Effects of Systemic or Adjunct Tramadol Addition to Lidocaine Used for IVRA in Patients Undergoing Hand Surgery
Condition: Anesthesia
Study type: Interventional
Phase: Phase 3

Summary: 
      Intravenous regional anesthesia (IVRA) is used in outpatient hand surgery as an easily
      applicable and cost-effective technique with clinical advantages. Nevertheless, IVRA has some
      disadvantages including anesthetic toxicity, slow-onset, poor muscle relaxation, tourniquet
      pain, and minimal postoperative pain relief. Providing an ideal anesthesia by overcoming
      these disadvantages is possible with the addition of some adjunct agents into local
      anesthetic substances. One of these adjunct agents used for IVRA is tramadol, a synthetic
      analgesic having opioid and nonopioid characteristics. The present study aimed to investigate
      the effects of addition of systemic tramadol or adjunct tramadol to lidocaine for IVRA in
      patients undergoing hand surgery..
    

Detailed description: 
      The present study included American Society of Anesthesiologists (ASA) I-II patients (n=60)
      who were planned to undergo hand surgery. Patients with Raynaud's disease, those with
      sickle-cell anemia, and those receiving any drug for history of allergy were excluded.
      Approval of the ethics committee and informed consents of the patients were obtained for the
      study.

      According to a computer-generated randomization list, the patients were divided into three
      groups, containing 20 subjects in each. In the first group, Lidocaine (LDC)+Adjunct Tramadol
      (TRA), IVRA was performed with 3 mg/kg lidocaine (10% Lidocaine) plus 50 mg tramadol, which
      were administered after diluting with saline to 40 mL. While performing IVRA, 30 mL saline
      was simultaneously administered to the systemic circulation. In the second group, lidocaine
      (LDC)+systemic tramadol (SysTRA), IVRA was performed with 3 mg/kg lidocaine, which was
      diluted with saline to 40 mL. While performing IVRA, 50 mg tramadol diluted with saline to 30
      mL was simultaneously administered to the systemic circulation. In the third group (LDC
      group), IVRA was performed with 3 mg/kg lidocaine, which was diluted with saline to 40 mL.
      While performing IVRA, 30 mL saline was simultaneously administered to the systemic
      circulation. All solutions were prepared by resident anesthesiologists, who were blinded to
      the study, using identical injectors.

      The patients received premedication 45 min before the surgery with intramuscular 0.07 mg/kg
      midazolam and 0.01 mg/kg atropine. Two intravenous cannulas, one into the vein in the dorsal
      aspect of the hand that would undergo surgery and the other into the vein in the dorsal
      aspect of the opposite hand, were inserted for crystalloid infusion. The arm that would
      undergo surgery was elevated for 2 min and Esmarch's bandage was used to control blood flow.
      A double pneumatic tourniquet was placed around the upper arm and the proximal cuff was
      inflated to 250 mmHg. The absence of radial artery pulse in the arm isolated from the
      circulation was confirmed by the disappearance of pulse oximeter waves in the index finger of
      the same hand. The solutions, which were pre-prepared according to the groups defined above,
      were injected to the patients for over 90 s by an anesthesiologist blinded to the contents of
      drugs.

      After the injection, the sensorial block was assessed every 30 s until the initiation of
      surgery by pinprick test using 22 gauge needle on the radial, ulnar and median nerve
      stimulation areas of the hand and of the anterior surface of the arm. Motor function was
      checked by asking the patient to bring the wrist and finger to extension and flexion and the
      time of complete motor block was recorded when spontaneous movement was impossible. The time
      elapsed from the injection of the study drug until the sensorial block was provided in all
      stimulation areas was recorded as the onset time of sensorial block. Likewise, the time
      elapsed from the injection of the study drug until achieving the complete motor block was
      recorded as the onset time of motor block. After achieving complete motor block and sensorial
      block, the distal tourniquet was inflated to 250 mmHg, the proximal tourniquet was deflated,
      and the surgical procedure was initiated. Mean arterial pressure (MAP), oxygen saturation
      (SpO2), and heart rate (HR) were monitored during the surgery, before and after tourniquet
      application, and until disappearance of anesthesia after deflating the tourniquet.

      Pain level of the patients was assessed by 10 cm visual analogue scale (VAS; 0=no pain;
      10=very severe pain). VAS scores were recorded before and after tourniquet application as
      well as at 5th, 10th, 15th, 20th, 30th, 40th, and 50th min during the surgery. If the patient
      had a VAS score of >4 and if required, 1 μg/kg fentanyl was administered for analgesia and
      the dosage and time were recorded.

