REVIEW ARTICLE

An Analysis of Current Techniques Used for Intraoperative Flap Evaluation Robert F. Lohman, MD, MBA, FACS,* Cemile Nurdan Ozturk, MD,* Can Ozturk, MD,* Vijayvel Jayaprakash, MBBS, PhD,* and Risal Djohan, MDÞ Background: Over the last decade, microsurgeons have used a greater variety of more complex f laps. At the same time, microsurgeons have also become more interested in technology, such as indocyanine green (ICG) angiography, dynamic infrared thermography (DIRT), and photospectrometry, for preoperative planning and postoperative monitoring. These technologies are now migrating into the operating room, and are used to optimize f lap design and to identify areas of hypoperfusion or problems with the anastomoses. Although relatively more has been published about ICG angiography, information is generally lacking about the intraoperative role of these techniques. Methods: A systematic analysis of articles discussing intraoperative ICG angiography, DIRT, and photospectrometry was performed to better define the sensitivity, specificity, expected outcomes, and potential complications associated with these techniques. Results: For intraoperative ICG angiography, the sensitivity was 90.9% (95% CI: 77.5Y100) and the accuracy was 98.6% (95% CI: 97.6Y99.7). The sensitivity of DIRTwas 33% (95% CI: 11.3Y64.6), the specificity was 100% (95% CI: 84.9Y100), and the accuracy was 80% (95% CI: 71.2Y89.7). The sensitivity of intraoperative photospectrometry was 92% (95% CI: 72.4Y98.6), the specificity was 100% (95% CI: 98.8Y100), and the accuracy was also 100% (95% CI: 98.7Y100). Conclusion: These technologies for intraoperative perfusion assessment have the potential to provide objective data that may improve decisions about f lap design and the quality of microvascular anastomoses. However, more work is needed to clearly document their value. Key Words: flap, perfusion, indocyanine green, photospectrometry, thermography (Ann Plast Surg 2015;75: 679Y685)

T

here has been a paradigm shift in reconstructive microsurgery that embraces complexity. Operations involving perforator flaps, chimeric flaps, and even cadaveric donors1,2 are becoming more common. This transition brings an increasing number of donor sites with more anatomic variability, and frequently requires dissection of smaller and more fragile blood vessels. Preoperative imaging can provide information about many anatomic details, including the number, size, and location of vessels supplying a flap. In some circumstances, such as breast reconstruction with perforator flaps, preoperative imaging is now standard.3Y10 After surgery, some form of adjunctive technology is usually employed for flap monitoring, and evidence is emerging that this practice can reduce costs and complications.11Y13 Although preoperative imaging can produce a vascular road map for f lap planning, it does not provide physiologic information,

Received January 24, 2014, and accepted for publication, after revision, March 22, 2014. From the *Department of Head, Neck & Plastic Surgery, Roswell Park Cancer Institute, State University of New York, Buffalo, NY; and †Department of Plastic Surgery, Cleveland Clinic, Cleveland, OH. Conflicts of interest and sources of funding: none declared. Reprints: Robert Lohman, MD, MBA, FACS, Department of Head, Neck & Plastic Surgery, Roswell Park Cancer Institute, State University of New York, Elm & Carlton Streets, Buffalo, NY 14263. E-mail: [email protected]. Copyright * 2014 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/15/7506-0679 DOI: 10.1097/SAP.0000000000000235

Annals of Plastic Surgery

and physiologic information is critical for many intraoperative decisions. For example, when preparing a vascularized fibula bone graft, it can be difficult to find the ideal position of the skin paddle. Doppler or other preoperative studies can be used to locate perforators under the skin, but these techniques often do not allow the surgeon to identify the dominant perforator, nor do they allow the surgeon to know how much skin is actually supplied by a given perforator.14 Physiologic information is also useful when there are alternative perfusion patterns for a f lap. Armed with only preoperative imaging studies, it is difficult to know what portions of the abdomen the superficial inferior epigastric vessels supply compared to the deep inferior epigastric vessels. On the other hand, the vascular territories of the superficial and deep inferior epigastric vessels can be readily defined using intraoperative perfusion studies.15 Furthermore, patterns of f lap perfusion are dynamic and can change for a variety of reasons including manipulation during dissection, inadvertent injury, vessel spasm, and thrombus. Lastly, blood f low to the f lap at the donor site may be quite different than blood f low to the f lap after it has been transferred to the recipient site. For all these reasons, perfusion studies performed at several stages during surgery can be more valuable than a single imaging study performed before surgery.16 Over the past 20 years, many systems capable of dynamic tissue evaluation have emerged. As initially designed, none were intended for use in reconstructive surgery. However, after seeing them at work in other specialties, plastic surgeons adapted these devices to serve their own needs. Three are now commercially available and frequently used in plastic surgery: indocyanine green (ICG) angiography, photospectrometry to measure composite tissue oxygen saturation (StO2), and dynamic infrared thermography (DIRT). Although there is a growing literature about these technologies for preoperative imaging and postoperative monitoring, very little has been published about their use during surgery. As a result, there is a paucity of information about how they can help with intraoperative decision-making. The indications for intraoperative perfusion studies have not been defined, nor and is much known about the relative risks and expected benefits of each method. The purpose of this article is to combine the data from authors who have used intraoperative ICG angiography, photospectrometry, or DIRT in an effort to open a dialog about these questions.

MATERIALS AND METHODS An online literature review was performed by searching the databases of the National Library of Medicine (PubMed) and Ovid MEDLINE. The following search terms were used: ‘‘f lap perfusion’’, ‘‘perforator f lap’’, ‘‘intraoperative’’, ‘‘free f lap’’, ‘‘microvascular’’ in combination with ‘‘imaging’’, ‘‘indocyanine green’’, ‘‘thermography’’, ‘‘photospectrometry’’, ‘‘tissue oximetry’’, and ‘‘near infrared spectrophotometry’’. The search was limited to clinical studies published in English. References from selected articles were also reviewed, although none were eventually included in the analysis. Data from the selected publications were used to calculate sensitivity, specificity, accuracy, and the rates of intraoperative anastomotic revision, flap necrosis, and reexploration. Because we were interested in assessing the value of intraoperative perfusion studies, data regarding flap monitoring after surgery was not used in the analysis.

