搜索结果：Journal of the Intensive Care Society

The intensive care unit (ICU) may be described as a 'deliriogenic' environment. Critically ill patients diagnosed with delirium are at increased risk of long-term cognitive impairment and hospital mortality. Best practice guidelines recommend early mobilisation interventions to manage and prevent delirium in ICUs. However, evidence evaluating the impact and role of early mobilisation upon delirium in ICUs from the patient perspective is lacking. The aim of this study was to understand the experience of early mobilisation from the perspective of patients diagnosed with delirium in the ICU. This qualitative study adopted a phenomenological approach. One focus group including three participants and seven semi-structured one-to-one interviews were conducted with patients previously diagnosed with delirium in the ICU. Data were analysed using Braun and Clarke's thematic analysis. Face validity of findings was reviewed by a public representative on the research team. Six main themes were identified: (1). The vivid reality and isolation of delirium, (2). Loss of control, (3). Delirium as a barrier to mobilisation, (4). The role of different methods of mobilisation (5). Facilitating mobilisation and recovery of self, and (6). Grounded back into reality. This qualitative study demonstrated the impact and role of mobilisation interventions going beyond the patients' physical recovery from critical illness. These findings support current best practice recommendations for the implementation of early mobilisation interventions in ICUs.

Severe community-acquired pneumonia (sCAP) is associated with a significant health burden, both in the UK and globally, with intensive care support needed for many patients. The high morbidity and mortality associated with sCAP has led to the exploration of adjunctive therapies that may help reduce disease burden and improve clinical outcomes. One such proposed treatment is corticosteroids, aiming to moderate the disproportionate inflammation caused by sCAP. Despite several studies suggesting potential benefits, the use of corticosteroids in patients with sCAP remains contentious, with recent large trials producing conflicting results. These variations in trial outcomes have resulted in conflicting national and international guidelines. Such discrepancies align with findings from a recent national survey that indicated ongoing clinical uncertainty regarding the use of corticosteroids for sCAP in UK intensive care units. Several factors contribute to these conflicting outcomes, including patient population, the severity classification utilised, the type and duration of interventions provided, and, perhaps most importantly, the lack of pre-phenotyping to identify patients who may benefit most from the treatment. This narrative review aims to examine the recent literature, current guidelines, and evidence for using corticosteroids in sCAP, while exploring the candidate phenotypes of relevance in the design of clinical trials.

Neurological emergencies such as stroke and traumatic brain injury are major contributors to morbidity and mortality in critically ill patients. These conditions frequently result in alterations in cerebral haemodynamics, including raised intracranial pressure, which require timely recognition and management to optimise outcomes. Neuro point-of-care ultrasound (NeuroPOCUS), incorporating transcranial Doppler (TCD), transcranial colour-coded duplex (TCCD) ultrasound, and optic nerve sheath diameter (ONSD) measurement, offers a non-invasive, bedside means of assessing cerebral physiology and is increasingly recognised as a valuable adjunct in neurocritical care. Despite the successful adoption of point-of-care ultrasound in critical care through established accreditation pathways such as FUSIC® and CACTUS®, the UK has lacked a dedicated framework for NeuroPOCUS. To address this gap, we have developed and launched a UK-specific NeuroPOCUS accreditation programme, combining structured theoretical teaching with supervised practical training. The pathway addresses the distinct needs of both paediatric and adult populations, combining theoretical learning with practical application. Core learning materials include neuroanatomy, Doppler principles, standardised insonation techniques, and interpretation of cerebral blood flow velocities and indices such as pulsatility (PI) and resistivity (RI). Supporting resources feature videos of transcranial colour-coded Duplex (TCCD) imaging in normal subjects and clinical case examples. Participants will complete a logbook of 50 supervised cases, facilitated by remote mentorship. A novel accreditation pathway provides an opportunity for further research into the use of NeuroPOCUS in neurocritical care. This article outlines the core techniques of NeuroPOCUS, the physiological insights it offers, key clinical applications, and the proposed accreditation pathway aimed at standardising practice and clinician training in the care of critically ill patients with neurological injury or dysfunction.

