War Surgery and Medicine
The discovery of penicillin and its use in the treatment of war wounds produced a revolutionary change and stimulated the surgeons to carry out the early suture of wounds, which, with the control of infection by penicillin, led to a marked improvement in wound healing and a marked diminution in hospitalisation. The first experience of 2 NZEF with the new antibiotic was in Cairo, page 14 where Pulvertaft of 15 Scottish Hospital produced some penicillin and made a small supply available to our hospitals for the treatment of special cases.
Then in August 1943 there was held at Tripoli an epoch-making conference, when Professor Florey and Brigadier Cairns came out from England to superintend experiments and evaluate the results of penicillin treatment of wounded from the Sicilian campaign.
Professor Florey described the following results of his experiments at Oxford:
Penicillin had been introduced through small tubes in the wound every 8 hours for 4–5 days. It had been found that there was consistent eradication of the streptococcus and staphylococcus, but no effect on the gram negative bacilli, such as the pyocyaneus and B. Coli. The wounds had healed well in spite of continuing gram-negative infection. Osteomyelitis had been cured by large doses of intravenous penicillin.
Professor Florey drew attention to the presence of resistant strains of staphylococci, and also to the fact that bacteria can become artificially resistant following administration of penicillin, so that adequate dosage should be given at once as was done in the case of the sulphonamides. He stated that fractures with longstanding infection had not been improved by penicillin.
The experimental treatment of the wounded from Sicily was carried out in two British hospitals and 3 NZ General Hospital in the Tripoli area. For the experiments penicillin was available as a calcium salt for local application, and as a sodium salt for parenteral use. The calcium salt was mixed with sulphanilamide to secure a penicillin content of three strengths—5000 units, 2000 units, and 500 units per gramme. The 5000-unit strength was used in a small number of cases when a single application was given prior to suture without tubes, while the 2000-unit strength was used as the routine wound application, and the 500 strength was prepared for use as a daily surface application for burns. It was also prepared in a solution of 250 units per cubic centimetre which was instilled into the wound through tubes, at first eight-hourly and later twice daily, the standard total dosage advised being 50,000 units.
The sodium salt was made into a solution containing 5000 units per cubic centimetre, and 500,000 units was given in doses of 15,000 units, intramuscularly or intravenously every three hours, for wounds with associated fracture of the long bones.page 15
Results in Soft-tissue Wounds
In a series of 171 soft-tissue wounds from Sicily most cases healed well with early closure and the use of penicillin, in spite of the presence of gram-negative pus. Some cases had wound toilet in Sicily; others arrived in North Africa without treatment and then the wounds were excised. At Sousse and Tripoli most wounds were sutured after the application of penicillin powder and then irrigated with penicillin solution introduced through small tubes into the wounds for some days afterwards.
Results in Fracture Cases
Fracture cases were dealt with in several different ways. The majority were given primary surgical treatment in Sicily; in a few cases penicillin was applied locally to the wound, but most had no penicillin. The cases were all sutured after arrival at Tripoli when the condition of the wound permitted mechanical closure, penicillin being applied locally. Parenteral penicillin was then given either intramuscularly or intravenously in dosages of 400,000 to 500,000 units over five days.
In the early cases some of the wounds were closed under considerable tension and the wounds broke down. Later the centre of the wound was left open whenever tension was great or a dead space was unavoidable. Constant inspection of the wounds was found to lead to fresh infection. Of the main group of twenty-three cases, twelve were wholly successful, five partially so, and six were failures, with one amputation. The humerus cases were more successful than the femurs.
Altogether the results were not such as to warrant the adoption of primary suture of fractures, or immediate suture on arrival at Base Hospital without previous penicillin treatment. Some very septic cases were observed, and drainage was necessary in the majority of cases. The results showed, however, that in the majority of cases infection had been satisfactorily controlled, and that with a larger amount of penicillin administered parenterally over a longer period better results could be hoped for.
Cultures taken from the wounds in Sicily showed infection by staphylococci in 23 per cent, haemolytic streptococci in 47 per cent, and claustridia in 30 per cent. Welchii was the predominant anaerobic organism.
Cultures taken at different periods from the wounds investigated in Tripoli showed that staphylococcus aureus was present in 53 per cent of the wounds, and streptococcus haemolyticus in 12 per page 16 cent. The streptococci were nearly always associated with staphylo-cocci. It was the exception for the wound to be free of cocci, though it might not be clinically septic. After wound treatment with penicillin the gram-positive organisms were got rid of in seven days, sometimes in two to three days. Pyocyaneus was very common, and its lack of pathogenity was doubted by the bacteriologist. Resistant strains of staphylococci, but not of streptococci, were encountered. In the cases of chronic infection seen at Algiers the organisms were nearly all streptococci.
Discussion on Results
In subsequent discussion Professor Florey summed up the opinion of the conference by stating that whereas the results in the treatment of simple flesh wounds had been satisfactory on the whole a larger dosage of penicillin intramuscularly over a longer period was necessary in the treatment of fractures, for which he suggested partial suture of the wound with drainage. The Consultant Surgeon MEF, Major-General Ogilvie, counselled concentration on the fracture cases as long as penicillin was in short supply. It was noted generally that gram-negative infections, especially of the pyocyaneus, were commonly present when the gram-positive organisms had been largely eliminated by penicillin. Profuse discharge was often noted, but there were no general ill-effects and no marked interference with the healing of the wound. Penicillin, besides preventing and dampening down acute infection, had produced a feeling of better health.
