General Principles of Managing
Poisoned Patients
General laboratory evaluations of a
poisoned patient
BPHA4552 Toxicology
Objectives
• Describe common approaches to a
poisoned patient
• Discuss the main labs in poisoned
patients
• Identify common poisons and their
management
Introduction
 The trained pharmacist can play a useful role in
the management of patients poisoned with drugs
or other chemicals.
 The clinical aspects of the diagnosis and
treatment of such patients must be understood.
 The pharmacist must therefore have a basic
knowledge of emergency medicine, intensive
care, and pharmacology. must be able to
communicate with clinicians.
Diagnosis of acute poisoning
 Establishing a diagnosis
 In the case of an unconscious (comatose) patient, the
circumstances in which the patient was found and whether any
tablet bottles or other containers (scene residues) were
present can be important.
 If the patient is awake, he or she should be questioned about
the presence of poisons in the home or workplace. The
patient's past medical history (including drugs prescribed and
any psychiatric illness), occupation and hobbies may also be
relevant, since they may indicate possible access to specific
poisons.
Physical examination
 Physical examination of the patient may indicate the
poison or class of poison involved.
 The combination of pin-point pupils hypersalivation
incontinence and respiratory depression suggests poisoning
with a cholinesterase inhibitor such as an organophosphorus
pesticide.
 If a patient is admitted with depressed respiration and pinpoint pupils, this strongly suggests poisoning with an opioid
such as dextropropoxyphene or morphine.
 If the pupils are dilated, then other hypnotic drugs such as
glutethimide may be present, or cerebral damage may have
occurred as a result of hypoxia secondary to respiratory
depression.
Physical examination
 Diagnoses other than poisoning must also be
considered.
 For example, coma can be caused by a
cerebrovascular accident or uncontrolled
diabetes as well as poisoning.
 The availability of the results of urgent
biochemical and hematological tests is obviously
important in these circumstances.
Classification of coma
 Loss of consciousness (coma) is common in acute
poisoning, especially if central nervous system
(CNS) depressants are involved.
 A simple system, the Edinburgh scale, is often used
to classify the depth or grade of coma of poisoned
patients.
 This system has the advantage that the severity of
an episode can be easily described in conversation
with laboratory staff and with, poisons information
services that may be consulted for advice.
Edinburg Scale
Treatment of acute poisoning:
General measures
 When acute poisoning is suspected, essential symptomatic
and supportive measures are often taken before the
diagnosis is confirmed.
 Inhaled poison: patient should first be removed from the
contaminated environment.
 If skin contamination has occurred, contaminated clothing
should be removed and the skin washed with an
appropriate fluid, usually water.
 In adult patients, gastric aspiration and lavage (stomach
washout) are often performed, if the poison has been
ingested, to minimize the risk of continued absorption.
Treatment of acute poisoning:
General measures
 Similarly, in children emesis can be induced by the oral
administration of syrup of ipecacuanha (ipecac).
 The absorption of any residue remaining after gastric lavage
can be minimized by leaving a high dose of activated
charcoal in the stomach.
 Oral charcoal should not be given when oral administration
of a protective agent, such as methionine following
paracetamol overdosage, is contemplated.
 Subsequently, most patients can be treated successfully
using supportive care alone.
Treatment of acute poisoning:
General measures
 Specific therapeutic procedures, such as antidotal
and active elimination therapy are sometimes
indicated.
 The results of either a qualitative or a quantitative
toxicological analysis may be required before some
treatments are commenced.
 In general, specific therapy is only started when the
nature and/or the amount of the poison(s) involved
are known.
Antidotes/protective agents
 Antidotes or protective agents are only available for
a limited number of poisons.
 Controversy surrounds the use of some antidotes,
such as those used to treat cyanide poisoning,
while others are themselves potentially toxic and
should be used with care.
 Lack of response to a particular antidote does not
necessarily indicate the absence of a particular
type of poison.
Active elimination therapy
 There are four main methods of enhancing
elimination of the poison from the systemic
circulation:
 repeated oral activated charcoal
 forced diuresis with alteration of urine pH
 peritoneal dialysis and hemodialysis
 hemoperfusion.
