Cardiopulmonary bypass in brain-dead organ donors

238

Subintimal

angioplasty for femoropopliteal artery occlusion

SIR,-Professor Lammer and colleagues (Nov 14, p 1183) compare laser with conventional angioplasty in femoropopliteal artery occlusions. Although the study is undoubtedly well designed and executed and the conclusions they make based on their data are valid, we feel that readers should be aware that there is an alternative form of angioplasty for femoropopliteal artery occlusionssubintimal angioplasty. The technique was developed in Leicester in 1987 and involves entering the subintimal space proximal to the occlusion, traversing the occlusion in the subintimal space, exiting distally to it, and then recanalising by inflating the angioplasty balloon within the subintimal space.’ We have reviewed the results of 200 consecutive attempted subintimal angioplasties for femoral artery occlusions (median length 11 cm, range 2-37). The initial technical success rate was 80% and was independent of occlusion length. The life-table analysis based on ankle brachial pressure indices showed a 71% patency at 12 months which compares favourably with the figure of 38% for conventional angioplasty produced by Lammer et al. We have just started a randomised prospective study to compare conventional percutaneous transluminal angioplasty (PTA) with subintimal PTA of femoropopliteal artery occlusion, and although we agree with Lammer’s conclusions we submit that subintimal angioplasty offers an alternative method of recanalisation which, on the basis of our data, seems to have a higher cumulative patency rate at one year. Notably, a third of our patients had occlusions more than 20 cm in length and none have received systemic anticoagulation therapy post PTA. In addition, subintimal angioplasty is considerably cheaper than laser recanalisation techniques. University of Leicester, School of Medicine, Clinical Sciences Building,

N. J. M. LONDON

Leicester Royal Infirmary, PO Box 65, Leicester LE2 7LX, UK

A. BOLIA P. R. F. BELL

1. Bolia A, Miles KA, Brennan J, Bell PRF. Percutaneous transluminal angioplasty of occlusions of the femoral and popliteal arteries by subintimal dissection. Cardiovasc Intervent Radiol 1990; 13: 357-63.

Histamine

H1 receptors in complex partial seizures

SIR,-Various neurotransmitters and their receptors have been

implicated in the initiation and termination of seizures in anin1alS.i A specific role for endogenous histamine and histamine Hi receptors in seizure mechanisms is emerging. Evidence that histamine in the brain is involved in the termination of seizures and has a role as an endogenous anticonvulsant has been obtained in various animal models of epilepsy, 2,3 and is supported by the fact that seizures are sometimes induced in childhood epilepsy by treatment with an antihistamine.4 Positron emission tomography (PET) makes it possible to localise and quantify neurotransmitter receptors non-invasively, permitting in-vivo measurements in patients with epilepsy.5.6 We have developed and validated in-vivo PET imaging to measure histamine H, receptors in normal volunteers.’ In our studies we have used two histamine Hi receptor ligands, the classic antihistamine [liC]mepyramine and an antidepressant [1’C]doxepin, which has higher affinity for H, receptors. Nine patients with complex partial seizures due to unilateral temporal and frontal seizure foci were studied by PET, with [l1C]doxepin to measure Hi receptors and i8F-fluoro-deoxy-Dglucose to measure cerebral glucose utilisation. The level of Hi receptors was 10-50% higher in the temporal neocortex on the side of the electrical focus than on the opposite side in eight of nine cases. A kinetic graphical analysis8 indicated that the rise in apparent

binding was due to increase in the binding potential (B/K). By contrast, glucose metabolism was decreased in the focus. Thus, glucose metabolism was inversely correlated with the binding of [mC]doxepin in the focus. Our finding of increased histamine H, receptor binding in the cortex of patients with epilepsy is consistent with data on the opioid

Cerebral

(right)

glucose utilisation (left) and histamine H, receptors patient with seizure focus in right temporal lobe.

