Critical Care - Research Publications

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    Recent developments of acupuncture in Australia and the way forward.
    Xue, CC ; Zhang, AL ; Yang, AW ; Zhang, CS ; Story, DF (Springer Science and Business Media LLC, 2009-04-29)
    Almost one in ten Australians has received acupuncture treatment by acupuncturists and/or medical doctors in private clinics. The majority of Australian health insurance funds offer rebates for acupuncture. Statutory regulations for acupuncture have been implemented in the State of Victoria, Australia. Six acupuncture degree courses have been approved by the Chinese Medicine Registration Board of Victoria and/or accredited by the Australian Acupuncture and Chinese Medicine Association. Furthermore, a number of clinical trials of acupuncture on allergic rhinitis, pain and women's health were carried out in Australia. Recent developments of acupuncture in Australia indicate that through adequate and appropriate evaluation, acupuncture begins to integrate into mainstream health care in Australia.
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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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    Baseline hospital performance and the impact of medical emergency teams: Modelling vs. conventional subgroup analysis
    Chen, J ; Flabouris, A ; Bellomo, R ; Hillman, K ; Finfer, S (BMC, 2009-12-19)
    BACKGROUND: To compare two approaches to the statistical analysis of the relationship between the baseline incidence of adverse events and the effect of medical emergency teams (METs). METHODS: Using data from a cluster randomized controlled trial (the MERIT study), we analysed the relationship between the baseline incidence of adverse events and its change from baseline to the MET activation phase using quadratic modelling techniques. We compared the findings with those obtained with conventional subgroup analysis. RESULTS: Using linear and quadratic modelling techniques, we found that each unit increase in the baseline incidence of adverse events in MET hospitals was associated with a 0.59 unit subsequent reduction in adverse events (95%CI: 0.33 to 0.86) after MET implementation and activation. This applied to cardiac arrests (0.74; 95%CI: 0.52 to 0.95), unplanned ICU admissions (0.56; 95%CI: 0.26 to 0.85) and unexpected deaths (0.68; 95%CI: 0.45 to 0.90). Control hospitals showed a similar reduction only for cardiac arrests (0.95; 95%CI: 0.56 to 1.32). Comparison using conventional subgroup analysis, on the other hand, detected no significant difference between MET and control hospitals. CONCLUSIONS: Our study showed that, in the MERIT study, when there was dependence of treatment effect on baseline performance, an approach based on regression modelling helped illustrate the nature and magnitude of such dependence while sub-group analysis did not. The ability to assess the nature and magnitude of such dependence may have policy implications. Regression technique may thus prove useful in analysing data when there is a conditional treatment effect.
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    Landmark survival as an end-point for trials in critically ill patients - comparison of alternative durations of follow-up: an exploratory analysis
    Taori, G ; Ho, KM ; George, C ; Bellomo, R ; Webb, SAR ; Hart, GK ; Bailey, MJ (BMC, 2009)
    INTRODUCTION: Interventional ICU trials have followed up patients for variable duration. However, the optimal duration of follow-up for the determination of mortality endpoint in such trials is uncertain. We aimed to determine the most logical and practical mortality end-point in clinical trials of critically ill patients. METHODS: We performed a retrospective analysis of prospectively collected data involving 369 patients with one of the three specific diagnoses (i) Sepsis (ii) Community acquired pneumonia (iii) Non operative trauma admitted to the Royal Perth Hospital ICU, a large teaching hospital in Western Australia (WA cohort). Their in-hospital and post discharge survival outcome was assessed by linkage to the WA Death Registry. A validation cohort involving 4609 patients admitted during same time period with identical diagnoses from 55 ICUs across Australia (CORE cohort) was used to compare the patient characteristics and in-hospital survival to look at the Australia-wide applicability of the long term survival data from the WA cohort. RESULTS: The long term outcome data of the WA cohort indicate that mortality reached a plateau at 90 days after ICU admission particularly for sepsis and pneumonia. Mortality after hospital discharge before 90 days was not uncommon in these two groups. Severity of acute illness as measured by the total number of organ failures or acute physiology score was the main predictor of 90-day mortality. The adjusted in-hospital survival for the WA cohort was not significantly different from that of the CORE cohort in all three diagnostic groups; sepsis (P = 0.19), community acquired pneumonia (P = 0.86), non-operative trauma (P = 0.47). CONCLUSIONS: A minimum of 90 days follow-up is necessary to fully capture the mortality effect of sepsis and community acquired pneumonia. A shorter period of follow-up time may be sufficient for non-operative trauma.
