Indocyanine Green Plasma Clearance Research Articles

Liver remnant volume to body weight ratio of 0.65% as a lower limit in right hepatic trisectionectomy with bile duct resection

BackgroundPrevious studies have suggested the utility of an indocyanine green plasma clearance rate of the future liver remnant (FLR) (ICGK-F) ≥0.05 in hepatobiliary resection to reduce the surgical risk. The present study aimed to verify whether future liver remnant size rather than ICGK-F matters in extended hepatobiliary resection. MethodsBetween 2004 and 2021, patients who underwent right hepatic trisectionectomy with bile duct resection were included. The effect of the FLR volume-to-body weight ratio (FLR/BW) and ICGK-F on posthepatectomy liver failure was evaluated along with other parameters. ResultsAmong 91 study patients, the median ICGK-F, FLR, and FLR/BW were 0.057 (range, 0.027–0.099), 392 mL (145–705), and 0.78% (0.40–1.37), respectively. Posthepatectomy liver failure occurred in 23 patients. The incidence was 10 (40%) in 25 patients with an ICGK-F <0.05 and 12 (18%) in 65 patients with an ICGK-F ≥0.05 (P = .053); 13 (52%) in 25 patients with a FLR/BW <0.65% and 10 (15%) in 66 patients with a FLR/BW ≥0.65% (P = .001). Multivariate analysis showed that a FLR/BW <0.65% (odds ratio, 11.7; P = .005), age ≥65 years (odds ratio, 31.7; P < .001), and blood loss ≥25 mL/kg (odds ratio, 22.1; P = .004) were independent predictors of posthepatectomy liver failure, but ICGK-F <0.05 was not (P = .499). According to the meeting number of 3 factors, posthepatectomy liver failure incidence was 0 of 22 (0%) in patients with 0 factors, 6 of 43 (14%) in patients with 1, and 17 of 26 (65%) in patients with 2 or 3 (P < .001). ConclusionA FLR/BW ≥0.65% may serve as a volumetric basis to reduce posthepatectomy liver failure after extended hepatobiliary resection.

Indocyanine green plasma clearance rate and 99mTc-galactosyl human serum albumin single-photon emission computed tomography evaluated preoperative remnant liver.

BACKGROUNDPreoperative evaluation of future remnant liver reserves is important for safe hepatectomy. If the remnant is small, preoperative portal vein embolization (PVE) is useful. Liver volume analysis has been the primary method of preoperative evaluation, although functional examination may be more accurate. We have used the functional evaluation liver using the indocyanine green plasma clearance rate (KICG) and 99mTc-galactosyl human serum albumin single-photon emission computed tomography (99mTc-GSA SPECT) for safe hepatectomy.AIMTo analyze the safety of our institution’s system for evaluating the remnant liver reserve.METHODSWe retrospectively reviewed the records of 23 patients who underwent preoperative PVE. Two types of remnant liver KICG were defined as follows: Anatomical volume remnant KICG (a-rem-KICG), determined as the remnant liver anatomical volume rate × KICG; and functional volume remnant KICG (f-rem-KICG), determined as the remnant liver functional volume rate based on 99mTc-GSA SPECT × KICG. If either of the remnant liver KICGs were > 0.05, a hepatectomy was performed. Perioperative factors were analyzed. We defined the marginal group as patients with a-rem-KICG of < 0.05 and a f-rem-KICG of > 0.05 and compared the postoperative outcomes between the marginal and not marginal (both a-rem-KICG and f-rem-KICG > 0.05) groups.RESULTSAll 23 patients underwent planned hepatectomies. Right hepatectomy, right trisectionectomy and left trisectionectomy were in 16, 6 and 1 cases, respectively. The mean of blood loss and operative time were 576 mL and 474 min, respectively. The increased amount of f-rem-KICG was significantly larger than that of a-rem-KICG after PVE (0.034 vs 0.012, P = 0.0273). The not marginal and marginal groups had 17 (73.9%) and 6 (26.1%) patients, respectively. The complications of Clavian-Dindo classification grade II or higher and post-hepatectomy liver failure were observed in six (26.1%) and one (grade A, 4.3%) patient, respectively. The 90-d mortality was zero. The marginal group had no significant difference in postoperative outcomes (prothrombin time/international normalised ratio, total bilirubin, complication, post-hepatectomy liver failure, hospital stay, 90-d, and mortality) compared with the not-marginal group.CONCLUSIONFunctional evaluation of the remnant liver enabled safe hepatectomy and may extend the indication for hepatectomy after PVE treatment.

