Introduction

Barbiturates are a leading cause of acute poisoning because of their ready

availability. Most of the cases are suicidal but some occur through error or
ungraded exploration in children. The poisoning is characterized by stupor or
coma, areflexia and in late cases, severe respiratory depression and
cardiovascular insufficiency. It is a potentially fatal form of poisoning with
overall mortality of about 7%.1The clinical outcome is solely related to the
level of supervision and care provided by attending physician and nurses. A
highly organized intensive care unit can reduce the mortality rate to less than
2%. We present here case of a young girl of barbiturate poisoning who was
managed successfully using charcoal adsorption and haemodialysis with
favourable outcome.

Case Report

An 18-year old girl was admitted in the medicine department in an unconscious

state with no response to deep painful stimuli (Grade III coma). History as elicited
from her attendants was suggestive of oral intake of phenobarbitone tablets a night
before, after which the patient was not arousable in the morning. There was no
history of convulsions, vomiting, urinary incontinence or tongue bite. Within few
hours of admission, patient became febrile and tachypnoeic with pulse rate 130
min-1, blood pressure 120/70 mmHg and arterial oxygen saturation 93%. Pupils
were of normal size and reaction. Plantar and deep tendon reflexes were absent. A
diagnosis of barbiturate poisoning was made and patient was shifted to ICU.
Shortly after admission, she had tonic clonic convulsions which subsided after
few seconds spontaneously. She became increasingly tachypnoeic and oxygen
saturation started falling. Blood gas analysis done showed hypocarbia with
metabolic acidosis. She was intubated nasally and ventilated by Evita-2 (Drager)
ventilator on intermittent positive pressure ventilation mode with tidal volume 400
ml, FiO2-80% and frequency – 14 min-1.
 Patient was catheterized. Continuous nasogastric suction was done. Central
venous pressure guided fluid therapy was started. Continuous temperature
monitoring was done and care was taken to avoid hypothermia. Antibiotics,
phenytoin, rantidine, low dose dopamine and bronchodilator were started. In
addition, ten tablets of activated charcoal 500mg (5g) with egg albumin were
given four hourly through Ryle’s tube. Forced alkaline diuresis was started. One
litre of lactated Ringer solution was rushed and injection sodabicarbonate 50cc
was given intravenously six hourly. Aim was to keep urinary pH between 8-8.5.

Her serum potassium was 2.5.eq lt-1 and SGOT and SGPT were 118 IU and
99IU respectively. Serum proteins were 6g%. Urine was positive for ketone
bodies and serum barbiturate assay was positive. As her consciousness level did
not improve, haemodialysis was planned. Haemodialysis was done using
Sresenius Haemodialyser. Within hours, the patient’s condition improved and she
stared responding to verbal commands. Her vitals were stable. She was extubated
once regular spontaneous respiration was restored. Oxygen therapy with
ventimask (FiO2 – 60%) was instituted. Gradually, the patient was weaned to FiO2
of 28%. SGOT and SGPT were still elevated (222 IU and 240 IU respectively).
Repeat serum assay now revealed no residual barbiturate. She was discharged
home a week later.

Discussion

Barbiturates are chemical derivatives of barbituric acid and depending on

their duration of action, they can be classified as long acting (>6 hours),
intermediate acting (3-6 hours) and short acting (<3 hours). All barbiturates bind
to Gamma amino butyric acid receptors and prolong the opening of chloride
channels, thus inhibiting excitable cells of the central nervous system.

Barbiturates are frequently involved in over dosage, and are generally taken
with suicidal intent. Short acting barbiturates are more dangerous than long
acting. Shock and anoxia appear much more quickly and coma is more severe
with short acting barbiturates are 10mg 100ml-1 and 3mg 100ml-1 respectively.
These are achieved after the ingestion of total dose of 3 gm for short acting
drugs and 5 gm for long acting drugs. The poisonous effect of barbiturates is
potentiated by alcohol, narcotics, tranquilisers and antidepressants. Death
occurs from respiratory failure, severe hypotension, vasomotor failure, non
cardiogenic pulmonary oedema, hypothermia (which aggravates shock) or
oliguria with renal failure.

Acute barbiturate intoxication should be clinically evaluated to

differentiate it from other forms of coma or central nervous injury. History of
possible trauma, previous psychiatric illnesses, attempts at suicide and drug
usage should be obtained with particular attention directed towards the type,
amount and time of drug ingestion, the duration of coma and associated
ingestion of alcohol. Evidence of preexisting diseases such as hypertension,
cirrhosis and diabetes mellitus should also be sought. In our case there was no
such history.

