Use Of DDAVP Research Articles

Desmopressin use in major cardiac surgery is associated with renal impairment: a retrospective single-center analysis

BackgroundDesmopressin acetate (1-deamino-8-d-arginine vasopressin—DDAVP) is a analogue of the antidiuretic hormone vasopressin. DDAVP is suggested to reduce bleeding after cardiac surgery using cardiopulmonary bypass. The aim of this study was to determine if DDAVP has any negative impact on renal function leading to acute kidney injury (AKI) and therefore increases the need for renal replacement therapy (RRT).MethodsWe performed a retrospective single institutional cohort analysis of 2,179 patients undergoing elective and urgent cardiac surgery with CPB from 2017 to 2021. Logistic regression analysis was used to investigate any association between DDAVP, the incidence of AKI KDIGO class 3 and the need for RRT, respectively. The model was adjusted for relevant covariates, including preexisting renal impairment, pharmacological hemodynamic support with vasopressors, complexity of the surgery and postoperative lactate. Secondary outcomes included, in hospital mortality and the need for allogenic blood transfusion.ResultsA total of 992 (45.5%) patients received DDAVP intraoperatively during surgery or shortly thereafter. The use of DDAVP was associated with a significant increase in in AKI KDIGO class 3 (OR 2.27; 95% CI 1.46–3.55; p < 0,001) and the need for RRT (OR 2.19; 95%CI 1.48–3.24; p < 0,001). Both findings persisted after covariate adjusting. No increased in-hospital mortality was associated with DDAVP.ConclusionIn cardiac surgery, the use of DDAVP was associated with an increased rate of server AKI and the requirement for RRT. Given the severity of the potential harm associated with DDAVP, an evidence-based reevaluation is needed to enable an accurate risk and benefit assessment.

Genotype-Dependent Response to Desmopressin in Hemophilia A and Proposal of a Predictive Response Score.

Desmopressin (DDAVP) is used in patients with moderate/mild hemophilia A (PWMHs) to increase their factor VIII (FVIII) level and, if possible, normalize it. However, its effectiveness varies between individuals. The GIDEMHA study aims to investigate the influence of F8 gene variants. The study collected the trajectory of FVIII levels from therapeutic intravenous DDAVP tests in four French hemophilia treatment centers. A pharmacological analysis was performed associated with efficacy scores according to F8 variants: absolute and relative responses, as well as new scores: absolute duration (based on duration with FVIII ≥ 0.50 IU.mL-1) and relative duration (based on half-life). From enrolled 439 PWMHs, 327 had a hot-spot F8 variant (with ≥5 PWMHs). For these, the median (min-max) basal and peak FVIII were 0.20 (0.02-0.040) and 0.74 (0.14-2.18) IU.mL-1 respectively, with FVIII recovery being 3.80 IU.ml-1 (1.15-14.75). The median FVIII half-life was 3.9 hours (0.7-15.9 hours). FVIII was normalized (≥0.50 IU.mL-1) in 224/327 PWMHs (69%) and the median time with normalized FVIII was 3.9 hours (0.0-54.1 hours). Following the response profiles to DDAVP defined by the four efficacy scores, four groups of F8 variants were isolated, and then compared using survival curves with normalized FVIII (p < 0.0001): "long-lastingly effective" [p.(Glu739Lys), p.(Ser2030Asn), p.(Arg2178His), p.(Gln2208Glu), and T-stretch deletion in intron 13]; "moderately effective" [p.(Ser112Phe), p.(Ala219Thr), p.(Thr2105Ile), p.Phe2146Ser), and p.(Asp2150Asn)]; "moderately ineffective" [p.Ala81Asp), p.(Gln324Pro), p.(Tyr492His), p.(Arg612Cys), p.(Met701Val), p.(Val2035Asn), and p.(Arg2178Cys)]; and "frequently ineffective" [c.-219C > T, p.(Cys2040Tyr), p.(Tyr2169His), p.(Pro2319Leu), and p.(Arg2326Gln)]. In view of our data, we propose indications for DDAVP use in PWMH based on F8 variants for minor and major invasive procedures.

Safety and efficacy of desmopressin (DDAVP) in preventing hematoma expansion in intracranial hemorrhage associated with antiplatelet drugs use: A systematic review and metaanalysis.

