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The Cochrane Database of Systematic... Jul 2017Blood transfusion is administered during many types of surgery, but its efficacy and safety are increasingly questioned. Evaluation of the efficacy of agents, such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood transfusion is administered during many types of surgery, but its efficacy and safety are increasingly questioned. Evaluation of the efficacy of agents, such as desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), that may reduce perioperative blood loss is needed.
OBJECTIVES
To examine the evidence for the efficacy of DDAVP in reducing perioperative blood loss and the need for red cell transfusion in people who do not have inherited bleeding disorders.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (2017, issue 3) in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1937), the Transfusion Evidence Library (from 1980), and ongoing trial databases (all searches to 3 April 2017).
SELECTION CRITERIA
We included randomised controlled trials comparing DDAVP to placebo or an active comparator (e.g. tranexamic acid, aprotinin) before, during, or immediately after surgery or after invasive procedures in adults or children.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified 65 completed trials (3874 participants) and four ongoing trials. Of the 65 completed trials, 39 focused on adult cardiac surgery, three on paediatric cardiac surgery, 12 on orthopaedic surgery, two on plastic surgery, and two on vascular surgery; seven studies were conducted in surgery for other conditions. These trials were conducted between 1986 and 2016, and 11 were funded by pharmaceutical companies or by a party with a commercial interest in the outcome of the trial.The GRADE quality of evidence was very low to moderate across all outcomes. No trial reported quality of life. DDAVP versus placebo or no treatmentTrial results showed considerable heterogeneity between surgical settings for total volume of red cells transfused (low-quality evidence) and for total blood loss (very low-quality evidence) due to large differences in baseline blood loss. Consequently, these outcomes were not pooled and were reported in subgroups.Compared with placebo, DDAVP may slightly decrease the total volume of red cells transfused in adult cardiac surgery (mean difference (MD) -0.52 units, 95% confidence interval (CI) -0.96 to -0.08 units; 14 trials, 957 participants), but may lead to little or no difference in orthopaedic surgery (MD -0.02, 95% CI -0.67 to 0.64 units; 6 trials, 303 participants), vascular surgery (MD 0.06, 95% CI -0.60 to 0.73 units; 2 trials, 135 participants), or hepatic surgery (MD -0.47, 95% CI -1.27 to 0.33 units; 1 trial, 59 participants).DDAVP probably leads to little or no difference in the total number of participants transfused with blood (risk ratio (RR) 0.96, 95% CI 0.86 to 1.06; 25 trials; 1806 participants) (moderate-quality evidence).Whether DDAVP decreases total blood loss in adult cardiac surgery (MD -135.24 mL, 95% CI -210.80 mL to -59.68 mL; 22 trials, 1358 participants), orthopaedic surgery (MD -285.76 mL, 95% CI -514.99 mL to -56.53 mL; 5 trials, 241 participants), or vascular surgery (MD -582.00 mL, 95% CI -1264.07 mL to 100.07 mL; 1 trial, 44 participants) is uncertain because the quality of evidence is very low.DDAVP probably leads to little or no difference in all-cause mortality (Peto odds ratio (pOR) 1.09, 95% CI 0.51 to 2.34; 22 trials, 1631 participants) or in thrombotic events (pOR 1.36, 95% CI, 0.85 to 2.16; 29 trials, 1984 participants) (both low-quality evidence). DDAVP versus placebo or no treatment for people with platelet dysfunctionCompared with placebo, DDAVP may lead to a reduction in the total volume of red cells transfused (MD -0.65 units, 95% CI -1.16 to -0.13 units; 6 trials, 388 participants) (low-quality evidence) and in total blood loss (MD -253.93 mL, 95% CI -408.01 mL to -99.85 mL; 7 trials, 422 participants) (low-quality evidence).DDAVP probably leads to little or no difference in the total number of participants receiving a red cell transfusion (RR 0.83, 95% CI 0.66 to 1.04; 5 trials, 258 participants) (moderate-quality evidence).Whether DDAVP leads to a difference in all-cause mortality (pOR 0.72, 95% CI 0.12 to 4.22; 7 trials; 422 participants) or in thrombotic events (pOR 1.58, 95% CI 0.60 to 4.17; 7 trials, 422 participants) is uncertain because the quality of evidence is very low. DDAVP versus tranexamic acidCompared with tranexamic acid, DDAVP may increase the volume of blood transfused (MD 0.6 units, 95% CI 0.09 to 1.11 units; 1 trial, 40 participants) and total blood loss (MD 142.81 mL, 95% CI 79.78 mL to 205.84 mL; 2 trials, 115 participants) (both low-quality evidence).Whether DDAVP increases or decreases the total number of participants transfused with blood is uncertain because the quality of evidence is very low (RR 2.42, 95% CI 1.04 to 5.64; 3 trials, 135 participants).No trial reported all-cause mortality.Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 2.92, 95% CI 0.32 to 26.83; 2 trials, 115 participants). DDAVP versus aprotininCompared with aprotinin, DDAVP probably increases the total number of participants transfused with blood (RR 2.41, 95% CI 1.45 to 4.02; 1 trial, 99 participants) (moderate-quality evidence).No trials reported volume of blood transfused or total blood loss and the single trial that included mortality as an outcome reported no deaths.Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 0.98, 95% CI 0.06 to 15.89; 2 trials, 152 participants).
