Should the internal thoracic artery be skeletonized?

Should the Internal Thoracic Artery Be Skeletonized? Thanos Athanasiou, MD, PhD, Mary-Clare Crossman, MRCS, George Asimakopoulos, FRCS, Ashok Cherian, MD, Arjuna Weerasinghe, FRCS, Brian Glenville, FRCS, and Roberto Casula, FECTS The National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Department of Cardiothoracic Surgery, St Mary’s Hospital, London, United Kingdom

Traditionally, the internal thoracic artery is harvested as a pedicle. In contemporary cardiac surgical practice, however, certain surgeons practice the internal thoracic artery-skeletonization technique. A systematic review of clinical studies reporting on the use of skeletonized internal thoracic arteries (SKT-ITA) has not yet been performed. The primary aim of this review article is to examine comprehensively the entire body of evidence

regarding the use of SKT-ITA. In particular, we aimed to analyze the effects of skeletonization on sternal blood supply, wall damage and blood flow in the harvested vessel, postoperative graft patency, and clinical outcome. Advantages and disadvantages of the skeletonization technique are highlighted and discussed. (Ann Thorac Surg 2004;77:2238 – 46) © 2004 by The Society of Thoracic Surgeons

T

vested vessel, postoperative graft patency, and clinical outcome.

REVIEWS

he left internal thoracic artery (LITA) is widely accepted as a superior conduit in coronary artery bypass (CABG) procedures. More recently, the use of bilateral internal thoracic arterial (BITA) grafts has been demonstrated to be more beneficial in comparison to single internal thoracic artery (ITA) with regard to survival, freedom from repeat angioplasty or reoperation [1, 2]. It has been suggested that revascularization by using BITA specifically on the left coronary system can potentially improve clinical outcome [3, 4]. The most serious objection to the use of BITA has been an increased risk of wound complications [5]. Advocates of ITA skeletonization postulate that this technique reduces sternal devascularization and wound healing problems, and may potentially increase the number of arterial anastomoses per patient by increasing the length of the ITA [6]. Traditionally, most ITA grafts are harvested as a pedicle. The skeletonized internal thoracic artery (SKT-ITA) may be defined as the arterial conduit that has been dissected from all surrounding tissues, the accompanying veins, fascia, lymphatics, adipose tissue, and chest wall. The technique leaves the adventitia as the outer most layer of the harvested conduit. The concept of skeletonization is not new. The technique was more described in detail by Keeley in 1987 [7]. A systematic review of clinical studies reporting on the use of SKT-ITAs has not yet been performed. The primary aim of this review article is to examine comprehensively the entire body of evidence regarding the use of the SKT-ITAs. In particular, we aimed to analyze information related to the effects of skeletonization on sternal blood supply, wall damage and blood flow in the harAddress reprint requests to Dr Athanasiou, Cardiothoracic Surgery, 70 St. Olaf’s Rd, Fulham, London SW6 7DN, UK; e-mail: [email protected].

© 2004 by The Society of Thoracic Surgeons Published by Elsevier Inc

Material and Methods Literature Search A literature search (MEDLINE) of studies reporting on the use of SKT-ITAs, published between 1965 and 2003, was performed. The following keywords were used: “skeletonized internal thoracic artery,” “internal thoracic artery and free flow,” and “bilateral skeletonized internal thoracic arteries.” Internal mammary artery was taken to be synonymous with internal thoracic artery throughout. Articles were also identified by using the function “related articles” in PubMed.

Data Extraction and Validation of the Studies The endpoints of interest were mortality, major inhospital morbidity, long-term follow– up, and angiographic patency following SKT-BITA or LITA harvesting. Studies of SKT-LITA and BITA are tabulated (Tables 1 – 4). Care was taken to avoid inclusion articles reporting on the same patient populations. Studies were excluded when both values (mean and standard deviation of the mean) for the free flow of ITA in each group were not reported or when results involved less than 10 ITAs in either group. The following information was extracted from each study: first author, year of publication, study population characteristics, study design (prospective, randomized, retrospective or other), selection criteria and exclusion criteria, number of patients operated on with each technique, timing of free flow measurement, and method of vasodilating agent used (Table 5). We also assessed the validity of the studies identified taking into consideration the source and the strength of the evidence 0003-4975/04/$30.00 doi:10.1016/j.athoracsur.2003.10.041

Ann Thorac Surg 2004;77:2238 – 46

REVIEW ATHANASIOU ET AL SHOULD THE INTERNAL THORACIC ARTERY BE SKELETONIZED?

2239

Table 1. Mortality and Major Morbidity After Use of Skeletonized BITA Morbidity Cardiac

Author and Reference

Year

Number of SKT-BITA

Operative Mortality

AMI

LCO

Arrythmias

Galbut et al [26]

1990

1087

NR

1996

560

NR

NR

Calafiore et al [6]

1999

842

2003

1000

27 3.2% NR

NR

Pevni et al [28] Kim et al [29]

2002

223

Bonacchi et al [30]

2001

114

Prapas et al [31]

2003

590

Sauvage et al [32]

2003

150

22 2% 17 3% 6 0.7% 10 1% 4 1.8% 4 3% 2 ⬍1% 1 0.8%

NR

Bical et al [27]

