Unconscious Patient

Etiology

RAS is an essential component in initiating and preserving consciousness, and it originates in the upper pons and midbrain and extends to the thalamus and hypothalamus, eventually reaching the cerebral cortex. Temporary or permanent damage to the RAS in the brainstem, the cerebral hemispheres, or any condition that alters cerebral metabolism can alter consciousness. Damage to the cerebral hemispheres is typically bilateral and diffuse. If the damage is unilateral, it must be extensive enough to affect the hemisphere or brainstem on the opposite side. The 3 primary mechanisms include structural brain lesions, widespread neuronal dysfunction due to systemic pathology, and, on rare occasions, psychogenic causes.[1]

Structural causes, such as a cerebral vascular accident or TBI, can either directly damage a specific area or indirectly harm through compression or increased intracranial pressure. Elevated intracranial pressure can hinder cerebral blood flow and potentially lead to tissue distortion and brain herniation.[3][2] Systemic causes, such as hypoglycemia or hypothermia, have mechanisms that are specific to each cause and typically hinder the delivery of oxygen or substrates. This disruption in cerebral metabolism results in impaired neuronal function. Psychogenic unresponsiveness encompasses a prolonged dissociative state in which the patient is either unresponsive or exhibits reduced responses to external stimuli. Maintaining a specific posture, exhibiting nystagmus upon caloric stimulation, or resisting passive eye-opening are clinical observations that align with the diagnosis of psychogenic unresponsiveness. The most prevalent causes of unconsciousness encountered in the emergency room typically include stroke, post-anoxic coma, drug toxicity or poisoning, and metabolic causes such as endocrine or acid-base disorders.[4]

Epidemiology

The prevalence and causes of altered consciousness levels differ among institutions and patient populations. For instance, high-volume trauma centers typically encounter many unconscious patients with TBIs. Among the most frequent non-traumatic causes, hemorrhagic strokes comprise 6% to 54%, anoxic brain injuries 3% to 42%, poisonings 1% to 39%, and metabolic conditions 3% to 42%. 

While strokes are the most common cause of non-traumatic coma in general, non-structural causes, with a prevalence ranging from 37% to 75%, slightly exceed the prevalence of structural causes, which falls within the range of 28% to 64%.[5] 

The overall mortality rate varies from 25% to 87%. Strokes and anoxic coma exhibit the highest mortality rates, ranging from 60% to 95% and 54% to 89%, respectively. On the contrary, epilepsy and poisoning have the lowest mortality rates, with less than 10%.[5]

Pathophysiology

The pathophysiology of unconsciousness results from neuronal dysfunction due to a reduction in the supply of glucose or oxygen to the brain.[6] In cases involving structural lesions of the central nervous system, coma can occur through either the direct destruction of brain arousal centers or secondary damage caused by the shifting of intracranial structures, vascular compression, or elevated intracranial pressure.[6]

The anatomical seat of arousal is the ascending RAS in the brainstem. Neurons of this system originate in the dorsal pons and midbrain, form connections in the thalamus, and project to various regions within the cortex. The cortex plays a pivotal role in processing, integrating, and providing context to the information it receives, ultimately generating awareness.[1] The RAS receives impulses from the spinal cord and cortex, facilitating awareness of the surrounding environment.[7][5]

Damage to the below-mentioned 3 significant areas of the brain results in unconsciousness.[2]

Bilateral Hemispheric Damage

Extensive damage to the cerebral cortex, resulting from conditions such as hypoxic or ischemic injuries or brain trauma, leads to neuronal death and denervation of cortical regions. Consequently, patients lose their ability to process and consciously respond to stimuli. Coma induced by systemic factors can also be classified within this category, as it creates an abnormal physiological environment that inhibits neuronal function. Typically, this pattern is reversible if the underlying systemic abnormality is corrected.

Diencephalic (Thalamic) Injury

The thalamus harbors relay nuclei responsible for directing afferent input to the cortex. Consequently, bilateral thalamic lesions can manifest findings similar to those observed in cases of bilateral cortical injury.

