Bala Venkatesh

University of Queensland, Brisbane, Queensland, Australia

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Publications (132)460.28 Total impact

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    ABSTRACT: We studied the association between admission serum 25-hydroxy vitamin D3 level and in-hospital mortality in a prospective cohort of critically ill patients admitted to the medical intensive care unit of a tertiary care referral center. Of the 180 patients enrolled, 129 were included. Vitamin D3 deficiency was observed in 37 % (n = 48) and supra-physiological levels (≥250 nmol/L) in 15.5 % (n = 20). Patients with supraphysiological vitamin D3 levels were grouped as outliers. There was no difference in mortality (p = 0.41) between vitamin D3 deficient (21/48) and non-deficient (36/81) patients in analysis with and without outliers. Patients with vitamin D3 ≥250 nmol/L had a significantly higher (p = 0.02) Simplified Acute Physiology Score (SAPS) II and mortality (p = 0.003) [mean (SD) 60.1 ± 17.1 and 75 % (15/20), respectively] when compared with the rest [45.6 ± 18 and 38.5 % (42/109), respectively]. The sensitivity, specificity and SAPS II independent odds ratio to predict mortality in patients with supraphysiological vitamin D3 levels were 26.3, 93.1 and 3.7 % (95 % confidence interval 1.2-11.4; p = 0.03), respectively. In conclusion, vitamin D3 deficiency in our cohort was not associated with mortality. A patient subset with supra-physiological vitamin D levels had higher illness severity scores and mortality. Extrinsic factors interfering with test results were ruled out. A biological hypothesis to explain this observation is proposed. Further clarification of mechanisms leading to this observation is warranted.
    Journal of Bone and Mineral Metabolism 04/2014; · 2.22 Impact Factor
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    ABSTRACT: To evaluate the use of high-fidelity simulation for summative high-stakes assessment of intensive care trainees, focusing on non-technical skills (NTS), testing feasibility and acceptability of simulation assessment, and the reliability of two NTS rating scales. Prospective observational study of senior intensive care trainees in a simulated specialist examination. Participants undertook a simulated patientmanagement scenario and were assessed using two rating scales: the Anaesthesia Non-technical Skills (ANTS) scale and the Ottawa Global Rating Scale (GRS). Assessors were trained, currently active, high-stakes examiners. Participants also completed a survey on simulation-based summative assessment. The inter-rater reliability of two rating scales for NTS assessment. We evaluated the feasibility of simulation-based assessment, and used survey results to assess acceptability to participants. Simulation assessment was feasible. Participants considered simulation-based high-stakes assessment to be acceptable and felt their scenario performance was reflective of real-world performance. Participants identified a need for debriefing following scenario-based assessment. Inter-rater reliability was fair for the ANTS and Ottawa GRS scores (intra-class correlation coefficient, 0.39 and 0.42, respectively). There was only fair agreement between raters for an NTS pass or fail (weighted kappa, 0.32) and for a technical skills pass or fail (weighted kappa, 0.36). Summative high-stakes assessment using a single simulated scenario was feasible and acceptable to senior intensive care trainees. The low inter-rater reliability for the ANTS and Ottawa GRS rating scales and for pass or fail discrimination may limit its incorporation into an existing examination format.
    Critical care and resuscitation: journal of the Australasian Academy of Critical Care Medicine 03/2014; 16(1):6-12. · 2.15 Impact Factor
  • Peter S Kruger, Bala Venkatesh
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    ABSTRACT: Statins have become the most widely used drugs for lowering cholesterol levels worldwide. At least 20 % of patients requiring admission to hospital are on established statin therapy, and this proportion is growing each year. Evidence from observational studies and basic science research suggests that statins might be associated with a reduced mortality in sepsis. Randomized trials are producing equivocal results but have not shown the marked improvement in outcome suggested by the observational studies. Continued use in current statin users appears a more fruitful area for future research than statin use de novo as an adjuvant therapy in sepsis. Statin use in patients with pneumonia, acute lung injury or early sepsis warrants further study. International practice of statin use in critically ill patients is variable, and potential toxicity mandates careful monitoring. Further studies are required to address fundamental issues such as efficacy, potential target patient populations, dose, class equivalence and safety.
