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Brain and Behavior May 2024One of the most serious complications associated with antiplatelet agents is antiplatelet-associated intracranial hemorrhage (AA-ICH). Desmopressin is a synthetic... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of desmopressin (DDAVP) in preventing hematoma expansion in intracranial hemorrhage associated with antiplatelet drugs use: A systematic review and metaanalysis.
INTRODUCTION
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.
METHODS
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 I test. The risk of bias in studies was calculated using the New Castle Ottowa Scale.
RESULTS
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, I = 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, I = 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, I = 0%). The risk of bias assessment showed a moderate to low level of risk.
CONCLUSION
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.
Topics: Deamino Arginine Vasopressin; Humans; Platelet Aggregation Inhibitors; Intracranial Hemorrhages; Hematoma; Hemostatics
PubMed: 38778788
DOI: 10.1002/brb3.3540 -
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 -
Perioperative Medicine (London, England) Jan 2024We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing... (Review)
Review
We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.
PubMed: 38263259
DOI: 10.1186/s13741-023-00358-4 -
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 -
Frontiers in Pediatrics 2023The desmopressin combined with anticholinergic agents for the treatment of nocturnal enuresis (NE) remains controversial. This meta-analysis assesses the efficacy and... (Review)
Review
BACKGROUND
The desmopressin combined with anticholinergic agents for the treatment of nocturnal enuresis (NE) remains controversial. This meta-analysis assesses the efficacy and safety of desmopressin compared with desmopressin plus anticholinergic agents for the treatment of NE.
METHODS
We searched MEDLINE, Embase, and Cochrane Controlled Trials Register databases for RCTs published for the treatment of NE. Systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. This meta-analysis used RevMan v.5.1.0 to analyze data.
RESULTS
Eight studies involving 600 patients (293 in the combination group and 307 in the desmopressin group) contained meaningful data. The results were as follows: after one month of treatment, compared with the desmopressin monotherapy group, the combination group was significantly better in treating NE in FR (full responders, = 0.003), FR + PR (partial responders) ( < 0.0001), and the mean number of wet nights ( = 0.004); also, the combination group had a better effect in FR ( < 0.00001), FR + PR ( = 0.02) and the mean number of wet nights ( = 0.04) after 3 months' treatment. For side effects, combination therapy does not cause more adverse events in treating NE ( = 0.42).
CONCLUSIONS
This study elucidates that desmopressin combined with the anticholinergic agent was demonstrated to be more effective in treating NE than desmopressin monotherapy, and the anticholinergic agent does not increase the risk of adverse events (AEs).
PubMed: 37928358
DOI: 10.3389/fped.2023.1242777 -
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 -
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 -
Cureus Aug 2023Von Willebrand disease (VWD) and hemophilia A are the most common inherited bleeding disorders. Quantitative or qualitative von Willebrand factor (VWF) anomalies cause... (Review)
Review
Von Willebrand disease (VWD) and hemophilia A are the most common inherited bleeding disorders. Quantitative or qualitative von Willebrand factor (VWF) anomalies cause this disorder in men and women. VWF, a plasma glycoprotein, relies on platelets for primary hemostasis. It also carries and stabilizes factor VIII in the blood. VWD has several categories. Types 1 and 3 have partial or total VWF quantitative deficiencies. However, type 2 and its subtypes have VWF quality issues. The major treatment is desmopressin (DDAVP), which replaces endogenous VWF and factor VIII (FVIII). Plasma-derived VWF/FVIII products may also be substituted exogenously. Treatment with plasma-derived or recombinant VWF concentrates without FVIII is also possible. The purpose of this retrospective, single-center research was to evaluate DDAVP's efficacy in treating VWD based on many criteria established in the current literature. We looked at the results on Google Scholar, the Cochrane Library, and PubMed/Medline. There were a total of 10 papers found, evaluated, and accepted for inclusion in this study. A comprehensive analysis of DDVAP's role in VWD was compiled from the aforementioned papers. Various aspects of DDVAP were captured by including an analysis of complementary treatments used in surgical and clinical settings. We also describe the treatment's intended impact on the different variations of the disease. Given these results, further investigation is required to determine the most effective method for managing VWD so that it may be included in standard clinical practice.
PubMed: 37649925
DOI: 10.7759/cureus.44310 -
Cureus May 2023The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate... (Review)
Review
The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate choices in pharmacologic treatment options for POTS and the challenges encountered in the studies. We searched numerous databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar for literature published before April 8, 2023. The search was done to retrieve potential peer-reviewed articles that explored drug therapy in POTS. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct the systematic review. Of the 421 potential articles assessed, 17 met the inclusion criteria. Results demonstrated that pharmacologic treatment options for POTS were effective in reducing symptoms of POTS, but most of the studies were underpowered. Several were terminated due to various reasons. Midodrine ivabradine, bisoprolol, fludrocortisone, droxidopa, desmopressin, propranolol, modafinil, methylphenidate, and melatonin have been studied with positive impact but sample sizes that were low in the range of 10-50 subjects. Therefore, we concluded the treatment options effectively improve symptoms of POTS and increase orthostatic tolerance, but more evidence is needed as most studies had a low sample size and thus are underpowered.
PubMed: 37313107
DOI: 10.7759/cureus.38887 -
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