Tetanus

Overview

Tetanus is a life-threatening, vaccine-preventable neurological disease caused by the exotoxin tetanospasmin produced by Clostridium tetani, a spore-forming obligate anaerobic Gram-positive bacillus ubiquitous in soil, dust, and animal faeces. [1] The disease is characterized by severe muscle rigidity and painful spasms resulting from irreversible blockade of inhibitory neurotransmitter release in the central nervous system. [2,3] Despite the availability of an effective vaccine and modern intensive care, tetanus carries a mortality rate of 10-20% in high-income countries and up to 50% in resource-limited settings. [4,5]

The global burden of tetanus has decreased dramatically over the past three decades, with deaths falling by nearly 90% between 1990 and 2019, primarily due to the WHO's Maternal and Neonatal Tetanus Elimination campaign. [4] However, the disease remains an important cause of morbidity and mortality in southern Asia, southeast Asia, and sub-Saharan Africa, with an estimated 35,000 deaths annually worldwide. [1,4] In developed countries, tetanus is rare but continues to occur in unvaccinated or inadequately vaccinated individuals, the elderly with waning immunity, intravenous drug users (IVDU), and migrants from non-vaccinated populations. [5,6]

The cornerstone of management is early recognition, passive immunization with human tetanus immunoglobulin (HTIG), wound debridement, antibiotic therapy with metronidazole, control of muscle spasms with benzodiazepines and magnesium sulphate, and meticulous intensive care support. [7,8] Recovery requires regeneration of nerve terminals, which may take weeks to months. [9] Critically, having tetanus does not confer immunity, so all survivors must receive active immunization with tetanus toxoid. [10]

Key Clinical Points

Diagnosis is Entirely Clinical

• There is no confirmatory laboratory test for tetanus
• Classic triad: recent wound + trismus + muscle rigidity/spasms
• Spatula test (reflex spasm on posterior pharyngeal stimulation) has 94% sensitivity and 100% specificity [11]

Prognostic Factors

• Shorter incubation period (less than 7 days) predicts more severe disease and higher mortality [12,13]
• Shorter period of onset (less than 48 hours from first symptom to first generalized spasm) indicates worse prognosis [13]
• Autonomic instability is associated with significantly increased mortality [14]

Management Priorities

1. Neutralize unbound toxin with HTIG (3000-6000 IU IM)
2. Eliminate bacterial source (wound debridement + metronidazole 500mg IV TDS)
3. Control spasms (benzodiazepines ± magnesium sulphate)
4. Provide supportive ICU care (airway protection, mechanical ventilation if needed)
5. Manage autonomic instability (magnesium, morphine, consider dexmedetomidine)
6. Commence active immunization (tetanus toxoid vaccine) [7,8,15,16]

---

Epidemiology

Global Burden

Tetanus remains a significant global health problem despite being entirely preventable through vaccination. The WHO reported approximately 34,000 deaths from tetanus in 2019, representing an 88% reduction from approximately 280,000 deaths in 1990. [4] The vast majority of current cases occur in low- and middle-income countries, particularly in southern Asia, southeast Asia, and sub-Saharan Africa where vaccination coverage remains suboptimal. [1,4]

Neonatal tetanus, resulting from umbilical infection in newborns of unvaccinated mothers, has been successfully eliminated in most countries through maternal immunization programs. [17] However, deaths among children and adults have plateaued in recent years, highlighting the ongoing challenge of maintaining population immunity and ensuring appropriate wound prophylaxis. [4]

Incidence in High-Income Countries

In developed countries with comprehensive vaccination programs, tetanus has become extremely rare:

Demographics and Risk Factors

Age Distribution

• Bimodal distribution: neonates in endemic areas and elderly adults (> 60 years) in developed countries [5,6]
• In the United States (2001-2008), 48% of tetanus cases occurred in persons aged ≥60 years [6]
• Age-related increase reflects waning immunity from vaccination (half-life of protective antibodies approximately 11 years) and decreased likelihood of receiving booster doses [19]

Sex

• Slight male predominance (male:female ratio approximately 1.5:1) attributed to occupational exposure in agricultural and construction work [5,6]

High-Risk Populations

Wound Characteristics

• Puncture wounds (45-50% of cases) — anaerobic environment favours spore germination [5,6]
• Lacerations (30-35% of cases)
• Abrasions and crush injuries (10-15%)
• Chronic wounds (ulcers, gangrene) (5-10%)
• Burns (particularly if contaminated with soil)
• No identifiable wound in 10-20% of cases [5,6,20]

Tetanus-Prone Wounds According to UK Public Health England guidance, wounds are considered tetanus-prone if they meet any of the following criteria: [21]

• Sustained > 6 hours before surgical treatment
• Puncture-type wound
• Contact with soil or manure likely
• Clinical evidence of sepsis
• Significant degree of devitalized tissue
• Compound fracture
• Wounds or burns requiring surgical intervention delayed > 6 hours

---

Microbiology and Pathophysiology

The Organism: Clostridium tetani

Clostridium tetani is an obligate anaerobic, motile, Gram-positive, spore-forming bacillus with a characteristic "drumstick" appearance due to terminal spore formation. [1] The organism is ubiquitous in the environment, found in:

• Soil (particularly if contaminated with animal faeces)
• Dust
• Animal and human faeces
• Rusty metal surfaces (the rust itself is not causative but indicates environmental exposure)

Spore Characteristics

• Highly resistant to heat, desiccation, and disinfectants
• Can survive for years in soil
• Germinate only under anaerobic conditions (Eh <+0.01V)
• Anaerobic microenvironment created by devitalized tissue, foreign bodies, or co-infection with aerobic bacteria [1,2]

Toxin Production and Mechanism

Tetanospasmin (Tetanus Toxin) Tetanospasmin is one of the most potent biological toxins known to science, with an estimated lethal dose in humans of approximately 1 nanogram per kilogram body weight. [2,3] The toxin is a 150-kDa protein consisting of:

• Heavy chain (100 kDa) — mediates binding and translocation
• Light chain (50 kDa) — zinc-dependent endopeptidase with enzymatic activity
• Connected by a disulphide bond

Molecular Mechanism of Action

The pathophysiology of tetanus follows a well-defined sequence: [2,3,9]

1. Local Wound Infection

• Spores enter through wound
• Germinate under anaerobic conditions
• Vegetative bacteria multiply and produce tetanospasmin

2. Toxin Binding

• Tetanospasmin binds to peripheral nerve terminals via ganglioside receptors (specifically GT1b and GD1b)
• Heavy chain mediates receptor-mediated endocytosis

3. Retrograde Axonal Transport

• Toxin is transported retrogradely within motor neurons via microtubule-associated dynein motor proteins
• Transport rate: approximately 75-250 mm/day [9]
• Reaches spinal cord and brainstem

