Загальні відомості про кому та порушення свідомості

1. 1. Maiese K, Chong ZZ, Shang YC, Wang S: Targeting disease through novel pathways of apoptosis and autophagy. Expert Opin Ther Targets 16 (12):1203–1214, 2012. doi: 10.1517/14728222.2012.719499 Epub 2012 Aug 27.

2. 2. Maiese K: Cognitive impairment and dementia: Gaining insight through circadian clock gene pathways. Biomolecules 11 (7):1002, 2021. doi: 10.3390/biom11071002

Medical identification bracelets or the contents of a wallet or purse (eg, hospital identification card, medications list) may provide clues to the cause. Caregivers, paramedics, police officers, and any witnesses should be questioned about the circumstances and environment in which the patient was found; containers that may have held food, alcohol, medications, or poisons should be examined and saved for identification (eg, substance identification aided by a poison center) and possible chemical analysis.

Caregivers should be asked about the following:

• The onset and time course of the problem (eg, whether seizure, headache, vomiting, head trauma, or ingestion of an illicit drug, medication, or other substance was observed; how quickly symptoms appeared; whether the course has been progressive or waxing and waning)

• Baseline mental status

• Recent infections and possible exposure to infections

• Recent travel

• Ingestions of unusual meals

• Psychiatric problems and symptoms

• Prescription medication history

• Use of alcohol or illicit drugs (eg, anesthetics, stimulants, depressants)

• Previous and concurrent systemic illnesses, including new-onset heart failure, arrhythmias, respiratory disorders, infections, and metabolic, liver, or kidney disorders

• The last time the patient was at their baseline mental status

• Any hunches they may have about what might be the cause (eg, possible occult overdose, possible occult head trauma due to recent intoxication)

Medical records should be reviewed if available.

Physical examination should be focused and efficient and should include thorough examination of the head and face, skin, and extremities. Examination of the heart and lungs is important to assess blood flow and oxygenation to the brain.

Signs of head trauma include periorbital ecchymosis (raccoon eyes), ecchymosis behind the ear (Battle sign), hemotympanum, instability of the maxilla, and cerebrospinal fluid (CSF) rhinorrhea and otorrhea. Scalp contusions and small bullet holes can be missed unless the head is carefully inspected.

If unstable injury and cervical spine damage have been excluded, passive neck flexion is done; stiffness when the neck is flexed suggests subarachnoid hemorrhage or meningitis.

Findings may suggest a cause:

• Hypothermia: Environmental exposure, drowning, sedative overdose, severe hypothyroidism, Wernicke encephalopathy, or, in older adults, sepsis

• Hyperthermia: Heatstroke, infection, stimulant overdose, or neuroleptic malignant syndrome

• Fever, petechial or purpuric rash, hypotension, or severe extremity infections (eg, gangrene of one or more toes): Sepsis or central nervous system (CNS) infection

• Needle marks: Overdose of a medication or an illicit drug (eg, opioids, insulin)

• A bitten tongue: Seizure

• Breath odor: Toxicity due to alcohol or another substance, or diabetic ketoacidosis

• Hypotension or pulse abnormalities: Cardiac dysfunction with hypoperfusion

• Difficulty breathing: Acute respiratory dysfunction due to bacterial or viral illness

The neurologic examination determines whether the brain stem is intact and where the lesion is located within the CNS. The examination focuses on the following:

• Level of consciousness

• Eyes

• Motor function

• Deep tendon reflexes

Level of consciousness is evaluated by attempting to wake patients first with verbal commands, then with nonnoxious stimuli, and finally (if necessary) with noxious stimuli (eg, pressure to the supraorbital ridge, nail bed, or sternum).

The Glasgow Coma Scale (see table Glasgow Coma Scale) was developed to assess patients with head trauma. For head trauma, the score assigned by the scale is valuable prognostically. For coma or impaired consciousness of any cause, the scale is used because it is a relatively reliable, objective measure of the severity of unresponsiveness and can be used serially for monitoring. The scale assigns points based on responses to stimuli.

