Epidemiology of Hypophosphatemia in Critical Illness: A Multicentre, Retrospective Cohort Study.

INTRODUCTION: Hypophosphatemia is common in critically ill patients. We have described the epidemiology of hypophosphatemia in patients admitted to the Intensive Care Units. METHODS: A multicentre, retrospective cohort study of 12 ICUs in Queensland, Australia from January 1st, 2015, to December 31st, 2021. Exclusions included readmissions, renal replacement therapy, end-stage renal disease, and palliative intent admissions and transfers from other ICUs. Patients were classified into four groups based on the severity of the first episode of low serum phosphate (PO4): "None" (PO4: ≥ 0.81 mmol/L, ``Mild" (PO4: ≥ 0.50 & < 0.81 mmol/L) "Moderate" (PO4: ≥ 0.30 & < 0.50 mmol/L) and "Severe" (PO4: < 0.30 mmol/L). A mixed-effect logistic regression model, including hospital as a random effect, was developed to examine factors associated with 90-day case fatality. RESULTS: Of the 89,776 patients admitted, 68,699 patients were included in this study, with 23,485 (34.2%) having hypophosphatemia with onset mostly on Day 2 of ICU admission and correcting to normal 3 days after hypophosphatemia was identified. There was substantial variation among participating ICUs in phosphate replacement; the threshold, and the route by which it was replaced. Day-90 case fatality increased with severity of hypophosphatemia (None: 3,974 (8.8%), Mild: 2,306 (11%), Moderate: 377 (14%); Severe: 108 (21%) (p < 0.001)). Multivariable regression analysis showed that compared to those without hypophosphatemia, patients with moderate (odds ratio (OR) 1.24; 95% confidence intervals (CI) 1.07-1.44; p = 0.004) or severe (OR 1.49; 95% CI 1.13-1.97; p = 0.005) hypophosphatemia had increased risk of 90-day case fatality. CONCLUSION: Hypophosphatemia was common, and mostly occurred on day 2 with early correction of serum phosphate. Phosphate replacement practices were variable among ICUs. Moderate and severe hypophosphatemia was associated with increased 90-day case fatality.

How a positive fluid balance develops in acute kidney injury: A binational, observational study.

PURPOSE: A positive fluid balance (FB) is associated with harm in intensive care unit (ICU) patients with acute kidney injury (AKI). We aimed to understand how a positive balance develops in such patients. METHODS: Multinational, retrospective cohort study of critically ill patients with AKI not requiring renal replacement therapy. RESULTS: AKI occurred at a median of two days after admission in 7894 (17.3%) patients. Cumulative FB became progressively positive, peaking on day three despite only 848 (10.7%) patients receiving fluid resuscitation in the ICU. In those three days, persistent crystalloid use (median:60.0 mL/h; IQR 28.9-89.2), nutritional intake (median:18.2 mL/h; IQR 0.0-45.9) and limited urine output (UO) (median:70.8 mL/h; IQR 49.0-96.7) contributed to a positive FB. Although UO increased each day, it failed to match input, with only 797 (10.1%) patients receiving diuretics in ICU. After adjustment, a positive FB four days after AKI diagnosis was associated with an increased risk of hospital mortality (OR 1.12;95% confidence intervals 1.05-1.19;p-value <0.001). CONCLUSION: Among ICU patients with AKI, cumulative FB increased after diagnosis and was associated with an increased risk of mortality. Continued crystalloid administration, increased nutritional intake, limited UO, and minimal use of diuretics all contributed to positive FB. KEY POINTS: Question How does a positive fluid balance develop in critically ill patients with acute kidney injury? Findings Cumulative FB increased after AKI diagnosis and was secondary to persistent crystalloid fluid administration, increasing nutritional fluid intake, and insufficient urine output. Despite the absence of resuscitation fluid and an increasing cumulative FB, there was persistently low diuretics use, ongoing crystalloid use, and a progressive escalation of nutritional fluid therapy. Meaning Current management results in fluid accumulation after diagnosis of AKI, as a result of ongoing crystalloid administration, increasing nutritional fluid, limited urine output and minimal diuretic use.

Current Fluid Management Practice in Critically Ill Adults on Continuous Renal Replacement Therapy: A Binational, Observational Study.

INTRODUCTION: In critically ill patients undergoing continuous renal replacement therapy (CRRT), a positive fluid balance (FB) is associated with adverse outcomes. However, current FB management practices in CRRT patients are poorly understood. We aimed to study FB and its components in British and Australian CRRT patients to inform future trials. METHODS: We obtained detailed electronic health record data on all fluid-related variables during CRRT and hourly FB for the first 7 days of treatment. RESULTS: We studied 1,616 patients from three tertiary intensive care units (ICUs) in two countries. After the start of CRRT, the mean cumulative FB became negative at 31 h and remained negative over 7 days to a mean nadir of -4.1 L (95% confidence interval (CI) of -4.6 to -3.5). The net ultrafiltration (NUF) rate was the dominant fluid variable (-67.7 mL/h; standard deviation (SD): 75.7); however, residual urine output (-34.7 mL/h; SD: 54.5), crystalloid administration (48.1 mL/h; SD: 44.6), and nutritional input (36.4 mL/h; SD: 29.7) significantly contributed to FB. Patients with a positive FB after 72 h of CRRT were more severely ill, required high-dose vasopressors, and had high lactate concentrations (5.0 mmol/L; interquartile range: 2.3-10.5). A positive FB was independently associated with increased hospital mortality (odds ratio: 1.70; 95% CI; p = 0.004). CONCLUSION: In the study ICUs, most CRRT patients achieved a predominantly NUF-dependent negative FB. Patients with a positive FB at 72 h had greater illness severity and haemodynamic instability. Achieving equipoise for conducting trials that target a negative early FB in such patients may be difficult.

Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes. A multicenter, observational study.

PURPOSE: The Acute Disease Quality Initiative (ADQI) Workgroup recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), combining Sepsis-3 and Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. This study aims to describe the epidemiology of SA-AKI. METHODS: This is a retrospective cohort study carried out in 12 intensive care units (ICUs) from 2015 to 2021. We studied the incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes of SA-AKI based on the ADQI definition. RESULTS: Out of 84,528 admissions, 13,451 met the SA-AKI criteria with its incidence peaking at 18% in 2021. SA-AKI patients were typically admitted from home via the emergency department (ED) with a median time to SA-AKI diagnosis of 1 day (interquartile range (IQR) 1-1) from ICU admission. At diagnosis, most SA-AKI patients (54%) had a stage 1 AKI, mostly due to the low urinary output (UO) criterion only (65%). Compared to diagnosis by creatinine alone, or by both UO and creatinine criteria, patients diagnosed by UO alone had lower renal replacement therapy (RRT) requirements (2.8% vs 18% vs 50%; p < 0.001), which was consistent across all stages of AKI. SA-AKI hospital mortality was 18% and SA-AKI was independently associated with increased mortality. In SA-AKI, diagnosis by low UO only, compared to creatinine alone or to both UO and creatinine criteria, carried an odds ratio of 0.34 (95% confidence interval (CI) 0.32-0.36) for mortality. CONCLUSION: SA-AKI occurs in 1 in 6 ICU patients, is diagnosed on day 1 and carries significant morbidity and mortality risk with patients mostly admitted from home via the ED. However, most SA-AKI is stage 1 and mostly due to low UO, which carries much lower risk than diagnosis by other criteria.

Glycaemic variability and its association with enteral and parenteral nutrition in critically ill ventilated patients.

BACKGROUND & AIMS: Extremes of dysglycaemia as well as glycaemic variability are associated with excess mortality in critically ill patients. Glycaemic variability is an increasingly important measure of glucose control in the intensive care unit (ICU) due to this association; however, there is limited data pertaining to the relationship between exogenous glucose from nutrition and glycaemic variability and clinical outcomes. The primary aim of this study was to determine if glycaemic variability is associated with an increase in mortality. Secondary objectives were to investigate any factors affecting glycaemic variability, and to characterise the role nutrition, particularly carbohydrate, plays as a contributing factor to glycaemic variability and other clinical outcomes (duration of ventilation and ICU length of stay). METHODS: Data on patients in a combined medical/surgical tertiary Australian Intensive Care Unit (ICU), ventilated for >24 h and exclusively fed by artificial nutrition support was extracted from a clinical database of prospectively collected information over an 18 month period. Glycaemic variability was defined as the coefficient of variation (GV; standard deviation/mean of blood glucose levels x 100). Statistical analysis was performed using logistic regression, zero-truncated negative binomial and linear regression as appropriate to the distribution of the outcome variable using R software. RESULTS: Data on up to 759 subjects was available. The average age of the study cohort was 56.9 years with a mean (standard deviation) APACHE III score of 72 (28). 66% of the study subjects were male. Glycaemic variability was associated with an increase in mortality (odds ratio 1.02; 95% CI: 1.00-1.04, p = 0.03). Factors associated with glycaemic variability included Acute Physiology and Chronic Health Evaluation III score (0.09, 0.06-0.11, p < 0.001), being male (-1.67, -2.97 to -0.38), p = 0.01) and mean units of insulin per day (0.08, 0.06-0.09, p < 0.001). There was no effect of any nutritional factor on glycaemic variability. Further exploratory analyses though showed that for those patients who required insulin during ICU admission, increased insulin dose was associated with increasing carbohydrate (incidence rate ratio (IRR) 1.003, 1.001-1.005, p = 0.001). Mean daily carbohydrate provision (grams) was associated with an increase in ventilation hours (IRR, 95% CI: 1.009, 1.008-1.009, p < 0.001) and length of intensive care unit stay (IRR, 95% CI: 1.007, 1.006-1.008, p < 0.001). CONCLUSION: This study confirms that GV was associated with excess mortality. Furthermore, administration of increasing doses of insulin was associated with increased GV. Increased carbohydrate intake was associated with an increased insulin requirement, as well as increased duration of mechanical ventilation and ICU length of stay. These findings provide important context for further prospective trials investigating the effect of carbohydrate provision in mechanically ventilated critically ill patients requiring artificial nutritional support.