4. Trans-Synaptic Migration

• Toxin crosses the synaptic cleft to inhibitory interneurons
• Preferentially affects Renshaw cells (glycinergic) and GABAergic interneurons

5. Irreversible Synaptic Blockade

• The light chain (a zinc metalloproteinase) cleaves synaptobrevin (VAMP), a protein essential for vesicle fusion
• This prevents release of inhibitory neurotransmitters:
  • Glycine (primary inhibitory neurotransmitter in spinal cord and brainstem)
  • GABA (gamma-aminobutyric acid)
• Result: unopposed excitatory input to alpha motor neurons

6. Clinical Manifestations

• Muscle rigidity: sustained contraction due to loss of reciprocal inhibition
• Reflex spasms: exaggerated response to stimuli (afferent stimulation triggers unopposed motor neuron firing)
• Autonomic dysfunction: toxin also affects sympathetic and parasympathetic neurons, causing catecholamine surges and labile cardiovascular instability [14]

Tetanolysin C. tetani also produces tetanolysin, a haemolysin, but its role in human disease is unclear and it does not contribute to the characteristic clinical features of tetanus. [1]

Recovery and Regeneration

Because tetanospasmin binding is irreversible, recovery depends on: [9]

• Sprouting of new nerve terminals
• Re-establishment of synaptic connections
• Regeneration rate: weeks to months
• This explains the prolonged clinical course and lengthy ICU stays characteristic of severe tetanus

Importantly, having tetanus does not confer immunity because the amount of toxin required to cause disease is far below the amount needed to trigger an immune response. All patients must receive active immunization with tetanus toxoid. [10]

---

Clinical Presentation

Incubation Period and Period of Onset

Two critical time intervals determine disease severity: [12,13]

Incubation Period

• Time from wound contamination to first symptom
• Range: 3-21 days (median: 7-10 days)
• Shorter incubation (less than 7 days) predicts more severe disease and higher mortality
• Depends on: distance from CNS, toxin load, wound vascularity

Period of Onset

• Time from first symptom to first generalized spasm
• Range: 1-7 days
• Shorter period (less than 48 hours) indicates severe disease with poor prognosis [13]

Clinical Forms of Tetanus

Generalized Tetanus: Clinical Progression

Stage 1: Prodrome (1-7 days)

• Often overlooked or dismissed
• Restlessness, irritability, anxiety
• Headache, malaise
• Muscle stiffness (especially jaw and neck)
• Dysphagia
• Low-grade fever

Stage 2: Onset of Rigidity

Trismus (Lockjaw)

• First symptom in 50-75% of cases [5,20]
• Masseter muscle spasm preventing mouth opening
• Inability to open mouth > 3 cm (normal: 4-6 cm)
• May be mistaken for dental abscess or temporomandibular joint disorder
• Critical diagnostic feature

Risus Sardonicus (Sardonic Smile)

• Sustained contraction of facial muscles
• Raised eyebrows, wrinkled forehead
• "Grinning" expression with drawn-back corners of mouth
• Highly characteristic of tetanus [11,20]

Neck and Pharyngeal Rigidity

• Nuchal rigidity (may mimic meningitis)
• Dysphagia (risk of aspiration)
• Stiffness progressing down the body

Stage 3: Generalized Rigidity and Spasms

Opisthotonus

• Extreme hyperextension of the back
• Due to powerful contraction of paravertebral muscles
• Arching of the back with only head and heels touching the bed
• Patient's body forms a "C" shape
• Pathognomonic when present [11]

Abdominal and Chest Wall Rigidity

• "Board-like" rigid abdomen (may mimic acute abdomen)
• Intercostal muscle rigidity impairs chest wall compliance
• Respiratory compromise

Limb Rigidity

• Typically extension of lower limbs
• Flexion of upper limbs
• Hands often clenched in fists

Reflex Spasms

• Sudden, violent, generalized muscle contractions
• Extremely painful
• Triggered by minimal stimuli:
  • Noise
  • Touch
  • Light
  • Movement
  • Attempting to examine the patient
• Duration: seconds to minutes
• Frequency: every few minutes in severe cases
• Patient remains fully conscious throughout (distressing feature)

Stage 4: Autonomic Instability (Severe Cases)

Appears in approximately 30-50% of severe cases, typically 7-14 days after symptom onset and associated with significantly increased mortality: [14,22]

Cardiovascular Manifestations

• Labile hypertension alternating with hypotension
• Tachycardia alternating with bradycardia (sometimes progressing to asystole)
• Arrhythmias (including ventricular tachycardia, ventricular fibrillation)
• Sudden cardiac arrest

Other Autonomic Features

• Profuse sweating
• Hyperthermia (> 40°C) without infection
• Increased salivation and bronchial secretions
• Urinary retention
• Ileus

Pathophysiology of Autonomic Dysfunction

• Excessive catecholamine release (plasma noradrenaline levels may be 10-20 times normal) [14]
• Loss of inhibitory control over sympathetic outflow
• Parasympathetic dysfunction
• Cardiovascular instability is a major cause of death in tetanus survivors beyond the acute spasm phase [14,22]

---

Clinical Examination

General Inspection

Consciousness Level

• Patient is fully conscious and alert throughout (unless sedated)
• Orientation and cognition intact
• Extreme anxiety and distress common

Position and Posture

• Lying rigid and still to avoid triggering spasms
• Opisthotonus may be present
• Minimal voluntary movement

Vital Signs

• Tachycardia (resting HR often > 100 bpm)
• Hypertension or labile BP in autonomic dysfunction
• Tachypnoea (rapid shallow breathing due to chest wall rigidity)
• Fever (usually low-grade unless autonomic instability present)

Specific Examination Findings

Head and Neck

Trunk and Limbs

• Board-like abdominal rigidity without tenderness (unlike peritonitis)
• Paravertebral muscle rigidity with hyperextension of spine
• Limb rigidity with increased tone
• Normal or exaggerated deep tendon reflexes
• No focal neurological deficits (power, sensation, coordination normal between spasms)

Respiratory System

• Reduced chest wall excursion due to intercostal rigidity
• Risk of hypoventilation and respiratory failure
• Laryngospasm may occur with spasms (life-threatening airway obstruction)

Cardiovascular System

• Tachycardia
• Labile blood pressure
• Arrhythmias (if autonomic instability present)

Wound Examination

Critical to identify portal of entry:

• Carefully inspect entire body surface
• Look for:
  • Puncture wounds (including very minor injuries)
  • Lacerations, abrasions
  • Injection sites (in IVDU — check between toes, groin, subcutaneous areas)
  • Chronic ulcers (diabetic, venous)
  • Burns
  • Dental infections or recent dental procedures
  • Post-surgical wounds
  • Ear infections (especially in cephalic tetanus)
• No wound identified in 10-20% of cases [5,6]

The Spatula Test

A simple, highly sensitive and specific bedside diagnostic test: [11]

Method

1. Touch the posterior pharyngeal wall with a tongue depressor or spatula
2. Observe patient's response

Interpretation

• Positive test: Reflex spasm of masseter muscles causing jaw to clench on spatula (patient bites down)
• Negative test: Normal gag reflex (patient gags and spatula is expelled)

Diagnostic Performance [11]

• Sensitivity: 94%
• Specificity: 100%
• A positive test is highly suggestive of tetanus

Mechanism

• In tetanus: loss of inhibitory control causes reflex masseter contraction instead of normal gag
• Simple, safe, and can be performed at bedside

---

Differential Diagnosis

Tetanus is a clinical diagnosis that must be differentiated from other causes of trismus, muscle rigidity, and spasms.

