COMELEDEFINITIE: pierderea starii de constienta; stare asemanatoare somnului din care bolnavul nu poate fi trezit, ochii sunt inchisi si raman inchisi in ciuda aplicarii de stimuli puternici Constienta: forma cea mai inalta de reflectare a realitatii proprie omului, produs al creierului uman in procesul muncii, al vietii in societate, caracterizata prin prezenta gandirii si a limbajului, prin faptul ca omul isi da seama de lumea inconjuratoare si actioneaza asupra acesteia in conformitate cu anumite scopuri dinainte stabilite (Dictionarul limbii romane). Prezenta constientei depinde de integritatea anatomica si functionala a : -sistemului reticulat activator (SRA): -incepe in portiunea medie a puntii lui Varolio -urca in partea dorsala a mezencefalului -sinapsa in thalamus, de unde pleaca fibrele talamo- corticale -proiectiilor corticale (C) FIZIOPATOLOGIE. Integritatea anatomica si functionala a SRA si C poate fi pierduta prin boli: - ale sistemului nervos:iritatie meningeala leziuni de masa ale emisferelor cerebrale leziuni de masa ale mezenceflului convulsii generalizate - metabolice: intoxicatii (CO, benzodiazepine, opioide, etc) Insuficienta hepatica Coma acido-cetozica din diabet Coma hipoglicemica Coma din tulburarile hidro-electrolitice si acido-bazice Hiponatremie cu hipervolemie si hiperhidratare cerebrala Acidoza metbolica (insuficienta renala) Acidoza respiratorie (insuficienta respiratorie) Iritatia meningeala: inflamatie, infectie, hemoragie subarahnoidiana (ultimile 2 pot sa nu prezinte elemente dg la CT) Mecanisme discutabile: eliberarea de citochine si interleukine care cresc permeabilitatea membranei hematoencefalice (IL-1, TNF, metabolite ai acidului arahidonic) sinteza crescuta de radicali liberi de O si de NO edem cerebral vasogen alterarea fluxului sanguine cerebral cresterea sintezei de aminoacizi neurotransmitatori excitatori neurotoxici tardiv: vasculita si tromboza a venelor meningeale, urmata de necroza difuza corticala si a substantei albe Leziuni de masa emisferice: Se extind spre:

linia mediana si emisferul opus pe care il comprima sau comprima SRA rostrala: hernie laterala mezencefal, prin cortul cerebelului, care separa compartimentul emisferelor cerebrale de mezencefal si fosa posterioara: hernie transtentoriala Coma apare in fiecare din aceste situatii, dar mai ales cand ele coexista. Apar semne neurologice de lateralitate Leziunile au elemente diagnostice la CT. Leziuni de masa mezencefalice: Comprima direct SRA Leziunile de fosa posterioara pot compromite functia cerebrala prin herniere in sus prin cortul cerebelului, blocand fluxul LCR din ventriculii laterali: hidrocefalie necomunicanta (cefalee intensa) Sunt afectate miscarile reflexe ale globilor oculari: centri pontini oculomoteri, nucleul n. lll, fasciculul longitudinal medial traverseaza SR ) Apar semne clinice de lateralitate Un bolnav comatos fara afectarea miscarilor reflexe de lateralitate ale globilor oculari nu are leziuni de masa mezencefalice in fosa posterioara CT poate san u detecteze unele leziuni din fosa posterioara. Convulsii generalizate: descarcare electrica anormala, difuza in SRA si cortex In faza postcritica apare o inhibitie a activitatii electrice-coma Coma postcritica apare mai ales la cei care fac convulsii pe un fond patologic al SNC Anomalii metabolice: toxicele exogene sau endogene afecteaza SRA Nu exista semne neurologice de lateralitate Coma cu paralizia miscarilor reflexe oculare Nu exista elemente diagnostice la CT

COME CU CT CRANIAN NORMAL Cauze meningee: hemoragie subarahnoidiana (rar) Meningita bacteriana Encefalita Empiem subdural Toxine exogene: sedative sau barbiturice Anestezice sau gamahidroxibutirat

