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.

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.

Sex differences in sepsis hospitalisations and outcomes in older women and men: A prospective cohort study.

PURPOSE: To examine the association of sex with hospitalisation due to sepsis and related outcomes. METHODS: Prospective cohort study of 264,678 adults, average age 62.7 years at recruitment (2006-2009) in Australia. Participants were followed for sepsis hospitalisation identified using the International Classification of Diseases coding. Outcomes included sex differences in the risk of an incident sepsis hospitalisation, mortality, length of ICU and hospital stay and readmissions during the following year. RESULTS: Over 2,070,343 years of follow-up there were 12,912 sepsis hospitalisations, 59.6% in men. Age-standardised risk of hospitalisation was higher in men versus women (10.37 vs 6.77 per 1,000 person years; age-adjusted HR 1.58; 95% CI 1.53-1.59) and did not attenuate after adjusting for sociodemographics, health behaviours and co-morbidities. Relative risks were similar for sepsis-related ICU admissions (adjusted HR 1.72; 95% CI 1.57-1.88). Death at one year was more common in men than women (39.3% vs 33.7% p<0.001). After adjusting for age, men had a longer hospital (12.0 vs 11.2 days; p<0.001) and ICU (6.5 vs 5.8 days; p<0.001) stays and were more likely to be readmitted to hospital for sepsis (22.3 vs 19.4%; p<0.001) or any reason (73.0% vs 70.7%; p<0.001) at one year. CONCLUSION: In older adults, compared to women, men are at an increased risk of sepsis hospitalisation, sepsis-related ICU admission, death and readmission to hospital within one year after a sepsis hospitalisation. Understanding these sex differences and their mechanisms may offer opportunities for better prevention and management and improved patient outcomes.

Long-term costs and cost-effectiveness of adjunctive corticosteroids for patients with septic shock in New Zealand.

OBJECTIVE: The aim of the study was to determine whether adjunctive hydrocortisone reduced healthcare expenditure and was cost-effective compared with placebo in New Zealand patients in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. DESIGN: This is a health economic analysis using data linkage to New Zealand Ministry of Health databases to determine resource use, costs, and cost-effectiveness for a 24-month period. SETTING: The study was conducted in New Zealand. PARTICIPANTS AND INTERVENTION: Patients with septic shock were randomised to receive a 7-day continuous infusion of 200 mg of hydrocortisone or placebo in the ADRENAL trial. MAIN OUTCOME MEASURES: Healthcare expenditure was associated with all hospital admissions, emergency department presentations, outpatient visits, and pharmacy expenditure. Effectiveness outcomes included mortality at 6 months and 24 months and quality of life at 6 months. Cost-effectiveness outcomes were assessed with reference to quality-adjusted life years gained at 6 months and life years gained at 24 months. RESULTS: Of 3800 patients in the ADRENAL trial, 419 (11.0%) were eligible, and 405 (96.7% of those eligible) were included. The mean total costs per patient over 24 months were $143,627 ± 100,890 and $143,772 ± 97,117 for the hydrocortisone and placebo groups, respectively (p = 0.99). Intensive care unit costs for the index admission were $50,492 and $62,288 per patient for the hydrocortisone and placebo groups, respectively (p = 0.09). The mean number of quality-adjusted life years gained at 6 months and mean number of life years gained at 24 months was not significantly different by treatment group, and the probability of hydrocortisone being cost-effective was 55% at 24 months. CONCLUSIONS: In New Zealand, adjunctive hydrocortisone did not reduce total healthcare expenditure or improve outcomes compared with placebo in patients with septic shock.

Incidence and outcomes of sepsis in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales: population-based cohort study.

