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Chapter 8

Battle Casualties in Korea: Studies of the Surgical Research Team, Volume IV

Wound Healing in Patients With Battle Wounds and Severe Renal Dysfunction

Stanley M. Levenson, M. D.

In January 1953, it was generally considered that delays in wound healing were infrequent among patients with battle injuries except among those patients who also had acute renal failure. This view was held by most of the Chiefs of Surgery at the American hospitals in Korea and Japan and by the Surgical Consultants to the Eighth Army in Korea and to the Far East Command. The occasional delay observed in the patients without renal dysfunction was considered a consequence of-

    (1) local infection (often associated with inadequate initial débridement);

    (2) local ischemia (tight sutures; rarely progressive vascular occlusion);

    (3) peculiarities of the site of injury (e. g., lower leg wounds are notoriously slow in healing).

Systemic factors were not considered important.

It should be stressed that there were clinical "impressions." No systematic tabulation of wound healing had been made, nor was there specific knowledge about the quality of wound healing.

In contrast, it was generally felt that serious wound infections and delays in wound healing were common in patients with serious renal dysfunction. In particular, the physicians at the Renal Center were of the firm opinion that wound healing was impaired in these latter patients and that wound complications contributed significantly to their high mortality (50 to 60 per cent). To obtain some specific data in this regard, all the clinical and autopsy records of the 70 patients admitted to the Renal Center from its opening in the spring of 1952 through the middle of February 1953 were reviewed by the author with Captain Teschan who had been in charge of the renal ward during most of this period.

The records of the first 16 patients were inadequate; of the remaining 54 patients, 12 were discarded either because of inadequate records (5) or because of short survival times (7). Forty-two records, then, were deemed adequate for analysis. However, it should be mentioned that the progress notes were written by internists, that the records were not specifically directed towards problems of wound healing, that bac-


128

teriologic studies were inadequate and that only casual attention was paid to the wounds at autopsy. No histologic studies of the wounds were done.

Among the 42 patients whose records were analyzed, gross impairment of wound healing was noted in 31. The term "impairment" is used in a broad sense and is not meant to imply a specific defect in wound healing. Mortality among the patients with impaired wound healing was high; wound complications were among the more frequent and important causes of death (Tables 1, 2, 3, 4 and 5).

Two general types of wounds were present in these patients-wounds closed primarily, such as laparotomy incisions, and wounds left open after débridement. Among the 42 patients whose records were analyzed, there were 28 who had laparotomies (Table 6). Six of these were in the group with unimpaired wound healing and, as indicated by group classification, none of these wounds ruptured. Among the 31 patients with impaired wound healing, 22 had laparotomies. There were five abdominal wound dehiscences in this group. This incidence of wound rupture was apparently higher than occurred in patients with serious battle wounds but without renal dysfunction. However, this cannot be stated with certainty, since no over-all systematic tabulation of wound healing among the battle casualties of the Korean conflict has been made. In this regard there has been considerable difference of opinion among the Surgical Chiefs and Consultants as to the incidence of postoperative hernias in laparotomized patients; opinions have varied from "very few" to "very many."

Table 1. Wound Healing in Patients With Battle Injuries and Renal Dysfunction

1. Group with Apparent Unimpaired Wound Healing

Patient Number

Initial Injury and Initial Operative Treatment

26

Bullet-left flank penetration (through and through); laceration of inferior vena cava below renal vein; 2 perforations of duodenum

Rx: Laparotomy
Repair of perforations of duodenum
Ligation of inferior vena cava

30

Land mine-traumatic amputation right leg, pen. wds. right wrist, left thigh, left knee

Rx: Guillotine amputation right lower leg, arthrotomy 1 knee joint, débridement of wounds

Transfusion reaction-4th pwd. day


129

Table 1. Wound Healing in Patients With Battle Injuries and Renal Dysfunction-Continued

1. Group with Apparent Unimpaired Wound Healing

Patient Number

Initial injury and Initial Operative Treatment

34

Small arms fire-pen. abd. left to right, with perforations splenic flexure of colon (2), laceration of inferior vena cava; fracture body L2, bruised duodenum, perforations (2) of hepatic flexure

Rx: Laparotomy; ligation inferior vena cava; exteriorization of splenic and hepatic flexures

48

Burp gun-4 perforations small bowel

Rx: Laparotomy; closure of perforations of small bowel

55

Mortar shell-penetrating wd. of abdomen, avulsion right colon, fecal contamination peritoneal cavity; penetrating wound left knee (into joint).

Rx: Laparotomy, right colostomy; ileo-transverse colostomy; Débridement left knee wound

58

Grenade Fx. 1, tibia, right lateral malleolus, 5 perforations of ileum, perforations rectosigmoid; penetrating wounds right buttock and penis

Rx: Laparotomy, resection of ileum with end-to-end anastomosis; suture of rectosigmoid diverting sigmoid colostomy; débridement of peripheral and buttock wounds with casting of extremities.

59

Shrapnel-lacerations cheek and forehead; avulsive type wound over left mid-humerus; lacerations left hand, lacerations both thighs, compound comminuted fracture left lower leg; laceration of penis; laceration right anterior chest (superficial)

Rx: Débridement, casting

60

Bullet-through-and-through wound of pharynx with fractured jaw

Rx: Wiring of jaw; débridement neck wounds with closure of pharyngeal perforation on left.

63

Gunshot wound-penetrating wounds, right and left chest, with lacerations left lower lobe, left lung, spleen, diaphragm, Fx. 5th and 6th ribs, left.

Rx: Formal thoracotomy, repair lacerations of lung; splenectomy, débridement of wounds.

64

Jeep accident-Transection prostatic urethra, lacerations of diaphragm, esophagus. Fractured pelvis with separation of symphysis

Rx: Laparotomy 1-cystotomy
Laparotomy 2-Same day, repair diaphragm and repair of esophagus.

65

105 mm. artillery gun exploded-penetrating missile wounds right forearm, right shoulder, right thigh, left hand, with separation right acromioclavicular joint, fracture right humerus, right forearm, left hand, traumatic amputation left thigh, MFB right thigh.

Rx: Débridements; ligation right brachial vein, amputation left thumb.


130

Table 2. Wound Healing in Patients With Battle Injuries and Renal Dysfunction
 

I. Group with Apparent Unimpaired Wound Healing

Patient Number

Oliguria* (No. of Days)

Day of Diuresis

Max. Plasma NPN

No. of Dialyses

Lived or Died**

Lap.

Dehiscence

Comments

 

 

 

(mg./100 ml.)

 

 

 

 

 

26

0

3

235

0

L

+

0

 

30***

0

8

273

0

L

0

---

30 lb. wt. loss in 14 days, then rapid wt. gain

34

0

2

109

0

L

+

0

Minor renal dysfunction, 30 lb. wt. loss, duodenal fistula-healed

48

0

3

228

0

L

+

0

23 lb. wt. loss

55

0

6

360

0

L

+

0

 

58

---

13

202

0

L

+

0

20 lb. wt. loss

59

2

4

225

0

L

0

---

 

60***

1

22

296

3

L

0

---

 

63

0

5

306

0

L

0

---

 

64

1

4

195

0

L

+

0

 

65

1

3

247

0

L

0

---

33 lb. wt. loss

*Urine volume less than 500 cc./24 hrs.
**Urine volume greater than 1,000 cc./24 hrs.
***Transfusion Reaction.


