TABLE 1


		Initial	Days		% Rate
		Wound	to	Fill	Increase
		Volume	Full	Rate	Due to
Animal	Wound	(cm³)	Granulation	(cm³/day)	Treatment

#1	Control	4.9	13	0.38	26.3
	Treated	5.3	11	0.48
#2	Control	7.2	8	0.90	28.9
	Treated	9.3	8	1.16
#3	Control	4.0	12	0.33	75.8
	Treated	3.5	6	0.58
#4	Control	4.7	11	0.43	65.1
	Treated	5.0	7	0.71
#5	Control	4.7	11	0.43	65.1
	Treated	5.1	7	0.71
Average	—	—	—	—	52.3

EXAMPLE 2Reduction of Infection

During the course of the experiment described as Example 1 above, it was observed that the reduced pressure-treated wounds were much cleaner and bled more spontaneously than non-treated wounds. It was therefore undertaken to determine the relative rates of clearance of a known bacterial inoculum from treated and non-treated wounds.

Five 15 kg pigs were obtained and wounds created as set forth in Example 1. Two 2.5 cm diameter defects were created on the dorsum of each pig using a sterile technique, with a 7.5 cm interval retained between the edges of the defects. Hemostasis was obtained by electrocautery. Prior to placement of the reduced pressure appliances,10⁸organisms ofStaphylococcus aureusin 1 ml saline solution were injected into each wound. The reduced pressure appliances of the type shown inFIGS. 2 and 11 were then attached as in Example 1. A reduced pressure of 5 in. Hg below atmospheric pressure was applied to one of the wounds upon each animal. Reduced pressure was not applied to the other wound upon each animal. T-shirts were placed over the animals and no antibiotics were given during the course of the study. The animals were sedated as in Example 1 at 24 hour intervals, and a 3 mm diameter full thickness biopsy was taken from each wound site daily. The devices were then reattached and reduced pressure re-applied. This routine was continued for one week.

The biopsy samples were weighed and sterile saline (99X biopsy weight) added. The tissue samples were homogenized in a tissue grinder and serial dilutions were made in triplicate. 100 microliters of each dilution was plated on a blood agar plate and incubated overnight. The number of colonies were counted on each plate and thus the number of organisms per gram of tissue was calculated. The data was recorded as the common logarithm of the number of organisms/gram tissue and is shown in Table 2.

	TABLE 2


	Average Log₁₄(organisms/gm)

Day	Day	Day	Day	Day	Day	Day
0	1	2	3	4	5	7

Control	8.44	8.04	8.17	7.13	7.13	8.82	7.08
Treated	7.69	7.36	7.37	6.79	6.43	3.98	4.32

As can be seen in Table 2, the common logarithm of the average number of organisms per gram of tissue present in the treated and non-treated wounds decreased slightly for all five animals over the first 4 days. In the treated wounds, the mean log of organisms/gm decreased dramatically between days 4 and 5. The mean log of organisms/gm within the non-treated wounds increased during the same period. Using the traditional baseline of 10⁵organisms/gm to define infection, the data of Table 2 shows that the average treated wound was disinfected after four days of treatment while the average non-treated wound was still infected after 7 days.

EXAMPLE 3Treatment of Burns

Use of reduced pressure appliances upon burns has been found to retard the progression of partial thickness burns into full thickness burns. A partial thickness burn is a burn in which the depth of cell death due to thermal trauma does not extend below the level of the deepest epidermal structures (i.e., the base of hair follicles, sweat glands, sebaceous glands, etc.). A burn that is initially a partial thickness burn will often deepen and progress into a full thickness burn due to insufficient blood circulation to the epidermal cells beneath the partial burn.

EXAMPLE 3A

The backs of five 15 kg pigs were shaved and scrubbed for surgery. A 1.5 inch diameter brass rod was heated to 190° C. in an oil bath. The rod was pressed onto the pig's skin for 15 seconds following a well-known technique of relating depth of burn to time and temperature. Three burns were created over the spine of each pig, separated by 5 cm intervals. Suction apparatus cups of the configuration shown inFIGS. 2 and 11 were placed over two of the burns, with silver sulphadiazine (Silvadine) cream, the standard antibiotic cream applied to human burns prior to excision of burned tissue, applied to the third. Cefaxolin (Kefzol) (500 mg) was administered intramuscularly (antibiotic). Suction (2-6 pounds vacuum) was applied to one of the cups. A small (2 mm) punch biopsy was taken of the wounded area and examined histologically for depth of burn.

Biopsies were analyzed by a dermatopathologist who was not told the nature of the study. It was concluded that the suctioned tissue specimens were healthier and healing more quickly than non-suctioned specimens.

