Massive transfusions and severe hypocalcemia: An opportunity for monitoring and supplementation guidelines.

BACKGROUND: Massive transfusion protocols (MTPs) are associated with severe hypocalcemia, contributing to coagulopathy and mortality in severely injured patients. Severity of hypocalcemia following massive transfusion activation and appropriate treatment strategies remain undefined. STUDY DESIGN AND METHODS: This was a retrospective study of all MTP activations in adult trauma patients at a Level 1 trauma center between August 2016 and September 2017. Units of blood products transfused, ionized calcium levels, and amount of calcium supplementation administered were recorded. Primary outcomes were ionized calcium levels and the incidence of severe ionized hypocalcemia (iCa ≤1.0 mmol/L) in relation to the volume of blood products transfused. RESULTS: Seventy-one patients had an MTP activated during the study period. The median amount of packed red blood cells (PRBCs) transfused was 10 units (range 1-52). A total of 42 (59.1%) patients had periods of severe hypocalcemia. Patients receiving 13 or more units of PRBC had a greater prevalence of hypocalcemia with 83.3% having at least one measured ionized calcium ≤1.0 mmoL/L (p = .001). The number of ionized calcium levels checked and the amount of supplemental calcium given in patients who experienced hypocalcemia varied considerably. DISCUSSION: Severe hypocalcemia commonly occurs during MTP activations and correlates with the number of packed red blood cells transfused. Monitoring of ionized calcium and amount of calcium supplementation administered is widely variable. Standardized protocols for recognition and management of severe hypocalcemia during massive transfusions may improve outcomes.

Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19.

BACKGROUND: The severity of Coronavirus Disease 2019 (COVID-19) is a multifactorial condition. An increasing body of evidence argues for a direct implication of vitamin D deficiency, low serum calcium on poor outcomes in COVID-19 patients. This study was designed to investigate the relationship between these two factors and COVID-19 in-hospital mortality. MATERIALS: This is a prospective study, including 120 severe cases of COVID-19, admitted at the department of Reanimation-Anesthesia. Vitamin D was assessed by an immuno-fluoroassay method. Total serum calcium by a colorimetric method, then, corrected for serum albumin levels. The association with in-hospital mortality was assessed using the Kaplan-Meier survival curve, proportional Cox regression analyses and the receiver operating characteristic curve. RESULTS: Hypovitaminosis D and hypocalcemia were very common, occurring in 75% and 35.8% of patients. When analyzing survival, both were significantly associated with in-hospital mortality in a dose-effect manner (pLog-Rank = 0.009 and 0.001 respectively). A cutoff value of 39 nmol/l for vitamin D and 2.05 mmol/l for corrected calcemia could predict poor prognosis with a sensitivity of 76% and 84%, and a specificity of 69% and 60% respectively. Hazard ratios were (HR = 6.9, 95% CI [2.0-24.1], p = 0.002 and HR = 6.2, 95% CI [2.1-18.3], p = 0.001) respectively. CONCLUSION: This study demonstrates the high frequency of hypocalcemia and hypovitaminosis D in severe COVID-19 patients and provides further evidence of their potential link to poor short-term prognosis. It is, therefore, possible that the correction of hypocalcemia, as well as supplementation with vitamin D, may improve the vital prognosis.

Hypocalcemia in sepsis: analysis of the subcellular distribution of Ca2+ in septic rats and LPS/TNF-α-treated HUVECs.

