Indocyanine Green Dye Clearance Research Articles

Indocyanine green dye clearance test: early graft (dys)-function and long-term mortality after liver transplant. Should we continue to use it? An observational study.

Early allograft dysfunction (EAD) can be a serious complication in the immediate postoperative period following liver transplantation. Our aim was to study the prognostic role of the indocyanine green plasma disappearance rate (ICG-PDR) in predicting early and late EAD and mortality at 3 and 12months and 5years after liver transplantation. ICG-PDR values were also assessed for association with the Donor Risk Index (DRI). 220 patients underwent orthotopic liver transplantation. In 77 patients, ICG-PDR was assessed on the 1st post-operative (PO) day. ICG, a water-soluble dye almost entirely excreted into the bile, was measured by spectrophotometry to evaluate graft (dys)-function. DRI was calculated in all patients. The primary study outcomes were the presence (or absence) of EAD after transplant and the results of mortality risk factor analysis. EAD occurred in 18 patients. 1st PO day ICG-PDR was significantly associated with EAD (p < 0.005). A threshold ICG-PDR value < 16%/min on the 1st PO day was also associated with patient probability to survive at 3 and 12months and 5years. The sensitivity and specificity of the AUC was good in predicting EAD, being 83% and 56%, respectively, for a 1st PO day ICG-PDR cut-off value < 16%/min. In this study, ICG-PDR on the 1st PO day following OLT can reliably predict EAD and survival at 3 and 12months and 5years. ICG-PDR should, therefore, be routinely performed on the 1st PO day following OLTx in all patients in light of its important prognostic role.

Clearance of Indocyanine Green in Severe Pediatric Burns.

Clearance of indocyanine green dye (ICGc) reflects sinusoidal perfusion and hepatocyte cell membrane function. Thus, ICGc is a reflection of the functional reserve of intact hepatocytes. The purpose of this study was to identify predictors of ICGc in severely burned children during the acute hospitalization and at the time of discharge from the intensive care unit (ICU). A secondary aim was to determine the relationship between liver size and patient ICGc. Twenty-six children (0.8-17 years old) with 35% or greater total body surface area burned (%TBSA-B) were included. Assessment of ICGc (in milliliters per minute per meter squared) was done during the acute hospitalization (median: 6 days after admission, median: 14 days postburn) and at the time of discharge from the ICU (median: 19 days after admission, median: 27 days postburn). Age, TBSA-B, % third-degree burns, inhalation injury, preexisting chronic malnutrition, hematocrit, liver dysfunction, and time from burn injury were incorporated in multiple linear regressions as predictive variables of ICGc. Only variables with p < 0.05 were retained in the final models. Time from injury and age were the strongest predictors of ICGc during the acute admission but not at the time of discharge from the ICU. Time from injury was negatively associated with ICGc, whereas age was positively associated. At the time of discharge from the ICU, ICGc was increased in proportion to the %TBSA-B, whereas inhalation injury and preexisting chronic malnutrition were associated with lower ICGc. There was no correlation between change-to-predicted liver length and ICGc. The intrinsic ability of the liver to extract ICG from plasma was lower in younger burned patients during the acute admission and in those with preexisting chronic malnutrition and inhalation injury at the time of discharge from the ICU. Prognostic/Epidemiologic, level III.

Infrared imaging of lymphatic function in the upper extremity of normal controls and hand transplant recipients via subcutaneous indocyanine green injection

