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Tecnologia LiMON

Limon technology

Tecnologia LiMON

Monitoraggio non invasivo della funzione epatica o della perfusione splancnica

Panoramica

LiMON è la tecnologia basata sull'eliminazione del verde indocianina per la misurazione non invasiva della funzione epatica e il monitoraggio della perfusione splancnica, (ICG). L'ICG è un colorante fluorescente. È destinato all'iniezione endovenosa. Lo spettro di assorbimento e di emissione del ICG sono entrambi nel infrarosso vicino e nell'infrarosso. Per questo motivo può essere rilevato e quantificato con procedure ottiche. 

La misurazione può essere effettuata in maniera non invasiva per via percutanea. Dato che l'ICG viene eliminato esclusivamente nel fegato, il tasso di rilevamento è un indicatore prezioso per la funzionalità epatica globale. L'importanza diagnostica del rilevamento dell'ICG come indicatore della funzionalità epatica è stata confermata in numerose pubblicazioni scientifiche ed è ormai comprovata da oltre 30 anni.

  • Individuazione precoce della disfunzione epatica
  • Da indicazione circa la funzionalità epatica attuale effettiva
  • Misurazione non invasiva
  • Disponibile a posto letto
  • LiMON® rileva immediatamente l'ipo-perfusione epatica
  • Maggiore affidabilità nella previsione della probabilità di sopravvivenza1
  • Un PDRICG inferiore al 16%/min richiede un intervento2
  • Fluidoterapia ottimizzata con LiMON® in combinazione con PiCCO3
  • Funge da indicatore di perfusione locale
  • Valutazione peri-operatoria della qualità e della funzionalità dell'innesto per ridurre la probabilità di necessità di un nuovo trapianto4
  • Fornisce un indicatore affidabile del risultato dell'innesto subito dopo l'intervento5
  • Aiuta a identificare precocemente le complicazioni6
  • LiMON® fornisce parametri decisivi nella valutazione del rischio pre-operatorio
  • Un PDRICG basso esclude i pazienti da interventi di resezione avanzati7
  • Identificazione precoce della disfunzione epatica post-operatoria
  • Capacità di previsione significativamente più alta dei marcatori convenzionali7
  • Le prime misurazioni pre-, peri- e post-operatorie di PDRICG possono essere utili per prevedere il trattamento prolungato in terapia intensiva8
  • Si possono considerare strategie mirate al miglioramento del PDRICG in pazienti cardiochirurgici a rischio per migliorare l'esito clinico8
  • Strumento prezioso per la valutazione della prognosi nei pazienti affetti da cirrosi epatica1
  • Permette di fare una prognosi sulla sopravvivenza nei pazienti affetti da malattia epatica intermedia avanzata1
  • Stima della massa funzionale delle cellule epatiche

Strumenti riutilizzabili

Modulo e sensore LiMON

Modulo LiMON

  • Tasso di scomparsa plasmatica del verde indocianina (PDR/ICG)
  • Misurazione continua di SpO2*
  • Non invasiva
  • Applicazione semplice
  • Riutilizzabile

Sensore LiMON: sensore tattile riutilizzabile

  • Monitoraggio non invasivo della funzionalità epatica
  • Monitoraggio continui di SpO2*

Materiali di consumo: verde indocianina

*Questo parametro non sarà disponibile sul monitor PulsioFlex dalla versione software 5.0

Metodologia

La misurazione LiMON si basa sull'eliminazione del farmaco diagnostico verde indocianina (ICG). L'ICG viene iniettato in una vena, si lega immediatamente e completamente alle proteine del plasma e viene eliminato dal sangue esclusivamente grazie al fegato. Questa eliminazione è abbastanza veloce con un tempo di emivita di 3,5-4 minuti.

