Potential role of intravenous lidocaine versus intravenous ketamine for pain management in fibromyalgia patients





Abstract


Introduction


Fibromyalgia syndrome (FMS) is a disease characterized by chronic, pain associated with impaired physical function and overall quality of life (QOL). Pain can be controlled by IV lidocaine which is considered a topical anesthetic drug. Also, ketamine is used as a potent anesthetic agent reducing the induction of synaptic plasticity and maintenance of chronic pain states.


This study aimed


to assess the efficacy of intravenous (IV) lidocaine versus IV ketamine in pain management and improvement in the QOL in FM patients.


Patients &methods


75 patients were divided equally into 3 groups in which group A received 5 mg/Kg lidocaine, group B received 0.5 mg/Kg ketamine sulphate and group C received a placebo of normal saline. This procedure was done weekly for 3 weeks.


Result


As regards pain perception using VAS group A&B showed a marked reduction in VAS with no difference between them, with no change in group C. Changes in the fibromyalgia impact questionnaire (FIQ) were analyzed and showed the mental part of the health score decreased significantly in all groups while the physical and overall parts of the health score decreased significantly only in the lidocaine and ketamine group and non-significantly changed in the placebo group. Overall QOL significantly improved in groups A&B assessed by Health-related quality of life (HrQOL) SF-12 questionnaire 4 weeks post-procedure.


Conclusion


IV lidocaine and ketamine are efficient not only in pain relief among patients with FM but also in improving physical function and QOL.


1


Introduction


Fibromyalgia syndrome (FMS) is a common disease characterized by chronic, persistent, and widespread pain that is associated with annoying fatigue, sleep disturbance, irritable bowel syndrome (IBS), impaired cognitive and physical function, and psychological distress.


The etiology and pathophysiology of fibromyalgia (FM) remain unclear despite extensive research. FM can be considered a multifactorial; biochemical, physiologic, and psychiatric disorder. Abnormalities underlying FM condition with genetic predisposition triggered by environmental factors including trauma, infections, emotional stress, catastrophic events, autoimmune disease, and other pain conditions.


FM can be treated by various approaches including both pharmacological and non-pharmacological treatments including cognitive behavioral therapy, exercise programs, recreational activities and sleep hygiene.


Regarding the pharmacological treatment; a wide range of agents have been employed including antidepressants, tricyclics, selective serotonin reuptake inhibitors (SSRI), serotonin/norepinephrine reuptake inhibitors (SNRI), 5-HT3 receptor antagonists, antiepileptic drugs, opioids, tramadol, muscle relaxants, and N-methyl- d -aspartate receptor (NMDAR) antagonists. Other drugs like, dopamine agonists, sedative-hypnotics, growth hormone, nonsteroidal anti-inflammatory drugs (NSAID), and pharmacotherapy of associated symptoms are used during the treatment. However, only a few of these medications have demonstrated effectiveness in controlled clinical trials.


One of the drugs that can be used in pain control is lidocaine which is considered a topical anesthetic drug used worldwide to treat specific clinical situations. It is used intravenously in chronic pain, treating arrhythmia and controlling symptoms of diabetic neuropathy. Another drug, ketamine can be used in FM patients as a potent anesthetic agent acting as NMDAR antagonist reducing the induction of synaptic plasticity and maintenance of chronic pain states.


This study aimed to assess the efficacy of intravenous (IV) lidocaine versus IV ketamine in pain management and hence improving the quality of life (QOL) in patients with FM.


2


Patients and methods


This study was a prospective randomized comparative controlled study following CONSORT 2010 Guidelines conducted in the Department of Anesthesia, Intensive Care Unit, and Pain Management and Physical Medicine, Rheumatology &Rehabilitation department in Ain Shams University hospitals. The proposal was registered in ClinicalTrials.gov (NCT06184958, December 2023) ( www.clinicaltrials.gov/ct2/show/NCT04425174 ) after the ethical approval of Ain Shams University (FMASU R 332/2023).


Informed consent was obtained from all patients and controls signed voluntarily by them at the Physical Medicine, Rheumatology, and Rehabilitation as well as the Anesthesia departments at Ain Shams University Hospitals after an explanation of the procedures in clear simple words.


The study included 75 patients with FM, diagnosed according to the American College of Rheumatology (ACR) 2016 diagnostic criteria for FM. The patients were recruited from the Physical Medicine, Rheumatology, and Rehabilitation Department and then transferred to the Anesthesia Department at Ain Shams University Hospitals where they received the medications under close monitoring and supervision. The selected patients were adult patients (25 to 50 years old) suffering from uncontrolled pain despite receiving the maximum medical treatment in the form of Cymbalta 60 mg/day, Triptyzol 25 mg/day, and gabapentin (Neurontin) 100 mg/day for at least 6 months.


FM patients with known hypersensitivity to any of the given drugs (lidocaine or ketamine) or one of their derivatives were excluded. Also, patients with known arrhythmia (Supraventricular or ventricular) were not enrolled in the study.


Patient preparation: All patients were subjected to full medical history, clinical examination, and ECG. Laboratory investigations were done including complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), kidney function tests, liver enzymes, rheumatoid factor (RF), antinuclear antibody titer (ANA) and urine analysis.


