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Fentanyl Prolongs Lidocaine Spinal Anesthesia Without Prolonging Recovery

Liu, Spencer MD; Chiu, Andrew A. MD; Carpenter, Randall L. MD; Mulroy, Michael F. MD; Allen, Hugh W. MD; Neal, Joseph M. MD; Pollock, Julia E. MD

Regional Anesthesia and Pain Management

Lidocaine spinal anesthesia is a popular anesthetic for short procedures due to its brief duration.The addition of fentanyl may improve the quality and duration of lidocaine spinal anesthesia. Eight volunteers received plain lidocaine 5% in dextrose (50 mg) both with and without 20 micro gram of fentanyl in a randomized, double-blind, cross-over fashion. Sensory analgesia was assessed with pinprick, cold, touch, transcutaneous electrical stimulation equivalent to surgical incision, and duration of tolerance of pneumatic thigh tourniquet. Motor block was assessed with isometric force dynamometry. Regression of pinprick, touch, and cold was prolonged with fentanyl. Duration of tolerance of electrical stimulation at the umbilicus, hip, knee, and ankle was increased with fentanyl (181% increase from plain lidocaine on average; P < 0.01). Duration of tolerance of tourniquet-induced pain was increased by an average of 48% with addition of fentanyl (P = 0.02). Neither motor block nor time to void was prolonged with fentanyl. Pruritus occurred in all subjects receiving fentanyl but was treated easily and were well tolerated. We recommend the addition of 20 micro gram of fentanyl to lidocaine spinal anesthesia as a means to improve duration of sensory anesthesia without prolonging recovery of motor function or time to micturition.

(Anesth Analg 1995;80:730-4)

Department of Anesthesiology, Virginia Mason Medical Center, Seattle, Washington.

Accepted for publication November 23, 1994.

Address correspondence to Spencer Liu, MD, Department of Anesthesiology, Virginia Mason Medical Center, 1100 Ninth Ave., PO Box 900, Seattle, WA 98111.

Spinal anesthesia with hyperbaric lidocaine is popular for short procedures due to its brief duration. However, it is often necessary to provide anesthesia for a period intermediate in duration between that provided by lidocaine and longer lasting local anesthetics (e.g., bupivacaine). Epinephrine is added to lidocaine to achieve intermediate duration of anesthesia, and indeed lumbosacral anesthesia can be prolonged [1]. Unfortunately, the addition of epinephrine to lidocaine does not prolong sensory block in dermatomes cephalad to the lumbar area [2]. Furthermore, adding epinephrine prolongs time until recovery of micturition, which may prolong time until discharge for same-day surgery patients [2]. Therefore, a method to prolong the duration of lidocaine spinal anesthesia without prolonging recovery would be valuable. The addition of fentanyl has been suggested as a method to accomplish these goals, however, results from previous studies are inconclusive [3,4]. Thus, this study was designed to quantitatively examine the effects of adding fentanyl to lidocaine spinal anesthesia on duration and recovery of sensory and motor block.

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After institutional review board approval and informed consent were acquired, eight healthy volunteers (four male and four female) participated in the study. All subjects were ASA class I and ranged in age from 28 to 42 yr. Each subject received both 50 mg lidocaine 5% in dextrose with 0.4 mL of saline and lidocaine with 20 micro gram (0.4 mL) fentanyl in a randomized, balanced, double-blind fashion. The two spinal anesthetics were separated by at least 5 days in each subject.

Subjects had nothing by mouth for 8 h before each study and voided immediately before each study. Lactated Ringer's solution was administered as a bolus of 6 mL/kg over 15 min prior to subarachnoid block, followed by 8 mL centered dot kg-1 centered dot h-1 for the first hour, then maintenance infusion at a rate of 2 mL centered dot kg1 centered dot h1. Lumbar puncture was performed (in the left lateral decubitus position) at the L2-3 interspace with a 25-gauge Whitacre spinal needle through a 20-gauge introducer with the orifice of the spinal needle turned cephalad. Cerebrospinal fluid (CSF) 0.2 mL was aspirated and the study solution was injected at a rate of 0.25 mL/ps. After injection, subjects were immediately placed supine and remained level for the duration of the study. All subjects were monitored with blood pressure cuff, electrocardiogram, and pulse oximetry every 5 min for the duration of the spinal anesthetic. Symptoms were treated as follows: hypotension (systolic blood pressure < 90 mm Hg) with 5-mg increments of ephedrine, bradycardia (heart rate < 50 bpm) with 0.4 mg of atropine, respiratory depression (pulse oximetry oxygen saturation < 90% on room air) with oxygen via a face mask, nausea with 5 mg of ephedrine (intravenous) followed by 10 mg of metoclopramide, and pruritus with 10 mg increments of propofol [5]. Side effects were noted.

