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A HAEMORHEOLOGICAL STUDY OF LIGNOCAINE
Br. J. Anaenh. (1986), 58, 306-309
A HAEMORHEOLOGICAL STUDY OF LIGNOCAINE J. E. ORR, G. D. O. LOWE, W. S. NIMMO, R. WATSON AND C. D. FORBES
The ex vivo haemorheological findings in eight J. E. ORR.t M.B., CH.B., F.F.A.R.OS.; Department of Anaesthetics, Western Infirmary, Glasgow G i l 6NT. G. D . O. LOWE, M . D . , M . R . C . P . ; C . D . FORBES, M.D., F.R.C.P.; University
Department of Medicine, Glasgow Royal Infirmary, Glasgow G31 2ER. W. S. NIMMO,* M.D., F.R.CP., F.F_A.R.C.S.; Univer-
sity Department of Anaesthetics, Western Infirmary, Glasgow G i l 6 N T . R. WATSON, B.SC., PH.D. ; University Department of
Anaesthetics, Glasgow Royal Infirmary, Glasgow G31 2ER. Present addresses: tDepartment of Anaesthetics, Royal Alexandra Infirmary, Paisley, Renfrewshire. •Department of Anaesthetics, The University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX.
SUMMARY Eight volunteers received lignocaine 75 mg i.m. Peak plasma lignocaine concentrations {mean 0.80 ng ml-1; range 0.31-1.86 fig ml-1) were attained at 30 min. Haematocrit and red cell deformability remained unchanged. Lignocaine caused small but significant decreases in plasma viscosity and whole blood viscosity at both high and low shear rates (94 and 0.94 s" 1 ). The small reductions in plasma viscosity and high shear blood viscosity observed ex vivo may be the result of alterations in plasma proteins. The reductions in low shear blood viscosity are considered to result from decreased red cell aggregation.
volunteers who received lignocaine i.m. are reported. SUBJECTS AND METHODS
Eight healthy unpaid volunteers (ASA grade I; five male; mean age 28.5 yr) gave informed consent for the study. Heart rate, arterial pressure, respiratory rate and a standard lead II ECG were monitored throughout. Venous blood samples (30 ml) were withdrawn with minimal venostasis from a vein in the antecubital fossa. After the withdrawal of a control blood sample, lignocaine 75 mg (1.5 ml of 5% solution) was administered by i.m. injection to the lateral aspect of the thigh. Three further blood samples were withdrawn at 30, 60 and 90 min. Haemorheological studies and lignocaine analysis were performed on all samples. Blood for the haemorheological studies was anticoagulated with solid dipotassium EDTA 1.5 mg ml"1 in plastic tubes (Steyne Laboratories) and analysed within 90 min of venepuncture. Haematocrit was measured in a Hawksley microhaematocrit centrifuge (13 000 g for 5 min). Plasma viscosity was measured at 25 °C in a Coulter-
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Significant differences in whole blood viscosity and red cell deformability between two matched groups of patients undergoing subarachnoid or general anaesthesia have been reported (Drummond et al., 1980): subarachnoid anaesthesia resulted in an increase in red cell deformability. Lignocaine itself has been shown to alter erythrocyte morphology in vitro, although in therapeutic concentrations it had no effect on the rheological behaviour of erythrocyte suspensions in vitro (Chen, Lee and Chien, 1979). In vitro haemorheological studies may be misleading as drugs may have in vitro effects on red cell deformability which are not substantiated by in vivo studies, and as dilutional effects may be introduced (Orr et al., 1982). Ex vivo studies are, therefore, more appropriate when investigating haemorheology, particularly when a drug has active metabolites, or when the pharmacodynamic effects of a drug may contribute to its haemorheological effects (Kaltreider, Meneely and Allen, 1942; Aronson, Magora and London, 1970). After the subarachnoid administration of lignocaine 75 mg and 100 mg, venous plasma lignocaine concentrations of 0.3 ng ml"1 have been reported (Giasi, D'Agostino and Covino, 1979; Axelsson and Hidman, 1981). Similar plasma lignocaine concentrations have been observed after i.m. injection of the drug with peak concentrations between 30 and 60 min (Jebson, 1971).