Active elimination therapy:
Activated Charcoal
 The systemic clearance of compounds such as barbiturates,
carbamazepine, quinine and theophylline (and possibly also
salicylic acid and its derivatives) can be enhanced by giving
oral activated charcoal at intervals of 4-6 hours until clinical
recovery is apparent.
 To reduce transit time and thus reabsorption of the poison,
the charcoal is often given together with a laxative. This
procedure has the advantage of being totally noninvasive.
 It is less effective if the patient has a paralytic ileus resulting
from the ingestion of, for example, phenobarbital.
Active elimination therapy:
Forced diuresis
 The aim of forced diuresis is to enhance urinary excretion of
the poison by increasing urine volume per unit of time.
 It is achieved by means of intravenous administration of a
compatible fluid.
 Renal elimination of weak acids such as chlorophenoxy
herbicides and salicylates can be increased by the intravenous
administration of sodium bicarbonate.
 Alkalization alone can be as effective as traditional forced
alkaline diuresis, and has the advantage that the risk of
complications resulting from fluid overload, such as cerebral or
pulmonary edema and electrolyte disturbance, is minimized.
Active elimination therapy:
Dialysis and haemoperfusion
 Dialysis and hemoperfusion remove the poison directly from the
circulation.
 In hemodialysis, blood is passed over a membrane which is in contact
with the aqueous compartment in an artificial kidney, while in
peritoneal dialysis an appropriate fluid is infused into the peritoneal
cavity and then drained some 2-4 hours later.
 In hemoperfusion, blood is pumped through a cartridge of adsorbent
material (coated activated charcoal or Amberlite XAD-4 resin).
 Hemodialysis is preferred for water-soluble substances such as ethanol,
and hemoperfusion for lipophilic poisons such as short- acting
barbiturates, which have a high affinity for coated charcoal or Amberlite
XAD-4 resin.
 The decision to use dialysis or hemoperfusion should be based on the
clinical condition of the patient, the properties of the poison ingested and
its concentration in plasma.
General laboratory evaluations of a
poisoned patient
 Biochemical tests
 Blood glucose
 Electrolytes, blood gases and pH
 Plasma osmolality
 Plasma enzymes
 Cholinesterase activity
 Hematological tests
 Blood clotting
 Carboxyhemoglobin and methemoglobin
 Erythrocyte volume fraction (hematocrit)
 Leukocyte count
General laboratory evaluations of a
poisoned patient
• Blood glucose
– Marked hypoglycaemia often results from overdosage with insulin,
sulfonylureas, such as tolbutamide, or other antidiabetic drugs.
– Hypoglycaemia may also complicate severe poisoning with a number of
agents including iron salts and certain fungi, and may follow ingestion of
acetylsalicylic acid, ethanol (especially in children or fasting adults) and
paracetamol if liver failure ensues.
– Hypoglycin is a potent hypoglycaemic agent found in unripe ackee
fruit (Blighia sapida) and is responsible for Jamaican vomiting sickness.
– Hyperglycaemia is a less common complication of poisoning than
hypoglycaemia, but has been reported after overdosage with
acetylsalicylic acid, salbutamol and theophylline.
General laboratory evaluations of a
poisoned patient
• Electrolytes, blood gases and pH
– Coma resulting from overdosage with hypnotics, sedativse,
neuroleptics or opioid drugs is often characterized by hypoxia
and respiratory acidosis.
– In contrast, overdosage with salicylates such as acetylsalicylic
acid initially causes hyperventilation and respiratory alkalosis,
which may progress to the mixed metabolic acidosis and
hypokalaemia characteristic of severe poisoning.
– Hypokalemia and metabolic acidosis are also features of
theophylline and salbutamol overdosage. Hypokalaemia
occurs in acute barium poisoning,
– Hyperkalaemia occurs in severe acute overdosage with
digoxin.
General laboratory evaluations of a
poisoned patient
• Plasma osmolality
– The normal osmolality of plasma (280-295 mOsm/kg)
is largely accounted for by sodium, urea and glucose.
– Unusually high values (>310 mOsm/kg) can occur in
pathological conditions such as gross proteinemia or
severe dehydration where the effective proportion of
water in plasma is reduced.
