Eliminating the need for preoperative intravenous hyperhydration: Sodium thiosulfate as nephrotoxicity prevention in HIPEC-treated patients - A retrospective analysis.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal metastases. However, HIPEC with cisplatin is associated with renal toxicity. Sodium thiosulfate (ST) has been shown to prevent cisplatin-induced toxicity. METHODS: A retrospective, single-center analysis of patients treated curatively for peritoneal surface malignancy, who underwent cytoreductive surgery with cisplatin-based HIPEC between 2015 and 2020. Patients were categorized into three groups based on the management of cisplatin-induced renal toxicity: preoperative hyperhydration alone (PHH), preoperative hyperhydration with ST (PHH + ST), and ST alone. Renal function and complications, in terms of Acute (AKI) and chronic kidney injury (CKI), were monitored and analyzed during 3 postoperative months. RESULTS: This study included 220 consecutive patients. Mean serum creatinine levels were 95, 57 and 61 mmol/L, for PHH, PHH + ST and ST groups, respectively (p < 0.001). Glomerular Filtration Rate (GFR) were 96, 94 and 78 ml/min/1.73 m2, respectively (p < 0.001). AKI and CKI are respectively for PHH, PHH + ST and ST groups were 21 % (n = 46), 1 % (n = 2) and 0 % vs 19 % (n = 42), 0 % and 0 % (p < 0.001), for pairwise analysis did not show any difference between PHH + ST and ST alone combination, regarding nephrological outcomes. All patients were followed 3 months postoperatively. CONCLUSION: There is no need for preoperative hyperhydration when sodium-thiosulfate is used to prevent cisplatin-induced nephrotoxicity in patients undergoing cytoreductive surgery with HIPEC. These findings have implications for improving and simplifying the management of patients with peritoneal metastases undergoing HIPEC with cisplatin.

Water intoxication in the course of stimulation of labor with oxytocin.

The antidiuretic attribute of oxytocin can cause many side effects. Water intoxication is one of the most serious complications. The authors describe a case of water intoxication with neurological symptoms and severe hyponatraemia in the course of natural labor stimulated by oxytocin in a low-dose regimen.

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.

Loss of body weight is accompanying cellular brain edema induced by water intoxication in the rat.

Induction of cellular cerebral edema (CE) was achieved by a standard method of water intoxication which consisted of fractionated intraperitoneal administration of distilled water (DW) together with the injection of desmopressin (DP). Using metabolic cage, fluid and food balance was studied in two groups of eight animals: group C - control; group CE - cellular edema induced by water intoxication. For each rat the intake (food pellets and water) and excretion (solid excrements and urine) were recorded for 48 h together with the initial and final body weight. CE animals consumed significantly less food, drank less water and eliminated the smallest amount of excrements. The induction of cellular cerebral edema was accompanied with a significant loss of body weight (representing on average 13 % of the initial values) mainly due to a reduction of food intake. This phenomenon has not yet been reported.

Exogenous Vasopressin-Induced Hyponatremia in Patients With Vasodilatory Shock: Two Case Reports and Literature Review.

Vasopressin has gained wide support as an adjunct vasopressor in patients with septic shock. This agent exerts its vasoconstriction effects through smooth muscle V1 receptors and also has antidiuretic activity via renal V2 receptors. This interaction with the renal V2 receptors results in the integration of aquaporin 2 channels in the apical membrane of the renal collecting duct leading to free water reabsorption. Thus, water intoxication with subsequent hyponatremia, although rare, is a potentially serious side effect of exogenous vasopressin administration. We present 2 patients who developed hyponatremia within hours of initiation of vasopressin infusion. Extensive diuresis followed its discontinuation with subsequent normalization of serum sodium. One of the patients required the use of hypertonic saline for more rapid normalization of serum sodium due to concerns for potential seizure activity. A review of the literature relevant to the incidence of vasopressin-induced hyponatremia is provided as well as discussion on additional factors relevant to septic shock that should be considered when determining the relative risk of hyponatremia in patients receiving vasopressin.