One of the most serious complications associated with antiplatelet agents is antiplatelet-associated intracranial hemorrhage (AA-ICH). Desmopressin is a synthetic antidiuretic hormone (ADH) analog. It has been linked to improving patient outcomes in antiplatelet-induced intracranial hemorrhage. The secondary outcomes included the incidence of thrombotic complications and neurological outcomes. A systematic search was conducted on three databases (PubMed, Cochrane, and ClinicalTrials.gov) to find eligible literature that compares desmopressin (DDAVP) versus controls in patients with AA-ICH. The Mantel-Haenszel statistic was used to determine an overall effect estimate for each outcome by calculating the risk ratios and 95% confidence intervals (CI). Heterogeneity was measured using the I2 test. The risk of bias in studies was calculated using the New Castle Ottowa Scale. Five studies were included in the analysis with a total of 598 patients. DDAVP was associated with a nonsignificant decrease in the risk of hematoma expansion (RR=.8, 95% CI,.51-1.24; p=.31, I2=44%). It was also associated with a non-significant decrease in the risk of thrombotic events (RR,.83; 95% CI,.25-2.76; p=.76, I2=30%). However, patients in the DDAVP group demonstrated a significant increase in the risk of poor neurological outcomes (RR, 1.31; 95% CI, 1.07-1.61; p=.01, I2=0%). The risk of bias assessment showed a moderate to low level of risk. DDAVP was associated with a nonsignificant decrease in hematoma expansion and thrombotic events. However, it was also associated with a significantly poor neurological outcome in the patients. Thus, until more robust clinical trials are conducted, the use of DDAVP should be considered on a case-to-case basis.

Rates and Predictors of Prophylaxis in Women with Von Willebrand Disease and Heavy Menstrual Bleeding

Background: Women with von Willebrand disease (vWD) suffer from heavy menstrual bleeding (HMB) often complicated by iron deficiency anemia (IDA) and reduced quality of life. Despite the American Society of Hematology (ASH) recommendations for long-term prophylaxis in patients with severe frequent bleeds, prophylaxis remains under-utilized in women with severe HMB. Given the scarcity of data on management of gynecological bleeding, it is critical to examine our practice patterns and identify factors associated with prophylaxis use. Aims: 1) To evaluate the management and outcomes of gynecological bleeding in vWD, including rates of desmopressin (DDAVP) and vWF prophylaxis for HMB and predictors of their use. 2) To examine the association between prophylaxis and severe HMB. Methods: This retrospective cohort study included women ≥18 years diagnosed with vWD in the Northern Alberta Bleeding Disorders Program. We assessed the rates of HMB, severe HMB and IDA, along with their management strategies. Prophylaxis rates with DDAVP and vWF concentrates, as well as predictors of their use, were examined. Severe HMB was defined as HMB requiring Emergency Department (ED) visits, hospitalizations, blood transfusions, or surgical management (dilation &amp; curettage [D&amp;C], endometrial ablation or hysterectomy). IDA was defined as ferritin &amp;lt;30 mcg/L and hemoglobin &amp;lt;120 g/L. Logistic regression was used to examine factors associated with severe HMB. Variables with P-value &amp;lt;0.20 on univariate regression were included in multivariable regression. Results: 168 women were evaluated with a median age of vWD diagnosis of 27 years (IQR 18-38): 140 (81%) type 1, 23 (13%) type 2, and 5 (3%) type 3 vWD. Among those with type 1 vWD, 43 (31%) had baseline vWF levels &amp;lt;0.30 IU/ml, 94 (67%) had vWF levels of 0.30-0.49 IU/ml, and 3 (2%) had missing values. DDAVP response was assessed in 124/140 (89%) type 1 vWD and 13/23 (57%) type 2 vWD. There were 145 (86%) women with HMB, managed most commonly by tranexamic acid (TXA) (112; 77%), followed by hormonal therapy (73; 50%), subcutaneous DDAVP (40; 28%), and levonorgestrel intrauterine system (39; 26%). vWF prophylaxis was used in only 11 (8%) women. Surgical procedures for HMB were common including hysterectomy (28; 19%), endometrial ablation (15; 10%) and D&amp;C (15; 10%). Over a quarter (39; 27%) received iron infusions. Of the 65 (45%) women with a history of IDA, 6 (9%) had persistent IDA &amp;gt;5 years, 6 (9%) had IDA lasting 2-5 years and 53 (65%) had IDA corrected within 2 years. Prophylaxis rates did not differ between the 68 (40%) women with severe HMB and the 77 (53%) with non-severe HMB, with comparable rates of VWF use (9% vs 6%, P=0.60). Compared with women who never received prophylaxis, those who received DDAVP or vWF prophylaxis were more likely to have received TXA (93% vs 70%, P=0.003), iron infusions (43% vs 19%, P=0.004) and to have been diagnosed before 2000 (22% vs 7%, P=0.03) (Table 1). Though non-significant, a higher proportion of type 3 vWD (9% vs 1%, P=0.06) and higher ISTH-BAT (median 8 vs 7, P=0.07) were observed in prophylaxis recipients. On multivariable logistic regression, time from first bleeding symptom to diagnosis (adjusted odds ratio [aOR] 1.04, 95% CI 1.01-1.07) and prophylactic DDAVP use (aOR 2.4, 95% 1.01-5.6) were associated with severe HMB. There was a non-significant trend towards lower odds of severe HMB in patients diagnosed in 2000-2010 and 2011-2021 as compared to pre-2000 (aOR 0.3, 95% 0.1-1.0). Diagnosis before age 18, vWD type and baseline vWF activity were not associated with severe HMB. Conclusion: Women with vWD experience high rates of HMB and its associated complications. In our study, there was a relatively high uptake of DDAVP prophylaxis, however vWF prophylaxis was under-utilized even in those with severe HMB. We failed to demonstrate an impact of either prophylactic therapy on severe HMB, though this may be due to confounding by indication. There was a significant association between prophylactic DDAVP and vWF with other quality of care indicators including TXA and iron infusions. It is unclear if this association is related to practice patterns or patient factors such as access to care or preference for early definitive treatment. Overall, our findings highlight a need to further understand the barriers to prophylaxis use and to consider earlier prophylaxis for severe HMB to decrease bleeding complications and the need for resource-intensive therapies.