HAEMORHEOLOGICAL STUDY OF LIGNOCAINE
chromatograph, fitted with a flame ionization detector was used. Samples and standards were spiked with bupivacaine before extraction and this was used as an internal standard for the assay procedure. Separation was effected on a 2 m x 2 mm i.d. glass column packed with 3 % SP 2250 on 100/120 mesh Supelcoport. Carrier gas was oxygen-free nitrogen at a flow rate of 20 ml min"1 and the column oven was maintained at 250 °C with the injection port and detector set at 275 °C and 300 °C, respectively. The results were analysed using the paired t test and linear regression analysis of the percentage change in plasma viscosity, high shear blood viscosity and low shear blood viscosity relative to lignocaine concentration. A probability of < 0.05 was taken as significant. RESULTS
Maximum venous plasma lignocaine concentrations ranging from 0.31 to 1.86 ug ml"1 (mean 0.80 ug ml"1) were attained 30 min after i.m. injection of lignocaine 75 mg. These concentrations were greater than those expected after subarachnoid anaesthesia with lignocaine. Haematocrit was unchanged after the administration of lignocaine (table I). Small but statistically significant decreases in plasma viscosity were observed at 30 min (P < 0.01) and 60 min (P < 0.05). High shear rate blood viscosity was significantly reduced at 30 min (P < 0.05). Low shear rate blood viscosity showed a mean decrease of 11 % and signficant reductions were attained 30 min (P < 0.01) and 60 min (P < 0.01) after the administration of lignocaine. Linear regression
TABLE I. Means of values ( ± SD) for lignocaine concentration, haematocrit, plasma and whole blood viscosities and red cell deformability in eight volunteers at 0, 30, 60 and 90 min. * P < 0.05, paired t test. ND = Not detected
Time (min)
Plasma lignocaine concn (jig ml"1) Haematocrit (%) Plasma viscosity (mPas) Blood viscosity (mPas) Shear rate 94 s"1 0.94 s-' Red cell deformability index PJPb P,/Pb
ND
30
60
0.80 (±0.50)
0.50 (±0.31)
90
034 (±0.20)
44.00(±3.12) 1.601 (±0.070)
43.75 (±3.41) 1.565 (±0.090)*
43.88 (±3.60) 1.566 (±0.098)*
43.75 (±3.69) 1.576 (±0.095)
5.58 (±0.37) 18.75 ( + 2.89)
5.36 (±0.28)* 16.68 (±2.81)*
5.43 (±0.36) 16.79 (±3.02)*
5.49 (±0.34) 1735 (±3.36)
1.07 (±0.11) 2.51 (±0.46)
1.05 (±0.2) 2.34 (±0.69)
1.16(±0.21) 3.07 (±0.95)
1.12(±0.17) 3.20(±l.ll)
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Harkness capillary viscometer. Whole blood viscosity was measured at high (94 s"1) and low (0.94 s"1) shear rates in a Contraves Low Shear 30 rotational viscometer at 37 °C and corrected to a standard haematocrit of 45% using regression equations derived from 200 subjects. For the measurement of red cell deformability, EDTAblood was depleted of contaminating leucocytes and proteins by prefiltration through treated cotton wool (Kenny, Meakin and Stuart, 1983). The absence of leucocytes was confirmed by examination of the nitrate in an improved Neubauer counting chamber. Red cells were resuspended at 5% haematocrit in phosphatebuffered saline (pH 7.4, 290 mosmol kg"1) and filtered for 6 min through special quality Nuclepore filters (pore size 5 urn) (Leiper et al., 1984). Red cell deformability was assessed by the ratio of the pressure generated by the cell suspension to the pressure generated by buffer alone (Pb). Two indices were calculated, PJPb and Pf/Pb where Pi is the initial pressure generated by cells reaching the filter face, and Pf is thefinalpressure generated by cells after 6 min filtration. Pt is greater than P4 as a result of progressive pore plugging by rigid red cells. Samples for the measurement of lignocaine concentration were anticoagulated in lithiumheparin tubes and centrifuged to separate the plasma which was stored at — 20 °C. Plasma samples were analysed for lignocaine by an adaptation of the method used by Zylber-Katz, Granit and Levy (1978) and described previously by this laboratory for the determination of bupivacaine (Dutton et al., 1984; Neill and Watson, -1984). A Pye Unicam 204 series gas
307
BRITISH JOURNAL OF ANAESTHESIA
308
DISCUSSION
