Nasal Desmopressin Research Articles

Desmopressin administration in children with central diabetes insipidus: a retrospective review

Central diabetes insipidus (DI) is a rare disorder in children caused by a deficiency of antidiuretic hormone arginine (vasopressin). Desmopressin is the first line agent in management of central DI. However, one of the side effects of desmopressin is water intoxication and hyponatraemia. This study reviews the patterns of desmopressin use and side effects in our institution. Retrospective chart review of all patients with central DI followed up in one tertiary centre between 1 January 2008 and 31 December 2010. Forty-one patients (22 males and 19 females) were included. Twelve patients (29.3%) had congenital and 29 patients (70.7%) had acquired DI, mostly as a result of intracranial tumours. Thirty-six (87.8%) patients were on oral desmopressin and the remaining on nasal formulation. The median oral dose was 9.5 (4.2-17.0) μg/kg/day with median frequency of 2.5 (2-3). The median nasal dose was 0.7 (0.4-1.4) μg/kg/day with median frequency of 2.0 (2-3.5). Fourteen patients (34.1%) were switched from nasal to oral desmopressin with the median dose conversion factor of 20.1 (10.7-31.8). Forty percent of patients on nasal desmopressin experienced hypo/hypernatraemia compared to 18.1% on oral, however, there were no significance difference between standardized hypo/hypernatraemia episodes per treatment year. Oral desmopressin is used in the majority of our patients including infants and toddlers. There is wide inter-individual variation in dose requirement and dosing intervals. Management of central diabetes insipidus remains a challenge in adipsic patients and in young children during intercurrent illness regardless of the desmopressin formulation.

Rare neonatal diabetes insipidus and associated late risks: Case report

BackgroundMost cases of neonatal central diabetes insipidus are caused by an injury, which often results in other handicaps in the patient. The infant’s prognosis will be determined by his or her own early age and disability as well as by the physician’s skill. However, the rarity of this condition prevents the acquisition of personal experience dealing with it.Case Presentation A neonatal hemorrhagic stroke, caused by an aortic coarctation, caused right lower limb paresis, swallowing disability, and central diabetes insipidus in a term infant. The scant oral intake, as a consequence of his disability, caused progressive undernutrition which closed a vicious circle, delaying his development and his ability to overcome the swallowing handicap. On the other hand, nasal desmopressin absorption was blocked by several common colds, resulting in brain bleeding because of severe dehydration. This even greater brain damage hampered the improvement of swallowing, closing a second harmful circle. Moreover, a devastating central myelinolysis with quadriplegia, caused by an uncontrolled intravenous infusion, consummated a pernicious sequence, possibly unreported.ConclusionsThe child’s overall development advanced rapidly when his nutrition was improved by gastrostomy: This was a key effect of nutrition on his highly sensitive neurodevelopment. Besides, this case shows potential risks related to intranasal desmopressin treatment in young children.

Inferior petrous sinus sampling after nasal desmopressin stimulation: A new technique in the diagnostic evaluation of ACTH-dependent Cushing′s syndrome

Inferior petrous sinus sampling after nasal desmopressin stimulation: A new technique in the diagnostic evaluation of ACTH-dependent Cushing′s syndrome

Nasal desmopressin no longer approved for bedwetting

Nasal desmopressin no longer approved for bedwetting

Nasal desmopressin no longer approved for bedwetting

Nasal desmopressin no longer approved for bedwetting

Efficacy and safety of nasal desmopressin in the long-term treatment of primary nocturnal enuresis

