sign in sign up
<<
Home , Coma, Induced coma, Obtundation

Journal of , , and 1993;56:589-598 589

NEUROLOGICAL EMERGENCY J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from

The management of medical

David Bates

The who is brought to the hospital of appropriate therapy. It is therefore essen- casualty department, or seen on the Intensive tial for the physician in charge to adopt a sys- Care Unit, though not having been exposed tematic approach initially to ensure to evident trauma, may be harbouring , and then to direct further tests delayed effects of trauma such as a subdural towards producing the most rapid diagnosis haematoma or meningitis arising from a basal and the most appropriate therapy. The devel- skull fracture. The problems of raised intra- opment of such a systematic approach cranial pressure following a parenchymal demands an understanding of the pathophysi- haematoma in a hypertensive patient, the ology of and the ways in which decompensation of a cerebral tumour or col- it may be deranged. lection of pus, means that all possible causes of loss of consciousness must be considered by the physician when dealing with a patient The causes of coma in coma. Thus in the diagnosis of medical The phenomenon of consciousness depends coma it is not easy to exclude the patient in upon an intact ascending reticular activating coma following head . substance in the to act as the alert- If one excludes with a transient ing or awakening element of consciousness loss of consciousness following , syn- together with a functioning of cope, cardiac dysrhythmia or hypoglycaemia both hemispheres which determines the con- and those unresponsive due to impending tent of that consciousness. The ascending , and considers patients who have been reticular activating substance is a continuous unconscious for some five to six hours, then isodentritic core extending from the medulla 40% of such patients seen in medical practice through the pons to the mid- which is will have taken some form of drugs continuous caudally with the reticular inter- with or without .' Of the remainder mediate grey lamina of the spinal cord and just over 40% will have suffered hypoxic rostrally with the subthalamus, the hypothala-

ischaemic insult as the result of mus and the .3 Its functions and http://jnnp.bmj.com/ or anaesthetic accident, a third will be uncon- interconnections are considerable and its role scious as a result of cerebrovascular acci- greater than that of a simple cortical dents, either haemorrhage or infarction, and system. There are named nuclei throughout about a quarter will be unconscious as a the and, although it was result of metabolic coma including , originally considered that cortical arousal renal failure, hepatic failure and complica- depended upon projections from the reticular tions of diabetes mellitus. If one considers formation via the midline thalamic nuclei to only those cases who are initially regarded as the thalamic reticular and the cortex, on September 24, 2021 by guest. Protected copyright. "of unknown aetiology" the proportion of it now seems unlikely that the thalamic retic- drug overdoses is about 30%, mass lesions ular nucleus is the final relay and the specific about 34% and diffuse metabolic causes role of the various links from the reticular for- account for 36%.2 mation to the thalamus has yet to be identi- Few problems are more difficult to manage fied. than the unconscious patient because the Similarly the neurotransmitters involved in potential causes of loss of consciousness are this arousal system are not fully determined considerable and because the time for diagno- though it seems likely that, in addition to sis and effective intervention is relatively cholinergic and monoaminergic systems, short. All alterations in arousal should be gamma aminobutyric acid (GABA) may be regarded as acute and potentially life threat- important in controlling consciousness." ening emergencies until vital functions are It follows from recognition of the anatomy stabilised, the underlying cause of the coma is and pharmacology of the ascending reticular diagnosed and reversible causes are corrected. activating substance that structural damage to Delay in instituting treatment for a patient this pathway or chemical derangement of the with raised may have neurotransmitters involved are mechanisms Department of obvious consequences in terms of pressure whereby consciousness may be impaired. Neurology, University coning but similarly the unnecessary investi- Such conditions will occur with focal lesions ofNewcastle Upon Tyne, UK gation of patients in metabolic coma with in the brainstem, mass lesions in the posterior D Bates imaging techniques may delay the initiation fossa impinging directly on the brainstem or 590 Bates

mass lesions involving the cerebral hemi- Definitions spheres causing tentorial pressure coning and There is a continuum from the individual in J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from consequently comproming the ascending full consciousness to the patient in deep reticular activating substance either by direct coma. The terminology which is most usually pressure or by a process of ischaemia. In employed derives from the Brain addition toxins, most commonly ingested Committee of the MRC7:- drugs, may have a significant A) Confusion-"disturbance of consciousness effect upon the brainstem ascending reticular characterised by impaired capacity to think activating substance and thereby result in loss clearly and with customary repetition and to of consciousness. perceive, respond to and remember current The content of consciousness resides in the stimuli; there is also disorientation". cerebral cortex of both hemispheres. Unlike Confusion involves a generalised disturbance those discrete cortical functions such as lan- of cortical cerebral function which is usually guage or vision which are focally located associated with considerable EEG abnormali- within the cortex, the content of conscious- ties. Some authors describe an intervening ness can best be regarded as the amalgum of state between normal consciousness and con- all cognitive function. Coma arising from dis- fusion, that of clouding of consciousness.2 ruption of this cortical activity requires a dif- B) Delirium-"a state of much disturbed con- fuse pathology such as generalised anoxia or sciousness with motor restlessness, transient ischaemia, commonly seen after cardiac arrest hallucinations, disorientation and perhaps or anaesthetic accidents, or the effects of pre- delusions". sumed cortical vasospasm seen in infective C) -"a disorder of alertness meningitis or the chemical meningitis follow- associated with psychomotor retardation". ing subarachnoid haemorrhage where gener- D) -"a state in which the patient, alised cortical ischaemia is believed to be the though not unconscious, exhibits little or no cause of disruption of function. spontaneous activity". Although the individ- For the physician attempting to diagnose ual appears to be asleep he or she will awaken the cause of coma consideration must be to vigorous stimulation but show limited given to:- motor activities and usually fail to speak. A) Supra or infra tentorial mass lesions. E) Coma-"a state of unarousable psycho- Typically these will provide evidence of logic unresponsiveness in which the subjects raised intracranial pressure and commonly lie with eyes closed and show no psychologi- produce focal signs. Pathologies such as neo- cally understandable response to external plasm or haematoma, infarction with cerebral stimulus or inner need". This may be short- oedema, abscess, focal encephalitis and ened to "a state of unarousable unresponsive- venous sinus thrombosis should be ness" which implies both the defect in arousal considered. and in of self or environment man- B) Subtentorial destructive lesions or the local ifest as an inability to respond. A more useful effect of toxin. These pathologies will directly assessment of coma is derived from the hier- damage the ascending reticular activating archical Glasgow Coma Scale8 in which substance as in brainstem infarction, patients who fail to show eye opening in rhombencephalitis, brainstem demyelination response to voice, perform no better than and the much more common effects of self- weak flexion in response to pain and make, at http://jnnp.bmj.com/ poisoning with sedative drugs. best, only unrecognisable grunting noises in C) Diffuse damage to the cerebral cortex. response to pain, are regarded as being in Bilateral cortical injury is most commonly coma. This allows the patients to have an eye seen in states of and ischaemia but opening response of two or less, a motor may be mimicked by hypoglycaemia, keto- response of four or less and verbal response of acidosis, electrolyte abnormalities, bacterial two or less. The sum Glasgow score of eight

