Key Concepts
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Coma is a state of depressed consciousness in which a patient is not aware, is not awake, and does not respond to vigorous stimulation. Consciousness consists of arousal (subcortical) and awareness (cortical).
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Damage to the dorsal brainstem, thalamus, axonal projections to the cortex, or extensive injury to bilateral cortices may result in depressed consciousness or coma.
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Toxicologic, metabolic, infectious, and other disorders causing diffuse brain injury cause 65% of coma cases; of these, toxins are the most common. Structural brain diseases account for most of the remaining cases.
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A patient with depressed consciousness is unlikely to provide a reliable history. Historical information should be elicited from other available sources, such as emergency medical services personnel, family members, the patient’s belongings, or medical records.
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An abrupt onset of coma suggests a stroke, seizure, or cardiac event.
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The neurologic examination should include an evaluation of level of consciousness, cranial nerves, brainstem reflexes, and motor responses.
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Pinpoint pupils may represent a pontine infarct or intoxication from opioids, clonidine, or cholinergic substances.
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Nonconvulsive status epilepticus should be suspected in cases of coma of undetermined cause and is diagnosed by electroencephalography.
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Hypoglycemia and hypoxia are two easily identified and reversible causes of coma.
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An empiric trial of naloxone will lead to rapid reversal of opioid toxicity and other select medication overdoses.
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Targeted temperature management is recommended in comatose adult patients with return of spontaneous circulation after cardiac arrest from either a shockable or nonshockable rhythm, with a goal temperature range of 32°C to 36°C. In children who are comatose post arrest, it is reasonable to target a temperature range of 36°C to 37.5°C. Hyperthermia should be strictly avoided for all comatose postarrest patients.
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Most patients with coma will require intensive care monitoring. If the cause of coma is not treatable in the initial facility and the patient needs a higher level of specialty care (e.g., structural lesion requiring neurosurgery), then a coordinated transfer should be facilitated.
Foundations
Coma is a state of depressed consciousness in which a patient is not aware, is not awake, and does not respond to vigorous stimulation. This stands in contrast to stuporous or lethargic patients, who also may have a decreased level of awareness or consciousness but can be aroused with external stimuli.
Epidemiology
Most cases of depressed consciousness or coma are the result of a metabolic derangement, usually a glucose disorder, drug overdose, or adverse drug effect, but other common causes include traumatic brain injury, systemic or central nervous system (CNS) infection, ischemic or hemorrhagic stroke, intracranial mass, and, less commonly, a psychiatric illness. Patients with depressed consciousness represent true emergencies because the potential causes are often life-threatening and must be rapidly diagnosed and reversed whenever possible. A review of relevant neuroanatomy and pathophysiology facilitates our understanding of how consciousness is affected in the setting of disease ( Fig. 12.1 ).
Relevant anatomy showing the ascending reticular activating system and adjacent structures important for arousal. The red box denotes area of interest. CN , cranial nerve.
From www.netterimages.com . © 2018 Elsevier Inc. All rights reserved.
Pathophysiology
To maintain normal consciousness, the brain requires a constant flow of sensory input and the ability to process this information. Visual, auditory, olfactory, gustatory, visceral, and somatosensory inputs are all synthesized and interpreted by the brain simultaneously. Disruption in this flow of information or inability to process it may lead to depressed consciousness.
Consciousness consists of two domains: arousal and awareness. Arousal ranges from fully awake, to arousable with verbal or tactile stimulation, to unarousable. Anatomically, arousal is maintained by the subcortical structures, including the brainstem nuclei, thalamus, basal forebrain, hypothalamus and, most notably, the ascending reticular activating system (ARAS). ARAS neurons are located predominately in the pons and midbrain, connect to the thalamus, and project to the cortex. Awareness consists of the content of consciousness, ranging from self-aware and coherent to confused, inattentive, or perhaps delusional. Awareness is generated by the bilateral cerebral cortices, which control the processing and understanding of sensory input. A patient’s level of arousal may be low enough that the domain of awareness is difficult to assess.
Consequently, damage to the dorsal brainstem, thalamus, axonal projections to the cortex, or extensive injury to bilateral cortices may result in depressed consciousness or coma. The clinical presentation may vary considerably depending on the location of the insult.
Diagnostic Approach
Differential Considerations
Differential diagnoses of depressed consciousness and coma are broad ( Table 12.1 ) and potentially involve dysfunction in any area of the brain, from the cortex to the brainstem. It may be the result of a global insult causing massive cortical neuronal dysfunction or a small injury to a critical area of the brainstem responsible for arousal. Toxicologic, metabolic, infectious, and other disorders causing diffuse brain injury or neuronal dysfunction cause 65% of coma cases; of these, toxins are the most common. Worldwide, the prevalence of unintentional drug overdose, particularly opioid overdose, is increasing. , Structural brain diseases account for most of the remaining cases. Common, largely reversible causes of depressed consciousness and coma, along with their clinical findings and emergency treatment, are listed in Table 12.1 .
