- Email: [email protected]
A comparison of the effects of intrathecal fentanyl and lidocaine on established postamputation stump pain
137
Pain, 40 (1990) 137-141 EIsevier
PAIN 01533
A comparison of the effects of intrathecal fentanyl and lidocaine on established postamputation stump pain Louis Jacobson,
Charles Chabal, Michael C. Brody, Anthony and Edmund F. Chaney *
J, ~ariano
*
Departments of Anesthesiologv and * Psjxhology, University of Washington, School of Medicine, RN-1 0, and VA Medica/ Center, Seattle, WA 98108 (U.S.A.) (Received
30 January
1989, revision received 18 May 1989, accepted
25 August
1989)
Eight patients with established lower limb postamputation stump pain were given lumbar intrathecal fentanyl 25 fig Summary and lidocaine 70 mg 2 weeks apart in an attempt to better understand the role of peripheral and central mechanisms in this condition. Baseline pain was recorded and then analgetic and side effects and their duration were assessed. Three self-administered questionnaires with appropriate psychometric proprieties were given to the patients. Intrathecal fentanyl always abolished the pain. Its onset was rapid being heralded within l-2.5 min by a pleasant sensation of warmth involving the lower trunk and legs. Analgesia was complete by 5-10 min and had a median duration of 8 h. The patients had a sense of well being and were unable to elicit discomfort by pain aggravating maneuvers. Normal motor and sensory functions were retained. Pruritus was the only adverse effect unique to intrathecal fentanyl. Intrathecal lidocaine usually relieved the discomfort but was unable to abolish it in 3 of 8 patients despite adequate neural blockade. Its onset of action was slower and duration of effect shorter than fentanyl. Intrathecal fentanyl provided profound analgesia associated with no~a~za~ion of stump sensations and euphoria, probably due to a segmental spinal action. The effects of lidocaine were inferior to fentanyl due to the associated motor and sensory paralyses as well as the absence of euphoria. This study suggests that, while peripheral mechanisms played a role, central mechanisms involving the spinal cord were more important in the modulation of established stump pain in the 8 subjects evaluated. Key words: Stump
pain; Opiates,
intrathecal;
Analgesics,
narcotics,
Introduction
Postamputation stump pain can be intractable and resistant to therapy. Stump pain is thought to arise from the peripheraf nervous system [22], possibly the sprouts of regenerating nerve fibers [26,28,30]. However, the central nervous system
Correspondence to: Louis Jacobson, M.D., Anesthesiology Service (112A), Veterans Affairs Medical Center, 1660 South Columbian Way, Seattle, WA 98108, U.S.A. 0304-3959/90/$03.50
0 1990 Elsevier Science Publishers
fentanyl;
Anesthetic
techniques,
spinal anesthesia
may also be involved in the modulation of stump pain [22,28]. In an attempt to better understand the role that peripheral and central mechanisms play in postamputation pain, this study investigated the effects of intrathecal fentanyl and lidocaine on patients with stump pain. Fentanyl is a lipid-soluble opioid with an effect presumably confined to the spinal cord when administered by the lumbar intrathecal route [23]. Although intrathecal lidocaine penetrates the spinal cord [7], it is thought to act primarily on the nerve fibers and not on the cord itself [4].