Sirs, We read with great interest the article entitled “Comparing alarms, desmopressin, and combined treatment in Chinese enuretic children” by Ng et al. [1]. The authors stated that the response rates decreased after the cessation of treatment (12 weeks) from 53% (20 of the 38 patients) to 21% (eight patients) for oral desmopressin alone, and from 78% (25 of the 32 patients) to 41% (13 patients) for the combination therapy with oral desmopressin plus alarms [1]. Two previous reports also described decreased continence after the cessation of nasal desmopressin therapy {six months, from 68% (60 of the 88 patients) to 10% (nine patients) [2], and 3–12 months, from 61% (245 of the 399 patients) to 16% (12 of the 73 patients) [3]}. In our study, the effect of nasal desmopressin for between 12 months and 24 months (from November 2003 to October 2005) was investigated at Dokkyo University School of Medicine Hospital in 56 children (18 girls, 38 boys) 6–15 years old (mean age 8.4±2.2 years) diagnosed with primary nocturnal enuresis (PNE), with urine osmotic pressure decreasing to below 800 mOsm/L at night [4]. We initially administered nasal desmopressin at a dose of 10 micrograms at bedtime. If the patient remained incontinent after four weeks, we increased the dose to 20 micrograms (the maximum dose allowed in Japan [4]). Medication was interrupted for one week every third month to test for a cure. Urinalysis (osmotic pressure, protein, sugar and occult blood), biochemical (serum alanine aminotransferase, aspartate aminotransferase, creatine kinase, sodium, potassium and creatinine), and hematological (red blood cell, white blood cell and hemoglobin) values were determined every three months for adverse events. “Nonresponse,” where the frequency decreased by less than 50% during the first three months following the start of treatment, was observed in six (11%) of the 56 children with PNE, similar to the results [8% (four of the 49 patients)] in Lee’s report [5]. The other 50 of the 56 children recruited were enrolled in long-term treatment, because they experienced a >50% reduction in the number of wet nights. Although there were repeated relapses off medication, the final results showed that 24 (48%) of the 50 children with PNE were relapse-free when the frequency of NE decreased to zero or to once-monthly off medication. Our results after the cessation of therapy showed greater efficacy than in the three previous reports {21% [1], 10% [2] and 16% [3]}, because the term of treatment in our study (between 12 and 24 months) was longer than three previous studies (between 3 and 12 months) [1–3]. There were no adverse events, except for one event of acute rhinitis and one event of excitement. In conclusion, our clinical study has provided evidence that nasal desmopressin is both safe and effective for longterm treatment (between 12 and 24months) in children with PNE.

Severe hyponatremia due to desmopressin

Nasal desmopressin (DDAVP) is a commonly prescribed antidiuretic hormone (ADH) analogue used for treatment of diabetes insipidus, polyuria and nocturnal enuresis. Although it is generally well tolerated, it can cause severe electrolyte imbalance. Numerous reports exist on cases of mild to moderate DDAVP-induced hyponatremia, yet few reports describe severe hyponatremia (Na < 115 mEq/L). We present a case of a 52-year-old woman with nearly symptom-free, DDAVP-induced hypotonic hyponatremia of 104 mEq/L following a gastrointestinal illness. We describe the appropriate correction of her hyponatremia and conclude by raising awareness of the potential for severe cases of desmopressin-associated hyponatremia, even in the rather symptom-free patient.

Nonhealing Perianal Ulcers—Quiz Case

CASE REPORT A 67-year-old heterosexual Chinese male presented with a one-year history of persistent multiple painful well-defined punched-out ulcers around the anus and in the perineum without involvement of anal mucosa (Fig. 1). There was no lymphoadenopathy on the groin. He had been treated as herpes simplex viral infection with topical and oral antiviral agents without improvement. In addition, he was known to have central diabetes insipidus for 14 years and received nasal desmopressin management. Cultures were obtained for viruses, fungi, and acid-fast bacilli, and all were negative. The results of complete blood cell count, differential count, chest and whole body bone X-ray, abdominal sonography, enhanced computed tomography of the brain with thin slice sections of the sella tursica were unremarkable. A biopsy specimen was obtained for histopathologic and electron microscopic analysis (Fig. 2 and 3).

Desmopressin

Desmopressin, a synthetic antidiuretic hormone analogue, is the only drug currently approved for the treatment of nocturia associated with nocturnal polyuria or multiple sclerosis (MS). Compared with vasopressin, desmopressin has a longer lasting and more potent antidiuretic effect and is devoid of vasopressor and uterotonic effects. In two large, randomised, double-blind phase III trials in adults with nocturia associated with nocturnal polyuria, 3 weeks of oral desmopressin therapy was significantly more effective than placebo in reducing the mean number of nocturnal voids and in normalising the rate of nocturnal urine production. Beneficial effects of desmopressin on nocturia were maintained and increased in patients completing 10 or 12 months of further treatment in a nonblind extension of short-term trials. In randomised, double-blind trials in MS patients with nocturia, nasal desmopressin reduced the mean number of nocturnal voiding episodes by 31-54%. In both patient populations, desmopressin increased the initial sleep period or mean maximum period of uninterrupted sleep by approximately 2 hours, an outcome significantly greater than that achieved with placebo. In trials of < or =6 weeks duration in adults with nocturia, desmopressin was generally well tolerated. Most desmopressin-related adverse events were transient and mild or moderate in severity. Clinically significant hyponatraemia was reported in approximately 5% and required withdrawal from studies in < or =3% of patients.

The risk of hyponatremia in older adults using desmopressin for nocturia: a systematic review and meta-analysis.

