Medical Science Publication No. 4, Volume 1
THE OCCURANCE OF INFECTION IN KOREAN WAR BATTLE CASUALTIES DURING MAY-JUNE 1953 (REPORT ON KOREAN TOUR)*
WILLIAM A. ALTEMEIER, M.D., AND LIEUTENANT COLONEL EDWIN J. PULASKI, MC
Wounds of all degrees of severity were observed in this group, including simple wounds without shock to the most complex wounds with severe shock culminating in death.
b. Causal Agents. In our tour the majority of wounds observed were produced by fragmentation missiles. Mortar shell, high-explosive shell, or hand grenade projectiles produced the majority of injuries; rifle or machinegun fire produced the minority. Land mine wounds were seen infrequently, only three being noted in the entire group of approximately 650.
The incidence of the causal agents producing wounds is shown in the following table based upon personal observations made during surgical rounds at the 11th Evacuation Hospital on 5 and 6 June 1953. Ninety-three patients having a total of 128 wounds were examined. Thirty-four of the patients were United States Army personnel, 58 were ROK soldiers, and 1 was a prisoner of war. The causes of the wounds were as follows:
Mortar fire | 48 |
Artillery shell | 11 |
Rifle | 21 |
Hand grenade | 11 |
Machine gun | 1 |
Land mine | 1 |
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These figures were similar to those reported in certain periods of World War II, and closely parallel those of Holmes for the Korean campaign:
Percent | |
Mortar wounds | 37 |
Bomb and grenade wounds | 21 |
Gunshot wounds | 17 |
Shell and high-explosive wounds | 12 |
Land mines | 6 |
Battle accidents | 6 |
Burns | 1 |
Many of the mortar wounds seen by us were relatively superficial and extended to the subcutaneous tissues and the fascia only with relatively little involvement of the underlying muscle.
c. Contamination of Wounds. Bacteriological studies of battle wounds have revealed that all war wounds were contaminated at the time of the first examination following injury (primary contamination). In reviewing the data of Colonel Lindberg on 234 Korean war wounds, it was found that all were contaminated with more than one species of bacteria.
Three principal classes of bacteria were found: the anaerobic sporeforming bacilli, micrococci, and gram-negative bacilli. Over 67 percent of the wounds were contaminated by one or more strains of Clostridia. An average of four species per patient and of two strains per tissue sample were recovered. The five pieces of imbedded clothing yielded 1.8 strains per sample, with 9 strains and 5 species being represented. The incidence of clostridial contamination was greatest in wounds caused by artillery fire (88 percent), less in those caused by mortar fire (65 percent), and least in those caused by small arms fire (55 percent). The average number of species of Clostridia per patient varied from 1.3 in the case of small arms fire to 6.0 in land mine wounds. The studies of the anaerobic flora yielded 19 species of Clostridia. Predominant among these were Cl. sporogenes, Cl. perfringens, Cl. bifermentans, Cl. multifermentans, and Cl. novyi. Toxigenic species (excluding Cl. tetani) included Cl. perfringens, Cl. novyi and Cl. sordelli. Pyogenic micrococcal contamination of wounds consisted primarily of Streptococci and Staphylococci. During the early phases of the wound, primary seeding with the beta hemolytic Streptococci (group A) was uncommon, the hemolytic Streptococci that were found usually being of enteric origin and variety. The hemolytic Staphylococci were present in over 50 percent of the wounds.
Gram-negative bacilli appeared initially in 15 percent of the wounds. B. proteus and Ps. aeruginosa were found infrequently during the periods of contamination immediately after wounding, coliform bacteria being found relatively more frequently.
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Serial studies showed that the bacterial flora of open wounds was rarely static, but usually changing or dynamic. Moreover, in patients with multiple wounds, variation of the bacterial flora from one wound to another was not uncommon.
Secondary contamination consisted of later inoculation of the wound by organisms from other sources. The bacteria most commonly participating in secondary contamination were the hemolytic Staphylococci, beta hemolytic Streptococci of human origin, and the gram-negative bacillary forms of B. proteus and Ps. aeruginosa.
Another interesting observation was that derived from culturing the skin of soldiers, both Korean and American. The cultures were done primarily for Clostridia. Contrary to expectations, the skin of Koreans showed less Clostridia than the skin of the United States soldiers, and the South Koreans did not have the marked bacterial flora which the Americans had. Their skin was free of Clostridia in most instances, and Clostridia were recovered in only 30 percent of the cases. This was difficult to understand after seeing the lack of cleanliness of the ROK soldiers. It conceivably may have been the result of the increased amount of hair that the American boys had on their skin in contrast to the exceedingly small amount which the Koreans had.
The presence and profusion of bacterial species in war wounds was remarkable in the face of the fact that each soldier had received, 1 to 4 hours previously, 600,000 units of procaine penicillin intramuscularly and 0.5 gram of streptomycin.
Inasmuch as surgical débridement represents physical cleansing of the wound, this form of therapy is not germicidal and bacteria remain as contaminants in the débrided wound. It is important to note, however, that the number and types of bacteria recovered 4 to 6 days after initial surgery were fewer in those wounds adequately débrided than in those inadequately débrided.
In a group of wounds closed 6 to 9 days after initial surgery, bacteria were recovered from the surface in every instance. The number of strains varied from one to eight. Forty-five percent showed the presence of beta hemolytic Streptococci resulting from secondary contamination. In the same way, 20 percent of the cases showed Ps. aeruginosa at this time and until healing. It was particularly noteworthy that the clostridial forms were found only in those wounds inadequately débrided in which variable amounts of necrotic tissue were still visible.
d. Nature and Severity of Infection. Our investigations indicated that infection continues to be an important complication of war wounds. Antibiotic therapy has not eliminated this complication, contrary to widespread belief of medical officers, particularly in the
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forward areas. Inasmuch as the total care of a casualty is the function of many medical officers at several widely separated hospitals in the chain of evacuation, observations on the incidence of infection were necessarily difficult. The impressions of the medical officers regarding this subject were usually limited to the level at which they worked.
Our tour afforded the opportunity of making initial observations on wounded personnel at the MASH level as well as subsequent observations on the same patients in many instances at the Evacuation Hospital and Tokyo General Hospital levels. These observations were very revealing and indicated that the incidence of injection varied considerably at each level.
At the MASH level, clinical evidence of infection was less common and was limited to instances of peritonitis, retroperitoneal phlegmon, and occasionally, necrotizing infections associated with large areas of devitalized tissue. In most instances of wounds other than penetrating wounds of the abdomen and head wounds, normal evacuation of the patients occurred from the MASH level 2 to 5 days after injury, depending upon the flow of casualties. During this period a great majority of wounds were covered with dressings or casts preventing close observation of the area of injury.
