Does adjunctive therapy with Minocycline improve pain and opioid effectiveness in complex lower limb trauma? - A prospective randomised controlled trial.

INTERVENTION: Minocycline 100 mg Twice daily (bd) introduced as soon as possible following trauma to lower limbs continued for 1 month. Minocycline may reduce the need for opioids which are normally used to treat severe pain caused by complex lower limb trauma. CONDITION: Glial activation by opioids acting at TLR4 receptors in Complex Lower Limb Trauma. Neuropathic Pain in Complex Lower Limb Trauma Opioid tolerance in Complex Lower Limb Trauma. PRIMARY OUTCOME: Leeds Assessment of Neuropathic Symptoms and Signs (LANNS) Numerical Rating scale of pain (NRS) average of worst two pain scores in a 24 h period. SECONDARY OUTCOME: Brief Pain Inventory. (questionnaire) Opioid Use. Inpatient and outpatient opioid use will be converted to oral morphine equivalents as per the following reference; ; Anderson R, Saiers J H, Abram S, Schlicht C. Accuracy in Equianalgesic Dosing:Conversion Dilemmas. Journal of Pain and Symptom Management. Vol. 21 No. 5 May 2001. 397‐406 Pittsburgh Sleep Quality index. (questionnaire) Profile of Moods States. (questionnaire) INCLUSION CRITERIA: 1. Aged between 18 and 65 years. 2. Admitted to The Alfred Hospital Emergency and Trauma Centre (ET&C) with complex lower limb trauma. These fractures would include Distal Femur types A2/3, B2/3, C2/3. Proximal Tibia Types A3, B3, C1/2/3. Tibial Shaft Types B2/3 C1/2/3. Distal Tibia Types A3, B3, C2/3.(20) Simple fractures not specified above with substantial full thickness tissue loss or compartment syndrome requiring fasciotomy or substantial crush mechanism will also be included.3. Low probability of requirement for prolonged ventilation (> 72 hours) 4. Patient is conscious and able to give informed consent OR patient’s person responsible is able to give informed consent on behalf of the patient. 5. Average of worst two pain scores(NRS)preceeding 24 h >6