GAS GANGRENE

Dr Mohammed Akbar KhanDr Mohammed Akbar Khan

DEFINITIONDEFINITION

Gangrene - Massive necrosis of tissue, superadded by putrefaction

Gas gangrene - Clostridial myonecrosis Myonecrosis - Bacterial infection - Necrotic damage

specific to muscle tissue - Gas tissues in gangrene. Deadly form of gangrene - Clostridium perfringens. Medical emergency

Microorganisms - opportunistic - Skin breakage - Body Myonecrosis - Bacteria - Specific exotoxins. Envenomation by snakes of the Bothrops genus

(family Viperidae), Ischemic necrosis - vascular blockage (II Diabetes) Tumours that block or hoard blood supply Disseminated intravascular coagulation (DIC) or other

thromboses

ORGANISMSORGANISMS Anaerobic - Gram-positive - Spore-forming

bacillus Genus Clostridium C. perfringens - Most common etiologic agent Other common clostridial species –

– Clostridium bifermentans – Clostridium septicum – Clostridium sporogenes – Clostridium novyi – Clostridium fallax – Clostridium histolyticum – Clostridium tertium

Gram stain of cysts with large rod-shaped bacteriaGram stain of cysts with large rod-shaped bacteria

True saprophytes - soil and dust. True saprophytes - soil and dust. Mucous membranes GI tract & Female genital tract. Mucous membranes GI tract & Female genital tract. Clostridia - Colonize in skin- mainly around perineum.Clostridia - Colonize in skin- mainly around perineum. Obligate anaerobes- some species - Aerotolerant. Obligate anaerobes- some species - Aerotolerant. Bacterial multiplication & production of soluble Bacterial multiplication & production of soluble

proteins called exotoxins require a low oxygen proteins called exotoxins require a low oxygen tension. tension.

Non-clostridial organisms - 60-85% cases Recent clinical series -gas gangrene in wound cultures

-83.3% of aerobic gram-negative bacilli -4.5% anaerobic gram-positive bacilli- Clostridium sp

Aerobic gram-negative bacteria – Escherichia coli – Proteus species – Pseudomonas aeruginosa – Klebsiella pneumoniae

C perfringens - 20 exotoxins. – Alpha toxin-lecithinase,necrotizing,hemolytic,cardiotoxic – Beta toxin - necrotizing – Epsilon toxin - permease – Iota toxin - necrotizing – Delta toxin - hemolysin – Phi toxin - Hemolysin, cytolysin – Kappa toxin - collagenase, gelatinase, necrotizing – Lambda toxin - Protease – Mu toxin - Hyaluronidase – Nu toxin - Deoxyribonuclease, hemolytic necrotizing

ALPHA-TOXINALPHA-TOXIN Zinc metalloenzyme - Phospholipase-c activity

(lecithinase) Cell destruction - hydrolysis of key cell membrane Lysis of erythrocytes- leukocytes- platelets- fibroblasts

& muscle cells. Strains that do not produce alpha-toxin are less

virulent Purified alpha-toxin has a myocardial suppressant

effect - shock

PREDISPOSING FACTORSPREDISPOSING FACTORS

Contamination - clostridial spores - posttraumatic or postoperative lesions

Local wound conditions > degree of clostridial contamination

Disrupted or necrotic tissue provides the necessary enzymes and a low oxidation/reduction potential, allowing for spore germination.

Foreign bodies, premature wound closure& devitalized muscle reduce the spore inoculum necessary to cause infection

Local effects - necrosis of muscle, subcutaneous fat &thrombosis of blood vessels.

Marked edema - compromise blood supply

Incubation period - short (<24 h) -1 hour to 6 weeks Self-perpetuating destruction of tissue - locally &

systemically acting exotoxins. Fermentation of glucose - gas production C septicum spontaneous gas gangrene Nitrogen is the predominant gas component (74.5%), -

oxygen (16.1%), H2 (5.9%), & CO2 (3.4%). Production of hydrogen sulfide and CO2 gas begins

late and dissects along muscle bellies & fascial planes.

Local effects - rapid spread of the infection. Systemic effects - exotoxins - severe hemolysis. Hemoglobin levels - very low levels Hypotension- acute tubular necrosis and renal failure

Very high mortality rate - 25% spontaneous gas gangrene/ Delay treatment -100%

Injury

Dead tissue, blood clots, foreign matter aerobic organisms

Develop Anaerobic Condition

(Exogenous infection) Germination of spores

Gas gangrene

Oedema, Necrosis, Gas production,

Toxaemia, Myositis

Crepitus

CLASSIFICATIONCLASSIFICATION

POST-TRAUMATIC POST-TRAUMATIC POST-OPERATIVEPOST-OPERATIVE SPONTANEOUS SPONTANEOUS

POSTTRAUMATICPOSTTRAUMATIC 60% of all gas gangrene 60% of all gas gangrene automobile collisions. automobile collisions. Other complications of trauma Other complications of trauma

– Crush injuries, Crush injuries, – Compound fractures, Compound fractures, – Gunshot wounds, Gunshot wounds, – Thermal Thermal – Electrical burns, Electrical burns, – Frostbite. Frostbite.

Farm or industrial injuries contaminated with soil Farm or industrial injuries contaminated with soil Rare causes- IM or SC injections with insulin, Rare causes- IM or SC injections with insulin,

epinephrine, quinine, or cocaine epinephrine, quinine, or cocaine

POSTOPERATIVEPOSTOPERATIVE

clostridial infections – clostridial infections – – colon resection colon resection – ruptured appendixruptured appendix– bowel perforationbowel perforation– biliary or other GI surgery, including biliary or other GI surgery, including

laparoscopic cholecystectomy and laparoscopic cholecystectomy and colonoscopy. colonoscopy.

