1.

General principles of treatment in poisoning and drug overdose

2. To know the supportive care and prevention of poison absorption

 3. To know the enhancement of poison elimination and prevention of exposure

Corporeal Treatments
 Intestinal Exsorption
 Multiple-Dose Activated Charcoal
Activated charcoal can be given to enhance elimination of certain poisons. This is
in contrast to the administration of single-dose activated charcoal to prevent
systemic absorption of large ingestions, bezoars, or sustained-release
preparations (decontamination). Multiple-dose activated charcoal (MDAC)
promotes clearance of poisons by two possible mechanisms: by interrupting
enterohepatic circulation of xenobiotics secreted in bile or by promoting the
passive diffusion of poisons down a concentration gradient from the intestinal
capillaries to the intraluminal gut space, a process also described as “exsorption”.
The intestinal mucosa serves as a dialysis membrane, and the term “gut dialysis”
seems to have first been introduced by Levy when commenting on the work of
Berg.
Literature on MDAC is heterogeneous: the evidence includes animal
experiments, human volunteer studies, case reports, as well as very few
randomized-controlled trials. This disparity in patient selection and study
designs makes the interpretation of the published results complex and
controversial for different poisons.
To add to the difficulty in comparing clearance data, MDAC regimens are not
uniform in their dose, frequency, and duration. Most centers recommend 1 g/kg
of aqueous activated charcoal given every 4 hours or 0.5 g/kg every 2 hours until
improvement in status or decline in poison concentrations in the blood. Efficacy
appears unaltered by different dosing regimens.
Ideal toxicokinetic properties of poisons amenable to MDAC therapy include a
small volume of distribution, low protein binding, prolonged half-life, low
intrinsic clearance, and a nonionized state at physiologic pH, although the data
are conflicting.
Contraindications to MDAC include an altered level of consciousness with an
unprotected airway, protracted vomiting unresponsive to antiemetic therapy,
and intestinal occlusion. Complications such as aspiration pneumonitis,
appendicitis, or charcoal bezoar with MDAC have also been reported
infrequently. The incidence of these complications seems to increase with the
amount of activated charcoal doses given.
At present, MDAC has been shown to increase total body clearance for a few
poisons, although it is unclear if this affects clinical outcomes. In a study of
carbamazepine poisoning, duration of coma and need for mechanical ventilation
were decreased in patients receiving MDAC.
In another randomized controlled trial of oleander seed poisoning, MDAC for 72
hours yielded fewer deaths and dysrhythmias.
In 1999, a joint initiative by the American Association of Clinical Toxicology
(AACT) and the European Association of Poison Centres and Clinical
Toxicologists (EAPCCT) published guidelines for the use of MDAC and
recommended its use for life-threatening poisoning with five substances:
theophylline, dapsone, carbamazepine, phenobarbital, and quinine.
 Resins
 Sodium Polystyrene Sulfonate
Sodium polystyrene sulfonate (SPS) is a cation exchange resin usually
administered for the treatment of hyperkalemia. SPS can also bind other cations
such as thallium and iron.
 Animal studies have shown that SPS can bind lithium (Li) in the GI tract and
enhance elimination of already absorbed Li. Furthermore, this effect is dose
dependent.
 In one retrospective human study of 48 patients, apparent Li half-life was
decreased nearly 50% in patients who received SPS, although fecal Li
measurements were lacking to document the contribution of SPS on total body Li
clearance.
 Complications associated with SPS include hypokalemia and intestinal necrosis,
although its true incidence and its association with sorbitol remain controversial.
 Prussian Blue
The crystal structure of the Prussian blue (PB) molecule binds potassium, but it
has higher affinity for cesium and thallium. It is given orally and it is not
absorbed by the GI tract. PH is currently used for decontamination and fecal
exsorption of radiocesium and thallium.
PB comes in two formulations: insoluble and soluble salts. Radiocesium
poisoning has been more often reported with soluble PB whereas the insoluble
form of PB has been used with thallium poisoning. It is unclear if both can be
used interchangeably for these two poisonings.
Cholestyramine
The use of cholestyramine, a lipid-lowering resin, has been used with success,
although anecdotally, to enhance elimination for the following poisons: digoxin,
digitoxin, ibuprofen, meloxicam, methotrexate, mycophenolate mofetil,
perfluorinated compounds, piroxicam, tenoxicam, and warfarin.
In the case of digoxin poisoning, the idea of resin binding has been largely
supplanted by the use of digoxin-specific Fab fragments. The role of
cholestyramine in digoxin poisoning when digoxin-specific Fab fragments are
unavailable remains unclear.
 Renal Elimination
 Forced Diuresis
The principle behind forced diuresis is to promote poison elimination by using a
large volume of intravenous crystalloids to which loop diuretics can be added.
The role of forced diuresis has been advocated for substances with kidney
excretion such as cyclophosphamide, thallium, isoniazid, meprobamate, fluoride,
iodide, 5-fluorouracil, cisplatin, bromides, barium, chromium, Li, salicylates, and
ethylene glycol. The efficacy of this technique has not been demonstrated. In the
case of salicylate poisoning, urine alkalinization is much more effective than
forced diuresis.
 Furthermore, forced saline diuresis has not been shown to enhance elimination
of Li compared with aggressive fluid repletion.
 Finally, complications such as fluid overload, pulmonary edema, cerebral edema,
hypernatremia, and hypokalemia are deterrents for its application.
 Urinary Alkalinization
Alteration in urine pH is used to alter undissociated acid or base in the tubular
lumen to its ionized form. Because charged particles diffuse poorly from the
renal tubular lumen back to blood, their urinary elimination is enhanced. Poisons
for which urinary clearances are likely to be increased with alkalinization need
to be predominantly eliminated by kidneys, distributed in the extracellular
compartment, be weak acids with a pKa in the range of 3.0-7.0, and minimally
protein-bound. Because pH is a logarithmic value, each 1.0 increment in urine pH
will increase elimination 10-fold; therefore, urine pH should be kept between 7.5
and 8.5 for maximal efficacy.
A direct relationship has been shown between urinary salicylate concentrations
and urine pH. Coma duration was shortened by 50% in phenobarbital-poisoned
patients who received urinary alkalinization, although MDAC is usually preferred
in this context despite the absence of clinical benefit in one prospective
randomized trial.

