- Email: [email protected]
Mechanical Adjuncts to Wound Healing
General Mechanical Adjuncts to Wound Healing Guest Reviewers: Edward M. Kwasnik, MD, Santiago Arruffat, MD, and Shirley M. Harkins, RN, Department of Surgery, Waterbury Hospital Health Center, Waterbury, Connecticut HYPERBARIC OXYGEN (HBO) THERAPY IN TREATMENT OF DIABETIC FOOT ULCERS. LONG TERM FOLLOW UP. Kalani M, Jorneskog G, Naderi N, Lind F, Brismar K. J Diabetes Complications. 2002;16:153-158. Objective: To investigate the long-term effect of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers. Design: Partially randomized prospective study comparing
hyperbaric oxygen (HBO) to conventional therapy of chronic foot wounds in diabetics. Endpoints included ulcer healing and need for amputation after a three-year follow-up period. Setting: Division of Emergency Medicine, Department of En-
docrinology and Diabetology, Division of Hyperbaric Medicine, Department of Anesthesiology and Intensive Care at Karolinska Hospital in Stockholm, Sweden. Participants: Thirty-eight diabetic patients with superficial chronic foot ulcers not eligible for vascular reconstruction with local tissue anoxia determined by transcutaneous oxygen tension (tcPO2) ⬍ 40 mmHg that increased significantly with the inhalation of pure oxygen. Seventeen patients were assigned to HBO and 21 patients to conventional treatment.
Results: Of the 38 patients evaluated, 76% (13/17) in the
HBO treatment group healed their ulcers with intact skin, 12% (2/17) had below knee amputations and another two patients (12%) died during treatment. In the conventional treatment group, 48% (10/21) healed their ulcers, 33% (7/21) underwent below knee amputations and 3 patients died. The mean healing time of 15 months was not statistically or clinically different between groups. In a comparison of 9 patients who underwent amputation with the 23 who were alive and healed at the 3 year follow-up, no significant difference in the baseline tcPO2 and toe blood pressure measurements were noted while the mean tcPO2 value during oxygen inhalation was significantly higher (p ⬍ 0.03) in those patients that healed (234 ⫾ 110 mmHg) compared to those who were amputated (142 ⫾ 65 mmHg). Complications of HBO therapy included one patient who developed cataracts and another patient who had ear pain, which was treated with decongestants. Conclusions: Hyperbaric oxygen therapy can be a valuable adjunct to chronic foot ulcer treatment in selected diabetic patients. The authors stated that it seemed to accelerate the rate of healing, reduce the need for amputation and increase the number of wounds that were healed during long-term followup. Further studies are needed to further define the role of HBO as part of a multidisciplinary program to preserve a functional extremity in diabetic patients with chronic foot ulcers.
REVIEWER COMMENTS
This study, one of a few that attempts to randomize patients to HBO vs. conventional therapy, illustrates many of the difficulties associated with the conduct of such trials. The authors state that the first 14 patients were randomized and then accrual of patients was stopped for 2 years due to lack of availability of HBO, after which the remaining patients were added in non-randomized fashion. This resulted in the introduction of confounding variables, such as a significantly younger population in the HBO group, and made proper statistical analysis problematic. While the authors report a
decreased rate of amputation in the HBO group, when we analyzed this data by Fisher’s exact test the difference between groups did not reach statistical significance at the customary p ⬍ 0.05. Perhaps the small patient population (n ⫽ 37), a consequence of the well-defined inclusion criteria for this study, increased the likelihood of a beta-error. Furthermore, while the authors state in their conclusions that HBO seemed to accelerate the rate of healing, their results clearly indicate that the rate of healing was the same for both groups.
VACUUM ASSISTED CLOSURE: A NEW METHOD FOR WOUND CONTROL AND TREATMENT; CLINICAL EXPERIENCE.
Objective: To investigate the application of subatmo-
Argenta LC, Morykwas MJ. Ann Plast Surg. 1997:38:563-577.
spheric pressure by a vacuum-assisted closure device (VAC) in the treatment of a wide variety of acute, subacute and chronic wounds.
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465
Design: Prospective evaluation of a non-randomized consecutive clinical series. Setting: Department of Plastic and Reconstructive Surgery,
Bowman Gray School of Medicine, Winston-Salem, NC. Participants: The first 300 patients treated with the VAC
were grouped as follows: (1) chronic wounds open for ⬎ 7 days with no progress toward healing (pressure sores, diabetic and stasis ulcers; N ⫽ 175); (2) subacute wounds open for ⬍ 7days but greater than 12 hours (infected and dehisced wounds, avulsions and open amputations; N ⫽ 94); and (3) acute wounds open ⬍12 hours (acute avulsions, evacuated hematomas, eviscerations etc; N ⫽ 31).
Results: Two hundred ninety-six patients in the study population responded favorably to VAC therapy. Of the chronic
wounds, 171 of 175 wounds showed favorable outcomes with 32% healed completely, and 61 % healed with the aid of flaps and grafts. The only treatment failures were noted in patients who died of other causes during the study. In the subacute category, 28% (26/94) healed completely while the remaining 68 wounds granulated and contracted to smaller wounds easily controlled with skin grafts, secondary closure or minor flaps. With the exception of 1 patient who died of pulmonary embolism, all patients in the acute group healed. Complications included transient pain with the institution of negative pressure, minor bleeding from in-growth into the sponge and one enteric fistula. Conclusions: The VAC is an effective mechanical adjunct for the treatment of chronic and difficult wounds.
