Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 7  |  Issue : 3  |  Page : 320-326

Clonidine in lumbar sympathetic block for lower limb complex regional pain syndrome


Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Web Publication27-Aug-2014

Correspondence Address:
Karim Y.K. Hakim
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain Shams University, 3, Hassan Aflaton street, 002 Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.139557

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  Abstract 

Background
Complex regional pain syndrome (CRPS) is a condition of continuing (spontaneous and/or evoked) limb pain. The pain is nondermatomal and usually has a distal predominance of abnormal sensory, motor, sudomotor, vasomotor, and/or trophic findings. Sympathetic nerve blockade of the upper and lower extremities using a local anesthetic and corticosteroids is one of the modalities in the treatment of severe, sympathetically mediated pain. This randomized controlled trial studies the effect of adding clonidine to levobupivacaine in repeated lumbar sympathetic blocks for patients suffering from lower limb CRPS type 1.
Methods
Thirty patients of ASA physical status I and II having CRPS-1 in the lower limb were enrolled. All patients underwent lumbar sympathetic block as treatment. They were assigned to one of two groups comprising 15 patients each. Group A patients were injected with 20 ml of levobupivacaine (0.5%) +8 mg dexamethasone (2 ml)+150 µg (1 ml) clonidine. Group B patients were injected with 20 ml of levobupivacaine (0.5%)+8 mg dexamethasone (2 ml)+saline (1 ml). Patients were seen in the clinic every week for 6 weeks. During each follow-up visit, edema score (grades 0-2) and range of motion at knee and ankle joints (grades 0-2) were assessed. Repeated blocks by the same technique were performed with a maximum of five blocks for each patient over a period of 6 weeks. Repetition of blocks was dependent on exacerbation of pain if visual analogue scale (VAS) score was greater than 50. The number of blocks needed during the 6-week period in each group was recorded. Side effects after each block, such as hypotension, bradycardia, and backache, were recorded. At 6 weeks, all patients were asked to fill out a satisfaction score (grades 0-10).
Results
Intergroup comparison showed that the VAS score was lower in group A than in group B, but there was no statistically significant difference between them except in the fifth week. Within-group comparison revealed a statistically significant decrease in the two groups in the 6 weeks in the measured VAS score compared with the baseline VAS scores. There was improvement in edema and motion in the two groups throughout the 6 weeks, but there was no statistically significant difference between the two groups. There was a statistically significant difference between the two studied groups as regards the number of blocks, where group A had a fewer blocks compared with group B. Patients in group A were significantly more satisfied after the 6 weeks compared with patients in group B.
Conclusion
Adding clonidine to levobupivacaine and steroids in repeated lumbar sympathetic blocks for patients suffering from lower limb CRPS type 1 prolongs analgesia and improves edema and tolerability to physical therapy.

Keywords: Clonidine, complex regional pain syndrome, levobupivacaine, lumbar sympathetic block


How to cite this article:
Hakim KY, Abd El Fatah AM. Clonidine in lumbar sympathetic block for lower limb complex regional pain syndrome. Ain-Shams J Anaesthesiol 2014;7:320-6

How to cite this URL:
Hakim KY, Abd El Fatah AM. Clonidine in lumbar sympathetic block for lower limb complex regional pain syndrome. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2019 May 23];7:320-6. Available from: http://www.asja.eg.net/text.asp?2014/7/3/320/139557


  Introduction Top


Complex regional pain syndrome (CRPS) is a condition of continuing (spontaneous and/or evoked) limb pain that is disproportionate to the degree of any known trauma or other lesion. The pain is nondermatomal and usually has a distal predominance of abnormal sensory, motor, sudomotor, vasomotor, and/or trophic findings [1]. A diversity of symptoms and signs in the form of sensory (allodynia, hyperesthesia), vasomotor (temperature or skin color changes), sudomotor/edema (sweating or edema in the affected limb), and motor/trophic (trophic changes or motor dysfunction) findings are usually met with [2]. Diagnosis is made by history and clinical examination. No laboratory tests to confirm the diagnosis of CRPS are available. The reason behind the development of CRPS remains unclear, which in turn makes treatment rather difficult.