B.V. (Biomedical
Division)
13x
Methods The project was approved by our Human Subjects Review Board and written informed consent was obtained from each patient preoperatively. Subjects for the study were 8 men with lower limb postamputation stump pain of longer than 4 months duration (Table I). No patients were suffering from phantom limb pain at the time of the study. A lumbar (L2/3 or L3/4) intrathecal injection of fentanyl 25 yg was given. This was followed 1-2 weeks later by intrathecal lidocaine 70 mg. The study was single-blinded in that the observer, but not the subject, was aware of the treatment. The subjects were informed about the drugs but not their order of administration. An intravenous cannula was inserted and monitoring established prior to each intrathecal injection. With the patient sitting, 25 pg fentanyl (0.5 ml), made up to 1 ml with CSF, or lidocaine 70 mg was injected through a 25-gauge spinal needle, whereupon the patient was placed supine. Assessments were done before each injection and repeated at 1 min, 2.5, 5, 10. 15, 30 min, 1 h, 1.5, 2, 3, and 4 h after both intrathecal injections. Pain and analgetic effects were assessed by verbal patient response using a numerical pain rating system (0 = no pain to 10 = worst pain imaginable) [14,18] and a modified rank pain scale [19]. Adverse effects monitored included pruritus, nausea. vomiting, excessive sedation, and prolonged urinary retention requiring bladder catheterization. Motor weakness and segmental sensory
TABLE
I
PATIENT
DETAILS
Data are median
(N = 8)
with range in parentheses. Duration of stump pain (years) 4.5 (0.4-16)
.Age (years) 64 (35-X)
Disease (no. of patients) Thromboangiitis obliterans (Buerger’s Diabetes Post-traumatic
d.)
4 2 2
&‘ccts were sought. If’ after 4 h the pain had nt)r returned to preblock levels. the patients were re,. quested to note the time ol the return of the discomfort and its progression back to baseline levels. Study participants were given 3 self-administered questionnaires which possess appropriate psychometric properties. These were administered on admission to the study, at a visit to the outpatient pain clinic, l--2 weeks prior to the initial intrathecal injection. They included the Multidimensional Pain Inventory (MPI) f20], the Inventory to Diagnose Depression [31,32] and the Satisfaction with Life scale [ 12]. In addition, information was gathered concerning demographic measures such as mental status, education, income and disability status, perceptions of general health and military/combat experience. Statistical analysis of the numerica pain scores and duratio~l of effect were a~omplished using the Wilcoxon’s rank sum test on unpaired data [15]. Qualitative data were analyzed by the Fisher Exact Probability test. A probability of less than 0.05 (P -c0.05) was considered statistically significant.
Results The baseline (pre-block) median pain score was 3.5 for both fentanyl and lidocaine (Table II). Intrathecal fentanyl provided complete pain relief in all of the patients. The analgesia was complete by 5-10 min. The time to best effect was markedly quicker with fentanyl than lidocaine (P < 0.05). Intrathecal lidocaine usually provided good stump pain relief with a median pain score of zero at the time of optimal effect (30 min) (Table II). Lidocaine, however, did not abolish the pre-block discomfort in 3 of 8 patients in whom the usual sensations of discomfort persisted albeit at a lower intensity than prior to the block. The median duration of analgesia was signific~tly longer with fentanyl {median duration 8 h; interquartile range 6-14 h) than with lidocaine {median duration 2 h; interquartile range 2-3 h) (P < 0.05). The quality of the sensations associated with the two agents was markedly different (P < 0.05).
139
TABLE II MEDIAN PAIN SCORES Verbal scale O-10. Interquartile range in parentheses. Time after injection
Fen tan yl
Lidocaine
0 min
3.5 (2-4)
3.5 (2-5)
lmin
1.5 ii-2j 0 (O-l)
3.0
0
(0)
0
(0)
o
(0)
0.75 (O-1) 0.25 (O-l) 0.25 (O-l)
0 0 0
(0) (0) (0)
0 (O-0.5) 0 (O-l) 0.5 (O-3)
0
(0)
o o
(0) (0)
2 3 4
2.5 min Smin 10 min 15 min 30 min fh 1.5 h 2h 3h 4h
(2-4j
1.0 (l-2)
(O-4) (2-6) (3-5)
I~trathecal fentanyl rapidly and dr~atically extinguished the pain. Its onset was heralded within l-2.5 min by a pleasant sensation of warmth involving the lower trunk and legs. Five patients were euphoric and expressed their sense of well being in a variety of spontaneous unsolicited comments, which included: ‘this is amazing,’ ‘it is incredible,’ ‘it is just a wonderful, warm and normal feeling,’ ‘I have a wonderful warm glow and total relief of pain,’ ‘ not only has the pain gone but all stump sensations are now pleasurable.’ Normal motor and sensory functions were restump sensations were tained. Furthermore, pleasurable with the stump feeling warm, comfortable and relaxed. Actions and maneuvers which usually aggravated the stump pain were comfortable, pain-free and pleastubble. Consequently, the patients walked comfortably on their prostheses and it felt good to touch and rub the stump. Intrathecal lidocaine 70 mg provided complete segmental sensory analgesia to TlO or higher which was associated with motor paralysis of the lower limbs. Sensations were numbed below the level of the block and the patients were unable to move their legs or walk. Furthermore, in a proportion of patients (3/8) some stump discomfort remained despite profound neural blockade. No pleasurable sensations accompanied the use of lidocaine. Pruritus, usually confined to the trunk and legs, was the only adverse effect unique to intrathecal
fentanyl. Drowsiness, lightheadedness, nausea, vomiting, clinical respiratory depression and prolonged urinary retention requiring catheterization were not encountered with either fentanyl or lidocaine. Case study analysis suggested that psychological factors did not appear to contribute strongly to differences in analgesic effectiveness.
