Long-term safety of desmopressin orally disintegrating tablets in men with nocturia due to nocturnal polyuria: Interim results of a specified drug use-results survey in Japan.

OBJECTIVES: This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 µg in Japanese men with nocturia due to nocturnal polyuria. METHODS: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set. RESULTS: The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 µg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia. CONCLUSIONS: Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period.

Safety and efficacy of proactive versus reactive administration of desmopressin in severe symptomatic hyponatremia: a randomized controlled trial.

This randomized controlled trial aimed to evaluate the safety and efficacy of proactive versus reactive desmopressin (DDAVP) strategies in treating severe symptomatic hyponatremia. Conducted from June 20, 2022, to February 20, 2023, it involved 49 patients with serum sodium levels below 125 mmol/L. Patients were assigned to either the proactive group, receiving DDAVP immediately upon diagnosis, or the reactive group, receiving DDAVP only if the serum sodium level tended to be overcorrected. The primary outcome was the incidence of overcorrection. The study revealed no significant difference in the overcorrection incidence between the proactive (16.7%) and reactive (28%) groups (p = 0.54). The change in serum sodium levels at 1, 6, 12, and 24 h were not different, however, at 48 h, the proactive group exhibited a higher but still safe change in serum sodium levels compared to the reactive group (10.3 ± 3.6 mmol/L vs. 7.7 ± 3.6 mmol/L, p = 0.013). Other parameters including time to symptom improvement, total intravenous fluid administered, DDAVP dose, urine volume, hospital stay duration, osmotic demyelination syndrome incidence, and 28-day mortality did not significantly differ between the groups. In conclusion, our findings suggest that there was no significant disparity in overcorrection rates between proactive and reactive DDAVP strategies for treating severe symptomatic hyponatremia. However, further large-scale studies are warranted to validate these results.

Efficacy and safety of desmopressin in nocturia and nocturnal polyuria control of neurological patients: A systematic review and meta-analysis.

PURPOSE: Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to evaluate the efficacy and safety of desmopressin treatment on nocturia in patients with underlying neurological diseases. METHODS: Studies were identified by electronic search of PubMed, Embase, Cochrane, CINAHL, and Google Scholar databases. Studies were considered if they provided information on the effectiveness and safety of desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) in the treatment of nocturia and their participants had acquired neurological pathology. Two researchers independently extracted the articles using specified datasets, such as quality-of-study indicators. Statistical meta-analysis was carried out using Review Manager (RevMan) 5.4 statistical software (Cochrane Collaboration). RESULTS: Of a total of 1042 articles in the initial search, 14 studies were included. Most of the published papers were related to MS (n = 7), two were on spinal cord injury, and other conditions were neural tube defect, myelodysplasia, Parkinson's disease, stroke, and multiple system atrophy. Overall, a total of 200 patients (mostly females) were enrolled. Thirteen studies evaluated the intranasal formulation of desmopressin and one study evaluated oral desmopressin. A significant decrease in nocturia episodes was reported in seven studies evaluating this topic. An increase in the maximum hours of uninterrupted sleep was reported in the three studies in which this outcome was assessed. A significant reduction in the volume of nocturnal incontinence was found in one study. Three studies were eligible to include in the meta-analysis. The results showed that desmopressin compared to placebo, significantly reduced nighttime urination (mean difference: -0.75, 95% CI: -1.10 to -0.41; p < 0.00001). The rate of adverse events ranged from 0% to 68.42%. The critical appraisal results for all trials showed that most of the studies had low or moderate quality. CONCLUSIONS: Our results emphasized desmopressin's safety and efficacy in reducing nocturia episodes, with transient adverse effects on neurological patients. However, the data were achieved from low or medium-quality trials, and further well-designed randomized controlled trials are needed.

Desmopressin Dose Requirements in Adults with Congenital and Acquired Central Diabetes Insipidus.

