-
The Cochrane Database of Systematic... Apr 2017In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure.
OBJECTIVES
To assess the effects of different pharmacological interventions in people with acute pancreatitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials.
SELECTION CRITERIA
We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model.
MAIN RESULTS
We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials.
SOURCE OF FUNDING
seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life.
AUTHORS' CONCLUSIONS
Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).
Topics: Acute Disease; Anti-Bacterial Agents; Antioxidants; Confidence Intervals; Gastrointestinal Agents; Humans; Pancreatitis; Pancreatitis, Acute Necrotizing; Probiotics; Randomized Controlled Trials as Topic
PubMed: 28431202
DOI: 10.1002/14651858.CD011384.pub2 -
International Journal of Molecular... Oct 2017Severe trauma constitutes a major cause of death and disability, especially in younger patients. The cerebral autoregulatory capacity only protects the brain to a... (Meta-Analysis)
Meta-Analysis Review
Severe trauma constitutes a major cause of death and disability, especially in younger patients. The cerebral autoregulatory capacity only protects the brain to a certain extent in states of hypovolemia; thereafter, neurological deficits and apoptosis occurs. We therefore set out to investigate neuroprotective strategies during haemorrhagic shock. This review was performed in accordance to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Before the start of the search, a review protocol was entered into the PROSPERO database. A systematic literature search of Pubmed, Web of Science and CENTRAL was performed in August 2017. Results were screened and evaluated by two researchers based on a previously prepared inclusion protocol. Risk of bias was determined by use of SYRCLE's risk of bias tool. The retrieved results were qualitatively analysed. Of 9093 results, 119 were assessed in full-text form, 16 of them ultimately adhered to the inclusion criteria and were qualitatively analyzed. We identified three subsets of results: (1) hypothermia; (2) fluid therapy and/or vasopressors; and (3) other neuroprotective strategies (piracetam, NHE1-inhibition, aprotinin, human mesenchymal stem cells, remote ischemic preconditioning and sevoflurane). Overall, risk of bias according to SYRCLE's tool was medium; generally, animal experimental models require more rigorous adherence to the reporting of bias-free study design (randomization, etc.). While the individual study results are promising, the retrieved neuroprotective strategies have to be evaluated within the current scientific context-by doing so, it becomes clear that specific promising neuroprotective strategies during states of haemorrhagic shock remain sparse. This important topic therefore requires more in-depth research.
Topics: Animals; Epinephrine; Fluid Therapy; Humans; Hypothermia, Induced; Hypovolemia; Ischemic Preconditioning; Mesenchymal Stem Cell Transplantation; Resuscitation; Shock, Hemorrhagic; Treatment Outcome; Vasopressins
PubMed: 29072635
DOI: 10.3390/ijms18112247 -
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 -
Surgical Neurology International 2022Data exist of the benefits of antifibrinolytics such as tranexamic acid (TXA) in general spine surgery. However, there are limited data of its use in oncological spine... (Review)
Review
BACKGROUND
Data exist of the benefits of antifibrinolytics such as tranexamic acid (TXA) in general spine surgery. However, there are limited data of its use in oncological spine patients.
METHODS
A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Cochrane, OVID, and Embase databases were searched. Search terms: ", "," "," "," "," and "." Included studies were full text publications written in English with patients treated with either agent or who had surgery for oncological spine disease (OSD).
RESULTS
Seven hundred results were reviewed form the different databases, seven were selected. A total of 408 patients underwent spine surgery for OSD and received antifibrinolytics. There was a male predominance (55.2%) and mean age ranged from 43 to 62 years. The most common tumor operated was metastatic renal cancer, followed by breast and lung. Most studies administered TXA as a bolus followed by an infusion during surgery. Median blood loss was of 667 mL (253.3-1480 mL). Patients with TXA required 1-2 units less of transfusion and had 56-63 mL less of postoperative drainage versus no TXA. The median incidence of deep venous thrombosis (DVT) was 2.95% (0-7.9%) and for pulmonary embolism (PE) was 4.25% (0-14.3%). The use of TXA reduced intraoperative blood loss, transfusions and reduced postoperative surgical drainage output compared to no TXA use in patients with OSD.
CONCLUSION
In this review, we found that TXA may diminish intraoperative blood loss, the need for transfusion and postoperative drainage from surgical drains when used in OSD without major increase in rates of DVT or PE.
