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Correlation among ionized calcium, citrate, and total calcium levels during hepatic transplantation
Clinical Biochemistry, Vol. 28, No. 3, pp. 315-317, 1995 Copyright © 1995 The Canadian Society of Clinical Chemists Printed in the USA. All rights reserved 0009-9120/95 $9.50 + .00
Pergamon 0009-9120(94)00094-8
Correlation Among Ionized Calcium, Citrate, and Total Calcium Levels During Hepatic Transplantation J. DiAZ, 1 F. ACOSTA, 2 P. PARRILLA, 3 T. SANSANO, 2 R.F. CONTRERAS, 2 F.S. BUENO 3 and P. MARTfNEZ ~ 1Department of Biochemistry, 2Department of Anesthesiology, and 3Department of Surgery, Liver Transplant Unit, University Hospital "V. Arrixaca", Murcia, Spain KEY WORDS: ionized calcium; hypocalcemia; transfusion; citrate; human hepatic transplantation; calcium chloride. Introduction
uring h u m a n hepatic transplantation, massive
D t r a n s f u s i o n s of h e m o d e r i v a t e s are needed, which represent a considerable supply of citrate
(1,2). In the anhepatic phase, the ability for citrate metabolism is greatly diminished (3). Citrate accumulates and chelates :increasing amounts of calcium, thereby decreasing the level of physiologically active ionized calcium (Ca2+), and causes ionized hypocalcemia, creating hemodynamic and myocardial depression despite adequate cardiac filling pressures, which can seriously affect neuromuscular and cardiovascular functions (4-6). Calcium supplements are routinely given on an empirical basis as prophylaxis during massive transfusion, but may in themselves be dangerous if requirements are exceeded (3,6). Thus, rational calcium administration to prevent and treat citrate toxicity during major surgical procedures such as hepatic transplantation ideally requires the perioperative monitoring of Ca 2+ levels (7). The objective was to describe the changes of blood Ca2+., serum citrate, and serum total calcium (Cat) levels and their relationship during hepatic transplantation, and assess the efficiency of treatment with calcium chloride (CaC12). Materials and methods PATIENTS
Following approval by our research committee, 91 consecutive a d u l t p a t i e n t s u n d e r g o i n g hepatic
transplantation were studied; 56 of them were men, and 35 were women. The decision to indicate hepatic transplantation was based on the following diagnosis: cirrhosis (n = 56), fulminant hepatic failure (n = 14), Wilson's disease (n = 6), familial amyloidotic polyneuropathy (n = 9), and others (n = 6). Their mean age was 42 years. The mean body weight was 65.1 kg. Calcium chloride was given both as a continuous infusion adjusted for patient's weight (3 mg/ kg/h) established from the start of the intervention, and intermittently as 0.5-1 g boluses when the blood Ca 2÷ level was less than 0.90 mmol/L (2,5). Anesthesia was induced with sodium thiopental and succinylcholine and maintained with an air/oxygen mixture (Fio2 = 0.5) and continuous infusion of fentanyl, pancuronium bromide, and midazolam (8). The Wisconsin preservation solution was used in all the cases. After the graft reperfusion, all patients received methylprednisolone (1 g) i.v., according to the established immunosuppression protocol. All the liver removals from the donor and implants in the recipient were performed using the technique described by Starzl et al. (9). Surgical procedure is divided into three well differentiated stages. The preanhepatic phase starts with the skin incision and ends when the hepatic vessels are completely dissected. The anhepaticphase begins when the hepatic circulation is interrupted by clamping the supra and infrahepatic vena cava, the portal vein, and the hepatic artery previous to the hepatectomy. This phase ends when the graft is reperfused, once the vascular anastomoses are established. Finally, the neohepatic phase elapses from the moment when the circulation of the new liver is resumed to the end of the surgical procedure (10). SPECIMENS AND INSTRUMENTATION
