SIADH and water intoxication related to ecstasy.

Recreational drug use is a significant societal issue and remains a clinical challenge in emergency and critical care departments. We report on a 19-year-old woman admitted to hospital semiconscious and with severe hyponatraemia. Urinalysis was positive for methamphetamine and supported a diagnosis of hyponatraemia related to ecstasy use together with a syndrome of inappropriate antidiuretic hormone secretion (SIADH). The woman was transferred to an intensive care unit, where a hypertonic saline infusion was started. Three hours postadmission she developed polyuria. Follow-up urinalysis at this point was consistent with water intoxication. This case is a reminder that hyponatraemia is a potentially fatal complication after the ingestion of 3,4-methylenedioxymethamphetamine, illustrates the sequential nature of an SIADH and water intoxication and highlights the importance of considering the sequence of onset of hyponatraemia, as the patient may be admitted at any stage.

Methylprednisolone modulates intracranial pressure in the brain cellular edema induced by water intoxication.

Continuous monitoring of the intracranial pressure (ICP) detects impending intracranial hypertension resulting from the impaired intracranial volume homeostasis, when expanding volume generates pressure increase. In this study, cellular brain edema (CE) was induced in rats by water intoxication (WI). Methylprednisolone (MP) was administered intraperitoneally (i.p.) before the start of CE induction, during the induction and after the induction. ICP was monitored for 60 min within 20 h after the completion of the CE induction by fibreoptic pressure transmitter. In rats with induced CE, ICP was increased (Mean+/-SEM: 14.25+/-2.12) as well as in rats with MP administration before the start of CE induction (10.55+/-1.27). In control rats without CE induction (4.62+/-0.24) as well as in rats with MP applied during CE induction (5.52+/-1.32) and in rats with MP applied after the end of CE induction (6.23+/-0.73) ICP was normal. In the last two groups of rats, though the CE was induced, intracranial volume homeostasis was not impaired, intracranial volume as well as ICP were not increased. It is possible to conclude that methylprednisolone significantly influenced intracranial homeostasis and thus also the ICP values in the model of cellular brain edema.

Recurrent rhabdomyolysis in a teenager with psychosis-intermittent hyponatremia-polydipsia syndrome.

OBJECTIVE: To report a case of recurrent hyponatremia and rhabdomyolysis in a teenager with psychogenic polydipsia. CASE SUMMARY: A 16-year-old boy was admitted with recurrent episodes of hyponatremia and rhabdomyolysis secondary to psychogenic polydipsia. He was treated with hypertonic saline, intravenous fluids, and supportive care. DISCUSSION: Psychogenic polydipsia is a condition characterized by compulsive drinking. Severe hyponatremia is a rare, but serious complication in patients with psychogenic polydipsia. Failure in cell volume regulatory mechanisms, defective osmoregulation, defective urinary dilution, and enhanced secretion of vasopressin are believed to play a role in the development of hyponatremia. Rhabdomyolysis can complicate severe hyponatremia, although the exact mechanism is not known. Antipsychotic drugs are also implicated in rhabdomyolysis. CONCLUSIONS: Severe hyponatremia and rhabdomyolysis can complicate psychogenic polydipsia. Patients receiving antipsychotic drugs with concomitant severe hyponatremia need to be monitored for rhabdomyolysis.

[A case of severe exercise-associated hyponatremia]. / Livstruende elektrolytforstyrrelser efter spinning.

The woman presented to the emergency department with lethargy after a spinning marathon. Severe electrolyte disturbances were measured (Na(+) 109 mmol/l, K(+) 3,2 mmol/l, Cl(-) 86, Ca(++) 0,95 mmol/l). A computed tomography showed signs of brain swelling. During her stay in the intensive care unit the patient had a negative fluid balance of 8,000 ml. She was discharged with habitual weight. We present a brief discussion of the genesis and treatment of EAH.

Effect of methylprednisolone on the axonal impairment accompanying cellular brain oedema induced by water intoxication in rats.

OBJECTIVES: Our previous experiments proved that methylprednisolone (MP) can significantly reduce axonal impairment accompanying extracellular oedema induced by the osmotic challenge (load) on the blood-brain barrier (BBB). The aim of the present work was to identify whether MP can affect myelin impairment accompanying intracellular oedema induced by water intoxication. METHODS: For induction of cellular brain oedema, the standard model of water intoxication was chosen. Animals received distilled water in amount corresponding to 15% of the animal's body weight. The volume was divided into three parts and administered intraperitoneally in 8 hours interval. Axonal changes were recognized as signs of myelin disintegration (oedematous distensions, axonal swelling, vesicles, varicosities) at histological sections stained with Black Gold and classified into four grades of myelin degradation. Hippocampal CA1 and CA3 areas and the dentate gyrus were selected for the study. Methylprednisolone was administered either intraperitoneally or intracarotically. Its effect was studied in two different time intervals: in the acute group (30 minutes after hyperhydration and MP application) and in chronic one (1 week after hyperhydration and MP application). RESULTS: In both the acute and chronic groups, cellular oedema induced by water intoxication brought about apparent damage of myelin (compared to control animals p<0.0001). Intracarotic injection of MP was not able to influence myelin integrity changes either in the acute or in chronic group. However, intraperitoneal administration of MP increased the level of myelin deterioration in the acute group (p 0.05), but improved myelin changes in the chronic group (p<0.005). CONCLUSION: The effect of MP on axonal impairment during cellular brain oedema induced by water intoxication differs from that during the extracellular osmotic oedema. In the extracellular oedema, cellular metabolism is not significantly affected and myelin changes can be influenced by the neuroprotective effect of MP. The primary cause of cellular oedema is a disorder of cellular metabolism and myelin impairment is one of the structural consequences of such disorder. That is why the myelin changes are not affected by MP administration in a consistent and specific manner.

Treatment of psychogenic polydipsia with acetazolamide: a report of 5 cases.

OBJECTIVE: Psychogenic polydipsia occurs frequently in patients with chronic psychiatric illness and is often unmanageable. We herein report 5 patients in whom acetazolamide was trialed for this symptom. METHODS: We encountered a case in which polydipsia improved with incidental administration of acetazolamide. We then used this treatment for 4 additional cases of treatment-resistant psychogenic polydipsia, some of which were accompanied by hyponatremia. RESULTS: Acetazolamide improved polydipsia and/or hyponatremia in 4 of the 5 cases. This treatment was well tolerated and allowed 3 of the patients to permanently leave isolation. CONCLUSION: Acetazolamide appears to have a beneficial effect in psychogenic polydipsia.

Management of loop diuretic resistance in the intensive care unit.

PURPOSE: The management of loop diuretic resistance in the intensive care unit (ICU) is reviewed. SUMMARY: Volume overload, a common complication of fluid resuscitation, is frequently encountered in the ICU and is associated with numerous adverse effects, including pulmonary and peripheral edema, acute lung injury, and pleural effusions. Loop diuretics are used to treat volume overload and acute renal failure and to ameliorate their associated complications. When administered intravenously, these drugs induce vigorous and prompt diuresis, which may result in negative fluid balance. This may also result in significant adverse effects, including electrolyte imbalance, ototoxicity, and volume contraction. Prolonged use of loop diuretics may lead to loop diuretic resistance, a frequent observation in the ICU. Three general mechanisms are used to explain loop diuretic resistance: rebound sodium retention, postdiuretic effect, and diuretic braking. While very few agents have joined the armamentarium and no new strategies have been developed to deal with this phenomenon, several options are available to clinicians for managing loop diuretic resistance, including salt restriction, administration of i.v. loop diuretics, continuous infusion of loop diuretics, and combination therapy using loop diuretics and thiazides. CONCLUSION: Loop diuretic resistance presents a challenge for clinicians in the ICU setting. Strategies to improve patients' responsiveness to these agents include fluid and salt restriction, switching from oral to i.v. loop diuretics, increasing diuretic dose, continuous infusion, and combination therapy with thiazides. Several of these strategies may be used concurrently to combat diuretic resistance and promote symptomatic relief of edema in the critically ill patient.

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.

Nephrogenic diabetes insipidus: treat with caution.

