Indigenous Australians critically ill with sepsis: Characteristics, outcomes, and areas for improvement.

BACKGROUND: Aboriginal and Torres Strait Islander Australians have amongst the highest incidence of sepsis globally. OBJECTIVE: The objective of this study was to describe the characteristics, short- and long-term outcomes of non-Indigenous, Aboriginal Australian and Torres Strait Islander Australians admitted with sepsis to an intensive care unit (ICU) to inform healthcare outcome improvement. METHODS: A retrospective cohort study of 500 consecutive sepsis admissions to the Cairns Hospital ICU compared clinical characteristics, short-term (before ICU discharge) and long-term (2000 days posthospital discharge) outcomes. Cohort stratification was done by voluntary disclosure of Indigenous status. RESULTS: Of the 442 individual admissions, 145 (33%) identified as Indigenous Australian. Indigenous and non-Indigenous Australians had similar admission Acute Physiology and Chronic Health Evaluation-3 scores (median [interquartile range]: 70 [52-87] vs. 69 [53-87], P = 0.87), but Indigenous patients were younger (53 [43-60] vs. 62 [52-73] years, P < 0.001) and were more likely to have chronic comorbidities such as type 2 diabetes (58% vs. 23%, P < 0.001), cardiovascular disease (40% vs 28%, P = 0.01), and renal disease (39% vs. 10%, P < 0.001). They also had more hazardous healthcare behaviours such as smoking (61% vs. 45%, P = 0.002) and excess alcohol consumption (40% vs. 18%, P < 0.001). Despite this, the case-fatality rate of Indigenous and non-Indigenous Australians before ICU discharge (13% vs. 12%, P = 0.75) and 2000 days post hospital discharge (25 % vs. 28 %, P = 0.40) was similar. Crucially, however, Indigenous Australians died younger both in the ICU (median [interquartile range] 54 (50-60) vs. 70 [61-76], P < 0.0001) and 2000 days post hospital discharge (58 [53-63] vs. 70 [63-77] years, P < 0.0001). CONCLUSIONS: Although Indigenous Australians critically ill with sepsis have similar short and long-term mortality rates, they present to hospital, die in-hospital, and die post-discharge significantly younger. Unique cohort characteristics may explain these outcomes, and assist clinicians, researchers and policy-makers in targeting interventions to these characteristics to best reduce the burden of sepsis in this cohort and improve their healthcare outcomes.

Trajectories of systolic blood pressure decline in kidney transplant donors prior to circulatory death and delayed graft function.

Background: Kidneys donated after circulatory death suffer a period of functional warm ischaemia before death, which may lead to early ischaemic injury. Effects of haemodynamic trajectories during the agonal phase on delayed graft function (DGF) is unknown. We aimed to predict the risk of DGF using patterns of trajectories of systolic blood pressure (SBP) declines in Maastricht category 3 kidney donors. Methods: We conducted a cohort study of all kidney transplant recipients in Australia who received kidneys from donation after circulatory death donors, divided into a derivation cohort (transplants between 9 April 2014 and 2 January 2018 [462 donors]) and a validation cohort (transplants between 6 January 2018 and 24 December 2019 [324 donors]). Patterns of SBP decline using latent class models were evaluated against the odds of DGF using a two-stage linear mixed effects model. Results: In the derivation cohort, 462 donors were included in the latent class analyses and 379 donors in the mixed effects model. Of the 696 eligible transplant recipients, 380 (54.6%) experienced DGF. Ten different trajectories, with distinct patterns of SBP decline were identified. Compared with recipients from donors with the slowest decline in SBP after withdrawal of cardiorespiratory support, the adjusted odds ratio (aOR) for DGF was 5.5 [95% confidence interval (CI) 1.38-28.0] for recipients from donors with a steeper decline and lowest SBP [mean 49.5 mmHg (standard deviation 12.5)] at the time of withdrawal. For every 1 mmHg/min reduction in the rate of decline of SBP, the respective aORs for DGF were 0.95 (95% CI 0.91-0.99) and 0.98 (95% CI 0.93-1.0) in the random forest and least absolute shrinkage and selection operator models. In the validation cohort, the respective aORs were 0.95 (95% CI 0.91-1.0) and 0.99 (95% CI 0.94-1.0). Conclusion: Trajectories of SBP decline and their determinants are predictive of DGF. These results support a trajectory-based assessment of haemodynamic changes in donors after circulatory death during the agonal phase for donor suitability and post-transplant outcomes.

