Successful Treatment of Lithium-Induced Nephrogenic Diabetes Insipidus with Celecoxib: A Promising Therapeutic Option.

BACKGROUND Nephrogenic diabetic insipidus (NDI) poses a challenge in clinical management, particularly when associated with lithium ingestion. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of numerous diseases worldwide, including NDI. However, many studies have reported the diverse adverse effects of long-term use of non-selective NSAIDs. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a better drug to relieve pain and inflammation in terms of long-term safety and efficacy than non-selective NSAIDs. Nevertheless, there are few reports describing the effectiveness of celecoxib in treating NDI. CASE REPORT We report a case of a 46-year-old woman with schizophrenia who presented with severe hypernatremia and refractory polyuria due to lithium-induced NDI. Cessation of lithium ingestion and traditional treatments, including trichlormethiazide and desmopressin, yielded minimal improvement in her hypernatremia and polyuria. Her sodium level needed to be strictly controlled with the infusion of dextrose 5% in water. Given the safety of celecoxib, we decided to initiate celecoxib as the treatment of lithium-induced NDI instead of indomethacin. Notably, the introduction of celecoxib led to a substantial and sustained amelioration of polyuria and hypernatremia without any celecoxib-associated adverse effects. Even after transfer to another hospital, stability in serum sodium levels persisted with celecoxib. CONCLUSIONS We presented a case of lithium-induced NDI successfully treated with celecoxib, a selective COX-2 inhibitor. To the best of our knowledge, this is the first reported case of successful treatment of lithium-induced NDI with celecoxib, and suggests celecoxib is a viable therapeutic option warranting further exploration. Physicians should consider its use when faced with the challenging management of lithium-induced NDI.

Persistent hypernatremia secondary to adipsic central diabetes insipidus in a patient with herpes-induced meningoencephalitis and COVID-19 infection: a case report.

Central diabetes insipidus (CDI) typically manifests as a polyuria-polydipsia syndrome, in which normonatremia is generally maintained through the polydipsia. A 53-year-old woman presented with diabetic ketosis and hyperosmolar hyperglycemic syndrome. Her medical history included herpes meningoencephalitis, which was associated with confusion and amnesia. On physical examination, she was apyretic, confused, and had signs of extracellular dehydration. Her capillary glucose concentration was high and her urine was positive for ketones. Laboratory investigations revealed severe hyperglycemia, hypernatremia (plasma hyperosmolarity of 393.6 mOsm/L), and mild acute renal failure. In addition, she had a paucisymptomatic COVID-19 infection. Intravenous rehydration with isotonic saline solution and insulin therapy were effective at controlling the ketosis and ameliorating the hyperglycemia, but failed to normalize the hypernatremia and hyperosmolarity. She was not thirsty and had a urine output of 1 L/day, with urinary hypotonicity. Desmopressin administration reduced the hypernatremia and hyperosmolarity to within their normal ranges, and the patient's urinary osmolarity increased to 743 mOsm/L. Therefore, adipsic CDI was diagnosed. Endocrine investigations revealed isolated central hypothyroidism. The results of pituitary magnetic resonance imaging were normal. Thus, patients with impaired thirst may have an atypical presentation of CDI. In addition, the diagnosis of adipsic CDI is particularly challenging.

Serum sodium level fluctuations following the resection of childhood-onset craniopharyngioma.