When the same patients were examined at the Evacuation Hospital level, however, an entirely different idea was obtained as to the incidence and types of infection. For example, it was possible to carefully inspect 93 patients with a total of 128 wounds at the 11th Evacuation Hospital on 5 June 1953. The cause of the wounds was previously described under item 4b. The area of the wounds and the incidence of infection observed are shown in table 1. Of the 128 wounds,
Table 1. Area of Wounds of Incidence of Infection
Area and type of wound | Number of wounds | Infection | |||
None | Slight | Moderate | Severe | ||
Penetrating wounds of abdomen | 8 | 2 | 1 | 4 | 1 |
Thoracic wounds | 4 | 2 | 1 | 1 | 0 |
Neck | 1 | 1 | 0 | 0 | 0 |
Upper extremity | 45 | 25 | 8 | 11 | 1 |
Lower extremity | 55 | 32 | 10 | 11 | 2 |
Buttocks | 10 | 7 | 2 | 0 | 1 |
Perineum | 2 | 1 | 0 | 1 | 0 |
Head | 2 | 1 | 1 | 0 | 0 |
Burns | 1 | 0 | 0 | 1 | 0 |
128 | 71 | 23 | 29 | 5 | |
Percent | ----- | 55. 4 | 17. 9 | 22. 6 | 3. 9 |
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15 were compound fractures of either the upper or lower extremity. Of the 15 compound fractures the presence or absence of infection was unknown in one. The casts were removed in every instance. No clinical evidence of infection was observed in five of these patients, slight infection was present in three, moderate infection in five, and severe infection in one.
Slight infections were interpreted as those having localized stitch abscesses, localized areas of cellulitis, temperature levels of 99° F. or less, and little or no exudate. Such infections were of no practical significance. Moderate infections were interpreted as those with temperatures of 100° to 102° F., evidence of actual wound suppuration with surrounding cellulitis, or localized myositis with discoloration of the muscle and herniation of the muscle through the incised fascia. Severe or serious infections were those in which there was evidence of extensive local infection with marked general manifestations of infection. Temperature in these cases usually varied between 103° and 104° F.
In the case of penetrating wounds of the abdomen or thorax, patients with slight infection were those with minimal clinical evidence of infection in the wound or the surgical working incision, and febrile response after the fourth day of 99° F. or less. Those with moderate infection had localized areas of exudation and cellulitis about the wound tract or the working incision, localized abscesses, and a temperature response of 100° to 102° F. Those with severe infection showed marked systemic reaction with high fever, rapid pulse, larger residual abscesses, persistent ileus, or a marked infection of the operative working wound or wound tract.
In analyzing this group of 128 wounds in this table, we see that 73.3 percent or approximately three-fourths of the wounds showed no evidence of infection or only slight infection which was of no clinical significance. Most wounds of this type came to successful delayed closure 4 to 7 days after initial surgery.
However, 22.6 percent of the cases showed moderate infection and 3.9 percent showed severe infection. One of the patients with severe infection died as a result of a proteolytic clostridial myositis. These figures may seem high compared to independent opinions of medical officers in the forward areas, but in reality they are commendable when one considers the difficulties in complete débridement which resulted from the multiplicity of wounds, the severity of injuries, the difficulties in adequate resuscitation, the immediate and delayed devastating effect on muscle by high-velocity missiles, and the number of vascular, bone and joint wounds.
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The number of casualties arriving simultaneously at the forward hospitals may so overload the facilities of that hospital that surgical treatment on some of the wounded necessarily is delayed. In addition, patients with extensive injuries may have severe shock or other conditions which preclude early operation and which are delayed until adequate resuscitation has been effected. Moreover, patients may have multiple wounds and treatment that necessarily may require staging because of deterioration while the patient is under anesthesia or in recurrent shock. Under such circumstances, it must be remembered that the threat of infection exists in all wounds and that this threat increases with time between wounding and definitive surgery. During the period when the Chinese took Sandbag Castle for 40 hours, a time lag between injury and definitive treatment was temporarily increased. At this time, Lindberg showed that 11 patients who were in shock had positive cultures for Clostridia. Since that time there has been no appreciable increase in the time lag and the incidence for positive cultures of Clostridia was quite low although Colonel Lindberg had noted five or six positive cultures in isolated wounded soldiers.
Penetrating Wounds of the Abdomen
In penetrating wounds of the abdomen, infection is still an important complication. At the MASH level information was obtained from the medical officers that peritonitis as a cause of death had been seen very infrequently and that although the defense against bacteria had been broken by the injury, early treatment and antibiotic therapy had proved very efficient in preventing or controlling infections. At this level we saw 10 patients with abdominal or thoraco-abdominal wounds and early signs of postoperative peritonitis. Two of these died. It would be impossible to say, however, that peritonitis was the cause of death in these.
At the Evacuation Hospital we obtained similar information regarding the infrequent incidence of peritonitis following casualties previously operated upon for penetrating wounds of the abdomen. However, careful examination of 31 patients with penetrating abdominal or thoraco-abdominal wounds at the Evacuation Hospital level proved that infection is still an important complication in these injuries. These patients were seen 4 to 14 days after laparotomy and all but two showed residual evidence of infection. Two had proven subphrenic abscesses and severe toxemia; three had serious wound infections with dehiscence in two; retroperitoneal or paravesical cellulitis coexisted in three others; paralytic ileus persisted after the fourth day in 20 percent of the cases. The temperature varied from 100.2° to
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103° F. and the WBC varied from 14,500 to 21,000 with 93 percent polys in these cases. Two of the patients still had continuous gastric suction 10 and 16 days postoperatively for "intractable ileus" which undoubtedly was due to active infection.
Because of the insidiousness of intra-abdominal infectious complications and their lack of local signs, they were often unrecognized until the condition was far advanced. It was apparent that all medical officers should become familiar with the masked or obscure signs and symptoms of postoperative peritonitis.
When penetrating abdominal injury was complicated by anuria, spreading peritonitis was common. Similarly, when definitive surgery was instituted late, peritonitis was already present and often severe. Retroperitoneal hematoma with contamination was also a serious complication unless treated early and drained adequately.
Another source of information regarding postoperative peritonitis was found in the pathology records of autopsies at the 11th Evacuation Hospital. The records of autopsies done between February 1952 and April 1953 revealed 25 with penetrating wounds of the abdomen or abdomen and chest with generalized peritonitis, and 12 of these had undrained and large intraperitoneal abscesses. These abscesses were as follows:
Subphrenic | 3 |
Subhepatic | 5 |
Pelvic | 3 |
Multiple | 1 |
Other evidences of infection in these 25 fatal cases were as follows:
Abscess of liver | 1 |
Brain abscess | 1 |
Wound infection | 2 |
Phlegmonous cellulitis | 1 |
Abscess of kidney | 1 |
Abscess of heart | 1 |
Empyema | 3 |
Lung abscess | 1 |
The causes of injury in these 25 cases were as follows:
Mortar | 12 |
Artillery shell | 5 |
Rifle | 5 |
Machine gun | 1 |
Vehicle accident | 1 |
Trip flare | 1 |
It is particularly interesting to note that all of these 25 patients had anuria and bad been sent to the Renal Center for special treatment.
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Compound Fractures
Compound fractures were still associated with many problems concerned with control of infection, especially when the lower half of the tibia and fibula was involved, arterial injury or expanding hematoma was present, the joint was involved or when débridement was delayed, inadequate or impossible.
At the MASH and evacuation hospital levels we saw relatively little evidence of infection in compound fractures. This was due to several factors including the short period of time after injury which had elapsed while patients were at these hospitals, and the difficulties in making direct observations because of encircling casts. At the 11th Evacuation Hospital, as noted on page 340, the cast and all dressings were removed from 15 patients with compound fractures of the extremities 4 to 7 days old. Inspection of 14 of these patients and their wounds showed slight infection in three, moderate infection in five and severe infection in one. Another severe and fatal infection developing in a compound fracture of the femur at this hospital was a case of clostridial myositis and anuria (page 347).
