Case Report
Tetanus is still a deadly disease: a report of six tetanus cases and reminder of our knowledge
Tropical Doctor 2014, Vol 44(1) 38–42 ! The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0049475513515213 tdo.sagepub.com
Mehmet Aksoy1, Erkan Cem Celık2, Alı Ahıskalıoglu3 and Muhammet Ahmet Karakaya2
Abstract We analysed the data in the medical records of six patients admitted for tetanus in the intensive care unit (ICU) of the anaesthesia department in the Medical Faculty of Ataturk University from 1 January 2010 to 31 December 2012. All patients received the generalized form of treatment for tetanus in the ICU. The average age of the patients was 65.33 13.45 years. Treatment modalities were administered to the patients in accordance with the literature. Four patients died despite all therapeutic interventions and two patients were discharged uneventfully. All those who died had chronic disease and infected wounds on their head, but only one patient had an infected wound on his leg. The surviving patients had no chronic illnesses but did have injuries on their legs. The presence of chronic disease increases tetanusrelated mortality. More information about the disease must be made available in order to make it preventable with regular vaccinations.
Keywords Autonomic dysfunction, intensive care unit, tetanus
Introduction Tetanus is a preventable disease caused by a bacterium called Clostridium tetani. However, it is still a deadly disease in many countries despite widespread vaccination programmes given from infancy to adulthood. The mortality rate of tetanus patients was reported to be 44% in Nigeria, 60.8% in Senegal, 52.4% in Congo and 58% in Turkey.1–4 C. tetani usually enters the body via a contaminated wound and releases tetanus toxin after completing the incubation time (the time from injury to the first symptom). Tetanus toxin reaches the central nervous system by travelling along axons of lower motor neurons.5 The toxin causes involuntary contraction (rigidity) and contraction in short periods of time (spasm) in the muscles. Clinical reflection of muscle contractions may occur as trismus (rigidity of temporal and masseter muscles), difficulty in opening the mouth and opistotonus (the backward arching of the columna as a result of the involuntary contraction of the back and neck muscles). Tetanus is clinically divided into four groups: neonatal; generalized; local; and cephalic. In the cephalic form, tetanus is localized to the head. Neonatal tetanus is a generalized form in children younger than 1 month. In generalized tetanus, the muscles of the whole body are
affected and opisthotonos, trismus, dysphagia, abdominal rigidity and respiratory failure may occur. The most significant cause of death in advanced stages is autonomic dysfunction defined as non-blocking, frequent fluctuations in blood pressure and heart rate depending on the affected area of the brain stem by toxin.5 With the approval of the Ethics Committee of the Medical Faculty, Ataturk University (reference number: B.30.2.ATA.0.01.00/135), we analysed data in the medical records of patients admitted with tetanus to the ICU of the Anaesthesia Department in the Medical Faculty of Ataturk University from 1 January 2010 to 31 December 2012. 1 Assistant Professor and Medical Doctor, Department of Anaesthesiology and Reanimation, Faculty of Medicine, Ataturk University, Erzurum, Turkey 2 Research Assistant and Medical Doctor, Department of Anaesthesiology and Reanimation, Faculty of Medicine, Ataturk University, Erzurum, Turkey 3 Anesthetist and Medical Doctor, Department of Anaesthesiology and Reanimation, Faculty of Medicine, Ataturk University, Erzurum, Turkey
Corresponding author: Mehmet Aksoy, Assistant Professor Doctor, Department of Anaesthesiology and Reanimation, Faculty of Medicine, Ataturk University, TR-25240 Erzurum, Turkey. Email: [email protected]
Downloaded from tdo.sagepub.com by guest on February 22, 2015
Aksoy et al.