AUTHORS' CONCLUSIONS
Most of the evidence derived by comparing DDAVP versus placebo was obtained in cardiac surgery, where DDAVP was administered after cardiopulmonary bypass. In adults undergoing cardiac surgery, the reduction in volume of red cells transfused and total blood loss was small and was unlikely to be clinically important. It is less clear whether DDAVP may be of benefit for children and for those undergoing non-cardiac surgery. A key area for researchers is examining the effects of DDAVP for people with platelet dysfunction. Few trials have compared DDAVP versus tranexamic acid or aprotinin; consequently, we are uncertain of the relative efficacy of these interventions.
Topics: Adult; Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Hemostatics; Humans; Orthopedic Procedures; Randomized Controlled Trials as Topic; Tranexamic Acid; Transplantation, Homologous; Vascular Surgical Procedures
PubMed: 28691229
DOI: 10.1002/14651858.CD001884.pub3 -
The Cochrane Database of Systematic... Jan 2016Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs... (Review)
Review
BACKGROUND
Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs can be great. Tricyclics have been used to treat enuresis since the 1960s.
OBJECTIVES
To assess the effects of tricyclic and related drugs compared with other interventions for treating children with enuresis.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Trials Register (containing trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings), on 30 November 2015, and reference lists of relevant articles.
SELECTION CRITERIA
We included all randomised and quasi-randomised trials comparing a tricyclic or related drug with another intervention for treating enuresis. We also included combination therapies that included tricyclics. We excluded trials for treating daytime wetting.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the quality of the eligible trials, and extracted data. We settled differences by discussion with a third review author.
MAIN RESULTS
Sixty-four trials met the inclusion criteria, involving 4071 children. The quality of many trials was poor, with comparisons addressed by single studies. Minor adverse effects were common, and reported in 30 trials. These included dizziness, headache, mood changes, gastrointestinal discomforts and neutropenia. More serious side-effects can occur but were not reported. Seven trials reported no adverse effects.Tricyclics are more effective than placebo, particularly for short-term outcomes. Compared to placebo, imipramine resulted in one fewer wet nights per week (mean difference (MD) -0.95, 95% confidence interval (CI) -1.40 to -0.50; 4 trials, 347 children), with fewer failing to achieve 14 consecutive dry nights (78% versus 95% for placebo, RR 0.74, 95% CI 0.61 to 0.90; 12 trials, 831 children). Amitriptyline and desipramine were more effective than placebo, but nortriptyline and mianserin showed no difference. Most tricyclics did not have a sustained effect after ceasing treatment, with 96% wetting at follow-up for imipramine versus 97% for placebo.Imipramine combined with oxybutynin is also more effective than placebo, with 33% failing to achieve 14 consecutive dry nights at the end of treatment versus 78% for placebo (RR 0.43, 95% CI 0.23 to 0.78; 1 trial, 47 children) and 45% wetting at follow-up versus 79% for placebo (RR 0.58, 95% CI 0.34 to 0.99; 1 trial, 36 children).There was insufficient evidence to judge the effect between different doses of tricyclics, and between different tricyclics. Treatment outcomes between tricyclic and desmopressin were similar, but were mixed when tricyclic was compared with an anticholinergic. However, when imipramine was compared with desmopressin plus oxybutynin (1 trial, 45 children), the combination therapy was more effective, with one fewer wet nights per week (MD 1.07, 95% CI 0.06 to 2.08) and 36% failing to achieve 14 consecutive dry nights versus 87% for imipramine (RR 2.39, 95% CI 1.35 to 4.25). Tricyclics were also more effective or showed no difference in response when compared to other drugs which are no longer used for enuresis.Tricyclics were less effective than alarms. Although there was no difference in the number of wet nights, 67% failed to achieve 14 consecutive dry nights for imipramine versus only 17% for alarms (RR 4.00, 95% CI 1.06 to 15.08; 1 trial, 24 children). Alarm therapy also had a more sustained effect after ceasing treatment with 100% on imipramine versus 58% on alarms wetting at follow-up (RR 1.67, 95% CI 1.03 to 2.69; 1 trial, 24 children).Imipramine was more effective than simple behavioural therapies during treatment, with one fewer wet nights per week compared with star chart plus placebo (MD -0.80, 95% CI -1.33 to -0.27; 1 trial, 250 children). At follow-up 40% were wet with imipramine versus 80% with fluids and avoiding punishment (RR 0.50, 95% CI 0.28 to 0.89; 1 trial, 40 children). However, imipramine was less effective than complex behavioural therapies, with 61% failing to achieve 14 consecutive dry nights for imipramine versus 33% for the three-step programme (RR 1.83, 95% CI 1.08 to 3.12; 1 trial, 72 children) and 16% for the three-step programme combined with motivational therapy and computer-led education (RR 3.91, 95% CI 2.30 to 6.66; 1 trial, 132 children) at the end of treatment, with similar results at follow-up.Tricyclics were more effective than restricted diet, with 99% failing to achieve 14 consecutive dry nights versus 84% for imipramine (RR 0.84, 95% CI 0.75 to 0.93; 1 trial, 147 children).There was insufficient evidence to judge the effect of