Discussion The lumbar intrathecal administration of fentanyl produced excellent analgesia, normalization of stump sensations, warmth confined to the lower half of the body, and positive feelings. There were a wide range of patient responses to intrathecal fentanyl, extending from unemotional verbal reports of beneficial effect, to ecstasy. However, analgesia, warmth, and normal stump sensations were present in all the subjects. The effects of lidocaine were inferior to fentanyl due to the concomitant motor and sensory paralyses, absence of euphoria, inability to normalize stump sensations, and the continued presence of some discomfort in 3 of 8 patients despite adequate neural blockade. Limitations of this study should be acknowledged. A small number of patients (8) participated, and caution should be exercised when extrapolating from a small sample size to the general population [17,24]. On a statistical basis, a significant proportion of patients with stump pain could fail to respond to intrathecal fentanyl, despite a uniformly favorable response by the subjects in this study. However, the incidence of failure should not exceed 31% [2]. Nevertheless, intrathecal fentanyl is capable of exerting powerful effects on stump pain and further investigations are warranted. The study was conducted under single-blinded controlled conditions. The treatments were not rando~zed and no measures were taken to eliminate observer bias. With the resources available to us, the latter would have been difficult to accomplish considering the effects of lidocaine (sensory and motor paralyses) and fentanyl (itching without gross motor or sensory effects). We decided against randomizing
140
the order of treatments, but rather to give fentanyl and lidocaine sequentially. We wished to avoid any preconceptions created by the administration of intrathecal lidocaine (sensory and motor cues) which would subsequently influence the assessment of the effects of fentanyl. The highly lipid-soluble opioid (fentanyl) apparently produced a segmental spinal effect. Calculations on the distribution of fentanyl between CSF and spinal cord indicate that 96% of the initial dose enters the spinal cord [5]. The rapid onset of action was too prompt for a supraspinal effect through rostra1 spread either via the cerebrospinal fluid circulation [ IO,1 1,251 or the spinal cord vasculature [21]. The warmth and itching were confined to the lower parts of the body. Supraspinal side effects such as drowsiness, lightheadedness, clinical respiratory depression. nausea and vomiting were absent. Stump pain is thought to arise from the peripheral nervous system [22,26], possibly the sprouts of regenerating nerve fibers [26,28,30]. Transected nerves acquire novel properties including spontaneous activity [16,28], mechanical sensitivity (Tinel’s sign) [3,28] and noradrenaline sensitivity [3, 28.301. These peripheral factors do contribute to postamputation stump pain as demonstrated by its diminution/abolition with intrathecal lidocaine which acts predominantly on the peripheral nervous system. During spinal anesthesia local anesthetics are found both in the nerve roots and within the substance of the spinal cord [7]. The major cause of loss of sensation and muscle relaxation during spinal anesthesia is, however, the presence of local anesthetics in spinal nerve roots and in dorsal root ganglia, not within the spinal cord [4]. After transection of a peripheral nerve, not only are there neurophysiological changes peripherally but they also occur centrally in the spinal cord [l&9,13,27-29]. There appears to be a cascade of events whereby the peripheral injury provides signals which trigger changes within the spinal cord. Consequently, neuronal mechanisms involved in the production and maintenance of postamputation stump pain might comprise central as well as peripheral components. Therefore, it is possible that the spinal cord plays an important
role in the modulation of postamputatron 4tump pain. The more dramatic and profound effects observed following intrathecal fentanyl rather than lidocaine lends credence to this hypothesis. In conclusion, although peripheral mechanism.< were operative, spinal modulation of established postamputation stump pain was more important in the 8 subjects of this study. Presumably. intrathecal fentanyl relieved the pain by a Legmental spinal effect. We postulate that through its action on spinal opioid receptors, subarachnoid fentany-1 altered the impulse pattern signaling pain in a way that was perceived as pleasant. Intrathecal opioids have the potential to contribute to an improved understanding, evaluation and therapy of postamputation stump pain.
