Pharmacological management of tetanus: an evidence-based review

Chaturaka Rodrigo, Deepika Fernando, Senaka Rajapakse, Chaturaka Rodrigo, Deepika Fernando, Senaka Rajapakse

Abstract

Tetanus is becoming rarer in both industrialized and developing nations due to an effective vaccination program. In 2010, the World Health Organization estimated there was a 93% reduction in newborns dying from tetanus worldwide, compared to the situation in the late 1980s. Due to its rarity, many diagnostic delays occur as physicians may not consider the diagnosis until the manifestations become overt. Without timely diagnosis and proper treatment, severe tetanus is fatal (mortality is also influenced by the comorbidities of the patient). The principles of treating tetanus are: reducing muscle spasms, rigidity and autonomic instability (with ventilatory support when necessary); neutralization of tetanus toxin with human antitetanus immunoglobulin or equine antitetanus sera; wound debridement; and administration of antibiotics to eradicate locally proliferating bacteria at the wound site. It is difficult to conduct trials on different treatment modalities in tetanus due to both logistical and ethical reasons. However, it is imperative that physicians are aware of the best evidence-based treatment strategies currently available to improve the outcome of patients. This review concentrates on analyzing the current evidence on the pharmacological management of tetanus.

References

    1. Chalya PL, Mabula JB, Dass RM, Mbelenge N, Mshana SE, Gilyoma JM. Ten-year experiences with tetanus at a tertiary hospital in Northwestern Tanzania: a retrospective review of 102 cases. World J Emerg Surg. 2011;6:20. doi: 10.1186/1749-7922-6-20.
    1. Brauner JS, Vieira SR, Bleck TP. Changes in severe accidental tetanus mortality in the ICU during two decades in Brazil. Intensive Care Med. 2002;28:930–935. doi: 10.1007/s00134-002-1332-4.
    1. Joshi S, Agarwal B, Malla G, Karmacharya B. Complete elimination of tetanus is still elusive in developing countries: a review of adult tetanus cases from referral hospital in Eastern Nepal. Kathmandu Univ Med J. 2007;5:378–381.
    1. Chukwubike OA, God'spower AE. A 10-year review of outcome of management of tetanus in adults at a Nigerian tertiary hospital. Ann Afr Med. 2009;8:168–172.
    1. Center for Disease Control. Tetanus surveillance - United States, 2001–2008. MMWR. 2011;60:365–369.
    1. Chaudhry R, Dhawan B, Mohanty S, Dey AB. Tetanus in the elderly: a forgotten illness. Lancet. 1805;2001:357.
    1. Immunization surveillance, assessment and monitoring: tetanus. .
    1. Maternal and Neonatal Tetanus (MNT) elimination: the initiative and challenges.
    1. Maternal and Neonatal Tetanus (MNT) elimination: progress towards global MNT elimination. .
    1. Abrutyn E. In: Harrison's Principles of Internal Medicine. 14. Isselbacher KL, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL, Longo DL, Hauser SL, editor. New York: McGraw Hill; 1998. Tetanus; pp. 901–904.
    1. Gilligan JE, Lawrence JR, Clayton D, Rowland R. Tetanus and the evolution of intensive care in Australia. Crit Care Resusc. 2012;14:316–323.
    1. Chun P, Ying-Zi H, Yi Y, Hai-Bo Q. Titration of high dose sedation is effective in severe tetanus: a case report. Cases J. 2009;2:6865. doi: 10.4076/1757-1626-2-6865.
    1. Firth PG, Solomon JB, Roberts LL, Gleeson TD. Airway management of tetanus after the Haitian earthquake: new aspects of old observations. Anesth Analg. 2011;113:545–547.
    1. Petitjeans F, Turc J, Coulet O, Puidupin M, Eve O, Benois A. The use of boluses of propofol for the management of severe tetanus in a child. Trop Doct. 2009;39:52–53. doi: 10.1258/td.2008.080236.
    1. Norredam K, Hainau B. Treatment of tetanus in tropical Africa: a comparison between a barbiturate and diazepam in the treatment of non-neonatal tetanus. Ann Soc Belges Med Trop Parasitol Mycol. 1970;50:239–246.
    1. Joseph A, Pulimood BM. Use of diazepam in tetanus - a comparative study. Indian J Med Res. 1978;68:489–491.
    1. Okoromah CN, Lesi FE. Diazepam for treating tetanus. Cochrane Database Syst Rev. 2004;CD003954
    1. Orko R, Rosenberg PH, Himberg JJ. Intravenous infusion of midazolam, propofol and vecuronium in a patient with severe tetanus. Acta Anaesthesiol Scand. 1988;32:590–592. doi: 10.1111/j.1399-6576.1988.tb02791.x.
    1. Peduto VA, Pisanu GM, Piga M. Midazolam, propofol, and clonidine for sedation and control of autonomic dysfunction in severe generalized tetanus. Minerva Anestesiol. 1993;59:171–178.
    1. Guzman JA, Guerrero A, Lopez-Obispo M, Artacho R, de la Cruz JIG, Alemany F, Sanchez-Lopez F. Continuous perfusion with midazolam and atracurium in a patient with severe tetanus. Rev Esp Anestesiol Reanim. 1993;40:375.
    1. Thwaites CL, Yen LM, Loan HT, Thuy TT, Thwaites GE, Stepniewska K, Soni N, White NJ, Farrar JJ. Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial. Lancet. 2006;368:1436–1443. doi: 10.1016/S0140-6736(06)69444-0.
    1. Gyasi HK, Fahr J, Kurian E, Mathew M. Midazolam for prolonged intravenous sedation in patients with tetanus. Middle East J Anesthesiol. 1993;12:135–141.
    1. Bhagwanjee S, Bosenberg AT, Muckart DJ. Management of sympathetic overactivity in tetanus with epidural bupivacaine and sufentanil: experience with 11 patients. Crit Care Med. 1999;27:1721–1725. doi: 10.1097/00003246-199909000-00004.
    1. Hahn BJ, Erogul M, Sinert R. Case report of tetanus in an immunized, healthy adult and no point of entry. J Emerg Med. 2004;27:257–260. doi: 10.1016/j.jemermed.2004.03.015.
    1. Bunch TJ, Thalji MK, Pellikka PA, Aksamit TR. Respiratory failure in tetanus: case report and review of a 25-year experience. Chest. 2002;122:1488–1492. doi: 10.1378/chest.122.4.1488.
    1. Karanikolas M, Velissaris D, Marangos M, Karamouzos V, Fligou F, Filos KS. Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series. J Med Case Reports. 2010;4:100. doi: 10.1186/1752-1947-4-100.
    1. Mathew PJ, Samra T, Wig J. Magnesium sulphate for treatment of tetanus in adults. Anaesth Intensive Care. 2010;38:185–189.
    1. The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet. 1995;345:1455–1463.
    1. Blake JA. The use of magnesium sulphate in the production of anaesthesia and in the treatment of tetanus. Surg Gynecol Obstetrics. 1906;2:541–550.
    1. James MFM, Manson EDM. The use of magnesium sulphate infusions in the management of very severe tetanus. Intensive Care Med. 1985;11:5–12.
    1. Attygalle D, Rodrigo N. Magnesium as first line therapy in the management of tetanus: a prospective study of 40 patients. Anaesthesia. 2002;57:811–817.
    1. Attygalle D. Magnesium sulphate in the management of severe tetanus averts artificial ventilation and sedation. Ceylon Med J. 1996;41:120.
    1. Thwaites CL, Yen LM, Cordon SM, Thwaites GE, Loan HT, Thuy TT, White NJ, Soni N, Macdonald IA, Farrar JJ. Effect of magnesium sulphate on urinary catecholamine excretion in severe tetanus. Anaesthesia. 2008;63:719–725. doi: 10.1111/j.1365-2044.2008.05476.x.
    1. Thwaites CL, Yen LM, Cordon SM, Binh NTTN, Nga N, White NJ, Soni N, MacDonald IA, Farrar JJ. Urinary catecholamine excretion in tetanus. Anaesthesia. 2006;61:355–359. doi: 10.1111/j.1365-2044.2006.04580.x.
