Coma

Overview

Definition

• A deep state of unarousable unresponsiveness
• Lowest level of responsiveness on the GCS = 3

Classification

• Pathologic (due to underlying pathology)
• Artificial or induced (e.g., by general anesthesia General anesthesia Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery. 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

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 Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification occurs, which can be direct (trauma, ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage, mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast 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 Comatose A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem reticular formation. Hyponatremia 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 Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, 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 Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia)
  • Use of medications, illegal drugs, or alcohol
  • Past medical history Past Medical History Adult Health Maintenance (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: Anatomy 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 Airway ABCDE Assessment:
    • Obstructed?
    • Compromised?
  • Breathing:
    • Spontaneous respiratory effort?
    • Maintaining O₂ saturation?
  • Circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment:
    • 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)

Brainstem examination: 

• Pupillary light reflex Pupillary Light Reflex Constriction of the pupil in response to light stimulation of the retina. It refers also to any reflex involving the iris, with resultant alteration of the diameter of the pupil. Pupil: Physiology and Abnormalities:
  • Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology: cranial nerve (CN) II
  • Efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology: 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. Pupil: Physiology and Abnormalities and observing the ipsilateral and contralateral pupils for response
  • Normal response is direct and consensual pupillary constriction.
  • Coma response is lack of constriction. 
• Oculocephalic maneuver:
  • Part of assessing the vestibuloocular reflex (VOR)
  • Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology: CN VIII
  • Efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology: CN III, IV, and VI
  • Performed by rotating the head from one side to the other (in a horizontal plane) 
  • Reflex is present (“positive”):
    • The eyes turn in the opposite direction of the head rotation Rotation Motion of an object in which either one or more points on a line are fixed. It is also the motion of a particle about a fixed point. X-rays (dolls eye reflex).
    • Indicates intact brainstem function (the brainstem keeps the eyes fixated on a single point, maintaining a steady gaze despite movement of the head)
  • Reflex is “negative”:
    • The eyes are fixed or move in the same direction as the head.
    • Indicates brainstem dysfunction 
  • Note: Make sure the cervical spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy is intact before performing.
• Cold caloric test:
  • Part of assessing the VOR
  • Apply a cold water stream to each auditory meatus/external canal and observe the eyes for oculomotor response. 
  • Normal response (as seen in conscious/awake people) is slow ipsilateral gaze to the irrigated ear, followed by rapid nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism in the opposite direction.
  • Coma response is the slow-phase gaze without the rapid-phase nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism.
• Corneal reflex:
  • Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology: CN V (ophthalmic division)
  • Efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology: CN VII
  • Performed by gently touching a soft-tipped swab to the cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy of each eye
  • Normal response is bilateral blink.
  • Coma response is no blink.
• Gag reflex Gag Reflex Cranial Nerve Palsies:
  • Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology: CN IX
  • Efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology: CN X
  • Performed by gently touching a soft-tipped swab to the uvula Uvula A fleshy extension at the back of the soft palate that hangs above the opening of the throat. Peritonsillar Abscess 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: Anatomy
  • Normal response is to gag.
  • Coma response: may still have a gag reflex Gag Reflex Cranial Nerve Palsies (depending on the remaining brainstem activity), but gag reflex Gag Reflex Cranial Nerve Palsies is absent in brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification death

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

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 CSF analysis Meningitis: urgent evaluation of suspected infection

Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant

CT/MRI to evaluate for:

• Cerebral perfusion Cerebral Perfusion Syncope 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. Thoracic Aortic Aneurysms or hemorrhage
• Cerebral edema Cerebral edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries. An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive hydrocephalus). Increased Intracranial Pressure (ICP)
• Intracranial mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast

Management

Initial (ABCs)

• Airway Airway ABCDE Assessment intubation Intubation Peritonsillar Abscess:
  • Persons with coma are incapable of protecting their own airway Airway ABCDE Assessment.
  • Trauma patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have a compromised airway Airway ABCDE Assessment.
• Breathing:
  • Even with an established airway Airway ABCDE Assessment, persons with coma may have 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.
  • Oxygen saturation Oxygen Saturation Basic Procedures should be maintained at  > 90%.
  • Mechanical ventilatory support may be required.
• Circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment:
  • 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 Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • Hypovolemia Hypovolemia Sepsis in Children
  • 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
    • Arterial line 
  • Chemical and/or mechanical circulatory support may be required:
    • CPR CPR The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. Cardiac Arrest/advanced cardiac life support (ACLS) protocols
    • Chemical vasopressors Vasopressors Sepsis in Children
    • Intraaortic balloon pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols

Continued management

• ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus admission
• Continuous monitoring
• Supportive care
• Management targeted at underlying etiology:
  • For example, naloxone Naloxone A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. Opioid Analgesics should be considered in cases of opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation overdose.
  • Antibiotics should be started for suspected 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.

Recovery

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

Complications

• Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification death: irreversible cessation of all brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and brainstem functions (regardless of the cause)
• Vegetative state:
  • State of wakefulness without awareness of self and the environment
  • Blink responses, primitive motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology responses, and sleep-wake cycles are present.
• 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 vegetative state lasting > 3 months in nontraumatic brain injury Nontraumatic Brain Injury Persistent Vegetative State, or > 12 months after traumatic brain injury Traumatic brain injury A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain. Le Fort Fractures
  • Previously known as apallic syndrome (awake unawareness) or neocortical death

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• The comatose Comatose A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem reticular formation. Hyponatremia 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 Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics (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 Hemorrhagic stroke Stroke due to rupture of a weakened blood vessel in the brain (e.g., cerebral hemispheres; cerebellum; subarachnoid space). Subarachnoid Hemorrhage, 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 Hypovolemia Sepsis in Children (e.g., hemorrhage, sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock)
• Overdose or toxic exposure (e.g., poisons, drugs, alcohol)
• Trauma (e.g., fall, motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology 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 Quadriplegia Severe or complete loss of motor function in all four limbs which may result from brain diseases; spinal cord diseases; peripheral nervous system diseases; neuromuscular diseases; or rarely muscular diseases. The locked-in syndrome is characterized by quadriplegia in combination with cranial muscle paralysis. Consciousness is spared and the only retained voluntary motor activity may be limited eye movements. This condition is usually caused by a lesion in the upper brain stem which injures the descending corticospinal and corticobulbar tracts. Locked-in Syndrome and bulbar palsy Bulbar Palsy Locked-in Syndrome as a consequence of injury to the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stem. Consciousness is present, as well as voluntary blinking and vertical eye movements.
• Akinetic mutism: rare condition characterized by pathologically slowed or nonexistent bodily movement (akinesia) and loss of speech (mutism) in an awake person. The condition stems from injury to the premotor or prefrontal areas.
• Psychogenic unresponsiveness: also called psychogenic coma. Psychogenic unresponsiveness is the complete lack of responsiveness to external stimuli, stemming from a 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.