Central diabetes insipidus is a rare disorder characterized by a deficiency of vasopressin. The first line drug to treat this disorder is a synthetic analogue of vasopressin, desmopressin.The primary aim of this retrospective register study was to compare desmopressin dose requirements in patients with acquired and congenital DI, and secondly to assess the influence of BMI on dose requirement and risk of hyponatremia with different drug administrations. We included all patients with suspected DI attending the endocrine department at Rigshospitalet, Copenhagen, Denmark in 2022. We identified 222 patients who were included whereof 130/222 (58.6%) were females and median age was 53 years (IQR 35 to 63). The etiology included 7/222 (3.2%) congenital and 215/222 (96.8%) acquired. After converting nasal and sublingual doses to equivalent oral doses, the median daily dose requirement was 600 µg in patients with congenital etiology compared to 200 µg in patients with acquired etiology (p=0.005). We found no association between BMI and desmopressin dose requirements (p=0.6). During the past 12 months, 66/215 (30.7%) had sodium levels<136 mmol/l including 20/215 (9.3%) with sodium levels<131 mmol/l. No increased risk of hyponatremia was found, when nasal and oral were compared (p=0.9). Daily desmopressin dose requirements were higher in patients with congenital DI compared to patients with acquired DI. However, this result was associated with uncertainty due to the small congenital group. BMI did not influence daily dose requirements and nor did type of administration influence the risk of hyponatremia.

Desmopressin to prevent and treat bleeding in pregnant women with an inherited bleeding disorder: a systematic literature review.

BACKGROUND: Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties. OBJECTIVES: We aimed to review the safety and effectiveness of DDAVP in women with an inherited bleeding disorder during pregnancy and delivery. METHODS: Databases were searched for articles up to July 25, 2022, reporting maternal and/or neonatal outcomes. PRISMA methodology for systematic reviews and meta-analyses was followed (PROSPERO CRD42022316490). RESULTS: Fifty-three studies were included, comprising 273 pregnancies. Regarding maternal outcomes, DDAVP was administered in 73 women during pregnancy and in 232 during delivery. Safety outcome was reported in 245 pregnancies, with severe adverse events reported in 2 (1%, hyponatremia with neurologic symptoms). Overall, DDAVP was used as monotherapy in 234 pregnancies, with effectiveness reported in 153 pregnancies (82% effective; 18% ineffective). Regarding neonatal outcomes, out of 60 pregnancies with reported neonatal outcomes after DDAVP use during pregnancy, 2 children (3%) had a severe adverse event (preterm delivery n = 1; fetal growth restriction n = 1). Of the 232 deliveries, 169 neonates were exposed to DDAVP during delivery, and in 114 neonates, safety outcome was reported. Two children (2%) experienced a moderate adverse event (low Apgar score n = 1; transient hyperbilirubinemia not associated with DDAVP n = 1). CONCLUSION: DDAVP use during pregnancy and delivery seems safe for the mother, with special attention to the occurrence of hyponatremia and for the child, especially during delivery. However, due to poor study designs and limited documentation of outcomes, a well-designed prospective study is warranted.

The pooled analysis evaluates the therapeutic efficacy of desmopressin combined with anticholinergic drugs in the treatment of pediatric nocturnal enuresis.