Eye opening, facial grimacing, and purposeful withdrawal of limbs from a noxious stimulus indicate that consciousness is not greatly impaired. Asymmetric motor responses to pain or deep tendon reflexes may indicate a focal hemispheric lesion.

As impaired consciousness deepens into coma, noxious stimuli may trigger stereotypic reflex posturing.

• Decorticate posturing can occur in structural or metabolic disorders and indicates hemispheric damage with preservation of motor centers in the upper portion of the brain stem (eg, rubrospinal tract).

• Decerebrate posturing indicates that the upper brain stem motor centers, which facilitate flexion, have been structurally damaged and that only the lower brain stem centers (eg, vestibulospinal tract, reticulospinal tract), which facilitate extension, are responding to sensory stimuli.

Decerebrate posturing may also occur, although less often, in diffuse disorders such as anoxic encephalopathy.

Flaccidity without movement indicates that the lower brain stem is not affecting movement, regardless of whether the spinal cord is damaged. It is the worst possible motor response.

Asterixis and multifocal myoclonus suggest metabolic disorders such as uremia, hepatic encephalopathy, hypoxic encephalopathy, and drug toxicity.

Psychogenic unresponsiveness differs from physiologically impaired consciousness in that, although voluntary motor response is typically absent, muscle tone and deep tendon reflexes remain normal, and all brain stem reflexes are preserved. Vital signs are usually not affected.

Клінічний калькулятор

Шкала коми Глазго

The following are evaluated:

• Pupillary responses

• Extraocular movements

• Fundi

• Other neuro-ophthalmic reflexes

Pupillary responses and extraocular movements provide information about brain stem function (see table Interpretation of Pupillary Response and Eye Movement). One or both pupils usually become fixed early in coma due to structural lesions, but pupillary responses are often preserved until very late when coma is due to diffuse metabolic disorders (called toxic-metabolic encephalopathy), although responses may be sluggish. If one pupil is dilated, other causes of anisocoria should be considered; they include past ocular trauma, certain headaches, and use of a scopolamine patch (if scopolamine comes in contact with the eyes).

The fundi should be examined. Papilledema may indicate increased ICP but may take many hours to appear; papilledema is usually bilateral. Increased ICP can cause earlier changes in the fundi, such as loss of retinal venous pulsations, disk hypermia, dilated capillaries, blurring of the medial disk margins, and sometimes hemorrhages. Subhyaloid hemorrhage may indicate subarachnoid hemorrhage.

The oculocephalic reflex is tested by the doll’s-eye maneuver in unresponsive patients: The eyes are observed while the head is passively rotated from side to side or flexed and extended. This maneuver should not be attempted if cervical spine instability is suspected.

• If the reflex is present, the maneuver causes the eyes to move in the opposite direction of head rotation, flexion, or extension, indicating that the oculovestibular pathways in the brain stem are intact. Thus, in a supine patient, the eyes continue to look straight up when the head is turned side to side.

• If the reflex is absent, the eyes do not move and thus point in whatever direction the head is turned, indicating the oculovestibular pathways are disrupted. The reflex is also absent in most patients with psychogenic unresponsiveness because visual fixation is conscious.

If the patient is unconscious and the oculocephalic reflex is absent or the neck is immobilized, oculovestibular (cold caloric) testing is done. After integrity of the tympanic membrane is confirmed, the patient’s head is elevated 30°, and with a syringe connected to a flexible catheter, the examiner irrigates the external auditory canal with 50 mL of ice water over a 30-second period.

• If both eyes deviate toward the irrigated ear, the brain stem reflex is functioning normally, suggesting mildly impaired consciousness.

• If nystagmus away from the irrigated ear also occurs, the patient is conscious and psychogenic unresponsiveness is likely. In conscious patients, 1 mL of ice water is often enough to induce ocular deviation and nystagmus. Thus, if psychogenic unresponsiveness is suspected, a small amount of water should be used (or caloric testing should not be done) because cold caloric testing can induce severe vertigo, nausea, and vomiting in conscious patients.

