Π
UNIVERSITY OF KHARTOUM
Faculty of Medicine
Postgraduate Medical Studies Board
PATIENTS WITH NON-TRAUMATIC COMA IN
KHARTOUM TEACHING HOSPITAL:
AETIOLOGY & OUTCOME
By
Dr. El Sadig Ibrahim Osman
M.B.B.S (U of K)
A thesis Submitted in partial fulfillment for the requirements
of the Degree of Clinical MD in Medicine,
April, 2002
Supervisor
Dr. Musa Mohammed Kheir
MBBS, MD, Khartoum
Faculty of Medicine,
University of Khartoum.
‫‪Π‬‬
‫ﻗﺎﻝ ﺍﷲ ﺗﻌﺎﻟﻰ ‪:‬‬
‫ﺍﻗﺮﺃ ﺑﺎﺳﻢ ﺭﺑﻚ ﺍﻟﺬﻱ ﺧﻠﻖ* ﺧﻠﻖ‬
‫}‬
‫ﺍﻹﻧﺴﺎﻥ ﻣﻦ ﻋﻠﻖ* ﺍﻗﺮﺃ ﻭﺭﺑﻚ ﺍﻷﻛﺮﻡ*‬
‫{‪.‬ﺍﻟﺬﻱ ﻋﻠﻢ ﺑﺎﻟﻘﻠﻢ* ﻋﻠﻢ ﺍﻹﻧﺴﺎﻥ ﻣﺎ ﻟﻢ ﻳﻌﻠﻢ‬
‫ﺻﺪﻕ ﺍﷲ ﺍﻟﻌﻈﻴﻢ‬
To
my family
&
friends
I am very grateful to my supervisor Dr. Musa Mohammed Kheir, Assistant professor of Medicine,
Faculty of Medicine, University of Khartoum and Khartoum Teaching Hospital. I should like to thank
him for his wise but forbearing guidance from the research conception to its completion. I have the
great pleasure and fortune being supervised by him.
Thanks to Mr. Hassan Ali, Department of Medical Statistics, Ministry of health, Sudan for the help
with the presentation & statistical interpretation of the data.
Thanks are extended to the Medical Registrars of Khartoum Teaching Hospital who helped much in
data collection.
The drafts, corrections, alterations and final copies have been cheerfully typed by Miss Widad
A/Magsood, without her the study wouldn’t have appeared.
I am also indebted to all colleagues who contributed in the collection of data.
To all these I owe and gladly acknowledge, a considerable debt.
RAS
Reticular activating substance
GABA
Gamma aminobutyric acid
GCS
Glassgo coma scale
EEG
Electroencephalography
CT
Computerized tomography
MRI
Magnetic resonance imaging
CSF
Cerebrospinal fluid
PET
Positron emission tomography
DKA
Diabetic ketoacidosis
HHS
Hyperglycaemic hyperosmolar syndrome
KTH
Khartoum Teaching Hospital
SUH
Soba University Hospital
ICUs
Intensive Care Units
ABSTRACT
………………….
‫ﻤﻠﺨﺹ ﺍﻷﻁﺭﻭﺤﺔ‬
‫>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>‬
LIST OF TABLES
Page
Table 1:
Antenatal variables
49
Table 2:
Intrapartum variables
50
Table 3:
Neonatal variables
51
Table 3-6: The relationship between GCS and the 2 week outcome
in patients with coma
59
Table 3-7: The relationship between age and final outcome in
patients with coma
60
Table 3-8: The relationship between coma duration and final
outcome in 100 Sudanese patients with coma
61
Table 3-9: GCS on admission and the 2 week outcome in
patients with cerebrovascular disease
62
Table 3-10: The effect of hypertension on the outcome of
Coma due to cerebrovascular disease
63
Table 3-11: The effect of diabetes on the outcome of
Coma due to cerebrovascular disease
64
LIST OF FIGURES
Page
Figure 1:
…………………….
37
Figure 1:
…………………….
37
Figure 1:
…………………….
37
Figure 1:
37
…………………….
CONTENTS
Page
Dedication ………………………………………………………………...I
Acknowledgment……………………………………………..…………..II
Abbreviations……………………………………………………………III
English abstract…………………………………………………………..V
Arabic abstract………………………………………...………………..VII
List of figures ………………………………………...…………………IX
List of tables………………………………………………………...…...X
CHAPTER ONE
INTRODUCTION………………………………………………………...1
LITERATURE REVIEW…………………………………………………2
OBJECTIVES…………………………………………………………...30
CHAPTER TWO
PATIENTS & METHODS ……………………………………………...31
CHAPTER THREE
RESULTS ……………………………………………………………….33
CHAPTER FOUR
DISCUSSION……………………………………………………………56
CONCLUSION ………………………………………………………….62
RECOMMENDATIONS ………………………………………………..63
REFERENCES…………………………………………………………..64
APPENDIX (Questionnaire)
INTRODUCTION & LITERATURE REVIEW
It is estimated that 3% of admissions to emergency wards are
due to diseases causing a disorder of consciousness. This makes it
necessary to acquire a systematic approach to their diagnosis and
management.(1) Few problems are more difficult to manage than the
unconscious patient, because the potential causes of coma are
considerable, and because the time for diagnosis and effective
intervention is relatively short. All alterations in arousal should be
regarded as acute and potentially life-threatening emergencies until
vital functions are stabilized, the underlying cause of the coma is
diagnosed, and reversible causes corrected.
Delay in instituting
treatment for a patient with raised intracranial pressure may have
obvious consequences in terms of pressure coning, but similarly the
unnecessary investigations of
patients in metabolic coma, with
imaging techniques may delay the institution of appropriate therapy.
It is therefore essential for the physician in charge to adopt a
systematic approach initially, to ensure resuscitation and then to
direct further tests towards producing the most rapid diagnosis and
the most appropriate therapy. The development of such a systematic
approach demands an understanding of the pthophysiology of
consciousness and the ways in which it may be deranged.
Causes of loss of consciousness:
Consciousness is dependent on activation of the cerebral hemispheres by the reticular activating system
(RAS) of the brainstem. Lesions affecting both cerebral hemispheres, the RAS of the brainstem or its
connections may cause coma. The lesion could be structural or more commonly a metabolic
derangement (Table 1-1). Hemispherical lesions may cause coma when bilateral, or when metabolic
derangements such as encephalitis, generalized seizures, drug ingestion, global ischaemia or
hypoglycaemia interfere with awareness. Masses or secondary brain swelling enlarging enough to
compress the contralateral hemishpere or the brainstem RAS may cause coma. Transtentorial
herniation by mass lesions with progressive brainstem compression causes coma with neurologic signs
corresponding to the level damaged. The anatomy of consciousness is illustrated in Fig 1-1.
Table 1-1: Systemic causes of coma:
Drug over dosage
Hypothyroidism.
Anoxia-ischaemia.
Hypertensive
D.M (DKA-HHS)
encephalopathy.
Respiratory failure.
Pituitary apoplexy.
Renal failure.
Alcohol.
Hepatic failure.
CO-poisoning.
Cardiac failure.
Werniche’s encephalopathy.
Hypoglycaemia.
Septicaemia.
Hypothermia
Hypo-hypernatraemia.
Hypo-hypercalaemia.