The small decrease in plasma viscosity reported here is difficult to explain. The central sedative action of lignocaine could lead to vasodilatation and, hence, decreases in haematocrit and plasma viscosity (Aronson, Magora and London, 1970; Orr et al., 1982). However, no significant reduction in haematocrit was observed, so this explanation is unlikely. As lignocaine is 64% bound to plasma protein at therapeutic concentrations (Tucker, 1983) a change in the plasma proteins, which are the main determinants of plasma viscosity (Harkness, 1971), may be a possible explanation. The observed reduction in high shear rate blood viscosity may be a reflection of the decrease in plasma viscosity. The 11 % decrease in low shear rate blood viscosity requires further explanation, as haematocrit, plasma viscosity and red cell deformability underwent little or no change. Low shear blood viscosity is greatly influenced by red cell aggregation. Lignocaine may decrease red cell aggregation, either by altering aggregating plasma proteins or the red cell membrane, and this may explain the decrease in blood viscosity at low shear rate. Amide-type local anaesthetics have been shown to reduce platelet adhesiveness (O'Brien, 1961) and, also, to decrease leucocyte adherence and migration (Giddon and Lindhej 1972; Stewart, Ritchie and Lynch, 1974). These effects have been attributed to a membrane-stabilizing effect of the amide-type local anaesthetics, and a similar effect on red cells might result in decreased red cell aggregation. Previous reports suggested that local anaesthetics may improve red cell deformability (Drummond et al., 1980; Thorburn, personal communication). However, the method used to determine red cell
deformability in these earlier studies did not remove the white cells before analysis. In the present study, removal of the white cells by pre-filtration ensured that only the red cells were included in the determinations of red cell deformability. No change in red cell deformability was observed. Previous reports of altered red cell deformability after local anaesthetic administration could, therefore, have been the result of effects on white cells. In conclusion, this communication does not support the view that local anaesthetics improve red cell deformability. The statistically significant decreases in plasma viscosity and whole blood viscosity which followed the administration of lignocaine may result from alterations in plasma proteins and from a reduction in red cell aggregation. ACKNOWLEDGEMENTS The authors wish to thank Mr P. Bums and Mr J. Anderson for invaluable technical assistance.
REFERENCES Aronson, H. B., Magora, F., and London, M. (1970). The influence of droperidol on blood viscosity in man. Br. J. Anaeith., 42, 1089. Axelsson, K., and Hidman, B. (1981). Blood concentrations of lidocaine after spinal anaesthesia using lidocaine and lidocaine and adrenaline. Acta Anaesthesiol. Scand., IS, 240. Chen, R. Y. Z., Lee, M. M. L., and Chien, S. (1979). Local anesthetics and the rheologic behaviour of erythrocyte suspensions. Antsthtsiology, 51, 245. Drummond, A. R., Drummond, M. M., MacKenzie, P. J., Lowe, G. D. O., Smith, G., Forbes, C. D., and Wishart, H. Y. (1980). The effects of general and spinal anaesthesia on red cell deformabUity and blood viscosity in patients undergoing surgery for fractured neck of femur; in Haemorheology and Diseases (eds J. F. StoltzandP. Drouin), p. 445. Paris: Doin Editeurs. Dutton, D. A., Moir, D. D., Howie, H. B., Thorbum, J., and Watson, R. (1984). Choice of local anaesthetic drug for extradural Caesarean section. Comparison of 0.5% and 0.75 % bupivacaine and 1.5 % etidocaine. Br.J. Anaesth., S6, 1361. Giasi, R. M., D'Agosrino, E., and Covino, B. G. (1979). Absorption of lignocaine following subarachnoid and epidural administration. Anesth. Analg., 58, 360. Giddon, D. B., and Lindhe, J. (1972). In vivo quantitation of local anesthetic suppression of leucocyte adherence. Am. J. Pathol., 68, 327. Harkness, J. (1971). The viscosity of human blood plasma: its measurement in health and disease. Biorheology, 8, 171. Jebson, P. (1971). Intramuscular lignocaine 2% and 10%. Br. Med. J., 3, 566.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
analysis of the percentage change in viscosities relative to lignocaine concentration failed to show any significant association — for plasma viscosity, P = 0.067; for high shear blood viscosity, P = 0.053; for low shear viscosity, P = 0.20. Red cell deformability was not significantly changed after the administration of lignocaine. There was an initial trend to improved filtrability and then a trend to decreased filtrability. No morphological changes in the red cells were observed on microscopy following the administration of the lignocaine.