meningitis, viral encephalitis and diffuse post- should not be regarded as being definitive of on September 24, 2021 by guest. Protected copyright. infectious encephalomyelitis. It is also the coma since the total score can be achieved in likely pathology of coma following subarach- several different ways (table 1). noid haemorrhage. F) Vegetative state. When the cortex of the cerebral hemispheres of the brain recover more slowly than the brain stem or when the cortex is irreversibly damaged there may arise a situation in which the patient enters a vege- tative state without cognitive function. It may Table 1 The be a transient phase through which patients Eyes Open Spontaneously 4 in coma pass as they recover or deteriorate To verbal command 3 but, and commonly after anoxic injuries to To pain 2 No response 1 the brain, there develops a state in which the Best motor response To verbal command Obeys 6 brain stem recovers function but the cerebral To painful stimulus Localises pain 5 Withdrawal 4 hemispheres are not capable of recovery. Flexion 3 When this occurs the patient enters a "persis- Extension 2 No response 1 tent vegetative state" described by Jennett Best verbal response Orientated 5 and Plum.9 Such patients may survive for Disorientated 4 Inappropriate words 3 long periods, on occasion for decades, but Incomprehensible sounds 2 never recover outward manifestations of No response 1 higher mental activity and the condition, The management of medical coma 591

which is comparatively newly recognised, are ensured and monitored, blood should be relates to the development of modem resusci- withdrawn for the determination of blood J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from tative techniques. Other terms have been , biochemical estimations and toxicol- used in the past to identify similar conditions. ogy. It is then reasonable to give a bolus of These include coma vigil, the apallic syn- 25-50g of dextrose despite the present con- drome, cerebral death, neocortical death, and troversy about the use of intravenous glucose total dementia. in patients with ischaemic or anoxic brain G) Akinetic mutism has been defined as a damage. It can be argued that extra glucose similar condition of unresponsiveness but in this situation may augment local lactic acid apparent alertness, as demonstrated by reac- production by anaerobic glycolosis and tive alpha and theta electroencephalographic potentially worsen ischaemic or anoxic dam- rhythms in response to stimuli. The major age. In practice in the situation of ischaemic difference from the vegetative state, in which or anoxic and even in the pres- there is tone in the muscles and extensor or ence of a the administra- flexor responses, is that patients with akinetic tion of such a quantity of glucose will not be mutism have flaccid tone and are unrespon- immediately harmful and in the hypogly- sive to peripheral pain. It is thought that this caemic patient it may well be life saving. A state is due to bilateral frontal lobe lesions, reasonable compromise would be to obtain diffuse cortical lesions or lesions of the deep an early assessment of the level of blood glu- .'0 cose by dextrostix testing but these are not H) The locked in syndrome. Feldman" sufficiently accurate to preclude the need for described a de-efferented state due to bilat- formal laboratory assessment. When glucose eral ventral pontine lesion involving damage is given in this situation an argument can be to the corticospinal, corticopontine and corti- made for giving a bolus of thiamine at the cobulbar tracts. The patient has total paraly- same time to prevent precipitation of sis below the level of the third nerve nuclei Wemicke's encephalopathy."2 and although able to open, elevate and An essential part of resuscitation includes depress the eyes has no horizontal eye move- the establishment of baseline, blood pressure, ments and no other voluntary eye movement. pulse, temperature, the establishment of an The diagnosis depends upon the physician intravenous line and the stabilisation of the being able to recognise that the patient can neck together with an examination for menin- open the eyes voluntarily and can signal gitis. It may be difficult in those patients who assent or dissent by responding numerically have sustained some degree of trauma in their with eye closure. Similar states are occasion- collapse to assess the stability of the neck but ally seen in patients with severe polyneurop- the establishment of an adequate airway cer- athy, myasthenia gravis and after the use of tainly takes precedence and the identification neuromuscular blocking agents. of meningismus in a febrile patient probably I) Pseudo coma. Rarely, patients who appear takes precedence over the stabilisation of in coma without structural, metabolic, toxic neck movements. In a comatose febrile or psychiatric disorder being apparent, can be patient with meningismus seen outside the shown by tests of brainstem function, to have hospital environment the intramuscular injec- intact brainstem activity and corticopontine tion of penicillin before transfer is now recog- projections and not to be in coma. nised to carry a significant advantage. http://jnnp.bmj.com/

