COMA

MOARTEA CEREBRALA

Sef de Disciplina Conf. Dr. Carmen Orban

Asist. Univ. Dr. Oana Dumitrascu
DEFINITIE:
Coma poate fi definita ca o stare de neresponsivitate in care pacientul
nu este constient asupra propriei persoane si nici asupra stimulilor din
mediul inconjurator si,
nu poate fi adus la starea de trezire sau nu poate raspunde la stimuli
din mediul inconjurator
Two components of conscious behavior

• content- the sum of cognitive and affective function

• arousal- appearance of wakefulness

Content depends on arousal but normal arousal does

not guarantee normal content
Structuri cheie implicate in starea de constienta:

- SRAA =sistemul reticulat activator ascendent

- Talamus

- Cortex

Anatomical structures and dorsal and ventral pathways involved

with the awake state

Wijdicks, Eelco F.M.. The Comatose Patient (Kindle Locations

1262-1263). Oxford University Press. Kindle Edition.
BIOCHIMIA STARII DE CONSTIENTA
-exista 4 circuite principale ale neurotransmitatorilor
implicati in starea de constienta
NEUROTRANSMITATORI IMPLICATI IN STAREA DE TREZIRE
=CONSTIENTA

• norepinephrine (originates in locus coeruleus and lateral tegmental area)

• dopamine (originates in ventral tegmental area, known as A10 neurons),
• serotonin (dorsal and medial raphe nuclei),
• acetylcholine (basal forebrain and brainstem),
• histamine (located in posterior hypothalamus),
• orexin-hypocretin (presumably located in the perifornical region of the
lateral hypothalamus).
• The reticular formation is largely active through the neurotransmitter
glutamate
• the reticular formation contains neurons that use gamma-amino butyric
acid (GABA), which has inhibitory control.
Cerințe obligatorii pentru starea de veghe

• Functia SRAA- sistem talamo- cortical depinde de:

o Integritatea anatomică a structurilor

o Integritatea lor metabolică (integritatea circulației)
o Integritatea comunicării (funcția neurotransmițătorilor)
 Diagnosticul diferential al comelor

Realizat in functie de:

• cauza producerii

• mecanism de producere,

• tipul leziunilor,

• responsivitate la stimuli
 Diagnosticul diferential al comelor

2 mari categorii:

- Come ,,structurale”
- (engl.:brainstem coma) - produse prin injurii sau compresiuni ale SRAA (herniere cingulară,
centrală, uncală, tonsiară, sau accident vascular de trunchi cerebral)
- Leziuni emsferice

- Come ,,metabolice/toxice” - produse prin injurii difuze, bilaterale ale cortexului şi trunchiului
cerebral (în general mai grave).
Unele date diagnostice pot orienta rapid către această grupă etiologică:
1. De obicei debutează insidios şi pot fi precedate de delir.
2. Tulburările respiratorii apar precoce
3. Reflexele pupilare şi oculocefalice sunt de obicei păstrate în fazele iniţiale ale stării
comatoase.
4. Semnele de focalizare neurologică sunt de obicei absente (în fazele iniţiale)
5. Tremorul, asterixis şi miocloniile multifocale sugerează comă metabolic/toxică.
Diagnosticul
diferential
al comelor
 Evaluarea generala a pacientului comatos

- Definire nivele constienta = alert / letargic / somnolent / obnubilat / comatos

- Comatos = fara posibilitatea de a fi trezit in ciudata stimularii viguroase; fara
miscari coordonate voluntare.