39
Case history A total of six patients with diagnosed tetanus were admitted to our ICU between January 2010 and December 2012. The distributions of patients according to age, gender, clinical course of the disease, treatments and outcomes are presented in Table 1. The diagnosis of tetanus was made according to the patient’s history of trauma, cervical rigidity, trismus, generalized contractions over the whole body and respiratory failure requiring oxygen due to laryngospasm. All patients received the generalized form of tetanus ICU admission. The average age of the patients was 65.33 13.45 (between 41 and 79 years). One was female and the others were male. None of the patients knew the time of their last vaccination. Tetanus vaccine and immunoglobulin were administered in the emergency department of our hospital. Four patients had chronic illness (Table 1). All patients were sedated with propofol and treated with diazepam and morphine to relieve the spasms. Wounds were debrided and metronidazole (500 mg 3 times/day) was initiated in order to reduce toxin production. Intubation and mechanical ventilation was required by all patients. In our clinic, tracheostomy is not applied routinely to patients with tetanus and is only performed in cases of acute airway obstruction caused by severe laryngeal spasm and after obtaining consent from the relatives of the patient. In this case report, tracheostomy was performed in all patients (on the 14th day in one case and on the 9th day in the other cases) because of severe laryngospasm. There was a short delay in tracheostomy because their relatives did not initially give their consent. Cardiovascular stability was improved with phentolamine (an alpha-adrenergic antagonist), calcium channel blockers and high doses of atropine where necessary. Adequate nutrition, prophylactic heparin and preventive treatments for gastric ulcer and pressure sore formation were also provided. Pneumonia was reported in all patients due to prolonged critical illness. Four patients died despite all therapeutic interventions. After stabilization of autonomic functions (35 days after admission), two patients were transferred from the ICU to the infectious diseases service in order to reduce the risk of infection associated with intensive care. Later, we learned that they had made a complete recovery.
Discussion We report on six patients (five men and one woman) with the generalized form of tetanus who were followed in our ICU. Treatment modalities were administered to the patients in accordance with the published literature. Four of them died despite all therapeutic interventions.
The prognosis was influenced by the presence of a chronic illness and the distance between the injury site and the central nervous system. C. tetani is a Gram-positive, anaerobe bacillus that leads to tetanus. Generally, entry into the body occurs via a wound contaminated by manure, soil or rusted metal. The entry site cannot be found in approximately 20% of cases.6 C. tetani produces an exotoxin named tetanospasmin and causes clinical signs by destroying the central nervous system.7 There are no specific laboratory tests for the diagnosis of tetanus. A diagnosis of tetanus is made according to clinical history and findings which include rigidity, spasms, trismus or generalized paroxysms without loss of consciousness.7 Generalized tetanus is the most common form of tetanus. Usually, difficulty in opening the jaw and trismus are the initial symptoms in generalized tetanus. Later, risus sardonicus (contraction of the facial muscles), dysphagia, opisthotonus, abdominal rigidity, dysarthria and respiratory failure occur depending on the affected muscles of the whole body.5 All patients in this report received the generalized form of tetanus ICU admission. Reducing the toxin levels in circulation, controlling muscle spasms and maintaining haemodynamic stability are the primary goals for the treatment of tetanus.6 Debridement and aeration of the wound are essential in order to remove an ideal environment for this bacterium and to prevent ongoing toxin production.7 At the same time, an antibiotic should be given to patients in order to eradicate the tetanus bacterium. The recommended antibiotic is metronidazole, 500 mg 3 times/ day for 7–10 days. One study8 showed that the use of penicillin in tetanus may potentiate the effect of tetanus toxin by inhibiting the GABAA (glycine and g-amino butyric acid) receptor in the central nervous system. However, Ganesh Kumar et al.9 reported that the use of metronidazole in tetanus is as equally effective as penicillin. All of our patients had an infected wound, and wound cleaning and metronidazole administration were applied to each of them. Human tetanus immunoglobulin (HTIG) should be given intramuscularly in order to neutralize unbound toxin in the body and tetanus toxoid immunization should be administered in order to provide long-term immunity. However, the correct doses of HTIG are unclear; doses of 500 IU, 3000 IU or higher have been administered. Blake et al.10 analysed the data of 545 cases with tetanus for 6 years and reported similar survival rates between cases using HTIG doses of 8000 units and those using HTIG doses of 500 units. In a meta-analysis,11 intrathecal administration of HTIG was reported to be more beneficial than intramuscular administration. Intramuscular HTIG and tetanus toxoid were applied to our cases.