REVIEWER COMMENTS
This seminal report introduced the modality of subatmospheric pressure as a mechanical adjunct in the treatment of chronic and difficult wounds. The authors presented a robust series of 300 patients with wounds of compromised primary healing potential and stratified them based on the chronicity of their wounds. While a randomized prospective design would have better delineated the effects of the VAC on the restoration of these defects, the authors point out that as many as 34 independent variables may have influenced wound healing in these individuals and would have required an extraordinary number of participants to be randomized into multiple treatment arms.
The strength of this observational study lies in the complete follow up of all patients to the point of wound closure or death. Furthermore, the authors emphasized that all patients were treated with conventional principles of wound care including debridement, infection control and tissue transfer with grafts or flaps with the VAC used as an adjunct to their treatment. Their study established the VAC as a technology that may be safely and effectively applied by properly trained health care professionals to patients in the hospital as well as ambulatory setting and motivated other investigators to evaluate its use in a variety of clinical situations.
WET WOUND HEALING.
wounds that did not heal, one healed after additional chamber treatment, one had a skin graft that did not take, and one required reamputation at a higher level. Antibiotic delivery through the device was less than one intravenous dose daily, yet
Vranckx J, Slama J, Preuss S, et al. Plast Reconstr Surg. 2000;110:1680-1687. Objective: To evaluate the clinical application of a flexible
transparent wound healing chamber in patients with chronic wounds. Design: Prospective study of chronic wounds treated with a
wound chamber containing saline and antibiotics (Fig. 1). Setting: Laboratory of Tissue Repair and Gene Transfer, De-
partment of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Boston, MA. Participants: A total of 28 wounds in 20 consecutive pa-
tients were treated with the wet wound chamber technique. Most wounds were chronically infected, represented multiple etiologies and had not responded to debridement or flap closure. Results: Twenty-five of the wounds (89%) healed and 5
wounds (18%) required additional conservative management after initial chamber treatment and grafting procedures. Of 3 466
FIGURE 1. Schematic drawing of a wound chamber prototype. Reprinted with permission from Elsevier Science. From Ericksson E, Vranckx J. Wet wound healing: from laboratory to patients to gene therapy. Am J Surg. 2004;188(Suppl 1):37S.
CURRENT SURGERY • Volume 62/Number 5 • September/October 2005
allowed concentrations of up to 10,000 times the minimal inhibitory concentration. Conclusions: Wet wound therapy is an effective and safe way of treating chronic wounds complicated by infection. The wet
wound chamber had no adverse effects on normal skin, reduced pain with direct administration of analgesics, promoted faster healing, produced less scarring, and facilitated delivery of any desired solution or pharmacologic agent.
REVIEWER COMMENTS
The authors described a new device called a “wet wound chamber” developed from laboratory experience with in-vivo tissue culture techniques designed to facilitate wound healing and tissue engineering. The round, flexible, transparent chamber provided a constant wet milieu in the treated wound that increased patient comfort through less physical wound manipu-
lation, and allowed access to the wound without compromising the surrounding normal tissue. The series was well documented in terms of the types of wounds included, their bacteriology and antibiotic susceptibility, and the surgical techniques employed. Complete follow-up was obtained on all patients entered into the series, further enhancing the conclusions of the study.
REVIEWER SUMMARY
Since antiquity, a working knowledge of wound healing has been an essential component of the surgeon’s armamentarium. Until recently, principles of wound treatment were derived empirically and were based on a rudimentary understanding of the biology of tissue repair. While the basic tenets of wound care including proper nutrition, gentle handling of tissues, maintenance of adequate blood supply, avoidance of tension, appropriate use of debridement and control of infection are sufficient to promote successful healing of the majority of wounds encountered in contemporary surgical practice, mechanical and pharmacological adjuncts to healing chronic wounds in disadvantaged hosts are actively being studied. Over the last two decades, advances in cell biology have elucidated details of systemic and molecular responses to tissue injury and produced a theoretical foundation for the pathogenesis of chronic wounds1. First, cellular and systemic changes of aging lead to altered gene expression resulting in decreased proliferative capacity, prolonged doubling times and eventual replicative senescence in tissue culture studies of aging cells. Second, cellular events associated with the cycle of ischemia-reperfusion, particularly the expression of inflammatory cytokines and release of destructive free radicals, impede progression of the normal stages of wound healing. Lastly, chronic wounds are frequently colonized by bacteria that produce a persistent inflammatory response. These concepts along with other detailed information about the etiologies and treatment of recalcitrant wounds are presented in two recent comprehensive journal supplements2,3 which deserve careful reading by all surgeons interested in acquiring more than a superficial knowledge of tissue repair and regeneration. The most challenging wounds – chronic diabetic and venous ulcers as well as pressure sores – often frustrate the individual physician and tax the resources of the health care delivery system. As a consequence, a multi-disciplinary specialty of wound care is emerging through the collaboration of basic scientists, general, plastic and vascular surgeons, podiatrists and nurse clinicians. These practitioners and their institutions often establish wound care centers4as repositories of the human and physical resources needed to advance knowledge in this area and provide comprehen-