Transcutaneous electrical stimulation (TES) has been demonstrated to be a stimulus as potent as surgical incision [6]. TES leads were placed in the midline at T-10 and T-12 dermatomes and bilaterally at L2-3 (medial aspect above knee) and L5-S1 (lateral aspect above ankle). Five seconds of 50 Hz tetanus at 60 mA with a commercially available nerve stimulator (Model NS252; Fisher & Paykel, Auckland, New Zealand) was considered equivalent to surgical incision [6]. This particular unit was tested by our bioengineering department to verify sustained delivery of displayed currents. Toleration to electrical stimulation was assessed 4 min after injection of spinal solution and measured every 10 min thereafter by initially testing with 10 mA and then increasing in 10 mA increments to a maximum of 60 mA for 5 s. Toleration of the maximum stimulus without pain was considered equivalent to surgical anesthesia [6]. Each TES location was tested in a systematic order moving from distal to proximal sites.

Dermatomal levels to pinprick (18-gauge needle), cold (iced test tube), and touch (self-assessed by subject) were measured at 1, 2, and 5 min after injection of spinal solution, every 5 min thereafter until 40 min postinjection, and then every 10 min until recovery of pinprick at S2.

Tourniquet pain was assessed using previously reported methods [7]. Thirty minutes after injection of spinal solution, the left leg was exsanguinated by gravity, and a 7-cm orthopedic pneumatic tourniquet inflated around the left midthigh to 300 mm Hg. At the first study, each subject was shown a visual analog scale (VAS) marked from 0 to 100 mm with 0 representing no discomfort and 100 representing the worst discomfort imaginable. The subjects were instructed that the tourniquet would be deflated due to discomfort at any time. They were then asked to rate their discomfort on the VAS scale and to fix the degree of discomfort in their mind. During the subsequent study, subjects were shown their level of discomfort on the VAS scale and instructed to request tourniquet deflation at the same level of discomfort. Tourniquets were left inflated until subjects requested deflation, or for a maximum of 2 h after inflation.

A commercially available isometric force dynamometer (Micro FET; Hoggan Health Industries, Draper, UT) was used to assess 5-s isometric maximum force contraction of the right quadriceps and gastrocnemius. Measurements were performed at 0 and 10 min after injection of spinal solution and every 10 min thereafter until return to 90% of baseline. Measurements were performed in triplicate and then averaged at each measurement period. Isometric force dynamometry has been previously shown to be reliable, quantitative methods for evaluation of motor block during spinal and epidural anesthesia [2,8].

All subjects received a standard fluid infusion as outlined above. Subjects attempted to void when the level of pinprick reached dermatomal level S-2. A bladder ultrasound (BladderScan BV12500; Diagnostic Ultrasound Corporation, Kirkland, WA) was used to quantify the volume of urine within the bladder prior to an attempt to void. If subjects were unable to void immediately, then repeat attempts were made every 15 min, and time from injection of spinal solution was recorded. Differences in onset and duration of sensory and motor block and time to micturition were assessed with paired t-test. Differences in dermatomal level to sensory block were assessed with Wilcoxon signed rank test at each measurement period. The incidence of side effects was analyzed with Fisher's exact test. Significance was P < 0.05. Results are reported as mean +/- SD.

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Onset of surgical anesthesia occurred within 14 min after injection at all sites and was not affected by the addition of fentanyl. Duration of surgical anesthesia was prolonged with addition of fentanyl at all sites tested Table 1. There was no difference in duration between the left and right sides, thus average values are displayed. Regression of pinprick, cold, and touch to dermatome L-5 were prolonged with addition of fentanyl. Only regression of pinprick is displayed Figure 1. Tourniquet time was increased with addition of fentanyl (43 +/- 14 min vs 62 +/- 10, plain vs fentanyl, P = 0.02). All subjects experienced pain prior to 2 h of tourniquet inflation.

Table 1

Table 1

Figure 1

Figure 1

Side effects were more common with fentanyl. In eight of eight subjects pruritus occurred with fentanyl (two received treatment with 10 mg of propofol); none of eight subjects had pruritus with plain lidocaine (P = 0.001). One of eight subjects experienced nausea in both the fentanyl and plain lidocaine groups (both subjects requested treatment). No subjects suffered from hypotension, bradycardia, or respiratory depression. Side effects were treated easily and were well tolerated.

There were no differences in onset or duration of motor block with addition of fentanyl Table 2.

Table 2

Table 2

All subjects were able to void immediately after recovery of sensation to pinprick at dermatome S-2 and there was no difference with addition of fentanyl: 144 +/- 20 vs 157 +/- 11 min from injection, plain vs fentanyl (P = 0.11). All subjects had significant amounts of urine in their bladders prior to attempting to void (range, 104-758 mL).

