Coma

Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Diagnosis is made clinically with a thorough neurologic examination, including assessment of the brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem to evaluate for the presence of brain death Brain death Brain death is a legal and clinical term describing the irreversible cessation of all cerebral and brainstem functions, including the ability of the brain stem to regulate vegetative and respiratory activities. Brain Death. Definitive management depends on the underlying cause.

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Overview

Definition

  • A deep state of unarousable unresponsiveness
  • Lowest level of responsiveness on the GCS = 3
Table: Glasgow coma scale (GCS)
Points Best eye-opening response Best verbal response Best motor response
6 Spontaneous Oriented Obeys commands
5 Spontaneous Oriented Localizes pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
4 Spontaneous Confused Withdraws from pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
3 To speech Inappropriate Decorticate posturing
2 To pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain Incomprehensible Decerebrate posturing
1 None None None

Classification

  • Pathologic (due to underlying pathology)
  • Artificial or induced (e.g., by general anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts)

Epidemiology

Difficult to determine because of:

  • Variation in assessments by different providers
  • Diagnostic coding for the etiology and not coma itself

Etiology

Table: Causes of coma
Structural Toxic Metabolic
  • Stroke
  • Brain tumor
  • Epidural hemorrhage Epidural Hemorrhage Epidural hemorrhage (EDH) is an event characterized by bleeding into the epidural space between the dural layers of the meninges and the skull. The primary mechanism triggering bleeding is trauma (i.e., closed head injury), which causes arterial injury, most commonly middle meningeal artery injury. Epidural Hemorrhage
  • Subdural hemorrhage Subdural Hemorrhage Subdural hemorrhage (SDH) is bleeding into the space between the dural and arachnoid meningeal layers surrounding the brain. The most common mechanism triggering the bleeding event is trauma (e.g., closed head injury) causing a tearing injury to the extracerebral "bridging" veins. Subdural Hemorrhage
  • Subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage (SAH)
  • Hydrocephalus
  • Herniation syndromes
  • Intoxication
  • Anesthetics
  • Dissociative agents
  • CO poisoning CO poisoning Carbon monoxide (CO) is an odorless, colorless, tasteless, nonirritating gas formed by hydrocarbon combustion (e.g., fires, car exhaust, gas heaters). Carbon monoxide has a higher affinity to hemoglobin than oxygen, forming carboxyhemoglobin (COHb). Increased levels of COHb lead to tissue hypoxia and brain damage. Carbon Monoxide Poisoning
  • Toxic alcohols
  • Antidepressants
  • Anticonvulsants
  • Asphyxia
  • Serotonin syndrome Serotonin syndrome Serotonin syndrome is a life-threatening condition caused by large increases in serotonergic activity. This condition can be triggered by taking excessive doses of certain serotonergic medications or taking these medications in combination with other drugs that increase their activity. Serotonin Syndrome
  • Neuroleptic malignant syndrome Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction. Neuroleptic Malignant Syndrome
  • Clonidine
  • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
  • Dysthermia
  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia/hyperglycemia
  • Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
  • Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
  • Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism (myxedema)
  • Thiamine deficiency
  • Nonconvulsive status epilepticus
  • Electrolyte disturbances

Pathophysiology

The specific sequence of events depends on the underlying etiology, but in general terms:

  1. An initial insult to the arousal areas of the brain occurs, which can be direct (trauma, ischemia, mass effect) or indirect (toxic, metabolic).
  2. If the cause of the initial insult is prolonged, secondary CNS damage and neuronal dysfunction follow.
  3. Because arousal areas are compromised, the individual enters a comatose state.

Clinical Presentation

History

  • First responders, family members, coworkers, or bystanders must be interrogated about the circumstances surrounding the loss of consciousness to determine the most likely etiology.
  • The following should be determined during interrogation:
    • Circumstances and rapidity of development of neurologic symptoms
    • Symptoms prior to loss of consciousness (e.g., headache, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, vomiting)
    • Use of medications, illegal drugs, or alcohol
    • Past medical history (e.g., chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease, ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease)

Physical examination

Evaluation and management may occur simultaneously.