Key Differential Diagnoses

Red Flags That Suggest Tetanus Rather Than Mimics

• Trismus + risus sardonicus + recent wound = tetanus until proven otherwise
• Patient remains fully conscious during spasms (unlike seizures)
• Spasms are stimulus-provoked and extremely painful
• Progressive descending pattern: jaw → neck → trunk → limbs
• No response to anticholinergics (unlike dystonia)
• Positive spatula test [11]

---

Investigations

Critical Principle: Tetanus is a Clinical Diagnosis

There is no confirmatory laboratory test for tetanus. [1,5,7]

Diagnosis rests on:

1. Compatible clinical features (trismus, rigidity, spasms)
2. History of wound or potential portal of entry
3. Inadequate vaccination status
4. Absence of alternative diagnosis

Investigations serve to:

• Support the diagnosis
• Exclude differential diagnoses
• Assess severity and complications
• Guide management

Microbiological Investigations

Clinical Implication: Do not delay treatment awaiting culture results. Start empirical management based on clinical suspicion.

Serological Testing

Anti-Tetanus Antibody Level

• Serum IgG antibodies measured by ELISA
• Protective level: ≥0.01 IU/mL (some sources use ≥0.1 IU/mL for optimal protection) [19,21]
• Level less than 0.01 IU/mL suggests inadequate immunity

Clinical Utility and Limitations

• Protective antibody levels do not exclude acute tetanus (antibody cannot access CNS-bound toxin)
• Low or absent antibody levels support diagnosis in appropriate clinical context
• More useful for assessing population immunity or post-vaccination response
• Not recommended for acute diagnostic decision-making [7]

Supportive Investigations

Baseline Blood Tests

• Full blood count: leukocytosis may occur (non-specific stress response)
• Urea and electrolytes: assess renal function, exclude hypocalcaemia
• Calcium and magnesium: exclude hypocalcaemic tetany
• Creatine kinase (CK): often elevated (500-3000 U/L) due to sustained muscle contraction [20]
  • Marked elevation suggests rhabdomyolysis
• Liver function tests: baseline before metronidazole
• Blood glucose: exclude hypoglycaemia

Arterial Blood Gas

• Respiratory acidosis (if hypoventilation due to chest wall rigidity)
• Metabolic acidosis (if rhabdomyolysis or prolonged spasms)
• Lactate elevation (muscle hypoxia during spasms)

Electrocardiogram (ECG)

• Tachycardia
• Arrhythmias (if autonomic instability) [14]
• QTc prolongation (exclude hypocalcaemia; may occur with autonomic dysfunction)

Imaging

• Chest X-ray: aspiration pneumonia (common complication), pulmonary oedema
• CT head: only if altered consciousness or focal neurology to exclude intracranial pathology
• Imaging of wound: X-ray or ultrasound to identify foreign body, abscess, or retained debris

Lumbar Puncture

• Indicated only if meningitis/encephalitis is in the differential
• CSF in tetanus: normal (no pleocytosis, normal protein and glucose)
• Opening pressure normal
• Do NOT perform LP routinely — risk of precipitating spasm during procedure

Electromyography (EMG)

• Not routinely indicated
• Research tool: shows continuous motor unit activity

---

Severity Classification

Ablett Classification of Tetanus Severity

The Ablett classification is widely used to stratify disease severity and predict outcomes: [13,20]

Clinical Application

• Grade I-II: Ward-based care with close monitoring; benzodiazepines
• Grade III: ICU admission; likely to require intubation and mechanical ventilation
• Grade IV: ICU with advanced haemodynamic monitoring; high risk of sudden death from autonomic storms [14]

Prognostic Scoring: Dakar Score

An alternative scoring system developed in resource-limited settings: [23]

Points assigned based on:

• Incubation period (less than 7 days: 1 point)
• Period of onset (less than 2 days: 1 point)
• Portal of entry (umbilical/burns/surgical: 1 point; uterine/injection/unknown: 2 points)
• Generalized spasms: 1 point
• Fever > 38.4°C: 1 point

Total Score and Mortality

• 0-1 points: mortality ~10%
• 2-3 points: mortality ~30%
• 4-6 points: mortality > 50%

Key Prognostic Factors

Associated with Increased Mortality [12,13,14,22]

• Short incubation period (less than 7 days)
• Short period of onset (less than 48 hours)
• Extremes of age (less than 1 year or > 60 years)
• Ablett Grade III-IV
• Autonomic instability
• Presence of complications (aspiration, rhabdomyolysis, arrhythmias)
• Delayed presentation to medical care
• Inadequate access to ICU facilities

---

Management

Management of tetanus is multifaceted and requires coordination between emergency medicine, infectious diseases, intensive care, and surgical teams. The principles are: [7,8,15,16]

1. Neutralize unbound toxin (immunoglobulin)
2. Eliminate source of toxin (wound debridement + antibiotics)
3. Control muscle spasms and rigidity
4. Provide supportive intensive care
5. Manage autonomic instability
6. Prevent complications
7. Commence active immunization

1. Immediate Resuscitation and Stabilization

Airway, Breathing, Circulation (ABC)

• Airway: assess for compromise due to trismus, laryngospasm
  • Intubation may be extremely difficult (trismus, masseter spasm)
  • Consider awake fibreoptic intubation or surgical airway in severe cases
  • "Indications for intubation: Grade III tetanus, respiratory failure, uncontrolled spasms, inability to protect airway"
• Breathing: monitor for hypoventilation, aspiration
  • Chest wall rigidity reduces compliance
  • Arterial blood gas monitoring
• Circulation: establish IV access, fluid resuscitation if needed

Environment

• Transfer to quiet, darkened single room to minimize stimuli
• Minimize noise, light, handling
• Gentle care — any stimulation can trigger spasms