29 2.7% 9 1.6% 18 2.1% 34 3.4% 3 1.3% 3 2% 6 1% 4 3.2%

NR

0 0% 5 4% 2 ⬍1% NR

27 12.1% 14 12.7% 88 15% NR

Neurological CVA/TIA

Respiratory ARDS

Renal ARF

Wound SI

20 1.8% 6 1.1% 10 1.2% 12 1.6% 0 0% 2 1% 0 0% NR

35 3.2% 9 1.6% 16 1.9% NR

NR

19 1.7% 6 1.1% 14 1.7% 22 2.2% 3 1.3% 2 1% 1 ⬍1% 9 7.2%

NR

NR 18 2.1% NR

NR

2 0.9% 7 6% NR

NR

NR

NR

Figure 1, squares indicate point estimates of treatment effect (WMD), with the size of the square representing the weight attributed to each study and 95% confidence intervals indicated by horizontal bars. The diamond represents the summary from the pooled studies with 95% confidence intervals. The point estimate is considered statistically significant at the p less than 0.05 level if the 95% confidence interval does not include the vertical bar. Analysis was conducted using the Review Manager, version 4.1 (The Cochrane Collaboration, Software Up-

by using the grading system of the US Preventive Services Task Force [8]. Accordingly, Grade A for strength of the evidence is awarded when there is “good evidence to support the recommendation,” Grade B when there is “fair evidence,” and Grade C when there is “insufficient evidence for or against.”

Statistical Analysis Statistical analysis was carried out by using the weighted mean difference (WMD) as the summary statistic. In Table 2. Mortality and Morbidity After Use of Skeletonized LITA

Morbidity Cardiac

Authors and Reference

Year

Number of SKT-LITA

Operative Mortality

AMI

LCO

Arrythmias

Cohen et al [19]

1999

10

NR

NR

NR

NR

Wendler et al [34]

2001

576

NR

1999

70

NR

Cartier et al [37]

2002

200

Takami et al [36]

2002

45

9 1% 5 7.1% 7 3.4% NR

NR

Deja et al [33]

Higami et al [15]

2001

200

Walpoth et al [35]

1996

10

12 2% 1 1.4% 3 1.5% 0 0% 1 0.5% 0 0%

2 1% 0 0%

Neurological CVA/TIA

Respiratory ARDS

Renal ARF

Wound SI

NR

NR

NR

NR

NR

1 10% 9 1% NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

NR

1

NR

4 2% 0 0%

0 0%

0 0%

1 10% 8 1% 0 0% 2 1% 1 2% 0 0% 0 0%

AMI ⫽ acute myocardial infarction; ARDS ⫽ airway respiratory distress syndrome; ARF ⫽ acute renal failure; CVA ⫽ cerebrovascular event; LCO ⫽ cardiac output; LITA ⫽ left internal thoracic artery; NR ⫽ non-recorded; Operative Mortality ⫽ death within 30 days of operation; SI ⫽ sternal infection; SKT ⫽ skeletonized; TIA ⫽ transient ischemic attack.

REVIEWS

AMI ⫽ acute myocardial infarction; ARDS ⫽ airway respiratory distress syndrome; ARF ⫽ acute renal failure; BITA ⫽ Bilateral Internal Thoracic Artery; CVA ⫽ cerebrovascular event; LCO ⫽ cardiac output; NR ⫽ non-recorded; Operative Mortality ⫽ death within 30 days of operation; SI ⫽ sternal infection; SKT ⫽ skeletonized; TIA ⫽ transient ischemic attack.

REVIEWS

2240

Table 3. Angiographic Patency and Follow-Up After Use of Skeletonized BITA

Author and Reference

Number of Number Patients of Underwent Year SKT-BITA Angiography

Galbut et al [26]

1990

1087

Bical et al [27]

1996

560

104 (19.8%)

Calafiore et al [6]

1999

842

133 (15.8%)

Pevni et al [28]

2003

650

41 (6.3%)

Kim et al [29] 2002 Sauvage et al [32] 2003

223 125

218 (97.7%) 32 (25.6%)

53 (4%)

BITA ⫽ bilateral internal thoracic artery;

Outpatient Follow-Up

Angiographic Patency

Number of Patients Followed Up as Outpatient

Length of Follow-Up (months)

84.9%–92.1% (53 months)

1041

39 (1–17 years)

97.9% (10 days) 95.2% (22 months) 98.2% (⬍30 days) 96.8% (7.6 ⫾ 2.3 months) 95.4% (23 ⫾ 6 months)

540

29 ⫾ 20

822

16.3 ⫾ 11

631

23 ⫾ 6

NR 100%

NR 117.6

98.1%–99% 85%– 87% (7.4 years)

NR ⫽ not recorded;

Event-Free Survival Number of (% asymptomatic Patients Actual patients of those Requiring Survival followed up) Reintervention

Actuarial Survival 80% ⫾ 3.2% (10 years) 60% ⫾ 5% (15 years) NR 96.4% ⫾ 0.8% 94.8% (1 year) 92.5% (3 years) NR 61.6 (10 years)

92.2%

90.6%

16 (1.6%)

95.9%

90.6%

2 (0.36%)

95.4%

95.4%

4 (0.48%)

NR

97.5%

NR 85.6%

NR 85% (9.1 years)

15 (2.3%) NR 109 (90%)

SKT ⫽ skeletonized.

REVIEW ATHANASIOU ET AL SHOULD THE INTERNAL THORACIC ARTERY BE SKELETONIZED?

Postoperative Angiographic Patency

Table 4. Angiographic Patency and Follow-Up After Use of Skeletonized LITA Outpatient Follow-Up

Postoperative Angiographic Patency

Author and Reference

Year

Number of SKT-LITA

Huddleston et al [38] Higami et al [15]

1986 2001

222 200

LITA ⫽ left internal thoracic artery;

Number of Patients Underwent Angiography

Angiographic Patency

222 (100%) 188, 1 month (94%) 20, 1 year (10%)

55.1% (120 months) 99.5% (1 month) 100% (1 year)

NR ⫽ not recorded;

Number of Patients Followed Up as Outpatient

Length of Follow-Up (months)

Actuarial Survival

NR 200

NR 14.8 ⫾ 6.1

NR NR

Actual Survival

Event-Free Survival (% asymptomatic patients of those followed up)

Number of Patients Requiring Reintervention

NR 98%

NR 100%

NR 0 (0%)

SKT ⫽ skeletonized.