Dose Error Reduction Software (DERS) are downloaded onto Smart Pumps with minimum and maximum infusion rate settings to reduce the risk of medication errors when administering intravenous medicines. There are no current national standards for the application of this technology on Adult Intensive Care Units (ICU), and clinical application and governance of this technology is currently unknown. A multicentre, cross-sectional survey was conducted using a self-administered questionnaire to explore practical aspects of Smart Pump containing DERS use, such as whether a DERS library was present, how it was managed, how propofol was administered, what kind of error reporting processes were in place, as well as nursing qualifications and competencies on ICUs in England. A response rate of 50.7% (136/268 responses) ICUs units in England was achieved and indicated that 63.2% (86/136 responses) of responding units had a Smart Pump containing a DERS library. Three administration strategies were used, mg/kg/h, mL/h and 'Other' (which most responses stated as mg/h) for propofol for continuous sedation in ICU Smart Pump containing DERS libraries. In 68.6% (49/86 responses) of ICUs, DERS use and DERS error rates are not reported through local operational and governance structures. DERS use was significantly associated with units having a Clinical Nurse Educator with a postgraduate education certificate (p = 0.005). There are no standardised DERS settings for the anaesthetic agent propofol and inconsistent approaches to Smart Pump containing DERS governance oversight across ICUs in England. Further research is required to understand the clinical significance of identified variability.

Artificial intelligence (AI) prediction models can accurately identify high-risk populations by integrating multi-dimensional clinical data, providing decision support for doctors in formulating individualized discharge plans and optimizing follow-up intervention strategies, thereby reducing the risk of readmission from the source. Currently, the number of AI prediction models for readmission of critically ill patients is increasing, but the quality and applicability of these models in clinical practice and future research remain uncertain. To systematically evaluate published studies on AI prediction models for critically ill patients. This study conducted a computerized search of the CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Cochrane, and Embase databases, with the time range from 2020 to June 25, 2025. Information such as study design, data sources, outcome definitions, sample size, predictors, model development, and performance was extracted from the selected studies. The Prediction Model Risk of Bias Assessment Tool (PROBAST) checklist was used to evaluate the risk of bias and applicability. A total of 387 studies were retrieved, and after screening, 31 studies with their 31 prediction models were included in this review. All studies developed risk prediction models for readmission of critically ill patients using artificial intelligence algorithms. The readmission risk of critically ill patients ranged from 1.3% to 13.7%. The most commonly used predictors were structured data. The reported area under the curve (AUC) ranged from 0.66 to 0.98. All studies had a high risk of bias, mainly due to poor reporting quality in the analysis domain and insufficient applicability. The pooled AUC of the 24 validation models was 0.82, with a 95% confidence interval of 0.77-0.87. These study results constitute a comprehensive set of high-quality evidence, demonstrating that AI prediction models exhibit moderate-to-high predictive performance and that their predictive performance is significantly higher than that of traditional prediction models. No Patient or Public Contribution. This Meta-analysis is based on the systematic review and statistical combination of the published clinical research data. The processes of research design, data extraction, and result interpretation did not involve the participation of patients or the public. The protocol for this study has been registered in PROSPERO (registration number: CRD42025637829).

