The Application of Indocyanine Green to Evaluate Duodenal Perfusion in Pancreas Transplantation

Authors


Abstract

In cases of suspected duodenal ischemia during pancreas transplantation, surgical decisions severely affect the outcome of the patient and the graft. The use of a nontoxic intravenous tracer, indocyanine green, allows the surgeon to evaluate the perfusion of tissues within seconds of injection. Its application to pancreas transplantation has not been reported previously.

Abbreviations
BMI

body mass index

ICG

indocyanine green

Introduction

In recent years, the use of indocyanine green (ICG) to evaluate tissue perfusion has improved surgical outcomes and helped with real-time decision-making during surgical procedures. It has proven to be a helpful tool in plastic surgery in assessing the viability of tissue flaps [1, 2], and in colorectal surgery for evaluating anastomotic tissues for the prevention of leaks [3, 4]. Additionally, in the fields of cardiovascular and peripheral vascular surgery, ICG has been applied in order to evaluate tissue-level perfusion after revascularization procedures [5]. Adequate organ and tissue perfusion is crucial during transplantation. In pancreas transplantation, insufficient perfusion to the head of the pancreas and the duodenum can result in an anastomotic leak, which presents severe consequences to the patient. While the use of ICG as a determinant of renal parenchyma and ureteric viability in kidney transplantation has been documented [6, 7], to the best of our knowledge, we report the first application of ICG in pancreas transplantation.

Case Report

Our recipient is a 37-year-old Hispanic male with a body mass index (BMI) of 38.5 kg/m2, who was diagnosed with type I diabetes mellitus at 7 years of age. Three years prior to his pancreas transplant, he received a living donor kidney transplant. The pancreas graft was obtained from an out-of-state donor. He was a 6-year-old Hispanic male who weighed 23 kg with a BMI of 16.2 kg/m2 and HbA1c of 5.7%. No significant medical history was noted and no report of cardiac arrest. The donor's cause of death was head trauma, with a total cold ischemic time of 17 h.

The bench preparation of the organ included a splenectomy, ligation of the mesenteric vessels and imbrication of the staple lines at the duodenum. Vascular reconstruction included a Y-graft interposition from the donor iliac artery bifurcation. The arteries were soft and elastic but small in caliber in correlation with the donor's age. During implantation, the distal vena cava and right common iliac artery were selected for an end-to-side anastomosis with the portal vein of the pancreas and Y-graft. The recipient's artery was soft and free of arteriosclerotic plaques. Upon reperfusion, the body and tail of the pancreas pinked up nicely; however, the duodenum remained bluish. On the table, the Doppler demonstrated a low signal in the head of the pancreas and the duodenal wall. There was a concern of ischemia due to the small-caliber vessels or the possibility of an inadvertent ligation of the inferior pancreatoduodenal artery.

The majority of surgeons will perform a bladder drainage procedure when concerned with the possibility of duodenal ischemia. In other instances, they remove the graft to avoid devastating complications. Since this was a pediatric donor, drainage to the urinary system would require extensive mobilization of the bladder in order to lift it to the promontorium and assure a tension-free anastomosis. At our institution, surgeons have experience in the application of ICG for assessing the perfusion of tissues in diverse surgical interventions. In this case, we administered 3 mL of ICG intravenously and recorded the perfusion of the pancreas with a fluorescent camera, SPY system (Novadaq Technologies, Vancouver, Canada). After a few heartbeats, the fluorescence was observed as it perfused the head of the pancreas and duodenum of the graft with similar intensity as in the rest of the pancreas and to the recipient's colon. The SPY system measures the intensity of fluorescence and compares it to a baseline chosen by the operator. The fluorescence of the targeted tissue is expressed as a percentage of the baseline tissue. In this case, the use of ICG allowed us to evaluate real-time duodenal wall perfusion compared with the recipient's baseline tissue perfusion. The duodenum of the graft revealed 100% uptake compared to the ascending colon of the recipient (Figure 1). With this information, the duodenum was safely anastomosed to the bowel of the recipient. Most importantly, when the duodenal was opened, bleeding was present as well as good coloration, confirming the information obtained with the infusion of ICG.

Figure 1.

Fluorescence image of the pancreas after indocyanine green administration. Pink-dotted line demarcated the pancreas graft. Labels indicate the percentage of uptake compared to a baseline tissue, chosen in the ascending colon.

The patient's postoperative course was unremarkable. Hospital length of stay was 9 days; amylase and lipase peaked at 60 and 90, respectively, in the first 24 h following transplantation. The patient remained normoglycemic during the entire postoperative course with unremarkable laboratory values. During the first month of follow-up, with excellent graft function, he continues to be afebrile, and has not required any imaging of the organs based on laboratory analysis or clinical condition.