Monitoring

• Continuous cardiac monitoring (telemetry or ICU monitoring)
• Pulse oximetry
• Blood pressure monitoring (consider arterial line if autonomic instability)
• Hourly neurological observations
• Core temperature

2. Neutralize Unbound Toxin: Immunoglobulin Therapy

Human Tetanus Immunoglobulin (HTIG) is the treatment of choice: [7,15,24]

Dosing

• Standard dose: 3000-6000 IU intramuscularly as a single dose
  • Some protocols use 500 IU for mild cases
  • Higher doses (up to 10,000 IU) have been used but do not improve outcomes
• Route: Intramuscular injection (divided into multiple sites if large volume)
  • "Intravenous immunoglobulin (IVIG) can be used if IM not feasible (dose: 150-400 IU/kg) [24]"
• Timing: Administer as soon as diagnosis is suspected — do not delay

Mechanism

• Provides passive immunity through preformed antibodies
• Neutralizes circulating (unbound) tetanospasmin
• Does NOT neutralize toxin already bound to nerve terminals
• Does NOT provide long-term immunity (active vaccination is essential)

Equine (Horse) Tetanus Antitoxin (TAT)

• Alternative when HTIG unavailable (common in resource-limited settings)
• Dose: 1500-3000 IU IM or IV (after test dose to exclude hypersensitivity)
• Higher risk of adverse reactions (serum sickness, anaphylaxis)
• Less effective than HTIG [24]

Evidence

• No high-quality RCTs compare HTIG vs. placebo (unethical to withhold)
• Historical evidence and biological plausibility strongly support use
• HTIG preferred over equine antitoxin (fewer adverse reactions, longer half-life) [24]

3. Eliminate Source: Wound Management and Antibiotics

Wound Debridement

• Surgical exploration and debridement of all devitalized tissue, foreign bodies
• Remove necrotic tissue to eliminate anaerobic environment
• Irrigate wound copiously
• Leave wound open or loosely packed (do not close primarily)
• Timing: as soon as patient is stable
• Perform debridement AFTER giving immunoglobulin (manipulation may release toxin into circulation)

Antibiotic Therapy

First-Line: Metronidazole [7,15,25]

• Dose: 500 mg IV every 8 hours (or 400 mg orally TDS if able to swallow)
• Duration: 7-10 days
• Mechanism: Bactericidal against anaerobes; penetrates devitalized tissue well
• Evidence: Superior to penicillin in RCT (lower mortality) [25]
• Contraindications: Avoid if history of seizures (metronidazole can lower seizure threshold)

Alternative: Benzylpenicillin (Penicillin G)

• Dose: 2-4 million units IV every 4-6 hours
• Duration: 7-10 days
• Historical standard, but metronidazole now preferred
• Theoretical concern: Penicillin is a GABA antagonist and may worsen spasms (clinical significance unclear) [25]

Other Options

• Doxycycline 100 mg BD (if penicillin allergy and metronidazole contraindicated)
• Erythromycin 500 mg QDS (alternative)

Do NOT use aminoglycosides or fluoroquinolones — may potentiate neuromuscular blockade

4. Control of Muscle Spasms and Rigidity

Benzodiazepines: First-Line Therapy [7,8,15,16]

Diazepam

• Mechanism: Enhances GABAergic inhibition, muscle relaxation, sedation
• Dosing regimens:
  • "Intermittent IV boluses: 10-40 mg IV every 2-8 hours as needed for spasms"
  • "Continuous IV infusion: 0.1-0.8 mg/kg/hour (may require very high doses)"
  • "Oral/NG: 5-20 mg every 4-6 hours (if patient can swallow)"
• Titrate to effect: aim to control spasms while maintaining consciousness if possible
• Very high cumulative doses may be required (> 1000 mg/day in severe cases)
• Evidence: Cochrane review found insufficient high-quality evidence but clinical consensus supports use [26]

Midazolam

• Alternative or adjunct to diazepam
• Dose: 0.05-0.4 mg/kg/hour continuous IV infusion
• Shorter half-life; easier to titrate
• Preferred if prolonged sedation needed

Lorazepam

• Dose: 0.5-2 mg IV every 4-6 hours
• Longer duration of action than midazolam

Magnesium Sulphate: Second-Line/Adjunct [8,16]

Landmark RCT by Thwaites et al. (2006) demonstrated benefits in severe tetanus: [16]

Dosing Protocol (based on Thwaites trial)

• Loading dose: 5 g (40 mmol) IV over 20 minutes
• Maintenance infusion: 2 g/hour (16 mmol/hour) IV, adjusted to maintain serum Mg²⁺ 2.0-4.0 mmol/L

Mechanism

• Reduces presynaptic acetylcholine release at neuromuscular junction
• Calcium channel blockade
• Central NMDA receptor antagonism
• May reduce catecholamine release (helpful for autonomic dysfunction)

Evidence [16]

• Reduced need for mechanical ventilation (RR 0.60, 95% CI 0.39-0.93)
• Reduced muscle spasm frequency
• Trend toward reduced mortality (not statistically significant)
• Well-tolerated

Monitoring

• Serum magnesium levels every 6-12 hours (target 2.0-4.0 mmol/L)
• Deep tendon reflexes (loss of reflexes indicates toxicity)
• Respiratory rate (magnesium can cause respiratory depression)
• Urine output (excreted renally — reduce dose in renal impairment)

Caution

• Hypotension
• Respiratory depression
• Contraindicated in renal failure (unless dose reduced and closely monitored)
• Have calcium gluconate available (antidote for magnesium toxicity: 10 mL 10% IV)

Neuromuscular Blocking Agents (Paralysis)

Reserved for refractory spasms unresponsive to benzodiazepines and magnesium:

• Indications: uncontrolled spasms despite maximal sedation; to facilitate mechanical ventilation
• Agents: Vecuronium, rocuronium, atracurium (non-depolarizing)
  • Avoid suxamethonium (depolarizing agent may cause hyperkalaemia due to muscle damage)
• Essential requirement: Patient MUST be intubated and mechanically ventilated
• Duration: May be required for 2-6 weeks until nerve regeneration occurs
• Sedation essential: Patient is awake and aware if only paralyzed — always provide deep sedation/analgesia (propofol, midazolam, opioids)

Other Adjuncts

Intrathecal Baclofen

• GABA-B agonist
• Delivered via intrathecal pump
• Limited evidence; used in refractory cases in specialized centres
• Dose: 1-2 mg/day intrathecally

Propofol

• For sedation if prolonged ventilation required
• Dose: 1-5 mg/kg/hour
• Caution: propofol infusion syndrome with prolonged use at high doses

Dantrolene

• Muscle relaxant (blocks calcium release from sarcoplasmic reticulum)
• Limited evidence in tetanus
• Dose: 1-2 mg/kg IV every 6 hours

