Clinical Toxicology

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Barbiturates

Henry Matthew

To cite this article: Henry Matthew (1975) Barbiturates, Clinical Toxicology, 8:5, 495-513, DOI:
10.3109/15563657508988095

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 CLINICAL TOXICOLOGY 8(5), pp. 495- 513 (1975)

Barbiturates
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HENRY MATTHEW, M.D.

Regional Poison Treatment Centre

Royal Infirmary
Edinburgh, Scotland, U.K.

I N T R OD U C T ION

It is now exactly 100 years since Adolph von Baeyer prepared

barbituric acid from the condensation of urea and malonic acid. It
remains uncertain as to whether the Barbara incorporated with urea
in the name of his discovery derived from the barmaid who assisted
in the celebrations o r whether the name came from St. Barbara,
which was the Saint's Day on which the discovery was made. At all
events, like so many scientific discoveries, much that was bad was
to be associated with the benefits of this new found substance. De-
spite the availability of barbituric acid, which is itself not a central
nervous system depressant, no derivatives appeared on the clinical
scene till 1903-barbital-and 1912-phenobarbital. Later the
medium- and short-acting preparations possessing valuable hyp-
notic rather than anticonvulsant properties became available.
Unfortunately these short- and medium-acting barbiturates have
been prescribed with increasing frequency. No doubt many millions
have allegedly benefitted from such barbiturate- induced sleep, but
the backlash has been the many thousands who die each year through-
out the world from acute barbiturate poisoning. Overdosage by
barbiturates, together with dependence, has become such a problem

495
Copyright 0 1976 by Marcel Dekker, Inc. All Rights Reserved. Neither this work nor any part
may be reproduced or transmitted in any form or by any means, electronic or mechanical, including
photocopying, microfilming, and recording, or by any information storage and retrieval system,
without permission in writing from the publisher.
 496 MATTHEW

that informed opinion is moving toward the philosophy that apart from
their anticonvulsant properties barbiturates should no longer be pre-
scribed [l-81. Such a view which might be thought to be extreme has
real substance as suitable alternatives are available, which curiously
enough a r e virtually nontoxic in overdose [9] and have comparatively
little risk of dependence.[5]. Statistical grounds for such a view a r e
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supported by the fact that almost 70% of suicides by drug ingestions

are due to barbiturates [7] ; barbiturates in some countries remain
the commonest drug taken in self-poisoning [lo] and a r e also the
most frequently used drug by teenagers to produce kicks [ll]. An
additional feature is that those indulging in the cult of the needle
may use barbiturates intended for oral administration a s their main-
line drug of choice. When further articles on this subject appear
ten years hence one would hope they would be very short reflecting a
sharp decrease in the use of barbiturates a s opposed to their current
status of being the most important and most common medicine taken
in overdose in most so-called developed countries of the world [lo].
Fortunately this introduction can end on an optimistic note for there
is evidence that fewer barbiturates a r e being prescribed. For ex-
ample acute barbiturate poisoning accounted for 60% of admissions
to the Regional Poisoning Treatment Centre at the Edinburgh Royal
Infirmary in 1965; in 1972 barbiturates accounted for but 19%. The
mortality from acute barbiturate poisoning has dropped from 41%
[12] to less than 1%over the past 30 years [13]. This improvement
in mortality figures must not, however, lead to the conclusion that
there is all that much less prescribing of barbiturates; the impressive
change simply reflects considerably improved treatment of barbiturate
poisoning. Immediately it must be recorded that improved treatment
should not be equated with the introduction of new sophisticated
methods o r machines. Improvement has largely been achieved by a
more widespread acceptance of conservative intensive supportive
therapy a s the most important basic management concept [ 14- 171.
Finally it must be appreciated that there a r e pitfalls inherent in
employing the single word barbiturate if it is not immediately recog-
nized that the word includes a range of individual substances that
have a duration of action lasting from seconds to days [18]. It is thus
evident that when writing of barbiturate overdose perhaps the most
important point after first incriminating the barbiturate group of
drugs is to specify the type of barbiturate involved, whether long-,
medium-, o r short-acting.

