’ Management of toxicity

Emergency Management (Resuscitation)

(ABCD)

Clinical evaluation
(History & Physical Examination)

Lab Investigation

Decontamination

Enhance elimination

Supportive treatment

Antidote therapy
’ Management of toxicity

5 corners are important:

 Resuscitation (ABCD)
 Prevent further absorption
 Enhance elimination
 Supportive treatment
 Antagonize actions of toxic agents
(Antidotal therapy)
 Enhance
elimination
’ Enhance elimination
Used when:
- The poison should be present in high concentration in the plasma relative to
that in the rest of the body i.e. it should have a small distribution volume (Freely
soluble in body water)
- The poison should dissociate readily from the plasma protein binding sites
- The substance or its active metabolites are excreted in the urine
- The effect of the poison should relate to its plasma concentration
- For dialysis: Low molecular weight and size
’ Enhance elimination
Enhance elimination

Extracorporeal
Forced diuresis Repeated dose of
techniques
Peritoneal
activated charcoal
Alkalinization of
urine dialysis

Hemodialysis
Acidification of
urine
Hemoperfusion
Diuretics
Haemofiltration

Plasmapheresis
’ A) Forced diuresis

Tubular
Reabsorption
I) Alkalinization of urine

 Mechanism: promotes excretion of weak acids by increasing

their ionization “ion trapping” in the renal tubules
 Administer intravenous sodium bicarbonate to increase
urinary pH to 7.5 - 8
 Uses: for weak acidic drugs: salicylate, phenobarbitone, TCA

N.B: serum pH and electrolytes should be monitored closely.

II) Acidification of urine
 Mechanism: promotes excretion of weak bases by
increasing their ionization “ion trapping” in the
renal tubules
 Administer intravenous ammonium chloride/ or
ascorbic acid to increase urinary pH to 7.5 - 8
 Uses: acute toxicity of amphetamine, quinine &
phencyclidine
• serum pH and electrolytes should be monitored
closely.
III) Diuretics
Forcing diuresis with furosemide and large volumes of i.v. fluid
does not add significantly to drug clearance and may cause fluid
overload

Procedure
The procedure involves a cycle of 1.5 L of fluid every 3 hours,
consisting of: normal saline, 5% dextrose
IV frusemide 20 mg is given at the end of each cycle.

N.B: serum electrolytes, Patient’s input and output & general condition and
vital signs should be monitored closely.
’ B) Extracorporeal techniques

Hemo-
Peritoneal Hemo- Hemo- Plasma-
dialysis
dialysis perfusion filteration pheresis
’ I) Peritoneal dialysis
• This type of dialysis uses the patient's peritoneum in the abdomen as
a membrane across which fluids and dissolved substances are
exchanged from the blood into dialysis fluid. Poison in the blood
enters the dialysis fluid down the concentration gradient
• Although widely available, today it is almost never recommended for
detoxification
• In general it is only 10-25% as effective as hemodialysis and slightly more
effective than forced diuresis.
• It is also time consuming requiring 24hr for successful completion (2-4hr for
hemodialysis and haemoperfusion)
’ I) Peritoneal dialysis
 Procedure:
1) A catheter is surgically inserted
with one end in the abdomen and
the other protruding from the skin

2) Instilling appropriate fluid into

peritoneal cavity (the fluid used
typically contains sodium,
chloride, lactate or bicarbonate
and a high percentage of glucose to
ensure hyperosmolarity of the
dialysate) .
-It takes about 10 minutes for the
dialysate to fill your belly.
’ I) Peritoneal dialysis
 Procedure:

3) When the filling is done, the catheter is capped so that it doesn't leak.
4) The fluid then drained and replaced

N.B: Adequate peritoneal blood flow is essential, so it is inefficient if

the pt is hypotensive

 Complications:
- Pain -Perforation of viscus
- Hemorrhage - Bacterial peritonitis
- Volume depletion/overload - Electrolyte imbalance
’ II) Hemodialysis
Hemodialysis is the process of altering the solute composition of blood
by removing it from an artery, diffusing it across a semipermeable
membrane (between the blood and a dialysis fluid ), then returning it
into a vein. The poison passes passively from the blood, where it is
present in high concentration into the fluid (passive diffusion)

- Suitable anticoagulation measures should first be taken.

- A catheter is usually placed in the femoral vein.
Through this, blood is passed through the dialyser
before being returned to the venous circulation
’ II) Hemodialysis
’ II) Hemodialysis
 Complications:
• Infections (especially
Hepatitis)
• Thrombosis
• Hypotension
• Bleeding due to use of
heparin as a systemic
anticoagulant
’ III) Haemoperfusion
This is a process by which blood is passed through a column containing
activated charcoal, activated carbon or ion-exchange resins, resulting in
adsorption of the poison.

An advantage of hemoperfusion over hemodialysis is that the total surface area

of the dialyzing membrane is much greater with the hemoperfusion cartridges.