Resuscitation History Although resuscitation is commonly per- Once the patient is stable it is important to formed by the casualty officer or the anaes- obtain as much information as possible from thetist in the rather than those who accompanied the patient to hospi-

by the neurologist it is appropriate that the tal or who watched the onset of coma. The on September 24, 2021 by guest. Protected copyright. neurologist remembers that, in patients who circumstances in which consciousness was are unconscious, protection of the airway, lost are of vital importance in helping to iden- respiration, support of the circulation and tify the diagnosis. Generally, coma is likely to provision of an adequate supply of glucose present in one of three ways; as the pre- are all important in stabilising the patient. It dictable progression of an underlying illness; is frequently necessary to intubate the trachea as an unpredictable event in a patient with a in a patient in coma, not only to ensure an previously known disease; as a totally unex- adequate airway but also to prevent the aspi- pected event. Distinctions between these pre- ration of vomit. It is also important to note sentations are often achieved by the history of the respiratory rate and pattern before intuba- the circumstances in which consciousness was tion and certainly before instituting mechani- lost. In the first category are patients follow- cal ventilation; since depressed respiration is ing focal brainstem infarction who deteriorate a frequent clue to or metabolic or those with known intracranial mass lesions disturbance, increased respiration to hypoxia, who show similar deterioration. In the second or acidosis and fluctuating respi- category patients with recognised cardiac ration may indicate a brainstem lesion. The arrhythmia or the known risk factor of possibility that is the cause from an intravenous line. In the final category of coma should always be considered in a it is important to determine whether there has patient with disordered respiration. been a previous history of , trauma, Once adequate oxygenation and circulation febrile illnesses, or focal neurological distur- 592 Bates

bances. The history of a sudden collapse in the possibility of a basal skull fracture and the midst of a busy street or office indicates bruising elsewhere in the body raises the J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from the need for different investigations from question of significant trauma. An exanthem those necessary for the patient who is discov- may indicate the presence of a viral infection ered at home in bed surrounded by empty causing meningoencephalitis, meningococcal bottles of sedative tablets. septicaemia or raise the question of haemor- rhagic disease. Hyperpigmentation raises the possibility of Addison's disease, and the pres- Examination and ence of bullous skin lesions is frequently seen The third phase of the management of the in barbiturate intoxication. Evidence of patient in coma involves a rapid but system- Kaposi sarcoma, anogenital herpetic lesions atic examination to identify possible causes of or oral candodiasis would raise the question the coma. of an acquired immune deficiency syndrome (AIDS) with the consequent plethora of Temperature possible CNS disease. Fever usually indicates infection and rarely a brainstem or diencephalic lesion affecting the Breath temperature centres."3 Most commonly the The odour of the breath of an unconscious combination of fever and coma indicates sys- patient may indicate the presence of intoxica- temic infection such as , septi- tion with alcohol, raise the question of dia- caemia or a cerebral cause such as meningitis, betes or suggest that the cause of coma is encephalitis or abscess. When seizures occur uraemic or hepatic. together with fever the possibility of encephalitis or cerebral abscess is greatly Cardiovascular increased. Heat may present as a Auscultation and examination of the heart febrile comatose patient when the clue to the may indicate valvular disease and raise the diagnosis is in the environment. possibility of endocarditis. Bruits over the is most commonly seen as a carotid vessels might indicate the presence of of an accident or cerebrovascu- cerebrovascular disease and splinter haemor- lar disease when an elderly patient is discov- rhages seen in the nail bed would raise the ered having lain for hours or days in an possibility of sub-acute bacterial endocarditis underheated room. It may also be seen fol- or collagen vascular diseases. lowing intoxication with alcohol or barbitu- rates, with peripheral circulatory failure and Abdomen rarely with profound myxoedema. Examination of the abdomen may reveal signs of trauma or rupture of viscera, Heart rate hepatomegaly or splenomegaly may indicate A tachyarrhythmia or bradyarrhythmia may the possibility of a portocaval shunt and the be significant in identifring the cause of cere- findings of polycystic kidneys would raise the bral hypoperfusion. Irregularity of the pulse possibility of subarachnoid haemorrhage. always raises the question of atrial fibrillation and associated embolic disease. Meningismus Examination of the skull and spine is impor- http://jnnp.bmj.com/ Blood pressure tant and the physician should always look for might indicate , myocar- neck stiffness. Kernig's test in which the resis- dial infarction, septicaemia or intoxication. It tance of flexion of the thigh with the leg may also indicate diabetes mellitus or extended is examined or Brudzinski's tests in Addison's disease. Hypertension is of less which flexing of one thigh is noted to cause help in the diagnosis of the patient in coma as flexion of the other thigh, should be per-

it may be the cause, as in cerebral haemor- formed to help in differentiating neck stiff- on September 24, 2021 by guest. Protected copyright. rhage or hypertensive encephalopathy, but it ness, due to meningeal irritation, from that can also be the result of the cerebral lesion. due to a developing tonsillar pressure cone. If the Kemig and Brudzinski tests are positive Respiration together with neck stiffness this implies For those reasons already given, assessment inflammation in the lumbar theca and sug- of respiration may be compromised by the gests a diffuse meningitic process. If these needs of resuscitation but generally, slow and tests are negative, however, then the neck shallow breathing raises the question of drug stiffness alone is more suggestive of a forami- intoxication. Deep, rapid respiration suggests nal pressure cone.'4 pneumonia or acidosis which may also occur in brainstem lesions causing central neuro- Fundal examination genic . The presence of papilloedema, fundal haem- orrhage or evidence of emboli, together with Integument the findings of hypertensive, vascular or dia- The appearance of the skin and mucous betic retinopathy are important. The fundal membrane may identify anaemia, jaundice, appearances may be diagnostic as in the find- cyanosis or raise the possibility of carbon ing of subhyaloid haemorrhage but more monoxide poisoning. Bruising over the scalp commonly only help to confirm or refute evi- or mastoids, the presence of blood in the dence of raised intracranial pressure. The external auditory meati or nostrils will raise absence of papilloedema does not necessarily The management ofmedical coma 593