Sympathetic nerve blockade of the upper and lower extremities using a local anesthetic and corticosteroids is one of the modalities in the treatment of severe, sympathetically mediated pain that cannot be managed appropriately with oral regimens [3] and serves as a diagnostic and therapeutic intervention for sympathetically mediated pain. The indications for lumbar sympathetic blockade include CRPS of the lower extremities, phantom limb pain, post-herpetic neuralgia, and vascular insufficiency including peripheral arteriosclerotic disease [4].

Clonidine is an α-2 agonist originally used in the treatment of hypertension, approved by FDA in the treatment of neuropathic pain states [5]. Epidural or intrathecal clonidine reduced associated pain for CRPS patients. Patients with CRPS and sympathetic maintained pain who experience symptomatic improvement following local anesthetic sympathetic blocks (SBs) may benefit from having a series of blocks incorporated into their treatment regimen [6]. We hypothesized that the addition of clonidine to sympathetic blockades could improve the quality and duration of the block.

This randomized controlled trial aimed to study the effect of adding clonidine to levobupivacaine in repeated lumbar SBs for patients suffering from lower limb CRPS type 1.


  Patients and methods Top


After obtaining approval from the ethics committee of Ain Shams University hospitals and written informed consent from patients, 30 patients of ASA physical status I and II, of both sexes, ages ranging from 20 to 60 years, and having CRPS-1 in the lower limb were prospectively enrolled in this study. Patients were eligible for participation in the study if they had CRPS-1 according to the criteria established by the International Association for the Study of Pain, which are:

(a) The presence of continuous pain, allodynia, or hyperalgesia disproportional to the inciting event;

(b) Evidence at some time of edema, abnormal skin blood flow, and sudomotor abnormalities in the region of pain;

(c) Exclusion of other causes of pain or dysfunction.

Other inclusion criteria were: CRPS in a single lower limb of less than 1 year duration; failure to achieve pain reduction plus persistent functional impairment after 3 weeks of continuous standard therapy, which includes twice a week 30 min active physical therapy session, ibuprofen 600 mg tds, 3600 mg gabapentin/day, tramadol 50 mg twice daily; mean visual analogue scale (VAS) score of 50 or more on a scale from 0 to 100 (with 0 meaning no pain at all and 100 meaning the worst imaginable pain).

Before offering lumbar SB as treatment, all patients received physical therapy aimed at active mobilization, according to a fixed protocol, which consisted of graded exercises aimed at restoring strength, mobility, and function of the affected extremity. Physical therapy was applied twice a week with a minimum duration of 30 min. Exclusion criteria were: pregnancy, presence of coagulation disorders, fever or local infection at the puncture site, drug or alcohol abuse, and presence of diabetic polyneuropathy.

Patients were randomly allocated into two groups using computer-generated software. To follow the double-blind nature of the study, drugs were prepared in syringes labeled by an independent technician. The pain specialist who attended the procedure and recorded the data was also blinded to both groups.

Patients in group A were administered 20 ml of levobupivacaine (0.5%) +8 mg dexamethasone (2 ml) +150 μg (1 ml) clonidine intravenously.

Patients in group B were administered 20 ml of levobupivacaine (0.5%) +8 mg dexamethasone (2 ml) +saline (1 ml) intravenously.

During the procedure patients were continuously monitored by ECG, pulse oximetry, and an automated noninvasive blood pressure monitor. Just before performing the SB an intravenous line was placed, and 500 ml of Ringer's solution was infused. Lumbar SB was performed with the patient placed in prone position. Sedation was induced by injecting with 2-3 mg midazolam plus 75 μg fentanyl. The C-arm fluoroscope (Simens, Germany) was used to identify the L2-L4 level. In this procedure the spinous process of L2 and L3 is identified and marked. A horizontal line is drawn through the midpoint of the L2 interspace and extended 5 cm to the right and left of the midline. Skin and deeper tissues are infiltrated with the local anesthetic. A 10-15 cm 22 G needle is inserted through the skin and angled 30-45° cephalad. The needle is advanced until it comes in contact with the transverse process. The depth of the needle is then marked. The needle is then withdrawn slightly, angled caudate, and walked inferiorly off the transverse process (usually in a direction perpendicular to the skin). A slight medial angulation is used in the hope of contacting the vertebral body. Once contact is made with the vertebral body, anterior repositioning of the needle is made to walk off that body (the needle tip should remain close to the vertebrae). Anteroposterior radiograph at this stage should show needle tip midway between the lateral edge of the vertebral body and spinous process. Injection of contrast solution should demonstrate linear spread in the longitudinal axis without any lateral or posterior extension.

