Wound Infections in Renal Transplant Wounds - NCBI

4 downloads 120 Views 1008KB Size Report
GEORGE K. KYRIAKIDES, M.D., RICHARD L. SIMMONS, M.D., JOHN S. NAJARIAN, M.D.. The factors contributing to transplant wound infection, as well as.
Wound Infections in Renal Transplant Wounds: Pathogenetic and Prognostic Factors

GEORGE K. KYRIAKIDES, M.D., RICHARD L. SIMMONS, M.D., JOHN S. NAJARIAN, M.D.

The factors contributing to transplant wound infection, as well as those determining its outcome, have been reviewed in 27 transplant patients with wound infection. Unrelated cadaver kidneys, diabetes, urinary fistulas and wound hematomas are all factors predisposing to wound infection. Overall incidence of wound infection in this series was 6.1% (27/439). When infections secondary to known preventable causes (i.e. hematomas and fistulas) were excluded, the incidence of wound infection was only 1.6%. Furthermore, if diabetics and retransplanted patients were excluded, the incidence of wound infection in non-diabetic patients who had their first transplant was only 0.7%. Perinephric infections are much more serious and carry a worse prognosis than superficial infections. Overall mortality of wound infections was 30% (8/27), most deaths being caused by sepsis from deep infection. Only three patients (11%c) healed their wounds and saved their kidneys, whereas the rest of the survivors (15/18) healed their wounds but lost their kidneys. It is emphasized that prevention of hematomas and urinary fistulas is the most important measure in the prevention of transplant wound infection.

S URGICAL WOUND INFECTION has been a subject of considerable clinical and experimental study *4,6,18 Transplant wound infections deserve particular attention, because of the special conditions associated with them and because of the serious consequences that wound infections may have for these patients. These special conditions are: 1) the uremic state of the patient at the time of surgery and sometimes in the immediate posttransplant period; 2) the presence of a "foreign" organ in the surgical wound; and 3) the increased susceptibility of heavily immuno-suppressed patients to infection. Submitted for publication June 24, 1975. Supported by Grant #AM 13083 from the United States Public Health Service. Reprint requests: Dr. Simmons, Box #185, Department of Surgery, University of Minnesota Hospitals, Minneapolis, Minnesota 55455.

From the Department of Surgery, University of Minnesota Hospitals, Minneapolis, Minnesota

Previous studies of transplant-wound infections reported an incidence ranging from 1.8% to 56% .551621 The purpose of this study is a detailed analysis of all causes and predisposing conditions leading to wound infection. An understanding of these conditions should lead to a decrease in the incidence of transplant-wound infections and the attending morbidity and mortality. Materials and Methods A retrospective analysis of the transplant-wound infections seen at the University of Minnesota Hospitals from August 1967 to July 1973 was made. During this period, 439 kidneys were transplanted to 378 patients; of these, 378 were first transplants, 51 second transplants, 7 third transplants and 3 fourth transplants. Two hundred and fifty-seven out of 439 kidneys were donated by living volunteer relatives and 182/439 were of cadaver origin. A wound was considered infected when there was pus in the wound and bacterial cultures were positive. Serous discharge or urinary leaks with negative bacterial cultures were not considered infected unless repeated cultures proved infection to be present. The operative technique and immunosuppressive regimen used at the University of Minnesota has been described in detail elsewhere.22 In adults, the kidney transplants were placed retroperitoneally in one of the iliac fossae through lateral lower quadrant incisions, whereas in children weighing less than 20 kg they were placed intra-abdominally through midline abdominal inci-

770

Vol. 182

TABLE 1. Age Distribution of Transplant Wound Infections Age (Years)

RATIO # Infections/ # Transplants

RATIO # Diabetics/ # Transplants

0-10 11-20 21-30 31-40 41-50 51-60 61-70 Total

1/47 (2.1%) 4/80 (5%) 8/85 (9.4%) 9/99 (9%O) 4/74 (5.4%) 1/49 (2%) 0/5 (0%) 27/439 (6.1%)