Objectives:The goal of this study was to define the parameters of movement of indocyanine green in the upper extremity of normal control and hand transplant recipients. The purpose was to establish a non-invasive method of determining the level of lymphatic function in hand transplant recipients. In hand transplantation (and replantation), the deep lymphatic vessels are rarely repaired, resulting in altered lymphatic connections. In most cases, the relatively rapid inosculation of superficial lymphatic networks and drainage via the venous systems results in sufficient interstitial fluid and lymph drainage of the graft to prevent edema. However, our group and others have determined that some transplant recipients demonstrate chronic edema which is associated with lymphatic stasis. In one case, a patient with chronic edema has developed chronic rejection characterized by thinning of the skin, loss of adnexal structures, and fibrosis and contracture of the hand.Methods:Lymphatic function was evaluated by intradermal administration of near-infrared fluorescent dye, indocyanine green, and dynamic imaging with an infrared camera system (LUNA). To date, the assessment of lymphatic drainage in the upper extremity by clearance of indocyanine green dye has been studied primarily in oncology patients with abnormal lymphatic function, making assessment of normal drainage problematic. To establish normal parameters, indocyanine green lymphatic clearance functional tests were performed in a series of normal controls, and subsequently compared with indocyanine green clearance in hand transplant recipients.Results:The results demonstrate varied patterns of lymphatic drainage in the hand transplant patients that partially mimic normal hand lymphatic drainage, but also share characteristics of lymphedema patients defined in other studies. The study revealed significant deceleration of the dye drainage in the allograft of a patient with suspected chronic rejection and edema of the graft. Analysis of other hand transplant recipients revealed differing levels of dye deceleration, often localized at the level of surgical anastomosis.Conclusion:These studies suggest intradermal injection of indocyanine green and near-infrared imaging may be a useful clinical tool to assess adequacy of lymphatic function in hand transplant recipients.

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.

Pharmacokinetic and pharmacodynamic interactions during multiple-dose administration of nisoldipine and propranolol

The pharmacokinetic and pharmacodynamic interactions after 7 days of oral treatment with nisoldipine (10 mg twice daily) and propranolol (80 mg twice daily) were investigated in a partially randomized, placebo-controlled crossover study of 12 healthy volunteers. At the end of each treatment period, pharmacokinetic parameters were measured, along with blood pressure, heart rate, cardiac function, systemic hemodynamics, plasma catecholamines, forearm blood flow, and apparent hepatic blood flow (estimated by the clearance of indocyanine green dye). After 7 days of treatment with nisoldipine and propranolol, neither drug altered the other's bioavailability or elimination parameters, and propranolol did not change the area under the plasma concentration-time curve of nisoldipine's metabolite, N-9425. Nisoldipine alone increased apparent hepatic blood flow and forearm blood flow compared with the other treatment groups but, with the addition of propranolol, both of these parameters were similar to those in the placebo group. Changes in the other hemodynamic parameters were consistent with the known effects of these drugs, and no differences in plasma catecholamine levels were detected. In contrast to the findings with single-dose treatment, administration of the combination of nisoldipine and propranolol for 7 days is not associated with any measurable kinetic interactions, although significant hemodynamic interactions do occur.

The effects of flosequinan on regional blood flow in normal man.

1. The effects of 100 mg and 200 mg flosequinan on limb, hepatic and renal blood flow were investigated in 14 healthy male volunteers in a placebo controlled double-blind randomised three-way crossover study. 2. Heart rate, blood pressure, forearm blood flow and venous capacitance measured by volume plethysmography, were recorded sequentially over 4 h, after oral dosing. 3. Apparent hepatic and renal blood flows were estimated 2 h post-dose by indocyanine green dye clearance and clearance of 125-iodohippuran respectively. 4. Flosequinan produced dose-dependent reductions in resting diastolic blood pressure, accompanied by a rise in heart rate. 5. Forearm blood flow increased to a maximum 4 h after 200 mg and this was accompanied by a fall in forearm vascular resistance. 6. Hepatic blood flow increased, compared with placebo, after 200 mg flosequinan, accompanied by a fall in hepatic vascular resistance. Renal blood flow remained unchanged but renal vascular resistance fell significantly, compared with placebo, following both doses of the drug. 7. In normal man blood flow to the limb, hepatic and renal vascular beds is preserved despite dose-dependent reductions in blood pressure following single doses of flosequinan.

Dissociation of adrenal androgen and cortisol levels in acute stress.

