choline deficiency associated with total parenteral nutrition
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this problem. Naturally, we advised our patients to carry theirhay bales and planks differently in future.
Department of Medicine,Leicester Royal Infirmary,Leicester LE1 5WW;and Department of Pharmacology,and Therapeutics,
University of Leicester,Leicester LE2 7LX
A. J. WILLIAMSA. J. FREEMONTD. B. BARNETT
PREVENTING POSTOPERATIVETHROMBOEMBOLISM
SIR,-We congratulate Dr Morris (Sept. 13, p. 572) on his usefulsurvey of the methods used by surgeons to prevent postoperativethromboembolism. We have recently undertaken a similar survey,the chief difference being that Morris’ was a simple questionnaireon a reply paid postcard while ours consisted of a complex threepage, computer based questionnaire. Perhaps predictably, this pro-duced a very poor response rate, with only 183 replies to 743questionnaires (25%). Of those who did reply, only one surgeonused no method of prophylaxis apart from early ambulation. InMorris’ survey, 38% indicated that they used no prophylaxis. Thesesurgeons were obviously insufficiently interested to complete ourquestionnaire.Besides Morris’ questions, we included a section on risk factors;
most surgeons regarding a history of DVT, the contraceptive pill,and obesity as of greater risk than malignancy. Age was also con-sidered significant. Abdominal operations, pelvic surgery, and sur-gery for the post-thrombotic syndrome were regarded as riskier thanlaparotomy and thoracotomy.Like Morris, we were fascinated by the wide variety of permuta-
tions and combinations of prophylaxis.We included a section on the complications of prophylactic
methods and found that of 149 surgeons using low-dose subcutan-eous heparin, 3 had experienced postoperative haemorrhage suffi-cient for them to reduce the dose from 5000 IU every 8 h to 5000 IU
12-hourly in subsequent- patients. 14 (9%) had seen haemorrhagegrave enough for them to abandon heparin prophylaxis altogether,and 2 surgeons reported fatal haemorrhages. Of the 78 surgeons us-ing low molecular weight dextran, 15(19%) had experienced signifi-cant blood loss and 1 had given up its use for this reason. 2 surgeonshad stopped using dextran following anaphylactic reactions and onereported fatal circulatory overloading.Morris’s questionnaire did not ask about mechanical methods.
Ours did. Of the surgeons who replied 62 (34%) use TED ’Anti-embolism’ or similar elastic stockings during and after the operationand the same number used intermittent calf compression. Electricalstimulation of the calf muscles was used by only 14 surgeons."We thank those members of the Association of Surgeons who took the
trouble to complete our questionnaire. ,
Lewisham Hospital,London SE13 6LH
Royal Infirmary,Edinburgh
DAVID NEGUS
C. VAUGHAN RUCKLEY
GLYCEROL LYSIS TIME FOR SCREENING FOR
&bgr;-THALASSÆMIA TRAIT
SIR,-The glycerol lysis time (GLT50) is a rapid, simple, andinexpensive measure of the time required by erythrocytes sus-pended in glycerol to halve initial values of optical density.’Patients with thalasssemia trait have significantly increasedGLT50 values. Our purpose was to evaluate the accuracy ofthis test in screening programs.
1. Gottfried EL, Robertson NA. Glycerol lysis time as a screening test for ery-throcytes disorders. J Lab Clin Med 1974; 83: 323.
In 203 normal subjects (age >12 years) the mean GLTsovalue was 33 s with a skewed distribution (range 16-64 s). In206 patients with p-thalassaemia trait the mean and range was121 s (46-300 s). This difference is highly significant(p<0-001). There is a small overlap (see figure); however, ifthe lowest value for thalassaemic patients is taken as the cut-offpoint there are, by definition, no false negatives for thalassae-mia trait and only 9% false positives.
Histogram showing distribution of GL T 50 in subjects with&bgr;-thalassaemia trait and controls.