Discussion

IC GREEN™ (Akorn, Inc., Lake Forest, Illinois) is a sterile, lyophilized green powder containing ICG and sodium iodide, packaged in sterile water for injection. It is a water-soluble, tricarbocyanine dye with a peak spectral absorption at 800 nm. Following intravenous injection, IC GREEN™ rapidly binds to plasma protein and is distributed only in the intravascular space; it has a 3- to 4-min half-life and is rapidly eliminated by the liver. The tracer ICG is activated by emitted light at a wavelength of 760 nm and filters out light with wavelengths under 820 nm. The light source from the SPY Elite system detects the tracer as it distributes throughout the perfused tissues. Upon injection and exposure to the SPY Elite laser, ICG fluorescence occurs nearly immediately and dissipates in a manner that allows for rapid image acquisition within the real-time operative setting. The intraoperative ICG images are evaluated using SPY-Q analysis software (Novadaq Technologies Inc., Bonita Springs, Florida), which contains two options to quantify the perfusion images. The first reports the fluorescence of an area of interest as a percentage compared with a reference point designated as 100% perfused. The second uses a 255-level gray-scale system, which corresponds to the image signal intensity.

Limited literature is available correlating the values of fluoroscopic intensity with the risk of necrosis or the risk for the development of postoperative complications. While some authors prefer to use the absolute measurements of intensity rather than relative percentages, larger studies need to be conducted in order to have conclusive results. Furthermore, operator technique may affect image quality. For example, fluorescence can be diminished with ambient lighting. The camera should be positioned perpendicular to the surface of interest for optimal imaging, and ICG should be injected through a large intravenous line. In addition, hypotension and hypoxia will affect tissue perfusion and distribution of the tracer. Therefore, both should be corrected prior to ICG administration and the recording of the infusion should coincide with maximal fluorescence [8].

Adequate perfusion of the head of the pancreas and the duodenum is crucial in pancreas transplantation. Ischemia of the duodenal wall will invariably lead to leakage of pancreatic content into the abdominal cavity. In an enterically drained pancreas, this results in spillage of enteric contents and peritonitis, which can potentially represent a life-threatening complication. Although a duodenal leak is a very rare complication, occurring in 0.5% of all pancreas transplant recipients, it nevertheless represents a potentially devastating complication that can result in graft loss or, most importantly, patient death [9]. Intraoperatively, signs of favorable perfusion include brisk bleeding from the duodenal wall, pink duodenal serosa/mucosa and the presence of a positive strong Doppler signal on the surface of the organ. Anything inferior to these findings does not ensure sufficient perfusion of the tissues. The use of the Doppler as an indirect measurement of vascularization has several limitations. It has more variability between users, is less selective and can be affected by signals from distant vessels, appropriating false positives. Importantly, unlike the SPY system, the Doppler ultrasound will not show microvascular perfusion. Evaluation of microvascular perfusion is crucial in several fields of surgery, and real-time assessment allows the surgeon to make significant clinical decisions. This is especially true in donation after cardiac death.

The application of ICG in transplantation is currently limited; however, its utility in the field has growing potential. In kidney transplantation, ICG can be used to evaluate ureteral perfusion in complex cases, for example, in the presence of multiple arteries that could compromise the blood supply of the ureter, potentially preventing future ureteral strictures due to ischemic injury. In addition, in cases where the kidney has to be implanted higher in the common iliac artery, the ureter will have to be longer and is at risk for ischemia; ICG can be used prior to ureteral anastomosis to guarantee good perfusion at the terminal end. In the assessment of organ perfusion, specifically in cases with multiple arterial reconstructions, the application of ICG can be very useful [6]. Another benefit of ICG includes its favorable value in identifying ischemic injury to both the organ and ureter of kidneys obtained from donors after circulatory determination of death. Last, ICG fluorescence also possesses potential applications in liver transplantation, as it is cleared by the liver and eliminated in the bile.

Conclusion

The application of ICG is a safe mechanism that provides a real-time, reliable assessment of tissue perfusion. The information obtained through its application can be crucial for intraoperative decision-making during pancreas transplantation. In the presence of an ischemic duodenum, most importantly, an anastomotic leak represents a potentially fatal outcome, which can be avoided. Larger studies need to be conducted to establish a correlation between the values obtained with the SPY-Q system and the risk of developing complications related to tissue hypoperfusion.

Disclosure

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

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