C L I N I C A L F E A T U R E S AND D I A G N O S I S

Since the barbiturates a r e sedative hypnotic, the clinical features

should be evident. They will of cgurse vary with the amount ingested
 BARBITURATES 497

and certain other factors to be considered later. It is often written

that the severity of poisoning and duration of coma can be ascertained
simply by measuring the level of barbiturate in the blood [19, 201. In
practice this is certainly not the case [16,211. The severity of poison-
ing is determined by the clinical features; the blood barbiturate level
simply confirms that an excess of barbiturate has been ingested.
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Identification of the specific barbiturate involved may on r a r e occa-

sions contribute to the management (211.
The important effects a r e respiratory depression, impaired level
of consciousness, cardiovascular damage, and hypothermia; less sig-
nificant a r e those on the skin and the gastrointestinal and renal tracts.
The effects on the central nervous system other than respiratory depres
sion and conscious level also have some importance.

ResDiratorv DeDression

The degree of respiratory depression is best measured by blood gas

analysis. However a reasonable assessment is achieved by measuring
the minute volume with a Wright's spirometer [IS]. If a minute volume
of less than 4 liters is recorded, then severe respiratory depression
necessitating immediate further action is present. Clearly one reading
is inadequate and the minute volume must be recorded frequently for
there may be a worsening in the degree of respiratory depression.
Another direct respiratory effect of acute barbiturate poisoning is
pulmonary edema [22]. However such a finding is extremely rare.
Other respiratory changes commonly seen a r e secondary and are the
result of bacterial infection o r congestive heart failure. Inhalation
into the lungs may result from attempts at vomiting o r from an injudi-
cious o r unskilled gastric aspiration and lavage.

L e v e 1 of C o n s c i o u s n e s s

There has been considerable debate regarding the best method of

recording the level of impaired consciousness. That of Reed et al. [23]
was popular for many years, but in practice with the various permuta-
tions and combinations of reflexes that have to be matched to impairment
of conscious level, hypotension, and respiratory depression, Reed's
classification has not generally found acceptance. Nor in practice is the
presence o r absence of the corneal reflex o r the size of the pupils, their
equality, o r their response to light of any real value in the assessment
or management of acute barbiturate poisoning [23]. The following classi-
fication [21] has the distinct merits of clarity and simplicity.
 498 MATTHEW

Grade I Drowsy but responds to vocal command

Grade 11 Unconscious but responds to minimal stimuli
Grade III Unconscious and responds only to maximal painful
stimuli
Grade IV Unconscious and no response whatever to maximal
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painful stimuli

The best form of painful stimulus is rubbing the sternum with the
knuckles. Usually the depth of coma correlates well with the severity
of the poisoning. However different systems may be more severely
involved in different patients. For example one patient may be in
Grade IV coma but have adequate ventilation and no shock, while
another patient may be in respiratory difficulties and be shocked yet
be in but Grade III coma. The peripheral limb reflexes may be unequal
and will be the more depressed the greater the depth of coma. The
plantar response is on occasion extensor.

Cardiovascular System

The cardiovascular system may be affected in three ways. The

barbiturate may have a direct toxic effect on the myocardium but very
large doses indeed are required to achieve this effect [24]. Secondly
the musculature of the smaller peripheral blood vessels may be reduced
in tone with escape of fluid into the extravascular space. The third
and uncommon effect is depression of the cardiac and vasomotor centers
in the brain. By far the most important action is that on the peripheral
vessels resulting in a reduction of plasma volume which may be absolute
but which is almost always due to an expanded vascular bed. Reviews
containing the more scientific aspects have been presented by Shubin
and Weil [25, 261 and Mark [27].

