Indocyanine Green for Perfusion: When It Helps, and When It Can Mislead
Abstract
Indocyanine green (ICG) fluorescence angiography has emerged as an important intraoperative imaging modality for assessing tissue perfusion and supporting surgical decision making. By providing real time visualization of blood flow, ICG fluorescence angiography enables surgeons to evaluate tissue vascularity before constructing an anastomosis, thereby offering an additional tool to optimize surgical outcomes. Its adoption has expanded across multiple surgical specialties, including colorectal, gastrointestinal, hepatobiliary, plastic, and vascular surgery. Among these applications, the strongest evidence currently supports its use during left sided colorectal resections, where it serves as an adjunct to conventional intraoperative assessment of bowel viability and anastomotic integrity.
Anastomotic leakage remains one of the most feared complications following colorectal surgery, contributing substantially to postoperative morbidity, mortality, prolonged hospitalization, reoperation, and increased healthcare costs. The development of an anastomotic leak is multifactorial, with impaired tissue perfusion representing one of the most important modifiable risk factors. Traditional assessment of bowel viability has relied largely on subjective clinical indicators such as tissue color, arterial pulsation, bleeding from the cut edge, and mesenteric perfusion. Although these parameters remain valuable, they are inherently operator dependent and may not accurately identify subtle areas of inadequate perfusion. ICG fluorescence angiography provides a more objective method of evaluating vascular supply by allowing direct visualization of tissue perfusion following intravenous administration of indocyanine green dye and near infrared imaging.
Current clinical evidence and international guideline recommendations support the incorporation of ICG fluorescence angiography into an anastomotic quality improvement strategy, particularly for left sided colorectal anastomoses. Multiple studies have demonstrated that intraoperative perfusion assessment frequently influences surgical decision making by identifying poorly perfused bowel segments that might otherwise have appeared clinically acceptable. In these situations, fluorescence imaging enables surgeons to modify operative plans before completing the anastomosis, potentially reducing the risk of postoperative complications.
The value of ICG fluorescence angiography lies not in the imaging itself but in the clinical actions it informs. Detection of inadequate perfusion may prompt revision of the planned transection margin to include better vascularized tissue, selection of an alternative bowel segment or conduit, reconstruction of the anastomosis, creation of a protective diverting stoma, or implementation of enhanced postoperative surveillance. These intraoperative adjustments represent the mechanism through which ICG may contribute to improved patient outcomes. Without appropriate interpretation and subsequent surgical decision making, fluorescence imaging alone cannot prevent anastomotic failure.
Despite its advantages, ICG fluorescence angiography should not be viewed as a definitive predictor of anastomotic healing. One of its most important limitations is the potential to provide false reassurance. A strong fluorescence signal confirms that the indocyanine green dye has reached the evaluated tissue at a particular point in time under the prevailing physiological conditions. However, this finding does not guarantee adequate tissue viability throughout the entire bowel wall or ensure sufficient oxygen delivery at the cellular level. Likewise, fluorescence imaging cannot reliably assess venous drainage, identify evolving venous congestion, quantify mechanical tension across the anastomosis, or predict the complex biological processes required for successful wound healing during the postoperative period.
Anastomotic healing depends on numerous interrelated factors beyond arterial perfusion. Excessive anastomotic tension, technical errors during construction, local contamination, systemic inflammation, patient nutritional status, diabetes mellitus, smoking, immunosuppressive therapy, corticosteroid use, and postoperative hemodynamic instability all contribute to healing outcomes. Consequently, satisfactory fluorescence findings should never replace comprehensive surgical judgment or diminish vigilance regarding these additional determinants of success.
Interpretation of ICG fluorescence angiography also presents practical challenges. Most current systems rely on qualitative visual assessment rather than standardized quantitative perfusion measurements, resulting in variability between surgeons and institutions. Factors such as imaging angle, camera distance, timing of dye administration, cardiac output, blood pressure, vasopressor use, and tissue edema may all influence fluorescence intensity and interpretation. Ongoing research seeks to develop objective perfusion metrics, standardized imaging protocols, and artificial intelligence assisted analysis to improve reproducibility and reduce interobserver variability.
Beyond colorectal surgery, ICG fluorescence angiography continues to demonstrate expanding clinical applications. Surgeons increasingly use the technology to assess gastric conduit perfusion during esophagectomy, evaluate tissue viability in reconstructive surgery, guide hepatic resections, identify biliary anatomy during cholecystectomy, assess intestinal ischemia, and evaluate vascular patency during complex surgical procedures. Although evidence supporting these applications continues to grow, the strength of clinical data varies considerably among specialties, and routine use should remain guided by procedure specific evidence.
For practicing surgeons, the practical role of ICG fluorescence angiography is clear. The technology is most valuable when it is used to answer a specific intraoperative clinical question rather than as a routine imaging exercise. Its greatest benefit occurs when fluorescence findings directly influence operative decision making in a manner that improves tissue selection, surgical planning, and postoperative management. At the same time, fluorescence imaging should always be interpreted within the broader clinical context, incorporating surgical experience, meticulous tissue handling, patient physiology, intraoperative hemodynamics, and established principles of anastomotic construction.
