Tetanus ======= ž TdaP - ACIP recommends that adults aged 65 years and older (e.g., grandparents, child-care providers, and health-care practitioners) who have or who anticipate having close contact with an infant less than 12 months of age and who previously have not received Tdap should receive a single dose of Tdap to protect against pertussis and reduce the likelihood of transmission. For other adults aged 65 years and older, a single dose of Tdap vaccine may be given instead of Td vaccine, in persons who have not previously received Tdap. Tdap can be administered regardless of interval since the last tetanus- or diphtheria-toxoid containing vaccine. After receipt of Tdap, persons should continue to receive Td for routine booster immunization against tetanus and diphtheria, according to previously published guidelines. - So, give to everyone over 11 in the ED - http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6001a4.htm?s_cid=mm6001a4_w ž ABLETT CLASSIFICATION OF SEVERITY Grade Clinical features I (mild) Mild trismus, general spasticity, no respiratory embarrassment, no spasms, no dysphagia II (moderate) Moderate trismus, rigidity, short spasms, mild dysphagia, moderate respiratory involvement, respiratory rate > 30, mild dysphagia III (severe) Severe trismus, generalized spasticity, prolonged spasms, respiratory rate > 40, severe dysphagia, apnoeic spells, pulse > 120 IV (very severe) Grade 3 plus severe autonomic disturbances involving the cardiovascular system ž British Anaesthesia literature on Tetanus INTRODUCTION Tetanus causes approximately 1 million deaths worldwide and remains endemic in the developing world. Approximately half of these deaths are in neonates and most occur in Africa and Asia. Immunization has dramatically reduced the number of cases in developed countries, with 12-15 cases per year reported in the UK (0.2 per million population). Tetanus is caused by a gram-positive bacillus, Clostridium tetani, which is commonly found in soil, but may also be isolated from animal or human faeces. It is a motile, spore-forming, obligate anaerobe. Spores are not destroyed by boiling but are eliminated by autoclaving at 120°C for 15 minutes 1 (at one atmosphere pressure). Tetanus is usually diagnosed clinically as the bacterium is rarely cultured. PATHOPHYSIOLOGY Under the anaerobic conditions found in infected or necrotic tissue, the bacillus secretes two toxins: tetanospasmin and tetanolysin. Tetanolysin damages the surrounding viable tissue and optimizes conditions for bacterial multiplication. Tetanospasmin causes the clinical syndrome of tetanus, by entering peripheral nerves and traveling via axonal retrograde transport to the central nervous system. Tetanospasmin disables release of neurotransmitter from presynaptic vesicles (particularly the inhibitory neurotransmitters GABA and glycine). The result is disinhibition of motor and autonomic neurons, causing rigidity, muscle spasms and autonomic dysfunction. A relative deficiency of synaptic acetylcholine (similar to that caused botulinum toxin) causes flaccid paralysis that is clinically mild in humans. High toxin load results in diffusion of toxin via the blood to nerves throughout the body. CLINICAL FEATURES Tetanus usually follows a recognized injury, which may be trivial or occur indoors. Other routes of entry include burns, ulcers, gangrene, snakebites, septic abortion, childbirth, intramuscular/intravenous injections and surgery. The incubation period (time from first injury to first symptom) averages 7-10 days (range 1-60 days), whilst the clinical onset time (time from first symptom to first spasm) varies between 1-7 days. Shorter incubation and onset times are associated with more severe disease. Muscle spasms and rigidity are predominant in the first week and reduce after 2-3 weeks. Autonomic disturbance usually starts several days after spasms, and persists for 1-2 weeks. Recovery from the illness occurs due to re-growth of axon terminals. The clinical triad consists of muscle rigidity, spasms and autonomic dysfunction. Early symptoms are neck stiffness, sore throat and poor mouth opening. Increased muscle tone may affect agonist and antagonist muscle groups together, resembling a convulsion. Spasms may be spontaneous or triggered by visual, auditory or emotional stimuli and can be severe enough to cause fractures or avulse tendons. Pharyngeal and laryngeal spasms may lead to aspiration or airway obstruction. Continual spasms may lead to respiratory failure. The most common form of tetanus (80 %) is generalized tetanus, with muscles throughout the body affected. Muscles of the head and neck are usually affected first, giving rise to masseter spasm (trismus or ‘lockjaw’) and a typical facial expression (risus sardonicus). Neck stiffness and dysphagia are also common. Truncal rigidity with predominant extensor spasm may lead severe arching of the back during spasm, called opisthotonus. Poor cough, inability to swallow, gastric stasis all increase the risk of aspiration. Respiratory failure continues to be a major cause of mortality in developing countries, whereas severe autonomic dysfunction causes most deaths in the developed world. Autonomic dysfunction results from paroxysmal increases in sympathetic activity, with basal catecholamine levels rising ten- fold. This results in tachycardia, hypertension and pyrexia, with a hyperkinetic circulation, low/normal systemic vascular resistance and normal right and left sided cardiac filling pressures. Other features include excessive salivation and sweating (may lead to dehydration), cardiomyopathy and myocardial infarction. Gastric stasis, ileus, diarrhea and high output renal failure may also be related to the autonomic disturbance. The effects on the parasympathetic system are less clear. Localized tetanus is seen with lower toxin loads or peripheral injuries. Mortality is much lower in this group unless the cranial nerves are involved (cephalic tetanus). Neonatal tetanus, with a particularly high mortality, is rare in developed countries but common in the developing world. Neonates present within a week of birth with fever, vomiting and ‘convulsions’. Differential diagnoses include sepsis and meningitis. The cause is usually poor umbilical hygiene and the disease is preventable by maternal vaccination, even when administered during pregnancy. MANAGEMENT OF TETANUS Three principles apply: 1. Prevent further toxin release. * Organise early surgical debridement of wounds, repeated as necessary. * Give antibiotics: Metronidazole 500mg IV 8 hourly is the antibiotic of choice and benzylpenicillin 1MU IV 6 hourly is an alternative (but is a GABA antagonist). Erythromycin, tetracycline, chloramphenicol and clindamycin are acceptable choices. Remember that heavily contaminated wounds need additional antibiotic cover for other bacteria. 2. Neutralise toxin present in the body outside the CNS. * Give human tetanus immunoglobulin (Ig) 150 units/kg IM into different sites within 24 hours of diagnosis. An intravenous preparation may be available in some centres (5000-10000iu). An alternative, where human Ig is unavailable, is to use 1500-10000 units anti-tetanus horse serum IM – anaphylaxis is a risk with this preparation and sensitivity tests are recommended. 3. Minimise the effects of the toxin already in the CNS. * Control rigidity and spasms with sedation, give respiratory support where necessary and control autonomic dysfunction. SPECIFIC TREATMENT Intensive care management is desirable, especially if respiratory and/or autonomic features are present. Sedation Sedation and avoidance of unnecessary stimulation is the primary treatment for controlling spasms and autonomic dysfunction. This is usually achieved using benzodiazepines (GABA agonists), such as diazepam or midazolam (both 0.1mg/kg IV or IM 1 - 4 hourly). Midazolam can be given as an intravenous infusion (2 -10 mg/hr). pethidine (1 mg/kg IV/IM 2-6 hourly) sedate well in combination with benzodiazepines and morphine can be infused intravenously (1 – 10 mg/hr). Where available, propofol is replacing these drugs as it has less accumulation. Anticonvulsants, particularly phenobarbitone (up to 200 mg IV or PO/NG 12-hourly), and phenothiazines (usually chlorpromazine) may be added as an adjunctive