Early Graft Dysfunction Evaluation by Indocyanine Green Plasma Clearance Rate in the Immediate Postoperative Period After Liver Transplantation

BackgroundLiver transplantation (LT) has evolved to improve graft and patient survival. Early graft dysfunction (EGD) and primary nonfunction are an important cause of morbi-mortality. We had formulated the scientific hypothesis that the liver function can be evaluated by the indocyanine green (IG) after LT. The aim was to evaluate the EGD by plasma disappearance rate (PDR) of IG after LT. MethodProspective and observational clinical study, from July 2014 to June 2015. IG evaluation by pulse densitometry, Limon system. Degree analysis of ischemia and reperfusion injury in groups as follows: 1 (G0/G1/G2) and 2 (G3/G4). Donor risk index (DRI), Wagener and Olthoff criteria, and prognostic predictors were evaluated. All tests were performed with bidirectional α of 0.05 and a confidence interval of 95% and support by IBM SPSS 25. ResultsA total of 40 patients, mean age 53.3 ± 14.0 years and a majority of men and hepatitis C virus. PDR were more relevant with high degrees of ischemia and reperfusion injury grades G3/G4 (P = .030). The PDR related to the donor risk index showed positive significance at DRI >1.5 (P = .066). The retention rate of IG at 15 minutes demonstrated potential in assessing graft loss or death (P = .063). ConclusionEGD can be assessed by PDR with high degrees of ischemia and reperfusion injury (G3/G4) and with marginal donors (DRI >1.5). The retention rate of IG at 15 minutes demonstrated potential in assessing graft loss or death of the patient.

Liver function assessment using indocyanine green plasma disappearance rate in a young male with icteric leptospirosis: a case report

BackgroundLeptospirosis is one of the leading global zoonotic causes of morbidity and mortality. It is induced by a pathogenic spirochete of the genus Leptospira. The icteric form of leptospirosis is characterized by pronounced hyperbilirubinemia and associated with significantly increased mortality. Conventional static liver function tests insufficiently assess hepatic damage and have limited prognostic value. Dynamic tests, such as indocyanine green plasma (ICG) clearance, more adequately reflect hepatic functional status. In this case report we describe the ICG plasma disappearance rates (ICG-PDR) in a patient with leptospirosis and massive hyperbilirubinemia, expanding our knowledge of liver dysfunction in icteric leptospirosis.Case presentationA 21-year-old Caucasian man presented with acute-onset jaundice, myalgia, fever and headaches. Laboratory tests upon admission revealed, most notably, acute kidney failure and hyperbilirubinemia of 17 mg/dl with mild elevation of aminotransferases. In the course of the following 4 days, total serum bilirubin increased to 54 mg/dl. The clinical outcome was favorable with intravenous ceftriaxone and doxycycline. Presumptive diagnosis of leptospirosis was later confirmed by PCR-based amplification of leptospiral DNA in the blood. ICG-PDR values, bilirubin as well as aminotransferases were recorded throughout hospitalization and a 3-month follow-up period. Initially dramatically reduced ICG-PDR (2.0%/min, normal range: 18–25%/min) rapidly normalized within 10 days, while bilirubin remained elevated up to week 7. Mild elevation of serum alanine aminotransferase was at its peak of 124 U/l by day 12 and reached close to normal levels by week 7 upon admission.ConclusionsMarkedly diminished ICG-PDR values presented in this case report suggest severe liver function impairment in the acute phase of icteric leptospirosis. Prolonged elevation of serum bilirubin may not adequately reflect recovery of liver injury in this disease. ICG clearance appears to be a promising marker for the detection of hepatic dysfunction and recovery in icteric leptospirosis in addition to the static tests.

