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Journal of Thrombosis and Haemostasis :... Jan 2024Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties.
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.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Blood Coagulation Disorders, Inherited; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Hyponatremia; Pregnant Women; Prospective Studies
PubMed: 37778511
DOI: 10.1016/j.jtha.2023.09.021 -
Lower Urinary Tract Symptoms May 2022Desmopressin acetate was recommended for nocturia in benign prostatic hyperplasia (BPH) patients recently, but its effect and safety is still controversial. We aimed to... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Deamino Arginine Vasopressin; Dizziness; Headache; Humans; Hyponatremia; Male; Nausea; Nocturia; Prostatic Hyperplasia; Quality of Life; Treatment Outcome
PubMed: 35034423
DOI: 10.1111/luts.12423 -
Asian Journal of Urology Jan 2022To evaluate the efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder (OAB) and nocturia. (Review)
Review
Efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder and nocturia, current clinical features and outcomes: A systematic review.
OBJECTIVE
To evaluate the efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder (OAB) and nocturia.
METHODS
A selective database search was conducted to validate the effectiveness of desmopressin in patients with OAB and nocturia. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were utilised. The meta-analysis included 378 women (five studies) with OAB. The clinical outcomes and adverse events were analysed.
RESULTS
The treatment strategy of all the studies included can be divided into three categories: (1) The effect of desmopressin compared with baseline, (2) desmopressin compared with placebo, and (3) desmopressin and anticholinergic combination versus desmopressin monotherapy. There was a significant (50%) reduction in nocturia and urgency episodes after using desmopressin alone. Combined desmopressin and anticholinergic led to a decrease in the frequency of nocturia voids when only using anticholinergic (65% 33.2%). The time increased in the middle to the first nightly voids in the combination arm (65.11 min; =0.045). The mean incidence (standard deviation) of leak-free episodes was higher under desmopressin than under placebo in the first 4 h (62% [35%] 48% [40%]) and in the first 8 h (55% [37%] 40% [41%]). The safety profile was comparable between treatments.
CONCLUSION
Available data indicate that desmopressin is efficacious in significantly reducing nighttime urine production, episodes of nocturia, and urgency episodes. The affectivity of the combination therapy was very high with least side effects for the treatment of OAB/nocturnal polyuria.
PubMed: 35198394
DOI: 10.1016/j.ajur.2021.05.005 -
The Cochrane Database of Systematic... Feb 2023Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion.
OBJECTIVES
To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss.
SEARCH METHODS
We searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs. We were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this review. Systemic drug treatments We identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants). Neither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding. Tranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision). There is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE). Topical drug treatments Most trials of topical drug treatments were at high risk of bias due to their open-label design (compared with usual care, or liquids were compared with sponges). All of the trials were small, most were very small, and few reported clinically relevant outcomes in the postoperative period. Fibrin sealant versus usual care was the topical drug comparison with the largest number of participants (5 trials, 784 participants). The five trials that compared fibrin sealant with usual care were all at high risk of bias, due to the open-label trial design with no measures put in place to minimise reporting bias. All of the trials were funded by pharmaceutical companies. None of the five trials reported the number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. The other three outcomes were associated with very low-certainty evidence with wide confidence intervals due to small sample sizes and the low number of events, these were: all-cause mortality up to 30 days; risk of requiring a repeat procedure due to bleeding; and risk of thromboembolic disease up to 30 days. We identified one large trial (500 participants) comparing fibrin sealant versus usual care in participants undergoing abdominal aortic aneurysm repair, which has not yet started recruitment. This trial lists death due to arterial disease and reintervention rates as primary outcomes.
AUTHORS' CONCLUSIONS
Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.
Topics: Adult; Humans; Aprotinin; Blood Transfusion; Deamino Arginine Vasopressin; Fibrin Tissue Adhesive; Hemorrhage; Network Meta-Analysis; Tranexamic Acid
PubMed: 36800489
DOI: 10.1002/14651858.CD013649.pub2 -
Blood Reviews Nov 2023Optimal peri-operative management for women with Von Willebrand disease (VWD) and heavy menstrual bleeding (HMB) remains undetermined. (Review)
Review
BACKGROUND
Optimal peri-operative management for women with Von Willebrand disease (VWD) and heavy menstrual bleeding (HMB) remains undetermined.
AIM AND METHODS
To evaluate (pre)operative management in relation to (post)operative bleeding after endometrial ablation (EA) and hysterectomy in VWD women with HMB by performing a database search between 1994 and 2023.
RESULTS
Eleven cohort studies and 1 case-report were included, of overall 'low' quality, describing 691 operative procedures. Prophylaxis (Desmopressin, clotting factor concentrates or tranexamic acid) to prevent bleeding was described in 100% (30/30) of EA procedures and in 4% (24/661) of hysterectomies. Bleeding complications despite prophylaxis were described in 13% (3/24) of hysterectomies vs 0% (0/30) in EA.