OBJECTIVE: This pooled analysis aims to demonstrate the clinical efficacy and safety of combined desmopressin and anticholinergic therapy in the treatment of pediatric nocturnal enuresis (NE). METHODS: A systematic search was conducted through PubMed, MEDLINE, EMBASE, ResearchGate, and Cochrane Library to identify all randomized controlled trials (RCTs) comparing monotherapy with desmopressin versus combined therapy with desmopressin and anticholinergic agents for the treatment of NE. Data analysis was performed using RevMan version 5.4.1. RESULTS: This study included 8 RCTs involving a total of 659 patients. The frequencies of complete response (CR), partial response (PR), and nonresponse (NR) were computed for both short-term treatment (1 month) and long-term treatment (3 months). Additionally, alterations in the mean number of NE episodes, adverse events, and relapse were assessed. Our analysis indicates that, in comparison to the monotherapy group, the combination therapy group plays a pivotal role in augmenting the CR odds and diminishing the NR ratios in both short-term and long-term treatments (1 month CR ratio [risk ratio (RR): 1.84; 95% confidence interval (CI): 1.22-2.76; p = 0.003, I2 = 72%]; 3 months CR ratio [RR: 1.48; 95% CI: 1.25-1.76; p < 0.00001, I2 = 0%]; 1 month NR ratio [RR: 0.67; 95% CI: 0.55-0.82; p = 0.0001, I2 = 0%]; 3 months CR ratio [RR: 0.37; 95% CI: 0.19-0.73; p = 0.004, I2 = 0%]). Furthermore, in both short-term and long-term treatment, the combined therapy group exhibits a greater magnitude of change in the average number of NE episodes compared to patients receiving monotherapy (1 month, mean difference [MD] = -2.97; 95% CI: -4.23 to -1.71, p < 0.0001; 3 months, MD = -4.30; 95% CI: -7.18 to -1.43, p = 0.003). Moreover, the combination therapy group exhibits a significant reduction in the recurrence rate (RR: 0.36; 95% CI: 0.15-0.86; p = 0.02). There is no significant difference in the incidence of adverse events between the two groups (RR: 1.16; 95% CI: 0.58-2.31; p = 0.67). CONCLUSION: Combining desmopressin with anticholinergic medications is more effective for NE than desmopressin alone, with lower recurrence and minimal adverse effects.

Investigation of Effect Predictors of Desmopressin in Nocturia Patients With Nocturnal Polyuria.

BACKGROUND/AIM: Effect predictors of desmopressin for nocturia associated with nocturnal polyuria are understudied. Herein, we investigated the effects of desmopressin on sleep and patient quality of life. We defined cases in which administration of desmopressin led to hours of undisturbed sleep (HUS) ≥3 hours as "marked response cases" and examined predictive factors of desmopressin treatment response. PATIENTS AND METHODS: Our study included 129 patients who were administered desmopressin 50 µg for nocturia associated with nocturnal polyuria at our hospital. Efficacy and safety of desmopressin were examined using bladder diaries, International Prostate Symptom Score, Overactive Bladder Symptom Score, Athens Insomnia Scale, Patient Global Impression of Improvement (PGI-I) score, physical examinations, blood tests, and body composition analyzers, and the predictors of desmopressin efficacy were investigated. RESULTS: Significant improvements in all endpoints were observed from the early stage onward after desmopressin treatment compared with before treatment. After treatment, HUS was significantly longer in patients with good PGI-I scores, which indicated patient satisfaction. Variation in nocturnal micturition frequency did not affect the improvement in patient satisfaction. Examination of cases defined as "marked response cases" showed that the mean night-time urine volume was an independent predictor of treatment response. CONCLUSION: Desmopressin can improve patients' quality of life and sleep by extending HUS. This suggests that desmopressin may be effective in patients with high mean night-time urine volumes based on their bladder diary.

Management of Central Diabetes Insipidus in Disabled Children with Diluted Oral Desmopressin Lyophilisate Formulation Administered Through Nasogastric Tube: A Retrospective Case Series.