Urinary Acidification
On the other hand, weak bases will have their kidney excretion promoted in acid
urine. Urinary acidification with ammonium chloride or ascorbic acid has been
proposed in amantadine, amphetamine, quinidine, or phencyclidine poisoning.
However, it is no longer recommended because of modest elimination enhancement
and the significant risk associated with metabolic acidosis, particularly in poisoned
patients.
A summary of poisons that can potentially be significantly eliminated by corporeal
treatments are presented

Extracorporeal Treatments

Extracorporeal treatments (ECTRs) are only used in approximately 0.1% of

poisonings treated in the United States however, this percentage is on the rise and
suggests that the indications of these techniques are either increasing or are becoming
better understood. Although ECTRs are often viewed as more efficient than corporeal
treatments, they are also more invasive, more costly, and require transfer to a
specialized center.

Hemodialysis
Hemodialysis (HD) remains the technique most often used for the treatment of ESRD
and AKI. Solute elimination is based on diffusion through a semipermeable
membrane. The molecular cutoff of most conventional dialyzers today is
approximately 5000 Da, with poisons of small size being preferentially eliminated.
Therefore, the circuit cannot remove poisons that are very large or are bound to
proteins. However, because protein binding sites may be saturated in overdose, a
larger portion of unbound poison is present that can then be eliminated

Hemofiltration
Hemofiltration (HF) is based on the principle of convection, in which convective
forces or solvent drag removes water and particles. Although most often
dispensed continuously in the intensive care unit (as continuous veno-venous
HF), several centers in Europe and North America are now offering this as an
intermittent therapy for ESRD. Because of the high permeability of hemofilters,
HF can clear larger molecules than HD (up to 50,000 Da).
 Hemoperfusion
In hemoperfusion (HP), blood passes through a charcoal or resin column to
which poisons are adsorbed. HP can remove small- and large-sized poisons
(including those that are highly protein bound). Compared with HD, HP is
associated with more complications than HD (namely hypocalcemia,
thrombocytopenia, leucopenia, hypoglycemia) as well as superior cost and early
saturation of columns.
 Exchange Transfusion
In exchange transfusion (ET), blood is exchanged milliliter per milliliter. It has
the advantage of eliminating poison tightly bound to erythrocytes. Although
clearances obtained with ET are lower than with other ECTRs, this technique can
be performed without the complex apparatus needed for HD. ET is also easier to
operate in neonates and has been used for poisoning due to theophylline and
salicylates in this population. ET is beneficial in poisoned-induced hemolysis,
which can follow exposure to xenobiotics such as in chromium, dapsone, and
arsine.