tricyclics compared to the other miscellaneous interventions studied.At the end of treatment there were about two fewer wet nights for imipramine plus oxybutynin compared with imipramine monotherapy (MD -2.10, 95% CI -2.99 to -1.21; 1 trial, 63 children) and 48% on imipramine plus oxybutynin failed to achieve 14 consecutive dry nights compared with 74% on imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.92; 2 trials, 101 children). At follow-up, 45% on imipramine plus oxybutynin were wetting versus 83% on imipramine monotherapy (RR 0.55, 95% CI 0.32 to 0.92; 1 trial, 36 children).When imipramine combined with desmopressin was compared with imipramine monotherapy, there was no difference in outcomes. However, when imipramine plus desmopressin was compared with desmopressin monotherapy, the combination was more effective, with 15% not achieving 14 consecutive dry nights at the end of treatment for imipramine plus desmopressin versus 40% for desmopressin monotherapy (RR 0.38, 95% CI 0.17 to 0.83; 1 trial, 86 children). Tricyclics combined with alarm therapy were not more effective than alarm monotherapy, alarm combined with desmopressin or alarm combined with nortriptyline. The addition of a tricyclic to other behavioural therapies did not alter treatment response.
AUTHORS' CONCLUSIONS
There was evidence that tricyclics are effective at reducing the number of wet nights during treatment, but do not have a sustained effect after treatment stops, with most children relapsing. In contrast, there was evidence that alarm therapy has better short- and long-term outcomes. There was some evidence that tricyclics combined with anticholinergics may be more effective that tricyclic monotherapy.
Topics: Antidepressive Agents, Tricyclic; Child; Child, Preschool; Clinical Alarms; Enuresis; Humans; Randomized Controlled Trials as Topic
PubMed: 26789925
DOI: 10.1002/14651858.CD002117.pub2 -
The Cochrane Database of Systematic... Dec 2012Enuresis (bedwetting) is a socially stigmatising and stressful condition which affects around 15% to 20% of five-year olds and up to 2% of young adults. Although there... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Enuresis (bedwetting) is a socially stigmatising and stressful condition which affects around 15% to 20% of five-year olds and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great. Drugs (including desmopressin, tricyclics and other drugs) have often been tried to treat nocturnal enuresis.
OBJECTIVES
To assess the effects of drugs other than desmopressin and tricyclics on nocturnal enuresis in children and to compare them with other interventions.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Register of trials (searched 15 December 2011), which includes searches of MEDLINE and CENTRAL, to identify published and unpublished randomised and quasi-randomised trials. The reference lists of relevant articles were also searched.
SELECTION CRITERIA
All randomised trials of drugs (excluding desmopressin or tricyclics) for treating nocturnal enuresis in children up to the age of 16 years were included in the review. Trials were eligible for inclusion if children were randomised to receive drugs compared with placebo, other drugs or behavioral interventions for nocturnal enuresis. Studies which included children with daytime urinary incontinence or children with organic conditions were also included in this review if the focus of the study was on nocturnal enuresis. Trials focused solely on daytime wetting and trials of adults with nocturnal enuresis were excluded.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the quality of the eligible trials and extracted data. Differences between review authors were settled by discussion with a third review author.
MAIN RESULTS
A total of 40 randomised or quasi-randomised controlled trials (10 new in this update) met the inclusion criteria, with a total of 1780 out of 2440 children who enrolled receiving an active drug other than desmopressin or a tricyclic. In all, 31 different drugs or classes of drugs were tested. The trials were generally small or of poor methodological quality. There was an overall paucity of data regarding outcomes after treatment was withdrawn.For drugs versus placebo, when compared to placebo indomethacin (risk ratio [RR] 0.36, 95% CI 0.16 to 0.79), diazepam (RR 0.22, 95% CI 0.11 to 0.46), mestorelone (RR 0.32, 95% CI 0.17 to 0.62) and atomoxetine (RR 0.81, 95% CI 0.70 to 0.94) appeared to reduce the number of children failing to have 14 consecutive dry nights. Although indomethacin and diclofenac were better than placebo during treatment, they were not as effective as desmopressin and there was a higher chance of adverse effects. None of the medications were effective in reducing relapse rates, although this was only reported in five placebo controlled trials.For drugs versus drugs, combination therapy with imipramine and oxybutynin was more effective than imipramine monotherapy (RR 0.68, 95% CI 0.50 to 0.94) and also had significantly lower relapse rates than imipramine monotherapy (RR 0.35, 95% CI 0.16 to 0.77). There was an overall paucity of data regarding outcomes after treatment was withdrawn.For drugs versus behavioural therapy, bedwetting alarms were found to be better than amphetamine (RR 2.2, 95% CI 1.12 to 4.29), oxybutynin (RR 3.25, 95% CI 1.77 to 5.98), and oxybutynin plus holding exercises (RR 3.3, 95% CI 1.84 to 6.18) in reducing the number of children failing to achieve 14 consecutive dry nights.Adverse effects of drugs were seen in 19 trials while 17 trials did not adequately report the occurrence of side effects.