sive treatment of these difficult clinical problems. In the ideal situation, such facilities offer patients cost effective application of the fundamental principles of wound care while functioning as stewards of more expensive resources such as hyperbaric chambers. As this review has demonstrated however, more data must be properly collected and analyzed to match specific modalities with deficiencies in the healing mechanism since, to paraphrase our sixteenth president, we still only “heal some of the wounds some of the time, but not all of the wounds all of the time.” The greatest challenge remains to translate advances made in the laboratory, where the large number of potential confounding variables involved in wound healing may be appropriately stratified or controlled, to the clinical setting where it is more difficult to isolate the effect of the treatment being studied. It is appropriate to critically discuss the interface between the basic science foundations and clinical applications of the mechanical adjuncts to wound healing presented above. Hyperbaric Oxygen The presence of at least some degree of tissue anoxia is well established in the pathogenesis of chronic wounds and provides a rational scientific basis for the use of hyperbaric oxygen (HBO) therapy to reverse an ischemic wound environment. In fact, HBO has been shown to do this in experimental and clinical studies5. Perhaps more intriguing are the recent observations6 that hyperoxia positively influences many of the cellular responses to tissue injury, acting as an intracellular signal transduction agent, and a modulator of gene function leading to increased production of platelet derived growth factor receptor proteins in ischemic tissues. The relevance of these experimental observations to the biochemical details of indolent human wounds will require more intensive investigation. Several studies5,7 measuring local tissue anoxia based on tcPO2 have defined the patients who will most benefit from HBO. When these parameters are applied as inclusion and exclusion criteria for clinical trials of HBO, patient accrual is limited. For example, in the study of HBO reviewed above, only 38 patients were enrolled from a possible 1.2 million inhabitants of Stockholm. In addition,
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467
this small number of patients was not properly randomized to control and treatment groups, precluding valid statistical analysis. Based upon this investigation, as well as the most recent Cochrane Review8 of hyperbaric oxygen therapy for chronic wounds, the benefit of HBO is limited to a trend toward fewer amputations in highly selected groups of diabetic patients treated with this modality. Furthermore, effectiveness for chronic venous or arterial ulcers, pressure sores or the majority of diabetic ulcers without documented tissue hypoxia has not been demonstrated. Despite the well-defined criteria which limit the number of patients who may benefit form HBO, these facilities continue to proliferate with 458 chambers located in North America that are currently registered with the Hyperbaric and Undersea Medicine Society9. These centers recently (2000) generated $49.9 million of charges to Medicare alone, with almost 32% of these charges found to be paid in error for uncovered or inadequately documented conditions10. Unfortunately, from a practical economic point of view, the need to amortize the significant capital outlays for the establishment of these centers makes the reporting of negative outcomes of studies of HBO less likely. Vacuum-assisted Closure (VAC) In a companion paper to the clinical study reviewed above11, the authors presented experimental animal studies that demonstrated positive effects of subatmospheric pressure on wound blood flow, rate of granulation tissue formation, and clearance of bacteria from infected wounds. The VAC is thought to produce these effects primarily through the removal of edema fluid, a process that simultaneously changes the physical characteristics of the wound by increasing tissue pliability. It also potentially enhances the metabolic microenvironment for wound healing by reducing the concentrations of matrix metalloproteases and other inhibitors of the normal cellular processes of tissue repair often found in chronic wounds12. In additional experimental studies Fabian et al.13compared the effects of the (VAC) and hyperbaric oxygen therapy (HBO) alone and in combination in a standardized ischemic wounds model. The VAC dressing to suction and VAC dressing alone both with and without the use of HBO produced a statistically significant increase for peak granulation tissue and granulation tissue gap. HBO did not significantly affect the rate of healing in this model. Subsequent studies have shown that the VAC enhances wound bed preparation for subsequent wound closure by grafting, flap formation, tissue transfer or delayed closure techniques in difficult clinical situations including sternal dehiscences14, and wounds with exposed bone15. It has also been successfully applied to secure skin grafts to difficult recipient beds16. No significant negative side effects have been identified, and more rapid healing times were demonstrated in a small study that randomized patients to VAC versus saline gauze dressings17. Nevertheless, a recent consensus report18 on the use of the VAC has cautioned that properly conducted randomized clinical studies to compare the VAC to either conventional therapy or other adjuncts to wound healing have been limited and further studies should be under taken to define its 468
use and to determine the financial implications of more widespread application of this device. Wet Wound Healing The wet wound healing chamber represents a simple device that bridges the gap between the laboratory where it was developed and the clinic. The chamber delivers antibiotics directly into the wound, achieving very high concentration levels of the antibiotic (between 1,000 and 10,000 times the MIC), resulting in rapid clearance of infection without associated systemic toxicities. Fortyeight hours after antibiotic application, 20% or more of the original antibiotic concentration was present in the chamber. In addition to the benefits of decreased scarring, faster healing times, and adequate analgesia, DNA constructs with inserted growth factors can be administered to the wound by injection with ease and controlled with an antibiotic regulator. Transplanted skin cells introduced through the chamber can proliferate, migrate and differentiate into epidermal cells. Thus, despite its simplicity, the wet wound chamber offers the opportunity for tissue engineering and genetic manipulation of the wound. In closing, the mechanical adjuncts healing chronic wounds discussed above have demonstrated efficacy in carefully defined clinical situations and as part of a coordinated approach to wound care that is based on the time-tested principles of wound healing. Clinicians concentrating their efforts in this field should participate in clinical trials that are properly designed to evaluate the role these modalities may play in treating chronic, difficult wounds and to more precisely define those patients who will benefit most from their use. Such trials should also examine the financial implications and cost-benefit ratios of these and other evolving concepts of wound care. doi:10.1016/j.cursur.2004.11.024
REFERENCES 1. Mustoe TA. Understanding chronic wounds: a unifying
hypothesis on their pathogenesis and implications for therapy. Am J Surg 2004;187(5 Suppl):S65-S70. 2. Brem H ed. Clinical wound healing of the diabetic foot.