Upper Brainstem Injury

The dorsal pons and midbrain contain the RAS. Lesions in this area can inhibit consciousness and result in a comatose state.

History and Physical

Obtaining a medical history from individuals familiar with the patient's recent background, such as witnesses, family members, or paramedics, is highly advantageous when evaluating an unconscious patient.[3] Examining the patient's medical history can provide valuable insights for diagnosing the condition. Additional sources of information may include reviewing previous hospital records and inspecting the patient's personal belongings, such as wallets, or checking for medical alert bracelets. Critical information to gather includes the timeline of the altered level of consciousness, the patient's current medications, any recent illnesses, episodes resembling transient ischemic attacks (TIAs), syncope, or seizures, and the symptoms experienced just before losing consciousness.

When assessed individually, vital signs, respiratory patterns, and cutaneous abnormalities can offer multiple potential diagnoses. The eyes, however, serve as a valuable source of information. For instance, papilledema can signal increased intracranial pressure, Roth spots might indicate bacterial endocarditis, and a disruption of the pupillary light reflex is most likely due to a downward herniation of mesial temporal structures or a brainstem lesion. With the exception of intoxication from substances known to cause miosis or mydriasis, toxic causes usually do not significantly impact pupil size. The presence of fractures and wounds typically indicates trauma.

The neurological examination determines the location and characteristics of the neurological lesion and assesses prognosis. This examination is particularly valuable when the patient is well-perfused, normothermic, normoglycemic, and free from the effects of neurologically active toxins or medications.[8] The GCS evaluates the severity of the coma and provides insight into the prognosis. Assessing spontaneous movements, muscle tone, and reflexes can assist in identifying conditions such as hemiplegia and cerebral lesions on the contralateral side or possibly the upper brainstem. 

Evaluation

ABCs

When assessing an unconscious patient, the initial step is to check for vital signs. According to the American Heart Association guidelines, this involves examining for a pulse and ensuring the airway is clear and that there is a regular breathing pattern. If the patient lacks a pulse or exhibits an irregular breathing pattern, it necessitates initiating basic or advanced cardiovascular life support. Consequently, the evaluation shifts to a general physical and neurological examination for patients with a pulse and breathing effectively. 

Responsiveness

One should assess an individual's reactivity using objective measures to measure responsiveness. The evaluator should start by addressing the patient verbally, then advance to gentle shaking and more intense mechanical stimulation. Adequate discomfort can be induced by applying sufficient stimulus to areas such as the supraorbital ridge, nail beds, or the temporomandibular joint without the risk of causing tissue injury. In the case of a focal spinal cord lesion, it is important to grade the response to these painful stimuli bilaterally. If these measures fail to elicit a response, the examiner should firmly press their knuckles up and down the sternum, thereby awakening any patient not in a profoundly comatose state.[2]

The best practice for reporting the level of responsiveness is to provide a detailed account of the patient's reaction to external stimuli.[2] Coma scales such as the GCS and Full Outline of UnResponsiveness (FOUR) have been developed to help standardize results for effective communication among clinicians and assess patient progress and prognosis.[9][10][11] The physical examination should be conducted daily in a systematic and sequential manner, and the findings should be documented consistently.[8]

GCS Scoring System [9]

Eye responses

• 4 = Eyes open spontaneously
• 3 = Eyes open to verbal command
• 2 = Eyes open to pain
• 1 = No eye opening

Motor responses

• 6 = Obey commands
• 5 = Localize pain
• 4 = Withdrawal from pain
• 3 = Flexion response to pain
• 2 = Extension response to pain
• 1 = No motor response

Verbal responses

• 5 = Oriented
• 4 = Confused
• 3 = Inappropriate words
• 2 = Incomprehensible sounds
• 1 = No verbal response
• GCS 8 or less = Severe
• GCS 9 to 12 = Moderate
• GCS 13 to 15 = Mild