CONCLUSION
VWD women often seem to experience bleeding complications during hysterectomy and all women with VWD received preprocedural hemostatic agents during EA, indicating potential under- and overdosing of current prophylactic strategies. Prospective studies are needed to determine the optimal (pre)operative strategy for gynecological surgical procedures in women with VWD.
Topics: Female; Humans; Hemorrhage; Menorrhagia; Prospective Studies; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor
PubMed: 37716881
DOI: 10.1016/j.blre.2023.101131 -
Frontiers in Endocrinology 2024We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome... (Meta-Analysis)
Meta-Analysis
UNLABELLED
We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome (EAS). A systematic review of studies on diagnostic test accuracy in patients with CD, NNH, or EAS subjected to the desmopressin test obtained from LILACS, PubMed, EMBASE, and CENTRAL databases was performed. Two reviewers independently selected the studies, assessed the risk of bias, and extracted the data. Hierarchical and bivariate models on Stata software were used for meta-analytical summaries. The certainty of evidence was measured using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation Working Group) approach. In total, 14 studies were included: 3 studies on differentiated CD versus NNH and 11 studies on differentiated CD versus EAS. Considering ΔACTH in 8 studies involving 429 patients, the pooled sensitivity for distinguishing CD from EAS was 0.85 (95% confidence interval [CI]: 0.80-0.89, I2 = 17.6%) and specificity was 0.64 (95% CI: 0.49-0.76, I2 = 9.46%). Regarding Δcortisol in 6 studies involving 233 participants, the sensitivity for distinguishing CD from EAS was 0.81 (95% CI: 0.74-0.87, I2 = 7.98%) and specificity was 0.80 (95% CI: 0.61-0.91, I2 = 12.89%). The sensitivity and specificity of the combination of ΔACTH > 35% and Δcortisol > 20% in 5 studies involving 511 participants were 0.88 (95% CI: 0.79-0.93, I2 = 35%) and 0.74 (95% CI: 0.55-0.87, I2 = 27%), respectively. The pooled sensitivity for distinguishing CD from NNH in 3 studies involving 170 participants was 0.88 (95% CI: 0.79-0.93) and the specificity was 0.94 (95% CI: 0.86-0.97). Based on the desmopressin test for differentiating CD from EAS, considering ΔACTH, Δcortisol, or both percent increments, 15%, 19%, or 20% of patients with CD, respectively, would be incorrectly classified as having EAS. For CD versus NNH, 11% of patients with CD would be falsely diagnosed as having NNH, whereas 7% of patients with NNH would be falsely diagnosed as having CD. However, in all hierarchical plots, the prediction intervals were considerably wider than the confidence intervals. This indicates low confidence in the estimated accuracy, and the true accuracy is likely to be different.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=85634, identifier CRD42018085634; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=68317, identifier CRD42017068317.
Topics: Humans; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; ACTH Syndrome, Ectopic; Pituitary ACTH Hypersecretion
PubMed: 38352712
DOI: 10.3389/fendo.2024.1332120 -
BMC Urology Oct 2023Patients with benign prostatic hyperplasia (BPH) receive α-blockers as first-line therapy to treat lower urinary tract symptoms; however, some individuals still... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with benign prostatic hyperplasia (BPH) receive α-blockers as first-line therapy to treat lower urinary tract symptoms; however, some individuals still experience residual storage symptoms. Antimuscarinics, β3-agonists, and desmopressin are effective add-on medications. Nevertheless, there is currently no evidence for the appropriate choice of the first add-on medication. This systematic review aimed to investigate the clinical benefits of antimuscarinics, β3-agonists, and desmopressin, in addition to α-blockers, for persistent storage symptoms in BPH patients.
METHODS
A comprehensive literature search of randomized controlled trials (RCTs) comparing the efficacy of different add-on medications in BPH patients with persistent storage symptoms despite α-blocker treatment was conducted. Clinical outcomes included the International Prostate Symptom Score (IPSS), IPSS storage subscore, nocturia, micturition, and urgency. A network meta-analysis was performed to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were used to rank the included treatments for each outcome.
RESULTS
A total of 15 RCTs were identified. Add-on imidafenacin and mirabegron resulted in significant improvement in all outcomes assessed. Other add-on medications such as desmopressin, tolterodine, solifenacin, fesoterodine, and propiverine showed positive benefits for most, but not all, outcomes. Based on the SUCRA rankings, add-on desmopressin was the best-ranked treatment for IPSS and nocturia, and add-on imidafenacin was the best for the IPSS storage subscore and micturition.