Septic back-street abortions - uterine gas Septic back-street abortions - uterine gas gangrene. gangrene.

SPONTANEOUSSPONTANEOUS without external wound or injury - serious underlying

conditions. Colorectal adenocarcinoma Hematologic malignancy Children - Neutropenia

chemotherapy spontaneous C septicum infections.

Diabetes or neutropenic colitis. Many cases - no predisposing condition C perfringens C septicum

SYMPTOMS SYMPTOMS Posttraumatic gas gangrene - serious injury - skin or

soft tissues or have experienced open fractures. Postoperative gas gangrene - undergone recent

surgery of the GI or biliary tract. History is usually unremarkable - occult malignancy–

associated spontaneous gas gangrene. Sudden onset of pain is usually the first symptom Pain gradually worsens but spreads only as the

underlying infection spreads. Feeling of heaviness in the affected extremity. Low-grade fever and apathetic mental status

SIGNSSIGNS Local swelling & serosanguineous exudate - onset of

pain. skin - bronze color - blue-black color with skin blebs

and hemorrhagic bullae. Within hours, entire region - markedly edematous. Nonodorous or may have a sweet mousy odor. Crepitus follows gas production crepitus may not be detected with palpation owing to

brawny edema. Pain and tenderness to palpation disproportionate to

wound appearance Tachycardia disproportionate to body temperature is

common, - feeling of impending doom. Late signs - include hypotension, renal failure, and a

paradoxical heightening of mental acuity.

SUMMARY C/PSUMMARY C/P Air under the skin (subcutaneous emphysema)Air under the skin (subcutaneous emphysema) Blisters filled with brown-red fluidBlisters filled with brown-red fluid Drainage from the tissues, foul-smelling brown-Drainage from the tissues, foul-smelling brown-

red or bloody fluid (serosanguineous discharge)red or bloody fluid (serosanguineous discharge) Increased heart rate (tachycardia)Increased heart rate (tachycardia) Moderate to high feverModerate to high fever Moderate to severe pain around a skin injuryModerate to severe pain around a skin injury Pale skin color, later becoming dusky and Pale skin color, later becoming dusky and

changing to dark red or purplechanging to dark red or purple Progressive swelling around a skin injuryProgressive swelling around a skin injury SweatingSweating Vesicle formation, combining into large blistersVesicle formation, combining into large blisters Yellow color to the skin (jaundice)Yellow color to the skin (jaundice)

Laboratory Studies Laboratory Studies Hemolytic anemia Increased lactate dehydrogenase (LDH) White blood cell – No leukocytosis. Toxic shock syndrome - C sordellii or C septicum

Hemoconcentration & leukocytosis. Gram stain - exudate or infected tissues

– Box-car & large gram-positive bacilli without neutrophils

< 1% of blood cultures - grow clostridial species. Metabolic abnormalities

– metabolic acidosis & renal failure – with tissue injuries and hypotension.

Gas gangrene C. perfringens type A (Principal),

Capsulated, non-motile

Lecithinase C - toxaemia

Nagler reaction

Colonies with haloes

Colonies withouthaloes

Incorporated withAntitoxins

C PerfringensC histolyticum

C septicumC novyii

C Perfringens Alpha toxin(lecithinase)

IMAGING STUDIES

Radiograph – Delineate the typical feathering pattern of gas in

soft tissue Gas may not be present in patients Gas in soft tissue does not confirm diagnosis

Gas feathering in the arm soft tissue

Extension of gas gangrene to the chest wall after initial Extension of gas gangrene to the chest wall after initial debridementdebridement

CT SCANCT SCAN

Abdominal cases Abdominal cases

OTHER TESTS

Rapid detection of alpha-toxin or sialidases - ELISA In vitro amplification of alpha-toxin or DNA - PCR

PROCEDURES

Surgical exploration confirms diagnosis– muscle appears pale – No contractile function -incised or electrically stimulated

Bedside biopsy with immediate frozen section under LA Develop massive hemolysis, shock, ARDS &R F

Require invasive procedures – Right-sided heart catheterization– Mechanical ventilation – Hemodialysis.

HISTOLOGIC FINDING

Destruction of other connective tissues and a paucity of neutrophils - infected area

Leukocyte aggregates - border regions

ANTIBIOTIC THERAPY DOC - penicillin G - 10-24 million U/d Combination of penicillin and clindamycin Protein synthesis inhibitors

– clindamycin, chloramphenicol, rifampin, tetracycline– Inhibit synthesis of clostridial exotoxins

Allergic to penicillin - Clindamycin & Metronidazole Combination of penicillin and metronidazole

– antagonistic and is not recommended. Daptomycin, linezolid, and tigecycline not be used as

primary antibiotics

INTENSIVE CAREINTENSIVE CARE

End-organ failure Other concomitant serious medical conditions that

require intensive supportive care.