Ann Thorac Surg 2004;77:2238 – 46

Ann Thorac Surg 2004;77:2238 – 46

2241

REVIEW ATHANASIOU ET AL SHOULD THE INTERNAL THORACIC ARTERY BE SKELETONIZED?

Table 5. Studies Comparing Free Flow of ITA Harvested as Pedicled Versus Skeletonized Conduit

Author and Reference

Year

PED/SKT Number of Patients

Choi et al [40] Deja et al [33] Noera et al [22]b Walpoth et al [35] Wendler et al [39]

1996 1999 1993 1996 1999

14/23 70/287 15/5 10/10 40/40

Matching Criteriaa

Timing of Free Flow Measurement

Nonrandomized Nonrandomized Nonrandomized Randomized Nonrandomized

2,3,4 1,2,5,6,7 1,2,3 2,5,8 1,2

On CPB, MAP ⫽ 50 –55 mm Hg On CPB On flow 2.2 L*min⫺1*m⫺2 Before CPB On normal SP Before CPB Before CPB MAP ⫽ 70 mm Hg

Spray Soaked swab Spray Soaked swab Intraluminal

Matching criteria: 1 ⫽ age; 2 ⫽ sex; 3 ⫽ body surface area; 4 ⫽ surgeon; 5 ⫽ number of distal anastomoses; 6 ⫽ angina status; 7 ⫽ diabetes; 8 ⫽

weight;

b

Excluded from the meta-analysis.

CPB ⫽ cardiopulmonary bypass; type of study.

MAP ⫽ mean arterial pressure;

PED ⫽ pedicled;

date, Oxford, United Kingdom). Sensitivity analysis was performed by reanalyzing the data using different statistical approaches (eg, using a random effects model instead of a fixed effect model) and by funnel plots to evaluate asymmetry [9].

Internal Thoracic Artery: Anatomy, Physiology and Harvesting Techniqe Anatomy and Physiology of the ITA The ITA originates bilaterally from the inferior aspect of the first part of the subclavian artery. It passes downwards posterior to the brachiocephalic vein and medial to the scalenus anterior muscle. Its further route is lateral to the border of the sternum until the sixth intercostal space where it divides into the superior epigastric and the musculophrenic arteries. The ITA is accompanied by two venae comitantes. It provides collateral blood flow to the sternum by giving off the perforating arteries, that originate from the anterior aspect of the ITA, and connect with the intercostal arteries or by giving off intercostal arteries directly to the sternum. Several anatomic variations of these two main types have been identified [10]. It is reasonable to suggest that harvesting of the ITA is more likely to impair sternal blood supply when this is provided by intercostal arteries arising directly from the ITA.

SKT ⫽ skeletonized;

SP ⫽ systemic pressure;

TOS ⫽

There is, however, absence of clinical proof for this assumption. The layers of the wall of the ITA are common to most vessels: the tunica intima, tunica media, and tunica adventitia. The tunica intima contains endothelial cells resting on a basal lamina. The tunica media consists chiefly of smooth muscle cells and is separated from the tunica intima by the internal elastic lamina. The tunica adventitia gradually becomes continuous with the enveloping connective tissue and contains vasa vasorum and lymphatics. The ITA, however, is not thought to be reliant on vasa vasorum. Luminal diffusion can reach a range of 350 to 600 ␮m [11] and the thickest part of the media measures approximately 150 ␮m. It is likely that the ITA does not suffer if the vasa vasorum are disrupted by skeletonization.

Which Harvesting Technique Should Be Preferred? Harvesting of skeletonized ITA is time consuming and requires higher level of surgical precision in comparison to pedicled conduit [12, 13]. There is a learning curveeffect related to the factor-surgeon. Cautery should be used on a low setting and kept away from the ITA. Exposure of the ITA after standard median sternotomy is by dissection of loose areolar tissue and pleural reflections posterior to the sternum. The vessel is teased away

Fig 1. Meta-analysis of studies comparing free flow of ITA harvested as pedicled or skeletonized conduit. The diamond represents the summary from the pooled studies showing that the weighted mean difference (WMD) of the ITA flow is 32.88 mls/min in favor of the skeletonized in comparison to the pedicled conduit. (CI ⫽ confidence interval; ITA ⫽ internal thoracic arteries; PED-ITA ⫽ pedicled ITA; SD ⫽ standard deviation; SKT-ITA ⫽ skeletonized ITA.)

REVIEWS

a

TOS

Application of Papaverine at the Time of Measurement

2242

REVIEW ATHANASIOU ET AL SHOULD THE INTERNAL THORACIC ARTERY BE SKELETONIZED?

from the chest wall, accompanying veins, fascia, lymphatics and adipose tissue using a cold cautery tip or scissors. Forceps should not touch the ITA directly. Branches are divided between two metallic clips using scissors. Throughout dissection, dilute papaverine is sprayed onto the internal mammary artery to prevent dessication and counteract spasm. Studies detailing the long-term follow-up of patency and outcome after harvesting the SKT-ITA by electrocauterization are lacking. Yoshida and coworkers [14] used light and electron microscopy, in a canine model, to demonstrate that monopolar cauterization was more commonly associated with intimal corrugation as compared with bipolar cauterization. Higami and colleagues [15] described an ultrasonic scalpel method for ITA harvesting. Two hundred patients underwent SKT-ITA harvesting using the ultrasonic scalpel and were examined for early angiographic patency at 1 month. Patency of 99.7% of LITAs and 100% of RITAs was demonstrated. Limited follow-up of 20 patients (34 ITAs) demonstrated 100% patency at 1 year. Bolotin and associates [16] tested the safety of robotic ITA skeletonization in dogs. Skeletonized harvesting technique was not associated with histologic or functional ITA damage although robotically harvested SKT-ITA required more operative time [16].