Objective: To estimate the incidence and outcomes of sepsis hospitalisations in Aboriginal and Torres Strait Islander and non-Indigenous residents of New South Wales. Design and participants: Prospective cohort study of residents aged 45 years and older, recruited between 2006 and 2009, and followed for hospitalisation for sepsis. Main outcome measures: Incidence and hazard ratio (HR) of sepsis hospitalisation and intensive care unit (ICU) admission identified using International Classification of Diseases (10th revision) coding on discharge data. Length of stay, readmission and mortality in those admitted for sepsis. Results: Of 264 678 participants, 1928 (0.7%) identified as Aboriginal and/or Torres Strait Islander. Sepsis hospitalisation was higher in Aboriginal and Torres Strait Islander participants (8.67 v 6.12 per 1000 person-years; age- and sex-adjusted HR, 2.35; 95% CI, 1.98-2.80) but was attenuated after adjusting for sociodemographic factors, health behaviour and comorbidities (adjusted HR, 1.56; 95% CI, 1.31-1.86). Among those hospitalised for sepsis, after adjusting for age and sex, there were no differences between the proportions of Aboriginal and Torres Strait Islander and non-Indigenous participants admitted to an ICU (18.0% v 16.1%; P = 0.42) or deceased at 1 year (36.1% v 36.8%; P = 0.92). Aboriginal and Torres Strait Islander participants had shorter lengths of hospital stay (9.98 v 11.72 days; P < 0.001) and ICU stay (4.38 v 6.35 days; P < 0.001) than non-Indigenous participants. Overall, more than 70% of participants were readmitted to hospital within 1 year. Conclusion: We found that the rate of sepsis hospitalisation in NSW was higher for Aboriginal and Torres Strait Islander adults. Culturally appropriate, community-led strategies targeting chronic disease prevention and the social determinants of health may reduce this gap. Preventing readmission following sepsis is a priority for all Australians.

The cost-effectiveness of adjunctive corticosteroids for patients with septic shock.

OBJECTIVE: To determine whether hydrocortisone is a cost-effective treatment for patients with septic shock. DESIGN: Data linkage-based cost-effectiveness analysis. SETTING: New South Wales and Queensland intensive care units. PARTICIPANTS AND INTERVENTION: Patients with septic shock randomly assigned to treatment with hydrocortisone or placebo in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. MAIN OUTCOME MEASURES: Health-related quality of life at 6 months using the EuroQoL 5-dimension 5-level questionnaire. Data on hospital resource use and costs were obtained by linking the ADRENAL dataset to government administrative health databases. Clinical outcomes included mortality, health-related quality of life, and quality-adjusted life-years gained; economic outcomes included hospital resource use, costs and cost-effectiveness from the health care payer perspective. We also assessed cost-effectiveness by sex. To increase the precision of cost-effectiveness estimates, we conducted unrestricted bootstrapping. RESULTS: Of 3800 patients in the ADRENAL trial, 1772 (46.6%) were eligible and 1513 (85.4% of those eligible) were included. There was no difference between hydrocortisone or placebo groups in regards to mortality (218/742 [29.4%] v 227/759 [29.9%]; HR, 0.93; 95% CI, 0.78-1.12; P = 0.47), mean number of QALYs gained (0.10 ± 0.09 v 0.10 ± 0.09; P = 0.52), or total hospital costs (A$73 515 ± 61 376 v A$69 748 ± 61 793; mean difference, A$3767; 95% CI, -A$2891 to A$10 425; P = 0.27). The incremental cost of hydrocortisone was A$1 254 078 per quality-adjusted life-year gained. In females, hydrocortisone was cost-effective in 46.2% of bootstrapped replications and in males it was cost-effective in 2.7% of bootstrapped replications. CONCLUSIONS: Adjunctive hydrocortisone did not significantly affect longer term mortality, health-related quality of life, health care resource use or costs, and is unlikely to be cost-effective.

Health-related quality of life in survivors of septic shock: 6-month follow-up from the ADRENAL trial.