• If the eyes do not move or movement is dysconjugate after irrigation, the integrity of the brain stem is uncertain and the coma is deeper. Prognosis may be less favorable.

Certain patterns of eye abnormalities and other findings may suggest brain herniation (see also figure Brain Herniation and table Effects of Herniation).

The spontaneous respiratory rate and pattern should be documented unless emergency airway intervention is required. It may suggest a cause.

• Periodic cycling of breathing (Cheyne-Stokes or Biot respiration) may indicate dysfunction of both hemispheres or of the diencephalon.

• Hyperventilation (central neurogenic hyperventilation) with respiratory rates of > 25 breaths/minute may indicate midbrain or upper pontine dysfunction.

• An inspiratory gasp with respiratory pauses of about 3 seconds after full inspiration (apneustic breathing) typically indicates pontine or medullary lesions; this type of breathing often progresses to respiratory arrest.

Initially, pulse oximetry, fingerstick plasma glucose measurements, and cardiac monitoring are done. If the cause is not immediately clear, further testing is done.

Blood tests should include a comprehensive metabolic panel (including at least serum electrolytes, blood urea nitrogen [BUN], creatinine, and calcium levels), complete blood count (CBC) with differential and platelets, liver tests, and ammonia level.

Arterial blood gases (ABGs) are measured, and if carbon monoxide toxicity is suspected, carboxyhemoglobin level is measured.

Blood and urine should be obtained for culture and routine toxicology screening; serum ethanol level is also measured. Other toxicology screening panels and additional toxicology tests (eg, serum drug levels) are done based on clinical suspicion.

ECG (12-lead) is also done to check for myocardial infarction and new arrhythmias.

Chest x-ray should be done to check for new lung disease that may affect brain oxygenation.

If the cause is still not immediately apparent, noncontrast head CT should be done as soon as possible to check for masses, hemorrhage, edema, evidence of bone trauma, and hydrocephalus. Initially, noncontrast CT rather than contrast CT is preferred to rule out brain hemorrhage; CT detects cerebral bleeding and bone injuries (eg, skull fractures) best within 72 hours of injury. MRI can be done instead if immediately available, but it is not as quick as newer-generation CT scanners and may not be as sensitive for traumatic bone injuries; however, MRI is now as sensitive as CT for detecting blood early as well as late. If noncontrast CT is not diagnostic, MRI or contrast CT can then be done; either of them may detect isodense subdural hematomas, multiple metastases, sagittal sinus thrombosis, herpes encephalitis, or other causes missed by noncontrast CT. MRI provides greater detail than CT when done > 72 hours after symptom onset but is more difficult logistically than CT if the patient is intubated.

КТ голови без контрастування

Епідуральний крововилив (КТ у фронтальній проекції)

Класична ділянка підвищеної щільності у вигляді двояковипуклої лінзи, яка не простягається через лінії швів.

© 2017 Elliot K. Fishman, MD.

Епідуральний крововилив (КТ в аксіальній проекції)

Класична ділянка підвищеної щільності у вигляді двояковипуклої лінзи, яка не простягається через лінії швів.

© 2017 Elliot K. Fishman, MD.

Субдуральний крововилив (КТ)

Класична ділянка підвищеної щільності у формі півмісяця, що простягається через лінії швів.

© 2017 Elliot K. Fishman, MD.

Субфальцинова грижа

Subfalcine herniation is the most common type of cerebral herniation. In this image, the left brain has herniated under the free edge of the falx cerebri (arrow) because hemorrhage from an infarct in the middle cerebral artery has increased intracerebral pressure.

... прочитати більше

© 2017 Elliot K. Fishman, MD.

Епідуральний крововилив (КТ у фронтальній проекції)

Класична ділянка підвищеної щільності у вигляді двояковипуклої лінзи, яка не простягається через лінії швів.

© 2017 Elliot K. Fishman, MD.

Епідуральний крововилив (КТ в аксіальній проекції)

Класична ділянка підвищеної щільності у вигляді двояковипуклої лінзи, яка не простягається через лінії швів.

© 2017 Elliot K. Fishman, MD.

Субдуральний крововилив (КТ)

Класична ділянка підвищеної щільності у формі півмісяця, що простягається через лінії швів.

© 2017 Elliot K. Fishman, MD.

Субфальцинова грижа

Subfalcine herniation is the most common type of cerebral herniation. In this image, the left brain has herniated under the free edge of the falx cerebri (arrow) because hemorrhage from an infarct in the middle cerebral artery has increased intracerebral pressure.

... прочитати більше

© 2017 Elliot K. Fishman, MD.

If coma is unexplained after MRI or CT and other tests, lumbar puncture (spinal tap) is done to check opening pressure and to exclude infection, subarachnoid hemorrhage, and other abnormalities. However, MRI or CT images should first be reviewed for intracranial masses, obstructive hydrocephalus, and other abnormalities that could obstruct CSF flow or the ventricular system and thus significantly increase ICP. Such abnormalities contraindicate lumbar puncture. Suddenly lowering CSF pressure, as can occur during lumbar puncture, in patients with increased ICP could trigger brain herniation; however, this outcome is uncommon.

CSF analysis includes cell and differential counts, protein, glucose, Gram staining, cultures, and sometimes, based on clinical suspicion, specific tests (eg, cryptococcal antigen test, cytology, measurement of tumor markers, Venereal Disease Research Laboratory [VDRL] tests, polymerase chain reaction [PCR] for herpes simplex, visual or spectrophotometric analysis for xanthochromia).

If increased ICP is suspected, CSF pressure may be measured if considered appropriate for the patient (1). If ICP is increased, ICP monitoring is done continuously, and measures to decrease it are taken.

If seizures may be the cause of coma, particularly if nonconvulsive status epilepticus (recurrent seizures without prominent motor symptoms) is being considered, or if the diagnosis remains uncertain, EEG may be done. In most comatose patients, EEG shows slowing and reductions in wave amplitude that are nonspecific but often occur in toxic-metabolic encephalopathy. In some patients with nonconvulsive status epilepticus, the EEG may show a combination of spikes, sharp waves, or spike and slow complexes (2). If psychogenic unresponsiveness or seizure activity (pseudoseizure) that results from a behavior disorder is possible, video EEG monitoring is required.

Depending on the destination, recent travel should prompt testing for bacterial, viral, and parasitic infections that may lead to coma.

Clinicians can consider evoked potentials such as brain stem auditory evoked potentials to assess brain stem function or somatosensory evoked potentials to assess the cortex, thalamic, brain stem, and spinal cord pathways (eg, after cardiac arrest).

1. 1. Le Roux P, Menon DK, Citerio G, et al: Monitoring in Neurocritical Care: A statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine. Neurocrit Care 21 Suppl 2 (Suppl 2):S1–26, 2014. doi: 10.1007/s12028-014-0041-5

2. 2. Zafar A, Aljaafari D. EEG criteria for diagnosing nonconvulsive status epilepticus in comatose - An unsolved puzzle: A narrative review. Heliyon. 2023 Nov 17;9(11):e22393. doi: 10.1016/j.heliyon.2023.e22393

Patients with any of the following have been traditionally managed with endotracheal intubation to prevent aspiration and ensure adequate ventilation:

• Infrequent, shallow, or stertorous respirations

• Low oxygen saturation (determined by pulse oximetry or ABG measurements)

• Impaired airway reflexes

• Severe unresponsiveness (including most patients with a Glasgow Coma Scale score ≤ 8)

However, in a randomized trial of comatose patients with suspected overdose, withholding intubation (except when respiratory distress, seizure, vomiting, or shock was present) resulted in lower rates of in-hospital death and shorter hospital and ICU stays (1).