BACKGROUND: Experience with nasogastric administration of oral DDAVP [desamino-D-arginine-8-vasopressin] lyophilisate (ODL) for central diabetes insipidus (CDI) in disabled children with swallowing coordination difficulties is limited. OBJECTIVE: We aimed to assess the safety and efficacy of nasogastric use of ODL in disabled children with CDI. Time to serum sodium normalisation was compared with that of children with normal intellect and CDI treated with sublingual DDAVP. METHODS: Clinical, laboratory and neuroimaging characteristics were evaluated for 12 disabled children with CDI treated with ODL through nasogastric tube at Dr Behcet Uz Children's Hospital, Turkey, between 2012 and 2022. RESULTS: Six boys and six girls with a mean (±SD) age of 43 (± 40) months were evaluated. These children (mean [±SD] weight standard deviation score [SDS] - 1.2 ± 1.7; mean [±SD] height SDS - 1.3 ± 1.4) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatraemia (mean serum sodium 162 [±3.6] mEq/L). At diagnosis, mean serum and urine osmolality were 321 (± 14) mOsm/kg and 105 (± 7.8) mOsm/kg, respectively. Arginine vasopressin (AVP) levels were undetectable (< 0.5 pmol/L) at diagnosis in all patients. Nasogastric tube administration of DDAVP lyophilisate (120 µg/tablet) dissolved in water (10 mL) was commenced at a dose of 1-5 µg/kg/day in two divided doses together with controlled water intake to avoid hyponatraemia. The frequency and dose of DDAVP were titrated based on urine output and serum sodium concentration. Serum sodium declined at a rate of 0.11 ± 0.03 mEq/L/h and reached normal range in a mean duration of 174 ± 46.5 h. Serum sodium declined faster in children with normal intellect and CDI treated with sublingual DDAVP (1.28 ± 0.39 mEq/L/h; p = 0.0003). Three disabled children needed rehospitalisation because of hypernatraemia due to unintentional DDAVP omission by caregivers. No episode of hyponatraemia was observed. Weight gain and growth were normal during the median (± interquartile range) follow-up duration of 32 ± 67 months. CONCLUSIONS: Nasogastric administration of oral DDAVP lyophilised formulation was safe and effective in the treatment of CDI in disabled children in this small retrospective series.

Desmopressin for patients with spontaneous intracerebral haemorrhage taking antiplatelet drugs (DASH): a UK-based, phase 2, randomised, placebo-controlled, multicentre feasibility trial.

BACKGROUND: The risk of death from spontaneous intracerebral haemorrhage is increased for people taking antiplatelet drugs. We aimed to assess the feasibility of randomising patients on antiplatelet drug therapy with spontaneous intracerebral haemorrhage to desmopressin or placebo to reduce the antiplatelet drug effect. METHODS: DASH was a phase 2, randomised, placebo-controlled, multicentre feasibility trial. Patients were recruited from ten acute stroke centres in the UK and were eligible if they had an intracerebral haemorrhage with stroke symptom onset within 24 h of randomisation, were aged 18 years or older, and were taking an antiplatelet drug. Participants were randomly assigned (1:1) to a single dose of intravenous desmopressin 20 µg or matching placebo. Treatment allocation was concealed from all staff and patients involved in the trial. The primary outcome was feasibility, which was measured as the number of eligible patients randomised and the proportion of eligible patients approached, and analysis was by intention to treat. The trial was prospectively registered with ISRCTN (reference ISRCTN67038373), and it is closed to recruitment. FINDINGS: Between April 1, 2019, and March 31, 2022, 1380 potential participants were screened for eligibility. 176 (13%) participants were potentially eligible, of whom 57 (32%) were approached, and 54 (31%) consented and were subsequently recruited and randomly assigned to receive desmopressin (n=27) or placebo (n=27). The main reason for eligible patients not being recruited was the patient arriving out of hours (74 [61%] of 122 participants). The recruitment rate increased after the enrolment period was extended from 12 h to 24 h, but it was then impaired due to the COVID-19 pandemic. Of the 54 participants included in the analysis (mean age 76·4 years [SD 11·3]), most were male (36 [67%]) and White (50 [93%]). 53 (98%) of 54 participants received all of their allocated treatment (one participant assigned desmopressin only received part of the infusion). No participants were lost to follow-up or withdrew from the trial. Death or dependency on others for daily activities at day 90 (modified Rankin Scale score >4) occurred in six (22%) of 27 participants in the desmopressin group and ten (37%) of 27 participants in the placebo group. Serious adverse events occurred in 12 (44%) participants in the desmopressin group and 13 (48%) participants in the placebo group. The most common adverse events were expansion of the haemorrhagic stroke (four [15%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group) and pneumonia (one [4%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group). INTERPRETATION: Our results show it is feasible to randomise patients with spontaneous intracerebral haemorrhage who are taking antiplatelet drugs to desmopressin or placebo. Our findings support the need for a definitive trial to determine if desmopressin improves outcomes in patients with intracerebral haemorrhage on antiplatelet drug therapy. FUNDING: National Institute for Health Research.