Locked-in Guillain-Barré syndrome: 'my living nightmare'.

A 48-year-old man with severe Guillain-Barré syndrome suffered complete paralysis, and for 31 days could not communicate with the outside world, while remaining fully conscious. After recovery, he provided feedback on aspects of his care, such as mechanical ventilation, physical therapy, and communication. Conventional low tidal volume normocapnic ventilation induced ongoing and profound dyspnoea, occasionally relieved by modest increases in minute ventilation. Routine and apparently benign physical therapy was extremely painful, which was not reflected in heart rate or blood pressure changes. When he eventually re-established communication after many weeks, via slight eye movements, his first message was to express a particular distressing symptom. His case is a valuable reminder of the sometimes large gap between clinical measurements and assumptions and the subjective patient experience. We propose several approaches to address such issues in other paralysed but conscious patients.

The Applicability of Commonly Used Severity of Illness Scores to Tropical Infections in Australia.

Many patients with leptospirosis, melioidosis, and rickettsial infection require intensive care unit (ICU) admission in tropical Australia every year. The multi-organ dysfunction associated with these infections results in significantly elevated severity of illness (SOI) scores. However, the accuracy of these SOI scores in predicting death from these tropical infections is incompletely defined. This retrospective study was performed at Cairns Hospital, a tertiary-referral hospital in tropical Australia. All patients admitted to ICU with laboratory-confirmed leptospirosis, melioidosis, and rickettsial disease between January 1, 1999 and June 30, 2020, were eligible for the study. The ability of Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Simplified Acute Physiology Scores (SAPS) II, and Sequential Organ Failure Assessment (SOFA) scores to predict death before ICU discharge was evaluated. Overall, 18 (12.1%) of the 149 included patients died: 15/74 (20.3%) with melioidosis, 2/54 (3.7%) with leptospirosis and 1/21 (4.8%) with rickettsial disease. However, the APACHE II, APACHE III, SAPS II, and SOFA scores significantly overestimated the case-fatality rate of all the infections; the disparity between the predicted and observed mortality was most marked in the cases of leptospirosis and rickettsial disease. Commonly used SOI scores significantly overestimate the case-fatality rate of melioidosis, leptospirosis, and rickettsial infections in Australian ICU patients. This may be at least partly explained by the unique pathophysiology of these infections, particularly leptospirosis and rickettsial disease. However, SOI scores may still be useful in facilitating the comparison of disease severity in clinical trials that examine patients with these pathogens.

The 4-Hour Cairns Sepsis Model: A novel approach to predicting sepsis mortality at intensive care unit admission.

BACKGROUND: Sepsis commonly causes intensive care unit (ICU) mortality, yet early identification of adults with sepsis at risk of dying in the ICU remains a challenge. OBJECTIVE: The aim of the study was to derive a mortality prediction model (MPM) to assist ICU clinicians and researchers as a clinical decision support tool for adults with sepsis within 4 h of ICU admission. METHODS: A cohort study was performed using 500 consecutive admissions between 2014 and 2018 to an Australian tertiary ICU, who were aged ≥18 years and had sepsis. A total of 106 independent variables were assessed against ICU episode-of-care mortality. Multivariable backward stepwise logistic regression derived an MPM, which was assessed on discrimination, calibration, fit, sensitivity, specificity, and predictive values and bootstrapped. RESULTS: The average cohort age was 58 years, the Acute Physiology and Chronic Health Evaluation III-j severity score was 72, and the case fatality rate was 12%. The 4-Hour Cairns Sepsis Model (CSM-4) consists of age, history of renal disease, number of vasopressors, Glasgow Coma Scale, lactate, bicarbonate, aspartate aminotransferase, lactate dehydrogenase, albumin, and magnesium with an area under the receiver operating characteristic curve of 0.90 (95% confidence interval = 0.84-0.95, p < 0.00001), a Nagelkerke R2 of 0.51, specificity of 0.94, a negative predictive value of 0.98, and almost identical odds ratios during bootstrapping. The CSM-4 outperformed existing MPMs tested on our data set. The CSM-4 also performed similar to existing MPMs in their derivation papers whilst using fewer, routinely collected, and inexpensive variables. CONCLUSIONS: The CSM-4 is a newly derived MPM for adults with sepsis at ICU admission. It displays excellent discrimination, calibration, fit, specificity, negative predictive value, and bootstrapping values whilst being easy to use and inexpensive. External validation is required.