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Only studies that included at least 5 f laps were used for the analysis. The 95% confidence intervals for the estimates were calculated using the efficient-score method, with continuity correction.17 Meta-analysis was then conducted using the estimates calculated, and the results for sensitivity and accuracy of intraoperative ICG imaging are presented as Forest Plots in Figures 1 and 2. We explored the heterogeneity between study specific results using the Q statistic at the significance level of P = 0.05. Both fixed and random effects models were used to obtain estimates; fixed effects estimates are presented as the studies did not show significant heterogeneity. For the studies that reported estimates of 0 and 100%, meta-analyses were conducted by adjusting the estimates by T1%. For estimates derived from very few studies, or when most of the component studies reported estimates of 0 or 100%, a meta-analysis was not feasible. This was the case for the specificity of intraoperative ICG imaging and all of the data about DIRT and photospectrometry. It was also not possible to calculate Q statistics for these studies. Therefore, pooled summary estimates are presented. STATA V.11 software was used for this analysis. Sensitivity, specificity, and accuracy were calculated from the results of intraoperative ICG imaging, photospectrometry, and DIRT testing used to help with perforator selection, location of the skin paddle, insetting, or other details related to flap design. Patient outcomes were separated into 2 clinically identifiable categories: uneventful healing and complications related to inadequate perfusion. The later category included the following events: partial flap necrosis requiring another operation, total flap necrosis, the need for unplanned revision at the time of the initial operation, including revision of the vascular anastomoses, excision of inadequately perfused areas, or adjustments in how the flap was inset. True negative was defined as a normal result after testing with ICG imaging, photospectrometry, or DIRT in a patient that had uneventful healing; false negative was defined as a normal test result in a patient that developed an early complication. True positive was defined as a positive test result in a patient that developed an early complication, and false positive was defined as a positive test in a patient that had uneventful healing. Re-exploration rates after surgery are also reported, but this event was not used as an outcome for calculating sensitivity, specificity, or accuracy.

RESULTS A total of 65 potentially relevant articles was identified by computer search. Another 77 potential component articles were identified by a hand search, primarily by reviewing the references of the initial 65 articles. After screening, 60 full-text articles were assessed in detail and 22 were used for the qualitative analysis while 19 were used for the quantitative analysis. A PRISMA f low chart is presented in Figure 3.18 A summary of the findings from the component articles is shown in Table 1.

Fluorescent Angiography With Indocyanine Green ICG angiography was first used by ophthalmologists and later adapted to monitor free flaps.19 Bolus doses of ICG are injected through

FIGURE 1. Forrest plot for sensitivity of ICG imaging. 680

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FIGURE 2. Forrest plot for accuracy of ICG imaging.

a peripheral vein, and at the area of interest the ICG is excited by an overhead light source (most commonly near-infrared laser or lightemitting diodes). The resulting cinegraphic image is displayed on a video monitor.20 Multiple injections, up to a maximal dose of 5 mg/kg, are possible.21Y24 Typically, the dye appears in the arterioles of the flap 10 to 20 seconds after injection; maximal fluorescence is seen in at 15 to 30 seconds, and the plasma half life is 3 to 4 minutes.16,19,22,25 Because ICG binds tightly to plasma proteins, it usually does not appear in extravascular tissue. ICG imaging effectively highlights vessels 3 to 5 mm under the tissue surface.19 Perforators appear as a ‘‘fluorescent blush’’ whereas ischemic areas are relatively dark. The raw image is displayed as a gray scale, but proprietary software can be used to add color and calculate contrast-to-background ratios. ICG imaging has been used to evaluate a variety of flaps, including skin, muscle, fascia, and bone.19,21,24,26Y29 There are several ways ICG imaging can be used during surgery.21,24,29Y37 Sacks et al used it to ensure that the skin paddle was centered over the most robust perforators in a series of anterior lateral thigh f laps.32 The authors thought this technique was more precise than using a handheld Doppler and might limit the need to explore multiple perforators, therefore reducing donor-site morbidity. Lee et al carried out a pilot study to determine if intraoperative ICG imaging could be used to facilitate preparation of perforator f laps.33 They noted that background f luorescence increased after repeated and larger doses of ICG, and as the background-to-contrast ratio diminished, the target vessels were somewhat obscured. Also, contrast in the selected perforators increased as surrounding perforators were ligated, illustrating that regional f low within a f lap changes as dissection proceeds. According to the study design, the surgeons were blinded to the imaging results, and in 2 of the 6 patients, the surgeons selected perforators that did not have the highest degree of contrast. This finding indicates that even experienced surgeons may have difficulty identifying the most robust perforators without some form of objective data. Holm’s group studied 25 patients and found that ICG imaging could be used to determine the vascular territories of the deep and superficial epigastric vessels.15 They point out that it is difficult to predict what tissue is supplied by each of these vessels based on preoperative imaging and clinical judgment, which may contribute to the fat necrosis commonly associated with these f laps. Holm et al preferentially select the superficial inferior epigastric artery (SIEA) flap for breast reconstruction, and ICG imaging enabled them to reliably predict if that flap would be large enough, or if a deep inferior epigastric perforator (DIEP) flap should be used instead. The results of intraoperative ICG imaging led them to change the operative plan and select a different flap in 11 (44%) of their patients. By using data from ICG studies to help with decisions about flap size and pedicle choice, partial flap necrosis became a rare event, occurring in only 1 patient (4%). Pestana et al used intraoperative ICG imaging in 29 selected flaps with a mixture of donor and recipient sites.24 They point out ischemic areas of a flap are difficult to recognize, even for experienced surgeons. The handheld Doppler, which is the most common tool for evaluating flaps during surgery, is not necessarily useful to differentiate between * 2014 Wolters Kluwer Health, Inc. All rights reserved.