Bibliografia

Sakka SG. 
Assessing Liver Function 
Curr Opin Crit Care 2007; 13(2):207-14

Bauer M, Winning J, Kortgen A 
Liver Failure 
Curr Opin Anaest 2005; 18:111-6

Sakka SG, Meier-Hellmann A 
Non-invasive liver function monitoring by indocyanine green plasma disappearance rate in critically ill patients 
Int J Intensive Care 2002; 9(2):66-72

Terapia intensiva

  • Inal MT, Memis D, Kargi M, Sut N.
    Prognostic value of indocyanine green elimination assessed with LiMON in septic patients
    J Crit Care 2009; 24(3): 329-34

Trapianto di fegato

  • Olmedilla L, Perez-Pena JM, Ripoll C, Garutti I, de Diego R, Salcedo M, Jimenez C, Banares R.
    Early noninvasive measurement of the indocyanine green plasma disappearance rate accurately predicts early graft dysfunction and mortality after deceased donor liver transplantation
    Liver Transpl 2009; 15(10): 1247-53

Resezione epatica

  • Scheingraber S, Richter Sn Igna D, Flesch S, Kopp B, Schilling MK.
    Indocyanine green disappearance rate is the most useful marker for liver resection
    Hepatogastroenterology 2008; 55(85): 1394-9

Purcell P, Kruger P, Jones M  
Indocyanine green elimination: a comparison of the LiMON and serial blood sampling methods  
ANZ J Surg 2006; 76: 75-7 

Sakka SG, van Hout N  
Relation between indocyanine green (ICG) plasma disappearance rate and ICG blood clearance in critically ill patients.  
Intensive Care Med 2006; 32(5):766-9 

Sakka SG, Koeck H, Meier-Hellmann A  
Measurement of indocyanine green plasma disappearance rate by two different dosages  
Intensive Care Med 2004; 30(3):506-9 

Faybik P, Krenn CG, Baker A, Lahner D, Berlakovich G, Steltzer H, Hetz H  
Comparison of invasive and noninvasive measurement of plasma disappearance rate of indocyanine green in patients undergoing liver transplantation: a prospective investigator-blinded study  
Liver Transpl 2004; 10(8):1060-4 

Sakka, SG, Reinhart K, Meier-Hellmann A  
Comparison of invasive and noninvasive measurements of indocyanine green plasma disappearance rate in critically ill patients with mechanical ventilation and stable hemodynamics 
Intensive Care Med 2000; 26(10): 1553-6 

Verde indocianina 

Leevy CM, Leevy CB, Howard MM  
Indocyanine green and the liver  
In: Davidson CS (Ed.), Problems in Liver Diseases, 1979, Georg Thieme Publishers Stuttgart-New York; 42-52 

Paumgartner G, Probst P, Kraines R, Leevy CM  
Kinetics of Indocyanine green removal from the blood  
NY Acad Sci 1970; 170:134-47 

Cardiochirurgia

Weis F, Kilger E, Beiras-Fernandez A, Hinske CL, Nassau K, Adnan L, Vicol C, Kur F, Mohnle P
Indocyanine green clearance as an outcome prediction tool in cardiac surgery: A prospective study
J Crit Care 2013; epub

Sander M, Spies CD, Berger K, Schroder T, Grubitzsch H, Wernecke KD, von Heymann C
Perioperative indocyanine green clearance is predictive for prolonged intensive care unit stay after coronary artery bypass grafting - an observational study
Crit Care 2009; 13(5): R149

Sander M, Spies CD, Foer A, Syn DY, Grubitzsch H, Von Heymann C
Peri-operative plasma disappearance rate of indocyanine green after coronary artery bypass surgery
Cardiovasc J Afr 2007;18(6): 375-9

Sakka S, Hofmann D, Thuemer O, Schelenz C, Van Hout N
Increasing cardiac output by epinephrine after cardiac surgery: effects on indocyanine green plasma disappearance rate and splanchnic microcirculation
J Cardiothorac Vasc Anesth 2007; 21(3):351-6

Hofmann D, Thuemer O, Schelenz C, van Hout N, Sakka SG
Increasing cardiac output by fluid loading: effects on indocyanine green plasma disappearance rate and splanchnic microcirculation
Acta Anaesthesiol Scand 2005; 49: 1280-6

Sepsi e shock settico

Hernandez G, Bruhn A, Luengo C, Regueira T, Kattan E, Fuentealba A, Florez J, Castro R, Aquevedo A,Pairumani R, McNab P, Ince C
Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study
Intensive Care Med 2013; 39(8): 1435-43

