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Topical Burn Agents
Topical Burn Agents The Pharmacists Role in Glntrolling Infection
first, second, and third degree burn are now most often called dermal partial thickness, with no grafting required, or full thickness with grafting required (see page 35).1 Death resulting from burns usually occurs within the first month of treatment. Once the patient has passed this critical point, chances of survival are good . Frequently, the cause of death during this early stage is infection. To prevent and control infection, many topical burn agents have been developed . One of the largest differences in burn management throughout the country is the use of different topical ointments. The efficacy of these agents varies. Silver nitrate, silver sulfadiazine, mafenide acetate, povidone-iodine, Neosporin (a combination product containing neomycin sulfate, polymyxin B sulfate, and bacitracin zinc), cerium nitrate, and gen tamicin are presently used in clinical burn care.
Silver Nitrate
By SONJA GEE Burned patients present a complex problem to the health care team. Depending on the severity of the burn, trea tmen t may involve the .hospital administrator, the nurse, the dietician, the surgeon, and the pharmacist.
Sonja Gee is a fifth-year pharmacy student at Wayne State University, Detroit, MI 48202. The author would like to acknowledge the assistance of James R. Lloyd, MD, clinical assistant professor of surgery at the Wayne State University School of Medicine and director of the burn unit at Children's Hospital of Michigan, Detroit; Elaine Emig, RN, also of the burn unit; and Percy R. McClain Sr., RPh, MS, director of pharmacy at Children's Hospital.
Because the practicing pharmacist is frequently asked to suggest a method of treatment for burns, it is important to know what kinds of therapy are appropriate. To help the pharmacist in making these important decisions, here is an overview of the topical drugs most often used in treating severe burns.
Varying Treatment Methods The treatment of burns varies considerably. Many factors contribute to the seriousness of thermal injury: the extent, depth, and location of the wound, the patient's age, and any past illnesses. Advances in therapeutic techniques have spawned more precise descriptive terminology. The terms
Silver nitrate (0 .5 percent) was one of the original agents used and is still used in some hospitals, including the University of Michigan in Ann Arbor. Silver nitrate (0.5 percent), the concentration most acceptable today, is available as a liquid or cream preparation. The liquid is applied as a soak, through t he bandages. Silver nitrate is effective against most bacteria common to burns e xcept some Enterobacter and Klebsiella. Because fungi are relatively insensitive and can cause extensive problems, silver nitrate should be applied from the time of admission . Since silver nitrate does not penetrate well into the wound, frequent cleaning and debridement (surgical re moval of dead scar tissue to speed healing) are necessary. Debridement is important in the topical treatment of burns because medications cannot be transported to the site of action without a viable capillary bed. Some of the problems this prepara tion presents are:
30 American Pharmacy VoI,NS19, No.2, Feb.1979/86
\ ~
r
• The need for constant reapplication and bulky dressings; • Possible electrolyte disturbances, especially sodium, calcium, and magnesium depletion; • Staining of skin, floors, and line ns; • Slight pain, often attributed to sliver nitrate's hydroscopic qualities (however, it is difficult to establish a cause and effect relationship); • A rare side effect, methemoglob~n emia , resulting from conversion by Aerobacter cloacae, sometimes present in burn wounds, of nitrate to nitrite; 2,3 • Lack of mobility due to heavy bandages, particularly troublesome when hands are burned-since they must remain mobile to attain proper healing-but avoidable by simply wra pping the bandages around the patient's fingers. 4
ity, which allows a choice between open and closed treatment techniques. In addition, silver sulfadiazine is painless, nons taining, and easy to apply and therefore can be used on an outpatient as well as an inpatient basis. 2 Dressings with silver sulfadiazine need changing less often (every 24 hours, as opposed to at least twice a day with silver nitrate).4,7 Although they could be left effectively with silver sulfadiazine for 48 hours, it was found that changing them every 24 hours improved debridement by softening the eschar (slough produced by burning). Because of the decrease in pain, ease of mobility, lack of constant reapplication, better appearance, and lesser concern with the burn injury, silver sulfadiazine is often popular for use with children. Silvadene (Marion Laboratories) is used alSilver Sulfadiazine most exclusively as the impregnated Kerlix gauze form at Children's As a solution to some of these Hospital of Michigan. 