The ascending RAS is a continuous isodentritic core extending from the
medulla through the pons, to the midbrain, which is continuous caudally
with the intermediate grey lamina of the spinal cord and rostrally with the
subthalamus, the hypothalamus and the thalamus.(2) Its functions and
interconnections are considerable and its role greater than that of a simple
arousal system. The content of consciousness is a function of the cerebral
cortex of both hemispheres. The neurotransmitters involved in this arousal
system are not fully determined though it seems likely that in addition to
cholinergic systems, gamma aminobutyric acid "GABA" may be
important in controlling consciousness.(3-5)It follows from recognition of
the anatomy and pharmacology of the ascending RAS that structural
damage to this pathway or chemical derangement of the neurotransmitters
involved are mechanisms whereby consciousness may be impaired. Such
conditions will occur with focal lesions in the brainstem, mass lesions in
the posterior fossa impinging directly on the brainstem, or mass lesions
involving the cerebral hemispheres causing tentorial pressure coning and
consequently compromising the ascending RAS either by direct pressure
or by a process of ischaemia (Fig 1-2).
In addition toxins, including drugs may affect the RAS and thereby result
in loss of consciousness.
The content of consciousness resides in the cerebral cortex of
both hemispheres. Unlike those discrete functions such as language
or vision, which are focally located within the cortex, the content of
consciousness can best be regarded as the amalgam of all cognitive
functions.
For a physician attempting to diagnose the cause of coma
consideration must be given to the following:
1-
Supra or infratentorial mass lesions.
Typically
these will show evidence of raised intracranial pressure and
commonly produce focal signs.
neoplasm,
haematoma,
infarction,
Processes such as
cerebral
oedema,
abscess, focal encephalitis or venous sinus thrombosis
should be considered.
2-
Subtentorial destructive lesions or the local effect
of toxins. These processes will directly damage the
ascending RAS, as in brainstem infarction and the much
more common effects of self-poisoning with sedative drugs.
3-
Diffuse damage to the cerebral cortex.
Bilateral
cortical injury is most commonly seen in states of hypoxia
and ischaemia, but may be mimicked by hypoglycaemia,
ketoacidosis, electrolyte abnormalities, bacterial meningitis,
viral
encephalitis
encephalopathy.
and
diffuse
post
infectious
It is also the likely cause following
subarachnoid haemorrhage.
DEFINITIONS:
There is a continuum from the individual in full consciousness
to the patient in deep coma. The terminology which is most usually
employed derives from the British injuries Committee of the medical
research council.(6)
1-
Confusion: impaired capacity to think clearly and to perceive
and respond to, and remember current stimuli.
disorientation.
Confusion implies a generalized disturbance of
cortical cerebral function.
consciousness
There is also
and
An intermediate state between normal
confusion
is
described
as
clouding
of
consciousness.
2-
Obtundation:
a
disorder
of
alertness
associated
with
psychomotor retardation.
3- Delerium: implies a much more disturbance of consciousness with
motor restlessness, transient hallucinations, disorientation
and
perhaps delusions.
4- Stupor: a state in which the patient exhibits little or no
spontaneous activity. Although the individual appears to be asleep,
he or she will awaken to vigorous stimulation, but shows limited motor
activities and usually fails to speak.
5- Coma: a state of unarousable psychologic unresponsiveness in
which the subject lies with eyes closed and show no psychologically
understandable response to an external stimulus or inner need. This
may be shortened to " a state of unarousable unresponsiveness",
which implies both a defect in arousal and awareness of self or
environment as an inability to respond.
A more useful assessment of coma is derived from the
hierarchical Glassgo Coma Scale(7) G.C.S "Table 1-2" in which
patients who fail to show eye opening in response to voice, perform
no better than weak flexion in response to pain and make at best only
unrecognizable grunting noises in response to pain are regarded as
being in coma.
6- Coma-like Syndromes: Include the vegetative state in which
cognitive function is lost but the brainstem functions are retained. It
was described by Jennet & Plum(8) and results from damage to the
cortical hemispheres commonly after anoxic injuries from which the
brainstem unlike the cortex is capable of recovery.
Another coma-like syndrome is termed akinetic mutism, in
which the patient seems alert but unresponsive. It differs from the
vegetative state by the flaccid tone and unresponsiveness to
peripheral pain.
It is due to bilateral frontal lobe lesions, diffuse
lesions of the cortex or lesions of the deep grey matter.(9)
Feldman describes the locked-in syndrome,
which is a deefferented state caused by bilateral
ventral pontine lesions damaging the corticospinal and corticobulbar tracts with total paralysis
below the level of the third cranial nerve nuclei.(10)
In pseudocoma, the patients appear in coma
without structural, metabolic, toxic or psychiatric
disorder being apparent and can be shown to
have intact brainstem activity and corticopontine
projections and not to be in coma.
Resuscitation:
The patient who is brought to the hospital
casualty department, though not having been
exposed to trauma may be harbouring delayed
effects of trauma such as a subdural haematoma
or meningitis following basal skull fracture. A
physician dealing with a comatose patient should
consider all possible causes of loss of
consciousness. Thus in the diagnosis of medical
coma, it is not easy to exclude the patient in coma
following head injury. If one excludes patients
with transient loss of consciousness following
seizures, syncope, cardiac dysrhythmias or
hypoglyacemia and those unresponsive due to
impending death and considers the patients who
have been comatose for six hours or more, then
40% will have suffered a hypoxic-ischaemic insult,
a third will be unconscious as a result of
cerebrovascular disease and a quarter will be
unconscious as a result of metabolic coma,
including infection, renal failure, hepatic failure
and complications of diabetes mellitus.(11) If one
considers only those cases which are regarded of
unknown aetiology, then diffuse metabolic causes
account for 36%, structural disease accounts for
34% and 30% are due to drug overdose.(12)
Resuscitation of an unconscious patient is
required before full assessment is undertaken.
Protection of the airway, respiration, support of
the circulation and provision of an adequate
supply of glucose are all important in stabilizing
the patient. Noting respiration (rate and pattern) is
important because depressed respiration is a clue
to drug overdose or a metabolic disturbance,
increased respiration is a clue to hypoxia,
hypercapnia or acidosis and fluctuating
respiration may indicate a brainstem lesion.
Once adequate circulation and oxygenation
are assured and monitored, blood should be
withdrawn for the determination of blood glucose,
biochemical estimations and toxicology. It is
reasonable to give a bolus of 25-50g of dextrose
despite the present controversy about the use of
I.V glucose in patients with ischaemic or anoxic
brain damage as it augments lactic acid
production by anaerobic glycolysis, and
potentially worsens ischaemic or anoxic
damage.(13) But the fact that such a small quantity
of glucose will not be immediately harmful, and
being life-saving in a hypoglycaemic patient
justifies its routine administration.
The establishment of baseline blood
pressure, pulse, temperature, the establishment
of an intravenous line and stabilization of the
neck, together with the examination for meningitis
is an essential part of resuscitation. In a comatose
patient who is febrile with meningism seen
outside the hospital environment, the
intramuscular injection of penicillin before
transfer is now recognized to carry a significant
advantage.
History:
Once the patient is stable, it is important to
obtain as much information as possible from
those who accompanied the patient to hospital or
who witnessed the onset of coma. The
circumstances in which consciousness was lost
are of vital importance in helping to identify the
diagnosis. Generally coma is likely to present in
one of three ways: as a predictable progression of
an underlying illness; as an unpredictable event
in a patient with a previously known disease, or a
totally unexpected event. Distinctions between
these presentations are often achieved by the
history of the circumstances in which
consciousness was lost. In the first category are
patients following focal brainstem infarction who
deteriorate or those with known intracerebral
lesions who show similar deterioration. In the
second category are patients with recognized
cardiac dysrhythmias or the known risk factor of
sepsis from an intravenous line. In the final
category it is important to determine whether
there has been a previous history of seizures,
trauma, febrile illness or focal neurological
disturbances. The history of a sudden collapse in
the midst of a busy street or office, indicates the
need for different investigations from those
necessary for the patient who is discovered at
home in bed, surrounded by bottles of sedative
tablets.
Examination:
Involves a rapid but systematic examination
to identify possible causes of coma.
Temperature: fever usually indicates
infection or rarely a diencephalic lesion affecting
the temperature regulating centers. Most
commonly the combination of fever and coma
indicates a systemic infection such as pneumonia
with septicaemia or a cerebral cause such as
meningitis, encephalitis or brain abscess.
Worldwide the commonest cause of fever and
non-traumatic coma is cerebral malaria. When
seizures occur together with fever the possibility
of encephalitis or cerebral abscess is greatly
increased.
On the other hand, hypothermia is seen with
alcohol or barbiturate intoxication; with peripheral
circulatory failure or elderly patients with stroke
who are discovered hours later in an underheated room and rarely in profound myxoedema.
Heart rate: Tachyarrhythmias or
bradyarrhythmias may be the cause of coma due
to cerebral hypoperfusion or the embolic disease
associated with atrial fibrillation.
Blood pressure: Hypotension may indicate
shock, myocardial infarction, septicaemia or
intoxication. It may also indicate Addison's
disease or diabetes mellitus. Hypertension is of
less help in the diagnosis since it may be the
cause of coma as in hypertensive encephalopthy,
intracerebral haemorrhage or be the result of the
cerebral lesion.
Respiration: Generally slow shallow
respiration raises the question of drug
intoxication. Deep, rapid respiration suggests
pneumonia or acidosis, which may also occur in
brainstem lesions causing central neurogenic
hyperventilation.
Breath: The odour of the breath of a
comatose patient may indicate intoxication with
alcohol, raise the question of diabetes or suggest
the coma is uraemic or hepatic.
Cardiovascular: Auscultation and
examination of the heart may indicate valvular
disease and raise the possibility of endocarditis.
Bruits over the carotids may indicate the
presence of cerebrovascular disease and splinter
haemorrhages in the nail-bed would raise the
possibility of subacute bacterial endocarditis or
collagen vascular diseases.
Abdomen: Examination of the abdomen may
reveal signs of trauma or rupture of viscera;
hepatomegaly or splenomegaly may indicate the
possibility of portocaval shunt and finding of
polycystic kidneys would raise the possibility of
subarachnoid haemorrhage.
Meningism: Examination of the skull and
spine is important and the physician should
always look for neck stiffness, Kernig's sign and
Brudzinski's test. The presence of neck stiffness
alone suggests a foraminal pressure cone, while
neck stiffness with positive Kernig's sign and
Brudzinski's test indicate a diffuse meningitic
process.
Fundal examination: The presence of
papilloedema or fundal haemorrhage or evidence
of emboli together with findings of hypertensive,
vascular, or diabetic retinopathy is important. The
fundal appearance may be diagnostic as in the
finding of subhyaloid haemorrhage but more
commonly help to confirm or refute evidence of
raised intracranial pressure. The absence of
papilloedema does not necessarily mean that
there is no raised intracranial pressure.
Neurological examination: Aimed to assess
the level of consciousness using the Glassgo
coma scale (Table 1-2), elicitation of various reflex
responses(14) to identify the activity of the
brainstem and to search for evidence of
lateralization
(Table 1-3). Neurological signs
of diagnostic importance are given in (Table 1-4).
Psychogenic coma is recognized by apparent
unresponsiveness, yet normal pupillary reactions
and nystagmus on caloric testing.(15).
The G.C.S provides the most useful
assessment of the level of consciousness.(16) The
responses to commands, calling the patient's
name and painful stimuli are observed for eye
opening, limb movement and voice. Painful
stimuli such as supraorbital pressure and nail-bed
pressure for central and peripheral stimulation
respectively, are useful and reproducible. The
best response is recorded is assessing the G.C.S.
The level of coma should be assessed serially and
is one of the most important indications for
further investigation and management.
Table 1-2: The Glassgo coma scale:
Eye opening:
Spontaneou
4
s.
3
To speech.
2
To pain.
1
Nil
Motor response:
Obeys.
6
Localizes.
5
Withdraws.
4
Abnormal
3
2
flexion.
Extensor
1
response.
Nil.
Verbal response:
Orientated.
5
Confused
conversation.
4
3
Inappropriat
e words.
2
1
Incomprehe
nsible sounds.
Nil.
Table 1-3: Neurological assessment in coma:
•
Level of consciousness:
- Assessed using the G.C.S.
•
Brainstem function:
-
Pupillary reaction.
-
Spontaneous eye movements.
-
Occulocephalic responses.
-
Vestibulo-occular responses.
-
Corneal responses.
-
Respiratory pattern.
•
Motor function:
-
Motor responses.
-
Tendon reflexes.
-
Muscle tone.
Table 1-4: Neurological signs in the common causes
of coma:
Causes
Coma type
Neurological signs
Drug coma
RAS
Depression
of
depression
brain stem reflexes.
Symmetrical signs
Supratentorial mass Unilateral
lesions: hemisphere
lesions
Tum
(Coning)
our.
Hemiparesis.
Third nerve palsy.
•
depression of
Hae
brainstem reflexes.
morrhage.
Brainstem
infarction or
haemorrhage
Subsequent
RAS
damage
Asymmetrical
signs.
Brainstem
reflex
abnormality.
Cerebellar mass
lesions:
- Tumour,
haemorrhage.
- Metabolic
disorders.
RAS
damage
Asymmetrical
signs.
Brainstem
reflex
abnormality.
•
Relative
preservation of
brainstem relexes
•
Hepatic failure
•
Uraemia
Diffuse
cortical
depression
Seizures.
Asymmetrical
Acid-base
signs.
disturbances
Endocrine
dysfunction.
•
Disorders of
temperature
regulation.
Subrachnoid
haemorrhage
meningitis
encephalitis
cerebral anoxia
Diffuse
Very
variable
cortical
signs.
damage
with or
Stiff neck.
without
•
Relative
coning
diffuse
preservation of
cortical
brainstem reflexes.
depression.
Seizures.
Brainstem function: Brainstem reflexes are
particularly important in helping to identify those
lesions that may affect the RAS, explain the
reason for coma and potentially help in identifying
the viability of the patient.
1.
Pupillary reactions: unilateral dilatation of the
pupil with loss of the light reflex indicates uncal
herniation or posterior communicating artery
aneurysm. Midbrain lesions cause loss of the
light reflex with mid position pupils, where as
potine
lesions
response.
meiosis
Fixed
but
dilatation
retained
of
the
light
pupils
indicates central diencephalic herniation. A
Horner's syndrome indicates an ipsilateral
lesion
in
the
hypothalamus,
thalamus
or
brainstem, but it can be due to disease affecting
the wall of the carotid artery when anhidrosis
will only affect the face.(17) Hepatic, renal failure
and other forms of metabolic coma make light
reflexes brisk and the pupils, therefore, appear
smaller, while most drug intoxications cause
sluggish reaction of the pupils and a pontine
haemorrhage
typically
cases
a
pin
point
pupil.(18)
2.
Corneal
responses:
absence
of
corneal
responses indicates very deep coma, and if
local corneal disease or drug overdose are
excluded, it is a poor prognostic sign.
3.
Spontaneous
eye
movements:
conjugate
deviation of the eyes indicates either an
ipsilateral hemisphere lesion or a contralateral
brainstem lesion. Dysconjugate eye movements
indicate damage to the ocular or abducens
nerves. Roving eye movements seen in light
coma (similar to those of sleep) help to exclude
psychogenic unresponsiveness.(19)Spontaneous
nystagmus is rare in coma and it reflects the
interaction between the vestibulo-ocular system
and the cerebral cortex. Rotatory nystagmus
and convergence nystagmus may be seen with
lesions.(20)
midbrain
Ocular
bobbing,
an
intermittent jerking downward eye movement, is
seen with destructive lesions in the low pons
and
with
cerebellar
haematoma
or
hydrocephalus.(21)
4.