EXAMPLE 3B

A set of 2 cm diameter standardized depth partial thickness burns were created by pressing a heated metal rod to each side of five anesthetized pigs to create 16 burns on each side of each pig. Reduced pressure appliances of the type shown inFIGS. 2 and 11 were secured over each of the burns on the left side of each animal and a continuous pressure of 6 in. Hg was supplied to the reduced pressure appliances. The animals were anesthetized daily, and elliptical full-thickness biopsies extending from non-injured tissue, through the center of each burn, and into non-injured tissue were harvested, fixed in formalin, processed for histological analysis and stained with Hematoxylin/eosin and Gomori's trichrome. The histologic slides were then given to a Dermatopathologist for blind determination of burn depth according to the Breslow Local Scale of maximum depth of cell death below the surface of the skin.

The Breslow Level (maximum total depth) for the burns treated by reduced pressure was 0.095 mm. The maximum depth of the burns which were not treated by reduced pressure was 0.885 mm. The use of reduced pressure appliances thus resulted in a 112% reduction in the maximum depth of burn progression.

EXAMPLE 3CTreatment of Burn with Negative Pressure

Patient B. is admitted with second and third degree burns over the face and upper extremities, including both hands, as a result of a house fire. A large mitten-shaped reduced pressure appliance of the general type shown inFIGS. 1 and 10 is placed over the patient's right hand, with open cell foam inserts placed between the fingers to apply reduced pressure to the interdigit spaces. Three pounds of vacuum is applied cyclically in a pattern of five minutes on, 5 minutes off. The appliance is changed on a three times per week schedule. Treatment is continued until the necrotic tissue sloughs off or is excised, followed by split thickness skin graft placement.

EXAMPLE 4Treatment of Flaps

In order to determine the effect of reduced pressure application upon skin flap survival, five 15 kg Chester pigs were obtained and acclimated for 1 week as described previously. Two dorsally-based 3 cm by 12 cm flap outlines were drawn using indelible ink on each side of the pigs, leaving 6 cm between each flap. The flaps were assigned to one of four groups as follows:

(1) Dual-treated flaps are flaps that were exposed to reduced pressure both prior to and following surgery;

(2) Pre-treated flaps are flaps that were exposed to reduced pressure prior to surgery, but were not exposed to reduced pressure after surgery;

(3) Post-treated flaps are flaps that were exposed to reduced pressure following surgery; and

(4) Control flaps are flaps that were not exposed to reduced pressure either pre- or post-surgery.

The pre-treated flaps were initially treated by covering an area surrounding one of the flap outlines on the left side of each animal with a reduced pressure appliance of the type shown inFIGS. 1 and 10 having a large piece of open cell foam into which a tube was inserted. The foam was covered and sealed to the flap area with impermeable adherent sheeting. A reduced pressure of 7 pounds was then continuously applied to the area for 7 days.

On the day of surgery, each pig was sedated as previously described and anesthesia was maintained by 1% halothane. Two 3 cm by 12 cm dorsally based flaps were created on each side of the pig following the flap outlines. The flaps were created at a depth immediately below thepanniculus carnosus(a subcutaneous muscle layer). The flaps were raised and then sutured back in place with single, interrupted sutures of 3-0 nylon. The reduced pressure appliances were then placed over the anterior flaps on each side of the animal. A reduced pressure of 5-7 pounds was continuously applied to the anterior flaps. Each suction tube ran from the appliances on the animals upward through a pulley suspended over the pens and down to a vacuum trap bottle to collect any liquid exudate. A hose was connected from each vacuum trap bottle to a vacuum pump to supply the reduced pressure to the appliances. The animals had free access to all areas of the pen.

The animals were anesthetized 72 hours after surgery and the appliances were removed. Photographs of each side of the animals were taken, and tracings of the flaps (and encompassing any discolored areas) were made on acetate to allow for planimetric calculation of percent survival. The appliances were then replaced and reduced pressure re-applied. This routine was continued at 48 hour intervals until no further necrosis or healing of the flaps was observed.

The distal portions of all flaps were discolored 72 hours post surgery, with the flaps exposed to reduced pressure being lighter in color. The distal ends of all flaps appeared to necrose and an eschar formed over the distal portion of each flap. Over time the eschar spontaneously desquamated, exposing the outline of the original flap. The eschar over the control and pre-treated flaps consistently desquamated sooner than the post-treated and the dual-treated flaps. The control flaps had contracted to a Y shape which was evident after the eschar had desquamated. The dual-treated flaps had contracted slightly and appeared as long, thin rectangles after dislodgement of the eschar. The pre-treated flaps and post-treated flaps were intermediate between the control and dual-treated flaps in regard to flap contraction.