mean that there is no increased intracranial serially and is one of the most important indi- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from pressure. cators of the need for further investigation. Thus when the level of consciousness can be seen to be improving there is no need to Neurological examination make urgent decisions but when deterioration The position, posture and spontaneous move- occurs then management decisions must be ments of the unconscious patient should be made. It may of course be correct, when the noted. The formal neurological examination prognosis is recognised to be hopeless, to consists of the elicitation of various reflex make a decision not to undertake further responses."3 The most important aspects of investigation or therapy. neurological examination are those which B) Brainstem function define the level of consciousness, identify the The brainstem reflexes are particularly impor- activity of the brainstem and search for tant in helping to identify those lesions which evidence of lateralisation (table 2). may affect the reticular activating substance, A) The level ofconsciousness explain the reason for coma and potentially The Glasgow Coma Scale8 provides the most help in identifying the viability of the patient. useful hierarchical assessment of the level of The reflexes used are predominantly related consciousness. The response to commands, to the eyes and the pattern of respiration:- calling the patient's name and painful stimuli are observed for eye opening, limb movement (1) PUPILLARY REACTIONS and voice. Painful stimuli such as supraorbital The size, equality and reaction of the pupils pressure for central stimulation and nail bed to light is recorded. Unilateral dilatation of pressure for peripheral stimulation are useful the pupil with loss of the light response sug- and reproducible. Eye opening is relatively gests uncal hemiation or a posterior com- easy to assess though the fixed and unrespon- municating artery aneurysm. Midbrain sive opening of the eyes sometimes seen in lesions typically cause loss of the light reflex deep coma must not be confused with the with midposition pupils, pontine lesions volitional or reflex opening of the eyes from a cause miosis but a retained light response. closed position in response to stimuli. All four Fixed dilatation of the pupils is an indication limbs are tested individually for movement of central diencephalic herniation and may be and the best response is recorded in assessing differentiated from the fixed dilatation due to the Glasgow Coma Scale but an asymmetry atropine like agents by the use of pilocarpine between responses may be of importance in eye drops which will cause miosis if the the overall assessment (vide infra). Patients in dilatation is due to loss of parasympathetic lighter grades of coma still retain the ability to innervation but be ineffective if it is pharma- vocalise and may grimace and withdraw their cological. A Homer's syndrome may be seen limbs from pain. These responses are pro- ipsilateral to a lesion in the hypothalamus, gressively lost as the coma deepens and it is thalamus or brainstem when it will be associ- important to test pain bilaterally in the ated with anhydrosis of the ipsilateral side of periphery and cranially since patients may the body, but can also be due to disease only vocalise or respond to painful stimuli on affecting the wall of the carotid artery when one side raising the possibility of hemianaes- anhydrosis will only affect the face."5 Hepatic http://jnnp.bmj.com/ thesia and providing evidence for a focal or renal failure and other forms of metabolic lesion. A grimace response to painful stimula- coma may make the light reflexes appear tion is believed to indicate intact corticobul- unduly brisk and the pupils therefore relative- bar function2 but there are patients in coma, ly small. Most drug intoxications tend to particularly after hypoxic ischaemic insults, cause small and sluggishly reactive pupils and who show grimace in response to minor a pontine haemorrhage will cause pin point peripheral stimulation yet have no associated pupils due to parasympathetic stimulation.16

peripheral motor response. When this situa- on September 24, 2021 by guest. Protected copyright. tion is seen it always raises the question of a (2) CORNEAL RESPONSES ventral pontine lesion or of a cervical cord The comeal reflex is usually retained until injury but more commonly evolves into a veg- coma is very deep. If it is absent in a patient etative state and is, generally, a poor prognos- who is in otherwise light coma then the possi- tic sign. bility of drug or of local causes The level of coma should be documented of anaesthesia to the should be consid- ered. The loss of the comeal response when drug overdose is excluded is a poor prognos- tic sign. Table 2 Neurological assessment ofcoma (3) SPONTANEOUS EYE MOVEMENT Glasgow coma scale Eye opening the and the pres- Motor response The resting position of eyes Verbal response ence of spontaneous eye movements should Brainstem fumction Pupillary reactions be noted. Conjugate deviation of the eyes Corneal responses Spontaneous eye movements raises the question of an ipsilateral hemi- Oculocephalic responses or contralateral brainstem lesion. Oculovestibular responses sphere Respiratory pattern Abnormalities of vertical gaze are less com- Motor function Motor response a in coma but of Muscle tone mon with patient depression Tendon reflexes the eyes below the meridian may be seen with Seizures damage at the level of the mid brain tectum 594 Bates

and in states of metabolic coma. The resting care units where their respiration is controlled position of the eyes is normally conjugate and complicates the assessment of normal respira- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from central but it may be dysconjugate when tory functions. If, however, the patient is seen there is damage to the oculo-motor or before respiration is controlled then the pres- abducens nerves within the brainstem or ence of long cycle periodic respiration sug- along their paths. gests a relatively high brainstem lesion, Roving eye movements seen in light coma central neurogenic hyperventilation implies a are similar to those of . They cannot be lesion at the level of the upper pons and short mimicked and their presence excludes psy- cycle periodic respiration, which carries a chogenic unresponsiveness.13 Periodic alter- poor prognosis, is seen with lesions lower in nating gaze or "ping pong" gaze is a repetitive the brainstem. In general the presence of conjugate horizontal ocular deviation which is regular rapid breathing correlates with pul- of uncertain aetiology."7 Spontaneous nystag- monary complications and a poor prognosis mus is rare in coma since it reflects interac- rather than with the site of neurological tion between the oculovestibular system and disease in patients with coma.20 the cerebral cortex. Retractory in which the eyes jerk irregularly back into the C) Motorfunction orbit and convergence nystagmus may be As part of the assessment of the Glasgow seen with mid brain lesions.'8 Ocular bob- Coma Scale it may have been appreciated bing, an intermittent jerking downward eye that there is lateralisation in the individual movement, is seen with destructive lesions in patient which implies a focal cause for the the low pons and with cerebellar haematoma coma. The observation of involuntary move- or . 19 ment affecting the face or limbs and asym- metry of reflexes will help to support this (4) REFLEX EYE MOVEMENTS possibility. Focal seizures are an important These are tested by the oculocephalic and indicator of a focal cause for the coma and oculovestibular responses. The oculocephalic the observation of more generalised seizures or doll's head response is tested by rotating or of multifocal myoclonus would raise the the patient's head from side to side and possibility of a metabolic or ischaemic-anoxic observing the eyes. In coma with an intact cause for the coma with diffuse cortical irrita- brainstem the eyes will move conjugately and tion. The testing of tone as part of the assess- in a direction opposite to the head move- ment of muscle function can be useful in the ment. In a conscious patient such a response comatose patient where it is possible to detect can be imitated by deliberate fixation of the asymmetry of tone not only in the limbs but eyes but is not common. In patients with also in the face. pontine depression the oculocephalic response is lost and the eyes remain in the By this stage of the management of the mid position of the head when turned. patient in coma it should be possible to iden- The oculovestibular response is more accu- tify those patients who are unconscious with rate and useful. It is elicited by instilling focal signs, those who are unconscious with- between 50-200ml of ice cold water into one out focal signs but with the presence of external auditory meatus. The normal meningismus and those who have loss of con- response in the conscious patient is the devel- sciousness without either focal signs or http://jnnp.bmj.com/ opment of nystagmus with the quick phase meningismus (table 3). away from the side of stimulation. A tonic response with conjugate movement of the eye towards the stimulated side indicates an Investigations ofthe patient in coma intact pons and suggests a supratentorial The relevant investigations to be undertaken cause for the coma. A dysconjugate response in the individual patient will be identified by

