Infusion Of Calcium Gluconate Research Articles

Medical Management of Primary Hyperparathyroidism in Pregnancy: A Case Report and Brief Literature Review

There is no established standard of care for the medical management of primary hyperparathyroidism in pregnancy for those patients who are not surgical candidates. We present a case of primary hyperparathyroidism in the third trimester that was managed with cinacalcet and a literature review on the various modalities for the medical management of primary hyperparathyroidism in pregnancy. The primary aim of this case report is to document a case of hyperparathyroidism in pregnancy that was managed medically and to perform a brief systematic review of the literature available on the medical management of primary hyperparathyroidism in pregnancy. The secondary aim is to contribute to the literature available on the use of cinacalcet in pregnancy. A 37-year-old woman with untreated primary hyperparathyroidism presented at 32 weeks of gestation with hypercalcemia that was not amenable to surgical intervention. We treated her with increasing doses of cinacalcet with improvement in her serum calcium until developing pre-eclampsia which prompted emergent cesarean delivery of the infant. The neonate developed respiratory distress after delivery but did not develop hypocalcemia after birth. The neonate became transiently hypercalcemic in the setting of calcium gluconate infusions given to prevent hypocalcemia. The patient underwent surgical removal of a parathyroid adenoma and required calcium supplementation for 1 month afterwards. Hypercalcemic crisis during pregnancy is associated with significant maternal and fetal morbidity. There is limited information regarding the medical management of primary hyperparathyroidism due to the lack of high-powered studies and prospective studies owing to the relative rarity of the condition. No serious adverse maternal events were reported for either bisphosphonate or cinacalcet use. Adverse neonatal events include transient hypocalcemia of the infant with cinacalcet use and possibly low birth weight, infantile hypocalcemia, and shortened gestational periods with bisphosphonate use. J Endocrinol Metab. 2020;10(2):49-53 doi: https://doi.org/10.14740/jem624

Severe Amlodipine Toxicity: A Case Rescued with Extracorporeal Membrane Oxygenation.

ABSTRACTAmlodipine is a widely prescribed drugs for the management of hypertension. Its toxicity is associated with severe myocardial depression and refractory hypotension. We present a case of a 28-year-old female known case of seizure disorder and depression who got admitted to our hospital with a history of consumption of 80 tablets of 5 mg amlodipine (total 400 mg). Patient presented to our hospital after 23 hours following consumption of the drug. Patient was managed in the intensive care unit (ICU) with mechanical ventilation support and intravenous infusion of noradrenalin, adrenalin, insulin-dextrose, and calcium gluconate. Due to refractory hypotension, venoarterial extracorporeal membrane oxygenation (VA-ECMO) was initiated on the same day. Patient was successfully managed and discharged home on the 8th day. This report highlights a rare case of a massive amlodipine overdose (400 mg) and ECMO as a rescue therapy.How to cite this articleSutar A, Venkategowda PM, Murthy A, Chikkaswamy SB. Severe Amlodipine Toxicity: A Case Rescued with Extracorporeal Membrane Oxygenation. Indian J Crit Care Med 2020;24(5):365–366.

HIGH DOSE AMLODIPINE POISONING TREATED WITH HIGH INSULIN EUGLYCEMIC THERAPY

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Calcium channel blockers (CCB) are one of the most commonly prescribed anti-hypertensive medications. CCB poisoning is life-threatening due to myocardial suppression and severe refractory hypotension. To date, there are no specific recommendations on when to initiate high insulin euglycemic therapy (HIET). Management has been aimed at achieving adequate vasopressor support with epinephrine, norepinephrine, and dopamine. fluid resuscitation, and calcium are also provided. Recently, case series have reported successful outcomes in treating CCB poisoning with HIET. CASE PRESENTATION: A 72 year old female presented to the ED with lethargy and dizziness after attempting to commit suicide by ingesting 100 tablets of Amlodipine 5 mg twelve hours prior to presentation, per report of the patient and family. Patient had a past medical history of macular degeneration, depression, cataract and hypertension. Upon presentation the patient’s physical exam was significant for a blood pressure of 87/53 mmHg, a temperature of 98.4 °F, a heart rate of 98 and a respiratory rate of 18. The cardiovascular exam showed a regular rhythm and normal heart sounds. The remainder of the exam was unremarkable. Electrocardiogram showed normal sinus rhythm of 97 with no evidence of any conduction delays. Abnormal labs included a serum sodium of 134, ALT of 110 and AST of 88. Renal function and blood counts were normal. The patient’s blood pressure began to decrease dramatically, prompting the initiation of HIET, calcium gluconate infusion and vasopressor support within the first 4 hours after presentation. The patient required continuous infusion of insulin with D10, calcium gluconate infusion, and close monitoring of both calcium and glucose for three days after admission. On day 6, she became normotensive and no longer required vasopressor support. DISCUSSION: Dihydropyridine CCB’s block L-type calcium channels, which cause smooth muscle relaxation with no-to-minimal effect on the myocardium in usual doses. At higher and more toxic doses, it can block sodium channels in the myocardium causing myocardial suppression. CCB poisoning in high doses can be fatal. However, there are no clear guidelines outlining the time to initiate HIET in CCB poisoning. In this case HIET had a positive outcome, but it was started almost 16-18 hours after ingestion of the calcium channel blocker. This presents the question of whether or not timing of HIET initiation could decrease ICU stay and mortality.In addition, it is unclear wether HIET should be used concurrently with vasopressor support as a first-line therapy. CONCLUSIONS: Patients who present with CCB poisoning due to higher dose ingestions require more aggressive therapy in order to demonstrate clinical improvement. Data in past years have supported the use of HIET in these patients, but appropriate time of HIET initiation has not been established. Reference #1: St-Onge M, Dubé PA, Gosselin S. et.al. Treatment for calcium channel blocker poisoning: a systematic review. Clinical Toxicology. 2014.1;52(9):926-44. Reference #2: Kumar K, Biyyam M, Bajantri B, et.al. Critical Management of Severe Hypotension Caused by Amlodipine Toxicity Managed With Hyperinsulinemia/Euglycemia Therapy Supplemented With Calcium Gluconate, Intravenous Glucagon and Other Vasopressor Support: Review of Literature. Cardiology research. 2018;9(1):46. Reference #3: St-Onge M, Anseeuw K, Cantrell FL, et.al. Experts consensus recommendations for the management of calcium channel blocker poisoning in adults. Critical care medicine. 2017;45(3):e306. DISCLOSURES: No relevant relationships by ahmad alkhatatneh, source=Web Response No relevant relationships by Razan Elsayed, source=Web Response

Feeding and postruminal infusion of calcium gluconate to lactating dairy cows

Gluconic acid was proposed as a prebiotic for nonruminants; however, a ruminant application is undescribed. The first experiment was a 5 × 5 Latin square with five test doses of calcium gluconate (...

Optimization of infusional calcium gluconate for prevention of hypocalcemic reactions during therapeutic plasma exchange.

We sought to optimize direct intravenous infusion of calcium gluconate (CaGlu) for maintaining plasma ionized calcium concentration ([Ca2+ ]) and preventing hypocalcemic reactions during 34 consecutive 1-volume therapeutic plasma exchanges (TPEs) in eight patients. CaGlu, 2 g in 50 mL of 0.9% NaCl, was prepared by our hospital pharmacy and infused at either 1.0 or 1.6 g/h during alternate TPE. Plasma [Ca2+ ] was monitored at intervals of 20 to 30 minutes. At 1 g/h of CaGlu, plasma [Ca2+ ] fell by 8.35% after 40 to 50 minutes and then plateaued. At 1.6 g/h of CaGlu, plasma [Ca2+ ] fell by 6% after 20 to 30 minutes and then plateaued. The difference at 40 to 50 minutes was significant (P = .015). Hypocalcemic reactions were noted in three patients during 5 of 17 TPE at 1.0 g/h (all after 40 to 60 minutes) but 0 of 17 TPE at 1.6 g/h (P = .044). CaGlu at 1.6 g/h stabilized plasma [Ca2+ ] and appears to prevent hypocalcemic reactions during TPE.

