Management of Urban Tetanus

Symposium on Acute Medicine

Management of Urban Tetanus Albert E. Heurich, M.D.,* John C. M. Brust, M.D.,** and Ralph W. Richter, M.D. ***

The problem of drug addiction has brought with it a resurgence of tetanus,1 a disease only recently on its way to extinction. When encountered in the drug addict, the disease almost invariably occurs in its severest forin. The symptoms of tetanus may be masked in the narcotized patient or may be wrongly attributed to drug withdrawal. In both cases, therapy will be delayed and vital time lost. Tetanus is diagnosed by the clinical picture, bacteriologic confirmation being rare. Trismus and/or paraspinal rigidity are the most common presenting symptom. These may remain localized when the disease is mild or may spread over hours or days in the moderate and severe forms, with superimposed, severe, generalized muscular spasms lasting seconds or minutes. The presence or absence of convulsions has been used as a basis for clarifying tetanus,1s as shown in Table 1. Conditions that must be considered in the differential diagnosis of tetanus are shown in Table 2. Prior to the use of controlled ventilation, the majority of deaths were respiratory.2.4 The introduction of controlled ventilation has reduced the number of deaths from respiratory causes. Cardiac disturbances are now the major mortality factor.12. 13. 15 The following regimen is based on experience with 34 patients treated by a team from the Department of Neurology, Medicine, Anesthesiology, Nursing and Surgery at Harlem Hospital Center, and 14 patients treated by the Department of Medicine at the Kings County "Instructor in Medicine and Director, Respiratory Care Unit. Kings County Hospital, State University of New York, Downstate Medical Center, Brooklyn •• Associate Director, Neurology Department, Harlem Hospital Center; Assistant Professor of Neurology, Columbia University College of Physicians and Surgeons, New York ···Director, Neurology Department, Harlem Hospital Center;· Associate Professor of Neurology, Columbia University College of Physicians and Surgeons, New York; Consultant on Central Nervous System Disease, Bureau of Infectious Disease Control, New York City Department of Health Supported in part by Grant No. 1 R01 MH 20490-01 from the National Institutes of Mental Health.

Medical Clinics of North America - Vo!. 57, No. 6, November 1973

1373

1374

ALBERT

E.

HEURICH, JOHN

Table 1. MILD

Hyperirritability Trismus Risus sardonicus Paraspinal muscle rigidity Opisthotonus No generalized convulsions

C. M.

BRUST, AND RALPH

W.

RICHTER

Grading of Tetanus MODERATE

SEVERE

Occasional generalized convulsions

Frequent generalized convulsions

Hospital from 1964 to 1971. Where modes of therapy differ between the two institutions, it is so stated.

IMMEDIATE MEASURES Immediately after the diagnosis of tetanus is made, the patient should be transferred to an intensive care facility which has personnel trained in both respiratory care and cardiac resuscitation. The most immediate life-threatening condition in the early stages of tetanus is the development of a tetanic seizure and respiratory arrest. During the initial assessment of the patient, seizures can be immediately treated by keeping an intravenous line open at all times and administering succinylcholine (80 mg). Since paralysis follows administration of succinycholine an oral airway, Ambu Bag, suction equipment, and oxygen must be available to ventilate the patient. This approach is most practical in the tetanus patient in whom oral trismus may delay orotracheal intubation, for it permits intubation and tracheostomy to be done as elective proceduressomething to be desired when prolonged controlled respiration will be required.

WOUND MANAGEMENT Immunotherapy and Wound Care With provision having been made for any immediate respiratory emergency, management can next be focused on immunotherapy. Circulating toxin and toxin that is present in wound sites must be inactivated Table 2.

Differential Diagnosis of Tetanus

Drug reaction (phenothiazines) Drug withdrawal Meningitis Subarachnoid hemorrhage Peritonsillar abscess Epilepsy

Temporomandibular joint disease Hypoca1cemic tetany Retroperitoneal hemorrhage Strychnine poisoning Decerebrate posturing

