Administration Of Hypertonic Saline Research Articles

Acute hyperosmotic stimulus of the Organum Vasculosum of the Lamina Terminalis leads to increase in the blood pressure dependent on release of ATP into the Paraventricular Nucleus of the Hypothalamus of rats

The neural network involved in hyperosmolality-induced hypertension includes the activation of the organum vasculosum of the lamina terminalis (OVLT) with monosynaptic connections to the paraventricular nucleus of the hypothalamus (PVN) that expresses an abundance of purinergic receptors including P2 receptors. Previously, we have shown that hyperosmotic-induced sympathoexcitation at the level of the PVN depends on the P2 receptors. More recently, we have shown that hyperosmotic stimulus induces the release of ATP in the PVN, at least in part, from astrocytes. Here we hypothesize that the increase in the blood pressure (BP) induced by acute hyperosmotic stimulus in the OVLT involves the release of ATP within the PVN neurons, acting on P2 receptors. Thus, we sought to determine (1) whether P2X7-expressing OVLT and PVN neurons are activated by hyperosmotic challenge, and (2) what effects P2 receptor antagonism on changes in the BP mediated by an acute hyperosmotic stimulus in the OVLT. Adult Wistar rats (10-12 weeks old; CEUA ICB/USP: #4895140819 and #1521230221) were used in two protocols: 1) Double-labeling immunofluorescence of P2X7 (anti-P2X7 receptor, 1:500) expressing neurons with FOS (anti-cfos, 1:3000) animals received i.v administration of hypertonic (NaCl, 3M, n=4) or isotonic saline (NaCl, 0.154M, n=4), followed by evaluation of immunostaining to FOS and P2X7 receptors in the OVLT and PVN; 2) OVLT-PVN microinjections and BP monitoring: under anesthesia rats (n=5), received catheters in the femoral vein and artery for the administration of urethane (1g/kg) and BP recording signals, respectively. Microinjections of 3M NaCl (50nL) were administered into the OVLT, before and after bilateral antagonism of P2 purinergic receptors (PPADS, 10uM-100nL on each side) in the PVN with simultaneous BP recording. Data were expressed as the mean ± SD, and statistical significance level of p<0.05 by Student’s T-test. Immunoreactive neurons for the P2X7 receptor subunit were observed in all compartments of the OVLT and PVN. Hyperosmotic stimulus significantly increased the number of Fos+ neurons in both the OVLT and PVN. While a small number of P2X7 receptors expressing OVLT and PVN neurons was observed in rats treated with isotonic saline, significantly more P2X7-expressing neurons expressed Fos+ in the OVLT with hypertonic saline. The stimulus of the OVLT with 3M NaCl elicited a significant increase in the BP. This effect was attenuated after bilateral injection of PPADS in the PVN (ΔMAP: NaCl OVLT:+10±1mmHg vs. NaCl OVLT post-PPADS PVN: +2.4±1.3mmHg, p<0.0001). Collectively, our findings indicate that hyperosmotic stimulation activates a subset of P2X7 expressing OVLT and PVN neurons and that the elevation in the BP induced by hyperosmotic stimulus in the OVLT involves the endogenous release of ATP within the PVN, likely as part of the neural control of circulation during osmotic challenges. Financial Support: FAPESP #2019/19894-8, CAPES #88887.364432/2019-00. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Approach to Hyponatremia in the ICU: A review article

Hyponatremia is a common condition in clinical practice and a major cause of morbidity and mortality. Differentiating between its acute and chronic forms is challenging because of their variable symptoms. A thorough approach is necessary to diagnose hyponatremia. Proper interpretation of the numerous laboratory tests aids in the differentiation of hyponatremia types. In the ICU, management varies for acute and chronic cases to prevent neurological issues. While fluid restriction and hypertonic saline administration are two common forms of management, however, individualized strategies are essential for illnesses like cirrhosis or Syndrome of Inappropriate Anti Diuretic Hormone. To successfully treat hyponatremia, use vaptans and other protocols while monitoring the patient's condition closely. Monitoring acute and chronic cases must adhere to specific monitoring frequency and indices, and should cease only when Na+ levels are deemed safe. Balancing the diagnosis and therapy provides patient safety and avoids side effects.