INTRODUCTION: Hypocalcemia has been widely recognized in sepsis patients. However, the cause of hypocalcemia in sepsis is still not clear, and little is known about the subcellular distribution of Ca2+ in tissues during sepsis. METHODOLOGY: We measured the dynamic change in Ca2+ levels in body fluid and subcellular compartments, including the cytosol, endoplasmic reticulum and mitochondria, in major organs of cecal ligation and puncture (CLP)-operated rats, as well as the subcellular Ca2+ flux in HUVECs which treated by endotoxin and cytokines. RESULTS: In the model of CLP-induced sepsis, the blood and urinary Ca2+ concentrations decreased rapidly, while the Ca2+ concentration in ascites fluid increased. The Ca2+ concentrations in the cytosol, ER, and mitochondria were elevated nearly synchronously in major organs in our sepsis model. Moreover, the calcium overload in CLP-operated rats treated with calcium supplementation was more severe than that in the non-calcium-supplemented rats but was alleviated by treatment with the calcium channel blocker verapamil. Similar subcellular Ca2+ flux was found in vitro in HUVECs and was triggered by lipopolysaccharide (LPS)/TNF-α. CONCLUSIONS: Ca2+ influx from the blood into the intercellular space and Ca2+ release into ascites fluid may cause hypocalcemia in sepsis and that this process may be due to the synergistic effect of endotoxin and cytokines.

Parathyroid hormone response in treatment of subclinical hypocalcemia in postpartum dairy cows.

The aim of this study was to evaluate different treatments of postpartum subclinical hypocalcemia in dairy cows with emphasis on PTH response. Twenty four cows with subclinical hypocalcemia (Ca 1.4-2.0 mmol/L), out of 180 Holstein cows tested, were assigned in one of three equal groups: (1) CON received no Ca supplementation, (2) PO-Ca received 1000 mL of oral Ca suspension, immediately after establishing hypocalcemia, and 500 mL of the suspension 12 h after, (3) IV-Ca intravenously received 500 mL of Ca immediately after establishing hypocalcemia. The blood samples were taken up to 48 h after initial treatment for determination of Ca, iP, Mg and PTH concentrations. Urine pH was also evaluated up to 48 h after initial treatment. Compered to CON cows that were hypocalcemic up to the 48 h, Ca concentrations were significantly higher in PO-Ca up to hour 8 and IV-Ca up to hour 24. At first 2 h, PTH concentrations were significantly lower, compared to CON, only in IV-Ca, while at hour 4 PTH concentrations were significantly lower in both treated groups. At hours 24 and 48, PTH concentrations were significantly lower only in PO-Ca compared to CON group. Urine pH values in CON indicate alkalosis and were significantly lower both in PO-Ca and IV-Ca group, up to 12 h and 24 h respectively. In conclusion, both treatments mitigated hypocalcemia in cows, but with significantly different PTH response. Due to adequate PTH response, normocalcemia is established in CON and expected transient hypocalcemia is avoided in IV-Ca cows.

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.

Preoperative Vitamin D Supplementation in Patients With Vitamin D Deficiency Undergoing Total Thyroidectomy.

BACKGROUND: Transient hypocalcemia due to parathyroid gland or vessel manipulation is a common complication following thyroidectomy. Considering the role of 25-hydroxyvitamin D (25(OH)D) in calcium hemostasis, this study aimed to evaluate the effect of preoperative vitamin D supplementation on hypocalcemia incidence in thyroidectomy patients. METHODS: In this randomized clinical trial, 100 patients scheduled for total thyroidectomy and suffering from preoperative moderate or severe vitamin D deficiency were enrolled. Patients were randomly allocated to either study or control groups using the sealed envelope method. Patients in the study group received vitamin D3 50,000-unit pearl weekly for 4 weeks prior to the operation. The control group received placebo. Total and ionized serum calcium levels were checked before surgery, the day after surgery, and 2 weeks postoperatively. RESULTS: No significant difference was observed in terms of demographic data. During serial total calcium checks (5 episodes), total calcium levels changed significantly in patients who had received vitamin D supplements compared to the control group (P = 0.043). Symptomatic hypocalcemia incidence was significantly lower in patients supplemented with 25-hydroxyvitamin D (25(OH)D) (P = 0.04). Also, the requirement for intravenous calcium administration in order to treat the hypocalcemia symptoms was significantly lower in the study in comparison to the control group (P = 0.03). CONCLUSIONS: Vitamin D supplementation in patients with vitamin D deficiency might lead to a lower incidence of early-onset symptomatic hypocalcemia; hence, requiring less calcium supplementation for the management of hypocalcemia.

