Hypophosphatemia (serum phosphate < 2.5 mg/dL) is a major concern when initiating nutritional support. We evaluated which factors contribute to hypophosphatemia development in critically ill patients, as well as the association between hypophosphatemia and mortality. A retrospective cohort study of patients who were ventilated for at least 2 days in a 16-bed mixed ICU. Data collected includes demographics, Acute Physiology & Chronic Health Evaluation 2 (APACHE2) admission score, Sequential Organ Failure Assessment score at 24 h (SOFA24), hourly energy delivery, plasma phosphate levels during the first 2 weeks of admission, ICU length of stay (LOS), length of ventilation (LOV), and mortality (ICU and 90 days). For the hypophosphatemia development model, we considered mortality as a competing risk. For mortality analysis, we used the Cox proportional hazards model considering hypophosphatemia development as a time-varying covariate. 462 patients were used in the analysis. 59.52% of the patients developed hypophosphatemia. Several factors were associated with a decreased risk of hypophosphatemia: age, BMI, pre-admission diabetes diagnosis, APACHE2, SOFA24, first kidney SOFA score, hospital admission time before ICU admission, and admission after liver transplantation. Admission due to trauma was associated with an increased risk of hypophosphatemia. Survival analysis with hypophosphatemia as a time-varying covariate showed a protective effect of hypophosphatemia from mortality (HR 0.447, 95% CI 0.281, 0.712). Age, APACHE2, and SOFA24 score were found to be significantly associated with ICU mortality. Fasting duration in the ICU before nutritional support initiation was not found to be significantly associated with hypophosphatemia. We examined several fasting intervals (12 h, 24 h, 36 h, 48 h, 60 h, 72 h). In each fast interval, we compared the prevalence of hypophosphatemia among patients who fasted the specified length of time, with those who did not fast for the same length of time. In each fasting interval, hypophosphatemia prevalence was lower in the fasting group compared to the non-fasting group. However, this difference was insignificant. BMI, APACHE2, and hospital LOS before ICU admission were inversely associated with hypophosphatemia development. Fasting for up to 72 h in the ICU before starting nutritional support did not affect hypophosphatemia occurrence. Hypophosphatemia was associated with lower mortality.

BACKGROUND: 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.
CONCLUSIONS: 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.

BACKGROUND: Aberrations in blood phosphate (Pi) levels, whether presenting as hypo- or hyperphosphatemia, appear to be associated with clinical complications and adverse outcomes in patients admitted to an intensive care unit (ICU). However, the prevalence of Pi disorders and the association with subsequent factors and organ failures leading to death in ICU patients are poorly described. Despite endeavors to understand the etiology and treatment of low Pi levels from systematic reviews and meta-analyses, the literature lacks comprehensive guidance for managing hypophosphatemia. Hyperphosphatemia, on the other hand, appears to be associated with higher mortality among critically ill patients, yet its prevalence among ICU patients, particularly following phosphate repletion, remains unknown. The present study aims to investigate the prevalence of Pi abnormalities upon ICU admission and their incidence during the first week of ICU stay, the factors associated with Pi alterations, and the effect of phosphate repletion on the normalization of Pi levels, and its associations with clinical outcomes.
METHODS: This multicentre, prospective, non-interventional cohort study will include at least 1000 consecutive adult ICU patients (≥18 years) as part B of the GUTPHOS study. Sites are eligible if an anticipated minimal inclusion of 50 eligible patients during eight weeks from January 2024 until June 2024 and daily phosphate measurements during the first seven days of ICU stay are expected. All consecutive adult patients admitted to a participating ICU during the recruitment period, lasting up to eight weeks, or up to 120 patients if enrollment reaches that limit earlier, will be included. Study parameters include study site characteristics, patient demographics, daily assessment of Pi levels, Pi-related treatment, feeding details, renal replacement therapy details, the incidence of refeeding-associated hypophosphatemia and administered medication (during the first seven calendar days of ICU stay). There will be a follow-up period of a maximum of 90 days to document 28- and 90-day all-cause mortality as the primary outcome. Multiple logistic regression will be used to assess independent associations with mortality in addition to Receiver Operating Characteristics curves to identify cut-off Pi values associated with mortality and overcorrection. Linear mixed models will be conducted to assess Pi treatment effects. Subgroup analyses will be performed based on Pi abnormalities observed during ICU admission, categorized as normo-, hypo-, hyper-, or mixed, along with its severity (mild, moderate, or severe).
CONCLUSIONS: The GUTPHOS study will be the first multicentre, prospective observational cohort study to investigate the prevalence, management practices, and consequent outcomes associated with Pi abnormalities during the first week of ICU admission. Its results may bridge the current evidence gap in repletion protocols while establishing the groundwork for a subsequent randomized controlled trial.
BACKGROUND: NCT05909722.