131

Table 3. Wound Healing in Patients With Battle Injuries and Renal Dysfunction
 

II. Group With Apparent Impaired Wound Healing

Patient Number

Initial Injury and Initial Operative Treatment

17

Truck Accident-blunt injury to abdomen, ruptured spleen, injured right kidney, avulsion of CBD, tear of portal vein, laceration of duodenum

Rx-Laparotomy, right nephrectomy, splenectomy, cholecystostomy, choledochoduodenostomy, repair of duodenum and repair of portal vein

18

Land mine-Bilateral thigh and lower leg wounds
FCC right femur, superficial wounds left thigh, left arm; right femoral vein severed near inguinal ligament

Rx-Débridement; right femoral vein ligated; amputation above knee, right

19

Pen. missile, shrapnel; penetrating wounds both thighs with laceration right femoral artery and vein below profunda

Rx-Anastomosis femoral artery; femoral vein ligated; débridements

20

Mortar-wounds both knees and thighs

Rx-Débridement-repair of left popliteal and femoral artery; ligation of vein

21

Shrapnel-Penetrating wound of abdomen with laceration of distal ileum, cecum, ascending colon, hepatic flexure, right kidney; penetrating wound left chest with hemopneumothorax

Rx-Laparotomy, resection of involved bowel; ileo-transverse colostomy, kidney packed and right lateral gutter drained; thoracentesis

22

Rifle-perforating wounds left groin, ileum, jejunum, sigmoid colon, dome of bladder

Rx-Laparotomy
Anastomosis of small bowel
Exteriorization of colon, repair of bladder
Suprapubic cystostomy

23

Bullet 45-Perforation abdominal wall; perforation left arm; perforation small bowel and sigmoid; laceration of mesentery with hemoperitoneum

Rx-Laparotomy; end-to-end anastomosis of small bowel closure of lacerations; transverse colostomy

28

Land mine-Extensive FCC Tibia, bilateral avulsion of skin of legs and thighs and upper arm; FCC third digit, left hand

Rx-Débridement of wounds-long leg cast

29

Burp gun-Abdominal perforation, macerated left kidney, perforation splenic flexure of colon, multiple perforations of jejunum, laceration of posterior prostate and prostatic urethra, perforation anterior wall of rectum

Rx-Laparotomy; débridements; resection and suture of small bowel injuries; colosomy; left nephrectomy


132

Table 3. Wound Healing in Patients With Battle Injuries and Renal Dysfunction-Continued
 

II. Group With Apparent Impaired Wound Healing

Patient Number

Initial Injury and Initial Operative Treatment

31

Mortar fragment-Penetrating wound chest; penetrating wound of heart; laceration right lung with right hemopneumothorax, embolization of MFB to left hypogastric artery

Rx-Laparotomy; embolectomy; cardiac arrest, which responded to massage; thoracentesis

32

Land mine-traumatic amputation left leg below knee; extensive avulsion skin of right thigh; FCC 4th finger.

Rx-Débridement of right wrist and forearm
Supracondylar amputation of left leg
Amputation proximal portion 4th finger and portion of thumb
Right orchidectomy

33

Mortar shell-left hemothorax; FCC ribs 5-8, hemopericardium with cardiac tamponade, lacerations diaphragm, perforations of stomach, jejunum, and splenic flexure of colon, lacerations of spleen and left kidney; FCC left humerus, tibia, fibula and carpal bones

Rx-Laparotomy; aspiration of pericardial space; repair of gastrointestinal perforations, with exteriorization of colon (left), splenectomy, repair of right kidney, thoracotomy

36

Gunshot wound-4" lacerations right lobe of liver; perforation right colon and its mesentery

Rx-Laparotomy-Suture of laceration with drainage; repair of colon with exteriorization

38

Mortar-Traumatic amputation of left leg; perforating wounds both buttocks, FCC of sacrum; perforation of rectosigmoid,
perivesical hematoma. Penetrating wounds right foot and avulsion of right calf; FCC right fibula and right 5th metatarsal bone

Rx-Laparotomy; colostomy, high right amputation; left leg with débridement of buttocks wounds and right leg wounds

40

Grenade-Large wound medial aspect left thigh with avulsion skin, adductor and some extensor muscles. Superficial laceration left temporal and frontal area of head, multiple deep lacerations of right thigh

Rx-Débridement

42

Bullet wound-pen. abdomen-2 wds. bladder, perf. rectum, shattered sacrum

Rx-Laparotomy-suprapubic cystostomy; closure of rectal wd.; diverting colostomy drain presacral area; débride sacrum and wounds

43

Shell fragment-pen. wd. right sacrum; laceration of rectum; retroperitoneal hematoma; small lac. extremities; FCC right tibia

Rx-Laparotomy, sigmoid colostomy; drainage of hematoma; débridement of wds., casting of right leg


133

Table 3. Wound Healing in Patients With Battle Injuries and Renal Dysfunction-Continued
 

II. Group With Apparent Impaired Wound Healing

Patient Number

Initial Injury and Initial Operative Treatment

45

Land mine-superficial laceration right foot, 10 x 8 cm. rent in liver; shattered right kidney; small jejunal perforation, rent in diaphragm; left thoracotomy tube

Rx-Laparotomy; débrided missile tract; rent diaphragm repaired; thoracotomy tube; right chest; right nephrectomy; suture jejunum and liver

47

Shell fragment-hemoperitoneum laceration of pancreas, colon, gastrohepatic omentum; superficial wound left wrist

Rx-Laparotomy; repair of omentum; exteriorization of right colon with loop colostomy

49

Shell fragment-large perforating wound right lateral chest wall external to pleura; contusion right kidney, superficial wounds right thigh, large pen. wd. right popliteal fossa with peroneal n. paralysis

Rx-Laparotomy; repair of kidney; débridement chest and extremity wounds

52

Shell fragment-right lower chest and flank-laceration right diaphragm, liver, shattered right kidney

Rx-Laparotomy; repair of diaphragm and suture of liver; right nephrectomy; right thoracotomy

53

Gunshot-right buttock and abdomen; comminuted fracture right acetabulum; laceration of rectum; perivesical hematoma, laceration several branches of hypogastric a. with hemoperitoneum laceration sciatic nerve and lower sacral plexus

Rx-Laparotomy-ligation of vessels; colostomy and presacral and perivesical drains; débridement

56

Perforating wounds of right and left lobes of liver, thru-and-thru perforation of gallbladder; 2 perforations ascending colon; 2 perforations duodenum; 1 perforation anterior stomach

Rx-Laparotomy; suture of liver; repair of perforations of duodenum; ascending colostomy; suprahepatic drains and drain foramen of Winslow; cholecystectomy

57

Shell fragment-penetrating wound right lower lateral chest, abdomen, right buttock, with laceration right lobe liver, perforation gallbladder and duodenum, pancreas, gastroduodenal artery

Rx-Laparotomy; suture of liver; cholecystectomy; exploration of CBD, suture of duodenum and pancreas; drainage of liver and pancreas

61

Mortar fragments-FCC of both tibiae and fibulae; fracture left cuboid, navicular, right med. malleolus; FCC 1st metacarpal left hand; many MFB and soft tissue wounds-legs and left arm

Rx-Left femoral artery explored-intact; ligated bilateral post-tibial artery; débridement; open reduction of fracture


134

Table 3. Wound Healing in Patients With Battle Injuries and Renal Dysfunction-Continued
 

II. Group With Apparent Impaired Wound Healing

Patient Number

Initial Injury and Initial Operative Treatment

62

Land mine-traumatic amputation right leg; penetrating wound left leg; post-popliteal area; penetrating wound of buttock with laceration of prostate, urethra, bladder, and rectum, right hand, fracture 4th and 5th metacarpal

Rx-Laparotomy; débrided; right AK amputation; ligation post-tibial vein; colostomy; repair bladder; suprapubic cystostomy

66

Shrapnel fragment-laceration spleen; left kidney; colon; stomach; small bowel

Rx-Laparotomy; splenectomy; left nephrectomy; gastrojejunostomy; colostomy

67

Grenade-large gaping thigh wound (left); FCC left upper femur
Rx-splinted left leg; débrided; Kirschner pin through femoral condyles

68

Shell fragments-penetrating wounds right lower anterior chest wall, abdomen; penetrating wound right forearm; penetrating wound right buttock; penetrating wound right heel with fracture of os calcis; 2° and 3° burns of right forearm, hand, and thigh

Rx-Laparotomy; evacuation and drainage of large retroperitoneal hematoma; débridement external wounds (inadequate débridement buttock wound)

69

Exploding parachute flare; penetrating wounds of right buttock and peroneal areas; massive blast concussion wound of the right buttock; lateral to rectum and perineum, with widespread devitalization of the perineal and ischiorectal tissue, including right bulbocavernosus and reaching up the right perineum with marked anterior and posterior hematoma. Severance of membranous urethra, with destruction of the apical portion of the prostate. Comminuted fracture of right posterior pubic ischium

Rx-Laparotomy; no intraperitoneal injury; bladder opened and closed; re-establishment of urethral continuity over a #24 Foley catheter; diverting sigmoid colostomy; drainage of perivesical space; pack placed in the right pelvis and buttock wound from above

70

Bullet (30 caliber)-Penetrating wounds left buttock, abdomen, chest; fractured left pelvis; perforations descending colon (3); perforations jejunum (3); laceration spleen, left kidney; perforation of diaphragm (left) laceration left lung

Rx-Laparotomy; nephrectomy; splenectomy; resection jejunum with end-to-end anastomosis; resection of sigmoid with double-barreled colostomy; repair diaphragm; débridement buttock wounds. Thoracotomy later for hemopneumothorax


135

Table 4. Wound Healing in Patients With Battle Injuries and Renal Dysfunction
 

II. Group with Apparent Impaired Wound Healing

Patient Number

Oliguria* (No. of Days)

Day of Diuresis**

Max. Plasma NPN (mg./100 ml.)

No. of Dialyses

Lived or Died

Lap.

Dehiscence (Postop. Day)

 


Cause of Death

 


Comments

17

0

 

321

3 D,

16 day

+

+ (14)

Portal vein thrombosis, subhepatic abscess, stricture of common bile duct, uremic colitis.

Peritonitis, ascites.

18

1 (?)

3

219

1

L

0

---

 

Malnutrition, infection in stump, decubitus ulcers.

19***

1

12

284

1

L

0

---

 

Wound infection.

20

1

18

263

2

L

0

---

 

Wound infection.

21

4

9

254

0

L

+

0

 

Infection of peripheral wounds.

22

0

14

265

0

L

+

0

 

Edema, dehydration, bleeding tendency.

23

0

6

394

0 D,

26 day

+

+ (16)

Pulmonary infarcts with abscess formation, bronchopneumonia and atelectasis.

Edema, dehydration cachexia, peripheral wound infection.

*Urine volume less than 500 ml./24 hrs.
**Urine volume greater than 1,000 ml./24 hrs.
***Transfusion reaction.


136

Table 4. Wound Healing in Patients With Battle Injuries and Renal Dysfunction-Continued

Patient Number

Oliguria (No. of Days)

Day of Diuresis

Max. Plasma NPN (mg./100 ml.)

No. of Dialyses

Lived or Died

Lap.

Dehiscence (Postop. Day)

 


Cause of Death

 


Comments

28

2

6

168

1

L

0

---

 

One stump wound clean, other stump wound infected.

29

1

10

268

2

L

+

0

 

Cachexia, osteomyelitis.

31

4

9

260

0

L

+

+(11)

 

No obvious reason for dehiscence (No stay sut.), cardiac arrest, shock, emaciation perit., intes. obst., sec. to dehiscence.

32

0

4

205

0     D,

13 day

0

---

Spreading infection of right arm, cerebral edema, marked bronchopneumonia

Retained foreign body

33

0

6

360

3     D,

29 day

+

0 (?)

Massive peritonitis, pelvic abscess, bilateral renal abscess, bilateral adrenal infarcts

Cachexia, wound infection; no gross dehiscence but held only by sutures

36

0

 

344

3     D,

10 day

+

0

Massive peritonitis, perihepatic abscess

Edema; infection of laparotomy wound, peritonitis


137

Table 4. Wound Healing in Patients With Battle Injuries and Renal Dysfunction-Continued

Patient Number

Oliguria (No. of Days)

Day of Diuresis

Max. Plasma NPN (mg./100 ml.)

No. of Dialyses

Lived or Died

Lap.

Dehiscence (Postop. Day)

 


Cause of Death

 


Comments

38

0

 

305

6     D,

16 day

+

0

Extensive necrosis of leg stump with infiltration of fascial plane; extensive necrosis of buttocks with infection

Retained foreign body

40

0

15

379

2

L

0

0

 

Retained foreign body

42

1

 

316

6     D,

17 day

+

0

Large subdiaphragmatic abscess; peritonitis

Bleeding, wound infection

43

0

 

183

2     D,

5 day

+

0

Massive necrosis of buttock wound and perirectal area, bronchopneumonia

Wound infection

45

0

 

336

2     D,

19 day

+

0

Left empyema, marked bilateral hydrothorax

Wound infection

47

0

 

367

1     D,

11 day

+

+ (10)

Peritonitis, subdiaphragmatic abscess

Peritonitis, infection lap. wound

49

0

 

228

0

L

+

0

 

Bleeding; wound infection

52

0

19

324

4     D,

25 day

+

0

Bronchopleural fistula with empyema

Malnutrition

53

0

11

345

2

L

+

0

 

Wound infection

56

0

 

321

0     D, 

10 day

+

0

Severe gastrointestinal bleeding with aspiration of bloody vomitus

Cachexia, bleeding, breakdown of sutured diaphragm

57

1

7

316

1     D,

13 day

+

0

Breakdown of duodenal suture line with adjacent abscess resulting in massive intra-abd. bleeding

Wound infection

61

0

16

322

3

L

0

 

 

Wounds apparently healed except wound infection right foot


138

Table 4. Wound Healing in Patients With Battle Injuries and Renal Dysfunction-Continued
 

Patient Number

Oliguria (No. of Days)

Day of Diuresis

Max. Plasma NPN (mg./100 ml.)

No. of Dialyses

Lived or Died

Lap.

Dehiscence (Postop. Day)

 


Cause of Death

 


Comments

62

1

23

316

3

L

+

0

 

Sutures too tight (?)

66

0

 

328

1     D,

8 day

+

0

Peritonitis, gastrointestinal fistula, septicemia (? clostridia)

Peritonitis

67

0

17

328

3

L

0

 

 

Malnutrition

68

14

 

325

2     D,

14 day

0

 

Spreading infection of buttock wound

Wound infection (inadequate initial débridement?)

69

?

10

309

1

L

+

+ (9)

 

Old hematoma leading to dehiscence

70

0

 

300

1     D,

8 day

+

0

Severe bronchopneumonia and atelectasis

At postmortem, lap. wound had minimal tensile strength


139

Table 5. Wound Healing in Patients With Renal Dysfunction

Group

Number of Patients

Number of Deaths

Average Day of Death

Patients with unimpaired wound healing

11

0

 

Patients with impaired wound healing

31

16

15

Table 6. Wound Healing in Patients With Renal Dysfunction

Group

Patients

Laparotomies

Dehiscences

Patients with unimpaired wound healing

11

6

0

Patients with impaired wound healing

31

22

5

The actual incidence of impaired healing of laparotomy wounds among the patients with renal dysfunction may well be higher than indicated by the figures of wound ruptures. Once it appeared that these patients might be having difficulty in wound healing, sutures were left in for many weeks. Under this circumstance, the wounds of some patients were described as held together only by the retention sutures, with no apparent healing having occurred. Further, a number of patients whose laparotomy wounds looked good and appeared to be healing normally, died 7 or more days after injury; no special examination of the abdominal incision was made routinely, but in an occasional instance, when the sutures were removed at autopsy, or an attempt was made to excise a portion of the wound for histologic study, the wound fell apart.