Hypot h e r m ia

Hypothermia results from depression of the temperature-regulating

mechanism in the pons. It is usually seen in fairly deeply unconscious
patients who have lain exposed for several hours, especially in cold
weather. However in short-acting barbiturate poisoning it may be of
rapid onset. When due to acute barbiturate poisoning, hypothermia
differs in no way from that due to other causes.
 BARBITURATES 499

Gastrointestinal

The gastrointestinal effects are of interest as it is they that are

responsible for the variations in the level of unconsciousnesd seen
during recovery from severe overdosage. As the patient recovers
from the severe effects, the paralyzed, narcotized gut regains function
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and motility and blood supply returns. Further barbiturate may then
be absorbed resulting in a deterioration in conscious level; the circle
then repeats itself.

Genitourinary

The life-threatening effects on the genitourinary system are all

secondary to hypovolemia, shock, hypothermia, hypotension, and an
increased secretion of antidiuretic hormone [28].
The changes in the kidneys directly attributable to the barbiturate
are albuminuria and the presence of hyaline casts.

Skin

Although not affecting the outcome, barbiturate blisters a r e of

considerable importance. They were first described in 1932 by Villaret
et al. [29] and later by Holten [30]. The histology has been carefully
studied by Beveridge and Lawson [31] and Beveridge [32] and others
[33-361. Their importance lies in their contribution to diagnosis in
unconscious patients. They occur not over a r e a s of maximum pressure
but most often where skin surfaces have been in contact. They are
present in 6% of acute barbiturate intoxications and can appear quite
early after ingestion, e.g., within 4 hr. If present they greatly assist
in attributing the unconsciousness to drug overdosage but a r e not spe-
cific for barbiturates [37].
Rarely extensive muscular necrosis or peripheral neuritis may be
seen after a prolonged period of unconsciousness [38]. It is dubious if
the barbiturate per se is responsible although this has been suggested.
It is more likely that the tissue necrosis is the combined result of
arterial compression, immobility, shock, and hypothermia.

Liver

Important changes occur in the liver. This is not a matter of

disturbed physiology resulting in elevation of serum bilirubin o r
 500 MATTHEW

other biochemical changes. The important effect is on the metabo-

lism of the barbiturates, which are well known as being potent
stimulators of the enzyme systems that metabolize barbiturates.
This important field has been extensively reviewed by Parke [39].
A stimulated microsomal enzyme system clearly results in an in-
creased breakdown of barbiturates by the liver microsomes, but
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whether in a particular instance of acute poisoning the system can

be induced rapidly enough to affect the metabolism during that epi-
sode is dubious [40]. There can be no doubt, however, that a given
dose of barbiturate will have much less serious effects on a patient
who is regularly taking barbiturates o r alcohol as their system will
be primed to metabolize the drug more rapidly. Tissue tolerance
will also play a considerable part in ameliorating the effect.
The future management of acute barbiturate poisoning may well
be considerably influenced if a safe substance can be discovered to
stimulate rapidly the liver microsomal enzyme system.

T h r o m b o p h l e b i tis

Persons who die from acute barbiturate poisoning usually do so

shortly after ingestion of a massive overdose. Such patients rarely
reach the hospital. Those who die after admission to the hospital
usually do so from irreversible shock o r a respiratory complication.
Occasionally the patient recovers from the serious effects and sudden
death occurs from a pulmonary embolus. It is important to note that
deep vein thrombosis and thromboembolization occur in about 6% of
.
the surviving patients treated for severe overdosage [41] In those
who die after a period of hospitalization, the incidence is very much
higher, thus raising the question of prophylactic anticoagulant therapy.
Recently it has been shown [42] that prolonged coma due to bar-
biturate poisoning is associated with a marked increase in the
activity of serum creatine kinase. The concentration of fibrin degen-
eration products has also been shown to be considerably increased,
together with abnormalities of other indices of coagulation. It is
probable that prolonged coma results in skeletal muscle damage that
in turn is related possibly via the microcirculation to the abnormal-
ities in coagulation.

Withdrawal Syndrome

It is important that the physician be aware that a withdrawal

syndrome may occur when the patient regains consciousness. This
is much more likely in the habituated patient but is also recognized in
 BARBITURATES 501

those whose overdose is their first ingestion of a barbiturate. Excite-

ment, sleeplessness, delirium, and a toxic psychosis together with
epileptiform fits characterize the abstinence syndrome of the with-
drawal phase [43].

