• 
• 

Three Part Question

In [patients with critical leg ischaemia] is the use of [sympathectomy] of any benefit in terms of [pain relief or limb survival]?

Clinical Scenario

You recently admitted an 82-year-old arteriopath who has had an 8-month history of critical leg ischaemia and who has debilitating pain at rest. Lower limb arteriogram confirms three-vessel disease not amenable to revascularisation. A below knee amputation was discussed with the patient. The patient asks you if anything could be done rather than an amputation. You have heard of sympathectomy, but wanted to confirm from the literature that this may be a viable option.

Search Strategy

Medline 1966–June 2005 using the OVID interface
[exp Ischemia/OR Ischaemia.mp OR Ischemia.mp OR Ischemic.mp OR Ischaemic.mp] AND [limb.mp or exp Extremities/OR leg.mp OR exp Leg/] AND [exp sympathectomy, chemical/OR exp sympathectomy/OR sympathectomy.mp] Limit to Humans.

Search Outcome

A total of 387 abstracts were found of which 11 were directly relevant. Two additional papers were identified on cross referencing. These are presented in the table

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Repealer van Driel et al, 1998, Holland	60 consecutive patients (66 legs) with severe lower limb ischaemia (rest pain, ischaemic ulcers, gangrenous lesions) surgical lumbar sympathectomy	Single centre cohort study (level 2b)	Good results (pain relief, healed ulcers, no amputations @ 6 months)	32/66 (48%)	Presence of diabetes or gangrene were considered as risk factors affecting outcome
			Urine sample PCR:	Sensitivity 55.6% (95% CI, 36.3% to 74.9%)
			Cervical sample PCR:	Sensitivity 94.2% (95% CI, 90.5% to 98.0%)
			Limb survival	6 months 43/66 (65%). 2 years 39/66 (59%).
			Mortality	none
Kim et al, 1976, USA	58 patients (61 limbs) with end stage occlusive vascular disease (ischaemic ulcers, rest pain, gangrene <1/2 foot, rapid progressive limiting intermittent claudication) surgical lumbar sympathectomy	Single centre cohort study (level 2b)	Good results (pain relief, healed ulcers, nonpainful useful limb @ 6 months)	32/53 (60%)	4 patients with concomitant surgery and 4 post-op deaths were excluded
			Amputation	21/53 (40%)
			Mortality	4/61 (6.5%)
Alexander JP, 1994, UK	489 patients (544 limbs) with peripheral vascular disease (rest pain, ulceration or limited gangrene) underwent chemical lumbar sympathectomy with 10% phenol	Single centre cohort study (level 2b)	Immediate results (favourable response as in improved rest pain relief and blood flow)	352/489 (72%)	20 patients lost to follow up at 8 months
			Long term results @ 8 months	52/148 (35%)
			Mortality @ 2 years	30/148 (20%)
			Amputation	34/148 (24%)
Keane FBV, 1977, UK	132 patients with critical leg ischaemia (rest pain, rapidly progressing intermittent claudication, ulcerative or gangrenous tissue necrosis, tissue necrosis without pain) underwent chemical lumbar sympathectomy with 4 ml of 6% phenol under image intensifier Non-diabetic (n=111) Diabetic (n=15)	Single centre cohort study (level 2b)	Good results (relief of rest pain, feeling of warmth and life in limb, amputation avoided at average @ 16.3 months	65/126 (52%)	6 patients excluded from study due to incomplete records or patients lost to follow up
			Good results/ Non diabetic/diabetic	62/111 (56%), 3/15 (20%)
			Amputation/Non diabetic/diabetic	31/111 (28%), 8/15 (53%)
Norman PE, House AK, 1988, Australia	153 patients (174 limbs) with claudication and rest pain underwent surgical lumbar sympathectomy Claudicant (n=109) Rest pain (n=65) Rest pain group consist of diabetic and non-diabetics	Single centre cohort study (level 2b)	Good results (avoided further surgery) at @ 5 years	73/109 (67%)	No statistical significant difference between diabetics and non diabetics