References
6
7 8
9
10
Barbut, D., Polak. J.M. and Wall, P.D., Substance P in spinal cord dorsal horn decreases following peripheral nerve inJury, Brain Res., 205 (1981) 289-298. Benefiel, D.J., Eisler, E.A. and Shepherd, R.. Use caution when extrapolating from a small sample size to the general population, Anesthesiology, 70 (1989) 160-161. Blumberg, H. and Jlnig, W., Neurophysiological analysis of efferent sympathetic and afferent fibers in skin nerves with experimentally produced neuromata. In: J. Siegfried and M. Zimmermann (Eds.), Phantom and Stump Pain, Springer, Berlin. 1989, pp. 15-31. Bridenbaugh. P.O. and Greene, N.M., Spinal (subarachnoid) neural blockade. In: M.J. Cousins and P.O. Bridenbaugh (Eds.), Neural Blockade in Clinical Anesthesia and Management of Pain. Lippincott, Philadelphia, PA. 1988, pp. 213-251. Bullingham, R.E.S., McQuay, H.J. and Moore, R.A., Extradural and intrathecal narcotics. In: R.S. Atkinson and C. Langton-Hewer (Eds.), Recent Advances in Anaesthesia and Analgesia, Churchill Livingstone, New York, 1982, pp. 141-156. Carlen, P.L.. Wall. P.D., Nadvorna, H. and Steinbach, T.. Phantom limbs and related phenomena in recent traumatic amputations, Neurology, 28 (1978) 211-217. Cohen, E.N.. Distribution of local anesthetic agents in the neuraxis of the dog, Anesthesiology. 29 (1968) 1002-1005. Devor, M. and Claman. D., Mapping and plasticity of acid phosphatase afferents in rat dorsal horn, Brain Res., 190 (1980) 17-28. Devor, M. and Wall, P.D.. Reorganization of spinal cord sensory map after peripheral nerve injury, Nature, 275 (1978) 75-76. Dichiro, G., Movement of the cerebrospinal fluid in human beings, Nature, 204 (1964) 290-291.