2,7 problems, especially the pain and The rare disadvantages of silver staining, silver sulfadiazine was sulfadiazine are occasionalleukopes developed. Introduced in 1967 by . nia, white blood counts below 3,000/ Dr. Charles Fox Jr., silver sulfadiazine was used in Children's Hospital of Michigan (Detroit) beginning in 1968 on both the burn wound itself and the donor site. The staff's clinical impression was that the wounds were less painful and healed more rapidly. In a comparison study of silver sulfadiazine, povidone-iodine, nitrofurazone, and other mixed medications, the range of healing time was 3-12 days on 31 donor sites using sulfadiazine. With nitrofurazone the range was 7-17 days on 42 sites, and with povidone-iodine it was 4-13 days on 13 sites . The average healing time was less with silver sulfadiazine, but there were insufficient data for the results to be certain. What the study did determine, however, was viable reharvesting of donor sites in a shorter time than previously had been thought possible. 6 Some advantages of silver sulfadiazine are its better effectiveness Keeping a mending burn clean and bacteria against Candida, Pseudomonas, and silver sulfadiazine cream. Klebsiella organisms and its versa til-
American Pharmacy VoI.NS19, No.2, Feb.1979/87
mm 3, and, very rarely, rash, fever, and tachycardia. 3,B The rash appears only in the area around the burn wound. All of these reactions occur so seldom that they should not affect silver sulfadiazine's usefulness.
Mafenide Acetate Another agent ased in severe burn therapy is mafenide acetate. This drug is sometimes applied to electrical burns because it is more penetrating that other agents. It is effective against all strains of bacteria, but not against Candida albicans. 3 Advantages of mafenide acetate are that it greatly limits the bacterial density of the wound and is stable chemically and biologically. It is easily applied and diffuses into the eschar to provide an effective drug level. However, mafenide acetate frequently produces a rash, and its carbonic anhydrase inhibitor effect often causes respiratory alkalosis and metabolic acidosis . It is also associated with severe pain on application. A study at the burn center at
free is simplified by the use of
31
::::;
Brooke Army Medical Center, San Antonio, Texas, suggests that in patients treated with mafenide acetate there is increasing mortality related to respiratory complications. The drug is no longer used at Brooke Army Medical Center; it has been replaced almost totally by silver sulfadiazine. 9
Gentamicin Some topical burn ointments contain gentamicin, an agent that is effective, especially against Pseudomonas aeruginosa, and has a broad spectrum of activity and low toxicity. Since it can develop resistant strains, it should, like all antibiotics, be used discrimina hay. Gentamicin is heat stable and therefore can be autoclaved when put into dressing material. 4 A study was done on gentamicin at St. Paul Ramsey Hospital in Minnesota. Fourteen patients with burns covering 25-85 percent of their bodies were treated for gramnegative burn wound infections. Using a computer program, researchers performed a nonlinear regression analysis of the serum concentration time data for each patient. They found that younger patients required higher doses to produce peak concentrations similar to those in older patients. The average peak gentamicin con-centrations for the youngest and oldest patients were 7.6 and 7.7 mgt liter, respectively. The average doses required to obtain these peak levels were 12.8 mg/kg/day for the younger patients and 7.2 mg/kg/day for the older patients,lO In a study of six patients with Pseudomonas ecthyma gangrenosum, which is usually fatal, three survived with gentamicin and carbenicillin treatment in average doses of 5.8 mg/kg/day and 803 mg/kg/day, respectively. The nonsurvivors received significantly lower doses,ll An in vitro study at the University of Michigan on neomycin, Betadine (povidone-iodine), silver nitrate, gentamicin, Sulfamylon (mafenide acetate), Silvadene (silver sulfadiazine), and Furacin (nitrofur-
32
of the staff. Cerium nitrate was azone) in liquid and cream ointfound to have none of the disadments was done in 1977. 12 The orvantages of silver nitrate, such as ganisms studied were common constaining, and did not leach minerals taminants of burns: Pseudomonas aerufrom wounds. ginosa, Proteus mirabilis, Enterobacter The use of cerium and silver sulcloacae, Group D Enterococcus, Staphylofadiazine treatment simultaneously coccus, Klebsiella, Escherichia coli, and was most effective. In eight patients Serratia marscens. studied the incidence of negative Comparative zones of inhibition wound cultures was always twice or showed that gentamicin, neomycin, and silver nitrate were most effec- more that obtained in patients with tive against the bacteria. Unfor- similar injuries treated with cerium nitrate alone. 13 tunately, in vitro studies are not completely accurate, and no clinical Proteolytic Enzymes studies have been published as a .