Sympatholysis after the block, measured in terms of increasing temperature in the affected extremity after the block in comparison with the contralateral extremity, was monitored with small, adhesive thermocouple probes using a Datex-Omeda monitor (Waukesa, Wisconsin, USA). Increase in temperature of more than 1.5°C in the affected extremity was suggestive of adequate sympatholysis. After the procedure, VAS scores were measured and patients were discharged home. Patients were seen in the clinic every week for 6 weeks. During each follow-up visit, edema score [0 - no edema; 1 - moderate edema; 2 - severe edema (skin is tight and shiny] and range of motion at the knee and ankle joints (0 - no restriction of active movement; 1 - moderate restriction of active movement; 2 - severe restriction of active movements) were assessed. All patients continued their other medications and physical therapy during the course of their treatment.

Repeated blocks by the same technique and pain specialist were performed with a maximum of five blocks for each patient over a period of 6 weeks. Repetition of blocks was dependent on exacerbation of pain if VAS score was greater than 50. The number of blocks needed during the 6-week period in each group was recorded.

Side effects after each block, such as hypotension (mean blood pressure < 55 mmHg), bradycardia (heart rate < 55/min), and backache (persistent after the block and requiring NSAIDs to bring relief from it), were measured during the week (between the two injections) and patients could contact the pain specialist in the event of any pain or complications.

At 6 weeks, all patients were asked to fill out a satisfaction score (patient satisfaction score - 0 = completely dissatisfied and 10 = fully satisfied).

Statistical methods

The required sample size was calculated using G*Power version 3.1.3 software (Heinrich Heine Universitδt, Institut fόr Experimentelle Psychologie, Dόsseldorf, Germany). The primary outcome measure was the difference between the two study groups as regards the pain score as assessed on the VAS. It was estimated that a sample size of 15 patients per group would achieve a power of 83% to detect a large effect size (Cohen's d) of 1.1. The test statistic used was the two-sided unpaired t-test and the type I error was set at 0.05.

Statistical analysis was carried out on a personal computer using IBM͹ SPSS͹ Statistics version 21 (IBM͹ Corp., Armonk, New York, USA).

Normality of numerical data distribution was tested using The D'Agostino-Pearson test. Normally distributed numerical data were presented as mean and SD and intergroup differences were compared using the independent-samples Student t-test. Within-group differences were compared with repeated-measures analysis of variance with application of the Bonferroni test for multiple post-hoc pairwise comparisons. Non-normally distributed numerical data were presented as median and interquartile range and the Mann-Whitney test was used for comparison of intergroup differences.

Categorical data were presented as number and percentage or as ratio, and between-group differences were compared using the Pearson χ2 -test or the χ2 -test for trends for nominal or ordinal data, respectively. Fisher's exact test was used in place of the χ2 -test if more than 20% of cells in any contingency table had an expected count of less than 5. All P values are two sided. P values less than 0.05 were considered statistically significant.


  Results Top


Patients' characteristics


The data of patients belonging to the two study groups are summarized in [Table 1]. Statistical analysis revealed nonsignificant differences (P > 0.05) between the two studied groups as regards age, sex distribution, weight, and duration of symptoms.
Table 1 Patient characteristics

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Visual analogue scale

Intergroup comparison of VAS scores showed that there was a statistically significant difference: patients in group A had lower VAS scores compared with patients in group B in the fifth week only (P < 0.001). In the other weeks, however, the VAS score in group A was less than that in group B, but there was no statistically significant difference between them (P > 0.05) [Table 2].
Table 2 Intergroup comparison of pain score

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There was a statistically significant lowering in post-block VAS score compared with preblock VAS score during the 6-week period (P < 0.001) in the two studied groups ([Figure 1] and [Table 3]).