When done for suspected increased ICP, intubation should be done via rapid-sequence oral intubation (using a paralytic medication) rather than via nasotracheal intubation; nasotracheal intubation in a patient who is breathing spontaneously causes more coughing and gagging, thus increasing ICP, which is already increased because of intracranial abnormalities.

To minimize the increase in ICP that may occur when the airway is manipulated, some clinicians recommend giving lidocaine 1.5 mg/kg IV 1 to 2 minutes before giving the paralytic; this may reduce ICP by preventing increases in heart rate, cardiac output, and systolic blood pressure (2) . Patients are sedated before the paralytic is given. Etomidate is a good choice in hypotensive or trauma patients because it has minimal effects on blood pressure; IV dose is 0.3 mg/kg for adults (or 20 mg for an average-sized adult) and 0.2 to 0.3 mg/kg for children. Alternatively, if hypotension is absent and unlikely and if propofol is readily available, propofol 0.2 to 1.5 mg/kg may be used.

Succinylcholine 1.5 mg/kg or rocuronium 1 mg/kg IV is typically used as a paralytic. Paralytics should be used only when they are deemed necessary for intubation and needed to avoid further increases in ICP. Otherwise, paralytics should be avoided because rarely, medications such as succinylcholine can lead to malignant hyperthermia and can mask neurologic findings and changes.

Pulse oximetry and ABGs (if possible, end-tidal CO2) should be used to assess adequacy of oxygenation and ventilation.

If intracranial pressure (ICP) is increased, clinicians should monitor intracranial and cerebral perfusion pressure, and pressures should be controlled. The goal is to maintain ICP at ≤ 20 mm Hg and cerebral perfusion pressure at 50 to 70 mm Hg. ICP is usually lower in children than in adults. In neonates, ICP can be below the atmospheric pressure. Thus, children are evaluated independently from adult guidelines.

Control of increased ICP involves several strategies (3):

• Sedation: Sedatives may be necessary to control agitation, excessive muscular activity (eg, due to delirium), or pain, which can increase ICP. Propofol is often used in adults (contraindicated in children) because onset and duration of action are quick; dose is 0.3 mg/kg/hour by continuous IV infusion, titrated gradually up to 3 mg/kg/hour as needed. An initial bolus is not used. The most common adverse effect is hypotension. Prolonged use at high doses can cause pancreatitis. Benzodiazepines (eg, midazolam, lorazepam) can also be used. Because sedatives can mask neurologic findings and changes, their use should be minimized and, whenever possible, avoided. Antipsychotics should be avoided if possible because they can delay recovery. Sedatives are not used to treat agitation and delirium due to hypoxia; oxygen is used instead.

• Hyperventilation: Hyperventilation causes hypocapnia, which causes vasoconstriction, thus decreasing cerebral blood flow globally. Reduction in PCO2 from 40 mm Hg to 30 mm Hg can reduce ICP about 30%. Hyperventilation that reduces PCO2 to 28 to 33 mm Hg decreases ICP for only about 30 minutes and is used by some clinicians as a temporary measure until other treatments take effect. Aggressive hyperventilation to < 25 mm Hg should be avoided because it may reduce cerebral blood flow excessively and result in cerebral ischemia. Other measures to control increased ICP may be used.

• Hydration: Isotonic fluids are used. Providing free water through IV fluids (eg, 5% dextrose, 0.45% saline) can aggravate cerebral edema and should be avoided. Fluids may be restricted to some degree, but patients should be kept euvolemic. If patients have no signs of dehydration or fluid overload, IV fluids with normal saline can be started at 50 to 75 mL/hour. The rate can be increased or decreased based on serum sodium, osmolality, urine output, and signs of fluid retention (eg, edema).

