Unit VI: Clinical toxicology

Management of poisoned patients, clinical methods to decrease absorption

and enhance excretion of toxicants from the body, use of antidotes.
Cassarette- Chapter-32

● The initial phases of treatment of a seriously poisoned patient usually

occur in the setting of a hospital emergency room but initial treatment in
other, less ideal settings such as the battlefield, workplace, home or street
setting can be required as well.
This section will refer primarily to the treatment of poisoned patients in the
Emergency. In that setting, the following general steps represent important
elements of the initial clinical encounter for a poisoned patient:
1. Stabilization of the patient
2. Clinical evaluation (history, physical, laboratory, radiology)
3. Prevention of further toxin absorption
4. Enhancement of toxin elimination
5. Administration of antidote
6. Supportive care and clinical follow-up
1. Clinical Stabilization
● The first priority in the treatment of the poisoned patient is clinical
stabilization.
● This is the so-called ABCs (Airway, Breathing,Circulation) of initial
emergency treatment.
● Assessment of the vital signs and the effectiveness of respiration and
circulation are the primary objectives of this initial encounter.
● Early in the course of some poisonings there is a varying range of
severity of demonstrated toxic effects by patients poisoned with even
lethal dosages of toxins.
● Some chemicals, such as a benzodiazepine can cause pronounced clinical
effects early such as sedation but can have a comparatively mild clinical
course; while other chemicals, such as camphor, show little clinical
effects initially but can produce a fatal outcome.
● Some chemicals can cause seizures early in the course of their
presentation.
 ● Control of chemical-induced seizures can be an important component of
the initial stabilization of the poisoned patient.
● The degree of initial clinical stabilization required for a poisoned patient
therefore is highly variable.

2. Clinical History in the Poisoned Patient

● The primary goal of taking a medical history in poisoned patients is to
determine, whenever possible, what substance the poisoned patient has
been exposed to and to determine the extent and time of exposure.
● Unfortunately, in contrast to most specialties of medicine, the clinical
history available during the initial clinical encounter in the treatment of
poisoned patients is sometimes not helpful because it may be either
unreliable or unobtainable.
● For these reasons, additional sources for the clinical history are often
incorporated to aid the clinical treatment.
● Examples of possible sources sometimes employed to obtain an accurate
history include family members, emergency medical technicians who
were at the scene, a pharmacist who can sometimes provide a listing of
prescriptions recently filled or an employer who can provide a list of
chemicals that are in the work environment.
The toxicologist can refer to various information resources to determine
what the range of expected clinical effects might be from the estimated
exposure.
Physical Examination
● One of the most important aspects of the initial clinical encounter in the
treatment of the poisoned patient is the physical examination.
● A thorough examination of the patient is required to assess the patient’s
condition, categorize the patient’s mental status and, if altered, determine
possible additional explanations for the abnormal mental status such as
trauma or central nervous system infection.

● One very helpful tool for the clinical toxicologist is to categorize the
patient’s physical examination parameters into broad classes referred to
as toxic syndromes. These toxic syndromes have been called toxidromes
Table 32-1 Clinical Features of Toxic Syndromes

Table 32-2 Characteristic Odours Associated with Poisonings

Laboratory Evaluation
● A common misconception concerning the initial treatment of poisoned
patients is that a definitive diagnosis of the specific agent or poison
responsible for the patient’s clinical presentation is frequently made by
the clinical laboratory during the initial patient evaluation.
● Specific assays for toxins available in clinical laboratories on a rapid
turnaround basis(STAT, e.g., within 1 hour) is very limited.
● 'Stat' in doctor lingo means 'immediately! '. "Stat" is derived from the
Latin word 'statum' meaning 'right away'. Doctors write stat on
prescriptions when they want their orders filled right away
Table 32.3 Drugs Commonly Measured in a Hospital Setting on a STAT Basis
There are two calculations that toxicologists can perform using clinical
laboratory values routinely obtained in an acute clinical setting.

The calculations performed on routine clinical labs are the anion gap and
the osmol gap.

● An abnormal anion gap or osmol gaps suggests a differential diagnosis

for significant exposure of a poisoned patient.
● Both calculations are used as diagnostic aids when the clinical history
suggests poisoning and the patient’s condition is consistent with exposure
to agents known to cause elevations of these parameters (i.e., metabolic
acidosis, altered mental status, etc.).
The anion gap is calculated as the difference between the serum Na ion
concentration and the sum of the serum Cl and HCO3 ion concentrations.

● When there is laboratory evidence of metabolic acidosis in a poisoned

patient, the finding of an elevated anion gap would suggest systemic
toxicity from a relatively limited number of agents.
A popular clinical pneumonic (AT MUD PILES) is commonly employed as a
memory aid for this differential diagnosis.
Table 32-4 lists the more common agents that have metabolic acidosis with an
elevated anion gap as part of the clinical presentation that are included in this
pneumonic.

