A Comparison of Articaine and Fentanyl-Supplemented Articaine for Hemodialysis Fistula Creation under Ultrasound-Guided Axillary Block

Abstract

The aim of this prospective randomized, double-blinded study was to evaluate the effect of fentanyl addition to articaine on the duration of sensory as well as motor blocks, and the duration of analgesia during hemodialysis fistula creation under ultrasound-guided axillary block. Fifty patients were randomly allocated to two groups, an articaine group (A), receiving 40 mL of articaine HCI (20 mg/mL) with 2 mL of isotonic sodium chloride solution, and an articaine-fentanyl group (AF), receiving 40 mL of articaine HCI (20 mg/mL) with 2 mL (100 µg) of fentanyl. The onset as well as the duration of sensory and motor blocks, the time necessary for first analgesic administration, the hemodynamic parameters, and the side effects were recorded. Three patients in Group A and two patients in Group AF due to incomplete block were excluded from the study. The duration of sensory and motor blocks was significantly longer in the AF group than in the A group. The first time for analgesic need was also significantly longer in group AF (363 ± 134 min) than in group A (244 ± 84 min) (p = 0.001). The addition of fentanyl did not improve the onset of sensory and motor block times. Hemodynamic parameters were similar in the two groups. In conclusion, the addition of fentanyl to articaine in axillary block prolongs the duration of sensory and motor blocks, as well as the time of first analgesic requirement.

• Hemodialysis fistula creation
• renal failure
• axillary plexus block
• articaine
• ultrasound guidance

INTRODUCTION

Many anesthesiologists prefer a brachial plexus block as a suitable technique for patients with renal disease undergoing arteriole-venous fistula (AVF) creation for hemodialysis access.¹ AVF blood flow was shown to be significantly increased in patients having brachial plexus blockade when compared to those having general anesthesia in the immediate postoperative period.² Following AVF operations, physiotherapy is needed for a properly working fistula. For a better physiotherapy, motor functions of the muscles should be in good condition with a complete analgesia. Thus, the duration of motor blockade should be shorter than sensorial blockade to be able to move the upper extremity earlier. An ideal drug for such patients should have a fast sensory onset time but with an earlier offset of motor than sensory blockade, enabling them to move their arm while having continued analgesia.³ Articaine is a fast-acting, short-duration, amide local anesthetic (LA). It is preferred to lidocaine because of the case reports and incidence studies that implicate the LA lidocaine as being more neurotoxic than other commonly used LAs.⁴ According to the best of our knowledge there is a paucity of data regarding an axillary neural block with articaine.

Although the addition of opioids in a brachial plexus block for improving success rate and postoperative analgesia has been reported by several authors,^5,6 others have found no effect.^7,8 There is no clinical trial that has evaluated the influence of fentanyl addition to articaine in axillary brachial plexus block. We hypothesize that addition of fentanyl to articaine will increase the duration of sensory and motor blocks and the time to first analgesia requirement. Therefore we compared the effects of articaine and fentanyl added to articaine on the duration of sensorial and motor block time, and the time of first analgesic requirement during AVF creation under ultrasound-guided axillary plexus block.

MATERIALS AND METHODS

Following local hospital ethics committee approval, informed consent was obtained from 50 patients (American Society of Anesthesiologists Grade III, age 25–75 years who were scheduled for radiocephalic AVF creation under ultrasound-guided axillary brachial plexus block) and they were enrolled in this prospective, randomized, double-blinded clinical study. The patients received physiotherapy on the same day as the AVF creation. Details of the anesthetic technique and the study protocol were fully explained at the preoperative visit, and written consent was obtained from each patient before inclusion in the study. Patients were excluded if they had infection at the injection site, allergy to LAs, chronic use of opioids, a history of neurological, neuromuscular, or severe hepatic or cardiopulmonary disease, a contraindication to regional anesthesia or patient refusal. Three patients in Group A and two patients in Group AF due to incomplete block were excluded from the study. The patients had normal prothrombin (PT) and partial thromboplastin (PTT) times before the procedure. On arrival at the operating room, standard monitoring was established with three lead electrocardiograms with non-invasive blood pressure measurement and pulse oximeter (SpO₂) (S/5, Datex-Ohmeda, Helsinki, Finland). After insertion of a 20-gauge intravenous cannula in the non-operated arm, an intravenous crystalloid solution was administered. Supplemental oxygen was supplied through nasal cannula. The oxygen flow was set at 3 L/min. The patients were randomized into one of the two groups using sealed envelopes. The operative arm was abducted and externally rotated, and the elbow flexed to 90°. The skin of the axilla and the medial upper arm was prepared in an aseptic fashion. Ultrasound examination of the axilla was performed using a Philips HD11 XE unit (Philips Healthcare, Best, Netherlands) with a 38-mm high-frequency (9–12 MHz) linear array transducer. Each nerve was identified individually. Nerve stimulation was not used to confirm needle-tip placement. A needle in-plane technique was used, and minor adjustment of scanning planes facilitated the identification of the median, ulnar, radial, and musculocutaneous nerves.

Patients received no premedication or additional medication before or during the block. All blocks were performed by one of the authors, who was unaware of the injected solution, and another observer unaware of the group identity performed assessment of the axillary block. The anesthetic solution was prepared according to a random-number table by an anesthesiologist not otherwise involved in the study.

The patients were allocated to one of two groups in a double-blinded manner: the articaine group (Group A, n = 25) received 40 mL of articaine HCI 2% (Ultracaine^® 20 mg/mL Aventis Pharma, Istanbul, Turkey) with 2 mL of isotonic sodium chloride solution, and the articaine-fentanyl group (Group AF, n = 25) received 40 mL of articaine 2% (20 mg/mL) mixed with 100 µg of fentanyl (fentanyl citrate 2 mL 50 µg/mL, Meditera, Turkey).

After infiltration of the skin with 2–3 mL of lidocaine (10 mg/mL), a 50-mm 24-gauge insulated short bevel needle (Stimuplex^® A 50, B/Braun, Melsungen, Germany) was directed under ultrasound guidance toward each of the four terminal nerves. The needle was moved to several points around each nerve to facilitate circumferential perineural LA spread. A total of 9–11 mL of LA solution was injected and then observed to make sure each nerve was surrounded. A maximum of 42 mL of LA mixture was injected.

The sensory and motor blocks were evaluated every 5 min for 30 min or until blocks were complete. An adequate surgical anesthesia was defined as a motor score of 2 or below, with an absence of cold and pinprick sensations in the area of all four terminal nerves. The zero time for onset of sensory and motor blocks was the completion of the LA injection. Sensory block assessment (0, no block, analgesia; 1, loss of sensation of pinprick, anesthesia; 2, loss of sensation of touch) was performed in the innervations of the four nerve areas [musculocutaneous (lateral side of forearm), radial (radial dorsum of the hand), median (thenar eminence), and ulnar nerves (hypothenar eminence)] corresponding to the nerve distributions in the forearm and hand using the pinprick test, and compared with the same stimulation on the contra-lateral arm. The degree of motor block was evaluated by thumb abduction (radial nerve), thumb adduction (ulnar nerve), thumb opposition (median nerve), and flexion of the elbow in supination and pronation of the forearm (musculocutaneous nerve) using a 3-point scale (0 = normal motor function, 1 = decreased motor strength, 2 = complete motor block). The onset times of the sensory block (the time between the end of the LA injection and the total abolition of the pinprick response) and motor block (time between the end of the LA injection and complete motor block) were recorded for each nerve. The duration of sensory and motor blocks was defined as the time interval between injection and complete recovery of sensation and motor blocks. Analgesia time (time interval between the administration of LA solution and onset of pain at the surgical site) was also recorded by one of the authors. Pain was assessed using a visual analog scale (0, no pain; 10, worst pain imaginable). Analgesic for the first pain was standardized and consisted of 75 mg of intravenous diclofenac sodium given for a pain visual analog scale score of 4. The time to first analgesic requirement was also recorded by the same author.

If the block was inadequate for surgery, the surgeon infiltrated lidocaine (10 mg/mL), and 0.05–0.15 mg of fentanyl was administered intravenously, as needed. Successful block was declared if additional LA infiltration was not needed. Patients who did not achieve satisfactory levels of anesthesia and needed supplementation of any nerve block were excluded from the study. Heart rate, peripheral oxygen saturation, respiratory rate, and blood pressure were measured before the axillary block and 5, 10, 20, 30, 45, and 60 min after the axillary block and thereafter every 60 min for 2 h postoperatively. Additional adverse events (bradycardia, dizziness, nausea and vomiting, and sedation) were recorded. Sedation score (1, awake and alert; 2, sedated, res- ponding to verbal stimulus; 3, sedated, responding to strong physical stimulus; 4, not arousable) were measured at the same time points.

Statistical analysis was performed with SPSS for Windows (SPSS Inc., Chicago, IL, USA), version 13.0. A sample size of 22 subjects was determined based on our preliminary study, in which statistical significance of the changes of time to first pain medication and the duration of motor block and sensory block time were ensured at a level of α error of 0.05 and β error of 0.8. All data had been checked for a normal distribution using the Shapiro–Wilk test and histogram. Patient demographic data and the onset and duration of blocks were compared using the Mann–Whitney U-test or Student's t-test. Categorical data were analyzed using the chi-squared test. Values are expressed as mean ± SD, median (25th–75th percentiles), or number (%). All tests were two-tailed, and a p-value of <0.05 was considered significant.