    1. Ali G, Kamal M, Khan AN. Comparison of the efficacy of magnesium sulphate and diazepam in the control of tetanus spasm. J Postgraduate Med Inst. 2011;25:106–110.
    1. Osalusi BS, Ogun SA, Ogunniyi A, Kolapo KO. Comparison of the efficacy of magnessium sulphate and diazepam in the control of tetanus spasms. Sci Res Essays. 2008;3:571–576.
    1. Rodrigo C, Samarakoon L, Fernando D, Rajapakse S. A meta-analysis of magnesium for tetanus. Anaesthesia. 2012;67:1370–1374. doi: 10.1111/anae.12020.
    1. Attygalle D, Rodrigo N. New trends in the management of tetanus. Expert Rev Anti Infect Ther. 2004;2:73–84. doi: 10.1586/14787210.2.1.73.
    1. Deibert E, Bhardwaj A, Staats PS, Ulatowski JA. Chronic intrathecal baclofen administration for the treatment of severe generalized tetanus via a synchromed infusion pump. Neuromodulation. 1998;1:2–5. doi: 10.1111/j.1525-1403.1998.tb00024.x.
    1. Muller H, Borner U, Zierski J, Hempelmann G. Intrathecal baclofen for treatment of tetanus-induced spasticity. Anesthesiology. 1987;66:76–79. doi: 10.1097/00000542-198701000-00016.
    1. Pellanda A, Caldiroli D, Vaghi GM, Bonelli S. Treatment of severe tetanus by intrathecal infusion of baclofen. Intensive Care Med. 1993;19:59.
    1. Boots RJ, Lipman J, O'Callaghan J, Scott P, Fraser J. The treatment of tetanus with intrathecal baclofen. Anaesth Intensive Care. 2000;28:438–442.
    1. Saissy JM, Demaziere J, Vitris M, Seck M, Marcoux L, Gaye M, Ndiaye M. Treatment of severe tetanus by intrathecal injections of baclofen without artificial ventilation. Intensive Care Med. 1992;18:241–244. doi: 10.1007/BF01709840.
    1. Cabrerizo Garcia JL, Homs Gimeno CA, Pacheco Arancibia G, Zalba Etayo B, Sanchez Marteles M. Treatment of tetanus with intrathecal baclofen. An Med Interna. 2008;25:372–373.
    1. Engrand N, Vilain G, Rouamba A, Benhamou D. Value of intrathecal baclofen in the treatment of severe tetanus in the tropical milieu. Med Trop (Mars) 2000;60:385–388.
    1. Francois B, Clavel M, Desachy A, Vignon P, Salle JY, Gastinne H. Continuous intrathecal injection of baclofen in generalized tetanus. A therapeutic alternative. Presse Med. 1997;26:1045–1047.
    1. Saissy JM, Raux O, Gohard R, Diatta B. Severe tetanus and intrathecal baclofen. Ann Fr Anesth Reanim. 1990;9:183–184. doi: 10.1016/S0750-7658(05)80058-9.
    1. Vitris M, Saissy JM, Demaziere J, Seck M, Ndiaye M, Gaye N, Marcoux L. Treatment of severe tetanus by repeated intrathecal injections of baclofen. Dakar Med. 1991;36:28–29.
    1. Solsona M, Miro G, Yebenes JC, Balanzo X, Almirall J, Mauri M. Tetanus treated with continuous baclofen intrathecal perfusion] Med Intensiva. 2007;31:204–206. doi: 10.1016/S0210-5691(07)74807-6.
    1. Dressnandt J, Konstanzer A, Weinzierl FX, Pfab R, Klingelhofer J. Intrathecal baclofen in tetanus: four cases and a review of reported cases. Intensive Care Med. 1997;23:896–902. doi: 10.1007/s001340050429.
    1. Brock H, Moosbauer W, Gabriel C, Necek S, Bidal D. Treatment of severe tetanus by continuous intrathecal infusion of baclofen. J Neurol Neurosurg Psychiatry. 1995;59:193–194. doi: 10.1136/jnnp.59.2.193.