In conclusion, indocyanine green fluorescence angiography represents a valuable adjunct that enhances intraoperative assessment of tissue perfusion and supports evidence based decision making during colorectal surgery. Its strongest role currently lies in improving the quality of left sided colorectal anastomoses by identifying areas of compromised perfusion before anastomosis construction. However, the technology should not be regarded as a standalone solution for preventing anastomotic leakage. Successful outcomes depend on thoughtful interpretation of fluorescence findings, appropriate intraoperative action, and continued attention to the multiple technical, physiological, and patient related factors that influence postoperative healing. When integrated into a comprehensive surgical strategy, ICG fluorescence angiography has the potential to improve operative precision while complementing, rather than replacing, sound clinical judgment.
Introduction
Indocyanine green (ICG) has been used in clinical medicine for more than half a century and has established an excellent safety profile across a wide range of diagnostic and therapeutic applications. Initially introduced for measuring cardiac output and hepatic blood flow, ICG later became an essential contrast agent in ophthalmology for retinal and choroidal angiography. In recent years, advances in near infrared fluorescence imaging technology have remarkably expanded its role in surgery, transforming ICG from a diagnostic dye into a valuable intraoperative imaging tool capable of providing real time assessment of tissue perfusion and vascular anatomy.
The widespread adoption of near infrared imaging platforms has enabled surgeons to visualize blood flow dynamically during operative procedures. Following intravenous administration, ICG rapidly binds to plasma proteins and remains largely confined to the vascular compartment until it is cleared by the liver. When exposed to near infrared light, the dye emits fluorescence that can be detected by specialized imaging systems, allowing surgeons to assess tissue perfusion almost instantaneously. This capability has led to the incorporation of ICG fluorescence imaging across numerous surgical specialties, including gastrointestinal surgery, vascular surgery, transplant surgery, hepatobiliary surgery, plastic and reconstructive surgery, microvascular surgery, gynecologic oncology, urology, and colorectal surgery.
The primary appeal of ICG fluorescence imaging lies in its ability to supplement conventional intraoperative assessment with objective visualization of tissue perfusion. Traditionally, surgeons have relied on clinical judgment to determine tissue viability using indicators such as tissue color, capillary bleeding, arterial pulsation, mesenteric appearance, conduit quality, tissue texture, temperature, and overall operative experience. Although these assessments remain fundamental components of surgical decision making, they are inherently subjective and may be influenced by operative conditions, patient physiology, and individual experience. ICG fluorescence imaging provides an additional source of information by revealing perfusion patterns that may not be visible under standard white light, thereby improving intraoperative confidence when evaluating tissue viability.
This technology has demonstrated particular value in procedures where adequate perfusion directly influences postoperative outcomes. In colorectal surgery, ICG fluorescence angiography is increasingly used to assess bowel perfusion before creation of an anastomosis, with the goal of reducing anastomotic leak rates. In esophageal and gastric surgery, it assists in evaluating conduit vascularity before reconstruction. In reconstructive and plastic surgery, ICG enables assessment of skin flap viability, free tissue transfer, and microvascular anastomoses by identifying areas of compromised arterial inflow or venous congestion. Similarly, in vascular surgery and organ transplantation, ICG supports evaluation of graft perfusion, organ viability, and technical success during complex procedures.
Beyond simple visualization of blood flow, ICG fluorescence imaging can facilitate more informed intraoperative decision making. Surgeons may modify resection margins, revise anastomotic sites, adjust flap design, or perform additional vascular reconstruction based on perfusion findings. Such intraoperative adjustments have the potential to reduce ischemic complications, improve tissue preservation, and optimize functional outcomes. As imaging systems continue to evolve, quantitative fluorescence analysis and artificial intelligence assisted interpretation may further enhance the precision and reproducibility of perfusion assessment.
Despite its considerable advantages, it is essential to recognize the limitations of ICG fluorescence imaging and avoid overstating its clinical capabilities. Fluorescence demonstrates tissue perfusion at a specific point in time, but it does not directly predict tissue healing or guarantee successful postoperative outcomes. Tissue repair is a complex biological process influenced by numerous physiological, surgical, and patient related factors that extend far beyond arterial blood supply.
Anastomotic leaks, flap necrosis, wound dehiscence, and delayed healing are multifactorial complications resulting from the interaction of local tissue characteristics, surgical technique, and systemic patient factors. Although adequate perfusion is a prerequisite for healing, it represents only one component of a much larger process. Excessive anastomotic tension, tissue edema, impaired venous drainage, local infection or contamination, prior radiation exposure, diabetes mellitus, cigarette smoking, malnutrition, anemia, hypotension, shock, immunosuppression, chronic corticosteroid therapy, and postoperative hemodynamic instability all substantially influence tissue viability and wound healing. Consequently, a well perfused tissue segment demonstrated by ICG fluorescence may still experience postoperative complications if these additional risk factors are present.