in

11 receptor obtained with [’1C]carfentanylWith the finding that histamine Hl and opioid11 receptors have similar pharmacological effects on seizures,2.9 the increased levels ofH1 receptors in regions adjacent to the foci may represent a defensive mechanism of an anticonvulsant system to prevent spread of electrical activity from epileptic foci. Our results provide neurochemical evidence supporting the clinical observation that antihistamines exacerbate seizures in some cases of epilepsy. Department of Paediatrics, Tohoku University School of Medicine; Division of Neurosurgery, National Miyagi Hospital, Department of Pharmacology I, Tohoku University School of Medicine, Sendai 980, Japan, and Cyclotron and Radioisotope Centre, Tohoku University

KAZUIE IINUMA HIROYUKI YOKOYAMA TAISUKE OTSUKI KAZUHIKO YANAI TAKEHIKO WATANABE TATSUO IDO MASATOSHI ITOH

G, Morselli P, Lioyd KG, Engel JJ, eds. Neurotransmitters, seizure and epilepsy III. New York. Raven Press, 1986. 2. Yokoyama H, Onodera H, Maeyama K, et al. Histamine levels and maximal electroshock seizure in mice: the effects of &agr;-fluoromethylhistidine and metoprine. Naunyn-Schmiedeberg’s Arch Pharmacol 1992; 346: 40-45. 1. Nistico

3. Tuomisto T, Tacke U. Is histamine an anticonvulsive inhibitory transmitter? Neuropharmacology 1986; 25: 955-58. 4. Schwartz JF, Patterson JH. Toxic encephalopathy related to antihistaminebarbiturate antiemetic medication. Am J Dis Child 1978; 132: 37-39. 5. Frost JJ, Mayberg HS, Fisher RS, et al. Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy. Ann Neurol 1988, 23: 231-37. 6. Savic I, Persson A, Roland P, et al. In-vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci. Lancet 1988; ii: 863-66. 7. Yanai K, Watanabe T, Yokoyama H, et al. Mapping of histamine H1 receptors in the human brain using [11C]pyrilamine and positron emission tomography. J Neurochem 1988; 59: 128-36. 8. Logan J, Fowler JS, Volkow ND, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(-)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab 1990; 10: 740-47. 9. Tortella FC. Opioid peptides: possible physiological roles as endogenous anticonvulsants. In: Ferrendelli JA, Collins RC, Johnson EM, eds. Neurobiology of amino acids, peptides and trophic factors. New York: Kluwer, 1988: 163-79.

Cardiopulmonary bypass in brain-dead organ donors

SIR,-Haemodynamic stabilisation in brain-dead organ donors difficult. Thus the idea of cardiopulmonary bypass to achieve adequate blood pressure and flow as suggested by Wheeldon et al.’ Nevertheless, some questions arise for the case described (eg, why was pharmacological resuscitation unsuccessful?). According to the haemodynamic data shown (table, column A), the donor was in severe shock (aortic pressure 31 mm Hg) due to extremely low systemic vascular resistance (SVR, 145 dyn s cm’), can be

which is

not uncommon

in brain-dead donors. He

was not

in

cardiogenic shock (cardiac output 6-6 L/min), as described by the investigators. Unfortunately, heart rate was not shown. With an aortic pressure of 31 mm Hg (was this a mean?) and a pulmonary capillary wedge pressure of 21 mm Hg, coronary blood flow and