Correspondence: Dr. D. Francisco Acosta, C/San Cristobal, 4, (3 B), 30001-Murcia, SPAIN. Manuscript received July 29, 1994; revised November 24, 1994; accepted November 25, 1994. C L I N I C A L BIOCHEMISTRY,, V O L U M E 28, J U N E 1995
Blood samples were collected from a radial artery line. The first 5 mL was discarded, and 5 mL collected for analysis. Specimens were taken immediately after anesthesia induction or baseline (A1): 5 315
DIAZ
min after the beginning and 5 min before the end of the preanhepatic (Ae, A 3) and anhepatic (B t, S 2) phases; at 5 and 60 min after the beginning of the neohepatic phase (C1, C2); at the end of surgery (C3), and at 24, 48 and 72 h after procedure (D1, De, and D3, respectively). The only exogenous source of citrate was hemoderivatives transfused by means of a rapid fluid infusion system (RIS ®, Haemonetics Inc., Braintree, MA). The pump was primed with a blood replacement mixture of approximately 1200 mL of red blood cells preserved with citrate, phosphate dextroseadenine, 800 mL of fresh frozen plasma, and 1200 mL of saline solution (Plasmalyte ®) providing a mean -+ SD of Ca2+: 0.04 -+ 0.03 mmol/L, Cat: 3.11 -+ 1.05 mmol/L, and citrate: 3.02 -+ 0.54 mmol/L. Intraoperatively, patients received blood in amounts sufficient to maintain a hematocrit of 30%. Blood Ca 2+ level were performed using a STAT PROFILE 5 analyzer (NOVA Biomedical, Boston, MA), C a t concentration was measured in serum from the same samples with a BM/HITACHI 717 analyzer (Boehringer Mannheim), which uses colorimetric o-cresolphthalein complexone method. Serum citrate level was analyzed enzymatically using citrate lyase (citric acid, UV-method, Boehringer Mannheim). Our laboratory reference ranges were blood Ca2+: 0.95-1.23 mmol/L, s e r u m C a t : 1.99-2.55 mmol/L and serum citrate: 0.07-0.14 mmol/L.
Statistical analysis The medians and interquartile range of hemoderivates transfused during each~Dhase of the procedure were calculated. Citrate, Ca z+, and C a t levels are presented as mean -+ SD. Analysis of variance for repeated measures and linear correlation were performed. A p value less than 0.05 was considered statistically significant.
ET AL.
progressively to become normal on the first postoperative day (D1). Serum Cat concentration increases significantly in the anhepatic phase (B1, B2) reaching its maximum value after reperfusion (C1), but decreases in the neohepatic phase and returns to reference range on the first postoperative day (Dr). The baseline blood Ca 2 + level is normal during preanhepatic phase, but in the anhepatic phase decreases significantly (B1, B2). After reperfusion (C1), C a 2 + concentration returns to reference range. The results are shown in Figure 1. There was an inverse correlation between Ca 2+ and citrate concentrations. The regression equation between ionized calcium (Ca 2+) and citrate level is expressed by the formula: [Ca 2+ ] = -0.12 [citrate] + 1.15 (r = - 0 . 6 3 ; p < 0.05). When we add a new f a c t o r , C a t concentration, the regression equation obtained was: [ C a 2+] = 0.23 [Cat] - 0.17 [citrate] + 0.62
(r = -0.93; p < 0.01). Discussion Citrate intoxication is defined as elevation of serum citrate level associated with ionized hypocalcemia and hemodynamic depression (1). Clinically, citrate intoxication rarely occurs during massive transfusion of citrated hemoderivates primarily because the liver metabolizes 100 times the normal level of serum citrate during a single pass through its vascular bed (11). During hepatic transplantation, transfusion of blood products dramatically increases serum citrate concentrations and results in e--e Ionized calcium • - - • Citrate • -?-- A Total calcium
3. -5
E E