To estimate the incidence of hyponatremia in older adults who use nasal or oral desmopressin to treat nocturia. A systematic review and meta-analysis of cohort studies and randomised controlled trials of the use of nasal or oral desmopressin for older adults with nocturia. The incidence of hyponatremia was estimated by a random effects model for binomial data. Seventy-five papers were identified by the literature review of which 14 were reports of randomised trials or cohort studies. Seven studies reported the incidence of hyponatremia. The pooled estimate for the incidence of hyponatremia was 7.6% (95% CI 3.7-15.1). Hyponatremia is a relatively common adverse effect of the use of desmopressin for the treatment of nocturia and caution and regular monitoring should be part of the use of this management option for nocturia in older adults.

Hemostatic and Fibrinolytic Response to Nasal Desmopressin in Hemodialysis Patients

Objective: To evaluate the effect of desmopressin (DDAVP) on hemostatic parameters during dialysis and in the interval between dialysis sessions. Subjects and Methods: Fifteen patients dialyzed twice weekly at least for 1 year and 15 healthy volunteers serving as a control group were enrolled in the study. Bleeding time, platelet count, prothrombin time, activated partial thromboplastin time, tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), euglobulin clot lysis time, protein C, protein S, fibrinogen, D-dimer, factor V, VII, VIII, IX, X and von Willebrand factor (VWF) values were studied at the beginning, at 2 and 4 h of dialysis with and without administration of DDAVP at a dose level of 2 µg/kg intranasally. Results: After dialysis, bleeding time shortened, PAI-1 and fibrinogen levels were lower, while VWF and D-dimer levels were higher. After DDAVP administration, bleeding time, PAI-1 levels were significantly lower (p < 0.01), while tPA, factor VIII and VWF levels increased significantly (p < 0.001). Conclusion: The findings indicate that DDAVP can be used for patients on dialysis with serious bleeding.

Effect of nasal desmopressin in treatment of acute renal colic

Effect of nasal desmopressin in treatment of acute renal colic

Comparison between nasal and intravenous desmopressin for the treatment of aminosalicylic acid-induced platelet dysfunction

Comparison between nasal and intravenous desmopressin for the treatment of aminosalicylic acid-induced platelet dysfunction

Von Willebrand's disease: an important cause of dysfunctional uterine bleeding

We assessed the prevalence of von Willebrand's disease (VWD) in patients with objectively confirmed dysfunctional uterine bleeding. A case-control study was designed to include 38 patients with objectively confirmed dysfunctional uterine bleeding and 38 age-matched controls with normal menstrual blood loss (MBL). Menorrhagia was defined as a mean MBL of greater than 80 ml on three consecutive menses as measured by the alkali haematin method. von Willebrand factor antigen, von Willebrand factor activity (VWF:Ac) and factor VIII:C were measured on three serial venous blood samples 1 week apart. VWD was diagnosed in five of 38 (13%) patients with menorrhagia and one of 38 (2.6%) patients with normal menstrual blood loss. The mean VWF:Ac value was significantly reduced in patients with menorrhagia (mean +/- standard deviation, 84.5 +/- 26.7 IU/dl versus 103.9 +/- 34.5 IU/dl; P < 0.01) and this effect persisted after exclusion of patients diagnosed with VWD. Failure to investigate patients for VWD will limit the potential benefits of medical therapies such as tranexamic acid or nasal desmopressin [1-desamino-8-D-arginine vasopressin, (DDAVP)] and, in addition, will lead to an increased risk associated with surgical intervention in patients with undiagnosed VWD.

Central diabetes insipidus and heart: effect of acute arginine vasopressin deficiency and replacement treatment with desmopressin on cardiac performance.

Besides its effects on water balance, arginine vasopressin (AVP) increases peripheral vascular resistance and decreases cardiac output, mainly by decreasing heart rate. The current study was designed to evaluate cardiac performance in patients with central diabetes insipidus (CDI), focusing on the acute effects of desmopressin replacement withdrawal and its subsequent reinstatement in patients with CDI. Twelve patients with CDI and 12 sex- and age-matched healthy subjects entered the study. All patients were receiving treatment with intranasal desmopressin at standard doses. All patients and controls were assessed for water balance, by measuring plasma osmolality and total body water, anterior pituitary function, heart rate, systolic and diastolic blood pressure. Left ventricular (LV), end-diastolic and end-systolic diameters (LVEDD, LVESD) and volumes (LVEDV, LVESD), end-diastolic and end-systolic interventricular septum thickness (EDIVST, ESIVST) and posterior wall thickness (LVEDPWT, LVESPWT), and mass (LVM) were measured by echocardiography. Moreover, LV systolic function was assessed by measuring the ejection fraction (EF), the fractional shortening (FS), the Suga index, the stroke volume and the cardiac output, while LV diastolic function was assessed by measuring early (M1) and late (M2) maximal transmitral blood flow velocities, the ratio between M1 and M2, the mitral deceleration time (MDT) and the isovolumetric relaxation time. All parameters were assessed in the patient group 24 h after discontinuing treatment with nasal desmopressin (baseline study) and 1 week after re-starting replacement treatment, while in the control group before (baseline study) and after 1-week of a nasally administered placebo. At baseline, compared to controls, patients with CDI had increased plasma osmolality (P < 0.01), plasma ACTH (P < 0.01), serum (P < 0.01) and urinary cortisol (P < 0.01) levels, and heart rate (P < 0.05), and decreased total body water (P < 0.05). Systolic and diastolic blood pressure and the other anterior pituitary hormones were similar in patients and controls. At echo-cardiography, EDIVST (P < 0.05), ESIVST (P < 0.01), LVEDPWT (P < 0.05) and LVESPWT (P < 0.01), EF (P < 0.01), Suga index (P < 0.05), FS (P < 0.05), M2 (P < 0.01) and IRT (P < 0.05) were significantly higher while LVESD (P < 0.01), LVESV (P < 0.01), LVEDD (P < 0.05), LVEDV (P < 0.05), M1 (P < 0.05), and M1/M2 (P < 0.01) were significantly lower in patients than in controls. LVM, stroke volume and cardiac output, were similar in patients and controls. In the patient group, after 1 week of replacement treatment with desmopressin, all echocardiographic parameters were normalized, except IVT, LVPWT and the diastolic parameters that were still abnormal compared to controls. No difference was found in any of the parameters in the control group one week after placebo administration. Patients with central diabetes insipidus have increased heart rate and left ventricular contractility, and impaired diastolic function. The altered heart rate and left ventricular contractility, reversible after desmopressin replacement, is likely to be due to stimulation of sympathetic nervous activity, induced by the hypovolemia associated with arginine vasopressin deficiency. Conversely, the impairment of diastolic function, persistent after desmopressin replacement, probably relates to a stable impairment of the left ventricular compliance.

Re: Advertisement for desmopressin (DDAVP spray)

I am writing about a recent advertisement for desmopressin (DDAVP spray) as a treatment for night-time enuresis. Your readers may wish to refer to the advertisement. It features a young boy in red superhero pyjamas with a bed in the background. The young boy is smiling and displaying a very confident demeanor. Overall, it is an attractive and eye-catching advertisement that effectively captures the joy and confidence that children display when they overcome bedwetting. The advertisement is deceptive and misleading. It claims that DDAVP spray causes children to be dry after treatment. In other words, it claims to cure enuresis. The headline proclaims “In just 3 months with DDAVP, the real superhero could be the one wearing the pyjamas”. The second sentence states “Recent studies show that 3 months of daily therapy with DDAVP Spray can end bedwetting”. A reasonable professional reading this advertisement would interpret that ‘ending bedwetting’ means that even when discontinued, DDAVP spray ends bedwetting. There is nothing in the advertisement that would suggest otherwise. Indeed, this is the interpretation that Ferring Pharmaceuticals (North York, Ontario), the manufacturer of the drug, has made (Dr Anne Brusby, personal communication, 1999). The data cited in support of the claim to end bedwetting are from the SWEET study. The study was originally published in 1995 by Hjalmas (1) in a company-sponsored supplement in the Scandinavian Journal of Urology. Subsequently, virtually the same study with the addition of eight subjects was published in the British Journal of Urology in 1998 by Hjalmas et al (2). The SWEET study (1,2) was an open, multicentre trial in which children aged six to 12 years were recruited. Following an observation period of four weeks, 399 children entered a dose-titration period on nasal desmopressin. If the number of wet nights decreased by more than half, they began a long term treatment study of desmopressin. There was no control group. The medication was interrupted for one week every third month for a year. During these off-medication weeks, 77 children (19% of the inception cohort) were dry for a week. Because of two significant methodological problems, these data in no way support the claim that desmopressin ends bedwetting. The first problem is that a placebo or no-treatment group was not used. Consequently, one cannot determine if the one-week remission rate after periods of treatment is greater or less than the placebo response or the natural history of the disorder. Hjalmas et al (2) note that the 19% response rate in their study might be an underestimate because data from the last period following a period of treatment were not included in their study. In any case, historical controls are inadequate to make claims such as those made by the company. The second problem is that the typical definition of the cure or successful treatment of bedwetting is several-fold longer than the one week of being dry used in the SWEET study. Ferring has said that six months of dryness is the standard definition (Dr Brusby, personal communication, 1999). I concur with this. Consequently, using standard outcome criteria, the SWEET study provides no data at all on the ending of bedwetting. It is clear that the evidence cited does not demonstrate that desmopressin ends bedwetting once the drug is discontinued. I know of no other data that would support this claim. However, when I contacted Ferring explaining the reasons why their claims were not supported and requesting a correction of their advertisement, the company claimed that the SWEET study did show long term effectiveness, and that the advertisement was approved by the Pharmaceutical Advertising Advisory Board (PAAB) (Dr Brusby, personal communication, 1999). I do not dispute the effectiveness of desmopressin while the drug is being taken, nor do I challenge the safety of the medication. I would appreciate it if Paediatrics & Child Health would publish this letter so that readers of the journal can make their own judgment.

