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.

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.

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.

Predictors of Infused Distending Fluid Volume in Hysteroscopic Myomectomy.

Background and Objectives: The use of a bipolar resectoscope has become popular due to the lower risk of hyponatremia. However, gynecologists might overlook the risk of water intoxication. Water intoxication is associated with the infusion of distending fluid. We were interested in the prediction of the infused distending fluid volume in the era of bipolar hysteroscopy. Thus, the aim of this study was to identify the predictors of the infused distending fluid volume for hysteroscopic myomectomy. Materials and Methods: All consecutive women who underwent monopolar (n = 45) or bipolar (n = 137) hysteroscopic myomectomy were reviewed. Results: Myoma diameter (cm, coefficient = 680 mL, 95% confidence interval (CI) = 334-1025 mL, p <0.001) and bipolar hysteroscopy (coefficient = 1629 mL, 95% CI = 507-2752 mL, p = 0.005) were independent predictors of infused distending fluid volume. A myoma diameter ≥4.0 cm was the optimal cutoff value to predict the presence of >5000 mL of infused distending fluid. One woman in the bipolar group developed life-threatening water intoxication. Conclusions: Myoma diameter is associated with an increase in infused distending fluid volume, especially for myomas ≥4 cm. Meticulous monitoring of the infused distension fluid volume is still crucial to avoid fluid overload during bipolar hysteroscopic myomectomy.

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 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.

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.

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.

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.

A Rare Case of Water Intoxication in Unusual Chiropratic Prescription: A Medico-Legal Analysis Due to Alleged Malpractice.

Introduction: Water intoxication is a well-recognized cause of symptomatic hyponatremia, whose often fatal consequences are de-scribed in a wide variety of conditions such as psychiatric disorders, metabolic dysfunctions, child abuse, drug abuse and several medical procedures. The case: We here report a rare case of a 67-year-old woman with severe acute hyponatremia due to an excessive voluntary water intake - 14 litres in two days - following a chiropractic prescription. The patient developed sudden severe symptoms, including water retention, sensory alteration, altered mental status and tonic-clonic seizures. She was thus admitted to the Intensive Care Unit with a diagnosis of coma due to electrolyte alterations following water intoxication. Conclusion: The evaluation, in the present case, of the medico-legal implications related to malpractice involving a practitioner of Complementary and Alternative Medicine, led to the admission of a professional liability of the chiropractor.

Life-threatening acute water intoxication in a woman undergoing hysteroscopic myomectomy: a case report and review of the literature.

BACKGROUND: Acute water intoxication after hysteroscopy is a rare, life-threatening condition, often accompanied with delayed diagnosis owing to masked symptoms because of general anesthesia. CASE PRESENTATION: Herein we presented a 39-year-old female who presented with cardiac arrest after hysteroscopic myomectomy because of acute water intoxication and survived after extracorporeal membrane oxygenation, continuous venous-venous hemofiltration, and aggressive high sodium fluid resuscitation. CONCLUSION: Failure to recognize and treat this condition appropriately may lead to potentially lethal cardiopulmonary complications.

Sounds unrealistic: an adolescent girl with anorexia nervosa consumes 19 L of fluid in a few hours: what happens to the physiology?

BACKGROUND: Adolescents with eating disorders (EDs) may present not only with abnormal eating behaviors but also with abnormal drinking behaviors varying widely. These behaviors include water loading to cheat on weight measurements, to feel full and suppress appetite and/or to induce vomiting; as well as restricting fluid intake in addition to food. METHOD: We present a 16-year-old female adolescent with anorexia nervosa restrictive type and major depressive disorder who was hospitalized due to acute food refusal and developed generalized seizures due to dilutional hyponatremia in consequence of consuming excessive amount of water. Psychiatric diagnoses were made according to 'The Diagnostic and Statistical Manual of Mental Disorders' (5th ed.; DSM-5) criteria. RESULTS: After starting nutritional rehabilitation with a low calorie meal plan to avoid refeeding syndrome, a weight gain of 2 kg was noted in the second day of hospitalization. At the bedside visit, she was observed in a disoriented manner and consecutively in seconds, lost consciousness with a generalized tonic-clonic seizure lasting 2 min. Her serum sodium level was measured as 116 mEq/L, which was normal at the time of admission. It was later learned that she secretly ingested 19 L of water in a short amount of time. She regained consciousness and no further seizures were observed after intravenous sodium deficit correction and fluid restriction therapy. Her serum sodium level was normalized (137 mEq/L) within 12 h. CONCLUSION: A thorough clinical assessment of hydration and drinking behaviors as well as eating behaviors is essential for patients with EDs to avoid serious medical complications with high mortality and morbidity during follow-up. It is interesting that this amount of fluid consumption in such a short period of time did not present to the clinic with vomiting, gastric dilatation or bowel irrigation symptoms in a case with acute food refusal and restriction for a year, instead absorbed very quickly causing acute and severe symptomatic hyponatremia with generalized seizures.