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Intraoperative Flap Evaluation

FIGURE 3. PRISMA f low chart from component studies.

critically ischemic and healthy tissue. On the other hand, they found that it was not difficult to identify ischemic areas using ICG. Furthermore, it ‘‘added minimal additional time’’ to the operation and caused no complications. Partial necrosis occurred in 2 flaps (6.9%). In one of these f laps, ICG imaging identified the area of ischemia, but the surgeon decided not to excise it. In at least 4 other patients, ischemic areas were identified and excised before the flaps were inset, and all these patients healed uneventfully. They also encountered a situation where they considered revising an anastomosis because the venous Doppler signal was absent. However, ICG imaging demonstrated the anastomosis was patent, so revision was not performed and this f lap healed uneventfully. There were 11 articles from 9 different lead authors describing intraoperative ICG imaging used for the quantitative analysis.15,23Y25,29,31,32,34,35,38,39 A total of 244 patients and 253 f laps were evaluated. No complications were specifically caused by ICG imaging. Employing meta-analysis techniques, data from 5 articles could be used to estimate sensitivity: 90.9% (95% CI: 77.5Y100) with a P value for heterogeneity of 0.93 (Q = 0.79) (Fig. 1). Data from 10 articles was adequate to calculate accuracy: 98.6% (95% CI: 97.6Y99.7), with a P value for heterogeneity of 0.77 (Q = 5.75) (Fig. 2). It was not possible to use meta-analysis techniques to estimate the specificity of intraoperative ICG imaging because 9 of the 10 studies with adequate data reported a specificity of 100%,15,23Y25,29,31,32,35,39 and one study reported a specificity of 94.9%.38 Therefore, a pooled summary estimate was calculated: 98.6% (95% CI: 94.5Y99.8). Using pooled data from the studies involving more than 5 f laps,15,23Y25,29,31,32,34,35,38,39 the rate the rate of re-exploration was 11.1% (95% CI: 7.4Y16.3). Interestingly, all of the instances of reexploration occurred in series published before 2010. For series published since 2010, the rate of re-exploration has been 0%. Also from the pooled data, the rate of intraoperative revision because of a positive ICG study was 13.3% (95% CI: 9.1Y18.5). Of these 26 f laps, 24 (92%) were salvaged without complications and 2 (8.3%) were * 2014 Wolters Kluwer Health, Inc. All rights reserved.

lost to total necrosis. There were also 9 instances when the surgeon took no action despite a positive angiogram (abnormalities at the anastomoses or filling defect in the f laps). This situation resulted in a complication rate of at least 89% including 6 episodes of partial f lap loss and 2 episodes of total f lap loss (there were incomplete details about the outcome of one these f laps). There were 146 negative angiograms that resulted in 8 instances of f lap necrosis, and several of these episodes appeared to be related to late compression of the pedicle by hematomas. The pooled rate of total flap loss when intraoperative ICG imaging was utilized was 5.1% (95% CI: 2.8Y9.1). Seven authors concluded intraoperative ICG imaging was potentially valuable, three did not comment on this issue, and one recommended additional studies.

Dynamic Infrared Thermography Infrared thermography uses a heat-sensing camera is used to generate a color-coded image of a flap. Warmer regions are coded red and correlate with areas of higher blood flow, whereas blue represents areas of reduced blood flow. ‘‘Hot spots’’ correspond to larger vessels and superficial perforators.40,41 Thermography is most commonly used for flaps that include a skin island, but it can be used for any flap accessible for imaging.40 The pattern of tissue rewarming closely correlates with underlying blood flow, and with dynamic thermography, a flap is imaged as it rewarms.42,43 Rewarming occurs after a flap has been transferred and is reperfused, or in the setting of a thermal challenge, which involves transiently cooling the flap using a fan or a metal plate.43 If the entire flap fails to rewarm, or if starts to cool after it has been reperfused, there may be a problem with arterial flow.40 Specific regions of the flap that fail to rewarm are ischemic, which may be the result of intra-flap emboli or inadequate perforators. With venous insufficiency, rewarming may occur but hot spots fail to appear. DIRT is a reliable way to detect perfusion problems,40,43Y46 and intraoperative studies can be used to facilitate flap design.41,43,46Y50 Several www.annalsplasticsurgery.com

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TABLE 1. Summary of Data From the Component Studies Author

N

ICG angiography Mothes 2004 11 Holm 2006 17 Holm 2008 25 Holm 2009 50 Pestana 2009 29 Newman 2009 10 Mohbali 2010 18 Francisco 2010 5 Komorowska 2010 6 Ida 2012 12 Sacks 2012 15 Dynamic infrared thermography Salmi 1995 8 De Weerd 2006 10 De Weerd 2009 20 De Weerd 2009 27 Near-infrared spectrometry Colwell 2008 7 Keller 2009 208 Holzle 2010 166 Steele 2011 75

Sensitivity

Specificity

Accuracy

Inraop Revision

Re-exploration

Flap Loss

100% n/r 91.2% 81.8% 83.3% 100% n/a n/a n/a n/a n/a

100% n/r 100% 94.9% 100% 100% 100% 100% 100% 100% 100%

100% n/r 96.9% 92% 96.9% 100% 100% 100% 100% 100% 93.3%

54.5% n/r 44.0% 6.0% 13.8% 20.0% 0% n/r n/r 0% 0%

54.5% 0% 12.0% 18.0% 10.3% 10.0% 0% 0% 0% 0% 0%

18.2% 0% 0% 14.0% 0% 0% 0% 0% 0% 0% 6.7%

n/a 100% n/a n/a

n/a 100% 100% 100%

n/a 100% 76.2% 62.5%

0% 40.0% 0% 0%

0% 0% 0% 0%

0% 20.0% 0% 0%

n/a 60% 100% 100%

100% 100% 100% 100%

100% 99.0% 100% 100%

0% 1.4% n/r 2.7%

0% 3.8% 7.2% 4.0%

0% 0% 3.6% 1.3%

n/a, not possible to calculate because the denominator is 0; n/r, not possible to calculate because insufficient data was reported.