BACKGROUND: Craniopharyngiomas are low-grade malignancies (WHO I) in the sellar region. Most cases of childhood-onset craniopharyngioma are adamantinomatous craniopharyngioma, and neurosurgery is the treatment of choice. Affected patients have postoperative complications, including water and electrolyte disturbances, because these malignancies develop near the hypothalamus and pituitary gland. Determining postoperative serum sodium fluctuation patterns in these patients can reduce postoperative mortality and improve prognosis. OBJECTIVE: To measure changes in serum sodium levels in pediatric patients who underwent craniopharyngioma surgery and identify influencing factors. METHODS: This retrospective study measured the serum sodium levels of 202 patients aged 0-18 years who underwent craniopharyngioma resection in Beijing Tiantan Hospital and Beijing Children's Hospital and identified predictors of severe hyponatremia and hypernatremia. RESULTS: The mean age of the cohort was 8.35 ± 4.35 years. The prevalence of hypernatremia, hyponatremia, and their severe forms (serum Na+  > 150 mmol/L and serum Na+  < 130 mmol/L) within 14 days after surgery was 66.3%, 72.8%, 37.1%, and 40.6%, respectively. The mean postoperative serum sodium level showed a triphasic pattern, characterized by two peaks separated by a nadir. Sodium levels peaked on days 2 (143.6 ± 7.6 mmol/L) and 14 (143.2 ± 6.7 mmol/L) and reached their lowest on day 6 (135.5 ± 7.5 mmol/L). A total of 31 (15.3%) patients met the diagnostic threshold for hyponatremia and hypernatremia of the triphase response, whereas 116 (57.4%) patients presented this pattern, regardless of met the diagnostic criteria or not. The prevalence of severe hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach. CONCLUSIONS: Serum sodium levels after craniopharyngioma resection in children showed a triphasic pattern in most cases. The risk of postoperative hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach.

Plasma sodium during the recovery of renal function in critically ill adult patients: Multicenter prospective cohort study.

BACKGROUND: Sodium increases during acute kidney injury (AKI) recovery. Both hypernatremia and positive fluid balances are associated with increased mortality. We aimed to evaluate the association between daily fluid balance and daily plasma sodium during the recovery from AKI among critical patients. METHODS: Adult patients with AKI were enrolled in four ICUs and followed up for four days or until ICU discharge or hemodialysis initiation. Day zero was the peak day of creatinine. The primary outcome was daily plasma sodium; the main exposure was daily fluid balance. RESULTS: 93 patients were included. The median age was 66 years; 68% were male. Plasma sodium increased in 79 patients (85%), and 52% presented hypernatremia. We found no effect of daily fluid balance on plasma sodium (ß -0.26, IC95%: -0.63-0.13; p = 0.19). A higher total sodium variation was observed in patients with lower initial plasma sodium (ß -0.40, IC95%: -0.53 to -0.27; p < 0.01), higher initial urea (ß 0.07, IC95%: 0.04-0.01; p < 0.01), and higher net sodium balance (ß 0.002, IC95%: 0.0001-0.01; p = 0.05). CONCLUSIONS: The increase in plasma sodium is common during AKI recovery and can only partially be attributed to the water and electrolyte balances. The incidence of hypernatremia in this population of patients is higher than in the general critically ill patient population.

Initial dysnatremia and clinical outcomes in pediatric traumatic brain injury: a multicenter observational study.

PURPOSE: We aimed to investigate the association between initial dysnatremia (hyponatremia and hypernatremia) and in-hospital mortality, as well as between initial dysnatremia and functional outcomes, among children with traumatic brain injury (TBI). METHOD: We performed a multicenter observational study among 26 pediatric intensive care units from January 2014 to August 2022. We recruited children with TBI under 18 years of age who presented to participating sites within 24 h of injury. We compared demographics and clinical characteristics between children with initial hyponatremia and eu-natremia and between those with initial hypernatremia and eu-natremia. We defined poor functional outcome as a discharge Pediatric Cerebral Performance Category (PCPC) score of moderate, severe disability, coma, and death, or an increase of at least 2 categories from baseline. We performed multivariable logistic regression for mortality and poor PCPC outcome. RESULTS: Among 648 children, 84 (13.0%) and 42 (6.5%) presented with hyponatremia and hypernatremia, respectively. We observed fewer 14-day ventilation-free days between those with initial hyponatremia [7.0 (interquartile range (IQR) = 0.0-11.0)] and initial hypernatremia [0.0 (IQR = 0.0-10.0)], compared to eu-natremia [9.0 (IQR = 4.0-12.0); p = 0.006 and p < 0.001]. We observed fewer 14-day ICU-free days between those with initial hyponatremia [3.0 (IQR = 0.0-9.0)] and initial hypernatremia [0.0 (IQR = 0.0-3.0)], compared to eu-natremia [7.0 (IQR = 0.0-11.0); p = 0.006 and p < 0.001]. After adjusting for age, severity, and sex, presenting hyponatremia was associated with in-hospital mortality [adjusted odds ratio (aOR) = 2.47, 95% confidence interval (CI) = 1.31-4.66, p = 0.005] and poor outcome (aOR = 1.67, 95% CI = 1.01-2.76, p = 0.045). After adjustment, initial hypernatremia was associated with mortality (aOR = 5.91, 95% CI = 2.85-12.25, p < 0.001) and poor outcome (aOR = 3.00, 95% CI = 1.50-5.98, p = 0.002). CONCLUSION: Among children with TBI, presenting dysnatremia was associated with in-hospital mortality and poor functional outcome, particularly hypernatremia. Future research should investigate longitudinal sodium measurements in pediatric TBI and their association with clinical outcomes.

