Feasibility and Usability of Intraoperative Fluorescent Angiography With Indocyanine Green in Penetrating Abdominal Trauma

The surgical management of penetrating bowel and intestinal injuries, inflicted via a gunshot or knife stabbing, has long been a topic of debate \[1-3\]. The surgical management principally consists of: (i) primary repair; (ii) primary diversion or (iii) an initial abbreviated so called "damage control" operation followed by a definitive surgical intervention once the patient is stabilized \[4-9\] . Different classifications systems have been proposed to help determine the best operative option \[2,3,10-14\], but intestinal injuries can be difficult to manage and despite improvements in the diagnostics and treatment of penetrating abdominal trauma, high mortality and morbidity rates are prevalent \[15,16\]. In order to determine the correct surgical option an accurate determination of intestinal viability is essential. But clinically assessing regional perfusion is challenging and surgeons' clinical risk assessment of anastomotic leaks have shown a low predictive value \[17\]. Hence, there is a need for more precise diagnostic tool helping the surgeon in assessing intestinal viability the extent of intestinal injury.

Indocyanine green (ICG) fluorescence angiography (ICG-FA) is an applied method for to assessing visceral perfusion worldwide. The obtained fluorescent signal after intravenous injection, is considered proportional to blood flow, thus aiding the surgeon to detect and address inadequate regional perfusion, despite satisfactory macroscopic appearance, intraoperatively \[18-21\]. Hence, the use of perioperative ICG-FA, has reduced the risk of anastomotic leaks after esophageal and colorectal surgery \[22-25\] and in the setting of acute mesenteric ischemia, significantly reduced the extent of intestinal resection \[26\]. In retrospective review of 186 war related trauma cases the use of ICG-FA was deemed useful however only 9 of these cases were truncal/abdomen/gastrointestinal and no objective definition of usability was provided \[27\]. Hence, data on the usability and feasibility of ICG-FA for in penetrating abdominal trauma is limited and to our knowledge has not been investigate in a civilian population previously.

The present study aimed to investigate the usability and feasibility of ICG-FA in patients undergoing open abdominal exploration for penetrating abdominal trauma

The surgical management of penetrating bowel and intestinal injuries has been the topic of debate since before the second world war \[1-3\]. The injury is most often inflicted via a gunshot or knife stabbing. Different classifications systems have been proposed to help determine the best operative option: (i) Flint Grading System (FGS); (ii) Penetrating Abdominal Trauma Index (PATI); (iii) Colonic/Rectal Injury Scale (CIS/RIS); and (iv) destructive/non-destructive colonic injuries; (v) Stone and Fabian's criteria \[2,3,10-14\].

Principally, a penetrating injury of the intestine can be managed by: (i) primary repair (suturing the hole in the intestine); (ii) primary diversion (the intestine, above the injury, is brought through the abdominal wall as a "stoma") or (iii) an abbreviated primary operation (laparotomy, where large bleeding is stopped and destroyed tissue is removed) and planned reoperation, within 24-48 hours, for definitive treatment (final treatment, for example reconnecting intestinal ends). The concept of abbreviated primary operation, also known as "damage control surgery", is today well established in trauma care \[4-6\]. A damage control operation with regards to intestinal injury, entails a primary resection/removal of the affected intestinal segment in which the remaining intestinal ends are closed off and not surgically connected (anastomosed) in the first operation.\[4-9\]. The abdomen is left "open" (the incision through the abdominal wall is not sutured closed but covered with a temporary dressing), and a relaparotomy (re-operation) is conducted once the patient is stabilized (at the end of which the abdominal wall is closed), usually after 24-48 h \[4-9\]. During the re-laparotomy, the intestines will then either be anastomosed (re-connected), or a stoma will be created if the intestine is deemed too damaged to be re-connected \[4-9\].