Determining the optimal initial dose for Japanese patients with nocturnal polyuria using an initial dose of desmopressin 50 µg.

OBJECTIVE: There is no consistent opinion on the optimal initial dose of desmopressin for patients with nocturnal polyuria. Over a period of 12 weeks, we investigated the safety and efficacy of an initial dose of 50 µg of desmopressin for elderly men. METHODS: Eighty patients (mean age: 78.8 years) were started on an initial dose of 50 µg of desmopressin for nocturia associated with nocturnal polyuria. Safety and efficacy were evaluated after 1, 4, and 12 weeks using a frequency-volume chart, Athens Insomnia Scale, Patient Global Impression of Improvement scale, physical examination, blood tests, and a body composition analyzer. RESULTS: Along with reduction in the frequency and volume of night-time urination, improvements in hours of undisturbed sleep, nocturnal polyuria index, and International Prostate Symptom Score, and Overactive Bladder Symptom Scores on quality of life measures were also observed. Hyponatremia was observed in 15 patients (18.7%). However, only 5.0% of patients had hyponatremia after the dose was reduced to 25 µg, and the continuation rate at 12 weeks was high at 87.5%. Age and other physical factors, such as body mass index, body water content, body fat mass, and muscle mass were not significant predictors of adverse events. CONCLUSIONS: Our study suggests that an initial dose of 50 µg is more effective than a uniformly minimum dose based on factors such as age and physique. Furthermore, a high continuation rate can be achieved by appropriately reducing the dose, if adverse events occur.

A multicenter retrospective study evaluating the impact of desmopressin on hematoma expansion in patients with antiplatelet-associated intracranial hemorrhage.

INTRODUCTION: Antiplatelet medications interfere with hemostasis which can contribute to increased risk of hematoma expansion and potentially worse outcomes in patients presenting with intracranial hemorrhages (ICH). Current Neurocritical Care Society guidelines recommend desmopressin (DDAVP) in patients with antiplatelet-associated ICH with evidence limited by small cohorts. MATERIALS AND METHODS: Patients were included in our multi-center, retrospective study if they had computed tomographic (CT) scan confirmed ICH and were taking antiplatelet medications. Patients were excluded if hospital length of stay was <24 h, administered DDAVP dose was <0.3 µg/kg, no follow-up head CT scan was performed within the first 24 h after baseline, major neurosurgical intervention was performed in between CT scans, or the injury was an acute on chronic ICH. The primary outcome was incidence of hematoma expansion (defined as >20 % increase from baseline). Secondary outcomes were incidence of thrombotic complications within 7 days, largest absolute decrease in serum sodium within the first 24 h, and patient disposition. RESULTS: Among the 209 patients included in the study, 118 patients received DDAVP while 91 did not. The frequency of hematoma expansion was similar between patients who received DDAVP and those who did not (16.1 % vs 17.6 %; P = 0.78). No difference in secondary outcomes was observed between the two groups. CONCLUSIONS: These findings in conjunction with recently published literature may suggest minimal benefit or harm with DDAVP treatment. However, further study could elucidate any potential impact on long-term function outcomes.

Nasal Septal Perforation Due to Desmopressin Nasal Spray Use.

Perforations of the nasal septum have many etiologies and occasionally result from intranasal medicated spray use. This case report describes a perforation related to the use of desmopressin nasal spray, which has not been previously reported in the literature. Clinical considerations presented in this article include appropriate technique of nasal spray application, appropriate monitoring of patients on intranasal sprays, and indications for evaluation by an otolaryngologist. Septal perforation treatment success is improved with an early diagnosis.

Laying the foundation for enhancing safety of desmopressin in older people: Validation of capillary blood sodium levels.

