1 Introduction

Chronic digital ischemia is a debilitating disorder characterised by gradual-onset and progressive ischemic symptoms in the hand and digits, such as cold intolerance, pain at rest, ulceration, tissue necrosis, and even digit loss. Although identifiable patterns of disease are seen if one of the major arteries to the hand are involved, digital ischemia is a more heterogeneous condition, where outcomes are largely dependent on the aetiology of ischemia.¹

Causes of chronic digital ischemia include vasculopathy, connective tissue disease, embolic disease, trauma, or extrinsic vascular compression.² In patients with scleroderma (SS) and Raynaud's phenomenon (RP), high rates of necrosis and amputation are observed.^3,4

Several diagnostic tests are available to investigate the ischemic hand, including vascular imaging (duplex ultrasound, CT or MR angiography) and catheter-based angiography.⁵ Cold stress testing and laser doppler flow studies can indicate disease severity and local anaesthesia can prognosticate possible gains from distal sympathectomy.^6,7 Non-invasive vascular studies such as digital plethysmography, wrist-brachial indices and pulse volume recordings, although used in the upper limb, have a limited role in the hand.

Important nonsurgical treatments include smoking cessation, lifestyle modification and analgesia. Medical management includes calcium channel blockers, anti-platelet agents, topical nitroglycerin ointment and sildenafil.⁸ The use of thrombolytics is uncommon.⁹ Botulinum toxin injection can provide temporary symptomatic relief.¹⁰

Surgical treatment options include simple debridement of ulcers, periarterial sympathectomy, microsurgical revascularization with vascular grafts, bypass or angioplasty, and amputation, or a combination of these.^6,11 Furthermore, sympathectomy is not limited to the peripheries (digital, palmar, radial and ulnar vessels) but cervical and thoracic sympathectomy has also been considered. The long-term results of these surgical procedures remain unclear.

Periarterial sympathectomy is not a new procedure¹² but there is conflicting evidence on how it is best performed. Different techniques include isolating and dividing the terminal branches of the sympathetic nerves, stripping the adventitia of the digital arteries, the common digital arteries and the fibrotic tissues encasing the palmar arch or the radial and ulnar arteries.⁷ The efficacy of sympathectomy is thought to result primarily from sympathetic denervation and subsequent vasodilatory effects. Secondary effects may result from decompression of the ischemic vessel through removal of a fibrotic and noncompliant adventitia.¹³

Therefore, patients who may benefit from distal sympathectomy are those with recurrent ischemic pain and/or non-healing digital ulcers refractory to nonsurgical treatment, in the absence of available distal target for vascular reconstruction of narrow or thrombosed distal arteries.

However, there is ongoing debate about the long-term outcomes of distal sympathectomy surgery and there are many aspects of the procedure that still require consensus, including patient selection, indications for surgery and the extent of dissection.¹⁴ The aim of this systematic review is to establish the effectiveness of distal sympathectomy as a treatment of chronic digital ischemia.

2 Methods

This study is a systematic review of the literature regarding treatment of chronic digital ischemia by distal sympathectomy surgery. As such, ethical approval was not required and no confidential patient data was used.

The literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement (PRISMA). The following databases were searched initially on March 25th^, 2022 using the NICE Evidence Service's healthcare databases advanced search (HDAS): Medline, Embase, Cinahl, AMED, BNI, Health Business Elite, HMIC and Psycinfo. The following search terms were used: "digital sympathectomy", "periarterial sympathectomy", "sympathectomy", "chronic digital ischemia", "raynauds", "scleroderma". Following closure of HDAS, subsequent repeats of the search were performed on the bibliographic databases via their provider interfaces with a final literature search performed on December 5th, 2022.

Identified studies were selected using the title or abstract and included if they reported clinical outcomes from surgical sympathectomies of the distal forearm, hand or digits, excluding more proximal sympathectomies above the radial or ulnar artery, or chemical sympathectomies. Included studies were level IV evidence and above, published in the English language.

Review articles containing no outcome data, individual case reports, letters to the editor and conference abstracts were excluded, as were studies where the full text was not available. Articles referring to vascular bypass surgery were also excluded.