    1. Santos ML, Mota-Miranda A, Alves-Pereira A, Gomes A, Correia J, Marcal N. Intrathecal baclofen for the treatment of tetanus. Clin Infect Dis. 2004;38:321–328. doi: 10.1086/380636.
    1. Thomas RM, Bellamy MC. Tetanus in a subcutaneous drug abuser: ineffectiveness of intrathecal baclofen. Anaesth Intensive Care. 2006;34:811–815.
    1. Checketts MR, White RJ. Avoidance of intermittent positive pressure ventilation in tetanus with dantrolene therapy. Anaesthesia. 1993;48:969–971.
    1. Ortega Cerda JJ, Portela Ortiz JM, Ramirez Acosta J. Successful treatment of tetanus with dantrolene (author's transl) Rev Invest Clin. 1981;33:53–55.
    1. Sternlo JE, Andersen LW. Early treatment of mild tetanus with dantrolene. Intensive Care Med. 1990;16:345–346. doi: 10.1007/BF01706370.
    1. Rocha H. Myo-relaxant action of sodium dantrolene in the treatment of tetanus. Rev Inst Med Trop Sao Paulo. 1975;17:257–262.
    1. Obanor O, Osazuwa HO, Amadasun JE. Ketamine in the management of generalised cephalic tetanus. J Laryngol Otol. 2008;122:1389–1391. doi: 10.1017/S0022215107001223.
    1. García-García A, Gandara-Rey JM, Crespo-Abelleira A, Jorge-Barreiro J. Botulinum toxin A for treating muscular contractures in cephalic tetanus. Br J Oral Maxillofac Surg. 2007;45:573–575. doi: 10.1016/j.bjoms.2006.08.002.
    1. Herrman H, Braekhus A, Aaserud O, Aukrust P, Stubhaug A, Hassel B. Early treatment of tetanus-induced trismus with botulinum toxin A. Anesth Analg. 2008;106:1591. doi: 10.1213/ANE.0b013e31816a30f0.
    1. Gregorakos L, Kerezoudi E, Dimopoulos G, Thomaides T. Management of blood pressure instability in severe tetanus: the use of clonidine. Intensive Care Med. 1997;23:893–895. doi: 10.1007/s001340050428.
    1. Dolar D. The use of continuous atropine infusion in the management of severe tetanus. Intensive Care Med. 1992;18:26–31. doi: 10.1007/BF01706422.
    1. Girgin NK, Iscimen R, Gurbet A, Kahveci F, Kutlay O. Dexmedetomidine sedation for the treatment of tetanus in the intensive care unit. Br J Anaesth. 2007;99:599–600.
    1. Dundee JW, Morrow WF. Labetalol in severe tetanus. Br Med J. 1979;1:1121–1122. doi: 10.1136/bmj.1.6171.1121.
    1. Domenighetti GM, Savary G, Stricker H. Hyperadrenergic syndrome in severe tetanus: extreme rise in catecholamines responsive to labetalol. Br Med J (Clin Res Ed) 1984;288:1483–1484. doi: 10.1136/bmj.288.6429.1483.
    1. Hanna W, Grell GA. Oral labetalol in the management of the sympathetic overactivity of severe tetanus. South Med J. 1980;73:653–654. doi: 10.1097/00007611-198005000-00030.
    1. Wesley AG, Hariparsad D, Pather M, Rocke DA. Labetalol in tetanus, The treatment of sympathetic nervous system overactivity. Anaesthesia. 1983;38:243–249.
    1. Esslinger P, Kistler W, Berger TM. Severe autonomic dysfunction in an 11-year-old girl with generalised tetanus. Eur J Pediatr Surg. 2003;13:209–212.
    1. Beards SC, Lipman J, Bothma PA, Joynt GM. Esmolol in a case of severe tetanus. Adequate haemodynamic control achieved despite markedly elevated catecholamine levels. S Afr J Surg. 1994;32:33–35.