RESULTS

Patients were recruited and data were collected during the period of January 2009—December 2009. Three patients in Group A (12%) and two patients in Group AF (8%) due to incomplete block were excluded from the study. There were no significant differences between the groups in terms of gender distribution, age, duration of surgery, weight, or height (Table 1).

Table 1. Demographic data and surgical characteristics

	Group A (n = 22)	Group AF (n = 23)	p-Value
Sex (female/male)	10/12	10/13	0.884
Age (years)	54 ± 8	56 ± 13	0.554
Weight (kg)	76 ± 14	74 ± 16	0.764
Height (cm)	166 ± 8	165 ± 8	0.828
Duration of surgery (min)	85 ± 42	68 ± 30	0.145

Note: Data given are means ± SD.

Sixteen patients in Group A and seventeen patients in Group AF underwent primary creation of an arteriovenous fistula. The rest of the procedures were reoperations. Before the block, all patients had normal sensory perception in the operated limb. Onset times of sensory and motor blocks in the different nerve distributions were similar in the two groups (Table 2). The durations of sensory and motor blocks in the different nerve distributions were significantly longer in Group AF than in Group A (Table 3). The mean duration of sensory blocks ranged from 172 to 185 min in Group A, whereas it ranged from 230 to 260 min in Group AF, according to each nerve. On the contrary, duration of motor blocks ranged from 150 to 165 min in Group A, whereas it was 220 min in Group AF for each nerve. The first times for necessity of analgesic were 244 ± 84 min in Group A and 363 ± 134 min in Group AF (p = 0.001). One patient in Group AF did not need analgesic in the postoperative 24 h period.

Table 2. Onset time of sensory and motor blocks of each nerve

	Onset time of sensory block (min)			Onset time of motor block (min)
	Group A (n = 22)	Group AF (n = 23)	p-Value	Group A (n = 22)	Group AF (n = 23)	p-Value
Median nerve	7 (5–10)	7 (5–8)	0.586	8 (7–12)	7 (7–9)	0.446
Ulnar nerve	6 (5–10)	7 (5–9)	0.804	7 (6–12)	8 (6–9)	0.758
Radial nerve	8 (5–10)	7 (5–8)	0.282	8 (7–12)	8 (7–9)	0.803
Musculocutaneous nerve	8 (6–11)	8 (6–9)	0.594	8 (7–11)	8 (7–9)	0.668

Note: Data given are median (25th–75th percentiles).

Table 3. Duration of sensory and motor blocks of each nerve

	Duration of sensory block (min)			Duration of motor block (min)
	Group A (n = 22)	Group AF (n = 23)	p-Value	Group A (n = 22)	Group AF (n = 23)	p-Value
Median nerve	185 (150–230)	250 (200–330)	0.001	165 (128–210)	220 (150–250)	0.013
Ulnar nerve	178 (148–230)	230 (190–270)	0.008	161 (130–203)	220 (150–250)	0.004
Radial nerve	180 (140–226)	250 (190–320)	0.002	165 (127–211)	220 (140–260)	0.010
Musculocutaneous nerve	172 (133–212)	260 (190–320)	0.001	150 (136–205)	220 (140–260)	0.026

Note: Data given are median (25th–75th percentiles).

There were no respiratory or hemodynamic side effects, such as hypotension, bradycardia, apnea, or hypoxia, in either group throughout the study period. In Group A, one patient had a sedation score of 2 and one patient had a score of 3. In Group AF, four patients had sedation scores of 2 and one patient had a score of 3. No statistically significant differences in sedation scores were noted between the two groups (p = 0.274). Major complications (e.g., unintentional intravascular injection and persistent neurological deficit) did not occur. One patient experienced some prodromal symptoms of systemic toxicity (numbness in his tongue), but these self-resolved after cessation of injection. No resuscitation or other treatment was required. No patient discharged on the day of surgery required hospital readmission.

DISCUSSION

This prospective, randomized, double-blinded study demonstrated that the standard dose of 40 mL of 2% articaine and the addition of 100 µg fentanyl to articaine for ultrasound-guided axillary block were associated with prolongation of the time of sensorial and motor block and of the first analgesic requirement, without increased side effects. We also found that the addition of fentanyl to articaine did not modify the rate of successful blocks and did not reduce the onset time of motor and sensorial blockade.