The Electroencephalogram
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While, as would be anticipated, there is no EEG pattern diagnostic

of acute barbiturate poisoning, certain EEG findings a r e of value in
this field. The EEG findings in acute barbiturate poisoning have been
extensively reviewed by Haider [44]. The most important contribu-
tion is the findbg by continuous EEG monitoring of complete electrical
silence, that is an isoelectric tracing. The importance lies in the fact
that such a record does not indicate irreversible brain damage and
death. Isoelectric records as long as 28 hr with subsequent full re-
covery of cerebral function have been described [45].
EEG monitoring can anticipate clinical improvement in patients
who a r e deeply comatose. An improvement in the electrical activity
always precedes that observed clinically [46]. The EEG is probably
the single most accurate indicator of the depth of coma. As less
cumbersome and complex apparatus become available, E EG monitor-
ing will have a place in the management of patients severely poisoned
with barbiturates.

The diagnosis of acute barbiturate poisoning is therefore founded

on some o r all of the clinical features already described. It will
however be facilitated by the fact that the majority of patients who
have indulged in self-poisoning by barbiturates have done so to draw
attention to some intolerable situation. Therefore they often will have
intimated their intention before taking the overdose. The true suicide
may provide the circumstantial evidence of a suicide note.
Confirmation of the involvement of a barbiturate along with the
presence or absence of other drugs or alcohol will be obtained by
laboratory analysis. The method of analysis and speed of obtaining
reliable results will however often be dictated by the equipment and
personnel available.

MANAGEMENT

Since it has been advocated that all patients who have ingested
more than a therapeutic dose of a barbiturate should be admitted to
a hospital, management will vary from simply permitting the patient
 502 MATTHEW

to sleep off the effects under observation, to a major exercise in

resuscitation. The form that this exercise takes has been reviewed
by lbsen [47]. In the period 1930- 1960, the major endeavor was to
provide antidotes and to indulge in vigorous gastric aspiration and
lavage. Analeptic therapy was widely advocated [48-501 and gained
further popularity when what was a t first thought to be a specific
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barbiturate antagonist, namely bemegride (Megimide), was introduced

by Shulman et al. [49]. Bemegride was the answer to doctors who
are not happy unless they are actively doing something for the patient-
a similar misplaced philosophy is to be seen today in the obsessive
desire to employ forced diuresis o r hemodialysis. Despite bemegride
having a dubious beneficial effect and indeed producing serious unde-
sirable effects such as cardiac dysrhythmias [51], convulsions [52],
hallucinations, and psychoses [53], it maintained a place in the treat-
ment of acute barbiturate poisoning. It was some years before it
was shown that mortality might be increased by its use [53] and that
it was not a specific barbiturate antagonist. Megimide then reverted
to its status of a mild analeptic. The situation up to 1967 w a s well
reviewed by Mark [54].
While the vogue for analeptic therapy continued in most countries,
Scandinavian workers [14] showed that supportive therapy of the vital
functions produced more favorable results than did vigorous attempts
at arousal. The debate was somewhat heated and although supportive
therapy itself entails considerable application of basic therapeutic
principles, it was stamped as "therapeutic nihilism" [48]. The
Scandinavian method has undergone certain modifications with further
reduction in mortality and is now the generally accepted regimen
[17, 211.

Intensive Supportive Therapy

This can be broadly divided into emergency treatment and general

care.

Emergency Treatment
As the majority of deaths are due to respiratory causes, attention to
the airway is the immediate priority. The mouth and upper passages
should be rid of debris and an oropharyngeal airway inserted. If the
patient is deeply unconscious a cuffed endotracheal tube should be
passed. This will provide for correct bronchial toilet, w i l l prevent
aspiration, and will be in situ should cardiac arrest occur. Above all
it will ensure a patent airway. An x-ray of the chest is mandatory
 BARBITURATES 503