I
American Pharmacy VoI.NS19, No.2, Feb.1979/88
I 1 (
treatment modality. However, it is usually clear from the studies done that a combination of agents is the best method of burn treatment. If it is possible to isolate the responsible species and test for sensitivity to various agents, this is the method of choicep ,12 In a 1966-1970 study of 350 patients at the Shriner's Burns Institute and Cincinnati General Hospital, Cincinnati, Ohio, the conclusion was that the influences of the topical antibacterial agents gentamicin and silver sulfadiazine paralleled each other and were slightly better than those exerted by silver nitrate and mafenide acetate. The study also seemed to show that none of the agents had a significant influence on survival for patients with burns over so percent of the total body surface area. Of course, in any such study it is impossible to control all the variables, so the results can serve only as guidelines in selecting a maximum broad spectrum antibiotic.4 Pharmacists should exercise caution in recommending a topical ointment for burn therapy. Because con trol of bacteria is so effective with these agents, the wound can be complicated by viral and fungal in(Continued on page 35)
Case Study Care of Bumed Children Silver sulfadiazine is especially useful as an addition to the physician's outpatient care of the burned patient . However, it is also very useful in more complicated cases and may con tin ue to be popular for pa tien ts wit h all types of burns. A four-year-old black girl weighing SO pounds and 511;2 inches tall, was admitted to Children's Hospital of Michigan, Detroit, with a 40 percent thermal injury of the face, scalp, neck, chest wall, anterior abdominal wall, upper and lower arms and legs, and feet. She had deep third-degree burns on her left hand and right foot . Her past medical history was normal at the time of admission. She had no obstructive problems with her airway and no history of fam ilial disease . Her blood pressure on admission was 100/70, temperature 101, and pulse 146. Her hemoglobin was 11 and urinalysis clear. Immediate resuscitation measures were instituted with lactated Ringer's solution. She was burned in a fire in her home. When a box in the kitchen exploded, she ran and hid, so when she was finally found and rescued by firemen, she had severe burns. The burns on her left hand and right foot were extensive and very deep, especially on her fingers and toes. On the day of admission her burns were cleaned, her scalp was shaved, and Silvadene {silver sulfadiazine} diessing was applied. These dressings were changed daily, and bacitracin was given every two to three hours . Silvadene dressings were put on her eyes, with Garamycin (gentamycin sulfate) and Neosporin (neomycin sulfate, polymyxin B sulfate, and bacitracin zinc) opththalmic ointment alternating every two to three hours.
Six days later, after initial escharotomy of her lower extremities and hands, the pa tien t underwent debridement of her wounds. Meanwhile, cultures of the wounds were taken daily. One month post admission, Escherichia cok Enterococcus, Candida, and Bacillus were discovered and treated with amphotericin B given intravenously, and the patient was watched for renal function, increased blood urea nitrogen, and/or creatinine clearance. Two weeks later, E. coli and coagulase neg. staphylococcus were treated with neomycin and gentamicin. Surgical debridement was performed on four occasions, including an amputation of the burned digits. Later, three grafting procedures and two plastic surgery operations were performed. . The patient was attended by Dr. Horrell of the hospital's hand service. Horrell, an orthopedic surgeon who limits his practice to reconstructive surgery of the hand, projected that prolonged surgery would be required for restitution of the hand and lower limbs. One and one-half months later the patient was readmitted for nonhealing burn scars of the abdomen and hand . She underwent skin debridement and skin grafting with no complica tions. Eight months after this follow-up treatment the patient was readmitted for release of burn contractures and full thickness skin graft of the right hand. One month later she underwent serial excision of a keloid (skin tumor) of the left side of the face with Z-plasty to nasal webbing and excision of the right upper eyebrow. In a separate operation a week later she had the same surgery on the right side of her face.
After soaking in glycerine, skin grafts are placed in frozen storage.
