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The Prevention and Treatment of Tetanus in the Burn Patient
The Prevention and Treatment of Tetanus in the Burn Patient ROGER T. SHERMAN, M.D., F.A.C.S.*
Despite the fact that tetanus toxoid, perhaps the most effective vaccine ever developed, is readily available and in widespread use, tetanus still remains a serious health problem in the United States. Figures from the National Communicable Disease Center document 535 cases of tetanus for the year 1965 to 1966. Three hundred sixtythree of these patients died. 7 Although tetanus morbidity and mortality rates have followed a gradual downward pattern since 1950, the fall in incidence and death rate has been parallel. Accordingly, the case fatality ratio has remained practically unchanged, at about 65 per cent. 2
Incidence It is difficult to determine the actual incidence of tetanus associated with burn injury. There are no reports in the American literature dealing specifically with tetanus following burns. Of the 535 cases cited above, 12 patients, or 2.9 per cent, were reported to be related to burns. Specific details of these cases, extent of burn, etc., are not available." The case fatality ratio was 66.1 per cent. The incidence of tetanus following burns in other reported series of cases varies from 2 to 6.6 per cent.L 3, 6 From 1945 through 1963 there were 220 patients with tetanus admitted to the City of Memphis Hospitals. A burn was considered as the probable portal of entry in four patients, or 1.8 per cent. The case fatality ratio was 75 per cent. All four patients with tetanus following burns seen in our institution had deep but small burns which had received inadequate or no medical therapy prior to admission of the patients to the hospital with tetanus. There have been no cases of tetanus observed in more than 2000 patients admitted since 1945 to the burn service of the City of Memphis Hospitals for treatment of acute thermal injury. The absence of tetanus in patients hospitalized for burn injury attests to the efficacy of tetanus prophylaxis, which should be an integral part of the management of all patients with burns. Professor of Surgery, University of Tennessee College of Medicine, Memphis, Tennessee
Surgical Clinics of North America- Vol. 50, No.6, December, 1970
1277
1278
ROGER
T.
SHERMAN
The full-thickness burn wound is particularly suited for growth of anaerobic organisms. In addition to occasional cases of tetanus, gas gangrene and mixed clostridial infections have been reported in burn patients. 9
TET ANUS PROPHYLAXIS The wise adage that the prophylaxis of tetanus begins in the wound and not in the pill bottle is appropriate for small burns which lend themselves to adequate debridement and conversion into aerobic wounds. On the other hand, major full-thickness burns of large areas of the body surface can seldom be adequately debrided. Measures other than wound debridement must therefore be relied upon in the prophylaxis of tetanus in burns involving large areas of the body surface. The basic principles of tetanus prophylaxis for all wounds apply in general to burns. They are: tetanus toxoid immunization prior to injury, proper surgical management of wounds, administration of toxoid boosters, use of antibiotics when indicated, and utilization of human immune globulin. A number of plans and outlines have been developed for prophylaxis against tetanus. No single plan can be appropriate to all patients and accordingly tetanus prophylaxis must be subject to modification on an individual basis. PROPHYLAXIS FOR PREVIOUSLY IMMUNIZED PATIENTS. For burned patients who have been previously immunized by a basic immunization series plus a reinforcing booster dose, 0.5 ml. of precipitated tetanus toxoid given intramuscularly at the time of initial treatment of the burn is adequate prophylaxis. If the interval from the last booster dose is greater than 10 years, or if there has been a delay from the time of burning to treatment, 500 units of human tetanus globulin should be given intramuscularly with a different syringe and in a different site from the precipitated toxoid injection. Adequate evidence that the patient has in fact received a basic immunizing series plus a reinforcing booster must be available. Former service in the Armed Forces, written immunization records, an American Medical Association Emergency Medical Identification card, and positive history from parents are helpful in establishing previous immunization. PROPHYLAXIS FOR PATIENTS NOT PREVIOUSLY IMMUNIZED. Patients who have not received or completed a basic immunizing series should receive an initial immunizing dose of 0.5 ml. of precipitated tetanus toxoid at the time of injury. A complete series of two injections of 0.5 mI. of precipitated toxoid at 4-week intervals should be carried out. A reinforcing injection of 0.5 ml. of precipitated toxoid should be given 6 months to one year after the last injection of the initial series. In addition to beginning a basic immunizing toxoid series, 500 units of human tetanus immune globulin should be administered intramuscularly with a different syringe at a different site.
