Oleh:
dr. Rizka Humardewayanti Asdie, SpPD-KPTI
PENDAHULUAN
Th
1998-2000 di AS
43 kasus tetanus/th
insidensi
> 96% anak-anak diimunisasi DPT 3 x
Tetanus
140.000
TETANUS
Definisi:
Etiologi
C. Tetani :
Epidemiologi
Sumber: http://www.vaccineprotection.com/images/charts/tetanus.gif
Th 1998-2000 di AS:
- insidensi 0,16 kasus/1 juta populasi atau 43kasus/th
25% dibanding th 1980
- 15% kasus pada pengguna obat suntik,
angka kematian 18%
- risiko tertinggi pada orang tua, tertinggi umur 60 th
0,35 kasus/1 juta populasi
Spanyol: 0,37 kasus/1 juta populasi, pasien tua dg DM
0,7 kasus/1 juta populasi
Inggris: 0,2 kasus/1 juta populasi, tertinggi umur 64 th
Eropa (tertinggi di Italia th 1970-1990):
- insidensi dari 0,5 0,2 kasus/100.000 populasi
- kematian dari 68% 39%
Negara berkembang:
- 1.000.000 kasus dalam beberapa tahun
- Nigeria: pasien gangguan neurologis 14% o.k.
tetanus
WHO th 2000: 300.000 kasus kematian tetanus
RS SARDJITO pasca gempa 24 pasien (20 pria & 4 wanita)
Orang dewasa > 60 tahun , risiko tinggi terjadi tetanus dan kematian
o.k tetanus populasi umur orang yang imunisasi TT di AS.
Th 1993-1997
Gambar 3. Patogenesis
Tetanus
Sumber: http:mywebpages.comcast.net/epollak/PSY255-pix/tetanus.JPG
PATOGENESIS
Sering terjadi: luka terkontaminasi
C.tetani
Tidak ada inflamasi & tenang pada port
dentrae (kecuali ada super infeksi)
Basil mengekskresi 2 macam toksin:
tetanospasmin: sindroma klinis (kejang)
tetanolisin: merusak jar sekitar untuk
multiplikasi bakteri
Toksin menyebar dari ujung syaraf axon
retrograd masuk sel syaraf otak & spinal
Pertama pada motoriksensorikotonom
Patogenesis
Luka dalam
Patogenesis
Toksin mudah diikat jaringan saraf dan bila telah terikat tidak dapat
dinetralkan oleh antitoksin spesifik.
Setelah mencapai spinal dan batang otak terikat kuat pada reseptor
pada saraf spinalis dan batang otak
Tetanospasmin bisa berreaksi pada motor end plate perifer, saraf spinal,
otak dan sistem saraf otonom hambatan arus refleks spinal. Hal ini
mungkin karena toksin memblok pelepasan neurotransmiter
penghambat glycine dan -amino butyric acid (GABA) mengurangi
penghambatan neuron motor- rigiditas dan hiperaktivitas simpatik
Toksin juga mempengaruhi neuron simpatik preganglio pada bagain
lateral substansia grisea medulla spinalis gangguan otonomik
PATOGENESIS
2. Tetanolisin
Bersifat hemolisis
Peran kurang berarti
MANIFESTASI KLINIS
Terjadi setelah ada trauma
Kontaminasi dg tanah, kotoran binatang,
logam berkarat
Dapat juga akibat luka bakar, ulkus gangren,
nekrosis krn gigitan ular, infeksi teliga
tengah, persalinan, aborsi septik, injeksi i.m.,
pembedahan.
Sebab trauma ringan (dalam gedung) 50%
15-25% tidak terdapat perlukaan baru
MANIFESTASI KLINIK
TETANUS GENERAL
Gejala klinis
Opisthotonus
Kontraksi otot punggung sehingga
melengkung
Risus Sardonicus
spasme otot muka, alis
tertarik ke atas, sudut mulut
tertarik ke luar/bawah, bibir
tertekan kuat pada gigi
Trismus
3.