    Current Atherosclerosis Reports 01/2014; 16(1):378. · 3.06 Impact Factor
  • Peter Kruger, Rinaldo Bellomo, Bala Venkatesh
    American Journal of Respiratory and Critical Care Medicine 10/2013; 188(7):874-875. · 11.04 Impact Factor
  • Anand Krishnan, Bala Venkatesh
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    ABSTRACT: Vitamin D deficiency, as measured by a random level of 25-hydroxyvitamin D is very prevalent in critically ill patients admitted to the ICU and is associated with adverse outcomes. Both 25(OH)vitamin D and 1α,25(OH)2D3 are difficult to analyse because of their lipophilic nature, affinity for VDBP and small concentrations. Also, the various tests used to estimate vitamin D levels show significant inter- and intra-assay variability, which significantly affect the veracity of the results obtained and confound their interpretation. The two main types of assays include those that directly estimate vitamin D levels (HPLC, LC-MS/MS) and competitive binding assays (RIA, EIA). The former methods require skilled operators, with prolonged assay times and increased cost, whereas the latter are cheaper and easy to perform, but with decreased accuracy. The direct assays are not affected by lipophilic substances in plasma and heterophile antibodies, but may overestimate vitamin D levels by measuring the 3-epimers. These problems can be eliminated by adequate standardization of the test using SRMs provided by NIST, as well as participating in proficiency schemes like DEQAS. It is therefore important to consider the test employed as well as laboratory quality control, while interpreting vitamin D results. A single random measurement may not be reflective of the vitamin D status in ICU patients because of changes with fluid administration, and intra-day variation in 25-hydroxyvitamin D levels. 1α,25(OH)2D3 may behave differently to 25-hydroxyvitamin D, both in plasma and at tissue level, in inflammatory states. Measurement of tissue 1α,25(OH)2D3 levels may provide the true estimate of vitamin D activity.
    Inflammation & allergy drug targets. 06/2013;
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    European Journal of Intensive Care Medicine 06/2013; · 5.17 Impact Factor
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    ABSTRACT: There is considerable global uncertainty on the role of low-dose corticosteroids in septic shock, which translates into variations in prescribing practices. To describe the protocol for a large-scale multicentre randomised controlled trial in critically ill patients with septic shock, comparing the effects of hydrocortisone and placebo (in addition to standard treatment) on 90-day mortality and other outcomes such as shock reversal, duration of mechanical ventilation and quality of life. We will recruit 3800 critically ill patients with septic shock treated in an intensive care unit, to concealed, randomised, parallel assignment of hydrocortisone or placebo. The primary outcome will be all-cause mortality at 90 days postrandomisation. Secondary outcomes will include ICU and hospital mortality, length of ICU stay and quality of life at 6 months. Subgroup analyses will be conducted in two predefined subgroups. All analyses will be conducted on an intention-to-treat basis. The run-in phase has been completed and the main trial commenced in February 2013. The trial should generate results that will inform and influence prescribing of corticosteroids in septic shock.