THE PREVENTION AND TREATMENT OF TETANUS IN THE BURN PATIENT
1279
Antibiotics Full-thickness burn wounds are characterized by total destruction of blood supply. The failure of parenteral antibiotics to control luxuriant bacterial colonization of these injuries is easily explained on this basis. Similarly, it would seem that administration of antibiotics alone as prophylaxis against tetanus in burns should not be relied upon. In fact, not surprisingly, tetanus following antibiotic prophylaxis alone has been reported. 10 Although tetanus organisms are sensitive in vitro to penicillin and tetracycline, reliance on these agents for tetanus prophylaxis is surely misleading. If prophylactic levels of these agents are to be achieved in vivo, adequate blood supply to the contaminated region must be present. Topical therapy with mafenide (Sulfamylon) has been shown to control clostridial infection (gas gangrene) in an experimental animal study.8 Based on these results it would seem appropriate to suggest the use of topical Sulfamylon in addition to tetanus toxoid and antitoxin as a useful agent in the prophylaxis of tetanus in burns. No cases of tetanus or other clostridial infection have been reported in burn wounds treated with Sulfamylon. Clostridial infections have however been reported in burns treated with silver nitrateY
GENERAL CONSIDERATIONS Tetanus infection develops in three stages, each of which lends itself to appropriate therapy. The first or focus of infection stage is characterized by deposition of Cl. tetani in tissues where the conditions are properly altered to suit its exacting metabolic requirements. Burn wounds fulfill these conditions admirably. The infection, once started, remains remarkably well localized, since the invasive powers of the organism are quite feeble. During this stage adequate wound care is all that is required. Failing this, the second stage ensues. This stage is characterized by the production and spread of a highly diffusible neurotoxin into the body fluids. Treatment during this phase of infection is neutralization of the tetanotoxin by tetanus antitoxin, either already present from active immunization, or administered passively. If adequate treatment has not been carried out, the third or neurologic stage, in which the toxin has combined with neuromotor cells in the central nervous system, appears. Antitoxin, regardless of dose, has no effect on tetanotoxin after it has combined with nervous system cells. Treatment during the neurologic or clinical tetanus stage depends on the severity of the disease. Mild, severe, or fulminating tetanus is presumably related to the amount of toxin combined with the nervous system. If the patient can be supported through the illness, detoxification occurs over a variable period of time. With recovery, there are no sequelae and the patient is not immune to tetanus. The diagnosis of tetanus is made entirely on clinical grounds. Typically, the onset of tetanus begins with an increase in tone of various
1280
ROGER
T.
SHERMAN
muscle groups, irritability, and dysphagia. Spasm of the masseter muscles with difficulty in opening the mouth is the most common initial symptom. As the disease progresses, stiffness of the neck, back and abdominal muscles appears. Tonic spasms (tetanospasms) occur in which violent contractions of the muscles produce firm clenching of the teeth, opisthotones, abdominal rigidity, and extension of the extremities. The slightest stimulus initiates these spasms. As the duration of the tetanospasms increases, serious interference with the mechanics of respiration may lead to hypoxia, cyanosis, and even sudden death.