American Pharm acy Vol.NS19, No.2, Feb.1979/89
33
SupportiveTherapy in Burn Care
I
Consensus Development Conference
~
Over the past decade, interdisciplinary basic and applied research into the body's total response to burn injury has produced an impressive array of more rational and effective modes of therapy. These measures, used in a few highly specialized research-oriented burn centers, have improved by as much as 50 percent the survival rate of people suffering burns covering up to 65 percent of the total body surface. As the overall morbidity and mortality figures clearly show, however, the management of severe burns remains a critical problem. Considering the significant promise of the therapeutic advances that already have occurred in some centers-for example, the use of cerium nitrate at St. John's Mercy Medical Center in St. Louis and the seemingly futuristic laser scalpel a't the University of Washington School of Medicine-attention logically can be given to evaluate the feasibility of their widespread application in other less specialized community hospitals. To this end, the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH), in cooperation with the American Burn AsI sociation, recently sponsored the Consensus Development Conference on Supportive Therapy in Burn Care.
Surgical Issues Debated At the NIH conference, held November 10-11,1978, burn medicine experts from 33 states and seven foreign countries considered topics in five major areas: fluid resuscitation techniques, infection control, nutritional balance and metabolism, effects of smoke inhalation, and the role of excisional therapy. In addition, two ethical issues were considered: Under what conditions, if any, of burn injury would it prove futile to attempt resuscitation, and what justification exists for administering steroids in response to smoke inhalation in view of their role in lower-
34
ing resistance to infection? After debate by a panel of physician-researchers and discussion from the audience, a plenary session was held during which panel moderators presented consensus recommenda tions for each topic. A look at some of the results may offer pharmacists the opportunity to examine an important aspect of burn therapy: surgical involvement. The panel on fluid resuscitation agreed that the keystones of effective therapy are sodium and water. Fluids should be replaced totally within 24 hours (2-4 ml/kg/percent burn). Formulas such as' Ringer's lactate playa vital role by serving as a standard from which adjustments and deviations can be made. Panelists also concurred that the physician has an ethical and moral responsibility to initiate therapy on all patients, regardless of the extent of burn. The panel on infection stressed the importance of nutritional balance in combating both systemic and local, infection, noting at the same time that the local wound and its ability to withstand infection may be influenced by the characteristics of the fluid resuscitation scheme chosen. Although panelists could not reach a consensus about the applicability of barrier systems (such as controlled air or bacteriafree ' nursing environments) or about the specific role of dressings, they did concur on the beneficial effect of topical agents. The group debating the role of nutritional requirements in overcoming the metabolic effects of burn injury concurred that patients who require nutritional replacement are either those who have greater than 20 percent total body surface burn, preinjury nutritional deprivation, or severe endocrine, pulmonary, or septic complications or those who suffer greater than 10 percent decrease in preburn body weight during hospitalization. A general formula (25 kcal/kg body
weight plus 40 kcal/percent total body surface burn) was developed for adults, but the panel members could not agree on a specific formula for children. According to the smoke inhalation panel, so many types of injuries can result that a more precise, universally accepted classification scheme should be developed. A recent study, in which steroid-treated patients suffered a mortality rate four times as great as the control group, suggests that the use of steroids is not indica ted for any degree of smoke inhalation.
Early Excision Recommended The last panel reviewed the role of excisional therapy. Participants noted that if recovery of skin function following thermal injury does not take place within a few weeks through healing of the partial thickness component and wound closure by skin grafting, the patient is likely to die. Thus the burn illness can be term ina ted by prompt burn wound closure, i.e., early excision of all deep components of the burn followed by skin grafting. In treating deep wounds, assessment of burn depth is critical. Excision-al therapy was not recommended for patients with associated smoke inhalation injury or other injuries in addition to the burn. In all cases, it was emphasized, excisional therapy should be performed only under controlled circumstances by skilled surgeons. In addition to these consensus opinions, each panel outlined promising areas of future research. The panel on excisional therapy, for example, was particularly enthusiastic about the potential of chemical debridement, which may obviate the requirement for anesthesia while permitting an accurate determination of burn wound depth. It is hoped that soon this type of research will be applied in all hospitals to help minimize the terrifying and long-lasting effects of severe burn injury. - Joan Welsh
American Pharmacy Vol.NS19, No.2, Feb.1979/90
?(
I
first, second, and third degree burn are now most often called dermal partial thickness, with no grafting required, or full thickness with grafting required (see page 35).1 Death resulting from burns usually occurs within the first month of treatment. Once the patient has passed this critical point, chances of survival are good . Frequently, the cause of death during this early stage is infection. To prevent and control infection, many topical burn agents have been developed . One of the largest differences in burn management throughout the country is the use of different topical ointments. The efficacy of these agents varies. Silver nitrate, silver sulfadiazine, mafenide acetate, povidone-iodine, Neosporin (a combination product containing neomycin sulfate, polymyxin B sulfate, and bacitracin zinc), cerium nitrate, and gen tamicin are presently used in clinical burn care.