The
oculocephalic
responses
identify
the
and
oculovestibular
intactness
of
the
brainstem and can differentiate infratentorial
from supratentorial lesions. They can also
differentiate genuine coma from psychogenic
coma.
5.
Respiration: Periodic breathing indicates a
lesion lower in the brainstem and carries a poor
prognosis. Regular, rapid breathing correlates
with
pulmonary
complications
and
poor
prognosis rather than the site of neurological
disease in patients in coma.(22)
Motor function: As part of the G.C.S it may
have been appreciated that there is laterlization in
the individual patient and implies a focal cause for
the coma. Involuntary movements affecting the
face or limbs and asymmetry of reflexes will help
to support this possibility. Focal seizures are an
important indicator of a focal cause for the coma.
Generalized seizures or multifocal myoclonus
would raise the possibility of a metabolic or
ischaemic-anoxic cause for the coma with diffuse
cortical irritation.
According to the above assessment the
comatose patient can be fitted into one of three
classes: coma without focal or lateralizing signs
and without meningism; coma without focal or
lateralizing signs but with meningial irritation and
coma with focal brainstem or lateralizing cerebral
signs (Table 1-5).
Table 1- 5: Classification of differential diagnoses of
coma:
•
Coma without focal or lateralizing signs and
without meningism:
1.
Anoxic-ischaemic conditions.
2.
Metabolic disturbances.
3.
Intoxications.
4.
Systemic infections.
5.
Hyperthermia/hypothermia.
6.
Epilepsy.
•
Coma without focal or lateralizing signs but
with meningism:
1.
Subarachnoid haemorrhage.
2.
Meningitis.
3.
Encephalitis.
•
Coma with focal brainstem or lateralizing
cerebral signs:
1.
Cerebral tumour.
2.
Cerebral haemorrhage.
3.
Cerebral infarction.
4.
Cerebral abscess.
Investigations of the patient in coma:
According to the differential diagnosis
(Table 1-5), the relevant investigations to be
undertaken in the individual patient will be
identified. Their purpose is to establish the
aetiology of coma, and they vary from simple
blood tests, through more complex blood tests,
examination of the cerebrospinal fluid,
electrophysiological and imaging investigations.
Although the electroencephalogram has some
hierarchical value in the assessment of the depth
of coma,(23,24) its major role is in identifying
patients who are in sub-clinical status epilepticus
or have complex partial seizures, because this will
significantly alter their management.(25) It may also
be useful in distinguishing psychiatric coma and
genuine cerebral disease. The prognostic value of
the EEG is probably not as great as that obtained
from careful observation of clinical signs.(23)
Evoked potentials, predominantly brainstem
evoked potentials and somatosensory evoked
potentials may give information relating to the
intactness of the brainstem and to the existence
of a cortical component. Theoretically, the use of
brainstem evoked responses could provide
evidence for the presence and site of brainstem
disease and as they are relatively unaffected by
drug coma, they provide evidence on the
aetiology.(26,27) However, there is as yet little
correlation between evoked response studies in
coma and prognosis, but it seems likely that the
use of somatosensory evoked potentials and
brainstem auditory evoked potentials will become
of value in identifying the prognosis of patients in
coma. Brain imaging techniques including
computed tomography (C.T) and magnetic
resonance imaging (M.R.I) are important in coma
in providing evidence of the diagnosis.(28) C.T has
a very important role to play in identifying those
patients who have a structural cause for coma.
M.R.I has the problem of inserting the patient in
coma, together with the necessary life support
system into the field of the M.R.I scan, but it may
give better information than C.T scan.
Other more complex techniques such as
intracranial pressure monitoring and cerebral
blood flow studies are limited by their
invasiveness.(29) Measurement of biochemical
parameters in the cerebrospinal fluid of comatose
patients, such as brain type creatinine kinase and
neuron specific enolase may help in determining
prognosis.(30)
Diagnostic classification:
On clinical grounds patients can be
allocated to one of the following three varieties of
coma.(31)
1.
Coma with focal signs: such patients should
have a C.T and or M.R.I scan to identify the
cause of coma. This will define whether or not
there is a structural abnormality and in many
instances gives a clue to the underlying nature.
If the C.T scan is normal, then the possibility of
a non-structural focal abnormality antedating
the onset of coma, or being part of the coma, as
occasionally occurs with hypoglycaemia or
hepatic encephalopathy must be considered. If
there is no focal lesion on C.T scan, then other
investigations including metabolic and C.S.F
examination should be carried out.
2.
Coma with meningeal irritation but without focal
signs: such patients will usually be suffering
from
subarachnoid
bacterial
meningitis
haemorrhage,
or
viral
acute
meningo-
encephalitis. The distinction between infective
and non-infective causes can usually be made
on the basis of fever and a lumbar puncture will
be expected to reveal the cause.
Because of the theoretical potential of a
collection of pus or identifying the site of the
subarachnoid haemorrhage, C.T should be
undertaken before lumbar puncture. However if
facilities for C.T scan are not available, the
presence of meningism, particularly if associated
with fever raises the possibility of meningitis and
indicates the need for an assessment of the C.S.F.
The possibility of coning following lumbar
puncture does not depend on the amount of C.S.F
taken but rather on the amount of C.S.F that will
leak after the dura and arachnoid are breached.
However, some authorities recommend taking
only a few mls for cell counts, bacterial culture,
total protein, sugar and antibody analysis.(12) In
centres where C.T is available the detection of
blood in the subarachnoid space, precludes the
need for lumbar puncture and transfer of such
patients to a neurosurgical unit is appropriate,
despite the fact that patients with subarachnoid
haemorrhage and coma are of less urgency than
those with a higher status of consciousness.
3.
Coma without focal signs or meningism: these
patients are likely to have a metabolic or anoxic
cause for their coma. Drug overdose should be
considered and blood withdrawn and sent to
the toxicology laboratories. Reliance is placed
upon the assessment of metabolic and toxic
metabolites in the blood and evidence should
be sought for hepatic failure, renal failure,
hyperglycaemia,
hypoglycaemia
and
disturbances of electrolytes or acidosis. In
those patients who used to consume alcohol,
blood alcohol level should be measured to see
if
it
is
Perhaps
contributing
to
the
important
single
unconsciousness.
cause
of
unresponsiveness, which is directly treatable, is
that of hypoglycaemia and this should have
already
been
covered
during
the
initial
resuscitation of the patient.
By this time, hypo-hyperglycaemia
treatment is instituted. Acid-base disturbances
need to be identified and corrected. Hypoxiaischaemia are identified by the mode of
presentation and the normality of investigations.
Blood pressure measurements will allow the
diagnosis of shock and hypertensive
encephalopathy. Temperature measurement will
identify disorders of temperature regulation (a
rectal thermometer is needed). In patients with
drug overdose, the possibility of using antidotes
should be considered. Naloxone in patients with a
high suspicion of opioid poisoning and
benzodiazepine antagonists in self poisoning with
benzodiazepines are used. The use of analeptic
agents in barbiturate poisoning can not now be
supported.(32) Consideration should be given to
clearing the ingested toxin from the stomach. The
passage of a nasogastric tube should usually be
considered, and this is one indication for
endotracheal intubation to prevent the risk of
aspiration. The importance of the diagnosis of
drug overdose coma is that it has a good
prognosis, provided there was adequate support
to the circulation and respiration, whatever the
level of coma (brainstem depression) they have.
Prediction of outcome in coma:
After making an assessment of the cause
and severity of coma and instituting appropriate
treatment, the physician should be able to identify
the likely outcome to colleagues, friends and
relatives of the patient. Sedative drugs and
alcohol are not usually lethal and carry a good
prognosis, provided support to the circulation
and respiration is adequate. In non-traumatic
coma other than that due to alcohol and sedatives
the outcome is determined by factors(31) relating to
the cause of coma, the duration of coma, the
depth of coma and certain clinical signs among
the most important of which are brainstem
reflexes.
Overall only 15% of patients in nontraumatic coma for more than 6 hours will make a
good or moderate recovery, 85% will die, remain
vegetative or reach a state of severe disability in
which they remain dependent. Patients whose
coma is due to metabolic reasons, including
infection, organ failure and biochemical
disturbances have a better prognosis. 35% of
these will achieve moderate or good recovery; of
those whose coma follows hypoxic-ischaemic
insults only 11% make such a recovery, of those
in coma due to cerebrovascular disease only 7%
can be expected to make a recovery. 20% of
patients in coma following hypoxic-ischaemic
injury will enter the vegtative state due to the
likelihood of hypoxic ischaemia resulting in
bihemispheric damage with relative sparing of the
brainstem.
The depth of coma influences the outcome
of coma regardless of the cause. Patients not
showing eye opening after 6 hours of coma have
only 10% chance of making a good or moderate
recovery, compared with 29% for those who
opened their eyes in response to painful stimuli.
The longer the duration of coma, the less
likely there is to be recovery, 15% of patients in
coma for 6 hours make a good recovery
compared with only 3% who remain unconscious
for a week.(33)
The study of 500 patients reported by Levy
et al.,(33) using prospective data from patients with
clearly defined levels of coma, diagnoses and
outcomes showed that some clinical signs are
significantly associated with a poor prognosis. In
the total cohort of 500 patients, corneal reflexes
were absent 24 hours after the onset of coma in
90 patients and this sign was incompatible with
survival. In a more uniform group who suffered
anoxic injury there were 210 patients, 52 of these
had no papillary reflexes at 24 hours, all of whom
died. By the third day 70 were left with a motor
response poorer than withdrawal and all died. By
the seventh day the absence of roving eye
movements was seen in 16 patients all of whom
died. The 95% confidence intervals for all of these
criteria are given in table 1-6.
At the other end of the scale, more than 25%
of patients who show roving conjugate eye
movements within 6 hours of the onset of coma,
or who show withdrawal responses to pain or eye
opening to pain will recover independence and
make a moderate or good recovery. The use of
combinations of clinical signs helps to improve
the accuracy of prognosis. At 24 hours the
absence of corneal reflexes, pupillary light
reactions or caloric or doll's eye response is not
compatible with recovery to independence.
People who are able to speak words within 24
hours or who show nystagmus on caloric testing
are likely to make a good recovery(34) (Table 1-7).
Table 1-6: Clinical signs and prognosis in comatose
patients:
Time (hours)
24
Signs
Absent corneal
Patients
False
95 %
with the
positive
confidence
sign
survivors
interval (%)
500
90
0
0-5
210
52
0
0-5
Cohort
response
24
Absent
pupillary
response
3
Motor
210
70
0
0 -5
210
16
0
0-5
response
poorer than
withdrawal
7
Absent roving
eye
movements
Summarized from Levy … et al,(33)
Table 1-7: Prediction of outcome of coma at 24 hours
by a combination of clinical signs:
No. of
patients
% of patients with
different outcome
D/PV S MD/G
S
D
R
500 patients
Any two reacting of,
Pupils, corneals or
No
120
97
2
1
No
83
80
8
12
No
135
69
14
17
occulovestibular
responses
Yes
Motor better
than flaccid
Yes
Motor withdrawal
Yes
Verbal moans
No
106
58
19
23
Yes
56
46
13
41
Summarized from Levy…… et al.
D/PVS: death or vegetative; SD: Severe disability,
MD/GR: moderate or good recovery.
The most accurate prediction of outcome in
coma is still that which is obtained from the use
of clinical signs, and there is little to be added by
more sophisticated testing other than in
identifying the cause of coma. It is possible to
predict those patients who will not make a
recovery and who will die in coma or who will
enter a vegetative state within the first week of
coma. It is rare for patients in medical coma who
are in a vegetative state at one month to show any
forms of recovery.(35)
In a prospective study of 188 patients with
non-traumatic coma in the intensive care unit of
Columbia-Presbyterian medical center, with G.C.S
determinations within 72 hours, 61% were dead or
in presistent coma by 2 weeks from onset. Age,
sex and ethnicity did not influence the outcome.
The 2 week outcome for patients with initial GCS
of 3-5 was 14.8%a wake; 85.2% were dead or in
persistent coma. For the G.C.S of 6-8 group,
46.9%were dead or in persistent coma; 53.1%
were awake. Hypoxic or ischemic coma had the
worst prognosis (79% dead or comatose by 2
weeks; coma caused by metabolic disease or
sepsis (68%), focal cerebral lesions (66%) and
general cerebral disease (55%) were intermediate,
while drug-induced coma had a favourable
outcome (27% dead or comatose). The
independent predictors of the 2 week outcome
were the first G.C.S and drug induced coma.
Drug-induced coma had eight times probability
for waking at 2 weeks compared to other causes
when the G.C.S was held constant.
Patients with G.C.S 6-8 initially, were seven
times more likely to waken than those with score
3-5. The motor subscore alone was a significant
independent predictor of 2 week outcome.
Modification of coma score to include
aetiology may give more accurate predictions of
the 2 week outcome after non-traumatic
coma.(36,37) Leaver, R.J found that the outcome of
comatose patients due to cerebral malaria
depended on the G.C.S(38) (Table 1-8).
The most important factors that affect the
outcome in the patient with the first ever stroke
are increasing age, a low G.C.S and the presence
of atrial fibrillation.(39,40) Other factors involved in
predicting outcome in ischaemic strokes include
infarct size. This was studied by Sharma, J.C, et
al., who classified patients into large infarct and
non-large infarct groups using C.T scan (large
infarcts affecting more than one lobe).
Table 1-8: G.C.S and outcome in cerebral malaria
G.C.S
No. lived
No. died
Mortality %
3-5
2
8
80%
6-8
18
7
28%
9 - 11
21
2
4%
The large infarct group had a significantly
higher mortality and was more associated with a
low G.C.S, incontinence, pyrexia and
dysphagia.(41,42) Hemphil, J.C, et al., found the
outcome of intracerebral haemorrhage was
adversely affected by old age (more than 80
years), the G.C.S (3-5) and the size of the
haematoma and he deduced the intracerebral
haemorrhage score(43) as a predictor of mortality
due to intracerebral haemorrhage. The occurrence
of onset seizures was a predictor of poor outcome
in coma due to acute stroke and influenced the
outcome. The nursing care of comatose patients
also influenced the outcome as was demonstrated
by the substantial reduction in mortality in
patients who were managed in a specialist stroke
unit compared to matched controls in routine
wards. This was demonstrated in one published
randomized trial.(44)
Continuation of care:
The long-term care of patients in coma may
be undertaken in an intensive care unit, in a
specialist ward, or later in a long stay hospital.
Patients with a hopeless prognosis should be
offered nursing care within routine hospital
wards. Patients with a potential for recovery
should be looked after in an intensive care unit or
a specialist ward.(45,46)Their respiration, skin,
circulation and bladder and bowel function need
attention, seizures should be controlled, and the
level of consciousness regularly assessed and
monitored.
