Acute hypernatremia and hypocalcemia after oral sodium phosphate administration to a dog.

A 15-year-old male neutered mixed breed dog weighing 28 kg presented to a referral center after developing severe tremors and altered mentation. There was hypocalcemia and hypernatremia after oral administration of sodium phosphate as a bowel cleansing agent in preparation for colonoscopy. The dog was treated intravenously with low sodium fluids and calcium gluconate. Neurologic status and electrolyte derangements normalized over the next 12 hours. Oral administration of sodium phosphate appeared to cause clinical electrolyte derangements in this dog.

Central Diabetes Insipidus in the Background of Lithium Use: Consider Central Causes Despite Nephrogenic as the Most Common.

BACKGROUND Nephrogenic diabetes insipidus is a well-known adverse effect of lithium use. Albeit rare, there have also been documented cases of central diabetes insipidus (CDI) associated with lithium use. CASE REPORT A 31-year-old woman with a past medical history of bipolar disorder, managed with lithium 300 mg by mouth every day for 3 years, was assessed for a 1-year history of polyuria with accompanying polydipsia. During her initial hospital stay, her estimated urine output was more than 4 L per day. Initial labs showed elevated serum sodium (149 mmol/L; reference range 135-145), elevated serum osmolality (304 mOsm/kg; reference range 275-295), urine osmolality of 99 mOsm/kg (reference range 50-1200), and urine specific gravity (1.005; reference range 1.005-1.030). Lithium was at a subtherapeutic level of 0.05 mEq/L (reference range 0.6-1.2). Magnetic resonance imaging of the brain revealed no abnormalities of the pituitary gland. Two different occasions of desmopressin administration resulted in >50% increase in urine osmolality, confirming the diagnosis of CDI. Common causes of CDI, including trauma, tumors, and familial CDI, were ruled out and chronic lithium use was determined as the most probable cause for the patient's CDI. CONCLUSIONS CDI in the background of chronic lithium use is rarely reported. We present this case to consider CDI as a differential diagnosis when evaluating polyuria and hypernatremia in patients with long-term lithium use. These presentations warrant the consideration of both types of diabetes insipidus in the differential diagnoses.

Central diabetes insipidus related to anti-programmed cell-death 1 protein active immunotherapy.

Cancer immunotherapy is a breakthrough strategy entwined with toxicity. Immune-related hypophysitis is conventionally considered distinctive of cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors. Immune-related central diabetes insipidus (CDI) is exceptional. CDI rarely manifests as hypernatremia, which is almost always euvolemic. We report a 71-years-old male patient with advanced lung cancer who experienced severe chronic hypernatremia presented as alterations in mental status five months after initiation of treatment with the anti-PD-1 checkpoint inhibitor nivolumab. Combination of persistenthypernatremia, polyuria, high plasma osmolality and hyposthenuria raised suspicion of diabetes insipidus, prompting measurement of serum concentration of arginine vasopressin(AVP). The inappropriately undetectable serum levels of AVP confirmed central diabetes insipidus (CDI). Nivolumab-related hypophysitis was recognized as possible cause of CDI. Further hormonal assessment excluded any endocrinopathy indicating disorder of posterior pituitary. Pituitary MRI was normal with persistence of hyperintensity of posterior pituitary on T1-weighted images (bright spot). The patient was scheduled to receive 1-deamino-8-D-arginine vasopressin (DDAVP), but he died suddenly due to cardiac arrest before initiation of treatment. Our report describes the first case of nivolumab related CDI, building on existing literature through: (I) underscoring hypovolemic hypernatremia as CDI manifestation; (ii) bringing into spotlight the rare anti-PD-1 treatment related hypophysitis; (iii) enriching the limited evidence on immune-related CDI. Increased awareness of nivolumab related CDI will enable prompt recognition and therapeutic intervention.

Hypernatremia-induced Neurologic Complications After Hepatic Hydatid Cyst Surgery: Pretreat to Prevent.

