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[Effect of neuroleptic, adreno- and cholinolytic agents on cerebral cortical function in edema].

Experiments on rats with experimental brain edema under water intoxication were made to study the effects of the neuroleptics aminazine and propazine, the central M-cholinoblocker amizyl and the alpha-adrenoblocker phentolamine on the time-course of the recovery of cortical electric activity after passing of the wave of Leao's spreading depression (SD). The drugs under study were demonstrated to have antiedematous properties under water intoxication and to make to a considerable degree for disorders in the processes of the recovery of cortical electrogenesis after SD. It is assumed that the action of the drugs on the electrophysiological parameters under study is associated with their effects on metabolic processes and with the presence of antiedematous properties.

Animals↗

COX-2 and the kidneys.

The kidney is the second most frequent target of serious adverse effects of non-steroidal antiinflammatory drugs (NSAIDs). The renal side effects of NSAIDs related to inhibition of cyclooxygenase (COX) comprise reduction in renal blood flow (RBF) and glomerular filtration rate (GFR), sodium/water retention, water intoxication and hyperkalemia. The discovery of two COX-isoenzymes, a constitutive COX-1, serving homeostatic prostanoid synthesis, and an inducible COX-2, responsible for proinflammatory prosta noid production, led to the development of new NSAIDs: Preferential and specific COX-2 inhibitors, promising minimal NSAID-typical toxicity with equivalent efficacy. However, we learned that there is no clear distinction in "physiologic" constitutive COX-1 and "inflammatory" inducible COX-2. This is particular true for the kidney of humans and other mammalians, where COX-2 was found constitutively in meaningful amounts. Animal experiments and clinical trials with preferential and specific COX-2 inhibitors revealed that COX-2 is the critical enzyme for sodium excretion, renin release and likely antagonism of antidiuretic hormone. Additionally, a significant role of COX-2 for nephro genesis is suggested. For renal hemodynamics the given evidence point to COX-1 as the predominant enzyme, but further investigations are required. In summary, the gain of renal safety by use of preferential or specific COX-2 inhibitors is small or negligible with respect to sodium retention, hyperkalemia and probably water intoxication. These drugs may be advantageous regarding renal perfusion, but presently the same precautions as for conventional NSAIDs must be used.

Animals↗

Comparison of diuretic effects of glycerol with furosemide after transurethral prostatectomy.

BACKGROUND: Diuretic therapy after transurethral prostatectomy (TURP) is primarily intended to induce diuresis against water intoxication and cystic clot retention. This study was undertaken to compare the diuretic effects of glycerol with furosemide after TURP. METHODS: Thirty patients (ASA I or II) undergoing TURP were studied. Spinal anesthesia was induced with bupivacaine. At the end of prostatic resection, the patients were randomly allocated into two groups. In one group (n = 15) the patients received furosemide 30 mg i.v., while in the other group (n = 15) they received glycerol 0.5 g/kg i.v. Blood samples were collected for measurements of osmolality, hematocrit, sodium and glucose concentration before anesthesia and after surgery. Urine output was also recorded after surgery in each group. RESULTS: Plasma osmolality in glycerol group was higher than furosemide group at 30 min (295.3 +/- 10.6 vs. 283.8 +/- 5.6 mOsm/kg, p < 0.01) and 1 h after operation (294.9 +/- 8.7 vs 286.3 +/- 6.7 mOsm/kg, p < 0.01). Blood glucose was higher in glycerol group than that in furosemide group at 2 h after operation (195.6 +/- 121.9 vs 152.9 +/- 70.1 mg/dl, p < 0.05). Measured urine output was significantly greater in furosemide group at 30 min after operation (904.6 +/- 491.5 vs. 248.4 +/- 143.4 ml, p < 0.05) but was greater in glycerol group at 12 h after operation. CONCLUSIONS: Since urine output is significantly less in glycerol group at 1 h after operation, glycerol is inferior to furosemide for preventing cystic clot retention after TURP. But glycerol may protect against water intoxication better for its merit of producing higher plasma osmolality.

