Indocyanine Green Clearance Research Articles

Indocyanine green clearance as a prognostic marker in acute liver failure

Aims: In patients suffering from acute liver failure (ALF) prediction of prognosis is of major importance to decide whether liver transplantation is needed. The King´s College criteria (KCC) are widely used to determine prognosis. However, the specificity of the KCC to predict the need for transplantation is low. Indocyanine green (ICG) is a dye that is biliary cleared from the blood and its plasma concentration can be determined non-invasively by the rate of absorption of infrared light. The clearance of ICG depends on hepatic blood flow and hepatocyte function.

Estimation of indocyanine green 15-minute retention rate using Hitachi 7180 automatic analyser

The indocyanine green (ICG) clearance test has been used to assess the reserve of hepatic function. This method is based on the spectrometric measurement of its plasma concentration at maximum wavelength of 805nm, which requires a spectrophotometer and associated maintenance. We established an ICG measurement method using a Hitachi 7180 automatic chemistry analyser that can be tuned to a wavelength of approximately 800nm. The retention rate of ICG at 15min was determined for 41 patients using a conventional method and our method. The ICG clearance test using the automatic analyser showed excellent agreement. It is expected that the ICG test using the automatic analyser can replace the conventional ICG clearance test.

Perioperative indocyanine green clearance is predictive for prolonged intensive care unit stay after coronary artery bypass grafting - an observational study

IntroductionDuring cardiac surgery with cardiopulmonary bypass (CPB) haemodilution occurs. Hepatic dysfunction after CPB is a rare, but serious, complication. Clinical data have validated the plasma-disappearance rate of indocyanine green (PDR ICG) as a marker of hepatic function and perfusion. Primary objective of this analysis was to investigate the impact of haemodilutional anaemia on hepatic function and perfusion by the time course of PDR ICG and liver enzymes in elective CABG surgery. Secondary objective was to define predictors of prolonged ICU treatment like decreased PDR ICG after surgery.Methods60 Patients were subjected to normothermic CPB with predefined levels of haemodilution anaemia (haemotacrit (Hct) of 25% versus 20% during CPB). Hepatic function and perfusion was assessed by PDR ICG, plasma levels of aspartate aminotransferase (ASAT) and α-GST. Prolonged ICU treatment was defined as treatment ≥ 48 hours.ResultsLogistic regression analysis showed that all postoperative measurements of PDR ICG (P < 0.01), and the late postoperative ASAT (P < 0.01) measurement were independent risk factors for prolonged ICU treatment. The predictive capacity for prolonged ICU treatment was best of the PDR ICG one hour after admission to the ICU. Furthermore, the time course of PDR ICG as well as ASAT and α-GST did not differ between groups of haemodilutional anaemia.ConclusionsOur study provides evidence that impaired PDR ICG as a marker of hepatic dysfunction and hypoperfusion may be a valid marker of prolonged ICU treatment. Additionally this study provides evidence that haemodilutional anaemia to a Hct of 20% does not impair hepatic function and perfusion.Trial registration[ISRCTN35655335]

Prädiktion der perioperativen Mortalität bei Patienten mit fortgeschrittener Lebererkrankung und abdominalchirurgischen Eingriffen anhand unterschiedlicher Score- und Testsysteme

Patients with advanced liver disease show increased morbidity and mortality after hepatic resection and non-hepatic digestive surgery. Furthermore, postoperative liver failure is associated with a poor outcome, representing an important clinical problem. For evaluation of the perioperative mortality and the hepatic function, several scoring systems, clinical parameters, and static and dynamic tests are available. Recently, the Model for End-Stage Liver Disease (MELD) has been shown to provide a complementary predictive value to the widely used Child Turcotte Pugh score. Patients with Child Turcotte Pugh class C cirrhosis and MELD scores >14 are generally not considered for surgical intervention. Patients with Child Turcotte Pugh class B cirrhosis and MELD scores >8-14 have an increased perioperative risk and the indication for surgery should be assessed carefully. In patients with Child Turcotte Pugh class A cirrhosis and MELD scores of <or= 8, perioperative mortality is low. Although not routinely used, dynamic tests can provide additional information on the expected residual hepatic function in patients with Child Turcotte Pugh class A cirrhosis and MELD scores of <or= 8 in whom hepatic resection is needed. Besides other dynamic tests, the indocyanine green (ICG) clearance and the monoethylglycinxylid (MEGX) clearance tests have been satisfactorily evaluated.