Among the five patients with actual wound rupture, a possible local reason for the dehiscence was apparent in three (Table 7). In one,

Table 7. Wound Healing in Patients With Renal Dysfunction
 

Dehiscences of Laparotomy Wounds

Number of patients with laparotomies

28

Number of dehiscences

5

Apparent "local cause" for dehiscence

3

Peritonitis with ascites

1; 14th day

Hematoma

1; 9th day

Wound infection

1; 10th day

No apparent "local cause" for dehiscence

2; 11th and 16th days


140

dehiscence occurred on the ninth postoperative day and examination revealed an extensive hematoma in the wound
(Pt. No. 69). In another, Pt. No. 47, dehiscence occurred on the tenth postoperative day-peritonitis and an infected abdominal wound were present; in the third, Pt. No. 17, dehiscence occurred on the fourteenth day-severe peritonitis with ascites was present. No specific local reason for dehiscence was noted in the other two patients. In one of these two, dehiscence occurred on the eleventh day (Pt. No. 31); in the other, (Pt. No. 23) on the sixteenth day. Disruption this late postoperatively is unusual and would suggest a definite delay in the healing process. At the time of the dehiscence, this last patient was emaciated. The abdominal wound was resutured and he lived for 9 more days. At autopsy, the resutured wound was described as follows: "There is a longitudinal midline abdominal surgical incision measuring approximately 12 cm. in length around which radiate multiple superficial draining sinuses measuring 2 cm. in length. Granulation tissue lines the upper half of the surgical incision which presents an opening measuring 5 x 1 cm. The base of this sinus tract is lined by dense yellow-red granulation tissue. Wire sutures support the incision." Two more of the patients whose ruptured laparotomy wounds were resutured died, but the wounds were not specifically examined at autopsy.

Two of the five patients with dehiscences lived (Table 8). The resutured wound apparently healed uneventfully in the patient whose dehiscence had been presumably secondary to the hematoma. The other patient who survived was the patient whose wound had ruptured 11 days postoperatively with no local cause for dehiscence being apparent. After resuturing, he developed peritonitis and intestinal obstruction. These complications were considered by those caring for the patient as subsequent to the dehiscence, rather than present before, and perhaps etiologically important for, the first dehiscence. A third laparotomy was performed on this patient through another incision

Table 8. Wound Healing in Patients With Renal Dysfunction
 

Healing of Resutured Dehisced Laparotomy Wounds

Number of secondary sutures of dehisced laparotomy wounds

5

Number of patients surviving

2

"Normal" healing of resutured wound

1

"Abnormal" healing of resutured wound

1

Number of patients dying

3

"Abnormal" healing of resutured wound

1

Quality of wound healing unknown

2


141

19 days after the resuturing of the first laparotomy wound. Localized intraperitoneal abscesses and obstructing adhesions were found. One week later, purulent material drained from the first and second abdominal incisions. Shortly thereafter, a fecal fistula appeared in the other abdominal incision. The patient had lost a considerable amount of weight (over 30 pounds) and was transferred to a general hospital in Japan for further therapy.

Among the 31 patients with gross impairment of wound healing, the open wounds were often described as indolent, with granulation tissue either absent, or when present, soggy and edematous. In a number of these patients, progressive necrosis and suppuration of the wounds was described. This was noted particularly in some of the patients with buttock wounds. ("The temperature was up to 104° and the buttock wound now contained a soupy sanguinopurulent exudate, with increasing extent of necrosis"-Pt. No. 68.)

It should be pointed out that the time of secondary closure of the open wounds was delayed in patients with renal failure. In patients without renal dysfunction, such wounds were usually closed 5 to 10 days after injury. Patients with renal dysfunction were often sickest during this time and secondary closure was rarely carried out during this period. Consequently, the wounds of patients with renal dysfunction remained open for significantly longer periods of time than in patients without renal dysfunction. Similarly, these patients were among the most seriously injured and usually were in severe shock in the early period after injury. Thus, it is possible that, under these circumstances, débridement might have been inadequate in certain of these patients. This will be discussed more fully in the section on infection. There is also some question as to the quality of the later surgical care of these patients.

A comparison between the two groups of patients (those patients with unimpaired wound healing vs. those with impaired wound healing) was made to determine some of the factors which might have had some bearing on the observed differences in wound healing. It appears that those patients with impaired wound healing were, in general, the more seriously injured, sicker, more uremic, required more dialyses, had greater changes in water and electrolyte metabolism with associated edema and/or dehydration, lost more weight, had more severe infections, and showed a higher incidence of abnormal bleeding. The severity of anemia could not be adequately estimated. No conclusive evaluation of the factors responsible for the delays in wound healing can be made from the available data, but it would appear that in the majority of patients multiple factors were operative and pre-


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sumably interrelated. Serious uremia, serious infection, and serious malnutrition were the most frequent factors. The following two case reports are indicative of the complexity of the problem:

Patient No. 33. This 21-year-old white male was injured at 1800 hours, 25 August 1952, by a mortar shell. When he reached the Clearing Company at 2100 hours, he was in shock and was given whole blood. He reached the 8209 MASH at 2300 hours in deep shock; blood pressure, 80/60. The heart sounds were almost inaudible; a cardiac tamponade was suspected and was confirmed by aspiration. Immediate transfusion raised the blood pressure promptly to 130/90 within 15 minutes; he received a total of 300 cc. blood preoperatively and was operated on at 1400 hours. At operation, he was found to have a hemopericardium, left hemothorax with fractures of ribs 5 to 8, contusion of the lower lobe of the left lung, laceration of the left diaphragm, multiple perforations of the stomach, jejunum, and splenic flexure of colon, laceration of the spleen and left kidney, compound, comminuted fracture of left humerus, left carpal bones, and left tibia and fibula. The following operative procedures were done: resection of the anterior thirds of the left sixth and seventh ribs with insertion of two thoracotomy tubes; repair and débridement of the left side of the diaphragm; closure of perforations of stomach and jejunum; exteriorization of splenic flexure of colon; splenectomy; removal of foreign body from cortex of left kidney; drainage tubes, left flank; débridement of left side of chest; irrigation and splinting of left wrist, humerus, and tibia and fibula. During the operation, he received an additional 3,000 cc. blood. After operation he required 1,500 cc. more blood before his blood was stabilized above shock levels, 7 hours postoperatively.

On 26 and 27 August (the first and second post-injury days) his urinary output was below 300 cc. daily. He was transferred to the 11th Evacuation Hospital the next day. On admission, he was in good general condition. Blood pressure, 130/80; pulse, 118, temperature, 100°; respirations, 26. The exteriorized loop of colon was opened to form a double-barreled colostomy. The extremity wounds were infected, and maggots were present in the wound in the left wrist. The thoractomy tubes were removed when a chest x-ray showed only slight atelectasis at the left base. Laboratory data on admission were as follows: K, 6.2 mEq./L. plasma; Na, 116 mEq./L. plasma; NPN, 154 mg. per 100 ml. plasma; hematocrit, 48 per cent; WBC, 9,450 cu. mm.; urine showed 1.014 specific gravity, 1+ protein, 15 to 20 RBC's per high-power field. Because of the hyperkalemia, an immediate hemodialysis was performed; the K fell to 3.8 mEq./L. plasma and the NPN to 92 mg. per 100 ml. plasma. An EKG was normal. On the next day he was given 60 gm. ion-exchange resins by rectum in an attempt to control hyperkalemia; no further difficulty with hyperkalemia was encountered.