Data Review HOW DOES SKELETONIZATION AFFECT BLOOD SUPPLY TO THE STER-

REVIEWS

NUM? (EVIDENCE GRADE A). A major factor in wound healing is adequate blood supply. Sternal devascularization following pedicled internal mammary artery harvesting is well documented [17]. It seems that there is a higher risk of damaging the collateral blood supply of the sternum (sternal/intercostal branches, sternal/perforating branches and persistent posterior intercostal artery) when the ITA is harvested as a wide pedicle [10]. Sternal blood supply after skeletonization has been investigated in a few studies. Lorberboym and colleagues [18] and Cohen and coworkers [19] produced similar studies that compared single photon emission computed tomography (SPECT) of two sides of the sternum of patients pre- and post-CABG. Loberboym and colleagues [18] randomized 23 patients in to either pedicled (12 patients) or skeletonized (11 patients) ITA harvesting. Results demonstrated significantly reduced postoperative sternal vascularity after harvesting as a pedicle. Cohen and coworkers [19] randomized LITA harvesting to either skeletonized (11 patients) or pedicled (12 patients) technique and came to similar conclusions. Parish and associates [20] used radioactive microspheres to examine chest wall vascularity after ITA harvesting in a canine model. They found a statistically significant reduction in residual blood flow to the sternum after pedicled harvesting when compared with skeletonized ITA [20].

Ann Thorac Surg 2004;77:2238 – 46

try with light and electron microscopy to study the vessel wall of harvested ITAs and compared the skeletonized technique with a pedicle method. Dissection with low voltage bipolar electrocautery was employed. Examination demonstrated no cases of vessel disruption, dissection or macroscopically detectable thrombosis in either group. Of note however, were two cases of microthrombi adherent to the endothelial layer in the skeletonized group [21]. In 1993, Noera and associates [22] used light microscopy to examine the ITA in 70 patients. Ten of these were skeletonized. No statistically significant difference was found between harvesting techniques although there was a tendency for skeletonized vessels to contain a larger number of lesions in the endothelium, microscopic intimal dissection and detachment and also injuries to the external elastic lamina [22]. Sasajima and coworkers [23] used light and electron microscopy to examine SKT-ITA specimens harvested using bipolar cautery in six dogs. The contralateral ITA was used as a control. Segments of specimens were taken at 3 and 12 weeks. Gross observation demonstrated no injury or deformity after skeletonization and light microscopy revealed no major differences in the vessel wall between control and skeletonized vessels. In a similar study in dogs, Ueda and colleagues [24] demonstrated that the expression of von Willebrand Factor and endothelial nitric oxide synthase, as markers of endothelial damage, was similar in skeletonized and pedicled ITAs. Skeletonization, however, induced more neovascularization in the adventitia [24]. Recently, in a randomized study, Gaudino and associates [25] compared skeletonized and pedicled ITAs in terms of early vasoreactive profile. Pharmacologic stimulation of the ITA was performed during postoperative angiogram on the second postoperative day, using an intraluminal infusion of serotonin and acetylcholine. No differences in vasoactive profile were identified between skeletonized and pedicled ITAs [25]. DOES MORTALITY AND MORBIDITY IMPROVE BY THE USE OF SKT-

The benefits of bilateral internal mammary arterial grafting have been well documented by many studies [1, 2]. With regard to SKTBITAs or SKT-LITAs, short- to mid-term outcome also appears to be similar to those achieved with pedicled BITA or LITA [6, 15, 19, 26 –37]. Tables 1 and 2 demonstrate that postoperative complications, including cardiac complications and sternal wound infections, after use of bilateral skeletonized conduits are consistently low and not offset by any increase in mortality. Only three studies were randomized [19, 30, 35].

BITAS OR LITAS? (EVIDENCE GRADE C).

IS THERE ANY EVIDENCE THAT EARLY AND LATE ANGIOGRAPHIC PATENCY OF SKT-BITAS IS SUPERIOR TO PED-BITAS? (EVIDENCE

DOES SKELETONIZATION CAUSE DAMAGE TO THE HARVESTED ITA? (EVIDENCE GRADE C). Graft failure may be caused by damage

to the vessel wall of the harvested conduit. Such injury may result in thrombus formation and graft occlusion. Gaudino and coworkers [21] used immunohistochemis-

GRADE C). Nine previous publications reported postoperative angiographic findings in patients who underwent CABG with SKT-BITA or LITA (Tables 3 and 4) [6, 15, 26 –29, 32, 38, 39]. Postoperative angiography was performed to investigate suspected recurrence of symptoms

REVIEW ATHANASIOU ET AL SHOULD THE INTERNAL THORACIC ARTERY BE SKELETONIZED?

and included only a small minority of the patients. Figures demonstrated levels of patency that were similar to patency rates for PED-ITA. Survival figures, both actuarial and actual were also satisfactory. The differing lengths of follow-up periods between studies make accurate comparison of the figures difficult. It is worth noting that no prospective randomized trial has been published comparing angiographic patency of SKT-ITA versus PED-ITA. IS THE FREE FLOW OF THE SKELETONIZED ITA SUPERIOR IN COMPAR-

