Problems in Pregnancy and Childhood
The catheter, which is disposable, is activated before use by steaming the tip and then inserted via an umbilical artery into the aorta. The PAO. is displayed on a meter and a continuous record produced on a pen recorder. Frequent calibration checks are performed by intermittent sampling of blood from the catheter. To date, the catheter has been used in 15 sick pre-term babies, the smallest weighing 1.28 kg. Accurate readings have been obtained in 12 of these babies for periods of 21 to 46 hours. In all babies, useful recordings were obtained for up to 96 hours, although accurate calibration was not always possible because of high output current or blockage of the sampling lumen. These problems appear to have been largely overcome with the final catheter design used in the last 5 babies. The catheter has been of great value in studying physiological fluctuations of PAO., in the management of acutely changing situations, and as a research tool. Physiological fluctuations of PAO. may be of the order of 10 to 15 mm. Hg at rest, but are greatly increased by activity such as crying. Moreover, a fall in PAO. of 30 mm. Hg or more may be induced by minor handling procedures such as injections, heel stabs, or napkin changing. These fluctuations cast doubt on the validity of the usual method of intermit-
tent sampling of arterial blood, which could be misleading. The catheter has been especially useful in the management of babies requiring mechanical methods of assisting breathing, enabling the optimal therapeutic regime to be quickly chosen. It has also been a valuable aid in managing recurrent apnoea. Comparison of catheter readings with simultaneous laboratory readings indicates a difference of < 10 mm. Hg in the majority, although some differ by > 15 mm. Hg. An error of < 10 mm. Hg would be very difficult to achieve with any method of analysis, because of the physiological fluctuations of PAO. described above. It is concluded that the catheter has been of great value in the intensive care of sick pre-term babies. Its use should, however, be confined to units where adequate staffing and laboratory facilities exist, so that frequent reference checks can be made by conventional blood gas analysis. REFERENCES
Dodd K. L. (1975). Continuous monitoring of arterial oxygen tension in the newborn. British Journal of Hospital Equipment, May 1975, 35 Harris, T. R., Nugent, M. (1973). Continuous arterial oxygen tension monotiring in the newborn infant. Journal ofPediatrics, 82, 929 Meldrum, S. J., Watson, B. W., Becker, G. A. (1973). A catheter tip transducer for continuous measurement of blood oxygen tension in neonates. Biomedical Engineering, 8, 470
PLASMAPHERESIS IN RHESUS DISEASE J. Graham-Pole Department of Child Health, Royal Hospital for Sick Children, Glasgow
I N spite of routine anti-D gammaglobulin to prevent rhesus isoimmunization by pregnancy, severe rhesus disease continues to occur. Since the absolute level of maternal antibody correlates with severity of fetal 168
erythroblastosis (Fraser et al., 1972), attempts at its removal are indicated in pregnancies where history, antibody levels and amniocentesis findings suggest the fetus will die before intrauterine transfusion (I. U.T.) is feasible.
Problems in Pregnancy aud Childhood
Previous attempts (Clarke et al., 1970; Fraser et al., 1974)have used non-replacement maternal plasmapheresis, allowing no dilution of residual antibody and simultaneously depleting normal plasma proteins and other constituents. We have previously reported (Graham-Pole et al., 1974 a & b) on the value of long-term exchange plasmapheresis with a continuous-flow cell separator (Aminco Celltrifuge, Maryland, V.S.A.), which achieves a greater lowering of antibody from an earlier stage of pregnancy than the non-exchange technique and avoids depletion of normal proteins. The cell separator has been shown to be safe and effective for exchange plasmapheresis (Powles et al., 1971; Graham-Pole et al., 1974a). A dual channel pump allows ml-for-ml exchange of the antibodycontaining plasma by donated plasma, which recombines with the maternal packed cells for return to the patient. Seven patients have now been treated, all but one having lost previous pregnancies from fetal erythroblastosis, and all having in the current pregnancy extremely high rhesus antibody and/or amniotic fluid bilirubin values (up to 55.7 flg./m!. anti-D immunoglobulin, and up to 0.3 optical density units (Liley, 1963) respectively, at 18 weeks gestation). Treatment was usually from 20 weeks gestation and differences from previous series were (i) much greater volumes (up to 180 litres) removed; (ii) invariable steep antibody falls; (iii) earlier stage of gestation from which patients were successfully treated without LV.T. To show clear-cut fetal benefit, amniotic fluid bilirubin levels were monitored. The first 3 patients underwent relatively gentle plasmapheresis (5-10 litres removed weekly) from 20 to 28 weeks followed by LV.T. Antibody falls were considerable (for example from 55.7 to 4/kg./ml.) but L V.T. caused fetal death in all three. The latter 4 patients had more intensive plasmapheresis (I5-18 litres removed weekly) with control not only of maternal antibody but also amniotic fluid bilirubin levels. Three had had previous hydropic stillbirths in spite of LV.T. before 30 weeks, yet all 4 delivered moderately-affected babies at 36+ weeks without recourse to LV.T.
