Prep. By :

Dr.Alaa Eldeen ElmassryEgyptian fellowship of internal medicine ( E.F.I.M.),Palestinian board of internal medicine ( P.B.I.M. ),Consultant internistHead of the medical dept.,Naser hospital.

Recognize the epidemiology of drug overdose?

What are the different toxidrome pattern seen in clinical practice?

What are the general lines of therapy of poisoned patient?

Different specific poisoning that might face in our practice.

1-A 24-year-old male is brought to the emergency department after taking cyanide in a suicide attempt. He is unconscious on presentation. What drug should be used as an antidote?A.A. AtropineB.B. Methylene blueC.C. 2-PralidoximeD.D. Sodium nitrite aloneE.E. Sodium nitrite with sodium thiosulfate

2-Which of the following findings suggests an opiate overdose?A. Anion gap metabolic acidosis with a normal lactateB. Hypotension and bradycardia in an alert patientC. MydriasisD. Profuse sweating and droolingE. Therapeutic response to naloxone

3-A patient with metabolic acidosis, reduced anion gap, and increased osmolal gap is most likely to have which of the following toxic ingestions?A. LithiumB. MethanolC. OxycodoneD. Propylene glycolE. Salicylate

4-Which of the following is true regarding drug effects after an overdose in comparison to a reference dose?A. Drug effects begin earlier, peak earlier, and last longerB. Drug effects begin earlier, peak later, and last longerC. Drug effects begin earlier, peak later, and last shorterD. Drug effects begin later, peak earlier, and last shorterE. Drug effects begin later, peak later, and last longer

5-Which of the following statements regarding gastric decontamination for toxin ingestion is true?A. Activated charcoal’s most common side effect is aspiration.B. Gastric lavage via NGT is preferred overthe use of AC in situations where therapeutic endoscopy may also be warranted.C. Syrup of ipecac has no role in the hospital setting.D. There are insufficient data to support or exclude abenefit when gastric decontamination is used morethan 1 h after a toxic ingestion.E. All of the above are true.

6-Which one of the following statements regarding paracetamol overdose is false?1. Metabolic acidosis with pH of <7.3 after fluid resuscitation is an indication for liver transplant2. The first bag of NAC in treatment of paracetamol overdose contains NAC 100mg/kg.3. NAC has anti-oxidant property4. Prognostic accuracy of Rumack-Matthew nomogram decreases after 15hours5. Paracetamol level is highest after 4 hours after ingestion

Analysis of 2001 data from US poisoning centers revealed the following statistics:95 % caused minor or no effects92 % were due to acute rather than chronic ingestions92 % involved a single substance85 % were unintentional59 % fatalities occurred in individuals aged 20 to 4952 % occurred in children younger than 6 years47 % involved pharmaceuticals

Adolf HitlerCyanide and gunshot simultaneously before capture

Socrate (d. 399 BC) , Greek philosopher — According to Plato, sentenced to kill himself by drinking poison hemlock

Is a former pediatric nurse who killed somewhere between 11 and 46 infants and children in her care.

British doctor acquitted in 1957 but suspected of killing 163 patients via morphine and barbiturates

The Bhopal disaster (commonly referred to as Bhopal gas tragedy) was a gas leak incident in India , considered one of the world's worst industrial catastrophes .

The official immediate death toll was 2,259

When to suspect the poisoning ?1.Rapid onset of symptoms like vomiting, abdominal pain or depressed consciousness.2.Mass affection. 3.Psychiatric patients.4.Specific toxic syndrome.

Is often unreliable when provided by a patient following intentional ingestion

Knowledge of drugs prescribed for the patient or the patient's family or friends to which (s)he could have had access

A thorough search of the exposure environment should be conducted for pill bottles or a suicide note

The mental status, vital signs, and pupillary examination are the most useful elements and allow classification of the patient into either a state of physiologic excitation or depression

Physiologic excitation, manifested by central nervous system stimulation and increased pulse, blood pressure, respiratory rate and depth, and temperature, is most commonly caused by anticholinergic, sympathomimetic, or central hallucinogenic agents, or by drug withdrawal states.