Results In Table 1 are presented the hemoderivate requirements during preanhepatic, anhepatic and neohepatic phases. The baseline serum level of citrate increases significantly and records its maximum increase at the end of the anhepatic phase (B2). After reperfusion (Ct), this concentration decreases
C 0
c ID 0 cO
2~ b 1'
A1
TABLE 1 Blood Products Requirements (Units) During Hepatic Transplantation Surgery
Erythrocytes FFP Cryoprecipitates Platelets
Preanhepatic Phase
Anhepatic Phase
Neohepatic Phase
7 (4-9) 8 (6-11) 2 (0-5) 2 (0-6)
5 (3-7) 6 (4-10) 1 (0-3) 1 (0-2)
9 (6-11) 10 (7-14) 9 (0-18) 6 (0-17)
F F P : F r e s h frozen p l a s m a . V a l u e s a r e m e d i a n s ( i n t e r q u a r t i l e range). 316
A2
A3
I B1
I B2
OLT
C1
C2
C3
D1
D2
D3
PHASES
Figure 1 - - Changes of the blood concentrations of ionized calcium, total calcium, and citrate during hepatic trans~plantation.Data are expressed as means -+ SD. ap < 0.05, < 0.01, and Cp < 0.001 compared with baseline (At) means. Blood samples were taken immediately after anesthesia induction (At); 5 min ai~r the beginning and 5 rain before the end of the preanhepatic (A2, As) and an-
hepatic (B1, B2) phases; at 5 and 60 min after the beginning of the neohepatic phase (C1, C2); at the end of the surgery (Ca), and at 24, 48, and 72 h after procedure (D1, D2, and D3, respectively). CLINICAL BIOCHEMISTRY, VOLUME 28, JUNE 1995
HEPATIC T R A N S P L A N T A T I O N
ionized hypocalcemia and cardiovascular depression
References
(1). The surgical procedure comprises t h r e e m a i n phases each with its attendant problems, which so often m a y prejudice operative hemostasis (12). The changes in the levels of the parameters studied have a multifactorial origin. Usually, during the preanhepatic phase considerable amounts of hemoderivates are transfused, rich in metabolites that can form complexes with Ca 2+, mainly citrate (1,13). However, efficient treal~ment with CaC12 prevents a decrease in Ca 2 + level despite the increase in citrate concentration. During the anhepatic phase, the risk of ionized hypocalcemia increases due to the absence of liver function (14), w:hich is responsible for citrate clearance (15). As the supply of hemoderivates continues, citrate level increases and induces a decrease in Ca 2+ concentration (2,4). Several investigations showed that the decrease in Ca 2+ levels was associated with the speed of transfusion and with the chelating effect of citrate in the blood preservative (7,13). Ca 2 + concentration returns to reference range after reperfusion as hepatic metabolism is restored and citrate is rapidly metabolized (3,11). In the neohepatic phase, the release of Ca 2÷ from the citrate molecule as a function of citrate metabolism m a y have contributed to the normalization of Ca 2+. Citrate began to decrease: after hepatic graft reperfusion and approached baseline values at 24 h after procedure. This m a y reflect the time necessary for the newly transplanted liver to become functional (14), because citrate clearance by the normally functioning liver is usually quite rapid (11). The degree of ionized hypocalcemia caused by the transfusion of hemoderivates is correlated to the levels of serum citrate (8,15). Use of calcium supplements should reflect the a m o u n t of calcium bound by citrate, which can be predicted from the slope of the line relating Cat to citrate concentration. However, Cote et al. (15) observe that an independent analysis of Ca t and Ca 2+ levels does not predict the amount of CaC12 needed to prevent ionized hypocalcemia, probably because they did not take into account the conc e n t r a t i o n of the m a i n chelating agent: citrate (8,16,17). We conclude t h a t ionized hypocalcemia is the most specific metabolic alteration in hepatic transplantation, caused mainly by the formation of complexes between Ca and citrate; however, the treatment with calcium chloride maintains normal Ca 2 ÷ level during surgical procedure.
