Current Management Of Tetanus

Tetanus in Indian ICU: Is it still a common problem? Tetanus is a preventable infectious disease with high mortality. Tetanus is a disease which affects people all over world. There are very few cases of tetanus in developed world. In US only 33 cases were reported in 1999. In developing countries it remains a major public health problem. There is no systematic collection of data available from India. In a recent stud y b y Anuradha, 217 cases of tetanus were reported over three years with mortality rate of 38% 1 . Such a high number of tetanus assumes much more significance in light of ver y limited ICU resources in India. In our institution, over a period of two years and four months (September 2004 – December 2006) 528 patients were admitted in medical ICU out of which 34 (6.43%) were of tetanus. This number of patients put tremendous pressure on alread y limited resources of ICU. Treatment of tetanus has undergone little pharmacological change since early 20th century. Tetanus has traditionally been treated with heavy sedation and supportive treatment in quite, dark room to minimize external stimulation. This treatment is still prevalent in those parts of world where mechanical ventilator y support is not readily available. These areas comprise of majority of developing world including a significant portion of India. A significant reduction in mortality due to tetanus was observed after introduction intensive

of

care

muscle in

relaxants,

routine

mechanical

management

of

ventilation

tetanus.

and

Mortality

decreased from 43 to 15% in a stud y b y Trujillo, analyzing 641 cases of tetanus managed by such intensive care 2 . In a similar stud y by

Udwadia, anal yzing 150 cases of tetanus, reported that intensive care, proper nutrition, earl y tracheostom y and ventilator support in severe tetanus were chiefly responsible for an overall reduction in mortality from 30 to 12% while the mortality in severe tetanus was reduced from 70 to 23% 3 . Both studies reported cardiac abnormality due to autonomic d ysfunction as major cause of mortality, instead of respirator y failure which has been predominant cause of mortality prior to use of intensive care practices in management of tetanus. The aspects which should be considered while managing a patient with tetanus are: 1.

Early diagnosis

2.

Specific treatment, which includes

wound management,

antibiotic therap y, neutralization of unbound toxin, control of muscle spasms, management of autonomic instability, 3.

Prevention of early complications

4.

Supportive treatment

Early diagnosis The

diagnosis

of

tetanus

is

primaril y

clinical

with

laboratory

investigations being virtually of no use. History of injur y, or presence of a wound aids in strengthening the diagnosis. Clinical diagnosis requires high index of suspicion especially in areas with lower incidence of disease. Tetanus follows an injur y with a median incubation period of 7 days; 15% of cases occur with in 3 da ys and 10% after 14 days. In 15 to 30% of patients, where the portal of entry is not evident, a careful search for signs of parentral drug abuse, otitis media, instrumentation like septic abortion, injections or minor surgical procedures should be inquired.

The first symptoms of tetanus is due supplied

by

cranial

nerves,

trismus

to rigidity of muscles

being

the

most

common

presentation, followed by risus sardonicus and neck stiffness. Patients complain of d ysphagia and stiffness in the jaw, abdomen, or back. Generalized rigidity of facial muscles causes the characteristic expression of risus sardonicus. Reflex spasms develop within 1 to 4 days of the first symptoms. Spasm may be precipitated b y minimal stimuli such as noise, light, or touch and last from seconds to minutes. In severe tetanus respiration may be compromised because of

generalized

spasms.

In

very

severe

tetanus

autonomic

d ysfunction predominates. Spatula test is a practical simple bedside test for early diagnosis of tetanus. A positive test result (reflex spasm of the masseters on touching the posterior phar yngeal wall) was seen in 359 (94%) of 380 patients with tetanus and in no patient without tetanus. The test performed

on

presentation

had a high specificity (100%) and

sensitivity (94%) for diagnosing tetanus 4 .

Differential

diagnosis

of

tetanus

includes

a

number

of

conditions that can simulate one or more of the clinical findings of tetanus. Early symptoms of tetanus may be mimicked b y either strychnine poisoning or a dystonic reaction to phenothiazines. Phenothiazine reactions can cause trismus, but the associated tremors, athetoid movements, and torticollis should make one suspect this drug reaction. Trismus tends to appear late, and s ymptoms and signs develop much more rapidly in strychnine poisoning than in tetanus. Most common local condition that results in trismus is an alveolar abscess. Purulent meningitis can be excluded by examination of the cerebrospinal fluid. Encephalitis is

occasionall y associated with trismus and muscular spasms, but the patient’s sensorium is usuall y clouded.

Specific treatment In cases of tetanus, life-threatening respiratory and cardiovascular complications can present with troubling rapidity following the initial diagnosis and admission to the intensive care unit is recommended for these patients. No specific drug has been discovered which can counteract the toxin once it is bound to nervous tissue.