A similar strategy is widely used for erythrocyte mean cor-puscular volume (MCV),2 with a value of 79 fl as cut-off.2None of our thalassaemic patients had an MCV over 78 fl. Themean for normal subjects was 84 fl (range 77-100 fl) and forthe thalassoemic patients the mean was 67 fl (range 56-78 fl).With this cut-off the false positives for MCV are 6%.Our data show that GLTso is a real alternative to MCV for
centres not equipped with the electronic counters needed forthe determination of erythrocytes indices.
Perfezionamento Clinical Institutesand Laboratory of Clinical Research,Anatomy and Histopathology,
20122 Milan, Italy
A. CANTÙ RAJNOLDIM. FERRARIS. PIETRIM. TRAVI
CHOLINE DEFICIENCY ASSOCIATED WITH TOTALPARENTERAL NUTRITION
SIR,-Choline is essential for the synthesis of phosphatidyl-choline and other phospholipids. Choline deficiency has beenreported in animals fed a choline deficient diet,’ but not inman. Choline deficiency causes fatty liver in animals’ and totalparenteral nutrition (TPN) formulae, none of which containfree choline, have been associated with abnormal liver func-
2. Pearson HA, McPhedran P, O’Brien RT, Aspnes GT, McIntosh S, GuilotisDK. Comprehensive testing for thalassemia trait. Ann NY Acad Sci 1974,232:135.
1. Best CH, Lucas CC. Choline malnutrition. In: Joliffe N, ed. Clinical nutri-tion, 2nd ed. New York: Harper. 1962: 227-60.
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Free plasma choline levels in fifteen patients during TPN.
Plasma choline was measured pre-TPN (day 0) and, on average, ondays 14, 26, and 41. Shaded area=normal levels.
tion.2-4 We decided to measure free plasma choline levels in fif-teen patients before and during TPN.Ten patients were referred for nutritional support and five lym-
phoma patients were taking part in a study of the effects of TPN ontolerance to chemotherapy.5 Of the thirteen patients with malignantdisease five were receiving chemotherapy concomitantly with TPN andeight patients had been treated with chemotherapy, surgery, or radia-tion and surgery before TPN began.A catheter was passed into the superior vena cava for administra-
tion of 20% glucose and 4-25% ’Freamine II’, a synthetic aminoacidsolution (McGaw Laboratories). Vitamins were supplemented as MVIconcentrate (USV Pharmaceuticals) 5 ml in 1 litre of TPN solutiontwice weekly and ’Bejex’ (Abbott Laboratories) 5 ml in 1 litre of TPNsolution five times per week. Neither vitamin formulation containscholine or methionine. The patients also received 10% ’Intralipid’, 500ml twice weekly, and trace metals (zinc, copper, manganese, iodine)were administered daily. --
Blood for choline determination was collected in cold, heparinisedglass tubes on ice and immediately centrifuged at 4°C. Free plasmacholine was determined by gas-chromatography/mass-spectrometry.6The normal range of choline in twenty-three healthy volunteers (meanage 34 years, range 17-85) was 6-10 nmovml.
Significance was tested by a two-tailed paired t-test with adjustmentfor multiple comparisons. Data are expressed as mean±SEM.
Free plasma choline levels 2, 4, and 6 weeks after the startof TPN were abnormally low and significantly below pre-TPNlevels (see figure). Pre-TPN the SGPT level was normal (18±2IU/1); activity rose at 2 weeks (61+15) and then fell to normalat 4 (36±8) and 6 weeks (23±3). SGOT, alkaline phosphatase,and total bilirubin levels were normal pre-TPN and did notchange significantly.Body weight increased significantly (p<0001) after TPN
(see table). The average intake of nitrogen (g/day) was
13-2±0-9 intravenously and 2-4±0-6 by mouth. The intake ofnon-protein calories (kcal/day) was 1889_+112 intravenouslyand 392±85 by mouth.