Am J Surg. 2004;187(5 Suppl):1S-86S. 3. Brem H. Clinical wound healing of pressure ulcers and ve-
nous stasis ulcers. Am J Surg 2004;188(1 Suppl):1S-78S. 4. Gottrup F, Holstein P, Jorgensen B, Lohmann M, Karls-
mar T. A new concept of a multidisciplinary wound healing center and a national expert function of wound healing. Arch Surg. 2001;136:765-772. 5. Niinikoski JHA. Clinical hyperbaric oxygen therapy,
wound perfusion, and transcutaneous oximetry. World J Surg 2004;28:307-311. 6. Davidson JD, Mustoe TA. Oxygen in wound healing: more
than a nutrient. Wound Repair Regen 2001;9:175-177. 7. Grolman RE, Wilkerson DK, Taylor J, Allinson P, Zatina
CURRENT SURGERY • Volume 62/Number 5 • September/October 2005
MA. Transcutaneous oxygen measurements predict beneficial response to hyperbaric oxygen therapy in patients with non-healing wounds and critical ischemia. Am Surg. 2001;67:1072-1080.
reliable method of securing skin grafts to the difficult recipient bed. Plast Reconstr Surg. 1998;102:1195-1198. 17. McCallon SK, Knight CA, Valiulus JP, Cunningham MW,
Mc Culloch JM, Farinas LP. Vacuum-assisted closure vs. saline-moistened gauze in the healing of postoperative diabetic foot wounds. Ostomy/Wound Management. 2000;46: 28-34.
8. Kranke P, Bennett M, Roeskel-Wiedmann M, Debus S.
Hyperbaric oxygen therapy for chronic wounds (Cochrane Review) In: The Cochrane Library, Issue2, 2004. Oxford: Updated Feb 24, 2004.
18. Sibbald RG, Mahoney J, and the VAC Therapy Canadian
Consensus Group. A consensus report on the use of vacuum-assisted closure in chronic difficult to heal wounds. Ostomy/Wound Management. 2003;49:52-66.
9. Chamber Directory; Undersea and Hyperbaric Medicine
Society Available from: http://www.uhms.org/Chambers/CHAMBER DIRECTORY2.asp. Accessed on August 12, 2004 10. Hyperbaric Oxygen Therapy: Its use and appropriateness.
Dallas(TX) Dept of Health and Human Services (US) . Office of the Inspector General; 2000 Oct. Available from URL : http://www.uhms.org/Legislation/ OIG Report on HBO 10-00.pdf 2000. Accessed on August 12, 2004
QUESTIONS AND ANSWERS Questions 1. Chronic wounds are characterized by all of the following except: a. b. c. d. e.
11. Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt
W. Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997;38:553-562. 12. Yager DR, Nwomeh BC. The proteolytic environment of
chronic wounds. Wound Rep Regen. 1999;7:433-441. 13. Fabian TS, Kaufman HJ, Lett ED, Thomas JB, Rawl DK,
Lewis PL et al. The evaluation of subatmospheric pressure and hyperbaric oxygen in ischemic full-thickness wound healing. Am Surg. 2000;55:1136-1143.
2. T or F: Positive response of low baseline tcPO2 values to oxygen inhalation in diabetic patients with foot ulcers and non-reconstructable arterial occlusive disease is a poor predictor of positive response to hyperbaric oxygen therapy. 3. Positive effects of sub-atmospheric pressure on wound healing include: a. removal of edema fluid. b. increased rate of granulation tissue formation. c. removal of inhibitors of wound healing such as matrix metalloproteases. d. enhanced bacterial clearance. e. all of the above.
14. Hersh RE, Jack JM, Dahman MI, Morgan F, Drake DB.
The vacuum-assisted closure device as a bridge to sternal wound closure. Ann Plast Surg. 2001;46:250-254. 15. DeFronzo AJ, Argenta LC, Marks MW, Molnar JA, David
LR, Webb LX, et al. The use of vacuum-assisted closure therapy for the treatment of lower- extremity wounds with exposed bone. Plast Reconstr Surg. 2001;108:1184-1191. 16. Schneider AM, Morykwas MJ, Argenta LC. A new and
altered gene expression. expression of inflammatory cytokines. shortened cellular doubling time. bacterial colonization. replicative senescence.
Answers 1. c 2. F 3. e
Neurosurgery Peripheral Nerve Injury Evaluation and Management Guest Reviewer: Christopher J. Winfree, MD, Department of Neurological Surgery, Columbia University Medical Center, New York, New York BRACHIAL PLEXUS INJURY: A SURVEY OF 100 CONSECUTIVE CASES FROM A SINGLE SERVICE. Dubuisson AS, Kline DG. Neurosurgery. 2002;51:673-683.
