Medicine (Austin & Northern Health) - Research Publications
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ItemNo Preview AvailablePro/con debate: Is etomidate safe in hemodynamically unstable critically ill patients?(BMC, 2012)Etomidate is an induction agent known for its smooth intubating conditions and cardiovascular stability. Studies, however, have shown that a single dose of etomidate can result in a prolonged adrenal insufficiency. The impact of this in patients with sepsis has been a matter for debate. This review presents a pro/con case for using etomidate in hemodynamically unstable critically ill patients and provides guidance for alternative induction techniques and when the use of etomidate might be justified despite these concerns.
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ItemLocalization of human breast-carcinoma xenografts using antibodies to carcinoembryonic antigen.(Springer Science and Business Media LLC, 1981-05)Affinity-purified antibodies to carcinoembryonic antigen (CEA) have been injected into immune-suppressed mice bearing xenografts of human breast tumours. It has been shown that the antibodies localized in the tumours but not in normal tissues. The degree of tumour localization correlates with the amount of tumour CEA, and is unaffected by levels of circulating CEA or CEA/anti-CEA immune complexes.
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ItemNo Preview AvailableLong-term quality of life in patients with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation for refractory hypoxaemia(BIOMED CENTRAL LTD, 2012)INTRODUCTION: The purpose of the study was to assess the long term outcome and quality of life of patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia. METHODS: A retrospective observational study with prospective health related quality of life (HRQoL) assessment was conducted in ARDS patients who had ECMO as a rescue therapy for reversible refractory hypoxemia from January 2009 until April 2011 in a tertiary Australian centre. Survival and long-term quality of life assessment, using the Short-Form 36 (SF-36) and the EuroQol health related quality of life questionnaire (EQ5D) were assessed and compared to international data from other research groups. RESULTS: Twenty-one patients (mean age 36.3 years) with ARDS receiving ECMO for refractory hypoxemia were studied. Eighteen (86%) patients were retrieved from external intensive care units (ICUs) by a dedicated ECMO retrieval team. Eleven (55%) had H1N1 influenza A-associated pneumonitis. Eighteen (86%) patients survived to hospital discharge. Of the 18 survivors, ten (56%) were discharged to other hospitals and 8 (44%) were discharged directly home. Sequelae and health related quality of life were evaluated for 15 of the 18 (71%) long-term survivors (assessment at median 8 months). Mean SF-36 scores were significantly lower across all domains compared to age and sex matched Australian norms. Mean SF-36 scores were lower (minimum important difference at least 5 points) than previously described ARDS survivors in the domains of general health, mental health, vitality and social function. One patient had long-term disability as a result of ICU acquired weakness. Only 26% of survivors had returned to previous work levels at the time of follow-up. CONCLUSIONS: This ARDS cohort had a high survival rate (86%) after use of ECMO support for reversible refractory hypoxemia. Long term survivors had similar physical health but decreased mental health, general health, vitality and social function compared to other ARDS survivors and an unexpectedly poor return to work.
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ItemSedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study(SPRINGER, 2013-05)PURPOSE: To ascertain the relationship among early (first 48 h) deep sedation, time to extubation, delirium and long-term mortality. METHODS: We conducted a multicentre prospective longitudinal cohort study in 11 Malaysian hospitals including medical/surgical patients (n = 259) who were sedated and ventilated ≥24 h. Patients were followed from ICU admission up to 28 days in ICU with 4-hourly sedation and daily delirium assessments and 180-day mortality. Deep sedation was defined as Richmond Agitation Sedation Score (RASS) ≤-3. RESULTS: The cohort had a mean (SD) age of 53.1 (15.9) years and APACHE II score of 21.3 (8.2) with hospital and 180-day mortality of 82 (31.7%) and 110/237 (46.4%). Patients were followed for 2,657 ICU days and underwent 13,836 RASS assessments. Midazolam prescription was predominant compared to propofol, given to 241 (93%) versus 72 (28%) patients (P < 0.0001) for 966 (39.6%) versus 183 (7.5%) study days respectively. Deep sedation occurred in (182/257) 71% patients at first assessment and in 159 (61%) patients and 1,658 (59%) of all RASS assessments at 48 h. Multivariable Cox proportional hazard regression analysis adjusting for a priori assigned covariates including sedative agents, diagnosis, age, APACHE II score, operative, elective, vasopressors and dialysis showed that early deep sedation was independently associated with longer time to extubation [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89-0.97, P = 0.003], hospital death (HR 1.11, 95% CI 1.05-1.18, P < 0.001) and 180-day mortality (HR 1.09, 95% CI 1.04-1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44%) of patients. CONCLUSION: Irrespective of sedative choice, early deep sedation was independently associated with delayed extubation and higher mortality, and thus was a potentially modifiable risk in interventional trials.