For the treatment of fractures it was recommended that sodium penicillin should be given continuously for a minimum of five days, either by three-hourly intramuscular injections or in continuous glucose saline drip infusion. The five-day course, totalling 500,000 units, was considered sufficient for fractures of the upper extremity, but for fractures of the femur and tibia a course lasting seven to ten days (700,000 to 1,000,000 units) was advised. These figures referred to severe comminuted fractures. An incomplete facture, or a fracture in other than the long bones, did not usually require more than 300,000 units, and calcium penicillin applied locally sometimes sufficed. Looking back it was clear that the length of the course (five days) for the experiments had been too arbitrarily fixed and was not related closely enough to the severity of the fracture. (Later in the war it became the custom to give much longer courses for the severe cases.)
The Consultant Surgeon 2 NZEF suggested at the conference that the better technique might be the delayed suture of wounds, following wound and intramuscular injection with penicillin, the wounds having previously been excised. Certain wounds, such as the page 17 large buttock wound, where severe infection from contamination would almost certainly follow if the wound were left open, might be primarily sutured and tubes for instillation of penicillin inserted. When tension was great, suturing was not advisable, especially in the lower third of the leg. Deep retained stitches could be obviated by employing a figure-of-eight stitch, and fairly thick silk drawn through sulphonamide paste might be used instead of silkworm gut; and stitches were better if not close together. The sooner a wound was closed the better, as infection was inevitable in every open wound. Fracture cases did not seem to be suitable for primary suture, but penicillin powder and penicillin fluid could be used to clean the wound for possible early secondary suture. In penicillin there was a powerful method of eradicating gram-positive organisms. With an adequate supply and improved technique a marked advance in the treatment of war wounds was likely to eventuate.
The New Zealand Medical Corps had been privileged to take part in these important and historical investigations and in the conference itself, and this, fortunately, made our Corps penicillin-minded and eager to adopt the new line of treatment. A complete resume was written by the Consultant Surgeon and sent to all our units, with full details of suggested forms of treatment.
Experiences in Italy
Further trials with penicillin were carried out in Italy. Lieutenant-Colonel J. S. Jeffrey, who was Surgical Divisional Officer in the main British hospital in Tripoli, had been appointed to superintend the supply and application of penicillin, and, as both our CCS and 3 NZ General Hospital had first-hand knowledge of the experiments in Tripoli, our hospitals were utilised in the further experiments.
From December 1943 the method employed in the wound treatment by penicillin was:
Spraying penicillin sulphathiazole powder in the primarily trimmed wounds.
Evacuating the patient to the Base, in a plaster splint if deemed necessary, without disturbance of dressing.
Carrying out a delayed primary suture on arrival at a base hospital, and
With regard to fractures, the same primary treatment was given, and again suture performed at the Base, but
The wound was not entirely sutured, a gap being left in the centre for drainage and relief of tension.
Sodium penicillin was injected intramuscularly three-hourly in doses of 15,000 units for five or more days.
The limb was- put in plaster or other splints and left untouched for three weeks unless there was some indication of complication.
At first in the Italian campaign penicillin was available in such small quantities that its use was restricted to wounds in the early stages, but the supplies increased steadily. By May 1944 full courses of parenteral penicillin were being given to severe burns, and in July most of the seriously infected wounds had at least one course of intramuscular penicillin, which led to a marked improvement in the general condition of the patient even if the infection did not clear up. By August sufficient penicillin was available for all purposes, and all serious cases were being given parenteral injections for the first forty-eight hours right from the time of wounding, and the sulphonamides had been displaced. Later came the administration of penicillin by continuous drip into the vastus externus from a glass container marked with bands showing the dosage for six-hour periods.
Established infection remained a difficult condition to deal with, and bacteriological investigation demonstrated the common presence of penicillin-resistant strains, especially of the staphylococcus, but penicillin was of great value in the treatment of streptococcal and anaerobic infections. Obviously penicillin was not as efficient bacteriologically as it was clinically, or else the suture of wounds could be successfully carried out in spite of the presence of pathogenic bacteria. Secondary suture was done more frequently following preparation by spraying with penicillin for several days.
In chest cases sodium penicillin, at first used intramuscularly with temporary success, was introduced into the pleural cavity, after the tapping of haemothoraces, with marked success. Penicillin was given by lumbar or cisternal puncture, 10 c.c. every four hours, to septic complications of cerebral wounds, and was also effective in meningeal infection. In head wounds sepsis was definitely reduced—in Italy it was responsible for only 34 per cent mortality as against 65 per cent at the beginning of the war. Abdominal cases were given parenteral penicillin during the final campaign in Italy with very definite reduction of intra-peritoneal infection and improved wound healing. In fracture cases parenteral penicillin was given just before, and for several days after, suture, and in much larger doses in the serious cases.page 19
In general, very little infection was noted at the base hospitals at the close of the Italian campaign. The introduction of penicillin was largely responsible for the saving of many lives and for the adoption of the delayed primary suture of wounds, with resultant marked reduction of hospitalisation and disability.