| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
 
|
|
|
||
|
|
© 2000 International Anesthesia Research Society
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Although effective in neuropathic pain, the efficacy of systemic lidocaine in non-neuropathic pain remains uncertain. We investigated the analgesic effect of systemic lidocaine on the heat/capsaicin sensitization model of experimental pain in 24 volunteers. Sensitization was produced by heating the skin to 45°C for 5 min, followed by a 30-min application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin. Subjects received IV lidocaine (bolus 2 mg/kg, then infusion 3 mg · kg · h), or saline for 85 min. Areas of secondary hyperalgesia, heat pain detection thresholds, and painfulness of stimulation with 45°C for 1 min (long thermal stimulation) were quantified. Systemic lidocaine reduced the area of secondary hyperalgesia to brush, but not to von Frey hair stimulation. Lidocaine did not alter heat pain detection thresholds or painfulness of long thermal stimulation in normal skin. We conclude that, at infusion rates in the low- to mid-antiarrhythmic range, lidocaine has no effect on acute nociceptive pain but does have a limited and selective effect on secondary hyperalgesia.
Implications: The efficacy of systemic lidocaine in nonneuropathic pain remains uncertain. This study investigates the effect of systemic lidocaine on experimental-induced hyperalgesia in 25 volunteers. Hyperalgesia was induced by using an experimental pain model that uses heat and capsaicin in combination. Systemic lidocaine showed a selective effect on secondary hyperalgesia.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Lidocaine, a local anesthetic and antiarrhythmic drug, has been administered for many years for a broad variety of painful conditions (1). Numerous anecdotal reports of pain relief with systemic lidocaine have been followed by well performed, prospective, controlled experimental and clinical studies in diabetic neuralgia and postherpetic neuralgia, as reviewed by Kalso et al. (2). In contrast, the clinical evidence for an analgesic effect of oral and IV sodium channel blockers in both acute and chronic non-neuropathic pain is equivocal. The limited results to date from human experimental pain models also suggest that the effect is modest, at best.
Studies in animals with experimental nerve injury, and humans with chronic neuropathic pain, have demonstrated that nerve injury leads to ectopic impulse generation in damaged and dysfunctional primary sensory neurons and their axons (3). The development of ectopic hyperexcitability is thought to be caused by remodeling of the local electrical properties of the axon membrane via changes in sodium channel distribution. This abnormal, ectopic discharge can be suppressed by anticonvulsants and local anesthetics with a sodium channel blocking effect at concentrations two to three orders of magnitude lower than needed to block the propagation of action potentials in normal nerves (3–5). Therefore, these drugs can be given systemically without fatal toxicity from failure of normal nerve conduction.
As originally described by Lewis in 1942 (6), human experimental models can simulate clinical pain conditions by intentionally inducing temporary cutaneous hyperalgesia using either thermal or chemical stimulation or a combination of both (7). Such models offer information about temporary inflammatory changes and sensitization of both the peripheral and the central nervous system (8). The heat/capsaicin sensitization model is a recently developed, noninvasive human experimental pain model that synergistically combines noninvasive thermal and chemical methods of nociceptor stimulation to produce stable and long-lasting secondary hyperalgesia. The stimuli from heat and capsaicin, respectively, can be diminished as a consequence of synergism. The model has a low potential for skin injury, and thus, only minor risk of permanent injury for the volunteers (7). The secondary hyperalgesia is reliably and potently suppressed by IV administration of opioids (9). Our goal for the present study was to investigate the effect of IV lidocaine on acute nociceptive pain and experimentally induced cutaneous hyperalgesia.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
We studied 25 healthy unmedicated male volunteers, aged 21–30 yr. Informed consent was obtained from all volunteers, and the study was approved by the regional ethics committee and the Danish National Health Board.
The study was performed in a quiet room with subjects in a semisupine position. Each volunteer had been familiarized with the measurement procedures on a separate day. All thermal stimulations and measurements were performed with a computer-controlled thermode (12.5 cm2) (Thermotest; Somedic A/B, Hörby, Sweden).