PURPOSE: To investigate the impact of hydrocortisone treatment and illness severity on health-related quality of life (HRQoL) at 6 months in septic shock survivors from the ADRENAL trial. METHODS: Using the EuroQol questionnaire (EQ-5D-5L) at 6 months after randomization we assessed HRQoL in patient subgroups defined by hydrocortisone or placebo treatment, gender, illness severity (APACHE II < or ≥ 25), and severity of shock (baseline peak catecholamine doses < or ≥ 15 mcg/min). Additionally, in subgroups defined by post-randomisation variables; time to shock reversal (days), treatment with renal replacement therapy (RRT), and presence of bacteremia. RESULTS: At 6 months, there were 2521 survivors. Of these 2151 patients (85.3%-1080 hydrocortisone and 1071 placebo) completed 6-month follow-up. Overall, at 6 months the mean EQ-5D-5L visual analogue scale (VAS) was 70.8, mean utility score 59.4. Between 15% and 30% of patients reported moderate to severe problems in any given HRQoL domain. There were no differences in any EQ-5D-5L domain in patients who received hydrocortisone vs. placebo, nor in the mean VAS (p = 0.6161), or mean utility score (p = 0.7611). In all patients combined, males experienced lower pain levels compared to females [p = 0.0002). Neither higher severity of illness or shock impacted reported HRQoL. In post-randomisation subgroups, longer time to shock reversal was associated with increased problems with mobility (p = < 0.0001]; self-care (p = 0.0.0142), usual activities (p = <0.0001] and pain (p = 0.0384). Amongst those treated with RRT, more patients reported increased problems with mobility (p = 0.0307) and usual activities (p = 0.0048) compared to those not treated. Bacteraemia was not associated with worse HRQoL in any domains of the EQ-5D-5L. CONCLUSIONS: Approximately one fifth of septic shock survivors report moderate to extreme problems in HRQoL domains at 6 months. Hydrocortisone treatment for septic shock was not associated with improved HRQoL at 6 months. Female gender was associated with worse pain at 6 months.

Opinions and practices of blood glucose control in critically ill patients with pre-existing type 2 diabetes in Australian and New Zealand intensive care units.

BACKGROUND: Approximately 9000 patients with type-2 diabetes mellitus (T2DM) are admitted to an intensive care unit (ICU) in Australia and New Zealand annually. For these patients, recent exploratory data suggest that targeting a more liberal blood glucose range during ICU admission may be safe and potentially beneficial. However, the current approach to blood glucose management of patients with T2DM in Australia and New Zealand ICUs is not well described, and there is uncertainty about clinician equipoise for trials of liberal glycaemic control in these patients. AIM: The aim is to describe self-reported blood glucose management in patients with T2DM by intensivists working in Australian and New Zealand ICUs and to establish whether equipoise exists for a trial of liberal versus standard glycaemic control in such patients. METHOD: An online questionnaire of Australia and New Zealand intensivists conducted in July-September 2016. RESULTS: Seventy-one intensivists responded. Forty-five (63%) used a basic nomogram to titrate insulin. Sixty-six (93%) reported that insulin was commenced at blood glucose concentrations >10 mmol/L and titrated to achieve a blood glucose concentration between 6.0 and 10.0 mmol/L. A majority of respondents (75%) indicated that there was insufficient evidence to define optimal blood glucose targets in patients with T2DM, and 59 (83%) were prepared to enrol such patients in a clinical trial to evaluate a more liberal approach. CONCLUSION: A majority of respondents were uncertain about the optimal blood glucose target range for patients with T2DM and would enrol such patients in a comparative trial of conventional versus liberal blood glucose control.

Sepsis incidence and mortality are underestimated in Australian intensive care unit administrative data.

OBJECTIVES: To compare estimates of the incidence and mortality of sepsis and septic shock among patients in Australian intensive care units (ICUs) according to clinical diagnoses or binational intensive care database (ANZICS CORE) methodology. DESIGN, SETTING, PARTICIPANTS: Prospective inception cohort study (3-month inception period, 1 October - 31 December 2016, with 60-day follow-up); daily screening of all patients in a tertiary hospital 60-bed multidisciplinary ICU. MAIN OUTCOMES: Diagnoses of sepsis and septic shock according to clinical criteria and database criteria; in-hospital mortality (censored at 60 days). RESULTS: Of 864 patients admitted to the ICU, 146 (16.9%) were diagnosed with sepsis by clinical criteria and 98 (11%) according to the database definition (P < 0.001); the sensitivity of the database criteria for sepsis was 52%, the specificity 97%. Forty-nine patients (5.7%) were diagnosed with septic shock by clinical criteria and 83 patients (9.6%) with the database definition (P < 0.001); the sensitivity of the database criteria for septic shock was 65%, the specificity 94%. In-hospital mortality of patients diagnosed with sepsis was greater in the clinical diagnosis group (39/146, 27%) than in the database group (17/98, 17%; P = 0.12); for septic shock, mortality was significantly higher in the database group (18/49, 37%) than in the clinical diagnosis group (13/83, 16%; P = 0.006). CONCLUSIONS: When compared with the reference standard - prospective clinical diagnosis - ANZICS CORE database criteria significantly underestimate the incidence of sepsis and overestimate the incidence of septic shock, and also result in lower estimated hospital mortality rates for each condition.

Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial.

IMPORTANCE: Systematic reviews suggest adult patients in intensive care units (ICUs) with relative contraindications to early enteral nutrition (EN) may benefit from parenteral nutrition (PN) provided within 24 hours of ICU admission. OBJECTIVE: To determine whether providing early PN to critically ill adults with relative contraindications to early EN alters outcomes. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, single-blind clinical trial conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zealand. Participants were critically ill adults with relative contraindications to early EN who were expected to remain in the ICU longer than 2 days. INTERVENTIONS: Random allocation to pragmatic standard care or early PN. MAIN OUTCOMES AND MEASURES: Day-60 mortality; quality of life, infections, and body composition. RESULTS: A total of 1372 patients were randomized (686 to standard care, 686 to early PN). Of 682 patients receiving standard care, 199 patients (29.2%) initially commenced EN, 186 patients (27.3%) initially commenced PN, and 278 patients (40.8%) remained unfed. Time to EN or PN in patients receiving standard care was 2.8 days (95% CI, 2.3 to 3.4). Patients receiving early PN commenced PN a mean of 44 minutes after enrollment (95% CI, 36 to 55). Day-60 mortality did not differ significantly (22.8% for standard care vs 21.5% for early PN; risk difference, -1.26%; 95% CI, -6.6 to 4.1; P = .60). Early PN patients rated day-60 quality of life (RAND-36 General Health Status) statistically, but not clinically meaningfully, higher (45.5 for standard care vs 49.8 for early PN; mean difference, 4.3; 95% CI, 0.95 to 7.58; P = .01). Early PN patients required fewer days of invasive ventilation (7.73 vs 7.26 days per 10 patient × ICU days, risk difference, -0.47; 95% CI, -0.82 to -0.11; P = .01) and, based on Subjective Global Assessment, experienced less muscle wasting (0.43 vs 0.27 score increase per week; mean difference, -0.16; 95% CI, -0.28 to -0.038; P = .01) and fat loss (0.44 vs 0.31 score increase per week; mean difference, -0.13; 95% CI, -0.25 to -0.01; P = .04). CONCLUSIONS AND RELEVANCE: The provision of early PN to critically ill adults with relative contraindications to early EN, compared with standard care, did not result in a difference in day-60 mortality. The early PN strategy resulted in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN012605000704695.

A multicenter, randomized controlled trial comparing early nasojejunal with nasogastric nutrition in critical illness.

