A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women.

Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater. Women aged 50 years or greater admitted to an intensive care unit for at least 24 h were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for 1 year. We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (± 40%), compared to an increase of 26% (± 55%) observed with placebo (absolute difference - 69%, 95% CI - 127% to - 11%), p = 0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded. In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment.Trial registration: ACTRN12617000545369, registered 18th April 2017.

Assessment of a novel marker of ICU strain, the ICU Activity Index, during the COVID-19 pandemic in Victoria, Australia.

Objectives: To validate a real-time Intensive Care Unit (ICU) Activity Index as a marker of ICU strain from daily data available from the Critical Health Resource Information System (CHRIS), and to investigate the association between this Index and the need to transfer critically ill patients during the coronavirus disease 2019 (COVID-19) pandemic in Victoria, Australia. Design: Retrospective observational cohort study. Setting: All 45 hospitals with an ICU in Victoria, Australia. Participants: Patients in all Victorian ICUs and all critically ill patients transferred between Victorian hospitals from 27 June to 6 September 2020. Main outcome measure: Acute interhospital transfer of one or more critically ill patients per day from one site to an ICU in another hospital. Results: 150 patients were transported over 61 days from 29 hospitals (64%). ICU Activity Index scores were higher on days when critical care transfers occurred (median, 1.0 [IQR, 0.4-1.7] v 0.6 [IQR, 0.3-1.2]; P < 0.001). Transfers were more common on days of higher ICU occupancy, higher numbers of ventilated or COVID-19 patients, and when more critical care staff were unavailable. The highest ICU Activity Index scores were observed at hospitals in north-western Melbourne, where the COVID-19 disease burden was greatest. After adjusting for confounding factors, including occupancy and lack of available ICU staff, a rising ICU Activity Index score was associated with an increased risk of a critical care transfer (odds ratio, 4.10; 95% CI, 2.34-7.18; P < 0.001). Conclusions: The ICU Activity Index appeared to be a valid marker of ICU strain during the COVID-19 pandemic. It may be useful as a real-time clinical indicator of ICU activity and predict the need for redistribution of critical ill patients.

The association of time and medications with changes in bone mineral density in the 2 years after critical illness.

BACKGROUND: Critical illness is associated with increased risk of fragility fracture and loss of bone mineral density (BMD), although the impact of medication exposures (bone anti-fracture therapy or glucocorticoids) and time remain unexplored. The objective of this study was to describe the association of time after ICU admission, and post-ICU administration of bone anti-fracture therapy or glucocorticoids after critical illness, with change in BMD. METHODS: In this prospective observational study, conducted in a tertiary hospital ICU, we studied adult patients requiring mechanical ventilation for at least 24 hours and measured BMD annually for 2 years after ICU discharge. We performed mixed linear modelling to describe the association of time, and post-ICU administration of anti-fracture therapy or glucocorticoids, with annualised change in BMD. RESULTS: Ninety-two participants with a mean age of 63 (±15) years had at least one BMD assessment after ICU discharge. In women, a greater loss of spine BMD occurred in the first year after critical illness (year 1: -1.1 ± 2.0% vs year 2: 3.0 ± 1.7%, p = 0.02), and anti-fracture therapy use was associated with reduced loss of BMD (femur 3.1 ± 2.4% vs -2.8 ± 1.7%, p = 0.04, spine 5.1 ± 2.5% vs -3.2 ± 1.8%, p = 0.01). In men anti-fracture and glucocorticoid use were not associated with change in BMD, and a greater decrease in BMD occurred in the second year after critical illness (year 1: -0.9 ± 2.1% vs year 2: -2.5 ± 2.1%, p = 0.03). CONCLUSIONS: In women a greater loss of spine BMD was observed in the first year after critical illness, and anti-fracture therapy use was associated with an increase in BMD. In men BMD loss increased in the second year after critical illness. Anti-fracture therapy may be an effective intervention to prevent bone loss in women after critical illness.

Changes in Bone Mineral Density in the Year after Critical Illness.

RATIONALE: Critical illness may be associated with increased bone turnover and loss of bone mineral density (BMD). Prospective evidence describing long-term changes in BMD after critical illness is needed to further define this relationship. OBJECTIVES: To measure the change in BMD and bone turnover markers (BTMs) in subjects 1 year after critical illness compared with population-based control subjects. METHODS: We studied adult patients admitted to a tertiary intensive care unit (ICU) who required mechanical ventilation for at least 24 hours. We measured clinical characteristics, BTMs, and BMD during admission and 1 year after ICU discharge. We compared change in BMD to age- and sex-matched control subjects from the Geelong Osteoporosis Study. MEASUREMENTS AND MAIN RESULTS: Sixty-six patients completed BMD testing. BMD decreased significantly in the year after critical illness at both femoral neck and anterior-posterior spine sites. The annual decrease was significantly greater in the ICU cohort compared with matched control subjects (anterior-posterior spine, -1.59%; 95% confidence interval, -2.18 to -1.01; P < 0.001; femoral neck, -1.20%; 95% confidence interval, -1.69 to -0.70; P < 0.001). There was a significant increase in 10-year fracture risk for major fractures (4.85 ± 5.25 vs. 5.50 ± 5.52; P < 0.001) and hip fractures (1.57 ± 2.40 vs. 1.79 ± 2.69; P = 0.001). The pattern of bone resorption markers was consistent with accelerated bone turnover. CONCLUSIONS: Critically ill individuals experience a significantly greater decrease in BMD in the year after admission compared with population-based control subjects. Their bone turnover biomarker pattern is consistent with an increased rate of bone loss.

Early diagnosis and treatment of necrotizing fasciitis can improve survival: an observational intensive care unit cohort study.

BACKGROUND: The aim of this study was to describe the clinical characteristics, causative pathogens, clinical management and outcomes of patients presenting to a tertiary adult Australian intensive care unit (ICU) with a diagnosis of necrotizing fasciitis (NF). METHODS: This retrospective observational study was conducted in a 19-bed, level III, adult ICU in a 450-bed tertiary, regional hospital. Clinical databases were accessed for patients diagnosed with NF and admitted to The Geelong Hospital ICU between 1 February 2000 and 1 June 2011. Information on severity of sepsis, surgical procedures and microbiological results were collected. RESULTS: Twenty patients with NF were identified. The median age was 52.5 years and 38% were female. The overall mortality rate was 8.3%. Common co-morbidities were diabetes (21%) and heart failure (17%), although 50% of patients had no co-morbidities. Group A Streptococcus was the identified pathogen in 11 (46%) patients, and Streptococcus milleri group in 5 (21%) patients. Hyperbaric oxygen therapy was not used in the majority of patients. The initial antibiotics administered were active against subsequently cultured bacteria in 83% of patients. Median time to surgical debridement was 20 h. Diagnosis and management was delayed in the nosocomial group. CONCLUSIONS: This study reports physiological data, aetiology and therapeutic interventions in NF for an adult tertiary hospital. We demonstrate one of the lowest reported mortality rates, with early surgical debridement being achieved in the majority of patients. The main delay was found to be in the diagnosis of NF.