PubMed: 36600747
DOI: 10.25259/SNI_837_2022 -
PloS One 2015Routine use of antifibrinolytic agents in spine surgery is still an issue of debate. (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of Antifibrinolytic Agents in Reducing Perioperative Blood Loss and Transfusion Requirements in Scoliosis Surgery: A Systematic Review and Meta-Analysis.
BACKGROUND
Routine use of antifibrinolytic agents in spine surgery is still an issue of debate.
OBJECTIVE
To gather scientific evidence for the efficacy and safety of antifibrinolytic agents including aprotinin, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA, traditionally known as Amicar) in reducing perioperative blood loss and transfusion requirements in scoliosis surgery.
METHODS
We conducted a systematic review and meta-analysis for randomized controlled trials (RCTs), retrospective case-control studies, and retrospective cohort studies on the use of antifibrinolytic agents in scoliosis surgery by searching in the MEDLINE and EMBASE databases and the Cochrane Database of Systematic Reviews and Controlled Trials of papers published from January 1980 through July 2014. Safety of the antifibrinolytic agents was evaluated in all included studies, while efficacy was evaluated in RCTs.
RESULTS
Eighteen papers with a total of 1,158 patients were eligible for inclusion in this study. Among them, 8 RCTs with 450 patients were included for evaluation of pharmacologic efficacy (1 RCT was excluded because of a lack of standard deviation data). Mean blood loss was reduced in patients with perioperative use of antifibrinolytic agents by 409.25 ml intraoperatively (95% confidence interval [CI], 196.57-621.94 ml), 250.30 ml postoperatively (95% CI, 35.31-465.30), and 601.40 ml overall (95% CI, 306.64-896.16 ml). The mean volume of blood transfusion was reduced by 474.98 ml (95% CI, 195.30-754.67 ml). The transfusion rate was 44.6% (108/242) in the patients with antifibrinolytic agents and 68.3% (142/208) in the patients with placebo. (OR 0.38; 95% CI; 0.25-0.58; P<0.00001, I2 = 9%). All studies were included for evaluation of safety, with a total of 8 adverse events reported overall (4 in the experimental group and 4 in the control group).
CONCLUSION
The systematic review and meta-analysis indicated that aprotinin, TXA, and EACA all significantly reduced perioperative blood loss and transfusion requirements in scoliosis surgery. There was no evidence that the use of antifibrinolytic agents was a risk factor for adverse events, especially thromboembolism, in scoliosis surgery.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Humans; Scoliosis; Spinal Fusion; Treatment Outcome
PubMed: 26382761
DOI: 10.1371/journal.pone.0137886 -
BMJ (Clinical Research Ed.) Sep 2012To estimate the relative risks of death, myocardial infarction, stroke, and renal failure or dysfunction between antifibrinolytics and no treatment following the... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To estimate the relative risks of death, myocardial infarction, stroke, and renal failure or dysfunction between antifibrinolytics and no treatment following the suspension of aprotinin from the market in 2008 for safety reasons and its recent reintroduction in Europe and Canada.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
A Cochrane review of antifibrinolytic treatments was chosen as the starting point for this systematic review. Medline, Embase, and the Cochrane register of trials were searched with no date restrictions for observational evidence.
STUDY SELECTION
Propensity matched or adjusted observational studies with two or more of the interventions of interest (aprotinin, tranexamic acid, epsilon-aminocaproic acid, and no treatment) that were carried out in patients undergoing cardiac surgery.
DATA ANALYSIS
Network meta-analysis was used to compare treatments, and odds ratios with 95% credible intervals were estimated. Meta-analyses were carried out for randomised controlled trials alone and for randomised controlled trials with observational studies.
RESULTS
106 randomised controlled trials and 11 observational studies (43,270 patients) were included. Based on the results from analysis of randomised controlled trials, tranexamic acid was associated on average with a reduced risk of death compared with aprotinin (odds ratio 0.64, 95% credible interval 0.41 to 0.99). When observational data were incorporated, comparisons showed an increased risk of mortality with aprotinin on average relative to tranexamic acid (odds ratio 0.71, 95% credible interval 0.50 to 0.98) and epsilon-aminocaproic acid (0.60, 0.43 to 0.87), and an increased risk of renal failure or dysfunction on average relative to all comparators: odds ratio 0.66 (95% credible interval 0.45 to 0.88) compared with no treatment, 0.66 (0.48 to 0.91) versus tranexamic acid, and 0.65 (0.45 to 0.88) versus epsilon-aminocaproic acid.