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

BackgroundAlthough desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties. ObjectivesWe aimed to review the safety and effectiveness of DDAVP in women with an inherited bleeding disorder during pregnancy and delivery. MethodsDatabases 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). ResultsFifty-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). ConclusionDDAVP 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.

Desmopressin (DDAVP) use in patients with von Willebrand disease: A single-centre retrospective review of test response and clinical outcomes.

Peri-procedural management of von Willebrand disease (VWD) utilizes von Willebrand factor (VWF) concentrates or desmopressin (DDAVP) to increase VWF levels. DDAVP is safe, easily administered, and inexpensive. Currently, a consensus definition for adequate DDAVP response is lacking, and outcomes of peri-procedural DDAVP use in VWD patients are seldom reported. This single-centre retrospective review aims to characterize DDAVP-responsiveness and assess clinical outcomes of peri-procedural DDAVP use in VWD. We reviewed records for all our adult VWD patients (age ≥18 years) who underwent DDAVP challenge testing between January 2007 and January 2022. DDAVP-responsiveness was assessed using six definitions. Bleeding outcomes following procedures covered by DDAVP were classified as excessive or expected bleeding. Eighty-four of 94 (89.4%) patients were DDAVP-responsive by our definition (1-h VWF Activity/Factor VIII ≥0.50 IU/mL). However, the proportion of DDAVP-responders varied from 53.2% to 91.5%, depending on the literature definition used. Ninety-nine procedures pre-treated with DDAVP were performed during the study period. Eighty-six (86.7%) procedures (31 major; 55 minor) were covered with only DDAVP±tranexamic acid (TXA). Excessive bleeding occurred following 4/31 major procedures and 2/55 minor procedures (both performed in a single patient with a bleeding score of 16). When covered with DDAVP+Factor±TXA, one each of 10 major and 3 minor procedures (performed in 2 patients with bleeding scores 15-16) resulted in post-procedural bleeding. Peri-procedural DDAVP prophylaxis appears to be effective among individuals with VWD. Beyond DDAVP-responsiveness, patient bleeding history and procedure invasiveness should be considered in determining suitability for DDAVP prophylaxis.

The Use of DDAVP During Overcorrection of Severe Hyponatremia

The Use of DDAVP During Overcorrection of Severe Hyponatremia

Comparison of the Effect of Injectable Tranexamic Acid and Inhaled Desmopressin in Controlling Bleeding and Ecchymosis in Open Rhinoplasty.

