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n, MDDepartment of Anesthesiology and Reanimation, Department of Orthopedics, and Traumatology Adnan Menderes University, Medical Faculty, Aydin, Turkey
Address correspondence and reprint requests to Selda Sen, MD, Adnan Menderes Üniversitesi Tp Fakültesi, Anesteziyoloji ve Reanimasyon A.D., 09100 Aydin, Turkey. Address e-mail to drseldasen{at}yahoo.com or uzmdrsenselda{at}mynet.com.
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Abstract |
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Introduction |
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Although several studies support the use of transdermal nitroglycerine (NTG) for various analgesic effects (5–11), the addition of IV NTG to lidocaine for IVRA has not been studied.
We evaluated the effect of NTG on intraoperative and postoperative analgesia, sensorial and motor block onset times, and tourniquet pain when added to lidocaine for IVRA.
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Methods |
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Sensory block onset time was noted as the time elapsed from injection of drug to sensory block achieved in all dermatomes. Motor block onset time was the time elapsed from injection of drug to complete motor block.
After sensory and motor block onset, the operative tourniquet (distal cuff) was inflated to 250 mm Hg, and the proximal tourniquet was released. MAP, HR, Spo2, and visual analog scale (VAS) scores (0 = no pain and 10 = worst pain imaginable) were monitored before and 1, 5, 10, 20, and 30 min after tourniquet inflation. Data were measured after release of the tourniquet; and postoperatively at 1 and 30 min and 2, 4, 6, and 24 h by an anesthesiology resident who was blinded as to the study group assignments. When tourniquet pain was >3 on the VAS, patients were given IV fentanyl 1 µg/kg (fentanyl citrate; Abbott, North Chicago, IL). Total administered fentanyl dose and time of administration were noted. Surgery was started 10 min after tourniquet inflation in all patients.
At the end of the operation, the patient was asked to rate the operative conditions such as tourniquet pain or incisional pain according to the following numeric scale: excellent, 4 = no pain; good, 3 = minor pain with no need for supplemental analgesics; moderate, 2 = pain which required supplemental analgesic; and unsuccessful, 1 = patient did not tolerate IVRA.
At the end of the operation, the surgeon, who was blinded as to patient randomization, was asked to score operative conditions such as disturbing movement of the arm and excessive bleeding according to the following numeric scale: 0 = unsuccessful, 1 = poor, 2 = acceptable, 3 = good, and 4 = excellent (4).
The tourniquet was not deflated before 30 min and was not inflated for more than 1 h postoperatively. At the end of surgery, the tourniquet deflation was performed by the cyclic deflation technique. Sensory recovery time was noted (time elapsed after tourniquet deflation up to recovery of pain in all dermatomes determined by pinprick test). Motor block recovery time was noted (the time elapsed after tourniquet deflation up to movement of fingers).
Patients received 75 mg of IM diclofenac (Voltaren; Ciba-Geigy, Istanbul, Turkey) when the VAS score was >3, and total diclofenac consumption was recorded in the first 8 h postoperatively. Patients were given oral paracetamol (Parol tablet 500 mg; Atabay, Istanbul, Turkey), 8–24 h postoperatively, when the VAS score was >3. The total administered paracetamol dose was noted. All evaluations were performed by an anesthesiology resident blinded as to the study group assignments.
First analgesic requirement time (the time elapsed after tourniquet release to first patient request of analgesic) was also noted. Patients were questioned about side effects during the first 2 h in the postanesthesia care unit and later in the ward every 2 h by an anesthesiology resident who was blinded as to the study group assignments. Skin rash, tachycardia, hypotension, hypertension, tinnitus, hypoxemia, headache, nausea, and other side effects were noted during the first 24 h postoperatively in the ward.
The statistical power of the matched analysis was computed in a pilot study performed before this study (10 cases in each group). We found a 70% clinically significant chance of the time to first analgesic requirement in the pilot study. We also found approximately 50% clinically significant changes of the sensory block onset and recovery times, motor block onset and recovery times, postoperative analgesic consumption and tourniquet pain in the pilot study. Based on these estimates, we calculated a sample size that would permit a type I error of 
= 0.05 and power of 90%. Enrollment of 15 patients in each group was required.
Independent samples Student's t-test were used for evaluation of the demographic data, intraoperative and postoperative hemodynamic data, the time of the onset and recovery of sensory and motor block, the duration of the operation and tourniquet, the duration of analgesia, and intraoperative and postoperative analgesic use. The Mann-Whitney U-test was used for intraoperative and postoperative VAS scores and the quality of anesthesia. Complications and operation type were compared with Fischer's exact 
2 test. Significance was determined at P < 0.05.
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Results |
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MAP, HR, and Spo2 were similar between the groups at any intraoperative or postoperative period (P > 0.05) (Table 2).
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Sensory and motor block onset times were statistically shorter in group NTG (Table 3). Sensory and motor block recovery times were also statistically prolonged in this group (Table 3).
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No patient suffered from incisional pain during the intraoperative period. VAS scores for tourniquet pain were lower at 10, 20, and 30 min in group NTG during the intraoperative period. The time to complaint of tourniquet pain (the time of fentanyl requirement for tourniquet pain) was prolonged in group NTG compared with group C (31 ± 9 min, 19.3 ± 7 min; P = 0.044, respectively). Two patients in group NTG and 6 patients in group C required fentanyl for tourniquet pain (P = 0.023). The amount of fentanyl requirement was also smaller in group NTG compared with group C during the intraoperative period (3.5 ± 13.3 µg, 21.4 ± 25.6 µg; P = 0.029, respectively). Postoperative VAS scores were significantly higher for the first 4 h postoperatively in group C compared with group NTG.