Inspection of the wounded with compound fractures evacuated to the Tokyo Army Hospital Annex revealed a different story. The incidence of infection in compound fractures of the tibia or tibia and fibula was very high. Evidence of acute or chronic infection was found in the majority of wounds, and the significance of the process was reflected in the number of cases with nonunion of the bone, sinus tracts, abscesses, active pus formation, or a lack of healing of the soft tissue. In all of the wounds with infection and incomplete healing, dependent through-and-through drainage had been established by a rubber tube approximately three-eighth inch in diameter inserted from the depth of the wound through a small stab wound to the undersurface of the leg. This kept the wound dry and free of pooling of the exudate. In addition, acetic acid compresses were routinely applied to these wounds to discourage the development of green pus.
In two patients recently evacuated from the Korean front to the Tokyo Army General Hospital Annex, careful examination of the wound was done. Although the greater part of the surface of both wounds looked clean and bright red, a discolored and boggy area of muscle was found in each. Neither patient had a temperature above 100° F. orally, but it was demonstrated that a deep abscess was present in each wound and that thick gray foul-smelling pus, necrosis and liquefaction of the muscle were associated with the abscesses. Cultures and smears were taken and sent to the 406th Medical General Laboratory. Smears of this pus showed a mixed bacterial flora and numerous large gram-positive bacilli with square ends.
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Inspection of a large ward filled with casualties having compound fractures of the femur was then made possible. Compound fractures of the femur in all stages of healing were seen. Some had completely healed, some had bony union and residual soft tissue infection including abscesses or sinus tracts, and a few had nonunion and active infection. Acetic acid dressings were commonly used in these wounds on this ward, also. The officers at this level indicated that the incidence of infection was high, but that, generally speaking, infection did not prevent satisfactory healing from occurring in fractured femurs, but that the period of morbidity was probably increased.
The case of one patient with a compound fracture of the femur and a persistent hemolytic Staph. aureus septicemia seen at this hospital on 25 May 1953 was of particular interest. Injury had occurred on 6 April 1953, but no débridement had been done because of his severe shock and subsequent anuria. In mid-April he developed the septicemia, thrombophlebitis at the site of a venous cutdown, and anuria. He was "dialysed" at the Renal Center of the 11th Evacuation Hospital on two occasions. His infection persisted in spite of treatment with all of the available antibiotics.
Examination of this patient revealed his temperature to be 104° F., pulse 136, and respiration 28. An unhealed compound fracture was being treated with balanced traction and severe local infection was present. Although there was no evidence of induration in the tissues of this thigh, a large abscess was easily demonstrated with pooling of a large amount of bloody pus. Further examination revealed septic embolic phenomena with petechiae of conjunctivae, bilateral areas of pneumonitis, splenomegaly and pericarditis. The hemolytic Staph. aureus cultured from the abscess and blood stream was resistant to penicillin, aureomycin and terramycin. It was sensitive to chloromycetin and erythromycin and slightly sensitive to bacitracin.
We were impressed with the fact that this patient had an extensive infection about the compound fracture with liquefaction of muscle and pooling of pus which had gone unrecognized and untreated surgically for a period of approximately 45 days. This case was presented to the Staff of the Tokyo Army General Hospital and discussed thoroughly. It was recommended that the patient be treated vigorously with erythromycin and that his abscess be promptly and thoroughly drained.
Clostridial Myositis
We were particularly interested in the incidence of clostridial infections in war wounds. Reports on this subject made previously and given to us indicated an extremely low incidence of clostridial infection in Korean casualties.
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The reports of Lieutenant Gordon D. Lazerte which we reviewed at the 406th Medical General Laboratory were based upon examinations during 1952 of the following:
1. All amputated extremities submitted to the 406th Medical General Laboratory in Tokyo from hospitals in the Tokyo-Yokohama area;
2. All autopsies and most surgical specimens in that Theater.
This report left certain gaps in our knowledge. Extremities removed at initial surgery in forward hospitals were not included but had been disposed of locally. However, limbs removed 3 to 60 days after injury were handled as laboratory specimens. His study was concerned with 108 amputated extremities from 104 patients wounded in Korea. The extremities involved were as follows:
Upper arm | 9 |
Disarticulation of elbow | 1 |
Forearm | 5 |
Hand | 2 |
|
|
|
Disarticulation of hip | 1 |
High thigh amputation | 1 |
Middle or lower thigh | 38 |
Disarticulation of knee | 3 |
Amputation of lower leg | 45 |
Transmetatarsal amputation | 2 |
Unknown | 1 |
|
|
|
Lazerte selected certain sites for histologic and bacteriological study and attempted to correlate these with clinical findings. The sites chosen included those of the original battle wounds, muscles distal to the battle wounds, and muscle compartments proximal to the battle wounds. Blocks of tissue were studied with hematoxylin and eosin and Goodpasture stain.
The causes of amputation were interpreted as follows:
1. Ischemic gangrene, or bland necrosis, although infection was a frequent complication;
2. Destructive trauma, in which the patient's limb underwent such severe trauma that healing or function was not possible; and
3. Gas gangrene, a rapidly spreading infection of muscles caused by Clostridia and characterized by great swelling, pain, and effects of "lethal toxins."
In one case described by Lazerte, No. 27126, devitalized tissue with gas in the absence of toxemia and in the presence of Cl. welchii, Cl.
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multifermentans and Cl. sporogenes was found. A diagnosis of gas gangrene was not made. The questions in this case were: (1) Was this an instance of localized clostridial myositis; and (2) Were these Clostridia nonvirulent and nontoxigenic strains or did the absence of blood supply diminish absorption of their toxins? In other words, was this growth saphrophytic because of low virulence of the anaerobes? These and several other questions arose during the study of this case.
In Lazerte's series of 108 amputations, there were 8 cases of gas gangrene occurring 2 to 7 days after injury. More than 50 percent of the remaining stumps amputated for ischemic gangrene or destructive trauma were complicated by infection. The results of bacteriological culture from these extremities were available in 72 cases. The aerobic bacteria isolated included the coliform bacilli, B. proteus, Staphylococci and various Streptococci varieties. Many species of anaerobic Clostridia were also found. The pathogenicity of the Clostridia in each instance was tested by guinea pig inoculation of the pure culture.
The anaerobes recovered from the 72 cases were as shown in table 2.
Table 2. Results of Bacteriological Culture
Clostridia | Gas gangrene, 6 cases | All amputation wound specimens, 66 cases | Routine culture of 204 wounds |
Welchii | 5 (83 percent) | 54 percent | 42 percent |
Novyi | 1 (17 percent) | 39 percent | 3 percent |
Sporogenes | 3 (50 percent) | ----- | ----- |
Aerofetidum | 1 (17 percent) | ----- | ----- |
Multifermentans | 1 (17 percent) | ----- | ----- |
Tetani | ----- | 6 percent | ----- |
Sordelli | ----- | 3 percent | ----- |
Unidentified | 1 (17 percent) | ----- | ----- |
One of Lazerte's cases of typical gas gangrene showed only the presence of sporogenes. Wineburg in 1918 reported two similar cases.
In a personal communication, Lieutenant Lazerte also noted that he found one case of fatal gas gangrene in 324 autopsies done on patients who died in hospitals as a result of battle wounds.
Discussions with the staff at the 46th MASH indicated that the incidence of gas gangrene was approximately 1 per 1,000 cases. Consultations with the staff of the 43d MASH revealed that 1 of 71 patients undergoing major arterial repair subsequently developed gas gangrene.