B. Onset
SKOR
< 7 hari
8-12 hari
> 12 hari
< 3 hari
4-6 hari
> 7 hari
C. Disfagia
D. Kejang
1
Spontan
Rangsang
G. Spasme laring
TETANUS LOKAL
jarang
restriksi otot atau kontraksi menetap di dekat luka
kontraksi menetap dalam beberapa minggu,
biasanya sembuh sendiri
prognosis baik
TETANUS SEFALIK
jarang
menyertai trauma atau luka di kepala/ infeksi telinga
(OMC)
ditandai trismus dan disfungsi 1 saraf kranial,
tersering N VII
Tetanus oftalmoplegi (varian) disfungsi N III dan
ptosis
masa inkubasi beberapa hari, angka kematian tinggi
bila tak diterapi tetanus general
TETANUS NEONATORUM
DIAGNOSIS
Prosedur lain:
Gangguan Konversi
Dislokasi Mandibula
Ensefalitis
Hipokalsemia
Meningitis
Abses Peritonsiler
Rabies
Stoke Hemoragik/perdarahan
Pendarahan Subarakhnoid
Spider envenomations widow
Keracunan, reaksi distonik yang diinduksi obat-obatan
Keadaan-keadaan lain:
- Penyakit Intraoral
- Infeksi Odontogenik
- Globus Hystericus
- Ensefalopati Hepatikum
- Histeria
- Keracunan Strychnine
- Akut abdomen
- Perdarahan intrakranial
Sumber: Dire, 2005
PENATALAKSANAAN
A.
Penatalaksanaan Umum
Tujuan terapi :
Mencegah kejang
Dengan :
B. ANTIBIOTIKA
1.
Penisilin G
2. Metronidazole
Tabel 3. Antibiotika
Drug Name
Penicillin G (Pfizerpen) -- Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting
in
bactericidal
activity
against
susceptible
microorganisms.
A 10- to 14-d course of treatment is recommended. Large IV doses of penicillin may cause hemolytic anemia
and neurotoxicity. Cardiac arrest has been reported in patients administered massive doses of penicillin G
potassium. Patients with renal failure are particularly at risk.
Adult Dose
Pediatric Dose
Contraindications
Documented hypersensitivity
Interactions
Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin
Pregnancy
Precautions
Drug Name
Metronidazole (Flagyl) -- Active against various anaerobic bacteria and protozoa. Appears to be absorbed into
cells, and intermediate-metabolized compounds that are formed bind DNA and inhibit protein synthesis, causing
cell
death.
A 10- to 14-d course of treatment is recommended. Some consider this the DOC since penicillin G is also a
GABA agonist, which may enhance effects of the toxin.
Adult Dose
Pediatric Dose
Contraindications
Interactions
Cimetidine may increase toxicity of metronidazole; may increase effects of anticoagulants; may increase toxicity
of lithium and phenytoin; disulfiramlike reaction may occur with orally ingested ethanol
Pregnancy
Precautions
Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy
Doxycycline (Vibramycin, Doxychel) -- Inhibits protein synthesis and thus bacterial growth by binding with 30S and
possibly 50S ribosomal subunits of susceptible bacteria. A 10- to 14-d course of treatment is recommended.
Adult Dose
Pediatric Dose
<8
years:
<100
lb
(45
kg):
2
>100 lb (45 kg): Administer as in adults
Contraindications
Interactions
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate;
tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral
contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy
D - Unsafe in pregnancy
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal
impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth
development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike
syndrome may occur with outdated tetracyclines
mg/lb/d
(4.4
Not
mg/kg/d)
PO/IV
recommended
divided
bid
C. ANTITOKSIN
untuk
Tetanus immune globulins (Hyper-Tet, Bay-Tet) -- Used as prophylaxis against tetanus and to treat
patients with circulating tetanus toxin. TIG provides passive immunity. TIG should be used to treat all
patients with active tetanus, in combination with other supportive and therapeutic treatments. Should
also be used to prevent tetanus in patients with inadequate or unknown immunization status after an
acute injury.