Physiologic depression, manifested by a depressed mental status, blood pressure, pulse, respiratory rate and depth, and temperature, is most commonly precipitated by cholinergic (parasympathomimetic), sympatholytic, opiate, or sedative-hypnotic agents, or alcohols

Characteristic odorsPupillary findings Neuromuscular abnormalities

Mental status alterationsSkin findingsTemperature alterationsBP and heart rate alterationsRespiratory disturbances

OdorAgent(s)Acetone

(fruity)Ethanol, isopropyl alcohol,

chloroform, salicylatesBitter

almondsCyanide

Garlic

Arsenic, organophosphates, phosphorus, thallium, selenium

MothballsNaphthalene,

paradichlorobenzene

KeroseneOrganophosphates,

parathionFreshly mown

hayPhosgene

Rotten eggsHydrogen sulfideWintergreenMethyl salicylate

MydriasisSympathomimeti

csCocaineCaffeineEphedrineAmphetaminesMethylphenidateAnticholinergicsAtropineScopolamine

TCAsAntihistaminesAntiparkinson agentsMuscle relaxantsAntispasmodicsPhenothiazines (some)Plants (with belladonna alkaloids)Hallucinogens

MiosisOpioids

Heroin

Morphine

Hydromorphone

Oxycodone

Hydrocodone

Codeine

Propoxyphene

Sedative-hypnotics

Barbiturates

Benzodiazepines

Organophosphate insecticidesCarbamate insecticides Pilocarpine EdrophoniumPhysostigmineSympatholyticsClonidineOxymetazolineTetrahydrazolineAntipsychoticsMiscellaneous

NystagmusBarbituratesCarbamazepinePhencyclidinePhenytoinLithiumEthanolToxic alcoholsOrganophosphatesStrychnineMAOIsSerotonin syndrome

CyanoticCyanideMethemoglobinemiaSulfhemoglobinemiaHypoxemia

Carbon monoxide MushroomsEthanolScombroid fish poisoningAnticholinergic agents  AntihistaminesTCAsAtropine

Hypertension with tachycardiaThyroid hormoneAnticholinergics Drug withdrawal statesOrganophosphatesSympathomimetics

MAOIs (foods with tyramine)Disulfiram reaction (early)Cholinergic agentsOrganophosphatesAlpha-adrenergic agonists

TCAsTheophyllineAlbuterolToxic alcoholsBeta-adrenergic agonists

BarbituratesBeta-blockersCalcium-channel blockersDigoxinCyanideOpiates

A toxidrome, or toxic syndrome, is a constellation of clinical examination findings that assists in the diagnosis and treatment of the patient who presents with an exposure to an unknown agent .

The toxicologic physical examination should include documentation of vital signs, pupillary diameter, skin findings (dry, flushed, or diaphoretic), as well as the presence or absence of bowel sounds and urinary retention.

There are five general toxidromes :1.Sympathomimetic2.Cholinergic3.Anticholinergic4.Opiate5.Sedative hypnotic

Hypertension Pyrexia . Pupillary dilatation, DiaphoresisAltered mental status. Drugs that can cause this type of toxidrome include : cocaine and the amphetamines. vasopressors and β-adrenergic agonists

Bradycardia Respiratory depression due to paralysis Bronchoconstriction and bronchorrhea. Pinpoint pupils SLUDGE syndrome of salivation, lacrimation, urination, defecation, gastrointestinal (GI) distress, and emesis.

Fasciculations and paralysis. Seizures and coma. These agents include organophosphate insecticides and nerve gases, as well as carbamate pesticides.

Tachycardia CNS effects include agitation, delirium, and in severe cases, seizures.

Mydriasis , Dry , flushed skin Urinary retention Decreased intestinal motility. Therapeutic agents that cause this toxidrome include atropine, scopolamine, and antihistamines.

Respiratory depression and oxygen desaturations

Miosis Decreased GI motility, and Coma . These agents include Morphine , Pethedin , Tramadol

Other agents that produce a similar toxidrome include the imidazolines, including clonidine, tetrahydrozoline, and oxymetazoline.