Another important consideration is the absence of universal standards for fluorescence interpretation. In many clinical settings, assessment remains qualitative and depends on the surgeon’s visual interpretation of fluorescence intensity and timing. Although quantitative fluorescence metrics are being actively investigated, standardized thresholds for defining adequate perfusion have not yet been universally established. Differences in imaging equipment, dye dosage, timing of administration, camera settings, and patient physiology may also affect fluorescence patterns and limit direct comparison across institutions.
Furthermore, successful implementation of ICG imaging requires familiarity with both the technology and its limitations. Surgeons must understand appropriate dosing protocols, timing of image acquisition, potential contraindications such as iodine hypersensitivity, and the possibility of false reassurance if fluorescence findings are interpreted without consideration of the broader clinical context. Integration of ICG imaging into surgical workflows should therefore complement, rather than replace, comprehensive clinical assessment and sound operative judgment.
Current evidence increasingly supports the use of ICG fluorescence imaging as an adjunct that enhances intraoperative decision making and may reduce certain postoperative complications in selected procedures. However, the quality of evidence varies across surgical specialties, and further large, multicenter randomized controlled trials are needed to establish standardized protocols, quantify long term clinical benefits, and determine cost effectiveness across diverse patient populations.
In conclusion, indocyanine green fluorescence imaging represents one of the most important advances in image guided surgery, providing surgeons with real time visualization of tissue perfusion that was previously unavailable using conventional techniques alone. Its applications continue to expand across multiple surgical disciplines, offering valuable information that can improve operative planning and intraoperative decision making. Nevertheless, fluorescence should be regarded as a decision support tool rather than a definitive predictor of successful healing. Optimal surgical outcomes continue to depend on meticulous operative technique, careful patient selection, management of systemic risk factors, and comprehensive perioperative care. When interpreted within this broader clinical framework, ICG fluorescence imaging serves as a powerful adjunct that complements surgical expertise while enhancing precision and patient safety.
Mechanism and Technical Principles
Indocyanine green (ICG) is a water soluble fluorescent dye that has become an increasingly valuable tool for intraoperative perfusion assessment across multiple surgical specialties, including colorectal, hepatobiliary, vascular, plastic, and oncologic surgery. Following intravenous administration, ICG rapidly binds to plasma proteins, particularly albumin, allowing it to remain largely within the intravascular compartment. When exposed to near infrared light, the dye absorbs energy at a specific wavelength and emits fluorescence that can be detected using specialized near infrared imaging systems. This fluorescence generates a real time visual representation of blood flow, enabling surgeons to evaluate tissue perfusion during operative procedures.
The ability to visualize tissue perfusion in real time has notably enhanced intraoperative decision making. In colorectal surgery, for example, ICG fluorescence angiography is frequently used to assess bowel perfusion before creating an anastomosis, with the goal of reducing the risk of anastomotic leakage. Similarly, in reconstructive surgery, ICG assists in evaluating flap viability, while in hepatobiliary surgery it facilitates anatomical identification and assessment of vascular supply. By providing immediate visual feedback regarding tissue vascularization, ICG imaging allows surgeons to modify operative plans when inadequate perfusion is identified, potentially improving surgical outcomes.
Despite these advantages, it is important to recognize that ICG fluorescence imaging has inherent physiological and technical limitations. The fluorescence signal represents the delivery of dye through the superficial vascular network rather than a comprehensive assessment of tissue viability. Near infrared light has limited tissue penetration, generally reaching only a few millimeters beneath the tissue surface. Consequently, the resulting image primarily reflects perfusion of superficial or near superficial tissues and may not accurately represent blood flow within deeper tissue layers. This limitation is particularly relevant in gastrointestinal surgery, where adequate perfusion of the full bowel wall is critical for successful healing.
Furthermore, fluorescence observed during surgery represents tissue perfusion at a single point in time rather than predicting future tissue viability. Intraoperative conditions frequently change during and after the procedure. Factors such as postoperative edema, increased anastomotic tension, systemic hypotension, vasospasm, hypovolemia, or the administration of vasopressor medications may alter tissue perfusion after the fluorescence assessment has been completed. As a result, tissue demonstrating satisfactory fluorescence intraoperatively may subsequently experience impaired perfusion, while areas with initially reduced fluorescence may recover under improved physiological conditions. For this reason, ICG imaging should be regarded as an adjunct to comprehensive surgical judgment rather than a definitive predictor of postoperative tissue healing.
Accurate interpretation of fluorescence images depends on careful attention to multiple technical variables that influence signal quality. The administered dose of ICG directly affects fluorescence intensity, and excessive dosing may result in signal oversaturation, reducing the ability to distinguish differences in tissue perfusion. Conversely, insufficient dosing may produce weak fluorescence that limits image interpretation. The timing of image acquisition following intravenous injection is equally important because fluorescence intensity changes dynamically as the dye circulates through the vascular system. Imaging performed too early or too late may not accurately reflect optimal tissue perfusion.