ADJUVANT THERAPY

Recombinant human activated protein C – Drotrecogin alfa activated– Adjuvant therapy for patients with severe sepsis

Serious bleeding – Drotrecogin alfa activated &repeated surgical

debridement– Frequent interruption of the continuous infusion – Not recommend this adjuvant therapy

Hyperbaric oxygen (HBO) therapyimportant adjunct to surgery and antimicrobial therapy increased survival - treatment with surgery & antibiotics Direct bactericidal effect on most clostridial species

inhibits alpha-toxin production enhance the demarcation of viable & nonviable tissue

prior to surgery. 100% oxygen at 2.5-3 absolute atmospheres for 90-120

minutes 3 timesPotential risks

Pressure-related trauma-barotraumatic otitis pneumothorax Oxygen toxicity (myopia, seizures). Claustrophobia. Most adverse effects - self-limiting & resolve after

termination therapy

SURGICAL CARE Fasciotomy for compartment syndrome - not be Fasciotomy for compartment syndrome - not be

delayed in patients with extremity involvement. delayed in patients with extremity involvement. Perform daily debridement - necrotic tissue. Perform daily debridement - necrotic tissue. Amputation of the extremity may be necessary and Amputation of the extremity may be necessary and

life-saving. life-saving. Abdominal involvement requires excision of the body Abdominal involvement requires excision of the body

wall musculature. wall musculature. Uterine gas gangrene following septic abortion Uterine gas gangrene following septic abortion

usually necessitates hysterectomy.usually necessitates hysterectomy.

Hemipelvectomy

SUMMARYSUMMARY Most devastating infections. extremity amputation or massive loss of muscles, skin, and soft

tissues, requiring extensive reconstructive surgery and physical rehabilitation.

spontaneous gas gangrene may have occult malignancies of the GI tract.

Aggressive surgical debridement and intensive medical therapy are the mainstays of treatment

HBO therapy has become an important adjunctive therapy compartment syndrome - do not delay fasciotomy Deterrence/Prevention Avoid suturing wounds due to a crush injury or open fractures

with devitalized muscle and soil contamination. Provide warnings and instructions of wound care to rescuers

and health care workers - clostridial infections, -tetanus and gas gangrene, in injured victims of natural disasters such as earthquake or tsunami.

COMPLICATIONS Massive hemolysis - repeated blood transfusion DIC- Severe bleeding – Complicate aggressive surgical

debridement Acute renal failure Acute respiratory distress syndrome Shock Prognosis -

– Failure to provide an early diagnose and inadequate surgical intervention

– dictate the outcome. – better if the incubation period is shorter than 30 hours, – Spontaneous gas gangrene worse prognosis than other

forms of gas gangrene.

TETANUSTETANUS

EPIDEMOLOGYEPIDEMOLOGY International health problem, as International health problem, as C. tetaniC. tetani spores are ubiquitous. spores are ubiquitous. Persons who are unvaccinated or inadequately immunized.Persons who are unvaccinated or inadequately immunized. More common in hot, damp climates with soil rich in organic More common in hot, damp climates with soil rich in organic

matter. matter. Spores introduced into the body through puncture wounds. Spores introduced into the body through puncture wounds. Agricultural areas, a significant number of human adults may Agricultural areas, a significant number of human adults may

harbor the organism.harbor the organism. Spores can also be found on skin surfaces and in contaminated Spores can also be found on skin surfaces and in contaminated

heroin.heroin. Tetanus – particularly the neonatal form – remains a significant Tetanus – particularly the neonatal form – remains a significant

public health problem in non-industrialized countries. public health problem in non-industrialized countries. WHO estimated59,000 newborns worldwide died in 2008 WHO estimated59,000 newborns worldwide died in 2008

neonatal tetanus.neonatal tetanus. Tetanus is the only vaccine-preventable disease that is Tetanus is the only vaccine-preventable disease that is

infectious but is not contagiousinfectious but is not contagious..

HistoryHistory Ancient people -relationship between wounds and fatal Ancient people -relationship between wounds and fatal

muscle spasms.muscle spasms. Greek - τέτανο(tetanos) – taut & τείνειν(teinein) - StretchGreek - τέτανο(tetanos) – taut & τείνειν(teinein) - Stretch 18841884

– Isolated strychnine-like toxin of tetanus from free-living, Isolated strychnine-like toxin of tetanus from free-living, anaerobic soil bacteria. anaerobic soil bacteria.

– Etiology of the disease - demonstrated transmissibility Etiology of the disease - demonstrated transmissibility of tetanus for first time. of tetanus for first time.

– produced tetanus in rabbits by injecting pus from a produced tetanus in rabbits by injecting pus from a patient with fatal tetanus into their sciatic nerves. patient with fatal tetanus into their sciatic nerves.

1889,1889,– Kitasato ShibasaburōKitasato Shibasaburō -C. tetani -C. tetani was isolated from a was isolated from a

human victim human victim – organism could produce disease when injected into organism could produce disease when injected into

animalsanimals– toxin could be neutralized by specific antibodiestoxin could be neutralized by specific antibodies

HistoryHistory 1897, 1897,

– Edmond Nocard - tetanus antitoxin induced Edmond Nocard - tetanus antitoxin induced passive immunity in humans passive immunity in humans

– could be used for prophylaxis and treatment. could be used for prophylaxis and treatment. 1924 1924

– P. Descombey - Tetanus toxoid vaccine was P. Descombey - Tetanus toxoid vaccine was developed developed

– used to prevent tetanus induced by battle used to prevent tetanus induced by battle wounds during World War IIwounds during World War II

INTRODUCTIONINTRODUCTION TetanusTetanus - Prolonged contraction of skeletal muscle - Prolonged contraction of skeletal muscle

fibers. fibers. Primary symptoms – tetanospasminPrimary symptoms – tetanospasmin

– neurotoxin - Gram-positive, obligate anaerobic neurotoxin - Gram-positive, obligate anaerobic bacterium bacterium Clostridium tetaniClostridium tetani..

