Jofizal Jannis

Neurologist

National Brain Centre

Kesadaran adalah : is the body’s state of

arousal or awareness of self and environment

Koma : keadaan tidak sadar total terhadap

diri dan lingkungan meski di stimulasi dengan

kuat.

Diantara sadar dan koma terdapat variasi

status gangguan kesadaran.

Klinis dapat ditentukan dengan bedside.

OBJEKTIF

• Dokter mampu melakukan

stabilisasi, diagnosis, mengatasi

dan evaluasi pasien koma.

• Dokter dapat mengatur prioritas

pendekatan secara berurutan

Objektif Primer

• Airway

• Breathing

• Circulation

• Terapi progresif cepat (koma hipoglikemik)

• Evaluasi TTIK atau lesi massa

• Terapi TTIK, kemungkinan intervensi bedah

Objektif Sekunder

• Dokter mengenal perbedaan koma

struktural dan metabolik toksik

• Dokter mengerti dan mengenal

• Koma

• TTIK

• Sindrom Herniasi

• Tanda lesi massa supratentorial

• Tanda lesi massa infra tentorial

Dua (2) komponen kesadaran :

formasio retikularis dan hemisfer serebral

Formasio retikularis : a diffuse collection of

neurons that extends throughout the brainstem

(terpusat pons. Dari mes, pons dan m.o).

Reticular Activating System : a diffuse collection

of neuron in the reticular formation, plays an

essential role in keeping the concious brain.

ARAS : Blocking jaras asending antara formatio

reticular dan korteks serebri menyebabkan tidak

sadar

Supra orbital

Sternum

Kuku jari

Sendi temporo mandibular

WHAT YOUR FIND

PENILAIAN PENURUNAN KESADARAN

PENURUNAN

KESADARAN

KUALITATIF KUANTITATIF

APATIS SOMNOLEN SOPOR KOMAGLASGOW

COMA SCALE

EYES OPEN

4. Spontan3. Bicara2. Nyeri1. None

MOTORIK

6. Ikut Perintah5.Nyeri lokal4.Menolak3.Fleksi2.Ekstensi1. None

VERBAL

5. Orientasi baik4. Bingung3. Kata kata2. Suara1. None

DIAGNOSIS PENURUNAN

KESADARAN

KOMA STRUKTURAL KOMA METABOLIK

TANDA

LATERALISASI (+) LATERALISASI (-)

Kelainan difus

Ingat SAH

ETIOLOGI KOMA

GANGGUAN STRUKTURAL GANGGUAN METABOLIK

Kerusakan RAS Metabolisme energi

Multifaktor

Langsung TidakLangsung

PerdarahanInfarkTraumatumorInfeksi

Herniasi

Iskemi, anoksia, hipoksiaHipoglikemiHiper/ hipotermia

ImbalanselektrolitGangguanasam basaHiper/ hipoosmolarKejang umum

Kegagalanorgan

HepatikRenalPulmonerPankreatik

KeracunanInfeksi

Aktivitas neuronal membran

Koma Struktural

MeninggalSelamat

Komplikasi Mati Otak

Menolak

dibantu

Tidak

Sadar

Sadar

Pemulihan

DisabilitasPVS

MCS

Disabiltas Berat

Disabilitas

ringan

WHAT IT MEANS

Vaskular

Infeksi

Trauma

Alkohol

Metabolik

Neoplastik

Imunitas

PENYEBAB

PENURUNAN

KESADARAN

• Asending RAS, dari sisi bawah pons ke pons ke talamus ventromedial

• Sel yang berasal dari sistem ini menduduki area paramedian di brainstem

Kesadaran (arousal)

Korteks serebral

RAS

TALAMUS

HJPOTALAMUS

Consciousness

Kesadaran normal

Wakefulness

Awareness

BRAIN DEATH

Minimally Conciousness

DIAGNOSIS DIFERENSIAL

KOMA LOCK IN SYNDROME VEGETATIVE STATE PSIKIATRI

Koma

VEGETATIVE STATE

Vegetative

• Pasien tertolong dari koma, tapi berkembang

keadaan persistent unresponsif, tapi sleep–

wake cycles kembali.

• Setelah cedera kepala berat, fungsi brainstem

kenbali mengalami sleep–wake

cycles, membuka mata respons terhadap

stimuli verbal dan kontrol pernafasan normal.

Vegetative state (coma vigil, apallic syndrome)

Lock-in Syndrome

Locked-in

Locked in syndrome

• Pasien awake and alert, tapi tidak

sanggup bergerak atau bicara

• Lesi Pontine mempengaruhi pergerakan

mata ke lateral dan kontrol gerak.

• Lesi sering spare vertical eye movements

and blinking.

