Prolonged Hypophosphatemia and Intensive Care After Curative Surgery of Tumor Induced Osteomalacia: A Case Report.

Introduction: Rare FGF23-producing mesenchymal tumors lead to paraneoplastic tumor-induced osteomalacia (TIO) presenting with phosphate wasting, hypophosphatemia, chronic hypomineralization of the bone, fragility fractures and muscle weakness. Diagnosis of TIO requires exclusion of other etiologies and careful search for a mesenchymal tumor that often is very small and can appear anywhere in the body. Surgical removal of the tumor is the only definitive treatment of TIO. Surgical complications due to chronic hypophosphatemia are not well recognized. Case Description: The current case describes severe fragility fractures in a 58-year-old woman, who lost her ability to walk and was bedridden for two years. First, the initial diagnostic laboratory work-up did not include serum phosphorus measurements, second, the suspicion of adverse effects of pioglitazone as an underlying cause delayed correct diagnosis for at least two years. After biochemical discovery of hyperphosphaturic hypophosphatemia at a tertiary referral centre, a FGF23-producing tumor of the mandible was discovered on physical examination, and then surgically removed. Postoperatively, severe hypophosphatemia and muscle weakness prolonged the need for ventilation support, intensive care and phosphate supplementation. After two years of rehabilitation, the patient was able to walk short distances. The tumor has not recurred, and serum phosphate concentration has remained within normal limits during 3.5 years of follow-up. Conclusions: The case report illustrates knowledge gaps in the diagnostic work-up of rare causes of low bone mass and fragility fractures. Compared to other low phosphate conditions, surgical recovery from TIO-induced hypophosphatemia warrants special attention. Increased alkaline phosphatase concentration may indicate impaired postsurgical recovery due to prolonged hypophosphatemia, underlining the need for proactive perioperative correction of hypophosphatemia.

Severe hypophosphataemia following oral bisphosphonate treatment in a patient with osteoporosis.

A 76-year-old woman was treated with oral bisphosphonate, alendronate, for osteoporosis in an outpatient clinic. Routine blood tests 4 months after alendronate prescription surprisingly revealed severe hypophosphataemia. The patient was hospitalised and treated with intravenous and oral phosphate supplements. Alendronate was later reintroduced as treatment for osteoporosis and the patient once again presented with severe hypophosphataemia in subsequent routine blood tests. The patient had only presented with lower extremity pain, muscle weakness and difficulty walking. Blood tests in the emergency department both times reconfirmed severe hypophosphataemia. Plasma (p-)ionised calcium levels were normal or slightly elevated and p-parathyroid hormone levels were normal or slightly suppressed. The p-25-hydroxyvitamin-D and p-creatine were in the normal range. Critical illness, malabsorption, nutritional issues and genetics were reviewed as potential causes but considered unlikely. Phosphate levels were quickly restored each time on replacement therapy and the case was interpreted as bisphosphonate-induced severe hypophosphataemia.

Long-Term Follow-up of Hypophosphatemic Bone Disease Associated With Elemental Formula Use: Sustained Correction of Bone Disease After Formula Change or Phosphate Supplementation.

In this article, we describe the long-term outcomes of children who were previously reported to have developed hypophosphatemic bone disease in association with elemental formula use. An extended chart review allowed for an updated report of 34 children with regard to severity/duration of bone disease, extent of recovery, and time to correction using radiology reports and biochemical data. After implementation of formula change and/or phosphate supplementation, we found that serum phosphorus concentration increased and serum alkaline phosphatase activity decreased in all patients, normalizing by 6.6 ± 4.0 (mean ± SD) months following diagnosis. The decrease in serum alkaline phosphatase from diagnosis to the time of correction was moderately correlated with the concurrent increase in serum phosphorus (R = 0.48, P < .05). Age at diagnosis significantly correlated with time to resolution (R = 0.51, P = .01). This study supports the earlier report that bone disease associated with hypophosphatemia during elemental formula use responds to formula change and/or phosphate supplementation.

