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Chapter 14

Contents

CHAPTER XIV

Penicillin and Sulfonamide Therapy 
(2,410 Casualties)

James C. Drye, M. D.

Prior to May 1944, patients with abdominal injuries were treated with some one of the sulfonamide drugs, usually parenterally. At that time, penicillin was introduced, and thereafter it became part of the routine of treatment.

The basis for this analysis is formed by 2,410 patients who received a sulfonamide drug, penicillin, or both agents. The series is selective in that it excludes men who presented no intraperitoneal injury at operation, patients who died on the operating table, and patients whose records were deficient in data concerning antibacterial therapy. Since the analysis was not undertaken until the end of hostilities, no control series exists. For that matter, there would have been small justification for withholding these presumably beneficial agents from any wounded man in order to provide such controls.

METHODS OF ADMINISTRATION

Until penicillin became available, sulfadiazine sodium was given by the intravenous route, usually in amounts of 2.5 gm. at 12-hour intervals. The first dose was customarily given in the shock ward, as part of the routine of resuscitation. After penicillin had become available in sufficient quantities to be supplied in the division clearing stations, the first intramuscular injection was given at that echelon. Doses in the field hospitals ranged from 5,000 to 25,000 units at 3-hour intervals.

Although crystalline sulfanilamide was available for intraperitoneal use throughout the war, it was not used regularly by this route in the Mediterranean Theater of Operations, and the same was true of penicillin after it became available. Some surgeons used either agent, or both, with fair regularity, and most surgeons used one or the other in selected cases; the decision was always individual. There was a notable tendency to use the intraperitoneal route whenever wounds were severe or contamination was extensive. Crystalline sulfanilamide was used in doses of 5 to 10 gm. and penicillin in doses of 50,000 units.

The postoperative use of both agents also varied with the practices of individual surgeons. Some used one or the other routinely; some only when complications developed. Some preferred to employ both at the same time. Sometimes one was discontinued in favor of the other. Dosages varied widely.


198

CASE FATALITY RATES

Because of the variations in the use of the sulfonamides and penicillin, as well as the variations in methods of administration and dosages, a precise statistical analysis of the cases in which they were employed was not possible. The most practical means of determining their relative efficacy was to analyze the case fatality rates in peritonitis.

The case fatality rate from all causes in the 2,410 cases in which one or the other, or both, of these agents was used was 23.2 percent (560 deaths). There were 422 deaths (24.4 percent) in the 1,732 cases treated in 1944 and 138 (20.4 percent) in the 678 cases treated in 1945. These rates closely parallel the case fatality 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 down into two categories. As is pointed out elsewhere (p. 127), two types of fatalities from peritonitis were observed in abdominal injuries in World War II. In the first, so-called contamination type, there was massive peritoneal soiling, the casualties were in shock and did not respond to the usual measures of resuscitation, and death occurred within the first 48 hours after operation. In the second type of fatality, the patients presented the classical type of suppurative peritonitis. The clinical manifestations were those usually observed, including fever, vomiting, abdominal tenderness, distention, and ileus. Death from this variety of peritonitis commonly occurred between the 4th and 11th postoperative days. In this analysis, no deaths were attributed to the classical form of peritonitis if they occurred within the first 3 days after operation.

TABLE 28.-Comparative case fatality rates from massive peritoneal contamination (shock) and bacterial peritonitis in 2,410 abdominal injuries

Year

Cases


Massive peritoneal contamination

Bacterial peritonitis


Deaths

Case fatality rate

Deaths

Case fatality rate

1944

1,732

58

3.4

32

1.8

1945

678

37

5.5

10

1.5


Total

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 not have been expected to influence the final outcome. This group included the patients who were moribund on admission to the hospital, those who died from such accidents as aspiration of vomitus, those with serious intercurrent


199

disease, and those with serious or fatal noninfectious extra-abdominal injuries. No death in this group of cases was attributed to peritonitis in this analysis. 

On the basis of these criteria of selection, the case fatality rate for the classical type of peritonitis was found to be 1.7 percent, against 3.9 percent for the contamination type (table 28).

In an unplanned investigation such as this, in which there is no control series and complete statistical data are lacking, it would not be permissible to draw anything beyond tentative conclusions concerning the possible benefits of chemotherapeutic and antibiotic agents in abdominal injuries (tables 29 and 30). It would also not be permissible to attempt precise comparisons between the effects of the sulfonamides and penicillin, chiefly because the advent of penicillin coincided closely with two other events which greatly improved the management, and therefore improved the prognosis, of battle-incurred abdominal injuries in the Mediterranean Theater of Operations. The first of these events was the establishment of a theater blood bank in Naples. The second

TABLE 29.-Influence of antibacterial therapy on comparative case fatality rates in 1,526 abdominal injuries

Therapy

Cases


Deaths

Case fatality rate

Total


From peritoneal contamination

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


200

TABLE 30.-Influence of route of administration of antibacterial therapy on comparative case fatality rates in 2,410 abdominal injuries

Routes of administration

Cases

Deaths


Case fatality rate

Total

 

From peritoneal contamination

From bacterial peritonitis

Total


From peritoneal contamination

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, of portable machines for anesthesia, which thereafter was much more efficient. The decrease in the case fatality rates for abdominal injuries after the spring of 1944 therefore cannot be attributed solely to the advent of penicillin but must be regarded, at least in part, as a reflection of these other benefits. Finally, there must be taken into account the increasing experience of the surgical teams.

In addition to these major considerations, climatic and tactical factors must be taken into account in the comparison of the relative effects of the sulfonamides and penicillin in abdominal injuries. The sulfonamide-treated cases were all observed in 1944, most of them in the first 4 months of the year. This particular period covered the fighting before Cassino and on the Anzio beachhead. Conditions of weather and terrain and facilities for evacuation were notoriously unfavorable during both campaigns. As a rule, severe exposure was commonplace, and the evacuation timelag was frequently prolonged. The case fatality rate, which was markedly elevated at this time, was undoubtedly influenced by both factors. The corollary of this reasoning is that the improvement which occurred later in 1944 and continued into 1945 cannot fairly be attributed only to the greater efficiency of penicillin, and the figures (table 29) must be interpreted in the light of these facts.

When penicillin was substituted for the sulfonamide drugs (table 29), there was a very slight reduction in the case fatality rate in peritoneal con-


201

tamination but a very considerable reduction in the rate in bacterial peritonitis. The change in therapy, as already noted, occurred in May 1944. The case fatality rate for all abdominal injuries fell from 32.8 percent in the first quarter of 1944 to 22.4 percent for the April-December period (p. 216). This decrease was disproportionately less than the decline in the case fatality rate observed in peritonitis alone. It was the opinion of the surgeons of the 2d Auxiliary Surgical Group that the decline in deaths from peritonitis was too marked and too abrupt to be explained only by improvement in weather and combat conditions, even in combination with increasing experience in the management of abdominal injuries. They therefore concluded, at least tentatively, that penicillin was more efficacious than the sulfonamides in the prevention and treatment of peritonitis secondary to war wounds of the abdomen.

The case fatality rates calculated according to route of use might seem to suggest, on casual inspection, that deaths were more numerous when the combined parenteral-intraperitoneal method was employed than when the parenteral route alone was used (table 30). The conclusion would be completely unjustified. Analysis of the individual cases which make up the series shows that antibacterial agents were usually used by the intraperitoneal route only when wounds were extensive and contamination was serious. The higher case fatality rate therefore merely reflects the fact that these agents were used intraperitoneally only in the most severely wounded patients. Whether the rate would have been even higher if this route had not been employed it is, of course, not possible to say.

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