Alcool Stimulante: phencyclidine, cocaine sau amphetamine Medicamente psihotrope: antidepresive ciclice, phenophiazine, lithium Anticonvulsivante Opioide Clonidina Peniciline Salicilati Anticholinergice Monoxid de carbon, cian, methemoglobina Toxice endogene, deficiente sau deranjamente: Hipoxie sau ischemie Hipoglicemie Hipercalcemie Osmolar: hiperglicemie, hiponatremie, hipernatremie Insuficienta organica: encefalopatie hepatica, encefalopatie uremica, insuficienta pulmonara ( hipercapnie, narcoza) Convulsii : status postictal prelungit, spike-wave stupor Hipothermia sau hiperthermia Boli multifocale manifestate cu coma metabolica: CID, sepsis, pancreatita, vasculita, purpura trombotica trombocitopenica, embolii grasoase, encefalopatia hipertensiva, micrometastaze difuze Ischemia mezencefalica AVC de trunchi basilar Hemoragie mezencefalica sau cerebeloasa NB: Anestezicele generale similare cu acidul gama-aminobutiric pot induce coma; medicamentele de revigorare si de body-building duc la coma caracterizata prin debut si iesire din coma rapide, adesea cu miscari mioclonice sau confuzie, coma profunda (scala Glasgow 3), de 2-3 ore, cu mentinerea semnelor vitale Coma asociata cu agenti colinergici: lacrimare, salivatie, bronhoree, hipertermie Clonidina este activa pe sistemul de receptori opioizi; supradoza apare cand se administreaza pentru a trata sevrajul la opiacee

Clinica: ANAMNEZA. Antecedente patologice: HTA: encefalopatie hipertensiva, AVC ischemic, AVC hemoragic Insuficienta renala: coma uremica Valvulopatii, fibrilatie atriala: embolie cerebrala Diabet zaharat: coma hipoglicemica, coma acido-cetozica, coma hiperosmolara (hiperglicemie fara acido-cetoza), AVC (coma apopolectica, prin leziuni de macro si microangiopatie cerebrale) Ciroza hepatica: coma hepatica (insuficienta hepatica), coma hipoglicemica, coma hiponatremica

Insuficienta respiratorie cronica: coma hipercapnica Insuficienta respiratorie acuta: coma prin hipoxie si/sau hipercapnie acute, (de ex: intoxicatie cu CO) Neoplazii: metastaze cerebrale Epilepsie: coma postcriza; procese expansive, malformatii vasculare ce au produs si crizele epileptice Intoxicatii :CO,medicamente, droguri Fracturi: embolii grasoase Infectii locale: encefalite, meningite Sepsis, pancreatita, CID, purpura trombotica trombocitopenica (PTT) Vasculite cu determinari vasculare cerebrale Simptome care preced instalarea comei: Cefalee: acuta, dramatica: hemoragie subarahnoidiana sau intraparenchimatoasa cronica: tumora cerebrala Agitatie: intoxicatie alcoolica, meningte, encefalite, sevraj medicamentos Tulburari de comportament: encefalopatie hepatica, hipoxie, hipocapnie (inversarea ritmului somn /veghe, flapping tremor) Convulsii focale: leziuni supratentoriale: tumori, encefalita, tromboflebita Debut. Rapid, brusc minute-ore : coma vasculara-hemoragie subarahnoidiana sau intraparenchimatoasa; hemoragie intratumorala; procese chistice de ventricul lll coma hipoglicemica Lent, ore-zile: Neurologice: AVC ischemice, tumori cerebrale lent evolutive, meningita, encefalita Metabolice: cu exceptia comei hipoglicemice, EXAMEN CLINIC GENERAL: Tegumente: umede: hipoglicemie; infectii (+ febra); intoxicatie cu anticolinergice Uscate: coma diabetica; deshidratare, mixedem Culoarea tegumentelor: cianoza: coma hipercapnica; cianoza roz: CO icter: insuficienta hepatica teroasa: uremia hiperpigmentata predominant la pliuri: insuficienta suprarenala Hemoragii cutanate: o Petesii, purpura: coma hepatica, coma renala, endocardita bacteriana, PTT o Petesii, purpura + febra: meningoencefalita meningococica o Echimoze: coma traumatica Edem gambier sau extins: insuficienta cardiaca, insuficienta renala Temperatura: febra: infectii, hemoragie subarahnoidiana, hemoragie intraparenchimatoasa, ocluzia trunchiului bazilar scazuta: coma diabetica, coma hipoglicemica, coma hipotiroidiana, intoxicatia CO, intoxicatia alcoolica, intoxicatia barbiturica; hipotermie drept cauza comei COMELE PROFUNDE: HIPERTERMIE IN PLATOU, CU CARACTER PROGRESIV