Hypertonic Saline to Achieve Hyperdiuresis: A Case Report

Diuretic resistance can commonly occur following chronic diuretic use, leading to difficulty in diuresis. We report on a 59-year-old man with worsening dyspnoea and lower limb swelling. Clinical findings, alongside bedside echocardiography and lung ultrasound, were suggestive of acute decompensated heart failure (ADHF). Despite initial success with IV loop diuretic for diuresis, the patient’s urine output started to deteriorate soon after despite high-dose frusemide infusion, sequential nephron blockade and attempts at ultrafiltration. A decision was made to attempt hyperdiuresis using hypertonic saline, which led to marked improvement in clinical haemodynamic and urine output over the coming days. Several studies have investigated the utility of hypertonic saline in ADHF and demonstrated its effectiveness to varying degrees. A definitive mechanism as to how hypertonic saline exerts its beneficial effect remains unknown, although several hypotheses have been proposed. Diuretic resistance remains a major challenge when managing patients with ADHF. In cases of refractory ADHF with limited treatment options, there may be a role for hypertonic saline administration.

Primary central nervous system lymphoma with initial presentation of cerebral salt-wasting syndrome shifting to syndrome of inappropriate antidiuretic hormone secretion: A case report

Background. Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma which may affect brain parenchyma. Hyponatremia can be present as one of the complications, either due to neuronal injury arising from in-situ tumor and/or surgical resection (resulting in cerebral salt wasting syndrome/CSWS) or indolent, slowly progressing and often asymptomatic one as a consequence of ongoing chronic illness (so-called syndrome of inappropriate antidiuretic hormone/SIADH). Differentiating between the two is critical, since each diagnosis has a starkly different treatment approach which may exacerbate one another. Case presentation. Herein, we reported a case of a 48-year-old immunocompetent male who presented with diplopia, hallucination, imbalance, and dizziness, later to be diagnosed with PCNSL on multiple brain regions. He suffered from symptomatic hyponatremia post-surgically as a result of CSWS which in turn responding well to intensive dose of desmopressin acetate and fluid replenishment. However, as the disease progressed, hyponatremia also relapsed but was refractory to the same treatment approach. After subsequent investigations, patient was known to have SIADH. Treatments tailored to SIADH including fluid restriction and administration of hypertonic saline as well as tolvaptan lead to stabilization of sodium levels and significant clinical improvements. Conclusion. Post-operative hyponatremia in the setting of a PCNSL continues to be a complex issue. It underscores the importance of careful clinical assessment, monitoring, and the need for flexibility in diagnosis and management strategies. Furthermore, it highlights the challenges of distinguishing between CSWS and SIADH, two conditions with similar laboratory findings but divergent management approaches. Recognizing the subtleties in clinical presentation and responding appropriately can greatly influence patient outcomes. The rising incidence of PCNSL in immunocompetent individuals also needs a heightened awareness and understanding of its presentations and potential post-operative complications among clinicians.

Impact of a structured educational intervention on attitudes and clinical practices in heart failure among physicians in argentina

Abstract Introduction It is necessary to identify areas for improvement in the care of patients with heart failure (HF), and thus implement educational interventions to optimize the quality of care and their clinical outcomes. Objective The aim of this study was to evaluate the attitudes, knowledge, confidence and care pathways of patients with HF among physicians in Argentina and their subsequent changes after an educational intervention. Methods We conducted a cross-sectional study using a self-administered survey to evaluate clinical practice patterns and attitudes/perceptions regarding the diagnosis, treatment and follow-up of HF patients in the outpatient and inpatient settings. Survey respondents were physicians from 22 centers in Argentina who participated in a comprehensive educational programme for the care of HF patients conducted between March and July 2021. The educational intervention was based on a 30-hour training programme in heart failure clinics and a final examination. Simple road maps were created to address the knowledge gaps identified in the pre-intervention phase. Results A total of 50 physicians were surveyed; the mean age was 41±8 years and 86% were cardiologists. The educational intervention significantly increased physicians' confidence in diagnosing HFpEF, with 52% feeling "confident" or "very confident" before and 84% after the intervention (p<0.001). In outpatients with HFrEF, more physicians reported prioritizing quadruple therapy with SLGT-2i, mineralocorticoid receptor antagonists (MRA), beta-blockers and angiotensin receptor neprilysin inhibitors (ARNI) in the post-intervention period (p<0.05, figure 2). No differences were found in the reported time to optimal medical treatment (p=0.7). After the intervention, the proportion of physicians who felt "confident" or "very confident" in identifying patients who could benefit from an implantable cardioverter-defibrillator increased from 70% to 96% (p=0.01). After the intervention, more doctors considered "relevant" and "very relevant" the administration of hypertonic saline (22% to 52%; p=0.01), and intravenous iron (56% to 80%; p=0.041). Compared to the pre-intervention period, more physicians prioritized quadruple therapy with beta-blockers, MRA, ARNI and SGLT2i (p<0.05, figure 2) at hospital discharge. There was a significant increase in the use of the discharge checklist from 26% to 48% (p=0.05). Conclusions A multifaceted structured educational intervention was effective in improving knowledge and attitudes about the diagnosis and management of patients with HF among physicians in Argentina. The results of the present study demonstrate that an educational intervention can increase knowledge and improve clinical attitudes in the diagnosis of HFpEF and management of outpatients and hospitalized patients with HFrEF. Further studies are needed to determine the impact of such programmes in other countries.

Abstract 106: CHANTER Syndrome: A Case Report Of A 59 Year Old Man With Positive Outcome

Introduction Cerebellar, Hippocampal, and Basal Nuclei Transient Edema with Restricted Diffusion (CHANTER) syndrome was first described in 2019 [1] as a pattern of radiographic findings that are distinct from ischemic, anoxic, or toxic brain injury. Pathophysiology is still uncertain, but some proposed theories include a primary metabolic etiology or a mitochondrial failure of gray matter. Clinically, patients typically present with altered level of consciousness. Radiographically, diffusion weighted imaging shows restriction in the bilateral hippocampi, bilateral cerebelli, and basal nuclei. The cerebral cortex, thalamus, and subcortical white matter are usually spared. Despite the morbid clinical picture on presenation, positive outcomes were reported with early intervention. We describe a case of CHANTER syndrome in a 59 year old man with history of illicit substance abuse. Methods Case report with electronic medical record review. Results 59‐year‐old man with history of illicit substance abuse including cocaine, opioid, and phencyclidine presented to the hospital after being found down at a drug store. Patient did not respond to Naloxone and was eventually intubated due to respiratory compromise. Non‐contrast CT head showed hypoattenuation of the bilateral cerebellar hemispheres with mild effacement of the fourth ventricle. MRI brain showed diffusion signal abnormalities with corresponding T2 FLAIR hyperintensities in the bilateral cerebellar hemispheres, bilateral hippocampi, and bilateral basal ganglia with some involvement of the left occipital lobe suggestive of CHANTER syndrome. As vasogenic edema worsened, hydrocephalus ensued requiring administration of hypertonic saline and eventual external ventricular drain (EVD) insertion in the neurocritical care unit. Despite initial improvement in his level of consciousness after the EVD insertion, his intracranial pressure (ICP) continued to increase and midazolam and ketamine infusion drips were added. A fine balance between lowering the ICP and avoiding respiratory suppresion with sedating infusions was maintained. Consecutive MRI brain images over the course of the following 4 weeks of his stay showed decrease of the abnormal diffusion weighted imaging signal along with improvement in his overall mental status and eventual discharge 12 weeks from his initial presentation. Conclusion This case further strengthens the relationship between CHANTER syndrome and illicit substance use as a likely etiology along with other cases in the literature. Aggressive management in the neurocritical care to control vasogenic edema and avoid ICP elevation is essential to give patients the highest chance of recovery. Clinical improvement At least partial reversal of the radiographic findings of CHANTER syndrome can be attained with treatment, however, unclear if complete reversal is possible.

