Anaemia secondary to critical illness: an unexplained phenomenon.

Almost all patients suffering critical illness become anaemic during their time in intensive care. The cause of this anaemia and its management has been a topic of debate in critical care medicine for the last two decades. Packed red cell transfusion has an associated cost and morbidity such that decreasing the number of units transfused would be of great benefit. Our understanding of the aetiology and importance of this anaemia is improving with recent and ongoing work to establish the cause, effect and best treatment options. This review aims to describe the current literature whilst suggesting that the nature of the anaemia should be considered with reference to the time point in critical illness. Finally, we suggest that using haemoglobin concentration as a measure of oxygen-carrying capacity has limitations and that ways of measuring haemoglobin mass should be explored

Persistent inflammation, immunosuppression, and catabolism syndrome (PICS): a review of definitions, potential therapies, and research priorities.

Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) is a clinical endotype of chronic critical illness. PICS consists of a self-perpetuating cycle of ongoing organ dysfunction, inflammation, and catabolism resulting in sarcopenia, immunosuppression leading to recurrent infections, metabolic derangements, and changes in bone marrow function. There is heterogeneity regarding the definition of PICS. Currently, there are no licensed treatments specifically for PICS. However, findings can be extrapolated from studies in other conditions with similar features to repurpose drugs, and in animal models. Drugs that can restore immune homeostasis by stimulating lymphocyte production could have potential efficacy. Another treatment could be modifying myeloid-derived suppressor cell (MDSC) activation after day 14 when they are immunosuppressive. Drugs such as interleukin (IL)-1 and IL-6 receptor antagonists might reduce persistent inflammation, although they need to be given at specific time points to avoid adverse effects. Antioxidants could treat the oxidative stress caused by mitochondrial dysfunction in PICS. Possible anti-catabolic agents include testosterone, oxandrolone, IGF-1 (insulin-like growth factor-1), bortezomib, and MURF1 (muscle RING-finger protein-1) inhibitors. Nutritional support strategies that could slow PICS progression include ketogenic feeding and probiotics. The field would benefit from a consensus definition of PICS using biologically based cut-off values. Future research should focus on expanding knowledge on underlying pathophysiological mechanisms of PICS to identify and validate other potential endotypes of chronic critical illness and subsequent treatable traits. There is unlikely to be a universal treatment for PICS, and a multimodal, timely, and personalised therapeutic strategy will be needed to improve outcomes for this growing cohort of patients

Comorbid disease and ethnicity in emergency hospital admissions in east London

Statistical Analysis Plan – This aim of this comparative study is to determine in a cohort of non-COVID emergency hospital admissions within the same representative population in east London, whether there is a difference in outcomes in patients of different ethnicities. It will test the hypothesis that patients of Black, Asian and other ethnicities have poorer outcomes defined using mortality and length of stay. Data generated has the potential to influence and shape relevant policy and practice to improve health outcomes in BAME communities

An update on muscle wasting in ICU

© 2017, Pharmamed Mado Ltd. All rights reserved. Mortality rates from critical illness are decreasing worldwide, but survivors suffer from significant functional disability as a result of muscle wasting. In the short-term the functional effects are seen in increased time of mechanical ventilation, and increased length of stay. Muscle wasting is the most common complication of critical illness, occurring in 25-50% of patients. In a longitudinal observational study, daily loss of muscle mass averaged 2-3% over the first 10 days. The scale of wasting was related to the severity of organ failure and of acute lung injury. Changes in muscle mass are underpinned by alterations in muscle protein homeostasis. In stable isotope infusion experiments, muscle protein synthesis was reduced to levels of fasted controls despite the initiation of enteral feed. Protein synthetic levels recovered variably over the first week to levels comparable to fed controls. As a result, muscle protein breakdown was increased relative to muscle protein synthesis, leading to a net catabolic state. There is a need for secondary prevention measures to be instituted in current practise. Increased nutritional delivery cannot be recommended at this stage during acute critical illness and early mobilisation has been demonstrated to increase functional status. This is best achieved through the ABCDEF bundle. This bundle constitutes a co-ordinated package of care with sedation control to facilitate spontaneous breathing and decreasing delirium. This facilitates early mobilisation, which is currently the only preventative measure with an evidence base to decrease skeletal muscle wasting associated functional disability

Risk factors, biomarkers, and mechanisms for persistent inflammation, immunosuppression, and catabolism syndrome (PICS): a systematic review and meta-analysis.