authors have reported that hot spots correlate with the location of perforators identified by Doppler.44Y46,51 DIRT more accurately identifies the location of perforators immediately under the skin, whereas Doppler studies more accurately identifies where perforators pierce the muscular fascia. De Weerd et al investigated 27 DIEP and SIEA flaps and found that the perforator selected using DIRT was always one of the dominant perforators identified during surgery.49 They concluded that thermography allows for a qualitative assessment of perforators and facilitates flap design. There were 4 articles involving more than 5 f laps from 2 different lead authors about intraoperative DIRT.41,44,45,49 A total of 65 patients and 65 f laps were evaluated with no complications specifically caused by DIRT. The small number of component studies precludes the use meta-analysis techniques to estimate sensitivity, specificity, and accuracy. Using pooled data, the sensitivity of DIRT was 33% (95% CI: 11.3Y64.6), the specificity was 100% (95% CI: 84.9Y100) and the accuracy was 80% (95% CI: 71.2Y89.7). Also from the pooled data, the rate of re-exploration was 0%. There were 4 positive results (all from one study) and all of them lead to immediate revision; 2 (50%) of these f laps were salvaged without complications and 2 (50%) were lost to total necrosis. There were no episodes of f lap loss associated with negative studies and the overall rate of f lap loss was 3.1% (95% CI: 0.8Y10.4). Two authors concluded intraoperative DIRT was valuable, one did not comment on this issue, and one suggested further research.

Photospectrometry Photospectrometry employs a light-emitting sensor to measure StO2, which correlates closely with perfusion.52Y58 A portion of the light is absorbed, primarily by hemoglobin, and some is ref lected back to the sensor. Because the absorption characteristics of hemoglobin vary with the degree of oxygenation, the difference between the intensity of emitted light and that which is ref lected back to the sensor can be used to calculate StO2.52,56,59Y61 Photons can visit tissue (including capillaries, smaller vessels, and extravascular tissue) 682

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up to 20 mm below the sensor, but a depth of 2 to 5 mm is more common. Photospectrometry measures the hemoglobin saturation of all tissue immediately under the probe, and is usually less than capillary oxygen saturation (as measured by pulse oximetry) and can vary from one tissue type to another. Furthermore, isolated spot readings are difficult to interpret, and multiple readings over 20 to 30 minutes, especially when compared to baseline values, are preferable. Photospectrometry is commonly used for f lap monitoring,4,11,13,58,60,62Y70 but some authors have described intraoperative applications.60,62Y64,67 StO2 usually returns to baseline about 5 minutes after the f lap is reperfused at the recipient site. This may be followed by a period of hyperemia, lasting up to 3 days.60,62Y64,67 However, if StO2 is more than 20% to 30% below baseline after the microvascular anastomoses are complete, there is a risk of pending arterial thrombosis, as described by Keller.64 Keller was not as confident that StO2 could be used to identify pending venous thrombosis. He described 1 patient with a DIEP f lap congested because of venous insufficiency (despite a patent anastomosis) without a diminished StO2. The appearance of the f lap improved after the superficial epigastric vein was also anastomosed to the mammary vein to facilitate drainage.67 He postulated that changes in StO2 resulting from venous insufficiency might develop too slowly to be recognized in the operating room. However, it is impossible to know what would have happened to this f lap without the second venous anastomosis. With time, f low through the deep vein may have improved, resolving the congestion. Holzle et al used photospectrometry in combination with laser Doppler to evaluate f laps during surgery.62 They describe 7 f laps with clinical evidence of venous congestion (‘‘bluish color and accelerated capillary refill’’) but only a slight fall in StO2. These cases were managed expectantly and recovered with no complications. As with Keller, they believed changes in StO2 were more closely linked to arterial complications than venous complications. Our search identified 4 articles, with consecutive patients entered prospectively, describing intraoperative photospectrometry in * 2014 Wolters Kluwer Health, Inc. All rights reserved.

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377 patients with 456 flaps.62Y64,66 There were no complications caused by the monitoring system. Keller and Colwell used near-infrared systems and Holzle used an LED system. All the authors used StO2 data to identify potential problems with the microvascular anastomoses, but none specifically described using StO2 to identify poorly perfused areas of their flaps. Most of the patients in these series had perforator f laps for breast reconstruction. As with DIRT, the low number of component studies precluded the use of standard meta-analysis techniques, thus the following estimates are based on pooled data. The sensitivity of intraoperative photospectrometry was 92% (95% CI: 72.4Y98.6), the specificity was 100% (95% CI: 98.8Y100), and the accuracy was also 100% (95% CI: 98.7Y100). It was necessary to re-explore 5.0% (95% CI: 3.4Y7.5) of the flaps and 2.2% (95% CI: 1.2Y3.9) were lost to necrosis.