      The tourniquet was not deflated earlier than 30 min and it was not inflated more than 2 h.
      Tourniquet deflation after the surgery was performed by periodic deflation technique. The
      time of sensorial recovery was recorded (the time elapsed from the deflation of tourniquet to
      the highest pain felt by the patient via pinprick test performed every 30 s in all
      stimulation areas). The time of motor block recovery (time elapsed from the deflation of
      tourniquet to the spontaneous movement of the fingers) was also recorded.

      The patients were monitored in the postoperative care unit for the first 2 h and then in the
      observation room for 24 h by anesthesiologists who were blinded to the study. MAP, HR, SpO2
      monitoring and VAS measurement were performed at the postoperative 1st, 2nd, 4th, 6th, 12th,
      and 24th h. The patients with a VAS score of >4 were administered with 75 mg diclofenac
      sodium via intramuscular route. Analgesia requirement was recorded as duration and dosage.

      The patients were monitored for intraoperative and postoperative complications. In the event
      of hypotension (systolic arterial pressure <90 mmHg or a decrease of more than 50 mmHg from
      the normal value) during the surgery, 5 mg intravenous ephedrine was administered. In case of
      bradycardia (HR <50/min), 0.5 mg intravenous atropine was administered. Intravenous 4 mg
      ondansetron was administered for nausea and vomiting and oxygen was supplied via a facial
      mask when SpO2 decreased by more than 91%.

      An anesthesiologist and a surgeon, who were blinded to the content of study drug, assessed
      the quality of anesthesia at the end of surgery as follows: 4: excellent, patient does not
      complain; 3: good, patient complains a little, no need for supplemental analgesic; 2:
      moderate, patient complains, need for supplemental analgesic; 1: failed, need for general
      anesthesia.

      The Predictive Analytics Software (PASW) version 18.0 for Windows program (SPSS Inc.,
      Chicago, USA) was used for statistical analysis. Descriptive statistics were expressed as
      number and percentage for categorical variables and as mean, standard deviation, median, the
      25th percentile (Q1: the first quartile), and the 75th percentile (Q3: the third quartile)
      for numerical variables. For numerical variables, independent multiple group comparisons were
      performed by Kruskal-Wallis test for non-normally distributed data and by t-test for normally
      distributed data. Mann-Whitney U test with Bonferroni correction was used for subgroup
      analysis of non-normally distributed numerical variables. For multiple group comparisons of
      categorical variables, Chi-square test statistics was used in case the assumption of
      chi-square test was met, whereas Fisher's Exact test was used in case the assumption of
      chi-square test was not met. A p value of <0.05 was considered statistically significant.

      With the assumption that the difference in the VAS score at the 5th min between the two
      surgical techniques being 1 and the expected standard deviation for two groups being 0.9, it
      was estimated to include 20 patients in the groups for which the least difference was
      expected. The statistical significance level was calculated as 0.015 owing to the presence of
      3 groups and with the prediction that repeated measurement analysis would be performed
      assuming that the Bonferroni correction would be used. The power of the present study was 80%
      with these calculations.
    

Intervention name(s): Lidocaine; lidocaine+adjunct tramadol; lidocaine+systemic tramadol; Fentanyl; Atropine; Midazolam; Diclofenac sodium; Ephedrine; Ondansetron
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): IVRA was performed with 3 mg/kg lidocaine (10% Lidocaine) plus 50 mg tramadol, which were administered after diluting with saline to 40 mL. While performing IVRA, 30 mL saline was simultaneously administered to the systemic circulation; IVRA was performed with 3 mg/kg lidocaine, which was diluted with saline to 40 mL. While performing IVRA, 50 mg tramadol diluted with saline to 30 mL was simultaneously administered to the systemic circulation; If the patient had a VAS score of >4 and if required, 1 μg/kg fentanyl was administered for analgesia and the dosage and time were recorded.; The patients received premedication 45 min before the surgery with intramuscular 0.01 mg/kg atropine.
In case of bradycardia (HR <50/min), 0.5 mg intravenous atropine was administered.; The patients received premedication 45 min before the surgery with intramuscular 0.07 mg/kg midazolam; The patients with a VAS score of >4 were administered with 75 mg diclofenac sodium via intramuscular route.; In the event of hypotension (systolic arterial pressure <90 mmHg or a decrease of more than 50 mmHg from the normal value) during the surgery, 5 mg intravenous ephedrine was administered.; Intravenous 4 mg ondansetron was administered for nausea and vomiting.
Other intervention name(s): tramadol; tramadol
Intervention MeSH terms: Diclofenac; Lidocaine; Atropine; Ephedrine; Midazolam; Fentanyl; Tramadol; Ondansetron
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Systemic Tramadol; Adjunct Tramadol; Lidocain