for the DahLIA Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group 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.

Background Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS.Methods The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO 2 /FiO 2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50 X 10⁹/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0•9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60. Prespecified secondary outcomes, which are exploratory, included development of ARDS to day 5 among at-risk patients, deterioration of the Murray Lung Injury Score (MLIS) to day 5, mortality at day 60, residence of survivors at day 60, and serious adverse events. Analyses followed the intention-to-treat principle. There was no imputation of missing data. The trial is registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612000418875 .

Aural foreign bodies are a frequent presentation to the ED. Recognition of patients requiring early specialist referral is important. Adults present with a different profile of aural foreign objects to children and require different management. The use of cotton tips or cotton wool in the external ear canal and silicone ear plugs should be discouraged.

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The management of acute optic neuritis by neurologists and ophthalmologists in the north west of England was assessed in the light of the Optic Neuritis Treatment Trial (ONTT) recommendations. A questionnaire on a fictitious case of typical unilateral optic neuritis was mailed to all consultant ophthalmologists and neurologists working in the North West and Merseyside Health Authorities. They were then asked to comment on management of the case. Fifty two out of 86 ophthalmologists and 20 out of 28 neurologists replied. The overall response rate was 63%. Sixty five per cent of neurologists and 46% of ophthalmologists would investigate a typical case of acute optic neuritis further. Forty six per cent of neurologists and 36% of ophthalmologists were likely to arrange MRI of the brain or orbit. Significantly more neurologists (55%) than ophthalmologists (9%) chose to treat with intravenous methylprednisolone (p<0.005). Significantly more ophthalmologists (64%) than neurologists (32%) chose not to give steroids (p<0.025). Oral prednisolone alone was rarely selected for treatment. Respondents were more likely to discuss multiple sclerosis with the referring doctor than with the patient. Only 32% of ophthalmologists and 20% of neurologists would clearly mention the possibility of improvement to the patient. Clear differences in practice between ophthalmologists and neurologists remain. A consensus on practice guidelines on the issues raised might be useful.