FOUR Score Assessments [10][11]

Eye responses

• 4 = Eyelids are open or opened, tracking, or blinking to command
• 3 = Eyelids are open but not tracking
• 2 = Eyelids are closed but open to a loud voice
• 1 = Eyelids are closed but open to pain
• 0 = Eyelids remain closed with pain

Motor responses

• 4 = Thumbs-up, fist, or peace sign
• 3 = Localizing to pain
• 2 = Flexion response to pain
• 1 = Extension response to pain
• 0 = No response to pain or generalized myoclonic status

Brainstem reflexes

• 4 = Pupil and corneal reflexes are present
• 3 = One pupil is wide and fixed
• 2 = Pupil or corneal reflexes are absent
• 1 = Pupil and corneal reflexes are absent
• 0 = Absent pupil, corneal, and cough reflexes

Respiration rates

• 4 = Not intubated, regular breathing pattern
• 3 = Not intubated, Cheyne-Stokes breathing pattern
• 2 = Not intubated, irregular breathing
• 1 = Breaths above the ventilator rate
• 0 = Breaths at ventilator rate or below

Pupils

The initial eye position and movements should be noted. Although nystagmus is infrequently observed in unconscious patients, it may suggest the presence of an irritating brain lesion or occult seizure activity. Documenting the size of the pupils by utilizing a pupilometer and observing their responses to intense light is essential, as pupillary reactions can be sluggish in unconscious patients.[8][12] The presence of anisocoria, an abnormal light reflex, or irregular pupillary sizes may indicate increased intracranial pressure.[13]

Cranial Nerves

A funduscopic examination, if conducted, can reveal critical observations, such as papilledema or subhyaloid hemorrhage. The evaluation of eye movement through oculocephalic or oculovestibular testing can provide information regarding the functionality of cranial nerves III, IV, VI, and VIII. In general terms, individuals with intact brainstem function should exhibit a typical response to these maneuvers. Patients with a cleared cervical spine can undergo oculovestibular testing using caloric stimulation. 

The corneal reflex of a patient can be established by stimulating the cornea and observing for a blink response. Proper stimulation should result in both a direct and consensual response, indicating the normal functioning of cranial nerves V and VII in the brainstem. The cornea can be stimulated with normal saline drops to prevent corneal damage. Notably, this reflex can be markedly reduced when contact lenses are used. The presence of the gag and cough reflexes in a patient suggests the normal function of cranial nerves IX and X in the brainstem.[2]

Motor Function

Motor function is assessed by evaluating muscle tone, movement patterns, and peripheral tendon reflexes. Decorticate posturing is characterized by upper-extremity adduction and flexion at the elbows, wrists, and fingers, along with lower-extremity extension, including hip adduction and extension, knee extension, and ankle plantar flexion and inversion. Decorticate posturing indicates damage at or below the level of the cerebral cortex. In contrast, decerebrate posturing involves upper-extremity extension, adduction, and pronation, along with lower-extremity extension. Decerebrate posturing typically indicates damage to the brainstem below the red nucleus, which is often caused by pontine strokes. Both decerebrate and decorticate postures are associated with a poor prognosis.

Neuroimaging

Neuroimaging plays a crucial role in assessing unconscious patients, as it is imperative to promptly identify any intracranial abnormalities. Typically, a computed tomographic (CT) scan of the brain is the initial diagnostic study performed, offering valuable insights such as the presence of hemorrhage, infarction, space-occupying lesions, herniation, edema, and hydrocephalus. In cases where the initial neuroimaging is inconclusive, magnetic resonance imaging (MRI) is a valuable follow-up study.[1][3]

Lab Testing

Serum testing includes comprehensive evaluations, including complete blood counts, serum electrolytes such as calcium and glucose, renal and hepatic functions, coagulation panels, arterial blood gas analysis, and toxicology studies.[3] In addition, an electrocardiogram (ECG) should also be obtained. Depending on the patient's medical history and physical examination findings, additional tests to consider include carboxyhemoglobin levels in cases of suspected carbon monoxide poisoning, blood cultures, and evaluations of adrenal and thyroid function.