- Istoricul , anamneza familiei – instalare simptome: brusc, lent, ondulatoriu

- Importanta este diferentierea cauzei comei: cauza neurologica primara sau efectul secundar al unei
afectiuni sistemice
 Evaluarea generala a pacientului comatos

- Examen fizic general: - semne vitale (respiratie, alura ventriculara, tensiune arteriala, temperatura)

- observare si inspectie: - postura, pozitie, atitudine

- tegumente, mucoase

- miscari, raspuns verbal si motor la stimulare verbala, durere

Evaluarea
functiilor
SNC,
inclusiv a
trunchiului
cerebral
 Evaluarea
functiilor SNC,
inclusiv a
Trunchiului
cerebral
 Evaluarea functiilor SNC,
inclusiv a trunchiului
cerebral
 Evaluarea neurologica a pacientului comatos

- Nivel de responsivitate
- Raspunsuri pupilare
- Miscari oculare
- Examenul oftlmologic - fund de ochi – edem papilar / sd Terson
- Examinarea activitatii motorii
- Reflexe
- Semne meningeale – redoare cervicala
 Evaluarea neurologica a pacientului comatos

- Nivelul de resposivitate: se testeaza prin stimulare verbala intai, apoi aplicare stimul
dureros

- stimulul dureros poate fi: -presiunea nervului supraorbitar,

-presiune pat unghial
-presiune sternala
-presiune articulatie temporo-mandibulara
 Evaluarea neurologica a pacientului comatos

- Glasgow Coma Score

 Evaluarea neurologica a pacientului comatos
- Nivel de responsivitate:

- The FOUR Score

 Evaluarea neurologica a pacientului comatos
Comparare FOUR Score cu GCS :

- Pacientii cu cele mai mici scoruri Glasgow pot fi stratificati mai mult cu scorul FOUR
- FOUR pare superior ca scor deoarece - ofera mai mare detaliu neurologic,
- distinge sindromul “locked-in”
- detaileaza reflexele de trunchi cerebral,
- arata tipul de respiratie al pacientului
- diferentiaza stadia ale hernierii cerebrale
-Probabilitatea mortalitatii intraspit. in cazul celui mai mic scor FOUR > in cazul celui mai mic scor Glasgow
 Evaluarea neurologica a pacientului comatos

Examenul pozitiei oculare in repaus si miscarile oculare

- In repaus: asezare mediana, deviere, miscari conjugate

- Miscari: nistagmus, bobbing, dipping

- Reflex oculocefalic si caloric: declansarea aceluiasi reflex fie la miscarea pasiva a capului,
brusc dreapta, stanga/ fie la stimulare calorica(cu 30-50ml apa rece-33grde C sau calda-
44grde C se iriga conduct aud extern in 30”; dupa 5 min se testeaza cealalta parte). Devierea
ochilor se face spre stimul in mod normal. La stimulare bilaterala concomitenta cu rece ochii
deviaza in jos; la cald bilateral, deviaza in sus). / ! Pt miscarea capului atentie leziuni cervicale!
 Miscarile globilor oculari

Raspuns oculo- cefalic

“Doll’s Eyes Maneuver”
 Miscarile globilor oculari

Raspuns oculo vestibular

“Cold Caloric Testing”
 Evaluarea neurologica a pacientului comatos

- Examinare motorie
-tonus muscular – ridicare antebrat apoi lasat, flectare memebre pelvine pe pat apoi da
drumul
-raspuns la stimulare dureroasa – normal=localizeaza, retrage/flexie/extensie/fara raspuns
-reflexe osteotendinoase profunde (patelar, Achilian,biceps,brahioradial, triceps) - (0-4; normal=2)
-asimetrii, clonus
-reflexul Babinski = integralitate tract corticospinal
-reflexe cutanate superficiale (abdominal, cremasteric)
 Clasificarea comelor

• Leziunile cerebrale supratentoriale

- dau un efect de masa pe partea rostrala a trunchiului cerebral (pot da semne clinice
asimetrice)
- cand progreseaza spre coma au un patern disfunctional rostro-caudal (disfunctie
emisfere, apoi talamus, mezencefal, punte, bulb)
• Leziunile cerebrale infratentoriale
- afecteaza direct sistemul reticulat activator ascendent, nu are patern rostro-caudal al
instalarii simptomelor
 Clasificarea comelor

! Diferentiere come de:

• patologie psihiatrica - catatonie

- reactie de conversie
• Mutism akinetic (leziuni bilaterale frontale, talamice, in trunchiul cerebral periapeductal)
• “Locked-in” sd. (infarct in zona caudala punte)
• Stare vegetativa persistenta
• Stare de minima constienta
 Clasificarea comelor