Mirosul: foetor hepatic: insuficienta hepatica Acetone: diabet Alcool: coma alcoolica Amoniac: coma uremica TA: crescuta: encefalopatie hipertensiva, hemoragii subarahnoidiene sau in parenchim; boli renale; coma hipoglicemica DE OBICEI, COMA VASCULARA scazuta: coma acido-cetozica, soc cardiogen, soc hemoragic, tamponada, pneumotorax cu supapa, disectie de aorta, insuficienta suprarenala COMELE PROFUNDE: HTA + PULS BRADICARDIC, NEREGULAT, SLAB AV: tahicardie: infectii, Bradicardie: hemoragie intracerebrala, stari toxice, soc Hipersudoratia fara febra: leziune in inferioara a bulbului Hipoglicemie Intoxicatie cu anticolinesterazice Semne de traumatism: plagi ale scalpului, palparea unor fracturi depresive, echimoza retroauriculara (semnul Battle-asociat cu fractura bazei craniului), rino sau otolicvoree Respiratia: o Apnee posthiperventilatorie: apnee de 15-30 sec dupa 5-6 respiratii fortate; leziuni emisferice difuze o Respiratie Cheyne-Stokes: alternanta de perioade de polipnee neregulata si progresiva cu perioade de apnee de 15-30 sec; suferinta difuza a emisferelor cerebrale si diencefalului, metabolica (uremia) sau vasculara (ASC, encefalopatie hipertensiva); poate anunta o hernie transtentoriala o Respiratia Kussmaul: hiperpnee sustinuta, regulate, ampla, profunda, 40-70/min; apare in acidoza metabolica, leziuni ale tegmentului mezencefalo-pontin prin leziuni vasculare sau tumorale, sau lezarea acestei regiuni prin hernie transtentoriala o Respiratie Biot (in salve): este Cheyne-Stokes cu ciclu scurt: respiratii ample alternand cu perioade de apnee; leziune pontina cu localizare joasa o Respiratie ataxica: ritm complet neregulat, amplitudine variabila de la o miscare la alta, cu perioada de apnee de durata variabila: disfunctie a centrilor respiratori din regiunea dorso-mediala a bulbului EXAMEN NEUROLOGIC Semne de iritatie meningiana o Pozitie in cocos de pusca o Brudzinski: la flexia capului indoaie genunchii o Redoare de ceafa Deglutitia: o Pierderea timpului l (de a intindele buzele si a suge apa din lingurita apropiata de buze): leziune la limita superioara a trunchiului cerebral o Pierderea timpului ll ( de a inghiti apa introdusa printre dinti) Intarziat (tine apa in gura, apoi o inghite): leziune la nivelul nucleului n lX Abolit (tine apa in gura, se ineaca): lez la nuclei X-Xl Motilitatea palpebrala: ochii inchisi:

o Ochii inchisi: dupa ridicarea pleopelor ele tind sa se inchida rpid: come usoare Dupa ridicarea pleoapelor, ele tind sa se inchida lent si progresiv: come profunde rezistenta crescuta la ridicrea pleoapelor: blefarospasm reflex activitate psihogena inchiderea incomplete a ochilor: leziuni n Vll afectare punte o Clipit spontan: present: integritatea SRA din trunchi Absent: lezarea SRA din trunchi o Clipit reflex: la amenintare: integritate corticala La stimul luminos: integritatea corpului geniculat lateral La stimul acustic: integritate pontina inferioara Lipsa clipitului la stimul lminos sau acustic: leziune de trunchi cerebral