Forgot calcium? Admission ionized-calcium in two civilian randomized controlled trials of prehospital plasma for traumatic hemorrhagic shock.

BACKGROUND: Randomized clinical trials (RCTs) support the use of prehospital plasma in traumatic hemorrhagic shock, especially in long transports. The citrate added to plasma binds with calcium, yet most prehospital trauma protocols have no guidelines for calcium replacement. We reviewed the experience of two recent prehospital plasma RCTs regarding admission ionized-calcium (i-Ca) blood levels and its impact on survival. We hypothesized that prehospital plasma is associated with hypocalcemia, which in turn is associated with lower survival. METHODS: We studied patients enrolled in two institutions participating in prehospital plasma RCTs (control, standard of care; experimental, plasma), with i-Ca collected before calcium supplementation. Adults with traumatic hemorrhagic shock (systolic blood pressure ≤70 mm Hg or 71-90 mm Hg + heart rate ≥108 bpm) were eligible. We use generalized linear mixed models with random intercepts and Cox proportional hazards models with robust standard errors to account for clustered data by institution. Hypocalcemia was defined as i-Ca of 1.0 mmol/L or less. RESULTS: Of 160 subjects (76% men), 48% received prehospital plasma (median age, 40 years [interquartile range, 28-53 years]) and 71% suffered blunt trauma (median Injury Severity Score [ISS], 22 [interquartile range, 17-34]). Prehospital plasma and control patients were similar regarding age, sex, ISS, blunt mechanism, and brain injury. Prehospital plasma recipients had significantly higher rates of hypocalcemia compared with controls (53% vs. 36%; adjusted relative risk, 1.48; 95% confidence interval [CI], 1.03-2.12; p = 0.03). Severe hypocalcemia was significantly associated with decreased survival (adjusted hazard ratio, 1.07; 95% CI, 1.02-1.13; p = 0.01) and massive transfusion (adjusted relative risk, 2.70; 95% CI, 1.13-6.46; p = 0.03), after adjustment for confounders (randomization group, age, ISS, and shock index). CONCLUSION: Prehospital plasma in civilian trauma is associated with hypocalcemia, which in turn predicts lower survival and massive transfusion. These data underscore the need for explicit calcium supplementation guidelines in prehospital hemotherapy. LEVEL OF EVIDENCE: Therapeutic, level II.

Postoperative Hypoparathyroidism After Total Thyroidectomy in Children.

BACKGROUND: Postoperative hypocalcemia because of hypoparathyroidism is the most common complication of total thyroidectomy in children. We hypothesized that most children with postoperative hypocalcemia would be eucalcemic by 12 mo and sought to define risk factors for permanent hypoparathyroidism. METHODS: We retrospectively reviewed children who underwent total thyroidectomy at a single children's hospital from 2012 to 2019. Patients with prior neck surgery were excluded. Indication for operation, final pathologic diagnosis, and postoperative serum calcium up to 12 mo were recorded. Permanent hypoparathyroidism was defined as supplemental calcium requirement beyond 1 y postoperatively. RESULTS: Sixty-eight patients underwent total thyroidectomy. Graves' disease was the most common benign indication for surgery (38 patients). Twenty-six patients (38%) had cancer on final pathology. Central lymph node dissection (CLND) was performed in 12 cancer patients. Twenty-eight patients (41%) had postoperative hypocalcemia. Eight patients (12%) had hypocalcemia at 6 mo. Risk factors for hypoparathyroidism at 6 mo were a cancer diagnosis (odds ratio [OR] 6.7; P = 0.02), CLND (OR 12.6; P < 0.01), and parathyroid tissue in the surgical specimen on pathologic analysis (OR 19.5; P < 0.01). Only two patients (3%) developed permanent hypoparathyroidism, both of whom had thyroidectomy for cancer and underwent CLND. CONCLUSIONS: Children with thyroid cancer are at high risk for postoperative hypocalcemia after total thyroidectomy. The risk is further increased by CLND, which should be performed selectively. A majority of patients with hypoparathyroidism at 6 mo postoperatively regain normal parathyroid function by 1 y. Permanent hypoparathyroidism in children after total thyroidectomy at a pediatric endocrine surgery center is rare.