Preoperative remnant liver functional assessment in major hepatectomy after portal vein embolization using 99MTC-GSA scintigraphy /3D-CT fused imaging

Objective: The objective of this study was to elucidate the utility of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (99mTc-GSA) scintigraphy/3D-CT fusion imaging for remnant liver function assessment in major hepatectomy after portal vein embolization (PVE). Methods: From 2012 to September 2016, eleven patients who underwent major hepatectomy for various indications after right PVE were retrospectively analyzed. 3D-CT volumetry and 99mTc-GSA were performed before and after PVE. Indocyanine green plasma clearance rate (KICG) value was also examined and remnant % volume KICG (rem%V = KICG × 3D-CT volumetric rate) and remnant functional % KICG (rem%F = KICG × GSA/3D-CT fused imaging functional rate) were calculated. Optimal hepatectomy was performed when rem%F ≤ §0.05. Furthermore, postoperative liver function, morbidity and mortality were investigated. Results: The rem%V increased from 33.4 to 46.5, and the increment was 29.1%. The rem%F was also increased from 30.6 to 45.5, and the increment was 49.7%. The increment was 20.6% higher in the rem%F compared with rem%V (P < 0.01). Two cases of right trisectionectomy and 8 cases of right hepatectomy were performed according to rem%F criteria. In a case, right hepatectomy was abandoned due to the rem%F was under 0.05 after PVE, bisegmentectomy (S7-8) was undergone based on the criteria. Duration of postoperative hospitalization was 12.5 (7–96) days. One case has failed in Clavien–Dindo grade IIIb, and another one case has failed in grade A posthepatectomy liver failure. There was no peri-operative mortality. Conclusion: 99mTc-GSA/3D-CT fused imaging can estimate accurate future remnant liver function and suitability for major hepatectomy after PVE.

Liver function assessment using 99mTc-GSA single-photon emission computed tomography (SPECT)/CT fusion imaging in hilar bile duct cancer: A retrospective study

The objective of this study was to determine the utility of Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin ((99m)Tc-GSA) single-photon emission computed tomography (SPECT)/CT fusion imaging for posthepatectomy remnant liver function assessment in hilar bile duct cancer patients. Thirty hilar bile duct cancer patients who underwent major hepatectomy with extrahepatic bile duct resection were retrospectively analyzed. Indocyanine green plasma clearance rate (KICG) value and estimated KICG by (99m)Tc-GSA scintigraphy (KGSA) and volumetric and functional rates of future remnant liver by (99m)Tc-GSA SPECT/CT fusion imaging were used to evaluate preoperative whole liverfunction and posthepatectomy remnant liver function, respectively. Remnant (rem) KICG (=KICG×volumetric rate) and remKGSA (= KGSA×functional rate) were used to predict future remnant liver function; major hepatectomy was considered unsafe for values <0.05. The correlation of remKICG and remKGSA with posthepatectomy mortality and morbidity was determined. Although remKICG and remKGSA were not significantly different (median value: 0.071 vs 0.075), functional rates of future remnant liver were significantly higher than volumetric rates (median: 0.54 vs 0.46; P<.001). Hepatectomy was considered unsafe in 17% and 0% of patients using remKICG and remKGSA, respectively. Postoperative liver failure and mortality did not occur in the patients for whom hepatectomy was considered unsafe based on remKICG. remKGSA showed a stronger correlation with postoperative prothrombin time activity than remKICG. (99m)Tc-GSA SPECT/CT fusion imaging enables accurate assessment of future remnant liver function and suitability for hepatectomy in hilar bile duct cancer patients.

Indocyanine green clearance after cardiac surgery: the impact of cardiopulmonary bypass

Plasma clearance of indocyanine green has recently been established as a tool to monitor hepatic function and perfusion non-invasively. Reduced indocyanine green clearance has been associated with adverse outcome in cardiac surgery patients, and cardiopulmonary bypass has been hypothesized to be one important triggering factor. We performed a prospective observational study comparing the influence of off-pump and on-pump coronary surgery on perioperative indocyanine green clearance. Twenty-five consecutive adult patients without known pre-existing hepatic diseases scheduled for off-pump coronary artery bypass grafting were evaluated for hepatic dysfunction pre- and postoperatively with serial measurements of indocyanine green plasma clearance, specific laboratory values and liver function scores. Twenty-five matched patients who underwent coronary artery bypass grafting surgery with cardiopulmonary bypass in the same period served as controls. Parameters of postoperative hepatic function, including measurements of indocyanine green plasma clearance and specific laboratory values and scores, did not differ significantly between patients undergoing off-pump coronary artery bypass grafting and patients undergoing coronary artery bypass grafting with extracorporeal circulation. In patients without pre-existing hepatic diseases, a significant influence of cardiopulmonary bypass on perioperative indocyanine green plasma clearance as well as on liver specific laboratory parameters and scores cannot be proven.