THU239 Tolvaptan For SIADH Management In Children

Abstract Disclosure: M. Igarashi: None. T. Kashima: None. H. Doi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None. [Background] Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is common after brain surgery and its’ management is difficult. In Japan, tolvaptan was approved for SIADH management in adults, but there are limited reports on the use of tolvaptan for SIADH in children.We presented two cases which showed triphasic response after neurosurgery and was treated with tolvaptan for SIADH phase. We will also summarize other cases which were treated with tolvaptan for SIADH phase after neurosurgery in discussion. [Case] Case1 is a 5-month-old boy with choroid plexus papilloma.A tumor resection was performed after chemotherapy. After tumor resection, serum sodium level went up to 171 mEq/L with diluted polyuria. So he was diagnosed as diabetes insipidus and treated with vasopressin. The dose of vasopressin was decreased and it was stopped on postoperative day (POD) 6, but serum sodium level further decreased and he was diagnosed as SIADH. Water restriction and hypertonic saline administration were performed. Tolvaptan at a dose of 0.1mg/kg was administered and sodium level improved from 123 mEq/L to 137 mEq/L.However, urine volume was decreased again and sodium level went down to 132 mEq/L, so tolvaptan was administered again. After second administration of tolvaptan, polyuria lasted and sodium level went up to 145 mEq/L, which was managed with temporary use of vasopressin. Case 2 is a 6-year-old girl with craniopharyngioma. After tumor resection, polyuria was observed and she was diagnosed as diabetes insipidus, which was treated with vasopressin.On POD 4, she was diagnosed as SIADH. Since water restriction was not effective, tolvaptan was administered twice (0.1mg/kg and 0.4mg/kg respectively). After second administration of tolvaptan, due to polyuria and diluted urine sodium level went up to 161 mEq/L, which was treated with vasopressin. Diluted urine and polyuria lasted, so finally she was diagnosed as diabetes insipidus. [Discussion] Tolvaptan was used for the management of SIADH that was resistant to water restriction or salt supplementation and it was useful for improving or maintaining sodium level. However, in some case, hypernatremia due to excessive free water excretion was caused after the dose of tolvaptan was increased. The appropriate dosage of tolvaptan has not yet been established. The risk of rapid sodium elevation should be considered and monitoring of water balance and sodium level was needed after using tolvaptan. [Conclusion] Tolvaptan could be an effective option for the management of SIADH, but frequent monitoring of sodium level is needed. Presentation: Thursday, June 15, 2023

Management of noncytotoxic extravasation injuries: A focused update on medications, treatment strategies, and peripheral administration of vasopressors and hypertonic saline.

Extravasation is the leakage of intravenous solutions into surrounding tissues, which can be influenced by drug properties, infusion techniques, and patient-related risk factors. Although peripheral administration of vesicants may increase the risk of extravasation injuries, the time and resources required for central venous catheter placement may delay administration of time-sensitive therapies. Recent literature gathered from the growing use of peripheral vasopressors and hypertonic sodium suggests low risk of harm for initiating these emergent therapies peripherally, which may prevent delays and improve patient outcomes. Physiochemical causes of tissue injury include vasoconstriction, pH-mediated, osmolar-mediated, and cytotoxic mechanisms of extravasation injuries. Acidic agents, such as promethazine, amiodarone, and vancomycin, may cause edema, sloughing, and necrosis secondary to cellular desiccation. Alternatively, basic agents, such as phenytoin and acyclovir, may be more caustic due to deeper tissue penetration of the dissociated hydroxide ions. Osmotically active agents cause cellular damage as a result of osmotic shifts across cellular membranes in addition to agent-specific toxicities, such as calcium-induced vasoconstriction and calcifications or arginine-induced leakage of potassium causing apoptosis. A new category has been proposed to identify absorption-refractory mechanisms of injury in which agents such as propofol and lipids may persist in the extravasated space and cause necrosis or compartment syndrome. Pharmacological antidotes may be useful in select extravasations but requires prompt recognition and frequently complex administration strategies. Historically, intradermal phentolamine has been the preferred agent for vasopressor extravasations, but frequent supply shortages have led to the emergence of terbutaline, a β2 -agonist, as an acceptable alternative treatment option. For hyperosmolar and pH-related mechanisms of injuries, hyaluronidase is most commonly used to facilitate absorption and dispersion of injected agents. However, extravasation management is largely supportive and requires a protocolized multidisciplinary approach for early detection, treatment, and timely surgical referral when required to minimize adverse events.

