The delayed onset time of sensory block in epidural anesthesia is sometimes a drawback for clinical practice. Alkalinization of local anesthetic solution has been used to shorten the onset time (1). Likewise, the addition of fentanyl to lidocaine (2), bupivacaine (3), and mepivacaine (4) solutions produces a rapid onset of sensory block during epidural anesthesia. Conversely, other investigators have reported no change in the onset of analgesia with the addition of fentanyl to epidural mepivacaine (5). Ropivacaine, a long-acting amino-amide type local anesthetic, is widely used in epidural anesthesia. The aim of this study was to examine the effect of epidural fentanyl on the onset times of sensory and motor blocks during epidural ropivacaine anesthesia.
This was a randomized, double-blind, prospective study. After approval from the human research review committee of our institute, each patient gave informed consent. Forty-five young male patients, ASA physical status I, undergoing knee arthroscopic surgery were included. Exclusive criteria included bleeding disorders, infection at puncture site, a history of opioid dependence, allergy to study drugs, and morbid obesity. Using sealed envelops, the patients were randomly allocated into 3 groups: epidural fentanyl (EF), IV fentanyl (IF), and a control (C) group, with 15 patients in each group. The patients were monitored with electrocardiogram, arterial blood pressure, heart rate, and pulse oximetry during surgery. With the patient in the left lateral decubitus position, the epidural space was identified at L3-4 level with an 18-guage Tuohy needle (minipack, Portex, UK) by the loss of resistance method. With the bevel of the Tuohy needle in cephalic direction, an epidural catheter was inserted 5 cm into the epidural space. A test dose of 3 mL of 2% lidocaine (ASTRA, Sweden) containing 1:200,000 epinephrine (freshly added) was administered to detect intrathecal or IV injection. Three minutes later, the patients of group EF received the epidural administration of 15 mL of 1% ropivacaine plus 100 μg (2 mL) fentanyl, followed by an IV injection of 2 mL of normal saline. The patients of group IF received the epidural administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline, followed by an IV injection of 100 μg (2 mL) of fentanyl. The patients of group C received the epidural administration of 15 mL of 1% ropivacaine plus 2 mL of normal saline along with an IV injection of 2 mL of normal saline. The speed of epidural ropivacaine administration was consistent in all groups, with a rate of 3 mL/10 s.
The sensory block was assessed by pinprick method at 2.5-min intervals for 40 min. Pinprick sensation was examined using a blunt 21-gauge needle in a cephalic-to-caudal fashion along the left anterior axillary line. The onset of sensory block was defined as the time from epidural injection to the occurrence of sensory block at the T10 dermatome. The upper level of sensory block was recorded. The motor block was assessed at 2.5-min intervals for 40 min by a modified Bromage scale (0–3): 0, no motor impairment (able to move joints of hip, knee, and ankle); 1, unable to raise either extended leg (able to move joints of knee and ankle); 2, unable to raise extended leg and flex knee (able to move joint of ankle); 3, unable to move knee and foot. The onset of motor block was defined as the time from epidural injection to the occurrence of motor block at each scale. Both sensory and motor block data were assessed by a blinded observer. Arterial blood pressure and heart rate were measured every 2.5 min after epidural injection. Hypotension (systolic blood pressure <100 mm Hg or a decrease of more than 30% from baseline) was treated with 5 mg of IV ephedrine as needed. Side effects such as nausea, vomiting, pruritus, respiratory depression, or shivering were recorded during surgery, and difficulty in micturition was also recorded for 24 h postoperatively. The pH of the 2 mixed ropivacaine solutions used in this study was measured by using a pH meter.
Based on a previous study (6), an estimated standard deviation of 5 min for the onset of sensory block during epidural ropivacaine anesthesia was used. A decrease in the onset time of 30% was considered clinically significant. On the basis of these estimates, a sample size of 15 patients in each group would be sufficient to get a two-tailed type I error of 0.05 and a power of 80% (7). The results were expressed as mean ± sd or median (range) for the level of sensory block. The pH of the local anesthetic solutions was analyzed by Student’s t-test. The difference of onset times of sensory and motor block was analyzed using analysis of variance and the Student-Newman-Keuls test for post hoc comparison. The upper levels of sensory block were compared using the Kruskal-Wallis test and the Dunn’s multiple comparison procedure for post hoc comparison. The incidences of side effects among groups were analyzed by χ2 test. A P value <0.05 was considered significant.