INTRODUCTION: Surgery is effective treatment for echinococcosis; however, there is a risk of hypertonic saline resorption and acute hypernatremia. AIM: We report two cases of severe hypernatremia following hydatid cyst removal. CASE REPORTS: A 17-year-old girl underwent surgical removal of hepatic hydatid cyst. Following the surgery, she developed seizures evolving to status epilepticus, and was sedated and mechanically ventilated. Blood chemistry showed hypernatremia. Fluid resuscitation with 5% dextrose infusions was started in combination with furosemide. Electrolytes were monitored frequently until plasma sodium levels normalized, 30 hours later. The patient was seizure free 48 hours later. The second patient is a 70-year-old man with hepatic hydatid cyst. After the surgery he became somnolent and confused due to severe hypernatremia. Intravenous administration of five percentage dextrose was initiated and high doses of furosemide. Sodium level normalized within 38 hours. The patient's mental status improved. CONCLUSION: A hospital protocol was established aiming to prevent hypernatremia and neurological complications.

The association of hypernatremia and hypertonic saline irrigation in hepatic hydatid cysts: A case report and retrospective study.

RATIONALE: Hypernatremia is a rare but fatal complication of hypertonic saline (HS) irrigation in hepatic hydatid disease. It needs careful monitoring and treatment. PATIENT CONCERNS: A 28-year-old woman with hepatic hydatid cysts who received operation treatment developed electrolyte disturbances. We also conducted a retrospective study about influence of HS application on electrolytes in patients with hepatic hydatid disease receiving surgery. DIAGNOSES: Hypernatremia, developed after HS irrigation. INTERVENTIONS: Normal saline, 5% dextrose and other supportive treatment were administered. In the retrospective study, a comparison of electrolyte and glucose fluctuation was made among different HS application groups. OUTCOMES: The patient developed hypernatremia after irrigation with HS and died from severe complications. Although some cases of complications are found, no significant relationship between HS irrigation and hypernatremia was reported according to the retrospective study. LESSONS: Hypernatremia after HS irrigation remains rare but might cause severe complications. Monitoring and appropriate treatment are needed to improve prognosis.

Comparison of the incidences of hyponatremia in adult postoperative critically ill patients receiving intravenous maintenance fluids with 140 mmol/L or 35 mmol/L of sodium: retrospective before/after observational study.

PURPOSE: The purpose of this study was to compare the incidences of hyponatremia in adult postoperative critically ill patients receiving isotonic and hypotonic maintenance fluids. METHODS: In this single-center retrospective before/after observational study, we included patients who had undergone an elective operation for esophageal cancer or for head and neck cancer and who received postoperative intensive care for >48 h from August 2014 to July 2016. In those patients, sodium-poor solution (35 mmol/L of sodium; Na35) had been administered as maintenance fluid until July 2015. From August 2015, the protocol for postoperative maintenance fluid was revised to the use of isotonic fluid (140 mmol/L of sodium; Na140). The primary outcome was the incidence of hyponatremia (<135 mmol/L) until the morning of postoperative day (POD) 2. RESULTS: We included 179 patients (Na35: 87 patients, Na140: 92 patients) in the current study. The mean volume of fluid received from ICU admission to POD 2 was not significantly different between the two groups (3291 vs 3337 mL, p = 0.84). The incidence of postoperative hyponatremia was 16.3% (15/92) in the Na140 cohort, which was significantly lower than that of 52.9% (46/87) in the Na35 group (odds ratio = 0.17, 95% confidence interval 0.09-0.35, p < 0.001]. The incidences of hypernatremia, defined as serum sodium concentration >145 mmol/L, were not significantly different between the two groups. CONCLUSION: In this study, the use of intravenous maintenance fluid with 35 mmol/L of sodium was significantly associated with an increased risk of hyponatremia compared to that with 140 mmol/L of sodium in adult postoperative critically ill patients.

Does 2 L Polyethylene Glycol Plus Ascorbic Acid Increase the Risk of Renal Impairment Compared to 4 L Polyethylene Glycol?

