Failure of combination oral oseltamivir and inhaled zanamivir antiviral treatment in ventilator- and ECMO-treated critically ill patients with pandemic influenza A (H1N1)v.

OBJECTIVE: The objective of this study was to describe the clinical course of severe and complicated pandemic (H1N1)v infection treated with oral oseltamivir and inhaled zanamivir in a series of intensive care patients. METHODS: We investigated a case series of patients with respiratory failure and a positive (H1N1)v real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Treatment consisted of oseltamivir tablets 75 mg × 4 daily in a nasogastric tube plus zanamivir intravenous (i.v.) solution 25 mg × 4 daily as inhalation. Ventilator inspiratory plateau airway pressure in the ventilator was kept below 30 cmH2O, PaO2 above 8 kPa and pH above 7.30. If this could not be achieved, inhalational nitric oxide (NO) was added or extracorporeal membrane oxygenation (ECMO) was initiated. RESULTS: Twenty-one patients were admitted, with a median age of 50 y (range 6-69 y). Five patients (23.8%) died in the intensive care unit (ICU) and 1 patient died 2 weeks after ICU discharge. Nine patients received ECMO treatment, of whom 3 died during ECMO (33.3%; 3/9) and 1 at 2 weeks after. The mortality in patients not receiving ECMO treatment was 16.6% (2/12). Sixteen patients (76%) were influenza PCR-positive on day 7 after the start of antiviral treatment. Irreversible presumed lung fibrosis complicated with pneumothorax was common. A high Murray score at admission was significantly associated with a fatal outcome. CONCLUSIONS: The mortality in these patients was high despite combined antiviral treatment with oseltamivir and zanamivir. Patients shed virus for a long time despite intensive therapy. Optimal management of patients with bilateral pneumonia and respiratory failure caused by (H1N1)v still needs to be determined.

Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial.

BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS/DESIGN: The Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point. DISCUSSION: The TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.

[Use of anabolic androgenic steroids, growth hormone and erythropoietin by patients in general practice]. / Brug af androgene anabole steroider, erytropoietin og vaeksthormon som dopingmiddel blandt patienter i almen praksis.

INTRODUCTION: The goal of this study was to investigate the use and side effects of anabolic androgenic steroids (AASs), growth hormone (GH), erythropoietin (EPO) and other enhancing drugs by patients in general practice. MATERIALS AND METHODS: In a questionnaire, 702 general practitioners (GPs) in Denmark were asked to estimate the number of their patients who within the preceding year had admitted to using or were highly suspected of having used AASs, GH, EPO or other enhancing drugs. In addition, they were asked to describe the possible side effects of their use. RESULTS: Of 571 eligible GPs, 119 had within the preceding year treated patients who had admitted to or were highly suspected of having used AASs, GH, EPO or other enhancing drugs. 182 users were reported by the GPs during that period; 180 (99%) were males, and 156 (86%) were between 20 and 40 years of age. 125 of the patients (69%) had admitted the use to the GP; AASs had been used by 123 patients (98%). EPO was not reported in any case, but GH had been used by 9 patients (7%). 127 (70%) of the patients had experienced side effects, and 87 (49%) had contacted the GP due to these side effects. CONCLUSION: The use and side effects of AAS are commonly reported in general practice, whereas the use and side effects of GH and EPO seem to be uncommon. Their use is mainly by men under 40 years of age. The use of AAS is often connected with dermatological and musculoskeletal side effects. It is recommended also to consider possible use of AASs when consulted by a patient with unexplained symptoms of cardiovascular disease, psychological or sexual dysfunction, gynaecomastia or liver dysfunction.