etanus is a potentially preventable disease causedby a potent neurotoxin produced by Clostridium

tetani. The disease was first described in the 14thcentury by John of Arderne.1 Tetanospasmin isresponsible for its pathogenesis. After the toxin ofbotulism, it is the most potent neurotoxin known toman, with an estimated lethal dose of 2.5 ng/kg bodyweight.2 Tetanus is one of the target diseases of the

T

Tetanus

A clinical review

Juma M. Al-Kaabi, MRCP, DTM&H, Euan M. Scrimgeour, FRACP, DTM&H, Andre Louon, MD, Bazdawi M. Al-Riyami, FRCP, PhD.

World Health Organization (WHO) ExpandedProgram on Immunization (EPI). The overall annualincidence worldwide is 0.5-1 million cases. It isestimated that there are 140,000 fatal neonatal casesper annum. The disease is more common in tropicaland developing countries, where immunization isdeficient and opportunities for penetratingcontaminated wounds is higher.3 In Oman, tetanus

Objectives: Although tetanus is now uncommon inOman (The Expanded Program on Immunization wasintroduced in 1981), patients continue to present from timeto time at an average rate of 6 cases per year. Worldwide,the mortality rate for tetanus remains high (ranging from15-20% in developed countries). At the Sultan QaboosUniversity Hospital, Muscat, Oman, prolonged IntensiveCare Unit treatment and multi-disciplinary management isinvariably required for tetanus patients. This study wascarried out to evaluate our results over the past decade. Methods: All tetanus patients admitted to the SultanQaboos University Hospital from 1991 up to the end of1999 were retrospectively reviewed. Patients werediagnosed early, and aggressive treatment in the IntensiveCare Unit was instituted, with a coordinatedmultidisciplinary management.

Results: Ten cases were identified and included in thereview, comprising 9 adults and one infant aged 2 weeks.Adult patients were aged 36-75 years (mean 59 years), andthe average Intensive Care Unit stay of the 9 survivingpatients was 5.5 weeks (range 3-7 weeks). All patients

From the Departments of Medicine (Al-Kaabi, Scrimgeour, Al-Riyami) and Anesthesia (Louon), Sultan Qaboos University Hospital, Muscat, Oman.

Published simultaneously with special permission from Saudi Medical Journal.

Address correspondence and reprint request to: Dr. Juma M. Al-Kaabi, Senior Registrar, Department of Medicine, Sultan Qaboos University Hospital,PO Box 35, Al-Khod 123, Muscat, Oman. Tel. +968 513355 ext. 3404. Fax. +968 513419. E-mail: drkaabi@hotmail.com

presented with severe generalized tetanus. Two patientswith traditional cautery marks developed tetanus. A focusof infection could not be found in 2 patients. All patientshad early tracheostomy and assisted ventilation withappropriate sedation. One patient required almost 45 gmof diazepam throughout his Intensive Care Unit stay. Oneadult patient died on the 6th day of admission followingmyocardial infarction. The neonatal case survived after 35days care in the Intensive Care Unit. The mortality ratefor our patients was therefore 10%.

Conclusion: Tetanus in Oman remains an infrequent butimportant disease requiring costly and prolonged IntensiveCare Unit treatment. We attribute the comparatively lowmortality rate (10%) in this study, to early diagnosis,institution of aggressive treatment, good nursing as well asa well-coordinated multi-disciplinary management.

Keywords: Tetanus, tetanus management, cautery burns,immunization, Risus Sardonicus.

Neurosciences 2001; Vol. 6 (4): 220-223

ABSTRACT

220

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Neurosciences 2001; Vol. 6 (4) 221

toxoid was first included in the EPI in 1981 andaccordingly the majority of adults are notimmunized. Most Omanis live in rural areas and areinvolved in subsistence agriculture and livestockfarming, subsequently, exposure to tetanus iscommon. Sultan Qaboos University Hospital(SQUH) is a tertiary care teaching hospital in Muscatand patients with tetanus are referred from regionaland district hospitals.

