1211
PATIENT DETAILS
*Before discontinuation of therapy; t’Madopar’; t’Smemet’; §After 4 years of
levodopa
If any
patient without initial parkinsonism were later to have as a result of wrongly prescribed levodopa, the iatrogenic pathogenesis of the disorder would not easily be recognised. Our findings suggest that chronic levodopa treatment is not harmful in non-parkinsonian patients. It could of course be argued that only in patients with Parkinson’s disease or parkinsonism might the nigrostriatal system be susceptible to proposed cytotoxic effects of levodopa. However, our findings and those of others emphasise that the harmful effects of levodopa still remain to be proven.6-9 Thus the emergence of dyskinesias and fluctuations on long-term treatment seem to be dependent on the interaction of levodopa with the presence and severity of parkinsonism, rather than on levodopa intake alone. irreversible parkinsonism
Department of Neurology, University of Nijmegen, 6500 Nijmegen, Netherlands
N. ARTS C. VAN DE VLASAKKER T. TACKE M. HORSTINK
1. Horstink M, Zijlmans J, Pasman J, Berger H, Korten J, van ’t Hof M. Which nsk factors predict the levodopa response m fluctuating Parkinson’s disease? Ann Neurol 1990; 27: 537-43. 2. Duvoisin RC. To treat early or to treat late? Ann Neurol 1987; 22: 2-3. 3. Blin J, Bonnet A, Agid Y. Does levodopa aggravate Parkinson’s disease? Neurology
1988; 38: 1410-16 4. Melamed E. Inintation of levodopa therapy in Parkinsonian patients should be delayed until the advanced stages of the disease. Arch Neurol 1986; 43: 402-05. 5. Weiner WJ, Nausieda PA. Meige’s syndrome during long-term dopminergic therapy in Parkinson’s disease- Arch Neurol 1982; 39: 451-52. 6. Nygaard TG, Marsden CD, Fahn S. Dopa-responsive dystonia: long-term treatment response and prognosis. Neurology 1991; 41: 174-81. 7. Quaade F, Pakkenberg H, Juhl E. Levodopa as a treatment of obesity. Acta Med Scand 1974; 195: 129-30. 8 von Scheele C, Kempi V. Long-term effect of dopaminergic drugs in restless legs. Arch Neurol 1990; 47: 1223-24. 9. Cedarbaum J, Gandy S, McDowell F. "Early" initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias, or dementia in Parkinson’s disease. Neurology 1991; 41: 622-29.
Autotransfusion SIR,-Your editorial (Aug 17, p 418) presented a rather critical view of mediastinal drainage autotransfusion. There is no evidence to suggest that infusion of defibrinogenated blood collected from either serosal cavities or postoperative wounds after arthroplasty has ever led to a coagulopathy in the recipient. Although fibrin-split products, complement-activation products, and non-functioning platelets have been found in shed blood, this is a long way from clinically relevant coagulopathy. The quoted study purporting to show platelet dysfunction’ involved twenty mongrel dogs bled into their peritoneal cavities. Each received two exchange transfusions of citrated blood (a mean of 457 ml of citrate) over 4 h. To draw conclusions about non-anticoagulated mediastinal drainage fluid in humans from this work is stretching
credulity. There are two further prospective randomised studies of autotransfusion of shed mediastinal blood. Lepore and Radegrian randomised 135 patients to re-infusion of shed mediastinal blood or control? There was a significant reduction in bank-blood requirement, from 3-3 units in the control group to 2-7 units in the autotransfused group. There was no evidence of coagulopathy. This study examined reservoirs for infection. Although 19% of
transfusates
positive, no episode of clinical infection patients were randomised by Page et al to receive shed mediastinal blood or not.3 Homologous blood use fell modestly from a mean (SD) of 3-83 (2-58) units to 3-15 (2-05) units in the autotransfusion group. However, these differences became significant when drainage exceeded 500 ml and was most significant in patients with the greatest mediastinal loss. developed.
were
culture
100 cardiac
The message should be clear. Autotransfusion of shed mediastinal blood is useful in those patients with increased loss postoperatively. Any method that reduces exposure to donor blood must be included as part of an overall policy of blood conservation. The risks of re-infusion of mediastinal drainage blood are theoretical but the risks of homologous blood transfusion are real. Department of Surgery, University of Bristol, Bristol BS2 8HW, UK
J.