Infection - wound contamination Infection - wound contamination Cut or deep puncture wound.Cut or deep puncture wound. muscle spasms - jaw (lockjaw) and elsewhere in the muscle spasms - jaw (lockjaw) and elsewhere in the

bodybody Infection can be prevented by proper immunization Infection can be prevented by proper immunization

and by post-exposure prophalysis and by post-exposure prophalysis

INTRODUCTIONINTRODUCTION Skeletal muscleSkeletal muscle Cardiac or heart muscle cannot be tetanized - Intrinsic Cardiac or heart muscle cannot be tetanized - Intrinsic

electrical properties. electrical properties. Mortality rates - 48% to 73%. Mortality rates - 48% to 73%. Highest mortality rates - Unvaccinated & > 60 years Highest mortality rates - Unvaccinated & > 60 years Shorter the incubation period -More severe symptomsShorter the incubation period -More severe symptoms Neonatal tetanus, Neonatal tetanus,

– symptoms usually appear from 4 to 14 days after symptoms usually appear from 4 to 14 days after birthbirth

– averaging about 7 days averaging about 7 days

TypesTypes

Basis of clinical findings, four different forms of tetanusBasis of clinical findings, four different forms of tetanus Generalized tetanusGeneralized tetanus Neonatal tetanusNeonatal tetanus Local tetanusLocal tetanus Cephalic tetanusCephalic tetanus

GENERALIZED TETANUSGENERALIZED TETANUS Most common type of tetanus - 80% of cases.Most common type of tetanus - 80% of cases. Descending pattern. Descending pattern. First sign - trismus or lockjaw & facial spasms called risus First sign - trismus or lockjaw & facial spasms called risus

sardonicus,sardonicus, Stiffness of the neck, Stiffness of the neck, Difficulty in swallowing, Difficulty in swallowing, Rigidity of pectoral and calf muscles. Rigidity of pectoral and calf muscles. Other symptoms - elevated temperature, sweating, elevated Other symptoms - elevated temperature, sweating, elevated

blood pressure, and episodic rapid heart rate. blood pressure, and episodic rapid heart rate. Spasms may occur frequently and last for several minutes with Spasms may occur frequently and last for several minutes with

the body shaped into a characteristic form called opisthotonos.the body shaped into a characteristic form called opisthotonos. Spasms continue for up to 4 weeks, and complete recovery Spasms continue for up to 4 weeks, and complete recovery

may take monthsmay take months

NEONATAL TETANUSNEONATAL TETANUS

Generalized tetanus that occurs in newborns.Generalized tetanus that occurs in newborns. Infants - Not acquired passive immunity - Infants - Not acquired passive immunity -

mother has never been immunized - risk. mother has never been immunized - risk. Infection of the unhealed umbilical stump - Infection of the unhealed umbilical stump -

stump is cut with a non-sterile instrument. stump is cut with a non-sterile instrument. Neonatal tetanus - developing countries Neonatal tetanus - developing countries

-Responsible for about 14% neonatal deaths, -Responsible for about 14% neonatal deaths,

-Very rare in developed countries-Very rare in developed countries

LOCAL TETANUSLOCAL TETANUS UncommonUncommon Persistent contraction of muscles - same anatomic Persistent contraction of muscles - same anatomic

area as the injury. area as the injury. Contractions may persist for many weeks before Contractions may persist for many weeks before

gradually subsiding. gradually subsiding. Local tetanus is generally milder- 1% fatalLocal tetanus is generally milder- 1% fatal Generalized tetanus.Generalized tetanus.

CEPHALIC TETANUSCEPHALIC TETANUS Rare formRare form Otitis media (ear infections) in which Otitis media (ear infections) in which C. C. tetani is tetani is

present in the flora of the middle ear, present in the flora of the middle ear, Injuries to the head. Injuries to the head. Cranial nerves -FacialCranial nerves -Facial area. area.

ETIOLOGYETIOLOGY Tetanus – Rust- rusty nails,Tetanus – Rust- rusty nails, Objects with rust –outdoors or harbor anaerobic Objects with rust –outdoors or harbor anaerobic

bacteria bacteria Rust - not cause tetanus /contain more Rust - not cause tetanus /contain more C. C. tetani tetani

bacteria. bacteria. Rough surface of rusty metal merely provides a prime Rough surface of rusty metal merely provides a prime

habitat for a C. tetani endospore to reside, & nail - habitat for a C. tetani endospore to reside, & nail - puncture skin & deliver endospore into the wound. puncture skin & deliver endospore into the wound.

Endospore is a non-metabolizing survival structure - Endospore is a non-metabolizing survival structure - metabolize and cause infection once in an adequate metabolize and cause infection once in an adequate environment - Anaerobicenvironment - Anaerobic

Stepping on a nail (rusty or not) - tetanus infection – Stepping on a nail (rusty or not) - tetanus infection – – puncture wound, delivering endospores to a puncture wound, delivering endospores to a

suitable environment for growth. suitable environment for growth.