Non-destructive colonic injuries (Flint grades 1 \& 2 and CIS grades I to III) are generally treated with primary repair, which involves the identification, debridement and single-layer suture repair of perforation and then dressing the repaired site with omentum (an intra-abdominal layer of fat and vessels) \[1,2,10,12\]. Primary repair is generally considered the better option in this setting \[1-3,28\].

Destructive colon wounds (Flint grade 3 or CIS grades IV and V) encompass those injuries that require segmental resection (parts of the large intestine have to be removed) due to extensive damage or loss of blood supply or both \[10,12\]. The management of destructive colon wounds is less clear and is still debatable. However, primary repair has been deemed as a safe option, while primary diversion has been opted for in particular cases \[1-3,9,11,29-33\]. In unstable patients; those with hypovolemic shock (large blood loss), blood-poisoning due to intestinal content leaking into the abdominal cavity, systemic hypothermia (low body temperature), and complex intra-abdominal injuries; an abbreviated laparotomy is considered to be an appropriate course of action \[7,11,30,32-34\].

In colonic trauma, the anastomosis leak rate (the connection between to intestinal ends breaks down) is reported between 4-27% \[34-37\]. A leak in the sight of intestinal connection is a severe complication which greatly increases the length of hospitalization, increases patient morbidity and has a significant negative impact on patient's recovery. The mortality rate for an anastomotic leak around 10-15% \[38,39\]. Factors associated with anastomotic failure include co-morbid immune-compromising disorders such as diabetes mellitus, acquired immunodeficiency syndrome, cirrhosis and a transfusion requirement of more than six units of blood \[36\]. Other potential risk factors appear to be shock, significant associated injuries, and delay of operation \[35,36\].

In firearm injuries the tissue damage is proportionate to a variety of factors: Projectile velocity, -entrance profile, -calibre, -design, distance travelled within the body (penetrating projectiles deliver their total kinetic energy to the body, whereas perforating projectiles transfer significantly less), biologic characteristics of the impacted tissue and the mechanisms of tissue disruption (e.g. stretching, tearing, crushing) \[40\]. The extent of damage in the tissue surrounding the entered organ can be difficult to assess, and despite improvements in diagnostics and treatment of abdominal gunshot wounds, high mortality and morbidity rates are still found \[15,16\].

In conclusion, intestinal injuries can be difficult to manage. A primary repair is preferable but there is a need for more precise diagnostic tools helping the surgeon to access the extent of intestinal injury. Also, reducing the extent of intestinal removal has a high value for the patient as extensive resections can lead to nutritional difficulties even after discharge.

Fluorescence guided surgery Assessing intestinal blood supply is a challenging task even for experienced surgeons. One of the biggest concerns is the blood supply of the anastomosis (the surgical connection between to intestinal ends) since poor blood supply is regarded as a significant risk factor for anastomotic leak \[41-44\]. As mentioned above, an anastomotic leak is a severe complication in gastrointestinal surgery and has a significant negative impact on patients recovery with the mortality rate for an anastomotic leak around 10-15% \[38,39\].

Fluorescence guided surgery (FGS) enables visualization of structures that are otherwise hidden from the naked human eye. A fluorescent contrast agent is used, most often indocyanine green (ICG), and by illuminating the tissue with near-infrared light, the excited ICG can be detected by a camera with an optical filter. ICG is a tricarbocyanine dye with very few adverse events, a short half-life, and exclusively metabolized in the liver and excreted unchanged in the bile \[45,46\]. The safety of ICG well established and the contrast is used routinely in surgical settings worldwide, just as it has gained popularity in oncological surgery in recent years \[45-47\].

ICG binds to plasma proteins in the blood after intravascular injection, and by illuminating the tissue with near-infrared red light, the fluorescence intensity during the first passage in tissue is considered proportional to blood flow (perfusion). This real-time visualization of visceral perfusion (blood flowing to a given organ) may reduce the rate of anastomotic leakage because inadequate vascularization can be detected during the operation \[18-20\]. Also, the option for intraoperative visual assessment of blood flow to the intestine, stomach and surrounding tissues, allowing for modification to the surgical plan, may eliminate anastomotic break down or leak due to inadequate vascularization despite satisfactory blood supply on naked-eye appearance \[20,21,48\], (Figure 1).