239

myocardial oxygen supply must have been very low. Why did the infuse noradrenaline to raise systemic vascular resistance (SVR) to the lower limit of normal, thus stabilising blood pressure, blood flow, and cardiac function? Excessive (31 and (3Z stimulation, as used in this case (40 ug/kg per min dobutamine), raises myocardial oxygen demand, here in the presence of inadequate oxygen supply, and lowers SVR.2 More debatable was the use of antidiuretic hormone (ADH) in doses up to 12 IU/h in the presence of anuria. With this dose of ADH, some unfavourable haemodynamic effects arise. Global SVR rises, but distribution of bloodflow to splanchnic and mesenteric organs worsens,3 which may at least partly have accounted for the ischaemic bowel and blue congested liver. Infusion of ADH at 05-10,0 IU/h in brain-dead donors seems reasonable. We measured ADH plasma concentrations of 10-20 pg/mL (0-5 IU/h) or 50 pglmL (2 IU/h). With higher concentrations (75-880 pg/mL), coronary bloodflow worsens with resulting myocardial ischaemia and decreased myocardial contractility. This effect is certainly undesirable if the heart is to be transplanted. So why did Wheeldon and colleagues administer such excessive doses of ADH?. The infusion of triiodothyronine is also questionable. In two randomised trials there was no beneficial effect of triiodothyronine (and cortisone) on haemodynamic stability and organ function in brain-dead organ donors.5,6 Adequate volume therapy and electrolyte balance, pi stimulation if cardiac insufficiency occurs, and consequent ot stimulation if vascular tone is diminished (puhnonary artery catheter), together with low-dose dopamine (3-5 ug/kg per min) to enhance renal and splanchnic blood flow, ensures haemodynamic stability in brain-dead donors.’ Since 1979 we have treated 351 brain-dead donors according to these rules without cardiopulmonary bypass and without a "hormone package". Pre-term cardiac arrest occurred in only 3 cases, because of prolonged mismanagement. With a conventional approach to stabilise haemodynamics, there is only a very limited indication, if any, for cardiopulmonary bypass in organ donors. J. LINK Department of Anaesthesia and Intensive Care, M. SCHÄFER Steglitz Clinic,

investigators

not

Free University of Berlin, 1000 Berlin 45, Germany

initially and 26-7 g m finally) and there was a mild improvement in 130 fully instrumented donors with average initial haemodynamics3 over the past 2 years. We agree with the Berlin group that the adjunctive use of over

noradrenaline could have been beneficial in the case we described. However, their contention that our management gave rise to splanchnic and myocardial ischaemia is not borne out by the facts in that there was a rapid improvement in urine production and in all haemodynamic indices,’ and both kidneys and heart were

successfully transplanted. As regards the efficacy of triiodothyronine administration to organ donors, we have already referred to our results which show benefit. The study by Goarin et al5 involved the administration of a single bolus dose of 2 )ig with measurements at 30 min and that by Mariot et al used 2 or 4 gg bolus doses every 30 mins based entirely on systolic blood pressure. We have already found that bolus administration of triiodothyronine is much less effective than infusion and that the haemodynamic benefits are not manifest until 30-60 min after the start of therapy. The Berlin Group do not reveal what percentage of their 351 donors did not yield transplantable organs. However, using our regimen of loading doses of triiodothyronine and ADH (4 ug and 1 U, respectively) followed by infusions of 3 pg/h and 1-5 U/h, respectively, and with insulin infused to maintain a normal blood sugar, we found that about 5% of donors respond inadequately and require additional intervention. We propose that cardiopulmonary bypass is logical since it provides a means of optimising oxygen delivery, unloading the heart, restoring normothermia, and

providing stabilisation during splanchnic dissection. For the heart, Galimanes and Hearse confirm an earlier report8 in which ischaemically or metabolically damaged hearts could be shown to be capable of full restoration of function by unloading and normal perfusion. Cardiopulmonary bypass may have an important role, not only in resuscitating "untransplantable" hearts but also possibly in restoring borderline function to normal. We are, however, encouraged to know that there is at least one other group taking an active interest in maximising donor-organ function.