Heat Stimulation
Heat pain detection threshold (HPDT), defined as the lowest temperature perceived as painful, was determined in normal skin on the nondominant forearm. The baseline temperature of the thermode was 32°C and the rate of increase was 1°C/s. By pressing a button, subjects indicated when the threshold was reached. If the cutoff limit (52°C) was reached before the pertinent threshold, the thermode returned automatically to the baseline value and 52°C was registered. Each threshold was calculated as an average of four stimulations; stimulations were 6–10 s apart. Subjects were further asked to rate the painfulness of a 1-min-long 45°C heat stimulus (long thermal stimulation; LTS) on the electronic visual analog scale (VAS) consisting of a vertical bar on a computer screen (sample rate 2 Hz) anchored with the descriptors "no pain" (numeric value = 0) and "worst possible pain" (numeric value = 100). Each VAS mea- surement was independent of the previous measurement. The volunteer was able to see the VAS rating screen during each assessment. This measurement was performed in normal skin in another location on the nondominant forearm and repeated twice during each session.
Induction and Maintenance of Heat/Capsaicin Sensitization
Sensitization was produced by heating the skin of the dominant forearm to 45°C for 5 min with the thermode. Immediately thereafter, the skin was covered with capsaicin cream (0.075% capsaicin; Clay-Park Labs, Inc., Bronx, NY) for 30 min (see Fig. 1A). The sensitization was rekindled twice during each infusion session with the thermode at 40°C for 5 min. The first rekindle (RK-1) was performed 40 min after the capsaicin was removed (t = 80 min), the second rekindle (RK-2) was performed 40 min later (t = 120). The timing of the procedures is summarized in Figure 1B. During all thermal stimulation, pain was rated continuously by the volunteer by moving a lever that controlled the VAS.
|
Measurement of Secondary Hyperalgesia
Immediately after removal of the capsaicin cream (t = 40 min) and after each rekindle (t = 80 and 120 min) the area of secondary hyperalgesia was quantified with a foam paintbrush and with a 21.5-g von Frey hair. The borders of hyperalgesia were determined by stimulating along four linear paths arranged radially around the stimulation site in steps of 5 mm at intervals of 1 s. Stimulation started in normal skin and continued toward the stimulation site until subjects reported a clear change in sensations ("burning," "tenderness," "more intense pricking"). The borders were marked with a felt pen and the distances were measured for later surface area calculations.
Infusion and Side Effects
The study design was double blinded, the order of infusions was randomized, and the study was cross-over. On two separate days, subjects received IV lidocaine (bolus 2 mg/kg over 10 min, followed by infusion 3 mg · kg · h) or placebo for a total of 85 min. The infusion was initiated immediately after the heat/capsaicin sensitization was established and baseline measurements had been performed (Fig. 1B, t = 45 min) and continued until RK-2 and accompanying measurements were completed (Fig. 1B; t = 130 min). Heart rhythm was monitored through continuous electrocardiogram during the infusion. Side effects (light headedness, drowsiness, perioral numbness, metal taste, dryness of the mouth, nausea, muscular twitch, tinnitus, visual disturbances) were assessed immediately after bolus infusion (t = 55 min), and after each measurement cycle (85 min and 125 min; Fig. 1B). Subjects were asked to rate the side effects on a four-point verbal scale (0 = none, 1 = mild, 2 = moderate, 3 = severe).
The sample size was based on a power calculation that showed that 25 volunteers were necessary to achieve 80% power to detect a 20% treatment difference in the area of secondary hyperalgesia, with 
= 0.05 (two-tailed). The painfulness of the initial heating (45°C for 5 min), rekindling (40°C for 5 min), and LTS were each calculated as area under the curve and then converted to mean VAS values (0–100). Data are presented as medians (lower and upper quartiles). Variables were evaluated with Wilcoxon’s test for paired data. All significant P values were corrected with Bonferroni’s test for repeated measurements. Before entering statistical analyses, data were normalized in relation to values obtained before administration of study drugs, to achieve the same point of reference. For each subject, we calculated a percentage reduction in area of secondary hyperalgesia, and the percentage reduction in area, mentioned in the Results section, is median percentage reduction for the group. P < 0.05 was considered statistically significant. Calculations were performed by using Statgraphics Plus 7.0 (Manugistics, Inc., Rockville, MD).