    1. Rocke DA, Wesley AG, Pather M, Calver AD, Hariparsad D. Morphine in tetanus - the management of sympathetic nervous system overactivity. S Afr Med J. 1986;70:666–668.
    1. Buchanan N, Cane RD, Wolfson G, De Andrade M. Autonomic dysfunction in tetanus: the effects of a variety of therapeutic agents, with special reference to morphine. Intensive Care Med. 1979;5:65–68. doi: 10.1007/BF01686048.
    1. Sun S, Dolar D, Ozenc E. Intrathecal morphine in tetanus. Br J Anaesth. 1982;54:699–700.
    1. Jahan K, Ahmad K, Ali MA. Effect of ascorbic acid in the treatment of tetanus. Bangladesh Med Res Counc Bull. 1984;10:24–28.
    1. Hemila H, Koivula TT. Vitamin C for preventing and treating tetanus. Cochrane Database Syst Rev. 2008;CD006665
    1. Sun KO, Chan YW, Cheung RT, So PC, Yu YL, Li PC. Management of tetanus: a review of 18 cases. J R Soc Med. 1994;87:135–137.
    1. Miranda-Filho Dde B, Ximenes RA, Barone AA, Vaz VL, Vieira AG, Albuquerque VM. Randomised controlled trial of tetanus treatment with antitetanus immunoglobulin by the intrathecal or intramuscular route. BMJ. 2004;328:615. doi: 10.1136/bmj.38027.560347.7C.
    1. Ahmad A, Qaisar I, Naeem M, Mazhar AU, Ashfaq M. Intrathecal anti-tetanus human immunoglobulin in the treatment of neonatal tetanus. J Coll Physicians Surg Pak. 2011;21:539–541.
    1. Geeta MG, Krishnakumar P, Mathews L. Intrathecal tetanus immunoglobulins in the management of tetanus. Indian J Pediatr. 2007;74:43–45. doi: 10.1007/s12098-007-0025-y.
    1. Abrutyn E, Berlin JA. Intrathecal therapy in tetanus, A meta-analysis. JAMA. 1991;266:2262–2267. doi: 10.1001/jama.1991.03470160094039.
    1. Kabura L, Ilibagiza D, Menten J, Van den Ende J. Intrathecal vs. intramuscular administration of human antitetanus immunoglobulin or equine tetanus antitoxin in the treatment of tetanus: a meta-analysis. Trop Med Int Health. 2006;11:1075–1081. doi: 10.1111/j.1365-3156.2006.01659.x.
    1. Robert R, Rouffineau J, Cremault A, Bauple JL, Pourrat O, Gil R, Patte D. Reversible paraplegia following intrathecal injection of high doses of human gammaglobulins in the treatment of low-grade tetanus. Four cases. Presse Med. 1984;13:1947–1949.
    1. Campbell JI, Lam TM, Huynh TL, To SD, Tran TT, Nguyen VM, Le TS, Nguyen VV, Parry C, Farrar JJ, Tran TH, Baker S. Microbiologic characterization and antimicrobial susceptibility of Clostridium tetani isolated from wounds of patients with clinically diagnosed tetanus. Am J Trop Med Hyg. 2009;80:827–831.
    1. Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare the efficacy of procaine penicillin and metronidazole. Br Med J (Clin Res Ed) 1985;291:648–650. doi: 10.1136/bmj.291.6496.648.
    1. Cook TM, Protheroe RT, Handel JM. Tetanus: a review of literature. Br J Anaesth. 2001;87:477–487. doi: 10.1093/bja/87.3.477.
    1. Farrar JJ, Yen LM, Cook T, Fairweather NF, Binh N, Parry J, Parry CM. Tetanus. J Neurol Neurosurg Psychiatry. 2000;69:292–301. doi: 10.1136/jnnp.69.3.292.
    1. Ganesh Kumar AV, Kothari VM, Krishnan A, Karnad DR. Benzathine penicillin, metronidazole and benzyl penicillin in the treatment of tetanus: a randomized, controlled trial. Ann Trop Med Parasitol. 2004;98:59–63. doi: 10.1179/000349804225003037.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa