Case and Topic presentation on Tetanus including management and prevention

A case-based presentation on tetanus covering its clinical features, pathophysiology, diagnosis, and management. Emphasizes critical care aspects, complications, and preventive strategies through an illustrative patient case.

1. Case Presentation By : Noshirwan P. Gazder

2. History: 50 year old male, welder by profession, regular Pan consumer, known case Hypertension (Non-Compliant) was referred from JPMC ER with complaints of:   Jaw Stiffness for 2 days. Generalized Tonic Clonic Seizures for 1 day

3. History of Presenting Complains The patients attendant said the patient was in his usual state of health when 2 days back he started to develop difficulty in opening his jaw. The patient was initially taken to Abbasi Shaheed where the patient was managed for Hypertensive Urgency (BP of 175/100), the patient was then referred to JPMC. At JPMC the patient experienced an episode of Generalized Tonic Clonic Fits, there was up rolling of eyes along with urinary and fecal incontinence. The patient was later referred to ZU for admission and further management. The attendants did not give any history of fever, seizures, recent trauma and attendant was unsure of vaccination history.

4. Past Medical History: Hypertensive for the last 6 years, Non-compliant to meds. No H/o previous hospital admissions. Past Surgical History: No H/o Surgery or invasive procedures . No H/o blood transfusions. Drug history: Tab. Amlodipine 5 mg 1+0+0 (Non-Compliant) Family history: No history of Ischemic heart disease, tuberculosis, asthma, thyroid disorders, autoimmune diseases or cancers in the family

5. Personal History: Regular Pan Consumer; No other addictions. Sleep: Normal Bowel: Normal Micturition: Normal Social History: He is a resident of Aurangabad, Nazimabad. Lives in a 2 room house with his wife and daughter. Drinks boiled water and eats mostly meals cooked at home.

6. System Review Respiratory System Sputum Haemoptysis Chest pain SOB/ Dyspnoea Hoarseness Wheezing Cardiovascular Chest pain Paroxysmal Nocturnal Dyspnoea Orthopnoea Short Of Breath(SOB) Palpitations Cyanosis Gastrointestinal/Alimentary Difficulty in swallowing Oral ulcers Nausea/vomiting Abdominal pain/distension Regurgitation/heart burn Haematemesis , melaena , haematochagia Jaundice Nervous System Speech problem Seizures Visual/Smell/Taste/Hearing problem Head ache Muscle weakness Abnormal sensation Change of behaviour - ve - ve - ve - ve

7. System Review Urinary System Frequency Urgency Hesitancy Terminal dribbling Nocturia Back/loin pain Incontinence Character of urine Musculoskeletal System Pain Swelling Back or neck pain Red eyes Deformities Skin rash Painful/ cold fingers Endocrine System Swelling in neck Fatigue Thirst Sweating - ve - ve - ve HEMATALOGICAL System Bruises Epistaxis Lumps Gum bleeding - ve

8. Examination: General Impression: A middle aged male of average height and build lying on bed, unable to open his jaw, with stiffness in his entire body. Vitals: Blood Pressure:160/90 mm/Hg Pulse: 89/min, regular Temperature: A/F Respiratory Rate:23/min Oxygen saturation: 96% on 2 ltrs O2 via Nasal prongs

9. Examination CVS: S1+S2+0 Abdominal Exam: Soft Non-Tender; No visceromegaly. Respiratory Exam: B/L Harsh Vesicular Breathing. GCS: 12/15 (E4, V2, M6)

10. RIGHT UPPER LIMB RIGHT LOWER LIMB RIGHT LOWER LIMB LEFT LOWER LIMB BULK NORMAL NORMAL NORMAL NORMAL TONE INCREASED INCREASED INCREASED INCREASED POWER 4 4 5 4 REFLEXES +3 +3 +2 +2

11. Differential Diagnosis Tetanus. Meningits. CVA. Seizure Disorder

12. INVESTIGATIONS:

13. CBC   UNIT RANGE Hb 14.0 mg/dl 11.1-14.5 MCV 87 fL 80-100 WBC 12.1 10 9  per liter 4 to 10 PLATELETS 206 10 9  per liter 150-450 NEUT 81     LYMP 5     UCE       Na 138 Meq/L 135-145 K 4.3 Meq/L 3.5-5.5 CL 109 Meq/L 98-107 HCO3 22 Meq/L 22-29 UREA 38 mg/dl 10 to 50 CREATININE 0.76 mg/dl 0.6-1.5 LFT       TB 0.53 mg/dl <1.3 DB 0.25 mg/dl <0.3 SGPT 20 IU/L Upto 31 ALK P 80 U/L 39-117 GGT 9 IU/L 11 to 50

14. Trop I: 0.098- 0.069- 0.029 ng/ml (<0.010 ng/ml) LDH: 363 U/L (135-225 U/L ) CPK: 1154 U/L (46-171 U/L ) Ca: 8.44 mg/dl (8.6-10 mg/dl) CRP: 11.6 mg/L ( upto 5 mg/L ) CT Brain (from JPMC): No acute Infarct/ hemorrhage noted. Small hypodense area noted in Right posterior fossa.