Changes in the metabolic profiles of dairy cows before and after calving that were mainly fed fodder beet (Beta vulgaris vulgaris L.) during the dry period.

Case history: Two commercial pasture-based farms within the North Canterbury district of New Zealand were feeding fodder beet (Beta vulgaris vulgaris L.) as a large proportion of the diet to cows during the dry period. On each farm 25 multiparous cows were blood sampled up to six times from 28 days before, to 21 days after calving (Day 0). Plasma samples were analysed for concentrations of ß-hydroxybutyrate (BHBA), non-esterified fatty acid (NEFA), Ca, Mg and P, and aspartate aminotransferase (AST) activity. The first sampling visit was performed when cows were being fed their maximum intake of fodder beet. Clinical findings: The mean body condition score (BCS) of cows on Farm 1 was 5.4 (95% CI = 5.3-5.6) and on Farm 2, 5.4 (95% CI = 5.3-5.6) at first sampling. Mean concentrations of BHBA increased between Days -15 and Day -8 then decreased postpartum on Day 2 before increasing again on Day 21. On Farm 2, concentrations remained low (<1.2 mmol/L) on all days of sampling. Mean concentrations of NEFA in plasma remained low during the periparturient period on Farm 1, then increased on Day 2. On Farm 2, concentrations were elevated above 0.3 mmol/L between Days -28 and -17 then decreased on Day -10, before increasing on Day 2. Mean concentrations of Ca, Mg and P were higher than threshold values on both farms prepartum. However on Day 2, there were 8/23 (35%) cows on Farm 1 and 6/23 (26%) cows on Farm 2 with concentrations of Ca in plasma <2.0 mmol/L, and 10/23 (44%) cows on Farm 1 and 8/23 (35%) cows on Farm 2 with concentrations of P in plasma <1.3 mmol/L. Mean AST activities remained relatively constant and below 130 IU/L on both farms at all sampling times. Clinical relevance: On both farms, post-partum hypocalcaemia and hypophosphataemia were common after calving despite differing fodder beet feeding and mineral supplementation regimes. There was more variation in energy status, especially prior to calving. More research is required on factors affecting mineral and energy status in dry cows fed fodder beet.

Predictors of Hypophosphatemia and Outcomes during Continuous Renal Replacement Therapy.

INTRODUCTION: Hypophosphatemia occurs in up to 80% of patients undergoing continuous renal replacement therapy (CRRT) and has been associated with poor outcomes. Whether preemptive phosphate supplementation is warranted in select patients has not been adequately explored. This single-center, retrospective cohort study evaluates predictors of hypophosphatemia and characterizes treatment approaches in adult patients undergoing at least 12 h of CRRT. METHODS: Patients were divided into 2 groups based on the presence or absence of hypophosphatemia as defined by serum phosphorus <2.5 mg/dL. Select laboratory values at baseline and during CRRT, medications and nutritional sources affecting phosphorus, and CRRT parameters were compared. Patient outcomes including resolution of acute kidney injury (AKI), freedom from renal replacement therapy at hospital discharge, duration of intensive care unit (ICU) and hospital stay, duration of mechanical ventilation, and ICU mortality were evaluated. RESULTS: Seventy-two patients were included. The group was 43% female and 51% African American. CRRT was ordered for AKI in 83% and for end-stage renal disease in 15%. Hypophosphatemia occurred in 45 patients (63%). Mean time to development of hypophosphatemia was 34 ± 22 h. Patients who developed hypophosphatemia received a longer duration of CRRT (p = 0.001), were more likely to have a diet ordered (p = 0.005), less likely to have received calcium infusions (p = 0.045), and had lower phosphorus (p = 0.017) and potassium levels (p = 0.038) and higher calcium levels at baseline (p = 0.048). Development of hypophosphatemia was associated with an increased duration of ICU stay (p = 0.014) but not with the other patient outcomes evaluated. Twenty-seven of the 45 patients (60%) who developed hypophosphatemia received phosphorus supplementation with near equal use of intravenous, oral, and combination routes. Only 17 patients (38%) achieved resolution of hypophosphatemia while on CRRT. CONCLUSION: Hypophosphatemia is common, difficult to correct, and contributes to longer ICU stays in patients requiring CRRT. A preemptive approach to address hypophosphatemia including aggressive supplementation strategies to correct phosphorus is warranted in patients requiring CRRT.