The second calculated parameter from clinical chemistry values is the

osmol gap.
● The osmol gap is calculated as the numerical difference between the
measured serum osmolality and the serum osmolarity calculated from the
clinical chemistry measurements of the serum sodium ion, glucose, and
blood urea nitrogen (BUN) concentrations.

● An elevated osmol gap in the setting of a poisoned patient suggests the

presence of an osmotically active substance in the plasma that is not
accounted for by the Na, glucose or BUN concentrations.
Table 32-5 lists several substances that when ingested can be associated
with an elevated osmol gap in humans.
While calculation of both the anion gap and the osmol gap can provide very
useful information from readily available clinical chemistry measurements,
these determinations must be interpreted cautiously in certain clinical settings.
For example, even though a patient may have ingested a large, significantly
toxic amount of methanol, if measured late in the clinical course of the
exposure, the osmol gap may not be significantly elevated as most of the
osmotically active methanol has left the plasma and has been biotransformed or
cleared but still producing serious clinical effects.
Radiographic Examination
● Generally, plain radiographs can detect a significant amount of ingested
oral medication containing ferrous or potassium salts.
3. Prevention of Further Poison Absorption
● During the early phases of poison treatment or intervention for a toxic
exposure via the oral, inhalation or the topical route, the treatment team
may have an opportunity to prevent further absorption of the poison to
minimize the total amount that reaches the systemic circulation.
● For chemicals presented by the inhalation route, the main intervention to
prevent further absorption is removal of the patient from the environment
where the chemical is found and to provide adequate ventilation and
oxygenation for the patient.
● For topical exposures, patient clothing containing the toxin must be
removed and properly disposed in airtight wrappings or containers to
ensure that the rescuers and health care providers are adequately
protected from secondary exposure.

● Most topical exposures require gentle washing of the skin with water and
mild soap taking care not to cause cutaneous abrasions of the skin that
may enhance dermal absorption.
The optimal time to intervene to prevent continued absorption of an oral poison
is as soon as possible after the ingestion.
The four primary methods currently available for this purpose are:
1. Induction of emesis with syrup of ipecac,
2. Gastric lavage
3. Oral administration of activated charcoal and
4. Whole bowel irrigation.
● Induction of emesis with a variety of agents was the sole modality
employed to treat poisoning by seeking to reduce the gastrointestinal
absorption of poisons.
● Tartar emetic was an antimony salt used for induction of emesis and other
medicinal purposes.
● Other emetic agents used later on included mustard mixed in water,
concentrated solutions of copper and zinc salts and various botanical
substances.
● Currently syrup of ipecac is the only agent available for induction of
emesis in the treatment of a potentially toxic ingestion
● The use of gastric lavage, the technique of placing an orogastric tube
into the stomach and aspirating fluid then cyclically instilling fluid and
aspirating until the effluent is clear, has diminished significantly in recent
years.
● During the last 20–30 years there has been growing use of oral charcoal
as a therapeutic intervention for oral poisoning.
● For many years, orally administered activated charcoal has been
routinely incorporated into the initial treatment of a patient poisoned by
the oral route.
● The term “activated” refers to the substantially increased adsorptive
capacity that results from the processing of charcoal obtained from the
burning of carbonaceous substances such as wood pulp, sugars, organic
material and industrial wastes.
● The processing involves extensive treatment with steam, carbon dioxide,
oxygen, zinc chloride, sulfuric acid, or phosphoric acid at temperatures of
500–900 degrees Fahrenheit “activate” the residue oxidation which leads
to a significant increase in surface area through creation of small pores in
the material.
● Many organic molecules are significantly bound to activated charcoal.
● Generally low-molecularweight, and polar compounds, such as ethanol,
tend to be less well bound to activated charcoal.
● Substances such as lithium, iron and certain inorganic salts are also not
appreciably bound.
 ● In acute oral overdose, activated charcoal is typically administered at a
dosage of 1.0–1.5 g/kg.
● When the patient is unable to safely drink the charcoal it is placed into the
stomach via orogastric or nasogastric tube
● The usefulness of whole bowel irrigation for the treatment of the
poisoned patient is very limited.
● Whole bowel irrigation is a procedure that in essence “washes” the lumen
of the gastrointestinal tract clear of unabsorbed material.
● The procedure is accomplished with a poorly absorbed, osmotically
neutral polyethylene glycol electrolyte solution that is administered orally
to expel the contents of the intestines via the rectal route.
● This procedure is used to prepare the lower intestine for endoscopic
medical procedures of the large intestine.
● The primary role of this technique is for removal of ingested pack causing
toxic effects due to leakage.
● Other potential roles for this gastrointestinal technique are to treat
ingestion of sustained release formulations of drugs and ingestions of
substantial amounts of iron preparations

5. Enhancement of Poison Elimination

● There are several methods available to enhance the elimination of specific

poisons or drugs once they have been absorbed into the systemic
circulation.
The primary methods employed for this use today include:
● alkalinization of the urine,
● hemodialysis,
● hemoperfusion,
● hemofiltration,
● plasma exchange or exchange transfusion ,and
● serial oral activated charcoal.

