547INTRAMUSCULAR SULPHONAMIDES AND QUININE

I THE LANCETLONDON: SATURDAY, NOVEMBER 7, 1942

INTRAMUSCULAR SULPHONAMIDES ANDQUININE

TROUBLES with sulphonamides given intramus-

cularly have raised again the questions of techniquewhich have been thrashed out many times for quinine.With the non-irritant injections, such as liver extract,no complications arise, though even there correct

technique may save the patient pain at the time ofinjection and stiffness afterwards. Irritant injectionsare tolerated better by muscle than any other tissue,though THROWER 1 has demonstrated that localnecrosis is common when the highly alkaline sodiumsulphapyridine is given intramuscularly. Such slough-ing, however, as a rule produces nothing worse thantransient pain and disability. The serious troublesarise when the injected fluid reaches adjacent nerves.There was, for instance, the Trinidad case of ten yearsago in which an injection of quinine into the buttockled to a sciatic palsy and a mighty legal battle endingbefore the Privy Council.For the sulphonamides and antimalarial drugs the

technique is much the same. The safest and least

painful site is the upper and outer quadrant of thebuttock, at the junction of the upper and middlethirds of a line joining the posterior superior iliac spineto the tuber ischii, well away from the sciatic and

superior and inferior gluteal nerves. A sharp, fine-gauge serum needle is used-a hypodermic needle isnot long enough-and needles should be periodicallytested by applying a bending strain between hub andpoint. Needle and syringe must be clean and sterile ;this is best achieved by boiling. If spirit or anti-septics are used they must be washed off before theneedle is inserted. Injections should always be givenin a good light. The patient will usually be in thesemi-prone position with the upper knee drawn up.The injection site is painted with a coloured antiseptic.The syringe is then filled with the solution, a bubble ofair being included which will be injected after thefluid. It is important not to leave an open trackalong which fluid may leak back, and the left handtherefore draws the superficial tissues downwardsbefore the needle is inserted. The syringe and needleare held in the right hand as one holds a dart, thefinger-tips gripping the hub of the needle and thenozzle end of the syringe. A fairly accurate estimateof the depth of the subcutaneous fat must be made,for the needle must reach well into the gluteal muscles.The needle is inserted with one quick stab but notbeyond half an inch from the hub, the ulnar edge andlittle finger of the right hand acting as a stop. Thishalf an inch is an essential precaution against theneedle breaking, for any break usually occurs at thejunction of the needle and its hub. Aspiration is thenattempted to ensure that a vessel has not been entered,and thereafter the injection is given steadily andslowly followed by the air bubble to clear the needle.When the needle is withdrawn it should be inspectedto ensure it has not broken. Consecutive intra-

1. Thrower, W. R. Lancet. 1940, 1, 967.

muscular injections should be given on alternatesides. Some say that the buttock becomes less sensi-tive when injections are repeated, but it seems morelikely that the patient acquires a higher threshold todiscomfort. With sulphonamides and quinine, at anyrate, this route should be used as little as possible.If an indolent ulcer does develop at the site of anunlucky injection the quickest way to heal it, oncethe acute illness is over, is to excise it under generalanaesthesia and suture the wound without drainage.

There are usually urgent reasons for injecting solu-tions of the soluble sulphonamides. The patient maybe unable to swallow, and in severe infections it maybe necessary to supplement or precede oral by paren-teral therapy in order to raise the blood concentrationof the drug rapidly to an effective level. Intravenousmedication has many advantages in these cases,

principally because the peripheral circulatory collapseoften present in the very ill causes local stagnation ofany solution injected otherwise than into a vein. Butif veins are collapsed or inaccessible there is noalternative to intramuscular therapy except hypo-dermoclysis, a procedure of questionable value. The

sulphonamides given by injection fall into two mainclasses-those in which sulphanilamide is combinedwith a solubilising group to form neutral solutions,and the alkaline sodium salts of various derivatives ofsulphanilamide. The first class includes the dyecompounds, now largely superseded, and ’ Solu-septasine ’ ; the second group consists of the sodiumsalts of sulphapyridine, sulphathiazole, sulphadiazine,sulphacetamide and so on. Unlike the others of class2, the sodium salt of sulphacetamide is neutral, butunfortunately its antimicrobic potency is low. Therest of the sodium salts are highly alkaline ; sodium

sulphapyridine for instance is as alkaline as N/10caustic soda. The soluble derivatives of sulphanil-amide are administered in solutions up -to 10%,and up to 10 c.cm. can be given intramuscularly,but such a volume is painful merely for mechanical-reasons however carefully the injection is given. Thealkaline sodium salts are usually given intramuscularlyin 33 3 % aqueous solution, and if danger is to beminimised not more than 3 c.cm. should be given inone injection ; otherwise the pressure of fluid maylead it to track along the intramuscular planes toimportant structures.