Dysnatremia

Changes in serum sodium concentrations are frequently encountered by anesthesiologists, are complex and are often inadequately treated. Feared consequences include neurological complications, such as cerebral hemorrhage, cerebral edema and coma. Dysnatremia is always accompanied disturbances in the water balance. Accordingly, these are routinely classified based on the tonicity; however, in the daily routine and especially in the acute setting, the volume status and extracellular volume are often difficult to assess. Severe symptomatic hyponatremia with impending cerebral edema is treated by administration of hypertonic saline solution. If the rise in serum sodium is too rapid, there is arisk of central pontine myelinolysis. In asecond step, the cause of the hyponatremia can be investigated and the appropriate treatment can be initiated. In the case of hypernatremia, the etiology of the disorder must be clarified before treatment. The goal is to compensate for the water deficiency by correcting the cause, specific volume therapy and, if necessary, drug support. Aslow and controlled compensation must be closely monitored in order to avoid neurological complications. An algorithm has been developed that provides an overview of the dysnatremias, aids with making the diagnosis and gives recommendations for treatment measures in the clinical routine.

Safety of Administration of Hypertonic Sodium Chloride Solution Through Peripheral IV in Neuroscience Intensive Care Unit, KAMC, Makkah

Background: Infusions of 3% sodium chloride are routinely recommended to be given through central venous catheters, not peripheral IV lines. In addition, no data are available on the proper site for administration of a continuous intravenous infusion of 3% sodium chloride solution in adults. Some recent studies have illustrated that this theory may not be relevant, and that 3% sodium chloride may be safe for administration in peripheral IV lines. Aims and Objectives: To evaluate the incidence of infusion-related reactions in neuro intensive care patients treated with continuous intravenous infusion of hypertonic sodium chloride up to 3% solution via peripheral IV catheter. Methods: Data on patients treated with continuous intravenous infusion of hypertonic sodium chloride up to 3% solution through peripheral IV cannula for at least 24 hours at neuroscience intensive care unit were evaluated by using prospective observational design to determine the complications in administration site such as phlebitis, infiltration, extravasation, thrombosis and line infection. Results: Out of 43 patients with peripheral hypertonic saline infusion (up to 3%), no incidence of complications were reported after 24 hours of continuous infusion. Out of 34 patients who continued their infusion to second day, one incidence of phlebitis and 2 incidences of extravasation were reported. 20 patients were on continuous infusion towards day 3, where also one incidence of phlebitis and 2incidencese of extravasation were reported. Overall complications reported in all 97 peripheral hypertonic saline infusion days were 2 incidence of phlebitis and 4incidences of extravasation. Conclusion: Current recommendations that a central catheter is required for continuous intravenous infusion of hypertonic sodium chloride up to 3% should be reconsidered. Only a few patients who had peripheral infusions had infusion-related complications. Peripheral intravenous administration of hypertonic saline can be used safely and effectively in patients without a central line.

A step-by-step guide for the diagnosis and management of hyponatraemia in patients with stroke.

Hyponatraemia is common in patients with stroke and associated with adverse outcomes and increased mortality risk. The present review presents the underlying causes and provides a thorough algorithm for the diagnosis and management of hyponatraemia in stroke patients. Concomitant diseases and therapies, such as diabetes, chronic kidney disease and heart failure, along with diuretics, antidepressants and proton pump inhibitors are the most common causes of hyponatraemia in community. In the setting of acute stroke, the emergence of hyponatraemia might be attributed to the administration of hypotonic solutions and drugs (ie. mannitol and antiepileptics), poor solute intake, infections, as well as stroke-related conditions or complications, such as the syndrome of inappropriate secretion of antidiuretic hormone, cerebral salt wasting syndrome and secondary adrenal insufficiency. Diagnostically, the initial step is to differentiate hypotonic from non-hypotonic hyponatraemia, usually caused by hyperglycaemia or recent mannitol administration in patients with stroke. Determining urine osmolality, urine sodium level and volume status are the following steps in the differentiation of hypotonic hyponatraemia. Of note, specific parameters, such as fractional uric acid and urea excretion, along with plasma copeptin concentration, may further improve the diagnostic yield. Therapeutic options are based on the duration and symptoms of hyponatremia. In the case of acute or symptomatic hyponatraemia, hypertonic saline administration is recommended. Hypovolaemic chronic hyponatremia is treated with isotonic solution administration. Although fluid restriction remains the first-line treatment for the rest forms of chronic hyponatraemia, therapies increasing renal free water excretion may be necessary. Loop diuretics and urea serve this purpose in patients with stroke, whereas sodium-glucose transport protein-2 inhibitors appear to be a promising therapy. Nevertheless, it is yet unclear whether the appropriate restoration of sodium level improves outcomes in such patients. Randomized trials designed to compare therapeutic strategies in managing hyponatraemia in patients with stroke are required.