SUN-516 Fahr's Syndrome: A Rare Sequela of Hypoparathyroidism

Fahr’s syndrome (FS) is rare, progressive neurodegenerative disorder characterized by bilateral symmetric calcifications in the basal ganglia and cerebral cortex. Etiology of FS includes endocrine disorder, mitochondrial disease, dermatological or infectious disease. The prevalence of FS due to hypoparathyroidism (HP) is unknown. The presentation varies from movement disorders, pyramidal signs, neuropsychiatric manifestations to cognitive impairment. Case: We present a 46-year-old female with history of Grave’s disease s/p subtotal thyroidectomy, postsurgical HP and hypothyroidism for over two decades. She had history of chronic nonadherence with medications and clinic visits. Serum calcium levels were consistently below 7 mg/dl. She was found unresponsive and required intubation. Vital signs were within normal range. Physical examination except for neurological exam was unremarkable. Laboratory data: serum calcium- 6.2 mg/dl (8.4-10.2 mg/dl), ionized calcium- 0.77 mmol/L (1.13-1.32 mmol/L), phosphate - 6.4 mg/dl (2.7-4.5 mg/dl), 25 vitamin D- 21 ng/ml ( 30-100 ng/ml ), PTH- 7 pg/ml (15-65 pg/ml ), magnesium- 1.5 mg/dl (1.6-2.6 mg/dl ), creatinine - 5.16 mg/dl ( 0.4-1.1 mg/dl), WBC- 19.6 x 103/ uL (4-10 x 103/uL), TSH- 35 IU/ml (0.27-4.2 IU/ml), Free T4 – 0.96 ng/dl (0.9-1.7 ng/dl), lactate – 1.4 mmol/L (0.5 – 2.2 mmol/L). Urine toxicology was negative. EKG revealed prolonged QTc of 524 msec. Head CT showed no acute pathology however, revealed extensive bilateral calcifications of the dentate nuclei, basal ganglia, thalami and white matter, leading to consideration of FS. Calcium rose above 8 mg/dl with treatment (calcium gluconate infusion; oral calcium acetate and calcitriol via nasogastric tube). However, her mentation improved only after serum calcium remained above 8 mg/dl for the next five days. She regained consciousness and was oriented but mentation did not return to baseline. Conclusion: Although FS with extensive intracranial calcifications is a rare sequela of HP, HP is the most common cause of FS. The pathogenesis of these brain calcifications is not clear. Our patient had long standing HP and chronic non-adherence to medications. Her age at the time of diagnosis of FS rules out mitochondrial disorders. Her clinical presentation, extensive intracranial calcification with characteristic distribution and the absence of infection, dermatological lesions, traumatic or toxic causes or family history favor the diagnosis of FS. The progression of FS is thought to be associated with the calcium/phosphorus ratio, severity and duration of hypocalcemia. This emphasizes the importance of early stabilization of serum calcium level in HP to prevent development of complications. In most patients, clinical improvement and reversal of neuropsychiatric symptoms is notable after the correction of hypocalcemia. Hence, early recognition of HP as an etiology of FS is critical.

SUN-515 A Case report of Severe Persistent Hypocalcaemia due to Functional Hypoparathyroidism

Introduction: Severe Hypocalcaemia is generally seen in clinical practice in patients following thyroid or parathyroid surgery .We report a case of severe hypocalcaemia with unusual presentation and etiology with challenging management. Case report: A 49 year old gentleman presented to hospital with unexpected, unintentional severe weight loss (20kg over 2 months), vomiting, diarrhoea, muscle cramps and pins & needles in both hands. His past medical history included beta thalassemia trait. He had a recent bereavement in his family and therefore had attributed his symptoms to the grieving process. He had no significant or relevant family history of note.Physical examination revealed positive Chvostek and Trousseau’s signs. His initial biochemistry showed corrected calcium of 0.86 (Normal range:2.20-2.60 mmol/l), Magnesium 0.58 (Normal range:0.7-1.0mmol/l), K+:3.3(Normal range:3.5-5.3mmol/l),Parathyroid hormone(PTH) suppressed at 0.7(Normal range:1.1-4.7pmol/l) and 25 OH Vitamin D 25(Normal range:50-250nmol/l).ECG showed long QTc.He wasn’t taking any proton pump inhibitor. He was started on intravenous magnesium infusion (6g of MgSO4 in 500 ml Normal saline), Calcium Gluconate infusion (100ml of 10% Ca. Gluconate in 1000mls of Normal saline at 50-100 ml/hr), Calcium carbonate tablets and Cholecalciferol 20,000 units daily(for 10 days). His corrected calcium gradually improved and he noticed immediate resolution of his symptoms. His CT chest,Abdomen,Pelvis did not show any evidence of malignancy and Gastroscopy showed mild erosive gastritis.He was reviewed by Gastroenterology but no other cause for significant weight loss and gastrointestinal symptoms was found. He was thought to be having Severe Hypocalcaemia due to Functional Hypoparathyroidism caused by Magnesium and Vitamin D deficiency. He was discharged on oral calcium and cholecalciferol tablets. He represented to hospital a month later with corr. Ca+ of 1.57mmol/l. Vitamin D had improved to 90nmol/l, however, PTH was still suppressed at 0.8pmol/l.His calcium carbonate tablets were increased to daily dose of 3g per day and he was also started on 1-alfacalcidol 250 nanograms BD. Subsequent review in ambulatory clinic revealed that he was still hypocalcaemic at 1.75mmol/l. His 1-alfacalcidol was increased to 500 nanograms BD. He continues to be on this treatment, has gained weight and is asymptomatic. Conclusion: Although calcium abnormalities are commonly treated on medical wards, it is very rare to see such severe hypocalcaemia in the absence of any significant pathology. Understanding the physiology of calcium homeostasis is vital to guide appropriate management, especially in situations of clinical emergency which can be very challenging, as we have highlighted in our case.