MANAGEMENT OF URBAN TETANUS

1375

before further binding to tissue sites occurs. Six to ten thousand units of human tetanus immune globulin (Hu-Tet, Hyper-Tet) should be administered intramuscularly in the buttocks at the time of admission so that substantial circulating levels will be present when debridement is undertaken. Part of the immune globulin may also be infiltrated in the wound site. Debridement may be performed 1 to 2 hours after administration of the immune globulin and institution of antibiotic therapy. Abscesses should be irrigated with hydrogen peroxide and necrotic tissue widely excised. Frequently in the addict, multiple small indurated pockets of infection are encountered which make extensive debridement impossible. Tetanus originating in puncture wounds is associated with a higher mortality.17 This, together with the difficulty of obtaining adequate debridement in the addict, may account for the high mortality in these patients. The half life of immune globulin is 30 days, and thus it is necessary to initiate active immunization with tetanus toxoid for more permanent protection. During the first week, 0.5 cc. of alum-precipitated tetanus toxoid is given intramuscularly in a site distant from that used for the administration of immune globulin. Immune globulin activity is unaffected by toxoid, since the latter is slowly absorbed from the injection site. An additional 0.5 cc. is given again at 6 weeks and at 6 months. Infection with tetanus does not confer immunity against subsequent infection. Lasting active immunity is acquired only by administration of toxoid. In the nonimmunized individual, active immunity is demonstrable in the serum 7 to 10 days after the second injection.

Antibiotics Clostridium tetani is sensitive to penicillin, which is the drug of choice for eradication of the organism. Ten million units daily has proven adequate in our experience. In individuals with penicillin allergy, tetracycline can be given intramuscularly every 4 hours in 500 mg. doses. Antibiotic therapy will not alter the course of the disease, which is basically a reflection of the toxin already bound to tissue sites. Only by eradicating the organism can further toxin production be prevented. An outline of antibiotic therapy in tetanus in included in Table 3. MANAGEMENT OF VENTILATION During the initial course of the disease, the major problem is usually one of ventilation. Muscular rigidity can impair pulmonary gas exchange by three mechanisms. First, oropharyngeal muscle involvement can prevent normal swallowing and cause not only obstruction of the upper airways by mucous secretions, but also aspiration of secretions. Second, tetanus frequently causes generalized rigidity of the muscles, distinct from tetanospasms limiting respiratory excursion, and leading to atelectasis with hypoxemia and even hypercarbia. Third, during tetanic convulsions, the chest wall becomes fixed in inspiration or expiration, ventilation ceases, and during this time mechanical ventilation is ineffectual until the tetanic muscles relax.

1376

ALBERT

Table 3.

E.

HEURICH, JOHN

C. M.

BRUST, AND RALPH

W.

RICHTER

Program for the Treatment of Tetanus

Immunotherapy

6000 to 10000 units of human tetanus immune globin IM Tetanus toxoid 0.5 cc. IM at 1 and 6 weeks and at 6 months 10 million units daily aqueous penicillin IV

Antibiotic therapy

If penicillin allergy exists then tetracycline 500 mg. q 4 h IM Wound care

Debridement 1 to 2 hours following initial antibiotic therapy and immunotherapy Exposure of wounds tohydrogen peroxide Sodium luminal, 100 to 200 mg. IV or IM q 3-4 h plus

Muscle relaxation

Chlorpromazine hydrochloride, 75 to 100 IM q 3-4 h Morphine sulfate, 5-35 mg. IV or IM q 3-4 h Paraldehyde, 2.5 cc. IM prn Diazepam, 10 mg. IV q 1-3 h pm ~

Curare, 9 to 15 mg. IV over 10 minutes every hour for intractable spasms Succinylcholine for emergency in intractable spasm, not for maintenance If morphine not used, methadone 10 to 15 mg. IM q 4 h

to prevent narcotic withdrawal

Respiratory management

Table 4.

Tracheostomy for all but mild tetanus Intermittent positive pressure breathing with a volumecycled respirator

Tracheal and Respiratory Care Requirements

An intensive care unit with nurses trained in respiratory care Monitor respirator pressure q 1/2 h, minute ventilation q 1 h, and blood gases bid Rotation of the patient from side to side q 2 h and chest percussion bid Frequent suctioning using disposable gloves and sterile catheters Tracheal culturing twice a week Frequent sterilization of respirators Leaving initial tracheal cannula in until a tract has been established and then changing cannulas every 48 hours U se flexible tracheostomy tubes and low pressure cuff balloons

