Here we will discuss how to approach the patient in coma. This is similar to other sections in that it involves answering the following 4 questions. 1. Is the patient in coma? 2. Where is the lesion/process localization? 3. What caused the lesion/dysfunction? 4. What are we going to do about it?
To answer the first question it is helpful to review the following states-of-arousal and related terms. For example we need to distinguish between normal sleep, encephalopathy, coma, persistent vegetative state, minimally conscious state, brain death and locked-in syndrome. The physical examination is the first step to help you determine which of theses states the patient is in. Notice whether the patient is awake. Do they open their eyes? What is their response to verbal and painful stimuli? Is there evidence of cognitive/cortical/voluntary response to external stimuli? Are the brainstem reflexes intact?
Key states of awareness and arousal:
- Sleep
- Encephalopathy
- Coma
- Persistent Vegetative State and Permanent Vegetative State
- Minimally Conscious State
- Brain death (death)
- Locked-in syndrome
Here is a brief introduction to these states:
Sleep:
Normal sleep is something we all experience. It is a physiological state. The person will not be awake. Their eyes will be closed. However, the patient will be arousable to verbal stimuli or to pain. Sleep has characteristic findings on EEG that are different from normal wakefulness and also different from encephalopathy.
Encephalopathy:
Encephalopathy (also known as delirium) is a state of global cerebral dysfunction. This is different from sleep, and also different from normal wakefulness. The key features are loss of attention and concentration. Tests of attention like serial 7s, spelling WORLD backwards and naming the days of the week backwards are useful. The patient will have difficulty maintaining working memory. In more severe cases, the patient will be come drowsy, then obtunded and eventually, if very severe, will be in a non-structural coma. So encephalopathy encompasses a wide spectrum of states from abnormal wakefulness (eyes open) to non-structural coma (eyes closed even after painful stimuli). So a patient may be awake and encephalopathic. Alternatively the patient may have severe encephalopathy that progresses to non-structural coma. In the latter case, the patient does not open their eyes to pain, but have at least some intact brainstem reflexes. They should not have lateralizing signs i.e. asymmetric signs.
Coma:
Coma is a state of unarousable unresponsiveness. The patient is not awake. The patient does not open their eyes to pain. The patient has no awareness and no signs of intact cortical function and absent sleep-wakefulness cycle. The physiology is interruption of the reticular activating system and its ascending projections. The anatomy localizes to brain-stem, bilateral thalami or diffuse cortical dysfunction. There are two forms: coma due to non-structural causes and coma due to structural/focal causes.
For non-structural causes of coma, think of a patient with severe liver failure. The patient will initially become inattentive and have trouble concentrating. As the disease progresses, they will become disoriented and lethargic. As this progresses further the level of consciousness will drop further into obtunded states. Eventually, if this progresses the patient will no longer respond to painful stimuli by eye-opening. They may have flexor or extensor posturing. The pupils should be equal and reactive. This is the description of non-structural coma. The same clinical progression may occur with renal failure, hypoglyemic coma, myxoedema coma, severe metabolic acidosis, hypercapnea and respiratory failure if untreated.
For structural causes of coma, think of a focal area of injury that interrupts the reticular activating system and its projections in the brainstem, thalami or bilateral cerebral hemispheres. Examples are basilar artery occlusion with brainstem ischemia or infarction. Another example is brainstem intracerebral hemorrhage. Further examples include severe hydrocephalus, and mass lesions with herniation. Also traumatic brain injury with diffuse axonal injury is a structural cause of coma. In patients with structural causes, we look for abnormalities in pupillary responses. In particular unequal pupils may indicate herniation or midbrain lesions or pontine lesions. We also look for asymmetry in the limb responses. For example a patient with a large left cerebral hemorrhage infarct with herniation may have extensor response to pain on one side and flexor response to pain on the other side. To summarise, think of structural causes of coma when there are unequal pupils, disconjugate gaze or asymmetry in the limb responses.
Persistent Vegetative State and Permanent Vegetative State:
Persistent vegetative state and permanent vegetative states and a group of the outcomes that may follow after coma. The other possible outcomes after coma are: return of consciousness, evolution into minimally conscious state or progression to brain death.
Vegetative functions are just another word for autonomic functions. These are functions that occur without consciouss effort or voluntary effort. They include: sleep- wakefulness cycles, respiratory function, cardiac function, gastrointestinal motility and sweat gland function.
When we say the patient is in a persistent vegetative state, we mean that they have no evidence awareness or no evidence of cognitive/voluntary response to external stimuli and that the condition has lasted at least weeks/1 month. The patient is technically awake and has a higher state of arousal than coma, but has no evidence of awareness. Rarely, there may be crying or laughter or even grimacing.