0/47 (0o 0/80 (0%) 23/85 (27%) 33/99 (33.3% 8/74 (10.8%) 1/49 (2%) 0/5 (0%o) 65/439 (14.5%)

TABLE 3. Incidence of Infection in Cadaver and Related Kidney Recipients*

# patients

Incidence of Infection

Incidence of perinephric infections

182

18/182 (9.9%o)

12/182 (6.6%)

257

9/257 (3.5%)

4/257 (1.5%)

Cadaver Kidney

sions. All the wounds were irrigated with neomycin or neomycin-bacitracin solutions during the procedure, and some of the wounds were drained with a hemovac drain for 24-36 hours. Skin sutures were routinely removed on the tenth postoperative day. All patients were treated with prophylactic semisynthetic penicillin, starting the day before surgery and continuing for 10 days after operation. Results There were 27 wound infections in 439 kidney transplants carried out since August of 1967-an incidence of 6.1%. Eleven (2.5%) were subcutaneous infections, but 16 (3.6%) involved the perinephric tissues.

Effect of recipient age on incidence of wound infection Table 1 analyzes the distribution of wound infections in patients of various ages. The highest incidence of infection was in the third and fourth decades, 9.6% and 9% respectively, with a lower incidence in younger and older patients. This higher incidence in the third and fourth decades corresponds mainly to the higher incidence of infections in young adults with juvenile insulin dependent diabetes (Tables 1 and 2). Diabetic versus non-diabetic patients Of the total series of transplanted patients, 65 (14.5%) were diabetics and 374 were non-diabetics. The incidence of infection in the diabetic group was twice as high as in the non-diabetic group. Peri-nephric infections were also more common in the diabetic patients. Conversely, alTABLE 2. Incidence of Infection in Diabetic and Non-Diabetic Patients*

# Patients Total Infections

Diabetic patients Non-Diabetic patients

771

RENAL TRANSPLANT WOUND INFECTION

No. 6

65 374

7/65 (10.8%) 20/374 (5.3%)

Incidence of Perinephric Infection 5/65 (7.7%)

11/374 (2.9o)

*Chi squared analysis yields P '0.05 for this table.

Recipients

Related Kidney

Recipients

*Chi squared analysis yields P '0.005 for this table.

most half of the infections in non-diabetic patients were superficial (Table 2).

Cadaver versus related kidney recipients Table 3 demonstrates that recipients of cadaver kidneys had almost three times the incidence of wound infections when compared with recipients of related kidneys. Peri-nephric infections were also more common in recipients of cadaver kidneys (Table 3). Influence of pre-transplant organ perfusion on wound infection Of the 182 cadaver kidneys, 107 were perfused on the Mox-100 preservation machine for variable periods of time. Perfusion of the kidney did not predispose to wound infection since the incidence of infection in the perfused cadaver kidneys was 9/107 (8.4%) and in the non-perfused group was 9/75 (12%). The cryoprecipitated plasma perfusate was cultured during and after all perfusions. Perfusate bacterial cultures were positive in 25/107 cases. Staphylococcus was cultured in 18 cases, pseudomonas in four, unidentifiable gram negative rods in two, and ,-streptococcus in one case. There was no correlation between the types of bacteria found in positive perfusate cultures and that found in the wound infection, although three kidneys with staphylococcus in the perfusate later developed wound infection with gram negative organisms. Also the length of perfusion did not predispose to contamination of perfusate. On the contrary, 20 of the 25 perfusates which became contaminated did so in the first 6 hours of perfusion. The length of perfusion was also not a contributing factor to the incidence of infection (Table 4). The mean perfusion time of the non-infected group was 19.5 hours and of the infected group 18.3 hours. TABLE 4. Relation of Length of Preservation to Incidence of Wound Infection in 107 Perfusion-Preserved Cadaver Kidneys* Total Hours of Perfusion

Incidence of Wound Infection

12 13-24 25-36

1/23 (4.3%) 7/62 (11%) 1/22 (4.5%)

*Chi squared analysis is not significant (P ¢0.05)

KYRIAKIDES, SIMMONS AND NAJARIAN

772

Ann.

