Electroencephalography-based investigation of the effects of oral desmopressin on improving slow-wave sleep time in nocturnal polyuria patients (the DISTINCT study): A single-arm, open-label, single-assignment trial.

AIMS: To investigate changes in subjective and objective sleep quality after desmopressin administration in patients with nocturia due to nocturnal polyuria (NP) using electroencephalography (EEG) and the Pittsburgh sleep quality index (PSQI). METHODS: Twenty male patients (≥65 years old) with NP participated in this study. The inclusion criteria were nocturnal frequency ≥ 2, NP index (NPi) ≥ 0.33, first uninterrupted sleep period (FUSP) ≤ 2.5 h, serum sodium concentration ≥ 135 mEq/L, and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2. Participants were given 50 µg of desmopressin to be taken orally once daily before bed. The primary endpoint was the change in the duration of slow-wave sleep (nonrapid eye movement sleep stages 3 and 4), as evaluated by EEG 28 days from the baseline. The visual analog scale (VAS) was used as an additional indicator of sleep quality. RESULTS: Analysis of data from 15 participants (median age: 74.0 [70.5, 76.0] years) revealed that from before to after desmopressin administration, significant decreases occurred in the median nocturnal frequency (3.0 [2.0, 4.0] to 1.5 [1.0, 2.0]) and NPi (0.445 [0.380, 0.475] to 0.360 [0.250, 0.430]). Furthermore, FUSP was significantly prolonged from 120.0 (94.0, 150.0) min to 210.0 (203.8, 311.3) min. Although the VAS scores improved, slow-wave sleep duration and the PSQI global score showed no significant differences (68.50 [47.50, 75.50] and 48.00 [38.00, 66.50]; 5.0 [5.0, 10.0] and 7.0 [5.0, 9.0] min, respectively). CONCLUSION: Oral administration of 50 µg desmopressin improved nocturnal frequency and FUSP in older individuals with NP but did not significantly enhance sleep quality. In older adults, decreased nighttime urinary frequency may enhance quality of life; however, its influence on objective sleep quality may be limited.

Desmopressin nasal spray inhibiting parasympathetic function on isolated tracheal smooth muscle.

Objectives: Nocturia with or without asthma is one of the aging diseases. Desmopressin has been used as a nasal spray for patients who are suffering from nocturia. This study determined the effects of desmopressin on isolated tracheal smooth muscle in vitro. Methods: We evaluated desmopressin's efficiency on isolated rat tracheal smooth muscle. Desmopressin was evaluated for the following effects on tracheal smooth muscle: (1) effect on resting tension; (2) effect on contraction brought on by parasympathetic mimetic 10-6 M methacholine; and (3) effect on electrically produced tracheal smooth muscle contractions. Results: As the concentration grew, desmopressin by itself had no impact on the trachea's baseline tension. Addition of desmopressin at doses of 10-5 M or above elicited a significant relaxation response to 10-6 M methacholine-induced contraction. Desmopressin could also inhibit spike contraction of the trachea induced by electrical field. Conclusion: According to this study, desmopressin at high quantities may prevent the trachea's parasympathetic activity. Due to its ability to block parasympathetic activity and lessen the contraction of the tracheal smooth muscle brought on by methacholine, Desmopressin nasal spray might help nocturia sufferers experience fewer asthma attacks.

Effects of long-term desmopressin treatment for nocturia in older people.

OBJECTIVES: Desmopressin improves nocturia frequency; however, reports on its long-term efficacy and safety are few, and concerns regarding its effect on body composition exist. We thus investigated the efficacy and safety of long-term desmopressin administration and its effect on body composition. METHODS: This retrospective study, conducted at Chikugo City Hospital between August 2020 and December 2022, involved 133 men (mean age, 77.7 years) with nocturnal and persistent nocturia, who were administered an initial dose of 50 µg desmopressin. Efficacy endpoints included nocturnal urinary frequency, nocturnal urinary volume, hours of undisturbed sleep, nocturnal polyuria index, initial nocturnal urinary volume, and daily urinary frequency in a frequency-volume chart (3 days), before treatment and at 1, 4, 12, 24, and 52 weeks after desmopressin administration. Additionally, the effects of desmopressin on body composition were examined, including blood-brain natriuretic peptide and a chest radiography, before and 52 weeks after administration. RESULTS: Treatment improved most efficacy endpoint evaluation parameters. Around 87.6% of patients showed improved symptoms after 52 weeks compared with those before treatment (score ≤ 3). The blood-brain natriuretic peptide level rose; however, cardiothoracic ratio was unchanged. CONCLUSION: Long-term administration of desmopressin is thus effective and safe in older people with nocturnal polyuria, with little effect on body composition.