Clinically-defined preoperative serum phosphorus abnormalities and outcomes of coronary artery bypass grafting: Retrospective analysis using inverse probability weighting adjustment.

BACKGROUND: Serum phosphorus is a well-known marker of vascular calcification, but the effects of serum phosphorus abnormalities defined by clinical criteria on the outcomes of coronary artery bypass grafting (CABG) remain unclear. We aimed to evaluate whether preoperative serum phosphorus abnormalities defined based on clinical criteria are associated with outcomes of CABG using a relatively new statistical technique, inverse probability weighting (IPW) adjustment. METHODS: From January 2001 to December 2014, 4,989 consecutive patients who underwent CABG were stratified into normal (2.5-4.5 mg/dl; n = 4,544), hypophosphatemia (<2.5 mg/dl; n = 238), or hyperphophatemia (>4.5 mg/dl; n = 207) groups depending on preoperative serum phosphorus level. RESULTS: The primary outcome was all-cause death during a median follow-up of 48 months. Secondary outcomes were cardiovascular death, graft failure, myocardial infarction, repeat revascularization, and stroke. In multivariate Cox analysis, preoperative hypophosphatemia was significantly associated with all-cause death (hazard ratio [HR] 1.76; 95% confidence interval [CI] 1.13-2.76; P = 0.01). However, this association varied depending on chronic kidney disease and emergent operation (p for interaction = 0.05 and 0.03, respectively). In addition, analysis after IPW adjustment demonstrated that preoperative serum phosphorus abnormalities were not significantly associated with all-cause death (P = 0.08) or any secondary outcomes except graft failure. Graft failure was significantly associated with preoperative hypophosphatemia (HR 2.51; 95% CI 1.37-4.61; P = 0.003). CONCLUSION: Our study showed that preoperative serum phosphorus abnormalities in clinical criteria were not associated with outcomes after CABG except for graft failure. And, the association of hypophosphatemia with graft failure remains to be evaluated.

Changes in serum phosphorus level in patients with severe burns: A prospective study.

BACKGROUND: The second most abundant mineral in the body, phosphorus (P), is absorbed in the small intestine after ingestion enhanced by 1,25-dihydroxy vitamin D, and its excretion is exclusively regulated by the kidney. It is clinically significant, aside from its disturbance in burn ICU patient's P mechanism. The increasing rate of morbidity and mortality among the patients can be associated with severe hypophosphatemia. The current study aimed at investigating the changes in serum P levels in the early period after burns, the relationship between serum P level and TBSA (total body surface area) of burn, and the impact of hypophosphatemia on patients' clinical outcomes. MATERIAL AND METHODS: The current prospective, observational study was conducted on 137 patients hospitalized in the burn intensive unit (BICU) of Velayat Sub-specialty Burn and Plastic Surgery Center from December 2015 to May 2017. According to the TBSA percentage, the patients were divided into three groups. The level of serum P was determined in the 1st, 3rd, 5th, 7th, and 9th days of hospital stay and before discharge. To evaluate the trend of P changes in the sixtime-points, the average changes along with 95% confidence intervals (CI) were used for multivariate analysis of variance with repeated measures (repeated measures ANOVA). A P-value of 0.05 or less was considered statistically significant. The analyses were performed using SPSS software, version 19 (SPSS Inc.). RESULTS: Totally, 137 patients (70% male, mean age 32 ± 21years, and TBSA 32.6 ± 14%) were included in the study. The overall incidence of hypophosphatemia was 75.1%. Hypophosphatemia developed as early as 1.66 ± 0.136 (95%CI: 1.4-1.9) days after injury. The highest decrease in the serum P level was observed on the 3rd and 5th days after burn as 2.78 mg/dL and 2.85 mg/dL, respectively (P-value = 0.001). A correlation was observed between TBSA and serum P level. The mean serum P level decreased with increasing the percentage of burns. There was a correlation between serum P level and mortality; therefore, a decrease in serum P level increased the patient's mortality rate (P < 0.05). CONCLUSION: The current study highlighted that hypophosphatemia is often observed in patients with burn injuries during their hospitalization. It is potentially beneficial to identify patients at risk of hypophosphatemia. Therefore, it is suggested that P level be assessed regularly in patients with burn injuries for the timely initiation of P replacement therapy.