Within the same block, there was no statistically significant difference between VAS scores measured in the first, second, third, fourth, fifth, and sixth weeks in group A ([Table 3] and [Figure 1].

VAS scores in the second and sixth weeks were significantly lower than those in the fifth week in group B (P < 0.001). In the other weeks, the measured VAS scores showed no statistically significant difference (P > 0.05) ([Table 3] and [Figure 1].
Table 3 Within-group comparison of pain scores

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Figure 1: Mean VAS score in the two study groups at various assessment times. Error bars represent 95% confi dence limits. VAS, visual analogue scal e.

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Edema score

An improvement in edema was seen throughout the 6 weeks in the two groups, but there was no statistically significant difference between the two studied groups as regards edema score (P > 0.05) ([Table 4] and [Figure 2].
Table 4 Edema score

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Figure 2: Edema score in the two study groups at various assessment time s.

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Motion score

An improvement in motion was seen in the two groups throughout the 6 weeks, but there was no statistically significant difference between the two studied groups as regards motion score (P > 0.05) ([Table 5] and [Figure 3].
Table 5 Motion score

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Figure 3: Motion score in the two study groups at various assessment time s.

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Frequency of blocks

A statistically significant difference was seen between the two studied groups as regards the number of blocks: patients in group A needed fewer blocks compared with patients in group B (P < 0.001) [Table 6].
Table 6 Frequency of additional blocks and patient satisfaction score

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Thirteen (86.7%) patients in group B needed an additional block in the fifth week, whereas only 3 (20%) patients in group A needed an additional block; this was statistically significant [Table 6]. The number of patients who needed additional blocks in the other weeks showed no statistically significant difference between the two groups [Table 6].

Patient satisfaction

There was a statistically significant difference between the two studied groups as regards patient satisfaction score: patients in group A were more satisfied after 6 weeks compared with patients in group B (P < 0.05) ([Table 7] and [Figure 4].
Table 7 Satisfaction score in both study groups

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Figure 4: Box plot showing satisfaction score in the two study group s.

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Incidence of complications

There was no statistically significant difference between the two studied groups as regards the number of procedures complicated with hemodynamic instability or back pain (P > 0.05) [Table 8].
Table 8 Incidence of complications

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  Discussion Top


CRPS is a clinical diagnosis based on criteria that include hyperalgesia, sudomotor, and trophic changes [7]. We included only CRPS type I patients in this study and used the International Association for the Study of Pain diagnostic criteria to maintain uniformity in clinical diagnosis.

The pathophysiology of CRPS is not completely understood. Multiple mechanisms are considered to play a role in the generation and maintenance of CRPS. These include neurogenic inflammation, immunological mechanisms, and plastic changes in the sympathetic and central nervous system [8]. Multidisciplinary approaches like physiotherapy and pharmacological, interventional, and psychological therapy are used in the treatment of CRPS [8].

It is a great challenge to treat sympathetically mediated pain. Sympathetic nerve blockade of the upper and lower extremities is the treatment of choice for severe sympathetically mediated pain that cannot be managed appropriately with oral regimens [9].

The patients exhibit a prolonged response to sympathetic blockade than expected, despite the rapid metabolism of local anesthetics and clonidine, suggesting that a brief interruption of the sympathetic chain may have a prolonged effect on sympathetic neural firing. In addition to sympathetic blockade, a reduction in sympathetic tone by adding clonidine to the local anesthetic seemed to have a durable therapeutic effect on sympathetically mediated pain [10].

One study concluded through two case reports that repeated lumbar sympathetic blockade with lidocaine and clonidine reduced pain in CRPS type 1 patients [6]. In this study, we compared the effect of adding clonidine to levobupivacaine and steroids in repeated lumbar SBs for patients suffering from lower limb CRPS type 1. Repeated blocks using the same technique were performed with a maximum of five blocks for each patient over a period of 6 weeks.

The VAS score in each visit was recorded and a significant decrease in pain was noticed after the first block and it remained less than the baseline VAS score throughout the study in the two studied groups. The group administered clonidine (group A) also showed an insignificantly lower VAS score compared with the control group (group B). Jenna et al. [10] demonstrated that repetitive lumbar SB with a local anesthetic and clonidine improved pain in a female patient with idiopathic peripheral neuropathy for several weeks.