Silver Nitrate
By SONJA GEE Burned patients present a complex problem to the health care team. Depending on the severity of the burn, trea tmen t may involve the .hospital administrator, the nurse, the dietician, the surgeon, and the pharmacist.
Sonja Gee is a fifth-year pharmacy student at Wayne State University, Detroit, MI 48202. The author would like to acknowledge the assistance of James R. Lloyd, MD, clinical assistant professor of surgery at the Wayne State University School of Medicine and director of the burn unit at Children's Hospital of Michigan, Detroit; Elaine Emig, RN, also of the burn unit; and Percy R. McClain Sr., RPh, MS, director of pharmacy at Children's Hospital.
Because the practicing pharmacist is frequently asked to suggest a method of treatment for burns, it is important to know what kinds of therapy are appropriate. To help the pharmacist in making these important decisions, here is an overview of the topical drugs most often used in treating severe burns.
Varying Treatment Methods The treatment of burns varies considerably. Many factors contribute to the seriousness of thermal injury: the extent, depth, and location of the wound, the patient's age, and any past illnesses. Advances in therapeutic techniques have spawned more precise descriptive terminology. The terms
Silver nitrate (0 .5 percent) was one of the original agents used and is still used in some hospitals, including the University of Michigan in Ann Arbor. Silver nitrate (0.5 percent), the concentration most acceptable today, is available as a liquid or cream preparation. The liquid is applied as a soak, through t he bandages. Silver nitrate is effective against most bacteria common to burns e xcept some Enterobacter and Klebsiella. Because fungi are relatively insensitive and can cause extensive problems, silver nitrate should be applied from the time of admission . Since silver nitrate does not penetrate well into the wound, frequent cleaning and debridement (surgical re moval of dead scar tissue to speed healing) are necessary. Debridement is important in the topical treatment of burns because medications cannot be transported to the site of action without a viable capillary bed. Some of the problems this prepara tion presents are:
30 American Pharmacy VoI,NS19, No.2, Feb.1979/86
\ ~
r
• The need for constant reapplication and bulky dressings; • Possible electrolyte disturbances, especially sodium, calcium, and magnesium depletion; • Staining of skin, floors, and line ns; • Slight pain, often attributed to sliver nitrate's hydroscopic qualities (however, it is difficult to establish a cause and effect relationship); • A rare side effect, methemoglob~n emia , resulting from conversion by Aerobacter cloacae, sometimes present in burn wounds, of nitrate to nitrite; 2,3 • Lack of mobility due to heavy bandages, particularly troublesome when hands are burned-since they must remain mobile to attain proper healing-but avoidable by simply wra pping the bandages around the patient's fingers. 4
ity, which allows a choice between open and closed treatment techniques. In addition, silver sulfadiazine is painless, nons taining, and easy to apply and therefore can be used on an outpatient as well as an inpatient basis. 2 Dressings with silver sulfadiazine need changing less often (every 24 hours, as opposed to at least twice a day with silver nitrate).4,7 Although they could be left effectively with silver sulfadiazine for 48 hours, it was found that changing them every 24 hours improved debridement by softening the eschar (slough produced by burning). Because of the decrease in pain, ease of mobility, lack of constant reapplication, better appearance, and lesser concern with the burn injury, silver sulfadiazine is often popular for use with children. Silvadene (Marion Laboratories) is used alSilver Sulfadiazine most exclusively as the impregnated Kerlix gauze form at Children's As a solution to some of these Hospital of Michigan. 2,7 problems, especially the pain and The rare disadvantages of silver staining, silver sulfadiazine was sulfadiazine are occasionalleukopes developed. Introduced in 1967 by . nia, white blood counts below 3,000/ Dr. Charles Fox Jr., silver sulfadiazine was used in Children's Hospital of Michigan (Detroit) beginning in 1968 on both the burn wound itself and the donor site. The staff's clinical impression was that the wounds were less painful and healed more rapidly. In a comparison study of silver sulfadiazine, povidone-iodine, nitrofurazone, and other mixed medications, the range of healing time was 3-12 days on 31 donor sites using sulfadiazine. With nitrofurazone the range was 7-17 days on 42 sites, and with povidone-iodine it was 4-13 days on 13 sites . The average healing time was less with silver sulfadiazine, but there were insufficient data for the results to be certain. What the study did determine, however, was viable reharvesting of donor sites in a shorter time than previously had been thought possible. 6 Some advantages of silver sulfadiazine are its better effectiveness Keeping a mending burn clean and bacteria against Candida, Pseudomonas, and silver sulfadiazine cream. Klebsiella organisms and its versa til-
American Pharmacy VoI.NS19, No.2, Feb.1979/87
mm 3, and, very rarely, rash, fever, and tachycardia. 3,B The rash appears only in the area around the burn wound. All of these reactions occur so seldom that they should not affect silver sulfadiazine's usefulness.
Mafenide Acetate Another agent ased in severe burn therapy is mafenide acetate. This drug is sometimes applied to electrical burns because it is more penetrating that other agents. It is effective against all strains of bacteria, but not against Candida albicans. 3 Advantages of mafenide acetate are that it greatly limits the bacterial density of the wound and is stable chemically and biologically. It is easily applied and diffuses into the eschar to provide an effective drug level. However, mafenide acetate frequently produces a rash, and its carbonic anhydrase inhibitor effect often causes respiratory alkalosis and metabolic acidosis . It is also associated with severe pain on application. A study at the burn center at
free is simplified by the use of
31
::::;
Brooke Army Medical Center, San Antonio, Texas, suggests that in patients treated with mafenide acetate there is increasing mortality related to respiratory complications. The drug is no longer used at Brooke Army Medical Center; it has been replaced almost totally by silver sulfadiazine. 9
Gentamicin Some topical burn ointments contain gentamicin, an agent that is effective, especially against Pseudomonas aeruginosa, and has a broad spectrum of activity and low toxicity. Since it can develop resistant strains, it should, like all antibiotics, be used discrimina hay. Gentamicin is heat stable and therefore can be autoclaved when put into dressing material. 4 A study was done on gentamicin at St. Paul Ramsey Hospital in Minnesota. Fourteen patients with burns covering 25-85 percent of their bodies were treated for gramnegative burn wound infections. Using a computer program, researchers performed a nonlinear regression analysis of the serum concentration time data for each patient. They found that younger patients required higher doses to produce peak concentrations similar to those in older patients. The average peak gentamicin con-centrations for the youngest and oldest patients were 7.6 and 7.7 mgt liter, respectively. The average doses required to obtain these peak levels were 12.8 mg/kg/day for the younger patients and 7.2 mg/kg/day for the older patients,lO In a study of six patients with Pseudomonas ecthyma gangrenosum, which is usually fatal, three survived with gentamicin and carbenicillin treatment in average doses of 5.8 mg/kg/day and 803 mg/kg/day, respectively. The nonsurvivors received significantly lower doses,ll An in vitro study at the University of Michigan on neomycin, Betadine (povidone-iodine), silver nitrate, gentamicin, Sulfamylon (mafenide acetate), Silvadene (silver sulfadiazine), and Furacin (nitrofur-
32
of the staff. Cerium nitrate was azone) in liquid and cream ointfound to have none of the disadments was done in 1977. 12 The orvantages of silver nitrate, such as ganisms studied were common constaining, and did not leach minerals taminants of burns: Pseudomonas aerufrom wounds. ginosa, Proteus mirabilis, Enterobacter The use of cerium and silver sulcloacae, Group D Enterococcus, Staphylofadiazine treatment simultaneously coccus, Klebsiella, Escherichia coli, and was most effective. In eight patients Serratia marscens. studied the incidence of negative Comparative zones of inhibition wound cultures was always twice or showed that gentamicin, neomycin, and silver nitrate were most effec- more that obtained in patients with tive against the bacteria. Unfor- similar injuries treated with cerium nitrate alone. 13 tunately, in vitro studies are not completely accurate, and no clinical Proteolytic Enzymes studies have been published as a .
I
American Pharmacy VoI.NS19, No.2, Feb.1979/88
I 1 (
treatment modality. However, it is usually clear from the studies done that a combination of agents is the best method of burn treatment. If it is possible to isolate the responsible species and test for sensitivity to various agents, this is the method of choicep ,12 In a 1966-1970 study of 350 patients at the Shriner's Burns Institute and Cincinnati General Hospital, Cincinnati, Ohio, the conclusion was that the influences of the topical antibacterial agents gentamicin and silver sulfadiazine paralleled each other and were slightly better than those exerted by silver nitrate and mafenide acetate. The study also seemed to show that none of the agents had a significant influence on survival for patients with burns over so percent of the total body surface area. Of course, in any such study it is impossible to control all the variables, so the results can serve only as guidelines in selecting a maximum broad spectrum antibiotic.4 Pharmacists should exercise caution in recommending a topical ointment for burn therapy. Because con trol of bacteria is so effective with these agents, the wound can be complicated by viral and fungal in(Continued on page 35)
Case Study Care of Bumed Children Silver sulfadiazine is especially useful as an addition to the physician's outpatient care of the burned patient . However, it is also very useful in more complicated cases and may con tin ue to be popular for pa tien ts wit h all types of burns. A four-year-old black girl weighing SO pounds and 511;2 inches tall, was admitted to Children's Hospital of Michigan, Detroit, with a 40 percent thermal injury of the face, scalp, neck, chest wall, anterior abdominal wall, upper and lower arms and legs, and feet. She had deep third-degree burns on her left hand and right foot . Her past medical history was normal at the time of admission. She had no obstructive problems with her airway and no history of fam ilial disease . Her blood pressure on admission was 100/70, temperature 101, and pulse 146. Her hemoglobin was 11 and urinalysis clear. Immediate resuscitation measures were instituted with lactated Ringer's solution. She was burned in a fire in her home. When a box in the kitchen exploded, she ran and hid, so when she was finally found and rescued by firemen, she had severe burns. The burns on her left hand and right foot were extensive and very deep, especially on her fingers and toes. On the day of admission her burns were cleaned, her scalp was shaved, and Silvadene {silver sulfadiazine} diessing was applied. These dressings were changed daily, and bacitracin was given every two to three hours . Silvadene dressings were put on her eyes, with Garamycin (gentamycin sulfate) and Neosporin (neomycin sulfate, polymyxin B sulfate, and bacitracin zinc) opththalmic ointment alternating every two to three hours.
Six days later, after initial escharotomy of her lower extremities and hands, the pa tien t underwent debridement of her wounds. Meanwhile, cultures of the wounds were taken daily. One month post admission, Escherichia cok Enterococcus, Candida, and Bacillus were discovered and treated with amphotericin B given intravenously, and the patient was watched for renal function, increased blood urea nitrogen, and/or creatinine clearance. Two weeks later, E. coli and coagulase neg. staphylococcus were treated with neomycin and gentamicin. Surgical debridement was performed on four occasions, including an amputation of the burned digits. Later, three grafting procedures and two plastic surgery operations were performed. . The patient was attended by Dr. Horrell of the hospital's hand service. Horrell, an orthopedic surgeon who limits his practice to reconstructive surgery of the hand, projected that prolonged surgery would be required for restitution of the hand and lower limbs. One and one-half months later the patient was readmitted for nonhealing burn scars of the abdomen and hand . She underwent skin debridement and skin grafting with no complica tions. Eight months after this follow-up treatment the patient was readmitted for release of burn contractures and full thickness skin graft of the right hand. One month later she underwent serial excision of a keloid (skin tumor) of the left side of the face with Z-plasty to nasal webbing and excision of the right upper eyebrow. In a separate operation a week later she had the same surgery on the right side of her face.
After soaking in glycerine, skin grafts are placed in frozen storage.