Lumbar Puncture

If the diagnosis remains uncertain following the tests mentioned above or if there is suspicion of a cerebral infection, it is advisable to contemplate a lumbar puncture.[3] In cases where meningitis is suspected, it is crucial not to postpone the administration of empiric antibiotics and antivirals while waiting for the lumbar puncture results. The risk of herniation in patients with supratentorial mass effect is a subject of debate, but a CT scan is essential before performing a lumbar puncture.[2] The cerebrospinal fluid analysis should include measurements of opening pressure, cell count, gram stain, glucose, protein, culture, and viral testing.[8]

Electroencephalogram

Clinicians request an electroencephalogram (EEG) when a patient presents with signs of seizures or when the underlying cause remains unidentified despite other diagnostic testing.

Treatment / Management

As the underlying cause of unconsciousness is often unclear, initial treatment approaches are initiated before a complete evaluation or diagnosis is achieved. The initial step in managing the state of unconsciousness in patients involves starting empiric therapy while obtaining initial diagnostic studies.[1][2] Other steps of management or treatment are listed below. 

Oxygenation: Generally, unconscious patients with an oxygen saturation level below 90%, a GCS score lower than 8, or a weakened cough or gag reflex necessitate intubation.

Circulation: A mean arterial blood pressure below 70 mm Hg should be treated with fluids or vasopressors. Mean arterial pressures exceeding 130 mm Hg may require administering intravenous (IV) labetalol at a dose of 5 to 20 mg or as necessary.

Vital Signs: The vital signs of an unconscious patient should be obtained if this task has not yet been completed.

Glucose Administration: If the cause of the coma is unknown, 25 g of dextrose should be administered while awaiting the results of laboratory tests.

Thiamine Administration: In cases of malnourishment, a 100 mg dose of thiamine should be administered alongside or before administering glucose to the patient. 

Specific Antidotes: In patients strongly suspected of experiencing a specific drug overdose, it is advisable to consider naloxone and flumazenil. In addition, gastric lavage and activated charcoal are alternative options that can be considered.

Intracranial Pressure: If a patient exhibits a clinically evident herniation syndrome or if one is imminent based on CT findings, mannitol should be administered via IV route at a dosage of 1 g/kg, along with hyperventilation.

Seizures Control: In managing seizures in unconscious patients, the preferred drugs of choice are phenytoin and fosphenytoin. The potential treatments for patients with non-convulsive seizures may include phenytoin or lorazepam.  

Infection Treatment: In cases where bacterial meningitis or viral encephalitis is suspected, it is recommended to administer empiric antibiotics or antivirals. 

Acid-Base and Electrolyte Balances: Restoring acid-base and electrolyte balances in unconscious patients should be a priority.

Body Temperature: Maintaining a body temperature above 38.5 °C in patients with ischemia can exacerbate brain damage. Therefore, it is essential to use cooling blankets and antipyretics. In cases of cardiac arrest, inducing hypothermia is considered neuroprotective. Rewarming is generally unnecessary unless the patient's temperature falls below 33 °C.

Agitation Control: Once diagnostic testing results are obtained, management strategies can be customized accordingly to achieve optimal outcomes. Patients who are in a persistently comatose state despite initial interventions often necessitate a higher level of care, such as placement in an intensive care unit.