Hernandez G, Regueira T, Bruhn A, Castro R, Rovegno M, Fuentealba A, Veas E, Berrutti D, Kattan E, Martin C, Ince C
Relationship of systemic, hepatosplanchnic, and microcirculatory perfusion parameters with 6-hour lactate clearance in hyperdynamic septic shock patients: an acute, clinical-physiological, pilot study.
Ann Intensive Care 2012; 2(1): 44

Memis D, Inal MT, Sut N
The effects of levosimendan vs dobutamine added to dopamine on liver functions assessed with noninvasive liver function monitoring in patients with septic shock
J Crit Care 2012;27(3): 318.e1-6

Inal MT, Memis D, Kargi M, Sut N
Prognostic value of indocyanine green elimination assessed with LiMON in septic patients
J Crit Care 2009; 24(3): 329-34

Kortgen A, Paxian M, Werth M, Recknagel P, Rauchfu F, Lupp A, Krenn CG, Muller D, Claus RA, Reinhart K, Settmacher U, Bauer M
Prospective assessment of hepatic function and mechanisms of dysfunction in the critically ill
Shock 2009; 32(4): 358-65

Poeze M, Solberg BC, Greve JW, Ramsay G
Monitoring global volume-related hemodynamic or regional variables after initial resuscitation: What is a better predictor of outcome in critically ill septic patients?
Crit Care Med 2005; 33(11):2494-2500

Sakka SG, Reinhart K, Meier-Hellmann A
Prognostic value of the indocyanine green plasma disappearance rate in critically ill patients
Chest 2002; 122(5):1715-20

Chirurgico

Eryilmaz HB, Memis D, Sezer A, Inal M
The Effects of Different Insufflation Pressures on Liver Functions Assessed with LiMON on Patients Undergoing Laparoscopic Cholecystectomy
Scientific World Journal 2012: 172575

Sakka SG
Indocyanine green plasma disappearance rate as an indicator of hepato-splanchnic ischemia during abdominal compartment syndrome
Anesth Analg 2007; 104(4):1003-4

Poeze M, Ramsay G, Buuman WA, Greve JW, Dentener M, Takala J
Increased hepatosplanchnic inflammation precedes the development of organ dysfunction after elective high-risk surgery
Shock 2002; 17:451-8

Medico

Quintero J, Miserachs M, Ortega J, Bueno J, Dopazo C, Bilbao I, Castells L, Charco R
Indocyanine green plasma disappearance rate: a new tool for the classification of paediatric patients with acute liver failure
Liver Int 2013; epub

Ameloot K, Meersseman P, Wilmer A, Hermans G, Gerits A, Spriet I, Wauters J
The influence of continuous venovenous renal replacement therapy on the plasma disappearance rate of indocyanine green
Intensive Care Med 2013; 39(12): 2231-2232

Malbrain ML, Viaene D, Kortgen A, De Laet I, Dits H, Van Regenmortel N, Schoonheydt K, Bauer, M
Relationship between intra-abdominal pressure and indocyanine green plasma disappearance rate: hepatic perfusion may be impaired in critically ill patients with intra-abdominal hypertension
Ann Intensive Care 2012; 2 Suppl 1: S19

Steinvall I, Fredrikson M, Bak Z, Sjoberg J
Incidence of early burn-induced effects on liver function as reflected by the plasma disappearance rate of indocyanine green: A prospective descriptive cohort study
Burns 2012; 38(2): 214-24

Inal MT, Memis D, Sezer YA, Atalay M, Karakoc A, Sut N
Effects of intra-abdominal pressure on liver function assessed with the LiMON in critically ill patients
Can J Surg 2011; 54(2): 42709.