DISCUSSION Microsurgery is safer and more predictable because of advances in technology that help with preoperative planning and postoperative monitoring.6,8,9,71Y79 However, a surgeon’s intraoperative decisions are probably more important to the outcome of free tissue transfer, and very little objective data is available during surgery to help validate those decisions. For example, it can be difficult to predict how many perforators should be included with a f lap and which perforators are most robust; it can also be difficult to recognize ischemic areas of a f lap. Furthermore, patterns of blood f low change during dissection and transfer of a f lap. Traditionally, surgeons relied on experience, the f lap’s physical appearance (capillary refill, skin color, and bleeding from the f lap edges, etc.), and the handheld Doppler to support their decisions.3 With this approach, it is easy to select the wrong perforator, to misjudge the patency of anastomoses, and to include ischemic tissue in the f lap. When surgeons realized that the technology for preoperative imaging and postoperative monitoring could also provide quantitative data in real time about flap perfusion, they began to adapt some of these technologies for use during surgery. Recognizing the demand, industry started to supply technology for intraoperative functional perfusion assessment, which has been championed by a small cadre of early adopter surgeons. As they improve, intraoperative perfusion tools will probably be used more commonly. Presently, the indications for these systems and their sensitivity and specificity have not been defined, and it is not clear if they have any effect on outcomes such as flap necrosis, re-exploration rates, or cost. Intraoperative analysis of flap perfusion seems to be helpful for designing flaps and selecting perforators; however, it is not clear if it can be used to predict events such as partial flap necrosis or anastomotic thrombosis. Finally, it is not known if one technique has advantages or disadvantages relative to the others. Currently, there is not a large body of evidence, and none of it from level one studies, supporting any of the 3 methods we evaluated. The primary advantage of ICG imaging is its versatility: the entire f lap can be mapped so that perforators, potentially ischemic areas, and problems with the anastomoses can be easily identified.21,22,39,80 Authors reported adjusting the position of skin islands relative to ICG localized perforators, defining the extent of specific vascular territories, and, if needed, discarding ischemic tissue before f laps were inset. On the other hand, authors reported using DIRT to identify perforators and problems with the microvascular anastomoses, whereas StO2 measurements were only employed to identify occult problems at the anastomoses. It is not clear whether DIRT and photospectrometry are less useful for differentiating between wellperfused and ischemic tissue or if the authors had other reasons for utilizing the technologies differently. The primary disadvantages of ICG imaging are that the system is cumbersome to use, is expensive, and each new set of images requires additional f luorescent dye. Dynamic infrared thermography was studied in the fewest patients, and the equipment for this system is not widely available. Interpretation of rewarming patterns is subjective and requires * 2014 Wolters Kluwer Health, Inc. All rights reserved.

Intraoperative Flap Evaluation

experience. Furthermore, identification of the hot spots may require repeated cold challenges, and multiple different scans can be time consuming. It is also possible to mistake perforators for superficial veins and other areas with sluggish f low that retain heat.44,46 One important benefit of DIRT is that the system is less costly than the others. Overall, DIRT was the least sensitive of the 3 methods for predicting overall complications, but it was 100% sensitive for anastomotic problems. With intraoperative DIRT, the rate of reexploration was 0%, but 12.1% of all f laps were complicated by some degree of necrosis. Four different teams used photospectrometry for intraoperative StO2 sampling in 456 f laps. Photospectrometry is typically used for monitoring because a reduction in StO2 relative to the baseline value closely correlates with anastomotic problems. However, by sampling from multiple areas of a f lap, it is possible to create a perfusion map. Because StO2 responds rapidly to changes in blood f low, the map adjusts to changes in blood f low that occur during dissection and transfer of a f lap in real time. The primary advantages of photospectrometry are that it is reliable, quick, and simple to use. If StO2 monitoring is planned after surgery, the addition of intraoperative assessment adds nothing to the marginal cost of the operation. Except for very low numbers, a single StO2 measurement is generally not useful, whereas a series of StO2 readings over 20 to 30 minutes yields more information about f lap perfusion. However, StO2 values can f luctuate in both time and space as a result of noise, which can be difficult to separate from meaningful signals in the values. Interpretation of these values requires some experience,11,66Y68,81Y83 but the sensitivity and specificity of the technique appears to be very high. The ideal tool for intraoperative f lap assessment should produce objective data that can be used to generate an easily interpreted perfusion map, so that it is possible to differentiate between areas of local ischemia and problems with blood f low at the pedicle; it should respond rapidly to changes in blood flow, and it should be possible to collect data from a large area of tissue over a short time span. Furthermore, setup time should be minimal and the device should also be safe and inexpensive. None of the currently available methods satisfy all of these criteria. Nonetheless, there is considerable enthusiasm for intraoperative flap assessment: of the 24 papers included in our analysis, 17 (71%) endorsed intraoperative monitoring or recommended further studies. Table 2 outlines the attributes of each method. The greatest obstacle to preparation of this analysis was the low number of high-quality component studies. This forced us to pool data from articles about DIRT and photospectrometry rather than using standard methods of meta-analysis. It is also possible that unrecognized heterogeneity may have skewed the data from the component studies for these 2 techniques. The low number of component studies also means the calculations presented here may not be very precise, and this is ref lected by the wide 95% CIs. As more data become available, the estimates of sensitivity, specificity, and accuracy can be refined. This effort will allow the discussion of intraoperative perfusion technology to shift away from expert opinion and move toward numeric analysis. To facilitate this change, microsurgeons are encouraged to publish their experience with these techniques, especially with respect to indications, costs, and complication rates.

CONCLUSIONS Intraoperative perfusion assessment allows the surgeon to adjust how a f lap is designed and inset, and to judge the quality of the anastomoses in real time, using objective data rather than subjective impressions. Early data indicate that sensitivity and specificity of these technologies is high, and the available literature suggests that these systems are useful to facilitate intraoperative f lap planning, dissection, and inset. However, there is insufficient data to confidently say that they can reduce complications and costs associated www.annalsplasticsurgery.com

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TABLE 2. A Comparison of the Attributes of Indocyanine Green Angiography, Photospectrometry, and Dynamic Infrared Thermography Attribute

Indocyanine Green Angiography

Dynamic Infrared Thermography

Photospectrometry

Yes +++ + + +++ 250,000† $600/dose of dye

No + ++ + + $8,000Y$20,000 None

No ++ ++ ++ ++ Provided at no charge $1,200/probe

Requires drug injection Directly assesses perfusion Time consuming Ease of use Cost* Hardware Disposables

*Costs are approximate and vary depending on the supplier and hospital. †The supplier typically charges for either the hardware of the disposable supplies.