141 11 Dichiro, G., Observations on the circulation of the cerebrospinal fluid, Acta Radiol. Diagn., Suppl. (1966) 988-1002. 12 Diener, E., Emmons, R.A., Larsen, R.J. and Griffin, S., The satisfaction with life scale, J. Pers. Assess., 49 (1983) 71-75. 13 Dostrovsky, J.O., Millar, J. and Wall, P.D., The immediate shift of afferent drive of dorsal column nucleus cells following deafferentation: a comparison of acute and chronic deafferentation in gracile nucleus and spinal cord, Exp. Neurol., 52 (1976) 480-495. 14 Downie, W.W., Leatham, P.A., Rhind, V.M., Wright, V. and Branco, J.A., Studies with pain rating scales, Ann. Rheum. Dis., 37 (1978) 378-381. 15 Forrest, M. and Anderson, B., Ordinal scale and statistics in medical research, Br. Med. J., 292 (1986) 537-538. 16 Govrin-Lippman, R. and Devor, M., Ongoing activity in severed nerves, Brain Res., 159 (1978) 406-410. 17 Hanley, J.A. and Lippman-Hand, A., If nothing goes wrong, is everything all right?, JAMA, 249 (1983) 1743-1745. 18 Jensen, M.P., Karoly, P. and Braver, S., The measurement of clinical pain intensity: a comparison of six methods, Pain, 27 (1986) 117-126. 19 Keele, K.D., Pain chart, Lancet, ii (1985) 6-8. 20 Kerns, R.D., Turk, D.C. and Rudy, T.E., The West HavenYale Multidimensional Pain Inventory (WHYMPI), Pain, 23 (1985) 345-356. 21 Kotob, H.I.M., Hand, C.W., Moore, R.A., Evans, P.J.D., Wells, J., Rubin, A.P. and McQuay, H.J., Intrathecal morphine and heroin in humans: six-hour drug levels in spinal fluid and plasma, Anesth. Analg., 65 (1986) 718-722. 22 Merskey, H. et al., Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms, Pain, Suppl. 3 (1986) S26-S28.
23 Payne, R. and Inturrisi, C.E., CSF distribution of morphine methadone, and sucrose after intrathecal injection, Life Sci., 37 (1985) 1137-1144. 24 Rumke, C.L., Implications of the statement: no side effects were observed, New Engl. J. Med., 292 (1975) 372-373. 25 Sato, O., Asai, T., Amaro, Y., Hara, M., Tsugane, R. and Yagi, M., Formation of cerebrospinal fluid in spinal subarachnoid space, Nature, 233 (1971) 129-130. 26 Siegfried, J. and Zimmermann, M., Preface. In: J. Siegfried and M. Zimmermann (Eds.), Phantom and Stump Pain, Springer, Berlin, 1981, pp. v-vii. 27 Wall, P.D., The gate control theory of pain mechanisms: a re-examination and re-statement, Brain, 101 (1978) 1-18. 28 Wall, P.D., On the origin of pain associated with amputation. In: J. Siegfried and M. Zimmermann (Eds.), Phantom and Stump Pain, Springer, Berlin, 1981, pp. 2-14. 29 Wall, P.D. and Devor, M., The effect of peripheral nerve injury on dorsal root potentials and on transmission of afferent signals into the spinal cord, Brain Res., 209 (1981) 95-111. 30 Wall, P.D. and Gutnick, M., Ongoing activity in peripheral nerves. II. The physiology and pharmacology of impulses originating in a neuroma, Exp. Neurol., 43 (1974) 580-593. 31 Zimmermann, M., Coryell, W., Corenthal, C. and Wilson, S., A self-report scale to diagnose major depressive disorder, Arch. Gen. Psychiat., 42 (1986) 1076-1081. 32 Zimmermann, M. and Coryell, W., The inventory to diagnose depression (IDD): a self-report scale to diagnose major depressive disorder, J. Cons. Clin. Psychol., 55 (1987) 55-59.