Objective: To investigate the evaluation, management, and outcome of a large series of patients with brachial plexus injuries.
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469
hyperbaric oxygen (HBO) to conventional therapy of chronic foot wounds in diabetics. Endpoints included ulcer healing and need for amputation after a three-year follow-up period. Setting: Division of Emergency Medicine, Department of En-
docrinology and Diabetology, Division of Hyperbaric Medicine, Department of Anesthesiology and Intensive Care at Karolinska Hospital in Stockholm, Sweden. Participants: Thirty-eight diabetic patients with superficial chronic foot ulcers not eligible for vascular reconstruction with local tissue anoxia determined by transcutaneous oxygen tension (tcPO2) ⬍ 40 mmHg that increased significantly with the inhalation of pure oxygen. Seventeen patients were assigned to HBO and 21 patients to conventional treatment.
Results: Of the 38 patients evaluated, 76% (13/17) in the
HBO treatment group healed their ulcers with intact skin, 12% (2/17) had below knee amputations and another two patients (12%) died during treatment. In the conventional treatment group, 48% (10/21) healed their ulcers, 33% (7/21) underwent below knee amputations and 3 patients died. The mean healing time of 15 months was not statistically or clinically different between groups. In a comparison of 9 patients who underwent amputation with the 23 who were alive and healed at the 3 year follow-up, no significant difference in the baseline tcPO2 and toe blood pressure measurements were noted while the mean tcPO2 value during oxygen inhalation was significantly higher (p ⬍ 0.03) in those patients that healed (234 ⫾ 110 mmHg) compared to those who were amputated (142 ⫾ 65 mmHg). Complications of HBO therapy included one patient who developed cataracts and another patient who had ear pain, which was treated with decongestants. Conclusions: Hyperbaric oxygen therapy can be a valuable adjunct to chronic foot ulcer treatment in selected diabetic patients. The authors stated that it seemed to accelerate the rate of healing, reduce the need for amputation and increase the number of wounds that were healed during long-term followup. Further studies are needed to further define the role of HBO as part of a multidisciplinary program to preserve a functional extremity in diabetic patients with chronic foot ulcers.
REVIEWER COMMENTS
This study, one of a few that attempts to randomize patients to HBO vs. conventional therapy, illustrates many of the difficulties associated with the conduct of such trials. The authors state that the first 14 patients were randomized and then accrual of patients was stopped for 2 years due to lack of availability of HBO, after which the remaining patients were added in non-randomized fashion. This resulted in the introduction of confounding variables, such as a significantly younger population in the HBO group, and made proper statistical analysis problematic. While the authors report a
decreased rate of amputation in the HBO group, when we analyzed this data by Fisher’s exact test the difference between groups did not reach statistical significance at the customary p ⬍ 0.05. Perhaps the small patient population (n ⫽ 37), a consequence of the well-defined inclusion criteria for this study, increased the likelihood of a beta-error. Furthermore, while the authors state in their conclusions that HBO seemed to accelerate the rate of healing, their results clearly indicate that the rate of healing was the same for both groups.
VACUUM ASSISTED CLOSURE: A NEW METHOD FOR WOUND CONTROL AND TREATMENT; CLINICAL EXPERIENCE.
Objective: To investigate the application of subatmo-
Argenta LC, Morykwas MJ. Ann Plast Surg. 1997:38:563-577.
spheric pressure by a vacuum-assisted closure device (VAC) in the treatment of a wide variety of acute, subacute and chronic wounds.
CURRENT SURGERY • Volume 62/Number 5 • September/October 2005
465
Design: Prospective evaluation of a non-randomized consecutive clinical series. Setting: Department of Plastic and Reconstructive Surgery,
Bowman Gray School of Medicine, Winston-Salem, NC. Participants: The first 300 patients treated with the VAC
were grouped as follows: (1) chronic wounds open for ⬎ 7 days with no progress toward healing (pressure sores, diabetic and stasis ulcers; N ⫽ 175); (2) subacute wounds open for ⬍ 7days but greater than 12 hours (infected and dehisced wounds, avulsions and open amputations; N ⫽ 94); and (3) acute wounds open ⬍12 hours (acute avulsions, evacuated hematomas, eviscerations etc; N ⫽ 31).
Results: Two hundred ninety-six patients in the study population responded favorably to VAC therapy. Of the chronic
wounds, 171 of 175 wounds showed favorable outcomes with 32% healed completely, and 61 % healed with the aid of flaps and grafts. The only treatment failures were noted in patients who died of other causes during the study. In the subacute category, 28% (26/94) healed completely while the remaining 68 wounds granulated and contracted to smaller wounds easily controlled with skin grafts, secondary closure or minor flaps. With the exception of 1 patient who died of pulmonary embolism, all patients in the acute group healed. Complications included transient pain with the institution of negative pressure, minor bleeding from in-growth into the sponge and one enteric fistula. Conclusions: The VAC is an effective mechanical adjunct for the treatment of chronic and difficult wounds.
