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Hyperthermia following the application of porcine xenograft
Burns, 3, 119-l 22
119
Printed in Greet Britain
Hyperthermia following the application of porcine xenograft Donald H. Parks, Philip D. Thomson and Duane L. Larson University of Texas Medical Branch and Shriners Burns Institute, Divisions of Surgery and Microbiology, Galveston, Texas PORCINE xenograft has gained widespread popularity (Artz, 1976) since Bromberg (Bromberg et al., 1965) reported on its use as a temporary biological dressing. Modern bum treatment in particular has been influenced by the availability and beneficial properties of porcine xenograft. These benefits have been reported by several authors (Mahler and Hirshowitz, 1975; Reichenbather, 1975; Shuck, 1975) to include: 1. Temporary biological cover in case of autograft shortage. 2. Prevention and reduction of infection. 3. Prevention of loss of fluid, protein, electrolyte and energy from the bum surface. 4. Promotion of the growth of granulation tissue. 5. Reduction of local pain and acceleration of healing in second-degree burns. 6. Testing a surfacefor future takeof autograft. This popularity has generated prolific commercial production of porcine skin (Shuck 1974) as well as ‘home-made ’ production in some centres. The literature concerning porcine xenograft provides very little information on the possible complications of its use. Recent cases in our institute, in which three children have experienced dramatic temperature elevation immediately following xenografting with commercial xenograft, have prompted us to speculate on the possible causes of this hyperthermia and to consider the safety in using commercial porcine graft material.
CASE
REPORTS
Case 1. A. S., a 13-year-old white male, was admitted with a 22 per cent total body area (TBA) gasoline bum to the
lower extremities. Twenty-one days post bum, commercial frozen-irradiated porcine xenograft was applied to debrided wounds under ketamine anaesthesia. During the procedure, 600 ml of whole blood were given. His temperature did not exceed 100 “F and his wound cultures were negative prior to grafting. Six hours postoperatively his temperature reached 104”F, at which time no clinical evidence for an elevated temperature could be found. At this time all of his xenograft was removed. Twenty minutes later his temperature dropped to 102°F and within one hour he had reached his preoperative temperature (Fig. 1). His subsequent course was uncomplicated and he was autografted and discharged 45 days post bum. Case 2. E. N., a IO-year-old white male, was admitted with a 30 per cent TBA electrical contact and flash bum to the face, anterior neck and upper extremities. Two days post bum, commercial frozen-irradiated porcine xenograft was applied to tangentially excised wounds under ketamine anaesthesia. He received 150ml of whole blood during the procedure. His temperature was 1014 “F and his wound cultures showed Stquhylococcus aureus on his neck and alpha streptococci on his hand prior to grafting. Three hours postoperatively his temperature rose to 105.4 “F and no clinical source for the raised temperature could be found, so the xenograft was immediately removed. Three hours after xenograft removal his temperature fell to 100.8 “F (Fig. 2). He went on to an uneventful recovery and was discharged 32 days post burn. Case 3. K. W., a 13-year-old black male, was admitted with a 34 per cent TBA flame bum to the face and upper and lower extremities. Twenty-two days post burn, commercial frozen-irradiated xenagraft was applied to dkbrided wounds under ketamine anaesthesia. He received 900 ml of whole blood during the procedure. His temperature was 98.6”F and his cultures were
120
Burns Vol. ~/NO.
Fig. 1. Temperature
chart of patient A. S. showing fever spike of 104 “F. The inset in the upper left shows the temperature profile 7 days before and after the fever spike. The time of xenograft application and removal are indicated with the dark arrows.
101
ia 99.6
Fig. 2. Temperature chart of patient E. N. showing fever spike of 1054 “F. The inset in the upper left shows the temperature profile from admission to 8 days after the fever spike. The time of xenograft application and removal are indicated by the dark arrows.
2
121
Parks et al. : Hyperthermia Following Xenograff
a.m.
Fig. 3. Temperature chart of patient K. W. showing fever spike of 105 “F. The inset in the upper left shows the temperature profile from 7 days before to 8 days after the fever spike. The time of xenograft application and removal are indicated by the dark arrows. negative prior to grafting. Eight hours postoperatively his temperature rose to 105 “F and all xenograft was removed as no obvious clinical source for the raised temperature could be found. Two hours after xenograft removal, his temperature fell to 100~6°F (Fig. 3). He went on to an uneventful recovery and was discharged 58 days post burn.