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ItemNo Preview AvailableHyperlactatemia in critical illness and cardiac surgery(BIOMED CENTRAL LTD, 2010)
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ItemNo Preview AvailableCritical care services and the H1N1 (2009) influenza epidemic in Australia and New Zealand in 2010: the impact of the second winter epidemic(BMC, 2011)INTRODUCTION: During the first winter of exposure, the H1N1 2009 influenza virus placed considerable strain on intensive care unit (ICU) services in Australia and New Zealand (ANZ). We assessed the impact of the H1N1 2009 influenza virus on ICU services during the second (2010) winter, following the implementation of vaccination. METHODS: A prospective, cohort study was conducted in all ANZ ICUs during the southern hemisphere winter of 2010. Data on demographic and clinical characteristics, including vaccination status and outcomes, were collected. The characteristics of patients admitted during the 2010 and 2009 seasons were compared. RESULTS: From 1 June to 15 October 2010, there were 315 patients with confirmed influenza A, of whom 283 patients (90%) had H1N1 2009 (10.6 cases per million inhabitants; 95% confidence interval (CI), 9.4 to 11.9) which was an observed incidence of 33% of that in 2009 (P < 0.001). The maximum daily ICU occupancy was 2.4 beds (95% CI, 1.8 to 3) per million inhabitants in 2010 compared with 7.5 (95% CI, 6.5 to 8.6) in 2009, (P < 0.001). The onset of the epidemic in 2010 was delayed by five weeks compared with 2009. The clinical characteristics were similar in 2010 and 2009 with no difference in the age distribution, proportion of patients treated with mechanical ventilation, duration of ICU admission, or hospital mortality. Unlike 2009 the incidence of critical illness was significantly greater in New Zealand (18.8 cases per million inhabitants compared with 9 in Australia, P < 0.001). Of 170 patients with known vaccination status, 26 (15.3%) had been vaccinated against H1N1 2009. CONCLUSIONS: During the 2010 ANZ winter, the impact of H1N1 2009 on ICU services was still appreciable in Australia and substantial in New Zealand. Vaccination failure occurred.
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ItemNo Preview AvailableProspective meta-analysis using individual patient data in intensive care medicine(SPRINGER, 2010-01)Meta-analysis is a technique for combining evidence from multiple trials. However, meta-analyses of studies with substantial heterogeneity among patients within trials-common in intensive care-can lead to incorrect conclusions if performed using aggregate data. Use of individual patient data (IPD) can avoid this concern, increase the power of a meta-analysis, and is useful for exploring subgroup effects. Barriers exist to IPD meta-analysis, most of which are overcome if clinical trials are designed to prospectively facilitate the incorporation of their results with other trials. We review the features of prospective IPD meta-analysis and identify those of relevance to intensive care research. We identify three clinical questions, which are the subject of recent or planned randomised controlled trials where IPD MA offers advantages over approaches using aggregate data.
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ItemNo Preview AvailableBench-to-bedside review: Avoiding pitfalls in critical care meta-analysis-funnel plots, risk estimates, types of heterogeneity, baseline risk and the ecologic fallacy(BMC, 2008)Meta-analysis can be a powerful tool for demonstrating the applicability of a concept beyond the context of individual clinical trials and observational studies, including exploration of effects across different subgroups. Meta-analysis avoids Simpson's paradox, in which a consistent effect in constituent trials is reversed when results are simply pooled. Meta-analysis in critical care medicine is made more complicated, however, by the heterogeneous nature of critically ill patients and the contexts within which they are treated. Failure to properly adjust for this heterogeneity risks missing important subgroup effects in, for example, the interaction of treatment with varying levels of baseline risk. When subgroups are defined by characteristics that vary within constituent trials (such as age) rather than features constant within each trial (such as drug dose), there is the additional risk of incorrect conclusions due to the ecological fallacy. The present review explains these problems and the strategies by which they are overcome.