• Diuretics: Serum osmolality should be kept at 295 to 320 mOsm/kg. Osmotic diuretics (eg, mannitol) may be given IV to lower ICP and maintain serum osmolality. Osmotic diuretics do not cross the blood-brain barrier. They pull water from brain tissue across an osmotic gradient into plasma, eventually leading to equilibrium. Effectiveness of these diuretics decreases after a few hours. Thus, they should be reserved for patients whose condition is deteriorating (eg, those with acute brain herniation) or used preoperatively for patients with hematomas. Mannitol 20% solution is given 0.5 to 1 g/kg IV (2.5 to 5 mL/kg) over 15 to 30 minutes, then given as often as needed (usually every 6 to 8 hours) in a dose ranging from 0.25 to 0.5 g/kg (1.25 to 2.5 mL/kg). Mannitol must be used cautiously in patients with severe coronary artery disease, heart failure, renal insufficiency, or pulmonary vascular congestion because mannitol rapidly expands intravascular volume. Because osmotic diuretics increase renal excretion of water relative to sodium, prolonged use of mannitol may result in water depletion and hypernatremia. Furosemide 1 mg/kg IV can decrease total body water, particularly when transient hypervolemia associated with mannitol is to be avoided. Fluid and electrolyte balance should be monitored closely while osmotic diuretics are used. A 3% saline solution is another potential osmotic agent to control ICP (4).

• Blood pressure (BP) control: Systemic antihypertensives are needed only when hypertension is severe (> 180/95 mm Hg). How much BP is reduced depends on the clinical context. Systemic BP needs to be high enough to maintain cerebral perfusion pressure even when ICP increases. Hypertension can be managed by titrating nicardipine (5) as a drip (5 mg/hour, increased by 2.5 mg every 5 minutes to a maximum of 15 mg/hour) or by boluses of labetalol (10 mg IV over 1 to 2 minutes, repeated every 10 minutes to a maximum of 150 mg).

• Corticosteroids: Corticosteroids are useful for treating vasogenic brain edema. Vasogenic edema results from disruption of the blood-brain barrier, which may occur in patients with a brain tumor. Cytotoxic edema results from cell death and breakdown, which may occur in patients with stroke, cerebral hemorrhage, or trauma; it may also occur after hypoxic brain damage due to cardiac arrest. Treatment with corticosteroids is effective only for tumors and sometimes abscesses of the brain when vasogenic edema is present. Corticosteroids are ineffective for cytotoxic edema and can increase plasma glucose, exacerbating cerebral ischemia and complicating management of diabetes mellitus. For patients without brain ischemia, an initial dose of dexamethasone 20 to 100 mg, followed by 4 mg once a day appears to be effective while minimizing adverse effects. Dexamethasone can be given IV or orally.

• Removal of cerebrospinal fluid (CSF): CSF can be slowly removed through a shunt inserted into the ventricles to help lower increased ICP. CSF is removed at a rate of 1 to 2 mL/minute for 2 to 3 minutes. Continuous drainage of CSF (eg, through a lumbar drain) should be avoided because it may lead to brain herniation.

• Position: Positioning the patient to maximize venous outflow from the head can help minimize increases in ICP. The head of the bed can be elevated to 30° (with the head above the heart) as long as cerebral perfusion pressure remains at the desired range. The patient’s head should be kept in a midline position, and neck rotation and flexion should be minimized. Tracheal suctioning, which can increase ICP, should be limited.

If ICP continues to increase despite other measures to control it, the following may be used:

• Titrated hypothermia: When ICP is increased after head trauma or cardiac arrest, hypothermia in the range of 32 to 35° C has been used to reduce ICP to < 20 mm Hg. However, use of hypothermia to lower ICP is controversial; some evidence suggests that this treatment may not effectively lower ICP in adults or children and may have adverse effects (6).