DISCUSSION The acute febrile episodes seen in the above three cases had no obvious clinical basis. Similar surgical procedures under ketamine anaesthesia in 100 children with burns ranging from 4 to 90 per cent TBA have not demonstrated this febrile phenomenon. The onset of fever with the application of the xenograft and its rapid resolution with xenograft removal suggests that porcine xenograft may harbour pyrogenic material. Commercial porcine xenograft is available in four forms: fresh, fresh-frozen, frozen-irradiated and lyophilized. Certain preservatives used in processing of porcine xenograft may produce toxic effects (Sugarbaker et al., 1974). Any of the four forms can be contaminated with either live or dead bacteria, bacterial cell walls (endotoxin) or other pyrogenic materials such as viruses. These contaminants can be introduced
Fig. 4. Fractured porcine xenograft received from the manufacturer.
package
as
through technical error in processing or faulty packaging and storage (Fig. 4). Microbiological examination of random lots of allegedly sterile, frozen-irradiated xenograft used in our institute have revealed pure cultures of Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Escherichia coli, Enterobutter cloacae and diphtheroids. Contaminated
122
Burns Vol. ~/NO. 2
xenograft is not unique to our institute, as personal cotnmunlcations with other units has indicated. Unexplained rises in temperature after xenografting may be directly related to the xenograft, and at the onset of the fever the xenograft should be removed. It is our belief that all xenograft material should be checked for packaging flaws upon delivery to the hospital and monitored for bacterial content prior to its application. The manufacturer’s quality control of xenograft material may be inadequate in many cases and poses a threat to the graft recipient. The possible introduction of new flora directly on to the burn wound poses a potential hazard for the immunologically compromised burned patient. Xenograft as a source of free endotoxin and other toxic materials must be considered.
Harris for their invaluable production of this paper.
assistance
in the
REFERENCES Artz C. P. (1976) Burns updated. J. Trauma 16, 3. Bromberg B. E., Song J. C. and Mohn M. P. (1965) The use of pig skin as a temporary biologic dressing. Ph.
Reconstr. Surg. 36,80.
Mahler D. and Hirshowitz B. (1975) The use of xenografts in the treatment of bums. Burns 2,44. Reichenbacher F. W. (1975) Use of norcine skin in burn treatment. A.O.‘R.N.*21,652. Shuck J. M. (1974) Preparing and closing the burn wound. In: Moncrief J. (ed.) Clinics in Plastic Surgery. Philadelphia, Saunders, p. 582. Shuck J. M. (1975) The use of heteroplastic grafts. Burns 2,47. Sugarbaker P. H., Sabath L. D. and Morgan A. P. (1974) Neomycin toxicity from porcine skin xenografts. Ann. Surg. 179, 183.
Acknowledgements We wish to thank Mr Wade Berlin and Dr N. S.
Reqursts
for reprints
should be addressedto: Donald H. Forks, MD, Shrinem Burnt Institute. Galveston Unit, 610 Texas Avenue.
Galveston, Texas 77550, USA.
119
Printed in Greet Britain
Hyperthermia following the application of porcine xenograft Donald H. Parks, Philip D. Thomson and Duane L. Larson University of Texas Medical Branch and Shriners Burns Institute, Divisions of Surgery and Microbiology, Galveston, Texas PORCINE xenograft has gained widespread popularity (Artz, 1976) since Bromberg (Bromberg et al., 1965) reported on its use as a temporary biological dressing. Modern bum treatment in particular has been influenced by the availability and beneficial properties of porcine xenograft. These benefits have been reported by several authors (Mahler and Hirshowitz, 1975; Reichenbather, 1975; Shuck, 1975) to include: 1. Temporary biological cover in case of autograft shortage. 2. Prevention and reduction of infection. 3. Prevention of loss of fluid, protein, electrolyte and energy from the bum surface. 4. Promotion of the growth of granulation tissue. 5. Reduction of local pain and acceleration of healing in second-degree burns. 6. Testing a surfacefor future takeof autograft. This popularity has generated prolific commercial production of porcine skin (Shuck 1974) as well as ‘home-made ’ production in some centres. The literature concerning porcine xenograft provides very little information on the possible complications of its use. Recent cases in our institute, in which three children have experienced dramatic temperature elevation immediately following xenografting with commercial xenograft, have prompted us to speculate on the possible causes of this hyperthermia and to consider the safety in using commercial porcine graft material.
CASE
REPORTS
Case 1. A. S., a 13-year-old white male, was admitted with a 22 per cent total body area (TBA) gasoline bum to the
lower extremities. Twenty-one days post bum, commercial frozen-irradiated porcine xenograft was applied to debrided wounds under ketamine anaesthesia. During the procedure, 600 ml of whole blood were given. His temperature did not exceed 100 “F and his wound cultures were negative prior to grafting. Six hours postoperatively his temperature reached 104”F, at which time no clinical evidence for an elevated temperature could be found. At this time all of his xenograft was removed. Twenty minutes later his temperature dropped to 102°F and within one hour he had reached his preoperative temperature (Fig. 1). His subsequent course was uncomplicated and he was autografted and discharged 45 days post bum. Case 2. E. N., a IO-year-old white male, was admitted with a 30 per cent TBA electrical contact and flash bum to the face, anterior neck and upper extremities. Two days post bum, commercial frozen-irradiated porcine xenograft was applied to tangentially excised wounds under ketamine anaesthesia. He received 150ml of whole blood during the procedure. His temperature was 1014 “F and his wound cultures showed Stquhylococcus aureus on his neck and alpha streptococci on his hand prior to grafting. Three hours postoperatively his temperature rose to 105.4 “F and no clinical source for the raised temperature could be found, so the xenograft was immediately removed. Three hours after xenograft removal his temperature fell to 100.8 “F (Fig. 2). He went on to an uneventful recovery and was discharged 32 days post burn. Case 3. K. W., a 13-year-old black male, was admitted with a 34 per cent TBA flame bum to the face and upper and lower extremities. Twenty-two days post burn, commercial frozen-irradiated xenagraft was applied to dkbrided wounds under ketamine anaesthesia. He received 900 ml of whole blood during the procedure. His temperature was 98.6”F and his cultures were
120
Burns Vol. ~/NO.