HAEMORHEOLOGICAL STUDY OF LIGNOCAINE
O'Brien, J. R. (1961). The adhesiveness of native platelets and its prevention. J. Clin. Pathol., 14, 140. Orr, J. E., Davidson, R. J. L., Russell, I. F., and Robertson, G. S. (1982). A haemorheological study of Althesin. Br. J. Anaesth., 54, 1003. Stewart, G. J., Ritchie, W. G. M., and Lynch, P. R. (1974). Venous endothelial damage produced by massive sticking and emigration of leucocytes. Am. J. Pathol., 74, 507. Tucker, G. T. (1983). Chemistry and pharmacology of local anaesthetic drugs; in Practical Regional Anaesthesia (eds J. J. Henderson, and W. S. Nimmo), p.3. Oxford: Blackwcll Scientific Publications. Zylber-Katz, E., Granit, L., and Levy, M. (1978). Gas liquid chromatographic determination of bupivacaine and lidocaine in plasma. Clin. Chem., 24, 1573.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Kaltreider,N. L.,Meneely,G. R., and Allen, J. R.(1942).The effect of epinephrine on the volume of the blood. J. Clin. Invest., 21, 339. Kenny, M. W., Meakin, M., and Stuart, J. (1983). Methods for removal of leucocytes and platelets prior to study of erythrocyte deformability. Clinical Haemorheology, 3, 191. Leiper, J. M., Lowe, G. D. O., Anderson, J. Burns, P., Cohen, H. N., Manderson, W. G., Forbes, C. D., Barbenel, J. C , and McCuish, A. C. (1984). Effects of diabetic control and biosynthetic human insulin on blood rheology in established diabetes. Diabetes Research, 1, 27. Neill, R. S., and Wauon, R. (1984). Plasma bupivacaine concentrations during combined regional and general anaesthesia for resection and reconstruction of head and neck carcinomata. Br. J. Anaesth., 56, 485.
309
A HAEMORHEOLOGICAL STUDY OF LIGNOCAINE J. E. ORR, G. D. O. LOWE, W. S. NIMMO, R. WATSON AND C. D. FORBES
The ex vivo haemorheological findings in eight J. E. ORR.t M.B., CH.B., F.F.A.R.OS.; Department of Anaesthetics, Western Infirmary, Glasgow G i l 6NT. G. D . O. LOWE, M . D . , M . R . C . P . ; C . D . FORBES, M.D., F.R.C.P.; University
Department of Medicine, Glasgow Royal Infirmary, Glasgow G31 2ER. W. S. NIMMO,* M.D., F.R.CP., F.F_A.R.C.S.; Univer-
sity Department of Anaesthetics, Western Infirmary, Glasgow G i l 6 N T . R. WATSON, B.SC., PH.D. ; University Department of
Anaesthetics, Glasgow Royal Infirmary, Glasgow G31 2ER. Present addresses: tDepartment of Anaesthetics, Royal Alexandra Infirmary, Paisley, Renfrewshire. •Department of Anaesthetics, The University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX.
SUMMARY Eight volunteers received lignocaine 75 mg i.m. Peak plasma lignocaine concentrations {mean 0.80 ng ml-1; range 0.31-1.86 fig ml-1) were attained at 30 min. Haematocrit and red cell deformability remained unchanged. Lignocaine caused small but significant decreases in plasma viscosity and whole blood viscosity at both high and low shear rates (94 and 0.94 s" 1 ). The small reductions in plasma viscosity and high shear blood viscosity observed ex vivo may be the result of alterations in plasma proteins. The reductions in low shear blood viscosity are considered to result from decreased red cell aggregation.
