Andrew D Bersten

Flinders Medical Centre, Tarndarnya, South Australia, Australia

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Publications (154)818.82 Total impact

  • Shailesh Bihari · John G Laffey · Andrew D Bersten
    No preview · Article · Mar 2016 · Intensive Care Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Importance: Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation. Objective: To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation.Design, Setting, and Participants The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded. Interventions : Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician. Main Outcomes and Measures: Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori. Results: Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P = .01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P < .001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P = .01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P = .007).Conclusions and Relevance Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.Trial Registration Identifier: NCT01151865
    No preview · Article · Mar 2016 · JAMA The Journal of the American Medical Association
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Sucrose induced hyperosmolarity is lung protective but the safety of administering hyperosmolar sucrose in patients is unknown. Hypertonic saline is commonly used to produce hyperosmolarity aimed at reducing intra cranial pressure in patients with intracranial pathology. Therefore we studied the protective effects of 20% saline in a lipopolysaccharide lung injury rat model. 20% saline was also compared with other commonly used fluids. Methods: Following lipopolysaccharide-induced acute lung injury, male Sprague Dawley rats received either 20% hypertonic saline, 0.9% saline, 4% albumin, 20% albumin, 5% glucose or 20% albumin with 5% glucose, i.v. During 2hours of non-injurious mechanical ventilation parameters of acute lung injury were assessed. Results: Hypertonic saline resulted in hypernatraemia (160 (1) mmol/l, mean (SD)) maintained through 2h of ventilation, and in amelioration of lung oedema, myeloperoxidase, bronchoalveolar cell infiltrate, total soluble protein and inflammatory cytokines, and lung histological injury score, compared with positive control and all other fluids (p≤0.001). Lung physiology was maintained (conserved PaO2, elastance), associated with preservation of alveolar surfactant (p≤0.0001). Conclusion: Independent of fluid or sodium load, induced hypernatraemia is lung protective in lipopolysaccharide-induced acute lung injury.
    No preview · Article · Mar 2016 · Respiratory Physiology & Neurobiology
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Advancements in tracheostomy tube design now provide clinicians with a range of options to facilitate communication for individuals receiving ventilator assistance through a cuffed tube. Little is known about the impact of these modern design features on resistance to air flow. Methods: We undertook a bench model test to measure pressure-flow characteristics and resistance of a range of tubes of similar outer diameter, including those enabling subglottic suction and speech. A constant inspiratory ± expiratory air flow was generated at increasing flows up to 150 L/min through each tube (with or without optional, mandatory, or interchangeable inner cannula). Driving pressures were measured, and resistance was calculated (cm H2O/L/s). Results: Pressures changed with increasing flow (P < .001) and tube type (P < .001), with differing patterns of pressure change according to the type of tube (P < .001) and direction of air flow. The single-lumen reference tube encountered the lowest inspiratory and expiratory pressures compared with all double-lumen tubes (P < .001); placement of an optional inner cannula increased bidirectional tube resistance by a factor of 3. For a tube with interchangeable inner cannulas, the type of cannula altered pressure and resistance differently (P < .001); the speech cannula in particular amplified pressure-flow changes and increased tube resistance by more than a factor of 4. Conclusions: Tracheostomy tube type and inner cannula selection imposed differing pressures and resistance to air flow during inspiration and expiration. These differences may be important when selecting airway equipment or when setting parameters for monitoring, particularly for patients receiving supported ventilation or during the weaning process.
    Full-text · Article · Feb 2016 · Respiratory care
  • Shailesh Bihari · Andrew W. Holt · Shivesh Prakash · Andrew D. Bersten
    [Show abstract] [Hide abstract] ABSTRACT: Background: Fluid and sodium overload are a common problem in critically ill patients. Frusemide may result in diuresis in excess of natriuresis. The addition of indapamide may achieve a greater natriuresis, and also circumvent some of the problems associated with frusemide. The objective of this study was to examine the effect of adding indapamide to frusemide on diuresis, natriuresis, creatinine clearance and serum electrolytes. Methods: Fluid overloaded ICU patients were randomised to either intravenous frusemide (Group F) or intravenous frusemide and enteral indapamide (Group F + I). Comprehensive exclusion criteria were applied to address confounders. 24 hour urine was analysed for electrolytes and creatinine. Serum electrolytes were measured before and 24 hours after administration of diuretics. Results: Forty patients (20 in each group) were included in the study. The groups were similar in their baseline characteristics. Over the 24 h study period, patients in Group F + I, had a larger natriuresis (P = 0.01), chloride loss (P = 0.01) and kaliuresis (P = 0.047). Patients in Group F + I also had a greater 24 hour urinary creatinine clearance (P = 0.01). The 24 hour urine volume and fluid balance was similar between the groups. Patients in Group F had an increase in serum sodium (P = 0.04), while patients in Group F + I had a decrease in both serum chloride (P = 0.01) and peripheral oedema (P < 0.001) during the study duration. Conclusion: In fluid overloaded ICU patients, addition of indapamide to frusemide led to a greater natriuresis and creatinine clearance. Such a strategy might be utilised in optimising sodium balance in ICU patients.