Neuronal excitability after water intoxication in young rats.

OBJECTIVES: Our previous experiments with animal models revealed that water intoxication induces brain oedema and opens plasma membranes. Present study is aimed to determine whether the standard method of hyperhydration can influence cerebral microenvironment also in young rats. Neuronal functions were tested by standard electrical cortical stimulation. METHODS: Hyperhydration was induced by administration of distilled water (DW) intraperitoneally. Three groups of young rats were used: 12, 25, and 35-day-old. Cortical excitability was tested 19 to 20 hours after DW administration by electrical stimulation of the sensorimotor cortex with intensity necessary to elicit cortical afterdischarges (AD). Water content in the brain was estimated by dry/wet ratio and value of natremia by standard biochemical examination. Control animals of the same age groups were tested in the same way, only they did not receive DW. RESULTS: Brain water content in hyperhydrated animals was smaller than in controls in all studied age groups. Natremia was the same (normal) in both the hyperhydrated and control animals aged 25 days. Excitability of cortical neurons in young hyperhydrated animals was significantly inhibited in comparison to the same age groups of controls. CONCLUSION: Hyperhydration induced in young rats (12, 25, 35-day-old) had different effects than in adults. Absence of hyponatremia, lower water content in the brain and significant inhibition of cortical excitability can be explained on the basis of ontogenetically dependent aquaporine expression (AQP 4) and different activity of ionic membrane transporters.

Severe water intoxication secondary to the concomitant intake of non-steroidal anti-inflammatory drugs and desmopressin: a case report and review of the literature.

Most of the clinical data on the safety profile of desmopressin (DDAVP), which is an effective treatment for both polyuric conditions and bleeding disorders, originate from studies on the tailoring of drug treatment, whereas few reports exist describing severe side effects secondary to drug-drug interaction. We herein describe a case of severe hyponatremia complicated by seizure and coma due to the intake of non-steroidal anti-inflammatory drugs (NSAIDs) in a patient on DDAVP replacement therapy for central diabetes insipidus (DI). A 50-yr-old Caucasian man, with congenital central DI, developed an episode of generalized tonic-clonic seizure, resulting in coma immediately after being admitted to the Emergency Unit for weakness and emesis. Based on his medical history and clinical findings, water intoxication secondary to ketoprofen intake (200 mg/day for the last 3 days) concomitant with DDAVP replacement therapy (Minirin(®) 60 mcg 4 tablets a day) was hypothesized as being the cause of the severe euvolemic hypotonic hyponatremia (natremia 113 mEq/l, plasma osmolality 238 mOsm/Kg). After standard emergency procedures, appropriate gradual restoration of serum sodium levels to the normal range was achieved in 72 hours. Hydratation was maintained according to water excretion and desmopressin therapy was re-introduced. We discuss this case report in the context of the published literature. The present report first highlights the potentially life-threatening side effects associated with over-the-counter NSAIDs during DDAVP replacement therapy for central DI. Risks and benefits of co-treatment should be carefully considered and therapeutic alternatives to NSAIDs should be recommended to patients with central DI in order to improve DDAVP safety.

Two unusual pediatric cases of dilutional hyponatremia.

Dilutional hyponatremia, although not uncommon, is an underestimated problem in the pediatric population. In most cases, it results from excessive hydration or water retention, also described as the so-called water intoxication. One of the most known causes is the use of desmopressin in enuretic children. This drug enhances the free water reabsorption in the renal collecting ducts. The addition of the anticholinergic agent oxybutynin aggravated the condition by causing a dry mouth with excessive thirst and water intake in our first case. Dietary water overconsumption, either voluntary or involuntary, is a phenomenon seen in formula-fed babies. But in our second case, a game involving forced ingestion of large amounts of water had serious consequences including hyponatremia-related coma. An effort should therefore be made to inform caretakers about the risks of these games. These cases, provoked by rather unusual and peculiar causes, illustrate again that electrolytes and especially serum [Na(+)] are key points to be determined in a child with diminished consciousness. Moreover, an accurate history including the intake of medication and dietary information should be made.