Fig. 1. Temperature
chart of patient A. S. showing fever spike of 104 “F. The inset in the upper left shows the temperature profile 7 days before and after the fever spike. The time of xenograft application and removal are indicated with the dark arrows.
101
ia 99.6
Fig. 2. Temperature chart of patient E. N. showing fever spike of 1054 “F. The inset in the upper left shows the temperature profile from admission to 8 days after the fever spike. The time of xenograft application and removal are indicated by the dark arrows.
2
121
Parks et al. : Hyperthermia Following Xenograff
a.m.
Fig. 3. Temperature chart of patient K. W. showing fever spike of 105 “F. The inset in the upper left shows the temperature profile from 7 days before to 8 days after the fever spike. The time of xenograft application and removal are indicated by the dark arrows. negative prior to grafting. Eight hours postoperatively his temperature rose to 105 “F and all xenograft was removed as no obvious clinical source for the raised temperature could be found. Two hours after xenograft removal, his temperature fell to 100~6°F (Fig. 3). He went on to an uneventful recovery and was discharged 58 days post burn.
DISCUSSION The acute febrile episodes seen in the above three cases had no obvious clinical basis. Similar surgical procedures under ketamine anaesthesia in 100 children with burns ranging from 4 to 90 per cent TBA have not demonstrated this febrile phenomenon. The onset of fever with the application of the xenograft and its rapid resolution with xenograft removal suggests that porcine xenograft may harbour pyrogenic material. Commercial porcine xenograft is available in four forms: fresh, fresh-frozen, frozen-irradiated and lyophilized. Certain preservatives used in processing of porcine xenograft may produce toxic effects (Sugarbaker et al., 1974). Any of the four forms can be contaminated with either live or dead bacteria, bacterial cell walls (endotoxin) or other pyrogenic materials such as viruses. These contaminants can be introduced
Fig. 4. Fractured porcine xenograft received from the manufacturer.
package
as
through technical error in processing or faulty packaging and storage (Fig. 4). Microbiological examination of random lots of allegedly sterile, frozen-irradiated xenograft used in our institute have revealed pure cultures of Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Escherichia coli, Enterobutter cloacae and diphtheroids. Contaminated
122
Burns Vol. ~/NO. 2
xenograft is not unique to our institute, as personal cotnmunlcations with other units has indicated. Unexplained rises in temperature after xenografting may be directly related to the xenograft, and at the onset of the fever the xenograft should be removed. It is our belief that all xenograft material should be checked for packaging flaws upon delivery to the hospital and monitored for bacterial content prior to its application. The manufacturer’s quality control of xenograft material may be inadequate in many cases and poses a threat to the graft recipient. The possible introduction of new flora directly on to the burn wound poses a potential hazard for the immunologically compromised burned patient. Xenograft as a source of free endotoxin and other toxic materials must be considered.
Harris for their invaluable production of this paper.
assistance
in the
REFERENCES Artz C. P. (1976) Burns updated. J. Trauma 16, 3. Bromberg B. E., Song J. C. and Mohn M. P. (1965) The use of pig skin as a temporary biologic dressing. Ph.
Reconstr. Surg. 36,80.
Mahler D. and Hirshowitz B. (1975) The use of xenografts in the treatment of bums. Burns 2,44. Reichenbacher F. W. (1975) Use of norcine skin in burn treatment. A.O.‘R.N.*21,652. Shuck J. M. (1974) Preparing and closing the burn wound. In: Moncrief J. (ed.) Clinics in Plastic Surgery. Philadelphia, Saunders, p. 582. Shuck J. M. (1975) The use of heteroplastic grafts. Burns 2,47. Sugarbaker P. H., Sabath L. D. and Morgan A. P. (1974) Neomycin toxicity from porcine skin xenografts. Ann. Surg. 179, 183.
Acknowledgements We wish to thank Mr Wade Berlin and Dr N. S.
Reqursts
for reprints
should be addressedto: Donald H. Forks, MD, Shrinem Burnt Institute. Galveston Unit, 610 Texas Avenue.
Galveston, Texas 77550, USA.