The Four Primary Acid-Base Disturbances Type of Disturbance Primary Alteration Secondary Response Mechanism of Secondary Response Metabolic acidosis Decrease in plasma Decrease in Pa CO3 Hyperventilation [HCO3-] Metabolic alkalosis Increase in plasma Increase in PaCO3 Hypoventilation [HCO3-] Respiratory acidosis Increase in PaCO3 Increase in plasma Acid titration of [HCO3-] tissue buffers; transient increase in acid excretion and sustained enhancement of HCO3- reabsorption by kidney Respiratory alkalosis Decrease in Pa CO3 Decrease in plasma Alkaline titration of [HCO3 ] tissue buffers; transient suppression of acid excretion and sustained reduction in bicarbonate reabsorption by kidney

Multi-focal disorders (with no neuro-imaging signatures) that may mimic a metabolic coma

hypertensive encephalopathy DIC endocarditis sepsis thrombotic thrombocytopenic purpura (TTP) fat emboli syndrome diffuse small vessel vasculitis pancreatic encephalopathy superior saggital sinus thrombosis meningitis encephalitis malaria neuroleptic malignant syndrome serotonin syndrome thyroid storm malignant hyperthermia

Conditions causing coma + fever +/- increased muscle tone/hyperreflexia

heat stroke pheochromocytoma porphyria stimulant drug toxicity eg. phencyclidine, cocaine, amphetamines anticholinergic poisoning delirium tremens sepsis DIC leukemia with sepsis infection or hemorrhage caused by myelosuppression thrombotic thrombocytopenic purpura eclampsia (HELLP syndrome) alcoholism - portocaval shunt and hypersplenism ischemic stroke pituatry apoplexy cerebral venous sinus thrombosis ICH (aneursym, AVM, pre-eclampsia-eclampsia) hypertensive encephalopathy carbamoyltransferase deficiency carrier state (hyperammonemia and hyperglutinemia) porphyria migranous infarct opiates benzodiazepines, barbiturates and other sedatives tricyclics and other antidepressants phenothiazines and butyrophenones cocaine, amphetamines, phencyclidine gamma hydroxybutyrate salicylates ethyl alcohol, methanol, isopropyl alcohol, ethylene glycol hydrocarbons cyanide or carbon monoxide poisoning hyperglycemia (DKA and hyperosmolar coma) hypoglycemia

Conditions causing coma + thrombocytopenia

Conditions causing coma in pregnancy or the puerperium

Some toxic and metabolic causes of coma

Some toxic and metabolic causes of coma

opiates

benzodiazepines, barbiturates and other sedatives tricyclics and other antidepressants phenothiazines and butyrophenones cocaine, amphetamines, phencyclidine gamma hydroxybutyrate salicylates ethyl alcohol, methanol, isopropyl alcohol, ethylene glycol hydrocarbons cyanide or carbon monoxide poisoning hyperglycemia (DKA and hyperosmolar coma) hypoglycemia myxedema apathetic thyroid storm hyponatremia hypercalcemia hepatic failure, hyperammonemia hypoadrenalism porphyria hypoxia hypercarbia hereditary metabolic disorders (carbamoyltransferase deficiency carrier state)

Clinical clues suggesting some causes of metabolic coma that may not be readily detected by routine metabolic screening tests Clinical condition Methemoglobinemia

Clinical clues cyanosis unresponsive to oxygen therapy slate-gray skin color disproportionate tachycardia and tachypnea low pulse oximetry + high PaO2 + normal calculated oxygen saturation chocolate-brown blood - does not turn red when exposed to oxygen exposure history:- skin or po exposure to oxidising agents (eg. aniline, benzocaine - teething gels, phenazopyridine, naphthalene, nitroalkanes in nail-poish remover, chlorates, dapsone, increased nitrates - well water), or inhalant abuse in adolescents, or systemic acidosis from infectious diarrhea due to nitrite-forming bacteria in infants < 6 months more common during the winter months antecedent precipitating illness (CHF, pneumonia) or drugs (sedatives, narcotics, lithium or amiodarone) or discontinued thyroid medication hypothermia without shivering bradycardia +/- hypotension bradypnea + alveolar hypoventilation dry, coarse, scaly skin

