This experimental study shows that continuous organ-perfusion monitoring with ICG can assess changes in organ perfusion and adequately detect hypoperfusion in real time.

After inducing mild and severe hypoperfusion in the ventricle, ascending colon, rectum, and spleen, the effect on the recorded oscillation curves, compared to the previously recorded baseline perfusion, was visible almost immediately. Our results show that hypoperfusion resulted in either a lower curve amplitude, flattening or complete disappearance of the oscillation curves—indicating poor or absent perfusion to the target ROIs.

This was well reflected by Slope significantly decreased after the surgical intervention. As of today, no consensus has been reached about which perfusion metrics hold the most value in perfusion assessment, with some studies suggesting T0 to be the strongest indicator of hypoperfusion, while other research points to Slope being of high significance during perfusion monitoring [12,13,14, 19]. In an RCT including 68 patients, Slope furthermore appeared to mirror differences in the manipulation of the intestines accurately [20]. Our results strengthen the assumption that Slope seems most suitable to reflect changes in perfusion status, decreasing in most organs as soon as hypoperfusion was induced.

Four organ measurements show an increase in Slope after occlusion. This is likely due to insufficient priming of the organ before the baseline measurement.

While executing this study, we discovered that the pre-defined ICG priming dose was insufficient to achieve a clear perfusion signal recording in all organs. While measurement of Slope, as well as other metrics, was achieved in two/third of all measurements, the priming dose was too small to result in a proper ICG signal in one ventricle, two rectum, and one spleen measurements. During the experiment, our team decided to adhere to the protocol. However, looking at our results, we will, from now on, advocate that each organ requires an individual priming dose to achieve a good enough perfusion signal for monitoring. Furthermore, collateral arteries might have supplied the organ even after the surgical intervention.

A qualitative organ assessment of the ICG signal would have been misleading. Due to continuous bolus administration over the surgical course, the ICG concentration had led to visual saturation of the target organs, reflected by an increasing mean ICG intensity after each bolus in all organ recordings. Despite quantitatively well-documented hypoperfusion, bright fluorescence could be observed, making qualitative evaluation impossible or fallible.

Current perfusion monitoring during surgery is predominately done by measuring cardiac output, oxygen delivery, and oxygen consumption [21]. While these measurements provide general information on the patient’s hemodynamic status, they fail to address possible complications at the organ level.

To give an example, abdominal surgery often necessitates extensive surgical dissection of the mesentery, mobilization of organs, and ligation of vessels with varying anatomy. Limited oversight or clinical suspicion of hypoperfusion can make it difficult to detect it at occurrence.

To our knowledge, this is the first time continuous perfusion monitoring with ICG has been used to observe and detect organ hypoperfusion in real-time during surgery, addressing the abovementioned problem with a new, promising monitoring practice. Our research group recently reported in-depth on the methodology, showing that low-dose ICG can be used successfully to monitor baseline organ perfusion [15].

Our study has several strengths and limitations. Its strength lies in its standardized design, which followed a fixed protocol in all animals and organs, making the resulting data comparable and reproducible. It was conducted by a multidisciplinary team of medically trained surgeons and veterinary specialists and followed the ARRIVE guidelines for animal research.

Regarding limitations, we did only receive a sufficient quantification signal in 2 of the 3 spleens. This is most likely explained by insufficient priming with ICG at the beginning of the surgery. The dosage given to each study subject was weight-adjusted and did not consider that different organs might need different ICG quantities to provide a strong enough signal for quantitative perfusion assessment. While these results are suboptimal, they add new information to our knowledge of how ICG works in the bloodstream, addressing that different organs have an individual need for what we consider the minimum ICG dosage to achieve a detectable perfusion signal.

In future studies, each subject should receive an individual priming dose to facilitate usable baseline measurements in every organ. We used the Stryker 1588 platform, which necessitated switching between white light during surgery and “ICG-view” during the perfusion recording. This caused a delay in quantitative perfusion assessment after arterial occlusion and necessitated placing “new” ROIs each time the camera was switched to NIR light. While we aimed to select the same ROIs in every measurement, ROI selection varied slightly between conditions due to “white light disruption.” Ideally, a surgical platform with an integrated “overlay” function (or “split-screen”) should be used in future trials to allow the surgeon to operate while simultaneously running the perfusion assessment on the same camera image. Lastly, the camera had to be placed stationary, without movement, to ensure a usable perfusion recording. Movements of the camera result in futile measurements that cannot be used for quantitative analysis. The software mitigates small movements but needs to be developed further before being ready for clinical use as a “background surveillance” of hypoperfused tissue.

Low-dose, high-frequency ICG perfusion monitoring presents a new method for intraoperatively measuring and detecting target-specific hypoperfusion. Further research is needed to validate and improve the method until it can offer a substantial help to surgeons.

The methodology needs to be validated in humans. Based on our findings and since ICG is already widely used during surgical procedures and the cumulative ICG dosage administered stays below the max. recommended dosage, clinical testing is possible and should be the next step in development [22].

Technological improvements should be directed toward the software running “quietly” on the laparoscopic camera screen, continuously deploying a background analysis, and notifying the surgeon in real time when hypoperfusion is detected.

In conclusion, we found that continuous organ-perfusion monitoring using a high-frequency, low-dose ICG bolus regimen can detect organ hypoperfusion in real time. Further validation and development are needed.