Aged↗

Desmopressin for nocturnal enuresis in children.

BACKGROUND: Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great. OBJECTIVES: To assess the effects of desmopressin on nocturnal enuresis in children, and to compare desmopressin with other interventions. SEARCH STRATEGY: The following electronic databases were searched: MEDLINE to June 1997; AMED; ASSIA; BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974 to June 1997); PsycLIT and SIGLE. Organisations, manufacturers, researchers and health professionals concerned with enuresis were contacted for information. The reference sections of obtained studies were also checked for further trials. Date of the most recent search: July 1997. SELECTION CRITERIA: All randomised trials of desmopressin for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive desmopressin compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were reported. Trials focused solely on daytime wetting were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of the eligible trials, and extracted data. MAIN RESULTS: Twenty one randomised trials involving 948 children treated with desmopressin, met the inclusion criteria. The quality of many of the trials was poor. Desmopressin was compared with a tricyclic drug in two trials, and with alarms in one. Desmopressin was effective in reducing bedwetting in a variety of doses and forms. Each dose of desmopressin reduced bedwetting by at least one night per week during treatment (eg 20microg: 1.56 fewer wet nights per week, 95% CI -1.94 to -1.19). Participants on desmopressin were 4.6 times more likely to achieve 14 consecutive dry nights (95% CI 1.38 to 15.02) compared with placebo. However, there was no difference after treatment was finished. There was no apparent dose-related effect of desmopressin, but the evidence was limited. Data which compared oral and nasal administration were too few to be conclusive. Desmopressin and imipramine (a tricyclic drug) were equally effective in one small trial. Amitriptyline (another tricyclic) was not consistently better than desmopressin either alone or when used as a supplement. In a single trial, desmopressin was initially superior to using an alarm in reducing the number of wet nights per week: WMD -1.7 (95% CI: -2.96 to -0.45), but this result was not sustained; after three months of treatment, patients using the alarm had 1.4 fewer wet nights per week than with desmopressin: (95% CI: 0.14 to 2.65). Participants receiving the alarm intervention were also nine times less likely to relapse than those given desmopressin: RR 9.2 (95% CI: 1.28 to 65.9). Combining alarm and drug therapy was found to be superior to alarm treatment alone. The addition of desmopressin to an alarm schedule resulted in one less wet night per week: (95% CI: -1.55 to -0.45). REVIEWER'S CONCLUSIONS: Desmopressin rapidly reduced the number of wet nights per week, but there was some evidence that this was not sustained after treatment stopped. Comparison with alternative treatments suggested that desmopressin and tricyclics had similar clinical effects, but that alarms produced more sustained benefits. However, based on the available evidence, these conclusions can only be tentative. There was some evidence of minor side effects of desmopressin in the included trials, such as nasal irritation and nose bleeds. However, the risk of water intoxication associated with over-drinking before bedtime has been reported. Patients and their families need to be warned of potential adverse effects and advise

Child↗

Morbidity and mortality associated with vasopressin replacement therapy in children.

OBJECTIVE: To assess the incidence and associated risk factors of adverse reactions of DDAVP treatment of children with diabetes insipidus, comparing different routes of administration. DESIGN: We retrospectively studied 103 children (44 females, 59 males) with cranial diabetes insipidus (mean age 6.9 years at diagnosis) treated with intramuscular (59), intranasal (84) and/or oral (64) DDAVP, over a mean follow-up period of 5.2 years. RESULTS: Eight patients died. For at least two children death was related to water intoxication. Major complications (symptomatic water overload with or without seizures) or asymptomatic hyponatraemia were observed in 33 patients. The incidence of total complications was significantly higher in cortisol deficient patients than in those with normal cortisol reserve (36% vs 6%). In patients on concomitant carbamazapine treatment major complications were more frequent in comparison to the remaining patients (33% vs 10%). Although not achieving significance, there were fewer complications using the oral route. CONCLUSIONS: Caution is needed in managing patients with DI, especially if risk factors such as cortisol deficiency or concomitant carbamazepine treatment are present. The oral route of administration seems to be preferred for both convenience and safety. Major changes in dose and formulation should be undertaken in hospital.