AUTHORS' CONCLUSIONS
There was not enough evidence to judge whether or not the included drugs cured bedwetting when used alone. There was limited evidence to suggest that desmopressin, imipramine and enuresis alarms therapy were better than the included drugs to which they were compared. In other reviews, desmopressin, tricyclics and alarm interventions have been shown to be effective during treatment. There was also evidence to suggest that combination therapy with anticholinergic therapy increased the efficacy of other established therapies such as imipramine, desmopressin and enuresis alarms by reducing the relapse rates, by about 20%, although it was not possible to identify the characteristics of children who would benefit from combination therapy. Future studies should evaluate the role of combination therapy against established treatments in rigorous and adequately powered trials.
Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Antidiuretic Agents; Child; Child, Preschool; Cholinergic Antagonists; Clinical Alarms; Drug Therapy, Combination; Humans; Nocturnal Enuresis; Psychotropic Drugs; Randomized Controlled Trials as Topic
PubMed: 23235587
DOI: 10.1002/14651858.CD002238.pub2 -
The Cochrane Database of Systematic... Nov 2016Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common. This is an update of a previously published Cochrane Review.
OBJECTIVES
To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (25 August 2016), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013).
SELECTION CRITERIA
Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias.
MAIN RESULTS
Three cross-over studies, with 175 women were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported.
AUTHORS' CONCLUSIONS
Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.
Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menorrhagia; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 27841443
DOI: 10.1002/14651858.CD010338.pub3 -
The Cochrane Database of Systematic... Jun 2023Following hip fracture, people sustain an acute blood loss caused by the injury and subsequent surgery. Because the majority of hip fractures occur in older adults,... (Review)
Review
BACKGROUND
Following hip fracture, people sustain an acute blood loss caused by the injury and subsequent surgery. Because the majority of hip fractures occur in older adults, blood loss may be compounded by pre-existing anaemia. Allogenic blood transfusions (ABT) may be given before, during, and after surgery to correct chronic anaemia or acute blood loss. However, there is uncertainty about the benefit-risk ratio for ABT. This is a potentially scarce resource, with availability of blood products sometimes uncertain. Other strategies from Patient Blood Management may prevent or minimise blood loss and avoid administration of ABT.
OBJECTIVES
To summarise the evidence from Cochrane Reviews and other systematic reviews of randomised or quasi-randomised trials evaluating the effects of pharmacological and non-pharmacological interventions, administered perioperatively, on reducing blood loss, anaemia, and the need for ABT in adults undergoing hip fracture surgery.
METHODS
In January 2022, we searched the Cochrane Library, MEDLINE, Embase, and five other databases for systematic reviews of randomised controlled trials (RCTs) of interventions given to prevent or minimise blood loss, treat the effects of anaemia, and reduce the need for ABT, in adults undergoing hip fracture surgery. We searched for pharmacological interventions (fibrinogen, factor VIIa and factor XIII, desmopressin, antifibrinolytics, fibrin and non-fibrin sealants and glue, agents to reverse the effects of anticoagulants, erythropoiesis agents, iron, vitamin B12, and folate replacement therapy) and non-pharmacological interventions (surgical approaches to reduce or manage blood loss, intraoperative cell salvage and autologous blood transfusion, temperature management, and oxygen therapy). We used Cochrane methodology, and assessed the methodological quality of included reviews using AMSTAR 2. We assessed the degree of overlap of RCTs between reviews. Because overlap was very high, we used a hierarchical approach to select reviews from which to report data; we compared the findings of selected reviews with findings from the other reviews. Outcomes were: number of people requiring ABT, volume of transfused blood (measured as units of packed red blood cells (PRC)), postoperative delirium, adverse events, activities of daily living (ADL), health-related quality of life (HRQoL), and mortality.