Surg. * December 1975

TABLE 5. Multiple Factors Predisposing to Wound Infection: Deep Infections

Juvenile

Patient

Age, Sex

Transplant #

Diabetes

Cadaver Donor

ATN

Hematoma

Urinary Fistula

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

34, M 34, M 29, M 40, M 29, F 24, F 20, M 35, M 56, F 39, M 24, F 25, F 45, M 11, F 25, M 19, M

1 2 1 1 1 I 1 1 1 2 I 1 I 1 1 1

+

-

+

+

+

+

+

+

+ + +

+ + +

-

-

+

+

-

+ + + + + + +

+ + + +

+ + + +

+ + + + + +

-

-

-

+ + + + +

+

+ -

+ +

+

+ +

+ -

+

Effect of wound hematomas on the incidence of trans- hematoma (Table 5). Of the 11 superficial infections only plant wound infection: 4 were associated with a wound hematoma or urinary In the whole transplant series, there were 30 wounds fistula. (Table 6) which required re-exploration in the immediate post- Effect of posttransplant renal function on the incidence transplant period because of bleeding, an incidence of of wound infection 7%. The distribution of hematomas in the recipients of Of 439 transplant patients, 70 (16%) had acute tubular living related kidneys was 14/257 (5.4%) and cadaver kidnecrosis (ATN) as defined by a need for at least one neys was 16/182 (8.8%). Of these 30, 14 became infected in the posttransplant period. Forty-four of hemodialysis (46%). Ten of the infected hematomas were associated with those were of cadaver kidneys and 26 rerecipients perinephric infections and 4 with superficial infections. of related cipients kidneys. Eighteen out of 70 (25.7%) of Nine of 10 deep wound infections which followed wound the who patients required in the posttransplant dialysis bleeding were associated with renal malfunction which became infected. In period contrast, of the 369 patients required at least one posttransplant dialysis. Thus, alwho did not after require dialysis transplantation, only most half of the 27 wound infections in the entire series 9/369 became (2.4%) infected (P-'0.005). were related to excessive bleeding into the wound which It is likely that ATN itself does not predispose to required re-exploration and was associated with early wound infection and that other factors are at work. renal malfunction. Whereas 26 patients with related transplants required Effect of urinary fistulas on the incidence of transplant posttransplant hemodialysis, only three non-diabetic patients (patients 14, 15, and 16, Table 5) developed deep wound infections: wound infections. Two of these had intestinal fistulas, In the entire series there were 17 urinary fistulas, an (patients 14 and 16), one from an attempted transplant to incidence of 3.9%. Five of these never became infected. an ileal loop and one due to a known technical error Of the 12 that became infected, 11 were associated with during transplant when bowel was accidentally perinephric abscesses. Significantly, 5/67 (7.7%) dia- Only one patient without diabetes or intestinalentered. fistula betics developed urinary fistulas and all became infected. developed wound infection after requiring hemodialysis 12/374 (3.2%) non-diabetic patients developed uri- (patient 15). There was known bleeding into the wound nary fistulas and 7/12 became infected. Ten of the pa- on the night of transplantation and this hematoma was tients with wound infection after urinary fistulas had not evacuated. Thus, ATN by itself cannot be a cause of simultaneous urinary tract infection, and bacterial cul- deep wound infection in patients without complications. tures were identical in both wounds and urine. Interest- In fact, Tables 5 and 6 demonstrate that multiple factors ingly, 7 other patients with wound infections had identi- are present in most patients with wound infections. No cal cultures in wound and urine without a urinary fistula. patient with ATN developed wound infection without Of the total of 27 infections 11/27 were superficial and some other predisposing cause. Table 6 similarly dem16/27 were perinephric. Of the 16 deep infections all were onstrates only one patient who developed a superficial associated with either urinary leak or perinephric wound infection in whom ATN might have been the only