after inserting the tube as in as many as 10% of patients the tube may
pass into the right main bronchus [55]. The hazards of the cuffed
endotracheal tube during insertion, while in situ, and after extubation
should be recognized [56] but they do not outweigh its many benefits.
Expert nursing attention will offset many of the hazards. Tracheostomy
will only be required in a small minority of patients; the time when
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that procedure is advised varies. It should however be remembered

that with expert nursing care, changing of the tube, and the develop-
ment of materials less irritating to the air passages, the indications
for tracheostomy should considerably lessen.
Having secured an adequate airway, the next step is to determine
whether ventilation is sufficient. The assessment should be objective,
for a clinical impression that the unconscious patient is breathing
properly is dangerous. The arterial blood should be sampled by pH,
pCOz, and pOz. Unfortunately arterial blood has to be taken, for venous
and capillary blood can give fallacious results. When the pOz is reduced
but above 6 0 mm Hg and the p C 0 ~is between 40 and 50 mm Hg oxygen
is indicated and should be administered by a 24% Ventimask with a flow
rate of 4 liters/min. The blood gases should be repeated 30 min later,
and if the pCOz shows no rise, then it is safe to use a 28% Ventimask.
Continued monitoring of the arterial blood gases is desirable. If the p 0 ~
goes below 60 mm Hg and/or the pC0z is more than 50 mm Hg, then
mechanical ventilation is essential. If blood gas analysis is not readily
available, then the respiratory minute volume as determined by the
Wright spirometer is very helpful. The apparatus has its limitations
especially at high flow rates and in children but it is very simple to
operate. The critical figure is a minute volume of less than 4 liters,
in which event significant respiratory impairment must be assumed
and some method to assist respiration employed [21].
Improvement in respiratory function is often not achieved in isolation.
For example, there is no better way of reversing shock than securing
proper oxygenation and of course the reverse holds.

Circulatory Failure

This is difficult to a s s e s s but is best measured in the seriously

poisoned patient by estimation of the central venous pressure. In the
less severely poisoned patient, measurement of the blood pressure
in the a r m is all that is required. A systolic pressure above 90 mm Hg
in patients over 50 years of age and above 80 in those under indicates
that circulatory failure is absent.
As already stated the establishment of a clear airway and adequate
ventilation does much to relieve shock. A s acidemia is also likely to
 504 MATTHEW

be present in shock, the blood gas analysis should include measure-

ment of the standard bicarbonate. Correction of acidemia will help
reverse shock. However, the first measure is simply to elevate the
foot of the bed, since it is thought that the main cause of shock is
the existence of hypovolemia along with peripheral pooling. This will
be effective in over 50% of shock patients. If no benefit follows this
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positional change, then more specific treatment becomes necessary.

Infusion of plasma expanders would seem the logical step to restore
the blood volume. There is, however, some danger; although the
circulating blood volume is reduced, there may be, in the absence of
dehydration, excess tissue fluid. With recovery from shock, circu-
latory overload may develop, leading to cardiac failure and pulmonary
edema [21]. With this danger in mind, small doses of metaraminal,
2.5 mg I.V., should be given; if there is no initial effect a dose of 5 mg
should be given in 20 min. Only one additional dose of 5 mg after 20
min should be given. It has not been shown that these small doses of
a vasoconstrictor drug produce renal vessel constriction; in fact
renal blood flow may be improved [57].
Should elevation of the foot of the bed and the administration of
metaraminal fail to correct shock then plasma expanders such as
plasma o r low molecular weight dextran should be given in appropri-
ate amounts as dictated by the central venous pressure readings.

P r e v e n t i o n of F u r t h e r A b s o r p t i o n

Considerable debate continues to surround this subject. Much of

it is based on condemning certain methods because the author has not
used the correct technique [58]. There is no doubt that syrup of
ipecac will make the majority of conscious patients vomit within 20
min after a dose of 30 ml. The crucial point is whether the vomiting
has effectively removed the ingested poison, and therefore that the
physician need not attempt anything further in this direction. If there
is any doubt, then gastric aspiration and lavage should be undertaken.
There a r e still some who advocate apomorphine for the conscious
patient [59]. Its action is uncertain, probably on account of difficulty
in assessing the effective dose. Vomiting can be terminated by an
injection of naloxone.
Corby et al. [60],perturbed at what they regarded as the some-
what poor results of both syrup of ipecac and apomorphine in inducing
an effective emesis, have documented the value of activated charcoal.
This decontaminant could be given after the induction of emesis o r
introduced into the stomach via the tube used for gastric aspiration
and lavage prior to i t s withdrawal.
 BARBITURATES 505