To remember the clinical setting. Imagine a patient that was in a coma, who then starts to open their eyes, and later on is able to wean off of mechanical ventilation. The patient may then demonstrate sleep and wakefulness periods, but not interact at all with any external stimuli. There are strict definitions for this and legal implications for the condition. There are criteria for persistent vegetative state and permanent vegetative states, and they differ depending on the cause of injury. In traumatic brain injury the patient can be diagnosis with permanent vegetative state after 12 months. In non-traumatic brain injury the patient can be diagnosed the a permanent vegetative state after 3 months. Typical life expectancy is 2-5 years after permanent vegetative state.
Persistent vegetative state features:
- A state of pathologic unconsciousness;
- Unawareness
- Arousable
- Normal sleep-wake cycles
- Absence of sustained, reproducible, purposeful/voluntary behavioural responses to stimuli (visual, auditory, tactile, or noxious)
- Absence of language comprehension or expression
- Presence of sleep-wake cycles (intermittent wakefullness)
- Preserved hypothalamic and brain stem autonomic function to permit survival with medical and nursing care
- The following may occur:
- Roving eye movements
- Purposeless smiles
- Occasional verbalizations
Minimally Conscious State:
Minimally conscious state (MCS) is a disorder of consciousness that is different from coma and different from vegetative states. It can follow coma and can occur after a vegetative state. It can also evolve to coma or persistent vegetative state depending on the cause. To distinguish MCS from coma. The patient has more arousal and some wakefulness in minimally conscious state. To distinguish between persistent/permanent vegetative state and MCS, the patient has some but minimal cognitive response to external stimuli in the minimally conscious state. This requires demonstration of consistent discernible behavioural evidence of consciousness.
The causes include structural and non-structural causes of coma, and also include some neurodegenerative conditions. It is currently, the least well-studied of the disorders of consciousness in this section.
Minimally Conscious state features:
- A state of pathologic unconsciousness;
- Unaware
- Arousable
- Normal sleep-wake cycles.
- Presence of some of sustained, reproducible, purposeful/voluntary behavioral responses to stimuli (visual, auditory, tactile, or noxious)
- Presence of sleep-wake cycles (intermittently wakefullness)
- Preserved hypothalamic and brain stem autonomic function to permit survival with medical and nursing care
- Absence of language comprehension or expression
Brain death (death):
Brain death is death. Prior to the advent of mechanical ventilation and cardiopulmonary ventilation, the following three conditions occurred quickly and together when people die: 1. cardiac arrest 2. pulmonary arrest 3. brain death. It is only after the development of successful cardiopulmonary resuscitation and mechanical ventilation that we have needed a brain based definition to allow us to determine that the person is dead.
The outcomes of cardiopulmonary resuscitation include 1. failed cardiopulmonary resuscitation 2. successful cardiopulmonary resuscitation without brain injury 3. successful cardiopulmonary resuscitation but with brain injury 4. successful cardiopulmonary resuscitation but with fatal brain injury. Brain death criteria allows us to distinguish between patients who are severely brain injured and those who are already dead.
There are very strict criteria for brain death. I suggest you review the most up to date criteria and legal definitions in your country and city. The general common features is that there must be 1. evidence of catastrophic brain injury 2. loss of all brainstem function including loss of all brainstem reflexes 3. exclusion of all and any mimicking conditions or confounding factors. The process usually requires imaging or other testing to demonstrate catastrophic brain injury such as anoxic brain injury, intracerebral hemorrhage with herniation, or massive brainstem hemorrhage. This is followed by at least two clinical examinations separated in time to determine loss of all brainstem reflexes: pupillary reflexes, vestibulo-ocular reflexes, corneal reflex, gag reflex, and cough reflex. This is followed by an apnea test to determine absence of brainstem reflex breathing response to hypercapnia. The clinical reflex tests and apnea tests need to be performed off of sedation or any confounding abnormalities. In some scenario complete exclusion of these confounders is not possible. In these cases ancillary testing is necessary to help such as nuclear medicine cerebral blood flow studies. It is essential to be strict about adherence to brain death criteria before establishing the diagnosis. Being loose with the criteria will lead to mis-diagnosis.
Brain death features:
- Patients are unaware, unarousable, with absent sleep-wake cycles
- Absence of all brain stem reflex responses including:
- Papillary, corneal, oculovestibular, oculocephalic, oropharyngeal, respiratory reflex
- Certain time must have elapsed: at least 6 hrs
- Absent respiratory activity, the apnoea test:
- Absence of respiratory activity at PaCO2 = or > 60 mmHg
- Absence of seizures, hypothermia, CNS depressants
- Note: spinal reflexes may be present.