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On the other hand, one of the great problems confronting this group as well as other surgical teams was muscle breakdown and liquefaction by compartments after successful arterial anastomosis and repair. The anterior compartments of the leg were most commonly affected. It was impossible to get adequate information as to whether or not proteolytic clostridial infection was wholly or in part responsible for previously reported cases.
In an effort to get more information on this subject long discussions were held with the Staff at the 11th Evacuation Hospital and the Artificial Kidney Center. During these discussions and others held elsewhere, it was evident that the staff members associated the signs and symptoms of pyogenic infections with clostridial infections. In other words, high fever, high WBC, purulent exudate, cellulitis, lymphangitis and lymphadenitis were expected. This, of course, was erroneous since severe and fatal infections often are associated with normal or slightly elevated temperatures, no purulent exudate, but profound toxemia.
One severe and fatal case of clostridial myositis was found at the Renal Center at this hospital among the 93 casualties examined on 5 and 6 June 1953. Inasmuch as this case had been unrecognized before, it is presented here in detail.
J. B., Canadian airman: This man was accidentally injured at 2100 hours on 25 May, receiving a gunshot wound of his left thigh with a 303 rifle with a muzzle velocity of 3,600 feet. He received a compound cominuted fracture of the femur through the lower third. The wound of extrance was at the left patellar area and the wound of exit was through the perineum. When seen at the battalion aid station, this patient was in shock. He was given 2,000 cc. of dextran solution and 500 cc. of plasma within 2 hours. At the end of that time his blood pressure was 95/50. He was then sent to the Norwegian MASH and at 2:50 a. m. on 26 May his blood pressure was not obtainable. At 0400 his blood pressure was raised to 90/60 following the administration of six units of blood. Operation was done from 6:30 a. m. to 11:15 a. m. consisting of extensive débridement of the medical aspect of the thigh, arterial graft done by Lieutenant Colonel Paus, and débridement of the knee joint. During this period he received a total of 17 pints of blood, making a total of 23 units of blood and 2,000 cc. of dextran. He was also given 10 cc. of calcium gluconate.
On 27 May, the following day, his blood pressure was normal, but oliguria developed. The patient's temperature at that time was 98.6-99° F.; no blood counts were recorded. On 28 May, the foot was noted to be cold and blue and amputation was considered. The skin color was good to the middle of the leg. A sweetish foul odor became obvious and "venous" bloody discharge without gas bubbles was noted
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emanating from the wound through the cast. He was sent by plane on 29 May from the Norwegian MASH to the 11th Evacuation Hospital in Wonju. The fluid intake at the Norwegian MASH had not been recorded. When he arrived at the 11th Evacuation Hospital, his temperature was 99.2° F. rectally, his pulse 100, his blood pressure 130/80, and the patient was drowsy and thirsty. His WBC was 20,400 with 80 percent polys and 13 percent stabs. The RBC was 2.9 million, with 8.9 gm. hemoglobin. The hematocrit was 26. The cast was soaked with blood, and when it was removed, much clotted blood was found within the lumen of the cast and within the cast itself. An estimated 4,000 to 5,000 cc. of blood was lost in this manner.
On 30 May, the patient had been taken to the operating room and the cast was removed. A long linear medial incision was noted. The leg was markedly swollen and the sheet wadding had not been cut through when the cast was cut originally at the time of its application. The skin on the underside of the thigh was devitalized and showed numerous blebs on its surface at least 3 cm. in diameter. These were filled with clear serous fluid. The tops of the blebs rubbed off easily. The "packing" was taken out. The muscles were found to be edematous and herniated through the incision. The muscles were very dark in color and appeared nonviable and friable. They did not contract when pinched. Biopsies and cultures were taken. Muscle bellies were swollen to almost two or three times normal.
It was the opinion of those who saw the dressing that large masses of muscle were devitalized and infected. A guillotine amputation was done in the midthigh on 30 May and bleeding vessels were found to traverse the devitalized muscle bundles.
On 2 June the patient's temperature rose to 103.4° F. rectally, and the patient was placed on the artificial kidney for 6 hours. During this period he had a chill and again a rise in temperature to 103.4° F. His white count at that time was 22,900, and on 5 June, the white count was 24,000. He had been receiving 600,000 units of procaine penicillin b. i. d. and 0.5 gm. of streptomycin every 12 hours.
Date | Hematocrit | Blood transfusion (cc.) | Hemoglobin |
30 May | 25 | 1,350 | No determination made. |
31 May | 24 | 800 | No determination made. |
1 June | 31 | 400 | No determination made. |
2 June | 30 (Dialyzed) | 400 | No determination made. |
3 June | 16 | 2,500 | No determination made. |
4 June | 21 | 375 | 7.6 gm. |
5 June | 26 | 1,025 | 9.2 gm. |
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His temperature rose to 104° on the morning of 3 June and fell to 102° on 4 June. Temperature on 5 June varied between 100° and 100.4° F. rectally.
Following dialysis the patient bled into the stump and the smell of sour decomposing muscle was obvious.
Two blood cultures taken on this patient were negative; the urinalysis showed scanty urine containing many red blood cells. No blood volume studies were done.
Realizing the significance of the odor on this patient when I saw him in making rounds, I requested of Colonel Seymour, Major Meroney, and Captain Sako that the dressing be removed for inspection of the wound. The wound was found to be extensively infected and covered with a grayish-green, extremely foul-smelling exudate. The muscle was dark brown in appearance in some areas and light tan in others. The muscle was so edematous that it herniated out of the area of incised fascia and through the amputation stump.
In addition, the patient was extremely lethargic and presented the typical picture of an extensive and overwhelming clostridial myositis. These facts, diagnostic of clostridial myositis, were pointed out and it was decided that the patient should be immediately taken to the operating room and an attempt made to remove all of the devitalized and infected areas of myositis as a last desperate effort to save the life of this moribund patient. His blood pressure at the time was 90/60 in spite of a continuous infusion of blood. Three intravenouses were started, one in the leg and one in each arm. Blood was administered continuously in one, and 5 percent glucose with saline in the other. As rapidly as possible, the wound was carefully inspected. The infection, devitalization and proteolytic digestion of the muscles were shown conclusively to follow the muscle compartments. Areas of necrotic, infected and devitalized muscle were adjacent to other areas of vital muscle.
As rapidly as possible, the infected areas of muscle were excised since amputation was impossible, the infection having spread along the iliacus and soleus muscles and onto the abdominal wall through the perineum. During the period that the areas were excised the patient's blood pressure gradually fell and in spite of all types of resuscitation, cardiac arrest occurred. The chest was immediately opened and cardiac massage carried out for 45 minutes. It was only temporarily successful in reestablishing cardiac beat. On four occasions, the heart started to beat but soon stopped in dilatation. Sections of muscle were removed for pathological study and given to Captain Blake, the pathologist, at the 11th Evacuation. Other pieces of muscle were removed from this patient and placed in deep meat media. Half of these were given to Captain Blake for culture and the other
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pieces were retained by me and taken back to the United States for culture and study in order to identify the Clostridia present in this extensive proteolytic infection.
Subsequent cultures in the Surgical Bacteriology Laboratory of Cincinnati General Hospital revealed the presence of two Clostridia, one of which was intensely proteolytic, resembling but not identical with Cl. sporogenes. The other was a virulent Cl. perfringens.