In barbiturate intoxication, removal of the poison will be best

achieved by gastric aspiration and lavage, provided the correct size
of tube and amount of lavage fluid is used [61]. The size of the tube
in an adult is a 30 English gauge Jacques stomach tube and the lavage
fluid warm water. The indications a r e that the patient is seen within
4 h r of ingestion and that he is either sufficiently conscious to protect
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his own lungs from aspiration by having an adequate cough reflex, o r

he is so deeply unconscious that his lungs can be protected by a cuffed
endotracheal tube. If a tube is in situ and the time since ingestion
is not known, then nothing is lost by undertaking gastric aspiration
and lavage. The procedure should be undertaken with the patient in
the head low position and on the left side. Aspiration should be
attempted after the well-lubricated tube has been passed by applying
a Dakin's syringe or simply by the effect of gravity by lowering the
funnel attached to the tube well below the stomach. Lavage with warm
water (38°C) should then be undertaken with 300 ml aliquots until the
returning fluid is clear [21]. Twenty liters of lavage fluid may be
required to reach this point.

Hypo t h e r m ia

Hypothermia can be said to exist when the low reading rectal

thermometer records a reading of Iess than 36°C. However read-
ings down to 30°C seldom give rise to difficulties and a r e met by
nursing the patient in an environmental temperature of 28°C. Warm
blankets applied to prevent heat loss and not simply to dilate up the
vessels of the skin and thereby induce further heat loss, a r e of value.
In prolonged hypothermia hydrocortisone, 100 mg, should be given a t
six hourly intervals intravenously but this may delay metabolism of
the barbiturate.
Below 30°C hypothermia may be dangerous, cardiac dysrhythmias
and sudden a r r e s t occurring [62, 631. Active reheating is thus re-
quired. If the hypothermia is of short duration and the patient young
then immersion in a warm water bath at 40°C is indicated. If of
longer duration and the patient older, such rapid surface rewarming
may induce cardiac dysrhythmias. Central heating by the method of
Lloyd [64] in which the inspired air is warmed by reverse passage
through a Watter's cannister is appropriate. Repeated peritoneal [65]
o r hemodialysis [66] may also be used. A much more simple but effec-
tive method is to immerse the forearm in a water bath at 43°C [21].

Electrolyte and Acid-Base Upset

There is nothing particular to barbiturate poisoning that necessi-
tates other than conventional management. Hydration should be
 506 MATTHEW

maintained by intravenous infusion of 1 liter 5% dextrose followed

by 0.5 liter normal saline, the rate usually being 1500 ml in 24 hr
o r slightly more at the outset if unconsciousness has been present
for some time. Particular care must be paid to fluid and electrolyte
balance in severe hypothermia.
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Bladder Catheterization
The majority of patients who indulge in barbiturate overdosage
are young women who are already liable to bladder and ascending
urinary tract infection. Catheterization should be avoided and urine
obtained by fundal pressure. Only in severely poisoned patients in
whom fluid balance studies are essential should catheterization be
necessary.

Antibiotic Therapy

Frequently patients who have been hypothermic even to relatively

minor degrees will show a rise in temperature above normal as they
recover [42]. This is not to be interpreted as due to infection and
antibiotics given. Nor should antibiotics be given in a so-called
"prophylactic" manner [67, 681. Only when there is clinical o r
laboratory evidence to support a diagnosis should the appropriate
antibiotic be given and in adequate doses.

