Clinical prediction of weaning and extubation in Australian and New Zealand intensive care units

Our objective was to describe, in Australian and New Zealand adult intensive care units, the relative frequency in which various clinical criteria were used to predict weaning and extubation, and the weaning methods employed

Study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-II (HAS FLAIR-II) trial

Background: Fluid bolus therapy with 20% albumin may shorten the duration of vasopressor therapy in patients after cardiac surgery. Objective: To describe the study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-II (HAS FLAIR-II) trial. Design, Setting, Participants And Intervention: HAS FLAIR-II is a phase 2b, multicentre, parallel group, open-label, randomised controlled trial that will be conducted at six Australian intensive care units. Patients requiring fluid bolus therapy after cardiac surgery will be randomly assigned in a 1:1 ratio to the intervention of fluid bolus therapy with 20% albumin or a comparator of fluid bolus therapy with a crystalloid solution. Main Outcome Measures: The primary outcome measure is the cumulative duration of vasopressor therapy. Secondary outcomes include vasopressor use, service utilisation, and mortality. All analyses will be conducted on an intention-to-treat basis. Results And Conclusion: The study protocol and statistical analysis plan will guide the conduct and analysis of the HAS FLAIR-II trial, such that analytical and reporting biases are minimised.Geoffrey Wigmore, Adam M Deane, James Anstey, Michael Bailey, Shailesh Bihari, Glenn Eastwood, Rashmi Ghanpur, Matthew J Maiden, Jeffrey J Presneill, Jaishankar Raman and Rinaldo Bellomo, for the HAS FLAIR-II trial investigator

Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing beta-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 mu g/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the 12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5 mu g/kg/d produced only minor eosinophilia, and doses of 7.5 to 20 mu g/kg were required to induce greater than or equal to 1.5-fold neutrophil increments in the 3 patients who underwent dose-escalation. However, neutrophilic responses to 5 mu g/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4), In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1% +/- 8.9%; P = .042) or interleukin-3 (IL-3: 19.3% +/- 7.7%; P = .063), both of which utilize the beta-common chain of the GM-CSF receptor complex, were reduced among patients with acquired PAP (n = 4) compared with normal bone marrow donor controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one individual who had complete resolution of lung disease during the period of study, this was temporally associated with correction of this defective in vitro response to GM-CSF and IL-3 on serial assessment. These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease. Based on these observations, we propose a model of the pathogenesis of acquired PAP that suggests the disease arises as a consequence of an acquired clonal disorder within the hematopoietic progenitor cell compartment. (C) 1998 by The American Society of Hematology

Outcomes six-months after 100% or 70% of enteral calorie requirements during critical illness (TARGET): a randomized controlled trial

Rationale: The long-term effects of delivering approximately 100% of recommended calorie intake via the enteral route during critical illness compared to a lesser amount of calories are unknown. Objectives: Our hypotheses were that achieving approximately 100% of recommended calorie intake during critical illness would increase quality of life scores, return to work and key life activities and reduce death and disability six months later. Methods: We conducted a multicenter, blinded, parallel group, randomized clinical trial, with 3957 mechanically ventilated critically ill adults allocated to energy-dense (1.5 kcal/ml) or routine (1.0 kcal/ml) enteral nutrition. Measurements and Main Results: Participants assigned energy-dense nutrition received more calories (% recommended energy intake, mean (SD) (energy-dense: 103% (28) vs. usual: 69% (18)). Mortality at day-180 was similar (560/1895 (29.6%) vs. 539/1920 (28.1%); relative risk 1.05 (95%CI, 0.95 to 1.16)). At a median [IQR] of 185 [182, 193] days after randomization, 2492 survivors were surveyed and reported similar quality of life (EuroQol five dimensions five-level quality of life questionnaire visual analogue scale, median [IQR]: 75 [60-85]; group difference: 0 (95%CI, 0 to 0)). Similar numbers of participants returned to work with no difference in hours worked or effectiveness at work (n=818). There was no observed difference in disability (n=1208) or participation in key life activities (n=705). Conclusions: The delivery of approximately 100% compared to 70% of recommended calorie intake during critical illness does not improve quality of life, or functional outcomes, or increase the number of survivors six months later.Adam M. Deane, Lorraine Little, Rinaldo Bellomo, Marianne J. Chapman, Andrew R. Davies, Suzie Ferrie, Michael Horowitz, Sally Hurford, Kylie Lange, Edward Litton, Diane Mackle, Stephanie O’Connor, Jane Parker, Sandra L. Peake, Jeffrey J. Presneill, Emma J. Ridley, Vanessa Singh, Frank van Haren, Patricia Williams, Paul Young, and Theodore J. Iwashyna, on behalf of the TARGET Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Grou