Surgery (Austin & Northern Health) - Research Publications

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    Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?
    Egi, M ; Bellomo, R ; Reade, MC (BMC, 2009)
    Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P < 0.0001) of patients in the control group. If appropriately applied, such protocols should decrease both the mean blood glucose concentration and its variability (variation of blood glucose concentration). Thus, it is logically possible that the benefit of intensive insulin therapy in the first Leuven trial was due to a decrease in mean glucose levels, a decrease in their variability, or both. Several recent studies have confirmed significant associations between variability of blood glucose levels and patient outcomes. Decreasing the variability of blood glucose levels might be an important dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.
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    Effectiveness of the Medical Emergency Team: the importance of dose
    Jones, D ; Bellomo, R ; DeVita, MA (BMC, 2009)
    Up to 17% of hospital admissions are complicated by serious adverse events unrelated to the patients presenting medical condition. Rapid Response Teams (RRTs) review patients during early phase of deterioration to reduce patient morbidity and mortality. However, reports of the efficacy of these teams are varied. The aims of this article were to explore the concept of RRT dose, to assess whether RRT dose improves patient outcomes, and to assess whether there is evidence that inclusion of a physician in the team impacts on the effectiveness of the team. A review of available literature suggested that the method of reporting RRT utilization rate, (RRT dose) is calls per 1,000 admissions. Hospitals with mature RRTs that report improved patient outcome following RRT introduction have a RRT dose between 25.8 and 56.4 calls per 1,000 admissions. Four studies report an association between increasing RRT dose and reduced in-hospital cardiac arrest rates. Another reported that increasing RRT dose reduced in-hospital mortality for surgical but not medical patients. The MERIT study investigators reported a negative relationship between MET-like activity and the incidence of serious adverse events. Fourteen studies reported improved patient outcome in association with the introduction of a RRT, and 13/14 involved a Physician-led MET. These findings suggest that if the RRT is the major method for reviewing serious adverse events, the dose of RRT activation must be sufficient for the frequency and severity of the problem it is intended to treat. If the RRT dose is too low then it is unlikely to improve patient outcomes. Increasing RRT dose appears to be associated with reduction in cardiac arrests. The majority of studies reporting improved patient outcome in association with the introduction of an RRT involve a MET, suggesting that inclusion of a physician in the team is an important determinant of its effectiveness.
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    Guidance in sepsis management: navigating uncharted waters?
    Reade, MC ; Warrillow, SJ ; Myburgh, JA ; Bellomo, R (BMC, 2008)
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    The pursuit of a high central venous oxygen saturation in sepsis: growing concerns
    Bellomo, R ; Reade, MC ; Warrillow, SJ (BMC, 2008)
    In this issue of Critical Care, Dutch investigators report that, in a cohort of patients with sepsis/septic shock admitted to three different intensive care units (ICUs), low central venous oxygen saturation (ScvO2) was uncommon at the time of ICU admission, and hospital mortality was <30%. Their findings, taken together with those of recent reports from Australia and New Zealand (ANZ), raise serious concerns about the utility of early goal directed therapy (EGDT) outside the context of the original trial. Despite inclusion of EGDT into the Surviving Sepsis Guidelines, in response to growing uncertainty, ANZ and US investigators will soon begin randomization of patients into two large multicentre trials comparing EGDT to standard therapy. Until such studies are completed, basing international treatment guidelines on a single centre study performed in what may turn out to be a highly atypical environment would seem premature.
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    Bench-to-bedside review: The evaluation of complex interventions in critical care
    Delaney, A ; Angus, DC ; Bellomo, R ; Cameron, P ; Cooper, DJ ; Finfer, S ; Harrison, DA ; Huang, DT ; Myburgh, JA ; Peake, SL ; Reade, MC ; Webb, SAR ; Yealy, DM (BIOMED CENTRAL LTD, 2008)
    Complex interventions, such as the introduction of medical emergency teams or an early goal-directed therapy protocol, are developed from a number of components that may act both independently and inter-dependently. There is an emerging body of literature advocating the use of integrated complex interventions to optimise the treatment of critically ill patients. As with any other treatment, complex interventions should undergo careful evaluation prior to widespread introduction into clinical practice. During the development of an international collaboration of researchers investigating protocol-based approaches to the resuscitation of patients with severe sepsis, we examined the specific issues related to the evaluation of complex interventions. This review outlines some of these issues. The issues specific to trials of complex interventions that require particular attention include determining an appropriate study population and defining current treatments and outcomes in that population, defining the study intervention and the treatment to be used in the control group, and deploying the intervention in a standardised manner. The context in which the research takes place, including existing staffing levels and existing protocols and procedures, is crucial. We also discuss specific details of trial execution, in particular randomization, blinded outcome adjudication and analysis of the results, which are key to avoiding bias in the design and interpretation of such trials. These aspects of study design impact upon the evaluation of complex interventions in critical care. Clinicians should also consider these specific issues when implementing new complex interventions into their practice.