PATHOPHYSIOLOGYPATHOPHYSIOLOGY Clostridium tetani, Clostridium tetani,

– obligate nonencapsulated anaerobic gram-positive obligate nonencapsulated anaerobic gram-positive bacillusbacillus

– Rod-shaped bacteriaRod-shaped bacteria spores spores

– resistant to heat, desiccation, and disinfectants. resistant to heat, desiccation, and disinfectants. – soil, house dust, animal intestines, and human feces.soil, house dust, animal intestines, and human feces.– gain entry can persist in normal tissue for months to gain entry can persist in normal tissue for months to

years. years. – anaerobic conditions, geminate & elaborate anaerobic conditions, geminate & elaborate

tetanospasmin and tetanolysin. tetanospasmin and tetanolysin. Tetanolysin - no role - clinical course of tetanusTetanolysin - no role - clinical course of tetanus TetanospasminTetanospasmin

– neurotoxin neurotoxin – causes the clinical manifestations of tetanuscauses the clinical manifestations of tetanus..

TetanospasminTetanospasmin Toxin is inactive inside the bacteria, - Bacteria dies - Toxin is inactive inside the bacteria, - Bacteria dies -

Released and activated by proteasesReleased and activated by proteases Active tetanospasmin - Retrograde axonal transport to Active tetanospasmin - Retrograde axonal transport to

the spinal cord and brain stem the spinal cord and brain stem – Lymphatic & vascular circulations - End plates of all nerves. Lymphatic & vascular circulations - End plates of all nerves. – Enters nervous system peripherally - Myoneural jn. Enters nervous system peripherally - Myoneural jn. – Transported centripetally into neurons of the CNSTransported centripetally into neurons of the CNS

Most potent toxins Most potent toxins Minimum lethal dose - 2.5 nanograms per kilogram of Minimum lethal dose - 2.5 nanograms per kilogram of

body weight or 175 nanograms for a 70-kg body weight or 175 nanograms for a 70-kg Neurons - incapable of neurotransmitter release - Neurons - incapable of neurotransmitter release -

GABA and Glycine - Major inhibitory neurotransmittersGABA and Glycine - Major inhibitory neurotransmitters

TetanospasminTetanospasmin Failure of inhibition of motor reflex responses to sensory Failure of inhibition of motor reflex responses to sensory

stimulation. stimulation. Generalized contractions of the agonist and antagonist Generalized contractions of the agonist and antagonist

musculature characteristic of a tetanic spasm. musculature characteristic of a tetanic spasm. Shortest peripheral nerves - first to deliver the toxin to the CNS, Shortest peripheral nerves - first to deliver the toxin to the CNS,

- early symptoms of facial distortion & back & neck stiffness- early symptoms of facial distortion & back & neck stiffness Damaged UMN Damaged UMN

– cannot inhibit LMN ( Renshaw cells), cannot inhibit LMN ( Renshaw cells), – cannot control reflex responses to afferent sensory stimuli. cannot control reflex responses to afferent sensory stimuli.

Both mechanisms – hallmark - muscle rigidity and spasms.Both mechanisms – hallmark - muscle rigidity and spasms. Toxin becomes fixed to neurons, it cannot be neutralized with Toxin becomes fixed to neurons, it cannot be neutralized with

antitoxin.antitoxin. Recovery of nerve function from tetanus toxins requires Recovery of nerve function from tetanus toxins requires

sprouting of new nerve terminals and formation of new sprouting of new nerve terminals and formation of new synapses.synapses.

SYMPTOMSSYMPTOMS Tetanus are seen in Tetanus are seen in

– either never vaccinated oreither never vaccinated or

– completed primary series but no booster in preceding 10 yrscompleted primary series but no booster in preceding 10 yrs.. Patients with clinical manifestations occurring within 1 Patients with clinical manifestations occurring within 1

week of an injury have more severe clinical courses.week of an injury have more severe clinical courses. Patients with generalized tetanus present with trismus Patients with generalized tetanus present with trismus

(lockjaw)(lockjaw) Stiffness, Stiffness, Neck rigidity- Muscle rigidity - Major manifestationNeck rigidity- Muscle rigidity - Major manifestation Descending pattern - jaw & facial muscles over the Descending pattern - jaw & facial muscles over the

next 24-48 hours to extensor muscles of the limbsnext 24-48 hours to extensor muscles of the limbs Dysphagia - pharyngeal muscle spasmsDysphagia - pharyngeal muscle spasms

SYMPTOMSSYMPTOMS Restlessness, Restlessness, Reflex spasmsReflex spasms

– Triggered by minimal external stimuli - Noise, light, or touch. Triggered by minimal external stimuli - Noise, light, or touch. – Last seconds to minutes Last seconds to minutes – More intense More intense – Increase in frequency with disease progressionIncrease in frequency with disease progression– Cause apnea, fractures, dislocations, and rhabdomyolysis. Cause apnea, fractures, dislocations, and rhabdomyolysis. – Laryngeal spasms can occur - Asphyxia. Laryngeal spasms can occur - Asphyxia.

Other symptoms Other symptoms – Elevated temperature, sweating, elevated blood pressure, Elevated temperature, sweating, elevated blood pressure,

and episodic rapid heart rate.and episodic rapid heart rate. Sustained contraction of facial musculature produces Sustained contraction of facial musculature produces

a sneering grin expression known as risus sardonicus.a sneering grin expression known as risus sardonicus.

RISUS SARDONICUS.RISUS SARDONICUS.

