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PREVENTION OF VENOUS THROMBOSIS ANDPULMONARY EMBOLISM IN INJURED PATIENTS

SIR,-May I comment on Dr. Sevitt’s letter (June 23) ?He and I are in complete agreement over the value ofanticoagulant prophylaxis in preventing fatal thrombo-embolism in the injured. The questions at issue betweenus are which patients should be treated, how, and when.

The incidence of venous thrombosis in Sevitt and Gallagher’snecropsy material varied between 37% and 83%. (Theincidence is likely to have been exaggerated since, as the authorspoint out, " when embolism was diagnosed or suspected specialefforts to obtain permission for necropsy were often madewhilst many other deaths did not reach necropsy".) Thesefigures included minor and clinically insignificant thrombiwhich would not be indications for potentially dangerousprophylactic therapy. The decision to give anticoagulantsshould be based on the risk of the dangerous complication,pulmonary embolism; this was found to vary from 2-1% (headand chest injuries, 47 necropsies) to 60% (fractured tibia,10 necropsies). Thus the risk may well be related to the typeof injury, even if there is also good correlation with the age ofthe patient and the period of bed rest. The results of a study ofall kinds and degrees of injury should not be made the basis forgeneral conclusions concerning a common " standard " type ofinjury such as fracture of the femoral neck. Even between thetwo main types of this fracture, the subcapital and the per-trochanteric, the prognosis differs. 2 Therefore, my remarkswere, and will be, restricted to patients with fracture of the hip.When should prophylaxis begin? If my conclusion,

" Providedthe operation is not unduly delayed, anticoagulant therapy maybe postponed till after the operation be read in conjunctionwith the statement some lines above, "... provided the opera-tion is performed within a few days of the injury, anticoagulanttherapy may probably be started after the operation ", mymeaning can then hardly be misunderstood. In Dr. Sevitt’sown series,3 43 patients were started on phenindione after theoperation. As far as can be seen, the records of these 43 havenot been separately analysed; but of all 150 patients treated,pulmonary embolism was found in only 3, and in these phenin-dione therapy had been stopped days or weeks before death.From this I concluded that phenindione therapy had preventeddeath from pulmonary embolism not only in patients givenpreoperative prophylaxis but also in the 43 patients in whomthe therapy was started after the operation.

Citing Storm,4 I did not suggest that oral anticoagulants wereineffective during the first five to eight days after injury. Stormstarted dicoumarol treatment at least five to eight days beforethe operation in order to have the plasma-prothrombin stabilisedat the desired level on the day of operation.

The number of operated control patients is given as 125 intable ill of Dr. Sevitt’s article.3 But my arithmetic was based

upon the figures presented under his heading " Safety ofPhenindione ": the only operations there mentioned are Smith-Petersen pinning and the Neufeldt nail-plate operation, and thenumber of control patients subjected to these procedures was53 and 69 respectively. This adds up to 122 operated controls.The question arises: what operations were performed in the3 missing patients ?Whether the method of selection in Sevitt and Gallagher’s

study actually led to bias is, of course, unknown. But thecontrol group was, in many respects, the less favourable from a

surgical point of view. Over-representation of unfavourablefactors in this group may well have influenced both theincidence of thromboembolism and the number of fatalities.To specify the age-distribution of the fatal cases in the Ullevål

series seemed to me unnecessary since I explained that " nodeath occurred in patients below the age of seventy-five ".Thus anticoagulant prophylaxis given only to patients of overseventy-five would have eliminated death from pulmonaryembolism. Dr. Sevitt says that " restriction of prophylaxis to

1. Sevitt, S., Gallagher, N. G. Brit. J. Surg. 1961, 48, 475.2. Eskeland, G. Lancet, 1962, i, 1035.3. Sevitt, S., Gallagher, N. G. ibid. 1959, ii, 981.4. Storm, O. Thrombos. Diathes. hœmorrh., Stuttgart, 1958, 2, 484.

patients 75 years and older would prevent at most 50 to 60% offatal cases of embolism in our hospital ". Again, I emphasisethat my recommendation relates only to patients with a

fractured neck of the femur.

Is it possible to define certain groups of injured patientsin whom the risk of dangerous thromboembolism is solow that anticoagulant prophylaxis may justifiably beomitted ?

This question can be answered only by controlled trialson homogeneous groups of patients; extrapolations fromother groups confuse the issue. Anticoagulant therapycarries a definite risk and also imposes a considerableburden on the laboratory and clinical staff. For thesereasons, prophylaxis should be restricted to those patientsin whom the danger of thromboembolism is greatest, evenif this policy will not eliminate all thromboemboliccomplications.