Risk Factors for Development of Hypocalcemia in Patients With Cancer Treated With Bone-Modifying Agents.

BACKGROUND: This retrospective analysis describes the prevalence of and risk factors associated with the development of hypocalcemia in patients with cancer receiving bone-modifying agents (BMAs) as supportive care. PATIENTS AND METHODS: Patients with cancer treated with an intravenous or subcutaneous BMA, including pamidronate, zoledronic acid, or denosumab, at a tertiary care/safety net hospital in 2005 through 2015 were included in this retrospective review. We reviewed the medical records for predictive clinical and laboratory parameters and for patient outcomes. RESULTS: A total of 835 patients with cancer received at least one dose of a BMA during the specified time frame; 205 patients (25%) developed hypocalcemia of CTCAE grade ≥1 within 8 weeks of BMA initiation, 18 of whom (8.8%) had grade ≥3, and 3 patients died as a result. Multivariate analysis showed that patients with hematologic malignancy (odds ratio [OR], 1.956; P=.025), bone metastases (OR, 2.443; P=.017), inpatient status (OR, 2.592; P<.001), and deficient baseline vitamin D levels (OR, 2.546; P<.023) were more likely to develop hypocalcemia. Hypercalcemia before BMA administration (OR, 0.474; P=.032) was protective. CONCLUSIONS: Certain patient populations, including those with hematologic malignancies and/or bone metastases, warrant closer monitoring of calcium levels while receiving BMAs because of the high rate of hypocalcemia. Low pretreatment vitamin D levels are associated with the development of hypocalcemia. These data support close monitoring of calcium levels in patients with cancer receiving BMAs, in addition to adequate repletion of vitamin D before initiation of BMAs when possible.

Hipoparatiroidismo y calcificaciones cerebrales: reporte de caso / Hypoparathyroidism and brain calcifications: a case report

Introducción. El hipoparatiroidismo es una enfermedad caracterizada por la ausencia o concentraciones inadecuadamente bajas de hormona paratiroidea (PTH), que conduce a hipocalcemia, hiperfosfatemia y excreción fraccional elevada de calcio en la orina. Las calcificaciones del sistema nervioso central son un hallazgo frecuente en estos pacientes. Caso clínico. Mujer de 56 años con antecedente de hipotiroidismo, que ingresó por un cuadro de 6 días de evolución caracterizado por astenia, parestesias periorales y movimientos anormales de manos y pies. Las pruebas de laboratorio demostraron hipocalcemia, hiperfosfatemia y niveles bajos de hormona paratiroidea. Se realizó una tomografía computarizada de cráneo que mostró áreas bilaterales y simétricas de calcificaciones en hemisferios cerebelosos, ganglios basales y corona radiata. No se evidenciaron trastornos en el metabolismo del cobre y hierro. Se estableció el diagnóstico del síndrome de Fahr secundario a hipoparatiroidismo y se inició tratamiento con suplementos de calcio y vitamina D con evolución satisfactoria. Discusión. El síndrome de Fahr es un trastorno neurológico caracterizado por el depósito anormal de calcio en áreas del cerebro que controlan la actividad motora. Se asocia a varias enfermedades, especialmente, hipoparatiroidismo. La suplementación con calcio y vitamina D con el objetivo de normalizar los niveles plasmáticos de estos cationes es el tratamiento convencional. (AU)

