Harrisons: Tetanus

TETANUS 840 - 842

Ch 124 pp

Tetanus – neurologic disorder; ↑muscle tone & spasms; caused by tetanospasmin (toxin) from Clostridium tetani “Tetanos”: Greek … to “stretch” or to put” tension” Tetanus – specific disease caused by specific etiological agent; toxin blocks release of inhibitory neurotransmitters leading to over firing Tetany – non specific; a clinical syndrome usually caused by hypocalcemia; decreased firing threshold (easier firing) C tetani – anaerobic, motile, gram positive rod w/ oval c’less terminal spore ‘tennis racket’or drumstick found in soil and feces; resistant to boiling for 20 minutes (vegetative cells are susceptible to metronidazole & penicillin) Tetanoplasmin – formed in vegetative cells under plasmid control; a zinc metalloprotease; blocks neurotransmitter release; homologous with botulinum Epidemiology: occurs sporadically; affects non-immunized, partially immunized or fully immunized but w/o regular boosters associated w/ puncture wounds, lacerations, abcess, drug abuse (“skin popping”), etc Pathogenesis: contamination of wound w/ spores germination and toxin production  occur only @ wounds w/ low oxidation reduction potential (devitalized tissue, foreign bodies, active infxn… remember, it’s anaerobic! ) C TETANI DOES NOT ITSELF INVOKE INFLAMMATION  Blood culture is useless most of the time because u wont find any bacteria Toxin  binds to peripheral motor neuron  enter axon  goes to brainstem and spinal cord (RETROGRADE INTRANEURONAL TRANSPORT) Toxin  migrates across synapse  goes to PREsynaptic terminal  blocks GABA (CNS) and glycine (spinal cord)  ↓ inhibitory signal  rigidity  Glycine  reflex that limits polysynaptic spread of impulses. Renshaw cells at spinal cord use glycine to inhibit agonist-antagonist recruitment  W/o glycine, agonists and antagonists are recruited rather than inhibited  SPASMS

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Resting firing rate of α motor neurons ↑ … therefore, instead to the normal “resting tone”it becomes a “resting rigidity”

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↓ inhibitory signals  may also affect PREganglionic sympathetic neurons @ lateral gray matter of spinal cord   sympathetic hyperactivity & ↑ catecholamines

Toxin  neuromuscular junction  block neurotransmitter release  weakness/paralysis To recover  must make new nerve terminals Blood brain barrier blocks direct entry into the central nervous system Clinical Manifestations:

if it assumed that intraneural retrograde transport is equal for all nerves: short nerves (like in axial muscles) are affected first, thereby explaining the sequential involvement of nerves of the head  trunk  proximal extremities. Initially  ↑ tone @ masseter (trismus/ lockjaw) ; described as forceful apposition of the jaw Afterwards  dysphagia (may preclude oral feeding) and stiffnes @ neck, shoulder and back Subsequent involvement of other muscles eventually result into stiff proximal muscles; FEET and HANDS are SPARED Risus sardonicus  sustained contraction of facial muscles resulting into a grimace or sneer Opisthotonos  contraction of the back muscles, producing an arched back Constant threat during generalized spasm: low ventilation, apnea or laryngospasm Mentation is not impaired (because the toxin doesn’t cross the BBB) DTR ↑ Autonomic dysfunction  hypertension, tachycardia, dysrythmia, hyperpyrexia, profuse sweating, peripheral vasoconstriction, etc Generalized tetanus:  Most common  characterized by ↑ muscle tone and generalized spams  occurs when toxin is at lymphatics and bloodstream  Median time of onset is 7 days  Severity of illness  Mild: rigidity & a few spasms  Moderate: trismus, rigidity, more spasms  Severe: explosive spasms Neonatal tetanus  Generalized form  Inadequately immunized mothers  After unsterile treatment of the umbilical cord stump  First 2 wks of life  Poor feeding, rigidity and spasms Local tetanus  Only the nerves supplycng the affected muscle is involved (around the wound)  Prognosis is excellent Cephalic tetanus  Rare local tetanus after head injury or ear infection  Has trismus and dysfunction of one or more cranial nerves (usually CN7)  High mortality! Diagnosis Electromyogram  Continuous discharge of motor units  Shortening or absence of the silent interval w/c is normally seen after an action potential Muscle enzyme levels MAY be raised Serum antitoxin of >/= 0.15U/mL is considered protective DDx  Alveolar abcess (teeth), Strychnine poisoning, Phenothiazine, Metoclopromide and hypocalcemic tetany Treatment Antibiotic therapy  Eliminate vegetative cells, the source of the toxin  PCN  10-12M units IV daily of 10 days  Has antagonistic acty to GABA  Metronidazole  500mg / 6h or 1g/12h

LESSA 1

Higher survival rate Does NOT have antagonistic activity to GABA  Clindamycin & Erythromycin  for PCN allergci px. Antitoxin  Toxin already bound to neural tissue is UNaffected  TIG (human tetanus Ig)  Preparation of choice!  3K-6K units IM in divided doses  Pooled IV Ig  alternative  Equine tetanus antitoxin  has problem of hypersensitivity  Give antitoxin before manipulating the wound Control of muscle spasm  Ideal: abolish spasmodic activity without causing oversedation and hypoventilation  Diazepam  Benzodiazepine  GABA agonist  Needs large, titrated doses (>250mg/dL)  Lorazepam  Longer duration of action  Midazolam  Shorter t½  Barbiturates & Chlorpromazine  2nd line  Nondepolarizing neuromuscular blocking agent & mechanical ventilation  “therapeutic paralysis”  If px is unresponsive to medication and the spams threaten ventilation  Alternative agents:  Propofol  Dantrolene & intrathecal Baclofen  Succinylcholine – assoc w/ hyperK  Magnesium sulfate – need to monitor neurologic fxn (patellar reflex), respi fxn, Mg levels Respiratory care: intubation and tracheostomy Autonomic dysfunction  Labetalol - α & β adrenergic blocker  Esmolol - β blocker  Clonidine – central acting anti adrenergic drug  Morphine sulfate Vaccine … (see prevention)  

doses 3 doses

No, unless >10 years since last dose

No

No, unless >5years since last dose

No

Prevention: Active immunization  Primary series for adults  3 doses  1st dose & 2nd dose: 4-8 wks apart  3rd dose: 6-12 months after the 2nd  Booster dose: every 10 years @ mid decade ages (35, 45…)  Preferred for >7 years old = Combined tetanus + diptheria toxoid, adsorbed (Td for adult)  Adsorbed  bec produces more persistent Ab titers than fluid vaccine Wound management  Passive immunization w/ TIG  250 units IM  gives protective Ab for 46wks  TAT  Vaccine and TAT should be given in separate sites w/ separate syringes  Active immunization w/ vaccine  Prefereable Td if >7 yo Neonatal tetanus  Maternal immunization Table 124-1: WOUND MANAGEMENT Hx of adsorbed tetanus toxoid Unk or <3

Clean minor wound

All other wounds

Td

TIG

Td

TIG

Yes

No

Yes

Yes

LESSA 2