TABLE 12.1
Critical and Emergent Diagnoses of Coma
| Diagnosis | Cause | Findings | Treatment (Adult Dosage) | Comments |
|---|---|---|---|---|
| Metabolic | ||||
| Critical diagnoses | Hypoglycemia | Diaphoresis, insulin pump | D 50 W 50 mL IV | |
| Hyperglycemia (DKA, HHS) | Tachypnea, nausea, vomiting, abdominal pain, dehydration | Isotonic fluid; insulin | ||
| Adrenal crisis | Weakness, weight loss, hypotension, hyperpigmentation | D 5 NS volume repletion; correct hypoglycemia; hydrocortisone 100 mg IV | Expect hyperkalemia as well | |
| Pituitary apoplexy | Sudden headache, visual impairment, multihormonal dysfunction | Treat electrolyte abnormalities; hydrocortisone 100 mg IV | May have pituitary adenoma; consult neurosurgery | |
| Sepsis | Fever, hypotension, poor end-organ perfusion | Isotonic fluid; appropriate antibiotics; source control | ||
| Emergent diagnoses | Wernicke encephalopathy | CN III or CN VI palsy, nystagmus, sluggish pupillary response, anisocoria, gait instability, peripheral neuropathy | Thiamine 500 mg IV | Often seen in alcoholic or severely malnourished patients, seldom in hyperemesis gravidarum |
| Hyponatremia | Progressive confusion, headache, anorexia, seizure | Free water restriction; hypertonic saline for seizures | Side effect of many medications | |
| Hyperammonemia | Lethargy, irritability, vomiting, seizure, poor feeding | Monitor protein intake; hemodialysis; levocarnitine for valproic acid toxicity | Seen in liver disease, inborn errors of metabolism, or as side effect of valproic acid or bariatric surgery | |
| Hypercalcemia | Lethargy, polyuria, AKI, constipation | Isotonic fluid; bisphosphonates IV; calcitonin | Causes nephrogenic DI; suspect malignancy | |
| Uremia | Nausea, vomiting, anorexia, fatigue, uremic fetor | Treat hyperkalemia; hemodialysis | Check ECG for hyperkalemia changes | |
| Hepatic encephalopathy | Fetor hepaticus, asterixis, ascites, stigmata of cirrhosis | Lactulose or rifaximin | Evaluate for sepsis, GI bleeding, SBP | |
| Thyrotoxic crisis | Fever, tachycardia, diaphoresis, diarrhea | Isotonic fluid; propranolol 1 mg IV, PO; propylthiouracil 600 mg PO starting dose (variable) | May also need to treat adrenal insufficiency | |
| Myxedema coma | Sluggishness, weight gain, edema, depression, hair loss, constipation | Levothyroxine or liothyronine; hydrocortisone 100 mg IV (variable) | May be precipitated by acute illness | |
| Heat stroke | Hyperpyrexia (>41.1°C), flushing, exertion in heat, dehydration | Isotonic fluid; evaporative cooling | Classic in older adults with comorbidities unable to seek cool environment | |
| High altitude cerebral edema | Rapid ascent, headache, confusion, psychosis | Rapid descent from altitude; hyperbaric oxygen; dexamethasone 10 mg IV | More common >3500 m | |
| Toxic | ||||
| Critical diagnoses | Hypoglycemic agents | Older adult with worsening renal function, intentional overdose | Dextrose; octreotide if refractory hypoglycemia due to sulfonylurea toxicity | Sulfonylureas can be lethal with only one pill in children |
| Opioids | Stupor, apnea, miosis, needle tracks | Naloxone IV, IN, or IM | Check skin for fentanyl patches | |
| Simple asphyxiants | Sudden lightheadedness, collapse, syncope | 100% oxygen | Leaking CO 2 tank in enclosed space (e.g., walk-in freezer); also nitrogen, helium, argon, or methane gas | |
| Carbon monoxide | Combustion of fuel in enclosed space, headache, confusion, malaise, nausea | 100% oxygen; hyperbaric oxygen per toxicology | Multiple people may be affected simultaneously; consider hyperbaric oxygen, especially during pregnancy | |
| Histotoxic hypoxia | Confusion, seizure, collapse, hydrogen sulfide smells like rotten eggs, cyanide (bitter almond smell) may result from combustion of plastics | 100% oxygen; hydroxocobalamin 70 mg/kg (or 5 g) IV for cyanide | Consider cyanide in any house or car fire | |
| Methemoglobinemia | Use of medications, such as topical anesthetics or dapsone, cyanosis, pulse oximeter 85% | 100% oxygen; methylene blue 1–2 mg/kg IV | Also may result from severe diarrhea in infants | |
| Emergent diagnoses | Sedatives | Alcohol, benzodiazepines, and many others may be the culprit | Supportive; flumazenil for benzodiazepine toxicity | Avoid flumazenil in chronic benzodiazepine users, patients with proconvulsant drugs (cyclic antidepressants, isoniazid) |
| Toxic alcohols | Nausea, vomiting, intoxication, vision changes, early osmolar gap then anion gap acidosis, renal failure | Fomepizole 15 mg/kg IV load; correct electrolyte abnormalities; isotonic fluid 500 mL/h | Consult nephrology and toxicology to consider hemodialysis for elevated levels and metabolic acidosis | |
| Inhalants | Often young, paint on hands or face, diplopia, slurred speech, cardiac dysrhythmia | Check ECG and monitor on telemetry; definitive airway if lip or tongue edema | Inhalants may be cold, may cause frostbite and edema to mucous membranes and hands | |
