Postgrad Med J: first published as 10.1136/pgmj.22.246.118 on 1 April 1946. Downloaded from 118 POST-GRADUATE MEDICAL JOURNAL April, I946 If the patient is allowed fluid by mouth, it 4. If the apparatus does not appear to be work- should be given by the feeder between times of ing, the clips should be clamped, the appa- aspiration. ratus disconnected from the gastric tube and Aspiration is performed at regular intervals some water injected down the tube to make either every hour or half-hour according to sure that it is patent. instructions. The aspirated material must always be saved The Time for Removal of the Tube: The tube is for inspection. removed under the Doctor's instructions. In 2. Continuous Suction: A study of the diagram cases of intestinal obstruction this is usually (Fig. 2) will explain the work of the apparatus, after the patient has had one bowel action, and and attention must be to the has passed flatus on at least two occasions. particular paid After operations on the stomach, the tube is following points:- removed when the aspirated contents appear I. The reservoir A must never be allowed to clear contain bile. become empty. and 2. The end of the tubing in bottle B must be Vomiting: If a patient who is undergoing gastro- below the level of the water. intestinal suction vomits, it indicates that there 3. The clips D and E must be clamped before is some fault in the procedure, and is a reflection and during the changing of the bottles A and on the management of the suction. Every B. They are then released to re-commence effort should be made to discover and correct the suction. fault. RECENT DEVELOPMENTS IN WOUND ANTISEPTICS By H. E. DALE copyright. During recent years a considerable amount of appear that it was selected primarily for this work has been carried out with the object of reason as the bacteriostatic powers of acriflavine, finding a non-toxic antiseptic which would be neutral acriflavine (or euflavine) and proflavine effective against all the bacteria likely to be present against various organisms are approximately the in wounds. From I939 onwards sulphonamides, same. In I934 acriflavine was shown to be a especially sulphanilamide, have been used exten- mixture of the hydrochlorides of 2 : 8-diamino- local in the and chloride and 2 8-diamino- sively by application prevention Io-methylacridinium http://pmj.bmj.com/ control of wound infection, and they are undoubt- acridine, and neutral acriflavine a mixture of edly effective bacteriostatic agents. Their action 2: 8-diamino-io-methylacridinium chloride and. is, however, inhibited by pus and necrotic tissue, 2: 8-diaminoacridine hydrochloride. Proflavine is and they are ineffective against some organisms. however, not a mixture but a simple salt-- Penicillin has and will be used extensively, and 2 : 8-diaminoacridine sulphate. It is the precursorl may well replace many antiseptics, but it is not of acriflavine and neutral acriflavine and is therefore. effective against gram-negative organisms such as simpler to manufacture. Ps. pyocyanea and Proteus and supplies are at In I936 Albert Linnell and others began' on October 2, 2021 by guest. Protected present restricted. intensive investigations on the acridine series. They prepared all the possible aminoacridines and investigated the relation between chemical con- Acridines stitution and activity. They found that amino The acridines or flavines, as they have been groups in positions 2, 3, or 5 increased the activity called, were introduced by Browning in 1917, of the acridine molecule and gave compounds of and recent work on their properties and methods high bacteriostatic activity. 2: 7-diaminoacri- of application has brought to light many interesting dine and 5-aminoacridine were considered to be facts. For some time acriflavine was considered the best of the series. to be the most suitable acridine for use as an It is well known that chlorophenols are con- antiseptic, but in I94I proflavine sulphate was siderably more active than the parent phenol, included in the 4th Addendum to the British and experiments were also carried out to determine Pharmacopoeia. Acriflavine is much more soluble in the effect of introducing chlorine into amino- water than the other acridines, and it would acridines. New chloroacridines were prepared but Postgrad Med J: first published as 10.1136/pgmj.22.246.118 on 1 April 1946. Downloaded from Alpril, 2-946 WOUND ANTISEPTICS they were less active than the aminoacridines and More recently Albert et al. (i945) in a general possessed no therapeutic advantages. 