A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus.

BACKGROUND: The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin. METHODS: From 2013 to 2017, we recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked. RESULTS: A total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test. CONCLUSIONS: The direct measurement of hypertonic saline-stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614 .).

Variability in Oral Desmopressin Dose Requirements in Children with Central Diabetes Insipidus.

There is inconsistency in the amount of oral desmopressin that children with central diabetes insipidus require. We investigated whether clinical characteristics influenced desmopressin dose requirements in 100 children with central diabetes insipidus. Extremely large doses were associated with acquired etiology (P = .04), greater body mass index z score, intact thirst, and additional pituitary hormone deficiencies (P < .001).

Desmopressin effects on bleeding during functional endoscopic sinus surgery on patients with chronic rhinosinusitis.

OBJECTIVE: In this study we aimed to determine whether Desmopressin (DDAVP) can alter bleeding and improves surgeon visual field and decrease operation time or lessen use of anesthesiology medication in a clinical trial study. METHOD: This study is a randomized clinical trial using the permuted block randomization method. 44 patients were enrolled in study and divided into two equal intervention-control groups. The intervention group received maximum dose of 0/2 micrograms per kg of DDAVP. In the control group, 30 min before the surgery, 100 ml of normal saline will be injected. RESULTS: The amount of bleeding was 517/17 cc in control group during surgery while it was 387/72 cc in group receiving DDAVP which is significantly lower. The satisfaction of surgeon regarding suitable visual field was 6/45 in control group while it was 3/77 in DDAVP receivers which is lower. CONCLUSION: It seems that intravenous DDAVP can reduce bleeding during surgery and offer an enhanced vision for surgeon during surgery but it has no potential efficacy on reduction of period of surgery and need for anesthesiology medication like remifentanil and isoflurane.

Early Administration of Desmopressin and Platelet Transfusion for Reducing Hematoma Expansion in Patients With Acute Antiplatelet Therapy Associated Intracerebral Hemorrhage.

OBJECTIVES: To investigate the hemostatic efficacy of combined desmopressin (1-deamino-8-D-arginine vasopressin) and platelet transfusion in reducing hematoma expansion in acute, spontaneous intracerebral hemorrhage under antiplatelet treatment. DESIGN: Single-center, nonrandomized study, performed between 2006 and 2014. SETTING: Tertiary University Hospital of Tuebingen, Germany. PATIENTS: Adult patients with intracerebral hemorrhage under antiplatelet treatment and follow-up CT at 24 ± 12 hours were included. Exclusion criteria included other intracerebral hemorrhage causes, anticoagulation, coagulopathy, or immediate surgery after baseline-CT. INTERVENTIONS: Treatment with IV 1-deamino-8-D-arginine vasopressin (0.4 µg/kg) + platelet transfusion (2 U) within 60 minutes of intracerebral hemorrhage under antiplatelet treatment diagnosis on brain imaging. MEASUREMENTS AND MAIN RESULTS: Primary outcome was relative hematoma expansion from baseline to follow-up CT. Secondary outcomes included secondary intraventricular hemorrhage or hydrocephalus upon follow-up CT, thromboembolic events before discharge, and the 3-month functional outcome (assessed by modified Rankin Scale). One-hundred forty patients were included, 72 treated versus 68 controls. Times of symptom-onset-to-baseline-CT (hr) (median [interquartile range]: 3 [4] vs 5 [5]; p = 0.468) and follow-up CT (26 [18] vs 19 [12]; p = 0.352) were similar between groups. No between-group differences of total intracerebral hematoma expansion (%) (median [interquartile range]: 8.5 [12.4] vs 9.1 [16.5]; p = 0.825), intraparenchymal (10.7 [23.1] vs 9.2 [20.7]; p = 0.900), and intraventricular hematoma expansion (14.5 [63.2] vs 6.1 [40.4]; p = 0.304) were noted. Among patients with hematoma expansion greater than or equal to 33% compared with baseline, 16 (52%) received treatment versus 15 (48%) controls. The occurrence of hematoma expansion greater than or equal to 33% was similar between groups (p = 0.981). Rates of secondary intraventricular hemorrhage, hydrocephalus, and thromboembolic events were similar between groups. Treatment with 1-deamino-8-D-arginine vasopressin + platelet transfusion was not associated with the 3-month functional outcome (adjusted odds ratio, 1.570; 95% CI, 0.721-3.419; p = 0.309). CONCLUSIONS: In line with the randomized Platelet Transfusion Versus Standard Care After Acute Stroke Due to Spontaneous Cerebral Hemorrhage Associated With Antiplatelet Therapy trial, our results suggest no hemostatic efficacy of early platelet transfusion in intracerebral hemorrhage under antiplatelet treatment. Contrary to results of preclinical and clinical nonintracerebral hemorrhage studies, adjunct 1-deamino-8-D-arginine vasopressin showed no benefit in limiting hematoma expansion or improving functional outcome.

Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial.

Purpose The vasopressin analog desmopressin (dDAVP) is known to increase plasma levels of hemostatic factors, and preclinical studies in colorectal cancer models have demonstrated that it hampers tumor vascularization and metastatic progression. We evaluated safety and preliminary efficacy of dDAVP in rectal cancer patients with bleeding, before receiving specific oncologic treatment with surgery, chemotherapy and/or radiotherapy. Methods Patients with rectal cancer having moderate or severe rectal bleeding were enrolled in an open-label, dose-finding trial. Intravenous infusions of dDAVP were administered during two consecutive days in doses from 0.25 to 2.0 µg/kg, using single or twice daily regimen. Bleeding was graded using a score based on the Chutkan scale and tumor perfusion was evaluated by dynamic contrast-enhanced magnetic resonance imaging. Results The trial accrued a total of 32 patients. Dose-limiting toxicity occurred in patients receiving 1 µg/kg or higher. The most prominent treatment-related severe adverse event was hyponatremia. Most patients receiving the maximum tolerated dose of 0.5 µg/kg showed at least a partial hemostatic response and 58% developed a complete response with absence of bleeding at day 4 and/or at the last follow-up at day 14. Tumor perfusion was decreased in two-thirds of patients after dDAVP treatment. Conclusions dDAVP appeared as a promising hemostatic agent in rectal cancer patients with bleeding. Randomized clinical trials to confirm its effectiveness are warranted.Clinical trial registration www.clinicaltrials.gov NCT01623206.

Perioperative management for patients with von Willebrand disease: Defining the optimal approach.

von Willebrand disease (VWD) is the most common inherited bleeding disorder characterised by a quantitative or qualitative deficiency in von Willebrand factor (VWF). During invasive surgical procedures, patients with VWD require additional treatment to maintain haemostasis; however, due to the complexity of VWD, there is a lack of consensus on the optimal management. In the perioperative period, patients are usually treated with VWF and factor FVIII (FVIII)-containing concentrates to provide an immediate haemostatic response to prevent excessive bleeding during both elective and emergency surgery. With the introduction of recombinant VWF (rVWF), there is a need for guidance on the use of the various VWF products in the perioperative period for all types of patients and surgeries. This review provides an overview of the current evidence for the surgical management of patients with VWD and, summarises the optimal treatment approach during the perioperative period, and highlights key unanswered questions and the research needed to address the evidence gaps.

High accuracy of bilateral and simultaneous petrosal sinus sampling with desmopressin for the differential diagnosis of pediatric ACTH-dependent Cushing's syndrome.

PURPOSE: To analyze the bilateral and simultaneous petrosal sinus sampling (BIPSS) in a subgroup of children and adolescents with ACTH-dependent Cushing's syndrome (ADCS) METHODS: Retrospective study in a tertiary reference center. From 1993 and 2017, 19 children and adolescents (PED) were submitted to the BIPSS, median age of 14 years (range 9-19 years), 53% were males, 18 had Cushing's disease (CD) and one had ectopic ACTH syndrome (EAS). All procedures were performed with 10 µg of intravenous desmopressin. RESULTS: The catheter positioning was successful in all cases. The central ACTH gradient was met in 17/19 cases. At baseline, central gradient occurred in 16/19 (84%) with gradient values of 7.2 ± 6.0. After stimulation, there was an increase in the center-periphery gradient values (33.6 ± 44.3). In one case, central gradient was defined only after stimulation. Two cases presented without a central gradient; one case of CD with a false-negative and one EAS case. Lateralization occurred in all cases with a central gradient. Confirmation of the tumor location presumed by the procedure with the surgical description occurred in 60% of the cases. The BIPSS in this PED subgroup of ADCS presented a sensitivity of 94.4% and specificity of 100%. There were no complications of the procedure. CONCLUSION: In a series of children and adolescents with ADCS, BIPSS was safe and highly accurate in defining the central to peripheral ACTH gradient using desmopressin as secretagogue. Nevertheless, there was a limited value of the ACTH-gradient between the petrosal sinuses for the tumor location.