311: SEVERE HYPERAMMONEMIA CAUSED BY CARNITINE DEFICIENCY DURING ADULTHOOD

Introduction: Carnitine is a necessary co-factor in the oxidation of fatty acids as part of the urea cycle; deficiency of which may lead to heart or liver failure. Primary carnitine deficiency due to transporter defects or mutations is seen in infants. Secondary carnitine deficiency is the result of whole-body carnitine deficiency. Here, we discuss a case of secondary deficiency due to vegetarianism, leading to severe hyperammonemia. Description: A 23-year-old woman was admitted with one day of vomiting and diarrhea. On arrival, she was confused but alert, though rapidly decompensated and developed obtundation, clonus, rigidity, posturing, and non-reactive mydriatic pupils, requiring emergent intubation. Work-up was significant for elevated ammonia to 581 umol/L with CT head showing severe brain edema prompting placement of external ventricular drain for intracranial hypertension and frequent hypertonic saline administration. Given significant hyperammonemia with otherwise negative work-up, the patient’s presentation was concerning for a urea cycle defect. The patient was dialyzed and started on arginine, sodium benzoate/phenylacetate, citrulline, and buphenyl. Further history revealed a diet devoid of meat. Plasma amino acid analysis revealed decreased total carnitine 3 umol/L (27-73) and free carnitine 2 umol/L (20-55). There were no mutations in the carnitine transport gene or deficient enzymatic activity for the urea cycle. After one week, she was awake, alert, and was extubated shortly thereafter. Once tolerating oral intake, her diet of was supplemented with oral carnitine. She was able to make a full recovery and return home without deficits from baseline prior to admission. Discussion: Common causes of hyperammonemia are hepatic failure, genetic urea cycle defects, and organic academies, which were ruled out in this case. Carnitine is an important co-factor in the metabolism of long-chain fatty acids and its disruption impairs ammonia excretion through inhibition of the urea cycle. Secondary carnitine deficiency is seen in severe malnutrition, and causes hyperammonemia and encephalopathy. This case is particularly important to note, as fatty acid oxidation disorders based on pure dietary deficiency that presents during adulthood are uncommon and not frequently considered in the differentials.

ODP332 Maternal Central Diabetes Insipidus Immediately after Delivery, Owing to Vasospasm of the Internal Carotid Artery

Abstract Background Sheehan's syndrome is a cause of hypopituitarism during the postpartum period, but it rarely manifests immediately after birth. Clinical Case We report the case of a 30-year-old woman who delivered her second child, lost 1,050 mL of blood in the process, but did not receive a blood transfusion. A few hours after delivery, the patient complained of headache, nausea, and thirst, and her urine production increased to 9 L/day. No menstrual irregularities or abnormalities during pregnancy or childbirth had been reported. None of hypotension, external eye muscle paralysis, or visual impairment were identified on physical examination. The laboratory findings were low urine osmolality and high serum osmolality and sodium concentration. The concentrations of thyroid hormones, growth hormone (GH), and anti-diuretic hormone (ADH) were found to be low. The IgG4 concentration was not high (4.7 mg/dL; normal <105 mg/dL) and the patient was negative for anti rabphilin-3A antibody. Pituitary magnetic resonance imaging (MRI) on the day of admission showed enlargement of the pituitary gland and stalk, and magnetic resonance angiography showed stenosis of the left internal carotid artery. The patient showed a poor response to GH-releasing peptide 2 and thyroid releasing hormone stimulation. Hypertonic saline administration did not cause an increase in ADH concentration. We diagnosed adult growth hormone deficiency (aGHD), central hypothyroidism, and central diabetes insipidus (DI). The enlargement of the pituitary gland was slightly less marked and the stenosis of the left internal carotid artery improved 7 days after admission. After 6 months, the pituitary gland was almost normal in size, although the aGHD, central hypothyroidism, and central DI remained. Sheehan's syndrome or lymphocytic hypophysitis could have been responsible for the postpartum hypopituitarism. This case was not typical of lymphocytic hypophysitis with respect to the hormone deficiency pattern, the MRI findings, and the lack of anti rabphilin-3A antibody. Sheehan's syndrome is caused by ischemic necrosis of the anterior pituitary gland after severe postpartum hemorrhage. The prevalence of central DI is estimated to be 2%–3%. Typically, pituitary dysfunction progresses slowly and develops several years after childbirth. In contrast, in the present patient, stenosis of the left internal carotid artery developed and improved during short periods of time. The vasospasm of the internal carotid artery caused reductions in flow through the superior and inferior hypophysial arteries, which resulted in ischemia and necrosis of the pituitary gland, similar to Sheehan's syndrome. Clinical Lesson: Although rare, maternal central DI can be caused by ischemia and vasospasm immediately after the delivery of a child. The possibility of a pituitary stroke in the presence of neoplastic disease should not be ruled out, and imaging and pituitary gland function should be followed over the long term. Presentation: No date and time listed