BACKGROUND: The purpose was to explore the correlation between refeeding hypophosphatemia and delirium and analyze the related factors in critically ill patients.
METHODS: We conducted a retrospective review of critically ill patients admitted to Nanjing Drum Tower Hospital between September 2019 and March 2021. The patients were divided into delirium and nondelirium groups. Demographic data, underlying diseases, laboratory findings, comorbidities, nutritional intake and overall prognosis were collected and analyzed.
RESULTS: In total, 162 patients were included and divided into delirium (n=54) and nondelirium (n=108) groups. Serum phosphorus levels in the two groups decreased significantly in the first three days (P1, P2, P3) after nutrient intake compared with baseline before nutrient intake (Ppre). P1 and P2 were significantly lower in the delirium group compared to the nondelirium group. The maximum blood phosphorus reduction (Pmax) in the first three days after nutrient intake was significantly higher in the delirium group than in the nondelirium group. The time of Pmax in the delirium group was on the first day after nutrient intake. Multivariable logistic regression analysis identified starting route of nutrition and P1< 0.845 mmol/L as the independent predictors of delirium development in critically ill patients.
CONCLUSIONS: The incidence of delirium in critically ill patients is high and associated with refeeding hypophosphatemia. Delirium may occur with serum phosphorus levels less than 0.845 mmol/L on the first day.

BACKGROUND: Data is limited on the prevalence of hypophosphatemia in general hospitalized patients, and its association with length of hospital stay (LOS) and mortality remained unclear. We aimed to investigate the prevalence of admission phosphate abnormality and the association between serum phosphate level and length of hospital stay and all-cause mortality in adult patients.
METHODS: This was a multi-center retrospective study based on real-world data. Participants were classified into five groups according to serum phosphate level (inorganic phosphorus, iP) within 48 h after admission: G1, iP < 0.64 mmol/L; G2, iP 0.64-0.8 mmol/L; G3, iP 0.8-1.16 mmol/L; G4, iP 1.16-1.45 mmol/L; and G5, iP ≥ 1.45 mmol/L, respectively. Both LOS and in-hospital mortality were considered as outcomes. Clinical information, including age, sex, primary diagnosis, co-morbidity, and phosphate-metabolism related parameters, were also abstracted from medical records.
RESULTS: A total number of 23,479 adult patients (14,073 males and 9,406 females, aged 57.7 ± 16.8 y) were included in the study. The prevalence of hypophosphatemia was 4.74%. An \"L-shaped\" non-linear association was determined between serum phosphate level and LOS and the inflection point was 1.16 mmol/L in serum phosphate level. Compared with patients in G4, patients in G1, G2 or G3 were significantly associated with longer LOS after full adjustment of covariates. Each 0.1 mmol/L decrease in serum phosphate level to the left side of the inflection point led to 0.64 days increase in LOS [95% confidence interval (CI): 0.46, 0.81; p for trend < 0.001]. But there was no association between serum phosphate and LOS where serum levels of phosphate ≥ 1.16 mmol/L. Multivariable logistic regression analysis showed that adjusted all-cause in-hospital mortality was 3.08-fold greater in patients in G1 than those in G4 (95% CI: 1.52, 6.25; p for trend = 0.001). Similarly, no significant association with either LOS or mortality were found in patients in G5, comparing with G4.
CONCLUSIONS: Hypophosphatemia, but not hyperphosphatemia, was associated with LOS and all-cause mortality in adult inpatients. It is meaningful to monitor serum levels of phosphate to facilitate early diagnosis and intervention.

OBJECTIVE: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste.
METHODS: Prospective, randomized, parallel group, noninferiority clinical trial.
METHODS: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022.
METHODS: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L.
METHODS: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program.
RESULTS: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents).
CONCLUSIONS: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste.

