Mortality and readmission rates of patients discharged in-hours and out-of-hours from a British ICU over a 3-year period.

Excess in-hospital mortality following out-of-hours ICU discharge has been reported worldwide. From preliminary data, we observed that magnitude of difference may be reduced when patients discharged for end-of-life care or organ donation are excluded. We speculated that these patients may be disproportionately discharged out-of-hours, biasing results.

Real-world experience of SARS-CoV-2 antibody assays in UK healthcare workers.

Background: The seroprevalence of antibodies to SARS-CoV-2 in healthcare workers is variable throughout the world. This study compares the use of two antibody assays among large cohorts of healthcare workers in southern England.

Methods: This cohort study includes data obtained from staff at Western Sussex Hospitals NHS Foundation Trust (WSHT) and Brighton and Sussex University Hospitals (BSUH) during voluntary antibody testing, using Abbott and Roche SARS-CoV-2 antibody assays at each Trust respectively.

β-Lactam antimicrobial pharmacokinetics and target attainment in critically ill patients aged 1 day to 90 years: the ABDose study.

Background: The pharmacokinetics of β-lactam antibiotics in critical illness remain poorly characterized, particularly in neonates, children and the elderly. We undertook a pharmacokinetic study of commonly used β-lactam antibiotics in critically ill patients of all ages. The aims were to produce a whole-life β-lactam pharmacokinetic model and describe the extent to which standard doses achieve pharmacokinetic/pharmacodynamic targets associated with clinical cure.

Von Willebrand factor (vWF): marker of endothelial damage and thrombotic risk in COVID-19?

Background: COVID-19 infection is characterised, among other features, by a prothrombotic state with high rate of venous thromboembolism (VTE), D-dimer, and fibrinogen levels. Clinical observations have also highlighted that these patients have elevated von Willebrand factor (vWF) and factor VIIIc.

Methods: 24 consecutive COVID-19 positive patients were selected from the intensive care unit (ICU) or the high acuity ward of Brighton and Sussex University Hospitals NHS Trust.

Scaling beta-lactam antimicrobial pharmacokinetics from early life to old age.

Aims: Beta-lactam dose optimization in critical care is a current priority. We aimed to review the pharmacokinetics (PK) of three commonly used beta-lactams (amoxicillin ± clavulanate, piperacillin-tazobactam and meropenem) to compare PK parameters reported in critically and noncritically ill neonates, children and adults, and to investigate whether allometric and maturation scaling principles could be applied to describe changes in PK parameters through life.

Methods: A systematic review of PK studies of the three drugs was undertaken using MEDLINE and EMBASE.

An analysis of emergency tracheal intubations in critically ill patients by critical care trainees.

Introduction: We evaluated intensive care medicine trainees' practice of emergency intubations in the United Kingdom.

Methods: Retrospective analysis of 881 in-hospital emergency intubations over a three-year period using an online trainee logbook.

Results: Emergency intubations out-of-hours were less frequent than in-hours, both on weekdays and weekends.

Continuous Infusion of Low-Dose Iohexol Measures Changing Glomerular Filtration Rate in Critically Ill Patients.

Objective: Measurement of changing glomerular filtration rate in acute kidney injury remains problematic. We have previously used a continuous infusion of low-dose Iohexol to measure glomerular filtration rate in stable subjects and postulate that changes greater than 10.3% in critically ill patients indicate acute kidney injury.

Do statins prevent acute kidney injury?

Introduction: Statins were introduced as lipid-lowering agents with a specific action to decrease plasma cholesterol concentrations and they have led to significant reductions in cardiovascular morbidity and mortality. Since their introduction, they have been found to have highly pleiotropic effects and potential use in many medical conditions well beyond cardiovascular disease alone. With their widespread and increasing use, adverse effects have also become apparent and it is suggested from the interrogation of observational data from large datasets that an early complication of statin use may be acute kidney injury (AKI).

Validation of a continuous infusion of low dose Iohexol to measure glomerular filtration rate: randomised clinical trial.

Introduction: There is currently no accurate method of measuring glomerular filtration rate (GFR) during acute kidney injury (AKI). Knowledge of how much GFR varies in stable subjects is necessary before changes in GFR can be attributed to AKI. We have designed a method of continuous measurement of GFR intended as a research tool to time effects of AKI.

Xenobiotic metabolism: the effect of acute kidney injury on non-renal drug clearance and hepatic drug metabolism.

Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI.

The effects of acute renal failure on drug metabolism.