Diquafosol sodium reduces neuronal activity in trigeminal subnucleus caudalis in a rat model of chronic dry eye disease

Patients with persistent and severe dry eye disease (DED) have corneal hypersensitivity, resulting in ocular pain, and diquafosol sodium, a potent P2Y2 receptor agonist, is commonly used to improve the resultant tear film stability. This study determined the effects of diquafosol instillation on the suppression of trigeminal subnucleus caudalis (Vc) neuronal activity and ocular pain by enhancing tear film stability in the model for chronic DED. The effects of diquafosol on the ocular surface were assessed by the topical application for 28 days, starting from the 14th day since unilateral exorbital gland removal (chronic DED). Loss of tear volume secretion in chronic DED rats was significantly reversed by diquafosol instillation after 28 days, compared with saline treatment. The number of eyeblinks and pERK-IR neurons in the superficial laminae of Vc following hypertonic saline administration to the ocular surface was lower in diquafosol-treated chronic DED rats than in saline-treated rats. The neuronal activity evoked by hypertonic saline and mechanical stimulation along with the spontaneous neuronal activity in the superficial laminae of the Vc were suppressed in diquafosol-treated chronic DED rats. These findings suggest that ocular surface instillation of diquafosol for 28 days attenuates the neuronal hyperactivity in the Vc and the ocular pain that often occurs in chronic DED.

Catheter-associated deep vein thrombosis in children with severe traumatic brain injury: A single-center experience.

This study was performed to describe the single-center experience of deep vein thrombosis (DVT) in children with severe traumatic brain injury (sTBI) who were mechanically ventilated with a central line, and to identify potentially modifiable risk factors. It was hypothesized that children with DVT would have a longer duration of central venous line (CVL) and a higher use of hypertonic saline (HTS) compared to those without DVT. This was a retrospective study of children (0-18years) with sTBI, who were intubated, had a CVL, and a minimum intensive care unit (ICU) stay of 3days. Children were analyzed by the presence or absence of DVT. HTS use was evaluated using milliliter per kilogram (ml/kg) of 3% equivalents. Univariable and multivariable logistic regression models were used to determine which factors were associated with DVT. Seventy-seven children met inclusion criteria, 23 (29.9%) had a DVT detected in an extremity. On univariable analysis, children with DVT identified in an extremity had prolonged CVL use (14 vs. 8.5days, p=.021) and longer duration of mechanical ventilation (15 vs. 10days, p=.013). HTS 3% equivalent ml/kg was not different between groups. On multivariable analysis, mechanical ventilation duration was associated with DVT detection in an extremity, whereas neither CVL duration nor HTS use had an association. There was a high incidence of extremity DVT detected in children with sTBI who received invasive mechanical ventilation and had a CVL. HTS administration was not associated with DVT detection in an extremity.

