Modelling thirty-day mortality in the acute respiratory distress syndrome (ARDS) in an adult ICU

Publisher's copy made available with the permission of the publisher © Australian Society of AnaesthetistsVariables predicting thirty-day outcome from Acute Respiratory Distress Syndrome (ARDS) were analysed using Cox regression structured for time-varying covariates. Over a three-year period, 1996-1998, consecutive patients with ARDS (bilateral chest X-ray opacities, PaO₂/FiO₂ ratio of <200 and an acute precipitating event) were identified using a prospective computerized data base in a university teaching hospital ICU. The cohort, 106 mechanically ventilated patients, was of mean (SD) age 63.5 (15.5) years and 37% were female. Primary lung injury occurred in 45% and 24% were postoperative. ICU-admission day APACHE II score was 25 (8); ARDS onset time from ICU admission was 1 day (median: range 0-16) and 30 day mortality was 41% (95% CI: 33%-51%). At ARDS onset, PaO₂/FiO₂ ratio was 92 (31), 81% had four-quadrant chest X-ray opacification and lung injury score was 2.75 (0.45). Average mechanical ventilator tidal volume was 10.3 ml/ predicted kg weight. Cox model mortality predictors (hazard ratio, 95% CI) were: APACHE II score, 1.15 (1.09-1.21); ARDS lag time (days), 0.72 (0.58-0.89); direct versus indirect injury, 2.89 (1.45-5.76); PaO₂/FiO₂ ratio, 0.98 (0.97-0.99); operative versus non-operative category, 0.24 (0.09-0.63). Time-varying effects were evident for PaO₂/FiO₂ ratio, operative versus non-operative category and ventilator tidal volume assessed as a categorical predictor with a cut-point of 8 ml/kg predicted weight (mean tidal volumes, 7.1 (1.9) vs 10.7 (1.6) ml/kg predicted weight). Thirty-day survival was improved for patients ventilated with lower tidal volumes. Survival predictors in ARDS were multifactorial and related to patient-injury-time interaction and level of mechanical ventilator tidal volume.J. L. Moran, P. J. Solomon, V. Fox, M. Salagaras, P. J. Williams, K. Quinlan, A. D. Berstenhttp://www.aaic.net.au/Article.asp?D=200332

Reduced Surfactant Contributes to Increased Lung Stiffness Induced by Rapid Inspiratory Flow

Introduction The mechanism of fast inspiratory flow rate (VI′) induced lung injury is unclear. As fast VI′ increases hysteresis, a measure of surface tension at the air–liquid interface, surfactant release or function may be important. This experimental study examines the contribution of impaired surfactant release or function to dynamic-VILI. Methods Isolated perfused lungs from male Sprague Dawley rats were randomly allocated to four groups: a long or short inspiratory time (Ti = 0.5 s; slow VI′ or Ti = 0.1 s; fast VI′) at PEEP of 2 or 10 cmH₂O. Tidal volume was constant (7 ml/kg), with f = 60 breath/min. Forced impedance mechanics (tissue elastance (Htis), tissue resistance (Gtis) and airway resistance (Raw) were measured at 30, 60 and 90 min following which the lung was lavaged for surfactant phospholipids (PL) and disaturated PL (DSP). Results Fast VI′ resulted in a stiffer lung. Concurrently, PL and DSP were decreased in both tubular myelin rich and poor fractions. Phospholipid decreases were similar with PEEP. In a subsequent cohort, laser confocal microscopy-based assessment demonstrated increased cellular injury with increased VI′ at both 30 and 90 min ventilation. Conclusion Rapid VI′ may contribute to ventilator induced lung injury (VILI) through reduced surfactant release and/or more rapid reuptake despite unchanged tidal stretch.Andrew D. Bersten, Malgorzata Krupa, Kim Griggs, Dani, Louise Dixo

Disordered swallowing associated with prolonged oral endotracheal intubation in critical illness