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Our study demonstrates that the addition of 20 micro gram of fentanyl to lidocaine spinal anesthesia improves duration of sensory block without prolonging recovery of motor function or micturition. Furthermore, sensory block in both thoracic and lumbar dermatomes was prolonged with the addition of fentanyl. This is in contrast to the effects of epinephrine [2], and suggests that fentanyl may be a more useful additive when prolonged duration of sensory block is desired in thoracic dermatomes. In addition to measuring standard modalities of sensory block (pinprick, touch, and cold), an electrical stimulation model of surgical incision was used in an attempt to determine duration of surgical anesthesia. Although the utility of TES testing has not been assessed systematically during spinal anesthesia, it has been conclusively demonstrated to provide a stimulus equivalent to skin incision during general anesthesia [6]. Even if not exactly equal to a surgical stimulus during spinal anesthesia, TES is a much more realistic estimate of tolerance to surgical stimulation than pinprick [1]. We noted significant prolongation of duration of tolerance to maximum electrical stimulation at thoracic and lumbar dermatomes with the addition of fentanyl which suggests that the duration of surgical anesthesia may be clinically prolonged.

Our results are consistent with experimental effects of intrathecal opioids which show that combinations of opioids and local anesthetics are synergistic for somatic analgesia in animal models [9], and that intrathecal opioids can markedly enhance analgesia from subtheraputic doses of spinal lidocaine [10]. Intrathecal opioids appear to produce analgesia by inhibition of synaptic transmission in nociceptive afferent pathways (A delta and C fibers) [9] and yet, they do not inhibit conduction in sympathetic pathways or somatosensory evoked potentials [9,11]. Thus, we theorize that synergistic blockade of A delta and C afferents allowed subtherapeutic concentrations of hyperbaric lidocaine to maintain surgical anesthesia during regression of spinal anesthesia. Selective block of A delta and especially C fiber by intrathecal fentanyl may also explain the increased dermatomal spread and prolonged regression of sensory analgesia to pinprick and cold, and the prolonged toleration of pneumatic tourniquet seen in our fentanyl group. Sensation of pinprick, touch, and cold are mediated through A delta and C fibers [12], and it is commonly theorized that tourniquet pain is also mediated through C fibers [13]. Thus, our study results are consistent with an enhanced block of nociceptive afferents as a mechanism of improved anesthesia and analgesia with addition of fentanyl to lidocaine spinal anesthesia.

Pruritus occurred in all volunteers when fentanyl was added. However, it was treated easily and was well tolerated in our volunteers. As our volunteers were unsedated, it is possible that incidences of side effects may be reduced with judicious use of sedatives. Furthermore, since previous studies suggest that side effects from intrathecal fentanyl are dose-related [14], it is also possible that a lower dose of fentanyl may prolong anesthesia while reducing incidence of side effects. We note that respiratory side effects of fentanyl were not sensitively measured in our study. However, a previous study examining ventilatory response in elderly patients to intrathecal fentanyl found no respiratory effects with a dose of 25 micro gram [15]. Thus, we suggest that our dose of 20 micro gram of fentanyl is unlikely to have deleterious respiratory or nonrespiratory side effects.

Recovery of ambulation and ability to void are important factors determining length of recovery room stay, yet have received little attention in previous studies [16,17]. Our study quantitatively demonstrates that addition of fentanyl does not affect onset, quality, or duration of motor blockade of the quadriceps or gastrocnemius muscle groups. Thus, recovery of ambulation should not be delayed and should not contribute to an increased duration of recovery room stay. While previous studies observed that central neuraxial opioids may inhibit bladder function [18,19], our data demonstrate that the addition of a small dose (20 micro gram) of intrathecal fentanyl did not prolong time until subjects were able to void after lidocaine spinal anesthesia. We did not perform a dose-response study, therefore it is unknown whether a greater dose of fentanyl will further improve anesthesia without interfering with micturition. Indeed, it remains unclear whether inhibition of bladder function after administration of spinal opioids is a dose-dependent effect [20]. Nonetheless, a 20-micro gram dose of fentanyl prolonged the duration of surgical anesthesia and duration until of onset of tourniquet pain without a delay in recovery of motor function or ability to void.

Several aspects of study design deserve comment. First, the use of a cross-over design (using subjects as their own controls) was critical due to the large intersubject variability in duration of lidocaine spinal anesthesia [1,21]. Indeed, previous controversy over effects of adding epinephrine to tetracaine and lidocaine were resolved only after a cross-over study was performed [2,22]. Second, the use of objective measurements of sensory and quantitative measurements of motor block allowed for greater precision in identifying differences, whereas previous studies have used measures (e.g., pinprick or Bromage scale) that are subjective and nonquantitative [3,4]. Thus, our use of a cross-over design and use of objective measurements augmented our ability to detect differences from addition of fentanyl.

In conclusion, our study demonstrates that the addition of 20 micro gram of fentanyl to hyperbaric lidocaine spinal anesthesia can significantly prolong duration of sensory block without prolonging recovery of motor function and micturition. Although pruritus was common when fentanyl was added, this was easily treated and was well tolerated in our unsedated volunteers. Our findings suggest that adding fentanyl to lidocaine spinal anesthesia has clinical value as duration of sensory anesthesia may be prolonged without delaying recovery of ambulation or micturition.

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