or no response at all indicates brainstem the differential diagnosis. In general the role on September 24, 2021 by guest. Protected copyright. damage or depression. Both ears should be of investigation in the patient in coma is to stimulated separately and if unilateral irriga- help establish the aetiology of that coma and tion causes vertical eye movement the possi- bility of drug overdose arises because many drugs affect lateral eye movement. The value of oculovestibular testing in patients without lateralising eye signs is con- Table 3 Classification ofdifferential diagnosis ofcoma siderable because they identify the intactness Coma without focal or lateralising signs and without meningismus of the brainstem and corticopontine connec- 1 Anoxic-ischaemic conditions tions but may also reveal the presence of an 2 Metabolic disturbances 3 Intoxications intrinsic brainstem lesion by causing dyscon- 4 Systemic jugate eye posturing. In addition they are the 5 /Hypothermia 6 Epilesy definitive way of identifying patients in psy- Coma without focal or lateralising signs but with meningeal chogenic coma who will show normal nystag- irritation 1 Subarachnoid haemorrhage mus and frequently be distressed by the 2 Meningitis manoeuvre. 3 Encephalitis Coma with focal brainstem or lateralising cerebral signs 1 Cerebral tumour (5) RESPIRATION 2 Cerebral haemorrhage Modern techniques of assisted respiration 3 Cerebral infarction and the need to examine patients in intensive 4 Cerebral abscess The management ofmedical coma 595

will vary from simple blood tests through instances give a clue to the underlying nature. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from more complex blood tests, examination of the If the CT scan is normal then the possibility CSF, electrophysiological tests and imaging of a nonstructural focal abnormality antedat- investigation. Although the electroencephalo- ing the onset of coma or being part of the gram has some hierarchical value in the coma, as occasionally happens with hypogly- assessment of the depth of coma and has caemia or , must be been used to an extent to identify a prognosis considered. If there is no focal structural of coma,2'22 its major role is in identifying abnormality on a CT scan then other investi- patients who are in subclinical status epilepti- gations including metabolic and CSF exami- cus or have complex partial seizures because nation should be carried out. this will significantly alter their manage- Once the image has been obtained the ment.2' It may also be useful in distinguishing question of more definitive therapy, be it between feigned or psychiatric coma, in neurosurgical, the reduction of intracranial which it will be normal, and genuine cerebral pressure by the use of steroids and mannitol, disease when it may show diffuse abnormali- the application of a specific antibacterial or ties or help to identify a focal lesion. The antiviral agent, or the use of chemotherapy prognostic value of the-EEG is probably not may be considered. as great as that obtained from careful obser- 2) Coma with meningeal irritation but without vation of clinical signs.2' physical signs Evoked potentials, predominantly brain- Patients in this group will usually be suffering stem evoked potentials and somatosensory from subarachnoid haemorrhage, acute bac- evoked potentials, may give information relat- terial meningitis, or viral meningo-encephali- ing to the intactness of brainstem pathways tis. The distinction between infective and and to the existence of a cortical component. noninfective can usually be made on the basis Theoretically the use of brainstem evoked of fever and a lumbar puncture will be responses could provide evidence for the expected to reveal the cause. It is a counsel of presence and site of brainstem disease and, as perfection that, because of the theoretical they are relatively unaffected by drug coma, potential of a collection of pus or of identify- they may provide evidence on the aeti- ing the site of the subarachnoid haemorrhage, ology.2425 Regrettably there is as yet little cor- a CT scan should be undertaken before lum- relation between evoked response studies in bar puncture. In practice in many hospitals coma and prognosis but it seems likely that throughout the United Kingdom, CT head the use of somatosensory evoked potentials scanning is not easily available and the pres- and brainstem auditory evoked potentials will ence of meningismus, particularly if associat- become of value in identifying the prognosis ed with fever, raises the possibility of of patients in coma. One technical problem is meningitis and indicates the need for an the need to undertake these recordings in the assessment of the CSF. busy premises of an intensive care unit where When CSF examination is undertaken by considerable other electrical interference is lumbar puncture it is important to remember occurring. that an inadequate lumbar puncture does not Brain imaging techniques including CT preclude the possibility of a pressure cone but