Hepatic dysfunction and Indocyanine green clearance (LiMON) after coronary surgery: Impact of cardiopulmonary bypass

Aims: Hepatic dysfunction is a rare but serious complication after cardiac surgery. Plasma clearance of indocyanine green has recently been established as an excellent tool to measure even small changes in hepatic function. Reduced indocyanine green clearance has been associated with adverse outcome in cardiac surgery patients, and cardiopulmonary bypass (CPB) has been hypothesized to be one important triggering factor. Thus, we performed a prospective observational study comparing the influence of off-pump and on-pump coronary surgery on perioperative indocyanine green clearance.

Evaluation of Chemotherapy-Associated Liver Injury in Patients with Colorectal Cancer Liver Metastases Using Indocyanine Green Clearance Testing

Systemic chemotherapy may render initially unresectable colorectal cancer liver metastases resectable. Histopathologic examinations of resected nontumoral liver tissue revealed chemotherapy-associated liver injuries, which was recognized to impair the function of the remnant liver. We therefore evaluated whether indocyanine green (ICG) plasma clearance helps to assess chemotherapy-induced liver damage. Data of 101 liver resections performed between 2006 and 2008 for colorectal liver metastases were analyzed for this study. Eighteen patients had liver resection without preoperative treatment, whereas 83 patients underwent neoadjuvant chemotherapy before surgery. ICG clearance was assessed by pulse densitometry before surgery. Comparison of ICG retention clearances demonstrated that patients pretreated with systemic chemotherapy had a significantly lower plasma disappearance rate (ICG-PDR; 19.3±5.9 vs. 23.1±3.8%/min; P=0.002) and a significantly elevated ICG retention rate at 15min (7.9±6.6 vs. 3.8±1.9%; P<0.001). The percentage of subjects with an abnormal ICG-PDR (≤18%/min) was significantly higher in the pretreated group (48.2% vs. 5.6%; P=0.001). Patients with an ICG-PDR of ≤18 had a prolonged postoperative hospital stay and experienced four times more complications in their postoperative course. ICG clearance helps to identify patients with impaired liver function after neoadjuvant chemotherapy and aids in the estimation of the postoperative risk of morbidity after liver resection for colorectal liver metastases.

Noninvasive diagnosis and prognosis of liver cirrhosis: a comparison of biological scores, elastometry, and metabolic liver function tests

Recently, noninvasive methods for the diagnosis of liver cirrhosis have been extensively developed. We assessed the accuracy of liver stiffness measurement, aspartate aminotransferase-to-platelet ratio index (APRI) score, 13C-aminopyrine breath test, and indocyanine green plasma clearance for the diagnosis of cirrhosis in patients with chronic liver disease and for the prediction of severe complications in cirrhotic patients. A total of 296 consecutive patients with chronic liver diseases of various causes were studied. Diagnostic accuracy was assessed by receiver operating characteristic curve analysis. Areas under the receiver operating characteristic curve for the diagnosis of cirrhosis were (95% confidence interval) 0.93 (0.90-0.96) for liver stiffness measurement, 0.82 (0.77-0.87) for 13C-aminopyrine breath test, and 0.81 (0.76-0.86) for APRI score. Using cutoff values of 14.1 kPa for liver stiffness, 4.15% dose/h for 13C-aminopyrine breath test, and 1 for APRI score, the positive predictive value was approximately 90% for the diagnosis of cirrhosis. Using cutoff values of 65.2 kPa for liver stiffness, 1.17% dose/h for 13C-aminopyrine breath test, 2.82 for APRI score, and 51.1% for indocyanine green plasma clearance, the positive predictive value was approximately 80% for the occurrence of severe complications among cirrhotic patients. Liver stiffness measurement, 13C-aminopyrine breath test, indocyanine green plasma clearance, and APRI score are reliable noninvasive methods for the diagnosis of cirrhosis in patients with chronic liver diseases of various causes, and are also prognostic indicators for the occurrence of severe complications in cirrhotic patients.