Figure 1. A. Intestinal segment as viewed with the naked eye. B. Evaluation of blood flow after injection of ICG, viewed with the infra-red camera (ICG-FA). C. A computer generated combination of images A and B ("overlay") allowing the surgeon to evaluate intestinal blood supply.

In a prospective observational study on patients with a left-sided colorectal cancer, ICG fluorescence angiogram (FA) altered operative decisions in 34.5% of the cases (n=111) i.e. the site of resection was adapted after tissue perfusion evaluated with ICG FA. Also, the use of ICG FA significantly reduced the anastomotic leak rate in patients undergoing surgery for colorectal cancer \[49\]. In patients undergoing esophagectomy, the use of ICG FA with intervention was found to have a risk reduction for complications of 69% and a significantly lowered risk of anatomic leaks \[25\].

The use of ICG FA has been shown to improve patient outcome and reduce patients risks in elective settings, however, there is much need for evaluation in the acute/emergency setting. The risk of complications, patient morbidity and mortality are inherently higher in an emergency surgical setting compared to an elective/planned setting \[50\]. Thus, it is feasible to believe that the use of ICG FA in an emergency setting will improve patient outcome and reduce risk of complications. There is to date little literature on the use of ICG FA in an emergency/trauma setting. However, a recent retrospective study by Karampinis et al. 2018 deemed the use of ICG FA as a feasible and technically reliable technique in patients undergoing emergency surgery for acute mesenteric ischemia. Indocyanine Green FA provided additional information regarding intestinal perfusion in 18 of their 53 cases (35%). In 11 patients the surgical strategy was amended by ICG angiography, showing adequate perfusion, and thus no indication for intestinal resection. No further resections were performed on these patients during the second- and third- look laparotomies \[26\]. In March 2015, Green et al. presented a retrospective review of all war-related traumatic and reconstructive cases employing the intraoperative use of indocyanine green angiography within the US army over a three year period \[27\]. They concluded that - Intraoperative fluorescent angiography is an objective, useful tool to assess various war-related traumatic injuries \[27\].

The Department of Surgical Gastroenterology, Rigshospitalet, Denmark, have developed an ICG quantification algorithm which has been validated and described earlier \[51\]. This algorithm has now been incorporated into a touch screen tablet, allowing for live perioperative quantitative perfusion assessments with ICG (Q-ICG). A color-coded map of perfusion intensity is provided as an overlay on the white light visualized tissue (Figure 2). In a feasibility study of ten patients undergoing surgery for stomach cancer, significant alterations of optimal perfusion points selected by surgeons were found when comparing points selected in white light, ICG FA and Q-ICG (Nerup, in review).

Figure 2. The remaining stomach (gastric conduit) viewed by white light, Near-Infrared Light (ICG FA) and with Q-ICG overlay.

As ICG FA can assess micro-perfusion, we believe that it has the possibility to improve intraoperative evaluation of tissue integrity and as such improve the surgical plan and outcome in patients suffering gunshots to the abdominal viscera. We also believe that the quantification tool provided by Rigshospitalet will further assist the surgical decision-making.

Aim This study aims to evaluate the feasibility of perfusion assessment with traditional visual, visual ICG FA and Q-ICG.

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Eligibility Criteria:
Inclusion Criteria:

* Patients (above 18 years) scheduled for emergency laparotomy due to penetrating abdominal trauma

Exclusion Criteria:

* Allergy towards; iodine, indocyanine green or shellfish
* Liver insufficiency
* Thyrotoxicosis
* Pregnancy or lactation
* Legally incompetent for any reason