and MRI are important in coma in providing may prevent proper assessment of the CSF. http://jnnp.bmj.com/ evidence of the diagnosis.26 The former has a Although some authorities still recommend very significant role to play in identifying that only a few ml of fluid need be obtained those patients who have a structural cause for for bacterial culture and cell count,'2 in coma though the latter has not yet been for- practice once the dura and arachnoid are mally evaluated in this respect and there are breached by a lumbar puncture needle the problems in inserting the patient in coma possibility of herniation does not depend together with necessary systems solely upon the fluid which is collected but into the field of the MRI scan. rather upon that which may leak out during on September 24, 2021 by guest. Protected copyright. Other more complex techniques such as subsequent hours. It is therefore important intracranial pressure monitoring and cerebral that when a decision to undertake a lumbar blood flow studies are rarely of help in the puncture is made sufficient CSF is obtained diagnosis of medical coma and their role in to enable an adequate assessment of the cell prognosis is not fully evaluated though they count, a gram stain and provide fluid for cul- are likely to be limited by their invasiveness.2' ture and antibody analyses together with a Measures of biochemical parameters in coma measure of the total protein and sugar. are predominently diagnostic but some mea- In those centres in which a CT scan is avail- sures such as brain type creatinine kinase and able the detection of blood in the subarach- specific enolase in the cerebrospinal noid space at CT scan precludes the need for fluid may help in determining prognosis.28 lumbar puncture but whether or not lumbar On clinical grounds patients can be allocat- puncture has been carried out to identify the ed to one of three varieties of coma29:- presence of subarachnoid haemorrhage the 1) Coma with focal signs patient should then be transferred to a neuro- Except in those patients in whom an underly- surgical unit, probably be given intravenous ing and irreversible terminal disease is recog- nimodipine, and be subjected to angiography nised, it is obligatory that CT scan or MRI and . In general those patients who are scan be undertaken to identify the cause of in coma from subarachnoid haemorrhage are the coma. This will define whether or not a less of a surgical emergency than those who structural abnormality is present and in many have higher states of consciousness. 596 Bates

3) The presence of coma without focal signs or have a good prognosis provided they are J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from meningismus given adequate respiratory and circulatory These patients are likely to have a metabolic support during their . They or anoxic cause for their coma. One of the are, however, particularly liable to show commonest causes remains that of drug over- depression of brainstem responses and if the dose and it is appropriate to withdraw blood possibility of drug overdose is not considered to send to the toxicology laboratories in their level of coma may be misinterpreted and patients presenting in this way. In general their prognosis might be thought unduly there will be a clue from the circumstances in pessimistic. which the patient was discovered and from the previous history. Reliance is placed upon The prediction ofoutcome in coma the assessment of metabolic and toxic Having made an assessment of the cause of metabolites in the blood and evidence should coma, established its severity and introduced be sought for hepatic failure, renal failure, appropriate treatment, the physician should hyperglycaemia, hypoglycaemia, and distur- be able to identify the likely outcome to col- bances of electrolytes or acidosis. The ma- leagues and to friends and relatives of the jority of commonly available drugs can now patient. Sedative drugs or alcohol overdose be assayed within blood and serum enzymes are not usually lethal and carry a good prog- should also be estimated. Problems inevitably nosis provided that circulation and respira- arise when patients who are unconscious have tion is protected. The physician can been consuming alcohol and an assessment of reasonably give a good prognosis in patients the relevant importance of this in causing the suffering from self-poisoning with sedative unconsciousness may be difficult. Again the drugs provided that those complications of problem may be helped by the expedient of cardiac arrhythmia, measuring blood alcohol levels. and are avoided or correct- Perhaps the most important single cause of ed. In non-traumatic coma other than that unresponsiveness, which is directly treatable which is drug induced those factors which and correctable, is that of hypoglycaemia and determine the outcome have been defined"3 this should have already been covered during and include the cause of the coma, the depth the initial resuscitation of the patient. By this of the coma, the duration of coma and certain time in management the formal level of blood clinical signs, among the most important of sugar will have been estimated and appropri- which are brainstem reflexes. Overall only ate treatment for hypo and hyperglycaemia 15% of patients in non-traumatic coma for may be instituted. The treatment of acid base more than six hours will make a good or abnormalities will require not only the routine moderate recovery; the other 85% will die, biochemistry but arterial blood gas analysis to remain vegetative, or reach a state of severe monitor progress. Usually a patient who has disability in which they remain dependent. suffered from hypoxia or ischaemia will have Patients whose coma is due to metabolic been identified by the mode of presentation reasons, including infection, organ failure and and by the normality of investigations thus biochemical disturbances, have a better prog- far. The possibility of poisoning with carbon nosis. Thirty five per cent of patients will monoxide should be considered and excluded achieve moderate or good recovery; of those http://jnnp.bmj.com/ by the measurement of carboxyhaemoglobin. whose coma follows hypoxic ischaemic insult In general, patients who have suffered anoxic only 11 % make such a recovery; of those in or ischaemic insult should be given 100% coma due to cerebrovascular disease only 7% oxygen and the monitoring of PAO2 will be can be expected to make such a recovery. important together with the maintenance of Twenty per cent of patients in coma follow- adequate circulation and oxygenation. ing hypoxic ischaemic injury will enter the Patients who are in shock or hypertensive vegetative state due to the likelihood of encephalopathy will be diagnosed by the level hypoxic ischaemia resulting in bihemispheric on September 24, 2021 by guest. Protected copyright. of blood pressure and those with disturbed damage with relative sparing of the brain- temperature regulation by use of the ther- stem. mometer, though a rectal thermometer may Apart from the diagnosis the depth of be required. These causes can then be cor- coma affects the individual prognosis. Those rected. patients not showing eye opening after six In patients with drug overdose the possibil- hours of coma have only a 10% chance of ity of using specific antidotes should be con- making a good or moderate recovery whereas sidered. The use of Naloxone in patients in those whose eyes opened in response to whom there is a high index of suspicion of painful stimuli have a 20% chance of making opioid poisoning and antago- a good recovery. The longer the coma persists nists in self-poisoning with Benzodiazepine. the less likely there is to be recovery; 15% of The use of analeptic agents in barbiturate patients in coma for six hours make a good or poisoning cannot now be supported.'0 Con- moderate recovery compared with only 3% sideration should also be given to clearing the who remain unconscious at one week.3" ingested toxin from the stomach, the passage The study of 500 patients reported by of a nasogastric tube should usually be con- Levey et al 31 using prospective data from sidered and this is one indication for intuba- patients with clearly defined levels of coma, tion of the trachea to prevent the risk of diagnoses and outcomes, showed that some aspiration. The importance of the diagnosis clinical signs are significantly associated with of drug overdose coma is that such patients a poor prognosis: in the total cohort of 500 The management ofmedical coma 597