Monitoring global volume-related hemodynamic or regional variables after initial resuscitation: What is a better predictor of outcome in critically ill septic patients?*

Regional variables of organ dysfunction are thought to be better monitoring variables than global pressure-related hemodynamic variables. Whether a difference exists between regional and global volume-related variables in critically ill patients after resuscitation is unknown. Prospective diagnostic test evaluation. University-affiliated mixed intensive care unit. Twenty-eight critically ill patients. Using standardized resuscitation, hemodynamic optimization was targeted at mean arterial pressure, heart rate, occlusion pressure, cardiac output, systemic vascular resistance, and urine output. Primary outcome variable was in-hospital mortality. During resuscitation, global volume-related hemodynamic variables were measured simultaneously and compared with regional variables. At admission no variable was superior as a predictor of outcome. During resuscitation, significant changes were seen in mean arterial pressure, central venous pressure, oxygen delivery, systemic vascular resistance, total blood volume, right heart and ventricle end-diastolic volume, right ventricle ejection fraction, right and left stroke work index, intramucosal carbon dioxide pressure, gastric mucosal pH, mucosal-end tidal Pco2 gap, indocyanine green blood clearance, indocyanine green plasma clearance, and plasma disappearance rate. Multivariate analysis identified lactate, gastric mucosal pH, mucosal-end tidal Pco2 gap, mucosal-arterial Pco2 gap, indocyanine green plasma clearance, and plasma disappearance rate of dye as nondependent predictors of outcome. Patients who subsequently died had a significantly lower gastric mucosal pH, higher intramucosal carbon dioxide pressure and mucosal-end tidal Pco2 gap, and lower indocyanine green blood clearance, indocyanine green plasma clearance, plasma disappearance rate, and right ventricular end-diastolic volume index, of which gastric mucosal pH, mucosal-end tidal Pco2 gap, and indocyanine green blood clearance were the most important predictors of outcome. Initial resuscitation of critically ill patients with shock does not require monitoring of regional variables. After stabilization, however, regional variables are the best predictors of outcome.

Der Einfluss des kontinuierlich positiven Atemwegsdruckes (CPAP) auf die Blutflussgeschwindigkeit im venösen Leberstromgebiet - duplexsonographische Untersuchungen

In the last years, noninvasive techniques of artificial ventilation like continuous positive airway pressure (CPAP) have become more and more important. However, the effects of such procedures on the circulation of the hepatosplanchnic area are, except for the indocyanine green plasma clearance, not yet representative by means of noninvasive investigation methods. We studied maximum blood flow velocity in defined areas of hepatic and portal veins by duplex ultrasonography in 20 healthy volunteers (12 male, 8 female; age: 24,7 +/- 4,7 years [mean +/- SD]) before, during and after application of CPAP (10 cm H(2)O). As many measurements as possible were taken in both vascular systems. After division into five minute intervals arithmetical mean values were calculated for each interval. The experiment was divided into a control interval ("before CPAP"), three "CPAP" intervals and finally two "after CPAP" intervals. Heart rate and blood pressure were taken at the beginning of these intervals. Compared with the control interval, maximum blood flow velocity in the area of the hepatic vein decreased significantly by 13,2 %, 16,8 % and 15,7 % (p < or = 0,001 in each case) during each of the three "CPAP" periods. In the portal venous area blood flow velocity decreased by 4,3 %, 8,8 % and 7,0 %, respectively, with a significant decrease only in the second "CPAP" interval (p < or = 0,005). After CPAP, changes returned to baseline within a few minutes. Heart rate and blood pressure showed no significant differences during the whole experiment. Parameters taken in both venous vascular areas of the liver show clear correspondence with the results of former studies, which have been determined by means of more invasive investigation methods. Maximum blood flow velocity seems to be useful for monitoring liver blood flow and its individual time course during CPAP, noninvasively and semiquantitatively. Further trials under conditions of controlled mechanical ventilation should be performed to optimize ventilation strategies for the critically ill.

