Postoperative Tizanidine Use in Pelvic Reconstructive Surgery: A Pilot Study

This pilot study evaluates the effectiveness of postoperative tizanidine as an adjunct to existing postoperative pain regimens for patients undergoing pelvic reconstructive surgery. Enhanced Recovery After Surgery (ERAS) pathways in gynecologic surgery have been associated with decreased postoperative pain, need for analgesia, complications, re-admissions, and length of hospital stay, with an emphasis on multimodal regimens and minimizing opioid administration. However, postoperative pain after urogynecologic surgery remains multifactorial and may be related to pelvic floor muscle spasm or dysfunction following surgery. Tizanidine, a skeletal muscle relaxant that acts centrally as an alpha-2 adrenergic agonist, has the unique ability to address pelvic floor muscle spasm and its contribution to postoperative pain, while having fewer adverse events in older patients compared to other skeletal muscle relaxants. Although one randomized control trial demonstrated favorable effects of tizanidine on postoperative pain and recovery after inguinal hernia repair, no previous studies have examined its role in postoperative recovery and pain control for gynecologic patients.

The study will be conducted as a prospective, longitudinal, non-blinded, two-arm randomized controlled trial comparing the postoperative experience and pain control of patients utilizing tizanidine to those who are not taking tizanidine. Eligible participants include English- or Spanish-speaking women aged 18-89 years undergoing apical suspension with concomitant vaginal repairs. Participants will be randomized in a 1:1 ratio to either a control arm receiving standard ERAS postoperative care or an intervention arm receiving standard ERAS care plus tizanidine 4 mg three times daily for two weeks postoperatively.

Data collection will include demographic, medical, surgical, and healthcare utilization information, as well as validated surveys administered preoperatively, on postoperative day 1-2, at 2 weeks, and at 4-6 weeks postoperatively. The primary outcome is patient-reported outcome (PRO) assessed at 4-6 weeks postoperatively. Secondary outcomes include pain and recovery measures, opioid use, constipation, and healthcare utilization including readmissions, ED visits, telephone encounters, patient portal messages, and additional pain medication prescriptions. The study aims to recruit 186 patients to achieve 150 completed participants. Findings may help investigate a postoperative pain regimen that could decrease opioid use and improve postoperative recovery in urogynecologic patients.

Inclusion criteria

• female, age ≥18 and ≤89 years old

• any race/ethnicity
• English and/or Spanish fluency
• undergoing apical suspension:

• sacrocolpopexy (laparoscopic or robotic)
• uterosacral ligament suspension (vaginal, laparoscopic, or robotic)
• sacrospinous ligament fixation
• iliococcygeus suspension
• surgery being performed at Hartford Hospital

Exclusion criteria

• male

• age <18 or ≥90 years old
• pregnant
• breastfeeding
• documented diagnosis of hypotension in EMR problem list, BP in office or at pre-op PAC (confirmed on repeat) to be systolic <100 mm Hg and/or diastolic <70 mm Hg
• known intolerance or sensitivity to tizanidine
• current use of:

• CYP1A2 inhibitor:
• clonidine (alpha-2 agonist) antihypertensive
• opioid
• muscle relaxant
• pre-existing

• hepatic impairment as defined as transaminitis with ALT or AST >2x upper limit of normal
• diagnoses of cirrhosis, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD)
• renal impairment as defined by creatinine clearance <25 mL/min
• obstructive sleep apnea
• non-English or non-Spanish speaking
• past opioid dependence
• concurrent diagnosis of malignancy
• concurrent surgery apart from pelvic reconstructive surgery with another specialty
• unable/unwilling to consent to participate