CONCLUSIONS
BPH patients presenting with persistent storage symptoms despite α-blocker administration are recommended to include additional treatment. Desmopressin and imidafenacin may be considered high-priority add-on treatments because of their superior efficacy compared with other medications.
Topics: Male; Humans; Muscarinic Antagonists; Prostatic Hyperplasia; Nocturia; Network Meta-Analysis; Deamino Arginine Vasopressin; Treatment Outcome; Drug Therapy, Combination; Lower Urinary Tract Symptoms; Adrenergic alpha-Antagonists
PubMed: 37789333
DOI: 10.1186/s12894-023-01327-1 -
European Urology Focus Jan 2022Neurological disease can affect the rate of urine production and bladder storage function, increasing nocturia severity, with additional risks if mobility or cognition... (Review)
Review
CONTEXT
Neurological disease can affect the rate of urine production and bladder storage function, increasing nocturia severity, with additional risks if mobility or cognition is impaired.
OBJECTIVE
To conduct a systematic review (SR) of nocturia in neurological diseases and achieve expert consensus for management in clinics without neurologist input.
EVIDENCE ACQUISITION
Four databases were searched from January 2000 to April 2020. A total of 6262 titles and abstracts were screened and 43 studies were included for full-text screening. Eleven of these met the inclusion criteria and two studies were identified through other sources. The nominal group technique (NGT) was used to develop consensus in panel comprising experts and public representation.
EVIDENCE SYNTHESIS
Thirteen studies (seven in Parkinson's disease, five in multiple sclerosis) were included, all undertaken in secondary care. Neurological disease severity was incompletely described, and nocturia severity was generally measured subjectively. NGT consensus supported basic neurological assessment, and the use of bladder diaries where neurological impairment permits. Treatments include pelvic-floor muscle training, review of medications, risk mitigation, improving bowel function, therapy for overactive bladder syndrome (if urgency is reported in association with nocturia episodes), treatment of postvoid residual and desmopressin according to licence. Measures to improve mobility and mitigate risk when using the toilet overnight should be considered. Multifactorial issues such as obstructive sleep apnoea and hypoventilation must be considered.
CONCLUSIONS
Nocturia in neurological disease is complex and lacks a robust evidence base, with very little research done in the primary care context. Guidance should be pragmatic, with reduction of risk a key requirement, until a multidisciplinary evidence base can be developed.
PATIENT SUMMARY
People with a neurological disease can suffer severe sleep disturbance because of the need to pass urine several times overnight (called nocturia). We looked at published research and found very little information to help general practitioners in managing this condition. We assembled a group of experts to develop practical approaches for assessing and treating nocturia in neurological disease.
Topics: Consensus; Humans; Nervous System Diseases; Nocturia; Primary Health Care; Severity of Illness Index
PubMed: 35031351
DOI: 10.1016/j.euf.2021.12.012 -
CNS Spectrums Jan 2022Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis... (Review)
Review
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers.
METHODS
We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.
RESULTS
We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence.
CONCLUSIONS
Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.
PubMed: 35086595
DOI: 10.1017/S1092852922000050 -
International Urology and Nephrology Nov 2019To evaluate the efficacy and safety of desmopressin treatment in women with nocturia. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the efficacy and safety of desmopressin treatment in women with nocturia.
METHODS
The PubMed, EMBASE, ISI web of knowledge, and the Cochrane Controlled Trial Register of Controlled Trials were searched from their inception date till April, 2019. The meta-analysis was performed by Revman 5.3. This review also stratified each outcome by dose (< 25 μg, 25 μg versus > 25 μg) to explore the differences in the dose response for orally disintegrating tablet (ODT).
RESULTS
Seven publications with seven trials were included in this review. The methodological quality of these trials was fair, and four studies had low risk of bias. The number of nocturnal voids per night was significantly decreased by desmopressin when compared to the control [6 trials, Weighted Mean Difference (WMD) = 0.41, P < 0.00001], and the difference between < 25, 25 and > 25 μg dose ODT groups was also significant (P = 0.03). The duration of first sleep period was significantly increased by desmopressin [4 trials, WMD = 66.64, P < 0.00001], and the difference between these three doses ODT was not significant (P = 0.15). Overall, the risk ratios (RR) for 33% responder rate showed significance when compared with desmopressin to controls [3 trials, RR = 1.30, P = 0.0003]. The number of total adverse events was similar in both desmopressin and control groups [5 trials, RR = 0.95, P = 0.59], otherwise, showed no significant difference between different ODT dose groups (P = 0.82).
CONCLUSIONS
Desmopressin had certain efficacy and adequate safety in women with nocturia. The exploration of appropriate dose for female patients, and other influential factors, such as age should be conducted and considered in future.
Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Female; Humans; Nocturia; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31352583
DOI: 10.1007/s11255-019-02242-x