Introduction. Hypoparathyroidism is a disease characterized by absence or inappropriately low concentrations of circulating parathyroid hormone, leading to hypocalcaemia, hyperphosphataemia and elevated fractional excretion of calcium in the urine. Central nervous system calcifications are a common finding in these patients. Case report. 56-year-old woman with a history of hypothyroidism who was admitted for a 6-day course of illness characterized by asthenia, perioral paresthesias, and abnormal movements of the hands and feet. Laboratory tests showed hypocalcemia, hyperphosphatemia, and low parathyroid hormone levels. A cranial computed tomography was performed. It showed bilateral and symmetrical areas of calcifications in the cerebellar hemispheres, basal ganglia, and radiata crown. No disorders of copper or iron metabolism were evident. The diagnosis of Fahr syndrome secondary to hypoparathyroidism was established and treatment with calcium and vitamin D supplements was started with satisfactory evolution. Discussion. Fahr's syndrome is a neurological disorder associated with abnormal calcium deposition in areas of the brain that control motor activity. It is associated with various diseases, especially hypoparathyroidism. The conventional treatment is supplementation with calcium and vitamin D, with the aim of normalizing their plasma levels. (AU)

4-Hour postoperative PTH level predicts hypocalcemia after thyroidectomy in children.

BACKGROUND: Hypocalcemia occurs frequently after a total thyroidectomy in pediatric patients. Four hour postoperative PTH monitoring predicts the need for calcium supplementation in the adult thyroidectomy population. We evaluated the role of the 4 h postoperative PTH level in determining the need for calcium supplementation after thyroidectomy in the pediatric population. METHODS: This is a retrospective review of children undergoing total thyroidectomy by a single pediatric surgeon from July 2011 through July 2018. Intact PTH obtained four hours postoperatively determined the need for calcium supplementation for patients beginning in November 2014 onward. Serum total calcium levels were monitored concurrently with serum intact PTH levels. Serum calcium levels were followed in our Multispecialty Pediatric Endocrine Surgery clinic within the month following thyroidectomy. RESULTS: From July 2011 through July 2018, there were a total of 56 total thyroidectomies at our institution. Prior to November 2014, all pediatric total thyroidectomies received calcium supplementation per our institutional protocol. Based on ionized calcium levels, 26.3% (5/19) of children developed hypocalcemia. From November 2014 to July 2018, 37 pediatric patients required total thyroidectomies. 29.7% (11/37) had low 4-h postoperative PTH levels. 72.7% (8/11) patients with low 4-h postoperative PTH levels had corresponding postoperative day 1 total calcium levels less than 8.5 or ionized calcium levels less than 1.12, and five children (45.5%) developed symptomatic hypocalcemia. 70% (26/37) of children had normal 4-h postop PTH levels, with only 5 (19%) ever developing hypocalcemia. No patients with a normal postop PTH level developed symptomatic hypocalcemia or required IV calcium repletion. A single 4-h postoperative PTH <10 pg/dl for identifying hypocalcemia has a sensitivity of 81% and specificity of 91%, with AUC 0.81. CONCLUSION: The 4-h postoperative serum PTH level can help determine the need for calcium supplementation in pediatric patients undergoing total thyroidectomy, thereby reducing unnecessary calcium supplementation and serial lab draws to monitor for postoperative hypocalcemia. LEVEL OF EVIDENCE: Level II.

The most reliable time point for intact parathyroid hormone measurement to predict hypoparathyroidism after total thyroidectomy with central neck dissection to treat papillary thyroid carcinoma: a prospective cohort study.

PURPOSE: We assessed the optimal time for intact parathyroid hormone (iPTH) measurement for early detection of post-total thyroidectomy (TT) hypocalcemia in patients with papillary thyroid carcinoma (PTC). METHODS: In this single-center prospective cohort study, 143 patients who underwent TT with central neck dissection with or without lateral neck dissection for PTC were included. Biochemical profiles including iPTH, corrected total calcium, and ionized calcium within 24 h after surgery were analyzed. RESULTS: The 4-h postoperative iPTH was the most reliable predictor of post-TT transient or permanent hypoparathyroidism (cutoff for hypocalcemia was 3.75 pg/mL, AUC = 0.885, P < 0.001, sensitivity 81.6%, specificity 86.0%; cutoff for permanent hypocalcemia was 2.48 pg/mL, AUC = 0.819, P < 0.001, sensitivity 100%, specificity 57.8% calculated using ROC curves). CONCLUSIONS: The 4-h postoperative iPTH can most accurately predict hypoparathyroidism after TT with central neck dissection to treat PTC and facilitate the early discharge of low-risk postoperative hypoparathyroidism patients and decrease unnecessary overnight observation and calcium supplementation.

