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HALF-UFE OF PLASMA CHOLINESTERASE
Br. J. Anaetth. (1984), 56,903
HALF-UFE OF PLASMA CHOLINESTERASE G. M. HALL, G. J. WOOD AND J. L. PATERSON SUMMARY
The activity of plasma cholinestcrase (acylcholine acylhydrolase EC 3.1.1.8) is of interest to the anaesthetist as it determines the duration of action of suxamethonium. Although many of the general properties of the enzyme have been elucidated (Whittaker, 1980), information on its half-life is limited. In the studies reported to date the half-life has been determined by measuring the decrease in activity after the infusion of purified enzyme or plasma to anenzymic patients (Jenkins, Balinsky and Patient, 1967; Giinther et al., 1971; Garry, Prince and Notari, 1974; Ploier, 1975; Stovner and Stadskleiv, 1976; Schuh, 1977). These investigations have demonstrated considerable variability in half-lives — from 45 h (Schuh, 1977) to 12 days (Guntheretal.,1971). Plasma exchange is used to remove antibodies as part of the treatment of autoimmune diseases. A single plasma exchange removes about 60% of the circulating cholinesterase activity (Wood and Hall, 1978). In the present study, we report the rate of return of cholinesterase activity following repeated plasma exchange in two patients, as an estimate of the half-life of the enzyme. PATIENTS AND METHODS Two male leukaemic patients underwent repeated plasma exchanges as part of a treatment regimen before total body irradiation and bone marrow transplantation. Venous blood samples were collected at 09.00 h on the 2 days before treatment and daily for 8—9 days after the plasma exchanges, placed in heparinized tubes, centrifuged and the plasma stored at -20°C until analysis. During this G. M. HALL, M.B., B.S.,PH.D., M.I.BIOL., F.F.A.R.CS.;G. J. WOOD, B.SC, M.B., B.S., F.F.A.R.CS.; J. L. PATERSON, B.SC; Department
of Anaesthetics, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS. Correspondence to G. M. H.
time, no cytotoxic drugs or immunosuppressive agents were given, and liver function tests were within their physiological ranges. Plasma cholinesterase activity (u. litre"1) was estimated in duplicate at 25°C using the rate of hydrolysis of butyrylthiocholine to thiocholine and the subsequent reaction between thiocholine and 5:5' dithiobis-(2-nitrobenzoic acid), which was measured colorimetrically at 405 run (Knedel and Bottger, 1967). Values obtained after plasma exchange were used to estimate the half-life of cholinesterase by means of a semi-logarithmic plot of activity v. time. The regression line was determined by the least squares method, but the activity on the day immediately after plasma exchange was not included because of the possibility of redistribution from enzyme-rich tissues. RESULTS
The repeated plasma exchanges decreased the cholinesterase activity to 25-30% of the values obtained before treatment, but there was a rapid rate of resynthesis as shown by half-life values of 5.0 and 5.4 days in the two patients (table I). DISCUSSION
This is the first study in which the endogenous rate of reappearance of the enzyme has been used to assess its half-life. Our results agree most closely with the estimate of 3.4 days determined by the rate of disappearance of cholinesterase after the transfusion of 2 units of blood into an anenzymic patient (Garry, Prince and Notari, 1974). The close agreement in half-life values between the two patients is in marked contrast to the wide variability reported in previous studies. It is possible, however, that the short half-life found in the present study represents the maximal rate of resynthesis after severe depletion and that in normal individuals the half-life is longer. © The Macmilkn Press Ltd 1984
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
The half-life of plasma choJinesterase (acylcholine acylhydrolase, EC3.1.1.8) was determined by measurement of the rate of reappearance of enzyme activity after marked depletion associated with repeated plasma nrrhangn in two patients. Half-life values of S.O and 5.4 days were found.
BRITISH JOURNAL OF ANAESTHESIA
904
TABLE I. Rates of rtsynthais of plasma cholintsurase activity afur plasma axhangt Cholinesterase activity (u. litre"1)
Patient 1 Patient 2
Before plasma exchanges
After plasma
5257, 5063 2774, 2900
1675 692
ACKNOWLEDGEMENT
Miss Tracey Harrison provided skilled secretarial assistance.
9 8
345 200
5.0 5.4
DEMI-VIE DE LA CHOLINESTERASE PLASMATIQUE RESUME
La demi-vie de la cholinesterase plasmatique (acylcholine acylhydrolase EC 3.1.1.8) a ete determinee par la mesure de la vitesse de reapparition de l'activite enzymatique apres une depletion intense provoquee par des plasmaphereses repetees chez deux patients. Les valeurs de demi-vies obtenues tont de 5 et 5,4 jours.