VQIl. 1 82

,

773

RENAL TRANSPLANT WOUND INFECTION

NO 6

TABLE 6. Multiple Factors Predisposing to Wound Infection: Superficial Infections

Patient

Age, Sex

Transplant #

17 18 19 20 21 22 23 24 25 26 27

35, M 29, F 1,M 31, M 30, F 40, F 47, M 41, F 20, F 49, M 35, F

I 1 2 1 3 I I I

I 1 I

Juvenile Diabetes + +

-

predisposing cause (Patient 25). As will be seen below, renal malfunction in early posttransplant period due to accumulation of hematoma within the wound seems to be the combination which predisposes to wound infection rather than ATN alone. Effect of repeated transplantation on the incidence of wound infections: The incidence of wound infection in first transplants was 6% (23/378), in the second transplants, 6% (3/51), and in subsequent transplants, 10%o (1/10). It can be seen that the incidence of wound infection in first and subsequent transplants is approximately the same.

Bacteriology of wound infections: Gram negative rods accounted for the majority of wound infections. Enterococcus and staphylococcus were the only gram positive cocci recovered from infected wounds. The infecting organisms in the 27 wound infections are listed in Table 7. Of the 27 patients with wound infections, 17 had simultaneous bacteriuria usually with the same organisms (Table 7). Complications of wound infection: There were three main complications resulting from wound infection: Septicemia occurred in 10/27 (37%) cases development of mycotic aneurysm of the iliac vessels or the aorta in 7/27 (26%) cases, and transplant nephrectomy became necessary in 15/27 (55%) cases. Each of these three categories will be considered separately. Septicemia: Of the 10 cases, three were caused -by pseudomonas, three by enterococcus, two by E. coli, one by Klebsiella, and one by bacteroides. Pseudomonas was a particularly virulent organism in that it caused septicemia in 60% of the cases in which it was cultured from wounds whereas enterococcus septicemia occurred in 25% of these cases in which the organism was cultured, and for E. coli the incidence of septicemia was only 14%. There was no difference in incidence of systemic sepsis between diabetics and non-diabetics. Cadaver kidney re-

Cadaver Donor

ATN

Hematoma

+ + + +

+ + +

+ + -

-

+

+

+

+ +

-

+

-

Urinary Fistula

+

cipients accounted for 8 of the 10 cases of septicemia.

Half of the 10 cases survived and the other half died as a result of sepsis. Mycotic aneurysms of the iliac vessels occurred in 6 cases of 16 deep wound infections and one of these later developed a mycotic aneurysm of the aorta. Of these, 4 were diabetics, representing in incidence of 80% of the deep infections in diabetic patients; 3/11 deep infections in non-diabetic patients developed mycotic aneurysms. None of the patients with subcutaneous infections developed mycotic aneurysms. Three of the aneurysms necessitated transplant nephrectomy at the time of exploration; two aneurysms developed after transplant nephrectomy was done for perinephric abscess. One kidney was saved and retained good function after ligation of the involved external iliac artery. Another kidney retained excellent function after resection of the aneurysm with axillofemoral by-pass graft with retrograde perfusion of the kidney. There was only one death as a result of the aneurysm. This occurred as a result of later rupture of the aortic stump in the case described above. The rest of the patients survived the rupture of their aneurysms following successful ligation of the involved artery. TABLE 7. Bacteriology of 27 Wound and 17 Simulliltatneous Urinary Tract Infections

No. of No. of wound infections urine cultures with organisms* with organisms E. coli Enterococcus Candida albicans Staphylococcus Pseudomonas Klebsiella Proteus Bacteroides Citrobacter diversus

No. of

organisms in common

14/27 12/27 11/27 5/27 5/27 3/27 2/27 2/27

9 5 5 0 3 4 0 2

9 5 5 0 3 3 0 2

2/27

1

1

*Mixed infections account for a greater number of types of organisms cultured than number of wound infections.