Assessment of liver function for successful hepatectomy in patients with hepatocellular carcinoma with impaired hepatic function

This study aimed to construct a formula for assessing liver function in order to prevent post-hepatectomy liver failure. A formula was constructed by analyzing data from 28 patients with hepatocellular carcinoma (HCC) with liver cirrhosis operated on between 1981 and 1984. Next, we evaluated the validity of this formula in 207 hepatectomy patients operated on from 1985 to 1999. For 145 hepatectomy patients operated on from 2000 to 2006, this formula was calculated before surgery in order to assess their risk of hepatectomy. The formula for liver functional evaluation, constructed from preoperative hepatic function parameters, was: liver failure score = 164.8 - 0.58 x Alb - 1.07 x HPT + 0.062 x GOT - 685 x K. ICG - 3.57 x OGTT. LI + 0.074 x RW, where Alb is albumin (g/dl); HPT, hepaplastin test (%); GOT, glutamate oxaloacetate transaminase (U/l); K. ICG, K value of indocyanine green clearance test; OGTT. LI, 60-min/120-min glucose level in 75-g oral glucose tolerance test. linearity index of OGTT; and RW, weight of resected liver (g). We decided that a score below 25 would be safe for hepatectomy. The mortality rate decreased from 3.9% in 1985--1999 to 1.3% in 2000--2006. This finding allows us to conclude that the formula is valid for assessing the risk of post-hepatectomy liver failure.

Indocyanine Green Angiography in Experimental Choroidal Circulatory Disturbance

Purpose: To determine how choroidal venous congestion alters the indocyanine green angiograms (ICGA) of monkeys. Methods: Two vortex veins in each eye of 5 Japanese macaque monkeys were sutured and cauterized at their exit. ICGA and fluorescein angiography (FA) were performed immediately after the occlusions. The FA and ICGA findings were correlated with the histopathological changes. Results: ICGA showed a delay in filling the choroidal arteries in the field of the occluded vortex veins, and the choroidal veins were filled retrogradely in a pulsatile manner. The fluorescence intensity of the larger veins was higher in the occluded area. The clearance of the indocyanine green dye was delayed by approximately 15 min. Histology showed that the choroidal veins in the occluded field were engorged with red blood cells. Conclusion: The ICGA findings in eyes with choroidal venous congestion are a delay in the filling of the choroidal arteries, reflux of venous blood flow, increase in fluorescence intensity of the choroidal veins, and delayed indocyanine green dye clearance.

Effects of levosimendan on indocyanine green plasma disappearance rate and the gastric mucosal–arterial pCO2 gradient in abdominal aortic aneurysm surgery