RISPERIDONE ASSOCIATED HEMORRHAGIC CYSTITIS

Hemorrhagic cystitis is characterized by insidious or acute hematuria. Most cases of hemorrhagic cystitis in children are due to bacterial or viral cystitis. However, gross hematuria has been associated with psychotropic drugs, such as chlorpromazine, and antidepressant medication, such as amitriptyline.l,2 Risperidone is a recently approved, effective antipsychotic medication used in the treatment of schizophrenia and other psychiatric disorders. We report a case of acute hemorrhagic cystitis associated with this antipsychotic medication. CASE REPORT An 11-year-old white boy with a long-standing history of significant behavioral problems, including depression, and attention-deficit hyperactivity and oppositional defiant disorders, presented with acute onset of dysuria and increased frequency accompanied by gross hematuria. A viral prodrome or illness did not precede these symptoms. Urological history was significant for nocturnal enuresis. Medications included fluoxetine, valproic acid, benztropine, haloperidol, clonidine, trazodone and nasal desmopressin. One week before presentation risperidone had been substituted for haloperidol to improve behavioral control. At presentation urinalysis revealed macroscopic hematuria and urine cultures yielded no growth. Coagulation studies, complete blood count and serum electrolytes were normal. Ultrasonography showed a thickened bladder wall and

Nasal Spray Desmopressin Treatment of Bladder Dysfunction in Patients With Multiple Sclerosis

Nasal Spray Desmopressin Treatment of Bladder Dysfunction in Patients With Multiple Sclerosis

Nasal Spray Desmopressin Treatment of Bladder Dysfunction in Patients With Multiple Sclerosis

Bladder dysfunction with increased voiding frequency and incontinence is a common problem in patients with multiple sclerosis (MS). In the present study, the effect of the synthetic vasopressin analogue, desmopressin, was evaluated on the voiding frequency in 26 patients with MS suffering from socially handicapping voidings and incontinence problems during daytime. A two-week run-in observation period to establish normal voiding patterns was followed by a double-blind, placebo-controlled cross-over study with 20 micrograms intranasal desmopressin during daily activities. There was a significant decrease in the number of voidings during the 6-h period after intranasal intake of desmopressin. Side effects were well tolerated and there was no hyponatremia or hypertension registered. Intranasal desmopressin is an efficient and well-tolerated treatment of voiding problems in patients with MS during daily activities.

Vasopressin Secretion in the DIDMOAD (Wolfram) Syndrome

The diabetes insipidus which accompanies the DIDMOAD (Wolfram) syndrome is thought to be hypothalamic in origin, though no formal study of vasopressin secretion in the syndrome has been published, and some data in the literature suggest a renal tubular defect. We have studied vasopressin secretion in seven patients with the Wolfram/DIDMOAD syndrome during three dynamic stimuli: an osmotic stimulus (hypertonic saline infusion), hypoglycaemia (insulin tolerance test) and a baroregulatory stimulus (trimetaphan infusion). Hypertonic saline infusion demonstrated three patients to have complete and four to have partial hypothalamic diabetes insipidus; administration of (per nasal) desmopressin excluded nephrogenic diabetes insipidus in all seven patients. Insulin hypoglycaemia failed to stimulate vasopressin release, but trimetaphan-induced hypotension produced significant though subnormal rises in plasma vasopressin in three patients with partial diabetes insipidus, though it produced a negligible rise and no rise in plasma vasopressin in two patients with complete diabetes insipidus. The data suggest a much greater frequency of hypothalamic diabetes insipidus in the Wolfram/DIDMOAD syndrome than is reported, but did not identify nephrogenic diabetes insipidus. The absence of vasopressin responses to non-osmotic stimuli in patients with complete diabetes insipidus suggests global lack of vasopressin secreting neurones, rather than an isolated osmoreceptor defect or selective vasopressin secreting neuronal loss, as the lesion producing diabetes insipidus in the DIDMOAD syndrome.