Severe Burn Injuries - The Day the Sodium Starts Rising.

BACKGROUND/AIM: The current study was designed to evaluate the etiologies of hypernatremic episodes in patients with severe burn injuries in comparison to critically ill non-burn patients. PATIENTS AND METHODS: The retrospective data acquisition was limited to the first 14 days and to patients with at least 20% total body surface area (TBSA) 2nd degree burn injuries or more than 10% TBSA when including areas of 3rd degree burn injuries. The results were compared to the results of a previously published study that analyzed the risk factors for hypernatremia in 390 non-burn intensive care unit patients. RESULTS: In total, 120 patients with a total of 50 hypernatremic episodes were included. Compared to non-burn injury patients, no significant differences were detectable except for a lower rate of hypokalemia and a higher rate of mechanical ventilation. The main trigger for hypernatremic episodes was the loss of free water, while 24% of the hypernatremic episodes seemed to be at least partly triggered by a surplus sodium influx. Patients with hypernatremic episodes had a significantly higher mortality rate. However, in none of the cases was hypernatremia the decisive cause of death. CONCLUSION: Besides the unique phenomenon of high volume internal and external volume shifts, the overall risk factors and etiologies of hypernatremia in patients with severe burn injury do not seem to significantly differ from other ICU patient collectives. Remarkably, a surplus of sodium influx and therefore a modifiable factor besides the specific burn injury volume resuscitation had an impact on the hypernatremic episodes in 24% of cases.

Severe Hypernatremia During Hydatid Cyst Surgery: An Anusual Cause Of Acute Abdomen.

Treatment of liver hydatid cysts is still in most cases surgical. To avoid the recurrence of hydatid cysts injection of scolicidal products inside the cystic cavity is an important step in the surgical procedure. Many scolicidal solutions are used. Hypertonic Saline Solution (HSS) is widely used by surgeons; however, there is a risk of hypertonic saline resorption and acute hypernatremia. Iatrogenic hypernatremia can be life-threatening. We report three cases of hypernatremia secondary to HSS injection for hydatid cyst disease treatment. The objective of this study was to discuss the clinical features, and treatment of this rare complication.

Sodium and Its Impact on Outcome After Aneurysmal Subarachnoid Hemorrhage in Patients With and Without Delayed Cerebral Ischemia.

OBJECTIVES: To perform a detailed examination of sodium levels, hyponatremia and sodium fluctuations, and their association with delayed cerebral ischemia (DCI) and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). DESIGN: An observational cohort study from a prospective SAH Registry. SETTING: Tertiary referral center focused on SAH treatment in the Amsterdam metropolitan area. PATIENTS: A total of 964 adult patients with confirmed aSAH were included between 2011 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 277 (29%) developed DCI. Hyponatremia occurred significantly more often in DCI patients compared with no-DCI patients (77% vs. 48%). Sodium levels, hyponatremia, hypernatremia, and sodium fluctuations did not predict DCI. However, higher sodium levels were significantly associated with poor outcome in DCI patients (DCI onset -7, DCI +0, +1, +2, +4, +5, +8, +9 d), and in no-DCI patients (postbleed day 6-10 and 12-14). Also, hypernatremia and greater sodium fluctuations were significantly associated with poor outcome in both DCI and no-DCI patients. CONCLUSIONS: Sodium levels, hyponatremia, and sodium fluctuations were not associated with the occurrence of DCI. However, higher sodium levels, hypernatremia, and greater sodium fluctuations were associated with poor outcome after aSAH irrespective of the presence of DCI. Therefore, sodium levels, even with mild changes in levels, warrant close attention.

