Clinical trial NCT02658721: Effects of Systemic or Adjunct Tramadol Addition to Lidocaine Used for IVRA in Patients Undergoing Hand Surgery
Official title: Effects of Addition of Systemic Tramadol or Adjunct Tramadol to Lidocaine Used for Intravenous Regional Anesthesia in Patients Undergoing Hand Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anesthesia
Keywords: Systemic Tramadol
Adjunct Tramadol
Lidocain
Lead sponsor: Bagcilar Training and Research Hospital
Sponsor class: OTHER_GOV
First posted: 2016-01-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* American Society of Anesthesiologists (ASA) I-II patients who were planned to undergo hand surgery.

Exclusion Criteria:

* Patients with Raynaud's disease, those with sickle-cell anemia, and those receiving any drug for history of allergy

Primary outcomes:
measure: Onset time of sensory block
timeFrame: The sensorial block was assessed from the injection of the study drug until the initiation of surgery by pinprick test (approximately 175 seconds)
measure: Recovery time of sensory block
timeFrame: The time elapsed from the deflation of tourniquet to the highest pain felt by the patient via pinprick test (approximately 135 seconds)
measure: Onset time of motor block
timeFrame: 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 (approximately 220 seconds)
measure: Recovery time of motor block
timeFrame: Time elapsed from the deflation of tourniquet to the spontaneous movement of the fingers (approximately 165 seconds)
Secondary outcomes:
measure: Degree of intraoperative pain
timeFrame: VAS scores were recorded before (one minute ago) and after tourniquet (five minutes later) application as well as at 5th, 10th, 15th, 20th, 30th, 40th, and 50th min during the surgery
measure: Degree of postoperative pain with VAS measurement
timeFrame: VAS measurement was performed at the postoperative 1st, 2nd, 4th, 6th, 12th and 24th hour.
measure: Quality of anesthesia
timeFrame: From the initiation of surgery (30 minutes) up to 24 hours after surgery, an average of 24,5 hours
Other outcomes:
Locations:
Study officials:
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