Full articles were then reviewed, cross referenced and data extracted including study design, total number of patients, number of hands or digits affected, patient sex, mean age, aetiology of digital ischemia, level of sympathectomy, mean follow-up time and outcome data.

Primary outcome data were improvement of pain and resolution of digital ulceration. Secondary outcome measures were rates of digital amputation and other complications.

The database searches yielded 8009 sympathectomy articles, of which 416 related to chronic digital ischemia, containing 135 duplicate records, as summarised in Fig. 1. Reviewing article titles and abstracts lead to a further 211 exclusions, resulting in 70 full articles assessed for eligibility. Of these, 21 articles were included in the review.

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Fig. 1 Identification of studies and criteria for review.

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Data were independently extracted by two investigators (N.C-M. and G.S.), with masking of author names and paper titles. Quality and risk of bias of included studies were independently assessed by the investigators. Where there was disagreement between investigators, data were jointly extracted in consensus, any further disagreement was resolved through consultation with study supervisor (O.B.). The decision was made not to make any inferences about the studies; if information was not specifically stated in the papers, it was recorded as blank in our table.

3 Results

21 studies met our inclusion criteria and the reviewed studies are shown in Table 1. The included studies were published between 1991 and 2021.5 studies were prospective, 14 were retrospective, and 2 studies did not describe study design. The quality of included studies was generally considered as very low to low quality, as most were observational studies with no blinding, missing outcome data or high patient loss to follow-up. However, some studies were considered as low to moderate quality as they had a low risk of bias and significant reported outcome effect sizes.

Our analysis included 337 patients, 324 hands, and 398 digits. The mean age of patients ranged from 23.2 to 56.6 years. Mean follow-up time ranged from 12 to 120 months after sympathectomy surgery.

Sympathectomy was performed at the level of the proper digital artery (PDA) in 10 studies, the common digital artery (CDA) in 15 studies, the superficial palmar arch (SPA) in 11 studies, the deep palmar arch (DPA) in 3 studies, the radial artery (RA) in 10 studies and ulnar artery (UA) in 11 studies.

Causes of digital ischemia from the patients in the reviewed studies include Scleroderma (n = 124), RP (n = 47), CREST syndrome (n = 5), trauma (n = 66), atherosclerosis/Buerger's disease (n = 36), systemic lupus erythematosus/discoid lupus (n = 17), undifferentiated rheumatic disorder/mixed connective tissue disease (n = 11), and unknown/unspecified diagnoses (n = 40).

3.1

3.1 Effects of interventions

3.1.1

3.1.1 Pain

Symptomatic relief was reported in 11 studies, totalling 203 patients and 153 hands. Of these, distal sympathectomy was associated with decreased pain in 125 out of 132 patients (94.7 %) and 105 out of 114 hands (92.1 %), (excluding cases that did not record pain both before and after the intervention). Fig. 2 shows the proportion (%) of cases that reported decreased pain in each study.

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Fig. 2 Percentage of reported cases with improvement in pain after digital sympathectomy.

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Of these, 8 studies reported a long-term duration of this effect: pain relief persisted in all cases at 6 months postoperatively in 2 studies,^15,16 at 12 months postoperatively in 2 other studies,^17,18 and in 82–93 % cases at 2–12 years postoperatively in 4 other studies.^7,14,19,20 9 studies did not assess or specify any change in symptoms and 1 study reported subsequent discontinuation of analgesia.

3.1.2

3.1.2 Ulcer healing

Data on ulcer healing were reported in 17 studies, totalling 224 patients. Of these, 164 patients had complete resolution of ulceration after distal sympathectomy (73 %). Time to healing of ulcers ranged from 4 weeks to 6 months after surgery. Fig. 3 shows the proportion of cases that reported resolution of digital ulcers in each study.

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Fig. 3 Percentage of reported cases with resolution of digital ulcers after digital sympathectomy.