BACKGROUND: The use of polyethylene glycol (PEG)-based solutions is the gold standard for bowel preparation. However, PEG use might be associated with the risk of acute kidney injury. AIMS: We aimed to compare the safety of 2 L PEG plus ascorbic acid (AA) versus 4 L PEG. METHODS: Health examinees that underwent colonoscopy and blood tests on the same day at our center were included in this retrospective study. All subjects were prescribed either 2 L PEG plus AA or 4 L PEG for the bowel preparation prior to the colonoscopy. The incidences of electrolyte imbalance and renal impairment after colonic preparation were investigated. Renal impairment was determined if the subject's estimated glomerular filtration rate was measured less than 60 mL/min/1.73 m2. RESULTS: Of the 29,789 cases, 14,790 received 2 L PEG plus AA (group A) and 14,999 received 4 L PEG (group B) for colonic preparation. Renal impairment occurred more commonly in group A (n = 467, 3.2 %) than in group B (n = 189, 1.3 %). Electrolyte changes such as hypernatremia and hyperkalemia were more common in group A than group B, whereas hyponatremia, hypokalemia, and hypophosphatemia were more common in group B than group A. Old age, male sex, and the use of 2 L PEG plus AA were independent risk factors for renal impairment. CONCLUSIONS: The evidence strongly suggests that acute kidney injury is more likely to occur when 2 L PEG plus AA is used for the bowel preparation than when 4 L PEG is used. CLINICAL TRIAL REGISTRATION NUMBER: KCT0001703.

Plasma exchange successfully treats central pontine myelinolysis after acute hypernatremia from intravenous sodium bicarbonate therapy.

BACKGROUND: Osmotic demyelination syndrome (ODS) primarily occurs after rapid correction of severe hyponatremia. There are no proven effective therapies for ODS, but we describe the first case showing the successful treatment of central pontine myelinolysis (CPM) by plasma exchange, which occurred after rapid development of hypernatremia from intravenous sodium bicarbonate therapy. CASE PRESENTATION: A 40-year-old woman presented with general weakness, hypokalemia, and metabolic acidosis. The patient was treated with oral and intravenous potassium chloride, along with intravenous sodium bicarbonate. Although her bicarbonate deficit was 365 mEq, we treated her with an overdose of intravenous sodium bicarbonate, 480 mEq for 24 hours, due to the severity of her acidemia and her altered mental status. The next day, she developed hypernatremia with serum sodium levels rising from 142.8 mEq/L to 172.8 mEq/L. Six days after developing hypernatremia, she exhibited tetraparesis, drooling, difficulty swallowing, and dysarthria, and a brain MRI revealed high signal intensity in the central pons with sparing of the peripheral portion, suggesting CPM. We diagnosed her with CPM associated with the rapid development of hypernatremia after intravenous sodium bicarbonate therapy and treated her with plasma exchange. After two consecutive plasma exchange sessions, her neurologic symptoms were markedly improved except for mild diplopia. After the plasma exchange sessions, we examined the patient to determine the reason for her symptoms upon presentation to the hospital. She had normal anion gap metabolic acidosis, low blood bicarbonate levels, a urine pH of 6.5, and a calyceal stone in her left kidney. We performed a sodium bicarbonate loading test and diagnosed distal renal tubular acidosis (RTA). We also found that she had Sjögren's syndrome after a positive screen for anti-Lo, anti-Ra, and after the results of Schirmer's test and a lower lip biopsy. She was discharged and treated as an outpatient with oral sodium bicarbonate and potassium chloride. CONCLUSION: This case indicates that serum sodium concentrations should be carefully monitored in patients with distal RTA receiving intravenous sodium bicarbonate therapy. We should keep in mind that acute hypernatremia and CPM can be associated with intravenous sodium bicarbonate therapy, and that CPM due to acute hypernatremia may be effectively treated with plasma exchange.

Complications associated with prolonged hypertonic saline therapy in children with elevated intracranial pressure.