Diagnosticul diferential al comelor se bazeaza in principal pe:

- Simptomatologie, semne clinice

- Neuro imagistica –CT, RMN, RMNf, PET,
- EEG
- Analiza lichid cefalorahidian (dupa imagistica)
- Examen oftalmologic fundoscopic
 Clasificarea comelor

EEG - gradare in functie de nivelul severitatii comei

 Patologii specifice ce pot evolua spre moarte cerebrala

Principalele afecţiuni care pot duce la instalarea morţii cerebrale sunt:

• traumatismele cranio-cerebrale
(hemoragia subarahnoidiană, hematomul subdural sau intraparenchimatos,
dilacerarea cerebrală),
• accidentele vasculare cerebrale ischemice sau hemoragice,
• encefalopatia ischemică (post stop cardio-respirator resuscitat, inec sau asfixie),
• tumori cerebrale – primitive sau secundare
• malformatii vaculare cerebralerupte (MAV, anevrisme cerebrale)
• toxice (după negativarea testelor toxicologice şi excluderea altor cauze potenţial reversibile de
comă).
Leziuni structurale
cerebrale ce provoaca
come +/- moarte
cerebrala

Normal Hemoragie cerebrala

Normal Anoxie cerebrala
Normal Trauma
 Hemoragie
Normal subarahnoidiana
Cauze de moarte cerebrala

Normal Anoxie cerebrala

Normal Meningita
 Fiziopatologia mortii cerebrale

Leziuni
Neuronale Edem
neuronal
PIC>PMA
incompatibil
cu viata
Flux sanguin
cerebral scazut Presiune intracraniana
crescuta
 Patologii specifice ce pot evolua spre moarte cerebrala
! Diferentiere patologii ce pot mima
moartea cerebrala:

• Hipotermia
• Encefalopatia metabolica
• Substante administrate (sedative, curare,
• toxice SNC, etc)
• Sindromul “Locked-in”
• Sindromul Guillain-Barre
 Definirea mortii cerebrale
1968 – CRITERIILE HARVARD

- coma profunda / nu retrage la stimuli durerosi

- areflexie (craniala sau spinala)
- apnee (deonectare 3 minute de la ventilator
- Electroencefalograma isoelectrica
- excluderea hipotermiei sau intoxicatiilor cu substante
- repetarea evaluarii anterioare la 24 de ore
Definirea mortii cerebrale
-CRITERIILE ACTUALE :
(Wijdicks, 2004)

-valabile in 8 tari
-diferentele in alte tari constau in teste
confirmatorii/experienta medici/
-in Romania este obligatorie testarea repetata
EEG sau angiografie cerebrala
 Definirea mortii cerebrale
Diferente in criteriile aplicate pentru diagnosticul mortii cerebrale UK vs. USA:

In USA sunt necesare teste

confirmatorii spre deosebire de UK
 The clinical evaluation (prerequisites) for BRAIN DEATH
Establish irreversible and proximate cause of coma.

The cause of coma can usually be established by history, examination, neuroimaging, and
laboratory tests.

Exclude the presence of a CNS-depressant drug effect by history, drug screen, or, if available, drug
plasma levels below the therapeutic range. Prior use of hypothermia (e.g., after cardiopulmonary
resuscitation for cardiac arrest) may delay drug metabolism. The legal alcohol limit for
driving(blood alcohol content 0.08%) is a practical threshold below which an examination to
determine brain death could reasonably proceed.

There should be no recent administration or continued presence of neuromuscular blocking agents

(this can be defined by the presence of a train of 4 twitches with maximal ulnar nerve
stimulation).

There should be no severe electrolyte, acid-base, or endocrine disturbance.

 The clinical evaluation (prerequisites)

Achieve normal core temperature

In most patients, a warming blanket is needed to raise the body temperature and maintain a normal or
near-normal temperature (36°C).

Achieve normal systolic blood pressure.

Hypotension from loss of peripheral vascular tone or hypovolemia (diabetes insipidus) is common; vasopressors
or vasopressin are often required.