It is important that the mobility of joints and
circulation to pressure areas are maintained
during the long-term care of the patient, and the
possibility of aspiration pneumonia, peptic
ulceration and other complications of long-term
intensive care be considered and avoided. In
general, techniques such as mechanical
ventilation and the use of steroid therapy should
not be used routinely in the management of
comatose patients, since they do not improve
prognosis and may specifically compromise
recovery.(47)
Continuous vegetative state:
This state results from irreversible damage
to the cerebral hemispheres. Massive neocortical
damage is demonstrable at postmortem.(48) The
diagnosis is usually considered when the patient
has been in a continuing vegetative state for more
than six months.(49,50) Specialists in rehabilitation
are concerned that physicians are taking the
attitude that there is no point in treating such
patients, therefore, creating a self fulfilling
prophecy of poor prognosis, no treatment and
poor outcome.(51) Debate exists as to the
possibility of recovery for patients who suffered
non-traumatic injury such as anoxia and
ischaemia, the prognosis for recovery after the
first few weeks is poor.(52,54)
Investigations do not help to identify the
vegetative state because EEG patterns ranged
from near normality to flat records. C.T-scan
shows considerable cortical atrophy and
ventricular dilatation. Somatosensory evoked
responses show loss of cortical component.
Positron emission tomography (P.E.T) scan
shows cortical metabolic under activity. None is
diagnostic in its results.(55) The management
depends upon carers for the supply of liquids and
nutrients and the prevention of complications and
depends upon circumstances, other aspects of
the diagnosis and consideration of prognosis.(56)
Summary of the management of medical coma:
•
Ensure adequate circulation and oxygenation.
A sample of blood for glucose and other
parameters and once stability is ensured obtain
adequate history.
•
Assess the level of coma. Evaluate features
that may give a clue as to the aetiology,
including
temperature,
heart
rate,
blood
pressure, pattern of respiration, abnormalities
in the skin and focal signs in the chest,
abdomen or limbs.
•
The relevant investigations may then be
considered,
including
biochemical
and
serological assessments, radiological imaging
and the possibility of EEG. Lumbar puncture is
indicated in certain circumstances. Then the
diagnosis of the aetiology of the coma is
established, corrective therapies instituted and
continuation
established.(57)
of
care
and
protection
OBJECTIVES
1-
To investigate the causes of non-traumatic coma in patients who presented to Khartoum Teaching
Hospital during the study period and determine the frequency of each cause.
2-
To find out the final two week outcome.
PATIENTS & METHODS
Patients included in the study were those attending Khartoum Teaching Hospital in the period February
2001- December 2001 with unarousable medical coma i.e. those with a Glassgo coma scale of less than
II.
The duration of coma should be at least six hours before admission or the patient should continue to be
unconscious for at least six hours in order to exclude transient causes of loss of consciousness such as
syncope, seizures, cardiac arrhythmias and psychogenic coma.
Patients who are unresponsive due to impending death wee excluded from the study.
Patients who sustained head trauma over the past six months were excluded from the study.
After resuscitation of the patient, a detailed history from the relatives, friends or those who witnessed
the onset of loss consciousness was obtained with particular reference to the circumstances that
preceded the onset of loss of consciousness. Inquiry about a recent illness as well as the medical history,
previous medical cards, medications the patient is taking, whether the patient is known diabetic,
hypertensive or has cardiac, respiratory, neurologic, liver disease, renal disease or epilepsy, searching
for a potential cause for loss of consciousness.
A thorough physical examination was then undertaken systematically noting the pulse, temperature,
blood pressure and pattern of respiration. Assessment of the cardiovascular, respiratory systems as well
as looking for evidence of liver or renal disease. Then a detailed neurological examination was
undertaken including examination for features of meningism. A search for localizing neurological signs:
assessment of the brainstem function by examination of the pupils, corneal reflexes and the
occulocephalic reflexes. The fundi were examined and any abnormality noted. The level of
consciousness was assessed using the Glossgo Coma Scale.
All patients then had blood tests for malaria parasites, the leucocyte count and urine analysis for sugar,
acetone and bile. All patients had biochemical testing for random blood glucose, blood urea and
electrolytes, namely sodium, potassium and calcium.
Further investigations were requested as dictated by the clinical findings and the preliminary laboratory
results. All patients with evidence of lateralizing signs or evidence of raised intracranial pressure had a
CT or MRI scan. Patients with features of meningism had a lumbar puncture unless there is evidence of
raised intracranial pressure (evidenced by papilloedema). The CSF was analysed for protein, sugar and
cells.
The lumbar puncture was not done for patients with meningism whose CT scan revealed a structural
brain lesion or obvious subarachnoid haemorrhage.
For patients with jaundice and other signs of liver disease, liver function tests were obtained including
liver enzymes and the prothrombin time.
The diagnosis of structural brain disease was based mainly on radiological imaging techniques namely
CT or MRI scans.
The diagnosis of metabolic coma, including infections was based on the appropriate metabolic,
biochemical derangements and bacteriological results in addition to the clinical picture.
The diagnosis of coma due to drugs relied mainly upon the history due to lack of a toxicology
laboratory.
Appropriate treatment and nursing care were provided in routine medical wards, due to lack of intensive
care units and specialist units. The patients were then followed up for two weeks. Complications which
developed during hospital stay were noted and the final 2 week outcome identified.
Statistical analysis was done using computer statistical software SPSS (statistical Package for Social
Sciences). The results were then subjected to bivariate and multivariate analysis using the Chi-square
test.
RESULTS
Of the hundred patients studied, 58 were males and 42 were females. They came from different regions
in the Sudan. 37 patients came from Khartoum State, 20 patients from surrounding villages and 43
patients from outside Khartoum State. The distribution of patients according to age is shown in Table
3-1 and Fig. 3-1. It is evident that more than two thirds of patients are above 50 years. 40% of patients
were house-wives, 24% merchants, 14% farmers, 10% employees and 12% others.
The duration of coma before admission varied from a few hours to more than 3 days, 29% of patients
presented within six hours of the onset of coma, 28% within 24 hours, 35% within 72 hours and 8%
presented after more than 3 days.
The symptoms preceding or accompanying the onset of coma varied, 41% had headache, 46% had
fever, 30% had vomiting, 30% had convulsions, 10% had jaundice, 27% had weakness of one side of
the body, 6% had neck stiffness, 3% had haematemesis, 3% had blurring of vision, 2% had anuria, 3%
had foot sepsis and 8% of patients had no symptoms preceding the onset of coma. In one patient
sedative overdose (chlorpromazine) was reported by his relatives.
Previous history of coma was obtained in 9 patients, 3 of whom were due to hypoglycaemia, 2 due to
cerebrovascular disease, 2 due to epilepsy, one due to hepatic encephalopathy and one due to
hypertensive encephalopathy. 23 patients were known diabetic, 23 patients were hypertensive, 3
patients were epileptic, 3 patients had rheumatic heart disease and/or atrial fibrillation, 8 patients were
known cases of chronic renal disease, 9 patients were known to have liver disease, namely liver
cirrhosis (n= 4), periportal fibrosis (n= 1), hepatocellular carcinoma (n= 1), chronic active hepatitis (n=
1) and 2 had attacks of acute hepatitis.
The level of consciousness varied from 3-11: 58% had a GCS of (6-8), 38% had a GCS of (9-11), 4%
had a GCS of (3-5).
Evidence of localizing neurologicl signs was seen in 33 patients of whom 32 had hemiparesis and one
had quadriparesis. Features of meningism were observed in 12 patients and fever was demonstrated in
18 patients, jaundice was observed in 14 patients.
Aetiology of coma:
Table 3-2 and Fig. 3-2 illustrate the causes of coma in the 100 patients and the frequency of each cause.
It is obvious that the most frequent cause is cerebrovascular disease (33%), followed by cerebral
malaria (16%), liver disease (12%), renal disease (9%), hypoglycaemia (8%) and sepsis (5%). Diabetic
coma (ketoacidosis and the hyperglycaemic, hyperosmolar syndrome) accounted for 4%.
Complications encountered during hospital stay were aspiration pneumonia (n= 28), bed sores (n= 2),
septicaemia (n=1) and gastrointestinal haemorrhage (n=1).