Adult Dose
Prophylaxis:
250-500
U
IM
Clinical tetanus: 3,000-10,000 U IM
Pediatric Dose
Prophylaxis:
250
U
IM
Clinical tetanus: Administer as in adults
Contraindicatio
ns
Patients with hypersensitivity to horse or cow proteins should not receive the equine or bovine antitoxins;
do not inject in same site or with same syringe as tetanus toksoid; not to be administered intravenously
Interactions
Live-virus vaccines may not replicate successfully, and antibody response could be reduced when
vaccine is administered after tetanus immune globulin because of presence of antibodies in the immune
globulin; live-virus vaccines should ideally be administered at least 3 mo after therapy with tetanus
immune globulin; if administration of an immune globulin preparation becomes necessary because of
exposure to disease, live-virus vaccines can be given simultaneously with immune globulin at site
remote from that chosen for immune globulin; vaccine virus replication and stimulation of immunity
occurs 1-2 wk after vaccination, therefore, if interval between administration of vaccine and immune
globulin is <14 d or if they were administered simultaneously, vaccination should be repeated at least 3
mo after immune globulin preparation was given, unless serologic testing indicates that adequate
antibodies were formed
Pregnancy
Precautions
Caution in patients with prior systemic allergic reactions following administration human immunoglobulin
preparations; caution in severe thrombocytopenia or any coagulation disorder that would contraindicate
IM injections
in
in
opposite
opposite
extremity
extremity
to
to
tetanus
toksoid
tetanus
toksoid
D. ANTI KEJANG
kombinasi tx kejang, rasa nyeri,
gangguan ventilasi
ideal menghilangkan spasme tanpa menyebabkan
oversedasi dan hipoventilasi
1. Diazepam
benzodiazepine dan agonis GABA
efek sedasi (+)
dosis awal 10-30 mg iv 120 mg/kgBB/hari atau
0,5 -1,0 mg/kgBB/4 jam atau infus kontinyu
2. Meprobamate : 300-400 mg/4 jam im
3. Klorpromasin : 25-75 mg/4 jam
4. Fenobarbital : 50-100 mg/4 jam
bila terjadi hipoventilasi karena oversedasi atau spasme
laring intubasi atau trakeostomi dengan/tanpa
ventilasi mekanik
tunggal atau
Diazepam (Valium) -- Mainstay of treatment of tetanic spasms and tetanic seizures. Depresses all levels of CNS,
including limbic and reticular formation, possibly by increasing activity of GABA, a major inhibitory neurotransmitter.
Adult Dose
Mild
spasms:
5-10
mg
Moderate
spasms:
5-10
Severe spasms: Mix 50-100 mg in 500 cc D5W and infuse at 40 mg/h
Pediatric Dose
Mild
spasms:
0.1-0.8
Moderate or severe spasms: 0.1-0.3 mg/kg IV q4-8h
Contraindication
s
Interactions
Toxicity of benzodiazepines in CNS is increased when used concurrently with alcohols, phenothiazines, barbiturates, and
MAOIs; cisapride can increase diazepam levels significantly
Pregnancy
D - Unsafe in pregnancy
Precautions
Caution in patients receiving other CNS depressants; caution in patients with low albumin levels or hepatic failure since
diazepam toxicity may increase
Drug Name
Phenobarbital (Barbita, Luminal) -- Drug dose must be small enough so that respirations are not depressed. If patient is
already on a ventilator, higher doses may provide desired sedation.
Adult Dose
Pediatric Dose
Contraindication
s
Documented hypersensitivity; marked impairment of liver function; severe respiratory disease; nephritic patients
Interactions
Pregnancy
D - Unsafe in pregnancy
Precautions
In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism,
diabetes mellitus, and severe anemia since adverse reactions can occur; caution in myasthenia gravis and myxedema
mg/kg/d
PO
mg
PO
q4-6h
IV
divided
prn
prn
tid/qid
E. Penghambat Neuromuskuler
diberikan bila terapi sedativa tidak adekuat, a.l. atracurium,
pancuronium, vecuronium
1. Pancuronium:
- long acting
- efek samping menghambat pelepasan katekolamin
memperburuk instabilitas otonom
2. Vecuronium: infus kontinyu efek adekuat
3. Baclofen:
- menstimulasi reseptor beta post sinaps GABA
- bolus 1000 g intratekal atau infus kontinyu intratekal
- penelitian retrospektif di RS Portugal: dosis awal
40-200 g diikuti infus kontinyu 20 g /hari
mengontrol spasme dan kekakuan pada 21/22 pasien
tetanus derajat III
-
Vecuronium (Norcuron) -- Prototypic, nondepolarizing neuromuscular blocking agent that reliably results in muscular
paralysis.
For
maintenance
of
paralysis,
a
continuous
infusion
may
be
used.
