Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study.

BACKGROUND: Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS: In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS: Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS: Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.

Critical care pharmacy service provision and workforce in adult extracorporeal membrane oxygenation centres: a multicentre cross-sectional survey.

BACKGROUND: There is good evidence describing pharmacy workforce and service provision in general critical care units. However, no data exist from adult extracorporeal membrane oxygenation (ECMO) centres. AIM: To describe workforce characteristics, pharmacy service provision, and pharmaceutical care activities in critical care units (CCUs) providing an adult ECMO service in the United Kingdom (UK) and compare to national staffing standards for CCUs. METHOD: We conducted a multicentre, cross-sectional electronic survey inviting one pharmacy professional response per UK ECMO centre. We collated information on workforce, service provision, and pharmaceutical care activities provided by pharmacy teams in adult CCUs with an ECMO service. RESULTS: The survey response rate was 90.9%: representatives of 10/11 tertiary hospitals providing ECMO services responded. Median critical care pharmacist to critical care bed was 1:12.1 (IQR: 1:9.4-1:14.9). Most centres (90.0%) did not meet national standards for pharmacy professionals to critical care bed staffing ratios for weekday services. Total critical care beds covered by the critical care pharmacy team varied across the UK: median (IQR) - 45 (37-80) beds. Two centres funded pharmacist time for ECMO activity, and one centre funded a pharmacy technician post. Median peak ECMO activity was 4 ECMO patients in a single day (IQR: 3-5). Most respondents reported reduced pharmacy service at weekends compared to weekday, with limited on-site support. CONCLUSION: Most responding ECMO centres in the UK reported pharmacy staffing ratios below nationally agreed critical care standards. There was high variability in clinical pharmacy services to ECMO patients over 7 days.

Anti-Xa Assay Monitoring Improves the Precision of Anticoagulation in Venovenous Extracorporeal Membrane Oxygenation.

Unfractionated heparin (UFH) is the most used anticoagulant in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO). Its therapeutic levels are monitored using activated partial thromboplastin time ratio (aPTTr) or antifactor Xa (anti-Xa) assay. This was a retrospective, single-center, cohort study where all adult patients with viral etiology respiratory failure requiring VV-ECMO from January 2, 2015 to January 31, 2022 were included. Anticoagulation was monitored using aPTTr (until November 1, 2019) or anti-Xa assay (after November 1, 2019). We compared the accuracy and precision of anticoagulation monitoring tests using time in therapeutic range (TTR) and variance growth rate (VGR), respectively, and their impact on bleeding and thrombotic events (BTEs). A total of 254 patients, 74 in aPTTr and 180 in anti-Xa monitoring groups, were included with a total of 4,992 ECMO-person days. Accuracy was comparable: mean TTR of 47% in aPTTr and 51% in anti-Xa groups ( p = 0.28). Antifactor Xa monitoring group demonstrated improved precision with a lower variance (median VGR 0.21 vs. 1.61 in aPTTr, p < 0.05). Secondary outcome of less heparin prescription changes (adjusted rate ratio [RR] = 1.01, p = 0.01), fewer blood transfusions (adjusted RR = 0.78, p < 0.05), and ECMO circuit changes (adjusted RR = 0.68, p < 0.05) were seen with anti-Xa monitoring.

Identifying barriers and enablers for a robust independent second check of medication in adult intensive care.

BACKGROUND: Independent second-checking of medication is part of everyday practice across many parts of the NHS. A robust, independent second check is built into medication administration protocols to reduce the risk of drug errors affecting patients. AIM: This work aims to determine the barriers and facilitators regarding a robust independent second check of medication before administration to patients within adult critical care. METHOD: Nurses in adult critical care were invited to participate in focus groups. They were asked to discuss factors that they felt enabled or prevented a robust second check of medication. Thematic analysis was undertaken by three critical care pharmacists. FINDINGS: The major themes identified as barriers to an independent second check were: geography of the critical care unit; IT; routine; complex process; and personnel. CONCLUSION: There are complex barriers to undertaking a robust second check and addressing some of these could improve patient safety.

