Introduction: Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI, renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulation, which may offer mechanistic insight into the pathophysiology of septic AKI. The aim of the current study is to investigate the effects of vasopressin and angiotensin II on renal microcirculatory perfusion in a cohort of patients with septic shock. Methods and analysis: In this single centre, mechanistically focussed, randomised controlled study, 45 patients with septic shock will be randomly allocated to either of the study vasopressors (vasopressin or angiotensin II) or standard therapy (norepinephrine). Infusions will be titrated to maintain a mean arterial pressure (MAP) target set by the attending clinician. Renal microcirculatory assessment will be performed for the cortex and medulla using contrast-enhanced ultrasound (CEUS) and urinary oxygen tension (pO2), respectively. Renal macrovascular flow will be assessed via renal artery ultrasound. Measurement of systemic macrovascular flow will be performed through transthoracic echocardiography (TTE) and microvascular flow via sublingual incident dark field (IDF) video microscopy. Measures will be taken at baseline, +1 and +24hrs following infusion of the study drug commencing. Blood and urine samples will also be collected at the measurement time points. Longitudinal data will be compared between groups and over time. Discussion: Vasopressors are integral to the management of patients with septic shock. This study aims to further understanding of the relationship between this therapy, renal perfusion and the development of AKI. In addition, using CEUS and urinary pO2, we hope to build a more complete picture of renal perfusion in septic shock by interrogation of the constituent parts of the kidney. Results will be published in peer-reviewed journals and presented at academic meetings. Trial registration: The REPERFUSE study was registered on Clinical Trials.gov (NCT06234592) on the 30^th Jan 24.

Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate treatment, prolonged hospital stays, and increased morbidity and mortality. This issue is compounded by the increased toxicity profiles of the conventional antibiotics required to treat MDR-GNB infections. In recent years, several novel antibiotics have been licensed for the treatment of GNB nosocomial pneumonia. These novel antibiotics are promising therapeutic options for treatment of nosocomial pneumonia by MDR pathogens with certain mechanisms of resistance. Still, antibiotic resistance remains an evolving global crisis, and resistance to novel antibiotics has started emerging, making their judicious use crucial to prolong their shelf-life. This article presents an up-to-date review of these novel antibiotics and their current role in the antimicrobial armamentarium. We critically present data for the pharmacokinetics/pharmacodynamics, the in vitro spectrum of antimicrobial activity and resistance, and in vivo data for their clinical and microbiological efficacy in trials. Where possible, available data are summarized specifically in patients with nosocomial pneumonia, as this cohort may exhibit ‘critical illness’ physiology that affects drug efficacy.

Background: Critically ill patients are at risk of bleeding from stress ulcers. Comprehensive information regarding United Kingdom stress ulcer prophylaxis (SUP) practices are not available and may change over time. We aimed to describe SUP practices in 2020 and reevaluate the position in 2024. Methods: Critical care pharmacists provided observed SUP practice data for UK adult critical care units via an electronic repository in 2020 and 2024. One response was accepted from each critical care unit at each time point. Data collected included trigger criteria for commencing SUP, primary medication class used, primary SUP cessation criteria, and level of nutritional intake (if part of cessation criteria). Results: There were high response rates of 70.3% (2020) and 66.7% (2024) of registered UK adult critical care units. Few differences in primary SUP trigger criteria between 2020 and 2024 were seen, with small differences in the categories of ‘SUP not used’ ( p = 0.002) and ‘Shock’ ( p = 0.027) driving statistical significance (χ ² (7, 454) = 16.76, p = 0.019). There was a significant change in the primary medication class used for SUP (H2 receptor antagonist 49.4% 2020, vs 0.4% 2024, proton pump inhibitor 44.7% 2020 vs 97.8% 2024; χ ² (2, 458) = 159.62, p < 0.001). Primary SUP cessation criteria was ‘Patient fed’ (66.8% 2020, 64.6% 2024), with most describing this threshold as met when the patient receives full enteral feed (72.0% 2020, 78.8% 2024). Conclusion: The UK has moved towards proton pump inhibitors as the primary SUP medication class. SUP is most frequently discontinued on establishment of enteral nutrition.

Despite the strong face validity of electronic prescribing (EP), the empiric data in support of improved patient safety is sparse. The objective of this study was to compare the clinical significance of pharmacist contributions between an established EP and paper-based prescribing (PBP) system in the intensive care unit (ICU) to understand the EP impact on the quality of patient care. We conducted a prospective longitudinal study in two 18-bed ICUs; one with EP and the other, PBP. Pharmacist contributions were analysed over three months. Demographic, clinical and adjunctive intervention data were also collected. A multilevel ordinal logistic regression model was used and patients were followed up for 28 days. The primary outcome was the distribution of clinical significance levels of pharmacist contributions. There were 303 patients admitted to the ICU between April 1st and June 30th 2018. EP was used in 171 patients and PBP in 132 patients. 1658 contributions were analysed. There were 14.9% highly clinically significant contributions with EP compared to 44.6% with PBP. The EP group had lower odds (OR 0.05, 95% CI 0.02-0.12) for a higher clinical significance contribution compared to the PBP group, but this changed over the admission and differed between groups, with decreasing odds of a higher-level clinical contribution for each additional admission day with PBP (OR 0.57, 95%CI 0.42-0.78). This study showed a significant difference in the distribution of pharmacist contributions made over time, with clinical significance levels remaining stable in the EP group at low severity, as opposed to PBP which were initially high and then gradually decreased in severity over time. This contemporaneous controlled study found that the EP system required less significant input both in the severity and frequency of pharmacist contributions to maintain patient safety.