● The use of urinary alkalinisation results in the enhancement of the renal

clearance of certain weak acids. The basic principle is to increase urinary
filtrate pH to a level sufficient to ionize the weak acid and prevent renal
tubule reabsorption of the molecule. This is also referred to as ion
trapping.
 ● The ion-trapping phenomenon occurs when the pKa of the agent is such
that after glomerular filtration into the renal tubules, alteration of the pH
of the urinary filtrate can ionize and “trap” the agent in the urinary filtrate.
● Once the toxin is ionized, reabsorption from the renal tubules is impaired,
and as a result, more of the drug remains in the urinary filtrate and is
excreted in the urine.
● Clinical use of this alkalinization procedure requires adequate urine flow
and close clinical monitoring including that of the pH of the urine.
● The procedure is accomplished by adding sterile sodium bicarbonate to
sterile water with 5% dextrose for intravenous infusion and titrating the
urine pH to 7.5 to 8.5.
● The drugs for which this procedure has been shown clinically efficacious
include salicylate compounds and phenobarbital which have pKa’s of 3.2
and 7.4, respectively.
● The increase in total body clearance for salicylate for example, by
increasing urinary pH from 5.0 to 8.0 can be substantial.
The dialysis technique, either hemodialysis or peritoneal dialysis, relies on
passage of the toxic agent through a semipermeable dialysis membrane (or
the peritoneal membrane) so that it can equilibrate with the dialysate and
subsequently be removed.
● Hemodialysis incorporates a blood pump to pass blood next to a dialysis
membrane to allow agents permeable to the membrane to pass through
and reach equilibrium.
● In order for this method to be clinically beneficial the chemical must have
a relatively low volume of distribution, low protein binding a relatively
high degree of water solubility and low molecular weight.
● Use of hemodialysis to attempt to remove a chemical with the later three
characteristics but with a high volume of distribution, such as digoxin,
would not be clinically beneficial because the vast majority of the drug is
not in the physiologic compartment (blood) accessible to the dialysis
membrane.
● Therefore, despite hemodialysis being able to effectively clear the
digoxin in plasma during the dialysis run, most of the body burden of
digoxinis located outside of the blood compartment and is not appreciably
affected by the procedure.
Drugs and toxins for which hemodialysis has been shown to be clinically
effective in the treatment of poisoning by these agents is shown in Table
32-6.
● The technique of hemo perfusion is similar to hemodialysis except there
is no dialysis membrane or dialysate involved in the procedure.
● The patient’s blood is pumped through a perfusion cartridge where it is in
direct contact with adsorptive material (usually activated charcoal) that
has a coating of material such as cellulose or a heparin-containing gel to
prevent the adsorptive material from being carried back to the patient’s
circulation.
● The principle characteristics for a drug or toxin to be successfully
removed by this technique are low volume of distribution and adsorption
by activated charcoal.
● This method can be used successfully with lipid soluble compounds and
with higher molecular weight compounds than for hemodialysis.
● Protein binding does not significantly interfere with removal by
hemoperfusion.
● Because of the more direct contact of the patient’s blood with the
adsorptive material the medical risks of this procedure include
thrombocytopenia, hypocalcemia and leukopenia.