SIGNSSIGNS Site of antecedent acute injury Site of antecedent acute injury

– Lower Extremity 52% Lower Extremity 52% – Upper Extremity 34%, Upper Extremity 34%, – Head or Trunk 5%Head or Trunk 5%

Autonomic dysfunction Autonomic dysfunction – extremes in blood pressure, dysrhythmias, and cardiac extremes in blood pressure, dysrhythmias, and cardiac

arrest.arrest. Neonatal tetanus Neonatal tetanus

– Inability to suck 3-10 days after birth. Inability to suck 3-10 days after birth. – Presenting symptoms include irritability, excessive crying, Presenting symptoms include irritability, excessive crying,

grimaces, intense rigidity, and opisthotonus.grimaces, intense rigidity, and opisthotonus.– Tetanic seizures may occur and portend a poor prognosis.Tetanic seizures may occur and portend a poor prognosis.

Frequency and severity of seizures are related to severity of the Frequency and severity of seizures are related to severity of the disease. disease.

Seizures resemble epileptic seizures with the presence of a Seizures resemble epileptic seizures with the presence of a sudden burst of tonic contractionssudden burst of tonic contractions..

SIGNSSIGNS No LOC & experiences severe pain. No LOC & experiences severe pain. Seizures - muscle groups Seizures - muscle groups

– Opisthotonos, flexion and abduction of the arms Opisthotonos, flexion and abduction of the arms – Clenching of the fists against the thorax Clenching of the fists against the thorax – Extension of the lower extremitiesExtension of the lower extremities

Localized tetanus Localized tetanus – Painful spasms muscles in close proximity to the site of Painful spasms muscles in close proximity to the site of

injury. injury. – Disorder may persist for several weeks but is usually self-Disorder may persist for several weeks but is usually self-

limiting.limiting. Cephalic tetanus Cephalic tetanus

– Characterized by variable cranial nerve (CN) palsies Characterized by variable cranial nerve (CN) palsies – CN VII is most frequently involved CN VII is most frequently involved – Untreated progress to generalized tetanusUntreated progress to generalized tetanus

Ophthalmoplegic tetanus - variant Ophthalmoplegic tetanus - variant – Develops after penetrating eye injuries Develops after penetrating eye injuries – Results in CN III palsies and ptosisResults in CN III palsies and ptosis

SIGNSSIGNS Abdominal tenderness and guarding, Abdominal tenderness and guarding,

– Mimicking an acute abdomen. Mimicking an acute abdomen. – Exploratory laparotomies have been performed .Exploratory laparotomies have been performed .

Tetanospasmin –Tetanospasmin –– Disinhibitory effect on the ANSDisinhibitory effect on the ANS– level of toxin in the CNS increases. level of toxin in the CNS increases.

ANS disturbances, ANS disturbances, – Sweating, fluctuating blood pressure,Sweating, fluctuating blood pressure,– Episodic tachydysrhythmia, Episodic tachydysrhythmia, – Increased release of catecholamines Increased release of catecholamines

Drugs with beta-blocker effects Drugs with beta-blocker effects – Cardiovascular manifestations of ANS instability, Cardiovascular manifestations of ANS instability, – Associated with increased risk of sudden death.Associated with increased risk of sudden death.

TESTSTESTS No blood tests that can be used to diagnose tetanus. No blood tests that can be used to diagnose tetanus. Diagnosis - presentation of tetanus symptoms Diagnosis - presentation of tetanus symptoms Laboratory identification of Laboratory identification of C. tetaniC. tetani can only be can only be

demonstrated by production of tetanospasmin in mice.demonstrated by production of tetanospasmin in mice.

Spatula testSpatula test– Touching the posterior pharyngeal wall with a sterile, soft-Touching the posterior pharyngeal wall with a sterile, soft-

tipped instrument,tipped instrument,– Positive test -involuntary contraction of the jaw (biting down Positive test -involuntary contraction of the jaw (biting down

on the "spatula"), on the "spatula"), – Negative test - gag reflex attempting to expel the foreign Negative test - gag reflex attempting to expel the foreign

object. object. – High specificity and a high sensitivity High specificity and a high sensitivity

PREVENTIONPREVENTION Recovery from naturally acquired tetanus does not Recovery from naturally acquired tetanus does not

result in immunity to tetanus. result in immunity to tetanus. Extreme potency of the tetanospasmin toxin; even a Extreme potency of the tetanospasmin toxin; even a

lethal dose of tetanospasmin is insufficient to provoke lethal dose of tetanospasmin is insufficient to provoke an immune response.an immune response.

Tetanus can be prevented by vaccination with tetanus Tetanus can be prevented by vaccination with tetanus toxoidtoxoid

The CDC recommends that adults receive a booster The CDC recommends that adults receive a booster vaccine every ten yearsvaccine every ten years

PREVENTIONPREVENTION Standard care practice Standard care practice

– booster to any patient with a puncture wound who is booster to any patient with a puncture wound who is uncertain last vaccinated, uncertain last vaccinated,

– he or she has had fewer than 3 lifetime doses of the vaccinehe or she has had fewer than 3 lifetime doses of the vaccine Booster Booster

– not prevent a potentially fatal case of tetanus from the not prevent a potentially fatal case of tetanus from the current woundcurrent wound

– It take up to two weeks for tetanus antibodies to formIt take up to two weeks for tetanus antibodies to form children under the age of seven, children under the age of seven,

– tetanus vaccine is often administered as a combined tetanus vaccine is often administered as a combined vaccine,-DPT/DTaP diphtheria and pertussis. vaccine,-DPT/DTaP diphtheria and pertussis.