Survival rates for cardiac arrest remain low. Extracorporeal cardiopulmonary resuscitation (ECPR) may offer a survival advantage in carefully selected patients. There is limited published data on ECPR in the UK and therefore this study aims to describe the last 11 years provision and outcomes of ECPR in the UK. This was a multicentre retrospective cohort study in the UK. Centres offering Extracorporeal membrane oxygenation (ECMO) as a potential support in the UK were identified at the first UK ECPR Summit. All centres were asked to submit data on their veno-arterial (VA) ECMO and ECPR patients between 1st January 2012 and 31st December 2022. Over the 11-year period, 2117 patients received VA-ECMO in the UK with 963 survivors at 6 months (45.5%). Of these there were 302 ECPR runs with 92 survivors (30.5%). ECPR contributed to 14.3% of the total VA ECMO runs, with wide between-centre variation ranging from 5.4% to 73.3%. Centres provided a detailed dataset for 129 of the 172 consecutive ECPR cases for a 5-year period to 31st December 2022. The mean (SD) age was 46 ± 5 years, 77% were male and 48.9% presented with a shockable rhythm. The leading cause of cardiac arrest was ischaemic heart disease (45%). Only 14% achieved transient or sustained return of spontaneous circulation prior to initiation of ECMO flow, with mean time CPR to full ECMO flow of 52.5 ± 17.1 min. Percutaneous cannulation was performed in 85.3% of cases, with 51.9% of these procedures taking place in the cardiac catheter laboratory. In an UK cohort of VA ECMO and ECPR patients, the survival rates were comparable to other international registries. The variation in practice highlights the need to explore and address inequity of access to ECMO and ECPR services.

Despite advances in sepsis management, the relationship between appropriate empiric antibiotic therapy and acute kidney injury (AKI) in sepsis remains unclear. This study aimed to examine the association of appropriate empiric antimicrobial therapy with AKI in early onset sepsis caused by gram-negative bloodstream infections. We conducted a retrospective study of gram-negative bloodstream infection episodes in adult patients with early onset sepsis, using the Premier Healthcare Database from 2016 to 2020. The exposure was appropriate empiric antibiotic therapy determined by antibiotic regiments and antimicrobial susceptibilities of pathogens. The primary outcome was development of AKI or death by day 7 after the onset of sepsis. AKI was defined using the Kidney Disease Improving Global Outcome criteria based on serum creatinine levels, as urine output data were not available. The multivariable regression analysis was used to examine the association between appropriate empiric antibiotic therapy and the outcomes. We identified 8565 patients with gram negative sepsis. In the total sample, the proportion of appropriate empiric antibiotic therapy was 93.2%, and the prevalence of AKI was 85.3%. Appropriate empiric antibiotic therapy was associated with decreased risk of AKI or death (adjusted odds ratio 0.70, 95% CI 0.52-0.94). For secondary outcomes, appropriate empiric antibiotic therapy was associated with lower AKI, shorter hospital LOS, lower C. difficile infections. However, it was not associated with in-hospital mortality. Appropriate empiric antibiotic therapy was associated with lower AKI in gram-negative sepsis. Early administration of appropriate antibiotics may prevent development of AKI.

In January 2025 the Academy of Medical Royal Colleges published an updated Code of Practice for the Diagnosis and Confirmation of Death, the first major update for 17 years. It represents the authoritative medical consensus on the diagnosis and confirmation of death in all contexts (and in all age groups) in the UK. This paper reviews the new Code, highlighting the major updates from the 2008 guidance and their relevance for intensive care clinicians. It goes on to explore the wider legal history and context, in particular the role that previous versions of the Academy's guidelines have played during the emergence of a common law definition of death. It examines the important legal cases in which the Code of Practice was endorsed and ultimately adopted by the courts as the definitive medical and legal definition of death in the UK.

Occupational Therapy (OT) in the Intensive Care Unit (ICU) supports recovery in physical, cognitive, emotional domains, and activities of daily living (ADL), yet. Provision across the UK remains inconsistent, with variable staffing and role integration and no data illustrating the potential impact from such roles. A retrospective service evaluation was undertaken in a UK NHS adult ICU to examine the association of increased OT staffing with changes in rehabilitation activity and functional status. Patients with ICU stays over 7 days were included in line with NICE CG83 high rehabilitation risk criteria. Three 1-month timepoints were compared. Data included delivery of OT interventions, functional outcomes (Modified Barthel Index), and discharge destination. Ninety-nine patients were included. Increased OT staffing was associated with a greater proportion of patients receiving OT assessments, upper limb rehabilitation, personal activities of daily living retraining, cognitive screening, delirium management, and therapy handover. Modified Barthel index scores at hospital discharge increased across timepoints 1, 2 and 3 (55, 71.5 and 82, respectively (p = 0.02)). Discharge destination patterns varied and could not be attributed solely to staffing changes. Increased OT staffing was associated with greater delivery of rehabilitation interventions and potential improvements in functional outcomes. However, differences in patient clinical complexity across timepoints may also have influenced these results. Further evaluation is required to establish causal relationships.