– Large increases in plasma osmolality may follow the
absorption of osmotically active poisons (especially
methanol, ethanol or propan-2-ol) in relatively large
amounts.
General laboratory evaluations of a
poisoned patient
• Plasma enzymes
• The plasma activities of liver enzymes may increase
rapidly after absorption of toxic doses of substances
that can cause liver necrosis, notably paracetamol,
carbon tetrachloride, and copper salts.
• Shock, coma, and convulsions are often associated with
nonspecific increases in the plasma or serum activities
of enzymes (lactate dehydrogenase, aspartate
aminotransferase, alanine aminotransferase) commonly
measured to detect damage to the major organs.
General laboratory evaluations of a
poisoned patient
• Plasma enzymes
– The plasma activities of liver enzymes may increase rapidly after
absorption of toxic doses of substances that can cause liver necrosis,
notably paracetamol, carbon tetrachloride, and copper salts.
– The plasma activities of the aminotransferases may be higher than
normal in patients on chronic therapy with drugs such as valproic
acid, and serious hepatotoxicity may develop in a small proportion
of patients.
– Chronic ethanol abuse is usually associated with increased plasma
gamma-glutamyltransferase activity.
– In serious cases of poisoning, for example with strychnine,
myoglobinuria together with high serum or plasma potassium, uric
acid and phosphate concentrations may indicate the onset of acute
kidney failure.
General laboratory evaluations of a
poisoned patient
• Cholinesterase activity
– In practice, plasma cholinesterase is a useful indicator of
exposure to organophosphorus compounds or carbamates,
and a normal plasma cholinesterase activity effectively
excludes acute poisoning by these compounds.
– The difficulty lies in deciding whether a low activity is indeed
due to poisoning or to some other physiological,
pharmacological or genetic cause.
– The diagnosis can sometimes be assisted by detection of a
poison or metabolite in a body fluid.
– Pralidoxime is used as an antidote in poisoning with
organophosphorus pesticides
General laboratory evaluations of a
poisoned patient
• Hematological tests
– Blood clotting
• Prolonged prothrombin time is a valuable early
indicator of liver damage in poisoning with
metabolic toxins such as paracetamol.
• The prothrombin time and other measures of
blood clotting are likely to be abnormal in acute
poisoning with rodenticides such as coumarin
anticoagulants, and after overdosage with heparin
or other anticoagulants.
General laboratory evaluations of a
poisoned patient
• Carboxyhemoglobin and methemoglobin
– Measurement of blood carboxyhemoglobin can be used to assess the
severity of acute carbon monoxide poisoning and chronic dichloromethane
poisoning.
– However, carboxyhemoglobin is dissociated rapidly once the patient is
removed from the contaminated atmosphere, especially if oxygen is
administered, and the sample should therefore be obtained as soon as
possible after admission.
– Methemoglobin (oxidized hemoglobin) may be formed after overdosage
with dapsone and oxidizing agents such as chlorates or nitrites, and can be
induced by exposure to aromatic nitro compounds (such as nitrobenzene
and aniline and some of its derivatives).
– Methemoglobinaemia may be indicated by the presence of dark chocolatecoloured blood.
General laboratory evaluations of a
poisoned patient
• Erythrocyte volume fraction (hematocrit)
– Acute or acute-on-chronic overdosage with iron salts,
acetylsalicylic acid, indometacin, and other nonsteroidal antiinflammatory drugs may cause gastrointestinal bleeding
leading to anemia.
– Anemia may also result from chronic exposure to toxins that
interfere with haem synthesis, such as lead, or induce
hemolysis either directly (arsine, see arsenic) or indirectly
because of glucose-6-phosphate dehydrogenase deficiency
(chloroquine, primaquine, chloramphenicol, nitridazole,
nitrofurantoin).
General laboratory evaluations of a
poisoned patient
• Leukocyte count
– Increases in the leukocyte (white blood cell)
count often occur in acute poisoning,
– For example, in response to an acute
metabolic acidosis, resulting from ingestion of
ethylene glycol or methanol, or secondary to
hypostatic pneumonia following prolonged
coma.
References
• http://www.who.int/ipcs/publications/trainin
g_poisons/basic_analytical_tox/en/