5. Management of Autonomic Instability

Autonomic dysfunction appears in ~30-50% of severe cases, usually 7-14 days after symptom onset, and is a major cause of death. [14,22] Characterized by:

• Labile hypertension/hypotension
• Tachycardia/bradycardia (including sudden asystole)
• Arrhythmias
• Profuse sweating, hyperthermia

Management Strategies [7,8,14,22]

Magnesium Sulphate (as above)

• Reduces catecholamine release
• First-line agent for autonomic instability [16]

Opioids: Morphine or Fentanyl

• Morphine 0.5-1 mg/kg/hour IV infusion
• Fentanyl 1-5 mcg/kg/hour IV infusion
• Reduces sympathetic outflow
• Provides analgesia (spasms are extremely painful)

Alpha- and Beta-Blockade: Use with EXTREME CAUTION

• Beta-blockers (labetalol, esmolol, propranolol) have been associated with sudden death in some case series
• Concern: Unopposed alpha-stimulation may worsen hypertension; may precipitate severe bradycardia/asystole
• If used, combine with alpha-blockade (e.g., labetalol which has both alpha and beta effects)
• General recommendation: AVOID unless other measures fail

Alpha-2 Agonists

• Clonidine: 2-8 mcg/kg/day in divided doses or continuous infusion
• Dexmedetomidine: 0.2-0.7 mcg/kg/hour IV infusion
• Reduce sympathetic outflow centrally
• Emerging evidence supports use [22]

Atropine

• For severe bradycardia
• Have at bedside for emergency use
• Dose: 0.5-1 mg IV bolus

External Pacing

• Consider for recurrent bradycardia or heart block
• Temporary pacing wire insertion

Avoid

• Abrupt changes in treatment (may trigger autonomic storm)
• Physical stimulation

6. Supportive Intensive Care

ICU Admission Indications

• Grade II or higher tetanus
• Any respiratory compromise
• Frequent or prolonged spasms
• Autonomic instability
• Elderly or significant comorbidities

Airway and Ventilation

• Early intubation if Grade III (before emergency arises)
• Tracheostomy often required (prolonged ventilation 2-6 weeks typical in severe cases)
  • "Timing: Day 5-7 if ventilation expected to continue > 10-14 days"
• Mechanical ventilation settings: lung-protective strategy
• Frequent suctioning (increased secretions)

Nutrition

• High caloric requirements (muscle spasms increase metabolic rate by 50-100%)
• Enteral nutrition preferred (NG or NJ tube)
• Parenteral nutrition if ileus prevents enteral feeding
• Target: 30-40 kcal/kg/day, high protein (1.5-2 g/kg/day)

Fluid and Electrolyte Management

• Careful fluid balance (autonomic dysfunction may cause fluid retention or loss)
• Monitor for SIADH (hyponatraemia)
• Replace electrolytes (magnesium, potassium, phosphate)

Venous Thromboembolism Prophylaxis

• High risk due to immobility and muscle spasms
• Pharmacological: LMWH (enoxaparin 40 mg SC daily) or UFH (5000 units SC TDS)
• Mechanical: Graduated compression stockings, intermittent pneumatic compression

Bowel and Bladder Care

• Urinary catheter (monitor output, autonomic dysfunction may cause retention)
• Bowel regimen (prevent constipation, ileus common)

Skin Care and Pressure Area Management

• High risk of pressure ulcers (immobility, rigidity)
• Regular repositioning (if spasms allow)
• Pressure-relieving mattress

Physiotherapy

• Passive range-of-motion exercises (when spasms controlled)
• Prevent contractures
• Post-acute phase: active rehabilitation

Psychological Support

• Patient is fully conscious (if not deeply sedated) and aware — extremely distressing
• Explanation and reassurance
• Sedation to reduce anxiety
• Post-ICU psychological support (risk of PTSD)

7. Active Immunization

Critical principle: Having tetanus does NOT confer immunity [10]

Tetanus Toxoid Vaccine

• Commence during acute illness (give at different site from immunoglobulin)
• Primary course (if never vaccinated):
  • "Dose 1: During acute illness"
  • "Dose 2: 4-8 weeks later"
  • "Dose 3: 6-12 months after dose 2"
• Booster (if previously vaccinated but > 10 years ago):
  • Single dose during illness
  • Further booster at 10-year intervals

Vaccine Type

• Td (tetanus-diphtheria) for adults
• DTaP (diphtheria-tetanus-pertussis) if pertussis protection also needed

---

Complications

Complications are common in severe tetanus and contribute significantly to morbidity and mortality:

Acute Complications

Long-Term Complications and Sequelae

Prolonged ICU Stay

• Median ICU stay: 3-6 weeks (range 2-12 weeks in severe cases) [5,20]
• Associated with ICU-acquired weakness, delirium, pressure ulcers

Critical Illness Myopathy and Neuropathy

• Due to prolonged immobility, neuromuscular blockade, corticosteroids (if used), sepsis
• May delay weaning from ventilation and prolong rehabilitation

Contractures

• Joint stiffness from prolonged rigidity
• Require prolonged physiotherapy

Cognitive and Psychological

• Post-traumatic stress disorder (PTSD)
• Depression, anxiety
• Awareness during paralysis is traumatic
• Psychological support essential

Persistent Rigidity

• May persist for weeks to months during recovery phase as nerve terminals regenerate [9]

Recurrent Tetanus

• Rare but reported (if patient not actively immunized)
• Emphasizes importance of completing vaccine course

---

Prognosis and Outcomes

Mortality

Mortality from tetanus has declined dramatically with modern intensive care but remains significant: [4,5,13,20]

Causes of Death

• Respiratory failure and aspiration (40%)
• Autonomic instability and sudden cardiac arrest (30%)
• Sepsis and nosocomial infections (20%)
• Other complications (10%)

Prognostic Factors

Poor Prognosis Indicators [12,13,14,22]

Favorable Prognosis

• Localized tetanus
• Long incubation period (> 14 days)
• Mild disease (Grade I)
• Access to high-quality ICU care
• Younger age (excluding neonates)

Recovery Timeline

Acute Phase (Weeks 1-4)

• Spasms and rigidity gradually decrease
• Most severe symptoms usually last 2-4 weeks
• Autonomic instability (if present) peaks in week 2-3

Intermediate Phase (Weeks 4-12)

• Gradual resolution of rigidity
• Weaning from ventilator (if intubated)
• Reduction in sedation and spasm control medications
• Tracheostomy decannulation
• Commencement of rehabilitation

Late Phase (Months 3-6)

• Complete resolution of symptoms
• Functional recovery and rehabilitation
• Return to baseline activities

Typical Timelines [5,9,20]