Initial:

  • ABCs:
    • Airway:
      • Obstructed?
      • Compromised?
    • Breathing: 
      • Spontaneous respiratory effort?
      • Maintaining O2 saturation?
    • Circulation:
      • Palpable pulse?
      • Signs of perfusion?
      • Adequate BP?
  • Signs of trauma

Neurologic examination (level of response to stimuli):

  • Saying or yelling the individual’s name (verbal stimulation)
  • Shaking/tapping the individual (tactile stimulation)
  • Pressing on the individual’s nail beds (peripheral painful stimulation)
  • Sternal rub/supraorbital pressure (central painful stimulus)

Brain stem examination (determination of cerebral death): 

  • Pupillary light reflex:
    • Afferent: cranial nerve (CN) II
    • Efferent: CN III (parasympathetic)
    • Performed by shining a light into each pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil's size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Physiology and Abnormalities of the Pupil and observing the ipsilateral and contralateral pupils for response
    • Normal response is direct and consensual pupillary constriction.
    • Coma response is lack of constriction. 
  • Oculocephalic reflex/cold calorics:
    • Afferent: CN VIII
    • Efferent: CN III, IV, VI
    • Performed by applying cold water stream to each auditory meatus/external canal and observing the eyes for an oculomotor response 
    • Normal response is slow oculomotor ipsilateral gaze to side of cold followed by rapid oculomotor contralateral gaze back to midline.
    • Coma response is absence of rapid oculomotor contralateral gaze back to midline.
  • Corneal reflex:
    • Afferent: CN V (ophthalmic division)
    • Efferent: CN VII
    • Performed by gently touching a soft-tipped swab to the cornea of each eye
    • Normal response is bilateral blink.
    • Coma response is no blink.
  • Gag reflex
    • Afferent: CN IX
    • Efferent: CN X
    • Performed by gently touching a soft-tipped swab to the uvula and/or posterior pharynx Pharynx The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx
    • Normal response is to gag.
    • Coma response is no gag.

Remainder of the physical examination is guided by clinical suspicion of the underlying etiology. For example, if meningitis is suspected, testing for signs of meningeal irritation is warranted. 

Examination of brain reflexes

Pupillary light reflexes

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Diagnosis

Diagnosis of coma is strictly clinical and relies on a robust neurologic examination. Further investigation (imaging and labs) are carried out to determine etiology. 

Labs

The laboratory studies to be requested depend on the suspected underlying etiology. Some routine analyses include: 

  • Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
  • CBC
  • Arterial or venous blood gas analysis
  • Toxicology studies
  • CSF analysis: urgent evaluation of suspected infection

Neuroimaging

CT/MRI to evaluate for:

  • Cerebral perfusion abnormalities
  • Intracerebral aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Extremity and Visceral Aneurysms or hemorrhage
  • Cerebral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Intracranial mass

Management

Initial (ABCs)

  • Airway intubation:
    • Persons with coma are incapable of protecting their own airway.
    • Trauma patients may have a compromised airway.
  • Breathing:
    • Even with an established airway, persons with coma may have respiratory failure.
    • Oxygen saturation should be maintained at  > 90%.
    • Mechanical ventilatory support may be required.
  • Circulation:
    • Persons with coma may be in shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock from a variety of etiologies:
      • Cardiogenic causes
      • Sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock
      • Hypovolemia
    • Adequate vascular access should be established:
      • Peripheral IV
      • Central venous catheter Central Venous Catheter Central venous catheters are IV lines placed into the large central veins for monitoring of central venous pressure (CVP), prolonged drug administration, or administration of parenteral nutrition. The most common sites of insertion are the internal jugular and subclavian veins. Central Venous Catheter: Technique
      • Arterial line 
    • Chemical and/or mechanical circulatory support may be required:
      • CPR/advanced cardiac life support (ACLS) protocols
      • Chemical vasopressors
      • Intraaortic balloon pump

Continued management

  • ICU admission
  • Continuous monitoring
  • Supportive care
  • Management targeted at underlying etiology:
    • For example, naloxone should be considered in cases of opioid overdose.
    • Antibiotics should be started for suspected meningitis.