Paradoxical deterioration in seizure control due to anticonvulsant-induced hypocalcaemia.

Hepatic cytochrome P450 enzyme induction is associated with certain antiepileptic drugs (AEDs) and may result in hypocalcaemia secondary to vitamin D deficiency. We report a case of a 44-year-old man with a history of epilepsy, who presented with breakthrough seizures after having previously been seizure-free for 11 years. Investigations revealed severe hypocalcaemia with a corrected calcium of 1.7 mmol/L. His phenytoin dose was increased, and he was started on calcium supplementation. He was discharged with a corrected calcium level of 2.05 mmol/L but was readmitted 1 week later with further seizures and a corrected calcium of 1.89 mmol/L. 25-hydroxyvitamin D was low. AED-induced hypocalcaemia was suspected, which had been made paradoxically worse by the increase in phenytoin dose. Alfacalcidol was prescribed and he was switched from phenytoin to levetiracetam with resolution of hypocalcaemia and no further seizures. The authors recommend screening for calcium and vitamin D deficiency in patients on enzyme-inducing AEDs.

Prevalence and correlates of low serum calcium in late pregnancy: A cross sectional study in the Nkongsamba Regional Hospital; Littoral Region of Cameroon.

INTRODUCTION: Women from low and middle income countries are generally more likely to have sub-optimal calcium intake. The objective of this study was to assess serum calcium disorders and correlates in late pregnancy. METHODS: We conducted from December 2018 to April 2019, a cross-sectional hospital-based study targeting pregnant women in late pregnancy in the Nkongsamba Regional Hospital. Data were collected by measurement of parameters (weight, height, blood pressure and foetal birthweight), administration of a semi-structured questionnaire and analysis of blood samples collected from each participant. Absorption spectrophotometry was used to measure serum calcium and albumin concentrations and corrected serum calcium calculated from the Payne's equation. With a statistical significant threshold set at p-value = 0.05, the odds ratio was used as a measure of the strength of association between hypocalcaemia and maternofoetal variables. RESULTS: We enrolled a total of 354 consenting participants with a mean age of 27.41±5.84 years. The prevalence of hypocalcaemia in late pregnancy was 58.76 [53.42-63.90]%. The rate of calcium supplementation in pregnancy was 57.63[52.28-62.80]% with a mean duration of supplementation of 3.69±1.47 months. When controlled for marital status, age, level of education, and gestational age at delivery, pregnant women with systolic blood pressures below 130 mmHg were significantly less likely to have hypocalcaemia than their counterparts with higher systolic blood pressures (Adjusted Odds Ratio = 0.41[0.18-0.89], p-value = 0.020). No statistically significant associations were found between diastolic blood pressure, body mass index, foetal birth weight and hypocalcaemia. CONCLUSION: Hypocalcaemia in late pregnancy is highly prevalent (59%) among women accessing reproductive services at the Nkongsamba Regional Hospital. There is also a wide gap in calcium supplementation compared to World Health Organization recommendations. Hypocalcaemia is significantly associated to higher systolic blood pressure in pregnancy. Systematic calcium supplementation and consumption of high calcium containing locally available meals should be encouraged.

Post-thyroidectomy Hypocalcemia - Risk Factors and Management.