American Pharm acy Vol.NS19, No.2, Feb.1979/89
33
SupportiveTherapy in Burn Care
I
Consensus Development Conference
~
Over the past decade, interdisciplinary basic and applied research into the body's total response to burn injury has produced an impressive array of more rational and effective modes of therapy. These measures, used in a few highly specialized research-oriented burn centers, have improved by as much as 50 percent the survival rate of people suffering burns covering up to 65 percent of the total body surface. As the overall morbidity and mortality figures clearly show, however, the management of severe burns remains a critical problem. Considering the significant promise of the therapeutic advances that already have occurred in some centers-for example, the use of cerium nitrate at St. John's Mercy Medical Center in St. Louis and the seemingly futuristic laser scalpel a't the University of Washington School of Medicine-attention logically can be given to evaluate the feasibility of their widespread application in other less specialized community hospitals. To this end, the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH), in cooperation with the American Burn AsI sociation, recently sponsored the Consensus Development Conference on Supportive Therapy in Burn Care.
Surgical Issues Debated At the NIH conference, held November 10-11,1978, burn medicine experts from 33 states and seven foreign countries considered topics in five major areas: fluid resuscitation techniques, infection control, nutritional balance and metabolism, effects of smoke inhalation, and the role of excisional therapy. In addition, two ethical issues were considered: Under what conditions, if any, of burn injury would it prove futile to attempt resuscitation, and what justification exists for administering steroids in response to smoke inhalation in view of their role in lower-
34
ing resistance to infection? After debate by a panel of physician-researchers and discussion from the audience, a plenary session was held during which panel moderators presented consensus recommenda tions for each topic. A look at some of the results may offer pharmacists the opportunity to examine an important aspect of burn therapy: surgical involvement. The panel on fluid resuscitation agreed that the keystones of effective therapy are sodium and water. Fluids should be replaced totally within 24 hours (2-4 ml/kg/percent burn). Formulas such as' Ringer's lactate playa vital role by serving as a standard from which adjustments and deviations can be made. Panelists also concurred that the physician has an ethical and moral responsibility to initiate therapy on all patients, regardless of the extent of burn. The panel on infection stressed the importance of nutritional balance in combating both systemic and local, infection, noting at the same time that the local wound and its ability to withstand infection may be influenced by the characteristics of the fluid resuscitation scheme chosen. Although panelists could not reach a consensus about the applicability of barrier systems (such as controlled air or bacteriafree ' nursing environments) or about the specific role of dressings, they did concur on the beneficial effect of topical agents. The group debating the role of nutritional requirements in overcoming the metabolic effects of burn injury concurred that patients who require nutritional replacement are either those who have greater than 20 percent total body surface burn, preinjury nutritional deprivation, or severe endocrine, pulmonary, or septic complications or those who suffer greater than 10 percent decrease in preburn body weight during hospitalization. A general formula (25 kcal/kg body
weight plus 40 kcal/percent total body surface burn) was developed for adults, but the panel members could not agree on a specific formula for children. According to the smoke inhalation panel, so many types of injuries can result that a more precise, universally accepted classification scheme should be developed. A recent study, in which steroid-treated patients suffered a mortality rate four times as great as the control group, suggests that the use of steroids is not indica ted for any degree of smoke inhalation.
Early Excision Recommended The last panel reviewed the role of excisional therapy. Participants noted that if recovery of skin function following thermal injury does not take place within a few weeks through healing of the partial thickness component and wound closure by skin grafting, the patient is likely to die. Thus the burn illness can be term ina ted by prompt burn wound closure, i.e., early excision of all deep components of the burn followed by skin grafting. In treating deep wounds, assessment of burn depth is critical. Excision-al therapy was not recommended for patients with associated smoke inhalation injury or other injuries in addition to the burn. In all cases, it was emphasized, excisional therapy should be performed only under controlled circumstances by skilled surgeons. In addition to these consensus opinions, each panel outlined promising areas of future research. The panel on excisional therapy, for example, was particularly enthusiastic about the potential of chemical debridement, which may obviate the requirement for anesthesia while permitting an accurate determination of burn wound depth. It is hoped that soon this type of research will be applied in all hospitals to help minimize the terrifying and long-lasting effects of severe burn injury. - Joan Welsh
American Pharmacy Vol.NS19, No.2, Feb.1979/90
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