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Twenty-four of the 25 subjects completed both sessions. The data from the one subject who withdrew after completing the first session (because of adverse effects) were not used in the data analysis.
Placebo Infusion Day
Combined sensitization with heat and capsaicin produced areas of secondary hyperalgesia to brush and von Frey hair stimulation that could be mapped easily in all subjects (brush = 92 cm2 [range 69–113 cm2] and von Frey hair = 111 cm2 [range 89–154 cm2]). The areas decreased slightly during the observation period so that after the second rekindling, the areas were 76 cm2 (range 47–90 cm2) (brush) and 84 cm2 (range 70–122 cm2) (von Frey hair).
The baseline heat pain threshold in unstimulated skin was 43.6°C (range 41.2°-45.0°C) and remained stable throughout the observation period. Similarly, the painfulness of LTS, which the subjects rated as 33 mm (range 19–44 mm) on the 100-mm VAS at baseline, was stable throughout the observation period. The painfulness of rekindling decreased from 32 mm (range 9–43 mm) during the first rekindling to 12 mm (range 6–19 mm) during the second (Table 1).
|
IV Lidocaine Infusion Day
The baseline areas of secondary hyperalgesia to brush and von Frey hair stimulation were comparable to the placebo infusion day (brush 121 cm2 [range 89–141 cm2] and von Frey hair 148 cm2 [range 95–162 cm2]). During the infusion with lidocaine, the area of secondary hyperalgesia to brush stimulation was reduced to 59% of baseline after RK-1 and to 60% during RK-2 compared with 75% and 72%, respectively, during placebo infusion (P = 0.04 and 0.008) (Fig. 2A). The area of secondary hyperalgesia to von Frey hair stimulation was also reduced to 75% of baseline after RK-1 and to 57% after RK-2 compared with 84% and 83% during placebo. This difference, however, did not reach statistical significance (P = 0.39 and 0.07) (Fig. 2B).
|
The median painfulness of LTS (45°C for 1 min) was 31 mm (range 17–49 mm) on the 100-mm VAS scale at baseline and was not reduced by infusion with lidocaine (measurement 1: 38 mm [range 21–56 mm] and measurement 2: 37 mm [range 21–53 mm]). Similarly, the heat pain detection thresholds remained unchanged during infusion with lidocaine. The painfulness of rekindling was not affected by the lidocaine infusion and, as on the placebo infusion day, decreased throughout the study day (Table 1).
Side Effects
Light headedness, drowsiness, dryness of the mouth, and visual disturbances were significantly more frequent on the lidocaine day than on the placebo day (Table 2). Most side effects occurred immediately after the bolus injection. The side effects were less pronounced during the steady-state portion of the infusion. Only light headedness was significantly more pronounced during the steady-state infusion of lidocaine compared with placebo, and was rated as "mild" by all who experienced it. One volunteer wished to leave the study because of light-headedness and drowsiness after receiving lidocaine infusion. All volunteers were able to participate fully during the various assessments without problems. One subject developed a small blister corresponding to a single section of the thermode grid during the initial heat stimulation in one session. Blistering or skin pigmentation changes were not observed in any of the other volunteers.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In this study, systemic lidocaine decreased the area of heat/capsaicin-induced secondary hyperalgesia (allodynia) to brush stimulation. The area of secondary hyperalgesia to mildly noxious von Frey hair stimulation was also reduced, but the reduction did not reach statistical significance. Both the heat pain detection thresholds and painfulness of prolonged noxious heat stimuli (LTS) in normal skin were unaffected by lidocaine. It is noteworthy that acute nociception remained intact at a time when stimuli that had become painful because of the sensitization were suppressed. Together, these findings suggest a limited and selective antihyperalgesic effect of lidocaine. For comparison, IV opioid administration markedly suppressed heat/capsaicin-associated secondary hyperalgesia and LTS and increased HPDT (9).