Dual-treated flaps exhibited the greatest survival in terms of percent retention (72.2%) of the original flap size. The post-treated flaps had the second greatest survival (67.4%). The pretreated flaps had the third most flap survival (64.8%). The control flaps had the least flap survival (51.2%). All treated flaps (dual-treated; pre-treated; and post-treated) exhibited significantly greater surface area survival than the control flaps. The dual-treated flaps had significantly greater surface area survival than either the pre-treated or post-treated flaps. The pre-treated flaps were not significantly different than post-treated flaps in regard to flap survival.

EXAMPLE 5Treatment of Decubitus Ulcers

Application of reduced pressure was tested upon chronic decubitus ulcers and was found to be effective in the treatment thereof. Necrotic soft tissue was removed from the ulcers prior to placement upon the treatment site of a reduced pressure appliance of the type described in connection withFIGS. 1 and 10. Treatment of decubitus ulcers was tested using both continuous and cyclic application of reduced pressure. It was found that cyclic application of reduced pressure was both more effective and produced less discomfort for the patients than continuous application. Cyclic application of reduced pressure was conducted according to an application schedule of 5 minutes of suction followed by 5 minutes of non-suction. In 15 patients tested, successful treatment required from 2 to 13 weeks. Thirteen of the ulcers healed completely and every ulcer treated demonstrated progressive decrease in size during treatment. The following case histories demonstrate the manner in which various pressure sores were treated:

Case 1—A 39 year-old male T4 paraplegic had suffered from multiple recurrent pressure sores over a period of 8 years. He had been treated for a trochanteric decubitus with a tensor fascia lata flap which had developed a recurrent ulcer in the center of the flap 4 months prior to presentation. The ulcer was debrided of necrotic tissue to non-involved periosteum resulting in a wound measuring 12 cm by 5 cm with a depth of 5 cm. During the course of 4 weeks of cyclic reduced pressure application, the wound progressively closed and spontaneously re-epithelialized. Reduced pressure of 5 in. Hg below atmospheric pressure was applied cyclically with 5 minute intervals of applied pressure followed by 5 minute intervals with no applied pressure. The wound remained healed more than 5 months after treatment.

Case 2—A 45 year old male paraplegic suffered from a recurrent right ischial fossa pressure sore and abscess prior to treatment. Debridement of the wound was carried out with partial ischial resection. A week later, a re-advancement of the V-Y biceps femoris flap and rotation gluteus flap was performed. Six days later, the wound dehisced and the patient developed bilateral pneumonia requiring ventilatory support. The flap became progressively edematous and firm and resisted all efforts at mobilization. At this point, reduced pressure treatment providing continuous, non-cyclic suction or a vacuum at approximately five 5 in. Hg below atmospheric pressure was initiated. A total of 2 liters of fluid was removed by the reduced pressure appliance during the first 72 hours of treatment. Intravenous fluids were administered to replace the fluid removed from the wound. The appliance was replaced and the wound was examined three times each week. Treatment was continued for a total of six weeks during which the flap became progressively less indurated, granulation tissue formation rapidly progressed, the edges of the wound came into approximation, and the wound was healed completely.

Case 3—A 51 year-old T1 paraplegic had multiple previous pressure sores culminating in bilateral asynchronous hip disarticulations and bilateral total thigh flaps. Seven months prior to admission, he developed a 7 cm by 23 cm pressure sore over the remnants of both ischia. Bone was exposed and no tissue was available for wound closure. Dressing changes over a period of three months had failed to improve the wound. A reduced pressure appliance was then secured to the wound. During the first 3 weeks of treatment, reduced pressure of 5 in. Hg below atmospheric pressure was continuously applied. For the following 9 weeks, reduced pressure was applied cyclically in 5 minute intervals. The appliance was replaced every three days during treatment. In the course of the treatment, the wound first granulated to cover the bone completely and then the wound re-epithelialized from the margins. After 12 weeks of the treatment, a 2 cm by 5 cm scrotal flap was used to cover the midline area of the wound. The wound has remained stable beyond 6 months after treatment.

EXAMPLE 6Treatment of Dehisced Incisions

A 50 year old debilitated white male who had undergone a colostomy through a midline laparotomy was re-admitted to the hospital for wound dehiscence and evisceration following an upper respiratory infection. He was taken immediately to the operating room and the abdominal wall was closed with Prolene mesh. Six weeks after placement of the Prolene mesh, the wound was still open and measured 28 cm by 23 cm. Only sparse granulation tissue had grown through the Prolene mesh during the six weeks. At this time a large reduced pressure appliance of the type shown inFIG. 5 was placed on an underlying porous aquaplast sheet (WFR/Aquaplast Corp., Wycoff, N.J. 07481) over top of the Prolene mesh/wound surface and the space closed with a covering tent of Ioban. A continuous vacuum of 5 in. Hg below atmospheric pressure was applied. The appliance was changed three times per week. After 8 days of treatment, granulation tissue had grown through and totally covered the Prolene mesh. Two days later, the patient was taken to the operating room, where the surrounding tissue was undermined and used to close 75% of the wound. Split thickness skin grafts were used to cover the remainder of the wound, and were placed on the bed of granulation tissue. There was 80% take of the grafts, and the remaining areas healed spontaneously with wet to dry dressing changes. The wound has remained stable 16 months after surgery.

