Statin use and risk of delirium in the critically ill.

RATIONALE: Delirium is common in intensive care unit (ICU) patients and is a predictor of worse outcomes and neuroinflammation is a possible mechanism. The antiinflammatory actions of statins may reduce delirium. OBJECTIVES: To determine whether critically ill patients receiving statin therapy had a reduced risk of delirium than those not on statins. METHODS: A prospective cohort analysis of data from consecutive ICU patients admitted to a UK mixed medical and surgical critical care unit between August 2011 and February 2012; the Confusion Assessment Method for ICU was used to determine the days each patient was assessed as being free of delirium during ICU admission. MEASUREMENTS AND MAIN RESULTS: Delirium-free days, daily administration of statins, and serum C-reactive protein (CRP) were recorded. Four hundred and seventy consecutive critical care patients were followed, of whom 151 patients received statins. Using random-effects multivariable logistic regression, statin administration the previous evening was associated with the patient being assessed as free of delirium (odds ratio, 2.28; confidence interval, 1.01-5.13; P < 0.05) and with lower CRP (ß = -0.52; P < 0.01) the following day. When the association between statin and being assessed as free of delirium was controlled for CRP, the effect size became nonsignificant (odds ratio, 1.56; confidence interval, 0.64-3.79; P = 0.32). CONCLUSIONS: Ongoing statin therapy is associated with a lower daily risk of delirium in critically ill patients. An ongoing clinical trial, informed by this study, is investigating if statins are a potential therapy for delirium in the critically ill.

Missing link or not, mobilise against delirium.

Delirium is known to be a predictor of adverse outcomes. In a prospective study Abelha and colleagues showed that postoperative delirium was an independent risk factor for deterioration in functional capacity following discharge. While evidence for causality remains elusive, there is no doubt that patients who develop delirium are left with new functional and cognitive impairment. Finding a pharmacological treatment for the prevention and treatment of delirium is a priority in delirium research and the results of ongoing trials are awaited. Early mobilisation of ICU patients has been demonstrated to decrease delirium and improve functional outcomes. Resources should be directed to appropriate, progressive mobilisation of all critically ill patients as a priority.

Triggers and factors associated with moral distress and moral injury in health and social care workers: A systematic review of qualitative studies.

OBJECTIVE: At some point in their career, many healthcare workers will experience psychological distress associated with being unable to take morally or ethically correct action, as it aligns with their own values; a phenomenon known as moral distress. Similarly, there are increasing reports of healthcare workers experiencing long-term mental and psychological pain, alongside internal dissonance, known as moral injury. This review examined the triggers and factors associated with moral distress and injury in Health and Social Care Workers (HSCW) employed across a range of clinical settings with the aim of understanding how to mitigate the effects of moral distress and identify potential preventative interventions. METHODS: A systematic review was conducted and reported according to recommendations from Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches were conducted and updated regularly until January 2024 on 2 main databases (CENTRAL, PubMed) and three specialist databases (Scopus, CINAHL, PsycArticles), alongside hand searches of study registration databases and other systematic reviews reference lists. Eligible studies included a HSCW sample, explored moral distress/injury as a main aim, and were written in English or Italian. Verbatim quotes were extracted, and article quality was assessed via the CASP toolkit. Thematic analysis was conducted to identify patterns and arrange codes into themes. Specific factors like culture and diversity were explored, and the effects of exceptional circumstances like the pandemic. RESULTS: Fifty-one reports of 49 studies were included in the review. Causes and triggers were categorised under three domains: individual, social, and organisational. At the individual level, patients' care options, professionals' beliefs, locus of control, task planning, and the ability to make decisions based on experience, were indicated as elements that can cause or trigger moral distress. In addition, and relevant to the CoVID-19 pandemic, was use/access to personal protection resources. The social or relational factors were linked to the responsibility for advocating for and communication with patients and families, and professionals own support network. At organisational levels, hierarchy, regulations, support, workload, culture, and resources (staff and equipment) were identified as elements that can affect professionals' moral comfort. Patients' care, morals/beliefs/standards, advocacy role and culture of context were the most referenced elements. Data on cultural differences and diversity were not sufficient to make assumptions. Lack of resources and rapid policy changes have emerged as key triggers related to the pandemic. This suggests that those responsible for policy decisions should be mindful of the potential impact on staff of sudden and top-down change. CONCLUSION: This review indicates that causes and triggers of moral injury are multifactorial and largely influenced by the context and constraints within which professionals work. Moral distress is linked to the duty and responsibility of care, and professionals' disposition to prioritise the wellbeing of patients. If the organisational values and regulations are in contrast with individuals' beliefs, repercussions on professionals' wellbeing and retention are to be expected. Organisational strategies to mitigate against moral distress, or the longer-term sequalae of moral injury, should address the individual, social, and organisational elements identified in this review.