Sedation or coma in the setting of NORMAL vital signs.

A common misconception is that ingested benzodiazepines cause respiratory depression.

While this may be true in the setting of intravenously administered benzodiazepines, patients with a benzodiazepine ingestion generally do not develop respiratory compromise.

Blood sugar : This test should be considered one of the vital signs in the patient with altered mental status.

Chemistry (bicarbonate and the creatinine) Blood gases. Serum drug screen: In general, the studies included on this panel include acetaminophen, salicylate, and ethanol concentrations. Some laboratories include a tricyclic antidepressant (TCA) screen as well.

Rarely contributes to the management of the patient◦Amphetamines: commonly cross-reacts with over-the-counter cold medications.

◦Opioids: This assay frequently misses the presence of the synthetic opioids such as fentanyl and meperidine

◦Cocaine: This assay is not directed at the parent compound which is very short lived

◦Cannabinoids: its presence does not have any bearing upon the diagnosis of intoxication.

◦Benzodiazepines: detection of oxazepam; however, some commonly used benzodiazepines (such as lorazepam) don’t produce it and therefore often missed by this screening

Cardiac toxins tend to prolong the :

1.PR interval (reflecting nodal blockade)

2.The QRS (reflecting sodium channel blockade)

3.The QT interval (potassium channel blockade).

May reveal radiodense material in the stomach or gut in the following ingestions :◦Chloral hydrate◦Heavy metals◦Iron◦Phenothiazines◦Enteric-coated preparations◦Sustained-release preparations

(Goldfrank's Toxicologic Emergencies. 8th Ed. 2006:62)

1- Prevention of absorption Gastric lavageActivated charcoal (AC)Whole-bowel irrigationCathartics.Ipecac syrup.2- Increased elimination:Forced diuresis Urinary alkalinizationHemodialysis and hemoperfusion3- Antidote

Endoscopy Surgery Dilution

AC is an insoluble, nonabsorbable, inert, fine carbon powder.

AC is often the only GI decontamination measure needed to treat an overdose.

The greatest benefit from AC is seen when it is administered within one hour of ingestion, and when used AC should be administered as soon as possible after patient presentation.

The decision to use AC is not algorithmic and depends upon the toxin ( BLAST ), the clinical status of the patient, and the time since ingestion.

AC administration is not recommended:1.In patients who have ingested nonabsorbable acidic or alkaline corrosives (hydrochloric or sulfuric acid)

2.Pt who require endoscopy because charcoal will obstruct the view of the endoscopist.

3.In patients who have ingested low-viscosity hydrocarbons (eg, gasoline, kerosene, liquid furniture polish) and who are at high risk for aspiration.

4.If the agent ingested is not bound by charcoal.

CorrosivesArsenicAcidsLeadAlkaliMercuryHydrocarbonsIronAlcoholsSodiumAcetoneCalciumEthanolPotassiumEthylene glycol MagnesiumIsopropanol FluorideMethanolIodideEssential oils

Drugs not absorbed by AC

Common side effects include:Nausea , vomiting, abdominal cramps, and diarrhea, particularly when the drug is used with sorbitol .

Aspiration Constipation Mechanical bowel obstruction

Dose — The recommended dose of activated charcoal  (AC) is 1 g/kg

The usual single adult dose is 25 to 100 g mixed with water and administered as a slurry by mouth or nasogastric tube.

Doses larger than 100 g are not recommended in obtunded patients due to the increased risk of vomiting and aspiration.