MAIN RESULTS
We found 26 systematic reviews including 36 RCTs (3923 participants), which only evaluated tranexamic acid and iron. We found no reviews of other pharmacological interventions or any non-pharmacological interventions. Tranexamic acid (17 reviews, 29 eligible RCTs) We selected reviews with the most recent search date, and which included data for the most outcomes. The methodological quality of these reviews was low. However, the findings were largely consistent across reviews. One review included 24 RCTs, with participants who had internal fixation or arthroplasty for different types of hip fracture. Tranexamic acid was given intravenously or topically during the perioperative period. In this review, based on a control group risk of 451 people per 1000, 194 fewer people per 1000 probably require ABT after receiving tranexamic acid (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.46 to 0.68; 21 studies, 2148 participants; moderate-certainty evidence). We downgraded the certainty for possible publication bias. Review authors found that there was probably little or no difference in the risks of adverse events, reported as deep vein thrombosis (RR 1.16, 95% CI 0.74 to 1.81; 22 studies), pulmonary embolism (RR 1.01, 95% CI 0.36 to 2.86; 9 studies), myocardial infarction (RR 1.00, 95% CI 0.23 to 4.33; 8 studies), cerebrovascular accident (RR 1.45, 95% CI 0.56 to 3.70; 8 studies), or death (RR 1.01, 95% CI 0.70 to 1.46; 10 studies). We judged evidence from these outcomes to be moderate certainty, downgraded for imprecision. Another review, with a similarly broad inclusion criteria, included 10 studies, and found that tranexamic acid probably reduces the volume of transfused PRC (0.53 fewer units, 95% CI 0.27 to 0.80; 7 studies, 813 participants; moderate-certainty evidence). We downgraded the certainty because of unexplained high levels of statistical heterogeneity. No reviews reported outcomes of postoperative delirium, ADL, or HRQoL. Iron (9 reviews, 7 eligible RCTs) Whilst all reviews included studies in hip fracture populations, most also included other surgical populations. The most current, direct evidence was reported in two RCTs, with 403 participants with hip fracture; iron was given intravenously, starting preoperatively. This review did not include evidence for iron with erythropoietin. The methodological quality of this review was low. In this review, there was low-certainty evidence from two studies (403 participants) that there may be little or no difference according to whether intravenous iron was given in: the number of people who required ABT (RR 0.90, 95% CI 0.73 to 1.11), the volume of transfused blood (MD -0.07 units of PRC, 95% CI -0.31 to 0.17), infection (RR 0.99, 95% CI 0.55 to 1.80), or mortality within 30 days (RR 1.06, 95% CI 0.53 to 2.13). There may be little or no difference in delirium (25 events in the iron group compared to 26 events in control group; 1 study, 303 participants; low-certainty evidence). We are very unsure whether there was any difference in HRQoL, since it was reported without an effect estimate. The findings were largely consistent across reviews. We downgraded the evidence for imprecision, because studies included few participants, and the wide CIs indicated possible benefit and harm. No reviews reported outcomes of cognitive dysfunction, ADL, or HRQoL.
AUTHORS' CONCLUSIONS
Tranexamic acid probably reduces the need for ABT in adults undergoing hip fracture surgery, and there is probably little or no difference in adverse events. For iron, there may be little or no difference in overall clinical effects, but this finding is limited by evidence from only a few small studies. Reviews of these treatments did not adequately include patient-reported outcome measures (PROMS), and evidence for their effectiveness remains incomplete. We were unable to effectively explore the impact of timing and route of administration between reviews. A lack of systematic reviews for other types of pharmacological or any non-pharmacological interventions to reduce the need for ABT indicates a need for further evidence syntheses to explore this. Methodologically sound evidence syntheses should include PROMS within four months of surgery.
Topics: Humans; Aged; Tranexamic Acid; Erythrocyte Transfusion; Emergence Delirium; Systematic Reviews as Topic; Hip Fractures; Hemorrhage; Anemia; Iron
PubMed: 37294864
DOI: 10.1002/14651858.CD013737.pub2 -
The Cochrane Database of Systematic... Sep 2018People with thrombocytopenia often require a surgical procedure. A low platelet count is a relative contraindication to surgery due to the risk of bleeding. Platelet... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with thrombocytopenia often require a surgical procedure. A low platelet count is a relative contraindication to surgery due to the risk of bleeding. Platelet transfusions are used in clinical practice to prevent and treat bleeding in people with thrombocytopenia. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to surgery. Alternatives to platelet transfusion are also used prior surgery.
OBJECTIVES
To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count.
SEARCH METHODS
We searched the following major data bases: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), PubMed (e-publications only), Ovid MEDLINE, Ovid Embase, the Transfusion Evidence Library and ongoing trial databases to 11 December 2017.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs), as well as non-RCTs and controlled before-and-after studies (CBAs), that met Cochrane EPOC (Effective Practice and Organisation of Care) criteria, that involved the transfusion of platelets prior to surgery (any dose, at any time, single or multiple) in people with low platelet counts. We excluded studies on people with a low platelet count who were actively bleeding.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane for data collection. We were only able to combine data for two outcomes and we presented the rest of the findings in a narrative form.
