Administration of tranexamic acid to patients undergoing surgery for adolescent idiopathic scoliosis evokes pain and increases the infusion rate of remifentanil during the surgery

<div><p>Background</p><p>We recently reported that tranexamic acid (TXA) evokes pain in rats by inhibiting γ-aminobutyric acid and glycine receptors on neurons in the spinal dorsal horn. Although TXA is commonly used to reduce perioperative blood loss during various surgeries, its potential to induce intraoperative nociception, thereby increasing the need for more analgesics during surgery, has not been investigated. Therefore, this study aimed to investigate whether TXA evokes pain and increases the need for a higher infusion rate of remifentanil in patients undergoing surgery for adolescent idiopathic scoliosis (AIS).</p><p>Methods</p><p>Data were collected from patients with AIS who underwent posterior spinal fusion surgery from January 2008 to December 2015. All surgical procedures were performed under total intravenous anesthesia with propofol and remifentanil, by the same team of orthopedic surgeons and anesthesiologists at a single institution. Patients in the TXA group were administered TXA (loading and maintenance doses, 1000 mg and 100 mg/h) whereas those in the control group were not. Our primary outcome was the infusion rate of the intraoperative opioid analgesic remifentanil.</p><p>Results</p><p>The final analysis was based on data collected from 33 and 30 patients in the control and TXA groups, respectively. No differences were observed in the demographic data or the hemodynamic parameters between the two groups of patients. In the TXA group, the durations of surgery and anesthesia were shorter, intravascular fluid volume and total blood loss were lower, and the doses of fentanyl and ketamine administered were higher than they were in the control group (<i>P</i> < 0.05 for all). The mean infusion rate of intraoperative remifentanil was significantly higher in the TXA group than in the control group (control group: 0.23 ± 0.04 μg/kg/min; TXA group: 0.28 ± 0.12 μg/kg/min; <i>P</i> = 0.014).</p><p>Conclusions</p><p>Patients who received TXA during the AIS surgery required a higher infusion rate of remifentanil, indicating that TXA evoked pain during the surgery.</p></div

Demographic data of the patients in each group.

<p>Demographic data of the patients in each group.</p

Infusion rate of intraoperative remifentanil.

<p>The mean infusion rate of intraoperative remifentanil (the primary outcome of our study) was significantly higher in the tranexamic acid (TXA) group than that in the control group. Data are presented as mean ± standard deviation. *<i>P</i> < 0.05 using Student’s <i>t</i>-test.</p

Hemodynamic parameters.

<p>No significant differences were observed between the control and tranexamic acid (TXA) groups. HR: heart rate; SBP: systolic blood pressure; DBP: diastolic blood pressure; bpm: beats per min; T0: before anesthesia; T1: time at surgical skin incision; T2–T7: 60 min after skin incision and every 60 min thereafter; T8: end of surgery; T9: end of anesthesia.</p

Surgical data of patients in each group.

<p>Surgical data of patients in each group.</p

Changes in bone metabolism markers during long bedridden periods.

<p>Changes in bone metabolism markers during long bedridden periods.</p

Clinical characteristics in all study participants (n = 36).

<p>Clinical characteristics in all study participants (n = 36).</p

Baseline characteristics in 17 patients <30 years followed for 12 years.

<p>Baseline characteristics in 17 patients <30 years followed for 12 years.</p

Area under the curve and cut-off value.

<p>Area under the curve and cut-off value.</p

Changes in the bone mineral density and bone metabolism marker levels during a 12-year follow-up period in patients whose baseline age was <30 years.

<p>Red lines indicate the cutoff value for osteoporosis (bone mineral density) and those for predicting bone fracture (osteocalcin and N-terminal telopeptide), as proposed by the guidelines for the prevention and treatment of osteoporosis [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0156991#pone.0156991.ref017" target="_blank">17</a>].</p