Locked-in syndrome:
Locked-in syndrome is not a disorder of consciousness but may be confused with the disorders of consciousness. In this syndrome the patient is aware, awake but has severe paralysis and may appear to be comatose or brain-dead. The patient is usually quadriplegic, and has bilaterally facial weakness, and impairment of some of the extra-ocular movements. Some patients are able to follow commands with the minimal residual eye movements.
For illustrative examples, this can occur in patients after basilar artery occlusion where the reticular activating system is spared but the bilateral corticospinal tracts, bilateral facial nuclei and some of the nerves controlling the ocular muscles are involved. Another clinical scenario is with severe Guillain-Barre syndrome with quadriplegic, bilateral facial weakness and extra-ocular muscle involvement. Carefull assessment of these patients is necessary not to confuse them with the other conditions. The prognosis depends on the underlying condition and the patients capacity to recover.
Investigations to consider in Coma:
- Finger prick Glucose
- Pulse oximetry
- Blood tests:
- ABG
- FBC, Complete metabolic panel, creatinine, Ca++, phosphate, albumin, LFTs & coagulation screen, Blood glucose
- B1 thiamine,
- TFT: hypothyroidism i.e. myxoedema coma
- Toxicology screen: blood & urine: ethanol & drug levels
- CXR
- CT brain
- CTA: to assess for basilar artery thrombosis
- EEG: nonconvulsive status epilepticus
- Consider:
- Carboxyhemoglobin levels
- CSF analysis
- Malaria testing
- MRI
Causes of Coma:
Supratentorial lesions:
- Extradural hematoma
- Subdural hematoma
- Cerebral contusion
- Intracerebral hemorrhage
- Cerebral infarction (Ischemic stroke)
- Cerebral abscess or empyema
- Brain neoplasm
Infratentorial lesions:
- Brainstem stroke:
- Basilar artery thrombosis or embolis
- Pontine hemorrhage
- Cerebellar hemorrhage or infarction
- Posterior fossa hematoma (extradural or subdural)
Diffuse encephalopathy:
- Subarachnoid hemorrhage
- Meningitis
- Encephalitis
- Global cerebral ischemia a.k.a. anoxic-ischemic encephalopathy
- Drugs & toxins:
- Benzodiazepines, barbiturates
- Opioids
- Ethanol
- Drugs of abuse & overdose of medication
- Hypoglycemia
- Hyperglycemia:
- Diabetic ketoacidosis
- Hyperosmolar nonketotic hyperglycemia
- Hypernatremia or Hyponatremia
- Hypercalcemia >3.7 mmol
- B1 thiamine deficiency i.e. Wernike’s encephalopathy
- Hepatic encephalopathy
- Hypothermia or hyperthermia
- Others:
- Hypothyroidism (Myxoedema coma), DIC, Sepsis, pancreatitis, Vasculitis
- TTP, fat emboli
- Hypertensive encephalopathy
- Diffuse micrometastases
- Seizure or prolonged postictal state
Causes of Coma with small or pinpoint pupils:
- Opiate intoxication
- Cholinergic syndrome:
- Organophosphates, physostigmine
- Pontine lesions
Causes of Coma with dilated pupils:
Sympathomimetic syndrome:
- Amfetamines
- Cocaine, PCP,
Anticholingergic syndrome:
- Anticholinergics, antihistamines
- Tricyclic antidepressants
Supratentorial lesions with transtentorial herniation
DDx. of coma:
- Psychogenic unresponsiveness
- Persistent vegetative state, Permanent vegetative state, Minimally conscious state
- Locked-in syndrome
- Brain death
Glasgow Coma Scale (GCS)
Observe the patient, then give verbal and painful stimuli. Grade the eye opneing, verbal and motor response. Score ranges from 3-15.
Eye Opneing:
4 Spontaneous
3 To sound
2 To pressure
1 No response
Verbal Response:
5 Orientated
4 Confused
3 Words
2 Sounds
1 No response
Motor Response:
6 Obey commands
5 Localising
4 Normal flexion
3 Abnormal flexion
2 Extension (extensor posturing)
1 No response
Related articles and sections:
References:
- Wijdicks EF, Varelas PN, Gronseth GS, Greer DM; American Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010 Jun 8;74(23):1911-8. doi: 10.1212/WNL.0b013e3181e242a8.
- Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, Zasler ND. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002 Feb 12;58(3):349-53.
- The Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: assessment and management of persons in the persistent vegetative state. Neurology . 1995; 45: 1015–1018.
- The Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (first of two parts). N Engl J Med 1994;330:1499-1508.
- The Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (second of two parts). N Engl J Med 1994;330:1572-1579.
- Plum F, Posner J. The diagnosis of stupor and coma, 3rd ed. Philadelphia: FA Davis, 1982.