15. TREATMENT AND HOSPITAL COURSE: The patient was electively intubated after giving sedation. Patient was started on Inj. Benzallin Penicillin 4 MU x IV x 6 hrly. Inj. Metronidazole 500 mg x IV x 8 hrly. Tetanus Immunoglobulin 3000 IU x IM x Stat. Tetanus Toxoid x IM x Stat. Inj. R/L @ 80ml/hr. Inj. Decadron 4 mg x IV x 8 hrly. Inj. Hydralazine 10 mg x IV x SOS. Inj. Valium 3 cc x IV x SOS. Inj. L evetiracetam 1gm IV stat then 500 mg IV 12 hrly.

16. Neuro team advised that the patient will have to be intubated for 4 weeks or more. For prolonged intubation, the attendants were advised to carry out a tracheostomy. Due to rising costs the patients were referred to a Government Hospital.

17. Tetanus

18. Tetanus is a nervous system disorder characterized by muscle spasms that are caused by the toxin-producing anaerobe  Clostridium tetani , which is found in the soil . It is characterized by an acute onset of hypertonia, painful muscular contractions (usually of the muscles of the jaw and neck), and generalized muscle spasms without other apparent medical causes. It is the only vaccine preventable disease that is infectious but not contagious.

19. The majority of reported tetanus cases are birth-associated, occurring in low income countries among insufficiently vaccinated mothers and their newborn infants, following unhygienic deliveries and abortions and poor postnatal hygiene and cord care practices . The disease remains an important public health problem in many parts of the world where immunization programmes are suboptimal, particularly in third world countries. Case-fatality rates vary from 10% to 70% depending on treatment, age and general health of the patient. Patients in the youngest and oldest age groups without intensive care, have a 100 % case-fatality rate.

20. Tetanus occurs when spores of  Clostridium tetani , an obligate anaerobe normally present in the gut of mammals and widely found in soil, gains access to damaged human tissue. After inoculation,  C. tetani  transforms into a vegetative rod-shaped bacterium and produces tetanus toxin, also known as tetanospasmin. After reaching the spinal cord and brainstem via retrograde axonal transport within the motor neuron, tetanus toxin is secreted and enters adjacent inhibitory interneurons, where it stops the release of certain inhibitory neurotransmitters [ glycine and gamma-amino butyric acid (GABA) ]

21. The shortest peripheral nerves are the first to deliver the toxin to the CNS, which leads to the early symptoms of facial distortion and back and neck stiffness. Once the toxin becomes fixed to neurons, it cannot be neutralized with antitoxin. Recovery of nerve function from tetanus toxins requires sprouting of new nerve terminals and formation of new synapses.

22. Clinical Features Triad of muscle rigidity, spasms & autonomic dysfunction are most common. Early symptoms are neck stiffness, sore throat and poor mouth opening . Other presenting complaints include stiffness, neck rigidity, dysphagia, restlessness, and reflex spasms. Spasms usually continue for 3-4 weeks Muscle rigidity spreads in a descending pattern from the jaw and facial muscles over the next 24-48 hours to the extensor muscles of the limbs – stiff proximal limb muscles & relative sparing of hands & feet.

23. Risus sardonicus : Sustained contraction of facial musculature produces a sneering grin expression. Opisthotonus : Spasm of extensor of the neck, back and legs to form a backward curvature . Reflex spasms: Develop in most patients and can be triggered by minimal external stimuli such as noise, light, or touch. The spasms last seconds to minutes, become more intense with disease progression; and can cause apnea, fractures and dislocations.

24. Diagnosis The diagnosis of tetanus is generally based upon typical clinical findings . Tetanus should especially be suspected when there is a history of a tetanus-prone injury and a history of inadequate immunization for tetanus.

25. Treatment Treatment of tetanus is best performed in an ICU Setting in consultation with an anesthesiologist or critical care specialist trained in the management of the complications of this disease. -The goals of treatment include : Halting toxin production. Neutralization of the unbound toxin. Airway management. Control of muscle spasms. Management of dysautonomia. General supportive management.

26. Principle of Treatment Admit patients in an intensive care unit setting (ICU ) Due to risk of reflex spasms, a dark and quiet environment must be maintained for the patient . Attempting endotracheal intubation may induce severe reflex, preparations for emergency tracheostomy should be arranged beforehand. Prophylactic tracheostomy in all patients with moderate-to-severe clinical manifestations. (Tracheostomy has also been recommended after onset of the first generalized seizure) Prophylaxis of thromboembolism with heparin or other anticoagulants should be administered early.