sedative. Heavy sedation may be required, necessitating close monitoring of the need for formal airway control and mechanical ventilation. Muscle relaxation is indicated where sedation alone is inadequate. Vecuronium (0.1 mg/kg IV as needed) or atracurium (0.5 mg/kg IV) are appropriate. Pancuronium may worsen autonomic of aminosteroid muscle relaxants has been associated with critical illness neuropathy and myopathy. The use of other drugs, such as dantrolene and intrathecal baclofen (a GABA–B agonist) is unproven. Treatment of autonomic dysfunction Fluid loading is a useful in minimizing autonomic instability. Magnesium sulphate is an effective adjunct in relaxation, sedation and controlling the autonomic disturbance in tetanus. It is a pre-synaptic neuromuscular blocker, reduces catecholamine release from nerves and the adrenal medulla, and reduces receptor responsiveness to released catecholamines. A loading dose of 5g should be given over 20 minutes, followed by an intravenous infusion of 2g/hr. The dose may be increased by up to 0.5 g/hr until spasms are relieved, or the patellar reflex disappears. If infusion devices are unavailable, give 2.5g IV every 2 hours, titrating the frequency of administration to symptoms. By antagonizing calcium metabolism, magnesium causes weakness and paralysis in overdose. Monitoring of serum magnesium levels is important to prevent this: the normal serum magnesium level is 0.7 – 1.0 mmol/l, whilst an acceptable therapeutic level is 2 - 3.5 mmol/l. Beta-blockers (particularly long-acting agents) have been implicated in sudden cardiac death and are not recommended. The short-acting beta-blocker esmolol may be used to manage tachycardia and hypertension, where invasive monitoring is available. The alpha-2 agonist, clonidine inhibits the release of norepinephrine from prejunctional nerve endings and may have a useful role. GENERAL MANAGEMENT Enteral feeding should be started early in order to prevent malnutrition caused by inability to swallow, increased metabolic rate, autonomic gastrointestinal dysfunction and muscular activity. For patients needing artificial ventilation, steps should be taken to prevent ventilator-associated pneumonia, such as nursing in the semi-recumbent position. Prevention of respiratory complications by chest physiotherapy, mouth care and regular tracheal suctioning may be necessary due to increased secretions. Where ventilation is likely to be required for more than 8-10 days consider early tracheostomy. Adequate sedation for all procedures should minimize autonomic disturbance. As with all patients with long-term critical illness, measures to minimize the risks of thromboembolism, gastrointestinal haemorrhage and pressure sores should be implemented. Psychological support for both the patient and relatives should be provided. OUTCOME AND PREVENTION Mortality varies greatly amongst units and is about 5-10 % in mild-moderate cases but rises significantly where ventilation is required, particularly in developing countries. Autonomic dysfunction and hospital-acquired infections are common causes of death. All patients with tetanus require active immunization with tetanus toxoid, as infection does not confer immunity. In the UK, a course of five injections is recommended: a primary course at the age of 2, 3, 4 months and boosters at 5 and 15 years. In the USA, 10 yearly boosters are still recommended. Current UK guidelines for the management of wounds may be found at http://www.dh.gov.uk/assetRoot/04/11/78/31/04117831.pdf ž Tetanus as a Disease - 19% case fatality rate (CDC, 2003) - median hospital stay 16 days. - more than half had to be intubated ž Immunization Facts - takes 4 days after dT for titers to start rising - peaks at 2 weeks - may be more delayed in elderly - only 1/3 have protective levels 5-7 days after dT - however, protection may occur before detectable antibody levels [Roper M. Tetanus prophylaxis in the emergency department. Annals of Emergency Medicine 2004;43(3):315-7.] ž MMWR Statement on Tetanus Immunization ž TIG (Tetanus Immune Globulin) - is safe (and indicated) for patients with a contraindication to toxoid (such as anaphylaxis or neurological reactions) and have a tetanus-prone wound [ACEP. Tetanus Immunization Recommendations for Persons Seven Years of Age and Older. Ann Emer Med 1986;15:1111-1112.] [ACEP Tetanus Immunization Recommendations for Persons Less Than Seven Years Old. Ann Emer Med 1987;16:1181-1183.] - Local and febrile reactions to TIG are common and do not contraindicate further doses. Patients with a localized exagerated (Arthus-like) reaction to toxoid should not recieve it at less than 10 year intervals irrespective of the nature of the wound. - If immunization history is inadequate, tetanus toxoid will not be protective; give TIG if the history is suspect. [Nivedita N. Severe tetanus--in spite of tetanus toxoid. Med J Malaysia, 49: 1, 1994 Mar, 105-7.] Abstract: - However, many with "inadequate" immunization histories turn out to have good antibody titres: [Murphy NM, Olney DB, Brakenbury PH. Objective verification of tetanus immune status in an apparently non-immune population.Br J Clin Pract, 48: 1, 1994 Jan-Feb, 8-9.] Abstract: - "The rationale behind witholding TIG, of course, is that in patients who have completed the primary series, repeated doses of toxoid provide a sufficiently rapid amnestic response to obviate the need for TIG. Although the incubation period can be as short as 24 hours, on average it is 3 to 21 days. Certainly, protective antibodies would appear desirable to have by the fourth day, but it has been observed that in patients who have not received toxoid within the previous ten years (as in the hypothetical case that you mention) this does not occur." --H. Louzon, M.D. [Porter JD, Perkin MA, Corbel MJ, Farrington CP, Watkins JT, Begg NT. Lack of early antitoxin response to tetanus booster. Vaccine 1992;10(5):334-6.] Abstract: ž Tetanus Toxoid Reactions - Review: [Weisse ME, Bass JW Tetanus toxoid allergy. JAMA 1990 Nov 14;264(18):2448] - Cause: Reactions to Td may occur as a result of allergy to + either the tetanus or the diphtheria components [ACEP Tetanus Immunization Recommendations for Pesons Less Than Seven Years Old. Ann Emer Med 1987;16:1181-1183] + or of additives such as aluminum: [Nielsen AO, Kaaber K, Veien NK [Aluminum allergy caused by DTP vaccine] Hudklinikken, Herning. Ugeskr Laeger 1992 Jun 29;154(27):1900-1.] Abstract: + or merthiolate: [Lindemayr H, Drobil M, Ebner H [Reactions to vaccinations against tetanus and tick-borne encephalitis caused by merthiolate (thiomersal)] Hautarzt 1984 Apr;35(4):192-6.] Abstract: - Can you tell which caused it in the ED? No. "I am unaware of any data that would implicate one component over all the others. Thus if someone has had a serious allergic reaction to Td I can see no reasonable way of making this determination in the ED and thus its use should probably be avoided altogether." -- H. Louzon, M.D. - Types of reactions: local, fever, and anaphylactoid (roughly 1/3 each) [Jacobs RL; Lowe RS; Lanier BQ. Adverse reactions to tetanus toxoid. JAMA 1982 Jan 1;247(1):40-2.] Abstract: - Severe local reactions: + A severe local reaction occuring 2 - 8 hours after Td is probably an Arthus-type reaction. In that case Td may be administered BUT ONLY IF the last dose was greater than 10 years previously. [ACEP Tetanus Immunization Recommendations for Persons Seven Years of Age and Older. Ann Emer Med 1986;15:1111-1112.] + Severe local reactions often seen in patients who have recieved frequent boosters. [Jacobs et. al. Adverse Reactions to Tetanus Toxoid JAMA 1982;247:40-42.] - Anaphylactic reactions + Anaphylactic reactions are a contraindication to further use of the vaccine. "Persons with a history of anaphylaxis should undergo intradermal skin testing to document hypersensitivity to Td". (So refer to allergist.) [ACEP Tetanus Immunization Recommendations for Persons Seven Years of Age and Older. Ann Emer Med 1986;15:1111-1112.] ž Need for Tetanus Toxoid - [Bowen V, Johnson J, Boyle J, Snelling CF. Tetanus--a continuing problem in minor injuries. Can J Surg, 31: 1, 1988 Jan, 7-9.] Abstract: - Frequency of Boosters: + one shouldn't give them too often as it increases the frequency and severity of reactions.