Downloaded from tdo.sagepub.com by guest on February 22, 2015
Downloaded from tdo.sagepub.com by guest on February 22, 2015
9 days
Generalized tetanus Chronic obstructive pulmonary disease 500 IU
Contraction of the legs 30 days
Generalized tetanus No 500 IU þ Day 1 of admission Day 9 of admission Pneumonia 17 days 35 days Healthy discharge
First symptoms
The time between the onset of the first symptom and admission to the emergency department
Symptoms on admission The presence of a chronic illness
Applied HTIG doses
Applied tetanus vaccine
Requirement for mechanical ventilation
Required tracheostomy
Additional disease Duration of mechanical ventilation
Time of hospitalization (from the day of admission)
Outcome
HTIG, human tetanus immunoglobulin.
Speech difficulties
13 days
Incubation period
Farmer
Exitus because of cardiac arrhythmia
16 days
Pneumonia 15 days
Day 14 of admission
Day 1 of admission
þ
10 days
Head
Farmer Leg
Job
The wounded area
62 Female
79 Male
Age (year)
Case 2
Gender
Case 1
Table 1. Clinical and demographic characteristics of the cases.
Exitus because of cardiac arrhythmia
9 days
Renal failure, pneumonia 9 days
Day 9 of admission
Day 1 of admission
þ
500 IU
Generalized tetanus Congestive heart failure
15 days
Numbness of jaw
11 days
Head
Farmer
Male
75
Case 3
Exitus because of cardiac arrhythmia
15 days
Pneumonia 15 days
Day 9 of admission
Day 1 of admission
þ
500 IU
Generalized tetanus Type II diabetes mellitus
10days
Speech difficulties
13 days
Head
Hod carrier
Male
41
Case 4
Healthy discharge
35 days
Pneumonia 20 days
Day 9 of admission
Day 1 of admission
þ
500 IU
Generalized tetanus No
25 days
Contraction of the legs
10 days
Leg
Farmer
Male
70
Case 5
Exitus because of cardiac arrhythmia
20 days
Pneumonia 20 days
Day 9 of admission
Day 1 of admission
þ
500 IU
Generalized tetanus Chronic obstructive pulmonary disease
17 days
Speech difficulties
11 days
Leg
Farmer
Male
65
Case 6
40 Tropical Doctor 44(1)
Aksoy et al.
41
Muscle spasms should be treated effectively in order to reduce deaths caused by tetanus. For this purpose, the patient should immediately be placed in a dark, quiet room and sedated. Various drugs, including benzodiazepines, propofol, baclofen, barbiturates, dantrolene, magnesium and long-term neuromuscular blocking agents such as vecuronium have been used in clinics to treat muscle spasms. Circulatory collapse caused by autonomic instability is the major cause of death in patients with tetanus.5 Adequate sedation is provided and labetalol or morphine is used to treat autonomic dysfunction.12 Supportive treatment including enteral nutrition, tracheal suction, mouth care and thromboprophylaxis should be provided in order to reduce tetanus-related mortality.5 Pharmacologic management of tetanus was provided with the previously mentioned drugs in this current report. Tetanus is a fatal disease in both developing and developed countries. Pascual et al.13 reported 130 deaths due to tetanus infection during 1998–2000 in the USA. Sixteen of the patients were diabetic. They concluded that adults aged >60 years were at highest risk of tetanus and tetanus-related death. We report on six patients with tetanus, one of whom was under 60 and suffered from type II diabetes mellitus. It has been shown that diabetic patients had impaired ımmunity against tetanus14 and there have been no reports of deaths among patients who were up-to-date with their tetanus toxoid vaccination.13 However, there are reports of generalized tetanus in spite of prior vaccination and protective anti-tetanus antibody levels.15,16 We were unable to obtain information about the previous immunization status of our patients. It was found that the patient’s age, gender, duration of admission, incubation period, delays in diagnosis, delays in treatment and the characteristics of the wound affect mortality caused by tetanus infection.17,18 Additionally, incubation period varies due to the distance between the injury site and the central nervous system.17 Saltoglu et al.17 found that mortality is high in patients with an incubation period of
Tetanus is still a deadly disease: a report of six tetanus cases and reminder of our knowledge
Tropical Doctor 2014, Vol 44(1) 38–42 ! The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0049475513515213 tdo.sagepub.com
Mehmet Aksoy1, Erkan Cem Celık2, Alı Ahıskalıoglu3 and Muhammet Ahmet Karakaya2
Abstract We analysed the data in the medical records of six patients admitted for tetanus in the intensive care unit (ICU) of the anaesthesia department in the Medical Faculty of Ataturk University from 1 January 2010 to 31 December 2012. All patients received the generalized form of treatment for tetanus in the ICU. The average age of the patients was 65.33 13.45 years. Treatment modalities were administered to the patients in accordance with the literature. Four patients died despite all therapeutic interventions and two patients were discharged uneventfully. All those who died had chronic disease and infected wounds on their head, but only one patient had an infected wound on his leg. The surviving patients had no chronic illnesses but did have injuries on their legs. The presence of chronic disease increases tetanusrelated mortality. More information about the disease must be made available in order to make it preventable with regular vaccinations.