[Diagnosis and treatment of hypophosphatemia]. / Que faire de l'hypophosphatémie†?

Phosphate is widely spread in the human body, filling many roles across various tissues, both in the intra- and extracellular space. Serum phosphorus makes up only a slight fraction of the total body stocks but acts as an exchange between the different compartments. Hypophosphatemia is commonly found among hospitalized patients, especially those in an intensive care unit. Clinical manifestations associated with hypophosphatemia are mainly respiratory, neuromuscular, cardiac and hematologic, all of which are more common in the presence of severe hypophosphatemia. Interventional evidence on the benefit of correcting hypophosphatemia is lacking. Currently available recommendations vary and are based on weak evidence.

Le phosphate a un rôle physiologique essentiel dans l'organisme humain, il est ubiquitaire, tant en intracellulaire qu'en extracellulaire. La phosphatémie ne représente qu'une faible proportion du contenu corporel total de phosphate, mais joue un rôle important dans les échanges entre les différents compartiments de l'organisme. L'hypophosphatémie est fréquente chez les patients hospitalisés, en particulier aux soins intensifs. Des manifestations respiratoires, cardiologiques, neuromusculaires et hématologiques peuvent y être associées, pouvant même être à l'origine d'une surmortalité si elle est sévère. A ce jour, il n'existe pas d'évidence du bénéfice de corriger l'hypophosphatémie. Les recommandations pour la correction d'une hypophosphatémie varient et sont basées sur des évidences faibles.

Efficacy and safety of a phosphate replacement strategy for severe hypophosphatemia in the ICU.

BACKGROUND: Experience with individualized phosphate replacement is limited in patients with severe hypophosphatemia. This study compares the efficacy and safety of an individualized regimen of serum phosphate < 0.4 mmol/l treatment in ICU patients to patients with moderate hypophosphatemia (0.4-0.6 mmol/l). METHODS: This retrospective cohort study included 36 patients with severe and 35 patients with moderate hypophosphatemia. Supplementation dose was calculated according to the equation: phosphate dose (in mmol) = 0.5 x body weight x (1.25 - [serum phosphate]). Sodium-potassium-phosphate was infused at a rate of 10 mmol/hour. Blood samples were taken at baseline and the next morning at 06.00 hrs. RESULTS: Serum phosphate rose to a level > 0.40 mmol/l in all patients with severe hypophosphatemia. Serum phosphate increased to > 0.60 mmol/l in 56% of patients with severe hypophosphatemia and in 86% of patients with moderate hypophosphatemia (p = 0.01). Mild hyperphosphatemia was observed in one patient only (1.53 mmol/l), hyperkalemia was observed in three patients (all three had severe hypophosphatemia, average potassium after supplementation was 5.2 ±; 0.2 mmol/l) and serum calcium levels remained unchanged in both groups. CONCLUSION: Individualized phosphate replacement was effective and safe for both moderate and severe hypophosphatemia, but was more accurate in moderate hypophosphatemia.

