CHAPTER XIV
Penicillin and Sulfonamide Therapy
(2,410 Casualties)
James C. Drye, M. D.
Prior to May 1944, patients with abdominal injuries weretreated with some one of the sulfonamide drugs, usually parenterally. At thattime, penicillin was introduced, and thereafter it became part of the routine oftreatment.
The basis for this analysis is formed by 2,410 patients who received asulfonamide drug, penicillin, or both agents. The series is selective in that itexcludes men who presented no intraperitoneal injury at operation, patients whodied on the operating table, and patients whose records were deficient in dataconcerning antibacterial therapy. Since the analysis was not undertaken untilthe end of hostilities, no control series exists. For that matter, there wouldhave been small justification for withholding these presumably beneficial agentsfrom any wounded man in order to provide such controls.
METHODS OF ADMINISTRATION
Until penicillin became available, sulfadiazine sodium was given by theintravenous route, usually in amounts of 2.5 gm. at 12-hour intervals. The firstdose was customarily given in the shock ward, as part of the routine ofresuscitation. After penicillin had become available in sufficient quantities tobe supplied in the division clearing stations, the first intramuscular injectionwas given at that echelon. Doses in the field hospitals ranged from 5,000 to25,000 units at 3-hour intervals.
Although crystalline sulfanilamide was available forintraperitoneal use throughout the war, it was not used regularly by this routein the Mediterranean Theater of Operations, and the same was true of penicillinafter it became available. Some surgeons used either agent, or both, with fairregularity, and most surgeons used one or the other in selected cases; thedecision was always individual. There was a notable tendency to use theintraperitoneal route whenever wounds were severe or contamination wasextensive. Crystalline sulfanilamide was used in doses of 5 to 10 gm. andpenicillin in doses of 50,000 units.
The postoperative use of both agents also varied with the practices ofindividual surgeons. Some used one or the other routinely; some only whencomplications developed. Some preferred to employ both at the same time.Sometimes one was discontinued in favor of the other. Dosages varied widely.
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CASE FATALITY RATES
Because of the variations in the use of the sulfonamides and penicillin, aswell as the variations in methods of administration and dosages, a precisestatistical analysis of the cases in which they were employed was not possible.The most practical means of determining their relative efficacy was to analyzethe case fatality rates in peritonitis.
The case fatality rate from all causes in the 2,410 cases in which one or theother, or both, of these agents was used was 23.2 percent (560 deaths). Therewere 422 deaths (24.4 percent) in the 1,732 cases treated in 1944 and 138 (20.4percent) in the 678 cases treated in 1945. These rates closely parallel the casefatality rates for the whole series.
One hundred and thirty-seven of the 560 deaths were caused by peritonitis(table 28). These deaths cannot be properly discussed until they are broken downinto two categories. As is pointed out elsewhere (p. 127), two types offatalities from peritonitis were observed in abdominal injuries in World War II.In the first, so-called contamination type, there was massive peritonealsoiling, the casualties were in shock and did not respond to the usual measuresof resuscitation, and death occurred within the first 48 hours after operation.In the second type of fatality, the patients presented the classical type ofsuppurative peritonitis. The clinical manifestations were those usuallyobserved, including fever, vomiting, abdominal tenderness, distention, and ileus.Death from this variety of peritonitis commonly occurred between the 4th and11th postoperative days. In this analysis, no deaths were attributed to theclassical form of peritonitis if they occurred within the first 3 days afteroperation.
Year | Cases |
| Bacterial peritonitis | ||
| Case fatality rate | Deaths | Case fatality rate | ||
1944 | 1,732 | 58 | 3.4 | 32 | 1.8 |
1945 | 678 | 37 | 5.5 | 10 | 1.5 |
| 2,410 | 95 | 3.9 | 42 | 1.7 |
In some cases in which peritonitis developed, the peritoneal infection was,at the most, a contributory cause of death, and antibacterial agents could nothave been expected to influence the final outcome. This group included thepatients who were moribund on admission to the hospital, those who died fromsuch accidents as aspiration of vomitus, those with serious intercurrent
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disease, and those with serious or fatal noninfectious extra-abdominalinjuries. No death in this group of cases was attributed to peritonitis in thisanalysis.
On the basis of these criteria of selection, the case fatality ratefor the classical type of peritonitis was found to be 1.7 percent, against 3.9percent for the contamination type (table 28).