Patients’ recruitment, randomization, and control of potential bias: We used the sealed, opaque, sequentially-numbered envelopes method for randomization and allocation concealment. Identical, opaque, letter-sized envelopes were prepared; each containing a white allocation paper (Marked as “Treatment A”) and a sheet of single-sided carbon paper closest to the front of the envelope (with the carbon side facing the white paper). Finally, the envelopes had been sealed, and we signed across the seal. Likewise, we prepared 25 “Treatment B” envelopes and “Treatment C” envelopes.


The three sets (envelopes) had been combined and shuffled thoroughly. Using a pen, A number on the front of each envelope was written sequentially from 1 to 75. These envelopes were placed into a plastic container, in numerical order, ready for use.


Participants, care providers, outcomes assessors, and data analysts were all ignorant of the treatment allocation.


The procedure: IV access was applied for all patients using a 20 G cannula with continuous monitoring using pulse oximetry, electrocardiogram, and non-invasive blood measurement (every 5 min). The selected patients were randomized into three groups:



  • Ø

    GROUP A included 25 patients who received 5 mg/Kg lidocaine in 100 ml normal saline given in 40 min with 20 min follow-up to obverse any delayed complication. This procedure was repeated weekly for 3 weeks.


  • Ø

    GROUP B including 25 patients received 0.5 mg/Kg ketamine sulphate in 100 ml normal saline given in 40 min with 20 min follow-up to obverse any delayed complication. This procedure was repeated weekly for 3 weeks.


  • Ø

    Group C including 25 patients received a placebo of 100 ml of normal saline given in 40 min with 20 min follow up to obverse any delayed complication. This procedure was repeated weekly for 3 weeks.



All patients were monitored to detect any abnormalities either due to drug hypersensitivity or due to any potential side effects of lidocaine such as dizziness, fatigue, headache, itchy, warm, or red skin, or due to ketamine example hallucination (aborted by 2 mg midazolam), nausea or vomiting, panic attack or memory problems.


Post-procedure outcome: An FM Impact Questionnaire FIQ with special attention to visual analog scale (VAS) was evaluated as a primary outcome. The QOL measuring the patients’ physical and psychological well-being was also recorded four weeks after completion of a full course of infusion as a secondary outcome.


SF-12 is the QOL that had been used before medication and repeated after 4 weeks of receiving medications for all patients under study.


3


Sample size


By using Power Analysis and Sample Size Software (PASS 15) (Version 15.0.10), for sample size calculation, setting power at 80 %, alpha error 0.05 and after reviewing previous study results (Graven-Nielsen et al. , 2000) showing that among patients diagnosed with fibromyalgia, VAS scores at rest were progressively reduced during ketamine infusion compared with placebo infusion. Pain intensity (area under the VAS curve) to the post-drug infusion of hypertonic saline was reduced by ketamine (−18.4 ± 0.3 % of pre-drug VAS area) compared with placebo (29.9 ± 18.8 %); Based on that and after considering 10 % dropout rate, a sample size of at least 75 patients diagnosed with fibromyalgia divided randomly into 3 groups were sufficient to achieve study objective.


3.1


Statistical methods


The collected data were analyzed using IBM SPSS statistics (Statistical Package for Social Sciences) software version 28.0, IBM Corp., Chicago, USA, 2021. Qualitative data were described as numbers and percentages and were compared using Fisher’s Exact test. Quantitative data were tested for normality using the Shapiro-Wilk test, then were described as mean ± SD (standard deviation) if normally distributed and were compared using ANOVA, paired t -test, and RMANOVA tests. Bonferroni and Dunnett tests were used for post hoc comparisons. The level of significance was taken at p-value ≤0.050.


4


Results


This study involved 75 patients divided into three groups (each 25 patients), who met the inclusion criteria after excluding 16 patients; 9 of them didn’t meet the inclusion criteria and 7 refused to participate in the study ( Fig. 1 ) .




Fig. 1


CONSORT flow chart for the study cases.


There was no statistically significant difference between the three groups under study regarding the patient’s age, sex, BMI, and duration of illness ( Table 1 ) . However, a notice was made of the dominant female sex of the selected patients.



Table 1

Demographic characteristics between the study groups.








































Variables Lidocaine group
(Total=25)		 Ketamine group
(Total=25)		 Placebo group
(Total=25)		 p-value
Age (years) 43.6 ± 4.0 41.7 ± 4.3 43.1 ± 4.2 ^0.279
BMI (kg/m 2 ) 27.1 ± 2.4 27.2 ± 2.1 28.2 ± 2.4 ^0.230
Sex Male 4 (16.0 %) 3 (12.0 %) 3 (12.0 %) #0.999
Female 21 (84.0 %) 22 (88.0 %) 22 (88.0 %)
Duration of illness (years) 6.3 ± 1.6 6.7 ± 1.5 7.1 ± 1.7 ^0.225

Data are presented as mean ± SD or number and (%). BMI: Body mass index. ^ANOVA test. #Fisher’s Exact test.


No statistically significant differences were found between the studied groups regarding baseline pain perception score (VAS). Pain perception scores significantly decreased in the lidocaine and ketamine group beginning from week 1 and non-significantly changed in the placebo group. Pain perception scores in weeks 1, 2, and 3 became significantly highest in the placebo group with no significant differences between lidocaine and ketamine group. Reduction in pain perception score in week 3 as compared to baseline was significantly lowest in the placebo group with no significant differences between the lidocaine and ketamine group ( Table 2 ) ( Fig. 2 ) .


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May 22, 2025 | Posted by in ANESTHESIA | Comments Off on Potential role of intravenous lidocaine versus intravenous ketamine for pain management in fibromyalgia patients

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