Patients recovering from acute surgical stress often excrete increased 17-OH corticosteroids with no change in 17-ketosteroids. The explanation for these findings is unclear. In order to investigate possible divergence between cortisol and adrenal androgen metabolism in acute stress, repeated morning cortisol and dehydroepiandrosterone (DHA) measurements were made in patients undergoing ACTH stimulation 48 to 96 hours preoperatively, followed by determinations before and during major surgery, also performed in the morning. Cortisol and DHA are largely metabolized by the liver, so liver blood flow under a constant general anesthetic regimen known not to affect cortisol metabolism was monitored by pre- and intraoperative indocyanine green dye clearance. Results indicated no difference between the cortisol and DHA stimulation resulting from two hours of ACTH stimulation or major surgery, and a small (14.4%) decline in hepatic blood flow during general anesthesia. However, while DHA concentrations remained constant immediately preceding surgery, cortisol concentrations increased by 61% (P less than 0.05). Previous studies have also demonstrated increased concentrations of cortisol before surgical procedures, presumably due to psychological stress. However, this is the first demonstration of a dissociation between concentrations of cortisol and an adrenal androgen due to psychological stress.

Epoprostenol (prostacyclin,PGI 2) increases apparent liver blood flow in man

When epoprostenol (prostacyclin, PGI 2) is given by infusion to man, cardiac output is increased, and it appears that the gastrointestinal tract may receive a disproportionate share of this. We have used the clearance of indocyanine green dye to estimate liver blood flow in 8 healthy subjects. During an infusion of PGI 2 at a dose of 5 ng/kg/min, apparent liver blood flow increased from 925 ± 220 ml/min (Mean ± s.d) to 1320 ± 453 ml/min, an average increase of 41.1%. Significant changes in heart rate, headache, facial flushing, systolic blood pressure, and pulse pressure were noticed. We suggest that endogenous epoprostenol (PGI 2) May be of importance in the physiological regulation of liver blood flow in man. As this dose of epoprostenol could be tolerated readily, epoprostenol therapy could prove a therapeutic advance in some liver disorders, particularly liver transplantation, and possibly in the therapy of certain drug overdoses.

Response of choroidal vascular resistance to hyperglycemia.

We measured choroidal blood flow in cats by determining the rate of clearance of indocyanine green dye from the choroidal circulation. Measurements were made by rapidly injecting indocyanine green dye into the common carotid artery and photoelectrically monitoring its concentration in the superior anterior ciliary vein. We verified the validity of our method by measuring the indocyanine green dye clearance from an animal perfused with saline through the common carotid artery to eliminate recirculation. The curve was carried out past the time of the recirculation artifact and was accurately described by a monoexponential. Moreover, we found an inverse relationship between choroidal blood flow and intraocular pressure between approximately 15 and 100 mm Hg a fact well documented by other methods. Finally, sympathetic nerve stimulation, known to decrease choroidal blood flow, had a similar effect on our flow values measured by dye clearance. Choroidal vascular resistance is defined as the perfusion pressure (mean systemic blood pressure minus intraocular pressure) divided by the choroidal blood flow. In normal cats, the choroidal vascular resistance was transiently decreased by an abrupt increase in blood glucose level induced by the intravenous injection of glucose. The maximum reduction in choroidal vascular resistance occurred at approximately three minutes and averaged 40±4 percent (mean ± S.E.). This transient reduction in choroidal vascular resistance may play a role in the pathogenesis of diabetic retinopathy.

Effects of petroleum hydrocarbons on hepatic function in the duck

1. The indocyanine green dye clearance test for hepatic function was determined in mallard ducks before and during the chronic ingestion (7 months) of representative paraffinic or aromatic petroleum hydrocarbons (PH). 2. No mortality or visible symptoms of toxicity occured in any of the tests. Ingestion of 4000 ppm aromatic PH produced significant increases in liver (25%), plasma clearance of indocyanine green (33%) and hepatic blood flow (30%). 3. Although the aromatics elicited a greater hepatic stress response than the paraffins, the ducks tolerated high concentrations of PH for extended periods.