774

KYRIAKIDES, SIMMONS AND NAJARIAN

Transplant Nephrectomy: Transplant nephrectomy done in 15 cases. Of these, 12 were associated with perinephric abscess and three were done because of superficial wound infection associated with severe rejection. Thus, 12/16 of the patients with deep perinephric infections lost their kidney as a direct result of the infection. Outcome of Wound Infections: The overall mortality of wound infection was 29.6% (8/27). Five deaths were the result of septicemia complicating deep wound infection. One died later of a ruptured aortic mycotic aneurysm, one died of a myocardial infarction and one baby with superficial infection died of pneumonia. Eighteen of 27 wounds healed completely but only three healed with the transplant intact. All the rest (15/18) underwent neph-

was

rectomy.

Of patients who lost kidneys but survived wound infections, 4 were transplanted again. Two out of four had second wound infections, and both died of sepsis at some time after second transplant. Discussion Infection is frequently a life-threatening complication in the immunosuppressed transplant recipient and remains the most common cause of death in these patients.24 Previous reports pointed out that infections of transplant wounds are common5'16'21 and predisposing factors are not difficult to find. Uremia, immunosuppressive drugs, bacteremia during hemodialysis due to defects in the dialysis membrane, chronically infected hemodialysis catheters, the contamination of wounds with urine, cadaver kidneys from unknown or poorly defined sources, pre-existing infections of anuric bladders, and diabetes all appear to predispose to infection. Though prophylactic antibiotics can eliminate gram positive organisms,14 they have not proven effective against gram negative organisms. Immunosuppression seriously impairs the defense mechanisms of transplant patients. Steroids decrease the rate of healing of wounds9'12 and make them more vulnerable to infection.26 Azathioprine also causes leukopenia and impairs the immune response.27 Uremia is also associated with poor wound healing and wound dehiscence19 and increased risk of infection."5 In addition, uremic patients have a bleeding diathesis1,1'3 and this may lead to hematoma formation, particularly after dialysis,10 with subsequent infection. The overall incidence of wound infection in this series was 6.1%. If, however, those secondary to hematoma or urinary fistula are excluded (Tables 5 and 6) as being due to technical error and probably entirely preventable then the incidence of wound infection in the uncomplicated wound is only 1.6% (7/439). Furthermore, all 7 patients had superficial infections (17, 18, 19, 20, 21, 23, and 25).

Ann. Surg.

-

December 1975

Two of these were diabetics and 5 were recipients of cadaver kidneys. In two patients, infection followed second and third transplants respectively and one infection followed re-exploration of the wound for correction of arterial kink (Patient 25). If diabetics and retransplanted patients were thus excluded, the incidence of wound infection in non-diabetic patients who had their first transplant was only 0.7% (3/439), and all three infections were superficial. The 1.6% infection rate of uncomplicated transplant wounds was lower than the 1.81% rate of infection of clean general surgical procedures4'6 and definitely lower than the 4.7% rate of infection in herniorraphy and 14.3% infection rate in breast surgery.4