OBJECTIVE: Current guidelines recommend enteral nutrition in critically ill adults; however, poor gastric motility often prevents nutritional targets being met. We hypothesized that early nasojejunal nutrition would improve the delivery of enteral nutrition. DESIGN: Prospective, randomized, controlled trial. SETTING: Seventeen multidisciplinary, closed, medical/surgical, intensive care units in Australia. PATIENTS: One hundred and eighty-one mechanically ventilated adults who had elevated gastric residual volumes within 72 hrs of intensive care unit admission. INTERVENTIONS: Patients were randomly assigned to receive early nasojejunal nutrition delivered via a spontaneously migrating frictional nasojejunal tube, or to continued nasogastric nutrition. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion of the standardized estimated energy requirement that was delivered as enteral nutrition. Secondary outcomes included incidence of ventilator-associated pneumonia, gastrointestinal hemorrhage, and in-hospital mortality rate. There were 92 patients assigned to early nasojejunal nutrition and 89 to continued nasogastric nutrition. Baseline characteristics were similar. Nasojejunal tube placement into the small bowel was confirmed in 79 (87%) early nasojejunal nutrition patients after a median of 15 (interquartile range 7-32) hrs. The proportion of targeted energy delivered from enteral nutrition was 72% for the early nasojejunal nutrition and 71% for the nasogastric nutrition group (mean difference 1%, 95% confidence interval -3% to 5%, p=.66). Rates of ventilator-associated pneumonia (20% vs. 21%, p=.94), vomiting, witnessed aspiration, diarrhea, and mortality were similar. Minor, but not major, gastrointestinal hemorrhage was more common in the early nasojejunal nutrition group (12 [13%] vs. 3 [3%], p=.02). CONCLUSIONS: In mechanically ventilated patients with mildly elevated gastric residual volumes and already receiving nasogastric nutrition, early nasojejunal nutrition did not increase energy delivery and did not appear to reduce the frequency of pneumonia. The rate of minor gastrointestinal hemorrhage was increased. Routine placement of a nasojejunal tube in such patients is not recommended.

The status of trauma registry systems in Chinese hospitals.

Injuries are a major source of mortality and morbidity in China with approximately 66 million citizens requiring emergency medical care. Trauma registries provide the basis for quality assurance processes and inform the treatment of the injured patient. Against the backdrop of the recently established Chinese National Injury Surveillance System, the feasibility of establishing a multicentre trauma registry in a limited number of hospitals was examined. Seven hospital directors reported on a range of hospital characteristics including patient volume information and the types of patient information routinely collected. The findings indicate significant numbers of patients presenting due to injury, though little comparability in the type of information collected both between hospitals and with international trauma registry systems. The development of multicentre trauma registry is suggested as a way to monitor trauma system performance. The integration of clinical indicators into the National Injury Surveillance System in the long term is also recommended.

Epidemiology and 12-month outcomes from traumatic brain injury in australia and new zealand.

BACKGROUND: An epidemiologic profile of traumatic brain injury (TBI) in Australia and New Zealand was obtained following the publication of international evidence-based guidelines. METHODS: Adult patients with TBI admitted to the intensive care units (ICU) of major trauma centers were studied in a 6-month prospective inception cohort study. Data including mechanisms of injury, prehospital interventions, secondary insults, operative and intensive care management, and outcome assessments 12-months postinjury were collected. RESULTS: There were 635 patients recruited from 16 centers. The mean (+/-SD) age was 41.6 years +/- 19.6 years; 74.2% were men; 61.4% were due to vehicular trauma, 24.9% were falls in elderly patients, and 57.2% had severe TBI (Glasgow Coma Scale score

Advancing intensive care research in Australia and New Zealand: development of the binational ANZIC Research Centre.

Over the past 12 years, the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group and the broader intensive care community in Australia and New Zealand have established a track record for conducting high quality, investigator-initiated clinical research in critically ill patients. This is highlighted by the publication of the SAFE (Saline Albumin Fluid Evaluation) study in the New England Journal of Medicine and the MERIT (Medical Early Response Intervention and Therapy) study in the Lancet. Here, we discuss potential impediments to the further advancement of intensive care research in Australia and New Zealand, and suggest strategies to address them. We propose that there is a need to broaden the current research scope and develop more multifaceted research programs that address clinically important issues. We stress the need to also undertake phase II studies to assess safety, pharmacokinetics and biological plausibility of new and established therapies. In addition, we highlight limitations imposed by the relatively small regional population of Australia and New Zealand, and the need to develop international collaborations to allow trials requiring large sample sizes. We contend that the best chance of improving outcomes in many disease states requires studies to commence before patients enter the ICU, which will depend on collaboration with established and emerging craft groups, such as ambulance services, emergency medicine and anaesthesia. We also emphasise the need to study system factors affecting patient outcomes, as well as the translation of research findings into clinical practice. Finally, we describe the establishment and objectives of the Australian and New Zealand Intensive Care Research Centre (ANZIC-RC) and outline the Centre's current projects in the context of an integrated research framework.