Patient specific physiological factors also influence fluorescence characteristics. Cardiac output determines the rate at which ICG reaches the target tissue, while vascular disease, microcirculatory dysfunction, or impaired regional blood flow may alter fluorescence patterns. Tissue thickness, obesity, inflammation, edema, and fibrosis can attenuate the emitted signal because near infrared light penetrates tissue only to a limited depth. These variables may produce heterogeneous fluorescence that does not necessarily correspond to true perfusion deficits.
Equipment related factors further contribute to variability in image quality. The distance between the imaging camera and the tissue surface significantly affects fluorescence intensity, making consistent camera positioning essential during assessment. Different imaging platforms also use proprietary hardware, software, excitation wavelengths, image processing algorithms, and display characteristics, which may produce variations in fluorescence appearance between systems. Ambient operating room lighting can interfere with image acquisition if not appropriately controlled, while differences in camera sensitivity and calibration may influence interpretation across institutions.
Repeated ICG administration is generally safe and can be useful when reassessing perfusion at different stages of a procedure. However, repeated injections require careful planning because residual fluorescence from earlier doses may remain within tissues or circulating blood. This background fluorescence can reduce image contrast and complicate interpretation of subsequent assessments by masking subtle differences in perfusion. Appropriate intervals between injections and awareness of cumulative fluorescence are therefore important to maintain diagnostic accuracy.
Given these sources of variability, standardized imaging protocols are essential to ensure consistency and reproducibility. Institutions implementing ICG fluorescence imaging should establish clear procedural guidelines specifying the administered dose, method and speed of injection, timing of image acquisition, target tissue for assessment, camera positioning and distance, operating room lighting conditions, and objective criteria used to define adequate or inadequate perfusion. Standardization not only improves intraoperative decision making but also facilitates comparison of outcomes across clinical studies and healthcare centers.
An additional area of ongoing investigation is the development of quantitative fluorescence analysis. Most current applications rely on subjective visual interpretation by the operating surgeon, which introduces interobserver variability. Emerging software platforms are capable of measuring objective fluorescence parameters, including signal intensity, time to fluorescence onset, peak fluorescence, inflow slope, and washout kinetics. These quantitative approaches may improve reproducibility and reduce dependence on subjective assessment, although universally accepted thresholds for adequate tissue perfusion have yet to be established.
In summary, indocyanine green fluorescence imaging represents a valuable adjunct for real time assessment of tissue perfusion during surgery. Its ability to visualize vascular flow has improved intraoperative decision making and holds significant potential for reducing ischemic complications. Nevertheless, fluorescence imaging should not be interpreted as a direct measure of tissue viability or a guarantee of postoperative healing. The technique is influenced by numerous physiological, technical, and procedural factors that require careful consideration. Optimal use of ICG depends on standardized imaging protocols, an understanding of its inherent limitations, and integration of fluorescence findings with clinical judgment, anatomical assessment, and established surgical principles. As quantitative imaging technologies continue to evolve, ICG fluorescence is likely to become an increasingly reliable component of precision guided surgery.
FDA-label and Drug-safety Considerations
ICG is generally well tolerated, but it is not risk-free. Current labeling for IC-GREEN includes indications for fluorescence imaging of vessels, blood flow, and tissue perfusion before, during, and after vascular, gastrointestinal, organ transplant, plastic, microvascular, and reconstructive surgeries, including minimally invasive procedures. Use is established in adults and in pediatric patients aged 1 month and older for these perfusion-imaging indications.
For visualization of vessels, blood flow, and tissue perfusion, labeled adult dosing for a single image sequence is 1.25 mg to 5 mg intravenously using a 2.5 mg/mL solution. For perfusion in extremities through the skin, the adult dose is 3.75 mg to 10 mg intravenously. Additional doses may be administered during a procedure, but the total dose should not exceed 2 mg/kg. Institutional protocols may differ by imaging system and surgical indication, so local labeling and pharmacy guidance should be followed.
IC-GREEN is contraindicated in patients with a history of hypersensitivity to indocyanine green. Hypersensitivity reactions, including anaphylaxis, urticaria, and deaths from anaphylaxis, have been reported. Resuscitation equipment and trained personnel should be readily available, and patients should be monitored for hypersensitivity reactions.
The label also notes that IC-GREEN contains sodium iodide. This can interfere with thyroid radioactive iodine uptake studies for at least one week after administration. Older labels and some formulations also advise caution in patients with a history of allergy to iodides. Clinicians should avoid the nonspecific phrase “iodine allergy” as a blanket contraindication. A more accurate approach is to document prior ICG reaction, severe iodide-associated reaction, severe contrast reaction history, and the risk-benefit rationale for use.
ICG is unstable in aqueous solution and should be used within the labeled time after reconstitution. If precipitate is present, the solution should be discarded. Heparin preparations containing sodium bisulfite may reduce the absorption peak of ICG in blood and should not be used as anticoagulants for sample collection when ICG analysis is being performed.