The objectives of management of tetanus are: (1) To provide supportive care until the tetanospasmin that is fixed in tissue has been metabolized (2) To neutralize circulating toxin; and (3) To remove the source of tetanospasmin. Tetanus immunoglobulin neutralizes circulating tetanospasmin and toxin in wound. Even though tetanus immunoglobulin does not ameliorate the clinical symptoms of tetanus, it significantly reduces mortality. Although the optimal dose of tetanus immunoglobulin is unknown; the usual dose of equine preparation is 500-1000 IU/kg given intravenously or intramuscularl y. The dose of Human tetanus immunoglobulin is 5000-8000 IU intramuscularl y. It should be given before wound debridement, because exotoxin may be released during

wound

manipulation.

Repeated

doses

of

tetanus

immunoglobulin are unnecessary, because the half life of anti toxin

is 28 days 5 . In an attempt to inactivate the toxin bound to nervous tissue, antitoxin has been administered intrathecally. But further studies failed to support their use. Debridement of a wound is important to eradicate spores and change

conditions

for

germination,

thereby

preventing

further

elaboration and absorption of the neurotoxin. This is most effective after the injury but unfortunatel y most wounds implicated in tetanus are so trivial that it is either ignored or treated with home remedies. Linear wounds with sharp edges that are well vascularised and not obviously infected are usuall y non-tetanus prone. All other wounds, that have resulted from blunt trauma, bites and are obviously contaminated,

are

considered

potentially

predisposed.

Wound

debridement is of no value after the disease has been established and that antibiotics are of no value after debridement, still ensuring that no further toxin is produced at wound level may be preferable. Antibiotics administered.

are

of

questionable

Penicillin,

which

is

utility

but

effective

are

against

traditionall y almost

all

clostridial infections, has been drug of choice for many decades. But it is no longer recommended as it antagonizes GABA and potentiate effects of tetanospasmin. Metronidazole, a bactericidal against anaerobes, is preferred agent now . A randomized trial by Salim proved metronidazole to be more effective along with significantl y lower mortality rates in comparision to penicillin 6 . Metronidazole is given in a dose of 500 mg intravenousl y 8 hourly for 10 days. The

optimal

approach

to

a

tetanic

patient

with

respiratory

compromise lies in early intervention with airway and spasm control. Intubation of the trachea should be carried out when maintenance of the airway is in doubt. As the presence of the

endotracheal tube is in itself a strong stimulus for spasms, some authors recommend that a tracheotom y be performed immediatel y 7 . Tracheostom y should be carried out with in 24hr of diagnosis in all patients predicted to develop moderate and severe tetanus. Ablett has classified tetanus according its se verity 8 : Grade I Mild:

Mild to moderate trismus; general spasticity; no

respirator y embarrassment; no spasms; little or no dysphagia Grade II Moderate: Moderate trismus; well-marked rigidity; mild to moderate but short spasms; moderate respiratory embarrassment with an increased respirator y rate greater than 30, mild d ysphagia Grade III Severe: Severe trismus; generalized spasticity; reflex prolonged spasms; respiratory rate greater than 40; apnoeic spells, severe dysphagia; tachycardia > 120. Grade IV Very severe: Grade III and violent autonomic disturbances involving

the

cardiovascular

system.

Severe

hypertension

and

tach ycardia alternating with relative hypotension and bradycardia, either of which may be persistent Spasms in tetanus are potentiall y life threatening, for they impair respirator y function, produce exhaustion and often lead to aspiration of gastric contents. Control of tetatnic spasms should be carried out simultaneousl y as measures are being taken for airwa y control. Tetanospasmin

prevents

neurotransmitter

release

at

inhibitor y

interneurons, and terap y of tetanus is aimed at restoring normal inhibition. Benzodiazepines have been traditionall y used for control of spasms. Diazepam is usuall y the first drug to be used in the initial phase of the illness. The average dose used as an adjunct to muscle relaxants is 10-30 mg 6-8 hrl y, and is usuall y the starting dose even when

used

solely.

However,

the

large

intravenous

doses

of

diazepam required in tetanus may result in metabolic acidosis

secondar y to prop ylene glycol vehicle. Thus, the water soluble agent, midazolam, is the preferred agent for producing muscle relaxation

in

patients

with

tetanus.[5]

Propofol

has

been

successfull y used in a dose of 3.5 – 4.5 mg/kg/hr after a loading dose of 50mg. Propofol has advantages in terms of reduction in muscle rigidity and rapid recovery, but suspected contribution to cardiovascular instability during autonomic dysfunction and high cost has precluded routine use 9 . Neuromuscular blocking agents are used when sedatives are inadequate to prevent and control spasms. Vecuronium is drug of choice

because

of

minimal

cardiovascular

side

effects.

Pancuronium is avoided because of its hypotensive action, while Rocuronium

is

much

expensive.