Infants are more sensitive to neuromuscular blockade activity, and although the same dose is used, recovery is prolonged
by 50%. Not recommended for use in neonates.
Adult Dose
0.08-0.1 mg/kg IV; may reduce to 0.05 mg/kg if patient has been treated with succinylcholine
Maintenance for paralysis: 0.025-0.1 mg/kg/h IV; may titrate to desired train-of-four response (commonly 2 of 4 twitches)
Pediatric Dose
Contraindications
Interactions
When vecuronium is used concurrently with inhalational anesthetics, neuromuscular blockade is enhanced; renal or
hepatic failure as well as concomitant administration of steroids may result in prolonged blockade despite withdrawal of the
agent
Pregnancy
Precautions
In myasthenia gravis or myasthenic syndrome, small doses of vecuronium may have profound effects
Drug Name
Dantrolene (Dantrium) -- Stimulates muscle relaxation by modulating skeletal muscle contractions at a site beyond the
myoneural junction and by acting directly on the muscle. Not FDA approved for use in tetanus but has been described in a
small number of case reports.
Adult Dose
Pediatric Dose
0.5 mg/kg IV bid initial; increase to 0.5 mg/kg IV bid/qid, then by increments of 0.5-3 mg/kg bid/qid prn; not to exceed 100
mg qid
Contraindications
Interactions
Toxicity may increase with coadministration of clofibrate and warfarin; coadministration with estrogen may increase
hepatotoxicity in women >35 y
Pregnancy
Precautions
May cause hepatotoxicity (use only for recommended indications); caution in impaired pulmonary function and severe
cardiac insufficiency; may cause photosensitivity with exposure to sunlight
followed
initial
F. Terapi tambahan
Hidrasi
Nutrisi enteral atau parenteral
Fisioterapi cegah kontraktur
Heparin/antikoagulan lain cegah emboli paru
Monitor fungsi usus, kandung kemih, ginjal
Cegah perdarahan GI dan ulkus dekubitus
Tx infeksi sekunder
Penatalaksanaan GIZI
Penurunan BB sering pada tetanus
Tidak mampu menelan Trismus &
Disfagi
Metabolisme meningkat pireksia &
aktifitas muskuler/spasme
Masa kritis yang berkepanjangan
PEMBERIAN NUTRISI
Diberikan seawal mungkin
Nutrisi enteral dengan komplikasi yang
PENCEGAHAN
A.
Imunisasi Aktif
Pada dewasa 3 dosis TT (Td untuk umur > 7 tahun)
II
4-8 mgg
III
6-12 mgg
B. Penatalaksanaan Luka
Mencegah tetanus :
mencegah terjadi luka
merawat luka dengan adekuat
ATS 1.500 U im (skin test) kekebalan pasif,
memperpanjang masa inkubasi
Luka-luka lainnya
Tetanus sebelumnya
Td
TIG
Td
Ya
Tidak
Ya
Tidak, kecuali
Tidak
Tidak, kecuali
3 dosis
> 10 tahun
> 5 tahun
sejak dosis
sejak dosis
terakhir
terakhir
TIG
Ya
Tidak
Komplikasi
- produksi katekolamin
-
Tekanan darah
Takikardi
Disritmia
Hiperpireksia
Keringat >>
Vasokontriksi perifer
kadar katekolamin plasma dan urin
Komplikasi
Akibat penyakit: laringospasme, ruptur
ventilator
Komplikasi lain:
# tulang panjang
Dislokasi tempomandibula
dan glenohumeri
Hipoksia
Pneumonia aspirasi
Emboli paru
Ruptur otot
Tromboplebitis vena dalam
Ileus paralitik
Retensi urin
Pressure sores
Malnutrisi
Stress ulcers
Koma
Kelemahan saraf
Neuropati
Kontraktur
Ulkus dekubitus
Rhabdomiolisis
Efek psikologis paska
tetanus
PROGNOSIS
Tergantung :
masa inkubasi : waktu dari masuknya spora sampai
timbul gejala
waktu sejak timbul gejala spasme tetanik I
Neonatus
Umur > 55 tahun
Kenaikan suhu badan yang tinggi
Pengobatan terlambat
Periode trismus dan kejang semakin sering
Adanya penyulit spasme otot pernafasan dan
obstruksi jalan nafas
RINGKASAN