Myxedema coma

carotenemic pallor brittle nails puffy face and eyelid edema macroglossia thyroidectomy scar or thyromegaly quiet, distended abdomen (paralytic ileus) delayed "hung-up" DTR's associated hyponatremia, anemia, hypercholesterolemia, increased serum LDH and CK

AppendixGlasgow coma scale for all age groups 4 years to adult Eye opening 4 3 2 1 Verbal response 5 4 3 2 1 Motor response 6 5 4 3 2 1 Child < 4 years Infant

Spontaneous To speech To pain No response

Spontaneous To speech To pain No response

Spontaneous To speech To pain No response

Oriented, social, speaks, interacts Disoriented Confused speech, disoriented, conversation consolable, aware Speaking but Inappropriate words, nonsensical inconsolable, unaware Moans or Incomprehensible, agitated, unintelligble sounds restless, unaware No response No response

Alert and oriented

Coos, babbles Irritable cry Cries to pain Moans to pain No response

Follows commands Localises pain Movement or withdrawal to pain Decorticate flexion Decebrate extension No response

Normal, spontaneous movements Localises pain Withdraws to pain Decorticate flexion Decerebrate extension No response

Normal, spontaneous movements Withdraws to touch Withdraws to pain Decorticate flexion Decerebrate extension No response

A suggested sequence of medical therapy for increased intracranial pressure

elevate the head of the bed 30 degrees and maintain the neck in a neutral position emergent ET intubation and manual/mechanical hyperventilation to a PaCO2 of 30 - 35 mmHg IV mannitol - 0.5 - 1.0g/kg over 5 - 10 minutes IV thiopental - 0.5 g/kg IV boluses prn - if mean arterial blood pressure > 150 mmHg to lower the mean blood pressure to < 140 mmHg IV phenylephrine - 1 - 2 mug/kg boluses prn - if mean arterial blood pressure < 90 mmHg +/- IV normal saline fluid boluses prn to ensure euvolemia 0.5cc/kg of 23.4% sodium chloride over 15 minutes IV can be used as last resort if the above measures fail dexamethasone - 10mg - if tumor or abscess present pentobarbital infusion or surgical decompression therapy based on the CT scan results active resistance to passive opening of the eyelids a tendency for the eyelids to close abruptly and completely when the lifted upper eyelid is suddenly released (rather than slowly, asymmetrically and incompletely) fluttering of the eyelids when the eyelashes are gently stroked any spontaneous eye movements are rapid and jerking rather than slowly roving the patient actually makes eye contact with the examiner when the eyelids are opened; or the eyes always look to the side away from the examiner, or the eyes always look towards the ground the eyes are continuously rolled back into the head; or alternatively, the eyes are conjugately deviated downwards +/- converged equal, reactive pupils + conjugate eye movements rapid nystagmoid eye movements away from the irrigated earcanal occur during caloric testing of the oculo-vestibular reflex (or sudden patient arousal from coma as a result of caloric testing - testing should therefore be used as a last resort) active resistance or varying resistance to passive motor tone testing, or cogwheeling resistance with sudden "giving-away" phenomena the patient's hand always manages to avoid hitting the face when the passively uplifted hand is released directly over the central face, or the hand falls abnormally slowly onto the face no abnormal reflex posturing in response to painful stimuli the patient may occasionally make voluntary movements or change body position in bed provocative maneuvers (eg. ammonia capsule held under the nostrils, Q tip stuck up the nose) should not be used to induce responsiveness - a "good" doctor-patient relationship must be fastidiously maintained and the patient should be gently coaxed into a state of full consciousness

Clinical features suggesting psychogenic coma (feigned coma)