 Peritoneal Dialysis
In peritoneal dialysis (PD), a solution is inserted in the peritoneal cavity for a
short dwell during which poison can diffuse freely from capillaries to the
dialysate. Although technically occurring inside of the body, PD can be quickly
performed in patients after insertion of a peritoneal catheter, but it does not
provide equivalent efficacy compared with HD. Clearances obtained with PD are
15-20 mL/minute at best, compared with 200-250 mL/minute in HD. However,
PD may be considered when other more efficient ECTRs are unavailable, in the
neonatal patient where PD might be easier to perform than HD, and in poisoning
of marginal severity affecting patients already undergoing PD.
 Plasmapheresis
In plasmapheresis (PP), plasma (and all of its solutes) is separated from blood
and replaced by either 5% albumin or fresh frozen plasma during one or more
sessions. PP can usually eliminate very large poisons (up to 3,000,000 Da) such
as dextran and rituximab. However, most known poisons are small and are
therefore better removed by other ECTRs. Compared with HD, PP is also less
available and carries more complications.

 Liver Dialysis
Liver dialysis (such as single-pass albumin dialysis) is becoming more available
for the treatment of hepatic failure, sometimes as a bridge for liver
transplantation. Because liver dialysis can remove protein-bound poisons, it has
been used for treatment of various poisonings, such as for Amanita
phalloides and calcium-channel blockers.
 Although promising, these techniques are expensive and have yet to show better
toxicokinetic advantages than either PP or even HD.
 Combined ECTRs
ECTRs can be combined to optimize the respective advantages of convection,
diffusion, and adsorption. For example, HP and HP have been used in series.
 Continuous Versus Intermittent Techniques
Continuous techniques are usually dispensed continuously over 24 hours
whereas intermittent techniques are usually performed over a standard 4- to 6-
hour period (although they can be performed for much longer without expected
additional problems). In the critical care setting, continuous techniques are often
used for the treatment of oliguric AKI and preferred over conventional HD. This
is explained, amongst other reasons, by the possibility to remove fluid over
longer periods of time, reducing the risk of hypotension. 
Drugs and Medicines

 Only take prescription medications that are prescribed to you by a healthcare

professional. Misusing or abusing prescription or over-the-counter
medications is not a “safe” alternative to illicit substance abuse.
 Never take larger or more frequent doses of your medications, particularly
prescription pain medications, to try to get faster or more powerful effects.
 Never share or sell your prescription drugs. Keep all prescription medicines
(especially prescription painkillers, such as those containing methadone,
hydrocodone, or oxycodone), over-the-counter medicines (including pain or
fever relievers and cough and cold medicines), vitamins and herbals in a safe
place that can only be reached by people who take or give them.
 Follow directions on the label when you give or take medicines. Read all
warning labels. Some medicines cannot be taken safely when you take other
medicines or drink alcohol.
 Turn on a light when you give or take medicines at night so that you know you
have the correct amount of the right medicine.
 Keep medicines in their original bottles or containers.
 Monitor the use of medicines prescribed for children and teenagers, such as
medicines for attention deficit hyperactivity disorder, or ADHD.1
 Dispose of unused, unneeded, or expired prescription drugs. Follow federal
guidelines for how to do this (FDA 2011).External
  Participate in National Drug Take Back days recognized by the Drug
Enforcement Administration or local take back programs in your
communityExternal.

Household Chemicals and Carbon Monoxide

 Always read the label before using a product that may be poisonous.
 Keep chemical products in their original bottles or containers. Do not use food
containers such as cups, bottles, or jars to store chemical products such as
cleaning solutions or beauty products.
 Never mix household products together. For example, mixing bleach and
ammonia can result in toxic gases.
 Wear protective clothing (gloves, long sleeves, long pants, socks, shoes) if you
spray pesticides or other chemicals.
 Turn on the fan and open windows when using chemical products such as
household cleaners.