[Dysnatremias - concepts and clinical work-up]. / Dysnatriämien ­ Konzepte und klinische Aufarbeitung.

Osmotic gradients over cell membranes lead to water movement into or out of cells. An intact osmoregulation prevents osmotic gradients, thereby protecting cells from swelling or shrinking. Na+ is the major cation in the extracellular fluid (ECF) and the major determinant of the osmolarity in the ECF, including plasma. Therefore, the plasma-Na+ concentration needs to be tightly regulated. An excess of electrolyte-free water decreases the concentration of osmolytes leading to hyponatremia. In contrast, a free water deficit increases the osmolyte concentration leading to hypernatremia. Pathophysiology-oriented approaches to dysnatremic patients help both clinicians and patients. Therapeutic interventions depend on the differentiation between acute and chronic, asymptomatic, and symptomatic dysnatremia, and on the patient's extracellular volume status. The therapeutic armamentarium for hyponatremia consists of water restriction, hypertonic infusions, urea, V2 receptor-blockers, and sodium-glucose cotransporter 2 (SGLT2) inhibitors. Patients with hypernatremia are treated with electrolyte-free water or hypotonic sodium-containing solutions depending on their volume status. Basic concepts in the management of dysnatremic patients are discussed.

Updates in hyponatremia and hypernatremia.

PURPOSE OF REVIEW: Hyponatremia and hypernatremia are commonly encountered electrolyte abnormalities that require timely and careful intervention, as they can be associated with significant morbidity and mortality. RECENT FINDINGS: This review article addresses the etiology, presentation, diagnosis, and management of both hyponatremia and hypernatremia, emphasizing the latest advancements and emerging trends in pediatric care. SUMMARY: A methodical approach is needed to accurately assess and treat hyponatremia and hypernatremia. Both conditions continue to rely on serum and urine testing, however newer tests such as copeptin and stimulated testing may hold promise to further refine testing in the future.

Edelman Gamblegrams: a tool to teach and learn disorders of water/plasma tonicity homeostasis.

This article introduces an innovative teaching and learning tool called "Edelman Gamblegrams" that aims to help medical learners better understand disorders related to water/plasma tonicity homeostasis, i.e., hyponatremia and hypernatremia. Gamblegrams, named after physician James L. Gamble, are bar diagrams displaying the relative abundance of extracellular anions and cations and are commonly used in the analysis of acid-base disorders. The Edelman equation represents the physiological variables that determine plasma sodium concentration, namely, total body sodium mass, total body potassium mass, and total body water volume. Edelman Gamblegrams inspired by traditional Gamblegrams but using the components of the Edelman equation, visually demonstrate how sodium, potassium, and water contribute to plasma sodium concentration under normal and pathological conditions. Scenarios that lead to hypotonic hyponatremia and hypernatremia in Edelman Gamblegrams are also discussed. Furthermore, examples of how these visual aids can enhance understanding of the pathogenesis of dysnatremias are also presented. Overall, the use of Edelman Gamblegrams has the potential to improve comprehension and retention of concepts related to water/plasma tonicity homeostasis.NEW & NOTEWORTHY This article introduces a new teaching tool called "Edelman Gamblegrams," modeled after the conventional Gamblegrams used in acid-base disorder analysis and using the independent physiological variables that determine the plasma sodium concentration (Edelman equation), that aims to help medical learners understand disorders related to water/plasma tonicity homeostasis.

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.

Recurrent severe hypernatraemia in a young patient: a disconnect between osmoreceptor function and drinking behaviour.