Methods. All patients referred to, or presentingat, the SQUH from 1991 to 1999 were included inthis study. One or more of the authors had treatedeach patient. A retrospective evaluation of all thepatients was undertaken to determine the results oftreatment during this time. Medical records werereviewed to collect demographic information,circumstances of injury, anatomic site and type ofinjury, treatment and outcomes. Ten cases wereidentified including a neonate, 9 males and onefemale (Table 1). All but one patient, a Bangladeshi,were Omanis. All patients had full clinicalexaminations, including identification of the focus ofinfection. Severe generalized tetanus was the maindiagnosis in all the cases thus early ventilatorysupport and tracheostomy together with intensivenursing care, were instituted. The diagnosis oftetanus is purely clinical, as there are no specificlaboratory tests. However, the basic initialinvestigations have included full blood count,erythrocyte sedimentation rate, serum glucose, serum

calcium, arterial blood gases, urea and electrolytes,electrocardiogram, chest x-ray and wound cultures.All the patients received antibiotics, anti-tetanustoxoid and human tetanus immunoglobulin (TIG).Generalized muscle spasms, which occurred in allpatients, were well controlled with a combination ofsedative drugs and muscle relaxants. Initiallyparenteral then enteral nutrition was instituted in allpatients.

Results. Most patients presented with progressivedifficulty in swallowing, back pain and stiffness ofthe back and neck, of 2 days to one-week duration.Tetanic spasms were observed in only one patient.On admission, all patients were alert, agitated, hadtrismus, generalized rigidity associated withhyperreflexia and exhibited plantar withdrawal, theirsensorium was otherwise normal. A focus ofinfection could not be found in 2 patients. Risussardonicus and opisthotonos were noted in 2 patients.Two patients with traditional cautery burnsdeveloped tetanus. One of them was a female patientwith an unreported, infected cautery lesion on herscalp, which was found by chance by the nursingstaff when being washed. The other one had multipletraditional cautery marks on the neck and the trunk.We obtained only one positive culture out of the 8cases with a known focus of infection and the basicinitial investigations were unremarkable. Ourneonatal case was delivered by an old blind womanat home in a remote village (mother Gravida 7, Para

Table 1 - Tetanus cases admitted to the Intensive Care Unit at Sultan Qaboos University Hospital during the period from 1991 to 1999.

CaseNumber

1

2

3

4

5

6

7

8

9

10

Patient Age/Sex

59/M

66/M

67/M

63/M

47/M

6 days/M

75/F

36/M

68/M

52/M

Year ofadmission

1991

1992

1992

1993

1993

1995

1996

1997

1998

1999

ICU stay(days)

41

6

50

19

31

35

51

52

41

35

Source of tetanusinfection

Unknown

Left big toe

Right thigh

Left neck cautery

Unknown

Umbilical cord

Small scalp cautery

Left ear

Right foot

Right breast*

Incubationperiod (days)

NA**

10

7

4

NA**

5

6

8

12

15

Significantcomplications

Pneumonia, UTI

MI, cardiac arrest

2 x pneumonia

Pneumonia

Myoclonic epilepsy,pneumonia

Pneumonia

Pneumonia

DVT, Pneumonia, VT,SVT, arrhythmia

UTI, pneumonia,asystole, SVT

Pneumonia

Outcome

Recovered

Died

Recovered

Recovered

Recovered

Recovered

Recovered

Recovered

Recovered

Recovered

* Two weeks postoperative for abscess** NA: Not available as the wound or the history of penetrating injury have not been found.M - Male F - Female ICU - Intensive Care UnitUTI - Urinary Tract InfectionMI - Myocardial infarct

DVT - Deep vein thrombosisVT - Ventricular tachycardiaSVT - Supraventricular tachycardia

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222 Neurosciences 2001; Vol. 6 (4)

