Clinical trial NCT02016443: Tizanidine and Pain After Herniorrhaphy
Official title: Investigation of the Effectiveness of Tizanidine on Pain After Herniorrhaphy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Unilateral Inguinal Hernia
Keywords: inguinal hernia
Lead sponsor: Diskapi Teaching and Research Hospital
Sponsor class: OTHER
First posted: 2013-12-20
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* American Society of Anesthesiologist's physiologic state I-III patients undergoing unilateral inguinal herniorrhaphy

Exclusion Criteria:

* chronic pain
* bleeding disorders
* renal or hepatic insufficiency
* patients on chronic non-steroidal anti-inflammatory medications
* recurrent hernias
* emergency cases

Primary outcomes:
measure: Visual analog pain score
timeFrame: postoperative first hour
measure: Visual analog pain score
timeFrame: postoperative 6th hour
measure: Visual analog pain score
timeFrame: Postoperative 12th hour
measure: Visual analog pain score
timeFrame: Postoperative 24th hour
Secondary outcomes:
measure: Likert score
timeFrame: Postoperative 1 week
measure: SF-36 score
timeFrame: Postoperative first month
Other outcomes:
measure: hemodynamic parameters
timeFrame: intraoperative with 5 minutes intervals
measure: total analgesic consumption
timeFrame: postoperative 1 week
Locations:
city: Ankara
country: Turkey
facility: Diskapi Yildirim Beyazit training and research hospital
Study officials:
affiliation: Ministry of Health
name: Dilek Yazicioglu, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ward A, Brenner M. Guanylate cyclase from Dictyostelium discoideum. Life Sci. 1977 Oct 1;21(7):997-1008. doi: 10.1016/0024-3205(77)90267-3. No abstract available.
citation: Roseboom H, Perrin JH. Oxidation kinetics of phenothiazine and 10-methylphenothiazine in acidic medium. J Pharm Sci. 1977 Oct;66(10):1392-5. doi: 10.1002/jps.2600661010.
citation: Yazicioglu D, Caparlar C, Akkaya T, Mercan U, Kulacoglu H. Tizanidine for the management of acute postoperative pain after inguinal hernia repair: A placebo-controlled double-blind trial. Eur J Anaesthesiol. 2016 Mar;33(3):215-22. doi: 10.1097/EJA.0000000000000371.