CONCLUSION
Although meta-analyses of randomised controlled trials were largely inconclusive, inclusion of observational data suggest concerns remain about the safety of aprotinin. Tranexamic and epsilon-aminocaproic acid are effective alternatives that may be safer for patients.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Cardiac Surgical Procedures; Humans; Myocardial Infarction; Odds Ratio; Postoperative Complications; Renal Insufficiency; Risk; Stroke; Tranexamic Acid
PubMed: 22968722
DOI: 10.1136/bmj.e5798 -
The Cochrane Database of Systematic... May 2015Uncontrolled bleeding is an important cause of death in trauma victims. Antifibrinolytic treatment has been shown to reduce blood loss following surgery and may also be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uncontrolled bleeding is an important cause of death in trauma victims. Antifibrinolytic treatment has been shown to reduce blood loss following surgery and may also be effective in reducing blood loss following trauma.
OBJECTIVES
To assess the effect of antifibrinolytic drugs in patients with acute traumatic injury.
SEARCH METHODS
We ran the most recent search in January 2015. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), PubMed and clinical trials registries.
SELECTION CRITERIA
Randomised controlled trials of antifibrinolytic agents (aprotinin, tranexamic acid [TXA], epsilon-aminocaproic acid and aminomethylbenzoic acid) following acute traumatic injury.
DATA COLLECTION AND ANALYSIS
From the results of the screened electronic searches, bibliographic searches, and contacts with experts, two authors independently selected trials meeting the inclusion criteria, and extracted data. One review author assessed the risk of bias for key domains.Outcome measures included: mortality at end of follow-up (all-cause); adverse events (specifically vascular occlusive events [myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism] and renal failure); number of patients undergoing surgical intervention or receiving blood transfusion; volume of blood transfused; volume of intracranial bleeding; brain ischaemic lesions; death or disability.We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach.
MAIN RESULTS
Three trials met the inclusion criteria.Two trials (n = 20,451) assessed the effect of TXA. The larger of these (CRASH-2, n = 20,211) was conducted in 40 countries and included patients with a variety of types of trauma; the other (n = 240) restricted itself to those with traumatic brain injury (TBI) only.One trial (n = 77) assessed aprotinin in participants with major bony trauma and shock.The pooled data show that antifibrinolytic drugs reduce the risk of death from any cause by 10% (RR 0.90, 95% CI 0.85 to 0.96; P = 0.002) (quality of evidence: high). This estimate is based primarily on data from the CRASH-2 trial of TXA, which contributed 99% of the data.There is no evidence that antifibrinolytics have an effect on the risk of vascular occlusive events (quality of evidence: moderate), need for surgical intervention or receipt of blood transfusion (quality of evidence: high). There is no evidence for a difference in the effect by type of antifibrinolytic (TXA versus aprotinin) however, as the pooled analyses were based predominantly on trial data concerning the effects of TXA, the results can only be confidently applied to the effects of TXA. The effects of aprotinin in this patient group remain uncertain.There is some evidence from pooling data from one study (n = 240) and a subset of data from CRASH-2 (n = 270) in patients with TBI which suggest that TXA may reduce mortality although the estimates are imprecise, the quality of evidence is low, and uncertainty remains. Stronger evidence exists for the possibility of TXA reducing intracranial bleeding in this population.