The effectiveness of implementation of the medical emergency team (MET) system and factors associated with use during the MERIT study.

OBJECTIVE: The potential of the medical emergency team (MET) system to reduce adverse events may depend on the effectiveness of its implementation. We aimed to evaluate the effectiveness of the implementation of the MET system during the MERIT (Medical Early Response, Intervention and Therapy) study and to determine factors associated with the level of MET system utilisation. METHODS: Surveys were conducted on the nursing staff from the general adult wards of all 12 MERIT study intervention hospitals after the 4-month implementation period and again after the 6-month study period. Hospital level variables were assessed for their correlation with MET utilisation. We measured awareness and understanding of the MET system, attendance at a MET education session, knowledge of the activation criteria, intention to call the MET, attitude to the MET system and the level of MET utilisation. RESULTS: Across the 12 intervention hospitals, a median of 85.6% (interquartile range, 81.3%-88.8%) of MET activations were not related to a cardiac arrest or death. This measure of MET system utilisation varied significantly across the 12 hospitals (P = 0.002), and was significantly associated with knowledge of the activation criteria (P = 0.048), understanding of the purpose of the MET system (P = 0.01), perceptions of the hospital's readiness for a change in the way care was provided (P = 0.004), and an overall positive attitude to the MET system (P = 0.003). CONCLUSIONS: Measures of the process of implementation of the MET system were significantly associated with the level of MET system utilisation.

The SAFE study: a landmark trial of the safety of albumin in intensive care.

High-quality primary evidence from an Australian and New Zealand study provides a definitive answer.

Appropriateness of red blood cell transfusion in Australasian intensive care practice.

OBJECTIVE: To determine the incidence and appropriateness of use of allogenic packed red blood cell (RBC) transfusion in Australian and New Zealand intensive care practice. SETTING: Intensive care units of 18 Australian and New Zealand hospitals: March 2001. DESIGN: Prospective, observational, multicentre study. METHODS: All admissions to participating intensive care units were screened and all patients who received a transfusion of RBC were enrolled. The indications for transfusion were recorded and compared with Australian National Health and Medical Research Council guidelines. Transfusions conforming to these guidelines were deemed appropriate. MAIN OUTCOME MEASURES: RBC transfusion in intensive care and transfusion appropriateness. RESULTS: 1808 admissions to intensive care units were screened: 357 (19.8%) admissions (350 patients) received an RBC transfusion while in intensive care. Overall, 1464 RBC units were administered in intensive care on 576 transfusion days. The most common indications for transfusion were acute bleeding (60.1%; 880/1464) and diminished physiological reserve (28.9%; 423/1464). The rate of inappropriate transfusion was 3.0% (44/1464). Diminished physiological reserve with haemogloblin level > or = 100 g/L was the indication in 50% (22/44) of inappropriate transfusions; no indication was provided for 31% (15/44). CONCLUSION: The rate of inappropriate transfusion in Australian and New Zealand intensive care units in 2001 was remarkably low.

Life-threatening hyperkalaemia following therapeutic barbiturate coma.

OBJECTIVE: To report the occurrence of life-threatening hyperkalaemia following treatment with therapeutic thiopentone coma. SETTING: The neurosurgical intensive care units of Royal North Shore Hospital and Liverpool Hospital, Sydney, Australia. PATIENTS: Three patients treated with theraputic thiopentone coma. One patient with raised intracranial pressure secondary to a severe traumatic brain injury and two patients with refractory vasospasm secondary to subarachnoid haemorrhage. Two of the three patients developed hypokalaemia on starting thiopentone, which was resistant to potassium supplementation. All three patients developed severe hyperkalaemia during the recovery phase of coma. This was life-threatening in all three patients and fatal in one. CONCLUSIONS: Severe hypokalaemia refractory to potassium therapy may occur during therapeutic thiopentone coma. Severe rebound hyperkalaemia may occur after cessation of thiopentone infusion. Protocols for the management of patients with therapeutic barbiturate coma should recognise this potentially serious complication.