Pain, 40 (1990) 137-141 EIsevier
PAIN 01533
A comparison of the effects of intrathecal fentanyl and lidocaine on established postamputation stump pain Louis Jacobson,
Charles Chabal, Michael C. Brody, Anthony and Edmund F. Chaney *
J, ~ariano
*
Departments of Anesthesiologv and * Psjxhology, University of Washington, School of Medicine, RN-1 0, and VA Medica/ Center, Seattle, WA 98108 (U.S.A.) (Received
30 January
1989, revision received 18 May 1989, accepted
25 August
1989)
Eight patients with established lower limb postamputation stump pain were given lumbar intrathecal fentanyl 25 fig Summary and lidocaine 70 mg 2 weeks apart in an attempt to better understand the role of peripheral and central mechanisms in this condition. Baseline pain was recorded and then analgetic and side effects and their duration were assessed. Three self-administered questionnaires with appropriate psychometric proprieties were given to the patients. Intrathecal fentanyl always abolished the pain. Its onset was rapid being heralded within l-2.5 min by a pleasant sensation of warmth involving the lower trunk and legs. Analgesia was complete by 5-10 min and had a median duration of 8 h. The patients had a sense of well being and were unable to elicit discomfort by pain aggravating maneuvers. Normal motor and sensory functions were retained. Pruritus was the only adverse effect unique to intrathecal fentanyl. Intrathecal lidocaine usually relieved the discomfort but was unable to abolish it in 3 of 8 patients despite adequate neural blockade. Its onset of action was slower and duration of effect shorter than fentanyl. Intrathecal fentanyl provided profound analgesia associated with no~a~za~ion of stump sensations and euphoria, probably due to a segmental spinal action. The effects of lidocaine were inferior to fentanyl due to the associated motor and sensory paralyses as well as the absence of euphoria. This study suggests that, while peripheral mechanisms played a role, central mechanisms involving the spinal cord were more important in the modulation of established stump pain in the 8 subjects evaluated. Key words: Stump
pain; Opiates,
intrathecal;
Analgesics,
narcotics,
Introduction
Postamputation stump pain can be intractable and resistant to therapy. Stump pain is thought to arise from the peripheraf nervous system [22], possibly the sprouts of regenerating nerve fibers [26,28,30]. However, the central nervous system
Correspondence to: Louis Jacobson, M.D., Anesthesiology Service (112A), Veterans Affairs Medical Center, 1660 South Columbian Way, Seattle, WA 98108, U.S.A. 0304-3959/90/$03.50
0 1990 Elsevier Science Publishers
fentanyl;
Anesthetic
techniques,
spinal anesthesia
may also be involved in the modulation of stump pain [22,28]. In an attempt to better understand the role that peripheral and central mechanisms play in postamputation pain, this study investigated the effects of intrathecal fentanyl and lidocaine on patients with stump pain. Fentanyl is a lipid-soluble opioid with an effect presumably confined to the spinal cord when administered by the lumbar intrathecal route [23]. Although intrathecal lidocaine penetrates the spinal cord [7], it is thought to act primarily on the nerve fibers and not on the cord itself [4].
B.V. (Biomedical
Division)
13x
Methods The project was approved by our Human Subjects Review Board and written informed consent was obtained from each patient preoperatively. Subjects for the study were 8 men with lower limb postamputation stump pain of longer than 4 months duration (Table I). No patients were suffering from phantom limb pain at the time of the study. A lumbar (L2/3 or L3/4) intrathecal injection of fentanyl 25 yg was given. This was followed 1-2 weeks later by intrathecal lidocaine 70 mg. The study was single-blinded in that the observer, but not the subject, was aware of the treatment. The subjects were informed about the drugs but not their order of administration. An intravenous cannula was inserted and monitoring established prior to each intrathecal injection. With the patient sitting, 25 pg fentanyl (0.5 ml), made up to 1 ml with CSF, or lidocaine 70 mg was injected through a 25-gauge spinal needle, whereupon the patient was placed supine. Assessments were done before each injection and repeated at 1 min, 2.5, 5, 10. 15, 30 min, 1 h, 1.5, 2, 3, and 4 h after both intrathecal injections. Pain and analgetic effects were assessed by verbal patient response using a numerical pain rating system (0 = no pain to 10 = worst pain imaginable) [14,18] and a modified rank pain scale [19]. Adverse effects monitored included pruritus, nausea. vomiting, excessive sedation, and prolonged urinary retention requiring bladder catheterization. Motor weakness and segmental sensory
TABLE
I
PATIENT
DETAILS
Data are median
(N = 8)
with range in parentheses. Duration of stump pain (years) 4.5 (0.4-16)
.Age (years) 64 (35-X)
Disease (no. of patients) Thromboangiitis obliterans (Buerger’s Diabetes Post-traumatic
d.)
