Introduction: A protocol of no sedation has been shown to reduce the time patients receive mechanical ventilation and to reduce intensive care and total hospital length of stay. The long-term psychological effects of this strategy have not yet been described. The purpose of the study was to test whether a strategy of no sedation alters long-term psychological outcome compared with a standard strategy with sedation. Methods: During intensive care stay, 140 patients requiring mechanical ventilation were randomized to either no sedation or sedation with daily interruption of sedation. This study was done as a single-blinded cohort study. After discharge, patients were interviewed by a neuropsychologist assessing quality of life, depression, anxiety, and posttraumatic stress disorder. Results: Two years after randomization, 38 patients were eligible for interview, and 26 patients were interviewed (13 from each group). No difference was found with respect to quality of life (Medical Outcome Study, 36-item short-form health survey). Both mental and physical components were nonsignificant. The Beck depression index was low in both groups (one patient in intervention group versus three patients in the control group were depressed, p = 0.32). Evaluated with the Impact of Events Scale, both groups had low stress scores (one in the intervention group versus two in the control group had scores greater than 32; p = 0.50). State anxiety scores were also low (28 in the control group versus 30 in the intervention group, p = 0.58). Conclusions: Our data suggest that a protocol of no sedation applied to critically ill patients undergoing mechanical ventilation does not increase the risk of long-term psychological sequelae after intensive care compared with standard treatment with sedation.

Introduction: Intensive care unit (ICU) patients are predisposed to thromboembolism. Routine prophylactic anticoagulation is widely recommended. Low-molecular-weight heparins, such as enoxaparin, are increasingly used because of predictable pharmacokinetics. This study aims to determine the subcutaneous (SC) dose of enoxaparin that would give the best anti-factor Xa levels in ICU patients. Methods: The 72 patients admitted to a mixed ICU at Odense University Hospital (OUH) in Denmark were randomised into four groups to receive 40, 50, 60, or 70 mg SC enoxaparin for a period of 24 hours. Anti-factor Xa activity (aFXa) was measured before, and at 4, 12, and 24 hours after administration. An AFXa level between 0.1 to 0.3 IU/ml was considered evidence of effective antithrombotic activity. Results: Median peak (4 hours after administration), aFXa levels increased significantly with an increase in enoxaparin dose, from 0.13 IU/ml at 40 mg, to 0.14 IU/ml at 50 mg, 0.27 IU/ml at 60 mg, and 0.29 IU/ml at 70 mg (P = 0.002). At 12 hours after administration, median aFXa levels were still within therapeutic range for those patients who received 60 mg (P = 0.02). Conclusions: Our study confirmed that a standard dose of 40 mg enoxaparin yielded subtherapeutic levels of aFXa in critically ill patients. Higher doses resulted in better peak aFXa levels, with a ceiling effect observed at 60 mg. The present study seems to suggest inadequate dosage as one of the possible mechanisms for the higher failure rate of enoxaparin in ICU patients. Trial Registration: ISRCTN03037804

Purpose We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference − 4.3%; 99% confidence interval (CI) − 11.7–3.0; relative risk 0.89; 0.72–1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI − 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (− 3 to 10; P = 0.22). Conclusion Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.

Through 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.

Background: The coronavirus disease 2019 (COVID‐19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low‐dose corticosteroids have proven clinical benefit in patients with severe COVID‐19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID‐19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID‐19 is unclear.Methods: The COVID STEROID 2 trial is an investigator‐initiated, international, parallel‐grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID‐19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all‐cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health‐related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol.Discussion: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID‐19 patients with severe hypoxia with important implications for patients, their relatives and society.