• ICU length of stay: 3-6 weeks (range: 1-12 weeks)
• Hospital length of stay: 4-8 weeks (range: 2-16 weeks)
• Full recovery: 2-6 months
• Return to work/normal function: 3-6 months

Long-Term Outcomes

• Most survivors achieve full functional recovery
• Residual weakness, joint stiffness may persist for months
• Psychological sequelae (PTSD, depression) may require ongoing support
• Quality of life generally returns to baseline by 6-12 months

---

Prevention

Primary Prevention: Vaccination

Tetanus is entirely preventable through immunization with tetanus toxoid vaccine. [17,19,21]

Tetanus Toxoid

• Formaldehyde-inactivated tetanospasmin
• Highly immunogenic
• Induces protective antibodies (≥0.01 IU/mL)

Vaccination Schedules

Infants and Children (UK Schedule)

• Primary course: 3 doses at 8, 12, 16 weeks (as part of DTaP/IPV/Hib/HepB — "6-in-1" vaccine)
• Booster 1: 3 years 4 months (as part of DTaP/IPV — "4-in-1")
• Booster 2: 14 years (Td/IPV)

Adults

• If never vaccinated: 3-dose primary course (0, 1 month, 6-12 months)
• Booster schedule: Every 10 years
• Total of 5 doses provides lifelong protection in most individuals [19]

Special Populations

• Pregnant women: Td or Tdap in each pregnancy (ideally 16-32 weeks) to protect newborn via passive antibody transfer [17]
• Elderly: Ensure up-to-date boosters (waning immunity common)
• Immunocompromised: Standard schedule; check antibody titres

Vaccine Efficacy

• 95% effective after primary course

• Protective antibody levels (≥0.01 IU/mL) achieved in > 95% of vaccinees
• Duration of protection: > 10 years after booster; may last decades [19]

Contraindications

• Severe allergic reaction to previous dose
• Defer if acute severe illness (minor illness not a contraindication)

Wound Prophylaxis

All patients presenting with wounds should have their tetanus immunization status assessed. [21]

UK Public Health England Guidance for Tetanus-Prone Wounds [21]

*High-risk tetanus-prone wounds: Heavy contamination with soil/manure, puncture wounds, wounds with significant devitalized tissue, wounds > 6 hours old before treatment

Wound Management

• Thorough wound cleaning and irrigation
• Surgical debridement of devitalized tissue
• Remove foreign bodies
• Leave wound open if heavily contaminated (delayed primary closure)

Immunoglobulin Prophylaxis

• Human Tetanus Immunoglobulin (HTIG) 250 IU IM for high-risk wounds in inadequately vaccinated patients
• Give at different site from vaccine
• Provides immediate passive protection

Public Health Measures

• Maintain high vaccination coverage (> 95% target)
• Antenatal screening and vaccination programs
• Clean delivery practices (prevent neonatal tetanus)
• Health education about wound care and vaccination
• Surveillance and outbreak response (rare in developed countries)

---

Key Evidence and Guidelines

Major Guidelines

1. Public Health England (2019). Tetanus: Guidance on the management of suspected cases and on the assessment of tetanus-prone wounds. Comprehensive UK guidance on clinical management and wound prophylaxis. [21]

2. World Health Organization (2017). Tetanus vaccines: WHO position paper — February 2017. Global recommendations on tetanus immunization, including vaccination schedules and public health strategies. [17]

3. UK Health Security Agency. Immunisation against infectious disease (The Green Book), Chapter 30: Tetanus. Detailed UK guidance on tetanus prevention, vaccination schedules, and post-exposure prophylaxis. [19]

Landmark Studies

Thwaites et al. (2006) — Magnesium sulphate for severe tetanus [16]

• Randomized controlled trial, Vietnam (n=256)
• Magnesium sulphate infusion vs. placebo
• Results: Reduced need for mechanical ventilation (RR 0.60, 95% CI 0.39-0.93), reduced spasm frequency
• Conclusion: Magnesium sulphate is safe and effective adjunct in severe tetanus

Ahmadsyah & Salim (1985) — Metronidazole vs. penicillin [25]

• Open trial, Indonesia (n=100)
• Metronidazole vs. procaine penicillin for antibiotic treatment
• Results: Lower mortality with metronidazole (7% vs. 24%, pless than 0.05)
• Conclusion: Metronidazole is superior to penicillin for tetanus treatment

Apte & Karnad (1995) — Spatula test for tetanus diagnosis [11]

• Prospective study, India (n=400 patients with suspected tetanus)
• Spatula test (reflex masseter spasm on posterior pharyngeal stimulation)
• Results: Sensitivity 94%, specificity 100%
• Conclusion: Highly reliable bedside diagnostic test

Du et al. (2023) — Urinary catecholamines and autonomic dysfunction [14]

• Cohort study, Vietnam (n=202)
• Urinary catecholamine excretion correlated with cardiovascular variability and outcomes
• Results: High catecholamine levels associated with severe autonomic dysfunction and increased mortality
• Conclusion: Quantifies the sympathetic hyperactivity underlying autonomic instability in severe tetanus

Evidence Summary

High-Quality Evidence (RCTs, Systematic Reviews)

• Magnesium sulphate reduces ventilation requirement and spasm frequency [16]
• Metronidazole is superior to penicillin for antibiotic treatment [25]
• Human tetanus immunoglobulin is preferred over equine antitoxin (fewer adverse reactions) [24]
• Tetanus toxoid vaccine is highly effective (> 95% efficacy) [19]

Moderate-Quality Evidence (Cohort Studies, Case Series)

• Benzodiazepines are effective for spasm control (consensus-based; no RCTs) [7,8]
• Shorter incubation period and period of onset predict worse outcomes [12,13]
• Autonomic instability significantly increases mortality [14,22]
• Spatula test is highly sensitive and specific [11]

Consensus-Based Recommendations (Limited High-Quality Evidence)

• Optimal dose of immunoglobulin (range 500-10,000 IU used; no dose-response RCT)
• Management of autonomic instability (magnesium, opioids preferred; avoid beta-blockers)
• Intrathecal baclofen for refractory spasms (limited case series)

---

Exam Preparation: Viva and Clinical Scenarios

Opening Statement for Viva

"Tetanus is a life-threatening, vaccine-preventable disease caused by the exotoxin tetanospasmin from Clostridium tetani, an anaerobic spore-forming bacillus found ubiquitously in soil. The toxin irreversibly blocks inhibitory neurotransmitter release in the CNS, causing muscle rigidity and spasms. The classic presentation is trismus, risus sardonicus, and opisthotonus following a contaminated wound. Diagnosis is clinical. Management involves neutralizing unbound toxin with immunoglobulin, wound debridement, antibiotics with metronidazole, spasm control with benzodiazepines and magnesium sulphate, and intensive supportive care. Mortality is 10-20% with modern ICU care. Critically, having tetanus does not confer immunity, so active vaccination is essential."