Oliguria continued until the sixth post-injury day. By the twelfth post-injury day a peak was reached of 3,000 cc. urinary output. During this time the plasma NPN climbed to 360 mg. per 100 ml. on the tenth day. At this time he became lethargic and complained of marked lassitude. Tarry stools passed through the colostomy. He would not take fluids or food orally. A repeat dialysis was done with the following biochemical changes resulting:

Plasma

 

NPN

K

CL

CO2

NA

 

mg./100 ml.

mEq./L.

mEq./L.

mEq./L.

mEq./L.

Pre-dialysis

360

4.7

105

15.4

142

Post-dialysis

54

4.3

112

20.5

135


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During the next day the tarry stools from the colostomy continued and 1,000 cc. of blood was required to maintain his blood pressure. He began to run a fever, up to 103° rectally, and WBC rose to 28,000 with a shift to the left. Physical examination was unchanged at that time; a chest x-ray was negative save for minimal atelectasis at the left base. Antibiotic therapy was changed from terramycin to penicillin and streptomycin. Despite this, the fever continued to rise and on 9 September (the fifteenth post-injury day) he was found to have a large pelvic abscess by rectal examination. The extremity wound remained in poor condition, with no healing and much purulent drainage. He became weaker but was able to eat well. During this time, his urinary output continued to be around 1,500 cc. daily, with a specific gravity of 1.010-1.012, 1+ protein. The plasma NPN had fallen to 110 mg. per 100 ml. by this time but began to rise again despite a urinary volume of over a liter per 24 hours.

With the onset of the pelvic abscess and the high fever (reaching peaks of 105° daily) he began to deteriorate clinically, becoming weaker and less responsive. Weight loss was marked and he took on a cachetic appearance. On the eighteenth post-injury day, a large abscess appeared in the left anterior lower leg, at the site of a previous cut-down. He became intermittently delirious. The penicillin-streptomycin therapy was discontinued and terramycin reinstituted. A frequent cough productive of purulent sputum appeared, but physical examination and x-rays of the chest were negative. By the twenty-fourth post-injury day, the pelvic abscess seemed smaller and more fluctuant by rectal examination; temperature was 103° and WBC, 19,500. At this time he was weak and disoriented. Feedings through a gastric tube were begun. The plasma NPN was up to 196 mg. per 100 ml. with a plasma (mEq./L.) K 4.1, Na 158, Cl 120 and C02 21.5. The wounds, including the areas around the wire sutures of the laparotomy incision, were in extremely poor shape, with poor healing and several superficial sinuses.

On the twenty-sixth day, the plasma NPN was 240 mg. per 100 ml. and his clinical condition was rapidly deteriorating. It was felt by the clinical staff that the continued uremia might be accentuated by the necrotic tissue in the wounds and the massive infection in his peritoneal cavity. Another dialysis was done with the following chemical results:

Plasma

 

NPN

Na

K

Cl

CO2

mg./100 ml.

mEq./L.

mEq./L.

mEq./L.

mEq./L.

Pre-dialysis

240

160

4.2

118

14.0

Post-dialysis

99

138

 

114

20.2

During the dialysis, his blood pressure fell to below 60 systolic and remained there for an hour despite the use of 2,500 cc. blood. Following dialysis, the blood pressure came up to 100 systolic; the patient seemed more alert and oriented for about 24 hours. Two days later, his blood pressure fell to 80 to 60 systolic; he became much weaker and became almost nonresponsive. The plasma NPN was up to 203 mg. per 100 ml. The urinary volume, which had dropped abruptly to 200 cc. on the twenty-sixth day, rose to 1,300 cc. per day. His temperature was 102° and WBC, 26,000. On the twenty-ninth day, the blood pressure gradually fell and was unobtainable. His respirations became gasping and no cardiac sounds could be heard after a shift in his position on the Stryker frame. Intracardiac adrenalin gave a prompt and vigorous return of cardiac action. He was then given norepinephrine intravenously by slow drip. With this, the blood


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pressure and pulse were maintained at satisfactory levels, but the patient remained comatose and non-responsive. He remained in this state for some 16 hours. Nine hours prior to death he was given 500 mg. cortisone through the gastric tube; no appreciable effect was evident. He died on the thirtieth day after injury.

At autopsy, the body was described as that of a well developed, thin, white male. There was a large defect in the skin over the left lateral chest measuring 7 x 5 cm. This defect extended down to the ribs. A double-barreled colostomy was present in the right upper quadrant of the abdomen. The skin around the colostomy was retracted, revealing slightly purulent granulation tissue, over an area 8 x 5 cm. Multiple small satellite skin ulcers, 0.5 to 2.0 cm. in diameter, surrounded the colostomy. There was a compound, comminuted fracture of the neck of the humerus easily visible through a large defect in the skin of the axilla. The brachial plexus and axilliary vessels were plainly visible through this defect. Multiple small bone fragments protruded through a through-and-through wound of the left hand. A moderate amount of green-yellow pus exuded from both sides of this wound and probing of the wound revealed a large abscess pocket surrounded by necrotic bone and muscle. Granulation tissue covered a defect in the skin over the anterior of the left leg. This defect measured approximately 12 x 4 cm.

Pathologic diagnosis were-

    (1) Acute pyelonephritis with miliary abscesses.

    (2) Cystitis.

    (3) Peritonitis; abscesses of cul-de-sac, subhepatic region and upper left quadrant of abdominal cavity.

    (4) Massive necrosis of adrenals with abscesses.

    (5) Petechiae of cerebral cortex.

    (6) Acute tracheitis, bronchopneumonia.

    (7) Infected wounds of extremities.

Patient No. 67. This 20-year-old white Marine corporal was hit in the left thigh by an enemy grenade at 0430 hours on 22 December 1952. Arrived at C Company, 1st Medical Battalion at 0715 hours; blood pressure was 102/48; pulse, 90; a large gaping wound high on the left thigh with a large hematoma was noted, and an obvious compound fracture of the left upper femur. The peripheral pulses were good and no neurologic damage was detected. The wound was dressed, and the patient's leg was placed in a Thomas splint; 500 cc. whole blood was given.

The patient was then evacuated to a hospital ship by helicopter, where he arrived at 0900 hours 22 December. Said to be "shocky" on arrival. X-ray showed compound, comminuted fracture of left femur with overriding. Wound débrided under cyclopropane-ether anesthesia. No damage to major arteries or nerves noted. A Kirschner pin was inserted through femoral condyles for traction. Because of a fast, weak pulse (BP not stated) he was given 650 cc. whole blood during the operative procedure; it was stopped because of a reaction (tachycardia and fever). Macrodex was then started, and 1,000 cc. given. After operation he received another 1,000 cc. whole blood, at the end of which he became "ill" and 1,500 cc. more Macrodex was given. His urine became almost black.

The next day he vomited several times, and his total urine output was 400 cc.; postoperative intake, 1,330 cc. By the second post-injury day he had soreness in both kidney regions. Catheterization at this time produced only 100 cc. of dark


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urine. A BUN was 94 mg. per 100 cc. hemoglobin, 55 per cent. Because of his oliguria he was transferred to the 11th Evacuation Hospital, the Renal Center.

On admission, temperature was 98.4°; blood pressure, 160/100; pulse, 84. He appeared quite well, except for profound anemia, occasional vomiting and moderate dehydration.
 