We conducted a meta-analysis of studies including at least 20 patients and measuring free blood flow of the ITA after division (at zero distal resistance) and before the anastomosis to the coronary target [22, 33, 35, 39, 40]. Details of the studies identified are summarized in Table 5. Volume of free flow into a beaker from skeletonized ITA was measured. The results depicted in Figure 1 indicate better free flow from skeletonized vessels as compared with those harvested as a pedicle with a WMD of 32.88, and 95% confidence intervals of 29.51 to 36.25. No significant heterogeneity was identified between studies and funnel plot did not exhibit any asymmetry. Important drawbacks of this meta-analysis was the fact that numbers of patients in each group were not identical and that four out of the five studies were not randomized. In a large retospective study, short-term and long-term outcome of skeletonized and pedicled ITAs were assessed in 814 patients [38]. Findings demonstrated that neither free flow before grafting nor harvesting technique bore any relation to graft patency in the long-term. Two other studies [35, 36] measured intraoperatively transit time flow after grafting was completed. The first study revealed significantly greater intraoperative flow in the SKT group in comparison to the PED group. This difference was not identified in the second study. Further studies with longer-term follow-up would be important additions to the literature in this area.

ISON TO PEDICLED ITA? (EVIDENCE GRADE B).

DOES SKELETONIZATION AFFECT CLINICAL OUTCOME IN DIABETIC PATIENTS? (EVIDENCE GRADE C). CABG is the treatment of choice for coronary artery disease in diabetic patients [41], although the LITA is regarded as the superior graft for long-term function [1]. When both ITAs are used, the risk of sternal wound complications in diabetic patients is increased 4- to 20-fold [42, 43]. Wendler and coworkers [34] investigated 576 patients who underwent complete arterial revascularization using a skeletonized LITA and either RITA or radial artery. Of these patients, 174 were diabetic. Obesity, female sex, triple vessel disease, and impairment of left ventricular function were more frequent in the diabetic group. The incidence of BITA use was similar in the two groups (20% and 21%) and there was no significant difference in mortality or morbidity [44]. In a retrospective analysis, Uva and colleagues [45] examined 207 diabetic patients who underwent either SKT-BITA (n ⫽ 74) or single skeletonized ITA (n ⫽ 133) harvesting. The SKT-BITA group had fewer females,

2243

fewer emergency operations, and younger patients. Perhaps as a result, mortality was statistically greater in the single ITA group. Total numbers of postoperative complications were similar between the two groups. A more recent study by Lev-Ran and associates [46] examined the feasibility of SKT-BITAs in insulin-treated diabetic patients undergoing CABG. The comparison between the two ITAs and one ITA group revealed that sternal wound infection was not significantly higher (4% vs 2.7%) and in a multivariate analysis the use of two ITAs was found to have a protective effect in cardiac related event-free survival. Interpretation of this result is rather problematic because most surgeons would regard an infection sternal wound infection rate of 4% as unacceptable. DOES SKELETONIZATION AFFECT CLINICAL OUTCOME IN THE ELDERLY? (EVIDENCE GRADE C). Kramer and coworkers [47] addressed the question of whether skeletonizing the ITA reduces morbidity in the elderly. This study investigated 303 patients 70 years old and older who underwent CABG using skeletonized BITAs. Mortality of 2.6% and sternal wound infection rate of 2% compared favorably with reported outcomes after single ITA harvesting. Gurevitch and colleagues [48] retrospectively studied the effect of age on outcome in 634 patients undergoing CABG with skeletonized BITA. Older age was not associated with increased mortality or morbidity [48]. DOES SKELETONIZATION AFFECT POSTOPERATIVE RESPIRATORY

Postoperative respiratory complications after CABG have been related to factors such as anesthesia, bypass time, use of ITA and surgical technique. The effect of skeletonized versus pedicled ITA harvesting with or without pleurotomy was addressed by two studies. Bonacchi and associates [30] studied respiratory dysfunction after BITA harvesting. Patients were randomized into the following groups: 82 patients in the skeltonized group with closed pleura, 186 patients in the pedicled group with open pleura, and 31 patients in the skeletonized group with incidentally opened pleura. Postoperative respiratory complications were similar in the groups with open pleura regardless of harvesting technique. Mechanical ventilation time was significantly higher in the groups with pleurotomy. The pedicled group had significantly greater numbers requiring prolonged ventilation, unilateral pleural effusion, postoperative thoracentesis, and atelectasis when compared with the skeletonized group [30]. In a small study Matsumoto and coworkers [49] demonstrated that reduction in forced vital capacity postoperatively was significantly greater after pedicled ITA harvesting. Pleurotomy itself did not appear to affect postoperative forced vital capacity [49].

COMPLICATIONS RATES? (EVIDENCE GRADE C).

EFFECT OF SKELETONIZATION IN POSTOPERATIVE BLOOD LOSS AND

The effect of skeletonization in postoperative blood loss was documented in three comparative studies [6, 30, 37]. All three reported a significant reduction in total blood loss post-

STERNOTOMY-RELATED PAIN (EVIDENCE GRADE C).