4. To know specific poison and approach for organophosphate and carbamate

Carbamate
Decontamination
Due to the continued cutaneous absorption of carbamate pesticides, decontamination
should take place as soon as possible. Medical providers should avoid self-
contamination by wearing personal protective equipment (PPE). Neoprene or nitrile
gloves provide adequate protection from cutaneous exposures, and the provider
should wear full PPE with a minimum of a gown, mask, and face shield. Latex gloves
do not provide adequate protection for insecticides. All clothing should be removed
from the patients, and the skin should be triple-washed with water, then soap and
water, and then rinsed again with water. Vomitus and diarrhea may cause cutaneous
absorption in providers in cases of GI ingestions.
In massive, life-threatening ingestions, GI decontamination may be considered if (1)
the patient has not had bouts of emesis, (2) the ingestion occurred within 1 hour, and
(3) if the patient is protecting their airway. In this instance, nasogastric lavage can be
instituted. In severe toxicity, patients may have seizures, respiratory paralysis, and
coma. Airway protection should take place before GI decontamination if any of these
features are present. Data is disputed regarding carbamate toxicity's adequate
adsorption by activated charcoal. Some experts recommend administering 1 g/kg of
single-dose activated charcoal if the patient presents within 1 hour of a massive life-
threatening GI ingestion. Consultation with the poison center or regional toxicologist
before GI decontamination may be a reasonable approach given the risk of aspiration
of activated charcoal and the questionable benefit of this therapy.
Respiratory
Respiratory failure and hypoxemia is the primary cause of death after toxic exposure
to AChE inhibitors. This is multifactorial secondary to bronchorrhea, muscular
weakness with potential flaccid paralysis, and depression of CNS respiratory drive.
After decontamination, initial patient assessment should be directed at ensuring
adequate ventilation and oxygenation. Increased respiratory secretions may be treated
with atropine via competitive inhibition of the excessive muscarinic receptor
excitation. Early endotracheal intubation should be performed for patients with
difficulty managing their respiratory secretions, comatose or severely depressed
mental status, or significant skeletal muscle weakness. Depolarizing neuromuscular
blockers such as succinylcholine should be avoided, as serum cholinesterases are
inactivated by AChE inhibitors, and prolonged paralysis lasting up to several hours
can occur. Instead, paralysis should be induced using nondepolarizing neuromuscular
blockers such as rocuronium.  
Atropine
Atropine competitively antagonizes the increased acetylcholine levels at muscarinic
receptors and decreases symptoms of lacrimation, salivation, miosis, emesis, diarrhea,
diaphoresis, urinary incontinence, bronchospasm, and excessive respiratory
secretions. Atropine, starting at doses of 1 to 3 milligrams intravenously (IV) in adults
or 0.05mg/kg IV in pediatric patients with a minimum dose of 0.1mg, should be
administered. The dose should be doubled every five minutes if the previous dose
provides an inadequate response. Previous descriptions of “atropinization" (dry skin
and mucous membranes, decreased bowel sounds, tachycardia, an absence of
bronchospasm, and mydriasis) did not emphasize meaningful endpoints of
resuscitation, and treatment should be directed towards achieving cardiorespiratory
stability. The adequate dose of atropine is reached when there is attenuation of
tracheobronchial secretions and decreasing bronchoconstriction accompanied by
adequate blood pressure and heart rate for tissue perfusion. After a stabilizing dose of
atropine is reached, treatment response is maintained by a constant infusion of
atropine that is usually 10% to 20% of the bolus dose per hour. Tachycardia is not a
contraindication to atropine administration in patients presenting with carbamate
poisoning, as tachycardia may be secondary to hypoxia and excessive
bronchopulmonary secretions. Doses over 1000mg of atropine have been recorded
over 24 hours to treat severe AChE inhibitor poisonings. Atropine does not reverse
the skeletal muscle weakness caused by nicotinic receptor stimulation in carbamate
toxicity. Patients need to have continued monitoring for potential respiratory failure,
requiring mechanical ventilation after atropine administration.  
Oxime
Pralidoxime (2-PAM) is commonly given to patients with OP toxicity early in the
presentation to prevent the “aging” process as OPs irreversibly bind to AChE.
Carbamates will spontaneously disassociate from AChE and recover function within
24 to 48 hours. Studies have shown potentially increased AChE inactivation if
pralidoxime is administered in cases of carbaryl poisoning. However, potential benefit
from oxime therapy in aldicarb poisoning has been described. In cases of known
single-agent carbamate toxicity without concern for possible concomitant OP
exposure, pralidoxime therapy can be withheld. However, when faced with
undifferentiated insecticide toxicity, pralidoxime can be given, as administration in
carbamate toxicity is unlikely to be detrimental, and the benefit for OP intoxication is
well described. 
Benzodiazepines
Benzodiazepines are used for the treatment of seizures and agitation for intubated
patients after carbamate toxicity. Limited data exist evaluating the efficacy of
benzodiazepines for seizures secondary to insecticide poisonings, as seizures are
uncommon in large case series of carbamate and OP toxicity. Due to this lack of data,
standard abortive seizure therapy with benzodiazepines is commonly instituted.
Disposition
Carbamates typically have a more benign clinical course compared to OP poisonings
due to transient cholinesterase inhibition and rapid reactivation of AChE enzymatic
activity. Most patients will experience complete recovery within 24 hours. Patients
who have depressed levels of consciousness can have significant mortality. Patients
with mild initial symptoms not requiring atropine can be safely discharged after
observation. Moderate poisonings will necessitate 24 hours of observation, and
patients requiring atropine should be admitted to a monitored setting for continued
assessment of their respiratory status.
Organophosphate
The first step in the management of patients with organophosphate poisoning is
putting on personal protective equipment. These patients may still have the compound
on them, and you must protect yourself from exposure. Secondly, you must
decontaminate the patient. This means removing and destroying all clothing because it
may be contaminated even after washing. The patient’s skin needs to be flushed with
water. Dry agents such as flour, sand, or bentonite also can be used to decontaminate
the skin. In the case of ingestion, vomiting and diarrhea may limit the amount of
substance absorbed but should never be induced. Activated charcoal can be given if
the patient presents within 1 hour of ingestion, but studies have not shown a benefit.
The definitive treatment for organophosphate poisoning is atropine, which competes
with acetylcholine at the muscarinic receptors. The initial dose for adults is 2 to 5 mg
IV or 0.05 mg/kg IV for children until reaching the adult dose. If the patient does not
respond to the treatment, double the dose every 3 to 5 minutes until respiratory
secretions have cleared and there is no bronchoconstriction. In patients with severe
poisoning, it may take hundreds of milligrams of atropine given in bolus or
continuous infusion over several days before the patient improves.
Pralidoxime (2-PAM) also should be given to affect the nicotinic receptors since
atropine only works on muscarinic receptors. Atropine must be given before 2-
PAM to avoid worsening of muscarinic-mediated symptoms. A bolus of at least 30
mg/kg in adults or 20 to 50 mg/kg for children should be given over 30 minutes.
Rapid administration can cause cardiac arrest. After the bolus, a continuous infusion
of at least 8 mg/kg/hr for adults and 10 to 20 mg/kg/hr for children should be started
and may be needed for several days.