D u r a t i o n of C o m a

Attempts have been made to determine the duration of coma in a

particular patient. However there are such a variety of factors
influencing absorption, tissue tolerance, and metabolism that no
prediction can be made with any accuracy. Such factors include
whether the patient is regularly taking the drug involved, in which
event the microsomal enzyme system in the liver will be mobilized
and the drug more rapidly metabolized. Other drugs may also
influence the rate of metabolism, either increasing or decreasing
it. If alcohol has been taken a t the same time, then absorption of
the barbiturate will be promoted and confusion will arise from the
contribution of the alcohol to the coma. The patient may have liver
o r renal disease, which will tend to slow metabolism. There is also
the little understood factor of tissue tolerance in those accustomed
to taking the drug. Finally in this problem of endeavoring to deter-
mine duration of coma there is the important fact that there is an
 BARBITURATES 507

increasing tendency for more than one drug to be taken at the same
time as the barbiturate.
It might be thought that the laboratory would be of great help by
providing blood barbiturate levels so that a correlation between levels
and length of coma could be formulated. It is a frequent misconception
that this is so. There is no correlation between barbiturate levels and
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length of coma. It is foolhardy to quote potentially fatal levels. We

have seen many ambulant patients with levels said to be potentially
fatal [21]. Regrettably the laboratory role is severely limited in the
matter of prognosis. Clearly, however, the laboratory will confirm o r
refute whether a barbiturate has been taken but even then without wide
screening the laboratory may not be in a position to indicate that the
barbiturate is the chief drug producing the clinical state of the patient.
Should a barbiturate be present in a seriously ill patient, then the
laboratory should be requested to determine the precise barbiturate-
long-, medium-, o r short-acting-involved as this may influence
treatment.
As the patient starts to return to consciousness from the deepest
grades, the first sign will be a cough reflex when bronchial suction is
being undertaken with a catheter. The rectal temperature begins to
rise. Thereafter there will be an increasing response to painful stim-
uli but progress toward recovery is not uniform. It is to be anticipated
that fluctuations will occur as the narcotized gut recovers and resumes
absorbing barbiturate from the gut, only to once again reduce the
amount of absorption. This fluctuation must therefore not give rise to
anxiety as it is to be expected, especially in the more severely poisoned.
When the patient is in the twilight of consciousness he may become
difficult to manage due to disorientation and confusion. Small doses
(50 mg) of chlorpromazine intramuscularly deal adequately with the
situation.
More florid confusion, delirium, and fits may appear shortly after
consciousness is regained, especially in those habituated to the drug.
If the barbiturate were being used as an anticonvulsant, then it is
usual to restart the anticonvulsant therapy. If however the addict has
no such need, then treatment as for delirium tremens is indicated
and must be energetically pursued.

Blisters

Barbiturate blisters should be treated as if they were burns,

asepsis being important. The rare ischemic contractures will
require much painstaking corrective surgery.
 508 MATTHEW

METHODS ATTEMPTING TO ELIMINATE

BARBITURATES

It is hoped that readers will not be tempted to read this section

without first having carefully studied and implemented what has
already been written. It cannot be emphasized too strongly that
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successful treatment of acute barbiturate poisoning depends on

meticulous attention to what h a s been termed "Intensive Supportive
Therapy." Any question of attempting to increase elimination plays
a very minor role in management. It is perhaps surprising that
there is no well- controlled study to demonstrate that removing
some of the drug does in fact shorten the period of unconsciousness.
There a r e many papers giving the amount removed by the various
procedures compared with spontaneous metabolism, but in no in-
stance is there unequivocal proof that the period of coma was
significantly reduced.
It is also somewhat curious that there has been no attempt to
define the volume of infused fluid that would merit the procedure
being rated as forced diuresis and not simply rehydration. The
clinical improvement resulting from the infusion of a "forced diu-
resis" is often the result not only of rehydration but more impor-
tantly in treating the shock by reversing hypovolemia. The diuresis
in fact does not take place.
Doctors who are trained as activists must therefore critically
consider the contribution of any method employed and weigh the
possibility that the procedure itself may contribute further to the
patient's problems.
With these cautions in mind, the role of forced diuresis, peritoneal
dialysis, hemodialysis, exchange transfusion, o r passage of blood
through charcoal o r ion exchange resins can then be considered. A
critical assessment of forced diuresis and dialysis has been pre-
pared by Bloomer and Maddock [69]. The last sentence reads, "How-
ever the responsible physician should be aware of the distinct lim-
itations of these manoeuvres especially when short acting barbiturates
are involved."
Forced alkaline diuresis will remove reasonable amounts of long-
acting barbiturates [70] and should be used when a patient is severely
poisoned by such a preparation. Hemodialysis and to a lesser extent
peritoneal dialysis will also remove long-acting barbiturates in
worthwhile amounts in a severely poisoned patient. Lee has written
extensively on these methods [71]. The amount of medium- and
short-acting barbiturate removed is not substantial, and I have never
used either hemodialysis o r forced alkaline diuresis in short- o r
 BARBITURATES 509