Best-supported Use: Left-sided Colorectal Anastomosis
The most clinically mature evidence for ICG perfusion assessment is in colorectal surgery, particularly left-sided colorectal anastomosis. SAGES 2025 recommends fluorescence image-guided surgery with ICG for patients undergoing left-sided colorectal anastomosis for benign or malignant disease to improve anastomotic quality. This is a strong recommendation with moderate certainty of evidence.
That recommendation should not be broadened beyond the evidence. Recent randomized data are mixed. Some trials and meta-analyses suggest lower anastomotic leak rates when ICG is used, especially in left-sided and rectal resections. Other large trials did not show a significant overall reduction when broader colorectal populations were studied or when low anterior resections were excluded. The practical conclusion is not that ICG is ineffective. It is that benefit appears most plausible when baseline leak risk is meaningful and perfusion findings can change the operation.
PILLAR II should be described accurately as a prospective, multicenter study, not a randomized controlled trial. PILLAR III was randomized and focused on left-sided or low anterior resection, but it did not demonstrate a statistically significant reduction in anastomotic leak. These details matter because they prevent overstatement and make the article more credible for a physician audience.
How ICG May Reduce Leak Risk
ICG can reduce ischemia-related leak risk when it identifies poor perfusion that is not evident by standard inspection. A surgeon may then choose a more proximal transection point, revise an anastomosis, alter conduit placement, add diversion, or intensify postoperative surveillance.
This is the central mechanism: ICG improves decisions when the team acts on the information. The dye does not improve blood flow, strengthen tissue, reduce tension, treat infection, or correct shock. It only reveals a perfusion pattern. The outcome benefit depends on whether that pattern is interpreted correctly and incorporated into surgical judgment.
When ICG Can Provide False Reassurance
ICG can mislead when a good fluorescence signal is interpreted as proof that tissue will heal. A bright signal shows dye arrival at the time of imaging. It does not guarantee oxygen delivery, venous drainage, durable microvascular perfusion, or healing under postoperative stress.
Several scenarios deserve caution. A patient with anemia or hypoxemia may have visible blood flow but inadequate oxygen delivery. A patient on vasopressors may demonstrate acceptable perfusion during a controlled intraoperative moment, then develop impaired microcirculation later. Obesity and tissue thickness may reduce image reliability. Prior radiation, diabetes, peripheral vascular disease, smoking, severe atherosclerosis, edema, and malnutrition may lower healing reserve even when fluorescence appears acceptable.
Venous congestion is another important limitation. ICG is often interpreted as an arterial inflow test, but some complications arise from impaired outflow. A flap or conduit may fluoresce and still fail if venous drainage is inadequate. Slow washout, mottled signal, swelling, dark bleeding, and clinical appearance should remain part of the assessment.
Applications Beyond Colorectal Surgery
ICG has useful roles beyond colorectal surgery, but the strength of evidence varies.
In esophageal surgery, ICG can help assess gastric conduit perfusion before anastomosis. SAGES 2025 suggests its use for esophageal anastomosis in patients undergoing resection for esophageal cancer, but the certainty of evidence is very low. This should be presented as a reasonable adjunct rather than a proven leak-prevention standard.
In bariatric and revisional bariatric surgery, ICG may help when anatomy is altered or perfusion is uncertain. Current evidence is insufficient for a formal recommendation. It is reasonable to use in selected cases, but the article should avoid implying that ICG reliably prevents sleeve or gastrojejunal leaks.
In plastic and reconstructive surgery, ICG is commonly used to assess mastectomy skin flaps, autologous tissue transfer, perforator dominance, and flap perfusion. It can identify hypoperfused regions and guide intraoperative revision. Evidence is heterogeneous, thresholds vary, and qualitative interpretation can overpredict or underpredict tissue necrosis. ICG should complement clinical assessment and postoperative flap monitoring.
In small bowel ischemia, obstruction, trauma, and questionable bowel viability, ICG may help define resection margins or support a second-look strategy. The evidence base is less mature than in elective colorectal surgery. ICG should be integrated with hemodynamics, bowel appearance, lactate trend, Doppler assessment when appropriate, and clinical judgment.
Practical Intraoperative Framework
The best use of ICG begins before injection. The team should define the clinical question. Is the planned bowel margin adequately perfused? Is the gastric conduit tip viable? Is the flap edge at risk? Is there a better perforator? Is questionable bowel viable enough to preserve?
A practical workflow is simple. First, perform standard clinical assessment. Second, administer ICG according to the labeled dose, device requirements, and institutional protocol. Third, interpret inflow, homogeneity, demarcation, and washout in context. Fourth, decide whether the finding changes the operation. Fifth, document the dose, timing, imaging target, interpretation, and any surgical change.
The postoperative plan should not become less vigilant because ICG looked reassuring. Fever, tachycardia, ileus, pelvic pain, sepsis, rising inflammatory markers, drain changes, wound compromise, and unexplained clinical decline still require prompt evaluation.