Barbiturate poisoning is characterized by progressive CNS depression

culminating in paralysis of brainstem and medulla. In early stages, patient is
confused and lethargic with poor coordination, ataxia and dysarthria. This
progresses on to deep unremitting coma, total areflexia and unresponsiveness to
other stimuli as in our case. Corneal reflexes are lost. Conjugate doll’s eye
movement are absent. Pupils are usually constricted but may dilate in terminal
phases. Pupillary response to light is minimal. In late stages, respiration is
feeble, shallow and irregular and hypotension occurs. Apnea and cardiac arrest
may result.

Minimum laboratory evaluation include haematocrit, urine analysis

mainly for ketone bodies, WBC and differential counts. Plasma concentration
of electrolytes, blood urea, serum creatinine and liver function tests should be
 obtained. Chest X-ray and blood gas analysis are mandatory. A blood sample
should be sent for measurement is of little value except to confirm the presence
of barbiturate in plasma. Serial measurements provide a valuable guide to the
adequacy of therapy.

Management of barbiturate poisoning

1. Cardiorespiratory support

A clear airway is ensured by thorough suctioning and insertion of oral

airway. In addition, the passage of barbiturates across the blood brain barrier
into the central nervous system may be facilitated during hypoventilation and
respiratory acidosis. If the patient is comatose, prompt intubation (without
waiting for the PaO2 to fall to dangerously low levels) is strongly advocated
because of the fear of impending, worsening respiratory failure.

Dehydration is corrected by CVP guided fluid therapy depending on the serum

electrolyte reports. If hypotension persists, intravenous infusion of plasma volume
expanders and vasopressors is started. In refractory cases, steroids are given.

2. Measures to prevent absorption

a. Gastric lavage : If no more than 2-4 hours have passed since ingestion of the
barbiturate, gastric lavage is done.2

b. Activated charcoal : Is an inert non toxic adsorbent which binds high

molecular weight compounds due to intermolecular attractions. 1gKg-1 is
administered through nasogastric tube. Cathartic like magnesium sulphate
can be used along with it for further removal of barbiturates but
hypermagnesemia can occur.

3. Measures for removal of barbiturates

a. Frequent doses of activated charcoal : These adsorb the barbiturates when
they reenter the GIT through enterohepatic circulation. 1gKg-1 initial dose is
followed by 0.5gkg-1 every 2-4 hours.3

b. Forced diuresis with alkalinisation of urine: This is especially useful in

long barbiturates which are largely excreted by the kidney. At high rates of
urine flow (by the use of diuretics), the renal clearance of barbiturates is
increased. Thus, it shortens the duration of coma and decreases plasma
concentration of barbiturates. This should be avoided in older patients as it
can cause pulmonary oedema, hyponatraemia and increase in ICP.

In addition to diuresis, phenobarbitol excretion can be enhanced ten fold by

urinary alkalinization (pH 7.8 -8.0). Alkalinising urine causes ionization of
phenobarbitone after its filtration into renal tubular cells and trapping the
agent, thereby inhibiting its re-absorption from renal tubules and increasing
its excretion.

c. Haemodialysis and haemoperfusion: Is now being used extensively in

treatment of barbiturate intoxication to increase rate of removal of
barbiturates. Single six hour haemodialysis can remove an amount of
barbiturate which is comparable to that removed during 24 hours of sustained
diuresis or peritoneal dialysis.

Newer technique of lipid dialysis can extract long acting drugs such as
phenobarbitol in greater quantity. Removal of short acting barbiturates is more
limited because of lower plasma concentrations and greater binding to plasma
proteins.4 Our patient improved remarkably well after haemodialysis.

Analeptic Drugs
 These have minimal role now a days because under their influence, true clinical
assessment of patient becomes impossible. Also, they are associated with side
effects like convulsions, cardiac arrhythmias, vomiting, hyperpyrexia.

Supportive care

The most important aspect of management in these cases is close

observation and quality nursing care. Prophylactic antibiotics should be started.
Good oral hygiene, temperature maintenance, and posture change at regular
intervals.

Usually, recovery from barbiturate coma is without neurologic deficit even after
severe poisoning. Our patient also recovered fully without any deficit. The rarity
of permanent damage after barbiturate coma precludes immediate establishment
of adequate pulmonary ventilation as well as control of shock to be of prime
importance.
We were able to save our patient because of immediate control of ventilation,
temperature maintenance, early prevention of renal damage and haemodialysis.