Intravenous and Oral Tranexamic Acid Are Equivalent at Reducing Blood Loss in Thoracolumbar Spinal Fusion

A Prospective Randomized Trial

Charles C. Yu, MD; Omar Kadri, MD; Allen Kadado, MD; Morenikeji Buraimoh, MD; Jacob Pawloski, BS; Stephen Bartol, MD; Gregory Graziano, MD

Disclosures

Spine. 2019;44(11):755-761. 

In This Article

Materials and Methods

Study Design and Patients

This study was a single-center, randomized, prospective trial designed to test equivalence between IV and oral TXA in the setting of elective thoracolumbar fusion between February and December 2017. Our institutional review board approved the present study, and it was registered with the public ClinicalTrials.gov registry (NCT03037515). After obtaining informed consent, adult patients (age ≥ 18 yrs old) undergoing elective posterior thoracolumbar instrumented spinal fusions were enrolled in the study. Exclusion criteria included known allergy to TXA, history of renal failure or kidney transplant, history of arterial thromboembolic event (e.g., myocardial infarction, stroke) within the past year, placement of an arterial stent within the past year, a history of thromboembolic event, coagulopathy, or refusal to receive blood products.

Intervention

Enrolled patients were randomly assigned between the two treatment groups of IV and oral TXA using a random number algorithm. Because the number of fusion levels can influence blood loss, the sample was sub-categorized by the number of vertebral levels arthrodesed (1–2 levels, 3–5 levels, >5 levels). Serum and pharmacokinetic studies have demonstrated that IV TXA reaches therapeutic concentration rapidly but falls below the threshold after 5 hours; PO TXA reaches therapeutic levels after 2 hours and maintains levels above the therapeutic threshold for 6 hours after administration.[11] Based on pharmacokinetic data, the oral TXA group received 1950 mg TXA (three tablets of 650 mg) approximately 2 hours before incision. The IV TXA group received the standard dosing for our institution of 1 g TXA (diluted in 100 mL normal saline) given as an IV bolus immediately before incision and another 1 g TXA given before closure.

Surgical Technique and Postoperative Care

Posterior instrumented spinal fusions were performed prone on a Jackson table with the abdomen free. A forced-air warming device was used to maintain normothermia. A standard open midline approach was utilized, intertransverse fusion beds were prepared uniformly, and pedicle screws were inserted in the standard fashion. When indicated, transforaminal lumbar (TLIF) and direct lateral interbody (DLIF) fusions were also performed per surgeon preference. Before wound closure, hemostasis was achieved and drains were placed routinely. All cases were performed by surgeons with over 25 years experience in spine surgery.

Blood Management

An autologous blood recovery system (Cell Saver, Haemonetics, MA) was used when requested by the surgeon and salvaged red blood cells (RBCs) were returned to the patient. Suctioned blood from the surgical field was processed and given back to the patient if estimated blood loss (EBL) was greater than 500 mL or at the surgeon's discretion. As a result, not every patient may have been given salvaged RBCs. Intraoperative blood transfusion was given if hemoglobin (Hgb) dropped below 7.0 g/dL or at the anesthesiologist's discretion, such as if patient was unstable despite fluid resuscitation and salvaged RBC replacement. The postoperative transfusion protocol required transfusion for a Hgb level below 7.0 g/dL or if Hgb was between 7.0 and 8.0 g/dL and patients had symptomatic anemia including tachycardia, hypotension, or pallor.

Data Collection

Patient demographic and preoperative characteristics were documented for comparison between the treatment groups. All patients had postoperative labs including a complete blood count (CBC). Drain outputs were recorded three times a day (per 8 h shift). Drains were discontinued if output was below 30 mL per shift or by the end of postoperative day 2. The recorded characteristics included the following: age, sex, American Society of Anesthesiologists' physical status classification (ASA), weight, height, body mass index (BMI), and pertinent preoperative laboratory values (prothrombin time/international normalized ratio, creatinine, platelet count, hematocrit, and hemoglobin).

Outcome Measures

The primary outcome was reduction of Hgb, which was the difference between preoperative and the lowest postoperative Hgb values. Secondary outcomes included calculated blood loss, reduction of hematocrit, drain output, rate of postoperative transfusion, thromboembolic event, infections and length of hospital stay. In addition, intraoperative measures such as case length, calculated blood loss, intravenous fluid received and number receiving intraoperative cell saver, and blood transfusion were investigated. Blood loss was calculated as a function of patient characteristics including sex, weight, and height as well as preoperative and postoperative hemoglobin balance.[12–14]

Sample Size and Statistical Analysis

A pretest power analysis determined that 30 patients in each group were needed to show a 1.0 g/dL difference in hemoglobin drop, assuming an equivalence margin of ±1.0 g/dL, 5% alpha error, and 80% power. The primary outcome of Hgb drop and the secondary outcome of calculated blood loss were tested for equivalence using a two one-sided test (TOST). The remaining secondary outcomes and covariates were compared using traditional t tests. Ordinal scale outcome variables were tested using nonparametric methods such as chi-square, Fisher exact test, or Wilcoxon rank sum test. A P-value of <0.05 suggests statistical significance. All data were analyzed by Microsoft Excel 2011 (Microsoft, Seattle, WA) and XLSTAT 2017: Data Analysis and Statistical Solution for Microsoft Excel (Addinsoft, Paris, France).

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....