Vitamin D: too much testing and treating?

There is clinical uncertainty as to the testing of serum 25--Hydroxy vitamin D (25[OH]D) concentrations and when to use high-dose supplementation. Data show that there has been a rapid increase in the number of tests performed within the Northumbria Healthcare NHS Foundation Trust over the past 8 years and an increase in high-dose supplementation over the past 5 years. We performed a retrospective analysis of the 25(OH)D test requests over the period from January to -October 2017. A total of 17,405 tests were performed in this time period. The overall average concentration was 57.5 nmol/L and this figure was similar across age groups, although a larger proportion of patients aged over 75 had a concentration <25 nmol/L. Test requests were classified into 'appropriate', 'inappropriate' and 'uncertain' categories based on current expert opinion. We found that between 70.4% and 77.5% of tests could be inappropriate, depending on whether the 'uncertain' categories of falls and osteoporosis are considered to be justified. Tiredness, fatigue or exhaustion was the reason for testing in 22.4% of requests. We suggest that a more rational approach to testing, and subsequent treating, could lead to reductions in costs to the healthcare system and patients.

Refeeding syndrome: relevance for the critically ill patient.

PURPOSE OF REVIEW: To provide an overview of recent findings concerning refeeding syndrome (RFS) among critically ill patients and recommendations for daily practice. RECENT FINDINGS: Recent literature shows that RFS is common among critically ill ventilated patients. Usual risk factors for non-ICU patients addressed on ICU admission do not identify patients developing RFS. A marked drop of phosphate levels (>0.16 mmol/l) from normal levels within 72 h of commencement of feeding, selects patients that benefit from hypocaloric or restricted caloric intake for at least 48 h resulting in lower long-term mortality. SUMMARY: RFS is a potentially life-threatening condition induced by initiation of feeding after a period of starvation. Although a uniform definition is lacking, most definitions comprise a complex constellation of laboratory markers (i.e. hypophosphatemia, hypokalemia, hypomagnesemia) or clinical symptoms, including cardiac and pulmonary failure. Recent studies show that low caloric intake results in lower mortality rates in critically ill RFS patients compared with RFS patients on full nutritional support. Therefore, standard monitoring of RFS-markers (especially serum phosphate) and caloric restriction when RFS is diagnosed should be considered. Furthermore, standard therapy with thiamin and electrolyte supplementation is essential.

Suitability of oral administration of monosodium phosphate, disodium phosphate, and magnesium phosphate for the rapid correction of hypophosphatemia in cattle.

BACKGROUND: Hypophosphatemia is commonly associated with disease and decreased productivity in dairy cows particularly in early lactation. Oral supplementation with phosphate salts is recognized as suitable for the rapid correction of hypophosphatemia. Little information is available about the differences in efficacy between salts used for oral phosphorus supplementation. OBJECTIVES: Comparison of efficacy of oral administration of NaH2 PO4 , Na2 HPO4 , and MgHPO4 in treating hypophosphatemia in cattle. ANIMALS: 12 healthy dairy cows in the fourth week of lactation in their second to fifth lactation. METHODS: Randomized clinical study. Phosphorus deficient, hypophosphatemic cows underwent a sham treatment and were afterwards assigned to 1 of 3 treatments-NaH2 PO4 , Na2 HPO4 , or MgHPO4 (each provided the equivalent of 60 g of phosphorus). Blood samples were obtained immediately before and repeatedly after treatment. RESULTS: Treatment with NaH2 PO4 and Na2 HPO4 resulted in rapid and sustained increases of plasma phosphate concentrations ([Pi]). Significant effects were apparent within 1 hour (NaH2 PO4 : P = .0044; Na2 HPO4 : P = .0077). Peak increments of plasma [Pi] of 5.33 mg/dL [5.26-5.36] and 4.30 mg/dL [3.59-4.68] (median and interquartile range) were reached after 7 and 6 hours in animals treated with NaPH2 PO4 and Na2 HPO4 , respectively, whereas treatment with MgHPO4 led to peak increments 14 hours after treatment (3.19 mg/dL [2.11-4.04]). CONCLUSIONS AND CLINICAL IMPORTANCE: NaH2 PO4 and Na2 HPO4 are suitable to rapidly correct hypophosphatemia in cattle. Because of the protracted and weaker effect, MgHPO4 cannot be recommended for this purpose. Despite important differences in solubility of NaH2 PO4 and Na2 HPO4 only small plasma [Pi] differences were observed after treatment.