A loss of consciousness in a teenage girl with anorexia nervosa, due to polydipsia: case report and a minireview.

PURPOSE: Anorexia nervosa is a chronic disease which may result in various complications. In pediatric clinical practice, it is common to observe complications related to progressive cachexia caused by malnutrition; however, cases of severe complications, like electrolyte disorders, which represent a direct threat to life, due to polydipsia, are rarely observed. The purpose of this study is to highlight that excessive drinking is of primary importance in anorexia nervosa patients, as it can result in severe medical complications, including increased risk of death. METHODS: We report the case of a 13-year-old girl with anorexia nervosa, who was referred to hospital with seizures, disorders of consciousness, and cardiorespiratory failure. RESULTS: The unstable condition of the patient was attributed to hyponatremia (119 mmol/l), decreased serum osmolality (248 mmol/kg), and decreased urine osmolality (95 mmol/kg) caused by polydipsia (water intoxication) and persistent vomiting. The presented girl was drinking large amounts of water prior to a weigh-in to falsify her low body weight. CONCLUSIONS: Polydipsia is a common problem reported by patients with eating disorders, but one which rarely leads to serious clinical complications, due to severe hyponatremia. This case underscores the importance of careful evaluation of fluid intake and the need for regular monitoring of serum electrolytes in patients with anorexia nervosa. All clinicians treating patients with such disease, as well as the parents of sick children, should be familiar with this life-threatening condition. LEVEL IV: Evidence obtained from multiple time series with or without the intervention, such as case studies.

Characteristics and outcomes of patients with profound hyponatraemia due to primary polydipsia.

OBJECTIVE: Hyponatraemia due to excessive fluid intake (ie primary polydipsia [PP]) is common. It may culminate in profound hyponatraemia-carrying considerable risk of morbidity. However, data on patients with PP leading to hyponatraemia are lacking. Herein, we describe the characteristics of polydiptic patients hospitalized with profound hyponatraemia and assess 1-year outcomes. DESIGN: Substudy of the prospective observational Co-MED Study. PATIENTS: Patients with an episode of profound hyponatraemia (≤125 mmol/L) due to PP in the medical emergency were eligible and classified into psychogenic polydipsia (PsyP), dipsogenic polydipsia (DiP) and beer potomania (BP). MEASUREMENTS: Symptoms, laboratory findings and factors contributing to hyponatraemia (comorbidities, medication and liquid intake) were assessed. A 1-year follow-up was performed to evaluate recurrence of hyponatraemia, readmission rate and mortality. RESULTS: Twenty-three patients were included (median age 56 years [IQR 50-65], 74% female), seven had PsyP, eight had DiP and eight had BP. Median serum sodium of all patients was 121 mmol/L (IQR 114-123), median urine osmolality 167 mmol/L (IQR 105-184) and median copeptin 3.6 mmol/L (IQR 1.9-5.5). Psychiatric diagnoses, particularly dependency disorder (43%) and depression (35%), were highly prevalent. Factors provoking hyponatraemia were found in all patients (eg acute water load, medication, stress). During the follow-up period, 67% of patients were readmitted, 52% of these with rehyponatraemia, and three patients (38%) with BP died. CONCLUSION: Patients with PP are more likely to be female and to have addictive and affective disorders. Given the high recurrence, rehospitalization and mortality rate, careful monitoring and long-term follow-up including controls of serum sodium, education and behavioural therapy are needed.

"Bowel prep hyponatremia" - a state of acute water intoxication facilitated by low dietary solute intake: case report and literature review.

BACKGROUND: Symptomatic hyponatremia is considered a rare complication of oral bowel preparation for colonoscopy. The pathophysiology underlying this phenomenon has been widely regarded as a mere sequela of excessive arginine vasopressin (AVP) release. CASE PRESENTATION: This case describes a 61-year old woman who developed acute hyponatremic encephalopathy when preparing for elective outpatient lower endoscopy. She had had negligible oral solute intake for two days and ingested four liters of clear fluid within two hours. On admission, the patient was agitated and had slurred speech. Treatment with hypertonic saline lead to full recovery. A brisk aquaresis confirmed acute dilutional hyponatremia. CONCLUSION: Apart from elevated AVP-levels, the amount and speed of fluid intake and concomitant low-solute intake constitute important risk factors in the development of clinically relevant hyponatremias in patients undergoing colonoscopies. Understanding that the cause of sodium imbalance in this scenario is multifactorial and complex is pivotal to recognizing and ideally preventing this complication, for which we propose the term "bowel prep hyponatremia".

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.

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.

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.

[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.