MANAGEMENT OF URBAN TETANUS

1377

We have never encountered mild tetanus in drug addicts. The apparent initial mild symptomatology in these patients has, in our experience, been in reality moderate or severe tetanus masked by the addicting drugs. For this reason, we feel that early tracheostomy is indicated in every drug addict presenting with tetanus. Additional indications for tracheostomy are inability to effectively clear oropharyngeal secretions and a decrease in arterial oxygen saturation below 90 per cent, an arterial P0 2 less than 70 mm. Hg, or an arterial Pco 2 greater than 50 mm. Hg owing to muscle spasm. Long term mechanical ventilation requires meticulous tracheal toileting if the complications of tracheostomy are to be avoided. Some of the more important points in such care are outlined in Table 4. Arterial blood gases should be monitored at least twice daily and more often if necessary. Continuous monitoring of minute ventilation is desirable, but where this cannot be done then at least hourly monitoring should be obtained. Monitoring of respiratory pressures can be an excellent guide to early changes in the respiratory system. The total pressure generated by the respirator during a respiratory cycle will be a sum of the pressures required to overcome airway resistance, to inflate the lung, and to overcome chest and abdominal wall resistance. An increasing pressure requirement to deliver the same volume will signal the need for suctioning of secretions which increase airway resistance, for periodic hyperinflation to correct low lung compliance related to atelectasis, or for increased muscle relaxation because of increasing chest and abdominal wall rigidity. Variation in the latter imposes the requirement that only volume-cycled respirators be used, to insure delivery of constant volumes. Numerous sedatives have been recommended to control the often lethal tetanospasms; these include barbiturates ,5 chlorpromazine,1 paraldehyde,9 mephenesin,l chloral hydrate,13 diazepam,3 and morphine. 6 Our own clinical experience supports our impression that no one sedative or combination is preferable to any other. At Kings County Hospital it has been usual to begin with morphine sulfate, 5 to 35 mg., plus phenobarbital, 50 to 200 mg. intramuscularly or intravenously every 3 to 4 hours. At Harlem Hospital, phenobarbital plus chlorpromazine, 75 to 100 mg., are the usual initial agents, with methadone, 10 to 15 mg. every 4 to 6 hours, given to addicts. If spasms continue despite maximal doses of these agents, paraldehyde or diazepam is added as described in Table 3. If spasms still persist, the patient is curarized,s using the lowest dose necessary to abolish spasms, usually around 9 to 15 mg. given intravenouslyover 10 minutes every hour, with gradual tapering over the next days or weeks. The usual duration of such therapy is 2-3 weeks. Higher doses of curare can cause hypotension; we continue one or two of the above sedatives in curarized patients in order to use minimal curare doses, and also to depress the patient's level of awareness. The advantage of curare is that it permits total muscle relaxation. The disadvantages are that coughing is abolished and the patient cannot respond should mechanical failure of the respirator occur. Vigorous postural drainage and suctioning and extremely close observations are therefore essential, plus physical therapy to prevent contractures of the muscles.

1378

ALBERT

E.

HEURICH, JOHN

C. M.

BRU5T, AND RALPH

W.

RICHTER

CARDIAC MANAGEMENT Sudden cardiac standstill is currently the major cause of death in tetanus in this country, occurring during the second or third week in the course of the disease. The mechanism is not well understood. Blood gases are usually normal, and so hypoxemia and acid-base disturbance cannot be implicated. While tachycardia and bradycardia are frequently encountered, other electrocardiographic changes are less common. Blood pressure shows marked lability, with extremes of both hypertension and hypotension. Three types of arresthave been encountered. First and most frequent is sudden electrical asystole. The only premonitory sign is sudden marked blood pressure lability shortly before the arrest. This type usually responds very rapidly to usual resuscitative measure of external cardiac massage and intracardiac instillation of 2 ml. of 1: 10,000 epinephrine and 4 ml. of 10 per cent calcium chloride. Second and relatively rare is ventricular fibrillation, which usually occurs only in the presence of hypoxemia. Third and not infrequent is sudden mechanical asystole with continued normal electrical systole. This type of cardiac disturbance responds poorly to all resuscitative measures. Attempts to prevent asystole by the use of cardiac pacemakers have been unsuccessful. Elevated catecholamine levels have been demonstrated during the acute phase of tetanus, and it has been postulated that the cardiac arrest of tetanus may be the result of prolonged exposure of the heart to these catecholamines. ll . 12 Some workers have advocated the use ofalphaand/or beta adrenergic blocking agents. [4 At Kings County Hospital propranolol has been given via nasogastric tube in doses of 10 mg. four times daily to patients in whom the cardiac rate remains persistently above 100 beats per minute. At Harlem Hospital, on the other hand, those patients who arrested without hypoxia at the time have all showed either sudden cardiac standstill or bradycardia progressing to a standstill. Propranolol has therefore not been used, pending the availability of more data as to its efficacy. Other measures to be observed in cardiac management are shown in Table 5. Table 5.