Routine use of gastric lavage in the management of poisoned patients is not recommended by the American Academy of Clinical Toxicology or the European Association of Poison Centres and Clinical Toxicologists

Controlled studies in animals and human volunteers show that gastric lavage decreases the absorption of ingested poison by an average of 26 percent when performed 30 minutes after ingestion and 12 percent when performed at 60 minutes

Gastric lavage is less effective activated charcoal (AC) in reducing the absorption

Gastric lavage in combination with AC (administered either following lavage or both before and after) is more effective in reducing drug absorption than AC given alone

A corrosive agent (eg, strong alkali, concentrated acids, such as hydrochloric or sulfuric)

Low viscosity hydrocarbons (eg, gasoline, kerosene, liquid furniture polish)

The patient has a depressed mental status and tracheal intubation has not been performed

There is a risk of hemorrhage or perforation due to esophageal or gastric pathology or recent surgery

The patient is unable to cooperate with the procedure

1. Aspiration 2. Laryngospasm 3. Hypoxia and hypercapnia, 4. Esophageal and gastric erosions ,

bleeding, perforation 5. Inadvertent tracheal insertion and

pulmonary lavage, 6. Cardiac arrhythmias, cardiac ischemia, 7. Pneumothorax, 8. Fluid and electrolyte imbalances, and9. Hypothermia

 Syrup of Ipecac (SOI), which is derived from the dried rhizome and roots of the ipecacuanha, induces emesis in more than 90 percent of overdose patients with a mean time of onset of 20 minutes

Ipecac should NOT be administered routinely in the management of poisoned patients since there is no evidence from clinical studies that it improves important outcomes

Refers to the enteral administration of a polyethylene glycol balanced electrolyte solution (PEG-ELS) in order to rapidly cleanse the gastrointestinal (GI) tract of its contents and prevent intoxicant absorption.

An effective means of GI decontamination following ingestion of drug packets, sustained-release or enteric-coated preparations, or agents not well adsorbed by activated charcoal (AC).

 Isosmotic high molecular weight polyethylene glycol (PEG-3350) electrolyte lavage solution is administered by mouth or nasogastric tube at a rate of 2 L per hour in adults until the rectal effluent is clear; volumes required to accomplish this vary from 5 to 50 L

Complications — Abdominal cramps, bloating, nausea, vomiting, and aspiration pneumonitis

Cathartics are intended to decrease poison absorption by enhancing rectal evacuation of the poison-activated charcoal complex.

Two types of osmotic cathartics are used to treat poisoned patients:

1.Saline cathartics (eg, magnesium citrate, magnesium sulfate, sodium sulfate).

2.Saccharide cathartics (eg, sorbitol, mannitol).

Recommended adult doses of commonly used agents are: 1 g/kg (1 to 2 mL/kg) of 70 percent sorbitol (0.9 g/mL) 4 mL/kg or 250 mL of magnesium citrate 250 mg/kg or 15 to 20 g of magnesium sulfate

Dilution is recommended following the ingestion of acidic or alkaline corrosives

Dilution must be performed within minutes of exposure to be effective and does not prevent the absorption of poison.

The recommended volume for adults is up to 5 mL/kg or 250 mL of water or milk.

Antidote administration is appropriate when:

1.There is a poisoning for which an antidote exists.

2.The actual or predicted severity of poisoning warrants its use.

3.Expected benefits of therapy outweigh its associated risk.

4.there are no contraindications.

Poison/syndrome

Antidote(s)Adult dose

AcetaminophenN-acetylcysteine (Mucomyst 20 percent)

Initial oral dose: 140 mg/kg, then 70 mg/kg q 4 h x 17 doses

Anticholinergic agents

Physostigmine (Antilirium)Initial dose: 0.5-2.0 mg slow IV over 3-5 min

BenzodiazepinesFlumazenil (Romazicon)

Initial dose: 0.1-0.2 mg IV over 30-60 sec, repeat 0.1-0.2 mg IV every minute prn up to 1.0 mg

Beta-blockers

1) Glucagon1) Initial dose: 5-10 mg IV bolus, then 2-10 mg/hr IV infusion

2) Calcium2) Calcium chloride 10 percent: 1 gm (10 cc) IV; repeat as necessary

3) Insulin + dextrose

3) Insulin load: 0.5 units/kg IV bolus, then 0.5-1.0 U/kg/h IV

Dextrose 10 percent IV infusion (with KCl) - titrate to euglycemia

Calcium-channel blockers

1) Calcium1) Calcium chloride 10 percent: 1-4 gm (10-40 cc) IV; repeat as necessary

2) Glucagon2) Initial dose: 5-10 mg IV bolus, then 2-10 mg/hr IV infusion

3) Insulin + dextrose3) Insulin load: 0.5 units/kg IV bolus, then 0.5-1.0 U/kg/h IV

Carbon monoxide

Oxygen ± hyperbaric chamber

100 percent oxygen by ventilator or NRB; high-flow oxygen by tight-fitting facemask

Crotalid snakebite

Wyeth polyvalent crotalidae antivenin (equine)

Mild: 3-5 vials; moderate: 6-10 vials; severe: 10-20 vials

Mix reconstituted antivenin in 1000 mL NS over 4-6 hours

Cyanide

1) Amyl nitrate pearls1) One ampule by inhalation for 15 sec every 3 min until IV access

2) Sodium nitrite (3 percent solution)

2) 10 mL (300 mg) IV over 3 min

3) Sodium thiosulfate (25 percent)

3) 50 mL (12.5 g) IV over 10 min

DigitalisDigoxin immune Fab (Digibind)

1) (# mg ingested x 0.8) ÷ 0.6 = #vials needed2) (Dig concentration [in ng/mL] x 5.6 x kg [weight]) ÷ 600 = #vials3) Empiric dose: 10 vials (acute poisoning); 1-3 vials (chronic)4) Reconstitute Digibind in NS and administer IV over 5-30 min

Ethylene glycol

Methanol

1) Ethanol 10 percent in D5W ± hemodialysis

1) Initial load: 10 mL/kg IV of 10 percent ethanol over 30 min, then 1.5 mL/kg IV infusion (titrate drip to serum ethanol 100 mg/dL); double to triple infusion during hemodialysis

2) Fomepizole [4-MP] (Antizol) ± hemodialysis

2) Initial load: 15 mg/kg IV over 30 min, then 10 mg/kg every 12 hours IV over 30 min (re-bolus during HD)

Poison/syndrome

Antidote(s)Adult dose

HeparinProtamine sulfate1 mg neutralizes 90-115 U heparin; Initial dose: 1 mg/min to total dose 200 mg in 2 h

IronDeferoxamine (Desferol)

15 mg/kg/h IV infusion until urine color clears or patient clinically well (not to exceed 6 gm/24 h)

IsoniazidPyridoxine (Vitamin B6)

Initial dose: 1 gm pyridoxine for every gm INH ingested or empiric 5 gm IV over 10 min if amount ingested unknown

Lead

2,3-dimercaptosuccinic acid [DMSA] (Succimer); 100 mg cpsl

30 mg/kg po in three divided doses x 5 days, then 20 mg/kg in twice daily doses x 14 days; repeat therapy prn after 2 week rebound

Mercury

Arsenic

Gold

British antilewisite, dimercaprol (BAL); in peanut oil

Initial dose: 4-6 mg/kg IM every 4-6 h x 2 days

Methemoglobinemia

Methylene blue (1 percent solution)

Initial dose: 1-2 mg/kg (0.1-0.2 mL/kg) IV over 5 min; repeat prn

Opiates

Naloxone (Narcan)

Nalmefene, naltrexone

Initial dose: 0.1-2.0 mg IV push (opioid dependent patients should receive 0.1 mg IV every 30-60 sec until clinical response); synthetic opiates may need up to 10 mg for initial reversal dose

Organophosphates

Carbamates

Nerve agents

1) Atropine1) Initial dose: 0.5-2.0 mg IV; repeat q 3-5 min until sweat and secretions clear

2) Pralidoxime [2-PAM] (Protopam)

2) Initial dose: 1 gm IV over 15 min, then IV infusion of 3-4 mg/kg/h for 24-72 hrs or until clinical toxicity resolves

SulfonylureaOctreotide (Sandostatin) + dextrose

Initial dose: 50-100 mcg SQ or IV, then 50 mcg q 12 h until euglycemia maintained without supplemental dextrose

Tricyclic antidepressants

Sodium bicarbonate (NaHCO3)

Initial dose: 1-2 ampules (50-100 mEq) IV push, then IV infusion to maintain blood pH 7.45-7.55 and PCO2 30 mmHg (Usual ≅drip: 3 amps NaHCO3 in 1 L D5W infused at 200-250 mL/h)

◦Patients who have taken an overdose as a suicidal gesture should all receive a psychiatric evaluation prior to discharge.

◦In cases where the patient is stable and asymptomatic, a brief period of observation may be all that is necessary.

◦In cases where potentially toxic agents have been ingested, patients should be monitored for 4 to 6 hours before discharge.

N-acetyl-para-aminophenol (APAP) is the leading cause of toxicologic fatalities per year in the United States, and

APAP-induced hepatotoxicity is the most frequent cause of acute liver failure

APAP is often sold in combination preparations together with nonsteroidal anti-inflammatory drugs (NSAIDs), opiate analgesics, or sedatives

In general, a dose of 150 mg APAP per kilogram is the potentially toxic limit that requires therapeutic intervention.

Decreased glutathione stores (fasting, malnutrition, anorexia nervosa, chronic alcoholism, febrile illness, chronic disease).

P450 enzyme inducers (ethanol, INH, phenytoin and other anticonvulsants, barbiturates, smoking).

First 24 hours—asymptomatic stage:◦Early symptoms are very nonspecific and primarily related to the GI tract (nausea, vomiting, anorexia).

◦High-dose APAP can cause pallor or lethargy in some patients.

◦This initial phase is rare in symptoms and patients appear pretty unremarkable.

◦Always think of other coingestants if a patient exhibits extreme vital sign abnormalities or other significant symptoms during the first 24 hours.

24 to 48 hours—hepatotoxic stage:◦RUQ tenderness is the most common symptom.

◦Transaminitis, bilirubinemia, and elevated PT/INR are also common findings during the second phase.

2 to 4 days—fulminant hepatic failure stage: Significant hepatic dysfunction develops (i.e., a peak in hepatic enzyme elevation along with jaundice, coagulopathy with high risk of spontaneous bleeding, hypoglycemia, anuria, and cerebral edema with coma or even death).

4 to 14 days—recovery stage: If stage 3 is survived, the hepatic dysfunction usually resolves over the following days/weeks.

Assess airway, breathing, and circulation (ABCs) and mental status.

Especially in patients who are nauseated or vomiting, the assessment of mental status is crucial to intervene with airway protection in time.

Obtain an APAP serum level at 4 hours or later after ingestion.

Plot the APAP concentration on the Rumack-Matthew nomogram.

LFT—AST is a relatively sensitive nonprognostic marker for hepatic injury.

PT/INR, serum bicarbonate, blood pH, serum lactate, renal function panel, and serum phosphate level are the prognostic markers for hepatic injury.

◦pH < 7.3 two days post ingestion Or ,

◦All of the following: PT > 100, serum creatinine > 3.3 mmol/L, severe hepatic encephalopathy (grade III or IV).

Additional criterion Elevated serum phosphate levels > 1.2 mmol/L on days 2 to 4

Arterial serum lactate > 3.0 mmol/L after fluid resuscitation

Gastric lavage is not useful in APAP overdose; however, it may be indicated in presence of certain other coingestants.

Activated charcoal N-acetylcysteine (NAC)NAC replenishes depleted GSH glutathione stores.

It should be administered early (i.e., within 8 hours after ingestion) to prevent any liver damage

◦Any patient after acute poisoning with a toxic APAP level according to the nomogram.

◦Patients who present more than 24 hours after acute ingestion and still have a detectable serum APAP level or elevated AST.

◦Patients with chronic APAP exposure (i.e., >4 g/d in adults, > 120 mg/kg/d in children) who present with elevated transaminases.

◦Patients with signs of fulminant hepatic failure.

◦Oral dosing: Loading dose of 140 mg/kg PO, then 70 mg/kg PO every 4 hours for a total of 17 doses (i.e., 1,330 mg/kg over 72 hours).