The Characteristics and Clinical Course of Patients with Scrub Typhus and Queensland Tick Typhus Infection Requiring Intensive Care Unit Admission: A 23-year Case Series from Queensland, Tropical Australia.

Scrub typhus and Queensland tick typhus (QTT)-rickettsial infections endemic to tropical Australia-can cause life-threatening disease. This retrospective study examined the clinical course of all patients with laboratory-confirmed scrub typhus or QTT admitted to the intensive care unit (ICU) of a tertiary referral hospital in tropical Australia between 1997 and 2019. Of the 22 patients, 13 had scrub typhus and nine had QTT. The patients' median (interquartile range [IQR]) age was 50 (38-67) years; 14/22 (64%) had no comorbidity. Patients presented a median (IQR) of seven (5-10) days after symptom onset. Median (IQR) Acute Physiology and Chronic Health Evaluation II scores were 13 (9-17) for scrub typhus and 13 (10-15) for QTT cases (P = 0.61). Following hospital admission, the median (IQR) time to ICU admission was five (2-19) hours. The median (IQR, range) length of ICU stay was 4.4 (2.9-15.9, 0.8-33.8) days. Multi-organ support was required in 11/22 (50%), 5/22 (22%) required only vasopressor support, 2/22 (9%) required only invasive ventilation, and 4/22 (18%) were admitted for monitoring. Patients were ventilated using protective lung strategies, and fluid management was conservative. Standard vasopressors were used, indications for renal replacement therapy were conventional, and blood product usage was restrictive; 9/22 (41%) received corticosteroids. One patient with QTT died, and two (8%) additional patients with QTT developed purpura fulminans requiring digital amputation. Death or permanent disability occurred in 3/9 (33%) QTT and 0/13 scrub typhus cases (P = 0.055). Queensland tick typhus and scrub typhus can cause multi-organ failure requiring ICU care in otherwise well individuals. Queensland tick typhus appears to have a more severe clinical phenotype than previously believed.

Conflicts of interest in the context of end of life care for potential organ donors in Australia.

End-of-life (EOL) care has become an integral part of intensive care medicine and includes the exploration of possibilities for deceased organ and tissue donation. Donation physicians are specialist doctors with expertise in EOL processes encompassing organ and tissue donation, who contribute significantly to improvements in organ and tissue donation services in many countries around the world. Donation physicians are usually also intensive care physicians, and thus they may be faced with the dual obligation of caring for dying patients and their families in the intensive care unit (ICU), whilst at the same time ensuring organ and tissue donation is considered according to best practice. This dual obligation poses specific ethical challenges that need to be carefully understood by clinicians, institutions and health care networks. These obligations are complementary and provide a unique skillset to care for dying patients and their families in the ICU. In this paper we review current controversies around EOL care in the ICU, including the use of palliative analgesia and sedation specifically with regards to withdrawal of cardiorespiratory support, the usefulness of the so-called doctrine of double effect to guide ethical decision-making, and the management of potential or perceived conflicts of interest in the context of dual professional roles.

The applicability of commonly used predictive scoring systems in Indigenous Australians with sepsis: An observational study.

