caring for donor-eligible patients without registered donation preferences or aged ≤ 16 years. INTERVENTION: A multicomponent intervention including offers of deceased organ donation from specially trained designated requesters using a structured conversation separate to end-of-life discussions. MAIN OUTCOME MEASURE: Proportion of families consenting to organ donation. RESULTS: Consent was obtained in 87/164 cases (53%) during the intervention period compared with 14/25 cases (56%) pre-intervention (P = 0.83). The odds ratio (OR) of obtaining consent during the intervention period relative to preintervention was 1.13 (95% CI, 0.48-2.63; P = 0.78). During the intervention period, designated requesters obtained consent in 55/98 cases (56%), compared with 32/66 cases (48%) in which the medical team managing patient care raised donation (P = 0.34). Factors independently associated with increased consent were: family-raised organ donation (OR, 4.34; 95% CI, 1.79-10.52; P = 0.001), presence of an independent designated requester (OR, 3.84; 95% CI, 1.35- 10.98; P = 0.012), and multiple donation conversations per case (OR, 3.35; 95% CI, 1.93-5.81; P < 0.001). Consent decreased when patients were of non-Christian religion (OR, 0.18; 95% CI, 0.04-0.91; P = 0.038) and end-of-life and donation meetings were separate (OR, 0.38; 95% CI, 0.16-0.89; P = 0.026). CONCLUSION: Implementation of a multicomponent intervention did not increase consent rates for organ donation, although some components of the intervention exerted significant effect. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000815763. ClinicalTrials.gov: NCT01922310.

The comparative effects of 3% saline and 0.5M sodium lactate on cardiac function:a randomised, crossover study in volunteers.

OBJECTIVE: To investigate the metabolic and cardiac effects of intravenous administration of two hypertonic solutions - 3% saline (SAL) and 0.5M sodium lactate (LAC). DESIGN, SETTING AND PARTICIPANTS: A randomised, doubleblind, crossover study in ten human volunteers. Intravenous bolus of either SAL or LAC at 3 mL/kg over 20 min followed by a 2 mL/kg infusion over 60 min. MAIN OUTCOME MEASURES: Acid base parameters and echocardiographic indices of cardiac function, cardiac output (CO), left ventricular ejection fraction (LVEF) and mitral annular peak systolic velocity (Sm) before and after infusion of SAL or LAC. RESULTS: Despite haemodilution, we observed an increase in sodium (139 ± 2 mmol/L to 142 ± 2 mmol/L in both groups) and respective anions, chloride (106 ± 2 mmol/L to 112 ± 3 mmol/L) and lactate (1.01 ± 0.28 mmol/L to 2.38 ± 0.38 mmol/L) with SAL and LAC, respectively. The pH (7.37 ± 0.03 to 7.45 ± 0.03; P < 0.01) and simplified strong ion difference (SID) (36.3 ± 4.6 mmol/L to 39.2 ± 3.6 mmol/L; P < 0.01) increased during the LAC infusion. The pH was unchanged, but SID decreased during SAL infusion (36.3 ± 2.5 mmol/L to 33.9 ± 3.1 mmol/L; P = 0.01). Both solutions led to an increase in preload and cardiac function, CO (4.36 ± 0.79 L/min to 4.98 ± 1.37 L/ min v 4.62 ± 1.30 L/min to 5.13 ± 1.44 L/min), LVEF (61 ± 6% to 63 ± 8% v 64 ± 6% to 68 ± 7%). The averaged Sm improved in the LAC group as compared with the SAL group (0.088 ± 0.008 to 0.096 ± 0.016 v 0.086 ± 0.012 to 0.082 ± 0.012; P = 0.032). CONCLUSIONS: The administration of SAL or LAC has opposing effects on acid base variables such as SID. Hypertonic fluid infusion lead to increased cardiac preload and performance with Sm, suggesting better left ventricular systolic function during LAC as compared with SAL. Lactated hypertonic solutions should be evaluated as resuscitation fluids.