    Critical care and resuscitation: journal of the Australasian Academy of Critical Care Medicine 06/2013; 15(2):83-8. · 2.15 Impact Factor
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    ABSTRACT: CONTEXT: The anti-inflammatory role of adiponectin has prompted interest in a potential role in acute inflammatory conditions associated with critical illness. It is unclear whether a random adiponectin measurement adequately reflects the 24 hr profile in critically ill patients. OBJECTIVE: To assess the temporal profile of total and high-molecular weight (HMW) adiponectin and Interleukin-6 (IL-6) in 15 critically ill patients. DESIGN: A prospective, observational study. SETTING: Level II intensive care unit in a metropolitan hospital. PATIENTS OR OTHER PARTICIPANTS: Fifteen critically ill patients expected to stay in the ICU for longer than 48h were eligible for enrolment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serial, hourly measurements of total and HMW adiponectin and IL-6. RESULTS: Over a 24h period, total and HMW adiponectin display considerable within-patient variability, (coefficient of variation 34% and 87% respectively) and show no trend over time. Averaging 2 or 3 continuous measures reduced within patient variability of both total and HMW adiponectin by up to 50% compared to 1 measure. There was a negative correlation between serum glucose and adiponectin (total p=0.016, HMW p=0.039). No relationship existed between adiponectin and IL-6 (total p=0.62, HMW p=0.35). CONCLUSIONS: Marked within patient hourly variability in total and HMW adiponectin is evident in critically ill patients. A random measurement may not be reflective of the 24-hour profile in these patients. A negative correlation exists between adiponectin and blood glucose levels and a positive correlation between adiponectin and oxygen saturation. No clear relationship exists between adiponectin and IL-6. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 05/2013; · 3.35 Impact Factor
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    ABSTRACT: Despite the potential dangers of clinical tasks being forgotten, few researchers have investigated prospective memory (PM) - the ability to remember to execute future tasks - in health-care contexts. Visual cues help people remember to execute intentions at the appropriate moment. Using an intensive care unit simulator, we investigated whether nurses' memory for future tasks improves when visual cues are present, and how nurses manage PM demands. Twenty-four nurses participated in a 40-minute scenario simulating the start of a morning shift. The scenario included eight PM tasks. The presence or absence of a visually conspicuous cue for each task was manipulated. The presence of a visual cue improved recall compared to no cue (64% vs. 50%, p = 0.03 one-tailed, η p (2) = 0.15). Nurses used deliberate reminders to manage their PM demands. PM in critical care might be supported by increasing the visibility of cues related to tasks. Practitioner summary: Nurses must remember to execute multiple future tasks to ensure patient safety. We investigated the effect of visual cues on nurses' ability to remember future tasks. Experimental manipulation of cues in a representative intensive care unit simulation indicated that visual cues increase the likelihood that future tasks are executed.
    Ergonomics 03/2013; · 1.61 Impact Factor
  • Jeremy Cohen, Bala Venkatesh, Terrence Tan
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    ABSTRACT: To investigate the agreement between two methods of measurement of plasma free cortisol in acutely ill patients; an indirect method using the Coolens equation, and direct measurement using high-performance liquid chromatography-tandem mass spectrometry, which is the gold standard. Prospective observational study among patients with septic shock in a tertiary intensive care unit and patients with liver failure attending a hospital outpatient clinic while awaiting transplantation. Paired values of free cortisol levels obtained from direct measurement and from calculation were analysed to provide estimates of bias and precision for the two methods. Free and total plasma cortisol and corticosteroid binding globulin concentrations. 102 samples were analysed. The overall bias was -17%± 50%, with 95% limits of agreement of - 115% to 80%. Bias was noted to be greater in specimens with higher albumin concentration, and was proportional to free cortisol concentration. The observed bias between the two methods is of a magnitude that would be expected to produce clinically relevant discrepancies. Due to the proportional nature of the error, adding a correction factor is not feasible. Results obtained from using the Coolens method to calculate free cortisol concentration in acutely ill patients should be interpreted with caution.