Table 1. Evidence strength by surgical setting
| Setting | Evidence position | Practical wording |
|---|---|---|
| Left-sided colorectal anastomosis | Strongest support; guideline-recommended adjunct | Reasonable to use routinely or selectively, especially when leak risk is meaningful |
| Low anterior or rectal resection | Supportive but not uniformly positive RCT evidence | Most useful when perfusion is uncertain or baseline leak risk is high |
| Right-sided colectomy | Less certain | Consider selectively rather than presenting as routine leak prevention |
| Esophagectomy conduit | Suggested adjunct; very low-certainty evidence | Useful for conduit assessment, but not definitive |
| Bariatric or revisional bariatric surgery | Insufficient evidence for firm recommendation | Reasonable option in complex or revisional cases |
| Breast and flap reconstruction | Common use; heterogeneous evidence | Helps identify hypoperfused tissue, but thresholds vary |
| Small bowel ischemia or trauma | Limited outcome evidence | Adjunct to clinical judgment and possible second-look surgery |
Table 2. Why a reassuring ICG image may still mislead
| Limitation | Clinical implication | Practical response |
|---|---|---|
| Surface-weighted imaging | Deeper ischemia may be missed | Do not rely on fluorescence alone |
| Single time-point assessment | Perfusion can change after closure | Continue postoperative surveillance |
| Blood flow, not oxygenation | Anemia or hypoxemia may still impair healing | Optimize systemic physiology |
| Venous congestion may be underrecognized | Tissue may fluoresce but drain poorly | Assess swelling, bleeding quality, washout, and color |
| Background signal after repeat dosing | Later images may be harder to interpret | Standardize timing between injections |
| Qualitative interpretation | Marginal perfusion may look acceptable | Use structured interpretation; consider quantitative tools when available |
| Device and technique variability | Signal intensity may not be comparable across systems | Use local protocols and consistent imaging technique |
Table 3. ICG safety and administration checklist
| Domain | What to verify | Why it matters |
|---|---|---|
| Indication | Perfusion, bile duct imaging, lymphatic mapping, or ophthalmic use | Dosing and timing differ by indication |
| Allergy history | Prior ICG reaction; severe iodide-associated reaction; severe contrast reaction history | Hypersensitivity and anaphylaxis have been reported |
| Resuscitation readiness | Epinephrine, airway support, trained staff | Labeling calls for readiness to treat hypersensitivity |
| Dose | Single dose and cumulative dose | Total dose should not exceed labeled maximum |
| Reconstitution | Correct diluent and concentration | ICG is unstable in aqueous solution |
| Repeat dosing | Timing since prior injection | Background fluorescence can impair interpretation |
| Thyroid testing | Planned radioactive iodine uptake studies | Testing should be delayed for at least one week after ICG |
| Documentation | Dose, time, target, image interpretation, operative change | Supports quality review and medicolegal clarity |
Implementation Considerations
Hospitals adopting ICG should treat it as a structured clinical process, not just an imaging feature. Protocols should identify who administers the dye, how the dose is prepared, when imaging occurs, which camera settings are used, and how findings are documented.
Quality-improvement programs should track more than ICG use. They should track whether ICG changed management. Useful metrics include change in transection site, anastomotic revision, conduit revision, diversion decision, flap trimming, reoperation, leak, necrosis, infection, length of stay, readmission, and adverse drug reaction.
Training matters. Interpretation varies among users, and subjective assessment can be inconsistent. Future work should focus on quantitative fluorescence metrics, reproducible thresholds, device standardization, and integration with patient-level risk models.
Clinical Takeaways
Indocyanine green (ICG) fluorescence angiography has emerged as an important intraoperative imaging modality that provides surgeons with real time assessment of tissue perfusion. By enabling direct visualization of blood flow during surgery, ICG offers valuable physiological information that may enhance surgical decision making and improve patient outcomes. However, despite its growing adoption across multiple surgical specialties, ICG should be regarded as an adjunctive tool rather than a definitive determinant of surgical success. Its greatest clinical value lies in complementing, rather than replacing, established principles of surgical judgment and comprehensive patient assessment.
The most appropriate use of ICG occurs when the surgical objective is clearly defined, the patient presents with a meaningful baseline risk of ischemic complications, and the operative team is prepared to modify the surgical plan based on the imaging findings. In these situations, real time visualization of tissue perfusion can support critical intraoperative decisions, including the selection of resection margins, confirmation of vascular supply, or revision of an anastomotic site when inadequate perfusion is identified. The technology is particularly valuable because it provides immediate physiological information that cannot be reliably obtained through visual inspection or palpation alone.
Nevertheless, interpretation of ICG findings requires careful clinical judgment. A favorable fluorescence signal indicating adequate arterial perfusion should never be interpreted as evidence that all factors influencing surgical success have been optimized. Tissue perfusion represents only one component of successful wound healing and anastomotic integrity. Numerous additional variables contribute to postoperative outcomes, many of which cannot be assessed by fluorescence imaging. These include excessive anastomotic tension, technical errors during construction, local or systemic infection, venous congestion, tissue edema, malnutrition, hypoalbuminemia, anemia, immunosuppression, poor glycemic control, and postoperative hemodynamic instability. Each of these factors may independently impair tissue healing despite apparently satisfactory intraoperative perfusion.