Organophosphates and carbamates are used extensively in the United States as

insecticides. In addition, interest in these substances has grown in recent years
because of their association with bioterrorism and potential for mass
exposure.334 Organophosphates act as irreversible acetylcholinesterase (AChE)
inhibitors. Carbamates are reversible AChE inhibitors. Insecticides can be
absorbed through the mouth, skin, conjunctiva, gastrointestinal tract, or
respiratory tract. Toxicity occurs within 12 to 24 hours after exposure from
excess acetylcholine at neural end plates due to inhibition of AChE.335

The diagnosis of organophosphate poisoning is made on clinical grounds and

by measurement of cholinesterase activity in the blood. The history may
suggest attempted suicide, accidental ingestion, industrial/agricultural
exposure, terrorism, or rarely ingestion of contaminated food.336,337 Emergency
department personnel have also been inadvertently poisoned through contact
with patients.338The signs and symptoms of poisoning by both classes of
insecticides are virtually identical except that carbamates do not readily cross
the blood-brain barrier to cause CNS toxicity. Clinical features include miosis
(85%), vomiting (58%), excessive salivation (58%), respiratory distress
(48%), abdominal pain (42%), depressed mental status (42%), and muscle
fasciculations (40%).339 In one case series, tachycardia occurred more often
than bradycardia (21% vs 10% of cases). In early poisoning, there is a
transient period of intense sympathetic tone causing tachycardia, followed by
heightened parasympathetic tone and bradycardia, heart block, and ST- and T-
wave abnormalities.338 Breath or sweat may take on the odor of garlic.