After the personal observation of this overwhelmingly severe and fatal clostridial myositis, a search was made for other similar cases in the autopsy records of the preceding year at the 11th Evacuation Hospital. Twelve cases were found which appeared to have been clostridial infections.
1. C. W. S., who was seen in the artificial kidney ward at the 11th Evacuation Hospital. He was injured on the 10th of May at 0800 by mortar fire. He received a wound in the left flank which injured the left spleen, kidney, aorta, right common iliac artery. He also received a wound to his leg. He was operated on at the 44th MASH at 10:45 a. m. His spleen and kidney were removed on the left and his aorta was repaired. Previous to operation he was seen at the divisional clearing station where he received 200 cc. of albumin and 100 cc. saline. He was in shock with a blood pressure of 60/40 which then dropped to 0/0. He was given 2,000 cc. of blood rapidly and his blood pressure rose to 100/60. During operation at the 44th he received an additional 4,000 cc. of blood making a total of 6,000 cc. up to that time. During the operation as the wound in the aorta was explored, the patient developed uncontrolled hemorrhage and went into profound shock. A foreign body was removed from the common iliac artery. Surgery was completed at 1300. Fasciotomy was also done at that time. During the next 24 hours his pressure varied between 100 and 140 systolic, although he was maintained on levophed, taking a total of four ampules. He received 3,000 cc. more of blood throughout the afternoon of the first postoperative day. At that time his hematocrit was 60 and his serum showed hemolysis.
During the first 3 postoperative days, he excreted a total of 200 cc. of dark bloody urine. There was no mention of fever on his record. His hematocrit was 57, his WBC unknown.
He was admitted with pulmonary edema on 14 May to the Renal Center. Amputation was done on 16 May, 2 days after admission. At that time it was noted that the muscle bulged through the fasciotomy excision of the lower leg. The muscle was discolored, cooked and brownish in appearance. A watery discharge with an extremely foul sour odor emanated from the muscle wound. This odor, according to Captain Sako and Major Meroney, was similar to, if not identical with, the odor on J. B. who was also on the kidney ward.
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A below-knee amputation was done. The muscle was found to be infected and no bleeding occurred.
The patient underwent three dialyses on the artificial kidney. No cultures or biopsies of the wound were taken inasmuch as the changes in the leg had been considered to be due to trauma rather than infection.
The appearance of the wound, the limitation of the infection to the muscle bundles, the spread of the infection along the muscle areas, the profound toxemia, the falling red blood count and hematocrit indicated that this case was also an instance of the proteolytic type of clostridial myositis in all probability.
2. C. Y. K., who was injured 11 January 1953 with an artillery wound of the chest, abdomen, right forearm, and right buttock. A severe infection developed in the buttocks with muscle necrosis, edema and a very foul odor from which Clostridia were isolated.
3. T. B. was wounded on 3 May as a Marine in action. He received a severe wound of his thigh caused by an exploding hand grenade or mine. A compound comminuted fracture of the right femur developed and the patient was thrown into deep shock. He received 9 pints of blood preoperatively and 5 pints of blood during the operation. The popliteal vein and artery were divided and amputation was done. Postoperatively, he developed shock and an arterial transfusion was required followed by further transfusion of blood intravenously; 300 cc. of blood was given intra-arterially.
This patient was anuric for 19 days after which he excreted 1,000 cc. of urine. By 8 May (fifth day after injury) the patient was severely uremic, developing an unusually rapid course compared to previous experience.
Those in attendance "found no evidence of infection" until 15 days when the temperature rose to 103° F. The blood culture became positive for B. proteus. On the seventeenth day the patient again went into shock. He was treated with aureomycin and chloromycetin. On the 21st day nausea and vomiting developed and he was treated with gantrisin. The patient then developed marked weight loss, going from 158 to 119 pounds. This started when he developed his infection. Patient was evacuated to Japan for further treatment.
4. B. H., 21-year-old infantry private who was injured on 9 April 1953, sustained multiple missile wounds inflicted by a land mine. He had injuries to left arm, left thigh, left lateral chest, abdomen with perforation of left lobe of liver, right upper and lower extremities. Within an hour he was in the clearing station and had been given 1,000 cc. of blood and 500 cc. of albumin. He was transferred to the 44th Surgical Hospital and was given another 1,500 cc. of blood. Laparotomy, thoracotomy and amputation of left arm with débride-
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ment of other extremity wounds were done. He developed renal insufficiency and was again transferred. In the next 6 days his course was remarkable because of his continued inadequate kidney function and some hypertension. However, on his sixth hospital day he developed fever and "secondary shock." The following day he had hyperpyrexia, WBC of 21,000 and died that day. Postmortem examination showed the "left calf to be swollen to twice its normal size and to be filled with dark red fluid blood which runs from the cut surfaces of the swollen, boggy, purple, mushy calf muscles." All other wounds showed greenish yellow exudate. It is not noted whether these wounds were foul-smelling or not.
5. W. S., a 21-year-old infantry man wounded by mortar fire, 19 September 1952, with resulting traumatic amputation of left mid-thigh, penetrating wounds of lumbar region, right thigh, leg and foot, perforating wound of buttocks with perforation of colon. Five hours after injury he reached the collecting station where he was given 3,000 cc. of whole blood. Two hours later he was at the Mobile Surgical Hospital, arriving there with a blood pressure of 80/40. He was given 1,500 cc. more of whole blood to relieve his hypotension, then another 1,000 cc. of blood and was operated upon. Débridement of wounds, proximal colostomy, and high thigh amputation of the left leg were done. Following the operation he was in mild hypotension which was treated with another 1,000 cc. of whole blood, and because of oliguria he was transferred to the 11th Evacuation Hospital. On arrival there it was noted that all open wounds were foul-smelling and the left gluteal muscles were "necrotic from blast injury." During the next 11 days he was intensively treated for his oliguria. It is noted that there was "continued necrosis of buttocks and leg muscles associated with infection." On his fourteenth post-wound day he developed shock which would not respond to the usual measures plus 25 cc. of whole blood. He continued in shock and died on his sixteenth postoperative day. Autopsy showed the muscle tissue at the site of leg amputation and over both buttocks to be extensively destroyed and the remaining muscles to be hemorrhagic, soft and necrotic. The wound communicated with a "marked retroperitoneal pelvic hemorrhagic necrosis with abscesses."
6. M. McG., a 27-year old master sergeant, wounded by artillery shell fragments, 30 March 1953. In the next 8 hours he was resuscitated with 5,000 cc. of whole blood, 1,000 cc. of dextran and operated upon. Laparotomy revealed no intra-abdominal injury. Multiple wounds of the right thigh were débrided, anastomosis of posterior tibial artery of the right leg was made, and treatment of a compound fracture of right tibia and fibula was given. The left leg had been traumatically amputated. During and immediately following sur-
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gery, he was given 2,000 cc. of whole blood. Because of oliguria he was transferred to the 11th Evacuation Hospital. Three days later it was noted that his left leg amputation stump was grossly necrotic and disarticulation of the hip was necessary. This was associated with considerable shock. His course following this was hectic, manifested by alternating pleural edema and shock. He died in shock on the fifth post-wound day. Autopsy showed surface of the site of amputation of the extremity to be greenish-black, soft and foul-smelling.