volunteers who received lignocaine i.m. are reported. SUBJECTS AND METHODS
Eight healthy unpaid volunteers (ASA grade I; five male; mean age 28.5 yr) gave informed consent for the study. Heart rate, arterial pressure, respiratory rate and a standard lead II ECG were monitored throughout. Venous blood samples (30 ml) were withdrawn with minimal venostasis from a vein in the antecubital fossa. After the withdrawal of a control blood sample, lignocaine 75 mg (1.5 ml of 5% solution) was administered by i.m. injection to the lateral aspect of the thigh. Three further blood samples were withdrawn at 30, 60 and 90 min. Haemorheological studies and lignocaine analysis were performed on all samples. Blood for the haemorheological studies was anticoagulated with solid dipotassium EDTA 1.5 mg ml"1 in plastic tubes (Steyne Laboratories) and analysed within 90 min of venepuncture. Haematocrit was measured in a Hawksley microhaematocrit centrifuge (13 000 g for 5 min). Plasma viscosity was measured at 25 °C in a Coulter-
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Significant differences in whole blood viscosity and red cell deformability between two matched groups of patients undergoing subarachnoid or general anaesthesia have been reported (Drummond et al., 1980): subarachnoid anaesthesia resulted in an increase in red cell deformability. Lignocaine itself has been shown to alter erythrocyte morphology in vitro, although in therapeutic concentrations it had no effect on the rheological behaviour of erythrocyte suspensions in vitro (Chen, Lee and Chien, 1979). In vitro haemorheological studies may be misleading as drugs may have in vitro effects on red cell deformability which are not substantiated by in vivo studies, and as dilutional effects may be introduced (Orr et al., 1982). Ex vivo studies are, therefore, more appropriate when investigating haemorheology, particularly when a drug has active metabolites, or when the pharmacodynamic effects of a drug may contribute to its haemorheological effects (Kaltreider, Meneely and Allen, 1942; Aronson, Magora and London, 1970). After the subarachnoid administration of lignocaine 75 mg and 100 mg, venous plasma lignocaine concentrations of 0.3 ng ml"1 have been reported (Giasi, D'Agostino and Covino, 1979; Axelsson and Hidman, 1981). Similar plasma lignocaine concentrations have been observed after i.m. injection of the drug with peak concentrations between 30 and 60 min (Jebson, 1971).
HAEMORHEOLOGICAL STUDY OF LIGNOCAINE
chromatograph, fitted with a flame ionization detector was used. Samples and standards were spiked with bupivacaine before extraction and this was used as an internal standard for the assay procedure. Separation was effected on a 2 m x 2 mm i.d. glass column packed with 3 % SP 2250 on 100/120 mesh Supelcoport. Carrier gas was oxygen-free nitrogen at a flow rate of 20 ml min"1 and the column oven was maintained at 250 °C with the injection port and detector set at 275 °C and 300 °C, respectively. The results were analysed using the paired t test and linear regression analysis of the percentage change in plasma viscosity, high shear blood viscosity and low shear blood viscosity relative to lignocaine concentration. A probability of < 0.05 was taken as significant. RESULTS
Maximum venous plasma lignocaine concentrations ranging from 0.31 to 1.86 ug ml"1 (mean 0.80 ug ml"1) were attained 30 min after i.m. injection of lignocaine 75 mg. These concentrations were greater than those expected after subarachnoid anaesthesia with lignocaine. Haematocrit was unchanged after the administration of lignocaine (table I). Small but statistically significant decreases in plasma viscosity were observed at 30 min (P < 0.01) and 60 min (P < 0.05). High shear rate blood viscosity was significantly reduced at 30 min (P < 0.05). Low shear rate blood viscosity showed a mean decrease of 11 % and signficant reductions were attained 30 min (P < 0.01) and 60 min (P < 0.01) after the administration of lignocaine. Linear regression
TABLE I. Means of values ( ± SD) for lignocaine concentration, haematocrit, plasma and whole blood viscosities and red cell deformability in eight volunteers at 0, 30, 60 and 90 min. * P < 0.05, paired t test. ND = Not detected
Time (min)
Plasma lignocaine concn (jig ml"1) Haematocrit (%) Plasma viscosity (mPas) Blood viscosity (mPas) Shear rate 94 s"1 0.94 s-' Red cell deformability index PJPb P,/Pb
ND
30
60
0.80 (±0.50)
0.50 (±0.31)
90
034 (±0.20)
44.00(±3.12) 1.601 (±0.070)
43.75 (±3.41) 1.565 (±0.090)*
43.88 (±3.60) 1.566 (±0.098)*
43.75 (±3.69) 1.576 (±0.095)