    No preview · Article · Jan 2016 · Journal of critical care
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    Full-text · Article · Dec 2015 · Heart, Lung and Circulation
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    Full-text · Article · Dec 2015 · Critical care medicine
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    Shailesh Bihari · Michael Bailey · Andrew D Bersten
    Preview · Article · Nov 2015 · Intensive Care Medicine
  • No preview · Article · Sep 2015 · Critical care and resuscitation: journal of the Australasian Academy of Critical Care Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Rapid intravenous infusion of 0.9% saline alters respiratory mechanics in healthy subjects. However, the relative cardiovascular and respiratory effects of bolus intravenous crystalloid versus colloid are unknown. Six healthy male volunteers were given 30 ml/kg intravenous 0.9% saline, 4% albumin and 5% glucose at a rate of 100 ml/minute on three separate days in a double-blind randomized crossover study. Impulse oscillometry, spirometry, lung volumes, diffusing capacity and blood samples were measured before and after fluid administration. Lung ultrasound B-line score (indicating interstitial pulmonary edema) and Doppler echocardiography indices of cardiac preload were measured before, midway, immediately after and one hour after fluid administration. Infusion of 0.9% saline increased small airway resistance at 5 Hz (P = 0.04) and lung ultrasound B-line score (P = 0.01), without changes in Doppler echocardiography measures of preload. In contrast, 4% albumin increased diffusing capacity, decreased lung volumes, and increased Doppler echocardiopraphy mitral E velocity (P = 0.001) and E to lateral/septal e' ratio, estimated blood volume and NT-proBNP (P = 0.01), but not lung ultrasound B-line score; consistent with increased pulmonary blood volume without interstitial pulmonary edema. There were no significant changes with 5% glucose. Plasma angiopoietin-2 concentration increased only after 0.9% saline (P = 0.001), suggesting an inflammatory mechanism associated with edema formation. In healthy subjects 0.9% saline and 4% albumin have differential pulmonary effects not attributable to passive fluid filtration. This may reflect either different effects of these fluids on active signaling in the pulmonary circulation, or a protective effect of albumin. Copyright © 2015, Journal of Applied Physiology.
    Full-text · Article · Jul 2015 · Journal of Applied Physiology
  • [Show abstract] [Hide abstract] ABSTRACT: To derive and validate a mortality prediction model from information available at ED triage. Multivariable logistic regression of variables from administrative datasets to predict inpatient mortality of patients admitted through an ED. Accuracy of the model was assessed using the receiver operating characteristic area under the curve (ROC-AUC) and calibration using the Hosmer-Lemeshow goodness of fit test. The model was derived, internally validated and externally validated. Derivation and internal validation were in a tertiary referral hospital and external validation was in an urban community hospital. The ROC-AUC for the derivation set was 0.859 (95% CI 0.856-0.865), for the internal validation set was 0.848 (95% CI 0.840-0.856) and for the external validation set was 0.837 (95% CI 0.823-0.851). Calibration assessed by the Hosmer-Lemeshow goodness of fit test was good. The model successfully predicts inpatient mortality from information available at the point of triage in the ED. © 2015 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.