Seibel A, Muller M, Sakka S
Indocyanine green plasma disappearance rate for monitoring hepatosplanchnic blood flow
Intensive Care Med 2011; 37(2): 357-9

Sakka SG, Reinhart K, Meier-Hellmann A
Prognostic value of the indocyanine green plasma disappearance rate in critically ill patients
Chest 2002; 122(5):1715-20

Trapianto di fegato

Vos JJ, Scheeren TW, Lukes DJ, de Boer MT, Hendriks HG, Wietasch JK
Intraoperative ICG plasma disappearance rate helps to predict absence of early postoperative complications after orthotopic liver transplantation
J Clin Monit Comput 2013; 27(5): 591-8

Levesque E, Hoti E, Azoulay D, Adam R, Samuel D, Castaing D, Saliba F
Non-invasive ICG-clearance: a useful tool for the management of hepatic artery thrombosis following liver transplantation
Clin Transplant 2011; 25(2): 297-301

Levesque E, Saliba F, Benhamida S, Ichai P, Azoulay D, Adam R, Castaing D, Samuel D
Plasma disappearance rate of indocyanine green: a tool to evaluate early graft outcome after liver transplantation
Liver Transpl 2009; 15(10): 1358-64

Olmedilla L, Perez-Pena JM, Ripoll C, Garutti I, de Diego R, Salcedo M, Jimenez C, Banares R
Early noninvasive measurement of the indocyanine green plasma disappearance rate accurately predicts early graft dysfunction and mortality after deceased donor liver transplantation
Liver Transpl 2009; 15(10): 1247-53

Parker BM, Cywinski JB, Alster JM, Irefin SA, Popovich M, Beven M, Fung JJ
Predicting immunosuppressant dosing in the early postoperative period with noninvasive indocyanine green elimination following orthotopic liver transplantation
Liver Transpl 2008; 14(1): 46-52

Scheingraber S, Richter S, Igna D, Girndt M, Flesch S, Kleinschmidt S, Schilling MK
Indocyanine green elimination but not bilirubin indicates improvement of graft function during MARS therapy
Clin Transplant 2007; 21(6): p. 689-95

Hori T, Iida T, Yagi S, Taniguchi K, Yamamoto C, Mizuno S, Yamagiwa K, Isaji S, Uemoto S
K(ICG) value, a reliable real-time estimator of graft function, accurately predicts outcomes in adult living-donor liver transplantation
Liver Tranpl 2006; 12: 605-13

Faybik P, Krenn CG, Baker A, Lahner D, Berlakovich G, Steltzer H, Hetz H
Comparison of invasive and noninvasive measurement of plasma disappearance rate of indocyanine green in patients undergoing liver transplantation: a prospective investigator-blinded study
Liver Transpl 2004; 10(8):1060-4

von Spiegel T, Scholz M, Wietasch G, Hering R, Allen SJ, Wood P, Hoeft A
Perioperative monitoring of indocyanine green clearance and plasma disappearance rate in patients undergoing liver transplantation
Anaesthesist 2002; 51(5):359-66

Mandell MS, Wachs M, Niemann CU, Henthorn TK
Elimination of indocyanine green in the perioperative evaluation of donor liver function
Anesth Analg 2002; 95(5):1182-4

Niemann CU, Roberts JP, Ascher NL, Yost CS
Intraoperative hemodynamics and liver function in adult-to-adult living liver donors
Liver Transpl 2002; 8(12):1126-32

Krenn CG, Schafer B, Berlakovich GA, Steininger R, Steltzer H, Spiss CK
Detection of graft nonfunction after liver transplantation by assessment of indocyanine green kinetics
Anesth Analg 1998 Jul;87(1):34-6

Wesslau C, Krüger R, May G
Clinical investigations using indocyanine green clearance for evaluation of liver function in organ donors
Transplantology 1994; 5(1):7-9

Chirurgia del fegato / resezione

Tralhao JG, Hoti E, Oliveiros B, Botelho MF, Sousa FC
Study of perioperative liver function by dynamic monitoring of ICG-clearance
Hepatogastroenterology 2012; 59(116): 1179-83

de Liguori Carino N, O'Reilly DA, Dajani K, Ghaneh P, Poston GJ, Wu AV
Perioperative use of the LiMON method of indocyanine green elimination measurement for the prediction and early detection of post-hepatectomy liver failure
Eur J Surg Oncol 2009; 35(9):957-62