Adm. Lab.

 

 

Hct.-18%

Cl-92 mEq./L. plasma

EKG-Moderately tall and peaked precordial T waves. No QRS prolongation.

Na-145 mEq./L. plasma

CO2-21.6 mEq./L. plasma

K-7.1 mEq./L. plasma

NPN-193 mg./100 ml. plasma

On admission to the Renal Center, he was started on gastric drainage, K-exchange resins and intravenous hypertonic glucose and insulin. On 28 December, the sixth post-injury day, rapidly progressive EKG changes of K intoxication necessitated his first hemodialysis on the artificial kidney. There was little clinical change following dialysis except for a rise in blood pressure to hypertensive levels. His blood pressure remained high throughout both his oliguric and diuretic phases, ranging from 150 to 210 systolic and 70 to 110 diastolic. On the fifth post-injury day, he had been put in a 11/2 leg spica cast.

On 31 December, the ninth post-injury day, he developed a right parotitis. He had a low-grade spiking fever. That evening, he developed pulmonary edema with a loud gallop rhythm and mushy heart sounds. He was digitalized intravenously with considerable, but not complete, clearing of his heart failure. For the next several days, he continued to show recurrent pulmonary edema with marked respiratory distress. This occurred in the face of a markedly negative fluid balance, with a weight loss averaging over 1 kg. daily and with evidence of peripheral dehydration. This was considered evidence of intrinsic myocardial damage. The pulmonary edema was treated with the usual measures; extremity tourniquets seemed to be the most effective measure. On 6 January, the fifteenth post-injury day, he was dialyzed for the third time because of a rapid rise in the serum K to 9.5 mEq./L. Following this, he showed considerable improvement.

The next day he put out 550 cc. urine and 1,400 cc. on the following day. This urinary output then rapidly increased, and a massive diuresis began, reaching a peak of 6,350 cc. on the twenty-third post-injury day. With this diuresis, he showed further rapid weight loss. No further clinical pulmonary edema occurred.

His uremia, with drowsiness, nausea, vomiting and high plasma NPN, continued for about 1 week after the onset of his diuresis. Since he tolerated nothing by mouth, he required large volumes of parenteral fluids, including potassium. He was given cortisone from the twenty-second to twenty-sixth days post-injury in an effort to improve his anorexia and nausea. (No mention of efficacy made.) On the twenty-sixth day he underwent another débridement. The wound contained much necrotic tissue and showed no evidence of granulations or healing. Repeated cultures grew out A. aerogenes, Proteus, Staphylococcus albus, and B. pyocyaneus. In vitro, these showed greatest suspectibility to chloramphenicol but the patient received intravenous aureomycin, since no parenteral chloramphenicol was available.


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The patient presented a great nutritional problem, having virtually starved for about 4 weeks, with a 45-pound weight loss. In addition, his fracture was in a very poor alignment, and his wound was unhealed. His previous marked anemia (with hematocrit as low as 15 per cent) was corrected by a total of 3,200 cc. of blood given during his diuresis. His diuresis was subsiding, but he still could not take all of his required fluids by mouth at the time of his transfer to Japan on the thirtieth post-injury day.

As mentioned, among the factors which appear important in the pathogenesis of the impaired wound healing in these patients are serious uremia, serious malnutrition and serious infection.

Severity of the Renal Dysfunction: Dialysis

Renal dysfunction was greater in the group with impaired wound healing. The average time of diuresis among the patients with improved wound healing was 12 days after injury, as opposed to the average time of 5 days of 10 of the 11 patients with unimpaired wound healing (Table 9). In addition, 11 patients with impaired wound healing died 5 to 19 days after injury without ever diuresing. Similarly, whereas only 3 of the 11 patients with unimpaired wound healing had maximum levels of plasma nonprotein nitrogen over 275 mg. per 100 ml., two-thirds of the group with impaired healing had such high levels.

Among the patients with apparently unimpaired wound healing, there was only one who required dialysis (Table 9). This was a Korean soldier with wounds of the face and neck who developed a severe hemolytic reaction to a transfusion of 1,000 cc. of blood during his initial operative treatment. Following this, he developed oliguria and was transferred to the 11th Evacuation Hospital on the third post-injury day. During a prolonged period of oliguria (19 days), uremia, three dialyses on the artificial kidney, anemia (hematocrit 20 to 30 per cent, decreased plasma protein concentration (total plasma

Table 9. Wound Healing in Patients With Renal Dysfunction
 

 

Group

 


Number of Patients

 


Day of Diuresis

No. Patients with Maximum Blood NPN over 275 mg./100 ml.

 


Number of Patients Dialyzed

 


Number of Dialyses

Patients with unimpaired wound healing

10
1

5
22

2
1

0
1

0
3

Patients with impaired wound healing

31

*12

21

24

56

*Includes 11 patients who died 5 to 19 days after injury without ever diuresing.


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protein 4.4 to 6.0 gm./100 ml. plasma), and low dietary intake, the neck and face wounds, as well as the cut-down wounds, showed apparently "normal and entirely satisfactory healing." These wounds were in well vascularized areas in which healing is usually favorable.

Among the 31 patients with apparently impaired wound healing, there were 24 who required dialyses. The average number of dialyses in these patients was about 2.3. At the moment, there is no specific evidence to implicate the dialysis procedure per se as an important factor in the pathogenesis of the impaired wound healing-e. g., there were a number of patients with impaired wound healing who did not have dialyses. The fact that many more patients in the impaired healing group were dialyzed than in the group with unimpaired healing may be simply indicative of the severity of the hyperkalemia and uremia of the former group. On the other hand, one cannot definitely rule out the dialysis procedure itself as an important factor-e. g., what is the wash-out of the water soluble vitamins (specifically ascorbic acid) during dialysis?

Malnutrition

Weight loss is a constant feature of the patient with serious injuries and renal dysfunction. The average weight loss was greater among those patients with impaired wound healing. Weight losses of 20 to 25 pounds were common among the group with unimpaired healing, while among the group with impaired healing 30 to 40 pound weight loss was not uncommon. What the weight loss specifically represents in terms of body tissue, water, fat, etc., is not known. The first weights recorded are those on admission of the patient to the 11th Evacuation Hospital. At this time, many of the patients were presumably waterlogged. Insensible water loss must be an important fact in the weight loss of these patients, since prolonged hyperpnea is a common feature. However, examination of metabolic data available in a few patients reveals a large nitrogen loss (i. e., NPN accumulation in the body water, NPN lost by dialysis, and NPN excreted in the urine). In one patient, this amounted to about 45 gm. N per day, which represents the daily breakdown of about 2.5 pounds of body tissue (excluding fat). It is not possible at present to compare this figure with the nitrogen loss by patients with serious injury without associated renal dysfunction-the data are not available. Urinary nitrogen losses of 45 gm. of nitrogen per day (or greater) are not uncommon among young adult males with serious injuries without associated renal dysfunction, but these latter patients have not been on nutrient intakes as low as the patients studied at the 11th Evacuation Hospital. We know that the level of dietary intake makes a considerable difference in the amount of nitrogen excretion and net nitrogen loss after injury.