Bleeding during rhinoplasty surgery has a negative effect on the quality of surgery; so, it is important to reduce bleeding during rhinoplasty. We aimed to evaluate the effect of injectable tranexamic acid (TXA) and nasal spray of desmopressin (DDAVP) on reduction in intraoperative bleeding and ecchymosis after open rhinoplasty. In a Randomized Clinical Trial ( RCT) prepared since 2020 to 2021 in Razi Hospital and Imam Khomeini Hospital, Tehran, Iran on 42 patients who underwent open rhinoplasty were divided into three groups. In the first group, TXA was injected one hour before surgery at a dose of 10 mg / kg with a placebo inhalation spray. In the second group, DDAVP was administered as a nasal spray at a dose of 40 mcg with a placebo injection. The third group received a placebo spray and placebo injection. All required data were gathered and analyzed. In TXA group and DDAVP groups, the volume of bleeding during surgery significantly (P=0.022) decreased compared to placebo group, also, the quality of the surgical field and the surgeon's satisfaction significantly (P=0.007) improved compared to the placebo group but not with each other. Unlike placebo group, there were no reports of postoperative bleeding in the TXA and DDAVP groups. Duration of surgery, ecchymosis on the day after surgery and coagulation tests before and after surgery were not significantly different in three groups. Use of DDAVP and TXA can both reduce the amount of bleeding during surgery and postoperative bleeding in rhinoplasty and improve the quality of the surgical field and the surgeon 's satisfaction during surgery.

Desmopressin Stimulates Nitric Oxide Production in Human Lung Microvascular Endothelial Cells.

Desmopressin (dDAVP) is the best characterized analogue of vasopressin, the endocrine regulator of water balance endowed with potent vasoconstrictive effects. Despite the use of dDAVP in clinical practice, ranging from the treatment of nephrogenic diabetes insipidus to bleeding disorders, much remains to be understood about the impact of the drug on endothelial phenotype. The aim of this study was, thus, to evaluate the effects of desmopressin on the viability and function of human pulmonary microvascular endothelial cells (HLMVECs). The results obtained demonstrate that the vasopressor had no cytotoxic effect on the endothelium; similarly, no sign of endothelial activation was induced by dDAVP, indicated by the lack of effect on the expression of inflammatory cytokines and adhesion molecules. Conversely, the drug significantly stimulated the production of nitric oxide (NO) and the expression of the inducible isoform of nitric oxide synthase, NOS2/iNOS. Since the intracellular level of cAMP also increased, we can hypothesize that NO release is consequent to the activation of the vasopressin receptor 2 (V2R)/guanylate cyclase (Gs)/cAMP axis. Given the multifaceted role of NOS2-deriving NO for many physio-pathological conditions, the meanings of these findings in HLMVECs appears intriguing and deserves to be further addressed.

Treatment with ddAVP improves platelet-based coagulation in a rat model of traumatic hemorrhagic shock

ObjectivesTrauma-induced hemorrhagic shock is characterized by increased endothelial permeability and coagulopathy. Vasopressin analog ddAVP (desmopressin) acts by reorganizing and redistributing adhesive and tight junction molecules, enhancing endothelial barrier function. Furthermore,...

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

PurposeTo 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). MethodsThis 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. ResultsA 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. ConclusionsDDAVP 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.

Desmopressin acetate use in von Willebrand's disease: a survey on current practices in Brazil.

Introductionvon Willebrand’s disease (VWD) is the most common inherited bleeding disorder. The 1-desamino-8-d-arginine vasopressin (DDAVP) is the treatment of choice for most responsive patients with VWD. The aim of this study was to evaluate DDAVP use in the management of VWD.MethodWe implemented a survey targeting medical doctors involved in the management of VWD in Brazil. Data was collected during a national congress on Hematology in November 2017.Main resultsA total of 51/80 (63.8%) questionnaires were collected. Most participants (76.2%) were hematologists who assisted adult patients and approximately 60% worked at hemophilia treatment centers (HTCs). Approximately half of participants who reported treating patients with VWD, assisted on average, less than 5 patients per month, and approximately 60% declared not having used any DDAVP for treating VWD in the previous year. However, most participants (70%) prescribed FVIII-containing VWF concentrate (VWF/FVIII) for 1–10 patients in the previous year. More than 80% of the participants recognized the main indications for DDAVP. Physicians who recognized indication for DDAVP for type 1 VWD more often had prescribed DDAVP in previous year (p = 0.03). Barriers for prescribing DDAVP varied and included unavailability of laboratory facilities and consumables for DDAVP testing and lack of skills on its prescription.ConclusionThe DDAVP is currently underused in Brazil, as opposed to the excessive use of VWF/FVIII in VWD patients. We suggest the adoption of measures targeting educational and auditing programs. Furthermore, availability of laboratory reagents is needed to evaluate response and increment the correct use of DDAVP.