Severe hypophosphataemia: a rare cause of postoperative muscle weakness.

We report a case of severe generalised muscle weakness in a 66-year-old man who underwent revision of left knee arthroplasty. On postoperative day 1, he developed non-focal muscle weakness and shortness of breath which progressed over a 6-hour period. Serum phosphorus level was severely low at 0.5 mg/dL, along with mild degree of hypokalaemia, hypocalcaemia and hypomagnesaemia. His symptoms completely resolved after emergent phosphorus replacement. The authors believe this case is of educational interest to physicians as generalised muscle weakness is an uncommon presentation of severe hypophosphataemia. In a postoperative setting, hypophosphataemia is often multifactorial, thought to result from combination of perioperative catecholamine surge, administration of saline, diuretics, glucose and antacids, poor oral intake and respiratory alkalosis secondary to pain. We report this case to raise awareness among physicians on severe phosphate imbalance as the primary aetiology for acute generalised muscle weakness and respiratory failure, especially after a surgery.

Clinical features of hypophosphatemic osteomalacia induced by long-term low-dose adefovir dipivoxil.

OBJECTIVE: To investigate the predictors of hypophosphatemic osteomalacia induced by adefovir dipivoxil (ADV) and to monitor for early detection. PATIENTS AND METHODS: Hospitalized patients who were diagnosed with ADV-related hypo-phosphatemic osteomalacia were recruited and retrospectively analyzed in our hospital from January 2012 to December 2016. A telephone interview was conducted at 1, 3, 6, 9, 12, and 24 months after cessation of ADV. RESULTS: In the 8 patients enrolled in the study, the hypophosphatemic osteomalacia symptoms developed at an average of 5.14 (4-7) years since ADV treatment (10 mg/d). The average alkaline phosphatase (ALP) level was 279.50 (137-548) U/L, which was significantly higher than the normal level (45-125 U/L). The serum phosphorus level was an average of 0.59 (0.43-0.69) mmol/L, which was lower than the normal range (2.06-2.60 mmol/L). Serum calcium levels of the enrolled patients remained within normal limits. Reduced estimated glomerular filtration rate (eGFR <29 mL/min/1.73 m2) was seen in 4 cases. The clinical manifestations were mainly progressive systemic bone and joint pain, frequent fractures, trouble in walking, height reduction (4-6 cm), and so on. After cessation of ADV, symptoms like bone pain resolved gradually. Serum phosphorus level restored to normal in 4.5 months after the withdrawal of ADV. However, in 4 patients, renal function failed to return to normal in 24 months. CONCLUSION: More attention should be paid to the duration of ADV treatment. The level of serum phosphorus and ALP, as well as renal function, should be monitored for early detection of potential adverse drug reactions.

Sporadic primary hyperparathyroidism and stone disease: a comprehensive metabolic evaluation before and after parathyroidectomy.