Accordingly, ICG should be integrated into a broader framework of perioperative risk assessment rather than used as a standalone predictor of clinical outcomes. Surgeons must continue to evaluate patient specific factors, operative technique, tissue quality, and physiological status when making intraoperative decisions. The presence of strong fluorescence should reinforce, but never replace, sound surgical principles and meticulous operative technique.
Among the various surgical applications of ICG, the strongest body of evidence currently supports its use in left sided colorectal surgery for reducing the risk of anastomotic leakage. Anastomotic leak remains one of the most serious complications following colorectal resection, contributing to increased morbidity, mortality, prolonged hospitalization, reoperation, and impaired long term oncologic outcomes. Multiple clinical studies and meta analyses have demonstrated that intraoperative assessment of bowel perfusion using ICG can identify poorly perfused bowel segments that may not be apparent through conventional clinical assessment alone. In many cases, this information prompts revision of the planned transection site, potentially reducing the incidence of postoperative anastomotic failure.
Although evidence supporting ICG use in left sided colorectal anastomosis continues to strengthen, its role in other surgical procedures remains less well established. Promising applications have been reported in upper gastrointestinal surgery, reconstructive and plastic surgery, hepatobiliary procedures, vascular surgery, urology, gynecology, and organ transplantation. In these settings, ICG has demonstrated potential utility for evaluating tissue viability, assessing flap perfusion, identifying critical vascular anatomy, and supporting intraoperative decision making. However, the quality and consistency of evidence vary considerably among these indications, and many studies remain limited by small sample sizes, observational designs, or heterogeneous methodologies.
Consequently, recommendations regarding these broader applications should be framed cautiously and according to the certainty of available evidence. While early findings are encouraging, definitive conclusions regarding routine implementation require additional high quality randomized controlled trials, standardized imaging protocols, quantitative fluorescence assessment methods, and long term outcome data. Until such evidence becomes available, surgeons should avoid overstating the benefits of ICG in procedures where clinical efficacy has not yet been conclusively demonstrated.
An additional challenge involves the lack of universally accepted standards for fluorescence interpretation. Most current assessments rely on subjective visual evaluation by the operating surgeon, although quantitative perfusion analysis and artificial intelligence assisted image interpretation are emerging as promising approaches to improve reproducibility and reduce interobserver variability. Future technological advances may enable more objective assessment of tissue perfusion and facilitate broader standardization across surgical practice.
Ultimately, indocyanine green fluorescence imaging represents a valuable advancement in precision surgery by providing dynamic, real time physiological information during operative procedures. Its greatest strength lies in enhancing intraoperative decision making when used within a comprehensive clinical context. Current evidence most strongly supports its application in left sided colorectal anastomosis for the prevention of anastomotic leakage, while other surgical indications remain promising but require further validation. As evidence continues to evolve, ICG should be viewed as an important adjunct that complements clinical expertise, meticulous surgical technique, and individualized patient care rather than as a standalone solution for preventing postoperative complications.
Indocyanine green (ICG) fluorescence angiography has emerged as an important intraoperative imaging modality that enhances the surgeon’s ability to assess tissue perfusion in real time. By providing dynamic visualization of blood flow after intravenous administration of indocyanine green dye, this technology offers information that often cannot be obtained through conventional visual inspection or manual assessment alone. As minimally invasive and image guided surgical techniques continue to evolve, ICG fluorescence angiography has become an increasingly valuable adjunct across multiple surgical specialties, including colorectal, hepatobiliary, vascular, reconstructive, and gastrointestinal surgery. When incorporated thoughtfully into operative decision making, it has the potential to improve surgical precision and reduce ischemia related complications.
One of the greatest strengths of ICG fluorescence angiography lies in its ability to identify areas of inadequate tissue perfusion that may appear normal under standard white light visualization. Traditional assessment of bowel viability and tissue perfusion relies heavily on subjective indicators such as tissue color, arterial pulsation, bleeding from cut edges, and surgeon experience. Although these methods remain important, they are inherently limited by interobserver variability and may fail to detect subtle perfusion deficits. Fluorescence angiography provides an objective, real time assessment of tissue vascularization, allowing surgeons to identify hypoperfused regions before irreversible ischemic injury or anastomotic failure occurs.
The most robust clinical evidence supporting the use of ICG fluorescence angiography exists in colorectal surgery, particularly during the creation of left sided colorectal anastomoses. Anastomotic leak remains one of the most serious complications following colorectal resection, contributing to increased morbidity, prolonged hospitalization, reoperation, permanent stoma formation, impaired oncologic outcomes, and increased mortality. Numerous prospective studies and meta analyses have demonstrated that intraoperative assessment of bowel perfusion with ICG frequently leads surgeons to modify the planned transection margin or revise the anastomotic site. In many cases, these intraoperative changes have been associated with reductions in anastomotic leak rates, suggesting that improved assessment of tissue perfusion can directly influence patient outcomes.