The Role of Desmopressin on Hematoma Expansion in Patients with Mild Traumatic Brain Injury Prescribed Pre-injury Antiplatelet Medications.

Desmopressin (DDAVP) has been suggested for antiplatelet medication reversal in patients with traumatic brain injury (TBI) but there are limited data describing its effect on clinical outcomes. The purpose of this study was to evaluate the effect of DDAVP on hematoma expansion and thrombosis in patients with TBI who were prescribed pre-injury antiplatelet medications. Consecutive adult patients who were admitted to our level I trauma center and prescribed pre-injury antiplatelet medications between July, 2012, and May, 2018, were retrospectively identified. Patients were excluded if their hospital length of stay was < 24h, if DDAVP was administered by any route other than intravenous, if they received a DDAVP dose < 0.3 mcg/kg or there was no evidence of brain hemorrhage on computed tomography (CT) scan. Patients were stratified based on the use of DDAVP, and the incidence of hematoma expansion was compared between groups. Thrombotic events were reviewed as a secondary outcome. Multivariate analysis was utilized to control for confounding variables. Of 202 patients included in analysis, 158 (78%) received DDAVP. The mean age was 76 ± 12years; the most common injury mechanism was falls (76%); 69% had acute subdural hematoma, and 49% had multi-compartmental hemorrhage. Initial Glasgow coma score was between 13 and 15 for 91% of patients. Aspirin was the most common antiplatelet regimen prescribed (N = 151, 75%), followed by dual antiplatelet regimens (N = 26, 13%) and adenosine diphosphate (ADP)-receptor inhibitors (N = 25, 12%). The incidence of hematoma expansion was 14% and 30% for patients who did and did not receive DDAVP, respectively (p = 0.015). After controlling for age, injury severity score, multi-compartmental hemorrhage, and receipt of pre-injury high-dose aspirin (> 81mg), ADP-receptor inhibitors, oral anticoagulants, prothrombin complex concentrates or platelets in a multivariate analysis, the association between DDAVP and hematoma expansion remained significant (adjusted OR 0.259 [95% CI 0.103-0.646], p = 0.004). Thrombotic events were similar between the two groups (DDAVP, 2.5%, no DDAVP, 4.5%; p = 0.613). DDAVP was associated with a lower incidence of hematoma expansion in patients with mild TBI who were prescribed pre-injury antiplatelet medications. These results justify a randomized controlled trial to further evaluate the role of DDAVP for this indication.

A new experimental mouse model of water intoxication with sustained increased intracranial pressure and mild hyponatremia without side effects of antidiuretics.

The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg·kg−1 desmopressin acetate (dDAVP). Corresponding Sham groups were also studied. In the new WI protocol (mild WI), 10% body weight of a solution containing 6.5 mM NaHCO3, 1.125 mM KCl and 29.75 mM NaCl was intraperitoneally injected. By severe WI, ICP and mean arterial pressure increased until brain stem herniation occurred (23 ± 3 min after injection). The cardiovascular effects were accelerated by dDAVP. Severe WI induced a halt to urine production irrespective of the use of dDAVP. Following the new mild WI protocol, ICP also increased but was sustained at a pathologically high level without inducing herniation. Mean arterial pressure and urine production were not affected during mild WI. In conclusion, the new mild WI protocol is a superior experimental model to study the pathophysiological effects of elevated ICP induced by water intoxication.