Articaine is classified as an amide and contains a thiophene ring instead of a benzene ring like other amide LAs.⁹ A second molecular difference between articaine and other amide LAs is the extra ester linkage incorporated into the articaine molecule⁹ which results in quick hydrolysis of articaine by plasma esterases. Thus the articaine can be considered as less nephrotoxic. The rapid breakdown of articaine to the inactive metabolite articaine acid is related to a very low systemic toxicity, and consequently allows the possibility of repeat injections.¹⁰ Fentanyl is highly potent short-acting synthetic opioid. Fentanyl displays a large apparent volume of distribution, a short plasma half-life, and extensive biotransformation. The activity of fentanyl metabolites seems to be negligible. Fentanyl causes less histamine release and affords greater cardiovascular stability. Fentanyl may potentially offer advantages in patients with renal failure.¹¹

From our literature research we found a paucity of data regarding an axillary block with articaine. Simon and colleagues demonstrated that lidocaine and articaine show similar pharmacodynamics with a different pharmacokinetic behavior and can therefore be used according to clinical preference for axillary block.¹² However, no study has evaluated the effects of articaine in axillary brachial plexus block for AVF surgery.

Articaine is used as a LA for outpatient surgery because it offers rapid onset of anesthesia and a short-duration motor block.¹³ Despite evidence demonstrating safe hospital discharge of patients with an insensate limb,¹⁴ discharge without protective reflexes remains controversial because there are concerns of possible accidental injury.¹⁵ However, lack of prolonged analgesia may be a disadvantage. To limit side effects and improve the intensity of the motor block and the quality and duration of the analgesia, opioids are added to LAs. However, clinical studies concerning the benefit of opioids and LAs for peripheral nerve block are not clear. The addition of fentanyl in brachial plexus block is reported to improve the success rate and postoperative analgesia by some authors^5,6,16 whereas others have found no effect.^12,17 Opioid receptors are not readily detectable on normal peripheral nerve terminals but appear minutes to hours after initiation of an inflammatory reaction.¹⁸ Some receptors mediate nociception on peripheral sensory axons, and the peripheral administration of opioids has analgesic effects. The mechanisms of the analgesic effects of opioids are unclear. Opioids may directly act on the nerves with LA action and/or synergistic effects with injected LAs. When opioids are perineurally injected, they are carried by opioid-binding proteins to the dorsal horn neurons and may exert central effects.¹⁹ Although there are many studies of varying design using different LAs or opioids, and with different sites of the block (axillary, supraclavicular, interscalene), fentanyl and articaine have not previously been reported for ultrasound-guided axillary brachial plexus block. To the best of our knowledge this study is the first report on this topic. Our results showed that the addition of fentanyl to articaine caused no significant clinical difference in the onset of sensory or motor block, but the duration of analgesia was significantly longer than with articaine alone. Sensory and motor blocks were also prolonged with a fentanyl and articaine combination. These results suggest that the prolongation in sensory and motor block may be the result of the LA action of fentanyl affecting both sensory and motor neurons in the axillary sheath. In AVF operations, although prolonged motor blockade is a disadvantage, long times of sensorial blockade and for the first analgesic requirement are desirable. In previous studies, there have been many trials related to the addition of opioids to LAs to prolong motor block times. Karakaya et al.⁶ showed that the addition of fentanyl to bupivacaine prolonged motor block duration from 4.9 to 10.7 h in axillary brachial plexus block. This study also showed that the times of sensorial block were prolonged. There are also opposite studies showing that addition of fentanyl did not prolong motor block. Fletcher et al. and Kardash et al. demonstrated that the addition of fentanyl to lidocaine and mepivacaine did not affect the times of motor block, respectively.^8,16 In the present study, although the addition of fentanyl to articaine prolonged motor block from 169 to 240 min, these times were not much longer as compared to other LAs.

In our study, we applied an ultrasound-guided axillary plexus block with a 9–12-MHz probe that provided high-resolution imaging. This enhanced the observation of the needle during insertion as well as the spread of the LA solution within the plexus sheath. Our study yielded an 88% success rate in Group A and a 92% success rate in Group AF, achieving adequate analgesia.

We used 100 µg fentanyl as an adjunct in axillary brachial plexus block as most experience in the literature has been obtained with this dose.⁸ In previous studies investigating the addition of 100 µg of fentanyl to LAs for brachial plexus block, no difference was found in the occurrence of adverse effects or changes in HR or blood pressure when compared with the placebo group.⁸ This study showed that the hemodynamics remained unchanged in all patients throughout the study period. We also found no significant differences with regard to the respiratory parameters, sedation score, or side effects between the groups.

In conclusion, both articaine and fentanyl addition to articaine can be used safely and effectively for AVF operation under ultrasound-guided axillary plexus block. Fentanyl addition to articaine may be preferred to extend time to first analgesic requirement and sensorial block time without adverse effects. However, the disadvantage of prolonged motor block duration must be kept in mind.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.