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    Introduction of a rapid response system: why we are glad we MET
    Jones, D ; Bellomo, R (BIOMED CENTRAL LTD, 2006)
    Hospital patients can experience serious adverse events during their stay. To identify, review and treat these patients and to prevent serious adverse events, we introduced a medical emergency team (MET) service into our hospital in September 2000 following a 1-year period of preparation and education. The introduction of the MET into our institution has been associated with profound changes to cultural and medical practice that have affected the way in which the intensive care unit and the hospital view the roles of junior doctors, nurses, intensive care physicians, and senior doctors. These changes have also been associated with a progressive reduction in the incidence of cardiac arrests of close to 70%. Furthermore, they have allowed improved analysis and characterization of 'at-risk' patients and their needs. Four years later, we remain glad we MET.
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    Bench-to-bedside review: Inotropic drug therapy after adult cardiac surgery - a systematic literature review
    Gillies, M ; Bellomo, R ; Doolan, L ; Buxton, B (BMC, 2005-06)
    Many adult patients require temporary inotropic support after cardiac surgery. We reviewed the literature systematically to establish, present and classify the evidence regarding choice of inotropic drugs. The available evidence, while limited in quality and scope, supports the following observations; although all beta-agonists can increase cardiac output, the best studied beta-agonist and the one with the most favourable side-effect profile appears to be dobutamine. Dobutamine and phosphodiesterase inhibitors (PDIs) are efficacious inotropic drugs for management of the low cardiac output syndrome. Dobutamine is associated with a greater incidence of tachycardia and tachyarrhythmias, whereas PDIs often require the administration of vasoconstrictors. Other catecholamines have no clear advantages over dobutamine. PDIs increase the likelihood of successful weaning from cardiopulmonary bypass as compared with placebo. There is insufficient evidence that inotropic drugs should be selected for their effects on regional perfusion. PDIs also increase flow through arterial grafts, reduce mean pulmonary artery pressure and improve right heart performance in pulmonary hypertension. Insufficient data exist to allow selection of a specific inotropic agent in preference over another in adult cardiac surgery patients. Multicentre randomized controlled trials focusing on clinical rather than physiological outcomes are needed.
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    Acid-base status of critically ill patients with acute renal failure: analysis based on Stewart-Figge methodology
    Rocktaeschel, J ; Morimatsu, H ; Uchino, S ; Goldsmith, D ; Poustie, S ; Story, D ; Gutteridge, G ; Bellomo, R (BMC, 2003-08)
    INTRODUCTION: The aim of the present study is to understand the nature of acid-base disorders in critically ill patients with acute renal failure (ARF) using the biophysical principles described by Stewart and Figge. A retrospective controlled study was carried out in the intensive care unit of a tertiary hospital. MATERIALS AND METHODS: Forty patients with ARF, 40 patients matched for Acute Physiology and Chronic Health Evaluation II score (matched control group), and 60 consecutive critically ill patients without ARF (intensive care unit control group) participated. The study involved the retrieval of biochemical data from computerized records, quantitative biophysical analysis using the Stewart-Figge methodology, and statistical comparison between the three groups. We measured serum sodium, potassium, magnesium, chloride, bicarbonate, phosphate, ionized calcium, albumin, lactate and arterial blood gases. RESULTS: Intensive care unit patients with ARF had a mild acidemia (mean pH 7.30 +/- 0.13) secondary to metabolic acidosis with a mean base excess of -7.5 +/- 7.2 mEq/l. However, one-half of these patients had a normal anion gap. Quantitative acid-base assessment (Stewart-Figge methodology) revealed unique multiple metabolic acid-base processes compared with controls, which contributed to the overall acidosis. The processes included the acidifying effect of high levels of unmeasured anions (13.4 +/- 5.5 mEq/l) and hyperphosphatemia (2.08 +/- 0.92 mEq/l), and the alkalinizing effect of hypoalbuminemia (22.6 +/- 6.3 g/l). CONCLUSIONS: The typical acid-base picture of ARF of critical illness is metabolic acidosis. This acidosis is the result of the balance between the acidifying effect of increased unmeasured anions and hyperphosphatemia and the lesser alkalinizing effect of hypoalbuminemia.