Rationale, design, and methods of electroencephalography-based investigation of the effects of oral desmopressin on improving slow-wave sleep time in nocturnal polyuria patients (the DISTINCT study): protocol for a single-arm, open-label, single-assignment trial.

BACKGROUND: Nocturia is one of the most bothersome lower urinary tract symptoms and often impairs sleep quality in the elderly. Although previous studies on nocturia have indicated that the successful treatment of nocturia improves sleep quality, most used questionnaires and activity devices to analyze sleep/wake patterns. Therefore, there is little information about the treatment effects of desmopressin on objective sleep quality. The aim of the DISTINCT study is to investigate the change in subjective and objective sleep quality using electroencephalography (EEG) and the Pittsburgh Sleep Quality Index (PSQI) after the administration of desmopressin in patients with nocturia due to nocturnal polyuria. METHODS: A total of 20 male patients, ≥65 years old, with nocturnal polyuria, defined as a nocturnal polyuria index (NPi) (nocturnal urine volume / 24 h urine volume) value ≥0.33, will participate in this study. The participants must have a nocturnal frequency of ≥2 and the first uninterrupted sleep period (FUSP) must occur within < 2.5 h. Desmopressin 50 µg per day will be orally administered before going to bed for 4 weeks. Urinary frequency volume charts (FVC) and EEG will be recorded prior to treatment and at 1 week and 4 weeks after the initiation of treatment. The PSQI will be completed before and 4 weeks after treatment. The primary endpoint is the change from baseline in the mean time of slow-wave sleep (sleep stages N3 and N4) at 4 weeks. The secondary endpoints include the change in the mean value of each sleep variable, the mean delta power during the FUSP, the correlation between nocturnal urinary frequency and slow-wave sleep time, and the change in PSQI score before and after treatment. DISCUSSION: The DISTINCT study will provide valuable evidence to indicate that oral desmopressin treatment for nocturnal polyuria prolongs the FUSP, resulting in the extension of slow-wave sleep time associated with sleep quality. TRIAL REGISTRATION: The Japan Registry of Clinical Trials ( jRCTs051190080 ). Registered 9 December, 2019.

Thromboelastography versus bleeding time for risk of bleeding post native kidney biopsy.

Introduction: The risk of bleeding has led to screening of the primary hemostasis before renal biopsy. A bleeding time test (BT) is considered standard practice, but reliance on this test is controversial and its benefits remain questionable. A possible alternative is thromboelastography (TEG). However, data regarding TEG in patients with renal dysfunction is limited.Objectives: To determine TEG abnormalities and their consequences in patients who underwent a native kidney biopsy.Methods: A retrospective study of 417 consecutive percutaneous native renal biopsies performed in our Center. If serum creatinine >1.5 mg/dL, the patient underwent either a BT test (period A, January 2015-31 December 2016) or TEG (period B, January 2017-August 2018). In patients with prolonged BT, or an abnormal low maximal amplitude (MA) parameter of TEG, or suspected clinical uremic thrombopathy, the use of desmopressin acetate (DDAVP) was considered.Results: Most biopsies (90.6%) were done by the same dedicated radiologist. Fifty-one patients had a BT test, which was normal in all tested patients. Seventy-one patients underwent TEG, and it was abnormal in 34 of them, most patients had combined abnormalities. The only parameter related to abnormal TEG was older age (Odds Ratio 1.21 [95% CI 1.09-2.38] p = 0.04 for abnormal Kinetics; OR 1.37 (1.05-1.96) p = 0.037 for abnormal MA). Twenty-six patients (6.23%) had bleeding complications. Risk of bleeding was significantly related to age (1.4 [1.11-7.48] p = 0.04), systolic blood pressure (1.85 [1.258-9.65] p = 0.02), and serum creatinine (1.21 [1.06-3.134] p = 0.048).Conclusions: TEG abnormalities in patients with renal dysfunction are variable and fail to predict bleeding during kidney biopsy. The decision to administer DDAVP as a preventive measure during these procedures should be based on clinical judgment only.