			Good results Claudication group/Rest pain group	35/65 (54%)/4/153 (2.6%)
			Mortality @ 30 days	6/109 (6%)
			Amputation @ 2 years	15/65 (23%)
Perez-Burkhardt et al, 1999, Europe	93 patients (100 limbs) with claudication/rest pain, trophic lesions, previous failed reconstructive surgery or poor surgical risk underwent surgical lumbar sympathectomy Claudication and rest pain - Grade II Trophic lesions Grade III	Single centre cohort study (level 2b)	Good results @ 6 months Grade II	31/53 (58.5%)	9 patients died during the long term follow up
			Good results @ 6 months Grade III	29/47 (61.7%)
			Amputation	17/93 (18.3%)
			Mortality @ 30 day	7/93 (7.5%)
			Mortality @ long term	16/93 (17.2%)
Mashiah et al, 1995, Israel	373 patients with ischaemic lower limb, gangrene toes or ischaemic ulcers, with or without rest pain underwent chemical lumbar sympathectomy with 10 ml of 6% phenol Diabetic n=226 Non-diabetic n=147	Single centre cohort study (level 2b0	Good outcome (relief of pain, healing of ulcer and amputation not required)	219/373 (58.7%)	Diabetes with rest pain had favourable response in comparison to non-diabetics (61% vs 41%) p<0.05
			Amputation	75/373 (20%)
			Mortality	38/373 (9%)
Matarazzo et al, 2002, Europe	385 patients with rest pain, ischaemic dystrophic lesions and advanced intermittent claudication underwent surgical lumbar sympathectomy	Single centre cohort study (level 2b)	Good results (improvement in limb trophism with remission of pain, rise in cutaneous temperature of foot and leg) @ 1 year	245/385 (63.6%)	Surgical removal of 2nd and 3rd lumbar sympathetic ganglion
Baker et al, 1994, UK	118 patients (132 limbs) with severe peripheral vascular disease unsuitable for vascular reconstruction underwent surgical lumbar sympathectomy	Single centre cohort study (level 2b)	Good result (relief of rest pain) @ 6 months	101/118 (86%)	62 patients had local wound debridement or toe amputation at the same time
			Recovery from trophic changes @ 6 months	76/118 (64%)
			Amputation @ 6 months	54/118 (45%)
			Mortality @ 30 days	5/118 (4%)
Cross FW, Cotton LT, 1985, UK	37 patients (41 limbs) with ischaemic rest pain randomised to control (CG) or treatment (TG) Underwent chemical lumbar sympathectomy using 7.5 ml of 7.5% phenol in glycerine for the TG and 7.5 ml of 0.25% bupivicaine solution for CG TG= 24 limbs CG= 17 limbs	Double blind PRCT (level 1b)	Good results - relief of rest pain @ 1 week	TG 20/24 (83.55), CG 4/17 (23.5%) p<0.002	Control group lost at 6 months No differences in ankle brachial pressure index found
			Relief of rest pain @ 6 months	TG 14/24 (58.3%) CG 4/17 (23.5%) p<0.025
			Mortality @ 6 months	5/37 (13.5%)
Collins et al, 1981, USA	40 patients (45 limbs) with rest pain or advanced skin changes underwent surgical lumbar sympathectomy	Single centre cohort study (level 2b)	Good results (relief of rest pain and healed ulcers)	20/45 (44.4%)	3 patients lost to follow up
			(relief of rest pain and healed ulcers) @ 6 months	19/45 (42.2%)
Barnes et al, 1977, USA	51 patients undergoing operation for occlusive or aneurysmal disease 50 limbs randomised to sympathectomy and reconstruction 52 limbs randomised to reconstruction alone	PRCT (level 1b)	Foot vascular resistance measured by plethysmography	Significant reduction in foot vascular resistance seen
			Improvement in ABPI	No differences in ABPI seen
			Amputations	3 in treatment group, 1 in sympathectomy group
Fyfe T, Quin RO, 1975, UK	25 patients with intermittent claudication Randomized to injection of phenol into the lumbar sympathetic chain or by injection of local anaesthetic subcutaneously	PRCT (level 1b)	Subjective improvement in symptoms, treadmill testing, walking distance, APBI	Sympathectomy group 45% at 1 month, 25% at 3 months. Control group 64% at 1 month, 45% at 3 months. No objective differences in any testing between groups

