Delirium in ventilated patients receiving fentanyl and morphine for Analgosedation: Findings from the ANALGESIC trial.

PURPOSE: The differential effect of fentanyl vs. morphine analgosedation on the development of hospital inpatient delirium in patients receiving mechanical ventilation is unknown. We aimed to compare the incidence of coding for delirium and antipsychotic medication use in patients treated with fentanyl vs. morphine in the ANALGESIC trial. MATERIALS AND METHODS: We obtained data from a cluster randomized, cluster crossover trial of fentanyl vs. morphine for analgosedation on antipsychotic use and coding diagnosis of delirium and compared these outcomes according to treatment allocation. We assessed the relationship between opioid choice and dose, hospital inpatient delirium, and outcomes. RESULTS: Among 681 patients enrolled in the ANALGESIC trial, 160/344 (46.5%) in the fentanyl group vs. 132/337 (39.1%) in the morphine group (absolute difference 7.34% [95% CI -0.9 to 14.78]; RR: 1.19 [95%CI 1.00 to 1.41]; p = 0.053) developed hospital inpatient delirium. Antipsychotic use was linearly related to opioid dose. Antipsychotic use was not associated with increased mortality. CONCLUSIONS: Fentanyl is associated with a higher incidence of hospital inpatient delirium when used for analgosedation compared with morphine, and the dose of opioid is linearly related to the need for antipsychotic medication administration. The role of analgosedation in promoting delirium requires further investigation.

Expired Drugs in the Remote Environment.

INTRODUCTION: The British Antarctic Survey Medical Unit works in a very remote area of the world, with several Antarctic bases receiving only a single annual resupply of consumable goods. Pharmaceuticals supplied in this manner will often be approaching or past the end of their nominal shelf life before the following year's resupply. Drugs are transported from the UK via ship; the hold is not temperature controlled, and the ship crosses through the tropics (air temperature 25-30°C for approximately 3 wk). The drugs then must be transported from the ship to the base, often in temperatures substantially below freezing. This study assessed the stability of 5 expired drugs (atropine, nifedipine, flucloxacillin, naproxen, and bendroflumethiazide) returned from Antarctic bases. METHODS: Drugs were opportunistically obtained and tested using stability-indicating assays. RESULTS: All tested drugs were stable. CONCLUSIONS: The results suggest that the studied drugs may be stable beyond expiry, even when not maintained in strictly temperature-controlled conditions.

Poles Apart: Comparing Trends of Alien Hymenoptera in New Zealand with Europe (DAISIE).

Developing generalisations of invasive species is an important part of invasion biology. However, trends and generalisations from one part of the world may not necessarily hold elsewhere. We present the first inventory and analysis of all Hymenoptera alien to New Zealand, and compare patterns from New Zealand with those previously published from Europe (DAISIE). Between the two regions there was broad correlation between families with the highest number of alien species (Braconidae, Encyrtidae, Pteromalidae, Eulophidae, Formicidae, Aphelinidae). However, major differences also existed. The number of species alien to New Zealand is higher than for Europe (334 vs 286), and major differences include: i) the much lower proportion of intentionally released species in New Zealand (21% vs 63% in Europe); and ii) the greater proportion of unintentionally introduced parasitoids in New Zealand (71.2% vs 22.6%). The disharmonic 'island' nature of New Zealand is shown, as a high proportion of families (36%) have no native representatives, and alien species also represent >10% of the native fauna for many other families. A much larger proportion of alien species are found in urban areas in New Zealand (60%) compared to Europe (~30%), and higher numbers of alien species were present earlier in New Zealand (especially <1950). Differences in the origins of alien species were also apparent. Unlike Europe, the New Zealand data reveals a change in the origins of alien species over time, with an increasing dominance of alien species from Australasia (a regional neighbour) during the past 25 years. We recommend that further effort be made towards the formation, and analysis, of regional inventories of alien species. This will allow a wider range of taxa and regions to be examined for generalisations, and help assess and prioritise the risk posed by certain taxa towards the economy or environment.

Diagnostic accuracy of pulmonary host inflammatory mediators in the exclusion of ventilator-acquired pneumonia.

BACKGROUND: Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare. OBJECTIVES: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. METHODS: A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >10(4) colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1ß), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. RESULTS: Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (p<0.001). The area under the receiver operator characteristic curve for IL-1ß was 0.81; IL-8, 0.74; MMP-8, 0.76; MMP-9, 0.79 and HNE, 0.78. A combination of IL-1ß and IL-8, at the optimal cut-point, excluded VAP with a sensitivity of 100%, a specificity of 44.3% and a post-test probability of 0% (95% CI 0% to 9.2%). CONCLUSIONS: Low BALF IL-1ß in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

A national survey of the diagnosis and management of suspected ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) affects up to 20% of patients admitted to intensive care units (ICU). It is associated with increased morbidity, mortality and healthcare costs. Despite published guidelines, variability in diagnosis and management exists, the extent of which remains unclear. We sought to characterise consultant opinions surrounding diagnostic and management practice for VAP in the UK. METHODS: An online survey was sent to all consultant members of the UK Intensive Care Society (n=∼1500). Data were collected regarding respondents' individual practice in the investigation and management of suspected VAP including use of diagnostic criteria, microbiological sampling, chest X-ray (CXR), bronchoscopy and antibiotic treatments. RESULTS: 339 (23%) responses were received from a broadly representative spectrum of ICU consultants. All respondents indicated that microbiological confirmation should be sought, the majority (57.8%) stating they would take an endotracheal aspirate prior to starting empirical antibiotics. Microbiology reporting services were described as qualitative only by 29.7%. Only 17% of respondents had access to routine reporting of CXRs by a radiologist. Little consensus exists regarding technique for bronchoalveolar lavage (BAL) with the reported volume of saline used ranging from 5 to 500 mL. 24.5% of consultants felt inadequately trained in bronchoscopy. CONCLUSIONS: There is wide variability in the approach to diagnosis and management of VAP among UK consultants. Such variability challenges the reliability of the diagnosis of VAP and its reported incidence as a performance indicator in healthcare systems. The data presented suggest increased radiological and microbiological support, and standardisation of BAL technique, might improve this situation.