medium-acting barbiturate overdosage. The mortality in over 3000

such poisonings under my care is well under 1%. The role of these
methods in children is reviewed by Done [72].
The passage of blood through charcoal o r ion exchange resins in
barbiturate poisoning has its advocates “73, 741. Despite this method
being available for several years it does not yet appear to be gener-
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ally acceptable. This may be a tribute to the success of intensive

supportive therapy alone o r to the possible complications of platelet
reduction and charcoal emboli in the column perfusion method. If
these difficulties a r e overcome, then the perfusion of blood through
suitably coated charcoal o r ion exchange resins may prove accept-
able but it is hoped that this will not be used indiscriminately.

PSYCHIATRIC ASSESSMENT

All patients who have taken an overdose of a barbiturate should

be seen by a psychiatrist [75]. Despite official figures that show
that large numbers of patients die each year from accidental over-
dose of barbiturates, it is highly improbable that an adult ever
accidentally takes a barbiturate in overdose. Also the myth of bar-
biturate automatism has been exploded “761. Adult patients with
barbiturate poisoning have taken their overdose with a purpose o r
motive in mind. A small proportion will have done so with true
suicidal intent; the majority, however, a r e indulging in a conscious,
impulsive, manipulative act undertaken to secure redress of an
intolerable situation, thoughts of self destruction occupying little if
any part in their minds at the time of the act “751. They a r e uttering
a c r i de coeur, a warning to which attention must be paid o r they will
then indulge in true suicidal behavior.
It is also important to be aware that the size of the dose bears no
relationship to the immediate underlying psychiatric o r social dis-
tress [77]. Thus it should not be that the patient has to render him-
self sufficiently ill physically to impress the doctor that psychiatric
help is required.
Patients who a r e simply left a t home to sleep off the overdose a r e
three times more likely to repeat the overdose than those admitted
to hospital [78]. Although an occasional patient may be unresponsive,
such as one with a psychopathic behavioral problem, the majority
can and should be helped by psychiatric and sociak support.
The social aspects of those indulging in barbiturate poisoning in
the Edinburgh area have been reviewed in considerable detail by
McCulloch [79].
 510 MATTHEW

PREVENTION

It was suggested at the beginning of this article that apart from

their anticonvulsant property, barbiturates should no longer be
prescribed as sedative hypnotics. If this were implemented, then
clearly problems associated with barbiturate misuses would rapidly
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decline. Perhaps it is too much to hope for any rapid conversion of

the prescribing habits of doctors. However, those responsible for
the continuing education of doctors should be constantly reminding
them that there are now safe alternatives to barbiturates [80]and
that uncritical prescribing of a dangerous drug with strong addictive
properties should not be undertaken lightly. The changes arising in
the EEG sleep pattern after a barbiturate has been prescribed for
but a few days and then withdrawn have been described by Oswald
[81]. If barbiturates must be prescribed then their use lies in help-
ing a patient over some particular crisis such as a bereavement.
Therefore a large number are not required on each prescription.
Even when small amounts are provided, safety packaging is highly
desirable. They should not be prescribed for each and every tension
o r minor insomnia. Great care must be taken to ensure that insomnia.
is not a symptom of depression, for if the symptom is treated instead
of the cause then the barbiturate provides a ready means for suicide.

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