Levosimendan has a dual mechanism of action: it improves myocardial contractility and causes vasodilatation without increasing myocardial oxygen demand. In a laboratory setting, it selectively increases gastric mucosal oxygenation in particular and splanchnic perfusion in general. The aim of our study was to describe the effects of levosimendan on systemic and splanchnic circulation during and after abdominal aortic surgery. Twenty abdominal aortic aneurysm surgery patients were randomized to receive either levosimendan (n=10) or placebo (n=10) in a double-blinded manner. Both the mode of anaesthesia and the surgical procedures were performed according to the local guidelines. Automatic gas tonometry was used to measure the gastric mucosal partial pressure of carbon dioxide. Systemic indocyanine green clearance plasma disappearance rate (ICG-PDR) was used to estimate the total splanchnic blood flow. The immediate post-operative recovery was uneventful in the two groups with a comparable, overnight length of stay in the intensive care unit. Cumulative doses of additional vasoactive drugs were comparable between the groups, with a tendency towards a higher cumulative dose of noradrenaline in the levosimendan group. After aortic clamping, the cardiac index was higher [4(3.8-4.7) l/min/m(2) vs. 2.6(2.3-3.6) l/min/m(2); P<0.05] and the gastric mucosal-arterial pCO(2) gradient was lower in levosimendan-treated patients [0.9(0.6-1.2) kPa vs. 1.7(1.2-2.1) kPa; (P<0.05)]. However, the total splanchnic blood flow, estimated by ICG-PDR, was comparable [29(21-29)% vs. 20(19-25)%; NS]. Organ dysfunction scores (sequential organ dysfunction assessment) were similar between the groups on the fifth post-operative day. Levosimendan favours gastric perfusion but appears not to have a major effect on total splanchnic perfusion in patients undergoing an elective aortic aneurysm operation.

Reactive hyperemia in the human liver

We tested whether hepatic blood flow is altered following central hypovolemia caused by simulated orthostatic stress. After 30 min of supine rest, hemodynamic, plasma density, and indocyanine green (ICG) clearance responses were determined during and after release of a 15-min 40 mmHg lower body negative pressure (LBNP) stimulus. Plasma density shifts and the time course of plasma ICG concentration were used to assess intravascular volume and hepatic perfusion changes. Plasma volume decreased during LBNP (-10%) as did cardiac output (-15%), whereas heart rate (+14%) and peripheral resistance (+17%) increased, as expected. On the basis of ICG elimination, hepatic perfusion decreased from 1.67 +/- 0.32 (pre-LBNP control) to 1.29 +/- 0.26 l/min (-22%) during LBNP. Immediately after LBNP release, we found hepatic perfusion 25% above control levels (to 2.08 +/- 0.48 l/min, P = 0.0001). Hepatic vascular conductance after LBNP was also significantly higher than during pre-LBNP control (21.4 +/- 5.4 vs. 17.1 +/- 3.1 ml.min(-1).mmHg(-1), P < 0.0001). This indicates autoregulatory vasodilatation in response to relative ischemia during a stimulus that has cardiovascular effects similar to normal orthostasis. We present evidence for physiological post-LBNP reactive hyperemia in the human liver. Further studies are needed to quantify the intensity of this response in relation to stimulus duration and magnitude, and clarify its mechanism.

Extracorporeal Cardiopulmonary Support for Cardiogenic Shock Caused by Pheochromocytoma: A Case Report and Literature Review

Extracorporeal Cardiopulmonary Support for Cardiogenic Shock Caused by Pheochromocytoma: A Case Report and Literature Review

Sex Dimorphism in the Outcome of Preoperative Right Portal Vein Embolization

Although studies indicate that patient sex modulates the process of hepatic regeneration, it remains unknown whether sex has a role in the outcome of preoperative right portal vein embolization (PVE). We analyzed the effects of patient sex on the outcome of right PVE followed by major hepatectomy. Retrospective study. Academic research. Eighty-eight patients (42 men and 46 women) who underwent preoperative right PVE for bile duct carcinoma were analyzed retrospectively. The percentage liver volume change, the plasma indocyanine green clearance rate, and the rate of postoperative hepatic failure were compared between men and women. The mean (SD) volume of the nonembolized lobe after PVE in women (323 [61] mL/m(2)) was statistically significantly greater than that in men (287 [61] mL/m(2)) (P =.008). The mean (SD) ratio of the nonembolized lobe to the total liver volume was also statistically significantly greater in women (45.8% [5.8%]) than in men (42.0% [5.9%]) (P =.003). The mean (SD) indocyanine green clearance rate of the future liver remnant was 0.075 [0.014] in women and 0.056 [0.011] in men (P =.001). The incidence of postoperative hepatic failure was higher in men (12 of 42 [28.6%]) than in women (8 of 46 [17.4%]) (P =.16). These results indicate that sex dimorphism can be present in the outcome of preoperative right PVE.

Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment

The only curative treatment in biliary tract cancer is surgical treatment. Therefore, the suitability of curative resection should be investigated in the first place. In the presence of metastasis to the liver, lung, peritoneum, or distant lymph nodes, curative resection is not suitable. No definite consensus has been reached on local extension factors and curability. Measures of hepatic functional reserve in the jaundiced liver include future liver remnant volume and the indocyanine green (ICG) clearance test. Preoperative portal vein embolization may be considered in patients in whom right hepatectomy or more, or hepatectomy with a resection rate exceeding 50%–60% is planned. Postoperative complications and surgery-related mortality may be reduced with the use of portal vein embolization. Although hepatectomy and/or pancreaticoduodenectomy are preferable for the curative resection of bile duct cancer, extrahepatic bile duct resection alone is also considered in patients for whom it is judged that curative resection would be achieved after a strict diagnosis of its local extension. Also, combined caudate lobe resection is recommended for hilar cholangiocarcinoma. Because the prognosis of patients treated with combined portal vein resection is significantly better than that of unresected patients, combined portal vein resection may be carried out. Prognostic factors after resection for bile duct cancer include positive surgical margins, especially in the ductal stump; lymph node metastasis; perineural invasion; and combined vascular resection due to portal vein and/or hepatic artery invasion. For patients with suspected gallbladder cancer, laparoscopic cholecystectomy is not recommended, and open cholecystectomy should be performed as a rule. When gallbladder cancer invading the subserosal layer or deeper has been detected after simple cholecystectomy, additional resection should be considered. Prognostic factors after resection for gallbladder cancer include the depth of mural invasion; lymph node metastasis; extramural extension, especially into the hepatoduodenal ligament; perineural invasion; and the degree of curability. Pancreaticoduodenectomy is indicated for ampullary carcinoma, and limited operation is also indicated for carcinoma in adenoma. The prognostic factors after resection for ampullary carcinoma include lymph node metastasis, pancreatic invasion, and perineural invasion.

Indocyanine green clearance following minor liver resection

Indocyanine green clearance following minor liver resection

Indocyanine Green Plasma Disappearance Rate During the Anhepatic Phase of Orthotopic Liver Transplantation

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI] = 0.8–2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account.

Gastrointestinal Perfusion in Septic Shock

Septic shock is characterised by vasodilation, myocardial depression and impaired microcirculatory blood flow, resulting in redistribution of regional blood flow. Animal and human studies have shown that gastrointestinal mucosal blood flow is impaired in septic shock. This is consistent with abnormalities found in many other microcirculatory vascular beds. Gastrointestinal mucosal microcirculatory perfusion deficits have been associated with gut injury and a decrease in gut barrier function, possibly causing augmentation of systemic inflammation and distant organ dysfunction. A range of techniques have been developed and used to quantify these gastrointestinal perfusion abnormalities. The following techniques have been used to study gastrointestinal perfusion in humans: tonometry, laser Doppler flowmetry, reflectance spectrophotometry, near-infrared spectroscopy, orthogonal polarisation spectral imaging, indocyanine green clearance, hepatic vein catheterisation and measurements of plasma D-lactate. Although these methods share the ability to predict outcome in septic shock patients, it is important to emphasise that the measurement results are not interchangeable. Different techniques measure different elements of gastrointestinal perfusion. Gastric tonometry is currently the most widely used technique because of its non-invasiveness and ease of use. Despite all the recent advances, the usefulness of gastrointestinal perfusion parameters in clinical decision-making is still limited. Treatment strategies specifically aimed at improving gastrointestinal perfuision have failed to actually correct mucosal perfusion abnormalities and hence not shown to improve important clinical endpoints. Current and future treatment strategies for septic shock should be tested for their effects on gastrointestinal perfusion; to further clarify its exact role in patient management, and to prevent therapies detrimental to gastrointestinal perfusion being implemented.