Anesthesia quality, as determined by the patient and the surgeon, was better in NTG group (P = 0.024 and P = 0.001, respectively) (Table 4). The time to first postoperative analgesic request in group C and group NTG was 39 ± 33 min and 225 ± 74 min, respectively (P < 0.0001). Diclofenac was used in 8 patients in group NTG and 15 patients in group C (P = 0.0029). Paracetamol was also used for 11 patients in group NTG and 15 patients in group C (P = 0.001). Diclofenac consumption was smaller in group NTG (37 ± 38 mg) compared with group C (101 ± 37 mg) (P < 0.0001). Paracetamol consumption was also smaller in group NTG (535 ± 307 mg) compared with group C (1392 ± 212 mg) (P < 0.0001).
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No patient developed low MAP, tachycardia, or nausea in both groups. One patient in group C and two patients in group NTG developed headache (P > 0.05).
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Discussion |
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There are various proposed sites of action of IVRA. Raj et al. (12) reported that the action of LA is on major nerve trunks, possibly reaching to the nerve trunk via small venules within the nerve core, whereas Rosenberg (13) provided strong evidence concerning a peripheral site. It is now accepted that both the nerve endings and trunks are affected (14).
The beneficial effects of NTG, which we showed in this study, might depend on a direct strong vasodilatory effect that promotes distribution of lidocaine to nerves. This would explain the rapid onset of sensory and motor block.
NTG is metabolized to nitric oxide (NO) in the cell (6,15). NO causes an increase in the intracellular concentration of cyclic guanosine monophosphate, which produces pain modulation in the central and peripheral nervous system (5,6). NO generators also induce antiinflammatory effects and analgesia by blocking hyperalgesia and the neurogenic component of inflammatory edema by topical application (7). Another possible mechanism includes an analgesic effect through the direct stimulation of peripheral fibers mimicking the actions of locally applied acetylcholine (6,16). Mechanisms mentioned above, or their combinations, might contribute to the analgesic effects of NTG added to lidocaine in IVRA.
The clinical efficacy of transdermal NTG for acute pain relief has been documented in several studies (6–11). NTG was found to be useful for the treatment of shoulder pain (17) and thrombophlebitis (7,18) and for enhancing the effect of spinal sufentanil or neostigmine (6,19). Lauretti et al. (5) also showed that delivery of NO donors (transdermal NTG) together with opioids may be of significant benefit in cancer pain management, delaying morphine tolerance and decreasing the frequency of adverse effects related to large doses of opioid.
Data from the literature suggest that in humans, large doses of transdermal NTG, such as 30 mg daily, are hyperalgesic, whereas doses <6 mg daily are analgesic under various circumstances (17–19). Because of these data, we chose to add small dose (200 µg) NTG to lidocaine for an analgesic effect.
Sensory and motor block onset times were statistically shorter in group NTG in our study. This is an advantage for the surgeon and anesthesiologist. There were also lower VAS scores for tourniquet pain and prolonged first analgesic requirement time in group NTG.
Turan et al. (11) investigated the effects of transdermal NTG in IVRA. They used 2% prilocaine and a nitroderm TTS 10 (NTG transdermal patch) 2 hours before surgery in their study. They suggested that transdermal NTG exerts beneficial effects on sensory and motor block without side effects in IVRA. However, they did not evaluate postoperative analgesia in their study.
Although various adjuvants have been suggested for improving intraoperative and postoperative analgesia and maintaining better operative conditions, these adjuvants may cause side effects such as nausea, vomiting, sedation, dizziness, wound hematoma, skin rash, and hypotension (1–4,20). NTG may also cause dose-dependent side effects such as hypotension, tachycardia, or headache (15,21). In our study, there was no significant difference in side effects between groups. The tourniquet was not deflated before 30 min and the tourniquet deflation was performed by the cyclic deflation technique at the end of surgery. NTG has a very short half-life (15). These techniques, combined with the short half-life of NTG, may reduce the frequency and severity of unwanted side effects.
In conclusion, the addition of NTG to lidocaine in IVRA shortened sensory and motor block onset times, prolonged sensory and motor block recovery times, and improved tourniquet pain while prolonging the time for first analgesic requirement and decreasing total amount of analgesic without side effects. Further studies must be performed with experimental models and different doses to determine a relevant conclusion before NTG's routine use.
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Footnotes |
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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oglu B, Memis D, et al. Intravenous regional anesthesia using prilocaine and neostigmine. Anesth Analg 2002;95:1419–22.oglu B, Kaya G, Pamukcu Z. Transdermal nitrogliserinin rejyonel intravenöz anestezide etkileri. Trakya Universitesi Tp Fakultesi Dergisi 2002;19:100–5.This article has been cited by other articles:
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  P. F. White, H. Kehlet, J. M. Neal, T. Schricker, D. B. Carr, F. Carli, and the Fast-Track Surgery Study Group The Role of the Anesthesiologist in Fast-Track Surgery: From Multimodal Analgesia to Perioperative Medical Care Anesth. Analg., June 1, 2007; 104(6): 1380 - 1396. [Abstract] [Full Text] [PDF]
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