Injection of quinine is called for most often

in Plasmodium falciparum (subtertian, malignanttertian) infections. Coma in adults and convulsions inchildren are urgent indications. So are hyperpyrexiaand the persistent vomiting which is common in the" bilious remittent " type of subtertian fever. Ofteniri heavy infections although there is no vomiting theabsorption of quinine appears to be slow and feverwith headache persists ; such cases respond well toa single injection of quinine. Intramuscular injectionstill is more popular than intravenous although formore than thirty years writers have urged the advan-tage of the intravenous route. Intravenous quininehas the theoretical advantage of bringing the druginto rapid and immediate contact with the parasite,but if given rapidly or in concentrated solution it

may be followed by a fall of blood-pressure and bysudden death ; locally it may cause thrombosis in avein. Intramuscular injection has the disadvantageof being painful and of producing a local slough, which

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if technique is faulty may become infected giving riseto an abscess, or may even be followed by tetanus.In spite of the slow absorption by this route the smallamount of quinine which is absorbed seems to beextremely potent in bringing about beneficial andoften dramatic results. Possibly the drug acquiresadditional therapeutic virtue by coming into contactwith damaged tissues. The intramuscular route isused of necessity in children when injections are

required. Abscess formation and pain can be pre-vented by careful technique. Quinine dihydro-chloride is the salt used for injection and it is

preferable to use sterile ampoules of the solution whenavailable. There are reliable ampoules on the marketcontaining gr. 5 and 6 in 1 c.cm. and gr. 7 and 10 in2 c.cm. of water. The solution may, however, beprepared fresh and sterilised by boiling. Quininedihydrochloride is soluble 1 in 0.6 of water. It mayalso be made up as gr. 7 in 3 c.cm. of normal saline.The most important point in technique is to ensurethat the syringe is sterile ; with this precaution theincidence of abscess in one colonial hospital has beenless than 1 in 5000. The solution, which is of a syrupyconsistence, is injected very slowly to avoid pain,taking two or three minutes. A hasty injection isusually followed by agonising cramp travelling downthe leg. Local massage after injection is painful andunnecessary. The dose and frequency will dependon the particular case. Relatively large doses aregiven to children because the drug is absorbed slowlyand hence will have a prolonged action. Five grainscan be given to an infant. In adults, in severe cases,10 or 15 grains should be given at once. Ten grainsshould be repeated six-hourly in cases ef coma for 3 or4 doses. The site of injection should be varied eachtime. In milder cases a single injection of 7 or 10grains will often stop vomiting, relieve headache orreduce the temperature when full doses are given bymouth as well. Mepacrine injections are best given in-tramuscularly, the dose being O’05-O’l g. They do notcause sloughing and absorption is rapid. Toxic symp-toms including mepacrine " psychosis " are frequentafter large doses intravenously, and delayed collapseand sudden death after 12 hours have been recorded.The drug compares favourably with quinine in itseffect on the fever and parasites, though extravagantclaims were made in its early trials. Both mepacrineand quinine have been subject to abuse by givinginjections indiscriminately-often with the sole objectof gain and even in cases when the diagnosis of malariawas not established. This should not be allowed toobscure the fact that both drugs are safe and efficaciouswhen given intramuscularly within the correct indi-cations and with good technique.

EMOTIONS AND GASTRODUODENALFUNCTION

THE association of peptic ulceration with thenervous system has long been recognised, but therehave been few experimental observations on the

relationship of the emotions to gastroduodenalfunction, partly because of difficulties in assessingemotional states and excluding personal bias in theobserver. The experimental approach, too, has beenbaulked by the persistent idea that " functional " and"

organic " conditions are separate, rarely meetingand never mixing. An increasing volume of work on

the psychosomatic aspects of medicine is showing howfalse such a separation must be. The question is nolonger Has this patient an organic lesion or a neuro-sis ? but Which of the two is the primary conditionsince both are present ? 1 British medicine hasattached importance to the underlying nervous

constitution and the significance of anxiety and strainin the aetiology of peptic ulcer, but most studies on thissubject have correlated personality types and occupa-tional stresses with the incidence of such ulceration.MITTELMANN and others 1 in America have now set

out to relate emotional states to actual changes ingastric motility and secretion. Normal subjects andpatients with peptic ulcer were examined undercontrolled conditions in which some 160 observationswere made. The subject swallowed a double rubbertube, to one orifice of which a thin rubber balloon wasattached ; this was inflated in the stomach and thetube leading from it was connected to a kymographby way of a water manometer, and gastric contractionswere thus recorded. The second tube was open andgastric juice was withdrawn through it by continuoussuction. Movements of the chest wall and variationsin finger temperatures were also recorded. The samesubjects were repeatedly examined and, after controlperiods during which as much mental and physicalrelaxation as possible was achieved, several experi-mental periods were studied during which the emo-tions were excited in different ways. The mentalstimuli applied, judging from previous study of hischaracter and personality, were such as to challengeor undermine the subject’s sense of emotional securityand to reinforce old stresses. The type and intensityof emotions induced by carefully chosen situations orquestions naturally varied from subject to subject,and their physiological changes in gastric secretionand motility naturally differed too, even during periodsof apparently complete relaxation ; but allowing forthis the subjects showed remarkably consistentreactions to the emotions engendered. Tension,anxiety, resentment and anger were almost alwaysaccompanied by increase in secretion of hydrochloricacid and pepsin; peristaltic activity became con-

tinuous and the contractions increased in size ; the

respiration-rate became more rapid and breathingshallower and there was usually a drop in finger tem-perature. These reactions were seen in subjects withand without ulcer ; but in the ulcer patients painoften developed as well, and the changes on the wholewere ampler. When feelings of security and assur-ance were induced, however, gastric function revertedto normal. The observers suggest that besides thesevariations in secretion and motility under emotion,changes may be found in gastroduodenal vascularity ;thus in conditions of induced anger and resentmentthey saw the blood-vessels of a gastrostomy patientdilate. This implies a direct relationship between suchchanges and mucosal erosions or actual ulceration.When the responses of the normal subjects investi-

gated were closely analysed, some contradictions werenoted. In some people emotional stimuli may causegastric inhibition rather than stimulation, and inthese fear rather than resentment seems to be thedominant feeling. Among the peptic ulcer patientsno case of such inhibited action was noted ; and their

1. Mittelmann, B., Wolf, H. G. and Scharf, M. Psychosom. Med.January, 1942, p. 5.