with microvascular surgery. No head-to-head studies compare one technique to another. Furthermore, the devices are not universally available, and they can be expensive and cumbersome to use. Thus, there is substantial room for improvement. Surgeons can contribute to this process by documenting how intraoperative perfusion assessment is used and how it impacts outcomes. REFERENCES 1. Petruzzo P, Dubernard J-M. The International Registry on Hand and Composite Tissue allotransplantation. Clin Transpl. 2011;247Y253. 2. Siemionow M, Ozturk C. An update on facial transplantation cases performed between 2005 and 2010. Plast Reconstr Surg. 2011;128:707eY20e. 3. Nahabedian M-Y. Overview of perforator imaging and flap perfusion technologies. Clin Plast Surg. 2011;38:165Y174. 4. Smit J-M, Klein S, Werker P-M. An overview of methods for vascular mapping in the planning of free flaps. J Plast Reconstr Aesthet Surg. 2010;63: e674Ye682. 5. Mathes D-W, Neligan P-C. Current techniques in preoperative imaging for abdomen-based perforator flap microsurgical breast reconstruction. J Reconstr Microsurg. 2010;26:3Y10. 6. Greenspun D, Vasile J, Levine J-L, et al. Anatomic imaging of abdominal perforator flaps without ionizing radiation: seeing is believing with magnetic resonance imaging angiography. J Reconstr Microsurg. 2010;26:37Y44. 7. Masia J, Clavero J-A, Larranaga J, et al. Preoperative planning of the abdominal perforator flap with multidetector row computed tomography: 3 years of experience. Plast Reconstr Surg. 2008;122:80eY81e. 8. Rozen W-M, Anavekar N-S, Ashton M-W, et al. Does the preoperative imaging of perforators with CT angiography improve operative outcomes in breast reconstruction? Microsurgery. 2008;28:516Y523. 9. Rozen W-M, Garcia-Tutor E, Alonso-Burgos A, et al. Planning and optimising DIEP flaps with virtual surgery: the Navarra experience. J Plast Reconstr Aesthet Surg. 2010;63:289Y297. 10. Rosson G-D, Shridharani S-M, Magarakis M, et al. Three-dimensional computed tomographic angiography to predict weight and volume of deep inferior epigastric artery perforator flap for breast reconstruction. Microsurgery. 2011;31:510Y516. 11. Pelletier A, Tseng C, Agarwal S, et al. Cost analysis of near-infrared spectroscopy tissue oximetry for monitoring autologous free tissue breast reconstruction. J Reconstr Microsurg. 2011;27:487Y494. 12. Lohman R-F, Langevin C-J, Bozkurt M, et al. A prospective analysis of free flap monitoring techniques: physical examination, external Doppler, implantable Doppler, and tissue oximetry. J Reconstr Microsurg. 2013;1:51Y56. 13. Smit J-M, Zeebregts C-J, Acosta R, et al. Advancements in free flap monitoring in the last decade: a critical review. Plast Reconstr Surg. 2010;125:177Y185. 14. Ensat F, Babl M, Conz C, et al. The efficacy of color duplex sonography in preoperative assessment of anterolateral thigh flap. Microsurgery. 2012;32: 605Y610. 15. Holm C, Mayr M, Hofter E, et al. Interindividual variability of the SIEA Angiosome: effects on operative strategies in breast reconstruction. Plast Reconstr Surg. 2008;122:1612Y1620. 16. Lee B-T, Matsui A, Hutteman M, et al. Intraoperative near-infrared fluorescence imaging in perforator flap reconstruction: current research and early clinical experience. J Reconstr Microsurg. 2010;26:59Y65.

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17. Newcombe R-G. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998;17:857Y872. 18. Liberati A, Altman D-G, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62:e1Ye34. 19. Holm C, Tegeler J, Mayr M, et al. Monitoring free flaps using laser-induced fluorescence of indocyanine green: a preliminary experience. Microsurgery. 2002;22:278Y287. 20. Krishnan K-G, Schackert G, Steinmeier R. The role of near-infrared angiography in the assessment of post-operative venous congestion in random pattern, pedicled island and free flaps. Br J Plast Surg. 2005;58:330Y338. 21. Azuma R, Morimoto Y, Masumoto K, et al. Detection of skin perforators by indocyanine green fluorescence nearly infrared angiography. Plast Reconstr Surg. 2008;122:1062Y1067. 22. Liu D-Z, Mathes D-W, Zenn M-R, et al. The application of indocyanine green fluorescence angiography in plastic surgery. J Reconstr Microsurg. 2011;27: 355Y364. 23. Mohebali J, Gottlieb L-J, Agarwal J-P. Further validation for use of the retrograde limb of the internal mammary vein in deep inferior epigastric perforator flap breast reconstruction using laser-assisted indocyanine green angiography. J Reconstr Microsurg. 2010;26:131Y135. 24. Pestana I-A, Coan B, Erdmann D, et al. Early experience with fluorescent angiography in free-tissue transfer reconstruction. Plast Reconstr Surg. 2009;123:1239Y1244. 25. Mothes H, Donicke T, Friedel R, et al. Indocyanine-green fluorescence video angiography used clinically to evaluate tissue perfusion in microsurgery. J Trauma. 2004;57:1018Y1024. 26. Holm C, Dornseifer U, Sturtz G, et al. Sensitivity and specificity of ICG angiography in free flap reexploration. J Reconstr Microsurg. 2010;26:311Y316. 27. Betz C-S, Zhorzel S, Schachenmayr H, et al. Endoscopic measurements of free-flap perfusion in the head and neck region using red-excited Indocyanine Green: preliminary results. J Plast Reconstr Aesthet Surg. 2009;62:1602Y1608. 28. Jung E-M, Prantl L, Schreyer A-G, et al. New perfusion imaging of tissue transplants with Contrast Harmonic Ultrasound Imaging (CHI) and Magnetic Resonance Imaging (MRI) in comparison with laser-induced Indocyanine Green (ICG) fluorescence angiography. Clin Hemorheol Microcirc. 2009;43:19Y33. 29. Iida T, Mihara M, Yoshimatsu H. Versatility of the superficial circumflex iliac artery perforator flap in head and neck reconstruction. Ann Plast Surg. 2014; 72:332Y336. 30. Matsui A, Lee B-T, Winer J-H, et al. Image-guided perforator flap design using invisible near-infrared light and validation with x-ray angiography. Ann Plast Surg. 2009;63:327Y330. 31. Komorowska-Timek E, Gurtner G-C. Intraoperative perfusion mapping with laser-assisted indocyanine green imaging can predict and prevent complications in immediate breast reconstruction. Plast Reconstr Surg. 2010;125:1065Y1073. 32. Sacks J-M, Nguyen A-T, Broyles J-M, et al. Near-infrared laser-assisted indocyanine green imaging for optimizing the design of the anterolateral thigh flap. Eplasty. 2012;12:e30. 33. Lee B-T, Hutteman M, Gioux S, et al. The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in perforator flap breast reconstruction. Plast Reconstr Surg. 2010;126:1472Y1481. 34. Holm C, Mayr M, Hofter E, et al. Perfusion zones of the DIEP flap revisited: a clinical study. Plast Reconstr Surg. 2006;117:37Y43.