Liver Function After Irradiation Based on Computed Tomographic Portal Vein Perfusion Imaging

To determine whether individual and regional liver sensitivity to radiation could be assessed by measuring liver perfusion during a course of treatment using dynamic contrast-enhanced computed tomography scanning. Patients with intrahepatic cancer undergoing conformal radiotherapy underwent dynamic contrast-enhanced computed tomography (to measure perfusion distribution) and an indocyanine extraction study (to measure liver function) before, during, and 1 month after treatment. We hoped to determine whether the residual functioning liver (i.e., those regions showing portal vein perfusion) could be used to predict overall liver function after irradiation. Radiation doses from 45 to 84 Gy resulted in undetectable regional portal vein perfusion 1 month after treatment. The volume of each liver with undetectable portal vein perfusion ranged from 0 to 39% and depended both on the patient's sensitivity and on dose distribution. There was a significant correlation between indocyanine green clearance and the mean of the estimated portal vein perfusion in the functional liver parenchyma (p < 0.001). This study reveals substantial individual variability in the sensitivity of the liver to irradiation. In addition, these findings suggest that hepatic perfusion imaging may be a marker for liver function and has the potential to be a tool for individualizing therapy.

Effect of major liver resection on hepatic ureagenesis in humans

Changes in hepatic ureagenesis following major hepatectomy are not well characterized. We studied the relation between urea synthesis and liver mass before and after major hepatectomy in humans. Fifteen patients scheduled for resection of malignancies in otherwise healthy livers were studied. Pre- and postoperative liver volume was assessed by computerized tomography-volumetry. During surgery, a primed, continuous infusion of [(13)C]urea was administered intravenously, and arterial blood samples were obtained hourly. Indocyanine green clearance was determined before and after resection. Seven patients underwent major hepatectomy, and eight patients underwent minor [<5% functional liver volume (total volume -- tumor volume)] or no resection, serving as controls. Resected functional liver volume in the major hepatectomy group averaged 60%. Urea synthesis per gram of functional liver tissue increased 2.6-fold following major hepatectomy, maintaining whole body urea synthesis. Arterial ammonia remained unchanged throughout the study, whereas following hepatectomy a hyperaminoacidemia occurred. In conclusion, immediately following major hepatectomy, urea synthesis per gram of functional liver tissue increases rapidly and proportionately to the amount of liver tissue resected, maintaining whole body urea synthesis at preoperative levels. This rapid and complete adaptation suggests that the capacity of urea synthesis is not limiting the maximum resectable volume in otherwise healthy livers.

Assessing liver function

This is a review on the techniques for assessing liver function in critically ill patients. Actually, there is no ideal real-time and bedside technique for assessing liver function in critically ill patients. Though not allowing to differentiate between liver blood flow and cell function, dynamic tests, that is indocyanine green plasma disappearance rate and lidocaine metabolism (monoethylglycinxylidide test), are superior, however, to static tests. Recently, the indocyanine green plasma disappearance rate, which nowadays can be measured reliably by a transcutaneous system in critically ill patients, was confirmed to correlate well with indocyanine green clearance. In general, the indocyanine green plasma disappearance rate is superior to bilirubin, which is still used as a marker of liver function, and comparable or even superior to complex intensive care scoring systems in terms of outcome prediction. Furthermore, indocyanine green plasma disappearance rate is more sensitive than serum enzyme tests for assessing liver dysfunction and early improvement in the indocyanine green plasma disappearance rate after onset of septic shock is associated with better outcome. Since no ideal tool is currently available, dynamic tests such as indocyanine green plasma disappearance rate and monoethylglycinxylidide test may be recommended for assessing liver function in critically ill patients. The indocyanine green plasma disappearance rate has the advantage, however, of being measurable noninvasively at the bedside and providing results within a few minutes.