Improved survival from critical illness in recent years has led to an increase in patients with Post Intensive Care Syndrome (PICS). Routine, dedicated, specific and individualised assessment, rehabilitation and follow-up after critical care discharge is recommended but is currently inadequate in the UK. The aim of this study was to explore patients' and family members' experiences of a critical care admission, focussing on recovery and rehabilitation. As part of an intervention development programme, a series of iterative focus groups with survivors of critical illness and their family members was held. Parallel groups with staff involved in the care and rehabilitation of critically ill patients were also conducted. Participants mapped out their recovery journey identifying key moments and challenges and shared their recommendations for recovery and rehabilitation. Brokered dialogue was used to enable patient and staff groups to ask and answer questions of each other. Data analysis was completed using reflexive thematic coding. Thirty-four participants attended the focus groups, with 28 attending the first two groups discussed in this paper. Using the experiences described by the participants, three overarching themes were identified; fear, helplessness and frustration. Participants also reported both short and longer-term consequences of ICU admission and shared their priorities and advice for recovery and rehabilitation. Critical care admission is a traumatic experience for patients and family members. Our data highlights patients' needs for ongoing, holistic support during a stay in critical care and beyond.

Point-of-care echocardiography accreditation is not mandated within the Faculty of Intensive Care Medicine (FICM) training curriculum, yet it is commonly utilised to aid clinical decision making in the intensive care unit. We designed a survey to assess barriers to accreditation in point-of-care echocardiography across Scottish critical care units. The majority (70.1%) of respondents were unaccredited, with the most common barrier (n = 102) being 'lack of time with a mentor for supervised scanning'. This was amplified by the fact that only 25% of mentors received job planned time for scanning. Men were over-represented in those with accreditation, accounting for 61.4% of accredited clinicians, despite making up 51.0% of all respondents. In contrast, women represented 62.5% of unaccredited individuals who had undertaken at least one attempt at the process. We did not find a difference with other protected characteristics. This survey suggests that targeted support locally for those struggling to complete the process could address some of these concerns, and that further work needs to be taken to identify and address gender inequity in point of care echocardiography accreditation.

In 2023, the Intensive Care Unit at the Dudley Group NHS Foundation Trust became the first in the UK to achieve Gold Standards Framework (GSF) accreditation. This study evaluates the impact of GSF implementation on end-of-life care delivery and associated metrics. Coding of end-of-life care increased from 10.7% to 16.1% and the proportion of deaths recognised as GSF Amber/Red rose from 14.5% to 58.1% with an increased number of referrals to Specialist Palliative Care. GSF accreditation was associated with sustained improvements in key end-of-life care metrics in intensive care, enhancing collaboration with Specialist Palliative Care and supporting more individualised, patient-centred care.