Introduction: Acute kidney injury (AKI) is common in all hospital admissions and affects 10% of acute admissions in hospital. It increases the risk of adverse events and mortality, although the precise reasons for this are still unclear. The impact of chronic kidney disease (CKD) on nonrenal drug clearance is increasingly apparent and is now considered an important factor by the Food and Drug Administration for drug dose recommendations in CKD.

Renohepatic crosstalk: does acute kidney injury cause liver dysfunction?

The concept of hepatorenal syndrome is well recognized, although incompletely understood. The converse clinical problem of hepatic dysfunction in patients with acute kidney injury (AKI) is less well recognized yet may be a contributor to the high patient morbidity and mortality seen in this group. This review draws together the available evidence for AKI's effect on the liver from animal models, pharmacological studies and recent clinical data.

Estimated glomerular filtration rate correlates poorly with four-hour creatinine clearance in critically ill patients with acute kidney injury.

Introduction. RIFLE and AKIN provide a standardised classification of acute kidney injury (AKI), but their categorical rather than continuous nature restricts their use to a research tool. A more accurate real-time description of renal function in AKI is needed, and some published data suggest that equations based on serum creatinine that estimate glomerular filtration rate (eGFR) can provide this.

Clinical review: Biomarkers of acute kidney injury: where are we now?

The recognition that acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality has resulted in a substantial number of publications over the past 5 years or more. In no small part these have, to a degree, highlighted the inadequacy of conventional markers of renal insufficiency in the acute setting. Much effort has been invested in the identification of early, specific AKI markers in order to aid early diagnosis of AKI and hopefully improve outcome.

The interpretation of brain natriuretic peptide in critical care patients; will it ever be useful?

The measurement of B-type natriuretic peptide (BNP) is recommended for the diagnosis of decompensated heart failure, the prognosis of chronic heart failure is worse if BNP is increased and studies suggest that BNP is useful to guide therapy. A study by Di Somma and colleagues adds to the body of evidence showing that patients with a marked decrease in BNP concentrations during their hospital admission are less likely to be readmitted with a further adverse cardiac event than patients in whom BNP fails to decrease. However, the wider interpretation of BNP concentrations in critically ill patients with other conditions remains uncertain.

Using drug probes to monitor hepatic drug metabolism in critically ill patients: midazolam, a flawed but useful tool for clinical investigation of CYP3A activity?

Importance Of The Field: In the UK, acute kidney injury (AKI) occurs in 25% of patients admitted to intensive care. Outcome is worsened in the presence of AKI for reasons not easily explained. AKI unpredictably affects the pharmacokinetics and pharmacodynamics of drugs and dosing in patients with AKI is largely based on data from chronic kidney disease patients, but how appropriately is unknown.

Triaging for adult critical care in the event of overwhelming need.

Introduction: Predictions of the need for critical care within the H1N1 influenza pandemic suggested overwhelming need beyond potential resources, necessitating rationing of care via triaging.

Method: The triage model described was derived from informed discourse within a conjoined NHS and University Clinical Ethics Committee, supplemented by specialists in intensive care and infectious diseases. THE MODEL: The triage methodology described is justified ethically primarily upon 'utilitarian' principles within an aggregate public health model, with additional reference to 'fairness'.

Idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis: a case report.

Background: Pulmonary vein thrombosis represents a potentially fatal disease. This syndrome may clinically mimic pulmonary embolism but has a different investigation strategy and prognosis. Pulmonary vein thrombosis is difficult to diagnose clinically and usually requires a combination of conventionally used diagnostic modalities.

Using midazolam to monitor changes in hepatic drug metabolism in critically ill patients.

Objective: Critical illness and associated sequelae can cause severe metabolic disturbances. The effects these have on hepatic drug metabolism are poorly understood. In vivo, enzyme specific drug probes are used to measure changes in hepatic drug metabolism but they require multiple blood sampling and are time consuming.

Glucose homeostasis across human airway epithelial cell monolayers: role of diffusion, transport and metabolism.

Glucose in airway surface liquid (ASL) is maintained at low concentrations compared to blood glucose. Using radiolabelled [(3)H]-D: -glucose and [(14)C]-L: -glucose, detection of D: - and L: -glucose by high-performance liquid chromatography and metabolites by nuclear magnetic resonance, we found that glucose applied to the basolateral side of H441 human airway epithelial cell monolayers at a physiological concentration (5 mM) crossed to the apical side by paracellular diffusion. Transepithelial resistance of the monolayer was inversely correlated with paracellular diffusion.