Desmopressin is a synthetic analogue of the natural antidiuretic hormone arginine vasopressin. Over the years, it has been clinically used to manage nocturnal polyuria in children with enuresis. Various pharmaceutical formulations of desmopressin have been commercialized for this indication-nasal spray, nasal drops, oral tablet and oral lyophilizate. Despite the fact that desmopressin is a frequently prescribed drug in children, its use and posology is based on limited pediatric data. This review provides an overview of the current pediatric pharmacological data related to the different desmopressin formulations, including their pharmacokinetics, pharmacodynamics and adverse events. Regarding the pharmacokinetics, a profound food effect on the oral bioavailability was demonstrated as well as different plasma concentration-time profiles (double absorption peak) of the desmopressin lyophilizate between adults and children. Literature about maturational differences in distribution, metabolism and excretion of desmopressin is rather limited. Regarding the pharmacodynamics, formulation/dose/food effect and predictors of response were evaluated. The lyophilizate is the preferred formulation, but the claimed bioequivalence in adults (200 µg tablet and 120 µg lyophilizate), could not be readily extrapolated to children. Prescribing the standard flat-dose regimen to the entire pediatric population might be insufficient to attain response to desmopressin treatment, whereby dosing schemes based on age and weight were proposed. Moreover, response to desmopressin is variable, whereby complete-, partial- and non-responders are reported. Different reasons were enumerated that might explain the difference in response rate to desmopressin observed: different pathophysiological mechanisms, bladder capacity and other predictive factors (i.e. breast feeding, familial history, compliance, sex, etc.). Also, the relapse rate of desmopressin treatment was high, rendering it necessary to use a pragmatic approach for the treatment of enuresis, whereby careful consideration of the position of desmopressin within this treatment is required. Regarding the safety of the different desmopressin formulations, the use of desmopressin was generally considered safe, but additional measures should be taken to prevent severe hyponatremia. To conclude the review, to date, major knowledge gaps in pediatric pharmacological aspects of the different desmopressin formulations still remain. Additional information should be collected about the clinical relevance of the double absorption peak, the food effect, the bioequivalence/therapeutic equivalence, the pediatric adapted dosing regimens, the study endpoints and the difference between performing studies at daytime or at nighttime. To fill in these gaps, additional well designed pharmacokinetic and pharmacodynamic studies in children should be performed.

Nocturnal enuresis often causes considerable distress or functional impairment to patient and their parents necessitating a multidisciplinary approach from paediatrician, paediatric nephrologist, urologists and psychiatrist. Mechanisms of monosymptomatic nocturnal enuresis are mainly nocturnal polyuria, bladder overactivity and failure to awaken from sleep in response to bladder sensations. Goal oriented and etiology wise treatment includes simple behavioral intervention, conditioning alarm regimen and pharmacotherapy with desmopressin, imipramine and anticholinergic drugs. Symptoms often recurs requiring change over or combination of different modes of treatment.

Dilutional hyponatremia is a serious adverse effect of desmopressin, a vasopressin analog that is widely prescribed to manage monosymptomatic enuresis. The presentation of hyponatremia, largely related to cerebral dysfunction, can include severe signs like altered mental status and seizures.

We reviewed the literature dealing with altered mental status or seizures in enuretic subjects on desmopressin. The retained publications included patients who were described individually, revealing data on mode of administration, further identifiable factors predisposing to hyponatremia, presentation and clinical course.

We found 54 cases of hyponatremia secondary to desmopressin treatment presenting with altered mental status or seizures. In most cases the complication developed 14 days or less after starting desmopressin. An intranasal formulation had been used in 47 patients. Excess fluid intake was documented as a contributing factor in at least 22 cases. In 6 cases severe signs of hyponatremia developed in the context of intercurrent illnesses.

Altered mental status or seizures are very rare but recognized complications of desmopressin in enuresis. This complication mostly develops in subjects managed with the intranasal formulation 14 days or less after starting the medication, following excess fluid intake and during intercurrent illnesses.

Disorders of coagulation are common adverse drug events encountered in critically ill patients and present a serious concern for intensive care unit (ICU) clinicians. Dosing strategies for medications used in the ICU are typically developed for use in noncritically ill patients and, therefore, do not account for the altered pharmacokinetic and pharmacodynamic properties encountered in the critically ill as well as the increased potential for drug-drug interactions, given the far greater number of medications ordered. This substantially increases the risk for coagulation-related adverse reactions, such as a bleeding or prothrombotic events. Although many medications used in the ICU have the potential to cause coagulation disorders, the exact incidence will vary based on the specific medication, dose, concomitant drug therapy, ICU setting, and patient-specific comorbidities. Clinicians must strongly consider these factors when evaluating the risk/benefit ratio for a particular therapy. This review surveys recent literature documenting the risk for adverse drug reactions specific to bleeding and/or clotting with commonly used medications in the ICU.

Desmopressin is a well established and effective therapy for nocturnal enuresis. Water intoxication leading to hyponatremia is an infrequent but serious adverse event associated with desmopressin. We assessed the safety of desmopressin in children 18 years or younger with nocturnal enuresis with a focus on the relative safety of the oral compared with the intranasal formulation.

Published data (MEDLINE) from December 1972 to August 2006 and post-marketing safety data from December 1972 to June 2005 were analyzed.

A total of 21 clinical trials on desmopressin use in children with nocturnal enuresis were identified. There were no reports of hyponatremia. A total of 21 publications were identified that included 48 case reports of hyponatremia in children with nocturnal enuresis. In all case reports patients were treated with intranasal desmopressin. Post-marketing safety data included 151 cases of hyponatremia in children with nocturnal enuresis, of whom 145 were treated with intranasal desmopressin and 6 were treated with the tablet formulation. Prodromal symptoms of hyponatremia were identified as headache, nausea and vomiting.