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Annals of Plastic Surgery

& Volume 75, Number 6, December 2015

35. Francisco B-S, Kerr-Valentic M-A, Agarwal J-P. Laser-assisted indocyanine green angiography and DIEP breast reconstruction. Plast Reconstr Surg. 2010;125:116eY8e. 36. Narushima M, Yamamoto T, Yamamoto Y, et al. Lateral intercostal artery perforator-based reversed thoracodorsal artery flap for reconstruction of a chronic radiation ulcer of the lower back wall. Ann Plast Surg. 2011;67: 352Y356. 37. Okazaki M, Tanaka K, Kodaira S, et al. One-stage transfer of 2 paddles of thoracodorsal artery perforator flap with 1 pair of vascular anastomoses for Barraquer-Simons syndrome. J Craniofac Surg. 2012;23:883Y885. 38. Holm C, Mayr M, Hofter E, et al. Assessment of the patency of microvascular anastomoses using microscope-integrated near-infrared angiography: a preliminary study. Microsurgery. 2009;29:509Y514. 39. Newman M-I, Samson M-C. The application of laser-assisted indocyanine green fluorescent dye angiography in microsurgical breast reconstruction. J Reconstr Microsurg. 2009;25:21Y26. 40. Tenorio X, Mahajan A-L, Wettstein R, et al. Early detection of flap failure using a new thermographic device. J Surg Res. 2009;151:15Y21. 41. Salmi A-M, Tukiainen E, Asko-Seljavaara S. Thermographic mapping of perforators and skin blood flow in the free transverse rectus abdominis musculocutaneous flap. Ann Plast Surg. 1995;35:159Y164. 42. Wilson S-B, Spence V-A. Dynamic thermographic imaging method for quantifying dermal perfusion: potential and limitations. Med Biol Eng Comput. 1989;27:496Y501. 43. de Weerd L, Mercer J-B, Weum S. Dynamic infrared thermography. Clin Plast Surg. 2011;38:277Y292. 44. de Weerd L, Miland A-O, Mercer J-B. Perfusion dynamics of free DIEP and SIEA flaps during the first postoperative week monitored with dynamic infrared thermography. Ann Plast Surg. 2009;62:42Y47. 45. de Weerd L, Mercer J-B, Setsa L-B. Intraoperative dynamic infrared thermography and free-flap surgery. Ann Plast Surg. 2006;57:279Y284. 46. Itoh Y, Arai K. Use of recovery-enhanced thermography to localize cutaneous perforators. Ann Plast Surg. 1995;34:507Y511. 47. Whitaker I-S, Lie K-H, Rozen W-M, et al. Dynamic infrared thermography for the preoperative planning of microsurgical breast reconstruction: a comparison with CTA. J Plast Reconstr Aesthet Surg. 2012;65:130Y132. 48. Kalra S, Dancey A, Waters R. Intraoperative selection of dominant perforator vessel in DIEP free flaps based on perfusion strength using digital infrared thermographyVa pilot study. J Plast Reconstr Aesthet Surg. 2007;60:1365Y1368. 49. de Weerd L, Weum S, Mercer J-B. The value of dynamic infrared thermography (DIRT) in perforator selection and planning of free DIEP flaps. Ann Plast Surg. 2009;63:274Y279. 50. Theuvenet W-J, Koeyers G-F, Borghouts M-H. Thermographic assessment of perforating arteries. A preoperative screening method for fasciocutaneous and musculocutaneous flaps. Scand J Plast Reconstr Surg. 1986;20:25Y29. 51. Tenorio X, Mahajan AL, Elias B, van Riempst J-S, et al. Locating perforator vessels by dynamic infrared imaging and flow Doppler with no thermal cold challenge. Ann Plast Surg. 2011;67:143Y146. 52. Irwin M-S, Thorniley M-S, Dore C-J, et al. Near infra-red spectroscopy: a noninvasive monitor of perfusion and oxygenation within the microcirculation of limbs and flaps. Br J Plast Surg. 1995;48:14Y22. 53. Hunt T-K, Rabkin J, Jensen J-A, et al. Tissue oximetry: an interim report. World J Surg. 1987;11:126Y132. 54. Hirigoyen M-B, Blackwell K-E, Zhang W-X, et al. Continuous tissue oxygen tension measurement as a monitor of free-flap viability. Plast Reconstr Surg. 1997;99:763Y773. 55. Kamolz L-P, Giovanoli P, Haslik W, et al. Continuous free-flap monitoring with tissue-oxygen measurements: three-year experience. J Reconstr Microsurg. 2002;18:487Y491; discussion 492Y493. 56. Thorniley M-S, Sinclair J-S, Barnett N-J, et al. The use of near-infrared spectroscopy for assessing flap viability during reconstructive surgery. Br J Plast Surg. 1998;51:218Y226. 57. Cai Z-G, Zhang J, Zhang J-G, et al. Evaluation of near infrared spectroscopy in monitoring postoperative regional tissue oxygen saturation for fibular flaps. J Plast Reconstr Aesthet Surg. 2008;61:289Y296. 58. Whitaker I-S, Pratt G-F, Rozen W-M, et al. Near infrared spectroscopy for monitoring flap viability following breast reconstruction. J Reconstr Microsurg. 2012;3:149Y154. 59. Rao R, Saint-Cyr M, Ma A-M, et al. Prediction of post-operative necrosis after mastectomy: a pilot study utilizing optical diffusion imaging spectroscopy. World J Surg Oncol. 2009;7:91.