The complications of thyroidectomy vary from hypocalcemia and recurrent laryngeal nerve lesions to injury of vocal folds, local hematoma, cysts, granuloma. Post-operative hypocalcemia has an incidence of 1.2-40%. Permanent hyoparathyroidism is registered in 3% of cases. This is a brief narrative review focusing on the levels of calcium after performing a thyroidectomy and the need of calcium supplements under these circumstances. This complication, even it seems rather harmless at first, in fact it represents an important contributor to hospitalization delay and, especially for severe forms, to poor quality of life, including the risk of life threatening episodes. Devascularisation of parathyroid glands in addition to injury or dissection causes hypoparathyroidism. Hypocalcemia risk differs with sex (females have a higher risk), lymph node dissection (it increases the risk), it differs with type of thyroidectomy (larger dissections have a higher risk; also the intervention for recurrent goitre and second intervention for post-operatory bleeding increase the risk of hypocalcemia; while Basedow disease is probably at higher risk than multinodular goitre among benign conditions) and the duration of procedure. Pre-operatory low calcium, parathormon (PTH), 25-hydroxivitamin D increases the risk. The calcium drop rate matters as well: a decrease of 1 mg/dL calcium over 12 hours after surgery is independently correlated with the risk of symptomatic hypocalcemia. Early post-operatory PTH and calcium are best predictors for the need of oral calcium supplements. Routine post-operatory calcium and vitamin D supplementation statistically significant decreases the risk of developing transitory hypocalcemia and acute complications compare to calcium alone supplements or no supplements. In cases of hypoparathyroidism calcitriol is preferred.

kEDTA Sample Contamination: A Reappraisal.

BACKGROUND: Potassium EDTA (kEDTA) contamination of serum samples is common, causing spurious hyperkalemia, hypozincemia, and hypocalcemia that if unrecognized may adversely affect patient care. Gross kEDTA contamination is easy to detect, but identification of spurious electrolytes due to small amounts of contamination requires measurement of serum EDTA. We validated an EDTA assay on the Abbott Architect and reassessed its value in identifying kEDTA contamination and in studying mechanisms for contamination. METHODS: Within- and between-batch imprecision, linearity, recovery, interference, and carryover were assessed. Serum supplemented with k2EDTA plasma, to mimic sample contamination, was used to study its effect on potassium, calcium, zinc, magnesium, and alkaline phosphatase. Our current laboratory protocol for identification of kEDTA contamination, based on measurement of serum calcium, was compared to that of EDTA measurement. RESULTS: The EDTA assay displayed acceptable performance characteristics. Hemoglobin was a positive interferent. EDTA was detectable in serum contaminated with 1% (v:v) k2EDTA plasma. An increase in serum potassium of 0.54 mmol/L (11.9%) was observed at a measured EDTA concentration of 0.19 mmol/L, equivalent to 3.2% (v:v) contamination. At this EDTA concentration reductions were also observed in zinc (71%), calcium (1%), alkaline phosphatase (ALP) (4%), and magnesium (2.4%). The serum EDTA assay detected contamination in 31/106 patient samples with hyperkalemia (potassium ≥6.0mmol/L), 20 of which were undetected by the current laboratory protocol. CONCLUSIONS: The EDTA assay displayed acceptable performance, with the ability to reliably measure EDTA at low concentrations. Only a small amount of kEDTA causes significant spurious hyperkalemia and is only reliably detected with EDTA measurement.

Evaluating the impact of regulatory action on denosumab-induced hypocalcaemia in Japan.