6 and sera confirmed non-immunized state). Anunsterile knife cut the umbilical cord. On the 5th daythe baby showed failure of sucking, vomiting andlooked unwell. On the 6th day, he presented to thenearest hospital. He was dehydrated, showing tetanicspasms, risus sardonicus, opisthotonos with aninfected umbilical cord. As the tetanus diagnosis wasevident, the neonate was sedated, intubated andtransferred to our hospital. All patients had earlytracheostomy and assisted ventilation withappropriate sedation. It has been noted generally, thefurther distant the focus of infection from the centralnervous system (CNS) the longer the incubationperiod. The average Intensive Care Unit (ICU) stayof the 9 surviving patients was lengthy, 5.5 weeks(range 3-7 weeks). In this small sized sample themortality rate of our patients was therefore 10%. Thefollowing major complications were encountered. Allpatients developed multiple chest infections(pneumonia) and 2 patients contracted urinary tractinfections. One patient developed right subclavianvein thrombosis probably secondary to continuousdiazepam infusion. One patient with severe aorticstenosis (pressure gradient across the aortic valve 70-80mmHg) was revived from cardiac arrest (asystole)and underwent a successful aortic valve replacementafter a full recovery from tetanus. Unsuccessfulresuscitation of cardiac arrest occurred in a patientwith non-insulin dependent diabetes mellitus whosustained myocardial infarction on the 6th day of hisadmission. Myocardial infarction is a rarely observedcomplication of tetanus.4 All patients showed one ormore manifestations of autonomic dysfunction e.g.hypertension, hypotension, tachycadia, bradycardiaand dysrhythmias particularly in the 2nd and the 3rdweek. On discharge there were no major sequele toany patient and outpatient follow-up showed nomajor long-term complications.

Discussion. Tetanus remains an important causeof morbidity and mortality despite the wideimplementation of the EPI. The WHO estimated in1990 that worldwide, there were about 715,000deaths from neonatal tetanus.2 In Oman, tetanus is anotifiable disease, and there were 2 neonatal and 52adult cases (on average 6 cases per year) reportedover the period from 1991 up to the end of 1999.Tetanus is primarily a disease of the elderly indeveloped countries. Active immunization and betterhygiene, wound care and management of childbirthhave diminished its incidence. Mortality has beenreduced to 15% with the active employment ofintensive care facilities for the treatment of thiscondition.5 Our mortality rate is comparatively low at10%. The diagnosis of tetanus is purely clinical, asthere are no specific laboratory tests. It has beenestimated that wound cultures are positive in only32% of cases.6 Only one positive culture was

obtained. A simple bedside test, the "spatula test" (areflex spasm of the masseters on touching theposterior pharyngeal wall leading to biting of thespatula rather than a gag reflex), was described byApte et al. In 400 patients, this test had a sensitivityof 94% and a specificity of 100%.7 Pain and stiffnessof the back are the most common presentingsymptoms, followed by trismus and dysphagia.Spasms may be precipitated by minimal stimuli suchas noise, light or touch and may last from seconds tominutes. They can be painful or dangerous, causingapnea, fractures or rhabdomyolysis and thus ourpatients were kept in a quiet room and stimuli kept ata minimum until satisfactory sedation was achieved.Sera can be analyzed for tetanus antitoxin, thepresence of more than 0.01 antitoxin unit per ml isregarded as protective against clinical tetanus,although cases have occurred in patients withantibody concentrations at least 10-fold higher thanthis. In this study, tetanus serology was onlyperformed for the mother of the neonatal case, whichconfirmed her non-immunized state.

The major differential diagnoses which wereexcluded in our cases are hypocalcemia, meningitis,encephalitis, subarachnoid hemorrhage, peritonsilarabscess, dystonic reactions, rabies, spiderenvenomatoin (widow), strychnine poisoning andhysteria. There are 4 clinical forms of tetanus:neonatal, localized, cephalic and generalized. All theadult tetanus cases studied were of the generalizedform. In the literature, the source of infection is froman obvious injury in 58% of cases (8 out of 10 in ourseries). Two patients with traditional cautery remedydeveloped tetanus. It is probable, that the source oftetanus in these cases was ash applied by thetraditional healer to accelerate the wound healing.