2-chloro-5- survey of the acridine series have described three aminoacridine was found to be most active, but new drugs, I: 9-dimethyl-proflavine, 5-amino-I- also the most toxic and the 6- and 7-chloro-2- and aminoacridines methylacridine 2-nitro-5-aminoacridine. were quite inactive. Bacteriological tests showed that i : 9-dimethyl- Attention was again drawn to proflavine and proflavine is approximately five times as potent as the two new acridines 2: 7-diaminoacridine and proflavine against gram-positive and twice as 5-aminoacridine, when Russell and Falconer (I940) potent against gram-negative organisms without showed that buffered isotonic solutions of pro- any increase in toxicity. flavine sulphate with a pH approaching neutrality 5-amino-I-methylacridine is non-staining, less could safely be applied to the surface of a rabbit's toxic and more active than 5-aminoacridine. brain. They found that both acriflavine and The outstanding property of 2-nitro-5-amino- neutral acriflavine caused damage, but the newer acridine is its marked anti-streptococcal action compounds 2:7-diaminoacridine and 5-amino- suggesting a sphere of usefulness in the treatment acridine did not. The surprising fact that isotonic of haemolytic streptococcal infections and pro- solutions of proflavine could be applied to such phylactically in obstetrics. delicate tissues as brain tissues stimulated greater interest in this compound and also in the newer acridines 2: 7-diaminoacridine and 5-aminoacri- Relative dine. Clinical reports on the new acridines have Toxicity been published in this country and in Australia Selbie and McIntosh (I943), carried out experi- confirming their value as non-toxic antiseptics, mental work on the action of antiseptics on muscle but it is difficult to assess how these new compounds and connective tissue. The assessment of toxicity differ in their bacteriological action from proflavine. by this method was designed to avoid reactions It has been suggested that the divergence of opinion other than those arising from the toxicity of the on their relative toxicity to leucocytes and action substance to be tested, and to simulate as far as certain bacteria possible, in experimental animals, conditions likely against may be dependent upon copyright. the methods employed by different workers. to be found in wounds. A known quantity of the Generally, it can be said they do not differ very substance to be tested was dissolved in water, and much in their action from that of proflavine against o.I and 0.2 c.c. were injected into the thigh muscles most organisms. 5-aminoacridine, unlike most of mice. The mice were killed after 3 days and other acridine antiseptics, does not stain the skin it was found that any lesions were fully developed or fabrics. It is a yellow compound, but the by that time. Any visible reactions were noted yellow colour may be removed easily by washing and the injected muscles were examined histo- with water. As acridine stains are logically. Proflavine sulphate produced approxi- usually very mately the same degree of muscle necrosis and difficult to remove, this is a decided advantage. http://pmj.bmj.com/ Solutions of proflavine sulphate deposit on exposure connective tissue reaction as 2 : 7-diaminoacridine to but solutions of hvdrochloride and 5-aminoacridine hydrochloride, light, 5-aminoacridine hydro- but the acridine bases were chloride are stable. 2 7-diaminoacridine hydro- considerably more chloride and proflavine sulphate are stated to be toxic than their acid salts, producing more necrosis .ess toxic than 5-aminoacridine hydrochloride and and considerable cellular reaction. The toxicity also possibly effective against Ps. and of bases in pharmaceutical preparations was also Proteus. pyocyanea determined and it was shown that many had a Berry (I941) investigated the bacteriostatic high degree of tissue toxicity. This work is not on October 2, 2021 by guest. Protected values of the two components of acriflavine against yet completed, but experiments carried out so far various organisms and found that mixtures pos- show how important it is to examine the bases sessed no greater bacteriostatic power than either used in ointments and other pharmaceutical pre- compound. He suggested that the neutral hydro- parations for their toxicity to tissues before use. chloride of 2 : 8-diaminoacridine, i.e. proflavine monohydrochloride, would be the best acridine to use. Method of Application Albert (I943) described several salts of proflavine, The acridines, until recently, were only applied the more important being the monohydrochloride to wounds in solution in water or saline, but it and neutral sulphate, orange to red powders has now been shown that proflavine can safely be giving solutions which are nearly neutral. They applied in powder form to infected wounds, may replace the more acid proflavine sulphate provided small amounts only are employed. Sup- which is usually employed. purating wounds have been