    Critical care and resuscitation: journal of the Australasian Academy of Critical Care Medicine 03/2013; 15(1):39-41. · 2.15 Impact Factor
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    ABSTRACT: Bolus dose concentrations of hydrocortisone (50mg/mL) are reported to be incompatible with midazolam and ciprofloxacin in Y-site mixing studies. We evaluated the physical and chemical compatibility of low concentrations of hydrocortisone sodium succinate (1 mg/ mL) with midazolam (1 mg/mL and 2mg/mL) and ciprofloxacin (2 mg/mL) solutions during a simulated Y-site administration study. The midazolam 1mg/mL, midazolam 2mg/mL and ciprofloxacin 2mg/mL solutions were individually combined with hydrocortisone sodium succinate 1mg/mL solution in a 1:1 ratio and tested in triplicate. Physical compatibility was evaluated using a previously described method immediately on mixing, after 60 minutes and after 120 minutes. Chemical compatibility was determined by measuring the hydrocortisone sodium succinate concentration of the test solutions 120 minutes after mixing compared with that of a reference sample of hydrocortisone sodium succinate solution. At all time points, when hydrocortisone was mixed with midazolam (1 mg/mL and 2mg/mL) and ciprofloxacin (2 mg/mL), the solutions remained clear, with no haziness, colour change, gas or precipitate formation, thus showing total physical compatibility. There were pharmacologically significant reductions (>10%) in measured hydrocortisone concentration (18.6% with midazolam 2mg/mL, P = 0.06; and 21.3% with ciprofloxacin, P = 0.01) in all of the test samples, as compared with the reference sample. According to currently recommended criteria, combining hydrocortisone sodium succinate at a concentration of 1mg/mL with a 1mg/mL solution of midazolam appears to be both chemically and physically compatible. However, mixing 1mg/mL hydrocortisone sodium succinate with 2mg/mL midazolam or with 2mg/ mL ciprofloxacin cannot be recommended.
    Critical care and resuscitation: journal of the Australasian Academy of Critical Care Medicine 03/2013; 15(1):67. · 2.15 Impact Factor
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    ABSTRACT: RATIONALE: Observational studies link statin therapy with improved outcomes in patients with severe sepsis. OBJECTIVES: To test whether atorvastatin therapy affects biological and clinical outcomes in critically ill patients with severe sepsis. METHODS: Phase II, multicenter, prospective, randomized, double-blind, placebo controlled trial stratified by site and prior statin use. A cohort of 250 critically ill patients (123 statins, 127 placebo) with severe sepsis were administrated either atorvastatin (20 mg daily) or matched placebo. MEASUREMENTS AND MAIN RESULTS: There was no difference in IL-6 concentrations (primary end point) between the atorvastatin and placebo groups (p=0.76) and no interaction between treatment group and time to suggest that the groups behaved differently over time (p= 0.26). Baseline plasma IL-6, was lower among previous statin users [129(87-191) vs. 244 (187-317) pg/ml, p=0.01]. There was no difference in length of stay, change in SOFA scores or mortality at ICU discharge, hospital discharge, 28 days or 90 days (15 vs. 19%) or adverse effects between the two groups. Cholesterol was lower in atorvastatin treated patients [2.4(0.07) vs. 2.6(0.06) mmol/L, p=0.006]. In the pre -defined group of 77 prior statin users, those randomised to placebo had a greater 28 day mortality (28% vs.5%, P=0.01) compared to those who received atorvastatin. The difference was not statistically significant at 90 days (28 vs. 11%, p=0.06) CONCLUSIONS: Atorvastatin therapy in severe sepsis did not affect IL-6 levels. Prior statin use was associated with a lower baseline IL-6 concentration and continuation of atorvastatin in this cohort was associated with improved survival. Clinical trial registration information available at, i.d. = ACTRN12607000028404.