REVIEWS

Ann Thorac Surg 2004;77:2238 – 46

2244

REVIEW ATHANASIOU ET AL SHOULD THE INTERNAL THORACIC ARTERY BE SKELETONIZED?

operatively, but only the study by Calafiore and colleagues [6] identified significant reduction in blood transfusion requirements. A beneficial effect of skeletonization on chest pain and analgesia requirements postoperatively was found in two studies [19, 30]. DOES SKELETONIZATION AFFECT MORTALITY AND MORBIDITY IN OFF-PUMP CORONARY ARTERY SURGERY? (EVIDENCE GRADE C). Use of skeletonized vessels in offpump coronary artery bypass (OPCABG) procedures has been investigated in recent reports [29, 31, 37]. Cartier and coworkers [37] studied 440 patients undergoing pedicled ITA harvesting and 200 using skeletonization for OPCAB in a nonrandomized fashion. Groups were comparable for preoperative demographic characteristics except age: skeletonized patients were significantly older. BITAs were harvested more commonly in the skeletonized group (48% vs 27%). Mortality and morbidity were similar between the two groups [37]. Kim and associates [29] studied the use of skeletonized BITAs in OPCAB with different grafting arrangements and also found satisfactory mortality and morbidity rates. Early postoperative patency was 98.1% to 99% [29]. DOES SKELETONIZATION OF THE ITA AFFECT THE INCIDENCE OF POSTOPERATIVE HYPOPERFUSION SYNDROME? (EVIDENCE GRADE C).

REVIEWS

Hypoperfusion syndrome is a rare perioperative clinical condition associated with low cardiac output, left venticular failure, and cardiac arrest. The major pathophysologic factor to ITA hypoperfusion is a disproportion between ITA flow and myocardial demand due to severe venticular hypertrophy [51]. Takami and colleagues [36] reported that intraoperative measurement of flow with a transit-time flow meter is correlated with the diameter of the ITA just proximal to the anastomosis, and can be used as a quality control tool to identify patients at risk to develop this condition. Previously published incidence of use of intraaortic balloon pump perioperatively and of perioperative myocardial infarction (in comparative studies) was comparable between pedicled and skeletonized groups [6, 30, 33–35].

Comment This review article aims to analyze previously published literature concerning the use of the ITA as a skeletonized graft in patients undergoing CABG. Data, sternal blood supply, wall damage, blood flow in the harvested vessel, postoperative graft patency, and clinical outcome after skeletonization, compared with the more commonly used pedicled graft were the outcome points of the review. The performance of skeletonized conduits has been assessed in a number of retrospective trials. There is remarkable shortage of randomized trials investigating, in particular, the effects of LITA skeletonization. This is probably due to the fact that the technique is used only by a minority of surgeons worldwide. Also, most of the key outcome variables of interest (mediastinitis rates, graft patency) would be expected to occur at very low rates, thus necessitating a very large sample for statistical

Ann Thorac Surg 2004;77:2238 – 46

power to be achieved. This would necessitate large multicenter studies. Reduced damage of arterial branches supplying the sternum is one of the theoretical advantages of skeletonization. Careful dissection with scissors or bipolar diathermy is the recommended method of skeletonizing the ITA. With regard to sternal blood supply, studies demonstrated significantly lower sternal vascularity in patients and animals undergoing harvesting of pedicled as compared to skeletonized conduits. There is no evidence, however, that skeletonization is associated with less postoperative sternal wound complications . Quality of the harvested vessel is a further important variable by which the technique of skeletonization should be judged. A small number of human and animal studies reported no significant differences in the number of vessel wall lesions between the two techniques. There is a tendency, however, for skeletonised vessels to develop more vasa vasorum and to manifest microlesions and microthrombi, although the significance of this effect remains unknown. Blood flow of the conduit, both immediately after division of the distal end and after completion of the anastomosis, appears to be better with skeletonization. The mechanism by which skeletonization might improve flow has not been ascertained. One theory is that skeletonization increases graft diameter and, therefore, decreases resistance [36]. Other contributory factors may be that skeletonization facilitates the vasodilating action of papaverine because topical papaverine may reach more of the naked skeletonized internal mammary than when it is hidden in a pedicle. The clinical and experimental studies reviewed above used small numbers of patients, limiting the power of statistical analysis. Despite better early flow, most of the studies reporting on long-term angiographic patency have been performed in small selected patient groups. They demonstrated similar levels of patency between skeletonized and pedicled grafts. It should be noted that there is only one study by Sauvage and coworkers [32] that demonstrates patency rates of 85% to 87% for SKT-ITAs at a mean of 7.4 years of follow-up in a cohort of 125 patients undergoing exclusive ITA grafting, with an impressive average of 3.9 grafts per patient without excluding highrisk patients (diabetics and obese). In this study freedom from reintervention was 90.8% at a mean of 9.8 years. Furthermore, mortality and major morbidity appears to be unaffected by the technique of single or bilateral ITA harvesting, both in low- and high-risk patient groups. One exemption to this finding is postoperative lung function, which was demonstrated to be better after skeletonization in two small randomized trials. Potential advantages of the skeletonized ITA are the increased length and diameter of the available conduit. This may result in a higher number of distal arterial anastomoses performed per patient. It is worth noting, however, that there is no published study measuring objectively length of the ITA before and after skeletonization adjusting for length of the sternum, sex, height, and weight of the patient. Increased length may be useful in two situations. First, it may enable a sequential left ITA

REVIEW ATHANASIOU ET AL SHOULD THE INTERNAL THORACIC ARTERY BE SKELETONIZED?

to be grafted to the left anterior descending and diagonal vessels if indicated. The importance of such an arrangement is suggested by Huddleston and coworkers [38], who propose the choice of conduit and the recipient graft as the two factors that determine long-term patency. Secondly, skeletonization of the right ITA grafting allows it to reach distant target vessels, such as the distal left anterior descending artery in cross-arrangement and the branches of the right coronary artery. This enables complex and complete arterial revascularization [13, 32, 50]. Another potential advantage of skeletonization lies in the improved visualization of length, diameter, and vessel quality that it affords. The pulse of the conduit is also more easily assessed. An important disadvantage of skeletonization is that it comprises a technically demanding surgical technique, which may be time consuming and necessitate retraining. In conclusion, we believe that there is limited published literature on the use of skeletonized ITAs for coronary revascularization. It seems, however, that although skeletonization may be technically demanding with an appreciable learning curve, it is a safe and useful surgical technique for surgeons using the concept of total arterial revascularization. Further research is required to evaluate any effect in postoperative morbidity and longterm angiographic patency.