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Table 2 shows the causes of digital ischemia in these patients (excluding cases that did not record digital ulceration per diagnosis). For each cause of digital ischemia, ulcer healing occurred in; 37 out of 50 (74 %) patients with SSc, 11 out of 26 (42 %) patients with RP, 4 out of 11 (36 %) patients with Atherosclerosis/Buerger's, 4 out of 5 (80 %) patients with SLE/discoid lupus, and 28 out of 33 (85 %) patients with unknown or unspecified diagnosis. Complete ulcer healing was otherwise reported in patients with CREST (n = 2) and trauma-induced digital ischemia (n = 62). Where diagnoses were reported, 148 out of 189 (78 %) patients had complete resolution of ulceration after distal sympathectomy.

Table 2 Causes of digital ischemia in patients with presence of ulcers before and after digital sympathectomy.

Cause of digital ischemia	Pre-operative ulcers	Presence of ulcers at follow-up	Percentage improvement
Scleroderma	50	13	74 %
Raynaud's phenomenon	26	15	42 %
Atherosclerosis/Buerger's	11	7	36 %
SLE/discoid lupus	5	1	80 %
CREST	2	0	100 %
Trauma	62	0	100 %
Unknown/unspecified	33	5	85 %
TOTAL	189	41	78 %

3.1.3

3.1.3 Amputation

Data on digital amputations performed after the time of sympathectomy were reported in 17 of the included studies. In total, 56 out of 203 patients (28 %) required subsequent amputation. Common reasons for amputation included ‘failure to heal chronic wounds’, ‘secondary infection and persistence of severe pain’ and ‘end-stage gangrene’.Fig. 4 shows the proportion of cases that required subsequent amputation in each study. In four studies, no patients required subsequent amputation.

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Fig. 4 Percentage of reported cases undergoing amputation after digital sympathectomy.

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Table 3 shows the causes of digital ischemia in these patients (excluding studies that did not record amputations per diagnosis). For each cause of digital ischemia, those who required amputation were; 8 out of 75 (11 %) patients with SSc, 3 out of 35 (9 %) patients with RP, 7 out of 17 (41 %) patients with Atherosclerosis/Buerger's, 2 out of 13 (15 %) patients with SLE/discoid lupus, 1 out of 5 (20 %) patients with CREST, none (0 %) of the patients with undifferentiated rheumatological disease (n = 1), 1 out of 4 (25 %) patients with trauma-induced digital ischemia, 1 out of 7 (14 %) patients with idiopathic or other causes, and 14 of 27 (52 %) patients with unknown or unspecified diagnosis.

Table 3 Causes of digital ischemia in patients requiring amputation.

Cause of digital ischemia	Total number of patients	Patients requiring amputation	Rate of amputation
Scleroderma	75	8	11 %
Raynaud's phenomenon	35	3	9 %
Atherosclerosis/Buerger's	17	7	41 %
SLE/discoid lupus	13	2	15 %
CREST	5	1	20 %
Undifferentiated rheumatological/mixed connective tissue disease	1	0	0 %
Trauma	4	1	25 %
Idiopathic/other	7	1	14 %
Unknown/unspecified	27	14	52 %
TOTAL	184	37	20 %

3.1.4

3.1.4 Complications

Data on postoperative complications, excluding amputation, were reported in 11 studies. The combined data from these showed complications were reported in 45 out of 187 patients (24.1 %), 16 out of 44 hands (36.4 %) and 4 out of 22 digits (18.2 %) after distal sympathectomy. These included delayed surgical site wound healing in 22 patients (11.8 %) and 9 hands (20.5 %) and 2 digits (9.1 %), surgical site infection in 5 patients (2.7 %) and 7 hands (15.9 %), flexion contracture of the digit in 4 patients (2.1 %), distal numbness or paraesthesias in 9 patients (4.8 %) and other complications such as stiffness, fingernail detachment and complex regional pain syndrome reported in 1 or 2 patients respectively. Diagnosis or aetiology of chronic digital ischemia were not reported in these data. 10 studies did not report data on postoperative complications.

4 Discussion

This systematic review supports the role of periarterial sympathectomy in the surgical management of chronic digital ischemia. The data demonstrates that sympathectomy provides effective pain relief in 92.1–94.7 % cases and resolution of digital ulceration in 78 % cases, with 28 % cases still requiring subsequent digital amputation and 18.2–36.4 % cases resulting in other complications.

The overall completeness of data reporting is poor, with high variability of outcome measures used, limiting the clinical applicability of the dataset. Some studies indicate symptomatic relief after surgery but provide no specific numbers of patients, hands nor digits, in which this was found, and use no objective marker of symptomatology. Murata et al. assessed outcomes of sympathectomy using functional evaluation (VFUSS and DASH-JSSH scores), angiography, thermography and plethysmography, but do not report on clinical outcomes of pain, ulceration and digital amputation.²¹ Whereas, Ruch et al. utilise a novel symptom rating scale, alongside the Levine Symptom Severity Scale and Functional Status scale, McCabe Cold Sensitivity Severity Scale and isolated cold stress testing.⁷

The overall quality of evidence is limited to small cohort studies only, of which only 5 were of prospective study design. Thus, we acknowledge the risk of potential biases in the review process. Aside from the inevitable attrition bias from incomplete outcome data, the absence of any randomised control studies produces a high risk of allocation, selection and reporting bias within the included studies.

Nonetheless, our study provides the basis for further research into sympathectomy surgery. It is possible that relief from vasospastic pain after sympathectomy is temporary or diminishes over time. Of the studies that assessed duration of effect, four studies found that pain relief was effective in all cases at 6 or 12 months postoperatively.^15–18 Another four studies found that pain relief remained effective in only 82–93 % cases at 2–12 years postoperatively.^7,14,19,20 Still, it is the authors' view that even a temporary improvement in symptoms may significantly improve a patients’ quality of life.⁷ Despite a wide-range of mean patient follow-up in our data, from 8 to 120 months after surgery, the durability of symptomatic relief after sympathectomy warrants further consideration.

Similarly, long-term effects on ulceration are unclear. Elshabrawy et al. showed that rates of ulceration improve significantly between and 1 and 6 months postoperatively, alongside absolute digital pressure (mmHg) and oxygen saturations (%).¹⁵ However, Kotsis et al. found that 18 % patients experience recurrence of ulcers and there remains an anecdotal belief that this number may increase with time after surgery.^22,23

Although it is not possible to conclude from the analysis, the success of sympathectomy surgery is likely to be affected by the causative pathologies of digital ischemia. Rates of incomplete ulcer healing were greatest in the context of RP and atherosclerosis/Buerger's, in keeping with the current literature.^3,4 Amputation after sympathectomy, perhaps the greatest indicator of treatment failure, occurred mostly in 41.2 % cases with atherosclerosis/Buerger's as compared to 15.4 % cases with lupus, 10.7 % cases with Scleroderma and 8.6 % cases with Raynaud's, in whom sympathectomy surgery may be safer to perform.

Interestingly, rates of amputation appear to be higher than those observed in the respective comorbid population. For instance, only 4.8 % of patients with Scleroderma undergo digital amputation. This may be due to a greater disease severity or progression, in patients with chronic digital ischemia who undergo sympathectomy.²⁴ Coexistence of multiple such comorbidities further increases this risk.³

Importantly, existing concerns that sympathectomy is associated with increased rates of other complications, after operating on an ischemic surgical site,^17,25,26 are mirrored in this data with 9.1–20.5 % cases suffering delayed wound healing. It would be useful to know, if the risk of complications can be demonstrably reduced by a more proximal surgery, for example. However, although distal sympathectomy was most commonly reported at the common digital artery (CDA), insufficient data were available to compare outcomes according to level and the rationale for this decision was seldom specified.

Further comparisons to the gold standard treatment for chronic digital ischemia refractory to medical management are required. Thibaudeau et al. suggested that microsurgical revascularization is more likely to achieve pain relief, whereas effects on ulceration are comparable between sympathectomy and venous arterialisation.²⁵ However, it is also reported that although symptomatic relief is produced after revascularization, it is not maintained in 26 %–36 % of patients, requiring revision with digital amputation in some cases.^8,27 As such, vascular procedures are rarely being performed on this cohort of patients.³

Other treatments, such as perineurovascular Botulinum toxin injection, are thought to be effective temporising measures.¹⁰ As there is no standard of care at present, the traditional teachings, to let the necrotic digit demarcate and autoamputate, appear to be common practice and patients may be suffering as a result.³

Clearly, there is a scarcity of reliable outcome data following digital sympathectomy surgery. Moreover, the significant heterogeneity among studies in terms of the aetiology of ischemia, patient comorbidities, smoking status, the location and severity of disease, and the specific vessel undergoing sympathectomy, makes comparisons between patient groups challenging. This is a limitation of systematic reviews in general.

Comparative studies with subgroup analysis of outcomes according to diagnosis are required to inform patient selection for distal sympathectomy. Aside from the increased rates of surgical complications in SS, RP and Buerger's for instance, it is also suggested that patients with inflammatory pathologies of the hand, including autoimmune vasculitides or connective tissue disorders, are more likely to benefit from distal sympathectomy,²⁷ as the ischemic vessel is stripped of a more fibrotic and noncompliant adventitia, potentiating the distal microcirculatory effects.^11,13

Consensus is also needed on the optimal extent and anatomical location for sympathectomy surgery. The standardisation of reporting postoperative clinical outcome measures in hand surgery and the use of established classification systems based on the pattern of arterial involvement in the hands of patients with SS may be helpful.²⁸

Use of validated scores should be encouraged to mitigate the subjective nature of symptomatic improvement after sympathectomy and enable objective comparison of data. Patients should have digital ulceration recorded and monitored, with a DUCAS score for instance, combined with an assessment of functional outcome of surgery, such as DASH-JSSH, Hand-20 or MHQ-15, and patient-reported outcome measures.²⁹

We propose that patients in whom sympathectomy is performed are highlighted within a prospective database and a routine set of datapoints recorded in this way, including a minimum of.⁃Demographic data⁃Comorbidity data⁃Pain scores⁃Digital Ulcer scores⁃Functional outcome data

There are various treatment options for patients with chronic hand ischemia, and sympathectomy can be performed in isolation or in combination with these. An algorithmic approach can help determine the best operation for these patients,^25,30 and improvements in available outcome data will inform this treatment algorithm.

Ultimately, our study suggests that distal periarterial sympathectomy may be an effective option for certain patients with refractory digital ischemia. Improvement in pain and ulceration postoperatively is widely reported although amputation remains a risk. High-quality comparative data, with standardization of outcomes, are needed to better inform the surgical management of this heterogeneous cohort of patients.

Guardian/patient's consent

We wish to confirm that this study is a systematic review of the literature and no confidential or identifiable patient data was used and so no patient or guardian consent was required.

Funding statement

We wish to confirm that no funding was received for this work, there has been no significant financial support for this work that could have influenced its outcome and there are no known conflicts of interest associated with this publication.

Ethical Statement for Solid State ionics

Hereby, I Nicholas Cereceda-Monteoliva consciously assure that for the manuscript Number:

JOO-D-23-00534 - Distal periarterial sympathectomy surgery for chronic digital ischemia: a systematic review of the literature - the following is fulfilled.1)This material is the authors' own original work, which has not been previously published elsewhere.2)The paper is not currently being considered for publication elsewhere.3)The paper reflects the authors' own research and analysis in a truthful and complete manner.4)The paper properly credits the meaningful contributions of co-authors and co-researchers.5)The results are appropriately placed in the context of prior and existing research.6)All sources used are properly disclosed (correct citation). Literally copying of text must be indicated as such by using quotation marks and giving proper reference.7)All authors have been personally and actively involved in substantial work leading to the paper, and will take public responsibility for its content.

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CRediT authorship contribution statement

Nicholas Cereceda-Monteoliva: Methodology, data extraction, Writing – original draft. Yat Wing Smart: Writing – review & editing. Elizabeth Ojelade: Writing – review & editing. Gavin Schaller: Conceptualization, data extraction. Onur Berber: Investigation, Supervision, Validation.