Edema and motion restriction were assessed and they were improved at the end of the 6-week period. Improvement in scores was noticed more in group A but the difference was nonsignificant compared with group B. Decreased pain and improved tolerability to physical therapy may in turn lead to positive input to the motor regions in the brain [11]. This may help revert the plastic changes in the cortical areas seen with CRPS type I [11,12]. This could explain the significant improvement in functional restoration seen in our patients in both groups.

Clonidine, a partial α-2 adrenergic agonist, produces an antinociceptive effect and improves analgesic efficacy when combined with a local anesthetic. Clonidine enhances both sensory and motor blockade from the local anesthetic used for epidural or peripheral nerve block [13,14]. A postulated mechanism for this is that clonidine blocks the conduction of C and A-delta fibers and increases potassium conductance in isolated neurons in vitro, thus intensifying the conduction block. Second, clonidine causes local vasoconstriction in the clinical setting, thereby reducing vascular uptake of local anesthetic from around the neural structures. The α-2 adrenergic agonists also enhance analgesia from intraspinal opioids by interactions both presynaptically and postsynaptically within the spinal cord [13]. This explains why group A needed fewer blocks compared with group B during the 6 weeks of follow-up.

Further, patients in group A were more satisfied than patients in group B at the end of the study.


  Conclusion Top


Adding clonidine to levobupivacaine and steroids in repeated lumbar SBs for patients suffering from lower limb CRPS type 1 prolongs analgesia and improves edema and tolerability to physical therapy.


  Acknowledgements Top


 
  References Top

1.Harden RN, Bruehl S, Stanton-Hicks M, Wilson PR. Proposed new diagnostic criteria for complex regional pain syndrome. Pain Med 2007; 8:326-331.  Back to cited text no. 1
    
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4. Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndrome. Pain 1997; 73:123-139.  Back to cited text no. 4
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5. Mekhail N, Malak O. Lumbar sympathetic blockade. Tech Reg Anesth Pain Manag 2001; 5:99-101.  Back to cited text no. 5
    
6. Chen LC, Wong CS, Huh BK, et al. Repeated lumbar sympathetic blockade with lidocaine and clonidine attenuates pain in complex regional pain syndrome type 1 patients - a report of two cases. Acta Anaesthesiol Taiwan 2006; 44:113-117.  Back to cited text no. 6
    
7. Bruehl S, Harden RN, Galer BS, et al. External validation of IASP diagnostic criteria for complex regional pain syndrome and proposed research diagnostic criteria. Pain 1999; 81:147-154.  Back to cited text no. 7
    
8. Ghai B, Dureja GP. Complex regional pain syndrome: a review. J Postgrad Med 2004; 50:300-307.  Back to cited text no. 8
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9. Boas RA. Sympathetic nerve blocks: in search of a role. Reg Anesth Pain Med 1998; 23:292-305.  Back to cited text no. 9
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10.Jenna LW, Daniel FL, Robert DT, Tracy PJ. Idiopathic peripheral neuropathy responsive to sympathetic nerve blockade and oral clonidine: case report. Case Rep Anesthesiol 2012; 2012: p. 2.   Back to cited text no. 10
    
11.Gokul T, Rani S, Ronald T, Dureja GP. Management of complex regional pain syndrome type I in upper extremity - evaluation of continuous stellate ganglion block and continuous infraclavicular brachial plexus lock: a pilot study. Pain Med 2012; 13:96-106.  Back to cited text no. 11
    
12.Istemi Y, Yavuz D, Kutay O, Erdem D. Complex regional pain syndrome type I: efficacy of stellate ganglion blockade. J Orthop Traumatol 2009; 10:179-183.  Back to cited text no. 12
    
13.Eisenach JC, De Kock M, Klimscha W. α2-adrenergic agonists for regional anesthesia. A clinical review of clonidine. Anesthesiology 1996; 85:655-674.  Back to cited text no. 13
    
14.Tryba M, Gehling M. Clonidine - a potent analgesic adjuvant. Curr Opin Anaesthesiol 2002; 15:511-517.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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