Targeted overexpression of endothelin-1 in astrocytes leads to more severe cytotoxic brain edema and higher mortality.

Transgenic mice overexpressing endothelin-1 (ET-1) in astrocytes (GET-1) displayed more severe brain edema and neurologic dysfunction after experimental ischemic stroke. However, it was not clear whether astrocytic ET-1 contributed to cytotoxic or vasogenic edema associated with stroke. In this study, the role of astrocytic ET-1 in cytotoxic edema and brain injury was investigated. Upon acute water intoxication, the GET-1 mice had a lower survival rate and more severe neurologic deficits. Such an exacerbated condition in the GET-1 mice may be a result of a significant increase in cerebral water content and increased expression of the water channel protein, aquaporin 4 (AQP-4). The GET-1 mice treated with OPC-31260, a nonpeptide arginine vasopressin V(2) receptor antagonist, were alleviated from the cerebral water accumulation and neurologic deficit during the early time period after water intoxication. In addition, a significant reduction of AQP-4 expression was observed in astrocytic end-feet AQP-4 in the hippocampus of the GET-1 mice treated with OPC-31260. Therefore, ET-1-induced AQP-4 expression and cerebral water accumulation are the key factors in brain edema associated with acute water intoxication. The V(2) receptor antagonist, OPC-31260, may be one of the effective drugs for the early treatment of ET-1-induced cytotoxic edema and brain injury.

[The role of factors determining rheological properties of blood in mechanisms of adaptation and damage in water imbalance].

The study was made of hematological, rheological and biochemical blood parameters of white male rats in daily intramuscular injection of 0.02 mcg of desmopressin and regular periodic hyperhydration of the organism achieved by introduction of 10% water loading within 3, 6, 9 days. The results evidence for significant action of desmopressin on liquid homeostasis not only by antidiuretic effects on the kidneys, by changing the condition of connecting tissue of the matrix as shown by a marked rise of acid GAG in plasm but also by influence on rheological properties of blood which is an important element of management of transcapillary exchange in tissue microregions.

Assessment of hydration by means of bioelectrical impedance and arm muscle area during growth hormone (GH) replacement therapy: A prospective study of 130 GH-deficient patients.

OBJECTIVE: Growth hormone (GH)-deficiency is associated with a reduced extracellular volume (ECV), whereas GH replacement may cause fluid retention. We have tested a simple method to assess hydration in GH-deficient patients (GHD) based on concomitant measurements of body resistance by bioelectrical impedance analysis (BIA), and arm muscle area (AMA). DESIGN: We prospectively followed 130 patients (54 females, 76 males) with adult-onset GHD before and during 1-5 years GH replacement therapy. METHODS: Concomitant measurements of body resistance and AMA were done on four occasions: before treatment, after one month and one year of treatment, and at the most recent visit. Based on normative data obtained in 142 women and 84 men an inverse relationship was documented between body resistance and AMA. Assuming that linear height and the concentration of electrolytes remain constant, body resistance at a given AMA will reflect specific hydration. RESULTS: In the patients a gender-specific inverse correlation between body resistance and AMA existed, which was different from the control group and changed during GH replacement. A deviation between predicted (based on normative data) and measured body resistance at a given AMA was recorded in the patients before and during therapy compatible with relative dehydration in the untreated state followed by an increase in hydration during therapy. CONCLUSIONS: Concomitant measurements of BIA and AMA in GHD patients may provide a non-invasive and simple means to estimate hydration before and during GH replacement.

Acute pulmonary oedema following oxytocin administration: a life threatening complication.

Water Intoxication is not a common complication of oxytocin infusion. A 26 years primigravida developed acute onset severe pulmonary oedema in postpartum period to whom oxytocin was infused for the induction of labour and to prevent postpartum haemorrhage. The relative role of oxytocin and of electrolyte-free fluids in the pathogenesis of this problem is discussed.