OBJECTIVES: To characterize the stone risk and the impact of parathyroidectomy on the metabolic profile of patients with primary hyperparathyroidism (PHPT) and urolithiasis. PATIENTS AND METHODS: We analysed the prospectively collected charts of patients treated at our stone clinic between January 2001 and January 2016 searching for patients with PHPT and urolithiasis. Imaging evaluation of the kidneys, bones and parathyroid glands was assessed. We analysed the demographic data, serum and urinary variables before and after parathyroidectomy. We used a paired t-test, Fisher's test, Spearman's test and anova in the statistical analysis. RESULTS: A total of 51 patients were included. The mean patient age was 57.1 ± 12.1 years and 82.4% were women. Before parathyroidectomy, mean calcium and parathyroid hormone (PTH) levels were 11.2 ± 1.0 mg/dL and 331 ± 584 pg/dL, respectively. Hypercalcaemia was present in 84.3% of patients. All eight patients with normal calcium levels had elevated PTH levels. Only two patients did not have PTH above the normal range, although both had elevated calcium levels. The most common urinary disorders were low urinary volume (64.7%), hypercalciuria (60.8%), high urinary pH (41.2%) and hypocitraturia (31.4%). After parathyroidectomy, the number of patients with hypercalcaemia (n = 4; 7.8%), elevated PTH (n = 17; 33.3%) and hypophosphataemia (n = 3; 5.9%) significantly decreased (P < 0.001). The number of urinary abnormalities decreased and there was a reduction in urinary calcium (P < 0.001), pH (P = 0.001) and citrate levels (P = 0.003). CONCLUSION: Individuals with PHPT and nephrolithiasis frequently have elevated baseline PTH and calcium levels. Low volume, hypercalciuria, high urinary pH, and hypocitraturia are the most frequent urinary disorders. Parathyroidectomy is effective in normalizing serum calcium and PTH levels, although other urinary metabolic may persist. Patients should be monitored for the need for citrate supplementation.

Phosphate replacement in the critically ill: potential implications for military patients.

BACKGROUND: Severe hypophosphataemia in the intensive care unit (ICU) setting has been widely associated with adverse clinical outcomes across multiple organ systems, as well as increased mortality. However, the clinical significance of mild or moderate hypophosphataemia remains uncertain. This can lead to heterogeneous phosphate replacement protocols across different institutions. The aim of this study was to assess the significance of mild and moderate hypophosphataemia on clinical outcomes across several organ systems. METHOD: All patients over a 3-week period in our ICU were retrospectively analysed with admission serum phosphate compared with subsequent clinical outcomes after admission. Low serum phosphate (0.3-1.0 mmol/L), according to local protocol, was compared with normal serum phosphate (>1.0 mmol/L). RESULTS: Of the 72 patients admitted to intensive therapy unit during this period, 14/72 (19%) had phosphate levels deemed low (<1.0 mmol/L) and received phosphate supplementation. No significant difference was found between groups in terms of cardiac arrhythmias (p=0.55), capillary blood glucose (p=0.08) and serum lactate (p=0.32). Low phosphate (0.3-1.0 mmol/L) was not associated with increased likelihood of requiring ventilation. Platelet count was significantly lower in the low phosphate group (p=0.008). CONCLUSION: In our study, mild and moderate hypophosphataemia was not associated with adverse clinical outcome across most organ systems analysed. Given the current evidence and results of this study, we would suggest that there is a trend towards over-replacement of phosphate, representing a potential clinical safety issue as well as clear financial implications.

Risk Factors for the Development of Refeeding Syndrome-Like Hypophosphatemia in Very Low Birth Weight Infants.

BACKGROUND: Refeeding syndrome is characterized by metabolic disturbance including hypophosphatemia and hypokalemia upon reinstitution of nutrition in severely malnourished patients. OBJECTIVE: The present study sought to identify the risk factors for the development of refeeding syndrome-like metabolic disturbance in very low birth weight infants. METHODS: The correlations of severe hypophosphatemia with the serum levels of potassium and ionized calcium, daily calorie and phosphate intake, and umbilical cord blood flow on ultrasonography were analyzed in 49 very low birth weight infants. RESULTS: Fifteen infants (36%) presented with hypophosphatemia during the first postnatal week. Hypophosphatemia was significantly associated with birth weight z score (odds ratio, 1.60; 95% confidence interval, 1.04-2.47; p = 0.034) and umbilical artery resistance index (odds ratio, 7.72E-04; 95% confidence interval, 1.14E-06-0.523; p = 0.031). Multiple regression analysis revealed that umbilical artery resistance index was independently associated with hypophosphatemia. CONCLUSIONS: Umbilical artery resistance index may serve as a useful marker for future development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Close monitoring of serum phosphorus and potassium levels and early intervention are important for the management of very low birth weight infants with intrauterine growth restriction due to placental dysfunction.