is obtained from the use of clinical signs and Table 4 Clinical signs andprognosis J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from Patients there is little to be added by more sophisti- with False 95% cated testing other than in identifying the the positive confidence to Cohort sign survivors interval cause of the coma. It is possible predict Time Sign those patients who will not make a recovery 24 hours Absent 500 90 0 0-5% or who will enter a corneal and who will die in coma response vegetative state within the first week of coma. 24 hours Absent 210 52 0 0-5% in medical coma who are pupillary It is rare for patients response in a vegetative state at one month to show 3 days Motor 210 70 0 0-5% poorer than any form of recovery.33 withdrawal 7 days Absent 210 16 0 0-5% roving eye movements Continuation of care in coma from et al.' The long term care of patients Summarised Levy maybe undertaken in an intensive care unit, on a specialist ward or later in a long stay hospital. It is important that those patients in patients corneal reflexes were absent 24 hours whom prognosis is hopeless should not be after the onset of coma in 90 patients and this permanently exposed to the rigors of inten- sign was incompatible with survival. In a sive care , but should continue to more uniform group who suffered anoxic receive basic care within routine hospital injury there were 210 patients: 52 of these wards. So long as patients are considered to had no pupillary reflex at 24 hours, all of have a potential for recovery they should be whom died. By the third day 70 were left with looked after in intensive care units or on spe- a motor response poorer than withdrawal and cialist wards. Their respiration, skin, circula- all died. By the seventh day the absence of tion and bladder and bowel function need roving eye movements was seen in 16 patients , seizures controlled and the level of all of whom died. The confidence intervals consciousness regularly assessed and moni- for all of these criteria were 0 95 (table 4). tored. It is important that the mobility of At the opposite end of the scale more than joints and circulation to pressure areas are 25% of patients who show roving conjugate maintained during the long term care of the eye movements within six hours of the onset patient and the possibility of aspiration pneu- of coma or who show withdrawal responses to monia, peptic ulceration and other complica- pain or eye opening to pain, will recover inde- tions of long term intensive care be pendence and make a moderate or good considered and avoided. Techniques such as recovery. The use of combinations of clinical and the use of steriod signs help to improve the accuracy of progno- therapy are not to be used routinely in the sis: at 24 hours the absence of a comeal management of the comatose patient as they response, pupillary light reaction or caloric or do not improve prognosis and may specifi- doll's eye response is not compatible with cally compromise recovery.'4 recovery to independence. Patients who are

able to speak words within 24 hours or who The persistent vegetative state http://jnnp.bmj.com/ show nystagmus on caloric testing are likely The relative resilience of the brainstem allows to make a good recovery (table 5)." it to survive injuries which may create irre- The most accurate prediction of outcome versable damage to the cerebral hemispheres in a patient in medical coma is still that which and then the patient will enter that state defined as vegetative. Retrospectively, after postmortem examination, it may be possible Table S Prediction ofoutcome ofcoma at 24 hours by a combination ofclinical signs to identify massive neocortical damage which will indicate that the patient was permanently on September 24, 2021 by guest. Protected copyright. Percentage ofpatients with different outcomes in the vegetative state,35 but there are no DIPVS SD MDIGR clinical or laboratory means of confirming this before postmortem, and therefore the 500 patients term persistent vegetative state rather than permanent vegetative state is used clinically. + are concerned Any two reacting: Specialists in rehabillitation Pupils that physicians may take the attitude that Corneals > No (120) 97 2 1 there is no point in treating such patients Oculovestib therefore creating a self fulfilling prophecy of i Yes poor prognosis, no treatment and poor Motor better than flaccid No (183) 80 8 12 outcome.36 There is continuing debate as to the poten- Yes tial for recovery for patients who are vegeta- Motor withdrawal No (135) 69 14 17 tive. In patients who have suffered non traumatic injury such as anoxia and + Yes ischaemia, the prognosis for recovery from Verbal moans No (106) 58 19 23 the vegetative state is poor after the first few weeks. There are some reports of patients No- Yes (56) 46 13 41 who have suffered coma as a result of head Summarised from Levy et al.3' trauma in whom an improvement from the 598 Bates