7. R. H., a 19-year-old Marine injured by mortar fire, 5 March 1953, with lacerations and abrasions of the right upper extremity, compound comminuted fracture of right femur, wounds with avulsion of left popliteal artery of lower extremity. He was treated by the débridement of his wounds, and arterial graft to his left popliteal artery. His treatment from injury to completion of operation included 13,000 cc. of whole blood. He developed oliguria on the second post-wound day and was transferred to the 11th Evacuation Hospital. Four days after transfer it was noted that he had hypertension and tachycardia. Three days after this he developed pulmonary edema and a week later it was noted that he had subcutaneous emphysema of his neck ana chest. He died the following day, apparently in pulmonary edema. Autopsy revealed widespread necrosis of the gastrocnemius and soleus muscles of the left leg with hemorrhage along the fascial planes. There was marked subcutaneous emphysema of the chest, neck and mediastinum without any evidence that the lung was the source of the air.
8. D. M., a 22-year-old infantry man injured 12 January 1952 by mortar fire. He had apparent exposure to cold for several hours, and not until the second post-wound day were his wounds débrided. Post-operatively, he had severe shock for 8 hours, for which he required 2,000 cc. of whole blood. It was noted on this day that he had beginning gangrene of both feet. Because of anuria he was transferred to the 11th Evacuation Hospital on his fifth post-wound day. There his temperature was only 97° and his blood pressure 140/100. He was delirious and grossly disoriented. His feet were purple, blotched and edematous, and gross edema of the subcutaneous tissue of his chest was detected. Eighteen hours after admission to this hospital he suddenly became dyspneic and died. Autopsy showed that the muscle of the chest wall exuded fluid; there were numerous open wounds over both legs to the thighs. His liver was grossly enlarged and purplish in color.
9. W. C. S., 18-year-old, wounded 18 June 1952 by mortar fire. He was treated with 7 pints of blood prior to surgery on the date of injury. He had multiple wounds of both thigh and buttocks and a fracture of the left femur. Laparotomy was done revealing no
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injury. Postoperatively he developed shock and no further débridement was done. He developed anuria and on his fifth post-wound day was transferred to the 11th Evacuation where he was dead on arrival. It was noted that he had generalized edema including his face. There was no comment as to whether the undébrided wounds were infected.
10. R. B., 21-year-old soldier wounded 5 September 1952 by a land mine with multiple lacerations of the right leg and right hand. He was treated at the MASH 3 hours after injury. He required 5,000 cc. of whole blood to relieve his shock. Supracondylar amputation of the left leg and débridement of his arm wounds were done. He developed anuria and was transferred to the 11th Evacuation. At this hospital edema of the right forearm was noted. X-rays revealed fracture of the right radius with subcutaneous gas shadows. His course there was generally downward. It is noted that his thigh wounds continued to drain and that he developed a fever of 102° F., pulse 140. Investigation of his right arm revealed a large, foul abscess containing sanguino-purulent exudate extending from the wrist to the elbow. He continued to have delirium and signs of infection and died 13 days after injury. Autopsy showed all wounds to have evidence of infection with a foul-smelling exudate. Muscles of the forearm are described as soft, friable and purplish-red.
11. A. K. had an area of infected bone surrounded by an extensive amount of liquefied muscle excised in December 1952. Cl. sporogenes was cultured from the area of liquefied muscle.
12. D. P. was wounded 24 November 1952 by shell fragments with penetrating wounds of both legs, right arm and scrotum. Resuscitation and evacuation required 15 hours and 4,000 cc. of whole blood. All wounds were débrided. His course in the next 6 days was good. On the 30th of November it was noted that he had abdominal distention and tenderness, fever, and his WBC was 24,000. By 5 December his temperature was 104° F. He developed persistent hypotension and oliguria. He was transferred to the 11th Evacuation on 8 December. His shock state persisted as did his fever. No relief of his shock could be obtained. Autopsy revealed generalized peritonitis, lung abscess and clostridial myositis of legs.
Other possible cases of clostridial infection suggested by the description of the lesion only were:
1. D. M., a 22-year-old soldier injured by shell fragments 27 September 1952. Injuries were multiple wounds around the anus, rectum, left groin, left calf, with a comminuted fracture of the left ischium. Operation was done 20 hours after injury during which he had been evacuated and had received 4,500 cc. of whole blood. Operation revealed rupture of the bladder and intact femoral vessels. Colostomy was done as was débridement of the calf wounds. During opera-
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tion he had cardiac arrest, successfully treated. He remained unconscious from then until his death. He developed anuria and was transferred on his third post-wound day to the 11th Evacuation. On arrival his temperature was 102° F., pulse 130. It is noted that the inguinal incision was indurated. His anuria continued and his fever increased. His course was generally downward and he died on his fifth post-wound day. Autopsy revealed the operative wound of the left femoral canal area to contain a large abscess possessing grayish yellow pus and gas.
2. R. D., a 22-year-old soldier injured by shell fragments 17 December 1952. During the next 5 hours he was resuscitated with 2,500 cc. of whole blood and evacuated. Operation revealed laceration of spleen, kidney, stomach, small intestine and colon through a wound in the left flank. During operation he received 3,500 cc. of whole blood and had persistent hypotension. He developed renal insufficiency and was transferred. At the hospital it was noted that his flank wound continued to drain pink purulent material. Blood culture on 22 Deceinber grew Strep. fecalis, M. pyogenes, A. aerogenes and Clostridia. He died 3 days later. Autopsy revealed a retroperitoneal space injection with necrotic, hemorrhagic material adjacent. The muscle tissue in the area was soft, friable and pale pink, and empyema was present also containing Clostridia.
3. F. L., a 22-year-old private injured by multiple gunshot wounds 1 February 1953. He was evacuated to the MASH and there required 4,000 cc. of blood for resuscitation. Operation revealed laceration of the liver, perforation of the small intestine and cecum, compound fracture of the right femur. Cecostomy and repair of lacerations were done; his leg wound was débrided and casted. Postoperatively he had a recurrent bout of shock and on the second post-wound day he was evacuated because of renal insufficiency. He continued to have marked tachycardia and persistent hypotension. His temperature was 105° F. on his fourth post-wound day. He died on his sixth post-wound day. Autopsy revealed an abcess in the area of his liver wound, serosanguineous fluid in a wound of the right buttock in which area the muscle was necrotic and the skin was "macerated" and separated easily from the subcutaneous tissue. There was a hematoma in the riglit thigh-lateral area.
4. F. H., a 23-year-old soldier injured by a trip flare penetrating his abdomen. His abdominal wall was severely burned and most of the small intestine was charred and necrotic. Resection of this portion of intestine was done as well as much of the abdominal wall. Postoperatively he developed oliguria. During his first to seventh post-wound days he continued to run fever, and on his eighth post-wound day because of continued oliguria, was transferred to the
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11th Evac. On arrival there it was noted that he had fever of 101° F., that there was a subcutaneous emphysema over his lateral and anterior chest. His abdominal wound had profuse dirty watery discharge. His course was continually unfavorable and he died on his eleventh post-wound day. Autopsy revealed diffuse phlegmonous inflammation and necrosis of the muscle on the anterior abdominal and chest wall with subcutaneous emphysema.
5. G. R. was injured 27 March 1953 with a wound of the right buttock involving prostate, urethra, sigmoid colon and bladder and a wound of the right arm destroying 5 cm. of the brachial artery. He received 15,000 cc. of blood in the first 24 hours after injury. He developed oliguria and was transferred to the 11th Evacuation. On the ninth post-wound day he suddenly developed severe shock and jaundice, and the observer thought this was due to sepsis. His shock at first responded to blood transfusion and later to levophed temporarily, but he became worse and died on his tenth post-wound day. Autopsy revealed the arm wound to be covered with a blue green exudate with a sweetish odor. The muscles were soft and jelly-like. In the lower abdominal wall a large pocket of purulent materi al was found and adjacent muscle was soft, friable and hemorrhagic.
Other instances of localized septic liquefaction of muscle associated with putrid and butyric acid odor in wounds were seen at the 11th Evacuation, the 121st Evacuation, and the USS Haven.
It is difficult to compare the incidence of clostridial myositis in Korean casualties with those in World War II. DeBakey and Simeone during World War II summarized the cause of amputation in 3,177 cases in Europe and the Mediterranean Theater. Gas gangrene and other infections were responsible for 12 percent of the amputations. Destructive gangrene was responsible for 68.6 percent of the amputations. Lazerte's studies of 128 amputations done on 91 Korean casualties showed that gas gangrene was responsible for approximately 9 percent of the amputations.
During the North African campaign of World War II the incidence of gas gangrene was over 3 cases per 1,000 casualties (Heyningen: Bacterial Toxins. Charles C Thomas, 1950). The estimates given us by some medical officers that the incidence of clostridial myositis in the Korean campaign was 1 per 1,000 casualties seem to be too low. The difficulties in establishing the causal relationship of Clostridia to the foul-smelling liquefaction or necrosis of muscle with the limited information available are obvious. However, it is also obvious that clostridial myositis was more prevalent than previously believed. Furthermore, the proteolytic Clostridia seemed to play a relatively greater role in this theater than in other areas.
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It is certain that clostridial myositis did occur, both as the diffuse type (gas gangrene) and as the localized type. Liquefaction of muscle in localized myositis by proteolytic bacteria, presumably Clostridia, seemed to be more prevalent than the diffuse myositis typical of gas gangrene.
e. The Relationship of Secondary Shock and Anuria to Sepsis.. This subject was of special interest to us. Secondary shock developed 2 to 5 days after injury and usually followed operative intervention. It occurred most frequently in patients with abdominal injuries or with extremity wounds with large masses of muscle injury and necrosis. This hypotensive complication was characterized with oliguria or anuria, uremia, elevated potassium levels, extensive loss of weight, delayed or absent wound healing, a high incidence of severe infection, and a very high mortality rate of 80 percent or more. Other consultants have studied and reported on various aspects or manifestations of secondary shock. Our particular concern was the question of whether or not infection caused or contributed to the development of secondary shock.
This subject was reviewed at length with officers of the 406th Medical General Laboratory, the research team at the 46th MASH, the research team at the Renal Center at the 11th Evacuation Hospital, and with other officers. Reports of previous consultants and pathological and bacteriological data were made available and were studied by us. Microscopic sections of pathological specimens from autopsied patients were reviewed with members of the Pathology Department at the 406th Medical General Laboratory.
The time lag of 2 to 5 days between injury and the onset of secondary shock coincides with the incubation period of severe wound and peritoneal infections and is suggestive of the possibility of a causal relationship between certain infections and this condition. Captain Howard found that abdominal injuries were more apt to produce states of secondary anuria or oliguria. A review of the autopsy records at the 11th Evacuation Hospital between February 1952 and April 1953 revealed that severe infection unquestionably was present in practically all if not all of the patients dying of secondary shock. As previously noted (on page 342), there were 25 cases of generalized peritonitis resulting from penetrating wounds of the abdomen or chest and abdomen in the autopsy protocols of the patients with secondary shock and anuria. In addition, 12 of these had undrained large intraperitoneal abscesses. Other evidences of severe infection in these 25 fatal cases were wound infection in two cases, empyema in three, and abscesses of the liver, brain, kidney, lung and heart in one case each. Further study of the autopsy records during this same period showed 24 patients with severe infection of the wounds of the extremi-
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ties. Twelve of these had evidence of necrotizing myositis, probably clostridial. These have been described previously in this report. Of the remaining 12 patients with extremity wounds the available information is less indicative of myositis, but there is the possibility that it existed in some. Other severe forms of infection were manifest in these 12 cases by chills, septic fever, leukocytosis, pathological evidence and the elevations of the temperature which ranged between 101° and 108° F. The temperature was in excess of 105° F. in 7 of these 12 cases. The WBC reports were sketchy but varied between 15,700 and 44,500 in those recorded. Pathological evidence of infection recorded in these cases included: pyogenic pericarditis, infected burns, cortical abscesses of kidney, B. proteus septicemia, lung abscesses and extensive cellulitis. The autopsy records of some of these patients are very sketchy and incomplete, and therefore it is difficult to draw any but general impressions.
The fact remains, however, that infection was present in most if not all of the autopsy records studied during this period. The question remains whether the secondary shock with anuria and the severe infection were separate complications of the injuries, whether infection actually caused some or all of the cases of secondary shock, or whether the secondary shock developed first and the infection was superimposed as a result of some overwhelming impairment of the body's defense against bacteria.
Our knowledge, based upon previous experience and studies of cases seen before, reveals several important observations which are pertinent to this problem:
1. Severe or uncontrolled peritonitis has been responsible for hypotensive states occurring 2 to 5 days after peritoneal contamination and attributed to "vasomotor collapse." Oliguria, and anuria have been associated with the hypotension, and the mortality in such cases has approached 100 percent.
2. This peritoneal infection has been seen postoperatively in patients undergoing elective surgery of the colon or emergency operation for perforations of the appendix, peptic ulcers, as well as penetrating wounds of the abdomen. Often, one of the first manifestations of this severe postoperative infection is the sudden onset of hypotension.
3. Such peritoneal infections with septic shock have also been observed in individuals proved to have generalized peritonitis at autopsy in whom no operation had been performed.
4. Septic shock with hypotension has also been seen in cases of clostridial myositis, retroperitoneal cellulitis, urinary extravasation, septicemia and pneumonia. Most instances of
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septic shock have developed 2 to 8 days after the onset of the infection.
5. Once this complication develops, death usually follows in 12 to 72 hours.
6. In gas gangrene or other forms of clinical clostridial myositis, rapidity of the pulse may progress to circulatory collapse and hypotension which may be abrupt, progressive and severe. As the pulse rate becomes increasingly rapid, the amplitude becomes steadily smaller.
7. Animals with experimental gas gangrene, studied at the University of Cincinnati, have shown evidence of circulatory collapse and septic shock preceding death. These animals likewise exhibit anuria.
8. Animal (dog) experiments with intramuscular injections of lethal doses of Cl. welchii toxin (1951) have revealed some very interesting post-injection data:
(a) Fall in blood pressure over a 5-hour period;
(b) Decline in the urinary output after the first hour with complete suppression after 4 hours;
(c) Increase in blood urea nitrogen;
(d) Diminished excretion of urinary chlorides;
(e) Demonstrable histological alteration in the kidneys, visible after 21/2 to 3 hours with diminution of circulating blood in the glomeruli and swelling of the glomeruli, also widespread vasocontraction of the cortical arterioles and capillaries;
(f) Consequent functional alterations of glomerular and tubular action.