SUN-410 Central Diabetes Insipidus Refractory to Oral Desmopressin (DDAVP)

Background We report a case of CDI due to craniopharyngioma resection that became refractory to oral DDAVP after recurrence of tumor and subsequent surgical removal. Due to inability of patient to use the intranasal route, subcutaneous (SC) DDAVP was used successfully. Clinical Case An 11-year male developed CDI after craniopharyngioma removal and proton beam therapy. He developed also panhypopituitarism, hypothalamic obesity, and had an impaired thirst mechanism. CDI was managed with oral DDAVP and fix fluid intake. After 2 years he had a tumor recurrence and a surgical removal complicated by a stroke. Since then his DDAVP dose had to be increased progressively due to poor CDI control. He presented to our hospital with severe hypernatremia and a urine output of 4-5 liters a day. DDAVP dose was eventually titrated up to 800 mcg bid. He was placed on minimum fluid intake of 3 Liters a day. Even with this dose he was putting out 4 liters of urine daily. Intranasal DDAVP was not considered due to poor cooperation of patient and nasal mucosa scarring. SC DDAVP was started at a dose of 1 mcg (0.01 mcg/Kg) twice a day.Dose increments were made by 0.5 mcg every 2 days to avoid hyponatremia. Prior to therapy patient received 4 liters/day and was progressively decreased, as DDAVP dose was increased, to 1.7 liters/day. Patient was discharged home on 4.5 mcg in the morning and 5.5 mcg at night time (0.14 mcg/kg/day). Discussion The route of administration of DDAVP varies depending on the age and cooperation of the patient to use the different forms available. DDAVP has also haemostatic effect. It is used in the treatment or to prevent bleeding in patients with von Willebrand disease, haemophilia A and platelet function defects. We hypothesize that our patient became resistant to the action of oral DDAVP probably due to the development of antibodies that were interfering with the appropriate absorption from the gastrointestinal tract. The parenteral/SC route dose ranges from 0.1-1 mcg in one or two divided doses nevertheless our patient had a stroke and we were concerned about the maximum dose that it could be used without increasing the risk of causing a new thrombotic event. With no data available about the use of DDAVP in this specific setting, we decided to use as a limit the dose used to treat bleeding disorders (0.3 mcg/Kg).Since our patient had basically an adult weight (70kg) we have enough room to continue increasing the dose up until desire effect was reached keeping in mind that 20 mcg/day is the maximum dose used in adults with bleeding disorders. Since discharge his sodium has remained stable as also his urine output and he has been able to reassume his daily activities. Conclusion: We present a case of CDI refractory to oral DDAVP.SC DDAVP was used and after slow titration patient was able to reach stable sodium levels and urine output with no side effects. Final dose was less than 50% of the dose used to treat bleeding disorders.

Clinical observation of desmopressin in the treatment of 15 patients with DDAVP

目的探讨去氨加压素（DDAVP）在血管性血友病（VWD）诊断和治疗中的应用价值。方法对2016年3月至2018年8月期间15例接受DDAVP治疗的VWD患者进行分析，观察治疗反应及患者用药前及用药后2 h凝血因子Ⅷ活性及血管性血友病因子（VWF）相关指标变化。结果15例VWD患者中，男7例，女8例，中位年龄23（6~46）岁。9例1型VWD患者中，7例达完全反应；1例2A型VWD患者达完全反应，5例3型VWD患者无反应。对5例患者进行VWF多聚体分析，结合其他VWF相关检测指标，DDAVP治疗效果与患者疾病分型相符合。结论DDAVP对1型VWD患者可达到较好疗效，对部分2型VWD及3型VWD患者反应不佳；VWD患者对DDAVP的治疗反应对治疗选择具有重要意义。

Perioperative Desmopressin for Patients Undergoing Otolaryngologic Procedures: A Systematic Review.

