133 research outputs found
Disordered swallowing associated with prolonged oral endotracheal intubation in critical illness
No full textAbstract not availableMistyka S. Schar, Taher I. Omari, Robert J. Fraser, Andrew D. Bersten and Shailesh Bihar
Preclinical research in critical care - the Australasian perspective
No full textEditorialShailesh Bihari, Matthew Maiden, Adam Deane, Ralph Fuchs, John Fraser, Andrew D Bersten and Rinaldo Bellom
Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS): meta-analysis
No full textObjective To systematically review the efficacy of steroids in the prevention of acute respiratory distress syndrome (ARDS) in critically ill adults, and treatment for established ARDS.Data sources Search of randomised controlled trials (1966-April 2007) of PubMed, Cochrane central register of controlled trials, Cochrane database of systematic reviews, American College of Physicians Journal Club, health technology assessment database, and database of abstracts of reviews of effects.Data extraction Two investigators independently assessed trials for inclusion and extracted data into standardised forms; differences were resolved by consensus.Data synthesis Steroid efficacy was assessed through a Bayesian hierarchical model for comparing the odds of developing ARDS and mortality (both expressed as odds ratio with 95% credible interval) and duration of ventilator free days, assessed as mean difference. Bayesian outcome probabilities were calculated as the probability that the odds ratio would be ?1 or the probability that the mean difference would be ?0. Nine randomised trials using variable dose and duration of steroids were identified. Preventive steroids (four studies) were associated with a trend to increase both the odds of patients developing ARDS (odds ratio 1.55, 95% credible interval 0.58 to 4.05; P(odds ratio ?1)=86.6%), and the risk of mortality in those who subsequently developed ARDS (three studies, odds ratio 1.52, 95% credible interval 0.30 to 5.94; P(odds ratio ?1)=72.8%). Steroid administration after onset of ARDS (five studies) was associated with a trend towards reduction in mortality (odds ratio 0.62, 95% credible interval 0.23 to 1.26; P(odds ratio ?1)=6.8%). Steroid therapy increased the number of ventilator free days compared with controls (three studies, mean difference 4.05 days, 95% credible interval 0.22 to 8.71; P(mean difference ?0)=97.9%). Steroids were not associated with increase in risk of infection.Conclusions A definitive role of corticosteroids in the treatment of ARDS in adults is not established. A possibility of reduced mortality and increased ventilator free days with steroids started after the onset of ARDS was suggested. Preventive steroids possibly increase the incidence of ARDS in critically ill adults
Meta-analysis of controlled trials of ventilator therapy in acute lung injury and acute respiratory distress syndrome: an alternative perspective
No full textObjective: The role of protective ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is controversial. Evidence was sought from published randomised trials for a consistent treatment effect of protective ventilation and any covariate modification. Design: Meta-analysis of protective ventilation trials in ALI/ ARDS and meta-regression of covariates on treatment effect (log odds ratio), with respect to 28-day mortality. Heterogeneity impact on the meta-analysis was assessed by the H statistic (substantial impact, >1.5) and graphical analysis. Five trials with a total of 1,202 patients were considered. Measurements and results: Average 28-day mortality was 0.40 in the treatment group (protective ventilation, n=605) vs. 0.46 in the control group (control ventilation, n=597). The treatment effect (odds ratio) was: fixed-effects, 0.71 (95% CI 0.56–0.91, p=0.006; heterogeneity, p=0.06) and random effects: 0.80 (95% CI 0.49–1.31, p=0.37). Heterogeneity impact (H statistic=1.50) was adjudged as modest. The treatment effect was significant and (a) favoured protective ventilation for a tidal volume less than 7.7 ml/kg predicted (treatment group) and a mean plateau pressure of 30 cmH2O or higher (control group) but was not influenced by plateau pressure 21– 30 cmH2O (treatment group) and (b) depended upon plateau pressure difference greater than 5–7 cmH2O between protective ventilation and standard ventilation. Conclusions: Overall treatment effect estimate favoured protective ventilation but did not achieve statistical significance. Protective ventilation depended upon threshold levels of tidal volume, plateau pressure, and plateau pressure difference.John L. Moran, Andrew D. Bersten and Patricia J. Solomo
Modelling survival in acute severe illness: Cox versus accelerated failure time models
No full textBackgroundThe Cox model has been the mainstay of survival analysis in the critically ill and time-dependent covariates have infrequently been incorporated into survival analysis.ObjectivesTo model 28-day survival of patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), and compare the utility of Cox and accelerated failure time (AFT) models.MethodsProspective cohort study of 168 adult patients enrolled at diagnosis of ALI in 21 adult ICUs in three Australian States with measurement of survival time, censored at 28 days. Model performance was assessed as goodness-of-fit [GOF, cross-products of quantiles of risk and time intervals (P > or = 0.1), Cox model] and explained variation ('R2', Cox and ATF).ResultsOver a 2-month study period (October-November 1999), 168 patients with ALI were identified, with a mean (SD) age of 61.5 (18) years and 30% female. Peak mortality hazard occurred at days 7-8 after onset of ALI/ARDS. In the Cox model, increasing age and female gender, plus interaction, were