Cardiovascular Management in Tetanus

ABNORMALITY

Blood pressure lability Tachycardias

PREVENTION AND THERAPY

Adequate daily fluid replacement Maintenance of normal blood gases Minimize respirator inspiratory time Maintain normal electrolyte and acid· base balance Investigate for infection, embolism, hemorrhage Optional: Give propranolol, 10 mg. qid via nasogastric tube for persistent cardiac rates over 100 beats per minute

Bradycardia

Minimize reflex vagal stimulation (avoid prolonged suctioning and monitor EKG during suctioning)

MANAGEMENT OF URBAN TETANUS

1379

METABOLIC MANAGEMENT Perhaps related to the elevated catecholamines, tetanus is associated with a hypermetabolism that may require up to 7000 calories daily. A 30 lb. weight loss during the 3 weeks of the acute phase of the disease is not infrequent when the caloric demands cannot be met. Routine parenteral therapy is insufficient to meet these needs, and at Harlem Hospital hyperalimentation via a subclavian catheter has been used, as described elsewhere. 16 At Kings County Hospital the patient has usually received intravenous glucose during the first week and then nasogastric tube feedings have been added during the subsequent course. Vitamins, especially thiamine, vitamin C and vitamin K, iron, calcium, and magnesium are included. Conventional tracheal tube cuffs require periodic deflation to prevent tracheal pressure necrosis, and carried with it the risk of aspiration. This hazard has been avoided by the use of intravenous hyperalimentation. Newer pressure cuffs, where they are available, allow prolonged inflation and thus minimize the possibility of aspiration, making practical the use of nasogastric feeding. Metabolic requirements can be met, and gastrointestinal bleeding can be prevented and monitored.

MANAGEMENT OF OTHER COMMONLY ENCOUNTERED PROBLEMS Hyperthermia is common during the acute course of tetanus, related both to the presence of infection and to the severity of tetanic muscle contractions. The temperature in one of our patients rose to 109° F. Hyperthermia has responded dramatically to adequate muscle relaxation, and heat dissipation has been facilitated by the use of a combination of 50 mg. of meperidine, 25 mg. of thorazine, and 25 mg. of phenergan given intravenously. Even in the absence of hyperthermia, periodic profuse sweating is common and insensible water loss can be considerable, causing dehydration and contributing to hyperthermia. The sudden spasmodic convulsions of tetanic muscle require that all pharmacologic agents be delivered via a central venous line and that the line be checked for location of the catheter tip if such agents fail to produce an effect. A sudden tetanic convulsion can force the catheter tip through the vessel wall, making delivery of relaxant agents ineffectual. Gastrointestinal bleeding is common in patients receiving mechanical ventilation via tracheostomies. Lower gastrointestinal tract bleeding may be secondary to fecal impaction, and it is useful to clear the intestine with suppository laxatives. Upper gastrointestinal tract bleeding is a more serious problem, and we have attempted to prevent it by giving milk and antacids via nasogastric tube. Hypoprothrombinemia may be seen if vitamin K is not routinely included in the patient's therapeutic regimen. Myopathy in tetanus has only recently been recognized, but may play an important role during the recovery phase. The toxin produces muscle damage during the first 2 to 3 weeks of the disease, often leaving a patient with marked weakness of both respiratory and peripheral mus-

1380

ALBERT

E.

HEURICH, JOHN

C. M.

BRUST, AND RALPH

W.

RICHTER

cles. The cough reflex may be ineffective, and the patient can easily asphyxiate from sudden airway obstruction by a mucous plug. Thus the transition from mechanical to self-sustained ventilation must be made slowly during the recovery phase, with the patient initially off the respirator for short periods of 15 to 30 minutes in the daytime, this time interval being gradually increased using arterial blood gas and force vital capacity measurements as guidelines for the rate of weaning from the respirator. The arterial P0 2 should be above 60 mm. Hg on room air with a normal arterial Pco 2 , and the patient must have a vital capacity which is three times his predicted normal tidal volume before one considers complete cessation of mechanical ventilation. Metabolic alkalosis has been encountered during the third to fourth week of the disease in some of our patients. If urinary electrolytes are monitored, one finds progressively decreasing sodium concentrations and increasing potassium concentrations. The alkalosis is readily reversed with spironolactone. This effect suggests that hyperaldosteronism is responsible for the metabolic alkalosis. A causal relationship between alkalosis and cardiac arrhythmias has been demonstrated in other clinical conditions, and the additive effect of hypokalemia to muscles already functionally impaired by tetanus and/or prolonged paralysis can further endanger respiration and prolong recovery. Our patients have been relatively young, and perhaps for this reason thromboembolism has been rare. It is more common in series reporting on tetanus in the non-addict population, and some authors have recommended routine anticoagulation therapy.12 Other problems that have been reported in tetanus include hyperglycemia with and without ketosis, the latter being unresponsive to insulin therapy; anemia, which has not been well studied but which is associated with a shortened red cell survival; hypoalbuminemia, which has been attributed to the marked negative caloric balance that results in many of these patients; paralytic ileus and tracheal stenosis, sometimes occurring several weeks after a tracheostomy has closed. In conclusion, tetanus challenges the skills of several disciplines, including neuropharmacology, respiratory physiology, cardiology, physiotherapy, and intensive care nursing, and a team approach is the best assurance of a successful outcome.