5.58 (±0.37) 18.75 ( + 2.89)
5.36 (±0.28)* 16.68 (±2.81)*
5.43 (±0.36) 16.79 (±3.02)*
5.49 (±0.34) 1735 (±3.36)
1.07 (±0.11) 2.51 (±0.46)
1.05 (±0.2) 2.34 (±0.69)
1.16(±0.21) 3.07 (±0.95)
1.12(±0.17) 3.20(±l.ll)
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Harkness capillary viscometer. Whole blood viscosity was measured at high (94 s"1) and low (0.94 s"1) shear rates in a Contraves Low Shear 30 rotational viscometer at 37 °C and corrected to a standard haematocrit of 45% using regression equations derived from 200 subjects. For the measurement of red cell deformability, EDTAblood was depleted of contaminating leucocytes and proteins by prefiltration through treated cotton wool (Kenny, Meakin and Stuart, 1983). The absence of leucocytes was confirmed by examination of the nitrate in an improved Neubauer counting chamber. Red cells were resuspended at 5% haematocrit in phosphatebuffered saline (pH 7.4, 290 mosmol kg"1) and filtered for 6 min through special quality Nuclepore filters (pore size 5 urn) (Leiper et al., 1984). Red cell deformability was assessed by the ratio of the pressure generated by the cell suspension to the pressure generated by buffer alone (Pb). Two indices were calculated, PJPb and Pf/Pb where Pi is the initial pressure generated by cells reaching the filter face, and Pf is thefinalpressure generated by cells after 6 min filtration. Pt is greater than P4 as a result of progressive pore plugging by rigid red cells. Samples for the measurement of lignocaine concentration were anticoagulated in lithiumheparin tubes and centrifuged to separate the plasma which was stored at — 20 °C. Plasma samples were analysed for lignocaine by an adaptation of the method used by Zylber-Katz, Granit and Levy (1978) and described previously by this laboratory for the determination of bupivacaine (Dutton et al., 1984; Neill and Watson, -1984). A Pye Unicam 204 series gas
307
BRITISH JOURNAL OF ANAESTHESIA
308
DISCUSSION
The small decrease in plasma viscosity reported here is difficult to explain. The central sedative action of lignocaine could lead to vasodilatation and, hence, decreases in haematocrit and plasma viscosity (Aronson, Magora and London, 1970; Orr et al., 1982). However, no significant reduction in haematocrit was observed, so this explanation is unlikely. As lignocaine is 64% bound to plasma protein at therapeutic concentrations (Tucker, 1983) a change in the plasma proteins, which are the main determinants of plasma viscosity (Harkness, 1971), may be a possible explanation. The observed reduction in high shear rate blood viscosity may be a reflection of the decrease in plasma viscosity. The 11 % decrease in low shear rate blood viscosity requires further explanation, as haematocrit, plasma viscosity and red cell deformability underwent little or no change. Low shear blood viscosity is greatly influenced by red cell aggregation. Lignocaine may decrease red cell aggregation, either by altering aggregating plasma proteins or the red cell membrane, and this may explain the decrease in blood viscosity at low shear rate. Amide-type local anaesthetics have been shown to reduce platelet adhesiveness (O'Brien, 1961) and, also, to decrease leucocyte adherence and migration (Giddon and Lindhej 1972; Stewart, Ritchie and Lynch, 1974). These effects have been attributed to a membrane-stabilizing effect of the amide-type local anaesthetics, and a similar effect on red cells might result in decreased red cell aggregation. Previous reports suggested that local anaesthetics may improve red cell deformability (Drummond et al., 1980; Thorburn, personal communication). However, the method used to determine red cell
deformability in these earlier studies did not remove the white cells before analysis. In the present study, removal of the white cells by pre-filtration ensured that only the red cells were included in the determinations of red cell deformability. No change in red cell deformability was observed. Previous reports of altered red cell deformability after local anaesthetic administration could, therefore, have been the result of effects on white cells. In conclusion, this communication does not support the view that local anaesthetics improve red cell deformability. The statistically significant decreases in plasma viscosity and whole blood viscosity which followed the administration of lignocaine may result from alterations in plasma proteins and from a reduction in red cell aggregation. ACKNOWLEDGEMENTS The authors wish to thank Mr P. Bums and Mr J. Anderson for invaluable technical assistance.