Loss of blood cells & activation of the clotting system are largely overcome by
coating the charcoal with an acrylic hydrogel which does not reduce
adsorbing capacity

The patient must be anticoagulated with heparin

’ IV) Hemofiltration
During hemofiltration, a patient's blood is passed through a set of
tubing (a filtration circuit) via a machine to a semipermeable
membrane (haemfilter) where waste products and water (collectively
called ultrafiltrate) are removed by convection , a positive hydrostatic
pressure drives water and solutes across the filter membrane from the
blood compartment to the filtrate compartment, from which it is
drained

Thus convection overcomes the reduced removal rate of larger solutes (due to their
slow speed of diffusion) seen in hemodialysis.

It can remove compounds of large relative molecular weight such as

aminoglycosides and metal chelates (iron-desferrioxamine)
’ IV) Plasmaphresis
It is a technique of separating cellular blood components from
plasma. During plasmapheresis, blood (which consists of blood cells
and a clear liquid called plasma) is initially taken out of the body
through a needle or previously implanted catheter. Plasma is then
removed from the blood by a cell separator. Then the cells are re-
suspended in fresh frozen plasma and then re-infused

• Advantages: Very effective in eliminating toxic substances

• Disadvantages: A part of patient`s plasma proteins are sacrificed
’ IV) Plasmaphresis
’ V) Multi-Dose Activated Charcoal
Multiple doses of activated charcoal are believed to enhance
elimination of certain drugs excreted via biliary secretion. The
mechanism of action is thought to be interruption of the
enterohepatic circulation and a gastro-intestinal dialysis
effect.

It does not only prevent absorption of ingested drug in the gut but also
it adsorp drugs that is secreted into the bile or that diffuses from the
blood into the gut lumen
 Supportive
(Symptomatic)
treatment
’ Electrolyte Disturbances
 Hyperkalemia (K level > 5.5 mEq/L)
 Causes
- ACE inhibitors (Captopril) and angiotensin receptor blockers (ARBs)(Losartan)
- Potassium-sparing diuretics (e.g. amiloride and spironolactone)

 Treatment

Insulin infusion (to a shift of potassium ions into cells, secondary

to increased activity of the sodium-potassium ATPase), glucose,
& Ca gluconate
’ Electrolyte Disturbances
Hypokalemia (K level < 3.5 mEq/L)

 Causes
- NSAIDs, sreroids & liquorice

- All diuretics exceot potassium sparing diuretics

 Treatment

- Oral or IV potassium
’ Electrolyte Disturbances

 Hypernatraemia (Na > 150 mEq/L)

 Causes
- NSAIDs & sreroids

 Treatment
- loop diuretics
’ Electrolyte Disturbances
 Hyponatraemia (Na < 130 mEq/L)
 Causes
- Drugs that augments the action of endogenous ADH: chlorpropamide
- Drugs that increase the release of ADH e.g. carbamazepine
- Drugs with direct ADH like action on kidneys e.g. oxytocin

 Treatment
-Hypertonic saline
’ Agitation
 Causes

• Several drugs & poisons are associated with increased aggression which may
sometimes progress to psychosis and violent behavior

EX: Anticholinergic drugs : TCA

 Treatment

• Place the patient in quiet room, reducing sensory input and remove objects of
potential harm.

• Diazepam (5mg orally or intravenously) is the first choice. Haloperidol may reduce
agitation if diazepam is ineffective.
’ Delirium & Dementia
• Delirium used to denote such acute psychotic episodes and is characterized
by disorientation, irrational fear, hyperexcitability, hallucination and violence

• Dementia refers to a more gradual decline in mental processes mainly in

confusion and memory loss
- Elderly are more vulnerable

 Causes

- Anticholinergic drugs : TCA

 Treatment

- Diazepam / Haloperidol
’ Hypertension
Can cause stroke (usually cerebral hemorrhage), acute
myocardial infarction, pulmonary edema, and/or
hypertensive encephalopathy.

 Causes

- Amphetamines and cocaine

- Antidepressants (venlafaxine and desipramine)
- Caffeine
- Corticosteroids
- Cyclosporine
’ Hypertension
 Treatment
Nitroprusside is the drug of choice for hypertensive emergencies because its
effect begins immediately and ceases when the infusion stops.
• The use of nitroprusside requires constant monitoring of pressure and an
infusion pump.

• Precautions:
• The infusion must be covered with foil to protect the contents from
degradation by light.
• The solution should be discarded 4hr after mixing.
• Infusions above 6μg/kg/min may result in cyanide intoxication particularly
’ Hypertension
 Treatment

Other choices; vasodilator such as:

- Nitroglycerin

- The alpha blocker phentolamine

- A calcium channel blocker such as nifedipine.

’ Anaphylaxis
Anaphylaxis is a serious allergic reaction that is rapid in
onset and may cause death
 Signs & Symptoms
Itchy rash,
throat or tongue swelling (Angioedema)
shortness of breath (bronchospasm),
vomiting,
Hypotension.
’ Anaphylaxis
 Causes
- Insect bites and stings
- Foods : certain types of seafood
- Medications β-lactam antibiotics (such as penicillin )
, aspirin and NSAIDs

 Treatment
The primary treatment of anaphylaxis is epinephrine injection into
a muscle, intravenous fluids, and positioning the person flat.
Other measures, such as antihistamines, salbutamol and steroids
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