Chapter 19
The Plasma Concentration of Penicillin in Korean Battle Casualties
First Lieutenant Joseph G. Strawitz, MC, USAR
Koibong Li, M. D., Ph. D.
Lieutenant Colonel Robert B. Lindberg, MSC, USA
Major Arthur Newton, MSC, USAR
Captain John M. Howard, MC, USAR
Lieutenant Colonel Curtis P. Artz, MC, USA
This study of the concentration of penicillin in the plasma1 was a part of abroad program of investigation of the resuscitative tools used in the emergency treatment of the wounded soldier.
At the battalion aid station, in addition to vital restorative measures, the casualty received aqueous procaine penicillin intramuscularly in a dosage of 300,000 to 600,000 units. He was then transferred via ambulance or helicopter to a forward surgical hospital arriving from 1 to 5 hours after administration of the antibiotic. Throughout this period of evacuation, casualties often remained in varying degrees of blood volume deficiency.
The purpose of this study was to determine plasma levels of penicillin in severely injured soldiers after intramuscular injection of aqueous procaine penicillin. It was believed that, in the combat casualty, the adequacy of penicillin therapy could be better assessed from these levels.
Materials and Methods
Sixty-five casualties were selected for study at the time of admission to the forward hospital. A record was kept of the amount of penicillin received, the lapse of time after injection, and the vital signs of the patient. A heparinized venous sample was obtained by aseptic technic; then the plasma was separated and placed in a sealed test tube and frozen immediately. The specimens were shipped by air to the 406th Medical General Laboratory in Tokyo. Penicillin assays
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were based on the inhibition of hemolytic staphlococcus (Heatly strain) by a serial dilution technic.2 Control studies indicated that freezing did not inactivate the penicillin.
Thirty-nine patients received 300,000 units of penicillin. Of this number, 21 were considered hypotensive because the systolic blood pressure was less than 100 millimeters of mercury. Twenty-six patients received 600,000 unit of penicillin; 8 were hypotensive. Most of the casualties in the normotensive group had a blood volume deficiency, but were vasoconstricted.
Control studies of the plasma concentration of penicillin, following the intramuscular injection of 300,000 and 600,000 units of aqueous procaine penicillin respectively, were carried out in two subjects. Plasma levels were determined hourly for 6 hours post-injection.
Results
After injection of 300,000 units of penicillin, the plasma concentrations ranged up to 1.8 units per milliliter (Fig. 1). Between 1 and 6 hours after injection, only 4 casualties had a concentration below 0.2 unit per milliliter. No correlation could be made between the degree of circulatory insufficiency as determined by the blood pressure and the plasma concentration of penicillin.
Following injection of 600,000 units of penicillin, plasma levels ranged up to 2.2 units per mm. (Fig. 2). Although only six casualties had a plasma concentration below 0.2 unit per milliliter, all but three of the casualties had levels below the control values. The number of hypotensive patients was too small to permit any conclusions; however, no obvious relationship was noted between the blood pressure and penicillin concentration.
The control studies confirmed the previous observations of Romansky1 (Figs. 1 and 2).
Discussion
Altemeier3 and Cloud4 and their associates demonstrated that plasma levels were higher and remained higher for a longer period in the shocked animal than in control animals, in spite of the fact that penicillin was absorbed more slowly. Although absorption was slightly delayed, higher levels resulted because urinary excretion was markedly diminished. This diminution in urinary excretion was an important factor, because 40 per cent of penicillin is normally excreted in the urine within the first hour after injection.5
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The plasma levels obtained in this study of the battle casualty, as compared with those suggested for routine use, were well above the minimal therapeutic levels of 0.06 unit per milliliter6 and 0.05 unit per milliliter,7 but were often below the concentration found necessary to inhibit, in vitro, the clostridial organisms that colonized wounds of soldiers injured in Korea.8
Summary
Serial plasma levels were determined at varying periods up to 6 hours after the injection of aqueous procaine penicillin in 104 severely injured men. Most of the levels were below those of control subjects but well above the minimal therapeutic level. The levels obtained in hypotensive patients did not differ significantly from the levels obtained in normotensive patients.
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References
1. Romansky, M. J.: George Washington School of Medicine. Personal communication.
2. Strawitz, J. G., and Marshall, J. D.: A Comparison of Plasma and Muscle Concentrations of Antibiotics. In press.
3. Altemeier, W. A., Coith, R. L., and Culbertson, W. R.: Parenteral and Intestinal Absorption of Antibiotics in Traumatic Shock. Arch. Surg. 63: 403-407, 1951.
4. Cloud, T. M., Gaines, S., and Pulaski, E. J.: The Absorption and Excretion of Antimicrobial Agents in Hemorrhagic Shock. Surgical Forum, Proceedings of the Forum Sessions of the Thirty-seventh Clinical Congress of the American College of Surgeons, 1951. W. B. Saunders Company, Philadelphia, 1952.
5. Rammelkamp, C. H., and Keefer, C. S.: The Absorption, Excretion and Distribution of Penicillin. J. Clin. Investigation 22: 426, 1943.
6. Pratt, R., and Dufrenoy, J.: Antibiotics. J. B. Lippincott Company, Philadelphia, 1949.
7. Harries, E. H. R., and Mitman, M.: Clinical Practice in Infectious Diseases. E. and S. Livingston, Ltd., Edinburgh, 1951.
8. Newton, A., Strawitz, J. G., Lindberg, R. L., Howard,J. M., and Artz, C. P.: Sensitivities of Ten Species of Clostridia to Penicillin, Aureomycin, Terramycin, and Chloramphenicol. A Study of Battle Wounds in Korea. Surgery 37: 392, 1955. (Chapter 16 in Volume III of this series.)