REFERENCES
Garry, P. J., Prince, L. C , and Notari, R. E. (1974). Half-life of human serum cholinesterase following blood transfusion. Rts. Oman. Chan. Pathol. Pharmacol., 8, 371. Gunther, R., Ddnhardt, A., Altland, K., Jensen, M., andGoedde, J. W. (1971). Alkylphosphatintoxikation. Kasuistik einer schweren Vergiftung und Anwcndung eines gerinigten menschh'chen CholinesteraseprapSrats. Med. Klin., 66,785. Jenkins, T., Balinsky, D., and Patient, D. W. (1967). Cholinesterase in plasma: first reported absence in the Bantu, half-life determination. Science, 156,1748. Knedel, M., and Bottger, R.(1967). EinekinetscheMethodezur Besrimmiing der Aktivitat der Pseudocholinesterase. Klin. Wockenschr., 45, 325. Ploier, R. (1975). Eine Sippe mit vollstandiger Serumcholinesterasedefizienz. Zfiachr. KinderhuUainde, 119, 31. Schuh, F. T. (1977). Serum cholinesterase. Effect on the action of suxamethonium following administration to a patient with cholinesterase deficiency. Br. J. Anatsth., 49,269. Stovner, J., and Stadskleiv, K. (1976). Suxamethonium apnoea terminated with commercial serum cholinesterase. Acta Anatsthesioi. Scand., 20,211. Whittaker, M. (1980). Plasma cholinesterase variants and the anaesthetist. Anaesthesia, 35,174. Wood, G. J., and Hall, G. M. (1978). Plaunaphoresis and plasma cholinesterase. Br. J. Anaesth., 50,945.
HALBWERTSZEIT DER PLASMACHOLJNESTERASE ZUSAMMENFASSUNG
Die Halbwertszeit der Plasmacholinesterase (AcylcholinAcylhydrolase 3.1.1.8) wurde durch Messung der Erholung dcr Enzymaktivitat nach deutlicher Aktivitatsreduzierung durch wiederholten Plasmaaustausch bei zwd Patientec bestimmt. Es fanden rich Halbwertszeiten von 5,0 und 5,4 Tagen.
MEDIA-VIDA DE LA COLINESTERASA DEL PLASMA SUMARIO
Se determino la media-vida de la colinesterasa del plasma (acilcolina acilhidrolasa, EC 3.1.1.8) mediante la medicion de ritmo de reaparicion de la actividad enzimitica despues de una marcada depleci6n asociada con intercambios repetidos de plasma en dos pacientes. Los valores de mediavida se establecieron en 5,0y5,4dias.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
The results have important clinical implications, since they show that cholinesterase activity is rapidly restored when normal liver function is present. Thus, prolongation of the action of suxamethonium is unlikely to be a problem a few days after cessation of plasma exchange.
Rate of Duration increase Half-life inactivity of enzyme of study (u. litre"1 day"1) (days) (days)
HALF-UFE OF PLASMA CHOLINESTERASE G. M. HALL, G. J. WOOD AND J. L. PATERSON SUMMARY
The activity of plasma cholinestcrase (acylcholine acylhydrolase EC 3.1.1.8) is of interest to the anaesthetist as it determines the duration of action of suxamethonium. Although many of the general properties of the enzyme have been elucidated (Whittaker, 1980), information on its half-life is limited. In the studies reported to date the half-life has been determined by measuring the decrease in activity after the infusion of purified enzyme or plasma to anenzymic patients (Jenkins, Balinsky and Patient, 1967; Giinther et al., 1971; Garry, Prince and Notari, 1974; Ploier, 1975; Stovner and Stadskleiv, 1976; Schuh, 1977). These investigations have demonstrated considerable variability in half-lives — from 45 h (Schuh, 1977) to 12 days (Guntheretal.,1971). Plasma exchange is used to remove antibodies as part of the treatment of autoimmune diseases. A single plasma exchange removes about 60% of the circulating cholinesterase activity (Wood and Hall, 1978). In the present study, we report the rate of return of cholinesterase activity following repeated plasma exchange in two patients, as an estimate of the half-life of the enzyme. PATIENTS AND METHODS Two male leukaemic patients underwent repeated plasma exchanges as part of a treatment regimen before total body irradiation and bone marrow transplantation. Venous blood samples were collected at 09.00 h on the 2 days before treatment and daily for 8—9 days after the plasma exchanges, placed in heparinized tubes, centrifuged and the plasma stored at -20°C until analysis. During this G. M. HALL, M.B., B.S.,PH.D., M.I.BIOL., F.F.A.R.CS.;G. J. WOOD, B.SC, M.B., B.S., F.F.A.R.CS.; J. L. PATERSON, B.SC; Department
of Anaesthetics, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS. Correspondence to G. M. H.