There are theoretical reasons why beta-lactam antibiotics may be more effective in treating severe infections if administered by continuous infusion, rather than short intermittent infusions. The Beta-Lactam Infusion Group (BLING) III trial was a multinational randomised clinical trial (RCT) which tested this hypothesis in participants with sepsis who were cared for in an intensive care unit (ICU). The United Kingdom (UK) findings are reported here. The global trial was an open-label RCT conducted in the UK, Australia, New Zealand, Belgium, France, Sweden and Malaysia. Participants were critically ill adults being treated with meropenem or piperacillin/tazobactam due to a confirmed or presumed infection. Participants were randomised to receive the antibiotic by either continuous infusion or short intermittent infusion at equivalent daily doses as selected by the treating team. The primary outcome was 90-day all-cause mortality; secondary outcomes included clinical cure up to 14 days after randomisation, new infection and acquisition of resistant organisms, ICU and in hospital mortality. Overall, 7202 participants were randomised, with 2900 from the UK. The UK cohort had very similar baseline characteristics and outcomes to the global trial. For continuous versus intermittent infusion, the global trial showed 24.9% versus 26.8% participants had died by 90 days (odds ratio 0.91, 95% CI: 0.81-1.01, p = 0.08); and in the UK 26.7% versus 29.3% participants had died (odds ratio 0.88, 95% CI: 0.75-1.04, p = 0.13). Although not statistically significant, all outcomes showed point estimates in favour of continuous infusion. The findings in the UK cohort are consistent with the conclusions drawn from the global BLING III trial. It seems reasonable to conclude the finding are applicable to the UK.

Meningitis and encephalitis affect all ages, are prone to misdiagnosis and outcome can be devastating. We provide this common primer for all in the sepsis "chain-of-survival." Meningitis equals inflammation/infection of the protective membranes that cover the brain; whereas encephalitis affects the brain parenchyma. Meningitis is more common, but they can co-exist as meningoencephalitis. Encephalitis can also affect the spinal cord (encephalomyelitis). Worldwide, meningitis affects 2.5 million people annually, and kills over 200,000. Central nervous system (CNS) infections account for 3.9% of all UK intensive care unit (ICU) infections, and 0.7% of adult ICU admissions. While this means these are not common causes for admission, they do have high morbidity and mortality. The median ICU stay is 4 days, of which 3 days was the median spent requiring advanced respiratory support or support for more than one organ. The median in-hospital stay is 20 days. Most admissions come through the emergency department (ED). Signs and symptoms can be vague and varied; hence potential misdiagnosis as flu, psychiatric disorders, intoxication, even hangover. The median time between hospital admission and transfer to ICU is 1 day, and by this time approximately one-third are comatose and one-sixth need respiratory support. The risk of misdiagnosis matters given high mortality and morbidity: 18%-25% die in hospital and 1-in-10 survivors lose independence. During the past 20 years mortality has fallen, but those left with some form of permanent disability remains constant at nearly 40%. Fortunately, early recognition and treatment can greatly improve outcome. Regarding diagnosis, history and physical examination still have great value. Next, lumbar puncture (LP) should be expedited unless contraindicated by coagulopathy, skin infection, or raised ICP. LP testing should incorporate opening pressure, microscopy, culture and cell count, glucose and protein and often polymerase chain reaction (PCR) for meningococcus, pneumococcus, herpes simplex virus (HSV1&2), varicella (VZV) and enterovirus. Radiologically, head computed tomography (CT) is first line. It may reduce the risk of LP by excluding pathologies likely to trigger herniation. CT is indicated if their Glasgow Coma Score (GCS) is falling or ⩽9, or if seizures, focal neurological signs or papilloedema. Normal CT cannot rule out raised ICP, but LP is avoided if the CT shows herniation, basal cistern or foramen magnum effacement, cerebral swelling, intracranial lesions/collections with mass effect or obstructive hydrocephalus. Magnetic resonance imaging (MRI) is logistically tougher but better at detecting meningitis/encephalitis. MRI can suggest the causative organisms, along with complications such as infarct, pus and parenchymal changes. Treatment centres on prompt antimicrobials: usually a third-generation intravenous (IV) cephalosporin, typically within 1 h, and at an increased (i.e. "meningitis") dose. Intravenous amoxicillin is added in the elderly or immunocompromised, plus aciclovir if viral encephalitis is plausible. Treatment delays (over 4 h) are associated with increased mortality. Over half (57%) of patients that require ICU develop intracranial complications, most frequently ischaemia, cerebral oedema and ventriculitis. In short, these diseases are life-threatening but manageable if we do the simple stuff right. . .and right away.