Neurologic examination is usually reliable with a systolic blood pressure 100 mm Hg.
 The clinical evaluation (neurologic assessment)

Coma

• Patients must lack all evidence of responsiveness.

• Eye opening or eye movement to noxious stimuli is absent.

• Noxious stimuli should not produce a motor response other than spinally mediated reflexes.
presence or absence of motor responses to a standardized painful stimulus,
such as pressing on the supraorbital nerve, temporomandibular joint, or nail bed of a finger
 The clinical evaluation (neurologic assessment)

A common source of ambiguity is spontaneous and reflex movements in brain-dead bodies, which
are widely encountered and display ample variety.

Most movements seem to occur within the first 24 h, and rarely after 72 h.

- spontaneous movements of limbs (other than pathological flexion or extensionresponse),

respiration-like movements,deep tendon reflexes, superficial abdominal reflexes, triple
flexion response, and the Babinski sign.

- the incidence of brain death-related movements mostly stems from small case series, and
ranges from 13.4 to 79% of patients, with a wide array of phenomenology

- movements can be very subtle, such as fine finger tremors, or dramatic, such as the Lazarus sign
 Absence of brainstem reflexes
• Absence of pupillary response to a bright light is documented in both eyes.

• Absence of ocular movements using oculocephalic testing and oculovestibular reflex testing.
Movement of the eyes should be absent during 1 minute of observation. Both sides are tested, with
an interval of several minutes.

• Absence of corneal reflex. Absent corneal reflex is demonstrated by touching the cornea with a
piece of tissue paper, a cotton swab, or squirts of water. No eyelid movement should be seen.

• Absence of facial muscle movement to anoxious stimulus.

• Absence of the pharyngeal and tracheal reflexes. The pharyngeal or gag reflex is tested after
stimulation of the posterior pharynx with a tongue blade or suction device. The tracheal reflex is
most reliably tested by examining the cough response to tracheal suctioning. The catheter
should be inserted into the trachea and advanced to the level of the carina followed by 1 or 2
suctioning passes.
 EEG

• Minimum of eight scalp electrodes

• Interelectrode dependencies should be between 100 and 10,000
• Integrity of the entire recording system should be tested
• Electrode distances should be at least 10 cm
• Sensitivity should be increased to at least 2 µV for 30 minutes with inclusion of appropriate
calibrations
• High-frequency filter setting should be at 30 Hz, and low-frequency setting should not be
below 1 Hz
• There should be no electroencephalographic reactivity to intense somatosensory or
audiovisual stimuli
 Test apnee
-Absence of a Respiratory Drive.
-Absence of a breathing drive is tested with a CO2 challenge. Documentation of an increase in
--PaCO2 above normal levels is typical practice. It requires preparation before the test.
Prerequisites:
• normotension
• normothermia
• euvolemia
• eucapnia (PaCO2 35–45 mm Hg)
• absence of hypoxia
• no prior evidence of CO2 retention (i.e., chronic obstructive pulmonary disease, severe
obesity).
 Test apnee
Procedure:
• Adjust vasopressors to a systolic blood pressure _100 mm Hg.
• Preoxygenate for at least 10 minutes with 100% oxygen to a PaO2 _200 mm Hg.
• Reduce ventilation frequency to 10 breaths per minute to eucapnia.
• Reduce positive end-expiratory pressure (PEEP) to 5 cm H2O (oxygen desaturation with
decreasing PEEP may suggest difficulty with apnea testing).
• If pulse oximetry oxygen saturation remains_95%, obtain a baseline blood gas (PaO2, PaCO2, pH,
bicarbonate, base excess).
• Disconnect the patient from the ventilator.
• Preserve oxygenation (e.g., place an insufflations catheter through the endotracheal tube and close
to the level of the carina and deliver 100% O2 at 6 L/min).
 Test apnee
Procedure:
• Look closely for respiratory movements for 8–10 minutes. Respiration is defined as abdominal or
chest excursions and may include a brief gasp.
• Abort if systolic blood pressure decreases to _90 mm Hg.
• Abort if oxygen saturation measured by pulse oximetry is _85% for _30 seconds. Retry procedure
with T-piece, CPAP 10 cm H2O, and 100% O2 12 L/min.
• If no respiratory drive is observed, repeat blood gas (PaO2, PaCO2, pH, bicarbonate, base excess)
after approximately 8 minutes.
• If respiratory movements are absent and arterial PCO2 is _60 mm Hg (or 20 mm Hg increase in
arterial PCO2 over a baseline normal arterial PCO2), the apnea test result is positive(i.e.,
supports the clinical diagnosis of brain death).
• If the test is inconclusive but the patient is hemodynamically stable during the procedure, it may be
repeated for a longer period of time (10–15 minutes) after the patient is again adequately
pre- oxygenated.
 Test apnee
Complications:
The complication rate of apnea testing has been reported to be as high as 21% .