| Psychiatric medications | Hypotension, wide QRS, seizures | High-dose IV sodium bicarbonate for tricyclic antidepressant overdose | ||
| Anticonvulsants | Confusion, slurred speech, elevated drug levels | Supportive measures | Hyperammonemia may occur with valproic acid use | |
| Anticholinergics | Hyperpyrexia, pupillary dilation, urinary retention, visual hallucinations | Physostigmine; benzodiazepines may help in severe agitation | Consider physostigmine in severe anticholinergic toxicity; avoid if seizure, bradycardia, or abnormal QRS or QTc on ECG; administer via slow IV push over 5 minutes | |
| Clonidine | Bradycardia, hypotension, somnolence | Isotonic fluids; vasopressors | Discuss naloxone with toxicology | |
| Beta blockers | Bradycardia, hypotension, hypoglycemia, seizure | Isotonic fluid; glucagon IV (5 mg); atropine IV (0.5 mg); vasopressors IV; high dose insulin infusion; transcutaneous or transvenous pacing | High doses of vasopressors may be needed. Discuss lipid rescue therapy and ECMO with toxicology and perfusionist, respectively | |
| Salicylates | Nausea, vomiting, tinnitus, delirium, hyperpnea, anion gap metabolic acidosis with mixed respiratory alkalosis | Isotonic fluids; urinary alkalinization with sodium bicarbonate; correct hypokalemia; consider hemodialysis | May come from oil of wintergreen or other non-aspirin source | |
| Neuroleptic malignant syndrome | Hyperpyrexia, muscular rigidity, delirium, autonomic instability, elevated CPK | Cooling, isotonic fluid; benzodiazepines, bromocriptine | Pharmacologic paralysis with nondepolarizing agent if severe | |
| Serotonin syndrome | Multiple serotonergic agents, hypertension, tachycardia, hyperreflexia, muscular rigidity, tremor, nausea, diarrhea, clonus | Isotonic fluid; check CPK; benzodiazepines; cooling, hydration, cyproheptadine | Pharmacologic paralysis with nondepolarizing agent if severe | |
| Structural | ||||
| Critical diagnoses | Intracranial hemorrhage | Sudden onset headache, hypertension, neurologic deficits | CT without contrast; reversal of anticoagulation; blood pressure control, antihypertensives and/or hyperosmolar agents | Early neurosurgical consultation for possible evacuation |
| Cortical infarct | Sudden unilateral neurologic deficits | CT without contrast to evaluate for hemorrhage; neurology consultation; consider tPA and intraarterial clot retrieval; blood pressure control or antihypertensives | tPA contraindications must be excluded; tPA 0.9 mg/kg IV, not to exceed 90 mg total dose; administer 10% of total dose as initial IV bolus over 1 min and remainder infused over 60 min | |
| Cerebellar infarct | Sudden vertigo, nausea, ataxia, dysarthria | Consider tPA as above | Neurosurgery consultation if severe edema to consider decompressive craniectomy | |
| Basilar artery occlusion | Hemiparesis or quadriparesis, abnormal spontaneous movements, facial weakness, dysarthria, dysphagia | Consider tPA as above | May develop locked-in syndrome (loss of all voluntary movements except for eyes) | |
AKI , acute kidney injury; CN , cranial nerve; CO 2 , carbon dioxide; CPK , creatine phosphokinase; CT , computed tomography; D 5 NS , 5% dextrose in normal saline; D 5 W , 5% dextrose in water; D 50 W , 50% dextrose in water; DI , diabetes insipidus; DKA , diabetic ketoacidosis; ECG , electrocardiogram; GI , gastrointestinal; HHS , hyperosmolar hyperglycemic state; IV , intravenous; PO , per os (orally); SBP , spontaneous bacterial peritonitis; tPA , tissue plasminogen activator.
Special consideration is needed for specific populations of patients. Older patients are often prescribed multiple medications and are at risk for accidental overdose, drug-drug interactions, and adverse drug reactions. Seemingly minor infections such as a urinary tract infection, upper respiratory infection, or viral gastroenteritis with dehydration may cause depressed consciousness or coma. In addition, immunocompromised patients are susceptible to opportunistic infections that are less common in the general patient population. Immunocompromise may result from acquired immunodeficiency syndrome (AIDS) or may be seen in patients receiving chemotherapy, immunosuppressive medications related to organ transplantation, or biologic agents (e.g., for rheumatologic illness or inflammatory bowel disease). Psychogenic causes of coma are uncommon, and caution is advised when making this definitive diagnosis.
In the evaluation of an undifferentiated comatose patient, keeping a broad initial differential diagnosis may prevent premature clinical fixation that could lead to diagnostic error. A careful history and clues from the physical examination will often shorten the list of possibilities, allowing a focused evaluation and rapid initiation of treatment.
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