PRINCIPLES OF TREATMENT There is considerable variation in specific measures for the treatment of tetanus in those centers still treating significant numbers of patients. 1, 4, 5 There are, nevertheless, five major objectives which are the goals of all treatment plans. They are: neutralization of circulating toxin, removal of the source of toxin, adequate sedation to control tetanospasms, maintenance of adequate respiration, and supportive care. NEUTRALIZATION OF CIRCULATING TOXIN. There is no longer any necessity to rely on antitoxin from equine or bovine sources. The use of human tetanus antitoxin has considerably reduced the likelihood of serious reactions to antitoxin therapy. From 1000 to 5000 units of human tetanus antitoxin are administered in divided doses at several sites. Intravenous injection is avoided. REMOVAL OF THE SOURCE OF TOXIN. Excision of the presumed portal of entry of tetanus infection, after sufficient time for the antitoxin to be maximally absorbed, is indicated. Data to support the concept that excision is beneficial is lacking, but most authorities advocate this procedure. Excision of the presumed portal of entry in burn patients however is applicable only to those patients with small burns. Excision of major burns for treatment of tetanus is not recommended. Administration of penicillin or tetracycline may also help eliminate tetanus organisms and should accordingly be given. ADEQUATE SEDATION. There are a variety of drugs available for sedation and relaxation of muscular spasms in tetanus. The drug of choice currently being used at our institution is diazepam. Complete paralysis of patients with curare has been advocated in the treatment of fulminating tetanus. 4 Significant sedation to control tetanospasms and associated periods of apnea must be utilized. Toxic dosages of the sedative medication must be carefully avoided. MAINTENANCE OF RESPIRATION. The cause of death in severe tetanus is often related to respiratory arrest. All patients with severe tetanus should have a tracheostomy. Equipment for respiratory assistance and controlled respiration if necessary should be available. Meticulous pulmonary toilet and specific antibiotic therapy of pulmonary infections of consequence must be implemented.
THE PREVENTION AND TREATMENT OF TETANUS IN THE BURN PATIENT
1281
SUPPORTIVE CARE. Many centers have recognized the meticulous supportive care that tetanus patients require, by establishing a tetanus treatment team. Nurse, neurologist, internist, surgeon, and anesthesiologist are usually included. In addition to this basic team, the dietitian, physical therapist, and respiratory physiologist make significant contributions to patient care. Attention to water balance, electrolyte replacement, renal function, ventilation, nutrition and prophylaxis of pulmonary or urinary tract infections are important facets of supportive care. To provide the best care of these critically ill patients a knowledgeable professional must be in 24 hour attendance.
SUMMARY Despite the availability of tetanus toxoid, an excellent vaccine for prophylaxis against tetanus, cases still occur in the United States. The case fatality ratio is high. The incidence of tetanus following burns is unknown, but the burn wound is an ideal portal of entry for tetanus infection. Adequate tetanus prophylaxis should be utilized in all patients presenting with burns according to each individual circumstance. Other measures of prophylaxis, including debridement and topical and parenteral antibiotics, should be considered.
REFERENCES 1. Altemeier, W. A., Culbertson, W. R., and Gonzalez, L. L.: Clinical experiences in the treatment of tetanus. Arch. Surg., 80:977, 1960. 2. Annual Supplement to Morbidity and Mortality Weekly Report. National Communicable Disease Center, Atlanta, Georgia, 1966. 3. Christensen, N. A., and Thurber, D. L.: Clinical experience with tetanus: 91 cases. Proc. Mayo Clin., 32:146,1957. 4. Christensen, N. A.: Treatment of the patient with severe tetanus. SURG. CLIN. N. AMER., 49:1183,1969. 5. Crandell, D. L., and Whitcher, C. E.: Control of neuromuscular manifestations of severe systemic tetanus. J.A.M.A., 72:15,1960. 6. Dietrich, H. F.: Tetanus in childhood with special reference to treatment. Amer. J. Dis. Children, 59:693,1940. 7. LaForce, M. F., Young, L. S., and Bennett, J. V.: New Eng. J. Med., 280:569,1969. 8. Mendelson, J. A., and Lindsey, D.: Sulfamylon (mafenide) and penicillin as expedient treatment of experimental massive open wounds. J. Trauma, 2:239,1962. 9. Monafo, W. W., Brentano, L., Gravens, D. L., Kempson, R., and Moyer, C. A.: Gas gangrene and mixed clostridial infections of muscle complicating deep thermal burns. Arch. Surg., 92:212,1966. 10. Risk of tetanus prophylaxis. Foreign letters. J.A.M.A., 174:181,1960. 11. Young, L. S.: Personal communication. 951 Court Avenue Memphis, Tennessee 38103