With 10-years' worth of growth in the use of LUS by physiotherapists within the U.K., this survey explores their training, implementation and clinical practice experiences. A cross-sectional survey was delivered to U.K. Physiotherapists accredited in LUS. The 50-question survey was administered via JISC online and was open for 4-weeks in January 2025. Closed questions were presented descriptively; open questions underwent inductive conceptual content analysis and descriptive coding. Of the 223 invitations, 168 surveys were returned (75% response rate). Responses were highest from four U.K. regions which correlated with a higher number of regional mentors. Most respondents were in band 7 static roles, accredited via FUSIC® and worked on the ICU with respiratory or surgical patients. The primary indication to perform a LUS was an increase in the fraction of inspired oxygen, average scanning frequency was 1-2 per week and common pathological findings were consolidation (pneumonia and atelectasis) plus pleural effusion (transudative and exudative). The most common negative factors experienced overall were limited time to scan and access to an US machine. Additional negative factors were limited access to a mentor during training, limited support from other professions during implementation, limited access to an appropriate patient population to scan during clinical practice. This is the largest survey to investigate the experiences of physiotherapists using lung ultrasound in the U.K. and provides important insights during training, implementation and clinical use. The specific details of these findings will support both current and future LUS users to plan and develop robust physiotherapy LUS service.

This process evaluation explored delivery of a complex sedation intervention within the Alpha-2 Agonists for Sedation to Produce Better Outcomes from Critical Illness (A2B) trial, which compared dexmedetomidine- and clonidine-based sedation with propofol (usual care). All groups targeted lighter sedation levels. The objective was to understand bedside nurses' experiences delivering the interventions and identify factors influencing protocol adherence and implementation. A qualitative study using semi-structured interviews was conducted with intensive care unit (ICU) staff (consultants, bedside and research nurses) from A2B trial sites. Thematic analysis explored how participants experienced and delivered trial interventions, with particular focus on bedside nurses' abilities to manage sedation in line with the protocol. Nurses with greater ICU experience described more confidence and adaptability in using alpha-2 agonists, while less experienced staff required support due to limited familiarity with lighter sedation. Hesitancy to up-titrate alpha-2 agonists was common, driven by concerns about bradycardia and hypotension. Reluctance to down-titrate propofol was shaped by fears of agitation and self-extubation. Deep sedation norms, especially amongst nurses trained during the COVID-19 pandemic, further hindered protocol adherence. Research nurses were instrumental in supporting implementation and bridging knowledge gaps. Despite all three trial groups targeting lighter sedation, nurse confidence, safety concerns, and ingrained cultural practices limited adherence to alpha-2 agonist-based protocols. Addressing these barriers through training, support, and cultural change will be essential for future trials and practice shifts involving lighter sedation strategies in ICU. ClinicalTrials.gov NCT03653832 https://clinicaltrials.gov/study/NCT03653832.

Anaemia is prevalent after intensive care unit (ICU) discharge as a consequence of factors such as blood sampling, concurrent inflammation affecting erythropoiesis, and the use of restrictive ICU red blood cell (RBC) transfusion practice during inpatient stay. ICU survivors experience poor health-related quality of life (HRQoL). Prevalent symptoms include fatigue and weakness, to which anaemia may contribute. There are no trials exploring the effectiveness of treating anaemia with RBC transfusions post-ICU discharge. The ABC post-ICU trial is a multicentre prospective, parallel group, randomised trial, with embedded moderation and mediation analysis. Participants are adult ICU survivors with anaemia (haemoglobin (Hb) &#x2a7d;94&#x2009;g/L) fit for ICU discharge. Patients are randomised to usual care (default Hb transfusion trigger <70&#x2009;g/L, target 70-90&#x2009;g/L) or single-unit RBC transfusions to achieve Hb range 100-120&#x2009;g/L. The intervention is from randomisation to hospital discharge. Primary outcome is the physical component summary score (PCS) of the 36-item short form (SF-36) health survey, which measures HRQoL, assessed 90&#x2009;days post-randomisation. Secondary outcomes at 90&#x2009;days include: hospital length of stay, mortality, fatigue score, activities of daily living, and Mental Component Scale score (MCS) SF-36. Outcomes are also measured at 30 and 180&#x2009;days. Safety outcomes include: new infections, transfusion-related adverse events, and major adverse cardiac events. Analysis includes a moderation analysis based on baseline recalled PCS SF-36, comorbidity burden, mobility, and systemic inflammation (C-reactive protein (CRP) concentration). A mediation analysis based on 30&#x2009;days blood samples will explore whether anaemia severity (Hb) or persisting inflammation (CRP) mediates intervention effects. A health-economic analysis over 180&#x2009;days will be conducted. The sample size is 346, providing 90% power to detect a difference in PCS SF-36 of 5 points, assuming >70% completed SF-36 follow-up. NCT04591574.