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Providing an adequate nutrient intake was a very difficult problem in these patients. Many were unable to take food orally over long periods of time. Parenteral alimentation was limited by the policy of rigid fluid restriction during the period of oliguria (which in some cases has persisted for 2 to 3 weeks). The problem was further complicated by the policy of no protein administration during this same period. (One wonders whether in the face of a very low caloric intake the nitrogen load is any less in those patients not receiving protein than in those receiving some protein.) Consequently, the nutrient intake of these patients was very low and grossly inadequate. The average daily caloric intake when the patient had been on only parenteral fluids was 500 to 1,000 calories per day-supplied as glucose. No data are available as to the utilization of carbohydrates by these patients (cf. the "intolerance" to carbohydrates by individuals with extensive injuries) but the rate of infusion has been generally slow. When fluid intake was restricted, the glucose was usually given as a 25 or 50 per cent solution by continuous drip through a polyethylene cannula inserted into the iliac vein via the femoral vein. No instance of pulmonary infarction was noted, but at autopsy in one patient a large thrombus with one end unattached was found in the iliac vein at the site of the infusion.

The only parenteral vitamin preparations which were available were vitamin C (in 500 mg. ampules), thiamine chloride (50 mg./cc.), and various vitamin K preparations. This resulted in a markedly imbalanced vitamin intake.

It was not possible to determine the oral dietary intake of these patients from the available records, but it would appear that the oral food intake was low until long in the convalescent period. A high-carbohydrate, high-fat liquid feeding supplying about 2,500 calories had been tried as a tube feeding (continuous drip) in one or two patients for short periods of time. Oral vitamin intake had usually been three of the standard Army multivitamin capsules per day.

Infection

Infection was one of the major complications among the severely injured patients with renal dysfunction. Among the 31 patients with impaired wound healing, wound infection was almost universally present. Infection, either in the wound or elsewhere, is listed among the causes of death in all but 1 of the 16 patients in this group who died. Intra-abdominal abscesses are listed six times; peritonitis is listed four times; spreading infection of peripheral wounds, four times; severe bronchopneumonia, four times; septic infarcts (lung, kidney, etc.), twice; and empyema, twice. Inadequate bacteriologic data are available.


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In view of certain observations of an increased migration of bacteria across the intestinal wall in uremic dogs, the autopsy records were examined to see whether there had been any instances of peritonitis in the absence of intra-abdominal injury. No instance of peritonitis in the absence of a previous laparotomy was found. There were one or two instances of mild peritoneal infection in patients with a "negative" laparotomy, but the possibility of undiscovered intra-abdominal injury cannot be ruled out.

As mentioned, an important difference between the handling of wounds of the patients with renal dysfunction as compared with those without renal dysfunction was the time of secondary closure of open wounds. In patients without renal dysfunction, wounds were usually closed 5 to 10 days after injury. Patients with renal dysfunction were usually very sick during this time and secondary closure was rarely carried out during this period. Consequently, the wounds of patients with renal dysfunction remained open for significantly longer periods of time than in patients without renal dysfunction.

Adequacy of débridement is one of the important factors in wound infection. The question may be raised whether inadequate débridement may not have been more frequent among these patients than indicated by the finding of retained non-metallic foreign bodies noted in a few patients (Table 4). Many of these patients were very severely injured and were in profound shock before and during the initial operative treatment. It is possible that inadequate débridement or hasty closure of an abdominal wound, due to efforts to salvage life, might have been carried out.

At the time the Renal Center was first set up, it was not realized that a surgeon was needed whose only responsibility was the care of these patients. The surgical care of these patients was in the hands of the general surgical staff of the hospital. These surgeons had other duties and responsibilities and they were not able to give undivided attention to these patients. Under these circumstances, it is likely that the surgical care was not optimal in some instances.

Cross-infection was one of the factors possibly important in the high incidence of wound infection among this group of patients. These patients were kept on a single ward and it was not possible to carry out, either on the ward or in the dressing or operating rooms, many procedures which have been advocated for the prevention of cross-infections. There were no bacteriologic data available, however, to support or negate this opinion.

Bleeding Tendency

A number of the patients with renal dysfunction showed an abnormal bleeding tendency. During the second week in February 1953,


150

two of the four patients in the ward at the time had clotting times greater than 2 hours. This persisted over a period of days with associated excessive blood loss. This was an unusual proportion of "bleeders" but the problem was seen often enough to make its incidence significant.

A study of the basic defect (or defects) in the clotting mechanism is reported elsewhere.1

Wound healing is probably delayed in the presence of excessive bleeding into the wound, and perhaps indirectly by excessive bleeding elsewhere than in the wound.

Proposed Observations of Wound Healing

It is evident from reviewing the records of these patients that wound healing was a very important complication among the patients with renal dysfunction. It would appear that in the majority of the patients multiple factors were operative and presumably interrelated. However, it is apparent that with the available data, no specific conclusion as to the relative importance, or interrelationship, of the various factors can be made. Studies to define the problem specifically and thereby lead to improved prophylaxis and therapy are indicated.

Some of the problems which need solution are as follows:

1. What is the course of normal wound healing (open wounds, sutured wounds, etc.) in man?

There is a paucity of detailed correlated (clinical, histologic, bacteriologic, etc.) information regarding wound healing in man. There are very few controlled clinical studies and none specifically applicable to the problems at hand. Most of the specific data regarding wound healing have been obtained in animals. The differences in wound healing among various species make it imperative that caution be used in directly relating the results of animal experiments to man.

2. What is the effect of magnitude of injury on wound healing, and if an effect is present, to what factors may it be attributed? What is the significance of the "catabolic" reaction to injury?

Very few objective data of the physiological and clinical sequelae indirectly attributable to the early "catabolic" reaction to injury are available. There are conflicting opinions as to the harm resulting from this period, and depending on the viewpoint taken attempts are or are not made to reverse the process. Much of the conflict is due to the lack of objective indices of the benefits, or lack of benefits, of mitigating the early metabolic disturbances.

The injured man must heal his wounds for successful recovery; systematic observations of the healing of wounds, traumatic, operative


151

and experimental, would provide objective evidence in one important area as to the significance of the "catabolic" period. For example, the seriously injured individual acts biochemically like a scorbutic for some time after injury; does he also act like a scorbutic in regard to the healing of his wounds? Further, the intensity of the urinary nitrogen loss following injury may be decreased by the injection of testosterone propionate. Since the anabolic effects of testoterone are different for different tissues, what does the decrease in urinary nitrogen excretion mean in terms of wound healing?

It has been postulated by some that no attempt be made to reverse the "catabolic" reaction because it is a "defense mechanism" to supply metabolites to the injured area. There is no concrete evidence to support this. There is no reason, at the moment, to assume that the injured area is necessarily more proficient than other tissues in "utilizing" the circulating metabolites. We have recently studied the healing of experimental laparotomy wounds in normal and severely burned rats.2 Observations of the gross appearance, tensile strengths and histologic features of the incisions were made. The healing of laparotomy wounds in the burned rats was significantly different from that in the unburned controls. Epithelization was not affected, but there was a definite delay in the formation of granulation tissue in the incisional wounds of the burned animals with a lag in the appearance and maturation of the fibroblasts and the ground substance. The eventual number and amount of these two elements, however, did not appear to be affected, and abundant granulation formed in the wounds of the burned rats in time. In some of the burned rats the wound area appeared somewhat more edematous than that of the controls. The incidence of wound infection was also somewhat higher among the burned animals.

3. Is there a specific effect (direct or indirect) of renal dysfunction on wound healing? Or are the delays due to associated abnormalities in nutrition, water balance, ability to resist infection, etc.?

4. What is the basis for the apparent high incidence of wound infection in the patients with renal dysfunction?

Various degrees of renal dysfunction should be produced experimentally in a number of different ways. Emphasis should be directed towards simulating the clinical problem of "lower-nephron nephrosis." The course of wound healing in animals with renal dysfunction, untreated and treated in a variety of ways, including dialysis, should be studied. Observations on local and systemic infection and various immune responses should be made. These data may be correlated with various nutritional and metabolic measurements.