Despite the fact that tetanus toxoid, perhaps the most effective vaccine ever developed, is readily available and in widespread use, tetanus still remains a serious health problem in the United States. Figures from the National Communicable Disease Center document 535 cases of tetanus for the year 1965 to 1966. Three hundred sixtythree of these patients died. 7 Although tetanus morbidity and mortality rates have followed a gradual downward pattern since 1950, the fall in incidence and death rate has been parallel. Accordingly, the case fatality ratio has remained practically unchanged, at about 65 per cent. 2
Incidence It is difficult to determine the actual incidence of tetanus associated with burn injury. There are no reports in the American literature dealing specifically with tetanus following burns. Of the 535 cases cited above, 12 patients, or 2.9 per cent, were reported to be related to burns. Specific details of these cases, extent of burn, etc., are not available." The case fatality ratio was 66.1 per cent. The incidence of tetanus following burns in other reported series of cases varies from 2 to 6.6 per cent.L 3, 6 From 1945 through 1963 there were 220 patients with tetanus admitted to the City of Memphis Hospitals. A burn was considered as the probable portal of entry in four patients, or 1.8 per cent. The case fatality ratio was 75 per cent. All four patients with tetanus following burns seen in our institution had deep but small burns which had received inadequate or no medical therapy prior to admission of the patients to the hospital with tetanus. There have been no cases of tetanus observed in more than 2000 patients admitted since 1945 to the burn service of the City of Memphis Hospitals for treatment of acute thermal injury. The absence of tetanus in patients hospitalized for burn injury attests to the efficacy of tetanus prophylaxis, which should be an integral part of the management of all patients with burns. Professor of Surgery, University of Tennessee College of Medicine, Memphis, Tennessee
Surgical Clinics of North America- Vol. 50, No.6, December, 1970
1277
1278
ROGER
T.
SHERMAN
The full-thickness burn wound is particularly suited for growth of anaerobic organisms. In addition to occasional cases of tetanus, gas gangrene and mixed clostridial infections have been reported in burn patients. 9
TET ANUS PROPHYLAXIS The wise adage that the prophylaxis of tetanus begins in the wound and not in the pill bottle is appropriate for small burns which lend themselves to adequate debridement and conversion into aerobic wounds. On the other hand, major full-thickness burns of large areas of the body surface can seldom be adequately debrided. Measures other than wound debridement must therefore be relied upon in the prophylaxis of tetanus in burns involving large areas of the body surface. The basic principles of tetanus prophylaxis for all wounds apply in general to burns. They are: tetanus toxoid immunization prior to injury, proper surgical management of wounds, administration of toxoid boosters, use of antibiotics when indicated, and utilization of human immune globulin. A number of plans and outlines have been developed for prophylaxis against tetanus. No single plan can be appropriate to all patients and accordingly tetanus prophylaxis must be subject to modification on an individual basis. PROPHYLAXIS FOR PREVIOUSLY IMMUNIZED PATIENTS. For burned patients who have been previously immunized by a basic immunization series plus a reinforcing booster dose, 0.5 ml. of precipitated tetanus toxoid given intramuscularly at the time of initial treatment of the burn is adequate prophylaxis. If the interval from the last booster dose is greater than 10 years, or if there has been a delay from the time of burning to treatment, 500 units of human tetanus globulin should be given intramuscularly with a different syringe and in a different site from the precipitated toxoid injection. Adequate evidence that the patient has in fact received a basic immunizing series plus a reinforcing booster must be available. Former service in the Armed Forces, written immunization records, an American Medical Association Emergency Medical Identification card, and positive history from parents are helpful in establishing previous immunization. PROPHYLAXIS FOR PATIENTS NOT PREVIOUSLY IMMUNIZED. Patients who have not received or completed a basic immunizing series should receive an initial immunizing dose of 0.5 ml. of precipitated tetanus toxoid at the time of injury. A complete series of two injections of 0.5 mI. of precipitated toxoid at 4-week intervals should be carried out. A reinforcing injection of 0.5 ml. of precipitated toxoid should be given 6 months to one year after the last injection of the initial series. In addition to beginning a basic immunizing toxoid series, 500 units of human tetanus immune globulin should be administered intramuscularly with a different syringe at a different site.