REVIEWER COMMENTS
This seminal report introduced the modality of subatmospheric pressure as a mechanical adjunct in the treatment of chronic and difficult wounds. The authors presented a robust series of 300 patients with wounds of compromised primary healing potential and stratified them based on the chronicity of their wounds. While a randomized prospective design would have better delineated the effects of the VAC on the restoration of these defects, the authors point out that as many as 34 independent variables may have influenced wound healing in these individuals and would have required an extraordinary number of participants to be randomized into multiple treatment arms.
The strength of this observational study lies in the complete follow up of all patients to the point of wound closure or death. Furthermore, the authors emphasized that all patients were treated with conventional principles of wound care including debridement, infection control and tissue transfer with grafts or flaps with the VAC used as an adjunct to their treatment. Their study established the VAC as a technology that may be safely and effectively applied by properly trained health care professionals to patients in the hospital as well as ambulatory setting and motivated other investigators to evaluate its use in a variety of clinical situations.
WET WOUND HEALING.
wounds that did not heal, one healed after additional chamber treatment, one had a skin graft that did not take, and one required reamputation at a higher level. Antibiotic delivery through the device was less than one intravenous dose daily, yet
Vranckx J, Slama J, Preuss S, et al. Plast Reconstr Surg. 2000;110:1680-1687. Objective: To evaluate the clinical application of a flexible
transparent wound healing chamber in patients with chronic wounds. Design: Prospective study of chronic wounds treated with a
wound chamber containing saline and antibiotics (Fig. 1). Setting: Laboratory of Tissue Repair and Gene Transfer, De-
partment of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Boston, MA. Participants: A total of 28 wounds in 20 consecutive pa-
tients were treated with the wet wound chamber technique. Most wounds were chronically infected, represented multiple etiologies and had not responded to debridement or flap closure. Results: Twenty-five of the wounds (89%) healed and 5
wounds (18%) required additional conservative management after initial chamber treatment and grafting procedures. Of 3 466
FIGURE 1. Schematic drawing of a wound chamber prototype. Reprinted with permission from Elsevier Science. From Ericksson E, Vranckx J. Wet wound healing: from laboratory to patients to gene therapy. Am J Surg. 2004;188(Suppl 1):37S.
CURRENT SURGERY • Volume 62/Number 5 • September/October 2005
allowed concentrations of up to 10,000 times the minimal inhibitory concentration. Conclusions: Wet wound therapy is an effective and safe way of treating chronic wounds complicated by infection. The wet
wound chamber had no adverse effects on normal skin, reduced pain with direct administration of analgesics, promoted faster healing, produced less scarring, and facilitated delivery of any desired solution or pharmacologic agent.
REVIEWER COMMENTS
The authors described a new device called a “wet wound chamber” developed from laboratory experience with in-vivo tissue culture techniques designed to facilitate wound healing and tissue engineering. The round, flexible, transparent chamber provided a constant wet milieu in the treated wound that increased patient comfort through less physical wound manipu-
lation, and allowed access to the wound without compromising the surrounding normal tissue. The series was well documented in terms of the types of wounds included, their bacteriology and antibiotic susceptibility, and the surgical techniques employed. Complete follow-up was obtained on all patients entered into the series, further enhancing the conclusions of the study.
REVIEWER SUMMARY
Since antiquity, a working knowledge of wound healing has been an essential component of the surgeon’s armamentarium. Until recently, principles of wound treatment were derived empirically and were based on a rudimentary understanding of the biology of tissue repair. While the basic tenets of wound care including proper nutrition, gentle handling of tissues, maintenance of adequate blood supply, avoidance of tension, appropriate use of debridement and control of infection are sufficient to promote successful healing of the majority of wounds encountered in contemporary surgical practice, mechanical and pharmacological adjuncts to healing chronic wounds in disadvantaged hosts are actively being studied. Over the last two decades, advances in cell biology have elucidated details of systemic and molecular responses to tissue injury and produced a theoretical foundation for the pathogenesis of chronic wounds1. First, cellular and systemic changes of aging lead to altered gene expression resulting in decreased proliferative capacity, prolonged doubling times and eventual replicative senescence in tissue culture studies of aging cells. Second, cellular events associated with the cycle of ischemia-reperfusion, particularly the expression of inflammatory cytokines and release of destructive free radicals, impede progression of the normal stages of wound healing. Lastly, chronic wounds are frequently colonized by bacteria that produce a persistent inflammatory response. These concepts along with other detailed information about the etiologies and treatment of recalcitrant wounds are presented in two recent comprehensive journal supplements2,3 which deserve careful reading by all surgeons interested in acquiring more than a superficial knowledge of tissue repair and regeneration. The most challenging wounds – chronic diabetic and venous ulcers as well as pressure sores – often frustrate the individual physician and tax the resources of the health care delivery system. As a consequence, a multi-disciplinary specialty of wound care is emerging through the collaboration of basic scientists, general, plastic and vascular surgeons, podiatrists and nurse clinicians. These practitioners and their institutions often establish wound care centers4as repositories of the human and physical resources needed to advance knowledge in this area and provide comprehen-