G. ESKELAND.Ullevål Hospital,Oslo, Norway.

RITTER’S DISEASE(TOXIC EPIDERMAL NECROLYSIS)

BRIAN POTTER.University of Colorado.

SiR,ňThe examples of Ritter’s disease reported byDr. Benson and others (May 12) appear from the

description and photographs to be morphologically andhistopathologically similar to the reaction pattern recentlynamed toxic epidermal necrolysis by Lyell.1 Eruptions ofthis sort seem to represent a toxic reaction both to drugsand infections, including impetigo.

RESERPINE AND NORADRENALINE STORES

SIR,-Studies on laboratory animals have clearlyestablished that rauwolfia alkaloids, widely used in thetreatment of hypertension, produce depletion of nor-adrenaline stores throughout the body,23 and that thisdepletion is responsible for the antihypertensive propertiesof these drugs. But it is clear that (1) there is considerablespecies variation in the dose-depletion relationship, (2) thedoses used in the experimental animals have been inexcess of those employed clinically, and (3) the drug hasbeen administered parenterally in laboratory animals,whereas clinically it is usually given by mouth and its

absorption from the gastrointestinal tract is known to beerratic.4 It was therefore of great interest to determinewhether reserpine, administered orally to patients in dosescommonly employed clinically, would reduce tissuenoradrenaline concentration.

The concentration of noradrenaline was determined in

biopsy specimens of atrial appendages at the time of cardiacoperations on 22 patients who were in normal sinus rhythmand who had not been in congestive heart failure. Noradrena-line was measured fluorometrically by the trihydroxyindolemethod 5 and was found to average 1.87 µg. per g. (range0.54-5.14 µg. per g.). Determinations were also made in 3

patients who had received 0-25-0-50 mg. reserpine orally oncedaily for six to seven weeks before operation. In the first

patient, who had an atrial septal defect, the total cumulativedose was 0.23 mg. per kg. bodyweight and the atrial nor-adrenaline concentration was 0-36 µg. per g. The secondpatient, who had a coronary arteriovenous fistula, received atotal dose of 0-30 mg. per kg. and the concentration was 010µg. per g. The third patient, who had mitral stenosis, receiveda total dose of 0.-48 mg. per kg. and the concentration ofnoradrenaline in the atrium was 0-04 µg. per g.1. Lyell, A. Brit. J. Derm. 1956, 68, 355.2. Bertler, A., Carlsson, A., Rosengren, E. Naturwissenschaften, 1956,

43, 521.3. Holtzbauer, V., Vogt, M. J. Neurochem. 1956, 1, 8.4. Orlans, F. B. H., Finger, K. F., Brodie, B. B. J. Pharm. exp. Therap.

1960, 128, 131.5. Crout, J. R., Creveling, C. R., Udenfriend, S. ibid. 1961, 132, 269.

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These preliminary observations show that reserpine, givento patients in common clinical doses, is capable of reducingthe concentration of noradrenaline in the heart to levels com-

parable to those observed in laboratory animals receiving singlelarge parenteral doses of the drug. But, since the level towhich the noradrenaline concentration was depressed was notuniform, it may well be that the effects of this drug are depen-dent on the total cumulative dose in relation to bodyweight,and on the variable absorption of the drug.Because depletion of noradrenaline stores in tissues can be

effected clinically by the use of reserpine-a drug which doesnot by itself profoundly alter arterial pressure-factors otherthan the store of noradrenaline must be considered importantin the maintenance of arterial pressure.

CHARLES A. CHIDSEYEUGENE BRAUNWALDANDREW G. MORROW.

National Heart Institute,Bethesda, Maryland.

MANIPULATIVE TREATMENT IN GENERALPRACTICE

SIR,-I have practised manipulative surgery for overthirty years, and I take the view that any general practi-tioner should have at his finger tips the ability to carry outsimple manipulative techniques. The late James Mennelldescribed the fundamental principles of manipulation.He advised that each manipulation should be carried out

with traction and countertraction applied to separate the

component bones and to restore the extensibility and flexibilityof joint structures. While these separating forces are applied,involuntary movements-i.e., the gliding, rotatory, and slidingmovements of one bone on another-are executed.

Again, and still under traction and countertraction, the jointis guided through the range of active movement up to thepoint of pain. At no time must force be employed nor shouldthere be undue reaction, and the joint manipulated should feelbetter in 48 hours or sooner. Osteopaths have devised specialtechniques for the spine in order to

" articulate " the jointmanipulated. This implies ensuring full movements of thecomponent bones of one on the other, both voluntary andinvoluntary.Provided the. general practitioner has developed a

workable technique, he can employ it for recent injurieseither immediately or during some stage of recovery.For full function of a joint there must be full movements,both involuntary and voluntary, and the latter cannot bepresent without the former. He can also employ it toovercome the effects of postural, occupational, andrecreational strain, which may have devastating effects

throughout life. The muscles are affected for threereasons:

a. As the result of strain they do not support the circulationwithin them so that metabolites collect, and they becomepainful and lose some of their extensibility and flexibility. Thismay explain the so-called " nbrositis " in muscles and thecorresponding pannicular and areolar tissues, which oftenshows itself as a muscular condition by the age of 30. Radio-graphs of the joints show no bone involvement, and aftermanipulative techniques, the extensibility and flexibility arerestored to the affected muscles.

b. If the condition of strain persists, the corresponding jointswith their component parts become involved and the musclesthen go into protective spasm. This is most common around40. Even in the spine if the discs are involved, radiographs ofthe joints do not necessarily show pathological changes. Inthis early stage manipulative techniques can produce completerecovery.

c. If the condition of strain of the joint persists, in timeosteoarthritis will intervene or, in the case of the spine, spon-dylosis with disc degeneration and osteoarthritis will develop.At this stage true fibrositic infiltration of the muscle can have

taken place, and manipulative techniques, though possiblyimproving the range of joint movement, do not necessarilyproduce complete freedom from symptoms. Radiographs atthis stage confirm the arthritis or spondylosis.

’

Again, the practitioner can employ manipulation forrheumatic degenerative conditions in the paratenons of thetendons, which in the case of the shoulder, produce a typeof " frozen shoulder ":

In this type of shoulder the pathological process passesthrough what I call a " negative phase " of healing, whenadhesions are vascular and the patient’s sleep is disturbed bypain. Some of these cases can be aborted if rested in bed

completely, but often all forms of physical treatment, includingmanipulative techniques, aggravate. Deep X rays at this stageseem to dry up inflammatory swellings, and quickly producewhat I call the " positive healing phase "; immediately thepatient starts to get sleep. Gentle manipulative techniques canthen help to produce quick recovery.The field covered by these three types of cases is

enormous, and it includes all injuries, degenerativediseases, and rheumatic diseases. Before applyingmanipulative techniques the medical practitioner should:

a. Realise what phase and stage the condition is passingthrough.

b. Ensure that no septic or metabolic process exists.c. See that every patient has suitable radiological cover,

especially those associated with trauma and those over fifty,where there may be osteoporosis, arthritis, or spondylosis.

d. Apply gentleness and never employ a long lever. Ifthere is a reaction, it should have passed off within 48 hours.

e. Unless he is an expert manipulator, confine himself tomanipulations without anaesthetic and leave the others to theexpert.

f. Be very careful to see that the injured part is not in anyway pulled about or overtreated. There must be gradual dailyimprovement.

In all the conditions mentioned above where manipula-tion can help, there is often protective muscle spasm, andno doubt Dr. Stanton (June 9, p. 1243) is right in attribut-ing the benefits accruing from manipulative treatmentchiefly to the relief of muscle spasm. Independently ofMr. Ellis 1 I have used an ethyl-chloride spray for 15years, and even before the war I had a cold-water machinefor cooling inflamed joints. The procedure helped to

relieve spasm. So many conditions are covered by theabove, and so many patients can be relieved by manipula-tion, that the rudimentary principles described, and theiradministration, should be understood and practised byevery general practitioner.At the same time one must realise that, in everyday

practice, accidents, such as spontaneous fracture of anosteoporotic bone or one associated with secondaries orPaget’s disease, or displacement of a disc causing trans-verse myelitis or nerve-root damage, are not uncommon.If these happen in relation to manipulative treatmentwhen every normal precaution has been taken, it is unfairto blame that treatment, because these complicationswould probably have occurred spontaneously.

In 1934, when the Osteopathic Bill was being broughtup in Parliament,2 I suggested that " there is room in thephysiotherapeutic department of every hospital for thecreation of the post of two house-surgeons or clinical

assistants, whose work should be to carry out gentle dailymanipulative movements to the patients attending thedepartment, as the doctor in charge has no time to carrythese out daily ". If each hospital in England had beenturning out four good manipulators each year since 1934

1. Ellis, M. Brit. med. J. 1961. i, 250.2. Tucker, W. E. ibid. 1934, i, 595.