THE PREVENTION AND TREATMENT OF TETANUS IN THE BURN PATIENT
1279
Antibiotics Full-thickness burn wounds are characterized by total destruction of blood supply. The failure of parenteral antibiotics to control luxuriant bacterial colonization of these injuries is easily explained on this basis. Similarly, it would seem that administration of antibiotics alone as prophylaxis against tetanus in burns should not be relied upon. In fact, not surprisingly, tetanus following antibiotic prophylaxis alone has been reported. 10 Although tetanus organisms are sensitive in vitro to penicillin and tetracycline, reliance on these agents for tetanus prophylaxis is surely misleading. If prophylactic levels of these agents are to be achieved in vivo, adequate blood supply to the contaminated region must be present. Topical therapy with mafenide (Sulfamylon) has been shown to control clostridial infection (gas gangrene) in an experimental animal study.8 Based on these results it would seem appropriate to suggest the use of topical Sulfamylon in addition to tetanus toxoid and antitoxin as a useful agent in the prophylaxis of tetanus in burns. No cases of tetanus or other clostridial infection have been reported in burn wounds treated with Sulfamylon. Clostridial infections have however been reported in burns treated with silver nitrateY
GENERAL CONSIDERATIONS Tetanus infection develops in three stages, each of which lends itself to appropriate therapy. The first or focus of infection stage is characterized by deposition of Cl. tetani in tissues where the conditions are properly altered to suit its exacting metabolic requirements. Burn wounds fulfill these conditions admirably. The infection, once started, remains remarkably well localized, since the invasive powers of the organism are quite feeble. During this stage adequate wound care is all that is required. Failing this, the second stage ensues. This stage is characterized by the production and spread of a highly diffusible neurotoxin into the body fluids. Treatment during this phase of infection is neutralization of the tetanotoxin by tetanus antitoxin, either already present from active immunization, or administered passively. If adequate treatment has not been carried out, the third or neurologic stage, in which the toxin has combined with neuromotor cells in the central nervous system, appears. Antitoxin, regardless of dose, has no effect on tetanotoxin after it has combined with nervous system cells. Treatment during the neurologic or clinical tetanus stage depends on the severity of the disease. Mild, severe, or fulminating tetanus is presumably related to the amount of toxin combined with the nervous system. If the patient can be supported through the illness, detoxification occurs over a variable period of time. With recovery, there are no sequelae and the patient is not immune to tetanus. The diagnosis of tetanus is made entirely on clinical grounds. Typically, the onset of tetanus begins with an increase in tone of various
1280
ROGER
T.
SHERMAN
muscle groups, irritability, and dysphagia. Spasm of the masseter muscles with difficulty in opening the mouth is the most common initial symptom. As the disease progresses, stiffness of the neck, back and abdominal muscles appears. Tonic spasms (tetanospasms) occur in which violent contractions of the muscles produce firm clenching of the teeth, opisthotones, abdominal rigidity, and extension of the extremities. The slightest stimulus initiates these spasms. As the duration of the tetanospasms increases, serious interference with the mechanics of respiration may lead to hypoxia, cyanosis, and even sudden death.