sive treatment of these difficult clinical problems. In the ideal situation, such facilities offer patients cost effective application of the fundamental principles of wound care while functioning as stewards of more expensive resources such as hyperbaric chambers. As this review has demonstrated however, more data must be properly collected and analyzed to match specific modalities with deficiencies in the healing mechanism since, to paraphrase our sixteenth president, we still only “heal some of the wounds some of the time, but not all of the wounds all of the time.” The greatest challenge remains to translate advances made in the laboratory, where the large number of potential confounding variables involved in wound healing may be appropriately stratified or controlled, to the clinical setting where it is more difficult to isolate the effect of the treatment being studied. It is appropriate to critically discuss the interface between the basic science foundations and clinical applications of the mechanical adjuncts to wound healing presented above. Hyperbaric Oxygen The presence of at least some degree of tissue anoxia is well established in the pathogenesis of chronic wounds and provides a rational scientific basis for the use of hyperbaric oxygen (HBO) therapy to reverse an ischemic wound environment. In fact, HBO has been shown to do this in experimental and clinical studies5. Perhaps more intriguing are the recent observations6 that hyperoxia positively influences many of the cellular responses to tissue injury, acting as an intracellular signal transduction agent, and a modulator of gene function leading to increased production of platelet derived growth factor receptor proteins in ischemic tissues. The relevance of these experimental observations to the biochemical details of indolent human wounds will require more intensive investigation. Several studies5,7 measuring local tissue anoxia based on tcPO2 have defined the patients who will most benefit from HBO. When these parameters are applied as inclusion and exclusion criteria for clinical trials of HBO, patient accrual is limited. For example, in the study of HBO reviewed above, only 38 patients were enrolled from a possible 1.2 million inhabitants of Stockholm. In addition,
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this small number of patients was not properly randomized to control and treatment groups, precluding valid statistical analysis. Based upon this investigation, as well as the most recent Cochrane Review8 of hyperbaric oxygen therapy for chronic wounds, the benefit of HBO is limited to a trend toward fewer amputations in highly selected groups of diabetic patients treated with this modality. Furthermore, effectiveness for chronic venous or arterial ulcers, pressure sores or the majority of diabetic ulcers without documented tissue hypoxia has not been demonstrated. Despite the well-defined criteria which limit the number of patients who may benefit form HBO, these facilities continue to proliferate with 458 chambers located in North America that are currently registered with the Hyperbaric and Undersea Medicine Society9. These centers recently (2000) generated $49.9 million of charges to Medicare alone, with almost 32% of these charges found to be paid in error for uncovered or inadequately documented conditions10. Unfortunately, from a practical economic point of view, the need to amortize the significant capital outlays for the establishment of these centers makes the reporting of negative outcomes of studies of HBO less likely. Vacuum-assisted Closure (VAC) In a companion paper to the clinical study reviewed above11, the authors presented experimental animal studies that demonstrated positive effects of subatmospheric pressure on wound blood flow, rate of granulation tissue formation, and clearance of bacteria from infected wounds. The VAC is thought to produce these effects primarily through the removal of edema fluid, a process that simultaneously changes the physical characteristics of the wound by increasing tissue pliability. It also potentially enhances the metabolic microenvironment for wound healing by reducing the concentrations of matrix metalloproteases and other inhibitors of the normal cellular processes of tissue repair often found in chronic wounds12. In additional experimental studies Fabian et al.13compared the effects of the (VAC) and hyperbaric oxygen therapy (HBO) alone and in combination in a standardized ischemic wounds model. The VAC dressing to suction and VAC dressing alone both with and without the use of HBO produced a statistically significant increase for peak granulation tissue and granulation tissue gap. HBO did not significantly affect the rate of healing in this model. Subsequent studies have shown that the VAC enhances wound bed preparation for subsequent wound closure by grafting, flap formation, tissue transfer or delayed closure techniques in difficult clinical situations including sternal dehiscences14, and wounds with exposed bone15. It has also been successfully applied to secure skin grafts to difficult recipient beds16. No significant negative side effects have been identified, and more rapid healing times were demonstrated in a small study that randomized patients to VAC versus saline gauze dressings17. Nevertheless, a recent consensus report18 on the use of the VAC has cautioned that properly conducted randomized clinical studies to compare the VAC to either conventional therapy or other adjuncts to wound healing have been limited and further studies should be under taken to define its 468
use and to determine the financial implications of more widespread application of this device. Wet Wound Healing The wet wound healing chamber represents a simple device that bridges the gap between the laboratory where it was developed and the clinic. The chamber delivers antibiotics directly into the wound, achieving very high concentration levels of the antibiotic (between 1,000 and 10,000 times the MIC), resulting in rapid clearance of infection without associated systemic toxicities. Fortyeight hours after antibiotic application, 20% or more of the original antibiotic concentration was present in the chamber. In addition to the benefits of decreased scarring, faster healing times, and adequate analgesia, DNA constructs with inserted growth factors can be administered to the wound by injection with ease and controlled with an antibiotic regulator. Transplanted skin cells introduced through the chamber can proliferate, migrate and differentiate into epidermal cells. Thus, despite its simplicity, the wet wound chamber offers the opportunity for tissue engineering and genetic manipulation of the wound. In closing, the mechanical adjuncts healing chronic wounds discussed above have demonstrated efficacy in carefully defined clinical situations and as part of a coordinated approach to wound care that is based on the time-tested principles of wound healing. Clinicians concentrating their efforts in this field should participate in clinical trials that are properly designed to evaluate the role these modalities may play in treating chronic, difficult wounds and to more precisely define those patients who will benefit most from their use. Such trials should also examine the financial implications and cost-benefit ratios of these and other evolving concepts of wound care. doi:10.1016/j.cursur.2004.11.024
REFERENCES 1. Mustoe TA. Understanding chronic wounds: a unifying
hypothesis on their pathogenesis and implications for therapy. Am J Surg 2004;187(5 Suppl):S65-S70. 2. Brem H ed. Clinical wound healing of the diabetic foot.