Delirium is a severe neuropsychiatric clinical state presenting as an acute onset of cognitive deficits. Patients receiving invasive mechanical ventilation (IMV), have the highest incidence (50%-80%) of delirium amongst patients admitted to intensive care units. Preliminary data indicates that early mobilisation is associated with reduced delirium in critically ill patients. However, definitive evidence is lacking. Current practice varies due to many barriers to patients, who require IMV, receiving early mobilisation interventions. In-bed cycling may address some of these barriers. This research aims to evaluate the feasibility and acceptability of early in-bed cycling to reduce delirium in critically ill patients. This multi-site feasibility randomised controlled trial will evaluate early (&#x2a7d;48&#x2009;h following IMV), in-bed cycling as a method of early mobilisation, to reduce delirium. Eighty-four participants will be randomised across three sites in a 1:1 ratio, to receive either early in-bed cycling in addition to usual care or usual care alone. The primary outcome is feasibility (recruitment, retention, intervention fidelity). Secondary outcomes include different methods of measuring delirium, physical function, length of stay, ventilator free days, sedation free days, Richmond Agitation Sedation Scale, adverse events and mortality. Descriptive statistical analyses will be conducted. Hypothesis testing will be used for exploratory analysis of the mechanistic sub-study outcomes. An embedded qualitative interview study will evaluate the acceptability of this research. This trial has been prospectively registered (ISRCTN74277350) and received full ethical approval (REC reference: 24/SC/0096). The trial opened to recruitment in July 2024. Recruitment will take place across 18-months.

Critically ill patients with lower respiratory tract infections often fail to achieve therapeutic beta-lactam antibiotic concentrations, despite standard dosing. Therapeutic drug monitoring (TDM) may improve attaining drug exposure, but delayed turnaround times limit its clinical impact. The objective of this study was to evaluate the feasibility of delivering real-time beta-lactam TDM results within two dosing intervals. We conducted a single-centre prospective cohort feasibility study in two ICUs in Manchester, UK. Critically ill adult patients receiving piperacillin/tazobactam or meropenem for suspected or confirmed lower respiratory infection were enrolled. Blood samples were collected for analysis and drug quantification, with the primary outcome being the proportion of TDM results returned within two dosing intervals. Secondary outcomes included detailed time-to-result, clinical and microbiological outcomes. TDM results were not released to clinical teams. We recruited 30 participants, of whom 20 (67%) had TDM results available within two dosing intervals. The median time from blood sampling to TDM result was 10.9&#x2009;h, with a median time from antimicrobial initiation to result of 25.4&#x2009;h. At 28&#x2009;days, 70% of participants were alive, with a median (IQR) ICU and hospital length of stay of 7 (5-25) and 17 (10-27) days, respectively. Resistant pathogen strains were isolated in 4/21 (19%) participants. Recruitment of critically ill participants into a time-sensitive trial of TDM is feasible. Timely feedback of beta-lactam TDM results to clinicians is achievable, however, barriers to streamlined around-the-clock implementation remain. Future clinical trials of beta-lactam TDM should factor turnaround times into study design. NCT05971979.