Keywords Autonomic dysfunction, intensive care unit, tetanus
Introduction Tetanus is a preventable disease caused by a bacterium called Clostridium tetani. However, it is still a deadly disease in many countries despite widespread vaccination programmes given from infancy to adulthood. The mortality rate of tetanus patients was reported to be 44% in Nigeria, 60.8% in Senegal, 52.4% in Congo and 58% in Turkey.1–4 C. tetani usually enters the body via a contaminated wound and releases tetanus toxin after completing the incubation time (the time from injury to the first symptom). Tetanus toxin reaches the central nervous system by travelling along axons of lower motor neurons.5 The toxin causes involuntary contraction (rigidity) and contraction in short periods of time (spasm) in the muscles. Clinical reflection of muscle contractions may occur as trismus (rigidity of temporal and masseter muscles), difficulty in opening the mouth and opistotonus (the backward arching of the columna as a result of the involuntary contraction of the back and neck muscles). Tetanus is clinically divided into four groups: neonatal; generalized; local; and cephalic. In the cephalic form, tetanus is localized to the head. Neonatal tetanus is a generalized form in children younger than 1 month. In generalized tetanus, the muscles of the whole body are
affected and opisthotonos, trismus, dysphagia, abdominal rigidity and respiratory failure may occur. The most significant cause of death in advanced stages is autonomic dysfunction defined as non-blocking, frequent fluctuations in blood pressure and heart rate depending on the affected area of the brain stem by toxin.5 With the approval of the Ethics Committee of the Medical Faculty, Ataturk University (reference number: B.30.2.ATA.0.01.00/135), we analysed data in the medical records of patients admitted with tetanus to the ICU of the Anaesthesia Department in the Medical Faculty of Ataturk University from 1 January 2010 to 31 December 2012. 1 Assistant Professor and Medical Doctor, Department of Anaesthesiology and Reanimation, Faculty of Medicine, Ataturk University, Erzurum, Turkey 2 Research Assistant and Medical Doctor, Department of Anaesthesiology and Reanimation, Faculty of Medicine, Ataturk University, Erzurum, Turkey 3 Anesthetist and Medical Doctor, Department of Anaesthesiology and Reanimation, Faculty of Medicine, Ataturk University, Erzurum, Turkey
Corresponding author: Mehmet Aksoy, Assistant Professor Doctor, Department of Anaesthesiology and Reanimation, Faculty of Medicine, Ataturk University, TR-25240 Erzurum, Turkey. Email: [email protected]
Downloaded from tdo.sagepub.com by guest on February 22, 2015
Aksoy et al.