Desmopressin toxicity due to prolonged half-life in 18 patients with nocturnal enuresis.

PURPOSE: Desmopressin has been used extensively for primary nocturnal enuresis and it is associated with a low incidence of adverse effects. The only reported serious side effect is seizure or altered levels of consciousness resulting from water intoxication, which has been reported for the nasal spray. We describe 18 children with clinical symptoms of water intoxication due to the prolonged bioactivity of desmopressin nasal spray. MATERIALS AND METHODS: We evaluated 18 patients with clinical suspicion of prolonged desmopressin bioactivity during treatment with intranasal desmopressin for primary nocturnal enuresis. The control group consisted of 50 children with primary nocturnal enuresis and proven nocturnal polyuria who were treated with the same desmopressin regimen. RESULTS: All patients had prolonged maximal urinary concentration capacity and delayed restoration of daytime diluting capacity (p <0.01). Of the patients 15 had the characteristic clinical symptoms of water intoxication with vomiting, headache, decreased consciousness and hyponatremia. We suspect that these symptoms are secondary to prolonged desmopressin bioactivity. CONCLUSIONS: Prolonged desmopressin bioactivity may increase the risk of water intoxication.

Morbidity and mortality associated with vasopressin analogue treatment.

DDAVP is a drug that should be used with caution for each patient individually. Particular care is needed to avoid fluid overload and rapid fluctuations in sodium concentration. Not only families but physicians as well should be educated and aware of the adverse effects of DDAVP, especially in high risk patients. Extreme caution is needed in children with severe neurological and developmental problems who cannot control their fluid intake themselves. Similarly, caution is needed in patients with hypodipsia and DI who have difficulty in balancing water intake and DDAVP dose. The treatment of DI is water; however, DDAVP is given to avoid a large fluid intake which can result in medullary washout. Frequent home monitoring of body weight and regular determinations of serum sodium may help to disclose the early phase of over-hydration or dehydration. DDAVP therapy should be temporarily interrupted during acute illness, febrile episodes, hot days and other conditions with increased water intake. It should be used with considerable caution in patients with cystic fibrosis, or renal or cardiovascular diseases. In patients with enuresis, it is recommended that DDAVP medication should not be continued for longer than 3 months without stopping for 1 week for full reassessment. Fluid intake should be limited 1 hour before and 8 hours after the dose. Generally, undertreatment with vasopressin analogue is safer than overtreatment. A simple measure to avoid overtreatment is to miss one dose once a week; a rapid onset diuresis ('washout' effect) provides considerable reassurance.

Desmopressin associated symptomatic hyponatremic hypervolemia in children. Are there predictive factors?

PURPOSE: Desmopressin is widely used in primary nocturnal enuresis, bleeding disorders, central diabetes insipidus and diagnostic urine concentration testing. Hyponatremic hypervolemia leading to seizures has been reported as a rare but potentially life threatening side effect of desmopressin therapy. We sought to identify factors that predispose patients to hyponatremia and to find predictive factors associated with increased risk of water intoxication. MATERIALS AND METHODS: We report 13 novel cases of desmopressin associated water intoxication and review the literature. A total of 93 instances of symptomatic hyponatremia during desmopressin treatment in children were identified. Specific data were reported in 58 of 93 cases. These 58 cases, in addition to our 13 novel cases, were further analyzed. RESULTS: All children were treated with intranasal or intravenous desmopressin. No patient received oral desmopressin. Younger children are at greater risk for water intoxication than older children. The risk is particularly high at the beginning of desmopressin therapy. A total of 45 patients (63%) had prodromal symptoms, eg nausea, vomiting and headache. In 10 cases (14%) desmopressin was prescribed without an evident need. CONCLUSIONS: Based on this analysis, we conclude that the use of desmopressin should be cautiously considered, careful monitoring should be performed during the initiation of therapy, and particular care should be taken when treating young children and when prodromal symptoms such as nausea, vomiting and headaches occur.