time, no cytotoxic drugs or immunosuppressive agents were given, and liver function tests were within their physiological ranges. Plasma cholinesterase activity (u. litre"1) was estimated in duplicate at 25°C using the rate of hydrolysis of butyrylthiocholine to thiocholine and the subsequent reaction between thiocholine and 5:5' dithiobis-(2-nitrobenzoic acid), which was measured colorimetrically at 405 run (Knedel and Bottger, 1967). Values obtained after plasma exchange were used to estimate the half-life of cholinesterase by means of a semi-logarithmic plot of activity v. time. The regression line was determined by the least squares method, but the activity on the day immediately after plasma exchange was not included because of the possibility of redistribution from enzyme-rich tissues. RESULTS
The repeated plasma exchanges decreased the cholinesterase activity to 25-30% of the values obtained before treatment, but there was a rapid rate of resynthesis as shown by half-life values of 5.0 and 5.4 days in the two patients (table I). DISCUSSION
This is the first study in which the endogenous rate of reappearance of the enzyme has been used to assess its half-life. Our results agree most closely with the estimate of 3.4 days determined by the rate of disappearance of cholinesterase after the transfusion of 2 units of blood into an anenzymic patient (Garry, Prince and Notari, 1974). The close agreement in half-life values between the two patients is in marked contrast to the wide variability reported in previous studies. It is possible, however, that the short half-life found in the present study represents the maximal rate of resynthesis after severe depletion and that in normal individuals the half-life is longer. © The Macmilkn Press Ltd 1984
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
The half-life of plasma choJinesterase (acylcholine acylhydrolase, EC3.1.1.8) was determined by measurement of the rate of reappearance of enzyme activity after marked depletion associated with repeated plasma nrrhangn in two patients. Half-life values of S.O and 5.4 days were found.
BRITISH JOURNAL OF ANAESTHESIA
904
TABLE I. Rates of rtsynthais of plasma cholintsurase activity afur plasma axhangt Cholinesterase activity (u. litre"1)
Patient 1 Patient 2
Before plasma exchanges
After plasma
5257, 5063 2774, 2900
1675 692
ACKNOWLEDGEMENT
Miss Tracey Harrison provided skilled secretarial assistance.
9 8
345 200
5.0 5.4
DEMI-VIE DE LA CHOLINESTERASE PLASMATIQUE RESUME
La demi-vie de la cholinesterase plasmatique (acylcholine acylhydrolase EC 3.1.1.8) a ete determinee par la mesure de la vitesse de reapparition de l'activite enzymatique apres une depletion intense provoquee par des plasmaphereses repetees chez deux patients. Les valeurs de demi-vies obtenues tont de 5 et 5,4 jours.
REFERENCES
Garry, P. J., Prince, L. C , and Notari, R. E. (1974). Half-life of human serum cholinesterase following blood transfusion. Rts. Oman. Chan. Pathol. Pharmacol., 8, 371. Gunther, R., Ddnhardt, A., Altland, K., Jensen, M., andGoedde, J. W. (1971). Alkylphosphatintoxikation. Kasuistik einer schweren Vergiftung und Anwcndung eines gerinigten menschh'chen CholinesteraseprapSrats. Med. Klin., 66,785. Jenkins, T., Balinsky, D., and Patient, D. W. (1967). Cholinesterase in plasma: first reported absence in the Bantu, half-life determination. Science, 156,1748. Knedel, M., and Bottger, R.(1967). EinekinetscheMethodezur Besrimmiing der Aktivitat der Pseudocholinesterase. Klin. Wockenschr., 45, 325. Ploier, R. (1975). Eine Sippe mit vollstandiger Serumcholinesterasedefizienz. Zfiachr. KinderhuUainde, 119, 31. Schuh, F. T. (1977). Serum cholinesterase. Effect on the action of suxamethonium following administration to a patient with cholinesterase deficiency. Br. J. Anatsth., 49,269. Stovner, J., and Stadskleiv, K. (1976). Suxamethonium apnoea terminated with commercial serum cholinesterase. Acta Anatsthesioi. Scand., 20,211. Whittaker, M. (1980). Plasma cholinesterase variants and the anaesthetist. Anaesthesia, 35,174. Wood, G. J., and Hall, G. M. (1978). Plaunaphoresis and plasma cholinesterase. Br. J. Anaesth., 50,945.
HALBWERTSZEIT DER PLASMACHOLJNESTERASE ZUSAMMENFASSUNG
Die Halbwertszeit der Plasmacholinesterase (AcylcholinAcylhydrolase 3.1.1.8) wurde durch Messung der Erholung dcr Enzymaktivitat nach deutlicher Aktivitatsreduzierung durch wiederholten Plasmaaustausch bei zwd Patientec bestimmt. Es fanden rich Halbwertszeiten von 5,0 und 5,4 Tagen.
MEDIA-VIDA DE LA COLINESTERASA DEL PLASMA SUMARIO
Se determino la media-vida de la colinesterasa del plasma (acilcolina acilhidrolasa, EC 3.1.1.8) mediante la medicion de ritmo de reaparicion de la actividad enzimitica despues de una marcada depleci6n asociada con intercambios repetidos de plasma en dos pacientes. Los valores de mediavida se establecieron en 5,0y5,4dias.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 26, 2015
The results have important clinical implications, since they show that cholinesterase activity is rapidly restored when normal liver function is present. Thus, prolongation of the action of suxamethonium is unlikely to be a problem a few days after cessation of plasma exchange.
Rate of Duration increase Half-life inactivity of enzyme of study (u. litre"1 day"1) (days) (days)