39
Case history A total of six patients with diagnosed tetanus were admitted to our ICU between January 2010 and December 2012. The distributions of patients according to age, gender, clinical course of the disease, treatments and outcomes are presented in Table 1. The diagnosis of tetanus was made according to the patient’s history of trauma, cervical rigidity, trismus, generalized contractions over the whole body and respiratory failure requiring oxygen due to laryngospasm. All patients received the generalized form of tetanus ICU admission. The average age of the patients was 65.33 13.45 (between 41 and 79 years). One was female and the others were male. None of the patients knew the time of their last vaccination. Tetanus vaccine and immunoglobulin were administered in the emergency department of our hospital. Four patients had chronic illness (Table 1). All patients were sedated with propofol and treated with diazepam and morphine to relieve the spasms. Wounds were debrided and metronidazole (500 mg 3 times/day) was initiated in order to reduce toxin production. Intubation and mechanical ventilation was required by all patients. In our clinic, tracheostomy is not applied routinely to patients with tetanus and is only performed in cases of acute airway obstruction caused by severe laryngeal spasm and after obtaining consent from the relatives of the patient. In this case report, tracheostomy was performed in all patients (on the 14th day in one case and on the 9th day in the other cases) because of severe laryngospasm. There was a short delay in tracheostomy because their relatives did not initially give their consent. Cardiovascular stability was improved with phentolamine (an alpha-adrenergic antagonist), calcium channel blockers and high doses of atropine where necessary. Adequate nutrition, prophylactic heparin and preventive treatments for gastric ulcer and pressure sore formation were also provided. Pneumonia was reported in all patients due to prolonged critical illness. Four patients died despite all therapeutic interventions. After stabilization of autonomic functions (35 days after admission), two patients were transferred from the ICU to the infectious diseases service in order to reduce the risk of infection associated with intensive care. Later, we learned that they had made a complete recovery.
Discussion We report on six patients (five men and one woman) with the generalized form of tetanus who were followed in our ICU. Treatment modalities were administered to the patients in accordance with the published literature. Four of them died despite all therapeutic interventions.
The prognosis was influenced by the presence of a chronic illness and the distance between the injury site and the central nervous system. C. tetani is a Gram-positive, anaerobe bacillus that leads to tetanus. Generally, entry into the body occurs via a wound contaminated by manure, soil or rusted metal. The entry site cannot be found in approximately 20% of cases.6 C. tetani produces an exotoxin named tetanospasmin and causes clinical signs by destroying the central nervous system.7 There are no specific laboratory tests for the diagnosis of tetanus. A diagnosis of tetanus is made according to clinical history and findings which include rigidity, spasms, trismus or generalized paroxysms without loss of consciousness.7 Generalized tetanus is the most common form of tetanus. Usually, difficulty in opening the jaw and trismus are the initial symptoms in generalized tetanus. Later, risus sardonicus (contraction of the facial muscles), dysphagia, opisthotonus, abdominal rigidity, dysarthria and respiratory failure occur depending on the affected muscles of the whole body.5 All patients in this report received the generalized form of tetanus ICU admission. Reducing the toxin levels in circulation, controlling muscle spasms and maintaining haemodynamic stability are the primary goals for the treatment of tetanus.6 Debridement and aeration of the wound are essential in order to remove an ideal environment for this bacterium and to prevent ongoing toxin production.7 At the same time, an antibiotic should be given to patients in order to eradicate the tetanus bacterium. The recommended antibiotic is metronidazole, 500 mg 3 times/ day for 7–10 days. One study8 showed that the use of penicillin in tetanus may potentiate the effect of tetanus toxin by inhibiting the GABAA (glycine and g-amino butyric acid) receptor in the central nervous system. However, Ganesh Kumar et al.9 reported that the use of metronidazole in tetanus is as equally effective as penicillin. All of our patients had an infected wound, and wound cleaning and metronidazole administration were applied to each of them. Human tetanus immunoglobulin (HTIG) should be given intramuscularly in order to neutralize unbound toxin in the body and tetanus toxoid immunization should be administered in order to provide long-term immunity. However, the correct doses of HTIG are unclear; doses of 500 IU, 3000 IU or higher have been administered. Blake et al.10 analysed the data of 545 cases with tetanus for 6 years and reported similar survival rates between cases using HTIG doses of 8000 units and those using HTIG doses of 500 units. In a meta-analysis,11 intrathecal administration of HTIG was reported to be more beneficial than intramuscular administration. Intramuscular HTIG and tetanus toxoid were applied to our cases.