    American Journal of Respiratory and Critical Care Medicine 01/2013; · 11.04 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 09/2012; 186(5):463-4. · 11.04 Impact Factor
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    Jeremy Cohen, Carel Pretorius, Bala Venkatesh
    European Journal of Intensive Care Medicine 03/2012; 38(4):718; author reply 719-20. · 5.17 Impact Factor
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    ABSTRACT: Published data on adrenocortical function in septic shock have enrolled patients at various stages of critical illness and predominantly used plasma total cortisol, with minimal information on serial changes. Moreover, plasma free cortisol and tissue corticosteroid activity may not be strongly associated; however, few published data exist. The aim of this prospective observational study was to investigate serial changes in plasma total and free cortisol and tissue cortisol activity in septic shock. Twenty-nine adult patients admitted with septic shock to a tertiary-level intensive care unit were enrolled. A low-dose corticotropin test was performed on day 1. Plasma total and free cortisol, cortisone, transcortin, and urinary free cortisol and cortisone were analyzed on days 1 to 5, 7, and 10. Urinary and plasma cortisol-cortisone ratios (F:E ratio) were calculated as indices of 11-β hydroxysteroid dehydrogenase 2 and global 11-β hydroxysteroid dehydrogenase activity, respectively. Baseline total and free plasma cortisol values from 10 healthy control subjects were obtained for comparative analysis. Baseline plasma total and free cortisol levels were significantly higher than controls (457.8 ± 193 vs. 252 ± 66 nmol/L, P = 0.0002; and 50.83 ± 43.19 vs. 6.4 ± 3.2, P < 0.0001, respectively). Plasma free cortisol rose proportionately higher than total cortisol (124% ± 217.3% vs. 40% ± 33.2%, P = 0.007) following corticotropin. Baseline plasma and urinary F:E ratios were elevated over the reference ranges (13.13 ± 1.5, 1.69 ± 2.8) and were not correlated with plasma free cortisol values (r = 0.2, 0.3 respectively). Over the study period, total cortisol levels and plasma F:E ratios remained elevated, whereas plasma free cortisol levels and urinary F:E ratio declined. At baseline, plasma free cortisol levels were higher in patients who subsequently survived (23.7 ± 10.5 vs. 57.9 ± 45.8 nmol/L, P = 0.04). In septic shock, there is a differential response of plasma total and free cortisol over time and in response to corticotropin. Changes in plasma and urinary F:E ratios suggest tissue modulation of 11-β hydroxysteroid dehydrogenase activity. Total plasma cortisol measurements may not reflect the global adrenal response in septic shock.
    Shock (Augusta, Ga.) 01/2012; 37(1):28-33. · 2.87 Impact Factor
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    David J Sturgess, Bala Venkatesh
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    ABSTRACT: Previous studies of patients with septic shock have independently demonstrated alterations in plasma concentrations of B-type natriuretic peptide and plasma free cortisol. Previous data suggest that a reciprocal relationship might exist. However, the relationship between these hormones in patients with septic shock is unclear. We sought to compare paired measurement of both B-type natriuretic peptide and plasma free cortisol in a study of septic shock patients. Twenty-one consecutive adult patients from a tertiary level, multidisciplinary intensive care unit underwent blood collection within 72 hours of developing septic shock. Mean ± SD Acute Physiology and Chronic Health Evaluation III score was 80.1 ± 23.8. Hospital mortality was 29%. Log plasma free cortisol demonstrated positive correlation with log B-type natriuretic peptide (r=0.55, P=0.019). Log plasma free cortisol also correlated with Acute Physiology and Chronic Health Evaluation III score (r=0.67, P <0.001) and noradrenaline dose (r=0.55, P=0.01). Acute Physiology and Chronic Health Evaluation III (P=0.001) and noradrenaline dose (P=0.02) were independent predictors of plasma free cortisol. A model incorporating both variables explained 68% of variation in plasma free cortisol (R-square=0.682). This study of patients with septic shock demonstrates a previously unappreciated positive correlation between plasma free cortisol and b-type natriuretic peptide concentration. Acute Physiology and Chronic Health Evaluation III score and noradrenaline dose were independent predictors of plasma free cortisol.