Micronutrient Losses during Continuous Renal Replacement Therapy.

Acute kidney injury impacts the micronutrient status by various mechanisms including decreased enteral absorption, changes in redistribution, altered metabolism, and increased consumption. When renal replacement therapy (RRT) is applied, there are additional losses of vitamins, trace elements, and amino acids, and their derivatives due to diffusion or adhesion. Varied data exist regarding the degree of micronutrient losses and plasma concentrations in patients who receive RRT, and these differ by RRT modality, dose, duration, and type of micronutrient. Water-soluble vitamins, selenium, copper, and carnitine are among the most frequently reported depleted nutrients. The role of micronutrient supplementation in critically ill patients undergoing RRT and the optimal dose and mode of administration are yet to be determined.

Micronutrient use in critical care: Survey of clinical practice.

BACKGROUND & AIMS: Micronutrients, principally vitamins and minerals, play an important role both in health and in disease. Parenteral micronutrient products are commonly prescribed for critically ill patients both in line with the terms of the product's license, and for other indications where there is an underpinning physiological rationale, or precedent, for their use but little evidence. This survey sought to understand United Kingdom (UK) prescribing practice in this area. METHODS: A 12-question survey was circulated to healthcare professionals working in UK critical care units. The survey was designed to explore several aspects of micronutrient prescribing or recommendation practice by the critical care multidisciplinary team, including indications and underpinning clinical rationale for using these products, dosing, and considerations with respect to micronutrients delivered as part of nutrition. Results were analysed, exploring indications, considerations relating to diagnoses, therapies including renal replacement therapies, and method of nutrition. RESULTS: 217 responses were included in the analysis, with 58% from physicians and the remaining 42% from nurses, pharmacists, dietitians and other healthcare disciplines. Vitamins were most commonly prescribed or recommended for Wernicke's encephalopathy (prescribed or recommended by 76% of respondents), treatment of refeeding syndrome (64.5%), and for patients with unknown or uncertain alcohol intake history (63.6%). These clinically suspected or confirmed indications were cited more frequently as a reason to prescribe than laboratory identified deficiency states. 20% of respondents indicated that they would prescribe or recommend parenteral vitamins for patients requiring renal replacement therapy. The practice of vitamin C prescribing was heterogeneous, including dose and indication. Trace elements were prescribed or recommended less often than vitamins, with the most frequently reported indications being for patients requiring parenteral nutrition (42.9%), biochemically confirmed deficiency states (35.9%), and for treatment of refeeding syndrome (26.3%). CONCLUSIONS: Micronutrient prescribing in ICUs in the UK is heterogeneous, with clinical scenarios where there is an evidence base or an established precedent for their use often guiding decisions to use micronutrient products. Further work to examine the potential benefits and harms on patient-oriented outcomes of micronutrient product administration should be undertaken, to facilitate their judicious and cost-effective use, with a focus on areas where they have a theoretical benefit.

Discharge Documentation and Follow-Up of Critically Ill Patients With Acute Kidney Injury Treated With Kidney Replacement Therapy: A Retrospective Cohort Study.

Leading organisations recommend follow-up of acute kidney injury (AKI) survivors, as these patients are at risk of long-term complications and increased mortality. Information transfer between specialties and from tertiary to primary care is essential to ensure timely and appropriate follow-up. Our aim was to examine the association between completeness of discharge documentation and subsequent follow-up of AKI survivors who received kidney replacement therapy (KRT) in the Intensive Care Unit (ICU). We retrospectively analysed the data of 433 patients who had KRT for AKI during ICU admission in a tertiary care centre in the UK between June 2017 and May 2018 and identified patients who were discharged from hospital alive. Patients with pre-existing end-stage kidney disease and patients who were transferred from hospitals outside the catchment area were excluded. The primary objective was to assess the completeness of discharge documentation from critical care and hospital; secondary objectives were to determine cardiovascular medications reconciliation after AKI, and to investigate kidney care and outcomes at 1 year. The development of AKI and the need for KRT were mentioned in 85 and 82% of critical care discharge letters, respectively. Monitoring of kidney function post-discharge was recommended in 51.6% of critical care and 36.3% of hospital discharge summaries. Among 35 patients who were prescribed renin-angiotensin-aldosterone system inhibitors before hospitalisation, 15 (42.9%) were not re-started before discharge from hospital. At 3 months, creatinine and urine protein were measured in 88.2 and 11.8% of survivors, respectively. The prevalence of chronic kidney disease stage III or worse increased from 27.2% pre-hospitalisation to 54.9% at 1 year (p < 0.001). Our data demonstrate that discharge summaries of patients with AKI who received KRT lacked essential information. Furthermore, even in patients with appropriate documentation, renal follow-up was poor suggesting the need for more education and streamlined care pathways.