Szijarto A, Hargitai B, Fischer S, Darvas K, Kupcsulik P
Two-staged procedure of portal ligation and hepatectomy monitored by ICG clearance
J Invest Surg 2009; 22(1): 63-8

Scheingraber S, Richter S, Igna D, Flesch S, Kopp B, Schilling MK
Indocyanine green disappearance rate is the most useful marker for liver resection
Hepatogastroenterology 2008; 55(85): 1394-9

Akita H, Sasaki Y, Yamada T, Gotoh K, Ohigashi H, Eguchi H, Yano M, Ishikawa O, Imaoka S
Real-Time Intraoperative Assessment of Residual Liver Functional Reserve Using Pulse Dye Densitometry.
World J Surg 2008; 32(21): 2668-74

Sato S, Miyake T, Mishiro T, Furuta K, Azumi T, Oshima N, Takahashi Y, Rumi MA, Ishihara S, Adachi K, Amano Y, Kinoshita Y
Kinetics of indocyanine green removal from blood can be used to predict the size of the area removed by radiofrequency ablation of hepatic nodules
J Gastroenterol Hepatol 2006; 21:1714-9

Imamura H, Sano K, Sugawara Y, Kokudo N, Makuuchi M
Assessment of hepatic reserve for indication of hepatic resection: decision tree incorporating indocyanine green test
J Hepatobiliary Pancreat Surg 2005; 12: 16-22

Lee SG, Hwang S
How I do it: assessment of hepatic functional reserve for indication of hepatic resection
J Hepatobiliary Pancreat Surg 2005; 12: 38-43

Imamura H, Seyama Y, Kokudo N, Maema A, Sugawara Y, Sano K, Takayama T, Makuuchi M
One thousand fifty-six hepatectomies without mortality in 8 years
Arch Surg 2003; 138: 1198-1206

Thasler WE, Bein T, Jauch KW
Perioperative effects of hepatic resection surgery on hemodynamics, pulmonary fluid balance, and indocyanine green clearance
Langenbecks Arch Surg 2002; 387: 271-5

Ishikawa M, Yogita S, Miyake H, Fukuda Y, Harada M, Wada D, Tashiro S
Clarification of risk factors for hepatectomy in patients with hepatocellular carcinoma
Hepatogastroenterology 2002; 49: 1625-31

Eguchi H, Umeshita K, Sakon M, Nagano H, Ito Y, Kishimoto SI, Dono K, Nakamori S, Takeda T, Gotoh M, Wakasa K, Matsuura N, Monden M
Presence of active hepatitis associated with liver cirrhosis is a risk factor for mortality caused by posthepatectomy liver failure
Dig Dis Sci 2000; 45: 1383-8

Hsia CY, Lui WY, Chau GY, King KL, Loong CC, Wu CW
Perioperative safety and prognosis in hepatocellular carcinoma patients with impaired liver function
J Am Coll Surg 2000; 190: 574-9

Hanazaki K, Kajikawa S, Shimozawa N, Mihara M, Shimada K, Hiraguri M, Koide N, Adachi W, Amano J
Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma
J Am Coll Surg 2000; 191: 381-8

Epatologia/gastroenterologia

Zipprich A, Kuss O, Rogowski S, Kleber G, Lotterer E, Seufferlein T, Fleig WE, Dollinger MM
Incorporating indocyanin green clearance into the Model for End Stage Liver Disease (MELD-ICG) improves prognostic accuracy in intermediate to advanced cirrhosis
Gut 2010; 59(7): 963-8

Merle U, Sieg O, Stremmel W, Encke J, Eisenbach C
Sensitivity and specificity of plasma disappearance rate of indocyanine green as a prognostic indicator in acute liver failure
BMC Gastroenterol 2009; 9: 91

Herold C, Heinz R, Radespiel-Tröger M, Schneider HT, Schuppan D, Hahn EG 
Quantitative testing of liver function in patients with cirrhosis due to chronic hepatitis C to assess disease severity.
Liver. 2001; 21(1):26-30

Shock ipovolemico

Kisch H, Leucht S, Lichtwarck-Aschoff M, Pfeiffer UJ
Accuracy and reproducibility of the measurement of actively circulating blood volume with an integrated fiberoptic monitoring system.
Crit Care Med. 1995; 23(5):885-93