Clinical features of organophosphate poisoning result from overstimulation of

muscarinic, nicotinic, and central receptors (Table 124-25).340 Muscarinic
overstimulation results in sustained toxicity characterized by the mnemonic
SLUDGE (salivation, lacrimation, urination, diarrhea, gastrointestinal cramps,
and emesis). Blurred vision, miosis, bradycardia, and wheezing are also
muscarinic effects. Nicotinic effects are less sustained and characterized by
fasciculations, muscle weakness (that can progress to paralysis), hypertension,
and tachycardia. Organophosphates penetrate the blood-brain barrier to cause
anxiety, confusion, psychosis, seizures, and ataxia.

The two principal cholinesterases are RBC cholinesterase (also called

acetylcholinesterase or AChE), which is present in red blood cells and nerve
endings, and pseudocholinesterase (PChE), which is found primarily in liver
and serum. Carbamates and organophosphates inhibit both. Clinical toxicity is
due primarily to inhibition of AChE, but PChE is more readily quantified.
Levels may not correlate with the severity of poisoning.341 A falsely low PChE
may be seen in liver disease, anemia, and malnutrition, and as a normal
genetic variant (familial succinylcholine sensitivity). Normal levels of enzyme
activity do not exclude poisoning because of wide variations in normal levels.
In the absence of a baseline levels, serial measurements may confirm the
diagnosis.342

During initial patient stabilization, attention should be paid to the respiratory

status. Bronchoconstriction, excess secretions, muscle weakness, and an
altered mental status all increase the risk of respiratory failure requiring. In
agricultural exposures, it is important to remove all contaminated clothing and
cleanse hair and skin thoroughly to decrease skin absorption. Health care
workers must protect themselves from accidental exposure by wearing
appropriate gloves and gowns. Activated charcoal and gastric lavage may be
useful if done immediately after ingestion, but the airway must be protected.

Symptomatic patients should receive atropine immediately. Treatment should

not await results of AChE or PChE levels. Atropine competitively blocks
acetylcholine at muscarinic receptors but has no effect on nicotinic
receptors. Atropine crosses the blood-brain barrier and can cause CNS toxicity
that is difficult to distinguish from organophosphate toxicity. In this
situation, glycopyrrolate (which does not penetrate the CNS) is a reasonable
alternative to atropine.343 In addition, regimens including combinations
of atropine and glycopyrrolate have been proposed that would allow for
less atropine. One study suggests decreased mortality with this combination
when compared with a historical control of atropine alone patients.344 The dose
of atropine required to achieve atropinization (characterized by clear
pulmonary examination and heart rate >80 beats per minute)340varies
depending on the severity of poisoning. Doses of up to 40 mg/d may be
required. If atropinization occurs after 1 to 2 mg of atropine, the diagnosis of
acetylcholinesterase inhibitor poisoning should be questioned. The initial dose
of atropine is 2 mg IV. This dose should be doubled every 3 to 5 minutes until
atropinization has been achieved. Continuous atropine infusion can then be
started at 10% to 20% of the loading dose required to achieve atropinization
hourly while closely monitoring for atropine toxicity (delirium and
hyperthermia).340

Pralidoxime (2-PAM) reverses nicotinic and muscarinic effects of

organophosphate poisoning by reactivating AChE and protecting the enzyme
from further inhibition. In carbamate poisoning, pralidoxime may not be
needed because of the more rapid resolution of symptoms and reversible
nature of enzyme inhibition. It has historically been suggested
that pralidoxime may enhance carbaryl (or Sevin, a carbamate insecticide)
toxicity,345 although current recommendations recognize the difficulty
oftentimes present in distinguishing carbamate and OP toxicity and therefore
recommend oxime therapy in addition to atropine as needed.334 To be
effective, pralidoxime should be given within the first 6 hours of poisoning
(although treatment in the first 24-48 hours may still be effective), prior to
irreversible phosphorylation of cholinesterase (a process referred to as
“aging”). After this critical period, restoration of normal cholinesterase
function requires regeneration of the enzyme, a process that may take weeks to
complete. Antimuscarinic effects allow for atropinization more quickly, and
with lower doses of atropine. The initial dose of pralidoxime is 1 to 2 g IV
given over approximately 10 to 20 minutes. Clinical response should be
evident within 30 minutes. If there is no improvement in fasciculations or
weakness, the dose may be repeated once. A continuous infusion is then
administered at a rate of 200 to 500 mg/h, titrated to achieve the desired effect.
Continuous infusion of pralidoxime may be necessary for over 24 hours,
depending on the half-life and lipid solubility of the poison, after which the
dose may be gradually reduced and stopped while the patient is observed for
signs of recurrent muscle weakness.