    No preview · Article · Jul 2015 · Emergency medicine Australasia: EMA
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    Full-text · Dataset · Apr 2015
  • Claire E Baldwin · Andrew D Bersten
    [Show abstract] [Hide abstract] ABSTRACT: Purpose of review: Survivors of a critical illness may experience poor physical function and quality of life as a result of reduced skeletal muscle mass and strength during their acute illness. Patients diagnosed with sepsis are particularly at risk, and mechanical ventilation may result in diaphragm dysfunction. Interest in the interaction of these conditions is both growing and important to understand for individualised patient care. Recent findings: This review describes developments in the presentation of both diaphragm and limb myopathy in critical illness, as measured from muscle biopsy and at the bedside with various imaging and strength testing modalities. The influence of unloading of the diaphragm with mechanical ventilation and peripheral muscles with immobilisation in septic patients has been recently questioned. Systemic inflammation appears to primarily accelerate and accentuate dysfunction, which may be remedied by early mobilisation and augmented with developing muscle and/or nerve stimulation techniques. Summary: Many acute muscle changes in septic patients are likely to stem from pre-existing impairments, which should provide context for clinical evaluations of strength. During illness, sarcolemmal injury promotes a cascade of intra-cellular abnormalities. As unique characteristics of ICU acquired weakness and differential effects on muscle groups are understood, early diagnosis and management should be facilitated.
    No preview · Article · Mar 2015 · Current Opinion in Clinical Nutrition and Metabolic Care
  • [Show abstract] [Hide abstract] ABSTRACT: Large positive sodium balances, independent of fluid balance, may lead to expanded extracellular fluid volumes and adverse clinical outcomes in the critically ill, including impaired oxygenation. To estimate sodium and fluid balances in critically ill patients needing invasive mechanical ventilation (MV) for more than 48 hours and to evaluate the relationship between fluid balance, sodium balance and respiratory function (PaO2/FiO2 ratio and length of MV). A prospective, observational study of 50 patients on MV in four tertiary intensive care units. Daily sodium and fluid input and output, biochemistry, haemodynamic variables, oxygenation (PaO2/FiO2) and steroid and vasopressor administration were recorded for 3 days after study enrolment. Outcome data included the duration of invasive MV, ICU and hospital mortality and ICU and hospital lengths of stay. Fifty patients (33 men [66%]) with a mean age of 62.8 years (standard deviation, 14.6 years) and a median admission Acute Physiology and Chronic Health Evaluation III score of 82 (interquartile range [IQR], 61-99) were studied. By Day 3 after enrolment, the median cumulative fluid balance was 2668mL (IQR, 875-3507mL) and the cumulative sodium balance was +717mmol (IQR, +422 to +958mmol). Intravenous steroids and the presence of shock led to a lower daily sodium excretion (P=0.004 and P = 0.01, respectively). A positive sodium balance was associated with a reduction in the next day's PaO2/FiO2 ratio (?=-0.36, P = 0.001) and an increased length of MV (linear regression analysis, P< 0.01). The cumulative fluid balance was not associated with either parameter. The cumulative positive sodium balance, not the cumulative positive fluid balance, is associated with respiratory dysfunction and an increased length of MV.
    No preview · Article · Mar 2015 · Critical care and resuscitation: journal of the Australasian Academy of Critical Care Medicine
  • Shailesh Bihari · Andrew D Bersten
    No preview · Article · Feb 2015 · Critical Care Medicine
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    Arnaud W. Thille · Alain Vuylsteke · Andrew Bersten
    [Show abstract] [Hide abstract] ABSTRACT: Guérin et al. retrospectively examined all open lung biopsies (OLB) performed in patients with non-resolving acute respiratory distress syndrome (ARDS), without an identified cause [1]. Eighty-three of the 113 patients who underwent OLB over a 16-year period (1998–2013) met the clinical criteria for ARDS according to the Berlin definition [2, 3], which represents 14 % of all patients they diagnosed with ARDS over that period (83/597). Does this report help address the relevance of OLB for management of ARDS today?The authors’ main objective was to assess the proportion of patients with diffuse alveolar damage (DAD); they observed that 58 % of patients with ARDS (48/83) had hallmark signs of DAD. These findings are similar to those reported by Thille et al. from postmortem reports [4], where DAD was present in 56 % (118/229) of patients who met ARDS clinical criteria for longer than 72 h. In both studies, the authors also reported the distribution of DAD according to the ARDS severity. ...
    Full-text · Article · Jan 2015 · Intensive Care Medicine
  • Shailesh Bihari · Andrew D. Bersten
    [Show abstract] [Hide abstract] ABSTRACT: Critically ill patients are at risk of sodium retention. Current practices of patient management lead to high amount of sodium being administered often inadvertently and lead to high daily and cumulative sodium balance. Positive sodium balance may have adverse outcomes in addition to those observed with positive fluid balance as sodium being an extracellular ion leads to expansion of extracellular spaces with concomitant intracellular dehydration.