Administration, Intranasal↗

[Excessive water intake with intoxication as a manifestation of anorexia nervosa].

A case of anorexia nervosa revealed by water intoxication with severe hyponatremia is reported after a search of the literature demonstrated the rarity of such cases. Pathophysiological mechanisms involved are discussed. Hospitalization in a unit for adolescents in which pediatricians and psychiatrists work together allowed both prompt treatment of metabolic disorders and early management of anorexia nervosa, which is associated with improved prognosis.

Adolescent↗

[Hyponatremia after very heavy beer drinking (author's transl)].

Severe water and electrolyte disturbances were observed in a patient after a bout of very heavy beer drinking (30 liters in 6 days). On admission she was found to have hypokalemia (2.2 mEq/I), metabolic alkalosis (pHa: 7.55-total CO2: 40 mEq/I), and more particularly hyponatremia (109 mEq/I), responsible for the typical neurological signs of water intoxication (hyponatremic encephalopathy). There was a positive cumulative return of sodium (570 mEq) and chloride (900 mEq) levels, and normal conditions were restored without significant modifications in water balance or weight. No other etiology, apart from the beer, was discovered. Heavy drinking of beer alone can therefore provoke chloride and sodium depletion, probably because beer, which is poor in NaCl, must produce urinary loss of these electrolytes. The high osmolarity of beer may explain this latter phenomenon. This particular cause of hyponatremia should be recognized, if only to avoid confusing the clinical signs of alcoholic intoxication with those due to water intoxication.

Alcoholic Intoxication↗

Vasopressin in chronic psychiatric patients with primary polydipsia.

Twelve chronic in-patients with primary polydipsia were studied, during free drinking and after fasting, by concurrent measurements of plasma AVP, serum sodium and osmolality, and urine volume, AVP, osmolality, and creatinine. A majority of the patients showed inappropriately high levels of AVP: plasma AVP estimations demonstrated that seven had Type I SIADH and two had Type II SIADH. Urinary AVP estimations confirmed inappropriately raised AVP in seven of the subjects tested, and there was a significant agreement between the plasma and urine diagnoses. Although able to concentrate their urine in response to fluid deprivation, the patients showed a decreased renal sensitivity to AVP. Despite the mitigating effect of decreased renal sensitivity to AVP, the SIADH seen in these patients appears to contribute to the development of water intoxication caused by polydipsia.

Adult↗

[Water and potassium metabolism changes].

The disturbances of water and electrolyte metabolism in the body can be subdivided into three large groups: 1) disturbances of free water which are related to the whole body water and are always coupled with changes in the osmolality of the internal environment and also of the interior of the cells (hypertension due to loss of water, hypotension in water intoxication); 2) isotonic changes of the volume of the extracellular fluid-oedema or extracellular dehydration. The latter are always coupled with a hypovolaemia and with a danger to the circulation which may end in shock. There is also a cumulative loss of potassium as a result of the dehydration reaction; 3) disturbances of the intracellular water metabolism which are associated with disturbances of the potassium metabolism. These may have grave consequences for the function of striated and smooth muscles, for the function of the nerves and various enzyme systems. Since the disorders of the extracellular water balance are generally best known, the attention is principally drawn in this paper to the hypertonic dehydration and the status of the potassium metabolism. The symptomatology of both conditions is discussed, and also their diagnosis with the simplest laboratory effort not associated with great loss of time (which is essential if valuable time is not to be lost before the laboratory results can be obtained). The theoretical considerations are supplemented with clinical examples and explanations of the treatment.

Adult↗

[Biological changes in intra-uterine resections under glycine irrigation].