In an unplanned investigation such as this, in which there isno control series and complete statistical data are lacking, it would not bepermissible to draw anything beyond tentative conclusions concerning thepossible benefits of chemotherapeutic and antibiotic agents in abdominalinjuries (tables 29 and 30). It would also not be permissible to attempt precisecomparisons between the effects of the sulfonamides and penicillin, chieflybecause the advent of penicillin coincided closely with two other events whichgreatly improved the management, and therefore improved the prognosis, ofbattle-incurred abdominal injuries in the Mediterranean Theater of Operations.The first of these events was the establishment of a theater blood bank inNaples. The second
Therapy | Cases |
| Case fatality rate | ||||
Total |
| From bacterial peritonitis | Total | From peritoneal contamination | From bacterial peritonitis | ||
1944: |
|
|
|
|
|
|
|
| Parenteral sulfadiazine alone or with intraperitoneal sulfanilamide | 361 | 117 | 12 | 18 | 32.4 | 3.3 | 5.0 |
Parenteral penicillin alone or with intraperitoneal penicillin | 727 | 158 | 18 | 2 | 21.7 | 2.5 | .3 |
1945: |
|
|
|
|
|
|
|
| Parenteral sulfadiazine alone or with intraperitoneal sulfanilamide | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Parenteral penicillin alone or with intraperitoneal penicillin | 438 | 97 | 10 | 4 | 22.1 | 2.3 | .9 |
Totals, 1944-45: |
|
|
|
|
|
|
|
| Parenteral sulfadiazine alone or with intraperitoneal sulfanilamide | 361 | 117 | 12 | 18 | 32.4 | 3.3 | 5.0 |
Perenteral penicillin alone or with intraperitoneal penicillin | 1,165 | 255 | 28 | 6 | 21.9 | 2.4 | .5 |
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Routes of administration | Cases | Deaths |
| ||||
Total | From peritoneal contamination | From bacterial peritonitis | Total |
| From bacterial peritonitis | ||
1944: |
|
|
|
|
|
|
|
| Parenteral route only1 | 635 | 131 | 4 | 5 | 20.6 | 0.6 | 0.8 |
| Parenteral and intraperitoneal routes2 | 1,097 | 291 | 49 | 27 | 26.5 | 4.5 | 2.5 |
1945: |
|
|
|
|
|
|
|
| Parenteral route only1 | 341 | 55 | 8 | 2 | 16.1 | 2.3 | .6 |
| Parenteral and intraperitoneal routes2 | 337 | 83 | 29 | 8 | 24.6 | 8.6 | 2.4 |
Totals, 1944-45: |
|
|
|
|
|
|
|
| Parenteral route only1 | 976 | 186 | 12 | 7 | 19.1 | 1.2 | .7 |
| Parenteral and intraperitoneal routes2 | 1,434 | 374 | 78 | 35 | 26.1 | 5.4 | 2.4 |
1Penicillin or sulfadiazine.
2Intraperitoneal sulfanilamide with parenteral sulfadiazine or penicillin,or intraperitoneal and parenteral penicillin.
was the wide distribution, among the surgical teams, ofportable machines for anesthesia, which thereafter was much more efficient. Thedecrease in the case fatality rates for abdominal injuries after the spring of1944 therefore cannot be attributed solely to the advent of penicillin but mustbe regarded, at least in part, as a reflection of these other benefits. Finally,there must be taken into account the increasing experience of the surgicalteams.
In addition to these major considerations, climatic andtactical factors must be taken into account in the comparison of the relativeeffects of the sulfonamides and penicillin in abdominal injuries. Thesulfonamide-treated cases were all observed in 1944, most of them in the first 4months of the year. Thisparticular period covered the fighting before Cassino and on the Anziobeachhead. Conditions of weather and terrain and facilities for evacuation werenotoriously unfavorable during both campaigns. As a rule, severe exposure wascommonplace, and the evacuation timelag was frequently prolonged. The casefatality rate, which was markedly elevated at this time, was undoubtedlyinfluenced by both factors. The corollary of this reasoning is that theimprovement which occurred later in 1944 and continued into 1945 cannot fairly be attributed onlyto the greater efficiency of penicillin, and the figures (table 29) must be interpreted in the lightof these facts.
When penicillin was substituted for the sulfonamide drugs (table 29), there was a very slight reductionin the case fatality rate in peritoneal con-
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tamination but a very considerable reduction in the rate in bacterialperitonitis. The change in therapy, as already noted, occurred in May 1944. Thecase fatality rate for all abdominal injuries fell from 32.8 percent in thefirst quarter of 1944 to 22.4 percent for the April-December period (p. 216). This decrease wasdisproportionately less than the decline in the case fatality rate observed inperitonitis alone. It was the opinion of the surgeons of the 2d AuxiliarySurgical Group that the decline in deaths from peritonitis was too marked andtoo abrupt to be explained only by improvement in weather and combat conditions,even in combination with increasing experience in the management of abdominalinjuries. They therefore concluded, at least tentatively, that penicillin wasmore efficacious than the sulfonamides in the prevention and treatment ofperitonitis secondary to war wounds of the abdomen.
The case fatality rates calculated according to route of use might seem tosuggest, on casual inspection, that deaths were more numerous when the combinedparenteral-intraperitoneal method was employed than when the parenteral routealone was used (table 30). The conclusion would be completely unjustified.Analysis of the individual cases which make up the series shows thatantibacterial agents were usually used by the intraperitoneal route only whenwounds were extensive and contamination was serious. The higher case fatalityrate therefore merely reflects the fact that these agents were usedintraperitoneally only in the most severely wounded patients. Whether the ratewould have been even higher if this route had not been employed it is, ofcourse, not possible to say.
