University of Alabama at Birmingham 2004 Case #8 Universidad Peruana Cayetano Heredia
The following patient was seen in the ICU at Cayetano National Hospital.
Image for 03/15/04History: 63 yo shoemaker with a history of frequent local trauma to hands and fingers.  Four days prior to the onset of illness, he suffered a wound due to a sharp metal object.  Three days before admission he noted difficulty in opening his mouth, followed one day later by odynophagia and dysphagia.  No relevant past medical history.  No suspicious dietary ingestions, no animal bites, and no exposure to anyone that was ill.  He does not remember having received any type of vaccine for anything in the past.  Received an unknown IM drug elsewhere prior to arrival at our hospital.  On the day of admission, onset of periodic episodes of very painful generalized contractions affecting the lower back, and the masseter muscles.

Epidemiology: Born in Ayacucho in the highlands but lives in Lima.  Shoemaker with a history of multiple minor traumas in his fingers in the past.

Physical Examination: Afebrile, pulse 72, respirations 20, BP 130/90, trismus exaggerated during periods of spasm, very limited mouth opening [see image A]; paravertebral muscle spasm with constant arching of the back [see image B] was present.  All muscle groups spastic; sensory examination grossly normal.

Laboratory Examination: Hematocrit 42, WBC 12200 (3% bands, 85% PMNs); creatinine 0.85mg/dl, glucose 123 mg/dl, sodium 143 meq/l, potassium 3.9, chloride 106, AST 55, ALT 40; urine normal.  Chest x-ray was normal; EKG normal on admission.





Diagnosis: Tetanus, generalized form.

Discussion: Generalized tetanus is a purely clinical diagnosis with highly characteristic features and the diagnosis is usually made within a few minutes of arrival at a medical facility.  In general, disease begins with trismus or lockjaw, which are spasms of the masseter muscles, although, as in our patient, initial symptoms may occur in other muscle groups.  After a variable period the symptoms progress to generalized muscular rigidity, on which is superimposed increasingly severe generalized reflex muscular spasms manifested by the characteristic sardonic smile (risus sardonicus), opisthotonos (arched back), and spasm of respiratory muscles and larynx.  In severe cases there are prolonged spasms occurring less than 1 hour apart, and in very severe cases there is autonomic hyperactivity with sweating, fever, tachycardia, salivation, arrhythmias, hyper- or hypo-tension, hyperthermia, etc.  Some aspects of generalized disease can be mimicked by hypocalcemic tetany, phenothiazine induced dystonia, epilepsy, rabies, strychnine poisoning, or narcotic withdrawal, but the history of wound (not always elicited), epidemiology, and clinical course of tetanus usually lead to little confusion.  Mild localized tetanus in which trismus does not progress to generalized disease with reflex spasms is rare.  In the initial phase, the trismus itself has a broader differential diagnosis including dipththeria, partotitis, retropharyngeal abscess, and traumatic injury.

Disease is caused by a toxin, tetanospasmin, released by the Clostridium tetani, which infect the wound.  Spread of toxin is both retrograde through the affected axons as well as via blood to nerve endings in other parts of the body.  Masseters are usually affected first due to their short axons.  The action is pre-synaptic, irreversible, and blocks inhibitory neurotransmitter action leading to muscle spasm.  Poor prognostic indicators include short incubation period (<7 days) from time of the wound to onset of symptoms (4 days here), short period of onset (<48 hours), from onset of symptoms to first reflex spasm (3 days here), and high-risk portal of entry (compound fracture, gynecologic, postoperative, and burns).

Management is complex and must be done in a well-equipped Intensive Care Unit (ICU).  Non-ICU care is associated with almost universal mortality.  General principles are listed here, but detailed written dosing protocols must be available and used for most interventions.

  1. Airway - in severe generalized tetanus, immediate endotracheal intubation to protect against laryngeal spasm is indicated.  For those with poor prognostic signs, where even survivors will require weeks of intensive care while synapses regenerate, immediate or early tracheostomy is advised.
  2. Relaxation-Sedation - must be titrated to eliminate reflex spasm.  Large amounts of diazepam, up to 20 mg/kg/day by IV bolus need to be used.  Our patient received 100 mg of diazepam by IV push in the first hour in the ER.  Patients are relatively refractory to the sedating and respiratory depressive effects of diazepam.  Chlorpromazine can be used to augment the effect of diazepam.  If this regimen does not control spasm, artificial ventilation and complete neuromuscular blockade with vecuronium as the drug of choice is indicated.
  3. Neutralize toxin - either human hyperimmune globulin (ideal) or equine anti-tetanus globulin (preceded by an intradermal test dose) should be given intramuscularly.  Some centers give a portion of the globulin intrathecally.  A primary series of tetanus toxoid should be initiated, as disease does not protect against future infection.
  4. Treat portal of entry - surgical debridement and antibiotics.  Penicillin is classically used but many now use metronidazole due to a single study implicating penicillin as an antagonist of GABA, thereby decreasing diazepam effectiveness.
  5. General care - includes usual ICU considerations but also intense avoidance of light and stimuli as these readily precipitate reflex spasm.
  6. Treat any sympathetic hyperactivity - labetalol or esmolol (combined alpha and beta blockade) seems best for this; alternatively, morphine or clonidine can be used.  A recent study has reported efficacy of magnesium sulfate alone.

Our patient developed laryngeal spasm during the first few hours in the ICU, followed by unexplained tachycardia, systemic hypertension, increase bronchial secretions, and fever during the first 12 hours of hospitalization.  All these symptoms were interpreted as due to sympathetic over-activity.  He received human anti-tetanus immuneglobulin 750U IM.  He was intubated and treated with IV diazepam, vecuronium, and clonidine.  The ICU team treated him with IV penicillin and elected not to use alpha and beta blockade.  The patient now has a tracheostomy and will require full supportive care for several weeks if he is to survive.  This patient had poor prognostic indicators on arrival (short incubation, short time of onset).