Monitoraggio degli effetti terapeutici
Terapie farmacologiche
Shock settico

Lehmann C, Taymoorian K, Wauer H, Krausch D, Birnbaum J, Kox WJ
Effects of the stable prostacyclin analogue iloprost on the plasma disappearance rate of indocyanine green in human septic shock
Intensive Care Med. 2000; 26(10):1557-60

Meier-Hellmann A, Bredle DL, Specht M, Hannemann L, Reinhart K
Dopexamine increases splanchnic blood flow but decreases gastric mucosal pH in severe septic patients treated with dobutamine
Crit Care Med 1999; 27: 2166-71

Joly LM, Monchi M, Cariou A, Chiche JD, Bellenfant F, Brunet F, Dhainaut JF
Effects of dobutamine on gastric mucosal perfusion and hepatic metabolism in patients with septic shock
Am J Respir Crit Care Med 1999: 160; 1983-6

Chirurgia del fegato / disfunzione

Sheng QS, Lang R, He Q, Yang YJ, Zhao DF, Chen DZ
Indocyanine green clearance test and model for end-stage liver disease score of patients with liver cirrhosis.
Hepatobiliary Pancreat Dis Int 2009; 8(1): 46-9

Orii R, Sugawara Y, Hayashida M, Yamada Y, Chang K, Takayama T, Makuuchi M, Hanaoka K
Effects of amrinone on ischaemia-reperfusion injury in cirrhotic patients undergoing hepatectomy: a comparative study with prostaglandin E1.
Br J Anaesth. 2000; 85(3):389-95

Devlin J, Ellis AE, McPeake J, Heaton N, Wendon JA, Williams R
N-acetylcysteine improves indocyanine green extraction and oxygen transport during hepatic dysfunction.
Crit Care Med. 1997; 25(2):236-42

Terapie adiuvanti

Memis D, Inal MT, Sut N
The effects of levosimendan vs dobutamine added to dopamine on liver functions assessed with noninvasive liver function monitoring in patients with septic shock
J Crit Care 2012; 27(3): 318.e1-6

Abraldes J, Albillos A, Banares R, Turnes J, Gonzalez R, Garcia-Pagan J, Bosch J
Simvastatin Lowers Portal Pressure in Patients with Cirrhosis and Portal Hypertension: a Randomized Controlled Trial.
Gastroenterology 2009; 136(5): 1651-8

Link A, Girndt M, Selejan S, Mathes A, Bohm M, Rensing H
Argatroban for anticoagulation in continuous renal replacement therapy.

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Riferimenti

  1. Zipprich A. et al., Incorporating indocyanin green clearance into the Model for End Stage Liver Disease (MELD-ICG) improves prognostic accuracy in intermediate to advanced cirrhosis. Gut 2010, 59(7): 963-968.

  2. Sakka S. G. et al., Prognostic value of the indocyanine green plasma disappearance rate in critically ill patients. Chest 2002, 122(5): 1715-1720.

  3. Sakka S. G. et al., Non-invasive liver function monitoring by indocyanine green plasma disappearance rate in critically ill patients. Int J Intensive Care 2002, 9(2):66-72.

  4. Mandel M. S. et al., Elimination of indocyanine green in the perioperative evaluation of donor liver function. Anesth Analg 2002, 95(5): 1182-1184.

  5. Tsubono T. et al., Indocyanine green elimination test in orthotopic liver recipients. Hepatology 1996, 24(5): 1165-1171.

  6. Levesque E. et al., Plasma disappearance rate of indocyanine green: a tool to evaluate early graft outcome after liver transplantation. Liver Transpl 2009, 15(10):1358-1364.

  7. Scheingraber S. et al., Indocyanine green disappearance rate is the most useful marker for liver resection. Hepatogastroenterology 2008, 55(85): 1394-1399.

  8. Sander M. et al., Perioperative indocyanine green clearance is predictive for prolonged intensive care unit stay after coronary artery bypass grafting - an observational study. Crit Care 2009, 13(5): R149.