References 1. Lytle BW, Blackstone EH, Loop FD, et al. Two internal thoracic artery grafts are better than one. J Thorac Cardiovasc Surg 1999;117:855–72. 2. Buxton BF, Komeda M, Fuller JA, Gordon I. Bilateral internal thoracic artery grafting may improve outcome of coronary artery surgery. Risk-adjusted survival. Circulation 1998;98(19 Suppl):II1–6. 3. Schmidt SE, Jones JW, Thornby JI, Miller CC III, Beall AC Jr. Improved survival with multiple left-sided bilateral internal thoracic artery grafts. Ann Thorac Surg 1997;64:9 –14. 4. Calafiore AM, Di Giammarco G. Complete revascularization with three or more arterial conduits. Semin Thorac Cardiovasc Surg 1996;8:15–23. 5. Kouchoukos NT, Wareing TH, Murphy SF, Pelate C, Marshall WG Jr. Risks of bilateral internal mammary artery bypass grafting. Ann Thorac Surg 1990;49:210 –7. 6. Calafiore AM, Vitolla G, Iaco AL, et al. Bilateral internal mammary artery grafting: midterm results of pedicled versus skeletonized conduits. Ann Thorac Surg 1999;67:1637–42. 7. Keeley S. The skeletonized internal mammary artery. Ann Thorac Surg 1987;44:324 –5. 8. Report of the US Preventive Services Task Force. Guide to clinical preventive services. Second edition. Philadelphia: Williams & Wilkins, 1996. 9. Egger M, Smith G, Altman DG. Systematic reviews and healthcare: meta-analysis in context. Annapolis Junction, MD: BMJ Publishing Group, 1995. 10. De Jesus RA, Acland RD. Anatomic study of the collateral blood supply of the sternum. Ann Thorac Surg 1995;59:163–8. 11. Goff SG, Wu HD, Sauvage LR, et al. Differences in reendothelization after balloon catheter removal of endothelial cells, superficial endarterectomy, and deep endarterectomy. J Vasc Surg 1988;7:119 –29. 12. Cunningham JM, Gharavi MA, Fardin R, Meek RA. Considerations in the skeletonization technique of internal artery dissection. Ann Thorac Surg 1992;54:947–50. 13. Gurevitch J, Paz Y, Shapira I, et al. Routine use of bilateral

14.

15.

16. 17. 18.

19.

20. 21. 22.

23. 24.

25. 26. 27. 28.

29.

30.

31.

32.

33.

2245

skeletonized internal mammary arteries for myocardial revascularization. Ann Thorac Surg 1999;68:406 –11. Yoshida H, Wu MH, Kouchi Y, Onuki Y, Shi Q, Sauvage LR. Comparison of the effect of monopolar and and bipolar cauterization on skeletonized, dissected internal thoracic arteries. J Thorac Cardiovasc Surg 1995;110:504 –10. Higami T, Yamashita T, Nohara H, Iwahashi K, Shida T, Ogawa K. Early results of coronary grafting using ultrasonically skeletonized internal thoracic arteries. Ann Thorac Surg 2001;71:1224 –8. Bolotin G, Scott WW Jr, Austin TC, et al. Robotic skeletonizing of the internal thoracic artery: is it safe? Heart Surg Forum 2003;6(Supp 1):S39 –40. Seyfer AE, Shriver CD, Miller TR, Graeber GM. Sternal blood flow after median sternotomy and mobilization of the internal mammary arteries. Surgery 1988;104:899 –904. Lorberboym M, Medalion B, Bder O, Lockman J, Cohen N, Schachner A, Cohen AJ. 99mTc-MDP bone SPECT for the evaluation of sternal ischaemia following internal mammary artery dissection. Nucl Med Commun 2002;23:47–52. Cohen AJ, Lockman J, Lorberboym M, et al. Assessment of sternal vascularity with single photon emission tomography after harvesting of the internal thoracic artery. J Thorac Cardiovasc Surg 1999;118:496 –502. Parish MA, Asai T, Grossi EA, et al. The effects of different techniques of internal mammary artery harvesting on sternal blood flow. J Thorac Cardiovasc Surg 1992;104:1303–7. Gaudino M, Toesca A, Nori SL, Glieca F, Possati G. Effect of skeletonization of the internal thoracic artery on vessel wall integrity. Ann Thorac Surg 1999;68:1623–7. Noera G, Pensa P, Lodi R, Lamarra M, Biagi B, Guelfi P. Influence of different harvesting techniques on the arterial wall of the internal mammary artery graft: a microscopic analysis. Thorac Cardiovasc Surg 1993;41:16 –20. Sasajima T, Wu MH, Shi Q, Hayashida N, Sauvage LR. Effect of skeletonizing dissection on the internal thoracic artery. Ann Thorac Surg 1998;65:1009 –13. Ueda T, Taniguchi S, Kawata T, Mizuguchi K, Nakajima M, Yoshioka A. Does skeletonization compromise the integrity of internal thoracic artery grafts? Ann Thorac Surg 2003;75: 1429 –33. Gaudino M, Trani C, Glieca F, et al. Early vasoreactive profile of skeletonized versus pedicled internal thoracic artery grafts. J Thorac Cardiovasc Surg 2003;125:638 –41. Galbut D, Traad E, Dorman M, et al. Seventeen-year experience with bilateral internal mammary artery grafts. Ann Surg 1990;49:195–201. Bical O, Braunberger E, Fischer M, et al. Bilateral skeletonized mammary artery grafting: experience with 560 consecutive patients. Eur J Cardiothorac Surg 1996;10:971–5. Pevni D, Mohr R, Lev-Run O, et al. Influence of bilateral skeletonized harvesting on occurrence of deep sternal wound infection in 1,000 consecutive patients undergoing bilateral internal thoracic artery grafting. Ann Surg 2003;237: 277–80. Kim KB, Cho KR, Chang WI, Lim C, Ham BM, Kim YL. Bilateral skeletonized internal thoracic artery graftings in off-pump coronary artery bypass: early result of Y versus in situ grafts. Ann Thorac Surg 2002;74:S1371–6. Bonacchi M, Prifti E, Giunti G, Salica A, Frati G, Sani G. Respiratory dysfunction after coronary artery bypass grafting employing bilateral internal mammary arteries: the influence of intact pleura. Eur J Cardiothorac Surg 2001;19: 827–33. Prapas S, Kotsis V, Sidiropoulos A, et al. Morbidity and mortality rates in patients undergoing off-pump coronary surgery without aortic manipulations. Heart Surg Forum 2003;6(Supp1):S32. Sauvage LR, Rosenfeld JG, Roby PV, Gartman DM, Hammond WP, Fisher LD. Internal thoracic artery grafts for the entire heart at a mean of 12 years. Ann Thorac Surg 2003;75: 501–4. Deja MA, Wos S, Golba KS, et al. Intraoperative and labo-