The final outcome at 2 weeks is shown in Table 3-3.
Table 3-4 shows the association between aetiology and outcome.
Table 3-5 and Fig. 3-3 compare the outcome of different types of coma i.e. structural, metabolic or due
to drugs.
The relationship between the Glossgo Coma Scale and the 2 week outcome is illustrated in Table 3-6.
The relationship of patient’s age to outcome is shown in Table 3-7.
The relationship of the duration of coma at presentation was compared to the final outcome (Table 3-8).
The relationship of the GCS and final outcome in patients with cerebrovascular disease is shown on
Table 3-9.
The effects of hypertension and diabetes on the outcome of coma due to cerebrovascular disease is
shown in Tables 3-10 and 3-11 respectively.
Table 3-1: The distribution of 100 patients with coma
according to age
Age (years)
No. of patients
Percentage
10 – 19
02
02%
20 – 29
09
09%
40 – 49
08
08%
50 -59
17
17%
60 +
52
52%
Total
100
100
Table 3-2: Causes of coma in 100 adult Sudanese patients
Cause
Percentage
A.
Structural brain disease:
-
Cerebrovascular disease
-
Brain abscess
Hydrocephalus
33%
1%
1%
Metabolic diseases and infections:
- Cerebral malaria
16%
- Liver disease
12%
- Renal disease
9%
- Hypoglycaemia
8%
- Septicaemia
5%
- Meningitis
4%
- Diabetic ketoacidosis
3%
- Encephalitis
2%
- Epilepsy
2%
- Hyperglycaemic hyperosmolar
1%
syndrome
- Hypertensive encephalopathy
1%
1%
- Miliary tuberculosis
C. Drugs: - Sedative overdose
1%
Table 3-3: The 2 week outcome in 100 Sudanese
patients with coma
Outcome
Percentage
-
Recovery within 24 hours
23%
-
Recovery within 72 hours
27%
-
Recovery within 2 weeks
3%
12%
- Persistent coma after 2 weeks
- Death after 72 hours
- Death within 72 hours
- Death within 24 hours
12%
22%
1%
Table 3-4: The association between aetiology and outcome in 100 patients with coma
No. lived
No. died
Mortality %
Cerebrovascular disease
8
25
75.3%
Cerebral malaria
11
5
31.3%
Hepatic encephalopathy
3
9
75%
Uraemic encephalopathy
8
2
20%
Hypoglycaemia
8
0
0%
Septicaemia
4
1
20%
Meningitis
3
1
25%
Diabetic ketoacidosis
3
0
0%
Encephalitis
0
2
100%
Status epilepticus
2
0
0%
Brain abscess
1
0
0%
Hydrocephalus
0
1
100%
HHS
0
1
100%
Miliary TB
1
0
0%
Sedative overdose
1
0
0%
Cause
2
X = 27.41
P = 0.0004751
Table 3-5: Mortality of different types of coma in
a sample of 100 patients
No. lived
No. died
Mortality %
Structural brain disease
9
26
74.3%
Metabolic coma
43
21
32.9%
Drug coma
1
0
0%
Coma type
Table 3-6: The relationship between GCS and the 2 week outcome in patients with coma (n=100)
GCS
No. lived
No. died
Total
Mortality %
3-5
1
3
4
75%
6-8
28
31
59
52.6%
9 - 11
24
13
37
35.1%
Total
53
47
100
X2 = 4.08
P = 0.13019189
Table 3-7: The relationship between age and final outcome in patients with coma (n=100)
No. lived
No. died
Mortality %
10 - 29
9
2
18.2%
30 - 49
13
7
35%
50 +
31
38
53.8%
Age (years)
X2 = 6.63
P = 0.03636034
Table 3-8: The relationship between coma duration and final outcome in 100 Sudanese patients
No. lived
No. died
Mortality %
< 6 hours
20
8
28.6 %
6 - 72 hours
31
33
51.6 %
> 72 hours
2
6
75 %
Duration of coma
X2 = 6.87
P = 0.03222
Table 3-9: GCS on admission and 2 week outcome in patients with cerebrovascular disease
GCS
No. lived
No. died
Mortality %
3 -5
0
3
100 %
6-8
6
13
68.4 %
9 - 11
2
9
81.8%
Total
8
25
75.3%
X2 = 1.74
P = 0.419613
Table 3-10: The effect of hypertension on the outcome of coma due to cerebrovascular disease
No. lived
No. died
Mortality %
Hypertensives
1
8
88.9%
Normotensives
7
17
54.1 %
Total
8
25
75.3%
Blood pressure
X2 = 0.39
P = 0.534029
Table 3-11: The effect of diabetes on the outcome of coma due to cerebrovascular disease
No. lived
No. died
Mortality %
Diabetics
0
3
100%
Non-diabetics
8
22
73.3 %
Total
8
25
75.3%
Status
X2 = 0.10
P = 0.748111
DISCUSSION
Khartoum Teaching hospital is a central hospital receiving patients from all parts of the Sudan. It is
clear from this study that most patients admitted with non traumatic coma during the period of study
came from remote areas (43%), representing all states of Sudan. This also reflects deficiency of
facilities for investigation and management of such patients even in big cities like Port-Sudan,
Dongola…etc. This results in delay of diagnosis and probably lack of proper resuscitation and nursing
care during transport to Khartoum. This adversely affects the prognosis, as demonstrated by the
significantly increased mortality among comatose patients who presented after more them 24 hours
(Table 1-6) mostly referred from out side Khartoum state.
Regarding the age of patients, it is obvious that this is mainly a problem of the elderly as more than two
thirds of patients were above 50 years of age.
The age also determined the prognosis of coma on the whole. The mortality under 30 years was 28.6%
compared to 75% above 50 years (P= 0.03) this is party because metabolic coma, which on the whole
has a better prognosis than structural brain disease accounts for most of the cases in the younger age
group.
The diagnosis of the cause of coma is no longer a difficult problem, because the availability of
radiological imaging (CT and MRI scanning) has revolutionized the investigation of coma due to
cerebrovascular disease and other structural brain pathology.
The diagnosis of metabolic coma is mostly obvious if a proper clinical examination is undertaken,
supplemented by simple bedside tests and specific biochemical and bacteriological tests appropriate to
the individual patient.
Regarding the aetiology, metabolic coma (including infections) was more common than coma due to
structural brain disease. This compared well with the studies of Allan, H. and Bates, D.(1,57) The
difference lies in the rarity of drug coma in this study (1%), compared to up to 30% in their studies.
This can be explained by the unfamiliarity with sedatives in our society and the uncommon use of
alcohol now-a-days. The only case of sedative overdose was a psychotic on chlorpromazine who
ingested an overdose of the drug.
The contribution of cerebrovasculer disease is still considerable (33%) and accounted for most of the
mortalities (25 patients out of 47). This confirms that stroke patients who have disturbance of
consciousness will have a poor outcome. This result is comparable to worldwide studies conducted by
Hutchinson P.J.(58) It also compares well with that of the local study by Mohamed F in El Shaab
Hospital (1992-1993) who attributed the high mortality to lack of specialist units, nursing being offered
in general medical wards.(59) In this study the outcome of patients with cerebrovacular disease was not
affected by the GCS on admission (Table 3-9), this is because of the variability of the duration of coma
(GCS changes with time). The association of hypertension and diabetes with prognosis of coma due to
cerebrovascular disease is poor. Although all diabetic patients died (3), the association did not reach
significance, because of the small number of patients (Table 3-10 and 3-11). This is consistent with the
results of Arismendi, et al., who concluded that there is no correlation between systolic and diastolic
blood pressure and the outcome of acute stroke.(60) It is also compatible with the results of Hemphill J,
who stated that the volume of the haematoma was the determinant of the outcome of intracerebral
haemorrhage rather than the blood pressure.(61)
Two elderly patients were found to have subdural haematoma, despite they denied any history of head
injury or even minor trauma. This makes it necessary to consider this diagnosis in every elderly patient
with a disturbance of consciousness, regardless of whether they had trauma to the head or not.
Of metabolic coma, the commonest cause was cerebral malaria (16%) with a rather good outcome
(mortality 31.3%). This is because the diagnosis and treatment are initiated early enough with quinine to
which malaria resistance is uncommon. This is comparable to the study of Leaver RJ, et al., in LusakaZambia (1990) who reported a mortality of 29.3% from cerebral malaria.(62)
Hepatic encephalopathy had a high mortality rate (75%) comparable to that of cerebrovascular disease
(75.3%). This is also comparable to studies by Gebert T.(63) and Abou-Assi S.(64) who concluded that
hepatic encepalopathy has a poor prognosis unless liver transplantation is offered to patients with liver
cirrhosis. This is different from the result obtained by Omer M in Ibn Sina Hospital (1999) who
reported a mortality of 21.7% among patients with hepatic encephalopathy. However, in that study,
patients with renal impairment and those with malignancy were excluded, and this can account for the
difference in the total mortality.(65)
Uraemaic encephalopathy had a rather favourable outcome (mortality 20%). This is attributable to the
availability of dialysis units in Khartoum State, although the waiting list is so long and some patients
may die before having access to a dialysis unit, particularly those on haemodialysis. This is comparable
to the study conducted in Khartoum Teaching Hospital (1997) in patients with renal failure, where a
total mortality of 11% was reported (comatose plus conscious).(66) It differs from the results in Turkey
where the outcome of comatose patients with uraemic encephalopathy was 10.8% mortality.(67) It is also
different from the study done in 1999 in KTH when the mortality among comatose patients was found
to be 57.7%, blaming delayed presentation and lack of facilities in the casualty.(68)
Complications of dialysis, particularly peritonitis are common and may contribute to morbidity and
mortality (due to septicaemia).
The best of the metabolic comas, in terms of early diagnosis and reversibility is that due to
hypoglycaemia (8% of patients), mostly occurring in diabetic patients on treatment with oral
hypoglycaemic agents (7 patients). All of them recovered consciousness within a few hours after
admission. Early suspicion of the diagnosis and confirmation by a simple blood test for random blood
glucose is an important factor for the reversibility of the condition with no moralities or residual
neurological deficits.
Septicaemia was responsible for 5% of patients all of whom were elderly patients or those with diabetes
or chronic renal failure. The outcome was good (mortality 20%). Although blood cultures were not
done, the diagnosis based on clinical grounds, supplemented by the leucocyte count (the systemic
inflammatory response criteria) seems satisfactory for diagnosis of septicaemia.
Diabetic coma (DKA and HHS) accounted for 4% of cases. The outcome of DKA is favourable as all
patients recovered after treatment. This is different from the results obtained in Yemenese patients with
diabetic ketoacidosis in whom a poor outcome (44% mortality) was reported. Poor facilities and lack of
qualified medical personnel and lack of health education were blamed.(69)
The only patient who presented with the hyperglycaemic, hypersmolar syndrome died after he
developed cerebral thrombosis.
Meningitis was responsible for 4% of patients, who all recovered except one patient who was referred
from the west of Sudan, being comatose for 3 days. It seems to be reversible with treatment and
antibiotic treatment should be initiated as early as possible on clinical suspicion. This is comparable
with the study of Salman H. in KTH and SUH patients with cerebrospinal meningitis during the
epidemic of 1999, who reported an overall mortality of 10%, the level of consciousness having a
significant relationship to the outcome. The lower mortality is due to early detection and the high index
of suspicion during epidemics.(70)
Encephalitis had a poor prognosis, the two patients received no specific treatment, one of them died
and the other remained comatose after two weeks.
The only patient with miliary tuberculosis who had scattered tuberculomata on the brain (revealed on
MRI scan), showed good response to antituberculous treatment plus seteroids. The patient with brain
abscess regained consciousness after antibiotic treatment plus steroids and was referred for
neurosurgery.
Patients with status epilepticus (2) both regained consciousness on the same day after appropriate
treatment with anticonvulsants and supportive measures.
CONCLUSION
•
Non traumatic coma is mainly a problem of
the elderly.
•
Metabolic
constitutes
coma
the
(including
majority
of
infection)
cases
(64%).
Structural brain disease is considerable, mainly
cerebrovascular (33%). Drug coma is rare (1%).
•
The diagnosis of coma aetiology presents
little
difficulty
radiological
in
the
imaging
face
of
techniques,
available
simple
bedside
tests
guided
by
a
good
clinical
assessment.
•
The outcome of coma is related to the
aetiology.
•
Generally metabolic coma is associated with
a
better
prognosis
than
coma
due
to
cerebrovascular disease.
•
The mortality rate ranged from 0% with
hypoglycaemia, DKA and epilepsy to 75%with
cerebrovascular disease and hepatic coma.
Other causes had a modest mortality ranging
from 20 to 31%.
•
The other factors that influenced the outcome
are the age of the patient and the duration of
coma. The level of consciousness on admission
was not a predictor of the outcome.
RECOMMENDATIONS
1-
Emergency wards should be provided with 24
hours laboratory service capable of performing
necessary tests e.g. blood glucose, urea,
electrolytes, leucocyte count and blood films
for malaria parasites as well as having easy
access to radiological imaging e.g. CT, MRI
scanning and viral serology studies.
2-
Facilities for nursing comatose patients in the
wards should be improved e.g. provision of
suction
machines,
necessary
oxygen
instruments
e.g.
sphygmo-manometers….etc.
cylinders
and
thermometers,
Nurses
well
trained in ICUs should be available on a 24
hour.
3-
The hospital should have separate ICUs or
specialist neurology wards with well-trained
staff to deal with such cases.
4-
Neurosurgery
units
should
be
actively
involved in the management of patients with
intracerebral haemorrhage in cooperation with
the physicians in charge of such cases.
5-
The hospitals of the states should also be
provided with the necessary facilities and
physicians to diagnose and treat such cases
locally.
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presentation
and
Pupillary light reflexes [present][absent]- corneal
reflexes [present] [absent]-occulocephalic
reflexes [present][absent]- Fundi [normal]
[abnormal]
specify……………………………………………………
…..
4. Lab findings:
BF for malaria ………….. TWBC
……………./Cumm.
Urinalysis [sugar][ acetone][bilirubin][None]
RBG…………..mg/dl
Urea ………..mg/dl
Na+ ……mmol/L.
K+ ………mmol/L
Ca++ ……mg/dl.
ECG [Normal] [abnormal] specify
…………………………………..
CSF analysis [done] [not done] if done is it
[clear]
[turbid] [haemorrhagic]. CSF protein
..…………mg/dl
CSF leucocyte count…………/ml. % Lymph ……
% Neutrophils….
CT scan [Normal] [abnormal] [not done] if
abnormal, specify …….…..
…….….. MRI scan [Normal] [abnormal] [not
done] if abnormal, specify
…………………………………………………
……………………………………………………………
…………….
L.F.T. [Normal] [abnormal] [not done] if
abnormal, serum bilirubin …….…..mg/dl. P.T
……. I.N.R ……………………
6- What is the final diagnosis?
……………………………………………
……………………………………………………………
…………….
Other factors contributing to coma?
……………………………………
Did the patient have complications during his
stay in the ward [Yes] [No] specify?
……………………………………………………………
……
……………………………………………………………
…………….
What is the outcome? …………………………………
At 24 hours [death][persistent coma] [recovery].
At 3 days [death][persistent coma] [recovery].
At 2 weeks [death][persistent coma] [recovery].