PURPOSE: We aim to make desmopressin a safe treatment option for (older) patients at risk for hyponatremia, by introducing a new way of sodium monitoring. The goal is to reduce the risk of hyponatremia, enhance patient safety and ultimately introduce self-monitoring of sodium levels. The first step in the aforementioned is to validate capillary sodium. MATERIALS AND METHODS: 100 randomly selected patients admitted to the urology department received a single finger prick to collect capillary blood (250 µl) in a lithium-heparin tube. Each patient acted as its own control for the capillary and venous blood sample. Venous and capillary plasma sodium were analyzed by indirect ion-selective electrode measurement. The primary outcome was the agreement between capillary and venous sodium measurements, measured by the intra-class correlation coefficient (ICC). RESULTS: One hundred paired blood samples were obtained of which four were excluded. There was no significant statistical difference observed between venous and capillary sodium (-0.23 mmol/L, p = 0.374). The ICC for single measures between capillary and venous sodium was 0.82 (95% confidence interval 0.75-0.88). Inter-method differences analyzed by a Bland-Altman plot and a Passing-Bablock regression did not reveal a statistically significant difference between both groups. CONCLUSIONS: We demonstrated that venous and capillary sodium levels are interchangeable, taken into account the inter- and intravariability between analyses. We provided the first step towards a simple and safe solution for frequent sodium monitoring through a minimal invasive capillary blood collection. The results are of direct clinical relevance to safely use desmopressin in (older) patients at risk.

Seizure from water intoxication following bowel preparation: a case report.

BACKGROUND: Bowel preparation prior to colonoscopic examination is generally considered a safe process. Hyponatremia is a complication that has been reported in literature during bowel preparation. Individuals who develop severe symptomatic hyponatremia are often older and have comorbidities such as hypothyroidism, chronic kidney disease, or adrenal insufficiency. However, other mechanisms and circumstances can also lead to this potentially fatal complication. CASE PRESENTATION: We present a unique case of a patient who developed seizure prior to colonoscopy due to acute hyponatremia without any well-known risk factors. With the subsequent diagnosis of water intoxication, the use of desmopressin was believed to have contributed to this serious complication. CONCLUSION: In addition to the use of certain well-documented medications and the presence of comorbidities that can lead to hyponatremia, clinicians should also be aware of the use of desmopressin as an important risk factor. Thorough history taking can guide individualized bowel preparation regimens to minimize the risk of undesired complications.

Desmopressin Acetate in Percutaneous Ultrasound-Guided Native Kidney Biopsy in Patients with Reduced Kidney Function: A Double-Blind Randomized Controlled Trial.

INTRODUCTION: Bleeding events are the most common complications after kidney biopsy. This study aims to evaluate the effect of desmopressin administration on bleeding complication, in native kidney biopsy candidates with reduced kidney function. METHODS: This double-blind randomized clinical trial enrolled 18 to 80 years old patients with 15 < eGFR < 90 mL/min/ 1.73m² from July 2017 to August 2020. Patients were randomly assigned to receive either 3 µg/kg of intranasal desmopressin acetate or 1 mL/kg of intranasal sodium chloride 0.65%, one hour before ultrasound-guided, percutaneous native kidney biopsy. The primary outcome was the post-biopsy bleeding complications, and secondary outcomes were the volume of perirenal hematoma, and changes of post-biopsy hemoglobin and hematocrit level, plasma sodium and blood pressure (Clinical Trial Registration ID: IRCT20090701002112N3). RESULTS: A total of 120 patients (58 men and 62 women), 60 patients in each group, were analyzed. The mean age and eGFR of the patients were 45.29 ± 15.95 years and 51.77 ± 18.02 ml/min/ 1.73m², respectively. Desmopressin administration significantly decreased post-biopsy perirenal hematoma compared to placebo (7/60 [11.6%]) vs. 33/60 [40%]; P < .05), and the hematoma volume was significantly smaller in the desmopressin group, in case of hematoma formation (2.31 ± 1.17 vs. 7.72 ± 5.45 mm³, P < .05). CONCLUSION: Desmopressin administration before kidney biopsy is a safe and effective strategy to prevent bleeding complications. Considering absolute risk reduction of about 28%, the number needed to treat is about 4 procedures. We recommend considering desmopressin administration before percutaneous native kidney biopsy.  DOI: 10.52547/ijkd.6966.

Desmopressin therapy in children and adults: pharmacological considerations and clinical implications.

PURPOSE: This review aims to provide prescribing clinicians a deeper appreciation of desmopressin's clinical indications and formulation types, to better balance efficacy and safety through proper formulation selection. BACKGROUND: Since its discovery 50 years ago, desmopressin's antidiuretic properties have been used for central diabetes insipidus, primary monosymptomatic nocturnal enuresis and adult nocturnal polyuria, while its coagulant effects are useful for mild hemophilia A and von Willebrand Disease. During this time, newer formulations of desmopressin have also been introduced to the market raising questions on interchangeability, dose conversion and safety. The wide array of clinical indications and variable pharmacokinetic properties of different desmopressin preparations raises the possibility of medication error, especially the risk of hyponatraemia. METHODOLOGY: A narrative review to explore clinically relevant aspects of desmopressin therapy, synthesising information obtained from searches of published literature. RESULTS: We identified that the risk factors for developing hyponatremia include extremes of age, existing comorbidity, drug interaction, intranasal formulations and intercurrent illness. We describe the dose equivalence between all formulations to facilitate conversion. We highlight that in view of inter-subject variability, close monitoring is recommended when switching preparations. We found that paediatric data remains limited, leading to recent proposals for age- and weight-based dosing regimens. CONCLUSION: The risk of hyponatremia, albeit small, can be reduced by adhering to the indication-specific doses and taking steps to govern the safe prescription of the drug. Further paediatric clinical trials are awaited to expand the evidence base of childhood desmopressin therapy.

Effect of desmopressin acetate on acute spontaneous intracranial hemorrhage in patients on antiplatelet therapy.

PURPOSE: To evaluate the impact of desmopressin acetate (DDAVP) on poor outcomes, hematoma expansion, and adverse events in patients diagnosed with a non-traumatic, antiplatelet-associated intracranial hemorrhage (ICH). METHODS: This was a multicenter, retrospective, propensity-matched cohort study comparing DDAVP to control in patients diagnosed with a non-traumatic ICH previously on antiplatelet therapy. Notable exclusion criteria included admission to trauma service, subarachnoid hemorrhages, confounding coagulopathic factors, and hematoma evacuation. Poor outcome, defined as discharge to hospice or in-patient mortality, was the primary outcome. Secondary outcomes included intracranial hematoma expansion and occurrence of adverse events, which included hyponatremia and thromboembolic events. RESULTS: A total of 49 patients receiving DDAVP were compared to 107 controls in the unmatched cohort. Thirty-seven patients treated with DDAVP and 55 controls were included in the propensity-matched analysis, which was adjusted for age, ethnicity, history of diabetes, receipt of platelet transfusion, and thromboembolism prophylaxis. Poor outcome (16.2% DDAVP vs 29% control, p = 0.13), rates of hematoma expansion (11.8% DDAVP vs 11.1% control, p = 0.99), and adverse events (21.6% DDAVP vs 20% control, p = 0.99) were statistically similar between the matched groups. CONCLUSIONS: DDAVP administration in patients with spontaneous antiplatelet-associated ICH was not associated with a reduction in poor outcomes, hematoma expansion, or an increase in adverse events. Use of DDAVP in this patient population appears to be safe. Larger prospective studies are warranted to evaluate DDAVP utility in this patient population.

The efficacy and safety of desmopressin acetate applied for nocturia in benign prostatic hyperplasia patients: A systematic review and meta-analysis.