152

It is well recognized that infection, when present, is a detriment to wound healing. A careful study of wound infection is important, not only in the early post-injury period, but throughout the healing period. Why is wound infection so frequent, and so serious, in the severely wounded patient with renal dysfunction? Does the malnutrition predispose to wound infection, or does the wound infection accelerate the development of malnutrition? What is the ability of the seriously injured man in regard to antibacterial defense? Following simple starvation, lymphoid tissue is markedly depleted; chronically protein-depleted rats are unable to synthesize certain antibodies as well as normally nourished animals. What is the ability of the seriously wounded man who is on a totally inadequate diet to form antibodies? What is the efficiency of phagocytosis, etc., in such an individual? (A preliminary study on some aspects of these latter two problems is reported elsewhere by Balch.3) What is the effect of extracorporeal dialysis on resistance to infection? For example, in vitamin C deficiency, susceptibility to infection is increased; it is possible that there is a considerable "washout" of ascorbic acid during dialysis. Further, most of these patients may be on various antibiotics, certain of which, when given orally, may lead to nutritional disturbances under certain circumstances.

5. What are the effects of plasma substitutes and/or anemia on wound healing?

It would appear that in many instances a combination of whole blood and dextran (or some other plasma substitute) may be satisfactory for early replacement therapy of shock. Under this circumstance, a certain degree of anemia will be present at the time the patient is evacuated further to the rear. Ordinarily, surgeons feel that anemia per se is detrimental to wound healing and will be inclined to transfuse such patients prior to secondary closure, etc. Is this a necessary, or wise, procedure (considering possible shortage of blood, transfusion reactions, etc.)? Is there a direct effect of anemia on wound healing or is there, perhaps, an indirect effect? Is hemoglobin a very high priority protein in the severely injured patient during the catabolic period and, if so, will protein be diverted from the healing wound to form hemoglobin if anemia is present? No conclusive data on the influence of anemia on wound healing in man are available; the data in animals are controversial.

What is the effect of plasma expanders per se on wound healing? Data in this regard are meager. Rhoads and his co-workers observed that whereas there was a delay in the healing of abdominal wounds in hypoproteinemic edematous dogs, there was no delay in hypopro-


153

teinemic dogs given acacia intravenously in amounts sufficient to eliminate the edema, but which, at the same time, accentuated the decrease in plasma protein concentration.4 Thorsen has reported no delay in the healing of incisional wounds in rabbits given dextran.5 We have observed no gross abnormalities in the healing of burns in patients who have received large amounts of dextran, but no special studies of the wounds were made.

6. What are the optimal prophylactic and therapeutic nutritional (dietary, hormonal, etc.) regimens for the wounded patient with or without renal dysfunction?

If the period of metabolic derangement persists, progressive nutritional deterioration with its consequent well-known ill effects occurs. What is the optional nutritional (dietary, hormonal, etc.) care of these individuals?

What Is Needed

A study of the individual and his wounds directed toward a comprehensive correlation and evaluation of systemic and local phenomena is indicated. Such a study will entail the use of a variety of technics, clinical, metabolic, bacteriologic and pathologic. The clinical studies should be supplemented by animal studies in a variety of species.

Some Factors in Wound Healing Requiring Control:

A. Systemic Factors

    1. Extent and sites of wounds.

    2. Associated injuries (and/or illnesses).

    3. Circulatory system (shock, sludging, etc.).

    4. Metabolic and nutritional state (including anemia, antibiotics, all nutrients, etc.).

    5. Plasma substitutes (primary and secondary effects).

    6. Infection (including "resistance" of individual, etc.).

    7. Blood clotting mechanism.

B. Type of Wounds

    1. Contaminated wounds, débrided and secondary sutured (including time of secondary suture).

    2. Contaminated wounds débrided and primarily closed.

    3. Clean, incised wounds closed primarily (including type of closure, etc.).

C. Local Factors

    1. Extent and sites of wounds (including surrounding and supporting tissues; proximity to joints; direction of wound relative to lines of stress, etc.).


154

    2. Blood supply (arterial and venous).

    3. Infection (including antibiotics, etc.).

    4 . Wound edema or dehydration (local or systemic basis).

D. Medical and Surgical Care

    The quality and types of medical and surgical care are, of course, of paramount importance, but will not be discussed in this paper.

Conclusion. This analysis of wound healing among patients with serious battle injuries and renal failure confirmed the impressions of various physicians, that wound complications were frequent and important in these patients. Further, the analysis has indicated the complexity of the problem, some possible interrelationships among various factors and the need for concrete objective study, clinical and experimental.

Summary

1. The clinical and autopsy records of the 70 patients admitted to the Renal Center from its opening in the spring of 1952 through the middle of February 1953 were reviewed. Forty-two records were deemed adequate for analysis. However, the progress notes were written by internists, the records were not specifically directed towards problems of wound healing, bacteriologic studies were inadequate and only casual attention was paid to the wounds at autopsy. No histologic studies of the wounds were done.

2. Among the 42 patients whose records were analyzed, gross impairment of wound healing was noted in 31. The term "impairment" is used in a broad sense and is not meant to imply a specific defect in wound healing. Mortality among the patients with impaired wound healing was high; wound complications were among the more frequent and important causes of death.

3. It would appear that "impairment" of wound healing among these patients was greater than occurred in patients with serious battle wounds but without renal dysfunction. However, this cannot be stated with certainty, since no over-all systematic tabulation of wound healing among the battle casualties of the Korean conflict was made.

4. Among the patients with battle wounds and renal dysfunction, a comparison was made between those patients with unimpaired wound healing and those with impaired wound healing to determine some of the factors which might have had some bearing on the observed differences in wound healing. It appears that those patients with impaired wound healing were, in general, the more seriously injured, sicker, more uremic, required more dialyses, had greater changes in water and electrolyte metabolism, lost more weight, had more severe infections, and showed a higher incidence of abnormal


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bleeding. The severity of the anemia could not be adequately estimated.

5. It would appear that in the majority of these patients multiple factors were leading to wound healing difficulties. These factors were presumably interrelated in the apparent serious uremia, serious infection and serious malnutrition. Some aspects of the pathogenesis and significance of these factors are discussed.

6. With the data at hand, no specific conclusion can be made covering the relative importance, or interrelationship, of the various factors. Studies are needed to define the problem specifically and thereby lead to improved prophylaxis and therapy. Such studies will require various clinical, metabolic, bacteriologic and pathologic technics. Some of the problems which need solution are as follows:

a. What is the course of normal wound healing (open wounds, sutured wounds, etc.) in man?

b. What is the effect of magnitude of injury on wound healing, and if an effect is present, to what factors may it be attributed? What is the significance of the "catabolic" reaction to injury?

c. Is there a specific effect (direct or indirect) of renal dysfunction on wound healing? Or are the delays due to associated abnormalities in nutrition, water balance, ability to resist infection, etc.? What is the basis for the apparent high incidence of wound infection in the patients with renal dysfunction?

d. What are the effects of plasma substitutes and/or anemia on wound healing?

e. What are the optimal prophylactic and therapeutic surgical and nutritional (dietary, hormonal, etc.) regimens for the wounded patient with or without renal dysfunction?

7. Some factors requiring control in wound healing studies are discussed.

References

1. Crosby, W. H., and Stefanini, M.: J. Lab. & Clin. Med. 40: 374, 1952.

2. Levenson, S. M.: Surg., Gynec. & Obst. 99: 74, 1954.

3. Balch, H. H., Jr.: To be published.

4. Rhoads, J. E., Fliegelman, M. T., and Panzer, L. M.: J. A. M. A. 118: 21, 1942.

5. Thorsen, G.: Acta. Chir. Scandinav. 100: 422, 1950.