Adults and children >7, Adults and children >7, – Td vaccine (tetanus and diphtheria) Td vaccine (tetanus and diphtheria) – Tdap (tetanus, diphtheria, and acellular pertussis)Tdap (tetanus, diphtheria, and acellular pertussis)

TETANUS IMMUNE GLOBULINTETANUS IMMUNE GLOBULIN Recommended for treatment of tetanus. Recommended for treatment of tetanus. Remove unbound tetanus toxin, but it cannot affect toxin bound Remove unbound tetanus toxin, but it cannot affect toxin bound

to nerve endings. to nerve endings. A single intramuscular dose of 3000-5000 units is generally A single intramuscular dose of 3000-5000 units is generally

recommended for children and adults, with part of the dose recommended for children and adults, with part of the dose infiltrated around the wound if it can be identified. infiltrated around the wound if it can be identified.

WHO recommends WHO recommends – TIG 500 units by intramuscular injection or intravenously immediatly TIG 500 units by intramuscular injection or intravenously immediatly – administer age-appropriate TT-containing vaccine (Td, Tdap, DT, DPT, administer age-appropriate TT-containing vaccine (Td, Tdap, DT, DPT,

DTaP, or TT depending on age or allergies), 0.5 cc by intramuscular DTaP, or TT depending on age or allergies), 0.5 cc by intramuscular injection at separate site.injection at separate site.

Tetanus disease does not induce immunity; Tetanus disease does not induce immunity; Patients without a history of primary TT vaccination should Patients without a history of primary TT vaccination should

receive a second dose 1–2 months after the first dose and a receive a second dose 1–2 months after the first dose and a third dose 6-12 months later.third dose 6-12 months later.

TREATMENTTREATMENT The wound must be cleaned. The wound must be cleaned. Dead and infected tissue should be removed by surgical Dead and infected tissue should be removed by surgical

debridement. debridement. Administration of the antibiotic metronidazole decreases Administration of the antibiotic metronidazole decreases

the number of bacteria but has no effect on the bacterial the number of bacteria but has no effect on the bacterial toxin.toxin.

Penicillin was once used to treat tetanus, but is no longer Penicillin was once used to treat tetanus, but is no longer the treatment of choice, owing to a theoretical risk of the treatment of choice, owing to a theoretical risk of increased spasms. - Metronidazole is not available. increased spasms. - Metronidazole is not available.

Passive immunization with human anti-tetanospasmin Passive immunization with human anti-tetanospasmin immunoglobulin or tetanus immunoglobulin is crucial. immunoglobulin or tetanus immunoglobulin is crucial.

If specific anti-tetanospasmin immunoglobulin is not If specific anti-tetanospasmin immunoglobulin is not available, then normal human immunoglobulin may be available, then normal human immunoglobulin may be given instead. given instead.

All tetanus victims should be vaccinated against the All tetanus victims should be vaccinated against the disease or offered a booster shot.disease or offered a booster shot.

MILD TETANUSMILD TETANUS Muscle spasms - Diazepam or Other muscle relaxants Muscle spasms - Diazepam or Other muscle relaxants Extreme cases - Paralyze the patient with curare-like Extreme cases - Paralyze the patient with curare-like

drugs and use a mechanical ventilator.drugs and use a mechanical ventilator. Maintenance of an airway and proper nutrition Maintenance of an airway and proper nutrition Total parenteral nutrition Total parenteral nutrition

– Intake of 3500-4000 C & at least 150 g of protein per dayIntake of 3500-4000 C & at least 150 g of protein per day– liquid form -tube directly into stomach (Percutaneous liquid form -tube directly into stomach (Percutaneous

endoscopic gastrostomy) endoscopic gastrostomy) – drip into a vein drip into a vein – high-caloric diet maintenance - increased metabolic strain high-caloric diet maintenance - increased metabolic strain

brought on by the increased muscle activity. brought on by the increased muscle activity.

Full recovery takes 4 to 6 weeks because the body Full recovery takes 4 to 6 weeks because the body must regenerate destroyed nerve axon terminalsmust regenerate destroyed nerve axon terminals

SEVERE TETANUSSEVERE TETANUS

Admission to intensive care. Admission to intensive care.

Lockjaw symptoms are caused due to Clostridium tetani infection. Lockjaw symptoms are caused due to Clostridium tetani infection. Damaged upper motor neurons cause muscular rigidity leading to Damaged upper motor neurons cause muscular rigidity leading to Lock-jawLock-jaw

SURGICAL THERAPYSURGICAL THERAPY Debridement of wounds to remove organisms Debridement of wounds to remove organisms

and to create an aerobic environment.and to create an aerobic environment. Excise at least 2 cm of normal viable-appearing Excise at least 2 cm of normal viable-appearing

tissue around the wound margins. tissue around the wound margins. Incise and drain abscesses. Incise and drain abscesses. Delay wound manipulation - several hours after Delay wound manipulation - several hours after

administration of antitoxin - risk of releasing administration of antitoxin - risk of releasing tetanospasmin into the bloodstream.tetanospasmin into the bloodstream.