BACKGROUND: Desmopressin acetate was recommended for nocturia in benign prostatic hyperplasia (BPH) patients recently, but its effect and safety is still controversial. We aimed to establish a systematic review and meta-analysis to confirm its effect on symptom relief and adverse effects. METHODS: A systematic search was performed in PubMed, Cochrane Library, EMBASE, Medline, Web of Science and Science Direct databases from January 2000 to October 2021 for controlled trials of BPH patients comparing oral desmopressin with control groups. The mean difference (MD) and odds ratio (OR) were meta-analyzed. RESULTS: Four articles with 500 patients were included. Significantly greater benefit was detected for the desmopressin group in the improvement of nocturia (P = .004), international prostate symptom score - storage (IPSS-S) (P = .03), and quality of life (QoL) (P = .04) scores. Patients treated with desmopressin were at higher risk than the control group for short-term adverse events (P < .001), including nausea (4.71%, P = .04), headache (20%, P < .00001), dizziness (5.88%, P = .02) and hyponatremia (4.71%, P = .04), but the long-term incidence might decrease. CONCLUSION: Desmopressin acetate can reduce nocturia frequency and improve the IPSS-S and QoL score in BPH patients. Some adverse reactions of desmopressin, such as hyponatremia, headache, dizziness and nausea, may be mild and short-term. No significant difference of desmopressin was found in improving the overall IPSS score and maximum urine flow.

Platelet dysfunction in patients with traumatic intracranial hemorrhage: Do desmopressin and platelet therapy help or harm?

BACKGROUND: Pre-injury anti-platelet use has been associated with increased risk of progression of traumatic intracranial hemorrhage (TICH) and worse outcomes. VerifyNow® assays assess platelet inhibition due to aspirin/clopidogrel. This study assesses the outcomes of patients with TICH and platelet dysfunction treated with desmopressin and/or platelets. METHODS: We performed a retrospective chart review of patients with mild TICH at a level 1 trauma center 1/1/2013-6/1/2016. Patients with documented platelet dysfunction who received desmopressin and/or platelets were compared to those who were untreated. Primary outcomes were progression of TICH and neurologic outcomes at discharge. RESULTS: Of 565 patients with a mild TICH, 200 patients had evidence of platelet dysfunction (a positive VerifyNow® assay). Patients had similar baseline demographics, injury characteristics, and rate of TICH progression; but patients who received desmopressin and/or platelets had worse Glasgow Outcomes Score at discharge. CONCLUSION: Treatment of patients with mild TICH and platelet dysfunction with desmopressin and/or platelets did not affect TICH progression but correlated with worse neurologic status at discharge.

Safety of renal biopsy bleeding prophylaxis with desmopressin.

BACKGROUND: Percutaneous renal biopsy (PRB) is invasive, and bleeding-related complications are a concern. Desmopressin (DDAVP) is a selective type 2 vasopressin receptor-agonist also used for haemostasis. AIM: To evaluate the side effects of intravenous (IV) weight-adjusted desmopressin preceding PRB. METHODS: This was a retrospective study of renal biopsies performed by nephrologists from 2013 to 2017 in patients who received single-dose DDAVP pre-PRB. RESULTS: Of 482 PRBs, 65 (13.5%) received DDAVP (0.3 µg/kg); 55.4% of the PRBs were native kidneys. Desmopressin indications were altered platelet function analyser (PFA)-100 results (75.3% of the patients), urea >24.9 mmol/L (15.5%), antiplatelet drugs (6.1%) and thrombocytopaenia (3%). Of the 65 patients, 30.7% had minor asymptomatic complications, and 3 patients had major complications. Pre-PRB haemoglobin (Hb) <100 g/L was a risk factor for Hb decrease >10 g/L, and altered collagen-epinephrine (Col-Epi) time was a significant risk factor for overall complications. Mean sodium decrease was 0.6 ± 3 mmol/L. Hyponatraemia without neurological symptoms was diagnosed in two patients; no cardiovascular events occurred. CONCLUSION: Hyponatraemia after single-dose DDAVP is rare. A single IV dose of desmopressin adjusted to the patient's weight is safe as pre-PRB bleeding prophylaxis.