H.-J. GRAMM, for the Brain Death Study Group

1. Wheeldon DR, Potter CDO, Dunning J, et al. Haemodynamic correction in multiorgan donation. Lancet 1992; 339: 1175. 2. Robie NW, Goldberg LJ. Comparative systemic and regional hemodynamic effects of dopamine and dobutamine. Am Heart J 1975; 90: 340-45. 3. Cowley AW Jr. Vasopressin and cardiovascular regulation. In: Guyton AC, Hall JE, eds. Baltimore: University Park Press, 1982. 4. Boyle WA III, Segel LD. Direct cardiac effects of vasopressin and their reversal by a vascular antagonist. Am J Physiol 1986; 251: H734-41. 5. Mariot J, Jacob F, Voltz C, et al. Intérêt de l’hormonothérapie associant triiodothyronine et cortisone chez le patient en etat de mort cérébrale. Ann Fr Anesth Reanim 1992; 10: 321-28. 6. Goarin JP, Jacquens Y, Cohen S, et al. Effets de la triiodothyronine (T3) sur l’hémodynamique et la fraction d’éjection du ventricule gauche (FEVG) du donneur. 33rd Congress de la SFAR. Ann Fr Anesth Reanim 1992; 10 (suppl): R114. 7. Link J, Rohling R, Gramm H.-J. Zur Aufrechterhaltung der Homoostase nach Eintritt des Hirntods. Anaesthesiol Reanimat 1990; 15: 249-60.

Transplant Unit, Papworth Hospital, Cambridge CB3 8RE, UK

D. R. WHEELDON C. D. O. POTTER J. DUNNING S. GRAY A. ODURO J. WALLWORK S. R. LARGE

Novitzky D, Cooper DKC, Morrell D, Isaacs S. Change from aerobic to anaerobic metabolism after brain death, and reversal following triiodothyronine therapy. Transplantation 1988; 45: 32-36. 2. Darracott-Cankovic S, Wheeldon D, Wallwork J, English TAH. Does hormonal pretreatment improve myocardial function at transplantation?. J Heart Transplant 1990; 9: 79. 3. Wheeldon DR, Potter CD. Management of organ donors. British Transplantation Society Meeting, Glasgow, April 14-15,1992 (abstr). 4. Wheeldon DR, Potter CD, Ciulli F, et al. Multiorgan donor resuscitation. Perfusion 1.

1992; 7: 213-16.

JP, Jacquens Y, Cohen S, et al. Effets de la triodothyronine (T3) sur l’hemodynamique et al fraction d’ejection du ventricule gauche (FEVG) de donneur. 33rd Congress de la SFAR. Ann Fr Anesth Reanim 1992; 10 (suppl):

5. Goarin

Authors’reply S!R,—The treatment received by the donor was that prescribed by the doctors caring for the donor and not by the transplant team, and hence the haemodynamic picture of shock and the intitial surgical findings of congested ischaemic organs were related to management not under our control. For the past 3 years we have been investigating the effects of hormone replacement therapy in organ donors.! In a prospective randomised study, bolus administration of triiodothyronine, cortisone, and insulin

significantly reduced the inotropic requirements

of organ donors

R114. 6. Mariot J, Jacob F, Voltz C, Perrier JF, Strub P. Interet de l’hormonotherapie associant triiodothyroninbe et cortisone chez le patient en etat de mort cerebrale. Ann Fr

Anesth Reanim 1991; 10: 321-28. M, Hearse DJ. Brain death-induced impairment of cardiac contractile performance can be reversed by explanation and may not preclude the use of hearts for transplantation. Circ Res 1992; 71: 1213-19. 8. Burt JM, Larson DF, Copeland JG. Recovery of heart function following 24 hours preservation and ectopic transplantation. J Heart Transplant 1986; 5: 298-304. 7. Galines

compared with controls,2 despite the fact that serum concentrations

Aetiology of tuberculids

of triiodothyronine were still subnormal and cortisol concentrations were unpredictable. Our subsequent studies have shown that administering triiodothyronine, ADH, and insulin by a loading dose followed by an infusion results in significant functional improvement sustained for at least a month post-transplantation. In addition, we have found that pharmacological resuscitation was successful in 23% of donors with initially unacceptable haemodynamics (left-ventricular stroke work index 15-4 g m

SiR,—There is controversy about the cause of erythema induratum, a chronic nodular, ulcerative eruption on the lower legs, which is histologically characterised by a subcutaneous granulomatous vasculitis. Bazin, in 1861, initially reported erythema induratum as a manifestation of tuberculosis. The condition is considered to belong to the tuberculids, a group of skin eruptions, whose tuberculous aetiology has remained controversial since mycobacteria cannot be cultured from lesions.’ Because