Tizanidine and Pain After Herniorrhaphy

Unilateral Inguinal Hernia Clinical Trial

Official title:

Investigation of the Effectiveness of Tizanidine on Pain After Herniorrhaphy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02016443
• Other study ID #: TIZANIDINE
• Status: Completed
• Phase: Phase 4
• First received: October 10, 2013
• Last updated: April 21, 2015
• Start date: November 2013
• Est. completion date: June 2014

Study information

• Verified date: October 2013
• Source: Diskapi Teaching and Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Turkey: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hernia, Inguinal
• Unilateral Inguinal Hernia

Intervention

Drug:
• Tizanidine
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
• Placebo
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

Locations

Country	Name	City	State
Turkey	Diskapi Yildirim Beyazit training and research hospital	Ankara

Sponsors (1)

Lead Sponsor	Collaborator
Diskapi Teaching and Research Hospital

Country where clinical trial is conducted

Turkey, 

References & Publications (2)

Roseboom H, Perrin JH. Oxidation kinetics of phenothiazine and 10-methylphenothiazine in acidic medium. J Pharm Sci. 1977 Oct;66(10):1392-5. — View Citation

Ward A, Brenner M. Guanylate cyclase from Dictyostelium discoideum. Life Sci. 1977 Oct 1;21(7):997-1008. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	hemodynamic parameters	systolic, diastolic, mean arterial pressures and heart rate will be measured with 5 minutes intervals	intraoperative with 5 minutes intervals	No
Other	total analgesic consumption	total analgesic consumption will be determined at postoperative 1 week	postoperative 1 week	No
Primary	Visual analog pain score	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 and 24 hours postoperatively.	postoperative first hour	No
Primary	Visual analog pain score	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 and 24 hours postoperatively.	postoperative 6th hour	No
Primary	Visual analog pain score	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 and 24 hours postoperatively.	Postoperative 12th hour	No
Primary	Visual analog pain score	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 and 24 hours postoperatively.	Postoperative 24th hour	No
Secondary	Likert score	Difficulty with normal daily activity will be evaluated during the first week control 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	Postoperative 1 week	No
Secondary	SF-36 score	Health related quality of life will be evaluated 6 weeks after surgery; the SF-36 will be used for this purpose	Postoperative first month	No