INTRODUCTION

Fibromyalgia is a medical condition characterized by chronic widespread pain, associated with other symptoms, such as fatigue, insomnia, memory loss, mood swings, tremors, paresthesia, cramps, morning stiffness, and multifocal digital pressure hyperalgesia on physical examination. The pathophysiological substrate is the sensitization of the central nervous system, so pain perception is amplified from the peripheral pain signal that is transmitted through the spinal cord to the brain. There is no complementary examination capable of diagnosing this benign disease and the diagnosis is primarily clinical.

There is no known cure to date, although a palliative treatment of symptoms is available, so optimal treatment of fibromyalgia includes pharmacotherapy despite the limited scientific evidence about its efficacy ¹. Clinical experience corroborates this fact; pain relief while maintaining good tolerance for adverse effects is difficult to achieve in these patients, so there is a large group of patients who are refractory to oral analgesic treatments. This type of patients may be candidates for alternative analgesic treatments in the form of continuous intravenous infusion in an attempt to relieve their pain consistently over time.

Lidocaine was first synthesized in 1942 (initially called xylocaine) and marketed in 1948, and the first publications date from the decades of the 1950s and the 1960s ^2,3. In addition to its use as a local anesthetic and anti-arrhythmic drug, its analgesic properties were soon documented in various painful conditions. Intravenous lidocaine infusions have been shown to have an antihyperalgesic effect in chronic central and peripheral neuropathic pain conditions in short-term studies conducted with few patients ^4,5,6. In fibromyalgia, there are few studies on the efficacy of continuous infusions of lidocaine and, moreover, few studies report the duration of its analgesic effect and whether its benefit is consistent enough to maintain it as an appropriate treatment for these patients ⁷. There is evidence that lidocaine acts mainly by blocking the sodium channels by binding in segment 6 of domain 4 of the alpha subunit of the ion channel and inhibiting neuronal ectopic discharges, although the exact molecular mechanisms of action are not fully known, probably because preclinical studies suggest that it may be due to their cellular, subcellular, regional, and systemic actions that ultimately shape its analgesic properties ⁸.

The primary objective of this study is to evaluate the efficacy of intravenous lidocaine infusions in our fibromyalgia patients, as well as their impact on the quality of life of these patients during the next three months after treatment.

METHODOLOGY

The study was approved by the Ethics Committee of our hospital, and an informed consent was signed by the patients after obtaining verbal and written information. The clinical trial met the requirements of good clinical practice and established quality standards.

RESULTS

A total of 62 patients were included in the study, 9 of them withdrew due to the appearance of intolerable lidocaine adverse effects, 8 patients due to nausea and 1 patient due to worsening of the pain, that forced discontinuation of treatment, whereas 5 patients were lost to follow-up or failed to respond to questionnaires within the following months. Finally, 48 patients completed the study. Table 1 shows baseline data of the patients.

Table I.  Demographic data 

* Values expressed as mean ± standard deviation.

Table 2 shows the results of the questionnaires. Statistically significant differences were found between baseline and day 10 (end of treatment) in the BPI questionnaire, in both pain intensity (29.5 to 26.5; p < 0.001) and pain activity (56 to 53.5; p < 0.0019). Statistically significant differences were also found in the BFI questionnaire (71 to 68.5 p = 0.001) and in the BDI-II questionnaire (29.5 to 23; p < 0.01). However, these differences are not maintained within the following days after treatment except for the MOS questionnaire at day 30 (from 37 to 39; p = 0.037) and for patient expectations (from 5 to 2.5; p = 0.002). At three months, no differences in questionnaire results were found compared with the baseline situation.

Table II.  Questionnaires outcome measures on days 1, 10, 30 and 90 

*p < 0.005 statistically significant.

DISCUSSION

In our study, treatment with lidocaine infusions in patients with fibromyalgia showed a good initial efficacy in terms of decreased pain intensity, improved functional capacity and mood. However, this improvement at the end of treatment did not show consistency over time. Sleep quality and patient expectations only improved at the first month post-treatment, whereas no difference was found in the analyzed questionnaires at three months post-treatment compared with the baseline.

Similarly to previous studies, the majority of patients were women ^10,14 and the age of patients was similar to those reported in the literature, with a higher prevalence between 40 and 60 years old ¹⁵.

The doses of lidocaine infusions received by the patient based on our protocol established a progressive increase of the infusions according to the patient's tolerance to the medication administered. That is, the optimal titration of the administered dose was individualized and limited by the appearance of adverse effects, most of them were mild, such as metallic taste, dizziness, tremors and palpitations, or nausea and vomiting as more frequent, and it meant stabilization of optimal doses between 2 and 5 mg/kg/h until treatment completion in a two-hour infusion (i.e. total dose ranged from 1 to 10 mg/kg). The doses used by several researchers range from 1 to 5 mg/kg administered over an approximate period of 30-60 minutes ^11,16. However, a recent study reports that doses of 7.5 mg/kg are more effective than 5 mg/kg in terms of pain relief and duration of its analgesic effect ¹⁷.

Previous studies have shown the efficacy of lidocaine infusion in various pain syndromes including fibromyalgia. The prolonged efficacy of its analgesic effect has been shown in two case series published in 1995 for more than 30 days ¹² and another in 2015 for more than 5 weeks ¹⁸. In a retrospective study conducted with 50 patients, significant pain relief was reported for 11.5 ± 6.5 days after six days of intravenous lidocaine infusions ¹³. An open-label study found decreases in the scores of the Visual Analog Scale (VAS) and the FIQ immediately after the fifth day of perfusion and 30 days after the fifth infusion ¹⁹. In two randomized, controlled studies published in 1995 and 2000, a long-term pain relief was evidenced by decreased VAS score for more than 4 weeks ^20,21.

Therefore, the analgesic effect of lidocaine infusions appears to be longer than its pharmacokinetic half-life of approximately 120 minutes and its metabolites half-life (more than 12 hours) ²², probably due to the decrease of spinal sensitization as suggested by some authors ¹⁰.

Finally, intravenous lidocaine is associated with dose-dependent adverse effects including dizziness, sedation or tinnitus, and at higher doses it is associated with seizures and arrhythmia. No severe adverse effects were found in our study. In a randomized study with intravenous lidocaine infusions, the most common adverse effects were metallic taste, tremor, dry mouth, insomnia, allergic reactions, and tachycardia, and no severe adverse effects, such as heart arrhythmias or hemodynamic instability, were described ²³.

Our study has limitations due to the lack of a placebo-matched control group and it should have been randomized and double-blind. In addition, we suggest that other outcome variables should be included in further studies, such as daily pain relief, adverse effects during and after infusions, analgesic use, and concurrent use of medication after lidocaine infusions.

CONCLUSIONS

In our study in diagnosed patients, intravenous lidocaine infusions at optimal doses titrated according to individual tolerance between 2 mg/kg and 10 mg/kg administered for two hours showed efficacy immediately after 10 days. However, the questionnaire scores showed that the effect of these lidocaine infusions was not prolonged in time neither in the first nor in the third month after treatment. Currently in our usual practice we have discontinued the usual use of this therapy given the discouraging results and we reserve this treatment for those selected cases that report finding sustained relief with this therapy. The decision to use it in new cases is more complicated and it is left at the discretion of the physician in charge of the patient, but in general, intravenous lidocaine infusions are reserved for patients with poor quality of life not responding to other therapies.