BACKGROUND: Indigenous Australians suffer a disproportionate burden of sepsis, however, the performance of scoring systems that predict mortality in Indigenous patients with critical illness is incompletely defined. MATERIALS AND METHODS: The study was performed at an Australian tertiary-referral hospital between January 2014 and June 2017, and enrolled consecutive Indigenous and non-Indigenous adults admitted to ICU with sepsis. The ability of the ANZROD, APACHE-II, APACHE-III, SAPS-II, SOFA and qSOFA scores to predict death before ICU discharge in the two populations was compared. RESULTS: There were 442 individuals enrolled in the study, 145 (33%) identified as Indigenous. Indigenous patients were younger than non-Indigenous patients (median (interquartile range (IQR) 53 (43-60) versus 65 (52-73) years, p = 0.0001) and comorbidity was more common (118/145 (81%) versus 204/297 (69%), p = 0.005). Comorbidities that were more common in the Indigenous patients included diabetes mellitus (84/145 (58%) versus 67/297 (23%), p<0.0001), renal disease (56/145 (39%) versus 29/297 (10%), p<0.0001) and cardiovascular disease (58/145 (40%) versus 83/297 (28%), p = 0.01). The use of supportive care (including vasopressors, mechanical ventilation and renal replacement therapy) was similar in Indigenous and non-Indigenous patients, and the two populations had an overall case-fatality rate that was comparable (17/145 (12%) and 38/297 (13%) (p = 0.75)), although Indigenous patients died at a younger age (median (IQR): 54 (50-60) versus 70 (61-76) years, p = 0.0001). There was no significant difference in the ability of any the scores to predict mortality in the two populations. CONCLUSIONS: Although the crude case-fatality rates of Indigenous and non-Indigenous Australians admitted to ICU with sepsis is comparable, Indigenous patients die at a much younger age. Despite this, the ability of commonly used scoring systems to predict outcome in Indigenous Australians is similar to that of non-Indigenous Australians, supporting their use in ICUs with a significant Indigenous patient population and in clinical trials that enrol Indigenous Australians.

Acute kidney injury in Indigenous intensive care patients.

BACKGROUND: Patients presenting to intensive care units (ICUs) report high rates of acute kidney injury (AKI) requiring renal replacement therapy (RRT). Globally, Indigenous populations report higher rates of renal disease than their non-Indigenous counterparts. OBJECTIVES: This study reports the prevalence, presenting features, and outcomes of Indigenous ICU admissions with AKI (who require RRT) within an Australian ICU setting and compares these with those of Indigenous patients without AKI. METHOD: A retrospective database review examined all Indigenous patients older than 18 years admitted to a regional Australian ICU between June 2013 and June 2016, excluding patients with chronic kidney disease requiring dialysis. We report patient demography, presenting clinical and physiological characteristics, ICU length of stay, hospital outcome, and renal requirements at three months after discharge, on Indigenous patients with AKI requiring RRT. RESULTS: AKI requiring RRT was identified in 15.9% of ICU Indigenous patients. On univariate analysis, it was found that these patients were older and had a higher body mass index, lower urine output, and higher levels of creatinine and urea upon presentation than patients who did not have AKI. Patients with AKI reported longer ICU stays and a higher mortality rate (30%, p < 0.05), and 10% of these required ongoing RRT at 3 months. Multivariate analysis found significant associations with AKI were only found for presenting urine outputs, urea and creatinine levels. CONCLUSIONS: This study reports higher rates of AKI requiring RRT for Indigenous adults than non-Indigenous adults, as has been previously published. Benefits arising from this study are as follows: these reported findings may initiate early targeted clinical management and can assist managing expectations, as some patients may require ongoing RRT after discharge.

Severe leptospirosis in tropical Australia: Optimising intensive care unit management to reduce mortality.