Differential Diagnosis

As there are many possible causes of unconsciousness, the differential diagnosis is quite broad.[1] Although some etiologies are straightforward, such as anoxic brain injury, cerebrovascular accidents, seizures, and poisonings, certain categories have inherently wide differentials. For instance, metabolic causes of coma may include hepatic encephalopathy, uremia, electrolyte abnormalities, and endocrine disorders. Furthermore, infections, shock, disorders related to temperature regulation, respiratory failure, and trauma can also precipitate a coma.[14] 

When examining an unconscious patient, it is crucial to distinguish between organic causes and conditions that induce psychogenic unresponsiveness, such as catatonia, severe depression, conversion disorder, and malingering.[15][16] Psychogenic unresponsiveness is more likely to exhibit features such as actively closing eyelids, reactive pupils, nystagmus, variable motor tone, eupnea or hyperventilation, the absence of pathologic reflexes, and a normal EEG.[2] Structural brain disorders can sometimes resemble psychiatric conditions. The diagnosis of psychogenic coma should only be considered following a comprehensive medical and neurological evaluation.[1] 

Unconsciousness can arise from various structural, systemic, and psychogenic causes. The following list outlines the potential factors leading to unconsciousness:

Structural Causes

Unconsciousness can result from various structural causes, including stroke, TBIs, intracranial tumors, inflammation, venous thrombosis, acute hydrocephalus, locked-in syndrome, akinetic mutism, and intracranial, epidural, and subdural hemorrhages.

Systemic Causes

Unconsciousness can also result from various systemic causes, including hypoglycemia, hyperglycemia, hyponatremia, hypernatremia, hypercalcemia, seizures, systemic infections, meningitis, encephalitis, adrenal crisis, pituitary apoplexy with pituitary hormonal insufficiency, endocrine abnormalities, myxedema coma, medication overdose, illicit drug use, neuroleptic malignant syndrome, excessive alcohol intake, hepatic encephalopathy, uremia, heavy metal poisoning, malaria, aspergillosis, herbicides, carbon monoxide poisoning, and anesthesia.

Psychogenic Causes

In addition, psychogenic causes can also contribute to unconsciousness, which includes catatonia, severe depression, conversion disorder, and malingering.

Prognosis

The prognosis for unconscious patients varies significantly and highly depends on the etiology, the severity of brain injury, and individual patient characteristics. The GCS can be instrumental in assessing prognosis. Artificial ventilation and the administration of sedative medications can disrupt the accuracy of the GCS. Therefore, the optimal approach is to conduct a GCS assessment upon admission before any intervention.[17] The FOUR score exhibits comparable sensitivity and specificity to the GCS, although it is a more complex assessment and has not been used for as long as the GCS.

TBIs have been the most studied etiology of coma, likely due to their high prevalence and highly variable outcomes. The estimated mortality rate for patients in a coma resulting from TBI can range from 40% to 50%.[18] Predictors associated with outcomes encompass factors such as patient age, motor assessments, neuro-ophthalmological signs, secondary injuries, and the duration of coma.[2]

Patients with non-traumatic etiologies who do not recover quickly generally face a more unfavorable prognosis than the TBI cohort. The mortality rate for non-traumatic coma can range from 25% to 87%.[4][19] Patients who experience a non-traumatic loss of consciousness lasting more than 6 hours have a 1-month mortality rate of 76%.[20] The outcomes of non-traumatic coma can exhibit considerable variability depending on the underlying cause. Non-traumatic unconsciousness attributed to depressant overdose, demyelinating disease, seizures, poisoning, or autoimmune encephalitis typically presents a favorable prognosis when appropriate supportive care is provided. Vascular causes, such as a significant stroke or aneurysmal hemorrhage, are associated with a grave prognosis, as is hypoxic-ischemic injury. Predictors of long-term outcomes that remain relatively consistent include neuro-ophthalmological signs and motor function.[20]

Complications

The cause, circumstances, and duration of unconsciousness often influence the potential complications for patients. These complications may include permanent brain damage, secondary brain injury from anoxia, coma, aspiration pneumonia, bladder or bowel dysfunction, skin ulcers, trauma from falls, secondary infections from indwelling catheters, malnutrition, death, fractured ribs from CPR, limb weakness, executive dysfunction, emotional and behavioral changes, pituitary hormonal imbalances, memory difficulties, and visual, speech, and language difficulties.