Tizanidine and Pain After Herniorrhaphy
Condition: Unilateral Inguinal Hernia
MeSH terms: Hernia; Hernia, Inguinal
Study type: Interventional
Phase: Phase 4

Summary: 
      Herniorrhaphy is the most frequent general surgical procedure. There are moderate pain
      complaints after herniorrhaphy. Besides causing discomfort to the patients, pain, can delay
      recovery and discharge and cause cognitive dysfunction and difficulty with returning to
      normal daily activity.

      A combination of analgesics with different effect sites can reduce the doses needed and
      analgesic related side effects which is called multimodal analgesia .

      Opioids, acetaminophen, nonsteroid anti-inflammatory drugs and cox-2 inhibitors, alfa-2
      receptor agonists, steroids, gabapentin and pregabalin have been used for this purpose(4).

      Tizanidine is an alfa-2 receptor agonist, and is used for musculoskeletal pain conditions.
      Tizanidine reduced the local anesthetic requirement in spinal anesthesia.

      The aim of this study is to investigate the hypothesis that: Tizanidine can reduce the pain
      scores, analgesic consumption, analgesic related side effects and provide early return to
      normal daily activity compared to placebo after inguinal herniorrhaphy.
    

Detailed description: 
      Age, body mass index (BMI), concomitant diseases, and the ASA physiologic state will be
      recorded.

      Simple randomization will be accomplished with a computer-generated sequence of numbers and
      sealed envelopes will be used to allocate patients into 2 groups.

      Patients in GroupTizanidine will receive 4 mg tizanidine per oral twice a day during the
      postoperative first week and the first dose will be administered 1 hour before surgery,
      patients in Group Placebo will receive the same treatment with a placebo pill concurrently
      with a standard analgesic treatment: dexketoprofen trometamol; 25 mg intravenous (iv) before
      the induction of anesthesia and 25 mg per oral 3 times a day-1 week and acetaminophen; 1 g iv
      at the end of surgery. All patients will be instructed to use acetaminophen 500 mg up to 4
      times a day for rescue analgesia and to contact the hospital if they have pain despite all
      three medications.

      Heart rate (HR), peripheral oxygen saturation (SpO2), systolic arterial pressure (SAP),
      diastolic arterial pressure (DAP) and mean arterial pressure (MAP), end tidal CO2 pressure
      (EtCO2). Baseline values will recorded.

      Anesthesia induction and muscle relaxation will be standardized with 2 mg kg-1 propofol, 0.6
      mg kg-1 rocuronium and 50 µg fentanyl. Anesthesia will be maintained with oxygen in nitrous
      oxide and desflurane. The desflurane concentration will be titrated to keep BIS between
      40-60. The patients will receive 50 µg fentanyl boluses in case hemodynamic variables changed
      ≥30% from baseline values. Hypotension will be defined as ≥20% decrease in MAP from baseline
      values and will be treated with fluid boluses and/or ephedrine. Bradycardia will be defined
      as a heart rate <50 beat min and will be treated with atropine. All treatments will be
      recorded. At the end of surgery volatile anesthesia will be discontinued and the patients
      will be extubated according to clinical extubation criteria. The time elapsed from
      discontinuation of volatile anesthesia to eye opening with verbal commands will be recorded
      as time to emergence. The patients will be transferred to the post anesthesia care unit
      (PACU). The modified Aldrete score will be used to evaluate recovery in the PACU and the
      patients will be discharged from the PACU when the Aldrete score is ≥9 ( ). Post operative
      pain will be evaluated with a Visual Analogue Scale (VAS) score of 0-10 (0= no pain and 10=
      worst imaginable pain) at 1, 6, 12 and 24 hours postoperatively.

      During the control visit 1 week after surgery total analgesic consumption and analgesic
      related adverse events (nausea, vomiting, dizziness…) will be evaluated. Difficulty with
      normal daily activity will also be evaluated during this visit with the Likert score (1. no
      difficulty, 2. mild difficulty, 3. difficulty, 4. severe difficulty, 5. unable to perform
      daily activity due to pain). Health related quality of life will also be evaluated 1 month
      after surgery; the Short Form (SF)-36 will be used for this purpose.
    

Intervention name(s): Tizanidine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Group Tizanidine (Group T) will receive 4 mg tizanidine per oral twice a day during the postoperative first week and the first dose will be administered 1 hour before surgery; Group Placebo (Group P) will receive a placebo per oral twice a day during the postoperative first week and the first dose will be administered 1 hour before surgery
Other intervention name(s): Sirdalud; Placebo pill
Intervention MeSH terms: Tizanidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: inguinal hernia