Vitamin D levels in critically ill patients with acute kidney injury: a protocol for a prospective cohort study (VID-AKI).

INTRODUCTION: Acute kidney injury (AKI) affects more than 50% of critically ill patients. The formation of calcitriol, the active vitamin D metabolite, from the main inactive circulating form, 25-hydroxyvitamin D (25(OH)D), occurs primarily in the proximal renal tubules. This results in a theoretical basis for reduction in levels of calcitriol over the course of an AKI. Vitamin D deficiency is highly prevalent in critically ill adults, and has been associated with increased rates of sepsis, longer hospital stays and increased mortality. The primary objective of this study is to perform serial measurements of 25(OH)D and calcitriol (1,25(OH)2D), as well as parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels, in critically ill adult patients with and without AKI, and to determine whether patients with AKI have significantly lower vitamin D metabolite concentrations. The secondary objectives are to describe dynamic changes in vitamin D metabolites, PTH and FGF23 during critical illness; to compare vitamin D metabolite concentrations in patients with AKI with and without renal replacement therapy; and to investigate whether there is an association between vitamin D status and outcomes. METHODS AND ANALYSIS: 230 general adult intensive care patients will be recruited. The AKI arm will include 115 critically ill patients with AKI Kidney Disease Improving Global Outcome stage II or stage III. The comparison group will include 115 patients who require cardiovascular or respiratory support, but who do not have AKI. Serial measurements of vitamin D metabolites and associated hormones will be taken on prespecified days. Patients will be recruited from two large teaching Trusts in England. Data will be analysed using standard statistical methods. ETHICS AND DISSEMINATION: Ethical approval was obtained. Upon completion, the study team will submit the study report for publication in a peer-reviewed scientific journal and for conference presentation. TRIAL REGISTRATION NUMBER: NCT02869919; Pre-results.

Development and psychometric evaluation of the German version of the Medication Regimen Complexity Index (MRCI-D).

BACKGROUND: Several factors contribute to the complexity of pharmacotherapeutic regimens, like the total number of medications to be taken, the number of dosage units to take at a time, dosage frequency, as well as specific directions concerning the administration. The Medication Regimen Complexity Index (MRCI) is a validated instrument developed in English for the measurement of the complexity of a given pharmacotherapeutic regimen. OBJECTIVES: Translation of the MRCI into German and evaluation of the translated instrument (MRCI-D) in order to make it more easily accessible for use in German practice and research. METHODS: The process of validation included the translation of the English version to German, back-translation into English, comparison of the back-translated and the original versions, pre-tests, and pilot-testing of the German version by three raters using 20 medication regimens for inpatients. The subsequent psychometric evaluation included the calculation of inter-rater and test-retest reliability, as well as the assessment of convergent validity. RESULTS: The number of medications correlated highly and statistically significantly with the MRCI-D score (0.91, P < 0.001), indicating sufficient convergent validity of the instrument. Both inter-rater and test-retest reliability were very high (intraclass correlation coefficients above 0.80 in all cases). CONCLUSION: Our results demonstrate that the German version of the MRCI reflects the complexity of therapeutic regimens with similar validity and reliability as the established English version. Thus, it may be a valuable tool to analyse therapeutic regimens in both clinical practice and science.