Pharmacokinetic and Pharmacodynamic Properties of a Micro-Dose Nasal Spray Formulation of Desmopressin (AV002) in Healthy Water-Loaded Subjects.

PURPOSE: Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. METHODS: Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 µg and 0.12 µg desmopressin subcutaneous (SC) bolus injection. RESULTS: AV002 intranasal administration produced a time-to-maximum concentration (Tmax) between 15 and 30 min and a maximum concentration (Cmax) <10 pg/mL. Cmax and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 µg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5-6 h. CONCLUSIONS: AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).

Desmopressin and bleeding risk after percutaneous kidney biopsy.

BACKGROUND: Desmopressin is used to reduce bleeding after kidney biopsy but evidence supporting its use is weak, especially in patients with elevated creatinine. The present study was undertaken to evaluate efficacy of desmopressin in reducing bleeding after percutaneous kidney biopsy. METHODS: Retrospective cohort study. 269 of 322 patients undergoing percutaneous kidney biopsy between January 1, 2014 and January 31, 2018 were included. Patients had normal bleeding time, platelet count and coagulation profile. Primary outcome was defined as composite of hemoglobin drop ≥1 g/dL, hematoma on post biopsy ultrasound, gross hematuria, erythrocyte transfusion or angiography to stop bleeding. Association of desmopressin with outcomes was assessed using linear (for continuous variables) and logistic (for binary variables) regression models. Propensity score was used to minimize potential confounding. RESULTS: Desmopressin was administered to 100/269 (37.17%) patients. After propensity score adjustment patients who received desmopressin had increased odds of post biopsy bleeding [OR 3.88 (1.95-7.74), p < 0.001]. Creatinine at time of biopsy influenced bleeding risk; gender, emergent vs elective biopsy, obesity, AKI, diabetes, hypertension or bleeding time did not influence bleeding risk. Administration of desmopressin to patients with serum creatinine ≥1.8 mg/dL decreased bleeding risk [OR 2.11 (95% CI 0.87-5.11), p = 0.09] but increased bleeding risk when serum creatinine was < 1.8 mg/dL (OR 9.72 (95% CI 2.95-31.96), p < 0.001). CONCLUSION: Desmopressin should not be used routinely prior to percutaneous kidney biopsy in patients at low risk for bleeding but should be reserved for patients who are at high risk for bleeding.

Effect of local desmopressin administration on intraoperative blood loss and quality of the surgical field during functional endoscopic sinus surgery in patients with chronic rhinosinusitis: a triple-blinded clinical trial.

BACKGROUND: Bleeding during functional endoscopic sinus surgery always been a challenge for the quality of surgical field for surgeons. This study aimed to evaluate the effect of local nasal desmopressin premedication on blood loss and the quality of surgical field in functional endoscopic sinus surgery. METHODS: This study was conducted on 90 patients with chronic rhinosinusitis who were candidate for endoscopic sinus surgery. They were randomly assigned to two study groups. One group received a single puff of local desmopressin (10 µg) in each side of nasal cavity 30 min before the surgery and the other received normal saline instead. Blood loss and the quality surgical field were determined in 15, 30, 60 and 90 min during the surgery (scoring by BOEZAART grading system). All data were analyzed. RESULTS: Blood loss was significantly lesser in the desmopressin group (mean ± SD, 16.289 ± 5.605 ml) than in the control group (24.289 ± 5.2722 ml, P < 0.001).Surgeons were more satisfied with the surgical field in the desmopressin group than control group in all cutoff points (15, 30, 60, and 90 min during the surgery, P < 0.001). No side effects were observed using local desmopressin. CONCLUSIONS: Premedication with local desmopressin can reduce bleeding effectively and clear the surgical field during functional endoscopic sinus surgery.

The Hemostatic Effect of Desmopressin on Bleeding as a Nasal Spray in Open Septorhinoplasty.

