BackgroundThrough many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level. No randomised trial has been conducted comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.The objective is to assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients.Methods/DesignThe non-sedation (NONSEDA) trial is an investigator-initiated, randomised, clinical, parallel-group, multinational trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.Inclusion criteria are mechanically ventilated patients with expected duration of mechanical ventilation >24 hours.Exclusion criteria are non-intubated patients, patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2 < 9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.Experimental intervention is non-sedation supplemented with pain management during mechanical ventilation.Control intervention is sedation with a daily wake-up trial.The primary outcome will be all cause mortality at 90 days after randomization. Secondary outcomes will be: days until death throughout the total observation period; coma- and delirium-free days; highest RIFLE score; days until discharge from the intensive care unit (within 28 days); days until the participant is without mechanical ventilation (within 28 days); and proportion of patients with a major cardiovascular outcome. Explorative outcomes will be: all cause mortality at 28 days after randomisation; days until discharge from the intensive care unit; days until the participant is without mechanical ventilation; days until discharge from the hospital; organ failure.Trial size: we will include 700 participants (2 × 350) in order to detect or reject 25% relative risk reduction in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%).DiscussionThe trial investigates potential benefits of non-sedation. This might have large impact on the future treatment of mechanically ventilated critically ill patients.Trial registerClinicalTrials.gov NCT0196768, 09.01.2014.Electronic supplementary materialThe online version of this article (doi:10.1186/1745-6215-15-499) contains supplementary material, which is available to authorized users.
Changes in the lipid composition of cardiac myocytes have been reported during cardiac hypertrophy, cardiomyopathy, and infarction. Because a recent study indicates a relation between low phosphatidylinositol-bisphosphate (PIP 2 ) levels and reduced intercellular coupling, we tested the hypothesis that agonist-induced changes in PIP 2 can result in a reduction of the functional coupling of cardiomyocytes and, consequently, in changes in conduction velocity. Intercellular calmodulin, or arachidonic acid production did not affect the response to either angiotensin II or noradrenaline. Furthermore, decreasing or increasing PIP 2 also decreased and increased intercellular coupling, respectively. This supports the role of PIP 2 in the regulation of intercellular coupling. In beating myocytes, conduction velocity was reduced by angiotensin II stimulation, and recovery after wash out was prevented by inhibition of PIP 2 production. Reductions in PIP 2 inhibit intercellular coupling in cardiomyocytes, and stimulation by physiologically relevant agonists reduces intercellular coupling by this mechanism. The reduction in intercellular coupling lowered conduction velocity.
Background: Acute kidney injury (AKI) is common following abdominal aortic surgery. NGAL might be useful in the early diagnosis of AKI since it responds rapidly to ischaemic damage. Methods: Twenty patients undergoing elective infrarenal aortic surgery. U-NGAL was measured before surgery and 24, 48 and 72 hours postoperatively. Results: No significant rise in U-NGAL was seen in patients without AKI at any time. All patients who developed dialysisdependent AKI had a significant increase in U-NGAL. Conclusion: U-NGAL did not increase solely in response to the surgical trauma. U-NGAL may be a useful biomarker for AKI following abdominal aortic surgery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.