F. THOMPSON
1. Moore EE, Dunn EL, Breslich DJ, Galloway WB. Platelet abnormalities associated with massive autotransfusion. J Trauma 1980; 20: 1052-56. 2. Lepore V, Radegrian K. Autotransfusion of mediastinal blood in cardiac surgery. Scand J Thorac Cardiovasc Surg 1989; 23: 47-49. 3. Page R, Russell GN, Fox MA, Fabri BN, Lewis I, Williets T. Hard-shell cardiotomy reservoir for re-infusion of shed mediastinal blood. Ann Thorac Surgery 1989; 48: 514-17.
Prediction of bleeding and anaesthesia
regional
SIR,-Dr Mallett and Dr Platt (Sept 21, p 765) suggest that thromboeslastography (TEG) might have predictive value for bleeding associated with regional anaesthesia. The clinical implications of an abnormal TEG test are not known.
In view of
this, how can Mallett and Platt conclude that it is a safe and practical method to define potential bleeding diatheses? The clinical methodology for the evaluation of diagnostic tests is well established.1 When subjected to rigorous evaluation, with techniques such as receiver operating characteristic curves in addition to simple sensitivity and specificity estimations, the so-called most physiological haemostatic test, bleeding time, has no prognostic importance in prediction of surgical bleeding.2 With respect to epidural anaesthesia, the only major prospective clinical study, consisting of 1000 patients who were fully orally anticoagulated (international normalised ratio of about 2-3), showed no association with any clinically detectable epidural haematomata.3 The clinical correlates of abnormal laboratory tests with both interventional and non-interventional bleeding should be determined by direct observation rather than by extrapolation from poorly understood laboratory measures of haemostasis. Departments of Pathology and Medicine, University of British Columbia, Vancouver, British Columbia, Canada V6T 2B5
CEDRIC J. CARTER P. BALLEM
1. Sackett DL, Haynes RB, Tugwell P. Clinical epidemiology. Boston: Little Brown, 1985. 2. Rodgers RPC. A critical reappraisal of the bleeding time. Semin Thromb Hemostasis 1990; 16: 1-20. 3. Odoom JA, Sih IL. Epidural analgesia and anticoagulant therapy. Anaesthesia 1983; 38: 254-99.
PATIENT DETAILS
*Before discontinuation of therapy; t’Madopar’; t’Smemet’; §After 4 years of
levodopa
If any
patient without initial parkinsonism were later to have as a result of wrongly prescribed levodopa, the iatrogenic pathogenesis of the disorder would not easily be recognised. Our findings suggest that chronic levodopa treatment is not harmful in non-parkinsonian patients. It could of course be argued that only in patients with Parkinson’s disease or parkinsonism might the nigrostriatal system be susceptible to proposed cytotoxic effects of levodopa. However, our findings and those of others emphasise that the harmful effects of levodopa still remain to be proven.6-9 Thus the emergence of dyskinesias and fluctuations on long-term treatment seem to be dependent on the interaction of levodopa with the presence and severity of parkinsonism, rather than on levodopa intake alone. irreversible parkinsonism
Department of Neurology, University of Nijmegen, 6500 Nijmegen, Netherlands
N. ARTS C. VAN DE VLASAKKER T. TACKE M. HORSTINK
1. Horstink M, Zijlmans J, Pasman J, Berger H, Korten J, van ’t Hof M. Which nsk factors predict the levodopa response m fluctuating Parkinson’s disease? Ann Neurol 1990; 27: 537-43. 2. Duvoisin RC. To treat early or to treat late? Ann Neurol 1987; 22: 2-3. 3. Blin J, Bonnet A, Agid Y. Does levodopa aggravate Parkinson’s disease? Neurology
1988; 38: 1410-16 4. Melamed E. Inintation of levodopa therapy in Parkinsonian patients should be delayed until the advanced stages of the disease. Arch Neurol 1986; 43: 402-05. 5. Weiner WJ, Nausieda PA. Meige’s syndrome during long-term dopminergic therapy in Parkinson’s disease- Arch Neurol 1982; 39: 451-52. 6. Nygaard TG, Marsden CD, Fahn S. Dopa-responsive dystonia: long-term treatment response and prognosis. Neurology 1991; 41: 174-81. 7. Quaade F, Pakkenberg H, Juhl E. Levodopa as a treatment of obesity. Acta Med Scand 1974; 195: 129-30. 8 von Scheele C, Kempi V. Long-term effect of dopaminergic drugs in restless legs. Arch Neurol 1990; 47: 1223-24. 9. Cedarbaum J, Gandy S, McDowell F. "Early" initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias, or dementia in Parkinson’s disease. Neurology 1991; 41: 622-29.