4 2 2
&‘ccts were sought. If’ after 4 h the pain had nt)r returned to preblock levels. the patients were re,. quested to note the time ol the return of the discomfort and its progression back to baseline levels. Study participants were given 3 self-administered questionnaires which possess appropriate psychometric properties. These were administered on admission to the study, at a visit to the outpatient pain clinic, l--2 weeks prior to the initial intrathecal injection. They included the Multidimensional Pain Inventory (MPI) f20], the Inventory to Diagnose Depression [31,32] and the Satisfaction with Life scale [ 12]. In addition, information was gathered concerning demographic measures such as mental status, education, income and disability status, perceptions of general health and military/combat experience. Statistical analysis of the numerica pain scores and duratio~l of effect were a~omplished using the Wilcoxon’s rank sum test on unpaired data [15]. Qualitative data were analyzed by the Fisher Exact Probability test. A probability of less than 0.05 (P -c0.05) was considered statistically significant.
Results The baseline (pre-block) median pain score was 3.5 for both fentanyl and lidocaine (Table II). Intrathecal fentanyl provided complete pain relief in all of the patients. The analgesia was complete by 5-10 min. The time to best effect was markedly quicker with fentanyl than lidocaine (P < 0.05). Intrathecal lidocaine usually provided good stump pain relief with a median pain score of zero at the time of optimal effect (30 min) (Table II). Lidocaine, however, did not abolish the pre-block discomfort in 3 of 8 patients in whom the usual sensations of discomfort persisted albeit at a lower intensity than prior to the block. The median duration of analgesia was signific~tly longer with fentanyl {median duration 8 h; interquartile range 6-14 h) than with lidocaine {median duration 2 h; interquartile range 2-3 h) (P < 0.05). The quality of the sensations associated with the two agents was markedly different (P < 0.05).
139
TABLE II MEDIAN PAIN SCORES Verbal scale O-10. Interquartile range in parentheses. Time after injection
Fen tan yl
Lidocaine
0 min
3.5 (2-4)
3.5 (2-5)
lmin
1.5 ii-2j 0 (O-l)
3.0
0
(0)
0
(0)
o
(0)
0.75 (O-1) 0.25 (O-l) 0.25 (O-l)
0 0 0
(0) (0) (0)
0 (O-0.5) 0 (O-l) 0.5 (O-3)
0
(0)
o o
(0) (0)
2 3 4
2.5 min Smin 10 min 15 min 30 min fh 1.5 h 2h 3h 4h
(2-4j
1.0 (l-2)
(O-4) (2-6) (3-5)
I~trathecal fentanyl rapidly and dr~atically extinguished the pain. Its onset was heralded within l-2.5 min by a pleasant sensation of warmth involving the lower trunk and legs. Five patients were euphoric and expressed their sense of well being in a variety of spontaneous unsolicited comments, which included: ‘this is amazing,’ ‘it is incredible,’ ‘it is just a wonderful, warm and normal feeling,’ ‘I have a wonderful warm glow and total relief of pain,’ ‘ not only has the pain gone but all stump sensations are now pleasurable.’ Normal motor and sensory functions were restump sensations were tained. Furthermore, pleasurable with the stump feeling warm, comfortable and relaxed. Actions and maneuvers which usually aggravated the stump pain were comfortable, pain-free and pleastubble. Consequently, the patients walked comfortably on their prostheses and it felt good to touch and rub the stump. Intrathecal lidocaine 70 mg provided complete segmental sensory analgesia to TlO or higher which was associated with motor paralysis of the lower limbs. Sensations were numbed below the level of the block and the patients were unable to move their legs or walk. Furthermore, in a proportion of patients (3/8) some stump discomfort remained despite profound neural blockade. No pleasurable sensations accompanied the use of lidocaine. Pruritus, usually confined to the trunk and legs, was the only adverse effect unique to intrathecal
fentanyl. Drowsiness, lightheadedness, nausea, vomiting, clinical respiratory depression and prolonged urinary retention requiring catheterization were not encountered with either fentanyl or lidocaine. Case study analysis suggested that psychological factors did not appear to contribute strongly to differences in analgesic effectiveness.