This study was carried out to assess the relations between plasma glycine concentrations and the biochemical changes occurring during intra-uterine resections (IUR) under glycine irrigation. Sixty patients with benign uterine conditions were included. They were all ranked ASA 1 or 2. The biological parameters were assessed before surgery (T0), at the end of surgery (T1) and 60 min afterwards (T2). They included the blood count and blood concentrations of sodium, potassium, chloride, proteins, bicarbonates, glucose, urea nitrogen, creatinine and glycine. Plasma osmolarity was calculated. The irrigation of the uterine cavity resulted in an increase of glycine concentrations (28% of cases), and a decrease of sodium (22% of cases), proteins and haematocrit (32% of cases). Mean osmolarity remained unchanged. Blood glycine concentrations were directly correlated with the volume of irrigating solution, as well as with the duration of surgery. Protidaemia was inversely related to the blood glycine concentration. Multiparous patients had lower glycine concentrations than nulliparous patients. This was probably due to the uterine cavity being less compliant in the latter. On the other hand, there was no correlation with the uterine pathological condition. In this series, five cases of uterine perforation occurred with very large biological variations, especially a decrease in haematocrit and osmolarity. In these cases a clinical and biological water intoxication syndrome may occur as a result of large volumes of irrigating fluid passing into the peritoneal cavity.

Adult↗

Neuroendocrine responses to a cold pressor stimulus in polydipsic hyponatremic and in matched schizophrenic patients.

Schizophrenia, many believe, reflects an enhanced vulnerability to psychological stress. Controlled exposure to stressors, however, has produced inconclusive results, particularly with regards to neurohormones. Some of the variability may be attributable to the nature and psychological significance of the stimulus and failure to control physiologic confounds. In addition, it is possible that the heterogeneity of schizophrenia is an important factor. In a carefully designed study and in a controlled setting, we measured the neuroendocrine response of eight polydipsic hyponatremic (PHS), seven polydipsic normonatremic (PNS), and nine nonpolydipsic normonatremic (NNS) (ie normal water balance) schizophrenic in-patients as well as 12 healthy controls (HC) to two different stressors: one of which appears to influence neuroendocrine secretion through its psychological (cold pressor) and the other (upright posture) through its systemic actions. Subjects in the three psychiatric groups were stabilized and acclimated to the research setting, and all received saline to normalize plasma osmolality. Following the cold pressor, plasma adrenocorticotropin and cortisol levels showed a more prolonged rise in PHS patients relative to PNS patients. NNS patients, in contrast, exhibited blunted responses relative to both of the polydipsic groups and the HC. Peak vasopressin responses were also greater in PHS and blunted in NNS patients. Responses to the postural stimulus were similar across patient groups. These findings provide a mechanism for life threatening water intoxication in schizophrenia; help to reconcile conflicting findings of stress responsiveness in schizophrenia; and potentially identify a discrete patient subset with enhanced vulnerability to psychological stress.

Adult↗

[Pregnancy in diabetes insipidus--a case report with review of the literature].

A 32 year old I P II G with preexisting diabetes insipidus was treated with 1-(3-mercaptopropionic acid)-8-d-arginine vasopressin (DDAVP) during pregnancy. An otherwise normal pregnancy was marked only with an excessive weight increase. A healthy girl was delivered by secondary cesarean section at term. Postoperative the mother developed a water intoxication accompanying oxytocin-infusion. During nursing the diabetes insipidus improved significantly whereby DDAVP doses could be reduced to 20-10 percent. We suppose an overreaction to endogene oxytocin with an antidiuretic effect.

Administration, Intranasal↗

Neuropsychological manifestations of hyponatremia in chronic schizophrenic patients with the syndrome of psychosis, intermittent hyponatremia and polydipsia (PIP).