OBJECTIVES: Safe upper limits for therapeutic hypernatremia in the treatment of intracranial hypertension have not been well established. We investigated complications associated with hypernatremia in children who were treated with prolonged infusions of hypertonic saline. DESIGN: Retrospective chart analysis. SETTING: PICU in university-affiliated children's hospital. PATIENTS: All children from 2004 to 2009 requiring intracranial pressure monitoring (external ventricular drain or fiberoptic intraparenchymal monitor) for at least 4 days who were treated with hypertonic saline infusion for elevated intracranial pressure and did not meet exclusion criteria. INTERVENTION: Continuous hypertonic saline infusion on a sliding scale was used to achieve target sodium levels that would keep intracranial pressure less than 20 mm Hg once the conventional therapies failed. MEASUREMENTS AND MAIN RESULTS: Eighty-eight children met inclusion criteria. Etiologies of elevated intracranial pressure included trauma (n = 48), ischemic or hemorrhagic stroke (n = 20), infection (n = 8), acute disseminated encephalomyelitis (n = 5), neoplasm (n = 2), and others (n = 5). The mean peak serum sodium was 171.3 mEq/L (range, 150-202). The mean Glasgow Outcome Score was 2.8 (± 1.1) at time of discharge from the hospital. Overall mortality was 15.9%. Children with sustained (> 72 hr) serum sodium levels above 170 mEq/L had a significantly higher occurrence of thrombocytopenia (p < 0.001), renal failure (p < 0.001), neutropenia (p = 0.006), and acute respiratory distress syndrome (p = 0.029) after controlling for variables of age, gender, Pediatric Risk of Mortality score, duration of barbiturate-induced coma, duration of intracranial pressure monitoring, vasopressor requirements, and underlying pathology. Children with sustained serum sodium levels greater than 165 mEq/L had a significantly higher prevalence of anemia (p < 0.001). CONCLUSIONS: Children treated by continuous hypertonic saline infusion for intracranial hypertension whose serum sodium levels exceeded certain thresholds experienced significantly more events of acute renal failure, thrombocytopenia, neutropenia, anemia, and acute respiratory distress syndrome than those whose sodium level was maintained below these thresholds.

Acute hypernatremia exerts an inhibitory oxytocinergic tone that is associated with anxiolytic mood in male rats.

Anxiety disorders are the most common psychiatric illnesses and are associated with heightened stress responsiveness. The neuropeptide oxytocin (OT) has garnered significant attention for its potential as a treatment for anxiety disorders; however, the mechanism mediating its effects on stress responses and anxiety is not well understood. Here we used acute hypernatremia, a stimulus that elevates brain levels of OT, to discern the central oxytocinergic pathways mediating stress responsiveness and anxiety-like behavior. Rats were rendered hypernatremic by acute administration of 2.0 M NaCl and had increased plasma sodium concentration, plasma osmolality, and Fos induction in OT-containing neurons relative to 0.15 M NaCl-treated controls. Acute hypernatremia decreased restraint-induced elevations in corticosterone and created an inhibitory oxytocinergic tone on parvocellular neurosecretory neurons within the paraventricular nucleus of the hypothalamus. In contrast, evaluation of Fos immunohistochemistry determined that acute hypernatremia followed by restraint increased neuronal activation in brain regions receiving OT afferents that are also implicated in the expression of anxiety-like behavior. To determine whether these effects were predictive of altered anxiety-like behavior, rats were subjected to acute hypernatremia and then tested in the elevated plus maze. Relative to controls given 0.15 M NaCl, rats given 2.0 M NaCl spent more time in the open arms of the elevated plus maze, suggesting that acute hypernatremia is anxiolytic. Collectively the results suggest that acute elevations in plasma sodium concentration increase central levels of OT, which decreases anxiety by altering neuronal activity in hypothalamic and limbic nuclei.

Induced and sustained hypernatremia for the prevention and treatment of cerebral edema following brain injury.

Cerebral edema develops in response to and as a result of a variety of neurologic insults such as ischemic stroke, traumatic brain injury, and tumor. It deforms brain tissue, resulting in localized mass effect and increase in intracranial pressure (ICP) that are associated with a high rate of morbidity and mortality. When administered in bolus form, hyperosmolar agents such as mannitol and hypertonic saline have been shown to reduce total brain water content and decrease ICP, and are currently the mainstays of pharmacological treatment. However, surprisingly, little is known about the increasingly common clinical practice of inducing a state of sustained hypernatremia. Herein, we review the available studies employing sustained hyperosmolar therapy to induce hypernatremia for the prevention and/or treatment of cerebral edema. Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm.

Comparison of oral and intravenous Ibuprofen for medical closure of patent ductus arteriosus: which one is better?