27. Halting Toxin Production Wound management: W ound debridement to eradicate spores and necrotic tissue, which could lead to conditions ideal for germination( i.e anaerobic conditions) Antimicrobial therapy: Although antibiotics probably play a relatively minor role in the management of tetanus, they are universally recommended .   Appropriate antimicrobial therapy may fail to eradicate  C. tetani  unless adequate wound debridement is performed.

28. Metronidazole (500 mg intravenously [IV] every six to eight hours) is the preferred treatment for tetanus. But  penicillin G (2 to 4 million units IV every four to six hours) is a safe and effective alternative. A treatment duration of 7 to 10 days is usually recommended. Doxycycline, Clindamycin and Erythromycin are alternatives for penicillin allergic patients who can not tolerate metronidazole

29. Neutralization of Unbound Toxin   Since tetanus toxin is irreversibly bound to tissues, only unbound toxin is available for neutralization. Use of passive immunization to neutralize unbound toxin is associated with improved survival. A single dose of Human  tetanus immune globulin (HTIG ) 500 units intramuscularly is the preparation of choice (previously recommended dose range was 3000 to 6000 U) The dose should be given as soon as the diagnosis of tetanus is considered, with part of the dose infiltrated around the wound.

30. Airway Management Endotracheal intubation is justified initially. Early tracheostomy is frequently indicated due to likelihood of prolonged mechanical ventilation. As it allows for better tracheal suctioning and pulmonary toilet.

31. Control of Muscle Spasms Generalized muscle spasms are life threatening since they can cause respiratory failure, lead to aspiration, and induce generalized exhaustion in the patient . Benzodiazepines and other sedatives : Diazepam is most frequently used, Benzodiazepines are generally effective in controlling the rigidity and spasms associated with tetanus. Diazepam or Midazolam can be used as 5-10mg iv/im every 1-4 hrly.

32. Neuromuscular blocking agents : Used when sedation alone is inadequate Vecuronium (0.1 mg/kg IV) or atracurium (0.5 mg/kg IV) is appropriate. Baclofen, which stimulates postsynaptic GABA beta receptors, has been used in a few small studies. The preferred route is intrathecal, and it may be given either in a bolus of 1000 mcg or by continuous intrathecal infusion. It was found to control spasms and rigidity in 21 out of 22 patients with tetanus in a retrospective outcome study from a single medical center in Portugal. One of 22 patients developed meningitis secondary to infection of the intrathecal catheter.

33. Management of Autonomic Dysfunction Magnesium sulfate: A cts as a presynaptic neuromuscular blocker, blocking catecholamine release from nerves, and reduces receptor responsiveness to catecholamines. A loading dose of 5 gm should be given over 20 minutes, followed by intravenous infusion of 2gm/hr. The dose can be incresed by upto 0.5g/hr until spasms are relieved or the patellar reflex disappears . In a randomized, double blind trial in 256 hospitalized patients with severe tetanus in Vietnam, magnesium sulfate infusion compared with placebo controlled autonomic dysfunction. Magnesium infusion significantly reduced the requirement for other drugs to control muscle spasms. However, magnesium sulfate infusion did not reduce the need for mechanical ventilation.

34.  Labetalol (0.25 to 1 mg/min) can also be given due to its dual alpha- and beta-blocking properties . Morphine  sulfate (0.5 to 1 mg/kg per hour by continuous intravenous infusion) is commonly used to control autonomic dysfunction as well as to induce sedation. Other drugs for the treatment of various autonomic events, which have been reported to be useful, are   atropine , clonidine, and epidural bupivacaine.

35. Prevention Tetanus is completely preventable by active tetanus immunization . Immunization is thought to provide protection for 10 years . Immunization begins in infancy with the DTP series of shots. (DTP vaccine is a "3-in-1" vaccine that protects against diphtheria, pertussis, and tetanus)

36. Evaluating the immunization status of the patient is vital.   Unvaccinated persons or persons with uncertain history of receiving tetanus toxoid-containing vaccines. Should start and complete a primary series with an age-appropriate tetanus toxoid-containing vaccine (i.e., DTaP, TdaP, Td) as currently recommended by CDC. (They should complete a primary series.

37. Persons who have completed a 3-dose primary tetanus vaccination series: If the last dose of a tetanus toxoid-containing vaccine was received less than 5 years earlier, yhey do not require another dose of the vaccine as part of the current wound management. If the last dose of a tetanus toxoid-containing vaccine was received 5 or more years earlier, then administer a booster dose of an age-appropriate tetanus toxoid-containing vaccine.

38. Active and Passive Immunization In non immunized persons: Human tetanus immune globulin (HTIG) 500 units in one arm & 0.5 ml of adsorbed tetanus toxoid into other arm /gluteal region 6 wks later, 0.5 ml of tetanus toxoid. 1 yr later , 0.5 ml of tetanus toxoid.

39. Thank You