REVIEWS

Ann Thorac Surg 2004;77:2238 – 46

2246

34.

35.

36.

37. 38. 39.

40. 41. 42.

REVIEW ATHANASIOU ET AL SHOULD THE INTERNAL THORACIC ARTERY BE SKELETONIZED?

ratory evaluation of skeletonized versus pedicled internal thoracic artery. Ann Thorac Surg 1999;68:2164 –8. Wendler O, Hennen B, Markwirth T, Nikoloudakis T, Graeter T, Schaefers H. Complete arterial revascularization in the diabetic patient– early postoperative results. Thorac Cardiovasc Surg 2001;49:5–9. Walpoth BH, Monadjer A., Gersbach P, Rogulenko R, Walpoth BN, Althaus U. Intraoperative internal mammary artery transit–flow measurements: comparative evaluation of two surgical pedicle preparation techniques. Eur J Cardiothorac Surg 1996;10:1064 –70. Takami Y, Ina H. Effects of skeletonization on intraoperative flow and anastomosis diameter of internal thoracic arteries in coronary artery bypass grafting. Ann Thorac Surg 2002; 73:1441–5. Cartier R, Leacche M, Couture P. Changing pattern in beating heart operations: use of skeletonized internal thoracic artery. Ann Thorac Surg 2002;74:1548 –52. Huddleston CB, Stoney WS, Alford WC, et al. Internal mammary artery grafts: technical factors influencing patency. Ann Thorac Surg 1986;42:543–9. Wendler O, Tscholl D, Huang Q, Schafers HJ. Free flow capacity of skeletonized versus pedicled internal thoracic artery grafts in coronary artery bypass grafts. Eur J Cardiothorac Surg 1999;15:247–50. Choi JB, Lee SY. Skeletonized and pedicled internal thoracic artery grafts: effect on free flow during bypass. Ann Thorac Surg 1996;61:909 –13. Cosgrove DM, Lytle BW, Loop FD, et al. Does bilateral internal mammary grafting increase the surgical risk? J Thorac Cardiovasc Surg 1988;95:850 –6. Brooks MM, Jones RH, Bach RG, et al. Predictors of mortality and mortality from cardiac causes in the bypass angioplasty

43. 44.

45. 46. 47. 48. 49. 50. 51.

Ann Thorac Surg 2004;77:2238 – 46

revascularization investigation (BARI) randomized trial and registry. For the BARI Investigators. Circulation 2000;101: 2682–9. Grossi EA, Esposito R, Harris LJ, et al. Sternal wound infection and use of internal mammary artery grafts. J Thorac Cardiovasc Surg 1991;102:342–6. Wendler O, Landwehr P, Bandner-Risch D, Georg T, Schafers HJ. Vasoreactivity of arterial grafts in the patient with diabetes mellitus: investigations on internal thoracic artery and radial artery conduits. Eur J Cardiothorac Surg 2001;20: 305–11. Uva MS, Braunberger E, Fisher M, et al. Does bilateral internal thoracic grafting increase surgical risk in diabetic patients? Ann Thorac Surg 1998;65:2051–5. Lev-Ran O, Mohr R, Amir K, et al. Bilateral internal thoracic artery grafting in insulin-treated diabetics: should it be avoided? Ann Thorac Surg 2003;75:1872–7. Kramer A, Mastsa M, Paz Y, et al. Bilateral skeletonized internal thoracic artery grafting in 303 patients seventy years and older. J Thorac Cardiovasc Surg 2000;120:290 –7. Gurevitch J, Matsa M, Paz Y, et al. Effect of age on outcome of bilateral skeletonized internal thoracic artery grafting. Ann Thorac Surg 2001;71:549 –54. Matsumoto M, Konishi Y, Miwa S, Minakata K. Effect of different methods of internal thoracic harvest on pulnonary function. Ann Thorac Surg 1997;63:653–5. Prapas SN, Anagnostopoulos CE, Kotsis VN, et al. A new pattern for using both thoracic arteries to revascularize the entire heart: the pi-graft. Ann Thorac Surg 2002;73:1990 –2. Jones EL, Lattouf OM, Weintraub WS. Catastrophic consequences of internal mammary artery hypoperfusion. J Thorac Cardiovasc Surg 1989;98:902–7.

REVIEWS