Desmopressin (DDAVP) is a hemostatic agent used to manage bleeding in patients with hemostatic disorders, and there is a lack of published data to guide its use during otolaryngology procedures. The objective of this study was to conduct an evidence-based systematic review of the reported uses, efficacy, and adverse effects of DDAVP in the otolaryngology surgical setting. PubMed, MEDLINE, and EmBase were searched for articles on the use of DDAVP in otolaryngology. The Methodological Index for Non-Randomized Studies criteria and Cochrane bias tool were used to assess study quality. Patient demographics, DDAVP dosing and route, and outcomes such as bleeding and adverse events were collected. A summary of evidence table was created specifying levels of evidence, benefits, and harm. Nineteen studies encompassing 440 patients were included. Sixteen studies discussed DDAVP for prophylaxis, and 3 discussed postoperative use. DDAVP effectively prevented bleeding in high-risk patients and successfully facilitated a dry surgical field when necessary. DDAVP had a 100% success rate when used symptomatically. Five studies described adverse effects, including hyponatremia (12.3%), nausea (2.0%), emesis (0.9%), and seizure (0.2%). The aggregate level of evidence for its use was Level B for adenotonsillectomy, septoplasty, and turbinate procedures and Level C for rhinoplasty. Current literature supports the use of DDAVP in otolaryngology surgical procedures as both a perioperative prophylactic agent and a postoperative symptomatic intervention for bleeding. Both modalities are effective with minimal adverse events. Further well-designed randomized trials are necessary to conclusively formulate guidelines for DDAVP use in otolaryngology.

The Role of Desmopressin in the Management of Severe, Hypovolemic Hyponatremia: A Single-Center, Comparative Analysis.

Background:The role of desmopressin (DDAVP) to prevent or treat rapid serum sodium concentration ([Na]s) correction during hyponatremia management remains unclear.Objective:To assess DDAVP use during the first 48 hours of severe, hypovolemic hyponatremia management. The primary study hypothesis was that the use of DDAVP would slow the rate of [Na]s correction compared with those not receiving DDAVP.Design:A retrospective, observational, comparison study.Setting:A single, Canadian, tertiary center.Patients:All admitted patients referred to the nephrology service for severe, hypovolemic hyponatremia ([Na]s < 125 mmol/L) over a 12-month period from November 2015.Measurements:The primary outcomes measure was the [Na]s after medical management for 48 hours. The length of hospital stay was also measured.Methods:Patients were grouped based on whether they received DDAVP during the first 48 hours of treatment, and [Na]s correction was compared between groups using linear regression. An exploratory, multivariable, linear regression model was used to adjust for diabetes status, active malignancy, intensive care unit (ICU) admission, and hypertonic saline administration.Results:Twenty-eight patients were identified, with baseline mean [Na]s of 112.7 ± 6.6 mmol/L versus 117 ± 4.3mmol/L (P = .06) in those receiving (n = 16) and not receiving DDAVP (n = 12), respectively. The DDAVP group had a more rapid [Na]s correction on the first day compared with those not receiving DDAVP, 7.7 ± 3.8 mmol/L/d versus 5.1 ± 2.0 mmol/L/d (P = .04). On the second day, there was a similar rate of [Na]s correction between groups: 1.3 ± 4.3 mmol/L/d versus 2.6 ± 3.2 mmol/L/d (P = .39), respectively. Overall, there was no difference in [Na]s correction after 48 hours between those who received DDAVP and those who did not: 121.7 ± 7.5 mmol/L versus 124.8 ± 5.7 mmol/L (P = .24). Patients who had experienced an overcorrection were successfully treated with DDAVP (n = 5), so that no patient had an ongoing overcorrection by 48 hours.Limitations:The limited sample size and lack of randomization preclude definitive conclusion on the additional benefit of DDAVP to standard care.Conclusion:DDAVP appears to be safe and effective in the management of severe, hypovolemic hyponatremia, associated with similar [Na]s correction to those who did not receive DDAVP after 48 hours, despite an initial more rapid correction. A randomized trial should examine what benefit DDAVP confers in addition to standard care in the management of severe, hypovolemic hyponatremia.

Outcomes in Severe Hyponatremia Treated With and Without Desmopressin

BackgroundOvercorrection of plasma sodium in severe hyponatremia is associated with osmotic demyelination syndrome. Desmopressin (DDAVP) can prevent overcorrection of plasma sodium in hyponatremia. The objective of this study was to compare outcomes in hyponatremia according to DDAVP usage. MethodsThis was a retrospective observational study including all admissions to internal medicine with hyponatremia (plasma sodium concentration <123 mEq/L) from 2004 to 2014 at 2 academic hospitals in Toronto, Canada. The primary outcome was safe sodium correction (≤12 mEq/L in any 24-hour and ≤18 mEq/L in any 48-hour period). ResultsWe identified 1450 admissions with severe hyponatremia; DDAVP was administered in 254 (17.5%). Although DDAVP reduced the rate of change of plasma sodium, fewer patients in the DDAVP group achieved safe correction (174 of 251 [69.3%] vs 970 of 1164 [83.3%]); this result was driven largely by overcorrection occurring before DDAVP administration in the rescue group. Among patients receiving DDAVP, most received it according to a reactive strategy, whereby DDAVP was given after a change in plasma sodium within correction limits (174 of 254 [68.5%]). Suspected osmotic demyelination syndrome was identified in 4 of 1450 admissions (0.28%). There was lower mortality in the DDAVP group (3.9% vs 9.4%), although this is likely affected by confounding. Length of stay in hospital was longer in those who received DDAVP according to a proactive strategy. ConclusionsAlthough observational, these data support a reactive strategy for using DDAVP in patients at average risk of osmotic demyelination syndrome, as well as a more stringent plasma sodium correction limit of 8 mEq/L in any 24-hour period for high-risk patients. Further studies are urgently needed on DDAVP use in treating hyponatremia.