WHAT IS KNOWN AND OBJECTIVE: Since its introduction in April 2012, denosumab has been administered to approximately 7,300 patients as of August 2012, and 32 cases of serious hypocalcaemia after denosumab administration, including two deaths, have been reported in Japan. A Dear Healthcare Professional Letter of Rapid Safety Communication ('Blue letter') was released to warn about the risks of hypocalcaemia associated with denosumab. The goal of this study therefore was to measure the impact of regulatory action on denosumab-induced hypocalcaemia in Japan by using an electronic medical information database (MID). METHODS: We used two different aggregated data sets based on MIDs (data sets one and two). The patients studied were those who were newly prescribed denosumab or zoledronic acid between April 2012 and September 2014. We assessed four indicators: (a) the proportion of patients with calcium supplementation at the initial denosumab treatment, (b) the proportion of patients who underwent a serum calcium test, (c) the average number of serum calcium tests performed and (d) the prevalence of hypocalcaemia. All indices were aggregated by every 3 months. To evaluate the impact of regulatory action, we used difference in difference (DID) analysis. RESULTS AND DISCUSSION: The proportion of patients with calcium supplementation at the initial denosumab treatment increased year by year in both data sets. The average number of serum calcium tests increased year by year in data set two. There was a significant difference in the prevalence of hypocalcaemia in data set two. This suggests that the estimate of impact of the regulatory action may vary according to the database. In DID analysis, however, significant influences of the regulatory action on combination use with a calcium supplement were detected in both data sets. WHAT IS NEW AND CONCLUSION: There was a significant influence on combination use of denosumab with vitamin D and/or calcium supplement in both data sets. That there was no apparent increase in the prevalence of denosumab-induced hypocalcaemia, suggests that the regulatory action had an impact in the clinical setting studied. Such regulatory actions may play an important role in the promotion of drug safety.

Meta-analysis of routine calcium/vitamin D3 supplementation versus serum calcium level-based strategy to prevent postoperative hypocalcaemia after thyroidectomy.

BACKGROUND: The aim was to assess the effectiveness of routine administration of calcium +/- vitamin D3 compared with a serum calcium level-based strategy to prevent symptomatic hypocalcaemia after thyroidectomy. METHODS: RCTs comparing routine supplementation of calcium +/- vitamin D3 with treatment based on serum calcium levels measured after total thyroidectomy, published between 1980 and 2017, were identified in MEDLINE, Embase, LILACS and Google Scholar databases. Risk of bias was evaluated using the Cochrane Collaboration tool. Risk differences were calculated by random-effects meta-analysis. Meta-regression and cumulative meta-analysis were used to explore the best therapeutic approach. RESULTS: Fifteen studies with 3037 patients were included, and seven treatment comparisons were made. Routine supplementation with calcium + vitamin D3 offered a lower risk of symptomatic (risk difference (RD) -0·25, 95 per cent c.i. -0·32 to -0·18) and biochemical (RD -0·24, -0·31 to -0·17) hypocalcaemia than treatment based on measurement of calcium levels. The number needed to treat was 4 (95 per cent c.i. 3 to 6) for symptomatic hypocalcaemia. No publication bias was found; although heterogeneity was high for some comparisons, sensitivity analysis did not change the main results. CONCLUSION: Routine postoperative administration of calcium + vitamin D3 is effective in decreasing the rate of symptomatic and biochemical hypocalcaemia.

Mild hypotonia and recurrent seizures in an 8-month-old boy: Questions.

Hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder which manifests in early infancy with generalized seizures, other symptoms of neuromuscular irritability, and growth disturbances. Homozygous mutations in the magnesium transporter gene, transient receptor potential melastatin 6 (TRPM6), cause the disease. Here, we present an 8-month-old Turkish boy with a novel mutation of TRPM6. The patient, son of first-degree cousins, was hospitalized because of recurrent seizures and mild hypotonia. He had seizures since the newborn period and he had been treated with phenobarbital but there was no favorable response to therapy. His past history also revealed hypocalcemia detected on the newborn period but serum magnesium levels were not studied at that time. During hospitalization, we detected hypocalcemia, hypomagnesemia, and normal parathormone levels. Abdominal ultrasound was normal. Magnesium excretion was slightly increased. Considering the consanguinity of the parents and clinical features of the patients, genetic testing of the TRPM6 gene was performed and a novel homozygous mutation was detected as c.3178A>T. He was started on magnesium and calcium supplementation and he is symptom-free for 1 year. We would like to call attention to the measurement of serum magnesium levels in children with hypocalcemic convulsions. Early and appropriate treatment with magnesium supplementation is crucial.