Current therapy for congenital nephrogenic diabetes insipidus consists of appropriate water intake coupled with decreased urine output obtained by means of a low-sodium diet and a combination of thiazide diuretics with renal prostaglandins inhibitors or amiloride. We report a case of congenital nephrogenic diabetes insipidus that was complicated by paradoxical water intoxication secondary to liberal water intake and the initiation of hydrochlorothiazide and indomethacin combination therapy. This report emphasizes the importance of evaluating the water balance and of a quick response with strict protocols following the initiation of indomethacin and thiazide diuretics in nephrogenic diabetes insipidus.

Vasopressin dysregulation: hyponatremia, fluid retention and congestive heart failure.

Arginine vasopressin (AVP) plays a central role in the regulation of water and electrolyte balance. Dysregulation of AVP secretion, along with stimulation of AVP V2 receptors, is responsible for hyponatremia (serum sodium concentration <135 mEq/L) in congestive heart failure (CHF). The stimulation of atrial and arterial baroreceptors in response to hypotension and volume depletion results in the nonosmotic release of AVP. The predominance of nonosmotic AVP secretion over osmotic AVP release plays a key role in the development of water imbalance and hyponatremia in CHF and other edematous disorders. The AVP-receptor antagonists are a new class of agents that block the effects of AVP directly at V2 receptors in the renal collecting ducts. AVP-receptor antagonism produces aquaresis, the electrolyte-sparing excretion of water, thereby allowing specific correction of water and sodium imbalance. This review summarizes recent data from clinical trials evaluating the efficacy and safety of these promising agents for the treatment of hyponatremia.

NMDA receptor-antagonistic properties of hyperforin, a constituent of St. John's Wort.

Extracts of the medicinal plant St. John's wort (Hypericum perforatum) are widely used for the treatment of affective disorders. Hyperforin, a constituent of St. John's wort, is known to modulate the release and re-uptake of various neurotransmitters, an action that likely underlies its antidepressive activity. We now report that hyperforin also has N-methyl-D-aspartate (NMDA)-antagonistic effects. Hyperforin (10 microM) was found to inhibit the NMDA-induced calcium influx into cortical neurons. In rat hippocampal slices, hyperforin inhibited the NMDA-receptor-mediated release of choline from phospholipids. Hyperforin also antagonized the increase of water content in freshly isolated hippocampal slices, and it counteracted, at 3 and 10 microM, the increase of water content induced by NMDA. Hyperforin was inactive, however, in two in vivo models of brain edema formation, middle cerebral artery occlusion and water intoxication in mice. In conclusion, hyperforin has NMDA-receptor-antagonistic and potential neuroprotective effects in vitro. This effect may contribute to the therapeutic effectiveness of St. John's wort extracts in some situations, for example, for relapse prevention in alcoholism.

Successful treatment of polydipsia, water intoxication, and delusional jealousy in an alcohol dependent patient with clozapine.

The beneficial effect of clozapine on polydipsia and water intoxication in patients with schizophrenia has been demonstrated many times. The authors report a successful clozapine treatment of polydipsia, intermittent water intoxication, and delusional jealousy of an alcoholic. This is a rare case of clozapine treatment of a non-schizophrenic patient affected by polydipsia.

[Atypical antipsychotic-associated impaired glucose tolerance].

Some reports of impaired glucose tolerance associated with olanzapine (OLZ) treatment have been published before OLZ was marketed in Japan. In Japan, we have been prohibited from using OLZ for patients with diabetes mellitus, since several cases with OLZ-associated impaired glucose tolerance including two deaths from diabetic coma have been reported. Here, we report four cases of OLZ-associated impaired glucose tolerance and review the points to consider in treatment with OLZ. Of our four cases, three cases were new-onset (non diabetes mellitus cases) and the other case was a diabetes mellitus-existent (diabetes mellitus case). In the non DM cases, the time to the onset of impaired glucose tolerance after initiating treatment with OLZ was 8-9 months, and the impaired glucose tolerance immediately improved after discontinuing treatment with OLZ and initiating treatment for diabetes mellitus. Therefore, it is necessary to continue long-term monitoring of the parameters of glucose metabolism for all patients treated with OLZ. Should impaired glucose tolerance develop during treatment with OLZ, treatment with OLZ should be discontinued immediately and treatment for diabetes mellitus should be started if necessary. Although the condition of diabetes mellitus was stable befor initiating treatment with OLZ in the DM case, hyperglycemia developed immediately after initiating treatment with OLZ and the condition remained unstable even after early treatment for diabetes mellitus. Therefore, it is necessary to check for a previous history of diabetes mellitus and hyperglycemia befor initiating treatment with OLZ. Correlations between weight gain and occurrence of impaired glucose tolerance are not clear, so it is necessary to monitor the occurrence of impaired glucose tolerance even in cases without weight gain.