Chronic hypernatraemia is a rare clinical entity. In the younger population, hypernatraemia is often a consequence of failure to generate thirst in response to osmotic stimuli.We report the case of a male patient admitted with severe hypernatraemia (plasma sodium 175 mmol/L) on return from holidays. His urine was maximally concentrated at 894 mOsm/kg-suggestive of normal vasopressin reserve. MRI of the brain showed a large extra-axial cyst, with preservation of the posterior pituitary bright spot. Formal osmoregulatory studies demonstrated normal osmoregulated vasopressin secretion and normal thirst, but no appropriate drinking behaviour.This patient illustrates a unique pathophysiological disconnect between thirst appreciation and the central drive to drink, in the context of normal osmoregulatory function. It is likely that this disconnect is related to the patient's large intracranial cyst.The management challenge is to maintain appropriate fluid intake in order to prevent recurrent severe hypernatraemia.

Dapagliflozin induced hypernatremia via osmotic diuresis: a case report.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been widely used. They inhibit proximal tubular glucose reabsorption, resulting in glycosuria. Herein, we report the case of a 65-year-old woman who presented with hypernatremia during the perioperative period of a subarachnoid hemorrhage. The patient continued to take dapagliflozin postoperatively and subsequently developed severe hypernatremia. Based on the urinalysis findings, we diagnosed osmotic diuresis due to glycosuria as contributing to hypernatremia. Hypernatremia improved with the discontinuation of dapagliflozin and the administration of a hypotonic infusion. In the perioperative period, physicians should discontinue SGLT2 inhibitors owing to concerns about the development of hypernatremia.

Clinical Characteristics of Adipsic Diabetes Insipidus.

OBJECTIVE: Adipsic diabetes insipidus (ADI) is a life-threatening disease. It is characterized by arginine vasopressin deficiency and thirst absence. Data about clinical characteristics of ADI were scarce. This study investigated the clinical features of hospitalized ADI patients. METHODS: A retrospective study was conducted of hospitalized ADI patients admitted to the Endocrinology Department of Huashan Hospital between January 2014 and December 2021, and compared with central diabetes insipidus (CDI) patients with normal thirst. RESULTS: During the study period, there were a total of 507 hospitalized CDI patients, among which 50 cases were ADI, accounting for 9.9%. Forty percent of ADI patients were admitted due to hypernatremia, but there were no admissions due to hypernatremia in the control group. The lesions of ADI patients were more likely to be located in the suprasellar area (100% vs 66%, P < .05). Higher prevalence of hypothalamic dysfunction (76% vs 8%, P < .001), central hypothyroidism (100% vs 90%, P = .031), hyperglycemia (66% vs 32%, P < .001), dyslipidemia (92% vs 71%, P = .006), and hyperuricemia (64% vs 37%, P = .003) was found in the ADI group than in the control group. The proportions of hypernatremia were higher in the ADI group both at admission and at discharge (90% vs 8%, 68% vs 8%, respectively, both with P < .001), contributing to higher prevalence of complications, such as renal insufficiency, venous thrombosis, and infection. CONCLUSION: ADI patients were found with higher prevalence of hypernatremia, hypopituitarism, hypothalamic dysfunction, metabolic disorders, and complications, posing a great challenge for comprehensive management.

Association of admission serum sodium and outcomes following out-of-hospital cardiac arrest.

BACKGROUND: The prognostic association between dysnatremia and outcomes in out-of-hospital cardiac arrest (OHCA) is not well understood. Given hypernatremia is associated with poor outcomes in critical illness and hyponatremia may exacerbate cerebral edema, we hypothesized that dysnatremia on OHCA hospital admission would be associated with worse neurological outcomes. METHODS: We studied adults (≥19 years) with non-traumatic OHCA between 2009 and 2016 who were enrolled in the British Columbia Cardiac Arrest Registry and survived to hospital admission at 2 quaternary urban hospitals. We stratified cases by admission serum sodium into hyponatremic (<135 mmol/L), normonatremic (135-145 mmol/L), and hypernatremic (>145 mmol/L) groups. We used logistic regression models, adjusted for age, sex, shockable rhythm, admission serum lactate, and witnessed arrest, to estimate the association between admission sodium and favorable neurological outcome (cerebral performance category 1-2 or modified Rankin scale 0-3). RESULTS: Of 414 included patients, 63 were hyponatremic, 330 normonatremic, and 21 hypernatremic. In each respective group, 21 (33.3%), 159 (48.2%), and 3 (14.3%) experienced good neurological outcomes. In univariable models, hyponatremia (OR 0.53, 95% CI 0.30-0.93) and hypernatremia (OR 0.19, 95% CI 0.05-0.65) were associated with lower odds of good neurological outcomes compared to the normonatremia group. After adjustment, only hypernatremia was associated with lower odds of good neurological outcomes (OR 0.22, 95% CI 0.05-0.98). CONCLUSIONS: Hypernatremia at admission was independently associated with decreased probability of good neurological outcomes at discharge post-OHCA. Future studies should focus on elucidating the pathophysiology of dysnatremia following OHCA.