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Intraoperative Flap Evaluation

60. Holzle F, Loeffelbein D-J, Nolte D, et al. Free flap monitoring using simultaneous non-invasive laser Doppler flowmetry and tissue spectrophotometry. J Craniomaxillofac Surg. 2006;34:25Y33. 61. Wukitsch M-W, Petterson M-T, Tobler D-R, et al. Pulse oximetry: analysis of theory, technology, and practice. J Clin Monit. 1988;4:290Y301. 62. Holzle F, Rau A, Loeffelbein D-J, et al. Results of monitoring fasciocutaneous, myocutaneous, osteocutaneous and perforator flaps: 4-year experience with 166 cases. Int J Oral Maxillofac Surg. 2010;39:21Y28. 63. Colwell A-S, Wright L, Karanas Y. Near-infrared spectroscopy measures tissue oxygenation in free flaps for breast reconstruction. Plast Reconstr Surg. 2008;121:344eY345e. 64. Keller A. A new diagnostic algorithm for early prediction of vascular compromise in 208 microsurgical flaps using tissue oxygen saturation measurements. Ann Plast Surg. 2009;62:538Y543. 65. Repez A, Oroszy D, Arnez Z-M. Continuous postoperative monitoring of cutaneous free flaps using near infrared spectroscopy. J Plast Reconstr Aesthet Surg. 2008;61:71Y77. 66. Steele M-H. Three-year experience using near infrared spectroscopy tissue oximetry monitoring of free tissue transfers. Ann Plast Surg. 2011;66:540Y545. 67. Keller A. Noninvasive tissue oximetry for flap monitoring: an initial study. J Reconstr Microsurg. 2007;23:189Y197. 68. Colwell A-S, Buntic R-F, Brooks D, et al. Detection of perfusion disturbances in digit replantation using near-infrared spectroscopy and serial quantitative fluoroscopy. J Hand Surg Am. 2006;31:456Y462. 69. Lin S-J, Nguyen M-D, Chen C, et al. Tissue oximetry monitoring in microsurgical breast reconstruction decreases flap loss and improves rate of flap salvage. Plast Reconstr Surg. 2011;127:1080Y1085. 70. Whitaker I-S, Pratt G-F, Rozen W-M, et al. Near infrared spectroscopy for monitoring flap viability following breast reconstruction. J Reconstr Microsurg. 2012;28:149Y154. 71. Fukaya E, Kuwatsuru R, Iimura H, et al. Imaging of the superficial inferior epigastric vascular anatomy and preoperative planning for the SIEA flap using MDCTA. J Plast Reconstr Aesthet Surg. 2010;64:63Y68. 72. Rozen W-M, Phillips T-J, Ashton M-W, et al. Preoperative imaging for DIEA perforator flaps: a comparative study of computed tomographic angiography and Doppler ultrasound. Plast Reconstr Surg. 2008;121:9Y16. 73. Masia J, Clavero J-A, Larranaga J-R, et al. Multidetector-row computed tomography in the planning of abdominal perforator flaps. J Plast Reconstr Aesthet Surg. 2006;59:594Y599. 74. Masia J, Kosutic D, Clavero J-A, et al. Preoperative computed tomographic angiogram for deep inferior epigastric artery perforator flap breast reconstruction. J Reconstr Microsurg. 2010;26:21Y28. 75. Ting J-W, Rozen WM, Chubb D, et al. Improving the utility and reliability of the deep circumflex iliac artery perforator flap: the use of preoperative planning with CT angiography. Microsurgery. 2011;31:603Y609. 76. Haddock N-T, Greaney P, Otterburn D, et al. Predicting perforator location on preoperative imaging for the profunda artery perforator flap. Microsurgery. 2012;32:505Y511. 77. Alonso-Burgos A, Garcia-Tutor E, Bastarrika G, et al. Preoperative planning of DIEP and SGAP flaps: preliminary experience with magnetic resonance angiography using 3-tesla equipment and blood-pool contrast medium. J Plast Reconstr Aesthet Surg. 2010;63:298Y304. 78. Masia J, Kosutic D, Cervelli D, et al. In search of the ideal method in perforator mapping: noncontrast magnetic resonance imaging. J Reconstr Microsurg. 2010;26:29Y35. 79. Rozen W-M, Stella D-L, Bowden J, et al. Advances in the pre-operative planning of deep inferior epigastric artery perforator flaps: magnetic resonance angiography. Microsurgery. 2009;29:119Y123. 80. Holm C, Dornseifer U, Sturtz G, et al. The intrinsic transit time of free microvascular flaps: clinical and prognostic implications. Microsurgery. 2010;30: 91Y96. 81. Hayden R-E, Tavill M-A, Nioka S, et al. Oxygenation and blood volume changes in flaps according to near-infrared spectrophotometry. Arch Otolaryngol Head Neck Surg. 1996;122:1347Y1351. 82. Payette J-R, Kohlenberg E, Leonardi L, et al. Assessment of skin flaps using optically based methods for measuring blood flow and oxygenation. Plast Reconstr Surg. 2005;115:539Y546. 83. Scheufler O, Exner K, Andresen R. Investigation of TRAM flap oxygenation and perfusion by near-infrared reflection spectroscopy and color-coded duplex sonography. Plast Reconstr Surg. 2004;113:141Y152; discussion 153Y155.

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685

An Analysis of Current Techniques Used for Intraoperative Flap Evaluation.

Over the last decade, microsurgeons have used a greater variety of more complex flaps. At the same time, microsurgeons have also become more intereste...
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