Selective effects of a bacterial infection (Actinobacillus pleuropneumoniae) on the hepatic clearances of caffeine, antipyrine, paracetamol, and indocyanine green in the pig.

1. In order to investigate the effect of a bacterial acute phase response model on drug disposition in vivo, plasma clearances of antipyrine, caffeine, paracetamol and indocyanine green were investigated in the healthy and Actinobacillus pleuropneumoniae-infected pig. 2. Indocyanine green plasma and endogenous creatinine clearance were not changed during the infection, which indicates that hepatic blood flow and renal function were not significantly affected. 3. In the A. pleuropneumoniae-infected pig, plasma clearances of antipyrine and caffeine, both marker substrates for hepatic oxidative biotransformation, were decreased by 72 and 68% respectively. The clearance of paracetamol, a drug mainly glucuronidated in the pig, was reduced by 39%. 4. It is concluded that the most important change in drug elimination during an acute phase response induced by A. pleuropneumoniae is a suppression of oxidative hepatic biotransformation.

Clinical significance of the evaluation of hepatic reticuloendothelial removal capacity in patients with cirrhosis.

The reticuloendothelial system plays an important role in the prevention of bacterial infection in patients with cirrhosis. Few data are available, however, on its activity in such patients. The aim of this study was to evaluate the maximum removal capacity of hepatic reticuloendothelial system in patients with cirrhosis on the basis of study of the removal kinetics of increasing amounts of 99mTc millimicrospheres and to verify its value as a prognostic factor for death and development of spontaneous bacterial peritonitis. Common clinical and biochemical parameters, Pugh score, maximum removal capacity, aminopyrine metabolic capacity and galactose elimination capacity were measured in 43 patients with cirrhosis (33 with alcoholic cirrhosis, 8 with posthepatitic cirrhosis and 2 with cryptogenic cirrhosis). Hepatic plasma flow and indocyanine green plasma clearance were also measured in 16 of these patients. Reference range of maximum removal capacity was determined in seven normal subjects. Maximal removal capacity below the normal range was found in 24 patients (56%). In the whole series maximum removal capacity averaged 16 +/- 12 micrograms/kg body wt/min (mean +/- S.D.). Maximal removal capacity was significantly correlated with serum albumin, prothrombin index, Pugh score, aminopyrine breath test, galactose elimination capacity and indocyanine green plasma clearance but not with hepatic plasma flow. During follow-up of up to 48 mo, spontaneous bacterial peritonitis developed in six patients, all with impaired maximum uptake capacity, and 11 patients died. Survival was significantly shorter in patients with impaired maximum removal capacity than in those with normal maximum removal capacity (log-rank test: p = 0.024).(ABSTRACT TRUNCATED AT 250 WORDS)

HEPATIC FUNCTION AND INDOCYANINE GREEN CLEARANCE DURING AND AFTER PROLONGED ANAESTHESIA WITH PROPOFOL

We have studied the effects of propofol on hepatic function and clearance of indocyanine green (ICG) in 13 consecutive patients undergoing prolonged plastic and reconstructive surgery. Hepatic function was assessed using serum concentrations of liver-specific glutathione-S-transferase (GST). There were no significant changes in GST activity or plasma clearance of ICG throughout the study.

INDOCYANINE GREEN CLEARANCE AND HEPATIC FUNCTION DURING AND AFTER PROLONGED ANAESTHESIA: COMPARISON OF HALOTHANE WITH ISOFLURANE

Specific biochemical and physiological tests of liver function were used to assess 20 consecutive patients undergoing prolonged head and neck surgery with halothane or isoflurane anaesthesia. Hepatic function was assessed by measurement of serum concentrations of total bilirubin and albumin, and plasma activity of pseudocholinesterase, gamma-glutamyl transferase (GGT), aspartate transaminase (AST), alkaline phosphatase (ALP) and hepatic glutathione S-transferase. Plasma clearance of indocyanine green was used as an estimate of hepatic blood flow. No major differences were observed in serum concentrations of GGT, ALP, bilirubin, albumin or pseudocholinesterase. Serum AST activity in those patients receiving halothane was increased at 24 h and at 48 h compared with those who received isoflurane (not statistically significant). Glutathione S-transferase activity was increased significantly in the halothane group throughout the period of study, compared with those who received isoflurane. Similarly, there was a significant difference between the two groups as measured by plasma clearance of indocyanine green: in the halothane group there was a slower disappearance rate of the dye from plasma at specific times than in the patients who received isoflurane. Our data support the use of isoflurane rather than halothane for prolonged anaesthesia.

Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose.

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min-1 kg-1, mean (SD)], but this difference was not statistically significant (P = 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min-1 kg-1] and convalescent study [12.8 (2.1) ml min-1 kg-1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of anesthetic agents and abdominal surgery on liver blood flow

The cause of postoperative liver dysfunction is often unclear, but a decrease in liver blood flow during anesthesia and/or major surgery may be important. Plasma half-life and clearance of indocyanine green were therefore measured in 42 patients before, during and after anesthesia and abdominal surgery. In 13 patients, liver blood flow was also estimated from indocyanine green extraction using hepatic vein catheterization. The major finding was an early decrease in estimated liver blood flow after induction of anesthesia, but not later during or after surgery. Mean indocyanine green half-life increased by 26% (p less than 0.005), mean indocyanine green plasma clearance decreased by 19% (p less than 0.01) and mean estimated hepatic blood flow decreased by 36% (p less than 0.005) during the first 30 min of anesthesia. These changes were greater in males and in patients older than 55 yr, but changes were similar with each of three anesthetic groups. Half-life, but not indocyanine green clearance, was also significantly prolonged by mid-operation in the older (greater than 55 yr) patients and in those undergoing lower abdominal surgery. We suggest that this period of reduced liver blood flow during anesthesia is caused by the effects of neuromuscular blocking agents and may contribute to postoperative liver damage.

Assessment of hepatic excretory function in chronic liver disease by hepatobiliary scintigraphy.

Hepatobiliary scintigraphy was performed in 23 normal subjects and 47 patients with chronic liver disease (chronic hepatitis; n = 27, liver cirrhosis; n = 20) to evaluate its availability as a test of liver function. After intravenous administration of Tc-99m N-pyridoxyl-5-methyl-tryptophan, the data were acquired for 60 min and the time-activity curves of ROIs (the heart and liver) were generated. In two compartment model simulation, the early blood clearance rate (kl), late blood clearance rate (km), hepatic uptake rate (ku) hepatic excretion rate (ke), and hepatic excretion T 1/2 were calculated. There was no significant difference in those four k values in normal and chronic hepatitis. However, in liver cirrhosis each of them, except km, was lower than in normal subjects. The kl value correlated closely with the indocyanine green plasma clearance test, whereas the ke and T 1/2 values were closely correlated with the level of serum bilirubins. Only hepatobiliary scintigraphy showed the excretory function of the liver quantitatively and the ke value was helpful in detecting hepatic excretory dysfunction early in chronic liver disease before serum bilirubins increased.

Hepatic drug clearance in children: studies with indocyanine green as a model substrate.

For several drugs metabolized by the liver, higher dosages (mg/kg body weight) are required in children to attain serum concentrations comparable to those in adults. Indocyanine green (ICG), a commonly used model substrate for hepatic elimination of high intrinsic clearance drugs, has been extensively evaluated in adults but not in children. We evaluated the disposition of ICG in 115 children with leukemia and nine healthy adult volunteers. The mean (SD) ICG plasma clearance (CLp) for all 115 children (age 0.9-17.8 years) was significantly greater (p = 0.0006) than for adults [14.8 (7.8) versus 10.6 (2.4) mL/min/kg]. When clearances from only children less than 10 years of age (N = 85) were compared with those from adults, the difference was even greater [15.6 (7.3) versus 10.6 (2.4) mL/min/kg; p = 0.0001]. However, when ICG CLp was normalized to body surface area, values for children did not differ significantly from adults [378 (204) versus 422 (102) mL/min/m2]. These data provide insight as to why dosage (mg/kg) requirements of certain drugs are higher in children.