Data suggest that there is a decreased risk of hyponatremia with oral desmopressin compared with intranasal desmopressin. Identifiable and preventable risk factors for hyponatremia are inappropriately high fluid intake, administration of a larger than recommended dose, young age (less than 6 years) and concomitant administration of another medication. When desmopressin is prescribed, patients should be instructed to avoid high fluid intake when the medication is ingested, not ingest a higher than recommended dose and promptly discontinue the medication and seek assessment if headache, nausea or vomiting develops.

Enuresis nocturna is regularly treated by desmopressin, a vasopressin analog. Its side effects, notably neurological, are fortunately rare. We comment on 5 enuretic children on desmopressin who suffered from hyponatremic encephalopathy (natremia 115-127, median 117 mmol/l).

Side effects appeared at therapeutic doses (10-40 mg/d intranasal). An excessive fluid intake at night was often noted, leading to a dilutional hyponatremia. This may be due to a lack of correct information to the parents. These children presented after a period of warning symptoms, such as headache, vomiting and altered consciousness. Parents could have sought earlier medical attention if they had been informed about these symptoms.

In the absence of fluid restriction, severe hyponatremia can occur in enuretic children on desmopressin. It is therefore mandatory for the prescribing doctor to adequately inform patients and parents to limit fluids at night when desmopressin is used, and seek medical help quickly if any sign of intracranial hypertension appears.

Enuresis is a symptom that is frequently encountered in child psychiatric evaluations. Careful assessment is required to identify specific urologic, developmental, psychosocial, and sleep-related etiologies. For most children with enuresis, however, a specific etiology cannot be determined. Treatment then involves supportive approaches, conditioning with a urine alarm, or medications--imipramine or desmopressin acetate. The psychosocial consequences of the symptom must be recognized and addressed with sensitivity during the evaluation and treatment of enuresis.

Primary nocturnal enuresis is one of the most frequent complaints in paediatric and urologic practice. Physicians face the dilemma of whether or not to treat primary nocturnal enuresis since the trend towards spontaneous remission is countered by social disadvantages and reduced self esteem of the children affected and their families. We reviewed randomised, controlled trials investigating efficacy and adverse effects of current medical treatment for primary nocturnal enuresis. Only desmopressin and imipramine displayed significant effects in reducing wet nights: when compared with baseline bedwetting or placebo controls, 30-70% of the studied children achieved therapeutic success. For drugs such as indometacin or oxybutynin, convincing studies displaying a significant positive effect are still needed. However, considering the adverse effects profiles of desmopressin and imipramine it can be seen that imipramine is associated with about twice as many unwanted reactions. More importantly, a serious adverse effect of imipramine is sudden cardiac arrest. In general, adverse effects with desmopressin are rare and mild, but there have been a number of case reports of hyponatraemic hypervolaemia associated with coma and seizures. Of these, many cases were attributed to excess water intake before taking the drug and all children recovered fully. In summary, if medical treatment is considered, preference should be given to desmopressin.

Desmopressin diacetate arginine vasopressin (DDAVP) is a synthetic analogue of the mammalian arginine vasopressin used in the treatment of central diabetes insipidus, bleeding disorders, and incontinence. The primary adverse reaction associated with DDAVP is hypotonic hyponatremia. Hyponatremia has been reported in adults treated with DDAVP for Von Willebrand's disease and hemophilia and in children treated for enuresis, but as yet few cases of hyponatremia developing in enuretic adults treated with DDAVP have been reported. We report the cases of two elderly women taking DDAVP for nocturnal polyuria who developed severe hyponatremia. One patient died in the hospital.

To assess the incidence and associated risk factors of adverse reactions of DDAVP treatment of children with diabetes insipidus, comparing different routes of administration.

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.

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.

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.

A 42-year-old female with von Willebrand's disease was managed with desmopressin and tranexamic acid to aid haemostasis following a vaginal hysterectomy. Severe acute hyponatraemia (134 to 108 mmol/l) developed over two days, culminating in a generalized tonic-clonic seizure and cerebral oedema. Fluid restriction, cessation of desmopressin and hypertonic saline administration led to a full recovery. Desmopressin is known to reduce free water elimination and produce hyponatraemia, but its extent and rate of development in this patient was surprising. Close monitoring of serum sodium and fluid balance is recommended in these patients.

The case of a 6 year old child who presented with convulsions and coma after unsupervised self administration of intranasal desmopressin (DDAVP) for nocturnal enuresis is presented. Children with enuresis can be embarassed by their condition and may believe that multiple doses of their nasal spray may bring about a rapid resolution. Water intoxication is an uncommon but serious adverse effect of treatment with intranasal DDAVP. These patients may present with seizure, mental state changes, or both. Basic management consists of stopping the drug, fluid restriction, and suppressive treatment for seizures. Recovery is usually rapid and complete. Administration of the nasal spray in children should be supervised by parents to prevent highly motivated children from accidental overdose. The risks of high fluid intake need to be carefully explained to both parents and children.

Incontinence disorders are an important group of problems that clinicians manage in children and adolescents. This paper reviews the physiology of micturition, the epidemiology of enuresis, etiologic concepts of incontinence disorders, a general clinical approach to enuretic patients, laboratory evaluation and general principles of management. Neurological and nephrological concepts of enuresis are emphasized in this discussion.