Autotransfusion SIR,-Your editorial (Aug 17, p 418) presented a rather critical view of mediastinal drainage autotransfusion. There is no evidence to suggest that infusion of defibrinogenated blood collected from either serosal cavities or postoperative wounds after arthroplasty has ever led to a coagulopathy in the recipient. Although fibrin-split products, complement-activation products, and non-functioning platelets have been found in shed blood, this is a long way from clinically relevant coagulopathy. The quoted study purporting to show platelet dysfunction’ involved twenty mongrel dogs bled into their peritoneal cavities. Each received two exchange transfusions of citrated blood (a mean of 457 ml of citrate) over 4 h. To draw conclusions about non-anticoagulated mediastinal drainage fluid in humans from this work is stretching
credulity. There are two further prospective randomised studies of autotransfusion of shed mediastinal blood. Lepore and Radegrian randomised 135 patients to re-infusion of shed mediastinal blood or control? There was a significant reduction in bank-blood requirement, from 3-3 units in the control group to 2-7 units in the autotransfused group. There was no evidence of coagulopathy. This study examined reservoirs for infection. Although 19% of
transfusates
positive, no episode of clinical infection patients were randomised by Page et al to receive shed mediastinal blood or not.3 Homologous blood use fell modestly from a mean (SD) of 3-83 (2-58) units to 3-15 (2-05) units in the autotransfusion group. However, these differences became significant when drainage exceeded 500 ml and was most significant in patients with the greatest mediastinal loss. developed.
were
culture
100 cardiac
The message should be clear. Autotransfusion of shed mediastinal blood is useful in those patients with increased loss postoperatively. Any method that reduces exposure to donor blood must be included as part of an overall policy of blood conservation. The risks of re-infusion of mediastinal drainage blood are theoretical but the risks of homologous blood transfusion are real. Department of Surgery, University of Bristol, Bristol BS2 8HW, UK
J.
F. THOMPSON
1. Moore EE, Dunn EL, Breslich DJ, Galloway WB. Platelet abnormalities associated with massive autotransfusion. J Trauma 1980; 20: 1052-56. 2. Lepore V, Radegrian K. Autotransfusion of mediastinal blood in cardiac surgery. Scand J Thorac Cardiovasc Surg 1989; 23: 47-49. 3. Page R, Russell GN, Fox MA, Fabri BN, Lewis I, Williets T. Hard-shell cardiotomy reservoir for re-infusion of shed mediastinal blood. Ann Thorac Surgery 1989; 48: 514-17.
Prediction of bleeding and anaesthesia
regional
SIR,-Dr Mallett and Dr Platt (Sept 21, p 765) suggest that thromboeslastography (TEG) might have predictive value for bleeding associated with regional anaesthesia. The clinical implications of an abnormal TEG test are not known.
In view of
this, how can Mallett and Platt conclude that it is a safe and practical method to define potential bleeding diatheses? The clinical methodology for the evaluation of diagnostic tests is well established.1 When subjected to rigorous evaluation, with techniques such as receiver operating characteristic curves in addition to simple sensitivity and specificity estimations, the so-called most physiological haemostatic test, bleeding time, has no prognostic importance in prediction of surgical bleeding.2 With respect to epidural anaesthesia, the only major prospective clinical study, consisting of 1000 patients who were fully orally anticoagulated (international normalised ratio of about 2-3), showed no association with any clinically detectable epidural haematomata.3 The clinical correlates of abnormal laboratory tests with both interventional and non-interventional bleeding should be determined by direct observation rather than by extrapolation from poorly understood laboratory measures of haemostasis. Departments of Pathology and Medicine, University of British Columbia, Vancouver, British Columbia, Canada V6T 2B5
CEDRIC J. CARTER P. BALLEM
1. Sackett DL, Haynes RB, Tugwell P. Clinical epidemiology. Boston: Little Brown, 1985. 2. Rodgers RPC. A critical reappraisal of the bleeding time. Semin Thromb Hemostasis 1990; 16: 1-20. 3. Odoom JA, Sih IL. Epidural analgesia and anticoagulant therapy. Anaesthesia 1983; 38: 254-99.