EXAMPLE 7Treatment of Infected Wound

Infected wounds have been successfully treated via application of reduced pressure as described in the following cases:

Case 1—A 39 year old white male sustained severe avulsive trauma to his left lower extremity in amotor vehicle accident 10 years prior to presentation. He presented with a ten year history of chronic osteomyelitis and a 3 cm diameter open ulcer with exposure of bone of his left lateral malleolus. He had previously undergone7 local surgical procedures to attempt closure of the wound. An arteriogram demonstrated a one vessel foot with diffuse atherosclerosis and post traumatic changes. The extremity was debrided of necrotic soft tissue and all involved bone saucerized. The patient was placed on a five week course of antibiotics. The day after debridement, a reduced pressure device of the type shown inFIGS. 2 and 11 was applied over the wound and a reduced pressure of 5 in. Hg below atmospheric pressure was applied. The device was changed on a three times per week schedule. After 14 days of treatment, the wound was smaller and filled with granulation tissue which completely covered the previously exposed bone. A split thickness skin graft was placed over the wound and healed primarily. The wound has been stable for 13 months with no recurrence of osteomyelitis or tissue breakdown.

Case 2—A 51 year old white male T8 paraplegic was admitted to the hospital for an infected left trochanteric pressure sore which had been present for one year and measured 4 cm by 6 cm. The patient had previously undergone multiple procedures for treatment of this condition including a V-Y advancement flap 4 months prior to presentation. A scan revealed possible chronic osteomyelitis of the left femur. It was decided to treat the potential osteomyelitis with a five week course of IV antibiotics. The wound was debrided, then treated using a reduced pressure appliance of the type shown inFIGS. 1 and 10 for 6 weeks with cyclical reduced pressure (5 in. Hg below atmospheric pressure; 5 minutes on/5 minutes off). The wound rapidly granulated and decreased in size. After 6 weeks the wound had closed and the patient discharged. The patient was readmitted 1 month later with a draining sinus tract to the bone. The previously scanned head of the left femur was resected and the wound closed primarily over drains. The wound healed without further problems.

EXAMPLE 8Chronic Open Wound Secondary to Stasis Ulcers

A 45 year old black female patient with a 10 year history of bilateral stasis ulcers of the pretibial area was presented with bilateral 10 cm by 15 cm infected ulcers with exposed fascia. Two previous attempts at skin grafting in the previous year had failed. The patient was treated using a reduced pressure appliance of the type shown inFIGS. 1 and 10 for 14 days with cyclical (5 minutes on/5 minutes off) reduced pressure of approximately 5 in. Hg below atmospheric pressure. After 14 days treatment, quantitative bacterial counts of both ulcers were below 102 bacteria/gram tissue, and both ulcers appeared as healthy granulating beds. Split thickness skin grafts were then applied and exhibited100ttake. The patient is ambulating, and the wounds have remained healed for 2 months, which is the longest the wounds had been healed in the last 10 years.

EXAMPLE 9Enhancement of Blood Flow

It is believed that the efficacy of reduced pressure appliances in such treatments as have been described is due at least in part to enhancement of blood circulation within the treated wounds. In order to determine the effect of pressure application upon blood flow, a laser doppler needle probe was inserted into tissue adjacent to a pressure sore. A baseline flow level was recorded for thirty minutes. Then, the relative blood flow level was measured while a reduced pressure corresponding to 5 in. Hg below atmospheric pressure was continuously applied to the wound for 30 minutes using a reduced pressure appliance of the type shown inFIGS. 1 and 10. During continuous reduced pressure application, the relative blood flow level was only slightly higher than the baseline level.

Then the supply of reduced pressure to the appliance was cycled on and off at equal 5 minute intervals. During the “off” portions of the cycle, the relative blood flow level was twice as high as the baseline level. It is postulated that the increased blood flow during the off cycle is likely due to a “rebound” phenomenon. During the “on” cycle, blood is drawn toward the wounded tissue from both the venous and arterial branches of the vascular network in the vicinity of the wound. During the “off” cycle, this blood is transported toward the venous branch of the vascular network at a rate that is greater than would have been observed in the absence of the preceding “on” cycle.

The terms and expressions which have been employed are used as terms of description and not of limitation and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described, or portions thereof, but it is recognized that various modifications are possible within the scope of the claimed invention.