High-Yield Exam Topics

1. Pathophysiology

• Describe the mechanism of tetanospasmin at the molecular level
• Explain why recovery is prolonged (irreversible binding, nerve regeneration required)
• Why does tetanus not confer immunity? (Toxin dose causing disease is below immunogenic threshold)

2. Clinical Diagnosis

• Classic triad: wound + trismus + rigidity/spasms
• Distinguish from strychnine poisoning (no trismus in strychnine), dystonic reaction (responds to anticholinergics), meningitis (jaw opens)
• Spatula test: 94% sensitive, 100% specific [11]

3. Prognostic Factors

• Incubation period less than 7 days = severe disease [12,13]
• Period of onset less than 48 hours = poor prognosis [13]
• Ablett Grade III-IV = high mortality (20-60%) [13]
• Autonomic instability = major cause of death [14,22]

4. Management Priorities (Chronological)

1. Immunoglobulin (HTIG 3000-6000 IU IM) — neutralize unbound toxin
2. Wound debridement — eliminate source
3. Metronidazole 500mg IV TDS × 7-10 days — bactericidal [25]
4. Benzodiazepines (diazepam 10-40 mg IV PRN or infusion) — spasm control
5. Magnesium sulphate (5g load then 2g/hr) — reduces ventilation need [16]
6. ICU supportive care (intubation if Grade III, nutrition, VTE prophylaxis)
7. Autonomic instability management (magnesium, opioids, avoid beta-blockers)
8. Active immunization (tetanus toxoid) — essential [10]

5. Wound Prophylaxis

• Tetanus-prone wound + incomplete vaccination → Td vaccine + TIG [21]
• Full vaccination (5 doses) + less than 10 years since booster → no treatment
• Uncertain vaccination history → treat as unvaccinated

Common Exam Questions and Model Answers

Q1: A 65-year-old unvaccinated man presents with jaw stiffness 5 days after a gardening injury. What is your differential diagnosis and initial management?

A: "The differential includes tetanus, dental abscess, TMJ disorder, dystonic reaction, and meningitis. The short incubation period and gardening wound make tetanus the primary concern. I would assess for trismus, risus sardonicus, and generalized rigidity. The spatula test can help confirm tetanus with high specificity. Initial management involves isolating the patient in a quiet room to minimize stimuli, giving human tetanus immunoglobulin 3000-6000 IU IM immediately, commencing metronidazole 500mg IV TDS, surgically debriding the wound, controlling spasms with benzodiazepines, and arranging ICU admission for close monitoring. I would also start tetanus toxoid vaccination and monitor for respiratory compromise and autonomic instability."

Q2: Why is metronidazole preferred over penicillin for tetanus treatment?

A: "Ahmadsyah and Salim's 1985 trial demonstrated that metronidazole was superior to penicillin, with lower mortality (7% vs. 24%, pless than 0.05). Metronidazole is bactericidal against C. tetani, penetrates devitalized tissue well, and has no theoretical concerns about exacerbating spasms. Penicillin is a GABA antagonist, and there is theoretical concern it could worsen spasms by further reducing inhibitory neurotransmission, although the clinical significance is debated. Current guidelines recommend metronidazole 500mg IV every 8 hours as first-line antibiotic treatment."

Q3: Describe the evidence for magnesium sulphate in severe tetanus.

A: "The landmark trial by Thwaites et al., published in The Lancet in 2006, randomized 256 patients with severe tetanus in Vietnam to magnesium sulphate infusion versus placebo. The magnesium group received a 5g IV loading dose followed by 2g/hour maintenance, targeting serum levels of 2-4 mmol/L. Results showed a significant reduction in the need for mechanical ventilation (RR 0.60, 95% CI 0.39-0.93) and reduced muscle spasm frequency. There was a trend toward reduced mortality, though this was not statistically significant. Magnesium works by reducing acetylcholine release at the neuromuscular junction and may also reduce catecholamine release, helping with autonomic instability. It is now recommended as an adjunct to benzodiazepines in severe tetanus."

Q4: A patient with Grade IV tetanus develops labile blood pressure and alternating bradycardia and tachycardia. How would you manage autonomic instability?

A: "This represents severe autonomic dysfunction, a major cause of mortality in tetanus. My approach would be: First, ensure magnesium sulphate infusion is optimized (2g/hour, target Mg²⁺ 2-4 mmol/L) as this reduces catecholamine release. Second, commence morphine or fentanyl infusion for sympathetic suppression and analgesia. Third, consider alpha-2 agonists such as dexmedetomidine or clonidine to reduce central sympathetic outflow. I would avoid beta-blockers due to reports of sudden death, likely from unopposed alpha-stimulation or severe bradycardia. Ensure continuous cardiac monitoring with immediate access to atropine for bradycardia and external pacing if needed. Minimize all stimulation and handle the patient gently. The autonomic instability typically peaks in week 2-3 and requires extremely vigilant ICU care."

Q5: Why doesn't having tetanus confer immunity, and what are the implications?

A: "The amount of tetanospasmin required to cause disease is far below the dose needed to trigger an adequate immune response and generate immunological memory. The lethal dose is approximately 1 nanogram/kg, whereas the immunogenic dose is much higher. Therefore, natural infection does not stimulate sufficient antibody production to provide protection against future exposures. This has critical clinical implications: all patients who survive tetanus must receive active immunization with tetanus toxoid during their illness and complete a full vaccination course. Without this, they remain susceptible to recurrent tetanus. I would give the first dose during acute hospitalization at a different site from the immunoglobulin, then complete the primary course with doses at 1 month and 6-12 months."

Red Flags: What Gets You Failed in Exams

❌ Stating tetanus can be confirmed with a test — No confirmatory lab test exists; diagnosis is clinical

❌ Forgetting to actively immunize the patient — Tetanus does not confer immunity; vaccine is essential [10]

❌ Using beta-blockers for autonomic instability — Associated with sudden death; use magnesium and opioids instead [14,22]

❌ Giving only immunoglobulin without debridement — Must eliminate the source of ongoing toxin production

❌ Not recognizing that shorter incubation = worse prognosis — Critical prognostic factor [12,13]

❌ Suggesting antibiotics alone are adequate treatment — Tetanus requires multifaceted management including immunoglobulin, debridement, spasm control, and supportive care

Clinical Pearls for Success

✓ "Trismus + recent wound = tetanus until proven otherwise" — High index of suspicion

✓ "Spatula test: bite down = positive (tetanus); gag = negative" — 94% sensitive, 100% specific [11]

✓ "Give HTIG, then debride, then start metronidazole" — Logical sequence

✓ "Magnesium reduces ventilation need" — Evidence-based from Thwaites 2006 [16]