Role of Renal Compensation and dDAVP in a Mouse Model of Hyponatremia and Brain Edema induced by Water Intoxication

IntroductionHyponatremia is the most common electrolyte disorder in clinical practice. Acute hyponatremia can induce brain edema (BE), a condition for which no targeted therapeutical agent has been developed. A range of studies have previously used water intoxication (WI) to create experimental hyponatremia induced BE. Most of these studies have also used desmopressin acetate (dDAVP) to accentuate the effects of WI by inhibiting renal free‐water excretion. However, renal compensation in terms of urine production during WI induced BE has rarely been measured.Aim of the studyTo determine urine production and changes in cardiovascular parameters during WI and the effect of dDAVP on key physiological parameters.Methods4 groups of mice (n=6) (C57Bl/6) were anesthetized with isoflurane (ISO). WI‐groups received distilled water (20% BW), either with or without dDAVP (0.4 μg/kg) by IP injection. Sham‐ groups received no water load with or without dDAVP. Mean arterial pressure (MAP), heart rate (HR), end‐tidal CO2 (EtCO2), pH, pCO2, blood gasses, strong ion difference (SID) and urine production were evaluated during development of BE. Brain water content was evaluated post‐ mortem by wet‐dry method. In a separate group (n=4) intracranial pressure (ICP) was measured during WI + dDAVP.ResultsBrain water content (%) was significantly higher in WI groups compared to Sham (82.7±0.4 vs 80.9±0.7 for +dDAVP, 81.4±0.5 vs 80.2±0.3 for −dDAVP) (p=0.0089) and a borderline‐ significant increase in brain water was observed as effect of dDAVP (p= 0.068). Drastic increase in ICP was observed during WI further documenting BE development. MAP followed a very reproducible pattern for all experimental mice after WI, characterized by increasing hypertension/ peak / drop / hypotension. The use of dDAVP increased the magnitude of WI‐induced changes in MAP, resulting in a significant reduction of 2.9 ± 1.1 min to reach peak value during WI (p=0.036). Similarly, dDAVP had a significant effect on HR (~56 BMP higher than WI‐dDAVP (p= 0.0085)). In both WI groups, EtCO2 peaks pattern synchronized completely with artificial ventilation after 30 min, documenting compression of respiratory centers in the brain stem. Plasma ions (mmol/L) were significantly decreased in both WI groups already 5 min after water injection (Na+: 128±1.4 for +dDAVP, 130±5.0 for −dDAVP.) and metabolic acidosis developed (pH: 7.34±0.03; 7.34±0.05) (HCO3−:19±0.5; 17±0.75); (SID=−3.36; −3.10) for +dDAVP and − dDAVP, respectively. Surprisingly, dDAVP had no significant effect on urine production after WI (0.10 ± 0.11 for +dDAVP vs 0.21±0.15 for −dDAVP, μl/min*BW, p=0.757).ConclusionWater intoxication in this model results in rapid development of BE, cardiovascular changes and ICP‐changes leading to herniation irrespective of the use of dDAVP. No increased renal water excretion is seen upon WI. Urine water excretion in the model is drastically reduced irrespective of dDAVP injection. These results question the previously held assumption of renal compensation during experimental WI.Support or Funding InformationThe Danish Council for Independent Research | Medical Sciences, grant ID 4004‐00504 Title: Aquaporins: roles in pathogenesis and treatment of hyponatremia;MEMBRANE research center, Aarhus University;The Graduate School of Health, Aarhus University