Until the advent of TPN, man had not been subject to a dietdeficient only in choline. We have shown that free plasma cho-
2. Grant JP, Cox CE, Kleinman LM, Maher MM, Pittman MA, Tangrea JA,Brown JH, Gross E, Beazley RM, Jones RS. Serum hepatic enzyme andbilirubin elevations during parenteral nutrition. Surg Gynecol Obstet1977; 145: 573-80.
3. MacFadyen BV, Dudrick SJ, Baquero G, Gum ET. Clinical and biologicalchanges in liver function during intravenous hyperalimentation. J ParentEnter Nutr 1979; 3: 438-43.
4. Sheldon GF, Petersen SR, Sanders R. Hepatic dysfunction during hyperali-mentation. Arch Surg 1978; 113: 504-08.
5. Popp MB, Fisher RI, Simon RM, Brennan MF. A prospective randomizedstudy of adjuvant parenteral nutrition in the treatment of diffuse lympho-ma: I. Effect on drug tolerance. Cancer Treat Rep (in press).
6. Hanin I, Kopp U, Zahnisen NR, Shih TM, Spiker DG, Merikangas JR,Kupfer DJ, Foster FG. Acetylcholine and choline in human plasma andred blood cells: a gas chromatographic-mass spectrometric evaluation. In:Jenden DJ, ed. Cholinergic mechanisms and psychopharmacology. NewYork, Plenum Press, 1977: 181-96.
line levels fall during TPN and that the decrease was notrelated to pre-TPN nutritional status. Most of our patientswere malnourished, but some were not.
Choline requirements during TPN are not known. L-meth-ionine protects against choline deficiency,’ but the amount in4.25% freamine II does not seem sufficient- to prevent a
deficiency state. And, though intralipid contains some phos-phatidylcholine, the volume of emulsion used clinically clearlydoes not supply enough choline to prevent a significant fall infree plasma choline concentrations.The biological significance of this finding is uncertain. In
most animals studied, choline deficiency leads to the develop-ment of fatty liver.’ In man, abnormal liver function duringTPN has been observed,2-4 and in our patients the increase inSGPT coincided with the fall in plasma choline. Whether thesetwo observations are related has yet to be determined.
Kaminsky prevented the accumulation of hepatic lipid in ratson TPN by administering choline by gavage.8 Thus a fall infree plasma choline may be one reason for the transient liverfunction abnormalities seen during TPN.
This work was supported in part by NIMH grant MH 26320.
Surgical Metabolism Section,Surgery Branch,National Cancer Institute,N.I.H., Bethesda, Maryland 20205, U.S.A.;
and Department of Psychiatry,Western Psychiatric Institute and Clinic,Pittsburgh, Pennsylvania
MICHAEL E. BURTISRAEL HANINMURRAY F. BRENNAN
SURVIVAL OF PRETERM BABIES
SrR,—The fate of the baby born weighing less than 1501 ghas been discussed recently in a Lancet editorial.’ However,the evidence discussed was based on postnatal gestational as-sessment. As a guide for our own obstetricians, we haveassessed the survival of babies born at Queen Charlotte’s Ma-ternity Hospital and the Hammersmith Hospital, London, in1978 and 1979, using antenatal gestational information only.Because some babies die after more than 28 days of neonatal
care we defined survival as discharge home from hospital. Thegestational age was assessed according to mother’s dates unlessearly ultrasound cephalometry had altered the expected date of
7. Griffith WH. Choline metabolism: II. The interrelationship of choline, cys-tine, and methionine in the occurrence and prevention of hemorrhagic de-generation in young rats. J Biol Chem 1940; 132: 627-37.
8. Kaminski DL. The effect of hyperalimentation on hepatic lipid metabolism.Presented at the 41st annual meeting of the Society of University Sur-geons, Houston, Texas, Feb. 7-9, 1980.
1. Editorial. The fate of the baby under 1501 grams at birth. Lancet 1980; i:461-63.