Psikogenik unresponsif

• Pasien, walau tampak tidak sadar, biasa

menunjukkan beberapa respons stimuli

eksternal

• Refleks kornea menyebabkan kontraksi otot

orbikularis okuli

• Ditandai oleh resistensi gerak pasif tungkai

dan tanda penyakit organik tidak ada

PENILAIAN KLINIS

PENURUNAN KESADARAN

PERNAPASAN

Soma (isokor)AnisokorMidriasisMiosis

TENTUKAN SECARA KUALITATIF DAN KUANTITATIF

N. OkulerN. Facial

Lateralisasi

PUPIL N. KRANIAL MOTORIK

DIAGNOSIS PENURUNAN

KESADARAN

ANAMNESISPEMERIKSAAN

FISIK

PEMERIKSAAN

NEUROLOGI

History

Riwayat

makan

obat

Trauma

Infeksi

Tekanan

darah

Suhu

Pernapasan

Sklera

Lateralisasi

Gambaran Koma DVS Brain Death LOS AkinetikMutisme

Self awareness - - - + +

Sleep wave cycle - + - + +

Fungsi motorik - - - Terbatas +++

Fungsi pernafasan + - + +

EEG PolimortikTeta

DeltaSlow

- ~ Nonspesificslow wave

Cerebral metabolisme

<50% <5% -

Keadaan Perubahan Level Kesadaran

BILA MENGALAMI DELIRIUM

SEGERA ASES

PENYEBAB

NYERI RETENSIO URINE

HIPOKSIA HIPOTENSI DEHIDRASI

Abnormalitas pernafasan dapat

membantu lokalisasi tetapi tidak selalu

dalam konteks tanda lain seperti

hiperpnea refleks sentral (midbrain-

hipotalamus)

Apneustik, kluster, ataksik,(pons bawah)

Hilangnya pernafasan otomatis (medula)

Abnormalitas Penafasan

Deskripsi Lokalisasi

Cheyne – Stokes Pola pernafasan kresendo dekresendo diiluti oleh apnue atau hipobnea, menetap selama tidur

Bihemisfer (unilateral / bilateral), atau brainstem

Cluster Ireguler pernafasan diikuti periode apnue yang lamanya bervariasi

Bihemisfer /pons

Ataxic or irregular Kecepatan pernafasan yang tidak teratur irama dan amplitudo diputus oleh apnue

Tidak terlokalisasi atau medula dorsomedial

Apneustic Inspirasi panjang dengan 2-3 detik berhenti kemudian ekspirasi.

Tekmentum lateral dari pons bawah

Central neurogenetic hiperventilation

Hiperventilasi terus terusan kecepatan pernafasana tidak melebihi 40 kali/menit

Bihemisfer pons dan midbrain

Pernafasan cheyne stok

Hiperventilasi neurogenik sentral

apnestik

Pernafasan cluster & pernafasan ataxic

Apnoe

Pupil normal

Anisokor di pupil karena herniasi

Oval pupil (gambaran awal mati otak)

Midriasis

(ansietas, delirium, kejang, obat-obat

seperti atrofin, NE, dopamin)

Midposisi (mati otak, lesi mesenfalon)

Sindrom Hordner

Miosis (opioid, lesi pons

akut, hiperkapni, hiperglikemi non ketotik

Spektrum abnormalitas pupil dan penyebab

WHAT TO DO

Pendekatan DD

Glucosa, ABG, Lytes, Mg, Ca,Tox, ammonia

Unresponsif

ABCs

IV D50, narcan,

CT

Brainstem

at tanda

Fokal

Disfungsi otak difus

Metabolik / infeksi

Unconscious

Lesi fokal

Tumor, ICH/SAH/ infark

Pseudo-Coma

Psikogenik, Lo

oked-in,

NM paralysis

LP± CT

Y N

Y

N

Koma

Intubasi –ventilasi/stabilisasi tekanan darah

Sindrom

Neurologi

Pencitraan

otak

Hasil

Pilihan

pengobatan

Jaringan Otak dan

pergeseran batang otak

CT otak

Abnormal

Intrinsik batang otak

Bedah Evakuasi

Kraniektomi

Rx ICP

Stroke TBI Massa

Tumor Infeksi

CT otak

Normal

Trombolisis

Pengambilan

bekuan

Basilar

embolus

arteri

ICH TBI

Abnormal

Massa

Perawatan

medik

Perawatan

medik

Biopsi

Penyebab

N – Neck

A – Airway

B – Breathing

C – Circulation

D – Diabetes

Drug

E – Epilepsi

F – Fever

G – GCS

H – Herniation

I – Investigate

Resusitasi, memakai ABC Neurologi

Manajemen Gangguan Kesadaran

Kesadaran menurun

Neuroprotektan

Neuroproteksi

Tujuan untuk melindungi jaringan otak

yang hampir rusak.

