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Meta-analysis
ACE Report #8262

Antifibrinolytic agents in the setting of scoliosis surgery found to reduce blood loss


Study Type:Meta-analysis/Systematic Review
OE Level Evidence:3
Journal Level of Evidence:N/A

Efficacy and Safety of Antifibrinolytic Agents in Reducing Perioperative Blood Loss and Transfusion Requirements in Scoliosis Surgery: A Systematic Review and Meta-Analysis

PLoS One. 2015 Sep 18;10(9):e0137886.

Contributing Authors: M Wang XF Zheng LS Jiang

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Synopsis

18 publications (9 RCTs) were included in this systematic review and meta-analysis comparing the use of antifibrinolytic agents against placebo for the treatment of patients diagnosed with scoliosis undergoing correction surgery. The purpose of this study was to determine if the antifibrinolytic agents aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) were effective at safely reducing blood loss and transfusion requirements. Efficacy analyses were conducted using only randomized controlled trials and safety analyses were conducted using all included trials. The results of this study support the use of antifibrinolytic agents in the setting of scoliosis surgery as all three were found to successfully reduce total blood loss, blood loss during and after surgery, perioperative blood transfusion volume, and transfusion rate (RCTs) while having no effect on adverse events (all studies).

Publication Funding Details +
Funding:
Non-funded
Conflicts:
None disclosed

Risk of Bias

9/10

Reporting Criteria

18/20

Fragility Index

N/A

Were the search methods used to find evidence (original research) on the primary question or questions stated?

Was the search for evidence reasonably comprehensive?

Were the criteria used for deciding which studies to include in the overview reported?

Was the bias in the selection of studies avoided?

Were the criteria used for assessing the validity of the included studies reported?

Was the validity of all of the studies referred to in the text assessed with use of appropriate criteria (either in selecting the studies for inclusion or in analyzing the studies that were cited)?

Were the methods used to combine the findings of the relevant studies (to reach a conclusion) reported?

Were the findings of the relevant studies combined appropriately relative to the primary question that the overview addresses?

Were the conclusions made by the author or authors supported by the data and or analysis reported in the overview?

How would you rate the scientific quality of this evidence?

Yes = 1

Uncertain = 0.5

Not Relevant = 0

No = 0

The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.

4/4

Introduction

4/4

Accessing Data

4/4

Analysing Data

4/4

Results

2/4

Discussion

Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65

The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.

Why was this study needed now?

Scoliosis is a common deformity characterized by a lateral curvature of the spine. Surgical intervention is commonly associated with drastic blood loss requiring blood transfusion, which in itself carries the risk of further complications. Antifibrinolytic agents such as aprotinin, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) have been hypothesized to reduce blood loss and blood transfusion requirements by inhibiting serine protease and suppressing fibrinolysis, however, at the outset of the present study, the efficacy and safety of antifibrinolytic agents in the setting of scoliosis surgery had yet to be thoroughly investigated, thus warranting this systematic review and meta-analysis.

What was the principal research question?

Are antifibrinolytic agents including aprotinin, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) effective at safely reducing blood loss and the need for blood transfusion in the setting of scoliosis surgery?

Study Characteristics -
Data Source:
An electronic search of the databases MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews and Controlled Trials from January 1980 to July 2014 was conducted.
Index Terms:
Search terms included: antifibrinolytic agents, tranexamic acid, epsilon aminocaproic acid, aprotinin, spinal curvatures, scoliosis, kyphosis, lordosis, posterior lumbar spine fusion, randomized controlled trial and comparative study.
Study Selection:
Two independent investigators assessed articles for adherence to inclusion criteria. Inclusion criteria were randomized controlled trials, retrospective case-control studies, and retrospective cohort studies comparing the use of antifibrinolytic agents against placebo for the treatment of patients diagnosed with scoliosis undergoing correction surgery. Articles involving patients with severe cardiopulmonary disease, hepatic or renal dysfunction, extension of prothrombin time and activated partial thromboplastin time, a decreased platelet count or a medical history of coagulation disorders were excluded. 18 articles were selected for inclusion, 8 RCTs were pooled for meta-analysis to determine efficacy 18 studies were used to determine safety (9 RCTs, 7 retrospective case-control studies, 2 retrospective cohort studies 1,158 patients).
Data Extraction:
Two investigators independently extracted relevant data from included studies. Data extracted consisted of total blood loss, post-operative blood loss, blood transfusion volume, need for transfusion and adverse events. Disagreements were resolved at the discretion of a third reviewer.
Data Synthesis:
Review Manager 5.0 was used for the meta-analysis. Heterogeneity between trials was determined using the I2 statistic, and a random effects model was employed when a significant heterogeneity was found, otherwise a fixed effects model was employed. Heterogeneity was considered significant when I2> 50%. Odds ratios (OR) were calculated for dichotomous data and expressed with 95% confidence Intervals (CIs). Mean differences (MD) with corresponding 95% CIs were determined for all continuous data, while standardized mean differences (SMD) with corresponding 95% CIs were used when outcome measures were not uniformly standard. Included studies were segmented into categories based on intervention (aprotinin, TXA or EACA) for subgroup analysis. Publication bias was assessed using the Cochrane bias scale.

What were the important findings?

  • Antifibrinolytic agents were found to be significantly more effective than placebo in reducing total blood loss (8 RCTs, 450 patients, p<0.0001, I2=81%), intraoperative blood loss (8 RCTs, 450 patients, p=0.0002, I2=72%) and postoperative blood loss (6 RCTs, 322 patients=0.02, I2=93%). Significant heterogeneity was observed each comparison.
  • Antifibrinolytic agents were found to be significantly more effective than placebo in reducing perioperative blood transfusion volume (6 RCTs, 253 patients, WMD=-474.98 [95% CI -754.67 to 195.30]; p=0.0009, I2=83%).
  • Antifibrinolytic agents were found to be significantly more effective than placebo in reducing perioperative blood transfusion rate (8 RCTs, 450 patients, OR=0.38 [95% CI 0.25 to 0.58]; p<0.00001, I2= 9%).
  • The subgroup analysis found TXA, EACA and aprotinin to all be significantly more effective than placebo in reducing total blood loss (p-values: 0.0004, 0.004, 0.005, respectively) and perioperative blood transfusion requirements (p-values: 0.02, 0.04 and 0.0001, respectively), however only TXA and aprotinin were more effective than placebo in reducing intraoperative blood loss (p-values: 0.001 and <0.0001) and blood transfusion rate (p-values: 0.03 and <0.00001, respectively).
  • Safety analysis using all included trials (RCTs, cohorts and case controls) indicated no significant difference in terms of incidence of adverse events between antifibrinolytic agents and placebo (18 studies, 1,158 patients, OR=0.84 [95% CI 0.25 to 2.88]; p=0.78), where only 8 adverse events were recorded among all the included studies.
  • The incidence of adverse events was found to be similar with the use of both TXA and aprotinin when compared to placebo (p-values: 0.76 and 0.95, respectively), no adverse events were observed with the use EACA.

What should I remember most?

Efficacy analysis using only randomized controlled trials found that all antifibrinolytic agents were more effective than placebo in reducing total blood loss, blood loss throughout and after surgery, perioperative blood transfusion volume and transfusion rate while having no effect on adverse events. The overall effectiveness of each type of antifibrinolytic agent (TXA, EACA and aprotinin) was found to be similar, however it should be noted that only TXA was successful in reducing postoperative blood loss compared to placebo. Safety analysis using all levels of evidence found not difference in adverse events.

How will this affect the care of my patients?

The findings of this study support the use of antifibrinolytic agents in the setting of scoliosis surgery for the reduction of blood loss and blood transfusion. Despite the fact that this study presents evidence of reduced perioperative blood loss and transfusion requirements with no increased risk of adverse events with the use of antifibrinolytic agents, further multicenter, large-sample, double-blind RCTs are required to confirm the efficacy and safety of the three antifibrinolytic agents in spine surgery.

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