associated with an increased mortality hazard. Time-varying effects were established for patient severity-of-illness score (decreasing hazard over time) and multiple-organ-dysfunction score (increasing hazard over time). The Cox model was well specified (GOF, P > 0.34) and R2 = 0.546, 95% CI: 0.390, 0.781. Both log-normal (R2 = 0.451, 95% CI: 0.321, 0.695) and log-logistic (R2 0.470, 95% CI: 0.346, 0.714) AFT models identified the same predictors as the Cox model, but did not demonstrate convincingly superior overall fit.ConclusionsTime dependence of predictors of survival in ALI/ARDS exists and must be appropriately modelled. The Cox model with time-varying covariates remains a flexible model in survival analysis of patients with acute severe illness.John L. Moran, Andrew D. Bersten, Patricia J. Solomon, Cyrus Edibam, Tamara Hunt and The Australian and New Zealand Intensive Care Society Clinical Trials Grou
The efficacy of loop diuretics in acute renal failure: Assessment using Bayesian evidence synthesis techniques
No full textObjectiveTo quantify the therapeutic efficacy of loop diuretics in acute renal failure using Bayesian evidence synthesis, because despite widespread use, the role of diuretics is controversial.Data sourceRandomized controlled trials or nonrandomized studies, 1966 to January 2007, identified from MEDLINE and EMBASE databases and manual bibliographic search.Study selectionStudies with assessable predefined end points, exclusive of those pertaining to acute renal failure prophylaxis or chronic renal failure.Data extractionData extraction was performed jointly by the first two authors; independent study assessment was via standard checklist, unblinded.Data synthesisThe primary outcome was mortality; secondary outcomes were time to renal function normalization and total number of dialyses. Bayesian hierarchical random effects estimates of treatment effects were determined as risk ratio for mortality, incidence rate ratio for dialysis number, and mean difference for continuous measures. Bayesian outcome probabilities were calculated as probability (P) that risk ratio or incidence rate ratio of loop diuretics >1 and probability that mean difference >0. Five randomized controlled trials and eight nonrandomized studies were identified. Loop diuretics were not associated with decreased mortality in either randomized controlled trials or nonrandomized studies: overall risk ratio 1.10; 95% credible interval 0.85, 1.42; P(risk ratio >1) > 83.8%. The oliguric period was decreased by loop diuretics: overall mean difference -7.70 days; 95% credible interval -12.51, -2.08; P (mean difference >0) = 0.7%. Although the dialysis rate credible interval, loop diuretics vs. control, spanned unity (incidence rate ratio 0.71; 95% credible interval 0.47, 1.06), the probability that the incidence rate ratio exceeded unity indicated a substantial benefit: P (incidence rate ratio >1 = 4.1%. Uremic duration was not substantially different, loop diuretics vs. control: overall mean difference -1.54 days; 95% credible interval -5.62, 2.46; P [mean difference >0] = 17.8%).ConclusionsLoop diuretics were not associated with improved survival benefit in acute renal failure, despite reduction in oliguric period and high probability of a significant reduction in dialysis numbers. Further studies to clarify this dichotomy appear mandated.Sriram Sampath, John L. Moran, Petra L. Graham, Sue Rockliff, Andrew D. Bersten, Keith R. Abram
Does hyperglycemia affect arginine metabolites in critically ill patients? A prospective cohort and in vitro study
No full textAbstract Background Changes in the arginine metabolites asymmetric dimethyl-L-arginine (ADMA) and L-homoarginine and acute blood glucose concentrations have been shown to cause endothelial dysfunction and be independently associated with mortality in Intensive Care Unit (ICU) patients. The aim of this study was to investigate whether hyperglycemia potentially modulates these arginine metabolite concentrations to provide a mechanism that may link hyperglycemia and mortality in this patient group. Methods A clinical and in vitro study were undertaken. Glucose, glycosylated hemoglobin-A1c (HbA1c) and the stress hyperglycemia ratio (SHR) (to quantify absolute, chronic and relative hyperglycemia respectively) were measured in 1155 acutely unwell adult patients admitted to a mixed medical-surgical ICU. SHR was calculated by dividing the admission glucose by the estimated average glucose over the last 3 months, which was derived from HbA1c. ADMA and l-homoarginine were measured in a plasma sample collected at admission to ICU by liquid chromatography tandem mass spectrometry. The activity of dimethylarginine-dimethylaminohydrolase 1 (DDAH1), the main enzyme regulating ADMA concentrations, was assessed at varying glucose concentrations in vitro by quantifying the conversion of ADMA to citrulline in HEK293 cells that overexpress DDAH1. Results In the clinical study, plasma ADMA was not significantly associated with any measure of hyperglycemia. L-homoarginine was positively associated with glucose (β = 0.067, p = 0.018) and SHR (β = 0.107, p < 0.001) after correction for glomerular filtration rate. However, as l-homoarginine is a negative predictor of mortality, the direction of these associations are the opposite of those expected if hyperglycemia was affecting mortality via changes in l-homoarginine. In vitro DDAH1 activity was not significantly influenced by glucose concentrations (p = 0.506). Conclusion In critically ill patients the association between relative hyperglycemia and mortality is not mediated by changes in ADMA or L-homoarginine. Trial registration ANZCTR Trial ID ACTRN12615001164583
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