Spinal Cord Stimulation in Patients Suffering from Critical Lower Limb Ischemia

G. Colini Baldeschi, MD, FIPP
Past President, International Neuromodulation Society Italian chapter, 2016-2019
Pain Therapy Unit  
Salvator Mundi International Hospital  
Rome, Italy

Introduction

Chronic critical limb ischemia (CLI) is a serious, painful peripheral arterial disease defined by the presence of ischemic rest pain, non-healing wounds, or gangrene. Pain can be acute or chronic, and is divided into: 1) vascular pain, which originates from the vessel wall; 2) somatic pain, related to tissue ischemia; and 3) nerve pain, caused by ischemia of the nerve trunks. Chronic pain is generally mixed nociceptive pain (the peripheral nociceptors generate an action potential that propagates along the fibers to the central nervous system, and release into the surrounding environment vasoactive neuropeptides such as substance P, somatostatin and CGRP, which contribute to the state of neurogenic inflammation), and neuropathic pain due to ischemic degeneration of the nerves.

The severity of this condition is confirmed by a peer-reviewed summary of 19 studies, published in 2000, that found that within six months of initial treatment, 20% of CLI patients had died from various causes, 35% were alive with amputation, and 45% were alive without amputation.¹

Interventional Pain Treatments

A number of interventions are used to treat the pain of CLI:

• Sympathetic blockade (Reid, 1970)
• Sympathectomy (Adson & Brown, 1925)
• Epidural analgesia (Gutierrez, 1935; Harger, 1941)

• Spinal cord stimulation (SCS) (Cook, 1973)

Target of the Therapy

Therapy for CLI has several goals:

• Improve the quality of life
• Reduce swelling from a dependent position
• Increase the pharmacological action
• Reduce the intake of drugs
• Improve local perfusion

Indications for Spinal Cord Stimulation

Patients may be referred to SCS when they have arterial occlusive disease stage III-IV (according to Fontaine²), are unsuitable for surgical revascularization and not responding to medical therapy. Their diagnoses may be such conditions as diabetic neuropathy associated with arterial occlusive disease, Raynaud's Syndrome, or vasculitis.

What do we mean by "SUCCESS"

• Reduction of at least 50% of ischemic pain
• Limb salvage or the reduction of the extension of the amputation

Patient Selection

Criteria for referring a patient with peripheral vascular disease to SCS include:

• More conservative therapies have failed or are not feasible
• Further surgery is not indicated
• The patient is not suffering from drug addiction
• The patient is suitable for treatment with SCS
• The patient does not suffer from psychological disorders

• There are no major contraindications (coagulopathies, sepsis, etc.)

Possible Spinal Cord Stimulation Mechanisms

Several explanations have been proposed regarding the mode of action of SCS:

• Gating mechanism
• Modulation of neural transmission of electrochemical information
• Orthodromic impulses via the brain stem may activate descending inhibitory tracts
• Modulation of sympathetic nervous system
• Release of neuromodulators and neurotransmitters
• Reduced dorsal horn excitability
• Increased GABA levels
• Induced adenosine release

• Decreased release of excitatory amino acids: glutamate and aspartate

Conclusion

Spinal neuromodulation is an effective therapy option in the management of patients affected by non-reconstructable chronic critical limb ischemia.

Annotated References

1. Amann W, Berg P, Gersbach P, Gamain J, Raphael JH, Ubbink DT, et al. Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischaemia: results of the European Peripheral Vascular Disease Outcome Study (SCS-EPOS) Eur J Vasc Endovasc Surg. 2003;26:280-286.
   
   SCS treatment of non-reconstructable critical leg ischemia provides a significantly better limb survival rate compared with conservative treatment. Patient selection based on TcpO2 and the results of trial screening further increase the probability of limb survival after SCS therapy.
   
   
2. Ubbink DT, Vermeulen H. Spinal cord stimulation for non-reconstructable chronic critical leg ischemia. Cochrane Database of Systematic Reviews 2005.

   
   There is evidence that SCS is better than conservative treatment alone to achieve  amputation risk reduction, pain relief and improvement of the clinical situation in patients with non-reconstructable chronic stable critical limb ischemia.

3. Ubbink DT, Vermeulen H. Spinal Cord Stimulation for Critical Leg Ischemia: A Review of Effectiveness and Optimal Patient Selection. Journal of Pain and Symptom Management 2006;31(4):S30-S35.

   
   There was an 11% lower amputation rate after 12 months compared to those treated with optimum medical treatment.

   In addition, SCS patients required significantly fewer analgesics and showed a significant clinical improvement.
   
   
4. Gersbach PA, Argitis V, Gardaz JP, von Segesser LK, Haesler E. Late outcome of spinal cord stimulation for unreconstructable and limb-threatening lower limb ischemia. Eur J Vasc Endovasc Surg 2007 Feb 9.

   
   In chronic critical limb ischemia patients the beneficial effects of SCS persist far beyond the first year of treatment and major amputation becomes infrequent after the second year.

1. Colini Baldeschi G., Carlizza A. 2011. Spinal Cord Stimulation: Predictive Parameters of Outcome in Patients Suffering from Critical Lower Limbs Ischemia. A Preliminary Study. Neuromodulation 2011; 14: 530–533.

   
   Patients affected by non-reconstructable chronic limb ischemia can benefit from SCS not only in terms of relief from their ischemic pain, but also of wound healing and limb salvage. Pain relief is important in itself, as well as being correlated to limb salvage. As a matter of fact, tissue perfusion can be improved by the consequent reduction of edema by pain-relieving posture, and of reflected sympathetic vaso-constriction, and by greater patient mobility. The positive effect of SCS may be boosted by the selection of patients on the basis of local microcirculatory conditions, bearing in mind that microcirculatory perfusion deficit is the last cause of tissue loss. This study highlights the importance of transcutaneous oximetry with postural testing, a good outcome being indicated by a Δ TcPO2 of greater than 15 mmHg, but also by an absolute dependent limb value of ≥20 mmHg. These indicators suggest that even patients with baseline TcPO2 values of less than 10 mmHg can be “recovered” if they still have sufficient microcirculatory reserve capacity.

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   Footnotes:
   
   1) Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000;31(1 pt 2):S1–S296.
   
   2) In stage III peripheral arterial disease, patients experience pain at rest, especially at night when the patient is lying down, diminishing the effect of gravity on circulation; in stage IV disease, patients have ischemic ulcers or gangrene (which may be dry or humid).
   
   Fontaine R, Kim M, Kieny R. Die chirurgische Behandlung der peripheren Durch-bluntungsstorungen. Helvetia Chirurgica Acta 1954; 5/6: 199-233.