Abstract not availableMistyka S. Schar, Taher I. Omari, Robert J. Fraser, Andrew D. Bersten and Shailesh Bihar

ADMA and homoarginine independently predict mortality in critically ill patients

groups. We investigated whether arginine metabolites are associated with mortality in patients with critical illness and whether associations are independent of other factors affecting prognosis in an Intensive Care Unit (ICU). Methods: 1155 acutely unwell adult patients admitted to a mixed medical-surgical ICU were studied. Arginine, asymmetric dimethyl-L-arginine (ADMA), monomethyl-L-arginine (MMA), symmetric dimethyl-L-arginine (SDMA) and L-homoarginine were measured in a plasma sample collected at admission to ICU by liquid chromatography tandem mass spectrometry. Risk of death score was calculated using data submitted to the Australia and New Zealand Intensive Care Society. Results: In this cohort, 163 patients (14.1%) died. ADMA (odds ratio = 1.159 (1.033–1.300) per 0.1 μmol/L increment, p = 0.012), homoarginine (odds ratio = 0.963 (0.934–0.992), p = 0.013) and risk of death score (odds ratio = 1.045 (1.037–1.053) per 1% increment, p < 0.001) were independently associated with mortality in ICU patients. The area under the receiver operator characteristic curve for risk of death score, ADMA and homoarginine combined for mortality was greater than for risk of death score alone (0.815 (95% CI 0.790–0.837) vs 0.796 (95% CI 0.781–0.820), p = 0.019). Other arginine metabolites were not independently associated with mortality. Conclusions: ADMA is positively and homoarginine negatively associated with mortality in ICU patients, independent of other clinical factors. Measuring ADMA and homoarginine may refine models to predict ICU mortality. Reducing ADMA and increasing homoarginine are potential therapeutic targets to reduce mortality in critically ill patients.Tien F. Lee, Andrew D. Bersten, Leonie K. Heilbronn, Angelo Zinellu, Ciriaco Carru, Salvatore Sotgia, Arduino A. Mangoni, Morton G. Bur

Efficacy and safety of 20% albumin fluid loading in healthy subjects: A comparison of four resuscitation fluids

Recently, buffered salt solutions and 20% albumin (small volume resuscitation) have been advocated as an alternative fluid for intravenous resuscitation. The relative comparative efficacy and potential adverse effects of these solutions have not been evaluated. In a randomized, double blind, cross-over study of six healthy male subjects we compared the pulmonary and hemodynamic effects of intravenous administration of 30 ml/kg of 0.9% saline, Hartmann’s solution and 4% albumin, and 6 ml/kg of 20% albumin (albumin dose equivalent). Lung tests (spirometry, ultrasound, impulse oscillometry, diffusion capacity, and plethysmography), two- to three-dimensional Doppler echocardiography, carotid applanation tonometry, blood gases, serum/urine markers of endothelial, and kidney injury were measured before and after each fluid bolus. Data were analyzed with repeated measures ANOVA with effect of fluid type examined as an interaction. Crystalloids caused lung edema [increase in ultrasound B line (P = 0.006) and airway resistance (P = 0.009)], but evidence of lung injury [increased angiopoietin-2 (P = 0.019)] and glycocalyx injury [increased syndecan (P = 0.026)] was only observed with 0.9% saline. The colloids caused greater left atrial stretch, decrease in lung volumes, and increase in diffusion capacity than the crystalloids, but without pulmonary edema. Stroke work increased proportionally to increase in preload with all four fluids (R2 = 0.71). There was a greater increase in cardiac output and stroke volume after colloid administration, associated with a reduction in afterload. Hartmann’s solution did not significantly alter ventricular performance. Markers of kidney injury were not affected by any of the fluids administrated. Bolus administration of 20% albumin is both effective and safe in healthy subjects.Shailesh Bihari, Ubbo F Wiersema, Rebecca Perry, David Schembri, Tara Bouchier, Dani Dixon, Teresa Wong, and Andrew D Berste