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

BACKGROUND: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. METHODS: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. RESULTS: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ±â€…9.0 vs 17.5 ±â€…12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). CONCLUSION: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.

Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Delirium in critically ill patients is associated with poor clinical outcomes. Neuroinflammation might be an important mechanism in the pathogenesis of delirium, and since simvastatin has anti-inflammatory properties it might reduce delirium. We aimed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma. METHODS: We undertook this randomised, double-blind, placebo-controlled trial in a general adult intensive care unit (ICU) in Watford General Hospital (Watford, UK). We enrolled critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission. We randomly assigned patients (1:1 ratio) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days, irrespective of coma or delirium status. We assessed delirium using the Confusion Assessment Method for the ICU (CAM-ICU). The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being randomly allocated to receive treatment or placebo. ICU clinical and research staff and patients were masked to treatment. We did intention-to-treat analyses with no extrapolation. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN89079989. FINDINGS: Between Feb 1, 2013, and July 29, 2016, 142 patients were randomly assigned to receive simvastatin (n=71) or placebo (n=71), and were included in the final analysis. The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups (5·7 days [SD 5·1] with simvastatin and 6·1 days [5·2] with placebo; mean difference 0·4 days, 95% CI -1·3 to 2·1; p=0·66). The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal (eight [11%] in the simvastatin group vs three [4%] in the placebo group p=0·208). No patient had a serious adverse event related to the study drug. INTERPRETATION: These results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients. FUNDING: National Institute for Health Research.

The psychological and neurocognitive consequences of critical illness. A pragmatic review of current evidence.

Mortality rates alone are no longer a sufficient guide to quality of care. Due to medical advances, patients are surviving for longer following critical illness and major surgery; therefore, functional outcomes and long-term quality of life are of increasing consequence. Post-operative cognitive dysfunction has been acknowledged as a complication following anaesthesia for many years, and interest in persistent cognitive dysfunction following a critical illness is growing. Psychological and neurocognitive sequelae following discharge from intensive care are acknowledged to occur with sufficient significance to have recently coined the term 'the post-intensive care syndrome'. Rehabilitation following critical illness has been highlighted as an important goal in recently published national UK guidelines, including the need to focus on both physical and non-physical recovery. Neuropsychological and cognitive consequences following anaesthesia and critical illness are significant. The exact pathophysiological mechanisms linking delirium, cognitive dysfunction and neuropsychological symptoms following critical illness are not fully elucidated but have been studied elsewhere and are outside the scope of this article. There is limited evidence as yet for specific peri-operative preventative strategies, but early management and rehabilitation strategies following intensive care discharge are now emerging. This article aims to summarise the issues and appraise current options for management, including both neuroprotective and neurorehabilitative strategies in intensive care.

Evaluating early administration of the hydroxymethylglutaryl-CoA reductase inhibitor simvastatin in the prevention and treatment of delirium in critically ill ventilated patients (MoDUS trial): study protocol for a randomized controlled trial.

BACKGROUND: The incidence of delirium in ventilated patients is estimated at up to 82%, and it is associated with longer intensive care and hospital stays, and long-term cognitive impairment and mortality. The pathophysiology of delirium has been linked with inflammation and neuronal apoptosis. Simvastatin has pleiotropic properties; it penetrates the brain and, as well as reducing cholesterol, reduces inflammation when used at clinically relevant doses over the short term. This is a single centre randomised, controlled trial which aims to test the hypothesis that treatment with simvastatin will modify delirium incidence and outcomes. METHODS/DESIGN: The ongoing study will include 142 adults admitted to the Watford General Hospital Intensive Care Unit who require mechanical ventilation in the first 72 hours of admission. The primary outcome is the number of delirium- and coma-free days in the first 14 days. Secondary outcomes include incidence of delirium, delirium- and coma-free days in the first 28 days, days in delirium and in coma at 14 and 28 days, number of ventilator-free days at 28 days, length of critical care and hospital stay, mortality, cognitive decline and healthcare resource use. Informed consent will be taken from patient's consultee before randomisation to receive either simvastatin (80 mg) or placebo once daily. Daily data will be recorded until day 28 after randomisation or until discharge from the ICU if sooner. Surviving patients will be followed up on at six months from discharge. Plasma and urine samples will be taken to investigate the biological effect of simvastatin on systemic markers of inflammation, as related to the number of delirium- and coma-free days, and the potential of cholinesterase activity and beta-amyloid as predictors of the risk of delirium and long-term cognitive impairment. DISCUSSION: This trial will test the efficacy of simvastatin on reducing delirium in the critically ill. If patients receiving the statin show a reduced number of days in delirium compared with the placebo group, the inflammatory theory implicated in the pathogenesis of delirium will be strengthened. TRIAL REGISTRATION: The trial was registered with the International Standard Randomised Controlled Trial Registry ( ISRCTN89079989 ) on 26 March 2013.