• Pentobarbital coma:Pentobarbital can reduce cerebral blood flow and metabolic demands. However, its use is controversial because the effect on clinical outcome is not consistently beneficial, and treatment with pentobarbital can lead to complications (eg, hypotension). In some patients with refractory intracranial hypertension that does not respond to standard hyperventilation and hyperosmolar therapy, pentobarbital given as a last resort may improve functional outcome (5). Coma is induced by giving pentobarbital 10 mg/kg IV over 30 minutes, followed by 5 mg/kg/hour for 3 hours, then 1 mg/kg/hour. The dose may be adjusted to suppress bursts of EEG activity, which is continuously monitored. Hypotension is common and is managed by giving fluids and, if necessary, vasopressors. Other possible adverse effects include arrhythmias, myocardial depression, and impaired uptake or release of potentially neurotoxic glutamate in the brain.

• Decompressive craniotomy: Craniotomy with duraplasty can be done to provide room for brain swelling. This procedure can prevent deaths, but overall functional outcome may not improve much, and it may lead to complications such as hydrocephalus in some patients (7). It may be most useful for large cerebral infarcts with impending herniation, particularly in patients < 50 years.

Patients require meticulous long-term care. Stimulants, sedatives, and opioids should be avoided.

Enteral feeding is started with precautions to prevent aspiration (eg, elevation of the head of the bed); a percutaneous endoscopic jejunostomy tube is placed if necessary.

Early, vigilant attention to skin care, including checking for breakdown especially at pressure points, is required to prevent pressure ulcers. Patients require frequent turning and position changes to prevent pressure ulcers, but the head should be kept elevated. Special air mattresses may help manage pressure ulcers.

Topical ointments to prevent desiccation of the eyes are beneficial.

Passive range-of-motion exercises done by physical therapists and taping or dynamic flexion splitting of the extremities may prevent contractures. Initiating physical therapy early can improve functional outcome in patients with polyneuropathy and myopathy.

Measures are also taken to prevent urinary tract infections and deep venous thrombosis.

1. 1. Freund Y; Viglino D, Cachanado M, et al: Effect of noninvasive airway management of comatose patients with acute poisoning: A randomized clinical trial. JAMA 330 (23):2267–2274, 2023. doi: 10.1001/jama.2023.24391

2. 2. Mostafa HM, Ibrahim RW, Hasanin A, et al: (2023) Intravenous lidocaine for attenuation of pressor response after endotracheal intubation. A randomized, double-blinded dose-finding study. Egypt J Anaesthesia 39:1:241-248, 2023. doi: 10.1080/11101849.2023.2187142

3. 3. Cook AM, Jones GM, Hawryluk GWJ, et al: Guidelines for the acute treatment of cerebral edema in neurocritical care patients. Neurocrit Care 32 (3):647–666 2020. doi: 10.1007/s12028-02-00959-7

4. 4. Shi J, Tan L, Ye J, Hu L. Hypertonic saline and mannitol in patients with traumatic brain injury: A systematic and meta-analysis. Medicine (Baltimore). 2020;99(35):e21655. doi:10.1097/MD.0000000000021655

5. 5. Ragland J, Lee K: Critical Care Management and Monitoring of Intracranial Pressure. J Neurocrit Care 9(2):105-112, 2016. doi: 10.18700/jnc.160101

6. 6. Moler FW, Silverstein FS, Holubkov R, et al: Therapeutic hypothermia after in-hospital cardiac arrest in children. N Engl J Med 376 (4):318-329, 2017. doi: 10.1056/NEJMoa1610493

7. 7. Su TM, Lan CM, Lee TH, et al: Risk factors for the development of posttraumatic hydrocephalus after unilateral decompressive craniectomy in patients with traumatic brain injury. J Clin Neurosci 63:62–67, 2019. doi: 10.1016/j.jocn.2019.02.006 Epub 2019 Mar 1.

1. 1. Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Plum F. Predicting outcome from hypoxic-ischemic coma. JAMA. 1985;253(10):1420-1426.

2. 2. Sandroni C, Cariou A, Cavallaro F, et al. Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine. Intensive Care Med. 2014;40(12):1816-1831. doi:10.1007/s00134-014-3470-x