No major hazard of plasmapheresis was encountered. Though mothers were anticoagulated with heparin (approximately 10,000 units per run) and transient falls in platelet counts (to a nadir of 60,000/mm 3 ) were seen after intensive plasmapheresis, two short episodes of haematuria were the only haemorrhagic problems encountered. One patient needed an arteriovenous shunt, which was later removed; otherwise vein-to-vein procedures were used. We conclude that treatment of severe rhesus disease by plasmapheresis may to some extent replace LV.T., which is still a very hazardous procedure. The exchange technique allows much more intensive plasmapheresis and offers even the worst case a chance of fetal salvage. It is costly, and imposes a considerable strain on the patient, so should be undertaken only for the strongest indications. A C K NOW LED GEM E N T S. I wish to thank Professor I. Donald and Dr W. Barr, under whose care the patients were treated, Mrs M. Davie and I. Kershaw for their technical help and Dr M. L. N. Willoughby who directed all the work described. A large part of the cost of the cell-separator was met by Tenovus, Scotland.
REFERENCES
Clarke, C. A., Elson, C. J., Bradley, J., Donohoe, W. T. A., Lehane, D. (1970). Intensive plasmapheresis as a therapeutic measure in rhesusimmunised women. Lancet, I, 793 Fraser, I. D., Bennett, M., Bothamley, J. E. (1974). Ante-natal plasmapheresis in severe rhesus isoimmunisation British Journal of Haematology, 28, 147 Fraser, I. D., Tovey, G. H., Lockyer, W. J., Sobey, D. F. (1972). Antibody protein levels in the maternal serum in rhesus isoimmunization. Journal of Obstetrics and Gynaecology of the British Commonwealth, 79, 1074 Graham-Pole, J., Barr, W., Willoughby, M. L. N. (19740) Continuous flow exchange plasmapheresis in severe rhesus isoimmunization. Lancet, I, 105 Graham-Pole, J., Donald, I., Barr, W" Willoughby, M. L. N. (1974b). Plasmapheresis in rhesus isoimmunization. Lancet, 2, 1459. Liley, A. W. (1963). Errors. in the assessment of hemolytic disease from amniotic fluid. American Journal of Obstetrics and Gynecology, 86, 485 Powles, R., Smith, C., Kohn, J., Hamilton Fairley, G. (1971). Method of removing abnormal protein rapidly from patients with malignant paraproteinaemias. British Medical Journal, 3, 664 169
The catheter, which is disposable, is activated before use by steaming the tip and then inserted via an umbilical artery into the aorta. The PAO. is displayed on a meter and a continuous record produced on a pen recorder. Frequent calibration checks are performed by intermittent sampling of blood from the catheter. To date, the catheter has been used in 15 sick pre-term babies, the smallest weighing 1.28 kg. Accurate readings have been obtained in 12 of these babies for periods of 21 to 46 hours. In all babies, useful recordings were obtained for up to 96 hours, although accurate calibration was not always possible because of high output current or blockage of the sampling lumen. These problems appear to have been largely overcome with the final catheter design used in the last 5 babies. The catheter has been of great value in studying physiological fluctuations of PAO., in the management of acutely changing situations, and as a research tool. Physiological fluctuations of PAO. may be of the order of 10 to 15 mm. Hg at rest, but are greatly increased by activity such as crying. Moreover, a fall in PAO. of 30 mm. Hg or more may be induced by minor handling procedures such as injections, heel stabs, or napkin changing. These fluctuations cast doubt on the validity of the usual method of intermit-
tent sampling of arterial blood, which could be misleading. The catheter has been especially useful in the management of babies requiring mechanical methods of assisting breathing, enabling the optimal therapeutic regime to be quickly chosen. It has also been a valuable aid in managing recurrent apnoea. Comparison of catheter readings with simultaneous laboratory readings indicates a difference of < 10 mm. Hg in the majority, although some differ by > 15 mm. Hg. An error of < 10 mm. Hg would be very difficult to achieve with any method of analysis, because of the physiological fluctuations of PAO. described above. It is concluded that the catheter has been of great value in the intensive care of sick pre-term babies. Its use should, however, be confined to units where adequate staffing and laboratory facilities exist, so that frequent reference checks can be made by conventional blood gas analysis. REFERENCES
Dodd K. L. (1975). Continuous monitoring of arterial oxygen tension in the newborn. British Journal of Hospital Equipment, May 1975, 35 Harris, T. R., Nugent, M. (1973). Continuous arterial oxygen tension monotiring in the newborn infant. Journal ofPediatrics, 82, 929 Meldrum, S. J., Watson, B. W., Becker, G. A. (1973). A catheter tip transducer for continuous measurement of blood oxygen tension in neonates. Biomedical Engineering, 8, 470
PLASMAPHERESIS IN RHESUS DISEASE J. Graham-Pole Department of Child Health, Royal Hospital for Sick Children, Glasgow
I N spite of routine anti-D gammaglobulin to prevent rhesus isoimmunization by pregnancy, severe rhesus disease continues to occur. Since the absolute level of maternal antibody correlates with severity of fetal 168
erythroblastosis (Fraser et al., 1972), attempts at its removal are indicated in pregnancies where history, antibody levels and amniocentesis findings suggest the fetus will die before intrauterine transfusion (I. U.T.) is feasible.