● This technique Is primarily used for the treatment of serious theophylline

overdose and possibly amanita toxin exposure, paraquat and
meprobamate poisoning.
 ● The use of the technique of hemofiltration for the treatment of
poisoning is relatively new and consequently there is much less
experience with the modality for enhancement of chemical elimination.
● During this procedure,the patient’s blood is delivered through hollow
fiber tubes and an ultrafiltrate of plasma is removed by hydrostatic
pressure from the blood side of the membrane.
● Different membrane pore sizes are available for use so the size of the
filtered molecules can be controlled during the procedure.
● The perfusion pressure for the technique is either generated by the
patient’s blood pressure (for arteriovenous hemofiltration) or by a blood
pump (for veno venous hemofiltration).
● Needed fluid and electrolytes removed in the ultrafiltrate are replaced
intravenously with sterile solutions.
● The procedure has the advantage of continuous use compared to the 4–6
hour limitation for a hemodialysis run.
● One theoretical advantage of continuous filtration versus intermittent
hemodialysis is that the rebound phenomenon is not seen with
hemofiltration as it is with certain poisons after hemodialysis.
● The rebound of serum concentrations occurs when there is redistribution
of the dialyzed poison to the blood when dialysis is interrupted.
● This rebound is commonly seen during hemodialysis for lithium
overdose.
Serial oral administration of activated charcoal, also referred to as
multiple-dose activated charcoal (MDAC), has been shown to increase the
systemic clearance of various drug substances.
● The mechanism for the observed augmentation of non-renal clearance
caused by repeated doses of oral charcoal is thought to be translumenal
efflux of drug from blood to be adsorbed to the charcoal passing through
the gastrointestinal tract.
● In addition, MDAC is thought to produce its beneficial effect by
interrupting the entero enteric-entero hepatic circulation of drugs.
 The characteristics of toxins that favor enhanced elimination by MDAC
include:
(1) significant enteroenteric-enterohepatic circulation, including the formation
of active recirculating metabolites,
(2) prolonged plasma half-life after an overdose,
(3) small (<1.0 L/kg) volume of distribution,
(4) limited (<60%) plasma protein binding,
(5) a pK a that maximizes transport of drug across cell membranes,
(6) sustained-release/resin-form tablets and/or capsules, and
(7) onset of organ failure (e.g., kidney) that results in reduced capacity of the
major route of elimination of the toxin so that MDAC may make a considerable
contribution to total body clearance.
● The technique involves continuing oral administration of activated
charcoal beyond the initial dosage (described above) every 2–4 hours
with approximately one-half the initial dose, or 0.5 g/kg.
● The charcoal is generally mixed as an aqueous slurry and a cathartic
substance is not incorporated due to the potential for electrolyte
abnormalities with repeated administration of cathartic agents.
● An alternative technique for MDAC is to give the activated charcoal via
an orogastric tube or nasogastric tube a loading dose of 1.0 g/kg of an
aqueous slurry or activated charcoal (not the combination product that
contains the cathartic sorbitol) followed by a continuous infusion
intragastrically of 0.2 g/kg/h.
● The duration of gastric infusion depends on the clinical status of the
patient and repeated monitoring of plasma drug levels where indicated.
6. Use of Antidotes in Poisoning
● A relatively small number of specific antidotes are available for clinical
use in the treatment of poisoning.

● A chelating agent or Fab fragments specific to digoxin work by

physically binding the toxin, preventing the toxin from exerting a
deleterious effect in vivo and in some cases, facilitating body clearance of
the toxin.

● Atropine, an anti muscarinic, anticholinergic agent is used to

pharmacologically antagonize at the receptor level, the effects of
organophosphate insecticides or acetylcholinesterase inhibiting nerve
gases, which produce cholinergic, muscarinic effects, which if sufficient,
can be lethal.

● Sodium nitrite is given to patients poisoned with cyanide to cause

formation of methemoglobin, which serves as an alternative binding site
for the cyanide ion thereby making it less toxic to the body..

● Intravenous naloxone can have a dramatic effect on the level of

consciousness of an opiate poisoned patient within minutes.

● Chelating agents such as desferoxamine may require multiple dosages

over many days before a clinically detectable effect is seen in case iron
poisoning.

● N-Acetylcysteine is the drug of choice for the treatment of an

acetaminophen overdose. It is thought to provide cysteine for
glutathione synthesis and possibly to form an adduct directly with the
toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine.

● The oral chelator penicillamine or succimer (2,3-dimercaptosuccinic acid,

DMSA) is effective in removing arsenic from the body.
Dimercaptopropanesulfonic acid (DMPS) has also been used for acute
arsenic poisoning with fewer side effects.
● The oral chelating agent dimercaptosuccinic acid (DMSA, also called
Succimer) has advantages over EDTA in that it can be given orally and is
effective in temporarily reducing Blood Lead Level.

● Therapy for mercury poisoning should be directed toward lowering the

concentration of mercury at the critical organ or site of injury.

● For the most severe cases, particularly with acute renal failure,
hemodialysis may be the first measure, along with adminstration of
chelating agents for mercury, such as cysteine, EDTA, BAL, or
penicillamine.

● Caution should be taken to avoid inappropriate use of chelating agents in

putative mercury poisoning patients.

● Chelation therapy is not very helpful for alkyl mercury exposure.

● Biliary excretion and reabsorption by the intestine can be interrupted by

oral administration of a non-absorbable thiol resin, which can bind
mercury and enhance fecal excretion.

7. Supportive Care of the Poisoned Patient

● Once the initial treatment phase in the clinical management of the

poisoned patient has been completed, the care of the patient is generally
shifted to an inpatient hospital setting for those patients who will require
admission.
● This supportive care phase of poison treatment is very important.
Poisoned patients who are unstable or at risk for significant clinical
instability are generally admitted to a medical intensive care unit for close
monitoring.