Discussion The lumbar intrathecal administration of fentanyl produced excellent analgesia, normalization of stump sensations, warmth confined to the lower half of the body, and positive feelings. There were a wide range of patient responses to intrathecal fentanyl, extending from unemotional verbal reports of beneficial effect, to ecstasy. However, analgesia, warmth, and normal stump sensations were present in all the subjects. The effects of lidocaine were inferior to fentanyl due to the concomitant motor and sensory paralyses, absence of euphoria, inability to normalize stump sensations, and the continued presence of some discomfort in 3 of 8 patients despite adequate neural blockade. Limitations of this study should be acknowledged. A small number of patients (8) participated, and caution should be exercised when extrapolating from a small sample size to the general population [17,24]. On a statistical basis, a significant proportion of patients with stump pain could fail to respond to intrathecal fentanyl, despite a uniformly favorable response by the subjects in this study. However, the incidence of failure should not exceed 31% [2]. Nevertheless, intrathecal fentanyl is capable of exerting powerful effects on stump pain and further investigations are warranted. The study was conducted under single-blinded controlled conditions. The treatments were not rando~zed and no measures were taken to eliminate observer bias. With the resources available to us, the latter would have been difficult to accomplish considering the effects of lidocaine (sensory and motor paralyses) and fentanyl (itching without gross motor or sensory effects). We decided against randomizing
140
the order of treatments, but rather to give fentanyl and lidocaine sequentially. We wished to avoid any preconceptions created by the administration of intrathecal lidocaine (sensory and motor cues) which would subsequently influence the assessment of the effects of fentanyl. The highly lipid-soluble opioid (fentanyl) apparently produced a segmental spinal effect. Calculations on the distribution of fentanyl between CSF and spinal cord indicate that 96% of the initial dose enters the spinal cord [5]. The rapid onset of action was too prompt for a supraspinal effect through rostra1 spread either via the cerebrospinal fluid circulation [ IO,1 1,251 or the spinal cord vasculature [21]. The warmth and itching were confined to the lower parts of the body. Supraspinal side effects such as drowsiness, lightheadedness, clinical respiratory depression. nausea and vomiting were absent. Stump pain is thought to arise from the peripheral nervous system [22,26], possibly the sprouts of regenerating nerve fibers [26,28,30]. Transected nerves acquire novel properties including spontaneous activity [16,28], mechanical sensitivity (Tinel’s sign) [3,28] and noradrenaline sensitivity [3, 28.301. These peripheral factors do contribute to postamputation stump pain as demonstrated by its diminution/abolition with intrathecal lidocaine which acts predominantly on the peripheral nervous system. During spinal anesthesia local anesthetics are found both in the nerve roots and within the substance of the spinal cord [7]. The major cause of loss of sensation and muscle relaxation during spinal anesthesia is, however, the presence of local anesthetics in spinal nerve roots and in dorsal root ganglia, not within the spinal cord [4]. After transection of a peripheral nerve, not only are there neurophysiological changes peripherally but they also occur centrally in the spinal cord [l&9,13,27-29]. There appears to be a cascade of events whereby the peripheral injury provides signals which trigger changes within the spinal cord. Consequently, neuronal mechanisms involved in the production and maintenance of postamputation stump pain might comprise central as well as peripheral components. Therefore, it is possible that the spinal cord plays an important
role in the modulation of postamputatron 4tump pain. The more dramatic and profound effects observed following intrathecal fentanyl rather than lidocaine lends credence to this hypothesis. In conclusion, although peripheral mechanism.< were operative, spinal modulation of established postamputation stump pain was more important in the 8 subjects of this study. Presumably. intrathecal fentanyl relieved the pain by a Legmental spinal effect. We postulate that through its action on spinal opioid receptors, subarachnoid fentany-1 altered the impulse pattern signaling pain in a way that was perceived as pleasant. Intrathecal opioids have the potential to contribute to an improved understanding, evaluation and therapy of postamputation stump pain.
References
6
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