The higher incidence of wound infection in cadaver kidney recipients has been observed by others.16 This may be due to higher doses of immunosuppressants and possible kidney contamination during preservation. Although the 25 positive perfusate cultures did not correlate with clinical infections, they, however, indicate that contamination does take place. Diabetes in itself is known to predispose to infection.2 7'17 Furthermore, the incidence of urinary fistulas in diabetics is much higher than in non-diabetics (7.7% vs. 3.2%)23 and when this occurs, wound infection almost inevitably follows. The severity of infection depends on the number of factors involved in its development. All deep infections were associated with either hematoma or urinary fistula or both (Table 5), whereas of the superficial infections only 4 were associated with hematomas and only one with urinary fistula. Also 12/16 of deep infections were in cadaver kidney recipients but of the superficial infections only 6/11 were of cadaver recipients. Also 5/16 of deep infections were in diabetics and only 2/11 of superficial infections were in diabetics. Thus, the more frequent presence of predisposing factors such as diabetes, cadaver origin of kidneys, hematomas and urinary leaks leads to the more serious deep infections. The two surgical complications which predispose to all deep infections, i.e. hematomas and urinary fistulas, are potentially preventable by good surgical technique. In addition to surgical error, hematomas may result from the inherent bleeding diathesis of uremic patients,1113 or posttransplant renal malfunction which require anticoagulation during hemodialysis.'° The seriousness of hematomas as predisposing causes of infection and the role of local hematin compotents in the pathogenesis of infection has been also reported by others.25 The prevention of hematoma in transplant wound is of paramount importance. Wound hemostasis must be meticulous. Particularly in cadaver kidneys, which are usually hastily harvested, attention to hemostasis must be extreme. Small bleeding points in the kidney capsule and around the renal pelvis must be controlled after transplantation. This problem may be complicated since

Vol. 182

-

No. 6

RENAL TRANSPLANT WOUND INFECTION

775

Effect of Experimental Non-detotic Diabetes Mellitus on renal flow to the ischemic kidney may be delayed so that Antibacterial Defense: 1. Demonstr-ation of Defect in small vascular defects might not be noted. Recipients Phagocytosis. J. Exp. Med., 124:227, 1966. may also have recently received anticoagulants to main8. Glotzer, D.J., Goodman, W.S. and Geronimus. L.H.: Topical Antibiotic Prophylaxis in Contaminated Wounds. Arch. Surg.. tain patent shunts or fistulas, or may have required 100:589, 1970. emergency pretransplant dialysis; transplantation must 9. Green, J.P.: Steroid Therapy and Wound Healing in Surgical Pabe delayed until in vitro coagulation parameters have tients. Br. J. Surg., 52:523, 1965. 10. Hampers. C.L.. Blaufox, M.D. and Merrill. J.P.: Anticoagulation returned to normal. Rebound After Hemodialysis. N. Engi. J. Med., 275:776. 1966. We are in agreement with other investigators21 who 11. Horowitz, I.H.: Uremic Tloxins and Platelet Function. Arch. Intern have found that the consequences of wound infection are Med., 126:823, 1970. disastrous for both the kidney and the patients. Super- 12. Howes, E.L., Plotz, C.M., Blunt, J.W. and Ragan, C.: Retardation Wound Healing by Cortisone. Surgery, 28:177. 1950. ficial infections could be drained, but deep infections 13. vonofKaulla, K.N., von Kaulla, E.. Wasantupruck, S.. et al.: Blood led to the loss of kidney in 75% of the cases. Mycotic Coagulation in Uremic Patients Before and After Hemodialysis and Transplantation of the Kidney. Arch. Surg., 92:184, 1966. aneurysms occurred in 37.5% and septicemia in 62.5% W.D., Lillehei, R.C.. Aust, J.B.. et al.: Kidney Transplantaof deep wound infections. Half of the patients with 14. Kelly, tion: Experiences at the University of Minnesota Hospitals. septicemia died. The remainder of the patients had open Surgery, 62:704, 1967. wounds requiring prolonged hospitalization. Of 57 cases 15. Montgomerie, J.Z., Kalmanson. G.M. and Guze. L. B.: Renal Failure and Infection. Medicine, 47:1, 1968. of septicemia in transplant patients reported by Ander- 16. Moore, T.C. and Hume, D.M.: The Period and Nature of Hazard in son,' 10 cases were due to wound infection. Mycotic Clinical Renal Transplantation. 1. The Hazard to Patient Survival. Ann. Surg., 170:1, 1969. aneurysms are a serious complication and open infected A-G. and Baum, J.: Chemotaxis of Polymorphonuclear wounds should be assessed frequently for early detection 17. Mowat, Leukocytes from Patients with Diabetes Mellitus. N. i,nl. J. of this potentially lethal condition. Med., 282:123, 1970. W Treatment of transplant wound infection follows the 18. National Research Council: Postoperative Wound Infections: The Influence of Ultraviolet Irradiation of the Operating Room, and general surgical principles of drainage and irrigation. If of Various Other Ann. Surg., 160 (supp); 1, 1964. the presence of the graft prevents adequate drainage, as it 19. Nayman, J.: Effect ofFactors. Renal Failure on Wound Healing in Dogs. Response to Hemodialysis Following Uremia Induced by frequently does, transplant nephrectomy should be perNitrate. Ann. Surg., 164:227. 1966. formed. Appropriate antibiotics should be administered 20. Raij.Uranium L., Shapiro, F.L. and Michael, A.F.: Endotoxemia in Febrile but certain organisms like pseudomonas present serious Reactions during Hemodialysis. Kidney Intern., 4:57, 1973. and potentially lethal problems regardless of the anti- 21. Schweizer, R.T., Kountz, S.L. and Belzer, F.O.: Wound Complications in Recipients of Renal Transplants. Ann. Surg. 177:58, biotics chosen. 1973. 22. Simmons, R.L., Kjellstrand, C.M. and Najarian, J.S.: Kidney: References a