PRINCIPLES OF TREATMENT There is considerable variation in specific measures for the treatment of tetanus in those centers still treating significant numbers of patients. 1, 4, 5 There are, nevertheless, five major objectives which are the goals of all treatment plans. They are: neutralization of circulating toxin, removal of the source of toxin, adequate sedation to control tetanospasms, maintenance of adequate respiration, and supportive care. NEUTRALIZATION OF CIRCULATING TOXIN. There is no longer any necessity to rely on antitoxin from equine or bovine sources. The use of human tetanus antitoxin has considerably reduced the likelihood of serious reactions to antitoxin therapy. From 1000 to 5000 units of human tetanus antitoxin are administered in divided doses at several sites. Intravenous injection is avoided. REMOVAL OF THE SOURCE OF TOXIN. Excision of the presumed portal of entry of tetanus infection, after sufficient time for the antitoxin to be maximally absorbed, is indicated. Data to support the concept that excision is beneficial is lacking, but most authorities advocate this procedure. Excision of the presumed portal of entry in burn patients however is applicable only to those patients with small burns. Excision of major burns for treatment of tetanus is not recommended. Administration of penicillin or tetracycline may also help eliminate tetanus organisms and should accordingly be given. ADEQUATE SEDATION. There are a variety of drugs available for sedation and relaxation of muscular spasms in tetanus. The drug of choice currently being used at our institution is diazepam. Complete paralysis of patients with curare has been advocated in the treatment of fulminating tetanus. 4 Significant sedation to control tetanospasms and associated periods of apnea must be utilized. Toxic dosages of the sedative medication must be carefully avoided. MAINTENANCE OF RESPIRATION. The cause of death in severe tetanus is often related to respiratory arrest. All patients with severe tetanus should have a tracheostomy. Equipment for respiratory assistance and controlled respiration if necessary should be available. Meticulous pulmonary toilet and specific antibiotic therapy of pulmonary infections of consequence must be implemented.
THE PREVENTION AND TREATMENT OF TETANUS IN THE BURN PATIENT
1281
SUPPORTIVE CARE. Many centers have recognized the meticulous supportive care that tetanus patients require, by establishing a tetanus treatment team. Nurse, neurologist, internist, surgeon, and anesthesiologist are usually included. In addition to this basic team, the dietitian, physical therapist, and respiratory physiologist make significant contributions to patient care. Attention to water balance, electrolyte replacement, renal function, ventilation, nutrition and prophylaxis of pulmonary or urinary tract infections are important facets of supportive care. To provide the best care of these critically ill patients a knowledgeable professional must be in 24 hour attendance.
SUMMARY Despite the availability of tetanus toxoid, an excellent vaccine for prophylaxis against tetanus, cases still occur in the United States. The case fatality ratio is high. The incidence of tetanus following burns is unknown, but the burn wound is an ideal portal of entry for tetanus infection. Adequate tetanus prophylaxis should be utilized in all patients presenting with burns according to each individual circumstance. Other measures of prophylaxis, including debridement and topical and parenteral antibiotics, should be considered.
REFERENCES 1. Altemeier, W. A., Culbertson, W. R., and Gonzalez, L. L.: Clinical experiences in the treatment of tetanus. Arch. Surg., 80:977, 1960. 2. Annual Supplement to Morbidity and Mortality Weekly Report. National Communicable Disease Center, Atlanta, Georgia, 1966. 3. Christensen, N. A., and Thurber, D. L.: Clinical experience with tetanus: 91 cases. Proc. Mayo Clin., 32:146,1957. 4. Christensen, N. A.: Treatment of the patient with severe tetanus. SURG. CLIN. N. AMER., 49:1183,1969. 5. Crandell, D. L., and Whitcher, C. E.: Control of neuromuscular manifestations of severe systemic tetanus. J.A.M.A., 72:15,1960. 6. Dietrich, H. F.: Tetanus in childhood with special reference to treatment. Amer. J. Dis. Children, 59:693,1940. 7. LaForce, M. F., Young, L. S., and Bennett, J. V.: New Eng. J. Med., 280:569,1969. 8. Mendelson, J. A., and Lindsey, D.: Sulfamylon (mafenide) and penicillin as expedient treatment of experimental massive open wounds. J. Trauma, 2:239,1962. 9. Monafo, W. W., Brentano, L., Gravens, D. L., Kempson, R., and Moyer, C. A.: Gas gangrene and mixed clostridial infections of muscle complicating deep thermal burns. Arch. Surg., 92:212,1966. 10. Risk of tetanus prophylaxis. Foreign letters. J.A.M.A., 174:181,1960. 11. Young, L. S.: Personal communication. 951 Court Avenue Memphis, Tennessee 38103