War Surgery and Medicine
The sulphonamides were used as a means of combating infection in wounds during the early periods in the Middle East Forces, but it was some time before the treatment was organised and made universal.
As far as the New Zealand forces operating in the Greek and Cretan campaigns were concerned, the sulphonamides were only utilised in some of the serious cases by giving doses of sulphonamides by the mouth for the first forty-eight hours.
During the second Libyan campaign sulphanilamide was applied locally to the wound and the drug was also given orally four-hourly for at least forty-eight hours. Sulphanilamide powder was supplied to the Field Ambulances at this period. The local application was continued during the subsequent treatment at the Base, especially for the cleaner wounds.
Sometimes the sulphanilamide was mixed with oil, but absorption appeared unsatisfactory. It was noted that too much powder was often introduced locally so that at the base hospitals large lumps were often seen in the wound, thereby acting as foreign bodies.
It was generally thought that septic wounds did not benefit at all from local application.
Difficulties in ensuring the adequate and regular administration of sulphonamide tablets by the mouth led to some units instituting a special sulphonamide chart so that dosage, especially in the forward areas, could be recorded and checked. This was started page 12 during the second Libyan campaign and soon became universal, and it brought about a marked improvement in the administration of the drug. In spite of this, however, it was found that in the bustle of evacuation, and the priority that had to be given to the treatment of the seriously wounded, more often than not the giving of sulphonamides was forgotten and men got only minimal and erratic doses. This caused many to give larger doses twice daily instead of the small dose four-hourly. The Australians carried out this routine with success.
The value of the drug as a bacteriostatic was stressed, with the obvious inference that it had to be given in the first twenty-four hours to be of the maximum use.
In May 1942 Major-General Monro, the Consultant Surgeon MEF, advised the supply of suitable pepper-pot tins to every Field Ambulance and every RMO so as to make the application of the powder more satisfactory.
Sulphonamides orally were utilised for later sepsis, but it was found at this stage that they had to be used with great caution because of their destructive effect on the leucocytes, and their use was controlled by repeated blood counts. Although it was held to have been conclusively proved that sulphonamides were of great value in preventing severe infection and combating early infection, there was doubt of their value in established infection. In our main hospitals in Egypt there was from the beginning some doubt as to the efficacy of the sulphonamides in controlling wound infection, as large numbers of cases had been observed during the first Libyan campaign with little or no wound treatment, yet with little resultant sepsis. And in the second Libyan campaign many of the smaller perforating and penetrating wounds healed satisfactorily with no operative treatment and no sulphonamide. This produced a natural scepticism of the vaunted value of the new drugs. The British surgeons, however, with greater experience of the more serious cases, were satisfied that the treatment was really of great value, and the utilisation of the sulphonamides, both locally and orally, became standardised and the dosage chart universal.
The Consultant Pathologist MEF laid down approved details of the administration of sulphonamides at the first Cairo surgical conference held in February 1942 as follows:
Given in lemon; immediate primary dosage of 2 grammes, then 1 gramme 4 hourly for 48 hours. Then M & B (Sulphathiazole) 20–24 grammes in 4 days.
At the Alamein period, October 1942, the use of sulphonamides had become more widespread. Apart from the regular use locally in the wound, and orally by means of tablets, sulphadiazine was page 13 being used intravenously for anaerobic infection, and also used intra-abdominally. The usual dose given for gas gangrene was 60 grammes in forty-eight hours, or 15 grammes intravenously daily.
At the surgical conference held in Cairo in July 1943 an evaluation of sulphonamides as used locally in the wound showed that:
There was undue absorption from large wounds.
Clumps of powder acting as a foreign body were often seen.
There was a lack of continuous application.
Toxic skin and other reactions were often seen.
The toxic skin reactions were stressed by Lieutenant-Colonel R. Park, NZMC, skin specialist at 1 NZ General Hospital, who read a special paper on the subject at the conference. As a result, the continued local treatment by sulphonamides was largely given up in ordinary wound treatment.
It was considered that local sulphonamide treatment was of little use in septic cases, and that the sensitisation produced by its continued use would be a serious matter for any patient developing such infections as pneumonia and, because of the sensitisation, debarred from treatment by sulphonamides. Some serious cases of renal disturbance with anuria also occurred, and at post-mortem sulphonamide crystals were found blocking the urinary tubules.
This led to the discontinuance of prolonged sulphonamide therapy for septic wounds. Administration, except as a primary preventative measure, was thereafter restricted to cases of acute types of infection such as that due to the streptococcus. The dosage and period were also strictly limited and blood tests made in any doubtful cases.
The amount of sulphanilamide used locally was also strictly limited to 5 grammes, and this prevented any undue absorption.
Thereafter sulphonamide treatment was continued as a preventative locally and systemically till it was gradually displaced by penicillin, but it retained its place in the treatment of head wounds, where sulphadiazine was given in conjunction with penicillin, of eye wounds, and of penicillin-resistant infections.