Common complications are - hypoxemia,

- bradycardia,
- arterial hypotension
The Steps in a Clinical Examination to Assess Brain Death

• In step 1, the physician determines that there is no motor response and the eyes do not open
when a painful stimulus is applied to the supraorbital nerve or nail bed.

• In step 2, a clinical assessment of brain-stem reflexes is undertaken.

• In step 3, the apnea test is performed; the disconnection of the ventilator and the
use of apneic diffusion oxygenation require precautionary measures. The core
temperature should be 36.5°C or higher, the systolic blood pressure should be
90 mm Hg or higher, and the fluid balance should be positive for six hours
The Steps in a Clinical Examination to Assess Brain Death
The Steps in a Clinical Examination to Assess Brain Death
The Steps in a Clinical Examination to Assess Brain Death
 Teste confirmatorii pentru diagnosticul de moarte cerebrala

-angiografie cerebrala,
-angioCT
-PET scan
-echo Doppler transcranian,
-potentiale evocate SSN
 TESTE CONFIRMATORII MOARTE CEREBRALA
Cerebral angiography

• Contrast medium under high pressure in both anterior and posterior circulation
injections
• No intracerebral filling at the level of the carotid or vertebral artery entry to the skull
• Patent external carotid circulation
• Possible delayed filling of the superior longitudinal sinus
 TESTE CONFIRMATORII MC

ANGIOGRAFIE
CEREBRALA
Technetium-99 Isotope Brain Scan
SCINTIGRAFIE DE PERFUZIE

Liniile punctate incercuiesc emisferele

cerebrale - arata absenta perfuziei
(echivaland cu mortea cerebrala)
Sageata indica perfuzie crescuta in
zona
nasului= semnul nasului rosu
(perfuzie crescuta in teritoriul arterei
carotide externe)
 Criteriile obligatorii de diagnostic pentru moartea cerebrala in Romania si in
lume

-DIFERA ca: teste confirmatorii / interval de retestare/ expertiza personal medical implicat in diagnostic

-ROMANIA – necesar 1 test confirmatoriu (EEG, sau angiografie, sau scintigrafie, sau
angioCT)/ 2 medici primari: ATI+ ATI, sau neurolog, sau neurochirurg)/ 2 testari
complete la min 6 ore distanta pentru adult, 48 de ore pentru nou-născutul cu
vârsta între 7 zile şi 2 luni, 24 de ore pentru copilul cu vârsta între 2 luni şi 2 ani
şi 12 ore pentru copilul cu vârsta între 2 şi 7 ani. Pentru copiii cu vârsta peste 7
ani, intervalul este acelaşi ca la adulţi.
La nou-născutul cu vârsta mai mică de 7 zile nu se declară moartea cerebrală.
 Criteriile obligatorii de diagnostic pentru
moartea cerebrala in lume

There is no worldwide consensus on the medical criteria for determining brain death, the threshold question
of when brain death has occurred is particularly affected by the differences in diagnostic criteria
in each jurisdiction:

-EUROPE -11 of 25 European countries require a confirmatory test for the diagnosis of brain death,
- Half of European countries require that more than one physician be involved in the
clinical determination
- In cases of “anoxia” as the cause of brain death, several countries have specific
observational procedures.(ex: Hungary, “secondary brain damage” extends
observation time to 72 h)