REFERENCES Aronson, H. B., Magora, F., and London, M. (1970). The influence of droperidol on blood viscosity in man. Br. J. Anaeith., 42, 1089. Axelsson, K., and Hidman, B. (1981). Blood concentrations of lidocaine after spinal anaesthesia using lidocaine and lidocaine and adrenaline. Acta Anaesthesiol. Scand., IS, 240. Chen, R. Y. Z., Lee, M. M. L., and Chien, S. (1979). Local anesthetics and the rheologic behaviour of erythrocyte suspensions. Antsthtsiology, 51, 245. Drummond, A. R., Drummond, M. M., MacKenzie, P. J., Lowe, G. D. O., Smith, G., Forbes, C. D., and Wishart, H. Y. (1980). The effects of general and spinal anaesthesia on red cell deformabUity and blood viscosity in patients undergoing surgery for fractured neck of femur; in Haemorheology and Diseases (eds J. F. StoltzandP. Drouin), p. 445. Paris: Doin Editeurs. Dutton, D. A., Moir, D. D., Howie, H. B., Thorbum, J., and Watson, R. (1984). Choice of local anaesthetic drug for extradural Caesarean section. Comparison of 0.5% and 0.75 % bupivacaine and 1.5 % etidocaine. Br.J. Anaesth., S6, 1361. Giasi, R. M., D'Agosrino, E., and Covino, B. G. (1979). Absorption of lignocaine following subarachnoid and epidural administration. Anesth. Analg., 58, 360. Giddon, D. B., and Lindhe, J. (1972). In vivo quantitation of local anesthetic suppression of leucocyte adherence. Am. J. Pathol., 68, 327. Harkness, J. (1971). The viscosity of human blood plasma: its measurement in health and disease. Biorheology, 8, 171. Jebson, P. (1971). Intramuscular lignocaine 2% and 10%. Br. Med. J., 3, 566.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
analysis of the percentage change in viscosities relative to lignocaine concentration failed to show any significant association — for plasma viscosity, P = 0.067; for high shear blood viscosity, P = 0.053; for low shear viscosity, P = 0.20. Red cell deformability was not significantly changed after the administration of lignocaine. There was an initial trend to improved filtrability and then a trend to decreased filtrability. No morphological changes in the red cells were observed on microscopy following the administration of the lignocaine.
HAEMORHEOLOGICAL STUDY OF LIGNOCAINE
O'Brien, J. R. (1961). The adhesiveness of native platelets and its prevention. J. Clin. Pathol., 14, 140. Orr, J. E., Davidson, R. J. L., Russell, I. F., and Robertson, G. S. (1982). A haemorheological study of Althesin. Br. J. Anaesth., 54, 1003. Stewart, G. J., Ritchie, W. G. M., and Lynch, P. R. (1974). Venous endothelial damage produced by massive sticking and emigration of leucocytes. Am. J. Pathol., 74, 507. Tucker, G. T. (1983). Chemistry and pharmacology of local anaesthetic drugs; in Practical Regional Anaesthesia (eds J. J. Henderson, and W. S. Nimmo), p.3. Oxford: Blackwcll Scientific Publications. Zylber-Katz, E., Granit, L., and Levy, M. (1978). Gas liquid chromatographic determination of bupivacaine and lidocaine in plasma. Clin. Chem., 24, 1573.
Downloaded from http://bja.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on May 31, 2015
Kaltreider,N. L.,Meneely,G. R., and Allen, J. R.(1942).The effect of epinephrine on the volume of the blood. J. Clin. Invest., 21, 339. Kenny, M. W., Meakin, M., and Stuart, J. (1983). Methods for removal of leucocytes and platelets prior to study of erythrocyte deformability. Clinical Haemorheology, 3, 191. Leiper, J. M., Lowe, G. D. O., Anderson, J. Burns, P., Cohen, H. N., Manderson, W. G., Forbes, C. D., Barbenel, J. C , and McCuish, A. C. (1984). Effects of diabetic control and biosynthetic human insulin on blood rheology in established diabetes. Diabetes Research, 1, 27. Neill, R. S., and Wauon, R. (1984). Plasma bupivacaine concentrations during combined regional and general anaesthesia for resection and reconstruction of head and neck carcinomata. Br. J. Anaesth., 56, 485.
309