The three study groups were similar in age, weight, and height (Table 1). The pH of the 2 mixed ropivacaine solutions was no different: 4.65 ± 0.03 (n = 3) in the 15 mL of 1% ropivacaine plus 100 μg (2 mL) fentanyl, and 4.67 ± 0.02 (n = 3) in the 15 mL of 1% ropivacaine plus 2 mL of normal saline. The anesthetic characteristics of the 3 groups are shown in Table 2. Onset time of sensory block up to T10 dermatome was significantly more rapid in the EF group than in the IF and C groups. The upper level of sensory block did not differ among the 3 groups. Onset time of motor block to the modified Bromage scores 1 and 2 was significantly more rapid in the EF group compared with the IF and C groups. Changes of arterial blood pressure and heart rate were not different among the 3 groups. The incidence of shivering among the three groups (5 of 15 in EF group, 7 of 15 in IF group, and 9 of 15 in C group) was not significant. Two patients complained of dizziness in the IF group (not significant). Mild pruritus was observed by three and one patients in the EF and IF groups, respectively (not significant). Nausea, vomiting, respiratory depression, or urinary retention were not observed in any patients.
This study demonstrates that the addition of 100 μg fentanyl to 1% ropivacaine solution for epidural ropivacaine anesthesia accelerates the onset of sensory and motor blocks. Systemic fentanyl had no effect on this response. The mechanisms by which fentanyl speeds the onset of sensory and motor blocks are not clear. From an animal study, the combination of ropivacaine and fentanyl accelerated the onset of analgesia as compared with ropivacaine alone for caudal epidural anesthesia in mares (8). Power et al. (9) demonstrated that fentanyl increased the degree of nerve conduction block produced by bupivacaine in rabbit vagus nerve. In a clinical study, systemic fentanyl enhanced the spread of spinal analgesia produced by lidocaine (10). These results suggested that fentanyl might enhance the nerve block effect of local anesthetics.
A synergistic interaction between local anesthetics and opioids with epidural administration has been reported (11,12). It appears that local anesthetics and opioids exert their action independently via different mechanisms. Local anesthetics block propagation and generation of neural action potentials by a selective effect on sodium channels, whereas opioids act on the opioid receptors creating an increase in a potassium conductance. This action results in hyperpolarization of the nerve cell membrane and a decrease in excitability (13). Although sodium channel block is proposed to be the primary mode of action, local anesthetics also have an effect on synaptic transmission (14). Li et al. (14) showed that lidocaine inhibited both substance P binding and substance P-evoked increase in intracellular calcium. In contrast, in addition to the considered primary mode of action, opioids were found to directly suppress the action potential in nerve fibers (15). Frazier et al. (16) showed that morphine depressed both sodium and potassium currents associated with the action potential in squid giant axons. Therefore, the combination of local anesthetics and opioids may effectively inhibit multiple areas of neuronal excitability.
Regarding the possible mechanisms of the acceleration of sensory and motor blocks produced by fentanyl in this study, we postulate that fentanyl might enhance the nerve conduction block of spinal roots. Cousins and Veering (17) stated that the initial onset of epidural block is probably related to the conduction block of spinal roots within the dural cuff because large concentrations of local anesthetic solution build up rapidly and the dura is very thin in this region. Fields et al. (18) showed that primary afferent tissues (dorsal roots) contain opioid binding sites; thus fentanyl might act directly on the spinal nerve or penetrate the dura and act at the spinal roots. In addition, fentanyl has been reported to have a local anesthetic action. Smith et al. (19) reported a case in which the patient developed unilateral analgesia after injection of fentanyl near the lumbosacral plexus, and a local anesthetic effect of fentanyl was proposed. In an in vitro electrophysiological study, Gissen et al. (20) demonstrated that perineural fentanyl and sufentanil inhibited the action potential of A and C fibers, and naloxone pretreatment did not prevent this inhibitory effect. Similarly, Power et al. (9) showed that fentanyl blocked the nerve conduction of A and C fibers, and naloxone did not prevent this inhibitory effect. These results suggested that fentanyl may have some effect on nerve conduction that is not mediated via the opioid receptors.
In conclusion, addition of 100 μg fentanyl to 1% ropivacaine solution shortened the onset times of sensory and motor blocks during epidural anesthesia without increased side effects.
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