vegetative state has been recognised after 13 Fisher CM. The neurological examination of the comatose patient. Acta Neurol Scand 1969;45(suppl 46): J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.6.589 on 1 June 1993. Downloaded from months, but these anecdotal cases of recovery 1-56. from vegetative state are difficult to validate 14 De Jong RN. The neurological examination, 4th ed. Haggerstown: Harper and Rowe, 1979. and it seems possible that such patients were 15 Crill WE. Homer's syndrome secondary to deep cerebral not truly vegetative, rather in a state of pro- lesions. Neurology 1966;16:325-7. 16 Walsh FB, Hoyt WF. Clinical neuro-opthalmology, 3rd found disability but with cognition, at the ed. Baltimore: Williams and Wilkins, 1969. beginning of the observation.37-39 17 Stewart JD, Kirkham TH, Mathieson G. Periodic alter- nating gaze. Neurology 1979;29:222-4. Investigations do not help to identify vege- 18 Daroff RB, Hoyt FF. Supranuclear disorders of ocular tative state because many types of EEG pat- control systems in man. In: Bach-y-Rita, Collins, Hyde, eds. The control of eye movements. New York: Academic tern have been recorded from near normality Press, 1971. to a flat record and CT scans usually show 19 Fisher CM. Ocular bobbing. Arch, Neurol 1964;11:543-6. 20 Leigh RJ, Shaw DA. Rapid regular breathing in uncon- considerable cortical atrophy with ventricular scious patients. Arch Neurol 1976;33:356-61. dilatation. Somato-sensory evoked responses 21 Jorgensen EO, Malchow-Moloer A. Natural history of global and critical brain ischaemia. Resuscioion are said to show loss of the cortical compo- 1981;9:133-91. nent and PET scans to show cortical meta- 22 Synek VM. EEG abnormality grades and subdivisions of prognostic importance in traumatic and anoxic coma in bolic under activity. None is diagnostic in adults. Clin Electroencephalogr 1988;19:160-6. their results.40 23 Engle J, Ludwig BI, Fetell M. Prolonged partial complex : EEG and behavioural observations. Patients in a persisting vegetative state will Neurology 1978;28:863-9. often have received at 24 Papanicolaou AC, Loring DW, Eisenberg HM, et al. Auditory brain stem evoked responses in comatosed sometime during their initial coma or resusci- head injured patients. Neurosurgery 1986;18:173-5. tation, but they are not truly respirator 25 Walser H, Emry M, Janzer R Somatosensory evoked potentials in comatosed patients: correlation with out- dependent and, since they are able to breathe, come and neuropathological findings. J Neurol 1968; are only dependant upon carers for the supply 233:34-40. 26 Tasker RC, Matthew DJ, Kendall B. Computed tomo- of liquid and nutrients and the prevention of graphy in the assessment of raised intracranial pressure complications. The management of individ- in non-traumatic coma. Neuropaediatrics 1990;21:91-4. 27 Jaggi JL, Obrist WD, Jennarelli TA, Langfitt TW. ual patients will depend upon circumstances Relationship of early cerebral blood flow and metabo- of the and consid- lism to outcome inacute . J. Neurosurg and other aspects diagnosis 1990;72:176-182. ered prognosis.4' 28 Roine RO, Somer H, Caste M, et al. Neurological out- come after out of hospital cardiac arrest: prediction by cerebrospinal fluid enzyme analysis. Arch Neurol 1989; 46:753-6. 29 Adams RD, Victor M. Principles of neurology, 4th ed. New 1 Bates D, Cartlidge NEF. The Prognosis of Medical York: McGraw Hill, 1989. Coma. In: Tunbridge WMG, ed. Advanced medicine. 30 Schwartz GR. Emergency toxicology and general prin- London: Pittman Medical, 1981. ciples of medical management of the poisoned patient. 2 Plum F, Posner JB. 7he diagnosis of stupor and coma, 3rd In: Schwartz, Safar, Stone, et al, ed. Principles and prac- ed. Philadelphia: Davis, 1980. tice ofemergency medicine. London: WB Saunders, 1978. 3 Brodal A. Neurological anatomy in relation to clinical 31 Levy DE, Bates D, Caronna JJ, et al. Prognosis in non- medicine, 3rd ed. Oxford: Oxford University Press, traumatic coma. Ann Intern Med 1981;94:293-301. 1981. 32 Bates D. Coma. In: Swash, Oxbury, eds. Clinical 4 Jouvet M. The role of monoamines and acetyl choline neurology. Edinburgh: Churchill Livingston, 1991. containing neurones in the regulation of the sleep/wake 33 Bates D. Defining prognosis in medical coma. J Neurol cycle. Rev Physid 1972;64:166-307. Neurosurg Pswychiay 1991;54:569-71. 5 Defeudis FV. Cholinergic roles in consciousness. In: 34 Teasdale G. Prognosis of coma after head injury. In: Defeudis FV, ed. Central chonergic systems and behav- Tunbridge WMG, ed. Advanced medicine. London: iour. London: Academic Press, 1974. Pittman Medical, 1981. 6 Tinuper P. Idiopathic recurring stupor: A case with 35 Dougherty JH, Donald MD, Rawlinson DG, et al. possible involvement of the gamma aminobutyric Hypoxic-ischaemic brain Injury in the vegetative state.

acid(GABA)ergic system. Ann Neurol 1992 31:503-6. Neurol 1981;31:991-7. http://jnnp.bmj.com/ 7 Medical Research Council Brain Injuries Committee. A 36 Andrews K. Managing the persistent vegetative state. glossary of psychological terms commonly used in cases BMJ 1992;305:486-7. of head injury. MRC War Memorandum. London: 37 May PG, Kaelbling R Coma of over a year's duration HMSO, 1941. with favourable outcome. Dis Nerv Syst 1968;29: 8 Teasdale G, Jennett B. Assessment of coma and impaired 837-40. consciousness: a practical scale. Lancet 1974;2:81-4. 38 Rosenberg GA, Johnson SF, Brenner RP. Recovery of 9 Jennett B, Plum F. The persistent vegetative state: a syn- cognition after prolonged vegetative state. Ann Neurol drome in search of a name. Lancet 1972;1:734-7. 1977;2:167-8. 10 Cairns H. Disturbances of consciousness with lesions of 39 Snyder BD, Cranford RE, Rubens AB. Delayed recovery the brain stem and diencephalon. Brain 1952;75: from postanoxic persistent vegetative state. Ann Neurol

109-46. 1983;14:152-3. on September 24, 2021 by guest. Protected copyright. 11 Feldman MH. Physiological observations in a chronic case 40 Hansotia TI. Persistent vegetative state. Arch Neurol oflocked in syndrome. Neurol 1971;21:459-78. 1985;42:1048-52. 12 Harris JO, Berger JR Clinical approach to stupor and 41 ANA Committee on Ethical Affairs. Persistant vegetative coma. In: Bradley WG, Daroff RB, Fenichel GM, state: report of the American Neurological Association Marsden CD, eds. Neurology in nicalpractice. London: Committee on Ethical Affairs. Ann Neurol 1993;33: Butterworth, 1991. 386-90.