Comment(s)

Sympathectomy is proposed to act primarily via its vasodilator effects on the collateral circulation secondary to decreased sympathetic tone. This is deemed to improve tissue oxygenation and ulcer healing, and decrease tissue damage and pain. Pain is also deemed to be decreased by interrupting sympathetic–nociceptive coupling and by a direct neurolytic action on nociceptive fibres. We identified 3 randomised controlled trials. Cross et al. in 1985 performed a trial of chemical lumbar sympathectomy on 37 patients with critical limb ischaemia. There was relief of rest pain in 66.7% of patients in the treatment group and in 23.5% of those in the control group at 6 months. However, there was no difference in ankle-brachial-pressure-index between the two groups. Barnes et al. in 1977 performed a randomised trial in patients also receiving revascularisation. Although a reduction in peripheral vascular resistance was shown, no difference in ankle-brachial-pressure-index or graft survival was demonstrated. Fyfe et al. in 1975 performed a randomised trial using phenol sympathectomy vs. local anaesthetic controls in patients with intermittent claudication but found no subjective or objective differences between the two groups at either 1 or 3 months. The remaining studies were cohort studies. Van Driel et al. in 1988 performed a single centre retrospective study on 60 consecutive patients to evaluate the effect of surgical lumbar sympathectomy in the treatment of critical leg ischaemia. There were good results (defined as absence of rest pain, healing of ischaemic lesions and no major amputation) in 48% of limbs at six months. Limb survival at 6 months and 2 years were 65% and 59%, respectively. No operative deaths were reported. Kim et al. in 1976 performed 61 lumbar sympathectomies on 58 patients with lower extremity arterial disease. Overall improvement rate (defined as disappearance of rest pain, healing of tissue and a generally non-painful useful limb for at least 6 months post op) was 60% while early amputation rate was 40%. The immediate postoperative death was 6.5% from cardiac causes. Alexander et al. in 1994 performed 544 chemical lumbar sympathectomies on 489 patients with peripheral vascular disease. There was improvement in symptoms in 72% of the patients immediately and 35% at 8 months follow up. The amputation rate was 24% at 2 years. Keane et al. in 1977 performed chemical lumbar sympathectomy on 132 patients with critical limb ischaemia. Good results (defined as relief of rest pain, feeling of warmth and life in the limb, avoidance of amputation) were seen in 52% of the patients at 16 months. Thirty-five patients required amputation despite sympathectomy. Norman et al. in 1988 performed 174 surgical lumbar sympathectomies on 153 patients. Sixty-seven percent of the claudicant and 54% of the rest pain patients avoided further surgery after 5 years. Perez-Burkhardt et al. in 1999 performed 100 surgical lumbar sympathectomies on 93 patients for invalidant claudication, ischaemic rest pain and trophic lesions. Good results (judged by absent rest pain, healed ischaemic ulcers no major amputation at 6 months) were seen in 58.5% of patients with claudication or rest pain and 61.7% of patients with trophic lesions. Amputation rate was 18.3% at 30 days post operatively. Mashiah et al. in 1995 performed chemical lumbar sympathectomy on 373 patients with ischaemic lower limbs. Successful results (defined by termination of analgesic treatment, healed ulcers in 6–12 months and amputation not required) were achieved in 58.7% of the patients. Amputation rate was 20% and mortality 9%. Matarazzo et al. in 2002 performed surgical lumbar sympathectomy on 385 patients with lower limb occlusive arterial disease. Favourable results were achieved in 63.6% of patients at 1 year. Baker et al. in 1994 performed 132 surgical lumbar sympathectomy on 118 patients with severe peripheral vascular disease unsuitable for vascular reconstruction. Rest pain resolved in 86% within 6 months and 64% recovered from all trophic lesions over the same period. There was a 45% limb loss in the first 6 months. Peri-operative mortality rate was 4%. Collins et al. in 1981 performed 45 surgical lumbar sympathectomies on 40 patients with rest pain or advanced skin changes. There was a good result (characterised by relief of rest pain and healing of ulcers for at least 6 months) in 44.4% of the patients. Amputation was performed in 42.2% of patients.

Clinical Bottom Line

Lumbar sympathectomy is a minimally invasive procedure with a low complication rate. Randomised controlled trials have failed to identify any objective benefits for lumbar sympathectomy, but subjective improvements in symptoms for patients with highly symptomatic critical leg ischaemia have been consistently demonstrated in multiple cohort studies with sustained symptom improvements in approximately 60% of patients. Lumbar sympathectomy should be considered for symptomatic patients with critical leg ischaemia as an alternative to amputation in patients with otherwise viable limbs.

References

1. Repealer van Driel OJ, Van Bockel JH, Van Schilfgarde R. Lumbar sympathectomy for severe lower limb ischaemia: results and analysis of factors influencing the outcome. J Cardiovasc Surg 1998;29:310–314.
2. Kim GE, Ibrahim IM, Imparato AM. Lumbar sympathectomy in end stage arterial occlusive disease. Ann Surg 1976;183:157–160.
3. Alexander JP. Chemical lumbar sympathectomy in patients with severe lower limb ischaemia. The Ulster Med J 1994;137–143.
4. Keane FBV. Phenol lumbar sympathectomy for severe arterial occlusive disease in the elderly. Br J Surg 1977;64:519–521.
5. Norman PE, House AK. The early use of operative lumbar sympathectomy in peripheral vascular disease. J Cardiovasc Surg 1988;29:717–722.
6. Perez-Burkhardt JL, Gonzalez-Fajardo JA, Martin JF, Carpintero Mediavilla LA, Mateo Gutierrez AM. Lumbar sympathectomy as isolated technique for the treatment of lower limbs chronic ischaemia. J Cardiovasc Surg 1999;40:7–13.
7. Mashiah A, Soroker D, Pasik S, Mashiah T. Phenol lumbar sympathetic block in diabetic lower limb ischemia. J Cardiovasc Risk 1995;2:467–469.
8. Matarazzo A, Rosati-Tarulli V, Sassi O, Florio A, Tatafiore M, Molino C. Possibilities at present for the application of lumbar sympathectomy in chronic occlusive arterial disease of the lower limbs. Minnerva Cardioangiologica 2002;50:363–369.
9. Baker DM, Lamerton AL. Operative lumbar sympathectomy for severe lower limb ischaemia: still a valuable treatment option. Ann R Coll Engl 1994;76:50–53.
10. Cross FW, Cotton LT. Chemical lumbar sympathectomy for ischemic rest pain: a randomised, prospective controlled clinical trial. Am J Surg 1985;150:341–345.
11. Collins GJ, Rich NM, Clagett GP, Salander JM, Spebar MJ. Clinical results of lumbar sympathectomy. American Surgeon 1981;31–35.
12. Barnes RW, Baker WH, Shanik G, Maixner W, Hayes AC, Lin R, Clarke W. Value of concomitant sympathectomy in aortoiliac reconstruction. results of a prospective, randomised study. Arch Surg 1977;112:1325–1330.
13. Fyfe T, Quin RO. Phenol sympathectomy in the treatment of intermittent claudication: a controlled clinical trial. Br J Surg 1975;62:68–71.