Challenges in using fractional excretion of sodium in the assessment of salt poisoning.

AIM: Hypernatraemia typically reflects dehydration, yet in rare instances may be caused by salt poisoning. Identifying these rare cases is a difficult challenge. Making the diagnosis of salt poisoning can have severe consequences, such as the removal of the child from its home or even prison sentences for the implicated carer. It is therefore imperative to get the diagnosis right. Guidelines for the assessment of hypernatraemia emphasise the importance of the fractional excretion of sodium to distinguish between dehydration and salt poisoning, but no generally accepted cut-off value exists. Opinions about the diagnosis of salt poisoning in some cases consequently may differ. Here, we aim to highlight the challenges and stimulate discussion on how to improve the tools for the assessment of hypernatraemia. METHODS: Report of a case of unexplained hypernatraemia in which the treating paediatrician raised the suspicion of salt poisoning. RESULTS: Two consulted experts made opposing judgements about the aetiology of the observed hypernatraemia. CONCLUSION: Clear diagnostic criteria for the diagnosis of salt poisoning are lacking and more data are needed for their establishment. Without this, victims may experience further harm and carers are at risk of devastating, yet potentially erroneous accusations.

Association of postoperative hypernatremia with outcomes after elective craniotomy.

STUDY OBJECTIVE: Hypernatremia is a treatable biochemical disorder associated with significant morbidity and mortality in patients undergoing surgery. However, its impact on patients who undergo elective craniotomy is not well understood. This study aimed to investigate the prognostic implications of postoperative hypernatremia on the 30-day mortality of patients undergoing elective craniotomy. DESIGN: Retrospective cohort study. SETTING: The Department of Neurosurgery of a high-volume center. PATIENTS: Adult patients undergoing elective craniotomy except those with pituitary tumors, intracerebral hemorrhage, subarachnoid hemorrhage, or traumatic brain injury. INTERVENTIONS: None. MEASUREMENTS: Perioperative laboratory data were collected for all study participants, including sodium levels, neutrophil count, serum albumin, lymphocyte count, and blood glucose. These measurements were obtained as part of routine clinical care and provided valuable information for data analysis. MAIN RESULTS: Of the 10,223 identified elective craniotomy patients who met our inclusion and exclusion criteria, 14.9% (1519) developed postoperative hypernatremia. This population's overall postoperative 30-day mortality rate was 1.7% (175). After performing an adjusted logistic regression analysis, we found that the odds of 30-day mortality increased gradually with increasing severity of hypernatremia: 2.9 deaths (OR, 3.79; 95% CI, 2.46-5.85) in patients with mild hypernatremia, 13.9 deaths (OR, 17.73; 95% CI, 11.17-28.12) in those with moderate hypernatremia, and 38.3 deaths (OR, 67.00; 95% CI, 40.44-111.00) in those with severe hypernatremia. CONCLUSIONS: Hypernatremia is common after elective craniotomy, and its presence is associated with increased mortality and complications, particularly in cases of severe hypernatremia. These results emphasize the significance of risk evaluation in neurosurgical patients and propose the advantages of closely monitoring serum sodium levels in high-risk individuals. Future randomized controlled trials could provide more insight into the effect of treating postoperative hypernatremia in these patients.