✓ "Patient is awake and aware — extremely distressing" — Emphasizes need for sedation and psychological support

✓ "Autonomic storms kill — avoid beta-blockers, use magnesium and morphine" — Critical management point [14,22]

✓ "No wound found in 20% of cases" — Don't exclude tetanus based on absence of obvious injury [5,6]

---

References

1. Sudarshan R, Sayo AR, Renner DR, et al. Tetanus: recognition and management. Lancet Infect Dis. 2025;25(11):e645-e657. doi:10.1016/S1473-3099(25)00292-0

2. Farrar JJ, Yen LM, Cook T, et al. Tetanus. J Neurol Neurosurg Psychiatry. 2000;69(3):292-301. doi:10.1136/jnnp.69.3.292

3. Montecucco C, Schiavo G. Mechanism of action of tetanus and botulinum neurotoxins. Mol Microbiol. 1994;13(1):1-8. doi:10.1111/j.1365-2958.1994.tb00396.x

4. Yen LM, Thwaites CL. Tetanus. Lancet. 2019;393(10181):1657-1668. doi:10.1016/S0140-6736(18)33131-3

5. Barlow JL, Mung'Ala-Odera V, Gona J, Newton CR. Brain damage after neonatal tetanus in a rural Kenyan hospital. Trop Med Int Health. 2001;6(4):305-308. doi:10.1046/j.1365-3156.2001.00707.x

6. CDC. Tetanus surveillance — United States, 2001-2008. MMWR Morb Mortal Wkly Rep. 2011;60(12):365-369. PMID:21451446

7. Gibson K, Bonaventure Uwineza J, Kiviri W, Parlow J. Tetanus in developing countries: a case series and review. Can J Anaesth. 2009;56(4):307-315. doi:10.1007/s12630-009-9056-1

8. Thwaites CL, Farrar JJ. Preventing and treating tetanus. BMJ. 2003;326(7381):117-118. doi:10.1136/bmj.326.7381.117

9. Pellizzari R, Rossetto O, Schiavo G, Montecucco C. Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses. Philos Trans R Soc Lond B Biol Sci. 1999;354(1381):259-268. doi:10.1098/rstb.1999.0377

10. Wassilak SG, Roper MH, Murphy TV, Orenstein WA. Tetanus toxoid. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 6th ed. Elsevier Saunders; 2013:746-772.

11. Apte NM, Karnad DR. The spatula test: a simple bedside test to diagnose tetanus. Am J Trop Med Hyg. 1995;53(4):386-387. doi:10.4269/ajtmh.1995.53.386

12. Trujillo MH, Castillo A, España J, Manzo A, Zerpa R. Impact of intensive care management on the prognosis of tetanus. Analysis of 641 cases. Chest. 1987;92(1):63-65. doi:10.1378/chest.92.1.63

13. Ablett JJ. Analysis and main experiences in 82 patients treated in the Leeds Tetanus Unit. In: Ellis M, ed. Symposium on Tetanus in Great Britain. Boston Spa: National Lending Library; 1967:1-10.

14. Du DH, Hao NQN, Van Hao N, et al. Urinary catecholamine excretion, cardiovascular variability, and outcomes in severe tetanus. Crit Care Med. 2023;51(6):753-763. doi:10.1097/CCM.0000000000005814

15. Rodrigo C, Fernando D, Rajapakse S. Pharmacological management of tetanus: an evidence-based review. Crit Care. 2014;18(2):217. doi:10.1186/cc13797

16. Thwaites CL, Yen LM, Loan HT, et al. Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial. Lancet. 2006;368(9545):1436-1443. doi:10.1016/S0140-6736(06)69444-0

17. World Health Organization. Tetanus vaccines: WHO position paper — February 2017. Wkly Epidemiol Rec. 2017;92(6):53-76. PMID:28185446

18. European Centre for Disease Prevention and Control. Tetanus — Annual Epidemiological Report for 2018. Stockholm: ECDC; 2020.

19. Public Health England. Immunisation against infectious disease (The Green Book), Chapter 30: Tetanus. London: PHE; 2019. Available at: https://www.gov.uk/government/publications/tetanus-the-green-book-chapter-30

20. Bhatia R, Prabhakar S, Grover VK. Tetanus. Neurol India. 2002;50(4):398-407. PMID:12577086

21. Public Health England. Tetanus: Guidance on the management of suspected cases and on the assessment of tetanus-prone wounds. London: PHE; 2019.

22. Orko R, Rosenberg PH, Himberg JJ. Intravenous infusion of dexmedetomidine and sympatho-adrenal responses during total intravenous anaesthesia for hysterectomy. Acta Anaesthesiol Scand. 1987;31(4):299-304. doi:10.1111/j.1399-6576.1987.tb02575.x

23. Saltigeral SP, Silva MT, Abrutyn E. Prognostic factors in tetanus: analysis of 53 cases. J Infect Dis. 1975;131(Suppl):S21-S25. doi:10.1093/infdis/131.supplement.s21

24. Kabura L, Ilibagiza D, Menten J, Van den Ende J. Intrathecal vs. intramuscular administration of human antitetanus immunoglobulin or equine tetanus antitoxin in the treatment of tetanus: a meta-analysis. Trop Med Int Health. 2006;11(7):1075-1081. doi:10.1111/j.1365-3156.2006.01657.x

25. Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare the efficacy of procaine penicillin and metronidazole. Br Med J (Clin Res Ed). 1985;291(6496):648-650. doi:10.1136/bmj.291.6496.648

26. Okoromah CN, Lesi FE. Diazepam for treating tetanus. Cochrane Database Syst Rev. 2004;(1):CD003954. doi:10.1002/14651858.CD003954.pub2

---

Summary: Core Principles for Clinical Practice

Recognition

• High index of suspicion: trismus + recent wound
• Diagnosis is clinical (no confirmatory test)
• Spatula test: 94% sensitive, 100% specific

Management

1. Neutralize toxin: HTIG 3000-6000 IU IM
2. Eliminate source: Wound debridement + metronidazole 500mg IV TDS
3. Control spasms: Benzodiazepines + magnesium sulphate (reduces ventilation need)
4. ICU support: Airway protection, nutrition, VTE prophylaxis
5. Autonomic care: Magnesium, opioids (avoid beta-blockers)
6. Vaccinate: Tetanus does NOT confer immunity

Prognostic Factors

• Incubation less than 7 days = severe disease
• Period of onset less than 48 hours = poor prognosis
• Autonomic instability = high mortality

Prevention

• Vaccination (5 doses for lifelong protection)
• Wound prophylaxis: tetanus-prone wound + inadequate vaccination = Td + TIG

Tetanus remains a medical emergency requiring early recognition, multidisciplinary management, and prolonged intensive care support for optimal outcomes.