Early diagnosis of central pontine myelinolysis with diffusion-weighted imaging.

Central pontine myelinolysis (CPM) occurs in the setting of rapidly corrected hyponatremia, especially in chronically debilitated patients. Conventional CT and MR imaging findings lag the clinical manifestations of CPM. We present a case in which restricted diffusion was identified within the central pons by using MR diffusion-weighted imaging within 24 hours of onset of patient tetraplegia and before findings were conspicuous with conventional MR imaging sequences (T1, T2, and fluid-attenuated inversion recovery).

Adenosine type 1 receptor antagonists in fluid retaining disorders.

Adenosine is a vasoactive hormone whose action is mediated through at least four receptors. The most prevalent receptors are type 1, which promote vasoconstriction, and type 2, comprised of 2 subtypes (a,b) that promote vasodilation. In the kidney, type 1 receptors located on preglomerular vessels and in the tubule are involved in the regulation of glomerular filtration. Whole body fluid balance is strongly dependent on the ability of the kidney to maintain stable glomerular filtration. Several antagonists to adenosine type 1 receptors have been developed. These agents generate excess fluid (diuresis) and sodium (natriuresis) excretion in control animals and animal models of fluid retention, as well as in normal and oedematous humans. In both animals and humans, these effects are generally achieved without major changes in glomerular filtration. Animal studies have confirmed the location of adenosine type 1 receptors in relevant tissue sites in the kidney. More highly selective antagonists for adenosine type 1 receptors are regularly developed, improving their use in fluid retaining disorders. Clinical trials with these agents have commenced for the treatment of hypertension, renal failure and congestive heart failure, all disorders that include varying levels of fluid retention. The clinical trial results have been mixed. The early results with congestive heart failure suggest great promise for these agents, whereas trials in hypertension and renal failure have been equivocal.

Efficacy of clozapine in a non-schizophrenic patient with psychogenic polydipsia and central pontine myelinolysis.

Clozapine is an atypical antipsychotic drug that has been demonstrated to be a highly effective treatment for polydipsia in schizophrenic patients. The authors report the first case of a non-schizophrenic patient affected by polydipsia and central pontine myelinolysis who was successfully treated with clozapine.

Risperidone failed to improve polydipsia-hyponatremia of the schizophrenic patients.

The effect of risperidone on polydipsia-hyponatremia was evaluated in six hospitalized schizophrenic patients. The normalized diurnal weight gain (NDWG), urine-specific gravity (USG), urine and plasma osmolarity, and serum sodium were monitored during 9 months of risperidone treatment. The dose of risperidone (mean +/- SD=8.0 +/- 1.0, range=6-9 mg/day) was determined as approximately half of the haloperidol-equivalent dose of previous neuroleptics. Before risperidone treatment, the mean (+/- SD) BPRS score was 23.5 +/- 7.1; no significant improvement was observed after risperidone (22.0 +/- 7.5). The subjects showed relatively high serum prolactin before risperidone treatment (mean +/- SD=16.5 +/- 9.7 ng/mL), that was not significantly decreased by risperidone (14.2 +/- 7.9 ng/mL). The monthly means (+/- SD) of NDWG and USG before risperidone were 5.5 +/- 1.5 (%) and 1.002 +/- 0.001, respectively. These and other indices did not significantly improve throughout the study period. Although the sample size is relatively small, our preliminary data showed that risperidone might not be effective on polydipsia-hyponatremia of schizophrenic patients.