ACKNOWLEDGMENTS

Physicians who assisted in preparing parts of the treatment protocol included: Herbert G. Cave, M.D., Director, Department of Anesthesiology, Harlem Hospital Center; Kentauro Tseuda, M.D., Chief, Respiratory Intensive Care, Harlem Hospital Center; Pearl Foster, M.D., Visiting Physician, Department of Medicine, Harlem Hospital Center; Mohammed H. Parsa, MD., Department of Surgery, Harlem Hospital Center; Harold A. Lyons, M.D., Professor of Medicine, Downstate Medical Center, New York State University; John A. Adrizzo, M.D., Department of Medicine, Kings County Hospital, and Marvin D. Anderson, M. D., Department of Medicine, Henry Ford Hospital, Detroit, Michigan.

MANAGEMENT OF URBAN TETANUS

1381

REFERENCES 1. Adriani, J., and Kerr, M.: Mephenesin and the combination of mephenesin and chlorpromazine in the management of tetanus: report of 100 cases. Southern Med. J., 48: 858-862, 1955. 2. Altemeier, W. A., Culbertson, W. R., and Gonzalez, L. L.: Clinical experiences in the treatment of tetanus. Arch. Surg., 80:977-985, 1960. 3. Bacon, A. K.: Diazepam in tetanus. Brit. Med. J., 2:646-648, Dec. 1, 1968. 4. Blatt, A. N., and Anwihar, A. K.: Tetanus, a review of 888 cases. J. Ind. Med. Assoc., 38: 71-75, 1962. 5. Box, Q. T.: The treatment of tetanus. Pediatrics, 33:872-877, 1964. 6. Brown, H.: Tetanus. J.A.M.A. 204:614-616, May, 1968. 7. Cherubin, C. E.: Epidemiology of tetanus in narcotic addicts. N.Y. State J. Med., 70: 267-277, 1970. 8. Christensen, N. A., and Thurber, D. L.: Current treatment of clinical tetanus. Modern Treatment, 5:729-757, 1968. 9. Cole, L., and Youngman, H.: Treatment of tetanus. Lancet, 1: 1017-1020, May 17, 1969. 10. Ebisawa, I., and Matsukura, M.: Pulmonary and muscular changes in tetanus. Jap. J. Exper. Med., 38:27-36, 1968. 11. Keilty, S. R., Gray, R. C., Dundee, J. W., and McCullough, H.: Catecholamine levels in severe tetanus. Lancet, 2: 195, 1968. 12. Kerr, J H., Corbett, J. L., Prys-Roberts, C., et al.: Involvement of the sympathetic nervous system in tetanus, studies on 82 cases. Lancet, 2:236-241,1968. 13. Kloetzel, K.: Clinical patterns in severe tetanus. J.A.M.A., 185:559-567, 1963. 14. Lazar, M.: Zur Pathogenese and Therapie des Tetanus. Schweiz. Med. Wschr., 100: 1486-1491,1970. 15. Montgomery, R. D.: Cause of death in tetanus. W. 1. Med. J., 10:84,1961. 16. Parsa, M. D., Anderson, M. D., and Richter, R. W.: Central venous nutrition in severe tetanus. Arch. Surg., 105:420-423, 1972. 17. Patel, J. C., and Mehta, B. C.: Tetanus, a study of2007 cases. Ind. J. Med. Sci., 17:791-811, 1963. 18. Pichlmayr, I.: Der Wunderstarrkrampf. Miinchener Med. Wschr., 24:1325-1333, 1969. Department of Neurology Harlem Hospital Center 135th Street and Lenox Avenue New York, New York 10037 (Dr. Richter)