OBJECTIVE: Intravenous ibuprofen is an expensive drug that is being used currently for treating and preventing patent ductus arteriosus. Although oral ibuprofen is much cheaper, there is limited data published about its safety and efficacy. The aim of this study was to compare two forms of ibuprofen in terms of safety and efficacy in closure of patent ductus arteriosus. DESIGN: This is a single-center retrospective study. SETTING: Data were collected from patients' files of preterm infants who were hospitalized at the Neonatal Intensive Care Unit of Dr. Behcet Uz Children's Hospital between April 2009 and June 2010. PATIENTS: Six hundred sixty infants were evaluated by echocardiography between 24 and 48 postnatal hours. Clinically and hemodynamically significant ductus arteriosus was defined in 66 infants with gestational age less than 32 weeks and birth weight less than 1500 g. INTERVENTIONS: Oral or intravenous ibuprofen (loading dose: 10 mg/kg on day 1, followed by maintenance dose: 5 mg/kg on days 2 and 3) was administered. OUTCOME MEASURES: Treatment success was defined as a completely closed duct without reopening on follow-up. Drug-associated renal, gastrointestinal, cerebral, hematological, and metabolic side effects were monitored and compared between treatment groups. RESULTS: Ductal closure rates were 100% and 97.6%, respectively, in the oral and intravenous groups. Hypernatremia was the remarkable side effect in the intravenous group, whereas bronchopulmonary dysplasia and septicemia were prominent in the oral group. No statistically significant difference could be demonstrated between the groups in terms of mortality rates. CONCLUSION: Oral ibuprofen therapy is as efficacious as intravenous ibuprofen with some concerns about increased sepsis and bronchopulmonary dysplasia incidence. However, comprehensive and large-scale pharmacokinetic studies are required in order to prove this efficacy. On the other hand, intravenous ibuprofen still remains to be the drug of choice for patent ductus arteriosus but only with meticulous control of serum sodium levels in smaller infants.

Severe hypernatraemia associated with growth hormone replacement therapy in a patient with septo-optic dysplasia.

BACKGROUND: The anti-natriuretic properties of growth hormone (GH) are well established. Growth hormone deficiency (GHD) results in salt and water depletion and studies confirm that replacement leads to sodium and vasopressin-mediated water retention in patients with intact posterior pituitary function. METHODS: We report the case of a 20-year-old male patient with septo-optic dysplasia, fixed cranial diabetes insipidus (DI) and an abnormal thirst threshold. With careful parental support, his sodium levels remained stable for many years on a fixed dose of DDAVP and a supervised fluid intake of 2.5 l/day. Several years after the original diagnosis, he was found to be ACTH deficient and following commencement of hydrocortisone replacement therapy became hypernatraemic. A new sodium homoeostasis was established with a higher dose of DDAVP. Subsequently, he developed symptoms typical of GHD and, after biochemical confirmation, GH replacement was commenced. RESULTS: There was an immediate clinical improvement (increased alertness, improved concentration) but severe hypernatraemia developed (peak 169 mmol/l) necessitating revision of his desmopressin and fluid intake regimen. CONCLUSION: Most GHD patients have intact posterior pituitary function. This case report highlights the powerful anti-natriuretic properties of GH. Endocrine physicians should be alert to this in patients with fixed DI and an abnormal thirst threshold.

[Postoperative hypernatremia in liver hydatid disease: a case report]. / Karaciger Kist Hidatiginde Postoperatif Hipernatremi: Bir Olgu Sunumu.

Hydatid cyst, frequent in sheep raising countries, is a parasitic disease caused by a cestode, Echinococcus granulosus, and is spread to man by dog feces. A hydatid cyst, 7x8 cm in diameter, located on the dome of the liver of a 48 year old male patient was removed by thoracotomy. During the surgery, some hypertonic saline solution absorbed sponges were applied to the operation site. The same solution was used inside the cyst for scolocidal effect and the intraabdominal cavity was washed with the same solution. During the postoperative period, following extubation, a generalized convulsion developed. A serum sample of the patient was sent to the laboratory for testing of the serum sodium concentration. It was 185 mEq/L. The aim of this study was the consideration of hypernatremia and related neurologic signs depending upon the use of hypertonic saline solutions in hydatid cyst surgery for scolocidal effects. Because general anesthesia conceals neurological findings of hypernatremia, the serum sodium concentration should be followed carefully during surgery.