MAIN RESULTS
We identified five RCTs, all conducted in adults; there were no eligible non-randomised studies. Three completed trials enrolled 180 adults and two ongoing trials aim to include 627 participants. The completed trials were conducted between 2005 and 2009. The two ongoing trials are scheduled to complete recruitment by October 2019. One trial compared prophylactic platelet transfusions to no transfusion in people with thrombocytopenia in an intensive care unit (ICU). Two small trials, 108 participants, compared prophylactic platelet transfusions to other alternative treatments in people with liver disease. One trial compared desmopressin to fresh frozen plasma or one unit of platelet transfusion or both prior to surgery. The second trial compared platelet transfusion prior to surgery with two types of thrombopoietin mimetics: romiplostim and eltrombopag. None of the included trials were free from methodological bias. No included trials compared different platelet count thresholds for administering a prophylactic platelet transfusion prior to surgery. None of the included trials reported on all the review outcomes and the overall quality per reported outcome was very low.None of the three completed trials reported: all-cause mortality at 90 days post surgery; mortality secondary to bleeding, thromboembolism or infection; number of red cell or platelet transfusions per participant; length of hospital stay; or quality of life.None of the trials included children or people who needed major surgery or emergency surgical procedures.Platelet transfusion versus no platelet transfusion (1 trial, 72 participants)We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on all-cause mortality within 30 days (1 trial, 72 participants; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.41 to 1.45; very-low quality evidence). We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on the risk of major (1 trial, 64 participants; RR 1.60, 95% CI 0.29 to 8.92; very low-quality evidence), or minor bleeding (1 trial, 64 participants; RR 1.29, 95% CI 0.90 to 1.85; very-low quality evidence). No serious adverse events occurred in either study arm (1 trial, 72 participants, very low-quality evidence).Platelet transfusion versus alternative to platelet transfusion (2 trials, 108 participants)We were very uncertain whether giving a platelet transfusion prior to surgery compared to an alternative has any effect on the risk of major (2 trials, 108 participants; no events; very low-quality evidence), or minor bleeding (desmopressin: 1 trial, 36 participants; RR 0.89, 95% CI 0.06 to 13.23; very-low quality evidence: thrombopoietin mimetics: 1 trial, 65 participants; no events; very-low quality evidence). We were very uncertain whether there was a difference in transfusion-related adverse effects between the platelet transfused group and the alternative treatment group (desmopressin: 1 trial, 36 participants; RR 2.70, 95% CI 0.12 to 62.17; very-low quality evidence).
AUTHORS' CONCLUSIONS
Findings of this review were based on three small trials involving minor surgery in adults with thrombocytopenia. We found insufficient evidence to recommend the administration of preprocedure prophylactic platelet transfusions in this situation with a lack of evidence that transfusion resulted in a reduction in postoperative bleeding or all-cause mortality. The small number of trials meeting the inclusion criteria and the limitation in reported outcomes across the trials precluded meta-analysis for most outcomes. Further adequately powered trials, in people of all ages, of prophylactic platelet transfusions compared with no transfusion, other alternative treatments, and considering different platelet thresholds prior to planned and emergency surgical procedures are required. Future trials should include major surgery and report on bleeding, adverse effects, mortality (as a long-term outcome) after surgery, duration of hospital stay and quality of life measures.
Topics: Adult; Benzoates; Deamino Arginine Vasopressin; Hemostatics; Humans; Hydrazines; Plasma; Platelet Transfusion; Postoperative Care; Postoperative Hemorrhage; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin
PubMed: 30221749
DOI: 10.1002/14651858.CD012779.pub2 -
The Cochrane Database of Systematic... Feb 2019Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate (DDAVP) is found to be an effective...
BACKGROUND
Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate (DDAVP) is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of DDAVP in these groups of pregnant women should be evaluated.This is an update of a Cochrane Review first published in 2013 and updated in 2015.
OBJECTIVES
To evaluate the efficacy and safety of DDAVP in preventing and treating acute bleeding in pregnant women with bleeding disorders.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched several clinical trial registries and grey literature (27 August 2017).Date of most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register: 01 October 2018.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials investigating the efficacy of DDAVP versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible.
DATA COLLECTION AND ANALYSIS
No trials matching the selection criteria were eligible for inclusion.
MAIN RESULTS
No trials matching the selection criteria were eligible for inclusion.
AUTHORS' CONCLUSIONS
No randomised controlled trials were identified investigating the relative effectiveness of DDAVP for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high-quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with DDAVP.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high-quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using DDAVP in this population are needed.Given that there are unlikely to be any trials published in this area, this review will no longer be regularly updated.
Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Pregnancy; Pregnancy Complications, Hematologic
PubMed: 30758840
DOI: 10.1002/14651858.CD009824.pub4 -
The Cochrane Database of Systematic... May 2020Enuresis (bedwetting) affects up to 20% of five-year-olds and can have considerable social, emotional and psychological effects. Treatments include alarms (activated by... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Enuresis (bedwetting) affects up to 20% of five-year-olds and can have considerable social, emotional and psychological effects. Treatments include alarms (activated by urination), behavioural interventions and drugs.
OBJECTIVES
To assess the effects of enuresis alarms for treating enuresis in children.