CLINICAL BIOCHEMISTRY,VOLUME 28, JUNE 1995
1. M~rquez JM, Martin J, Virji MA, et al. Cardiovascular depression secondary to citrate intoxication during hepatic transplantation in man. Anesthesiology 1986; 65: 457-61. 2. Diaz J, Acosta F, Martinez P, Parrilla P. Tratamiento de la hipocalcemia idnica durante el trasplante hep~tico. Med Clin (Barc) 1994; 103: 118-9. 3. Gray TA, Buckley BM, Sealey MM, Smith SC, Tomlin P, McMaster P. Plasma ionized calcium monitoring during liver transplantation. Transplantation 1986; 41: 335-9. 4. Drop JL. Ionized calcium, the heart and hemodynamic function. Anesth Analg 1985; 64: 432-51. 5. Acosta F, Diaz J, Sansano T, et al. Prophylactic treatment of metabolic alterations at revascularization in liver transplantation. Transplant Proc 1994; 26: 4259-60. 6. Martin TJ, Kang Y, Robertson KM, Virji MA, Marquez JM. Ionization and hemodynamic effects of calcium chloride and calcium gluconate in the absence of hepatic function. Anesthesiology 1990; 73: 62-5. 7. Kost GJ, Jammal MA, Ward RE, Safwat AM. Monitoring of ionized calcium during human hepatic function. Am J Clin Pathol 1986; 74: 135-50. 8. Carton E, Rettke S, Plevak D, Geiger H, Kranner P, Coursin D. Perioperative care of the liver transplant patient: Part 1. Anesth Analg 1994; 78: 120-33. 9. Starzl T, Iwatsuki S, Van Thiel DH. Evolution of liver transplantation. Hepatology 1982; 2: 614-36. 10. Carton E, Plevak D, Kranner P, Rettke R, Geiger H, Coursin D. Perioperative care of the liver transplant patient: Part 2. Anesth Analg 1994; 78: 382-99. 11. Delinger JK, Nahrwold ML, Gibbs PS, Lecky JH. Hypocalcaemia during rapid blood transfusion in anaesthetized man. Br J Anaesth 1976; 48: 995-1000. 12. Porte R, Knot E, Bontempo F. Hemostasis in liver transplantation. Gastroenterology 1989; 97: 488-501. 13. Kahn RC, Jascott D, Carlon GC, Schweizer O, Howland WS, Goldiner PL. Massive blood replacement: correlation of ionized calcium, citrate, and hydrogen ion concentration. Anesth Analg 1979; 58: 274-8. 14. Diaz J, Acosta F, Martinez P, Parrilla P. Blood ammonia levels as early indicator of allograft viability in human orthotopic liver transplantation. Am J Gastroenterol 1994, 89: 2283-4. 15. Cote CJ, Drop l_J, Hoaglin DC, Daniels AL, Youngs ET. Ionized hypocalcemia after fresh frozen plasma administration to thermally injured children. Anesth Analg 1988; 67: 152-60. 16. Suleiman MY, Zaloga GP. How and when to manage ionized hypocalcaemia in critically ill patients. J Crit Illness 1993; 8: 372-90. 17. Kang Y, Aggarwal S, Pasculle R. Clinical evaluation of autotransfusion during liver transplantation. Anesth Analg 1991; 72: 94-9.
317
Pergamon 0009-9120(94)00094-8
Correlation Among Ionized Calcium, Citrate, and Total Calcium Levels During Hepatic Transplantation J. DiAZ, 1 F. ACOSTA, 2 P. PARRILLA, 3 T. SANSANO, 2 R.F. CONTRERAS, 2 F.S. BUENO 3 and P. MARTfNEZ ~ 1Department of Biochemistry, 2Department of Anesthesiology, and 3Department of Surgery, Liver Transplant Unit, University Hospital "V. Arrixaca", Murcia, Spain KEY WORDS: ionized calcium; hypocalcemia; transfusion; citrate; human hepatic transplantation; calcium chloride. Introduction
uring h u m a n hepatic transplantation, massive
D t r a n s f u s i o n s of h e m o d e r i v a t e s are needed, which represent a considerable supply of citrate
(1,2). In the anhepatic phase, the ability for citrate metabolism is greatly diminished (3). Citrate accumulates and chelates :increasing amounts of calcium, thereby decreasing the level of physiologically active ionized calcium (Ca2+), and causes ionized hypocalcemia, creating hemodynamic and myocardial depression despite adequate cardiac filling pressures, which can seriously affect neuromuscular and cardiovascular functions (4-6). Calcium supplements are routinely given on an empirical basis as prophylaxis during massive transfusion, but may in themselves be dangerous if requirements are exceeded (3,6). Thus, rational calcium administration to prevent and treat citrate toxicity during major surgical procedures such as hepatic transplantation ideally requires the perioperative monitoring of Ca 2+ levels (7). The objective was to describe the changes of blood Ca2+., serum citrate, and serum total calcium (Cat) levels and their relationship during hepatic transplantation, and assess the efficiency of treatment with calcium chloride (CaC12). Materials and methods PATIENTS
Following approval by our research committee, 91 consecutive a d u l t p a t i e n t s u n d e r g o i n g hepatic
transplantation were studied; 56 of them were men, and 35 were women. The decision to indicate hepatic transplantation was based on the following diagnosis: cirrhosis (n = 56), fulminant hepatic failure (n = 14), Wilson's disease (n = 6), familial amyloidotic polyneuropathy (n = 9), and others (n = 6). Their mean age was 42 years. The mean body weight was 65.1 kg. Calcium chloride was given both as a continuous infusion adjusted for patient's weight (3 mg/ kg/h) established from the start of the intervention, and intermittently as 0.5-1 g boluses when the blood Ca 2÷ level was less than 0.90 mmol/L (2,5). Anesthesia was induced with sodium thiopental and succinylcholine and maintained with an air/oxygen mixture (Fio2 = 0.5) and continuous infusion of fentanyl, pancuronium bromide, and midazolam (8). The Wisconsin preservation solution was used in all the cases. After the graft reperfusion, all patients received methylprednisolone (1 g) i.v., according to the established immunosuppression protocol. All the liver removals from the donor and implants in the recipient were performed using the technique described by Starzl et al. (9). Surgical procedure is divided into three well differentiated stages. The preanhepatic phase starts with the skin incision and ends when the hepatic vessels are completely dissected. The anhepaticphase begins when the hepatic circulation is interrupted by clamping the supra and infrahepatic vena cava, the portal vein, and the hepatic artery previous to the hepatectomy. This phase ends when the graft is reperfused, once the vascular anastomoses are established. Finally, the neohepatic phase elapses from the moment when the circulation of the new liver is resumed to the end of the surgical procedure (10). SPECIMENS AND INSTRUMENTATION
Correspondence: Dr. D. Francisco Acosta, C/San Cristobal, 4, (3 B), 30001-Murcia, SPAIN. Manuscript received July 29, 1994; revised November 24, 1994; accepted November 25, 1994. C L I N I C A L BIOCHEMISTRY,, V O L U M E 28, J U N E 1995
Blood samples were collected from a radial artery line. The first 5 mL was discarded, and 5 mL collected for analysis. Specimens were taken immediately after anesthesia induction or baseline (A1): 5 315
DIAZ
min after the beginning and 5 min before the end of the preanhepatic (Ae, A 3) and anhepatic (B t, S 2) phases; at 5 and 60 min after the beginning of the neohepatic phase (C1, C2); at the end of surgery (C3), and at 24, 48 and 72 h after procedure (D1, De, and D3, respectively). The only exogenous source of citrate was hemoderivatives transfused by means of a rapid fluid infusion system (RIS ®, Haemonetics Inc., Braintree, MA). The pump was primed with a blood replacement mixture of approximately 1200 mL of red blood cells preserved with citrate, phosphate dextroseadenine, 800 mL of fresh frozen plasma, and 1200 mL of saline solution (Plasmalyte ®) providing a mean -+ SD of Ca2+: 0.04 -+ 0.03 mmol/L, Cat: 3.11 -+ 1.05 mmol/L, and citrate: 3.02 -+ 0.54 mmol/L. Intraoperatively, patients received blood in amounts sufficient to maintain a hematocrit of 30%. Blood Ca 2+ level were performed using a STAT PROFILE 5 analyzer (NOVA Biomedical, Boston, MA), C a t concentration was measured in serum from the same samples with a BM/HITACHI 717 analyzer (Boehringer Mannheim), which uses colorimetric o-cresolphthalein complexone method. Serum citrate level was analyzed enzymatically using citrate lyase (citric acid, UV-method, Boehringer Mannheim). Our laboratory reference ranges were blood Ca2+: 0.95-1.23 mmol/L, s e r u m C a t : 1.99-2.55 mmol/L and serum citrate: 0.07-0.14 mmol/L.
Statistical analysis The medians and interquartile range of hemoderivates transfused during each~Dhase of the procedure were calculated. Citrate, Ca z+, and C a t levels are presented as mean -+ SD. Analysis of variance for repeated measures and linear correlation were performed. A p value less than 0.05 was considered statistically significant.
ET AL.
progressively to become normal on the first postoperative day (D1). Serum Cat concentration increases significantly in the anhepatic phase (B1, B2) reaching its maximum value after reperfusion (C1), but decreases in the neohepatic phase and returns to reference range on the first postoperative day (Dr). The baseline blood Ca 2 + level is normal during preanhepatic phase, but in the anhepatic phase decreases significantly (B1, B2). After reperfusion (C1), C a 2 + concentration returns to reference range. The results are shown in Figure 1. There was an inverse correlation between Ca 2+ and citrate concentrations. The regression equation between ionized calcium (Ca 2+) and citrate level is expressed by the formula: [Ca 2+ ] = -0.12 [citrate] + 1.15 (r = - 0 . 6 3 ; p < 0.05). When we add a new f a c t o r , C a t concentration, the regression equation obtained was: [ C a 2+] = 0.23 [Cat] - 0.17 [citrate] + 0.62
(r = -0.93; p < 0.01). Discussion Citrate intoxication is defined as elevation of serum citrate level associated with ionized hypocalcemia and hemodynamic depression (1). Clinically, citrate intoxication rarely occurs during massive transfusion of citrated hemoderivates primarily because the liver metabolizes 100 times the normal level of serum citrate during a single pass through its vascular bed (11). During hepatic transplantation, transfusion of blood products dramatically increases serum citrate concentrations and results in e--e Ionized calcium • - - • Citrate • -?-- A Total calcium
3. -5
E E
Results In Table 1 are presented the hemoderivate requirements during preanhepatic, anhepatic and neohepatic phases. The baseline serum level of citrate increases significantly and records its maximum increase at the end of the anhepatic phase (B2). After reperfusion (Ct), this concentration decreases
C 0
c ID 0 cO
2~ b 1'
A1
TABLE 1 Blood Products Requirements (Units) During Hepatic Transplantation Surgery
Erythrocytes FFP Cryoprecipitates Platelets
Preanhepatic Phase
Anhepatic Phase
Neohepatic Phase
7 (4-9) 8 (6-11) 2 (0-5) 2 (0-6)
5 (3-7) 6 (4-10) 1 (0-3) 1 (0-2)
9 (6-11) 10 (7-14) 9 (0-18) 6 (0-17)
F F P : F r e s h frozen p l a s m a . V a l u e s a r e m e d i a n s ( i n t e r q u a r t i l e range). 316
A2
A3
I B1
I B2
OLT
C1
C2
C3
D1
D2
D3
PHASES
Figure 1 - - Changes of the blood concentrations of ionized calcium, total calcium, and citrate during hepatic trans~plantation.Data are expressed as means -+ SD. ap < 0.05, < 0.01, and Cp < 0.001 compared with baseline (At) means. Blood samples were taken immediately after anesthesia induction (At); 5 min ai~r the beginning and 5 rain before the end of the preanhepatic (A2, As) and an-
hepatic (B1, B2) phases; at 5 and 60 min after the beginning of the neohepatic phase (C1, C2); at the end of the surgery (Ca), and at 24, 48, and 72 h after procedure (D1, D2, and D3, respectively). CLINICAL BIOCHEMISTRY, VOLUME 28, JUNE 1995
HEPATIC T R A N S P L A N T A T I O N
ionized hypocalcemia and cardiovascular depression
References
(1). The surgical procedure comprises t h r e e m a i n phases each with its attendant problems, which so often m a y prejudice operative hemostasis (12). The changes in the levels of the parameters studied have a multifactorial origin. Usually, during the preanhepatic phase considerable amounts of hemoderivates are transfused, rich in metabolites that can form complexes with Ca 2+, mainly citrate (1,13). However, efficient treal~ment with CaC12 prevents a decrease in Ca 2 + level despite the increase in citrate concentration. During the anhepatic phase, the risk of ionized hypocalcemia increases due to the absence of liver function (14), w:hich is responsible for citrate clearance (15). As the supply of hemoderivates continues, citrate level increases and induces a decrease in Ca 2+ concentration (2,4). Several investigations showed that the decrease in Ca 2+ levels was associated with the speed of transfusion and with the chelating effect of citrate in the blood preservative (7,13). Ca 2 + concentration returns to reference range after reperfusion as hepatic metabolism is restored and citrate is rapidly metabolized (3,11). In the neohepatic phase, the release of Ca 2÷ from the citrate molecule as a function of citrate metabolism m a y have contributed to the normalization of Ca 2+. Citrate began to decrease: after hepatic graft reperfusion and approached baseline values at 24 h after procedure. This m a y reflect the time necessary for the newly transplanted liver to become functional (14), because citrate clearance by the normally functioning liver is usually quite rapid (11). The degree of ionized hypocalcemia caused by the transfusion of hemoderivates is correlated to the levels of serum citrate (8,15). Use of calcium supplements should reflect the a m o u n t of calcium bound by citrate, which can be predicted from the slope of the line relating Cat to citrate concentration. However, Cote et al. (15) observe that an independent analysis of Ca t and Ca 2+ levels does not predict the amount of CaC12 needed to prevent ionized hypocalcemia, probably because they did not take into account the conc e n t r a t i o n of the m a i n chelating agent: citrate (8,16,17). We conclude t h a t ionized hypocalcemia is the most specific metabolic alteration in hepatic transplantation, caused mainly by the formation of complexes between Ca and citrate; however, the treatment with calcium chloride maintains normal Ca 2 ÷ level during surgical procedure.