Our treatment followed the recommendedguidelines: Neutralization of the toxin andelimination of the source of infection by carefulsurgical excision and wound care. As soon as thediagnosis of tetanus was made, Human TIG 1000units were given and repeated for an additional 2days in most patients. This at best neutralizes onlycirculating toxins, but does not affect toxins alreadyfixed to the CNS. Intrathecal administration ofantitetanus toxin has not been used as large meta-analyses reported it to be ineffective in reducing themorbidity and mortality.8 Once the Human TIG hasbeen given, the infected site should be thoroughlycleaned and all the necrotic tissue extensivelydebribed. Antibiotics destroy tetanus spores. Thefavorite choice was Metronidazole 500mgintravenously (IV) 8 hourly for 10 days as the drughas a spectrum of activity against anaerobes, it is ableto penetrate necrotic tissue and has been shown to bemore effective than penicillin in this situation.9However, penicillin or a 3rd-generationcephalosporin have also been used in a few patients.Natural immunity to tetanus does not occur, tetanus

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Neurosciences 2001; Vol. 6 (4) 223

may both relapse and recur, so victims of tetanusmust be actively immunized. Immunization withtetanus toxoid was given at the time of the diagnoses.A 2nd and 3rd toxoid injection were given one and 2months later, with planned booster injections one-year later and then 10 yearly intervals. In the case ofa neonate, the mother also was given the vaccine.

The main aims of treatment are to relieve thepatients distress, controlling the spasms and rigidityand to maintain adequate respiration. If endotrachealintubation was necessary, tracheostomy wasperformed within 10 days. As the endotracheal tubeseems to be a strong stimulus for spasms, in the last 3patients a tracheostomy was carried out earlier, onthe 2nd day of ventilation. Benzodiazepines reduceanxiety, induce amnesia, sedation and musclerelaxation as well as being anticonvulsant.10 Thesedrugs are Gama-amniobutyric acid A (GABA-A)agonists, thereby functioning as indirect antagonistsof the effect of the toxin on inhibitory systems.Diazepam or midazolam by continuous infusion havebeen used. Diazepam is less expensive compared toother benzodiazepines. The disadvantages ofdiazepam include slow onset, prolonged action, andirritation to tissues and thrombophlebitis (one patientdeveloped subclavian vein thrombosis). Most of ourpatients received diazepam IV infusions rangingbetween 10 to 60 mg/hr. One of our patients required4500 ampoules of 10 mg diazepam (45000 mg)throughout his ICU stay. Other antispasmodics usedincluded magnesium sulphate, morphine and musclerelaxants.

It is known that the mortality in tetanus associatedwith autonomic dysfunction is as high as 50%.Unexpected cardiac arrest is the most common causeof death in patients with tetanus admitted to the ICUand no obvious cause of death can be found atautopsy in up to 20% of deaths. It is generalconsensus that no drug singly, or in combination, hasproved consistently effective in the control ofautonomic disturbances. The armamentarium ofdrugs used in our patients included benzodiazepines,morphine,11 alpha blockers, beta blockers, or agentswith both properties, calcium antagonists,magnesium sulphate,12 and atropine. Physiotherapyand nursing played a major rule in preventingcontractures and deep vein thrombosis in ICU andwere the mainstay of rehabilitation in the ward.Other factors known to contribute to morbidity andmortality in tetanus were also prevented. Theseinclude hypoxia, malnutrition, and complications ofmechanical ventilation (barotrauma), fluid andelectrolytes disturbances. Bed sores and embolicphenomena were avoided thanks to excellent nursingcare. Supportive psychotherapy was offered to bothpatient and family. Prevention of tetanus is the key

to its elimination and loss of life in an easilypreventable disease is unacceptable. Primary careand emergency physicians can reduce the morbidityand mortality of tetanus through properimmunization. As a patients tetanus immunizationhistory is often unreliable in routine woundmanagement, liberal use of tetanus toxoids andappropriate TIG is recommended.3

In conclusion, tetanus is a potentially preventabledisease. However, it remains a frequent cause ofdeath and hospitalization in most developingcountries. Proper attention, strict adherence toimmunization schedules and appropriate wound carewill reduce the incidence of this potentially fataldisease. Active immunization is the clear solution.Early recognition of tetanus and early use ofintensive care facilities can reduce the mortalityconsiderably.

Acknowledgments. Our sincere thanks go to all thoseinvolved in the management of these unfortunate patientsstricken by a deadly disease. Their commitment probably savedtheir lives. We also like to thank Dr. Deleu, HoD ofPharmacology and Consultant Neurologist, for his editorialadvice.

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