AUTHORS' CONCLUSIONS
TXA safely reduces mortality in trauma patients with bleeding without increasing the risk of adverse events. TXA should be given as early as possible and within three hours of injury, as further analysis of the CRASH-2 trial showed that treatment later than this is unlikely to be effective and may be harmful. Although there is some promising evidence for the effect of TXA in patients with TBI, substantial uncertainty remains.Two ongoing trials being conducted in patients with isolated TBI should resolve these remaining uncertainties.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Blood Transfusion; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Tranexamic Acid; Wounds and Injuries
PubMed: 25956410
DOI: 10.1002/14651858.CD004896.pub4 -
American Journal of Transplantation :... Jan 2007Although several randomized controlled trials (RCTs) have shown the efficacy of antifibrinolytic drugs in liver transplantation, their use remains debated due to concern... (Meta-Analysis)
Meta-Analysis Review
Although several randomized controlled trials (RCTs) have shown the efficacy of antifibrinolytic drugs in liver transplantation, their use remains debated due to concern for thromboembolic complications. None of the reported RCTs has shown a higher incidence of these complications in treated patients; however, none of the individual studies has been large enough to elucidate this issue completely. We therefore performed a systematic review and meta-analysis of efficacy and safety endpoints in all published controlled clinical trials on the use of antifibrinolytic drugs in liver transplantation. Studies were included if antifibrinolytic drugs (epsilon-aminocaproic acid, tranexamic acid (TA) or aprotinin) were compared with each other or with controls/placebo. Intraoperative red blood cell and fresh frozen plasma requirements, the perioperative incidence of hepatic artery thrombosis, venous thromboembolic events and mortality were analyzed. We identified 23 studies with a total of 1407 patients which met the inclusion criteria. Aprotinin and TA both reduced transfusion requirements compared with controls. No increased risk for hepatic artery thrombosis, venous thromboembolic events or perioperative mortality was observed for any of the investigated drugs. This systematic review and meta-analysis does not provide evidence for an increased risk of thromboembolic events associated with antifibrinolytic drugs in liver transplantation.
Topics: Adult; Aged; Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Transfusion; Controlled Clinical Trials as Topic; Female; Hepatic Artery; Humans; Liver Transplantation; Male; Middle Aged; Survival Rate; Thromboembolism; Thrombosis; Tranexamic Acid; Treatment Outcome; Venous Thrombosis
PubMed: 17227567
DOI: 10.1111/j.1600-6143.2006.01591.x -
The Cochrane Database of Systematic... Jan 2011Uncontrolled bleeding is an important cause of death in trauma victims. Antifibrinolytic treatment has been shown to reduce blood loss following surgery and may also be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uncontrolled bleeding is an important cause of death in trauma victims. Antifibrinolytic treatment has been shown to reduce blood loss following surgery and may also be effective in reducing blood loss following trauma.
OBJECTIVES
To quantify the effect of antifibrinolytic drugs in reducing blood loss, transfusion requirement and mortality after acute traumatic injury.
SEARCH STRATEGY
We searched the Cochrane Injuries Group's Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, Science Citation Index, National Research Register, Zetoc, SIGLE, Global Health, LILACS, and Current Controlled Trials. The Cochrane Injuries Group Specialised Register, CENTRAL, MEDLINE and EMBASE searches were updated in July 2010.
SELECTION CRITERIA
We included all randomised controlled trials of antifibrinolytic agents (aprotinin, tranexamic acid [TXA] and epsilon-aminocaproic acid) following acute traumatic injury.
DATA COLLECTION AND ANALYSIS
The titles and abstracts identified in the electronic searches were screened by two independent authors to identify studies that had the potential to meet the inclusion criteria. The full reports of all such studies were obtained. From the results of the screened electronic searches, bibliographic searches, and contacts with experts, two authors independently selected trials meeting the inclusion criteria, with any disagreements resolved by consensus.
MAIN RESULTS
Four trials met the inclusion criteria. Two trials with a combined total of 20,451 patients assessed the effects of TXA on mortality; TXA reduced the risk of death by 10% (RR=0.90, 95% CI 0.85 to 0.97; p=0.0035). Data from one trial involving 20,211 patients found that TXA reduced the risk of death due to bleeding by 15% (RR=0.85, 95% CI 0.76 to 0.96; p=0.0077). There was no evidence that TXA increased the risk of vascular occlusive events or need for surgical intervention. There was no substantial difference in the receipt of blood transfusion between the TXA and placebo groups. The two trials of aprotinin provided no reliable data.
AUTHORS' CONCLUSIONS
TXA safely reduces mortality in bleeding trauma patients without increasing the risk of adverse events. Further trials are needed to determine the effects of TXA in patients with isolated traumatic brain injury.
Topics: Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Blood Transfusion; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Tranexamic Acid; Wounds and Injuries
PubMed: 21249666
DOI: 10.1002/14651858.CD004896.pub3 -
The Cochrane Database of Systematic... May 2015Achilles tendinopathy is a common condition, often with significant functional consequences. As a wide range of injection treatments are available, a review of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Achilles tendinopathy is a common condition, often with significant functional consequences. As a wide range of injection treatments are available, a review of randomised trials evaluating injection therapies to help inform treatment decisions is warranted.
OBJECTIVES
To assess the effects (benefits and harms) of injection therapies for people with Achilles tendinopathy.
SEARCH METHODS
We searched the following databases up to 20 April 2015: the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, CINAHL and SPORTDiscus. We also searched trial registers (29 May 2014) and reference lists of articles to identify additional studies.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials evaluating injection therapies in adults with an investigator-reported diagnosis of Achilles tendinopathy. We accepted comparison arms of placebo (sham) or no injection control, or other active treatment (such as physiotherapy, pharmaceuticals or surgery). Our primary outcomes were function, using measures such as the VISA-A (Victorian Institute of Sport Assessment-Achilles questionnaire), and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from the included studies. We assessed treatment effects using mean differences (MDs) and 95% confidence intervals (CIs) for continuous variables and risk ratios (RRs) and 95% CIs for dichotomous variables. For follow-up data, we defined short-term as up to six weeks, medium-term as up to three months and longer-term as data beyond three months. We performed meta-analysis where appropriate.
MAIN RESULTS
We included 18 studies (732 participants). Seven trials exclusively studied athletic populations. The mean ages of the participants in the individual trials ranged from 20 years to 50 years. Fifteen trials compared an injection therapy with a placebo injection or no injection control, four trials compared an injection therapy with active treatment, and one compared two different concentrations of the same injection. Thus no trials compared different injection therapies. Two studies had three trial arms and we included them twice in two different categories. Within these categories, we further subdivided injection therapies by mode of action (injury-causing versus direct repair agents).The risk of bias was unclear (due to poor reporting) or high in six trials published between 1987 and 1994. Improved methodology and reporting for the subsequent trials published between 2004 and 2013 meant that these were at less risk of bias.Given the very low quality evidence available from each of four small trials comparing different combinations of injection therapy versus active treatment and the single trial comparing two doses of one injection therapy, only the results of the first comparison (injection therapy versus control) are presented.There is low quality evidence of a lack of significant or clinically important differences in VISA-A scores (0 to 100: best function) between injection therapy and control groups at six weeks (MD 0.79, 95% CI -4.56 to 6.14; 200 participants, five trials), three months (MD -0.94, 95% CI -6.34 to 4.46; 189 participants, five trials) or between six and 12 months (MD 0.14, 95% CI -6.54 to 6.82; 132 participants, three trials). Very low quality evidence from 13 trials showed little difference between the two groups in adverse events (14/243 versus 12/206; RR 0.97, 95% CI 0.50 to 1.89), most of which were minor and short-lasting. The only major adverse event in the injection therapy group was an Achilles tendon rupture, which happened in a trial testing corticosteroid injections. There was very low quality evidence in favour of the injection therapy group in short-term (under three months) pain (219 participants, seven trials) and in the return to sports (335 participants, seven trials). There was very low quality evidence indicating little difference between groups in patient satisfaction with treatment (152 participants, four trials). There was insufficient evidence to conclude on subgroup differences based on mode of action given that only two trials tested injury-causing agents and the clear heterogeneity of the other 13 trials, which tested seven different therapies that act directly on the repair pathway.
AUTHORS' CONCLUSIONS
There is insufficient evidence from randomised controlled trials to draw conclusions on the use, or to support the routine use, of injection therapies for treating Achilles tendinopathy. This review has highlighted a need for definitive research in the area of injection therapies for Achilles tendinopathy, including in older non-athletic populations. This review has shown that there is a consensus in the literature that placebo-controlled trials are considered the most appropriate trial design.
Topics: Achilles Tendon; Adrenal Cortex Hormones; Adult; Aprotinin; Athletes; Fibroblasts; Glycosaminoglycans; Hemodialysis Solutions; Humans; Injections, Intralesional; Middle Aged; Platelet Transfusion; Polidocanol; Polyethylene Glycols; Randomized Controlled Trials as Topic; Sodium Chloride; Tendinopathy; Young Adult
PubMed: 26009861
DOI: 10.1002/14651858.CD010960.pub2