CLINICAL BIOCHEMISTRY,VOLUME 28, JUNE 1995
1. M~rquez JM, Martin J, Virji MA, et al. Cardiovascular depression secondary to citrate intoxication during hepatic transplantation in man. Anesthesiology 1986; 65: 457-61. 2. Diaz J, Acosta F, Martinez P, Parrilla P. Tratamiento de la hipocalcemia idnica durante el trasplante hep~tico. Med Clin (Barc) 1994; 103: 118-9. 3. Gray TA, Buckley BM, Sealey MM, Smith SC, Tomlin P, McMaster P. Plasma ionized calcium monitoring during liver transplantation. Transplantation 1986; 41: 335-9. 4. Drop JL. Ionized calcium, the heart and hemodynamic function. Anesth Analg 1985; 64: 432-51. 5. Acosta F, Diaz J, Sansano T, et al. Prophylactic treatment of metabolic alterations at revascularization in liver transplantation. Transplant Proc 1994; 26: 4259-60. 6. Martin TJ, Kang Y, Robertson KM, Virji MA, Marquez JM. Ionization and hemodynamic effects of calcium chloride and calcium gluconate in the absence of hepatic function. Anesthesiology 1990; 73: 62-5. 7. Kost GJ, Jammal MA, Ward RE, Safwat AM. Monitoring of ionized calcium during human hepatic function. Am J Clin Pathol 1986; 74: 135-50. 8. Carton E, Rettke S, Plevak D, Geiger H, Kranner P, Coursin D. Perioperative care of the liver transplant patient: Part 1. Anesth Analg 1994; 78: 120-33. 9. Starzl T, Iwatsuki S, Van Thiel DH. Evolution of liver transplantation. Hepatology 1982; 2: 614-36. 10. Carton E, Plevak D, Kranner P, Rettke R, Geiger H, Coursin D. Perioperative care of the liver transplant patient: Part 2. Anesth Analg 1994; 78: 382-99. 11. Delinger JK, Nahrwold ML, Gibbs PS, Lecky JH. Hypocalcaemia during rapid blood transfusion in anaesthetized man. Br J Anaesth 1976; 48: 995-1000. 12. Porte R, Knot E, Bontempo F. Hemostasis in liver transplantation. Gastroenterology 1989; 97: 488-501. 13. Kahn RC, Jascott D, Carlon GC, Schweizer O, Howland WS, Goldiner PL. Massive blood replacement: correlation of ionized calcium, citrate, and hydrogen ion concentration. Anesth Analg 1979; 58: 274-8. 14. Diaz J, Acosta F, Martinez P, Parrilla P. Blood ammonia levels as early indicator of allograft viability in human orthotopic liver transplantation. Am J Gastroenterol 1994, 89: 2283-4. 15. Cote CJ, Drop l_J, Hoaglin DC, Daniels AL, Youngs ET. Ionized hypocalcemia after fresh frozen plasma administration to thermally injured children. Anesth Analg 1988; 67: 152-60. 16. Suleiman MY, Zaloga GP. How and when to manage ionized hypocalcaemia in critically ill patients. J Crit Illness 1993; 8: 372-90. 17. Kang Y, Aggarwal S, Pasculle R. Clinical evaluation of autotransfusion during liver transplantation. Anesth Analg 1991; 72: 94-9.
317