    No preview · Article · Jan 2015
  • [Show abstract] [Hide abstract] ABSTRACT: We hypothesized that the thromboelastometry (ROTEM; Pentapharm GmbH, Munich, Germany) fibrinolysis parameter "maximum lysis" (ML) would have an independent inverse association with the severity of organ failure in sepsis. Selected adult patients with sepsis (n = 77) were recruited within 24 hours of antibiotic commencement. Patients with Sequential Organ Failure Assessment score higher than 1 (n = 57) were followed for 72 hours. Prothrombin fragments 1 + 2, plasminogen activator inhibitor-1 (aPAI-1), ROTEM, and routine coagulation tests were measured daily along with Sequential Organ Failure Assessment scores. The activity of functional aPAI-1 increased with increasing severity of organ failure (P = .01) and was higher as compared with healthy controls (95% confidence interval, -65.4 to -29.9; P < .001). There was a decreasing trend in ML with increased organ failure (P = .001); however, there was no trend in d-dimer. Among all tests, only the lower ML (ß = -0.38, P < .001) and higher international normalized ratio (INR; ß = 0.32, P = .002) values significantly contributed to greater severity of organ failure (R(2) = 0.35, F2,73 = 19.29, P < .001). Despite an increase in INR, the prothrombin fragment remained unchanged (P = .89). Strong correlations were observed between early (24 hours) increase in fibrinolysis and recovery of organ failures for 48 hours (ML: r = 0.679, P = .001; aPAI-1: r = 0.694, P < .001). Lower ML and higher INR values predicted greater severity of organ failure at presentation. Further studies are required, as ROTEM could aid selection of patients and guide interventions aimed at fibrinolysis in severe sepsis. Copyright © 2014 Elsevier Inc. All rights reserved.
    No preview · Article · Oct 2014 · Journal of Critical Care
  • [Show abstract] [Hide abstract] ABSTRACT: Background Chronic heart failure (CHF) following coronary artery ligation and myocardial infarction in the rat leads to a homeostatic reduction in surface tension with associated alveolar type II cell hyperplasia and increased surfactant content, which functionally compensates for pulmonary collagen deposition and increased tissue stiffness. To differentiate the effects on lung remodelling of the sudden rise in pulmonary microvascular pressure (Pmv) with myocardial infarction from its consequent chronic elevation, we examined a hypertensive model of CHF. Methods Cardiopulmonary outcomes due to chronic pulmonary capillary hypertension were assessed at six and 15 weeks following abdominal aortic banding (AAB) in the rat. Results At six weeks post-surgery, despite significantly elevated left ventricular end-diastolic pressure, myocardial hypertrophy and increased left ventricular internal circumference in AAB rats compared with sham operated controls (p≤0.003), lung weights and tissue composition remained unchanged, and lung compliance was normal. At 15 weeks post-surgery increased lung oedema was evident in AAB rats (p = 0.002) without decreased lung compliance or evidence of tissue remodelling. Conclusion Despite chronically elevated Pmv, comparable to that resulting from past myocardial infarction (LVEDP >19 mmHg), there is no evidence of pulmonary remodelling in the AAB model of CHF.
    No preview · Article · Sep 2014 · Heart, Lung and Circulation
  • D Bihari · S Prakash · A Bersten
    No preview · Article · Sep 2014 · Anaesthesia and intensive care

Publication Stats

3k Citations
818.82 Total Impact Points


  • 1986-2015
    • Flinders Medical Centre
      • Department of Cardiology
      Tarndarnya, South Australia, Australia
  • 1991-2012
    • Flinders University
      • • Flinders Medical Centre
      • • Department of Critical Care Medicine
      • • Department of Human Physiology
      Tarndarnya, South Australia, Australia
  • 2008
    • Catholic University of Louvain
      • School of Medicine
      Louvain-la-Neuve, WAL, Belgium
  • 2004
    • Royal Perth Hospital
      Perth City, Western Australia, Australia
  • 2002-2004
    • The Queen Elizabeth Hospital
      • Intensive Care Unit
      Tarndarnya, South Australia, Australia
  • 1999
    • Northern Inyo Hospital
      Bishop, California, United States