Impacts of Age and Gender on Brain Edema in a Mouse Water Intoxication Model.

Brain edema causes abnormal fluid retention and can be fatal in severe cases. Although it develops in various diseases, most treatments for brain edema are classical. We analyzed the impacts of age and gender on the characteristics of a water intoxication model that induces pure brain edema in mice and examined the model's usefulness for research regarding new treatments for brain edema. C57BL/6J mice received an intraperitoneal administration of 10% body weight distilled water, and we calculated the brain water content by measuring the brain-tissue weight immediately after dissection and after drying. We analyzed 8-OHdG and caspase-3 values to investigate the brain damage. We also applied this model in aquaporin 4 knockout (AQP4-) mice and compared these mice with wild-type mice. The changes in water content differed by age and gender, and the 8-OHdG and caspase-3 values differed by age. Suppression of brain edema by AQP4- was also confirmed. These results clarified the differences in the onset of brain edema by age and gender, highlighting the importance of considering the age and gender of model animals. Similar studies using genetically modified mice are also possible. Our findings indicate that this water intoxication model is effective for explorations of new brain edema treatments.

Infantile Status Epilepticus: A Case of Excessive Water Intake in a Five-Month-Old Girl.

Hyponatremia in children, especially in normal infants below the age of six months, is a common cause of the first onset of afebrile convulsions, which can be rarely associated with water intoxication and can lead to a state of encephalopathy and status epilepticus if not diagnosed and managed properly early. Water intoxication is an uncommon but potentially lethal cause of hyponatremia. We report a five-month-old girl who presented to our hospital with status epilepticus, facial puffiness, cyanosis, and severe hyponatremia secondary to water intoxication. Proper investigations and labs were done, and the patient was managed successfully. The aim of reporting this case is to highlight the importance of water intoxication with secondary status epilepticus in infants below six months of age.

Water insecurity among seasonal agriculture workers: perspectives from Spanish professionals.

BACKGROUND: Migrant seasonal agricultural workers face conditions of material vulnerability such as inadequate housing difficulties prevent access to running water supplies. The purpose of this study is to explore the perceptions of professionals involved in the care and support of seasonal migrant agricultural workers, as it relates to water access and water consumption and their impact on these workers' health, in a context of COVID-19 pandemic. METHODS: A qualitative exploratory and descriptive study was conducted in 2021 as part of a larger research project, based on 63 personal semi-structured interviews with professionals who provided support to seasonal migrant agricultural workers in three Spanish autonomous regions. COREQ checklist was used for reporting. The interviews were recorded, transcribed, and imported into ATLAS.ti-9 for an inductive thematic analysis. RESULTS: The results have been structured into two main themes: (1) Accessing and obtaining water; and (2) Health problems related to water consumption. Seasonal migrant agricultural workers experience barriers to obtaining safe water for hygiene, cleaning, food preparation and drinking. The implementation of regulations to reduce COVID-19 transmission resulted in improved hygiene levels in the migrants' quarters, including access to safe drinking water. CONCLUSION: This study suggests that water insecurity experienced by migrant seasonal agricultural workers in Spain results from their poor living conditions and causes health problems related to a lack of hygiene and the use of unsafe water. Sustainable solutions are needed beyond the pandemic in order to provide migrant workers with adequate living conditions and ensure their water needs are fulfilled.

Oxytocin: physiology, pharmacology, and clinical application for labor management.

Oxytocin is a peptide hormone that plays a key role in regulating the female reproductive system, including during labor and lactation. It is produced primarily in the hypothalamus and secreted by the posterior pituitary gland. Oxytocin can also be administered as a medication to initiate or augment uterine contractions. To study the effectiveness and safety of oxytocin, previous studies have randomized patients to low- and high-dose oxytocin infusion protocols either alone or as part of an active management of labor strategy along with other interventions. These randomized trials demonstrated that active management of labor and high-dose oxytocin regimens can shorten the length of labor and reduce the incidence of clinical chorioamnionitis. The safety of high-dose oxytocin regimens is also supported by no associated differences in fetal heart rate abnormalities, postpartum hemorrhage, low Apgar scores, neonatal intensive care unit admissions, and umbilical artery acidemia. Most studies reported no differences in the cesarean delivery rates with active management of labor or high-dose oxytocin regimens, thereby further validating its safety. Oxytocin does not have a predictable dose response, thus the pharmacologic effects and the amplitude and frequency of uterine contractions are used as physiological parameters for oxytocin infusion titration to achieve adequate contractions at appropriate intervals. Used in error, oxytocin can cause patient harm, highlighting the importance of precise administration using infusion pumps, institutional safety checklists, and trained nursing staff to closely monitor uterine activity and fetal heart rate changes. In this review, we summarize the physiology, pharmacology, infusion regimens, and associated risks of oxytocin.

Rhabdomyolysis Complicated with Hyponatremia Due to Water Intoxication and Severe Aspiration Pneumonia: Description of a Patient with Chronic Schizophrenia and Literature Review.

Hyponatremia due to water intoxication is frequently observed in patients with chronic schizophrenia. We herein present a 49-year-old man who developed schizophrenia at the age of 23 and had been admitted to the closed ward of our hospital for 7 years. He was found by a round nurse standing at the bedside, covering both ears with his hands and making groaning noises. He was disoriented and immediately after being returned to bed, a general tonic-clonic seizure occurred. Severe hyponatremia (Na 104 mEq/L) was noted and intravenous sodium correction was started. A few hours later, due to glossoptosis and massive vomiting, ventilation got worse to the point where he had to be put on a ventilator. On the following day, he developed aspiration pneumonia and antimicrobial treatment was started. In addition, a blood sample taken 36 hours later revealed an extensive elevation of creatine kinase (41,286 U/L), pointing to a possibility of rhabdomyolysis as a complication. Subsequently, the general condition gradually improved with antimicrobial therapy and sodium correction. He eventually recovered without any complications including central pontine myelinolysis. He had no history of polydipsia before this event but it was later found that esophageal stricture triggered complusive fluid intake, resulting in acute hyponatremia, seizure, aspiration pneumonia and rhabdomyolysis. A brief discussion will be provided on the issues surrounding hyponatremia, rhabdomyolysis and schizophrenia.

Treatment of Psychogenic Polydipsia and Hyponatremia: A Case Report.

Psychogenic polydipsia occurs during water or fluid intoxication and can lead to electrolyte disturbances, such as hyponatremia. Hyponatremia can give rise to signs and symptoms, including lethargy, psychosis, seizures, or death. Psychogenic, or primary polydipsia, can be compared to other medical conditions that cause excessive thirst. This case report will focus on the symptoms, disease, and treatment involved in the care and hospitalization of a 30-year-old male patient who reported ingesting up to 40 liters of water a day for the last three years. This patient with psychogenic polydipsia, chronic schizophrenia, and active psychosis was diagnosed with metabolic encephalopathy secondary to severe hyponatremia (day one sodium level: 108 mEq/L). The management goal was to stabilize electrolytes and increase sodium levels without causing osmotic demyelination syndrome. During subsequent hospitalization, the psychiatry team worked towards the normalization of sodium levels and managed behavioral patterns contributing to water consumption. The patient achieved a normal sodium level on day 21 of inpatient psychiatric treatment with the following medication regimen: acetazolamide, candesartan, olanzapine, sodium chloride, and trazodone.

The Catastrophic Effects of Psychogenic Polydipsia: A Case Report.

Patients with hyponatremia are at risk of severe complications including seizures, coma, and death. Psychiatric patients are particularly susceptible to death from hyponatremia due to the association between psychiatric conditions and psychogenic polydipsia, characterized by water intoxication. We report a case of a schizophrenic patient who presented with altered mental status, leading to a differential diagnosis narrowed through clinical investigations to include hypovolemic hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and psychogenic polydipsia. This case underscores the need to inquire about schizophrenic patients' water intake, advocating for a standardized approach. The timely diagnosis of disorders causing electrolyte abnormalities can prevent severe complications and aid in the management of psychiatric patients.

Acute water intoxication in hysteroscopic myomectomy: a rare case report.

Water intoxication is rarely seen in forensic practice and is typically associated with excessive water consumption, amphetamine intake, and child abuse. Iatrogenic water intoxication is rare but usually related to medical disputes. Here, we report a 44-year-old female was admitted to the hospital due to a 3-month history of excessive menstrual bleeding. B-ultrasound revealed multiple substantial intrauterine masses, leading to a diagnosis of multiple uterine fibroids. After admission, she underwent submucous myomectomy, endometrial resection, and transcervical resection of endometrial polyps. During the procedure, the patient suffered dizziness and chest tightness, her blood pressure decreased to 89/52 mmHg, and moist rales were heard in her both lungs; she died despite medical efforts. A forensic autopsy was performed and revealed severe pulmonary edema. Considering the patient's clinical history, acute water intoxication was considered to be the cause of death. This highlights the need for forensic pathologists to be vigilant of postoperative water intoxication, a rare complication in obstetrics, to ensure accurate assessments.

[Hyponatremia : Etiology, diagnosis and acute therapy]. / Hyponatriämie : Ätiologie, Diagnostik und Akuttherapie.

Hyponatremia is one of the most common electrolyte disorders in emergency departments and hospitalized patients. Serum sodium concentration is controlled by osmoregulation and volume regulation. Both pathways are regulated via the release of antidiuretic hormone (ADH). Syndrome of inappropriate release of ADH (SIADH) may be caused by neoplasms or pneumonia but may also be triggered by drug use or drug abuse. Excessive fluid intake may also result in a decrease in serum sodium concentration. Rapid alteration in serum sodium concentration leads to cell swelling or cell shrinkage, which primarily causes neurological symptoms. The dynamics of development of hyponatremia and its duration are crucial. In addition to blood testing, a clinical examination and urine analysis are essential in the differential diagnosis of hyponatremia.

Seizure from water intoxication following bowel preparation: a case report.

BACKGROUND: Bowel preparation prior to colonoscopic examination is generally considered a safe process. Hyponatremia is a complication that has been reported in literature during bowel preparation. Individuals who develop severe symptomatic hyponatremia are often older and have comorbidities such as hypothyroidism, chronic kidney disease, or adrenal insufficiency. However, other mechanisms and circumstances can also lead to this potentially fatal complication. CASE PRESENTATION: We present a unique case of a patient who developed seizure prior to colonoscopy due to acute hyponatremia without any well-known risk factors. With the subsequent diagnosis of water intoxication, the use of desmopressin was believed to have contributed to this serious complication. CONCLUSION: In addition to the use of certain well-documented medications and the presence of comorbidities that can lead to hyponatremia, clinicians should also be aware of the use of desmopressin as an important risk factor. Thorough history taking can guide individualized bowel preparation regimens to minimize the risk of undesired complications.

AQP4-A25Q Point Mutation in Mice Depolymerizes Orthogonal Arrays of Particles and Decreases Polarized Expression of AQP4 Protein in Astrocytic Endfeet at the Blood-Brain Barrier.

Aquaporin-4 (AQP4) is characterized by the formation of orthogonal arrays of particles (OAPs) comprising its M1 and M23 isoforms in the plasma membrane. However, the biological importance of OAP formation is obscure. Here, we developed an OAP depolymerization male mouse model by transgenic knock-in of an AQP4-A25Q mutation. Analyses of the mutant brain tissue using blue native polyacrylamide gel electrophoresis, super-resolution imaging, and immunogold electron microscopy revealed remarkably reduced OAP structures and glial endfeet localization of the AQP4-A25Q mutant protein without effects on its overall mRNA and protein expression. AQP4A25Q/A25Q mice showed better survival and neurologic deficit scores when cerebral edema was induced by water intoxication or middle cerebral artery occlusion/reperfusion. The brain water content and swelling of pericapillary astrocytic endfeet processes in AQP4A25Q/A25Q mice were significantly reduced, functionally supporting decreased AQP4 protein expression at the blood-brain barrier. The infarct volume and neuronal damage were also reduced in AQP4A25Q/A25Q mice in the middle cerebral artery occlusion/reperfusion model. Astrocyte activation in the brain was alleviated in AQP4A25Q/A25Q mice, which may be associated with decreased cell swelling. We conclude that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.SIGNIFICANCE STATEMENT Aquaporin-4 (AQP4) is characterized by orthogonal arrays of particles (OAPs) comprising the M1 and M23 isoforms in the membrane. Here, an OAP depolymerization male mouse model induced by AQP4-A25Q mutation was first established, and the functions of OAP depolymerization in cerebral edema have been studied. The results revealed that AQP4 lost its OAP structure without affecting AQP4 mRNA and protein levels in AQP4-A25Q mice. AQP4-A25Q mutation mice has neuroprotective effects on cerebral edema induced by water intoxication and middle cerebral artery occlusion/reperfusion through relieving the activation of astrocytes and suppressed microglia-mediated neuroinflammation. We concluded that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.

Acute water intoxication in an adult man: 'dental hyponatraemia' revisited.

The differential diagnosis of hyponatraemia is notoriously wide. However, only a minority is acute, ie develops in less than 48 hours. We describe an unusual cause of water intoxication due to toothache. A 30-year-old man with no medical history of note presented in an acute confusional state. Laboratory results disclosed profound hyponatraemia. Urinary indices were consistent with overdrinking, but in the absence of a reliable history, other aetiologies had to be excluded. This case highlights the benefit of a structured approach in the assessment of electrolyte disturbances.

The mysterious death of the beer drinking champ: potential role for hyperacute water loading and acute hyponatremia.

Hyponatremia is acute when present for <48 h. Most cases of acute hyponatremia involve both excess free water intake and an at least partial urinary free water excretion defect. By contrast, hyperacute water intoxication may result from a large excess electrolyte-free water intake in such a short time that properly working urinary free water excretion mechanisms cannot cope. A hyperacute decrease in serum sodium may lead to death before medical intervention takes place. Well-documented cases have been published in the military medicine literature. In addition, news reports suggest the existence of cases of voluntary ingestion of excess free water by non-psychiatric individuals usually during 'dare' activities. Education of the public is required to prevent harm from these high-risk activities. Adequate training of emergency medical units may prevent lethal outcomes. Spanish media reported the case of a male who died following his triumph in a 20-min beer drinking contest. 'From a heart attack. Man dies after drinking six litres of beer in a contest' ran the news. We now review the physiology underlying hyperacute water intoxication and discuss the potential contribution of hyperacute water loading and acute hyponatremia to the demise of this patient.

Case Report: A Patient With Neuroleptic Malignant Syndrome, Water Intoxication and Hyponatremia Associated With Severe Cerebral Edema and Coma.

Background: Water intoxication is typically caused by primary or psychogenic polydipsia that potentially may lead to fatal disturbance in brain functions. Neuroleptic malignant syndrome (NMS) is a serious complication induced by administration of antipsychotics and other psychotropic drugs. The combination of inappropriate secretion of antidiuretic hormone (SIDAH), NMS and rhabdomyolysis have been rarely reported. Our patient also developed severe water intoxication. Case presentation: Herein we report a comatose case of NMS complicated with water intoxication, syndrome of SIADH and rhabdomyolysis. This patient had severe cerebral edema and hyponatremia that were improved rapidly by the correction of hyponatremia within a couple of days. Conclusions: Malignant neuroleptic syndrome water intoxication, SIADH and rhabdomyolysis can occur simultaneously. Comatose conditions induced by cerebral edema and hyponatremia can be successfully treated by meticulous fluid management and the correction of hyponatremia.

High- vs low-dose oxytocin in lean and obese women: a double-blinded randomized controlled trial.

BACKGROUND: Women with obesity are likely to experience longer lengths of labor and are at an increased risk of cesarean delivery. We hypothesized that high-dose oxytocin would decrease the time to delivery in a cohort of women with obesity undergoing induction of labor. OBJECTIVE: This study aimed to assess whether women with obesity benefited from higher doses of oxytocin for induction of labor. STUDY DESIGN: A double-blinded randomized controlled trial was conducted to evaluate the effect of low-dose and high-dose oxytocin on length of labor. We recruited women who were undergoing induction of labor at ≥37 weeks of gestation. Patients were randomly assigned in a 1:1 ratio to receive low-dose or high-dose oxytocin stratified by obesity level (obese and lean). The primary outcome was length of time (minutes) to vaginal delivery. The secondary outcomes included overall cesarean delivery rate, cesarean delivery for labor arrest, maximum oxytocin infusion rate, oxytocin infusion discontinuation, oxytocin infusion decrease, blood loss, neonatal intensive care unit admission, and neonatal Apgar scores. RESULTS: A total of 140 patients were randomized into receiving low-dose and high-dose oxytocin stratified into obese and lean stratum (35 for all strata). The primary outcome, time to vaginal delivery, was similar between the low-dose and high-dose oxytocin groups in the lean stratum (796 [±411] vs 694 [±466] minutes; P=.363) and the stratum with obesity (715 [±497] vs 762 [±594] minutes; P=.733). Kaplan-Meier curves between the low-dose and high-dose oxytocin groups were not significantly different in the lean stratum (P=.391) and the stratum with obesity (P=.692). There were 5 cesarean deliveries (14.29%) in the low-dose oxytocin lean stratum vs 2 cesarean deliveries (5.71%) in the high-dose oxytocin lean stratum (P=.232). There were 4 cesarean deliveries (11.43%) in the low-dose oxytocin stratum with obesity vs 1 cesarean delivery (2.86%) in the high-dose oxytocin stratum with obesity (P=.164). There was no difference in the incidence of postpartum hemorrhage between the lean stratum (P=0.526) and the stratum with obesity (P=0.212). There was no difference in mean estimated blood loss between the lean stratum (P=.472) and the stratum with obesity (P=.215). CONCLUSION: There was no difference in time to delivery between the low-dose and high-dose oxytocin protocols in either the lean cohorts or cohorts with obesity undergoing induction of labor. We did observe a trend toward a lower rate of cesarean delivery in both lean women and women with obesity when high-dose oxytocin was used.

Hypertonic Saline for Hyponatremia: Meeting Goals and Avoiding Harm.

Hypertonic saline has been used for the treatment of hyponatremia for nearly a century. There is now general consensus that hypertonic saline should be used in patients with hyponatremia associated with moderate or severe symptoms to prevent neurological complications. However, much less agreement exists among experts regarding other aspects of its use. Should hypertonic saline be administered as a bolus injection or continuous infusion? What is the appropriate dose? Is a central venous line necessary? Should desmopressin be used concomitantly and for how long? This article considers these important questions, briefly explores the historical origins of hypertonic saline use for hyponatremia, and reviews recent evidence behind its indications, dosing, administration modality and route, combined use with desmopressin to prevent rapid correction of serum sodium, and other considerations such as the need and degree for fluid restriction. The authors conclude by offering some practical recommendations for the use of hypertonic saline.

Acute Water Intoxication With Resultant Hypo-Osmolar Hyponatremia Complicated by Hypotension Secondary to Diffuse Third-Spacing.

Hypotonic hyponatremia secondary to acute water intoxication is most commonly associated with primary polydipsia in the setting of psychiatric illness. However, in certain circumstances, otherwise healthy individuals can be compelled to consume large enough volumes of water to overwhelm the kidney's dilutional capacity of urine and cause a potentially life-threatening rapid decline in serum sodium. We present such a case of a 20-year-old basic military trainee with acute symptomatic hypotonic hyponatremia after drinking five to six liters of water prior to urine drug testing. The clinical manifestations of this disorder are non-specific and can be seen with many different pathologic processes, presenting a diagnostic challenge to the emergency clinician. This challenge can be further complicated by unclear or unobtainable history depending on clinical presentation. The authors will discuss key diagnostic and treatment elements of this potentially life-threatening disease to encourage clinicians to utilize social history when evaluating cases of acute water intoxication and resultant symptomatic hypotonic hyponatremia.

Neuronal Swelling: A Non-osmotic Consequence of Spreading Depolarization.

An acute reduction in plasma osmolality causes rapid uptake of water by astrocytes but not by neurons, whereas both cell types swell as a consequence of lost blood flow (ischemia). Either hypoosmolality or ischemia can displace the brain downwards, potentially causing death. However, these disorders are fundamentally different at the cellular level. Astrocytes osmotically swell or shrink because they express functional water channels (aquaporins), whereas neurons lack functional aquaporins and thus maintain their volume. Yet both neurons and astrocytes immediately swell when blood flow to the brain is compromised (cytotoxic edema) as following stroke onset, sudden cardiac arrest, or traumatic brain injury. In each situation, neuronal swelling is the direct result of spreading depolarization (SD) generated when the ATP-dependent sodium/potassium ATPase (the Na+/K+ pump) is compromised. The simple, and incorrect, textbook explanation for neuronal swelling is that increased Na+ influx passively draws Cl- into the cell, with water following by osmosis via some unknown conduit. We first review the strong evidence that mammalian neurons resist volume change during acute osmotic stress. We then contrast this with their dramatic swelling during ischemia. Counter-intuitively, recent research argues that ischemic swelling of neurons is non-osmotic, involving ion/water cotransporters as well as at least one known amino acid water pump. While incompletely understood, these mechanisms argue against the dogma that neuronal swelling involves water uptake driven by an osmotic gradient with aquaporins as the conduit. Promoting clinical recovery from neuronal cytotoxic edema evoked by spreading depolarizations requires a far better understanding of molecular water pumps and ion/water cotransporters that act to rebalance water shifts during brain ischemia.