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    Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial
    Reade, MC ; O'Sullivan, K ; Bates, S ; Goldsmith, D ; Ainslie, WRSTJ ; Bellomo, R (BMC, 2009)
    INTRODUCTION: Agitated delirium is common in patients undergoing mechanical ventilation, and is often treated with haloperidol despite concerns about safety and efficacy. Use of conventional sedatives to control agitation can preclude extubation. Dexmedetomidine, a novel sedative and anxiolytic agent, may have particular utility in these patients. We sought to compare the efficacy of haloperidol and dexmedetomidine in facilitating extubation. METHODS: We conducted a randomised, open-label, parallel-groups pilot trial in the medical and surgical intensive care unit of a university hospital. Twenty patients undergoing mechanical ventilation in whom extubation was not possible solely because of agitated delirium were randomised to receive an infusion of either haloperidol 0.5 to 2 mg/hour or dexmedetomidine 0.2 to 0.7 microg/kg/hr, with or without loading doses of 2.5 mg haloperidol or 1 mug/kg dexmedetomidine, according to clinician preference. RESULTS: Dexmedetomidine significantly shortened median time to extubation from 42.5 (IQR 23.2 to 117.8) to 19.9 (IQR 7.3 to 24) hours (P = 0.016). Dexmedetomidine significantly decreased ICU length of stay, from 6.5 (IQR 4 to 9) to 1.5 (IQR 1 to 3) days (P = 0.004) after study drug commencement. Of patients who required ongoing propofol sedation, the proportion of time propofol was required was halved in those who received dexmedetomidine (79.5% (95% CI 61.8 to 97.2%) vs. 41.2% (95% CI 0 to 88.1%) of the time intubated; P = 0.05). No patients were reintubated; three receiving haloperidol could not be successfully extubated and underwent tracheostomy. One patient prematurely discontinued haloperidol due to QTc interval prolongation. CONCLUSIONS: In this preliminary pilot study, we found dexmedetomidine a promising agent for the treatment of ICU-associated delirious agitation, and we suggest this warrants further testing in a definitive double-blind multi-centre trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT00505804.
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    Effect of the medical emergency team on long-term mortality following major surgery
    Jones, D ; Egi, M ; Bellomo, R ; Goldsmith, D (BIOMED CENTRAL LTD, 2007)
    INTRODUCTION: Introducing an intensive care unit (ICU)-based medical emergency team (MET) into our hospital was associated with decreased postoperative in-hospital mortality after major surgery. The purpose of the present study was to assess the effect of the MET and other variables on long-term mortality in this patient population. METHODS: We conducted a prospective, controlled, before-and-after trial in a University-affiliated hospital. Participants included consecutive patients admitted for major surgery (surgery requiring hospital stay > 48 hours) during a four month control phase and a four month MET phase. The intervention involved the introduction of a hospital-wide ICU-based MET service to evaluate and treat ward patients with acutely deranged vital signs. Information on long-term mortality was obtained from the Australian death registry. The main outcome measure was patient mortality at 1500 days. Data on patient demographics, surgery undertaken and whether the surgery was scheduled or unscheduled was obtained from the hospital electronic database. Multivariable analysis was conducted to determine independent predictors of 1500-day mortality. RESULTS: There were 1,369 major operations in 1,116 patients during the control period and 1,313 operations in 1,067 patients during the MET (intervention) period. Overall survival at 1500 days was 65.8% in the control period and 71.6% during the MET period (P = 0.001). Patients in the control phase were statistically less likely to be admitted under orthopaedic surgery, urology and faciomaxillary surgery units, but more likely to be admitted under cardiac surgery or neurosurgery units. Patients in the MET period were less likely to undergo unscheduled surgery. Multivariable analysis revealed that age, unscheduled surgery and admission under thoracic surgery, neurosurgery, oncology and general medicine were independent predictors of increased 1500-day mortality. Admission during the MET period was also an independent predictor of decreased 1500-day mortality (odds ratio 0.74; P = 0.005). CONCLUSION: Introduction of a MET service in a teaching hospital was associated with increased long-term survival even after adjusting for other factors that contribute to long-term surgical mortality.