Impact of non-congestive graft size in living donor liver transplantation: New indicator for additional vein reconstruction in right liver graft

Addition of the middle hepatic vein (MHV) or reconstruction of its tributaries to increase noncongestive graft volume is expected to improve graft function in right liver living donor liver transplantation (LDLT). However, the relationship between noncongestive graft volume and graft function after transplantation has not been clarified and definitive criteria for the reconstruction of MHV tributaries have yet to be established. We analyzed 29 right liver LDLT cases. The noncongestive graft weight was calculated as the total weight of the graft regions drained by hepatic veins reconstructed without postoperative occlusion. We calculated the noncongestive graft-to-recipient weight ratio (ncGRWR) by comparing it to the GRWR. Indocyanine green (ICG) clearance results on days 1 and 3 were significantly correlated with ncGRWR, but not with GRWR. Patients were then divided into 2 groups based on ncGRWR: lower than the median (L-ncGRWR group) and above the median (H-ncGRWR group). ICG clearance in the H-ncGRWR group was significantly better on days 1 and 3. For a different analysis, the patients were again divided into 2 groups, those with and without prolonged cholestasis after transplantation. ncGRWR was significantly lower in patients with prolonged cholestasis, and 7 of 9 patients with an ncGRWR value lower than 0.65 suffered from prolonged cholestasis. Our results demonstrated that the noncongestive volume of a right liver graft has a significant association with early graft function. Further, ncGRWR can play a key role in preoperative determination for additional vein reconstruction of MHV tributaries. When the estimated ncGRWR value with reconstruction of only the right hepatic vein (RHV) (+ inferior right hepatic vein [IRHV]) is less than 0.65, additional vein reconstruction of MHV tributaries should be planned.

Predictive value of indocyanine green clearance in acute liver failure in children: comparison with King's College and Clichy scores

Indocyanine green clearance (ICG), measured by the percentage disappearance rate (PDR), detects alterations in liver function and may be used as a noninvasive determinant of hepatic reserve in liver failure as well as a marker of graft function following liver transplantation. The administration of blood products does not interfere with the ICG-PDR as occurs with other prognostic scores (King's College and Clichy scores). The aims of this study were to compare in acute liver failure the ICG-PDR with King's College and Clichy scores and to determinate its predictive value.

Is there any effect of renal failure on the hepatic regeneration capacity following partial hepatectomy in rats?

The effects of renal dysfunction on liver regeneration capacity have not been fully elucidated before, although many patients with renal failure are subjected to hepatectomy due to hepatobiliary diseases. In this study, we sought to determine the effects of renal dysfunction on the hepatic regeneration capacity using rat chronic renal failure model. After establishing chronic renal failure (CRF group) by semi-total renal resection, the rats were subjected to 70% partial hepatectomy (PHx). Rats without renal failure were used as control (Sham group). The hepatic regeneration rate, histology of the liver, clearance of indocyanine green into the bile, and the expression of hepatic regeneration-associated genes in the liver were evaluated. The hepatic regeneration rate was lower in CRF group as compared to Sham group on day 1 after PHx. Mitotic index evaluated by histologic examination on day 1 after PHx was also significantly lower in CRF group. However, no difference in these indices was observed on day 2 and 7 between Sham and CRF. Indocyanine green clearance rate was almost identical between Sham and CRF on day 7 following PHx. The baseline expressions of the hepatic regeneration-associated genes, such as IL-6, TNF-α, HGF, c-fos, and c-jun, in the liver of CRF were significantly lower than those of Sham. However, the rate of upregulation of these genes was not significantly different between Sham and CRF. These results clearly demonstrate that the renal dysfunction, although initially delayes the onset, does not suppress the total hepatic regeneration capacity following partial hepatectomy. The function of the regenerated liver on day 7 after PHx also was not different. Our results provide a possibility that the hepatectomy can be indicated even for the patient with a chronic renal failure.