Downloaded from tdo.sagepub.com by guest on February 22, 2015
Downloaded from tdo.sagepub.com by guest on February 22, 2015
9 days
Generalized tetanus Chronic obstructive pulmonary disease 500 IU
Contraction of the legs 30 days
Generalized tetanus No 500 IU þ Day 1 of admission Day 9 of admission Pneumonia 17 days 35 days Healthy discharge
First symptoms
The time between the onset of the first symptom and admission to the emergency department
Symptoms on admission The presence of a chronic illness
Applied HTIG doses
Applied tetanus vaccine
Requirement for mechanical ventilation
Required tracheostomy
Additional disease Duration of mechanical ventilation
Time of hospitalization (from the day of admission)
Outcome
HTIG, human tetanus immunoglobulin.
Speech difficulties
13 days
Incubation period
Farmer
Exitus because of cardiac arrhythmia
16 days
Pneumonia 15 days
Day 14 of admission
Day 1 of admission
þ
10 days
Head
Farmer Leg
Job
The wounded area
62 Female
79 Male
Age (year)
Case 2
Gender
Case 1
Table 1. Clinical and demographic characteristics of the cases.
Exitus because of cardiac arrhythmia
9 days
Renal failure, pneumonia 9 days
Day 9 of admission
Day 1 of admission
þ
500 IU
Generalized tetanus Congestive heart failure
15 days
Numbness of jaw
11 days
Head
Farmer
Male
75
Case 3
Exitus because of cardiac arrhythmia
15 days
Pneumonia 15 days
Day 9 of admission
Day 1 of admission
þ
500 IU
Generalized tetanus Type II diabetes mellitus
10days
Speech difficulties
13 days
Head
Hod carrier
Male
41
Case 4
Healthy discharge
35 days
Pneumonia 20 days
Day 9 of admission
Day 1 of admission
þ
500 IU
Generalized tetanus No
25 days
Contraction of the legs
10 days
Leg
Farmer
Male
70
Case 5
Exitus because of cardiac arrhythmia
20 days
Pneumonia 20 days
Day 9 of admission
Day 1 of admission
þ
500 IU
Generalized tetanus Chronic obstructive pulmonary disease
17 days
Speech difficulties
11 days
Leg
Farmer
Male
65
Case 6
40 Tropical Doctor 44(1)
Aksoy et al.
41
Muscle spasms should be treated effectively in order to reduce deaths caused by tetanus. For this purpose, the patient should immediately be placed in a dark, quiet room and sedated. Various drugs, including benzodiazepines, propofol, baclofen, barbiturates, dantrolene, magnesium and long-term neuromuscular blocking agents such as vecuronium have been used in clinics to treat muscle spasms. Circulatory collapse caused by autonomic instability is the major cause of death in patients with tetanus.5 Adequate sedation is provided and labetalol or morphine is used to treat autonomic dysfunction.12 Supportive treatment including enteral nutrition, tracheal suction, mouth care and thromboprophylaxis should be provided in order to reduce tetanus-related mortality.5 Pharmacologic management of tetanus was provided with the previously mentioned drugs in this current report. Tetanus is a fatal disease in both developing and developed countries. Pascual et al.13 reported 130 deaths due to tetanus infection during 1998–2000 in the USA. Sixteen of the patients were diabetic. They concluded that adults aged >60 years were at highest risk of tetanus and tetanus-related death. We report on six patients with tetanus, one of whom was under 60 and suffered from type II diabetes mellitus. It has been shown that diabetic patients had impaired ımmunity against tetanus14 and there have been no reports of deaths among patients who were up-to-date with their tetanus toxoid vaccination.13 However, there are reports of generalized tetanus in spite of prior vaccination and protective anti-tetanus antibody levels.15,16 We were unable to obtain information about the previous immunization status of our patients. It was found that the patient’s age, gender, duration of admission, incubation period, delays in diagnosis, delays in treatment and the characteristics of the wound affect mortality caused by tetanus infection.17,18 Additionally, incubation period varies due to the distance between the injury site and the central nervous system.17 Saltoglu et al.17 found that mortality is high in patients with an incubation period of