SAT-512 Severe Hypocalcemia Presenting as Status Epilepticus after Denosumab Use in Metastatic Prostate Cancer

Introduction: Denosumab decreases the incidence of skeletal-related events in patients with metastatic bone disease and is used routinely as part of the therapeutic strategy for various cancers. However, it is associated with a high risk of hypocalcemia with incidence of high-grade hypocalcemia (defined as total calcium < 7mg/dl) as high as 5.1% in patients with castrate-resistant prostate cancer. We present a case of severe hypocalcemia presenting with status epilepticus 32 days after administration of denosumab. Case: A 83 year old African American man presented to the emergency room with status epilepticus. Initial labs revealed a critically low calcium (Ca) of <5mg/dl (8.5-10.1) with albumin 2.2 g/dl (3.4-5.0), ionized calcium 1.09 mg/dl (4.6-5.1) and creatinine (Cr) 3.68 mg/dl (0.67-1.17). QTC was prolonged at 544ms (<400ms). He was intubated for airway protection and a continuous infusion of intravenous calcium gluconate was initiated. Three months prior, he had been diagnosed with prostate cancer with diffuse osteoblastic metastases to his ribs, cervical, thoracic, lumbar and sacral vertebrae, right humerus and bilateral iliac bones. He received a first dose of conventional chemotherapy and 120mg denosumab subcutaneously 32 days prior to hospital admission. Lab investigations then were pertinent for Ca of 9 mg/dl, Cr 1.46 mg/dl, and alkaline phosphatase 362 Units/L (25-125). A 25-hydroxy vitamin D (25-D) was not checked. Further evaluation demonstrated intact parathyroid hormone 677.2 pg/ml (18.4-80.1), alkaline phosphatase 397 Units/L, phosphorus 3.6 mg/dl (2.5-4.9) and 25-D 18 ng/ml (30-100). He was also found to have metastatic obstruction of both ureters which had resulted in acute kidney injury. He was slowly weaned off the intravenous calcium and started on calcitriol 2mcg twice daily, 4 gram elemental calcium daily via feeding tube and cholecalciferol 6000 units daily. Calcium levels remained stable at 8.0-8.5mg/dl on this regimen. Given the extensive metastatic disease, the patient’s family elected to pursue hospice care, and he passed away 9 days later. Conclusion: Patients with osteoblastic metastases and renal impairment are at particularly increased risk of hypocalcemia after denosumab, which can be potentially life-threatening. Physicians caring for patients with metastatic prostate cancer should ensure that vitamin D levels are replete and calcium levels are normal prior to administration of denosumab, monitor calcium levels closely, and counsel them about the signs and symptoms of hypocalcemia to allow prompt diagnosis and treatment.

SAT-508 A Case Report Of Severe Hypercalcaemia Due To Iatrogenic (oral Supplements), Aki And Immobility

Introduction: Hypercalcaemia is a commonly encountered electrolyte imbalance.We report a case of severe hypercalcaemia which was resistant to conventional treatment approach. Case Report: A 52 year old lady presented to hospital with tiredness, constipation, confusion and reduced mobility for 3 weeks.She had complex past medical history including Papillary carcinoma of thyroid treated with total thyroidectomy and parathyroidectomy and Radioactive Iodine ablation 16 years ago and depression. She was taking Levothyroxine , oral calcium & 1-alfacalcidol. On physical examination, she was dehydrated and confused. Her biochemistry revealed Acute kidney Injury(AKI) with Urea: 15.6 (n:2.5-7.8mmol/l), Creatinine: 177 (n: 50-104 micromol/l), eGFR:32ml/min and corrected Calcium 5.71 (n:2.20-2.60mmol/l). PTH was suppressed at 0.1 (n:1.1-4.7pmol/l) and Vitamin D of 30 (n:50-250nmol/l). ECG showed shortened QTc. Initial management of her severe hypercalcaemia was by stopping her oral Calcium tablets and 1 alfacalcidol. She was treated with normal saline infusion.Pamidronate infusion was contraindicated because of AKI. She was therefore given Calcitonin infusion 400 International units resulting in improvement in her corr. Ca+ to 4.77 mmol/l within 24 hours. She continued to receive normal saline and her biochemistry improved. ECG changes were also resolved. Work up for non PTH dependent severe hypercalcaemia included a CT Thorax Abdomen Pelvis, which did not show any evidence of malignancy, bone lesions or nephrocalcinosis. Her Immunoglobulin electrophoresis was normal. Her severe hypercalcaemia was thought to be multifactorial - contributed by her oral calcium and 1 alphacalcidol supplements and exacerbated by immobility and acute kidney injury. After 5 days of hospital admission, her corr. Ca+ dropped to 2.11 mmol/l. Her calcium tablets and 1 alfacalcidol 1.5microgram OD were restarted.However, her bloods showed worsening hypocalcaemia with corr. Ca+ 1.50 mmol/l despite ongoing treatment with calcium gluconate infusion for 10 days. She was therefore started on Indapamide 2.5 mg once daily which was uptitrated to 5mg once daily. Her corr. Ca+ improved to 2.15mmol/l and she was discharged from hospital. Her bone profile has been followed up since discharge and calcium levels have been in normal range. Her Indapamide has now been discontinued. Conclusion: Although disorders of bone homeostasis are very commonly treated on medical wards, sometimes these electrolyte imbalances can be extremely severe and subsequent management could be quite challenging. Markedly high calcium levels due to primary hyperparathyroidism secondary to adenoma(parathyroid crisis) and malignancy have been reported in the past. However, our case report is the first to highlight such severe hypercalcaemia due to iatrogenic (oral supplements), AKI and immobility causes.

A Case of Life-threatening Amlodipine and Atenolol Overdose

ABSTRACTTreating a patient of amlodipine-atenolol poisoning is nightmare for a physician. In high dose both the drugs individually cause severe bradycardia and hypotension. In combination they cause severe cardiovascular depression. Here we report a case of 66-year-old obese, hypertensive, depressed male, who presented to emergency 9 hours after consumption of 25 tablets of amlodipine-atenolol (5 mg+50 mg). On evaluation, he had refractory bradycardia, hypotension and acute kidney injury (AKI). Eventually he developed cardiac arrest. He was revived after 5 minutes of cardio-pulmonary resuscitation (CPR). He was successfully managed with gastric lavage, fluids, inotropes, atropine, isoprenaline and subsequently with calcium gluconate infusion, high-dose insulin euglycemia therapy (HIET) and lipid emulsion therapy. Glucagon infusion was also planned but it was not available. Patient hemodynamics improved and on 8th day he got the discharge. Our case exemplifies the importance of timely and aggressive management of lethal overdose of amlodipine-atenolol poisoning.How to cite this article: Tale S, Kumar M, Ghosh S, Bhalla A. A Case of Life-threatening Amlodipine and Atenolol Overdose. Indian J Crit Care Med 2019;23(6):281–283.

Extracorporeal life support for severe cardiogenic shock induced by diltiazem intoxication

Introduction. Management of cardiogenic shock caused by severe drug intoxication is always challenging. In case of multidrug intoxication, a result, despite aggressive medical therapy, is often unpredictable. Utilization of extracorporeal life support devices in these cases has been suggested and reported results are promising. Case report. We presented a case of profound cardiogenic and distributive shock caused by suicidal intoxication with diltiazem and anionic surfactant ingestion in a 36-year-old woman. The patient ingested more than 90 tablets of diltiazem of 90 mg (ingested dose of 8.1 g), and 4 pieces of household toilet refresh agent containing anionic surfactant. During the admission, systemic blood pressure was 65/40 mmHg, heart rate 45 beats per minute, with signs of metabolic acidosis. The patient underwent several repeated gastric lavages. Emergent fluid resuscitation, calcium gluconate, insulin and vasopressive agents (dopamine and noradrenaline) infusions were administered with negligible effect. Due to progressive and refractory cardiogenic shock with signs of multiorgan failure, a decision was made to put the patient on venoarterial extracorporeal membrane oxygenator. Immediately after starting the extracorporeal membrane oxygenation, diuresis was established. During the next 36 h, an adequate end-organ perfusion was achieved with complete reversal of multiorgan failure. After the successful restoration of all major organ functions, the patient was successfully decannulated and discharged from the hospital after 10 days in a good condition. Conclusion. In severe cases of refractory cardiogenic and distributive shock due to diltiazem and other poison intoxication, venoarterial extracorporeal membrane oxygenation could allow additional circulatory support providing the bonus time for endogenous clearance of toxins. Venoarterial extracorporeal membrane oxygenation could be used in conjunction with the optimal medical therapy aiming to the restoration of end-organ perfusion and allowing for intrinsic drug and toxin metabolism and natural elimination.

Postruminal infusion of calcium gluconate increases milk fat production and alters fecal volatile fatty acid profile in lactating dairy cows

Gluconic acid is a carboxylic acid naturally occurring in plants and honey. In nonruminant animals, gluconic acid has been shown to increase gastrointestinal butyrate concentrations and improve growth performance, but a ruminant application remains undescribed. This experiment examined the effects of postruminal calcium gluconate (CaG) on milk production, fecal volatile fatty acid concentrations, and plasma metabolite concentrations in lactating dairy cows. Six rumen cannulated multiparous Holstein cows (60 ± 6 d in milk) were randomly assigned to 6 treatment sequences within a 6 × 6 Latin square design in which each experimental period consisted of 5 d of continuous postruminal infusion followed by a 2 d wash-out period. Test treatments included a negative control (CON; 0.90% NaCl wt/vol), positive control (Na-butyrate, 135 g/d), and 4 doses of CaG (44, 93, 140, and 187 g/d). Cows received a total mixed ration (31% corn silage, 28% alfalfa silage, 5% hay, 36% concentrate) with dry matter intake fixed (25.3 ± 1.7 kg/d) throughout the experiment. On d 5 of each infusion period, samples of milk, feces, and blood were collected from each animal. Calcium gluconate treatments increased milk fat concentration, and a tendency was observed for increased milk fat yield and energy-corrected milk yield above levels achieved by CON, with maximal treatment responses of 4.43% (CON 3.81%), 2.089 kg/d (CON 1.760 kg/d), and 51.8 kg/d (CON 47.1 kg/d), respectively. Concentrations of iso-butyric acid in feces were greater in cows infused with CaG (13.3 µmol/g) treatments compared with CON (9.7 µmol/g). Arterial concentrations of glucose and nonesterified fatty acids were lower (glucose: CaG 2.98 mmol/L, CON 3.29 mmol/L and nonesterified fatty acids: CaG 0.130 mmol/L vs. 0.148 mmol/L) and β-hydroxybutyrate higher (CaG 1.703 vs. CON 0.812) in cows infused with CaG than CON. Together, these results suggest that postruminal infusion of CaG may alter metabolic mechanisms to support a milk fat production response.

Calcium infusion plus or minus cabergoline for prevention of ovarian hyperstimulation syndrome: Randomized double-blind placebo-controlled trial

Aim: To evaluate the interaction of adding oral cabergoline (OC) to calcium infusion as a preventive modality for ovarian hyperstimulation syndrome (OHSS) in risky women undergoing controlled ovarian hyperstimulation (COH) in context of in- vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI).Patients and Methods: This prospective, double-blind, randomized, placebo-controlled trial was conducted at Benha IVF center of Obstetrics and Gynecology Department of Benha University and Nour Al Hayah Fertility Center Between January 2015 and February 2016. 220 risky women for OHSS undergoing ICSI were included, they were randomized to 110 women received once daily OC for eight days, starting at HCG triggering and infusion of calcium gluconate 10 ml 10% in 200 ml 0.9% saline daily for 4 days beginning at ovum pick up (OPU), coined as calcium infusion plus group (CI+) and 110 women received only calcium infusion in the same fashion as in CI+ coined as calcium infusion minus group (CI-). The primary outcome was the overall incidence of OHSS while the secondary issues were OHSS types and grades as well as other ICSI outcomes.Results: The incidence of overall OHSS was significantly lower in calcium infusion plus oral cabergoline (CI+) group compared to calcium infusion alone (CI-) group [8/110(7.2%) in CI+ versus 18/110 (16.3%) in CI- with difference in proportion percentage point (ΔPP)=-9.1%, 95% CI: -0.49, -17.4; P = 0.036]. Despite the incidence of moderate and severe OHSS was lower in CI+ than in CI-, this difference didn't reach the significance level (2.7% vs 5.4%; p = 0.3) and (0.9% versus 2.7%; ), respectively. The other COH and ICSI outcomes didn't show any statistically significant differences.Conclusion: Adding oral cabergoline to calcium infusion is effective than calcium infusion alone in the reduction of overall OHSS incidence as well as its severity at comparable pregnancy outcomes

Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation

This study evaluated the impact of calcium and magnesium on the in vitro degradation and in vivo clearance of oxaliplatin. Intact oxaliplatin and Pt(DACH)Cl2 were measured in incubation solutions by HPLC-UV. A clinical study determined changes in plasma concentrations of calcium and magnesium in cancer patients and their impact on oxaliplatin clearance. Kinetic analyses modelled oxaliplatin degradation reactions in vitro and contributions to oxaliplatin clearance in vivo. Calcium and magnesium accelerated oxaliplatin degradation to Pt(DACH)Cl2 in chloride-containing solutions in vitro. Kinetic models based on calcium and magnesium binding to a monochloro-monooxalato ring-opened anionic oxaliplatin intermediate fitted the in vitro degradation time-course data. In cancer patients, calcium and magnesium plasma concentrations varied and were increased by giving calcium gluconate and magnesium sulfate infusions, but did not alter or correlate with oxaliplatin clearance. The intrinsic in vitro clearance of oxaliplatin attributed to chloride-, calcium- and magnesium-mediated degradation predicted contributions of <2.5% to the total in vivo clearance of oxaliplatin. In conclusion, calcium and magnesium accelerate the in vitro degradation of oxaliplatin by binding to a monochloro-monooxalato ring-opened anionic intermediate. Kinetic analysis of in vitro oxaliplatin stability data can be used for in vitro prediction of potential effects on oxaliplatin clearance in vivo.

Severe ovarian hyperstimulation syndrome: Can we eliminate it through a multipronged approach?

BackgroundPrevention of severe Ovarian Hyperstimulation Syndrome (OHSS), a potentially fatal complication of controlled ovarian hyperstimulation has been the aim of all fertility experts. Various pharmacologic and non-pharmacologic interventions have been instituted but the results have been conflicting. These preventive strategies were administered in isolation or as a combination of few aiming to eliminate this iatrogenic sequel. This study aimed to eliminate severe OHSS by multipronged approach incorporating almost all preventive modalities available in patients at high risk for this dreadful complication. MethodsIt was a prospective observational study wherein 112 high risk patients planned for IVF were studied. The multipronged approach was in the form administering calcium gluconate infusion, cabergoline, albumin infusion, GnRH antagonist in luteal phase in addition to elective cryopreservation of embryos. The primary outcome measure was incidence of severe OHSS in the study group and the rate of hospitalisation. The secondary outcome measure was the number of days required for complete recovery and resolution of signs and symptoms. ResultsOut of the 112 high risk patients only one patient (1/112; 0.9%) developed severe OHSS with an overall incidence of 0.095% of severe OHSS in all the cycles. There was no biochemical or haematological derangement in any of the high risk patients. ConclusionAlthough this is the first study evaluating the multipronged approach in preventing the dreaded complication of severe OHSS, it does add to the knowledge that targeting the various pathophysiological pathways at different time frames will bring about prevention of OHSS but further randomised studies may reveal superiority of one intervention over the other.

Slight hypercalcemia is not associated with positive responses in the Comet Assay in male rat liver

Maintenance of physiological levels of intracellular and extracellular calcium is essential for life. Increased intracellular calcium levels are involved in cell death (apoptosis and necrosis) and are associated with positive responses in the Comet assay in vitro. In addition, high calcium and vitamin D intakes were reported to induce apoptosis in adipose tissue in obese mice and to increase DNA-migration in the Comet assay. To investigate increased serum concentration of calcium as a potential confounding factor in the regulatory Comet assay in vivo, we induced mild hypercalcemia in male Wistar rats by 3-day continuous intravenous infusion of calcium gluconate and performed the Comet assay in the liver in line with regulatory guidelines.The results of the study showed that mild increases in serum calcium concentration (up to 1.4 times above the concurrent control) and increased urinary calcium concentration (up to 27.8 times above the concurrent control) results in clinical signs like mild tremor, faster respiration rate and decreased activity in a few animals. However, under the conditions of the study, no increase in the %Tail DNA in the Comet assay and no indication of liver damage as determined by histopathological means were observed. Thus, mild increases in plasma calcium did not lead to positive results in a genotoxicity assessment by the Comet assay in the rat liver. This result is important as it confirms the reliability of this assay for regulatory evaluation of safety.

Citrate shows protective effects on cardiovascular and renal function in ischemia-induced acute kidney injury

BackgroundIschemia and reperfusion (I/R) is one of the major causes of acute kidney injury (AKI). Citrate reduces hypoxia-induced mitochondrial energetic deficits in isolated proximal tubules. Moreover, citrate anticoagulation is now frequently used in renal replacement therapy. In the present study a rat model of I/R-induced AKI was utilized to examine renal protection by citrate in vivo.MethodsAKI was induced by bilateral renal clamping (40 min) followed by reperfusion (3 h). Citrate was infused at three different concentrations (0.3 mmol/kg/h; 0.6 mmol/kg/h and 1.0 mmol/kg/h) continuously for 60 min before and 45 min after ischemia. Plasma calcium concentrations were kept stable by infusion of calcium gluconate. The effect of citrate was evaluated by biomonitoring, blood and plasma parameters, histopathology and tissue ATP content.ResultsIn comparison to the normoxic control group bilateral renal ischemia led to an increase of creatinine and lactate dehydrogenase activity and a decrease in tissue ATP content and was accompanied by a drop in mean arterial blood pressure. Infusion of 1.0 mmol/kg/h citrate led to lower creatinine and reduced LDH activity compared to the I/R control group and a tendency for higher tissue ATP content. Pre-ischemic infusion of 1.0 mmol/kg/h citrate stabilized blood pressure during ischemia.ConclusionsCitrate has a protective effect during I/R-induced AKI, possibly by limiting the mitochondrial deficit as well as by beneficial cardiovascular effects. This strengthens the rationale of using citrate in continuous renal replacement therapy and encourages consideration of citrate infusion as a therapeutic treatment for AKI in humans.

Improvement of Fabry disease pain with calcium gluconate infusions given at time of agalsidase beta therapy

Fabry disease (FD) is a lysosomal storage disorder (LSD) that involves the cochleovestibular system. Tinnitus and progressive sensorineural hearing loss are frequent complains. A stabilization of hearing function has been reported with enzyme replacement therapy (ERT). This study aims to characterize the inner ear involvement, identify factors associated to hearing loss and evaluate the effect of ERT on the hearing function of FD patients.We reviewed the clinical records of patients with confirmed diagnosis of FD followed in a Reference Centre on LSD in the North of Portugal.We included a total of 122 patients with a mean age of 47.1 ± 17.6 years and 48.3% males. Hearing loss was reported by 26.2% of the patients and 23.0% mentioned tinnitus. Pure tone audiometry revealed sensorineural hearing loss in 36.9% of the cases. FD patients presented worse age-adjusted hearing thresholds in all analysed frequencies compared to the normal population (p = .001). Patients with hearing loss presented a significantly higher value of microalbuminuria (p = .001) and a higher frequency of acroparesthesias (p = .032). Patients presented a comparable hearing level one year after starting ERT (p = .384).In FD, hearing loss is common and age-matched hearing thresholds by frequency are worse than in the general population. Hearing loss was associated to the presence of acroparesthesias and higher values of microalbuminuria. Hearing loss stabilized in patients under ERT. A careful cochleo-vestibular evaluation should be part of the clinical assessment of FD.

Hypocalcaemia, Hypoglycaemia, Macrosomia and Congenital Cryptorchidism in a Male Offspring of a Mother with Overweight and Gestational Diabetes Mellitus

AbstractThis paper reports a case of a male infant born to a 32-year-old multiparous mother with overweight (BMI 28.5kg/m2) and gestational diabetes mellitus (GDM). The mother had fasting hyperglycaemia (range 5.7- 6.0mmol/L) noted at 24 weeks of pregnancy and was managed with diet alone. There is no family history of diabetes mellitus and the mother did not have pre-eclampsia. Physical examination of the infant revealed macrosomia (birthweight, 4600g) and bilateral congenital cryptorchidism. The baby suffered severe hypoglycaemia (blood glucose 1.7mmol/L) and hypocalcaemia (total serum calcium 1.03mmol/L), manifesting with seizures. He was successfully managed with 10% dextrose water and calcium gluconate infusion, using standard protocol. His karyotype is 46 XY. The patient was discharged from admission at the age of 10 days and was referred to the paediatric endocrinologist at the tertiary hospital. By 8 weeks of age, the right testis was noticed to have descended into the right scrotum. At the age of 3 months, the left testis was still not palpable either in the inguinal canal or the scrotal sac. The patient was lost to follow up. Conclusion: Diet-treated maternal overweight in association with GDM could potentially increase the risk for hypocalcaemia, hypoglycaemia, macrosomia and congenital cryptorchidism in the offspring, highlighting the need for physicians to assess for the presence of these morbidities in such infants.

Near-fatal cardiac arrhythmia during intravenous calcium administration for symptomatic neonatal hypocalcemia: A case report

A seven-day-old male neonate presented with symptomatic hypocalcemia in the form of generalized seizure activity for three minutes. He arrived at the pediatric emergency department in a postictal state. His clinical examination was unremarkable, but his initial laboratory evaluation revealed marked hypocalcemia and hypomagnesemia. The patient received intravenous boluses of calcium gluconate for correction. The patient had bradycardia during the first calcium gluconate infusion, and on the second infusion, he developed frequent premature ventricular contractions, which progressed into polymorphic ventricular tachycardia. Arrhythmia reverted to sinus rhythm after discontinuation of the calcium gluconate infusion without the need for chemical/electrical cardioversion. Subsequently, two extra doses of intravenous calcium gluconate for persistent hypocalcemia were administered safely. The patient was discharged home successfully in a good general condition after stabilization. The emergence of bradycardia during calcium gluconate infusion should be considered a red flag since it can trigger serious cardiac arrhythmia, especially in the presence of electrolyte abnormalities such as hypocalcemia and hypomagnesemia. We report this case to stress the need for continuous cardiac monitoring of children on calcium gluconate infusion even if proper dose, dilution, and rate of infusion are used, as serious cardiac arrhythmia can be unpredictable and may develop at any time.