We examined the neuropsychological sequelae of water intoxication in nine schizophrenic patients with the syndrome of psychosis, intermittent hyponatremia and polydipsia (PIP). Patients were assessed using a standardized test battery on two occasions following laboratory blood work: once during hyponatremia (serum sodium < 130 mmol/l) and once during normonatremia (serum sodium > 136 mmol/l). Results revealed significant deficits during hyponatremia involving complex information processing skills such as mental flexibility and verbal fluency. In contrast, short-term memory was intact and no deficits in sustained attention or visual-motor scanning were observed. Our results underscore the dramatic fluctuations in neuropsychological functioning due to metabolic and osmotic changes during water loading in PIP syndrome patients. In addition, we found that the neuropsychological effects of hyponatremia are remarkably consistent across patients. These complications, if not recognized, are likely to contribute to worsening of psychosis despite appropriate pharmacological treatment while severely limiting patient ability to actively participate in behavioral interventions.

Adult↗

A possible role for taurine in osmoregulation within the brain.

Intracranial microdialysis was used to measure changes in extracellular amino acids within the rat brain during local osmotic alteration of the extracellular microenvironment or during systemic water intoxication. Increased cellular hydration produced by either of these methods was accompanied by a marked increase in extracellular taurine levels without affecting the other amino acids measured. With local osmotic alteration, this increase was osmolarity dependent and reversible. The specificity, sensitivity, and reversibility of the increase in extracellular taurine strongly suggest a functional role in osmoregulation in the brain under normal as well as pathological conditions.

Animals↗

[Increased plasma antidiuretic hormone in the presence of hyponatremia in primary hypothyroidism].

A 70-year-old woman was admitted because of disturbance of her consciousness. Physical examinations and laboratory data suggested hypothyroidism. Primary hypothyroidism was subsequently confirmed with endocrinological examinations. Antidiuretic hormone (ADH) levels were elevated despite severe hyponatremia. On admission, urinary sodium concentration was 10mEq/l. The patient was treated with saline intravenously; serum sodium level increased from 120 to 125mEq/l and urinary sodium concentration increased from 10 to 54mEq/l. Mental confusion developed and serum sodium level dropped with urinary sodium concentration above 20mEq/l when thyroid replacement was started with the cessation of saline infusion. The patient's state of consciousness, elevated ADH levels, decreased serum sodium level and urinary sodium concentration were improved by thyroid replacement together with hydrocortisone therapy. Effects of acute water loading were abnormal with the administration of iodothyronine (T3) alone but were normalized with the administration of hydrocortisone together with T3. On discharge she was treated with the oral administration of levothyroxine alone. Pituitary hormones were normal. These results suggest that the patient was in a state of hypoadrenocorticism. Impaired water excretion in a state of hypoadrenocorticism due to hypothyroidism may give rise to an inappropriate secretion of ADH thereby resulting in hyponatremia, which in turn leads to hypotonic dehydration induced by water intoxication.

Adrenal Cortex↗

Prehospital cardiac arrest in diabetic ketoacidemia: why brain swelling may lead to death before treatment.

An adolescent is reported with type 1 diabetes mellitus and diabetic ketoacidemia (DKA) who died from brain herniation prior to treatment with intravenous fluids and intravenous insulin. The pathophysiology of raised intracranial pressure (ICP) and water intoxication is discussed. As DKA evolves, water and electrolyte losses are replaced by very hypotonic fluids taken orally, leading to a physiologic excess of free water that would cause brain swelling prior to treatment. Central nervous system acidosis may interfere with normal compensatory mechanisms that help prevent small increases in ICP. The pathophysiology of pre-treatment brain swelling has important implications for rehydration with intravenous fluids and treatment with insulin. Prevention of DKA is paramount as well as complete postmortem evaluation of patients who die from this disease.

Adolescent↗

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH): an overview.

We have reviewed 14 cases of water intoxication in psychiatric patients. In these cases the possibility of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was suspected or diagnosed. The SIADH should be suspected in psychotic patients who drink water excessively, develop seizures, disorientation and deterioration of mental status.

Adult↗