SEARCH METHODS
We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP, and handsearching of journals and conference proceedings (searched 25 June 2018), and reference lists of relevant articles.
SELECTION CRITERIA
We included randomised or quasi-randomised trials of enuresis alarms or alarms combined with another intervention for treating nocturnal enuresis in children between 5 and 16 years old.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed risk of bias and extracted data.
MAIN RESULTS
We included 74 trials (5983 children). At treatment completion, alarms may reduce the number of wet nights a week compared to control or no treatment (mean difference (MD) -2.68, 95% confidence interval (CI) -4.59 to -0.78; 4 trials, 127 children; low-quality evidence). Low-quality evidence suggests more children may achieve complete response (14 consecutive dry nights) with alarms compared to control or no treatment (RR 7.23, 95% CI 1.40 to 37.33; 18 trials, 827 children) and that more children may remain dry post-treatment (RR 9.67, 95% CI 4.74 to 19.76; 10 trials, 366 children; low-quality evidence). At treatment completion, we are uncertain whether there is any difference between alarms and placebo drugs in the number of wet nights a week (MD -0.96, 95% CI -2.32 to 0.41; 1 trial, 47 children; very low-quality evidence). Alarms may result in more children achieving complete response than with placebo drugs (RR 1.59, 95% CI 1.16 to 2.17; 2 trials, 181 children; low-quality evidence). No trials comparing alarms to placebo reported the number of children remaining dry post-treatment. Compared with control alarms, code-word alarms probably slightly increase the number of children achieving complete response at treatment completion (RR 1.11, 95% CI 0.97 to 1.27; 1 trial, 353 children; moderate-quality evidence) but there is probably little to no difference in the number of children remaining dry post-treatment (RR 0.91, 95% CI 0.79 to 1.05; moderate-quality evidence). Very low-quality evidence means we are uncertain if there are any differences in effectiveness between the other different types of alarm. At treatment completion, alarms may reduce the number of wet nights a week compared with behavioural interventions (waking, bladder training, dry-bed training, and star chart plus rewards) (MD -0.81, 95% CI -2.01 to 0.38; low-quality evidence) and may increase the number of children achieving complete response (RR 1.77, 95% CI 0.98 to 3.19; low-quality evidence) and may slightly increase the number of children remaining dry post-treatment (RR 1.39, 95% CI 0.81 to 2.41; low-quality evidence). The evidence relating to alarms compared with desmopressin in the number of wet nights a week (MD -0.64, 95% CI -1.77 to 0.49; 4 trials, 285 children) and the number of children achieving complete response at treatment completion (RR 1.12, 95% CI 0.93 to 1.36; 12 trials, 1168 children) is low-quality, spanning possible harms and possible benefits. Alarms probably slightly increase the number of children remaining dry post-treatment compared with desmopressin (RR 1.30, 95% CI 0.92 to 1.84; 5 trials, 565 children; moderate-quality evidence). At treatment completion, we are uncertain if there is any difference between alarms and tricyclics in the number of wet nights a week, the number of children achieving complete response or the number of children remaining dry post-treatment, because the quality of evidence is very low. Due to very low-quality evidence we are uncertain about any differences in effectiveness between alarms and cognitive behavioural therapy, psychotherapy, hypnotherapy and restricted diet. Alarm plus desmopressin may reduce the number of wet nights a week compared with desmopressin monotherapy (MD -0.88, 95% CI -0.38 to -1.38; 2 trials, 156 children; low-quality evidence). Alarm plus desmopressin may increase the number of children achieving complete response (RR 1.32, 95% CI 1.08 to 1.62; 5 trials, 359 children; low-quality evidence) and the number of children remaining dry post-treatment (RR 2.33, 95% CI 1.26 to 4.29; 2 trials, 161 children; low-quality evidence) compared with desmopressin alone. Alarm plus dry-bed training may increase the number of children achieving a complete response compared to dry-bed training alone (RR 3.79, 95% CI 1.85 to 7.77; 1 trial, 80 children; low-quality evidence). It is unclear if there is any difference in the number of children remaining dry post-treatment because of the wide confidence interval (RR 0.56, 95% CI 0.15 to 2.12; low-quality evidence). Due to very low-quality evidence, we are uncertain about any differences in effectiveness between alarm plus bladder training versus bladder training alone. Of the 74 included trials, 17 reported one or more adverse events, nine reported no adverse events and 48 did not mention adverse events. Adverse events attributed to alarms included failure to wake the child, ringing without urination, waking others, causing discomfort, frightening the child and being too difficult to use. Adverse events of comparator interventions included nose bleeds, headaches and abdominal pain. There is probably a slight increase in adverse events between code-word alarm and standard alarm (RR 1.34, 95% CI 0.75 to 2.38; moderate-quality evidence), although we are uncertain because of the wide confidence interval. Alarms probably reduce the number of children experiencing adverse events compared with desmopressin (RR 0.38, 95% CI 0.20 to 0.71; 5 trials, 565 children; moderate-quality evidence). Very low-quality evidence means we cannot be certain whether the adverse event rate for alarms is lower than for other treatments.