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ItemThe microbiological and clinical outcome of guide wire exchanged versus newly inserted antimicrobial surface treated central venous catheters(BIOMED CENTRAL LTD, 2013)INTRODUCTION: The management of suspected central venous catheter (CVC)-related sepsis by guide wire exchange (GWX) is not recommended. However, GWX for new antimicrobial surface treated (AST) triple lumen CVCs has never been studied. We aimed to compare the microbiological outcome of triple lumen AST CVCs inserted by GWX (GWX-CVCs) with newly inserted triple lumen AST CVCs (NI-CVCs). METHODS: We studied a cohort of 145 consecutive patients with GWX-CVCs and contemporaneous site-matched control cohort of 163 patients with NI-CVCs in a tertiary intensive care unit (ICU). RESULTS: GWX-CVC and NI-CVC patients were similar for mean age (58.7 vs. 62.2 years), gender (88 (60.7%) vs. 98 (60.5%) male) and illness severity on admission (mean Acute Physiology and Chronic Health Evaluation (APACHE) III: 71.3 vs. 72.2). However, GWX patients had longer median ICU lengths of stay (12.2 vs. 4.4 days; P < 0.001) and median hospital lengths of stay (30.7 vs. 18.0 days; P < 0.001). There was no significant difference with regard to the number of CVC tips with bacterial or fungal pathogen colonization among GWX-CVCs vs. NI-CVCs (5 (2.5%) vs. 6 (7.4%); P = 0.90). Catheter-associated blood stream infection (CA-BSI) occurred in 2 (1.4%) GWX patients compared with 3 (1.8%) NI-CVC patients (P = 0.75). There was no significant difference in hospital mortality (35 (24.1%) vs. 48 (29.4%); P = 0.29). CONCLUSIONS: GWX-CVCs and NI-CVCs had similar rates of tip colonization at removal, CA-BSI and mortality. If the CVC removed by GWX is colonized, a new CVC must then be inserted at another site. In selected ICU patients at higher central vein puncture risk receiving AST CVCs GWX may be an acceptable initial approach to line insertion.
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ItemGlycaemic control in Australia and New Zealand before and after the NICE-SUGAR trial: a translational study(BMC, 2013)INTRODUCTION: There is no information on the uptake of Intensive Insulin Therapy (IIT) before the Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation (NICE-SUGAR) trial in Australia and New Zealand (ANZ) and on the bi-national response to the trial, yet such data would provide important information on the evolution of ANZ practice in this field. We aimed to study ANZ glycaemic control before and after the publication of the results of the NICE-SUGAR trial. METHODS: We analysed glucose control in critically ill patients across Australia and New Zealand during a two-year period before and after the publication of the NICE-SUGAR study. We used the mean first day glucose (Glu1) (a validated surrogate of ICU glucose control) to define practice. The implementation of an IIT protocol was presumed if the median of Glu₁ measurements was <6.44 mmol/L for a given ICU. Hypoglycaemia was categorised as severe (glucose ≤2.2 mmol/L) or moderate (glucose ≤3.9 mmol/L). RESULTS: We studied 49 ICUs and 176,505 patients. No ICU practiced IIT before or after NICE-SUGAR. Overall, Glu1 increased from 7.96 (2.95) mmol/L to 8.03 (2.92) mmol/L (P <0.0001) after NICE-SUGAR. Similar increases were noted in all patient subgroups studied (surgical, medical, insulin dependent diabetes mellitus, ICU stay >48/<48 hours). The rate of severe and moderate hypoglycaemia before and after NICE-SUGAR study were 0.59% vs. 0.55% (P =0.33) and 6.62% vs. 5.68% (P <0.0001), respectively. Both crude and adjusted mortalities declined over the study period. CONCLUSIONS: IIT had not been adopted in ANZ before the NICE-SUGAR study and glycaemic control corresponded to that delivered in the control arm of NICE-SUGAR trial. There were only minor changes in practice after the trial toward looser glycaemic control. The rate of moderate hypoglycaemia and mortality decreased along with such changes.