Recovery

Recovery is defined as the return of the ability to convincingly and consistently follow commands.

Complications

  • Brain death: irreversible cessation of all brain and brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem functions, regardless of the cause
  • Persistent vegetative state Persistent vegetative state The term "persistent vegetative state," also called unresponsive wakefulness, describes the condition of individuals with severe anoxic brain injury who have progressed to a state of wakefulness without any meaningful response to their environment. A persistent vegetative state is distinguished from a coma in that individuals in a persistent vegetative state have intermittent sleep-wake cycles. Persistent Vegetative State: a state of wakefulness without awareness, where vegetative functions are preserved but cognition is lost because of irreversible damage to the cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex
  • Apallic syndrome: After awakening, the brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem, the interbrain, and the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord maintain vegetative functions, while the higher mental processes are no longer present. 

Prognosis

  • The comatose state itself can last for an indefinite period of time.
  • Outcomes depend on the underlying etiology and interpatient variability.
  • Effects of diffuse neuronal injury may linger for the remainder of the individual’s lifetime.

Clinical Relevance

Potential underlying etiologies of coma

  • Loss of cardiac output (e.g., massive pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism (PE), cardiac arrhythmia, massive MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction)
  • Cerebrovascular accident Cerebrovascular accident An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. Ischemic Stroke (e.g., hemorrhagic stroke, ischemic stroke Ischemic Stroke An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. Ischemic Stroke)
  • Severe hypovolemia (e.g., hemorrhage, sepsis)
  • Overdose or toxic exposure (e.g., poisons, drugs, alcohol)
  • Trauma (e.g., fall, motor vehicle accident, electrocution)

Differential diagnosis of coma

  • Locked-in syndrome Locked-in syndrome Locked-in syndrome (LIS) is a rare neurological disorder in which patients are awake and conscious but are unable to move their limbs or speak. The disorder is a result of brain injury to the ventral aspect of the pons and caudal ventral midbrain; etiologies include brainstem stroke, tumors, intracranial bleeding, and demyelinating disorders. Locked-in Syndrome: neurologic condition characterized by quadriplegia and bulbar palsy as a consequence of injury to the brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem.
  • Akinetic mutism: rare condition characterized by pathologically slowed or nonexistent bodily movement (akinesia) and loss of speech (mutism)
  • Psychogenic unresponsiveness: also called psychogenic coma. Psychogenic unresponsiveness is the complete lack of responsiveness of psychiatric etiology with no organic cause.
  • Neuromuscular paralysis: characterized by acute-onset neuromuscular weakness progressing to paralysis over days to weeks (< 1 month). Bulbar and respiratory muscle involvement is variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables.
  • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope: brief loss of consciousness followed by an immediate return to complete alertness.

References

  1. Huff JS, Tadi P. (2021). Coma. StatPearls. http://www.ncbi.nlm.nih.gov/books/NBK430722/ 
  2. Josephson S, Ropper AH, Hauser SL (2018). Coma. IN: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J (Eds.), Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill. https://accessmedicine-mhmedical-com.ezproxy.unbosque.edu.co/content.aspx?bookid=2129&sectionid=192032318 
  3. Young GB. (2021). Stupor and coma in adults. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/stupor-and-coma-in-adults
  4. Mayer  MD, FCCM, S. A., & Marshall  MD, MS, R. S. (2021). Stupor and coma (S. A. Mayer  MD, FCCM & R. S. Marshall  MD, MS (eds.); pp. 68–87). https://doi.org/http://dx.doi.org/10.1016/B978-0-323-54694-2.00005-0 

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