Am J Surg. 2004;187(5 Suppl):1S-86S. 3. Brem H. Clinical wound healing of pressure ulcers and ve-
nous stasis ulcers. Am J Surg 2004;188(1 Suppl):1S-78S. 4. Gottrup F, Holstein P, Jorgensen B, Lohmann M, Karls-
mar T. A new concept of a multidisciplinary wound healing center and a national expert function of wound healing. Arch Surg. 2001;136:765-772. 5. Niinikoski JHA. Clinical hyperbaric oxygen therapy,
wound perfusion, and transcutaneous oximetry. World J Surg 2004;28:307-311. 6. Davidson JD, Mustoe TA. Oxygen in wound healing: more
than a nutrient. Wound Repair Regen 2001;9:175-177. 7. Grolman RE, Wilkerson DK, Taylor J, Allinson P, Zatina
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MA. Transcutaneous oxygen measurements predict beneficial response to hyperbaric oxygen therapy in patients with non-healing wounds and critical ischemia. Am Surg. 2001;67:1072-1080.
reliable method of securing skin grafts to the difficult recipient bed. Plast Reconstr Surg. 1998;102:1195-1198. 17. McCallon SK, Knight CA, Valiulus JP, Cunningham MW,
Mc Culloch JM, Farinas LP. Vacuum-assisted closure vs. saline-moistened gauze in the healing of postoperative diabetic foot wounds. Ostomy/Wound Management. 2000;46: 28-34.
8. Kranke P, Bennett M, Roeskel-Wiedmann M, Debus S.
Hyperbaric oxygen therapy for chronic wounds (Cochrane Review) In: The Cochrane Library, Issue2, 2004. Oxford: Updated Feb 24, 2004.
18. Sibbald RG, Mahoney J, and the VAC Therapy Canadian
Consensus Group. A consensus report on the use of vacuum-assisted closure in chronic difficult to heal wounds. Ostomy/Wound Management. 2003;49:52-66.
9. Chamber Directory; Undersea and Hyperbaric Medicine
Society Available from: http://www.uhms.org/Chambers/CHAMBER DIRECTORY2.asp. Accessed on August 12, 2004 10. Hyperbaric Oxygen Therapy: Its use and appropriateness.
Dallas(TX) Dept of Health and Human Services (US) . Office of the Inspector General; 2000 Oct. Available from URL : http://www.uhms.org/Legislation/ OIG Report on HBO 10-00.pdf 2000. Accessed on August 12, 2004
QUESTIONS AND ANSWERS Questions 1. Chronic wounds are characterized by all of the following except: a. b. c. d. e.
11. Morykwas MJ, Argenta LC, Shelton-Brown EI, McGuirt
W. Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997;38:553-562. 12. Yager DR, Nwomeh BC. The proteolytic environment of
chronic wounds. Wound Rep Regen. 1999;7:433-441. 13. Fabian TS, Kaufman HJ, Lett ED, Thomas JB, Rawl DK,
Lewis PL et al. The evaluation of subatmospheric pressure and hyperbaric oxygen in ischemic full-thickness wound healing. Am Surg. 2000;55:1136-1143.
2. T or F: Positive response of low baseline tcPO2 values to oxygen inhalation in diabetic patients with foot ulcers and non-reconstructable arterial occlusive disease is a poor predictor of positive response to hyperbaric oxygen therapy. 3. Positive effects of sub-atmospheric pressure on wound healing include: a. removal of edema fluid. b. increased rate of granulation tissue formation. c. removal of inhibitors of wound healing such as matrix metalloproteases. d. enhanced bacterial clearance. e. all of the above.
14. Hersh RE, Jack JM, Dahman MI, Morgan F, Drake DB.
The vacuum-assisted closure device as a bridge to sternal wound closure. Ann Plast Surg. 2001;46:250-254. 15. DeFronzo AJ, Argenta LC, Marks MW, Molnar JA, David
LR, Webb LX, et al. The use of vacuum-assisted closure therapy for the treatment of lower- extremity wounds with exposed bone. Plast Reconstr Surg. 2001;108:1184-1191. 16. Schneider AM, Morykwas MJ, Argenta LC. A new and
altered gene expression. expression of inflammatory cytokines. shortened cellular doubling time. bacterial colonization. replicative senescence.
Answers 1. c 2. F 3. e
Neurosurgery Peripheral Nerve Injury Evaluation and Management Guest Reviewer: Christopher J. Winfree, MD, Department of Neurological Surgery, Columbia University Medical Center, New York, New York BRACHIAL PLEXUS INJURY: A SURVEY OF 100 CONSECUTIVE CASES FROM A SINGLE SERVICE. Dubuisson AS, Kline DG. Neurosurgery. 2002;51:673-683.
Objective: To investigate the evaluation, management, and outcome of a large series of patients with brachial plexus injuries.
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