Beyond colorectal surgery, ICG fluorescence angiography has shown promising applications in several other surgical disciplines. In reconstructive surgery, it assists in evaluating flap viability and reducing flap necrosis. In hepatobiliary surgery, it facilitates identification of biliary anatomy and assessment of liver perfusion. In vascular surgery, it aids in evaluating limb perfusion and graft viability. In upper gastrointestinal procedures, fluorescence imaging is increasingly used to assess gastric conduit perfusion during esophagectomy and gastric surgery. Although evidence continues to accumulate across these fields, the strength of clinical data varies considerably depending on the specific procedure and patient population.
Despite its many advantages, ICG fluorescence angiography has important limitations that must be recognized to ensure appropriate clinical use. Most importantly, fluorescence imaging demonstrates the delivery of dye through the vascular system, but it does not directly measure tissue oxygenation, cellular viability, or the biological processes required for wound healing. Adequate fluorescence indicates that blood reaches the tissue at the time of imaging, but it cannot guarantee that the tissue will heal successfully following surgery. Healing depends on numerous additional factors, including microvascular integrity, inflammatory responses, collagen synthesis, nutritional status, infection, and patient specific comorbidities.
Furthermore, ICG fluorescence angiography provides only a single intraoperative assessment of perfusion. It represents a snapshot of tissue vascularization at one point in time rather than a prediction of postoperative physiological changes. Tissue perfusion may deteriorate after surgery because of hypotension, vasoconstriction, edema, thrombosis, or evolving microvascular compromise. Consequently, a satisfactory intraoperative fluorescence study should never be interpreted as definitive assurance that postoperative ischemic complications will not occur.
Clinical interpretation of fluorescence findings also remains subject to several technical and physiological variables. Factors such as timing of dye injection, camera positioning, ambient lighting, imaging system characteristics, patient cardiac output, vasopressor administration, and individual vascular anatomy can all influence fluorescence intensity and image quality. In addition, there is currently no universally accepted quantitative threshold defining adequate tissue perfusion. While qualitative visual interpretation remains the most common approach, ongoing research seeks to establish standardized quantitative perfusion metrics that may improve reproducibility and clinical decision making.
For these reasons, ICG fluorescence angiography should always be integrated within a comprehensive surgical assessment rather than functioning as a standalone decision making tool. Operative planning should continue to incorporate meticulous surgical technique, direct clinical examination, knowledge of vascular anatomy, patient specific risk factors, anesthetic management, and intraoperative hemodynamic optimization. Patient characteristics such as diabetes mellitus, peripheral vascular disease, smoking history, malnutrition, obesity, chronic kidney disease, previous radiation therapy, and immunosuppression all influence healing potential independently of intraoperative perfusion findings. Likewise, maintaining adequate blood pressure, oxygen delivery, and tissue perfusion throughout the perioperative period remains essential for successful surgical outcomes.
Equally important is the role of vigilant postoperative monitoring. Even when fluorescence angiography demonstrates satisfactory perfusion, patients remain at risk for delayed ischemic complications, infection, or anastomotic failure. Early recognition of postoperative deterioration through careful clinical assessment, laboratory evaluation, and appropriate imaging continues to be fundamental to improving outcomes and reducing morbidity.
The most balanced interpretation of current evidence is that ICG fluorescence angiography represents a valuable adjunct that enhances, rather than replaces, surgical judgment. It has the potential to prevent selected ischemia related complications by identifying areas of compromised perfusion that might otherwise go unnoticed and by prompting intraoperative modifications that improve tissue viability. However, clinicians must remain aware that fluorescence imaging can occasionally provide false reassurance if interpreted as a simple pass or fail test for tissue healing. Successful surgical outcomes depend on multiple biological and technical factors that extend beyond perfusion alone.
Accordingly, the safest and most effective implementation of ICG fluorescence angiography involves standardized, protocol driven use within clearly defined clinical pathways. Imaging protocols should specify dye dosage, timing of administration, image acquisition techniques, interpretation criteria, and documentation requirements. Most importantly, fluorescence findings should be directly linked to predefined intraoperative decision making processes, ensuring that observed perfusion abnormalities result in appropriate surgical action. Such structured implementation promotes consistency, facilitates quality improvement, and supports future research aimed at refining quantitative assessment methods and expanding the evidence base.
In conclusion, indocyanine green fluorescence angiography represents a significant advancement in intraoperative perfusion assessment. Its greatest value lies in providing objective information that complements clinical expertise and enhances surgical decision making. Although it cannot predict postoperative healing with certainty, when used within standardized protocols and interpreted alongside comprehensive clinical assessment, ICG fluorescence angiography can contribute meaningfully to safer surgery, improved tissue preservation, and better patient outcomes.

References
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