INTRODUCTION: Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS. METHODS: MEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian-Laird method. Risk of bias assessment was done using the Newcastle-Ottawa Scale. RESULTS: Six papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L-1 higher C-reactive protein (95% confidence interval [CI] 12.7-56.2 mg L-1; P<0.01), a 4.4 g L-1 lower albumin (95% CI 0.5-8.3 g L-1; P<0.01), and a 0.36×109 L-1 lower lymphocyte count (95% CI 0.25-0.47×109 L-1; P=0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly. CONCLUSIONS: While older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions. CLINICAL TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749)

Designing nutrition-based interventional trials for the future: addressing the known knowns

Abstract The consistent decline in critical illness mortality has a significant effect on trial design, whereby either an improbable effect sizes or large number of patients are required. The signal-to-noise ratio is of particular interest for the critically ill. When considering the potential signal, interventions need to match outcomes in regard to biological plausibility. Provision of nutrition is a complex decision with many underappreciated aspects of noise. However, a fundamental interaction is often not accounted for time. Working as a community to evolve trial design will be our challenge for nutrition interventions in the critically ill for the future

Health Resource Utilisation and Disparities: an Ecological Study of Admission Patterns Across Ethnicity in England Between 2017 and 2020.

BACKGROUND AND AIM: The COVID-19 pandemic highlighted adverse outcomes in Asian, Black, and ethnic minority groups. More research is required to explore underlying ethnic health inequalities. In this study, we aim to examine pre-COVID ethnic inequalities more generally through healthcare utilisation to contextualise underlying inequalities that were present before the pandemic. DESIGN: This was an ecological study exploring all admissions to NHS hospitals in England from 2017 to 2020. METHODS: The primary outcomes were admission rates within ethnic groups. Secondary outcomes included age-specific and age-standardised admission rates. Sub-analysis of admission rates across an index of multiple deprivation (IMD) deciles was also performed to contextualise the impact of socioeconomic differences amongst ethnic categories. Results were presented as a relative ratio (RR) with 95% confidence intervals. RESULTS: Age-standardised admission rates were higher in Asian (RR 1.40 [1.38-1.41] in 2019) and Black (RR 1.37 [1.37-1.38]) and lower in Mixed groups (RR 0.91 [0.90-0.91]) relative to White. There was significant missingness or misassignment of ethnicity in NHS admissions: with 11.7% of admissions having an unknown/not-stated ethnicity assignment and 'other' ethnicity being significantly over-represented. Admission rates did not mirror the degree of deprivation across all ethnic categories. CONCLUSIONS: This study shows Black and Asian ethnic groups have higher admission rates compared to White across all age groups and when standardised for age. There is evidence of incomplete and misidentification of ethnicity assignment in NHS admission records, which may introduce bias to work on these datasets. Differences in admission rates across individual ethnic categories cannot solely be explained by socioeconomic status. Further work is needed to identify ethnicity-specific factors of these inequalities to allow targeted interventions at the local level

Reducing sound and light exposure to improve sleep on the adult intensive care unit: An inclusive narrative review.

Purpose: Sleep disturbance is common in intensive care units. It is associated with detrimental psychological impacts and has potential to worsen outcome. Irregular exposure to sound and light may disrupt circadian rhythm and cause frequent arousals from sleep. We sought to review the efficacy of environmental interventions to reduce sound and light exposure with the aim of improving patient sleep on adult intensive care units. Methods: We searched both PubMed (1966-30 May 2017) and Embase (1974-30 May 2017) for all relevant human (adult) studies and meta-analyses published in English using search terms ((intensive care OR critical care), AND (sleep OR sleep disorders), AND (light OR noise OR sound)). Bibliographies were explored. Articles were included if reporting change in patient sleep in response to an intervention to reduce disruptive intensive care unit sound /light exposure. Results: Fifteen studies were identified. Nine assessed mechanical interventions, four of which used polysomnography to assess sleep. Five studies looked at environmental measures to facilitate sleep and a further two (one already included as assessing a mechanical intervention) studied the use of sound to promote sleep. Most studies found a positive impact of the intervention on sleep. However, few studies used objective sleep assessments, sample sizes were small, methodologies sometimes imperfect and analysis limited. Data are substantially derived from specialist (neurosurgical, post-operative, cardiothoracic and cardiological) centres. Patients were often at the 'less sick' end of the spectrum in a variety of settings (open ward beds or side rooms). Conclusions: Simple measures to reduce intensive care unit patient sound/light exposure appear effective. However, larger and more inclusive high-quality studies are required in order to identify the measures most effective in different patient groups and any impacts on outcome.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: HM and the Institute for Sport Exercise and Health are supported by the University College London Hospitals NHS Trust/University College London (UCLH/UCL) NIHR Comprehensive Biomedical Research Centre