Choroidal blood flow measurement in the monkey by clearance of indocyanine green dye

We measured choroidal blood flow in the rhesus monkey by determining the rate of clearance of indocyanine green dye from the choroidal circulation. Measurements were made by rapidly (0·2 sec) injecting indocyanine green dye (5 mg/ml), in 0·1 ml increments, into the common carotid artery and photoelectrically monitoring its concentration in a vortex vein. Light with peak transmittance 797 nm (half bandwidth 15 nm) was transmitted to the vein using a specially constructed fiber optic bundle. Transmitted light was collected with a second fiber optic bundle and conducted to a photodetector-amplifier circuit. The output of this circuit was a voltage linearly proportional to the amount of transmitted light and hence the venous concentration of indocyanine green dye. This was recorded on both a polygraph and an FM analog tape recorder. The clearance curves were analyzed to give the blood flow rate, which was based on the rate of washout of the dye. Within the normal range of perfusion pressures (90–110 mmHg), curves were all monoexponential which allowed us to analyze them with a first order model of the choroidal circulation. At normal perfusion pressure the choroidal blood flow rate was 17±6 ml/min/ml of choriocapillaris (mean± s.d.). With measured values of the choriocapillaris volume this indicates a blood flow rate of approximately 0·2 ml/min in the choroid.

Carotid and cardiopulmonary baroreceptor control of splanchnic and forearm vascular resistance during venous pooling in man

1. This study evaluated the contribution of carotid and cardiopulmonary baroreceptors to reflex splanchnic and forearm vascular adjustments during venous pooling in man. We compared (a) responses to lower body suction which produces venous pooling with (b) responses to lower body suction plus simultaneous application of neck suction. The rationale was that simultaneous application of neck suction, which stretches carotid baroreceptors, would minimize the contribution of carotid baroreceptors to circulatory adjustments produced by lower body suction.2. Lower body suction at 40 mmHg decreased central venous pressure and arterial pulse pressure and increased forearm vascular resistance (plethysmography), splanchnic vascular resistance (indocyanine green dye clearance), and heart rate. Simultaneous application of neck suction prevented the tachycardia and most of the splanchnic vasoconstriction during lower body suction, but did not significantly attenuate the forearm vasoconstriction.3. The major findings in this study are first, that the splanchnic vasoconstrictor response during venous pooling is mediated primarily through carotid baroreceptors, and secondly, that carotid and cardiopulmonary baroreceptors produce strikingly contrasting and non-uniform regional vascular responses during venous pooling. Cardiopulmonary baroreceptors exert the predominant influence on forearm vascular resistance, but appear to have only a minor influence on splanchnic vascular resistance. Carotid baroreceptors produce most of the splanchnic vasoconstriction during venous pooling. but have a minor role in the forearm vasoconstriction.

Can general anesthetics produce splanchnic visceral hypoxia by reducing regional blood flow?

Thirty-five normal adult males were studied before and during either cyclopropane or halothane anesthesia in an effort to learn whether these agents cause a critical reduction in the availability of oxygen to the splanchnic viscera. Although hepatic blood flow was markedly reduced during the inhalation of either agent, splanchnic oxygen utilization was not consistently affected, and restoration of blood flow to the initial level gave no clear evidence that an oxygen debt has been incurred during the period of reduced flow. Clearance of indocyanine green dye was reduced in proportion to blood flow when either cyclopropane or halothane was inhaled, but restoration of flow rate to normal did not correct the deficiency in clearance. “Excess” lactate was produced by the splanchnic viscera during cyclopropane but not during halothane anesthesia. This effect could be abolished by a beta adrenergic blocking drug. Therefore, “excess” lactate apparently resulted not from splanehnic ischemia but from metabolic action associated with increased sympathetic nervous activity in these viscera.