Bone fracture in severe small-for-gestational-age, extremely low birth weight infants: A single-center analysis.

INTRODUCTION: Bone fracture is a complication of extremely low birth weight infants (ELBWIs). This study aimed to analyze risk factors for bone fracture in a population of severe small-for-gestational-age (SGA) ELBWIs. METHODS: We retrospectively studied data from ELBWIs with a birth weight <1000g and <-2 standard deviations (SDs) born at the National Center for Child Health and Development, Japan, from 2013 to 2015. Infants were divided into fracture and control groups. Serum calcium (Ca) and phosphorus (P) levels, perinatal factors, and previously reported risk factors were analyzed. RESULTS: Of 25 cases of severe SGA ELBWIs, 5 cases of bone fracture were identified. Gestational age was 27.7±2.2, 29.1±2.6weeks (mean difference [MD] -1.4, 95% confidence interval [CI]: -4.0, -1.2, p=0.280), birth weight (BW) 448±105, 673±216g (MD -225, 95% CI: -433, -17, p=0.036) and BW-SD -4.1±0.1, -3.4±0.8 (MD -0.8, 95% CI: -1.5, -0.02, p=0.045) in the fracture and control groups, respectively. Minimums of serum Ca and P were 6.6±1.4, 8.1±0.8mg/dl (MD -1.5, 95% CI: -2.5, -0.6), p=0.003) and 2.3±0.6, 3.5±1.1mg/dl (MD -1.2, 95% CI: -2.2, -0.1, p=0.027) in the fracture and control groups, respectively. CONCLUSION: Lower BW and BW-SD were possible risk factors for bone fracture. Hypocalcemia and hypophosphatemia may also contribute to the condition.

Hypophosphatemia: nutritional status, body composition, and mortality in hemodialysis patients.

PURPOSE: The aim of the present study was to investigate the relationship between serum phosphate levels, clinical parameters, body composition, and mortality. METHODS: Multicenter longitudinal observational study of a cohort of 3552 patients in hemodialysis (HD) from 34 Nephrocare dialysis units in Portugal with 24 months of follow-up. Patients were divided into three groups depending on their serum phosphorus (<3.5; 3.5-5.5; >5.5 mg/dL). Statistical tests were performed with SPSS, version 20.0. A p < 0.05 was considered significant. RESULTS: On the one hand, hypophosphatemia was significantly associated with better dialysis adequacy, higher age and overhydration. On the other hand, it was associated with lower albumin, protein intake, creatinine, hemoglobin, calcium, potassium, magnesium, body mass index (BMI), body cell mass index, fat tissue index and lean tissue index. These patients had lower survival rates compared with those with normo- and hyperphosphatemia. Hypophosphatemia was a predictor of death when adjusted for age, diabetes, HD vintage, gender, and Kt/V. Comparing the mortality predictors in hypo- and hyperphosphatemia, we found that low albumin, BMI, and high overhydration increased the mortality risk in the hypophosphatemic group, whereas in hyperphosphatemic patients data were not statistically significant. CONCLUSION: Currently, a high prevalence of hypophosphatemia exists in Portuguese HD patients. This condition is associated with worst nutritional and body composition parameters. In the context of additional indices of malnutrition (low albumin, low BMI or severe overhydration), hypophosphatemic patients presented higher mortality risk.