    Anaesthesia and intensive care 01/2012; 40(1):95-8. · 1.47 Impact Factor
  • Karin Amrein, Bala Venkatesh
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    ABSTRACT: To summarize the current knowledge on vitamin D with a special focus on critically ill patients. Vitamin D deficiency is associated with adverse health outcomes including increased risk of cardiovascular disease, morbidity and mortality in the general population. In critically ill patients, the pleiotropic effects of vitamin D including its role in immune function are of great interest. To date, it is not clear whether vitamin D deficiency is a surrogate marker for increased morbidity or whether treatment with sufficiently large doses of vitamin D may improve patient outcome in an intensive care setting.
    Current opinion in clinical nutrition and metabolic care. 12/2011; 15(2):188-93.
  • European Journal of Intensive Care Medicine 11/2011; 38(1):177-9. · 5.17 Impact Factor
  • Bala Venkatesh, Jeremy Cohen
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    ABSTRACT: A central feature of the endocrine pathophysiology of septic shock is thought to be the existence of adrenal dysfunction. Based on changes in glucocorticoid secretion and responsiveness, protein binding, and activity. These changes have been described by the terms "Relative Adrenal Insufficiency" (RAI), or "Critical Illness Related Corticosteroid Insufficiency" (CIRCI), and form part of the rationale for trials of glucocorticoid treatment in septic shock. Diagnostic criteria for these conditions have been based on plasma cortisol profiles and have proven notoriously difficult to establish. The uncertainty in this area arises from the inability of current tests to clearly identify who is truly glucocorticoid "deficient" at a cellular level, and hence who requires supplemental glucocorticoid administration. Emerging data suggest that there may be abnormalities in the tissue activity of glucocorticoids in patients with severe sepsis and plasma profiles may not be reliable indicators of tissue glucocorticoid activity, We put forward an alternative point of view, that is the spectrum of adrenocortical dysfunction in sepsis - plasma and tissue, can be grouped under the umbrella of a "sick euadrenal syndrome" rather than an adrenocortical insufficiency.
    Best Practice & Research: Clinical Endocrinology & Metabolism 10/2011; 25(5):719-33. · 4.91 Impact Factor
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    ABSTRACT: Metabolic support in intensive care is a rapidly evolving field with new information being gathered almost on a daily basis. In endocrine practice, over the last 20 years, researchers have focussed on a new entity, termed the "metabolic syndrome". This describes the constellation of abnormalities which include central adiposity, insulin resistance and inflammation. All of these predispose the individual to a greater risk of cardiovascular events. Of interest is the observation that some of the metabolic abnormalities in sepsis and multiple organ dysfunction syndrome of critical illness share several common features with that of the metabolic syndrome. In this chapter we describe the features of the metabolic syndrome as is understood in endocrine parlance, the metabolic abnormalities of critical illness and explore the common threads underlying the pathophysiology and the treatment of the two syndromes. The role of adiponectin in the metabolic abnormalities in both the metabolic syndrome and in sepsis are reviewed. The potential role of the pleiotropic effects of statins in the therapy of sepsis is also discussed.
    Best Practice & Research: Clinical Endocrinology & Metabolism 10/2011; 25(5):835-45. · 4.91 Impact Factor

Publication Stats

985 Citations
460.28 Total Impact Points


  • 1999–2014
    • University of Queensland
      • • Princess Alexandra Hospital
      • • Burns Trauma and Critical Care Research Centre
      • • Intensive Care Unit
      Brisbane, Queensland, Australia
  • 2007–2013
    • Wesley Hospital
      Brisbane, Queensland, Australia
  • 2002–2013
    • Princess Alexandra Hospital (Queensland Health)
      • • Intensive Care Unit (ICU)
      • • Division of Medicine
      Brisbane, Queensland, Australia
  • 2011
    • Medical University of Graz
      Gratz, Styria, Austria
  • 2010
    • Queensland University of Technology
      • School of Nursing
      Brisbane, Queensland, Australia
  • 1995–2009
    • Royal Brisbane Hospital
      • • Department of Surgery
      • • Department of Intensive Care Medicine
      Brisbane, Queensland, Australia
  • 2008
    • Queensland Government
      Brisbane, Queensland, Australia