Beberapa obat yang pernah dipakai

Citicholin

Piracetam

Piritinol

Jaringan Saraf

Lipid : 51-54%

Komponen lipid terdiri:

Phospholipid : 28%

(lecithins, cephalins & sphingomyelin)

Kolesterol : 10%

Cerebroside (galactolipids) : 7%

Lipid mengandung sulfur, aminolipid : 9%

Level lesithin pada trauma kapitis

- Secara eksperimental

- Pada sisi cedera :

3 hari pertama cedera terjadi

penurunan lecithin

- Pada sisi lain tidak terjadi perubahan

FARMAKODINAMIK SITIKHOLIN

Bekerja langsung pada SSP

Mengaktifkan for. retikularis di Batang Otak

sehingga menurunkan ambang rangsang reaksi

arousal untuk membantu membangkitkan

kesadaran

Mengaktifkan fungsi pyramidal dan ekspiramidal

yang tersisa

Menurunkan ambang rangsang evoke muscular

discharge shg merangsang aktivitas system

piramidal yang berkaitan dg fungsi motorik

Efek sitikholin pada CDP Kholin sinthetase endogen

dan penggunaan FFA

CDP Kholin (sitikholin)

Sistidin kholin

Sistidin kholin

CTP FOSFORIL KHOLIN

SITIKHOLIN

FFA

DYACYL GLYCEROL +

FOSFATIDIL KHOLIN

MEMBRAN SEL

Mekanisme kerja citikholin

Sebagai derivate asam nukleat melakukan

biosintesis lecithin dan stabilisasi membran sel

Memperbaiki aktivitas membrane ATP ase

Mengaktifkan kembali metabolisme serebral

Memperbaiki sirkulasi serebral secara selektif

Pembentukan neurotransmitter

Mencegah akumulasi asam lemak toksik shg

mencegah luas infark dan kerusakan jaringan

Terapeutik Window citikholin 24 – 48 jam

Citikholin mempunyai efek neuroproteksi

Mengurangi lesi pada membran saraf

dengan cara meningkatkan sintesis

fosfolipid dan mengurangi kadar asam

lemak bebas

Beberapa studi membuktikan bahwa

citikholin mempunyai.terapeutik window

24 – 48 jam

Treatment of acute cerebral

infarction with a choline precursor in

a multicenter

A multicenter double-blind placebo-controlled study of cytidine 5'-

diphosphocholine (CDP-choline) was conducted to evaluate possible

clinical benefits of the drug in patients with acute, moderate to

severe cerebral infarction. The patients included also suffered from

moderate to mild disturbances of consciousness, and all were admitted

within 14 days of the ictus. Patients were allocated randomly to treatment

with either CDP-choline (1,000 mg/day i.v. once daily for 14 days) or with

placebo (physiological saline). One hundred thirty-three patients received

CDP-choline treatment, and 139 received placebo. The group treated with

CDP-choline showed significant improvements in level of consciousness

compared with the placebo-treated group, and CDP-choline was an

entirely safe treatment. (Stroke 1988; 19:211-216)

Oral Citicoline in Acute Ischemic Stroke

An Individual Patient Data Pooling

Analysis of Clinical Trials

Treatment with oral citicoline within the

first 24 hours after onset in patients with

moderate to severe stroke increases the

probability of complete recovery at 3

months. (Stroke. 2002;33:2850-2857.)

Citicoline Preclinical and

Clinical Update 2009–2010Abstract—Citicoline is a neuroprotectant

and neurorestorative drug that is used in the

treatment of acute ischemic stroke in some

countries. The research with this compound

continues. In this review, we focus on the

latest publications or communications or

both and on the major ongoing experimental

and clinical projects involving citicoline in

stroke recovery. (Stroke. 2011;42[suppl

1]:S36-S39.)

Citicoline in the treatment of acute ischaemic

stroke:

an international, randomised, multicentre,

placebo-controlled study (ICTUS trial)

Results 2298 patients were enrolled into the study from Nov 26,

2006, to Oct 27, 2011. 37 centres in Spain, 11 in Portugal, and 11 in

Germany recruited patients. Of the 2298 patients who gave

informed consent and underwent randomisation, 1148 were

assigned to citicoline and 1150 to placebo. The trial was stopped

for futility at the third interim analysis on the basis of complete

data from 2078 patients. The fi nal randomised analysis was based

on data for 2298 patients: 1148 in citicoline group and 1150 in

placebo group. Global recovery was similar in both groups

(odds ratio 1ÅE03, 95% CI 0ÅE86–1ÅE25; p=0ÅE364). No

significant diff erences were reported in the safety variables nor in

the rate of adverse events.

The Role of Citicoline in Neuroprotection

and Neurorepair in

Ischemic Stroke

Advances in acute stroke therapy resulting from thrombolytic treatment,

endovascular procedures, and stroke units have improved significantly

stroke survival and prognosis; however, for the large majority of

patients lacking access to advanced therapies stroke mortality and

residual morbidity remain high and many patients become

incapacitated by motor and cognitive deficits, with loss of independence

in activities of daily living. Citicoline has therapeutic effects at several

stages of the ischemic cascade in acute ischemic stroke and has

demonstrated efficiency in a multiplicity of animal models of acute

stroke. Long-term treatment with citicoline is safe and effective,

improving post-stroke cognitive decline and enhancing patients’

functional recovery. Prolonged citicoline administration at optimal doses

has been demonstrated to be remarkably well tolerated and to enhance

endogenous mechanisms of neurogenesis and neurorepair contributing

to physical therapy and rehabilitation.