BACKGROUND: Rhinoplasty is associated with intraoperative bleeding which affects the quality of the operation and may increase the time of surgery. The aim of this study was to assess the role of nasal spray of desmopressin on reduction in intraoperative bleeding during elective open rhinoplasty. METHODS: Conducting an interventional study in our hospital, all patient data including demographic information, medical history and laboratory tests before surgery were collected. Patients who were randomly divided into two study groups, received nasal desmopressin spray or placebo spray, 60 min before starting open septorhinoplasty. The measured variables included: bleeding volume, the operative field quality in regard to bleeding (Boezaart score), the surgeons' satisfaction in regard to bleeding during surgery (Likert scale), postoperative bruising, postoperative bleeding and menstruation. RESULTS: Thirty cases were studied; 13 (46.3%) people received placebo and 17 (56.7%) received desmopressin. The Boezaart score, satisfaction scores, bleeding volume, upper eyelid ecchymosis in the group receiving desmopressin were significantly better than the control group. Postoperative bleeding was also less in the desmopressin group, but not significant as other variables. In women of each group, menstruation had no effect on the amount of bleeding, surgical field quality and surgeon satisfaction compared with non-menstruation women. CONCLUSION: Nasal desmopressin use is an effective method for reducing intraoperative and postoperative bleeding and diminished postoperative ecchymosis which improves surgeons' satisfaction. So using the nasal form of desmopressin could be considered as method of controlling bleeding and ecchymosis in open rhinoplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Do independent geriatric outpatients with nocturnal polyuria profit from desmopressin?

OBJECTIVE: To compare the efficacy of desmopressin and placebo in independent geriatric outpatients with nocturnal polyuria (NP). METHODS: A prospective, randomized, single-center, national, double blind, placebo-controlled, fixed-dose, parallel group comparative trial was carried out. The study included 110 geriatric outpatients, 55 patients per treatment group using desmopressin acetate nasal spray (strength: 0.1 mg/ml) once daily of 10 µg/spray blast or placebo. MEASUREMENT: The NP positive geriatric outpatients with >33% nocturnal urine output volume, antidiuretic hormone (ADH) positive or negative were treated over 10 days with intranasal spray in the evening time (7 p.m.), drug or placebo. On day 1 voiding frequency, voiding volumes day and night, serum osmolarity and arginine-vasopressin (AVP) were measured at 7 p.m. On days 2, 5 and 10 creatinine, blood urea nitrogen (bun), blood count and C­reactive protein (CrP), vena cava diameter and bioimpedance were measured and a structured interview was implemented (voiding frequency, sleeping behavior and subjective and cognitive behavior). RESULTS: The NP patients showed a mean night voiding volume of 50.60%, 39.21% (n = 102) showed a low AVP level at baseline with no correlation to sodium concentration or voiding frequencies. The primary efficacy criterion, a decrease of the nocturnal voiding frequency during the course of the clinical trial as change from baseline at day 10 (visit 4) was 50% versus 41.40% in the verum versus placebo group, respectively but the differences were not significant. The U­test showed superiority of AVP-positive NP patients to a positive reaction on desmopressin. Sleeping time hours increased in both groups without significant differences. CONCLUSION: In this 10-day clinical trial desmopressin was not proven to be therapeutically superior to placebo with respect to micturition frequency or sleeping hours. Independent geriatric outpatients with decreased ADH levels seemed to respond and benefit from active treatment with desmopressin. The unexpected results in the placebo group may be due to the effect of intensive outpatient care and information on NP outpatients with normal AVP levels.

Efficacy and Safety of SER120 Nasal Spray in Patients with Nocturia: Pooled Analysis of 2 Randomized, Double-Blind, Placebo Controlled, Phase 3 Trials.