Problems in Pregnancy aud Childhood
Previous attempts (Clarke et al., 1970; Fraser et al., 1974)have used non-replacement maternal plasmapheresis, allowing no dilution of residual antibody and simultaneously depleting normal plasma proteins and other constituents. We have previously reported (Graham-Pole et al., 1974 a & b) on the value of long-term exchange plasmapheresis with a continuous-flow cell separator (Aminco Celltrifuge, Maryland, V.S.A.), which achieves a greater lowering of antibody from an earlier stage of pregnancy than the non-exchange technique and avoids depletion of normal proteins. The cell separator has been shown to be safe and effective for exchange plasmapheresis (Powles et al., 1971; Graham-Pole et al., 1974a). A dual channel pump allows ml-for-ml exchange of the antibodycontaining plasma by donated plasma, which recombines with the maternal packed cells for return to the patient. Seven patients have now been treated, all but one having lost previous pregnancies from fetal erythroblastosis, and all having in the current pregnancy extremely high rhesus antibody and/or amniotic fluid bilirubin values (up to 55.7 flg./m!. anti-D immunoglobulin, and up to 0.3 optical density units (Liley, 1963) respectively, at 18 weeks gestation). Treatment was usually from 20 weeks gestation and differences from previous series were (i) much greater volumes (up to 180 litres) removed; (ii) invariable steep antibody falls; (iii) earlier stage of gestation from which patients were successfully treated without LV.T. To show clear-cut fetal benefit, amniotic fluid bilirubin levels were monitored. The first 3 patients underwent relatively gentle plasmapheresis (5-10 litres removed weekly) from 20 to 28 weeks followed by LV.T. Antibody falls were considerable (for example from 55.7 to 4/kg./ml.) but L V.T. caused fetal death in all three. The latter 4 patients had more intensive plasmapheresis (I5-18 litres removed weekly) with control not only of maternal antibody but also amniotic fluid bilirubin levels. Three had had previous hydropic stillbirths in spite of LV.T. before 30 weeks, yet all 4 delivered moderately-affected babies at 36+ weeks without recourse to LV.T.
No major hazard of plasmapheresis was encountered. Though mothers were anticoagulated with heparin (approximately 10,000 units per run) and transient falls in platelet counts (to a nadir of 60,000/mm 3 ) were seen after intensive plasmapheresis, two short episodes of haematuria were the only haemorrhagic problems encountered. One patient needed an arteriovenous shunt, which was later removed; otherwise vein-to-vein procedures were used. We conclude that treatment of severe rhesus disease by plasmapheresis may to some extent replace LV.T., which is still a very hazardous procedure. The exchange technique allows much more intensive plasmapheresis and offers even the worst case a chance of fetal salvage. It is costly, and imposes a considerable strain on the patient, so should be undertaken only for the strongest indications. A C K NOW LED GEM E N T S. I wish to thank Professor I. Donald and Dr W. Barr, under whose care the patients were treated, Mrs M. Davie and I. Kershaw for their technical help and Dr M. L. N. Willoughby who directed all the work described. A large part of the cost of the cell-separator was met by Tenovus, Scotland.
REFERENCES
Clarke, C. A., Elson, C. J., Bradley, J., Donohoe, W. T. A., Lehane, D. (1970). Intensive plasmapheresis as a therapeutic measure in rhesusimmunised women. Lancet, I, 793 Fraser, I. D., Bennett, M., Bothamley, J. E. (1974). Ante-natal plasmapheresis in severe rhesus isoimmunisation British Journal of Haematology, 28, 147 Fraser, I. D., Tovey, G. H., Lockyer, W. J., Sobey, D. F. (1972). Antibody protein levels in the maternal serum in rhesus isoimmunization. Journal of Obstetrics and Gynaecology of the British Commonwealth, 79, 1074 Graham-Pole, J., Barr, W., Willoughby, M. L. N. (19740) Continuous flow exchange plasmapheresis in severe rhesus isoimmunization. Lancet, I, 105 Graham-Pole, J., Donald, I., Barr, W" Willoughby, M. L. N. (1974b). Plasmapheresis in rhesus isoimmunization. Lancet, 2, 1459. Liley, A. W. (1963). Errors. in the assessment of hemolytic disease from amniotic fluid. American Journal of Obstetrics and Gynecology, 86, 485 Powles, R., Smith, C., Kohn, J., Hamilton Fairley, G. (1971). Method of removing abnormal protein rapidly from patients with malignant paraproteinaemias. British Medical Journal, 3, 664 169