1. Anderson, R.J. Schafer, L.A., Olin, D.B. and Eickhoff, R.C.: Septicemia in Renal Transplant Patients. Arch. Surg., 106:692, 1973. 2. Bagdade. J.D., et al.: Host Defenses in Diabetes Mellitus: The Feckless Phagocyte During Poor Control and Ketoacidosis. Diabetes, 19:364, 1970. 3. Belzer, F.O., Salvatierra, O., Schweizer, R.T. and Kauntz, S.L.: Prevention of Wound Infections by Topical Antibiotics in High Risk Patients. Am. J. Surg., 126:180, 1973. 4. Brunn, J.N.: Postoperative Wound Infection. Predisposing Factors and the Effect of a Reduction in the Dissemination of Staphylococci. Acta Med. Scand. (suipp.), 514:3, 1970. 5. Burgos-Calderon, R.. Pankey, G.A. and Figueroa, J.E.: Infection in Kidney Transplantation. Surgery, 70:334, 1971. 6. Cruse, P.J.E. and Foord, R.: A Five-year Prospective Study of 23,649 Surgical Wounds. Arch. Surg., 107:206, 1973. 7. Drachman, R.H., Root. R.K. and Wood, W.B.: Studies of the

23.

24. 25.

26. 27.

Technique, Complications and Results. In Najarian, J.S., and Simmons, R.L., Transplantation. Philadelphia. Lea & Febiger, 1972, pp. 445-495. Simmons, R.L., Kjellstrand, C.M. Kvriakides. G.K.. et al.: Surgical Aspects of Transplantation in Diabetic Patients. Kidney Internat. 6 (Supplement 1): S-15, 1974. Simmons, R.L., Kjellstrand, C.M. and Najarian. J.S.: Sepsis Following Kidney Transplantation. In Hardy J.. Critical Surgical Illness. 1971, pp. 559-580. Simmons. R.L., Diggs, J.W. and Sleeman, H.K.: Pathogenesis of Peritonitis. III. Local Adjuvant Action of Hemoglobulin in Experimental E. coli Peritonitis. Surgery. 63:810, 1968. Stephens, F.O., Hunt, T.K., Jowetz, E.. et al.: Effect of Cortisone and Vitamin A on Wound Infection. Am. J. Surg.. 121:569. 1971. Swanson, M.A. and Schwartz, R.S.: The Relation Between Clinical Response and Immunologic Competence. N. EngI. J. Med.. 277: 163, 1967.