BACKGROUND: Severe leptospirosis can have a case-fatality rate of over 50%, even with intensive care unit (ICU) support. Multiple strategies-including protective ventilation and early renal replacement therapy (RRT)-have been recommended to improve outcomes. However, management guidelines vary widely around the world and there is no consensus on the optimal approach. METHODOLOGY/PRINCIPAL FINDINGS: All cases of leptospirosis admitted to the ICU of Cairns Hospital in tropical Australia between 1998 and 2018 were retrospectively reviewed. The patients' demographics, presentation, management and clinical course were examined. The 55 patients' median (interquartile range (IQR)) age was 47 (32-62) years and their median (IQR) APACHE III score was 67 (48-105). All 55 received appropriate antibiotic therapy, 45 (82%) within the first 6 hours. Acute kidney injury was present in 48/55 (87%), 18/55 (33%) required RRT, although this was usually not administered until traditional criteria for initiation were met. Moderate to severe acute respiratory distress syndrome developed in 37/55 (67%), 32/55 (58%) had pulmonary haemorrhage, and mechanical ventilation was required in 27/55 (49%). Vasopressor support was necessary in 34/55 (62%). Corticosteroids were prescribed in 20/55 (36%). The median (IQR) fluid balance in the initial three days of ICU care was +1493 (175-3567) ml. Only 2/55 (4%) died, both were elderly men with multiple comorbidities. CONCLUSION: In patients with severe leptospirosis in tropical Australia, prompt ICU support that includes early antibiotics, protective ventilation strategies, conservative fluid resuscitation, traditional thresholds for RRT initiation and corticosteroid therapy is associated with a very low case-fatality rate. Prospective studies are required to establish the relative contributions of each of these interventions to optimal patient outcomes.

The impact of the introduction of a toxicology service on the intensive care unit.

Objective: To examine the impact of a clinical toxicology service on toxicology patients admitted to an intensive care department Methods: The authors performed a retrospective chart audit of all patients presenting to Cairns Emergency Department (ED) over a five-year period from 2011 to 2016 with a toxicology diagnosis requiring Intensive Care Unit (ICU) admission. They were divided into two groups: pre-toxicology (1 April 2011 to 30 September 2012), and post-toxicology service (1 October 2012 to 31 of March 2016) introduction. Patients were identified using ED and ICU databases. Patient charts were manually searched, and data entered on a preformatted data extraction tool. The data were statistically compared pre- versus post-toxicology service introduction using univariate (t-tests and Pearson's Chi Square) and multivariate modelling. Where appropriate, continuous variables were log transformed to enable parametric analyses. Results: There were 37 patients in the pre-toxicology and 102 in the post-toxicology group, with an increased median APACHE III J score in the post toxicology group (39 vs. 49). The introduction of a toxicology service was associated with statistically significant reductions in median ICU length of stay (LOS) (32.9 vs. 20.6 h), median duration of mechanical ventilation (29.1 vs. 20.6 h) and median time to psychiatry review (19.4 vs. 6.7 h). The reduction in ICU LOS remained statistically significant (p = 0.036) when adjusted by sex, age and duration of mechanical ventilation. There was neither increase in mortality, nor readmissions from EDSSU to ICU. Conclusions: This study has demonstrated that the introduction of a toxicology service was associated with a reduction in median ICU LOS, duration of mechanical ventilation and time to psychiatric review in patients with a toxicology diagnosis admitted to our ICU.

Is ED length of stay before ICU admission related to patient mortality?

OBJECTIVE: To describe and identify the relationship between ED length of stay (LOS) and mortality after ICU admission. METHODS: We undertook a retrospective cohort study of records from the Australian and New Zealand Intensive Care Society Adult Patient Database (from 1 January 2000 to 31 December 2006). Data from 45 hospitals and 48 803 ED patients directly transferred to ICU were included. Patients were divided into ED LOS<8 h and ED LOS>or=8 h. Univariate and multivariate analyses were performed. RESULTS: Median ED LOS was 3.9 h (interquartile range 2.0-6.8). Patients transferred within 8 h (80.9%) were younger (P<0.001) and more seriously ill (higher mortality and mechanical ventilation rate) than those transferred>or=8 h. There was no clear relationship between ED LOS and hospital survival for patients admitted directly to ICU (odds ratio=1.01 per hour, 95% confidence intervals 0.99-1.02). CONCLUSION: Although 20% of critically ill patients spend more than 8 h in ED before transfer to ICU, we were unable to demonstrate an adverse relationship between time in ED and hospital mortality.