Korean Society of Nephrology 2022 recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

WATER INTOXICATION: A CASE OF HYPONATREMIA AND ACUTE RENAL FAILURE

WATER INTOXICATION: A CASE OF HYPONATREMIA AND ACUTE RENAL FAILURE

SPECT/CT imaging reveals CNS-wide modulation of glymphatic cerebrospinal fluid flow by systemic hypertonic saline

SummaryIntrathecal administration enables central nervous system delivery of drugs that do not bypass the blood-brain barrier. Systemic administration of hypertonic saline (HTS) enhances delivery of intrathecal therapeutics into the neuropil, but its effect on solute clearance from the brain remains unknown. Here, we developed a dynamic in vivo single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging platform to study the effects of HTS on whole-body distribution of the radiolabeled tracer 99mTc-diethylenetriaminepentaacetic acid (DTPA) administered through intracisternal, intrastriatal, or intravenous route in anesthetized rats. Co-administration of systemic HTS increased intracranial exposure to intracisternal 99mTc-DTPA by ∼80% during imaging. In contrast, HTS had minimal effects on brain clearance of intrastriatal 99mTc-DTPA. In sum, SPECT/CT imaging presents a valuable approach to study glymphatic drug delivery. Using this methodology, we show that systemic HTS increases intracranial availability of cerebrospinal fluid-administered tracer, but has marginal effects on brain clearance, thus substantiating a simple, yet effective strategy for enhancing intrathecal drug delivery to the brain.

Effects of 7.2% hypertonic saline solution on cardiovascular parameters and endogenous arginine vasopressin secretion in euvolemic isoflurane-anesthetized horses.

To compare the effects of 7.2% hypertonic and 0.9% isotonic saline (sodium chloride) solutions on cardiovascular parameters and plasma arginine vasopressin (AVP) concentrations in healthy, isoflurane-anesthetized horses. 8 healthy horses. In a prospective, randomized, crossover study, horses were anesthetized with isoflurane twice with a 14-day washout period between anesthetic episodes. While anesthetized, horses received a bolus (4 mL/kg) of 7.2% hypertonic saline solution (HS) or 0.9% isotonic saline solution (IS). Heart rate; systolic, mean, and diastolic arterial blood pressures; and central venous and pulmonary artery pressures were measured every 5 minutes; cardiac output was measured by means of thermodilution every 15 minutes. Systemic vascular resistance (SVR) was calculated. Blood samples were collected before and during anesthesia, and plasma AVP concentrations were determined with a validated ELISA. Data were analyzed with repeated-measures ANOVA and Pearson correlations. HS caused an increase in systolic (P = .003) and mean (P = .023) arterial blood pressures that lasted for 30 minutes. The SVR was increased (P < .001) for 45 minutes with HS compared with the SVR after IS administration. Mean plasma AVP concentration increased (P = .03) 15 minutes after HS administration, with the increase lasting 90 minutes. A bolus of HS resulted in a clinically relevant increase in blood pressure in healthy, isoflurane-anesthetized horses. This effect was attributed to volume recruitment and an increase in SVR. Administration of HS offers an option for improving arterial blood pressure in anesthetized horses.

The Incidence and Risk Factors of Hyponatremia in Pulmonary Tuberculosis.

ContextThe syndrome of inappropriate antidiuresis (SIAD) with euvolemic hyponatremia may occur in patients with pulmonary tuberculosis (PTB), but little is known about the clinical characteristics of SIAD-associated hyponatremia in PTB patients.ObjectiveThis study aimed to investigate the frequency and risk factors of hyponatremia in PTB patients.MethodsIn this retrospective chart review, we examined the incidence and severity of hyponatremia in PTB patients. Multivariate analysis was conducted to identify risk factors for hyponatremia in PTB patients.ResultsOf the 161 patients who were screened, after excluding patients with hyperglycemia and renal failure, we enrolled and analyzed data from 113 participants. Hyponatremia occurred in 40.7% patients (<135 mEq/L). Univariate analysis revealed that the presence of hyponatremia was associated with old age, female sex, low body mass index, high glycosylated hemoglobin, C-reactive protein (CRP), and N-terminal pro-brain natriuretic peptide. Multivariable analysis indicated that hyponatremia was strongly associated with old age (odds ratio, 1.06; 95% CI, 1.03-1.09 for every 1-year age increase) and CRP values (odds ratio, 1.15; 95% CI, 1.03-1.30 for every 1-mg/dL increase in CRP). For 86 patients with blood cortisol measurements, the cortisol level was significantly high in the hyponatremia group.ConclusionsHyponatremia was less frequently associated with hyperglycemia, heart failure, renal failure, and other diseases that cause euvolemic hyponatremia; thus, PTB patients may have euvolemic hyponatremia due to SIAD. Administration of hypertonic saline or fluid restriction should be considered in PTB patients with hyponatremia.