Dexmedetomidine on Tourniquet Induced -Systemic Effects
Condition: Arthropathy of Knee; Spinal Anesthesia; Tourniquet; Ischemia-reperfusion Injury
MeSH terms: Reperfusion Injury; Ischemia
Study type: Interventional
Phase: Phase 4

Summary: 
      Eighty patients were randomly assigned to either control (CON) or dexmedetomidine (DEX)
      group. DEX group received a loading dose of 0.5 µg/ kg of intravenous dexmedetomidine over 10
      minutes, followed by a continuous infusion of 0.5 µg/kg/h until completion of the surgery.
      CON group received the same calculated volume of normal saline. Pain outcomes, metabolic and
      coagulative changes after tourniquet application, and after tourniquet release were
      investigated.
    

Detailed description: 
      A total of 80 patients aged between 20 and 80 years, American Society of Anesthesiologists
      (ASA) physical status class I-III, who were scheduled to undergo elective TKA were enrolled
      in this study. Patients with history of rheumatoid arthritis, diabetes mellitus, hepatic or
      renal disease, allergy to drug being studied, heart block greater than first degree, left
      ventricle ejection fraction < 55%, or chronic administration of anti-inflammatory drugs, or
      opioids were excluded. Patients with tourniquet times of less than 60 minutes or longer than
      150 minutes or with conversion to general anesthesia during surgery were also excluded.

      Randomization Randomization sequence was created using Stata 9.0 (Stata Corp, College
      Station, TX, USA) statistical software and was stratified by center with a 1:1 allocation
      using random block sizes of 4. Assignments were concealed in sealed envelopes. Participants
      were randomly assigned following simple randomization procedures (computerized random
      numbers) to 1 of 2 treatment groups: DEX group (n = 40) received intravenous dexmedetomidine
      (0.5 μg/kg bolus over 10 minutes, followed by 0.5 μg/kg/h infusion from 10 min before the
      start of surgery to the end of surgery), and CON group (n = 40) received an equivalent volume
      of normal saline bolus and infusion as placebo until the end of surgery.

      Patients, attending anesthesiologists responsible for patient care, and nurses were all
      blinded to the anesthetic agent during the study period.

      Anesthesia and perioperative care Standard monitoring included electrocardiography,
      noninvasive arterial blood pressure monitoring, and pulse oximetry. All patients received
      spinal anesthesia performed by an attending anesthesiologist and 500 mL Ringer's lactate
      solution was administered for hydration before spinal anesthesia.

      Spinal anesthesia was performed in the lateral decubitus position with the operative knee
      uppermost. These patients received an intrathecal injection of 0.5% bupivacaine 15 mg in 5%
      glucose at the level of L4-5 via using a 25-gauge needle. Patients were then turned to the
      supine position and the level of sensory block evaluated by pinprick.

      Peak level of sensory block, sensory dermatome at tourniquet pain, time between tourniquet
      application and onset of pain, and tourniquet pain were performed by an independent
      researcher at 5, 10, 15 and 20 min after the spinal injection and then at 10-minutes
      intervals until the complete resolution of the sensory block.

      The affected extremity in all patients was exsanguinated with an Esmarch bandage, and a
      tourniquet was applied at a pressure of 300 mmHg during surgery.

      When a poorly localized, diffuse pain is felt by the patient at variable times after
      tourniquet inflation, despite adequate sensory blockade during surgery, it was considered to
      be induced by the tourniquet if it was unrelated to the surgical field, described as
      tourniquet pain in the affected extremity. Supplemental analgesia with intravenous fentanyl
      100 μg was to be administered if any patient experienced tourniquet pain at any time during
      the procedure. General anesthesia would be induced if intravenous fentanyl supplementation
      was insufficient. The need for supplemental intravenous fentanyl and any conversion to
      general anesthesia were recorded.

      When intraoperative bleeding occurred, volume replacement with Ringer's lactate solution was
      managed according to the decision of an attending anesthesiologist instead of blood products.

      Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure
      (MAP) and heart rate (HR) were monitored every five minutes until the end of surgery.

      Hypotension was defined as a 30% reduction of basal MAP, which was treated with ephedrine 5
      mg iv. When the HR was <50 beats/minute (bradycardia), glycopyrrolate 0.2 mg was administered
      intravenously.

      Before the start of surgery, femoral nerve block to reduce postoperative pain were performed
      using a bolus of 20 mL of ropivacaine 0.75%. Concurrently, patient-controlled analgesia (PCA)
      pump containing fentanyl 1000 μg, ketorolac 150 mg, and ramosetron 0.6 mg in a total volume
      of 150 mL of saline was set to deliver a basal infusion of 2 mL/h and bolus doses of 1 mL,
      with a 15-min lockout period for postoperative analgesia. PCA volume consumed at 24 and 48
      hours after surgery and total PCA volume consumed for 48 hr after surgery. Postoperative pain
      intensity at rest was measured using a 100 mm linear visual analog scale (VAS). The VAS score
      for pain at rest was measured at 24 and 48 hours after surgery.

      Fentanyl 100 μg was administered for a pain VAS ≥ 50 or ketorolac 30 mg was given for a pain
      VAS < 50 or upon patient request.

      Measurements of metabolic, coagulative and temperature changes. The arterial blood samples
      were obtained from a radial artery at 1 minute just before the start of spinal anesthesia as
      a baseline and at 10 min after tourniquet release.

      5 mL of blood samples were extracted through radial artery and then 1 mL were collected in
      the heparinized syringe; following this, the remaining blood samples were immediately sent
      through the pneumatic tube system, guaranteeing their processing in the least amount of time
      possible, not greater than 5 minutes by institutional standards. The metabolic variables
      included pH, lactate, calcium, potassium, bicarbonate, CO2, base excess and coagulative
      change included antithrombin III activity.

      Tympanic temperature measurements were made using Braun Thermoscan (Thermoscan Inc., San
      Diego, CA) inserted into the auditory canal at 1 minute just before the start of spinal
      anesthesia as a baseline and at 10 minutes after tourniquet release
    

Intervention name(s): Dexmedetomidine Hydrochloride, or Saline
Intervention type(s): Drug
Intervention description(s): drug infusion from 10 min before the start of surgery to the end of surgery
Other intervention name(s): precedex
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: dexmedetomidine (0.5 μg/kg bolus over 10 minutes, followed by 0.5 μg/kg/h infusion from 10 min before the start of surgery to the end of surgery), and CON group (n = 40) received an equivalent volume of normal saline bolus and infusion as placebo until the end of surgery.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment