Effects of Prophylactic Antibiotics on Colonic Healing Harry H. LeVeen, MD, Brooklyn, New York Simon Wapnick, MD, Brooklyn, New York Gerald Falk, MS, Brooklyn, New York 0. Olivas, MD, Brooklyn, New York D. Bhat, MD, Brooklyn, New York M. Gaurdre, MD, Brooklyn, New York M. Patel, MD, Brooklyn, New York
In many fields of surgery, concepts have arisen de novo without the impact or bias of past experience. Current concepts in colon surgery have been strongly influenced by historical development since the first successful colectomy performed by Martini and Gussenbauer [I] in 1877. In the recent past, the bowel to be resected was delivered onto the abdominal wall and the peritoneum closed, a septum was created between the proximal and distal bowel, and without reentering of the peritoneal cavity, intestinal continuity was restored by application of a spur crusher. Technical development and ancillary therapy was directed toward the prevention of fatal peritonitis by avoidance of operative soiling. Today, surgeons are still preoccupied with initial spillage from the divided bowel. The advent of antibiotics was hailed as a method for reducing the initial contamination at surgery and thereby avoiding subsequent sepsis. This reasoning required that antibiotics be administered as a preoperative bowel preparation. Observations and logic tell us that, since the peritoneum tolerates a modicum of soilage, initial sepsis has ceased to be a problem. Therefore, antibiotics must exert their primary beneficial effect on the healing of colonic
From the Department of Surgery, Veterans Administration Hospital, and State University of New York, Downstate Medical Center, Brooklyn, New York. Reprint requests should be addressed to Harry H. LeVeen. MD, VA Hospital, Brooklyn, New York 11209. Presented at the Sixteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, San Antonio, Texas, May 20-21. 1975.
Vohano 131, January 1978
anastomoses. Leakage consequent to the failure of a colonic wound to heal must be responsible for serious sepsis more often than the limited contamination that may occur during the performance of elective surgery. Since the colonic bacterial flora reestablishes itself within twenty-four hours after the discontinuance of antibiotics [2], the anastomosis must heal in the presence of fecal contamination. Wound sepsis is the most frequent cause of wound disruption, and colonic anastomoses like other contaminated wounds have been observed to disrupt [3]. Also, the late leakage of colonic content after anastomoses seems to be a regular occurrence. Bacteria that are not present in normal bowel flora can be injected intraluminally as markers after completion of a colonic anastomosis. These marker organisms are demonstrable on the peritoneal side of the anastomosis within forty-eight hours in 20 per cent of dogs with inverted anastomoses [4]. Furthermore, leakage and fatal peritonitis occur from experimental everted and inverted colonic anastomoses that are wrapped with silicone rubber sheeting. The silicone sheeting prevents the adjacent viscera from adhering to the anastomotic site and thus sealing it. This is the usual mechanism that so fortuitously prevents leakage 1.51.Anastomotic leakage can be viewed mainly as the failure of the colonic anastomosis to heal because of an adverse influence exerted by the colonic bacteria. Will antibiotics favorably modify the healing process? It was to shed light on this problem that our experiments were undertaken.
47
LeVeen
et al
Figure 1. The tensile strength of bowel anatomoses Is tested by excising a 7 cm strip of bowel across the anatomosis and distracting it on a motor-driven tensometer.
Material and Methods The midsigmoid colon was divided and anastomosed in fifty healthy mongrel dogs weighing from 15 to 23 kg. The dogs were randomly divided into five groups of ten to test the different oral antibiotic colon preparations. Three days prior to surgery all of the animals were placed on a low residue diet and given a purgative drug (5 mg of bisacodyl). This regimen was continued on the second preoperative day. In addition, each animal was given a saline enema until the enema returned clear fluid. One day preoperatively all groups received only a fluid diet and saline enema. The control group (group I) received no additional pre- or postoperative medication. Group II received 500 mg of kanamycin three times a TABLE I
Tensile Strength (gm) Group
Mean Note:
I
II
III
IV
v
i55 187 220 215 205 195 185 165 150 205
270 250 255 227 245 220 165 210 275 165 228
355 380 290 365 290 280 290 330 317 290 319
295
188
240 290 295 315 295 295 279 245 265 250 277
The strengths
of the anastomoses
280 250 260 290 279 251 315 245 315 278
are tabulated
according to groups. Statistical analysis of mean values (Student’s t test, unpaired value): I vs II, p < 0.025; I vs III, IV. v, p < 0.001; IV vs II, p < 0.001; IV vs III, p < 0.01; I I vs V, p < 0.025.
48
day for three preoperative days. Group III received 500 mg of kanamycin with 250 mg of erythromycin for three preoperative days. Group IV had preoperative kanamytin and erythromycin but in addition received 500 mg of kanamycin and 250 mg of erythromycin three times a day for six days starting the day after the operation. Group V received preoperative kanamycin and erythromycin as in group III but postoperatively received only erythromycin. On day zero, following preoperative preparations as described, the dogs underwent surgery. All groups were operated on by the same team of surgeons. The animals were premeditated with atropine and anesthetized with pentobarbital sodium (30 mg/kg). The abdominal area, after being shaved and painted with 70 per cent ethyl alcohol and I per cent tincture of iodine, was entered through a midline incision..The middle portion of the sigmoid colon was identified and divided between nonoccluding bowel clamps. Care was taken to avoid fecal spillage. The divided ends were anastomosed with a single layer of interrupted through-and-through black silk sutures. The peritoneum and fascia of the midline incision were closed with continuous #0 chromic catgut sutures, and the skin with a continuous 3-O nylon suture. Clear fluids were given the day after surgery and in limited amounts for the week after surgery. Exactly one week after the initial colon anastomosis a second laparotomy was performed. The external appearance of the anastomosis was inspected. The peritoneum was examined and the extent of adhesion formation noted. A segment of colon 5 cm proximal to and 5 cm distal to the anastomosis was excised. The divided bowel was reanastomosed. The excised segment was then opened longitudinally close to the mesenteric border and the silk sutures were carefully identified from the interior of the bowel and removed without disturbing the anastomosis. Several
The American Journal of Surgery
Prophylactic and Antibiotics
Colonic Healing
Ill GROUPS
Figvre 2. The tensile strengths in each group are compared to a simple mechanical preparation as 100 per cent. Note that all the antibiotkally prepared bowels have sJlghtly greater tensile strengths. Dogs receiving kanamycln and erythKnnycin pre- and postoperatively (group IV) almost doubled their tensile strengths.
longitudinal strips were then cut along the length of the bowel using a special double blade knife. Since these strips passed across the anastomosis, the tensile strength of the anastomosis could be tested by exerting traction from either side of the anastomosis and measuring the force required to rupture the anastomosis. This was done with a specially constructed motor-driven tensometer. (Figure 1.) The tensile strength was taken as the average of three separate readings from three different strips. The remainder of the bowel anastomosis was fixed in formalin solution for histologic examination.
Results
Table I shows the individual and mean tensile strengths of anastomoses in animals receiving the different bowel preparation schedule. Preoperative kanamycin had a slight advantage over mechanical preparation. The addition of erythromytin to the antibiotic preparation significantly (p
In many fields of surgery, concepts have arisen de novo without the impact or bias of past experience. Current concepts in colon surgery have been strongly influenced by historical development since the first successful colectomy performed by Martini and Gussenbauer [I] in 1877. In the recent past, the bowel to be resected was delivered onto the abdominal wall and the peritoneum closed, a septum was created between the proximal and distal bowel, and without reentering of the peritoneal cavity, intestinal continuity was restored by application of a spur crusher. Technical development and ancillary therapy was directed toward the prevention of fatal peritonitis by avoidance of operative soiling. Today, surgeons are still preoccupied with initial spillage from the divided bowel. The advent of antibiotics was hailed as a method for reducing the initial contamination at surgery and thereby avoiding subsequent sepsis. This reasoning required that antibiotics be administered as a preoperative bowel preparation. Observations and logic tell us that, since the peritoneum tolerates a modicum of soilage, initial sepsis has ceased to be a problem. Therefore, antibiotics must exert their primary beneficial effect on the healing of colonic
From the Department of Surgery, Veterans Administration Hospital, and State University of New York, Downstate Medical Center, Brooklyn, New York. Reprint requests should be addressed to Harry H. LeVeen. MD, VA Hospital, Brooklyn, New York 11209. Presented at the Sixteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, San Antonio, Texas, May 20-21. 1975.
Vohano 131, January 1978
anastomoses. Leakage consequent to the failure of a colonic wound to heal must be responsible for serious sepsis more often than the limited contamination that may occur during the performance of elective surgery. Since the colonic bacterial flora reestablishes itself within twenty-four hours after the discontinuance of antibiotics [2], the anastomosis must heal in the presence of fecal contamination. Wound sepsis is the most frequent cause of wound disruption, and colonic anastomoses like other contaminated wounds have been observed to disrupt [3]. Also, the late leakage of colonic content after anastomoses seems to be a regular occurrence. Bacteria that are not present in normal bowel flora can be injected intraluminally as markers after completion of a colonic anastomosis. These marker organisms are demonstrable on the peritoneal side of the anastomosis within forty-eight hours in 20 per cent of dogs with inverted anastomoses [4]. Furthermore, leakage and fatal peritonitis occur from experimental everted and inverted colonic anastomoses that are wrapped with silicone rubber sheeting. The silicone sheeting prevents the adjacent viscera from adhering to the anastomotic site and thus sealing it. This is the usual mechanism that so fortuitously prevents leakage 1.51.Anastomotic leakage can be viewed mainly as the failure of the colonic anastomosis to heal because of an adverse influence exerted by the colonic bacteria. Will antibiotics favorably modify the healing process? It was to shed light on this problem that our experiments were undertaken.
47
LeVeen
et al
Figure 1. The tensile strength of bowel anatomoses Is tested by excising a 7 cm strip of bowel across the anatomosis and distracting it on a motor-driven tensometer.
Material and Methods The midsigmoid colon was divided and anastomosed in fifty healthy mongrel dogs weighing from 15 to 23 kg. The dogs were randomly divided into five groups of ten to test the different oral antibiotic colon preparations. Three days prior to surgery all of the animals were placed on a low residue diet and given a purgative drug (5 mg of bisacodyl). This regimen was continued on the second preoperative day. In addition, each animal was given a saline enema until the enema returned clear fluid. One day preoperatively all groups received only a fluid diet and saline enema. The control group (group I) received no additional pre- or postoperative medication. Group II received 500 mg of kanamycin three times a TABLE I
Tensile Strength (gm) Group
Mean Note:
I
II
III
IV
v
i55 187 220 215 205 195 185 165 150 205
270 250 255 227 245 220 165 210 275 165 228
355 380 290 365 290 280 290 330 317 290 319
295
188
240 290 295 315 295 295 279 245 265 250 277
The strengths
of the anastomoses
280 250 260 290 279 251 315 245 315 278
are tabulated
according to groups. Statistical analysis of mean values (Student’s t test, unpaired value): I vs II, p < 0.025; I vs III, IV. v, p < 0.001; IV vs II, p < 0.001; IV vs III, p < 0.01; I I vs V, p < 0.025.
48
day for three preoperative days. Group III received 500 mg of kanamycin with 250 mg of erythromycin for three preoperative days. Group IV had preoperative kanamytin and erythromycin but in addition received 500 mg of kanamycin and 250 mg of erythromycin three times a day for six days starting the day after the operation. Group V received preoperative kanamycin and erythromycin as in group III but postoperatively received only erythromycin. On day zero, following preoperative preparations as described, the dogs underwent surgery. All groups were operated on by the same team of surgeons. The animals were premeditated with atropine and anesthetized with pentobarbital sodium (30 mg/kg). The abdominal area, after being shaved and painted with 70 per cent ethyl alcohol and I per cent tincture of iodine, was entered through a midline incision..The middle portion of the sigmoid colon was identified and divided between nonoccluding bowel clamps. Care was taken to avoid fecal spillage. The divided ends were anastomosed with a single layer of interrupted through-and-through black silk sutures. The peritoneum and fascia of the midline incision were closed with continuous #0 chromic catgut sutures, and the skin with a continuous 3-O nylon suture. Clear fluids were given the day after surgery and in limited amounts for the week after surgery. Exactly one week after the initial colon anastomosis a second laparotomy was performed. The external appearance of the anastomosis was inspected. The peritoneum was examined and the extent of adhesion formation noted. A segment of colon 5 cm proximal to and 5 cm distal to the anastomosis was excised. The divided bowel was reanastomosed. The excised segment was then opened longitudinally close to the mesenteric border and the silk sutures were carefully identified from the interior of the bowel and removed without disturbing the anastomosis. Several
The American Journal of Surgery
Prophylactic and Antibiotics
Colonic Healing
Ill GROUPS
Figvre 2. The tensile strengths in each group are compared to a simple mechanical preparation as 100 per cent. Note that all the antibiotkally prepared bowels have sJlghtly greater tensile strengths. Dogs receiving kanamycln and erythKnnycin pre- and postoperatively (group IV) almost doubled their tensile strengths.
longitudinal strips were then cut along the length of the bowel using a special double blade knife. Since these strips passed across the anastomosis, the tensile strength of the anastomosis could be tested by exerting traction from either side of the anastomosis and measuring the force required to rupture the anastomosis. This was done with a specially constructed motor-driven tensometer. (Figure 1.) The tensile strength was taken as the average of three separate readings from three different strips. The remainder of the bowel anastomosis was fixed in formalin solution for histologic examination.
Results
Table I shows the individual and mean tensile strengths of anastomoses in animals receiving the different bowel preparation schedule. Preoperative kanamycin had a slight advantage over mechanical preparation. The addition of erythromytin to the antibiotic preparation significantly (p