At racuronium

and

Cisatracuronium can be used in severe hepatic and renal disease. Use of steroids concomitantl y with these neuromascular blockers is strongly discouraged because of high risk of m yopath y. Intathecal baclofen therapy has been proved to be efficacious in management of tetanus in a number of series although largest series is of 14 cases only. Baclofen has relatively narrow therapeutic range and its administration

requires

surgical

expertise

which

is

not

easily

available. Autonomic dysfunction is diagnosed in most cases b y presence of spontaneous fluctuations in blood pressure and heart rate, in absence of an y external stimulus and spasms, in patients on adequate sedation. Prompt recognition and treatment of autonomic d ysfunction are important in reducing the mortality. Drugs have been used with the aim to produce adrenergic blockade or to prevent release

of

catecholamines

h yperactivity 1 0 .

and

thereby

suppress

autonomic

Labetolol has been frequentl y used to treat adrenergic overactivity for it produces dual adrenergic blockade, although the β-blocking effect is more significant. However, concerns about unopossed release of catecholamines cauing m yocardial damage and cardiac arrest were raised. Suppression of catecholemines release has been recognized as the more effective method of controlling dysautonomia in tetanus. Morphine acts centrally to reduce sympathetic tone in the heart and vascular system resulting in brad ycardia and hypotension. It has excellent sedative properties and minimal effect on cardiovascular performance. It reduces mean arterial pressure, heart rate and s ystemic vascular resistance while having minimal effect on the cardiac output 11 . But tolerance develops rapidl y and it has minimal effect instability occurring with spasms and stimulation. Clonidine, a centrall y acting sympathol ytic, has also been used with mixed resuts. Magnesium blocks neuromuscular transmission and also controls d ysautonomia. Magnesium competes with calcium at presynaptic junction

and

inhibits

release

of

acetylcholine,

resulting

in

neuromuscular blockade. Magnesium spares respirator y muscles making its profile more favourable 1 2 . The fact that magnesium can control spasms and dysautonomia while patients remain conscious and co-operative and mobilized is a tremendous advantage. This enables simplified nursing care, which should contribute significantly to a better outcome. Parameter which are to be observed are oliguria <30 ml/hr, absence of deep tendon reflexes and respirator y rate < 11/min. Magnesium bolus of

5 mg is given over 20 min

followed by dose titration to control muscle spasms and rigidity, which may be as higher as 4-5 gm/ hr. Magnesium therapy seems to

be better than conventional tetanus therapy in a number of wa ys. Magnesium controls spasms without other drug supplementation except in a ver y severe disease and is non sedative 1 3 . It is a feasible regimen in developing world and is recommended as firstline therap y in tetanus management. Finall y, supportive treatment in the form of good critical care and expert nursing care pla y a vital role in reducing complications and preventing death. These measures include ensuring patent airwa ys and tracheostom y care; maintaining adequate tissue oxygenation and mechanical ventilation if required; expert chest physiotherap y especiall y in between spasms;

fluid, electrolyte and acid-base

balance; prevention, early detection and control of infection and sepsis;

supportive

h yperp yrexia.

nutrition;

detection

and

treatment

of

References 1. S Anuradha. Tetanus in adults- A continuing prolem: Anal ysis of 217 patients over 3 year from Delhi, India, with special emphasis on predictors of mortality. Med J Malaysia 2006; 61:7-14. 2. Trujillo MH, Castillo A, Espana J et al: Impact of intensive care management on the prognosis of tetanus. Chest 1987; 92: 6365. 3. Udwadia FE, Lall A, Udwadia ZF, Sekhar M, Vora A. Tetanus and

its

complications:

intensive

care

and

management

experience in 150 Indian patients. Epidemiol Infect. 1987 Dec; 99(3):675-84. 4. Apte NM, Karnad DR: Short report - the spatula test: a single bedside test to diagnose tetanus. Am J Trop Med Hyg 1995; 53: 386-387. 5. Ernst

ME,

Klesper

Pathoph ysiology

and

ME,

Fouts

management.

M Ann

et

al.

Tetanus:

Pharmocother31:

1507, 1997. 6. Ahmadsyah I, Salim A: Treatment of tetanus: An open stud y to compare the efficacy of procaine penicillin and metronidazole. BMJ 1985; 291: 648-650. 7. Mukherjee DK. Tetanus and tracheostom y. Ann Otol 1977; 86:67-72. 8. Ablett JJL: Analysis and main experiences in 82 patients treated in the Tetanus unit. In: Symposium on tetanus in Great Britain. Ellis M (Ed). Boston Spa, National Lending Librar y, U.K. 1967; 1-10. 9. Borgeat A, Popovic V, Schwander D: Efficacy of a continuous infusion of propofol in a patient with tetanus. Crit Care Med 1991; 19: 295-297.

10. Domenighetti GM, Savary G, Stricker H. Hyperadrenergic syndrome in severe tetanus: extreme rise in catecholamines responsive to labetalol. Br Med J 1984; 288:1483-1484. 11. Rocke DA, Pather M, Calver AD et al : Morphine in tetanus – the management of sympathetic nervous system overactivity. S Afr Med J 1986; 70 : 666-668 12. Lee

C

Zhang,

Kwan

WF.

Electom yographic

and

mechanom yographic characteristic of neuromuscular block by magnesium sulphate in the pig. Br J Anaesth 1996; 76,278283. 13. Attygalle D, Rodrigo N. Magnesium Sulphate for control of spasms in severe tetanus. Anaesthesia 1997; 52: 956-962.