Our results are consistent with previous studies of IV lidocaine in other human experimental pain models. At a total IV lidocaine dose of 2 to 5 mg/kg, resulting in plasma levels between 2 to 3.4 µg/mL (11–13), pain thresholds to thermal, mechanical, or laser stimulation were unchanged (10–12,14,15). A study of ischemic pain using prolonged tourniquet stimulation found no analgesic effect of IV lidocaine (10). In contrast, the pain of repeated two-minute-long mechanical pinching of the interdigital web in humans was reduced during lidocaine infusion (15). In studies using intradermal capsaicin to produce cutaneous secondary hyperalgesia, Wallace et al. (12) observed a nonsignificant reduction of capsaicin-evoked secondary hyperalgesia to pinprick and stroke, but Gottrup et al. (14) found a reduction of secondary hyperalgesia to von Frey hair stimulation.
The clinical evidence of the analgesic effect of oral and IV sodium channel blockers in both acute and chronic non-neuropathic pain is equivocal. In all of the infusion studies, lidocaine was given in the 2 to 3 mg/min range, which resulted in plasma levels between 1 to 5 µg/mL. Cassuto et al. (16) administered IV lidocaine or placebo at 2 mg/min from preincision to 24 h after surgery in a study of 20 patients undergoing cholecystectomy. Patients who received lidocaine reported less pain and required less concomitant analgesia in the postoperative phase. In three other studies, however, no (17,18) or only minor (19) effects on postoperative pain were observed. In a study of seven patients with burn pain caused by second-degree burns (10%–30% of body surface), IV lidocaine was administered at 40 µg · kg–1 · min–1 for three days. The infusion was turned off for six hours every day as a control. Pain ratings were significantly reduced during infusion compared with when the infusion was off (20).
In contrast, there is strong evidence that IV lidocaine infusions temporarily relieve neuropathic pain (2). A total dose of 5 mg/kg lidocaine has been the dose most often administered. It is possible that studies of acute and chronic nonneuropathic pain and experimental pain mainly have been negative because the peak infusion rate of lidocaine has been less than in the studies of neuropathic pain. In trials of neuropathic pain, the effect of IV lidocaine is rate- and dose-dependent (13,21). In most neuropathic pain trials, lidocaine was given as a brief large-dose infusion, such as 5 mg/kg over 30 to 60 min, equivalent to an infusion rate of 5.8 to 11.7 mg/min in a 70-kg subject. In contrast, lidocaine was administered at 2 to 3 mg/min in studies of postoperative pain for periods ranging from 2 to 48 h. In most studies of experimental pain, lidocaine doses were 3–4.5 mg/min (11). However, in the present study and that of Gottrup et al. (14), both of which showed a reduction by lidocaine in the area of secondary hyperalgesia, the doses were closer to those used in studies of neuropathic pain.
Our findings are also in accordance with results from a number of animal experimental studies (22–25). Abram and Yaksh (22) compared the effect of systemic lidocaine in three rat pain models—the formalin test, partial ligation of the sciatic nerve, and normal paw withdrawal to noxious heat. A small dose of lidocaine markedly reduced neuropathic hyperalgesia and mechanical allodynia in the sciatic nerve ligation model, but did not affect the withdrawal latency to noxious heat in the normally innervated paw and did not affect either phase of the formalin test (22,23). Larger doses of lidocaine reduced only the second phase of the formalin test, which is thought to be attributed, in part, to the development of central sensitization. In summary, these results suggest the following rank ordering of lidocaine effects on pain: (a) small doses suppress ectopic impulse generation in chronically injured peripheral nerve; (b) moderate doses suppress central sensitization and central neuronal hyperexcitability; (c) large doses have general analgesic effects; (d) very large doses are associated with seizure activity, cardiac arrhythmias, and cardiovascular collapse; and (e) when death occurs, blood levels are still far below those needed to block normal axonal impulse conduction.
Although the greatest interest has been in lidocaine effects on ectopic impulse generation in chronically injured nerves, some studies have suggested that an independent central action of systemic lidocaine contributes to its antihyperalgesic effects. In three patients with diabetic neuropathy, Bach et al. (11) found that lidocaine increased the threshold at which the spinally organized nociceptive flexion reflex was elicited, suggesting a central effect. Other studies suggest a possible central, antihyperalgesic action of systemic lidocaine (24). Nagy and Woolf (25) found that small concentrations of lidocaine-reduced N-methyl-D-aspartate- and NK receptor-mediated postsynaptic depolarizations of spinal neurones, without affecting impulse transmission in the periphery. The central inhibitory actions of lidocaine that underlie its anticonvulsant effects are incompletely characterized.
Side effects were more frequent during lidocaine infusions, but were mostly mild to moderate. Thus, there was a possible unblinding of the treatment, and possible investigator bias. However, the study of small- and large-dose lidocaine infusions in patients with peripheral neuropathy by Galer et al. (21) showed dose-dependent pain relief without a dose-dependent difference in side effect scores, suggesting that the analgesic effect of lidocaine was not mediated by production of side effects.
One subject developed a small blister corresponding to a single grid element during heat stimulation with the thermode at 45°C for 5 min. This has not been observed in previous studies of the heat/capsaicin sensitization model (7,9). The thermode used in the present study consisted of a grid of individual thermal elements. The stimulation temperature was based on the average of all the elements, thus allowing individual elements to be above or below the intended temperature. In contrast, the thermode used in the former studies had a single thermal plate, which may have resulted in a more even temperature. The incidence of blistering was much less than in previous studies of the burn injury model (7).
In summary, our study confirms the lack of effect of systemic lidocaine on acute nociceptive pain and the limited and selective effect on secondary hyperalgesia seen in other studies.
|
Acknowledgments |
|---|
This work was supported by the Danish Medical Research Council, number 28809, and the Novo Nordisk Foundation. KLP’s salary is supported by the VZV Foundation, Inc.
We gratefully acknowledge technical assistance from Pia S. Larsen.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
- Petersen KL, Rowbotham MC. Will ion channel blockers be useful for management of non-neuropathic pain? Pain. In press.
- Kalso E, Tramer MR, McQuay H, Moore RA. Systemic local-anaesthetic-type drugs in chronic pain: a systematic review. Eur J Pain 1998:3–14.
- Devor M, Zeltzer Z. Pathophysiology of damaged nerves in relation to chronic pain. In: Wall PD, Melzack R, eds. Textbook of pain. 4th ed. Edinburgh, UK: Churchill Livingstone, 2000: 129–65.
- Glazer S, Portenoy RK. Systemic local anesthetics in pain control. J Pain Symptom Manage 1991; 6: 30–9.[Web of Science][Medline]
- Tanelian D, MacIver B. Analgesic concentrations of lidocaine suppress tonic A-delta and C fiber discharges produced by acute injury. Anesthesiology 1991; 74: 934–6.[Web of Science][Medline]
- Lewis T. Pain. New York: Macmillan, 1942.
- Petersen KL, Rowbotham MC. A new human experimental pain model: the heat/capsaicin sensitization model. Neuroreport 1999; 10: 1511–6.[Web of Science][Medline]
- Treede RD, Meyer RA, Raja SN, Campbell JN. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 1992; 38: 397–421.[Web of Science][Medline]
- Petersen KL, Segredo JB, Gaspar V, et al. The effect of remifentanil on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers: abstract—9th World Congress on Pain. Seattle: IASP Press, 1999.
- Rowlingson JC, DiFazio CA, Foster J, Carron H. Lidocaine as an analgesic for experimental pain. Anesthesiology 1980; 52: 20–2.[Web of Science][Medline]
- Bach FW, Jensen TS, Kastrup J, et al. The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy. Pain 1990; 40: 29–34.[Web of Science][Medline]
- Wallace MS, Laitin S, Licht D, Yaksh TL. Concentration-effect relations for intravenous lidocaine infusions in human volunteers: effects on acute sensory thresholds and capsaicin-evoked hyperpathia. Anesthesiology 1997; 86: 1262–72.[Web of Science][Medline]
- Wallace MS, Dyck JB, Rossi SS, Yaksh TL. Computer-controlled lidocaine infusion for the evaluation of neuropathic pain after peripheral nerve injury. Pain 1996; 66: 69–77.[Web of Science][Medline]
-
Gottrup H, Hansen PO, Arendt-Nielsen L, Jensen TS. Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans. Br J Anaesth 2000; 84: 155–62.
[Abstract/Free Full Text] - Koppert W, Zeck S, Sittl R, et al. Low-dose lidocaine suppresses experimentally induced hyperalgesia in humans. Anesthesiology 1998; 89: 1345–53.[Web of Science][Medline]
-
Cassuto J, Wallin G, Hogstrom S, et al. Inhibition of postoperative pain by continuous low-dose intravenous infusion of lidocaine. Anesth Analg 1985; 64: 971–4.
[Abstract/Free Full Text] -
Birch K, Jorgensen J, Chraemmer-Jorgensen B, Kehlet H. Effect of i.v. lignocaine on pain and the endocrine metabolic responses after surgery. Br J Anaesth 1987; 59: 721–4.
[Abstract/Free Full Text] - Insler SR, O’Connor M, Samonte AF, Bazaral MG. Lidocaine and the inhibition of postoperative pain in coronary artery bypass patients. J Cardiothorac Vasc Anesth 1995; 9: 541–6.[Web of Science][Medline]
- Groudine SB, Fisher HA, Kaufman RP Jr, et al. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth Analg 1998; 86: 235–9.[Abstract]
- Jonsson A, Cassuto J, Hanson B. Inhibition of burn pain by intravenous lignocaine infusion. Lancet 1991; 338: 151–2.[Web of Science][Medline]
- Galer BS, Harle J, Rowbotham MC. Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. J Pain Symptom Manage 1996; 12: 161–7.[Web of Science][Medline]
- Abram SE, Yaksh TL. Systemic lidocaine blocks nerve injury-induced hyperalgesia and nociceptor-driven spinal sensitization in the rat. Anesthesiology 1994; 80: 383–91.[Web of Science][Medline]
- Chaplan SR, Bach FW, Shafer SL, Yaksh TL. Prolonged alleviation of tactile allodynia by intravenous lidocaine in neuropathic rats. Anesthesiology 1995; 83: 775–85.[Web of Science][Medline]
- Woolf CJ, Wiesenfeld-Hallin Z. The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre evoked activity in the spinal cord. Pain 1985; 23: 361–74.[Web of Science][Medline]
- Nagy I, Woolf CJ. Lignocaine selectively reduces C fibre-evoked neuronal activity in rat spinal cord in vitro by decreasing N-methyl-D-aspartate and neurokinin receptor-mediated post-synaptic depolarizations: implications for the development of novel centrally acting analgesics. Pain 1996; 64: 59–70.[Web of Science][Medline]
This article has been cited by other articles:
|
|
 |
|
  C. P. Kuo, S. W. Jao, K. M. Chen, C. S. Wong, C. C. Yeh, M. J. Sheen, and C.T. Wu Comparison of the effects of thoracic epidural analgesia and i.v. infusion with lidocaine on cytokine response, postoperative pain and bowel function in patients undergoing colonic surgery Br. J. Anaesth., November 1, 2006; 97(5): 640 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. W. Tremont-Lukats, V. Challapalli, E. D. McNicol, J. Lau, and D. B. Carr Systemic Administration of Local Anesthetics to Relieve Neuropathic Pain: A Systematic Review and Meta-Analysis Anesth. Analg., December 1, 2005; 101(6): 1738 - 1749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-T. Wu, C. O Borel, M.-S. Lee, J.-C. Yu, H.-S. Liou, H.-D. Yi, and C.-P. Yang The Interaction Effect of Perioperative Cotreatment with Dextromethorphan and Intravenous Lidocaine on Pain Relief and Recovery of Bowel Function After Laparoscopic Cholecystectomy Anesth. Analg., February 1, 2005; 100(2): 448 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cahana, A. Carota, M.-L. Montadon, and J. M. Annoni The Long-Term Effect of Repeated Intravenous Lidocaine on Central Pain and Possible Correlation in Positron Emission Tomography Measurements Anesth. Analg., June 1, 2004; 98(6): 1581 - 1584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Koppert, M. Weigand, F. Neumann, R. Sittl, J. Schuettler, M. Schmelz, and W. Hering Perioperative Intravenous Lidocaine Has Preventive Effects on Postoperative Pain and Morphine Consumption After Major Abdominal Surgery Anesth. Analg., April 1, 2004; 98(4): 1050 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Hood, R. Curry, and J. C. Eisenach Intravenous Remifentanil Produces Withdrawal Hyperalgesia in Volunteers with Capsaicin-Induced Hyperalgesia Anesth. Analg., September 1, 2003; 97(3): 810 - 815. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