OBJECTIVE: Late-onset sepsis (LOS) is common in extreme prematurity. These infants are at risk of refeeding syndrome-associated hypophosphataemia. Our objective was to investigate whether hypophosphataemia predisposes to LOS in extremely premature neonates.
METHODS: A retrospective case-control study of neonates born before 29 weeks\' gestation in an Australian NICU from 2016 to 2020. Cases developed LOS or localised infection. Two controls, matched within 2 gestational weeks and 90 calendar days, were selected per case.
RESULTS: Amongst 48 cases and 93 controls, cases were smaller at birth (767 g vs. 901 g, P = 0.01), but were otherwise comparable. Hypophosphataemia was more common in cases (26% vs. 15%, P = 0.18). Increased intravenous protein intake in the first week was protective against LOS (OR = 0.9, 95% CI 0.76-1.00, P = 0.04); median 2.1 g/kg/day in cases, 2.3 g/kg/day in controls.
CONCLUSIONS: Hypophosphataemia as part of refeeding syndrome is prevalent and under-recognised in extremely premature neonates. We did not find an association between hypophosphataemia and LOS. Low intravenous protein may be an independent risk factor for infection.

BACKGROUND: Refeeding syndrome (RFS) is a life-threatening metabolic derangement occurring when nutrition is reintroduced after prolonged starvation. Limited data exist regarding RFS prevalence, risk factors, and outcome, particularly in critically ill patients.
METHODS: A retrospective cohort study was conducted in a medical intensive care unit from June 2018 to August 2020. RFS diagnostic criteria from the National Institute for Health and Care Excellence (NICE) and the American Society for Parenteral and Enteral Nutrition (ASPEN) were used. The primary outcome was 30-day mortality.
RESULTS: Among 216 patients, RFS was diagnosed in 22.7% and 27.3% of patients per the NICE and ASPEN criteria, respectively. There was no significant difference in 30-day mortality between patients with and without RFS (22/59 [37.3%] vs 53/157 [33.8%]; P = 0.627). Independent predictors of RFS were malignancy (odds ratio [OR] = 2.09; 95% CI = 1.06-4.15; P = 0.035), septic shock (OR = 2.26; 95% CI = 1.17-4.39; P = 0.016), and high NICE RFS risk classification (OR = 2.52; 95% CI = 1.20-5.31; P = 0.015). Factors associated with reduced RFS risk were Sequential Organ Failure Assessment (SOFA) scores >12 (OR = 0.45; 95% CI = 0.23-0.88; P = 0.020) and high-dose vasopressor treatment (OR = 0.34; 95% CI = 0.14-0.79; P = 0.012).
CONCLUSIONS: RFS affected one-fourth of the critically ill patients but did not significantly impact 30-day mortality. Malignancy, septic shock, and high NICE RFS risk classification were positively associated with RFS, whereas high SOFA scores and extensive vasopressor use were linked to decreased risk.

Diabetic ketoacidosis (DKA) is one of the most serious complications of type 1 diabetes mellitus. Its treatment requires fluid and electrolyte replacement and insulin. Hypophosphatemia as a complication of treatment has been scarcely evaluated.
OBJECTIVE: To estimate the incidence of hypophosphatemia in children with DKA, treated with subcutaneous regular insulin (IRS), and to explore factors associated with this complication.
METHODS: Prospective, observational study. Patients diagnosed with DKA hospitalized in the general care ward were included. Data on phosphatemia, glycemia, acid-base status, and IRS amount (U/kg) received were recorded at baseline and after 24 h of treatment. Hypophosphatemia was defined as values below 2.5 mg/dl. The correlation between initial phosphate and at 24 h of treatment was evaluated; the incidence of hypophosphatemia at 24 h was expressed as a percentage of the total number of patients.
RESULTS: 30 patients were included, 15 were female, mean age 11.4 ± 3.2 years. At 24 h of treatment with IRS, 36.7% (95%CI 22-55%) presented hypophosphatemia, mean value 1.9 ± 1.5 mg/dl. Initial bicarbonate < 10 mmol/L acted as a predictor of hypophosphatemia (OR 7.5; 95%CI 1.4-39.8%; p = 0.01). No patient required intravenous phosphate correction, and no associated clinical complications were observed.
CONCLUSIONS: In the group studied, the incidence of hypophosphatemia reached 36.7% at 24 hours of treatment. Initial bicarbonate lower than 10 mmol/L was significantly associated with hypophosphatemia. No complications associated with hypophosphatemia were observed.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.