These observations indicate that secondary shock states can unquestionably be produced by severe and uncontrolled infection. They also give strong suggestive evidence to the possibility that sepsis has been a major and basic cause of the secondary shock occurring in Korea. In any event, this possibility is a real one which is worthy of intensive investigation.
f. Appraisal of the Influence of Antibiotic Treatment in the Prophylaxis and Control of Infections. The main reliance on antibiotic prophylaxis and therapeusis was procaine penicillin in dosages of 300,000 to 600,000 units with or without 0.5 gm. of streptomycin administered intramuscularly. Several studies indicate that this regimen was illusory and inadequate:
1. The absorption of intramuscularly administered antibiotics has been shown to be retarded and inadequate in shock by the individual investigations of the two authors of this report.
2. The blood and tissue levels obtained in shock by this route
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and with this type of penicillin are significantly lower than those obtained with aqueous penicillin G given intravenously. Studies by Colonel Lindberg of the concentrations of penicillin in wounded tissues showed an average level of only 0.23 unit per gram, and in some instances no trace of penicillin was found.
3. The lower the concentration of penicillin in the tissues, the greater the number and variety of mixed bacterial species which were present.
4. In the study of injured limbs coming to amputation, Lindberg and Lazerte found active proliferation of bacteria in muscle biopsies in the presence of therapeutic concentrations of penicillin in the tissues. Although fewer numbers and varieties of organisms were present in the tissues with the higher concentrations of penicillin, none of the blocks of tissue tested were sterile. Although the reasons for the failure of antibiotics to halt bacterial action in dead tissue are not understood, the fact remains that this failure does exist.
5. Culture sensitivity studies revealed that approximately 40 to 60 per cent of the Clostridia isolated from wounds in Korea were not inhibited by this average concentration of 0.23 unit.
6. This therapeutic schedule does not prevent colonization of bacteria within wounds.
7. The data available support our impression that the combination of procaine penicillin and streptomycin as employed in Korea was successful in inhibiting infection only by the highly sensitive bacteria such as the hemolytic Streptococcus. On the other hand, it was inadequate against infections caused by mixtures of other less sensitive or resistant organisms. The course of peritonitis and proteolytic infections of muscle did not appear to be significantly influenced by this type of antibiotic treatment.
8. The presence of necrotic tissue in wounds rendered the antibacterial effect of the antibiotics inadequate.
g. Potential Usefulness of Clostridial Toxoid Immunization. Although it was apparent that clostridial myositis occurred more frequently in Korean casualties than was previously reported, it will be difficult to evaluate the potential usefulness of clostridial toxoid immunization in areas such as Korea until representative strains of Clostridia from actual war wounds can be studied with reference to their toxigenicity, virulence, hyaluronidase production, etc.
It seemed apparent, however, that the proteolytic action of Clostridia was more prevalent than the saccharolytic or toxic activity. This has posed a question as to whether or not a method of immuniza-
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tion should be developed against digestion of muscles by the proteolytic enzymes of the Clostridia. A toxoid against the proteolytic activity of Cl. histolyticum is in the process of development at the University of Cincinnati now.
The possibility that clostridial enzymes may be related to secondary shock also needs investigation in a consideration of the future potential usefulness of clostridial toxoid immunization.
It must be remembered that the excellent record for the suppression of infections in war wounds in the Korean conflict was made under conditions which would not be operating in the event of an atomic attack, namely:
1. A relatively stable line.
2. A time lag between injury and definitive treatment of less than 4 hours.
3. Excellent surgical treatment by skilled surgical teams trained to do standard operative procedures.
4. Adequate supplies, materials and medical officers.
5.An intact chain of evacuation.
In the event of an atomic attack in such Oriental areas as Korea with destruction of medical installations, medical personnel and supplies, it would be impossible to treat the many thousands of casualties effectively. Under such conditions, the anticipated results would be:
1. Heavy clostridial contamination of wounds of all types in mass numbers. This high incidence of clostridial contamination in Korean casualties has been proven and is a reflection of the fertilization.
2. A necessarily long time lag of 24 to 72 hours or more between injury and treatment.
3. Medical and surgical treatment delayed until the end of this lag period and probably administered by less competent surgical teams and even unskilled personnel.
This long time lag, the inadequate supply of materials, the limited number of medical personnel, the delayed antibiotic therapy, and the impossibility of performing definitive surgery in mass casualties during the stage of wound contamination would almost certainly result in a very high incidence of wound infection and a conceivably high incidence of clostridial myositis. Under such circumstances gas gangrene toxoid immunization of troops before injury would be a major hope for the prevention or suppression of clostridial infections.
h. Recommendations. That the currently employed antibiotic regimen be changed as follows:
1. (a) Aqueous penicillin G should be given intravenously at the battalion level as soon after wounding as possible in
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doses of 500,000 to 1,000,000 units every 8 to 12 hours depending upon the severity and multiplicity of the injuries. This may be given with other intravenous fluids.
(b) Streptomycin in doses of 0.5 gram should be given intravenously concomitantly.
(c) After 24 hours, if the patient's blood pressure is no longer reduced, the same agents should be given intramuscularly.
(d) After 72 hours the antibiotic therapy should be re-evaluated and changed as indicated.
(e) Streptomycin therapy should be discontinued after 5 days.
(f) If antibiotic treatment is indicated after 5 days, one of the broad-spectrum drugs should be considered.
(g) In cases of penetrating wounds of the abdomen and gross peritoneal soilage or in patients with extensive devitalization of muscle, terramycin, aureomycin, or chloromycetin should be given in doses of 0.5 gram intravenously at the time of initial surgery along with penicillin in the above-mentioned doses and continued as indicated. When blood pressure is normal and oral intake is possible, the broad-spectrum agents should be given by mouth in dosages of 0.5 gram every 4 to 6 hours. This therapy should be reviewed every 72 hours and varied or discontinued as indicated.
(h) In patients with septicemia every effort should be made to identify the organism and establish its sensitivity to the various antibiotics.
These recommendations were adopted by General Ginn and put into immediate effect.
2. Active surgical consultants should be made available in MASH Evacuation Hospital levels for teaching, consulting, and maintaining continuity of knowledge and surgical technic accumulated in previous wars and in research.
3. Emphasis should be placed on the fact that there is no substitute for frequent and careful clinical examination of the patients. This should be done particularly to detect masked or hidden infection.
4. There should be wider dissemination of existing knowledge to aid in the recognition of clostridial infections, hidden infections and infections masked by antibiotic therapy.
5. Careful investigation should be instituted to measure quantitatively the toxigenicity and pathogenicity of the Clostridia found in Korean war wounds. These results should be correlated with those previously made in other parts of the world.
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6. The relationship, causal or complicative, of infection to secondary shock and anuria should be intensively studied. There is considerable evidence that uncontrolled peritonitis and necrotizing and spreading myositis are intimately associated with this syndrome.
7. Electrolyte imbalance in patients with severe infections warrants further study.
8. The cause of progressive anemia and hemodilution associated with extensive extremity wounds should be determined.
9. The fate of massive transfusion two or more times the total circulating blood volume in shock should be intensively studied further.
10. The possibility of residual toxic factors being caused by infection in patients with anuria after dialysis should be investigated.
11. Detailed clinical and laboratory studies should be made of patients with penetrating wounds of abdomen along a pattern similar to that established for neurosurgical and vascular injuries.
12. The recommendation of clostridial toxoid immunization is deferred temporarily pending comprehensive study of available data and aforementioned quantitative study of the virulence of Clostridia infecting muscle.
13. The relationship of infection to severe and progressive weight loss should be investigated further.
14. Practical means of completely sterilizing the artificial kidney apparatus should be sought.
15. The studies correlating bacterial flora of wounds and antibiotic sensitivity should be continued and expanded.