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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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    Angiotensin II in experimental hyperdynamic sepsis
    Wan, L ; Langenberg, C ; Bellomo, R ; May, CN (BMC, 2009)
    INTRODUCTION: Angiotensin II (Ang II) is a potential vasopressor treatment for hypotensive hyperdynamic sepsis. However, unlike other vasopressors, its systemic, regional blood flow and renal functional effects in hypotensive hyperdynamic sepsis have not been investigated. METHODS: We performed an experimental randomised placebo-controlled animal study. We induced hyperdynamic sepsis by the intravenous administration of live E. coli in conscious ewes after chronic instrumentation with flow probes around the aorta and the renal, mesenteric, coronary and iliac arteries. We allocated animals to either placebo or angiotensin II infusion titrated to maintain baseline blood pressure. RESULTS: Hyperdynamic sepsis was associated with increased renal blood flow (from 292 +/- 61 to 397 +/- 74 ml/min), oliguria and a decrease in creatinine clearance (from 88.7 +/- 19.6 to 47.7 +/- 21.0 ml/min, P < 0.0001). Compared to placebo, Ang II infusion restored arterial pressure but reduced renal blood flow (from 359 +/- 81 ml/min to 279 +/- 86 ml/min; P < 0.0001). However, despite the reduction in renal blood flow, Ang II increased urine output approximately 7-fold (364 +/- 272 ml/h vs. 48 +/- 18 ml/h; P < 0.0001), and creatinine clearance by 70% (to 80.6 +/- 20.7 ml/min vs.46.0 +/- 26 ml/min; P < 0.0001). There were no major effects of Ang II on other regional blood flows. CONCLUSIONS: In early experimental hypotensive hyperdynamic sepsis, intravenous angiotensin II infusion decreased renal blood while inducing a marked increase in urine output and normalizing creatinine clearance.
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    The impact of early hypoglycemia and blood glucose variability on outcome in critical illness
    Bagshaw, SM ; Bellomo, R ; Jacka, MJ ; Egi, M ; Hart, GK ; George, C (BMC, 2009)
    INTRODUCTION: In critical illness, the association of hypoglycemia, blood glucose (BG) variability and outcome are not well understood. We describe the incidence, clinical factors and outcomes associated with an early hypoglycemia and BG variability in critically ill patients. METHODS: Retrospective interrogation of prospectively collected data from the Australia New Zealand Intensive Care Society Adult Patient Database on 66184 adult admissions to 24 intensive care units (ICUs) from 1 January 2000 to 31 December 2005. Primary exposure was hypoglycemia (BG < 4.5 mmol/L) and BG variability (BG < 4.5 and >or= 12.0 mmol/L) within 24 hours of admission. Primary outcome was all-cause mortality. RESULTS: The cumulative incidence of hypoglycemia and BG variability were 13.8% (95% confidence interval (CI) = 13.5 to 14.0; n = 9122) and 2.9% (95%CI = 2.8 to 3.0, n = 1913), respectively. Several clinical factors were associated with both hypoglycemia and BG variability including: co-morbid disease (P < 0.001), non-elective admissions (P < 0.001), higher illness severity (P < 0.001), and primary septic diagnosis (P < 0.001). Hypoglycemia was associated with greater odds of adjusted ICU (odds ratio (OR) = 1.41, 95% CI = 1.31 to 1.54) and hospital death (OR = 1.36, 95% CI = 1.27 to 1.46). Hypoglycemia severity was associated with 'dose-response' increases in mortality. BG variability was associated with greater odds of adjusted ICU (1.5, 95% CI = 1.4 to 1.6) and hospital (1.4, 95% CI = 1.3 to 1.5) mortality, when compared with either hypoglycemia only or neither. CONCLUSIONS: In critically ill patients, both early hypoglycemia and early variability in BG are relatively common, and independently portend an increased risk for mortality.
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    Very old patients admitted to intensive care in Australia and New Zealand: a multi-centre cohort analysis
    Bagshaw, SM ; Webb, SAR ; Delaney, A ; George, C ; Pilcher, D ; Hart, GK ; Bellomo, R (BMC, 2009)
    INTRODUCTION: Older age is associated with higher prevalence of chronic illness and functional impairment, contributing to an increased rate of hospitalization and admission to intensive care. The primary objective was to evaluate the rate, characteristics and outcomes of very old (age >or= 80 years) patients admitted to intensive care units (ICUs). METHODS: Retrospective analysis of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were obtained for 120,123 adult admissions for >or= 24 hours across 57 ICUs from 1 January 2000 to 31 December 2005. RESULTS: A total of 15,640 very old patients (13.0%) were admitted during the study. These patients were more likely to be from a chronic care facility, had greater co-morbid illness, greater illness severity, and were less likely to receive mechanical ventilation. Crude ICU and hospital mortalities were higher (ICU: 12% vs. 8.2%, P < 0.001; hospital: 24.0% vs. 13%, P < 0.001). By multivariable analysis, age >/= 80 years was associated with higher ICU and hospital death compared with younger age strata (ICU: odds ratio (OR) = 2.7, 95% confidence interval (CI) = 2.4 to 3.0; hospital: OR = 5.4, 95% CI = 4.9 to 5.9). Factors associated with lower survival included admission from a chronic care facility, co-morbid illness, nonsurgical admission, greater illness severity, mechanical ventilation, and longer stay in the ICU. Those aged >or= 80 years were more likely to be discharged to rehabilitation/long-term care (12.3% vs. 4.9%, OR = 2.7, 95% CI = 2.6 to 2.9). The admission rates of very old patients increased by 5.6% per year. This potentially translates to a 72.4% increase in demand for ICU bed-days by 2015. CONCLUSIONS: The proportion of patients aged >or= 80 years admitted to intensive care in Australia and New Zealand is rapidly increasing. Although these patients have more co-morbid illness, are less likely to be discharged home, and have a greater mortality than younger patients, approximately 80% survive to hospital discharge. These data also imply a potential major increase in demand for ICU bed-days for very old patients within a decade.