DRUGS DRUGS

Muscle spasm, rigidity, and tetanic seizures Muscle spasm, rigidity, and tetanic seizures – sedative-hypnotic agents, sedative-hypnotic agents, – general anesthetics, general anesthetics, – centrally acting muscle relaxants, centrally acting muscle relaxants, – neuromuscular blocking agents.neuromuscular blocking agents.– Antibiotics are used to prevent multiplication of Antibiotics are used to prevent multiplication of C C

tetani,tetani, thus halting production and release of toxins. thus halting production and release of toxins. Antibiotics - prevent multiplication of Antibiotics - prevent multiplication of C tetani,C tetani,

thus halting production and release of toxinsthus halting production and release of toxins

ANTICONVULSANTSANTICONVULSANTS Sedative-hypnotic agents - mainstays of tetanus treatment. Sedative-hypnotic agents - mainstays of tetanus treatment. Benzodiazepines - primary agents for muscle spasm Benzodiazepines - primary agents for muscle spasm

prevention and work by enhancing GABA inhibition. prevention and work by enhancing GABA inhibition. Diazepam is the most frequently studied and used drug. Diazepam is the most frequently studied and used drug. Diazepam reduces anxiety, produces sedation, and Diazepam reduces anxiety, produces sedation, and

relaxes muscles.relaxes muscles. Lorazepam is an effective alternative. Large amounts (up Lorazepam is an effective alternative. Large amounts (up

to 600 mg/d). to 600 mg/d). Phenobarbital is another anticonvulsant that may be used Phenobarbital is another anticonvulsant that may be used

to prolong effects of diazepam. to prolong effects of diazepam. Phenobarbital is also used to treat severe muscle spasms Phenobarbital is also used to treat severe muscle spasms

and provide sedation when neuromuscular blocking agents and provide sedation when neuromuscular blocking agents are used.are used.

OTHER AGENTSOTHER AGENTS Spasm control Spasm control

– baclofen, baclofen, – Dantrolene, Dantrolene, – Short-acting barbiturates Short-acting barbiturates – Chlorpromazine.Chlorpromazine.

Magnesium sulphate can +/- benzodiazepines Magnesium sulphate can +/- benzodiazepines – Control spasm and autonomic dysfunctionControl spasm and autonomic dysfunction– 5 g (or 75 mg/kg) intravenous loading dose, then 2-3 g/h until 5 g (or 75 mg/kg) intravenous loading dose, then 2-3 g/h until

spasm controlledspasm controlled– Monitor patellar reflex, - Areflexia - Upper end of the therapeutic Monitor patellar reflex, - Areflexia - Upper end of the therapeutic

range (4 mmol/L). range (4 mmol/L). – Areflexia develops, dose should be decreased to avoid overdose. Areflexia develops, dose should be decreased to avoid overdose. – Does not reduce need for mechanical ventilation in adults with Does not reduce need for mechanical ventilation in adults with

severe tetanus, severe tetanus, – Reduce requirement for other drugs to control muscle spasms and Reduce requirement for other drugs to control muscle spasms and

cardiovascular instability. cardiovascular instability.

COMPLICATIONSCOMPLICATIONS

Prior to 1954, asphyxia from tetanic spasms was the usual Prior to 1954, asphyxia from tetanic spasms was the usual cause of death. cause of death.

Advent of neuromuscular blockers, mechanical ventilation, and Advent of neuromuscular blockers, mechanical ventilation, and pharmacologic control of spasms, sudden cardiac death has pharmacologic control of spasms, sudden cardiac death has become the leading cause of death. become the leading cause of death.

Sudden cardiac death has been attributed to excessive Sudden cardiac death has been attributed to excessive catecholamine productions, direct action of tetanospasmin, or catecholamine productions, direct action of tetanospasmin, or tetanolysin on the myocardium.tetanolysin on the myocardium.

Nosocomial infections are common when hospitalization is Nosocomial infections are common when hospitalization is prolonged. prolonged.

Secondary infections may include sepsis from decubitus ulcers, Secondary infections may include sepsis from decubitus ulcers, hospital-acquired pneumonias, and indwelling catheters. hospital-acquired pneumonias, and indwelling catheters.

Pulmonary embolism is particularly a problem in drug users and Pulmonary embolism is particularly a problem in drug users and elderly patients.elderly patients.

Further complications include the following:Further complications include the following: Long bone fractures Long bone fractures Glenohumeral joint and temporomandibular joint Glenohumeral joint and temporomandibular joint

dislocations dislocations Hypoxic injury and aspiration pneumonia is a common Hypoxic injury and aspiration pneumonia is a common

late complication of tetanus, found in 50–70% of late complication of tetanus, found in 50–70% of autopsied cases. autopsied cases.

Adverse effects of autonomic instability, including Adverse effects of autonomic instability, including hypertension and cardiac dysrhythmias hypertension and cardiac dysrhythmias

Paralytic ileus, pressure sores, and urinary retention Paralytic ileus, pressure sores, and urinary retention Malnutrition and stress ulcers Malnutrition and stress ulcers Coma, nerve palsies, neuropathies, psychological Coma, nerve palsies, neuropathies, psychological

aftereffects, and flexion contracturesaftereffects, and flexion contractures

PROGNOSISPROGNOSIS Dependent on incubation period, time from spore Dependent on incubation period, time from spore

inoculation to first symptom, and time from first inoculation to first symptom, and time from first symptom to first tetanic spasm.symptom to first tetanic spasm.

shorter intervals indicate more severe tetanus and a shorter intervals indicate more severe tetanus and a poorer prognosis.poorer prognosis.

Survive tetanus and return to their predisease state of Survive tetanus and return to their predisease state of health.health.

Recovery is slow and usually occurs over 2-4 months.Recovery is slow and usually occurs over 2-4 months. Some patients remain hypotonic.Some patients remain hypotonic. Clinical tetanus does not produce a state of immunity; Clinical tetanus does not produce a state of immunity;

patients who survive the disease require active patients who survive the disease require active immunization with tetanus toxoid to prevent a immunization with tetanus toxoid to prevent a recurrence.recurrence.

Thank you