PURPOSE: SER120 desmopressin intranasal spray is the first U.S. Food and Drug Administration approved pharmacotherapy for nocturia. We evaluated its efficacy and safety in 2 randomized, double-blind, placebo controlled studies, DB3 and DB4. MATERIALS AND METHODS: A total of 1,333 intent to treat patients 50 years old or older with 2.16 or more nocturic voids per night during a 2-week screening period were randomized equally to SER120 intranasal spray 1.66 or 0.83 mcg, or placebo for a 12-week treatment. Co-primary end points were the mean change from baseline in nocturic episodes per night and the percent of patients with a 50% or greater reduction in mean nocturic episodes per night. Secondary end points were the validated INTU (Impact of Nighttime Urination) quality of life questionnaire in DB4, time to the first nocturic void and the percent of nights with 1 or fewer nocturic voids. RESULTS: Each SER120 dose showed statistical significance vs placebo for the 2 co-primary end points, including the mean nocturic episodes per night (-1.4 with 0.83 mcg and -1.5 with 1.66 mcg vs -1.2 with placebo, each p <0.0001), the percent of patients with a 50% or greater reduction in mean nocturic episodes per night (37.9% with 0.83 mcg and 48.7% with 1.66 mcg vs 30.3% with placebo, p = 0.0227 and <0.0001, respectively) as well as for all secondary end points in the pooled analyses. The 1.66 mcg dose demonstrated significant improvements in the INTU score (p = 0.0255). The incidence of hyponatremia, defined as serum sodium 125 mmol/l or less regardless of symptoms or less than 130 mmol/l with symptoms, was 1.1%, 0% and 0.2% in the 1.66 and 0.83 mcg, and placebo groups, respectively. Other adverse events were similar across treatment groups. CONCLUSIONS: SER120 demonstrated significant improvements over placebo for co-primary and secondary efficacy end points that corresponded with quality of life improvements. SER120 at each dose had an acceptable safety profile.

Desmopressin stimulation testing: Response to intravenous and intranasal forms.

INTRODUCTION: Desmopressin is commonly used to reduce bleeding in patients with mucocutaneous bleeding disorders and is available in both intravenous and intranasal forms. Given the variability in response to desmopressin at an individual level, its effectiveness should be assessed with a test dose prior to being advised for use. At this time, no trial has extensively compared the use of intranasal desmopressin to intravenous desmopressin. AIMS: To determine whether both forms of desmopressin are equally effective in yielding a positive response in laboratory assays in paediatric patients with von Willebrand disease or probable von Willebrand disease. METHODS: We evaluated medical record data for 58 patients who underwent desmopressin stimulation testing in our haematology clinic during a 1-year period. Data were collected on demographic information and haematologic laboratory assays prior to desmopressin administration and one hour following desmopressin. RESULTS: There was an absolute increase in von Willebrand antigen to levels appropriate for haemostasis following both forms of desmopressin, although this increase was significantly greater in the intravenous group compared to the intranasal group. There was also a significant absolute increase in Ristocetin Cofactor and Factor VIII levels following desmopressin in both groups. CONCLUSION: Both intravenous and intranasal forms of desmopressin produce a positive response during desmopressin stimulation testing and can be used to identify patients for whom this medication would be effective.

Comparison of Two Weight-Based Desmopressin Dosing Strategies for Spontaneous Bleeding.

BACKGROUND: The pharmacokinetics and pharmacodynamics of desmopressin are appropriate for adjusted body weight-based dosing, particularly in obese patients. OBJECTIVE: The objective of this study was to describe desmopressin dosing strategies, with emphasis on hemostatic outcomes among patients without preexisting bleeding disorders. METHODS: This was a single-center, retrospective cohort study of patients who received intravenous weight-based desmopressin for a hemostatic indication. Demographics, comorbidities, treatment setting, indication, site of bleeding, and outcomes were collected from the medical record. Primary outcomes included need for procedural intervention to achieve hemostasis, transfusion requirement, and death. Association between desmopressin dose and outcome was evaluated using χ2 or Fischer's exact tests and logistic and linear regression models. Multiple regression analysis was conducted to identify other predictors of outcome in the data set. RESULTS: A total of 109 patients were included (n = 26, dose adjustment; n = 83, no dose adjustment). Baseline characteristics were well-matched between groups: mean (SD) age of 57.0 (13.5) years; mean (SD) Charlson Comorbidity Score of 6.5 (2.8); 37% were obese; 76% were critically ill; 81% were actively bleeding without differences in site of bleeding; and crude mortality was 39%. No differences in death, mean units of packed red blood cells transfused, or need for procedural hemostasis were observed between adjusted weight- and actual weight-based desmopressin dosing. CONCLUSIONS: When used adjunctively to blood product transfusion in actively bleeding patients, use of adjusted body weight-based desmopressin did not negatively affect clinical outcomes. More data are needed to confirm this dosing strategy.