AUTHORS' CONCLUSIONS
Alarm therapy may be more effective than no treatment in reducing enuresis in children. We are uncertain if alarm therapy is more effective than desmopressin but there is probably a lower risk of adverse events with alarms than with desmopressin. Despite the large number of trials included in this review, further adequately-powered trials with robust randomisation are still needed to determine the full effect of alarm therapy.
Topics: Absorbent Pads; Case-Control Studies; Child; Child, Preschool; Clinical Alarms; Combined Modality Therapy; Deamino Arginine Vasopressin; Humans; Nephrology; Nocturnal Enuresis; Placebos; Randomized Controlled Trials as Topic; Renal Agents; Treatment Outcome
PubMed: 32364251
DOI: 10.1002/14651858.CD002911.pub3 -
The Cochrane Database of Systematic... Jan 2024Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care.
OBJECTIVES
To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology.
SEARCH METHODS
We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP).
SELECTION CRITERIA
We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants.
DATA COLLECTION AND ANALYSIS
We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received.
MAIN RESULTS
We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials).
AUTHORS' CONCLUSIONS
We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review.
Topics: Male; Female; Adult; Humans; Tranexamic Acid; Aprotinin; Deamino Arginine Vasopressin; Network Meta-Analysis; Hemorrhage; Aminocaproic Acid; Stroke; Orthopedic Procedures; Fibrin
PubMed: 38226724
DOI: 10.1002/14651858.CD013295.pub2 -
The Cochrane Database of Systematic... 2000Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults. Although there is a... (Review)
Review
BACKGROUND
Enuresis (bedwetting) is a socially disruptive and stressful condition which affects around 15-20% of five year olds, and up to 2% of young adults. Although there is a high rate of spontaneous remission, the social, emotional and psychological costs to the children can be great.
OBJECTIVES
To assess the effects of desmopressin on nocturnal enuresis in children, and to compare desmopressin with other interventions.
SEARCH STRATEGY
The following electronic databases were searched: MEDLINE to June 1997; AMED; ASSIA; BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974 to June 1997); PsycLIT and SIGLE. Organisations, manufacturers, researchers and health professionals concerned with enuresis were contacted for information. The reference sections of obtained studies were also checked for further trials. Date of the most recent search: July 1997.
SELECTION CRITERIA
All randomised trials of desmopressin for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive desmopressin compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were reported. Trials focused solely on daytime wetting were excluded.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed the quality of the eligible trials, and extracted data.
MAIN RESULTS
Twenty one randomised trials involving 948 children treated with desmopressin, met the inclusion criteria. The quality of many of the trials was poor. Desmopressin was compared with a tricyclic drug in two trials, and with alarms in one. Desmopressin was effective in reducing bedwetting in a variety of doses and forms. Each dose of desmopressin reduced bedwetting by at least one night per week during treatment (eg 20microg: 1.56 fewer wet nights per week, 95% CI -1.94 to -1.19). Participants on desmopressin were 4.6 times more likely to achieve 14 consecutive dry nights (95% CI 1.38 to 15.02) compared with placebo. However, there was no difference after treatment was finished. There was no apparent dose-related effect of desmopressin, but the evidence was limited. Data which compared oral and nasal administration were too few to be conclusive. Desmopressin and imipramine (a tricyclic drug) were equally effective in one small trial. Amitriptyline (another tricyclic) was not consistently better than desmopressin either alone or when used as a supplement. In a single trial, desmopressin was initially superior to using an alarm in reducing the number of wet nights per week: WMD -1.7 (95% CI: -2.96 to -0.45), but this result was not sustained; after three months of treatment, patients using the alarm had 1.4 fewer wet nights per week than with desmopressin: (95% CI: 0.14 to 2.65). Participants receiving the alarm intervention were also nine times less likely to relapse than those given desmopressin: RR 9.2 (95% CI: 1.28 to 65.9). Combining alarm and drug therapy was found to be superior to alarm treatment alone. The addition of desmopressin to an alarm schedule resulted in one less wet night per week: (95% CI: -1.55 to -0.45).
REVIEWER'S CONCLUSIONS
Desmopressin rapidly reduced the number of wet nights per week, but there was some evidence that this was not sustained after treatment stopped. Comparison with alternative treatments suggested that desmopressin and tricyclics had similar clinical effects, but that alarms produced more sustained benefits. However, based on the available evidence, these conclusions can only be tentative. There was some evidence of minor side effects of desmopressin in the included trials, such as nasal irritation and nose bleeds. However, the risk of water intoxication associated with over-drinking before bedtime has been reported. Patients and their families need to be warned of potential adverse effects and advise
Topics: Child; Deamino Arginine Vasopressin; Enuresis; Humans; Renal Agents
PubMed: 10796860
DOI: 10.1002/14651858.CD002112