◦IV dosing ( 20 h protocol ) : Load with a dose of 150 mg/kg NAC IV over 1 hour. Then 50mg/kg over 4hours then 100 mg / kg over 16 h

◦IV dosing : as oral dosing ( 72 h protocol )

Treatment can be stopped when the serum acetaminophen concentration is undetectable, the ALT is clearly decreasing or in the normal range, and the INR is less than two.

Salicylate toxicity may result from acute or chronic ingestion of acetylsalicylic acid.

Toxicity is usually mild after acute ingestions of <150 mg/kg, moderate after ingestions of 150 to 300 mg/kg, and generally severe with overdoses of 300 to 500 mg/kg.

Toxicity from chronic ingestion is typically due to intake of >100 mg/kg/d over a period of several days

Nausea, vomiting, tinnitus, tachypnea, hyperpnea, and malaise are common.

Hyperthermia Severe intoxications may include lethargy, convulsions, and coma

Noncardiogenic pulmonary edema may occur and is more common with chronic ingestion

Obtain electrolytes, BUN, creatinine, glucose, and salicylate concentration.

ABGs may reveal an early respiratory alkalosis, followed by metabolic acidosis.

Serum salicylate concentrations◦Salicylate concentrations > 70 mg/dL at any time represent moderate to severe intoxication.

◦Salicylate concentrations > 100 mg/dL are very serious and often fatal.

Imaging : may shows Salicylate concretions

Administer 50 to 100 g AC if presentation is within 1 hour of ingestion

Alkaline diuresis is indicated for symptomatic patients with salicylate blood concentrations > 40 mg/dL.

Administer 150 mEq (three ampules) sodium bicarbonate in 1,000 mL D5W at a rate of 10 to 15 mL/kg/hr (target urine pH, 7 to 8)

Give 40 mEq potassium chloride IVPB over 4 to 5 hours to maintain serum potassium concentration above 4 mEq/L.

Treat altered mental status with IV dextrose, despite normal blood glucose.

Treat cerebral edema with hyperventilation and osmotic diuresis.

Treat seizures with a benzodiazepine (diazepam, 5 to 10 mg IV q15min up to 50 mg) followed by phenobarbital, 15 mg/kg IV.

Hemodialysis if : persistent acidosis, severe CNS symptoms, progressive clinical deterioration, pulmonary edema, or renal failure.

Organophosphates (OPs) are commonly used as pesticides and insecticides (e.g., parathion). Some of them also have medical indications (e.g., malathion in lice shampoo).

In the developing world, OP and other pesticide poisonings represent the most common causes of death from intoxications

Inhibition of ACh breakdown through blocked AChE leads to accumulation of ACh at nicotinic and muscarinic receptors resulting in excessive cholinergic stimulation

Most OPs bind AChE initially in a reversible way. Some OPs, however, become permanently bound over time, a phenomenon known as “aging.” If aging occurs, the only way to overcome the inhibitory effect is for the body to synthesize new enzyme.

OPs are hepatically metabolized.

The cholinergic toxidrome is a result of overstimulation of nicotinic and muscarinic receptors

Muscarinic effects:◦SLUDGE syndrome: Salivation, Lacrimation, Urination, Diarrhea, GI cramping, Emesis.

◦Bradycardia, bronchorrhea, bronchoconstriction

◦Other effects: miosis, diaphoresis.◦NOTE: intoxicated patients may present with tachycardia instead of bradycardia due to hypoxia (bronchoconstriction, bronchorrhea).

◦Ganglionic: tachycardia, hypertension, diaphoresis, mydriasis.

◦Neuromuscular: neuromuscular depolarization, fasciculations, motor weakness, paralysis with respiratory failure (analogous to succinylcholine, which is related to ACh).

◦Central: confusion, agitation, lethargy, seizures, coma.

Cholinesterase levelsrelatively useless in assessing the severity of exposure in acute intoxications because of its wide range of normal values.

Remove patient from potential source of poisoning.

All clothing, especially leather, should be removed from the patient and discarded in a ventilated area

Skin and hair decontamination requires thorough irrigation with water and might be enhanced through use of alcohol-based soaps.

Ocular decontamination should be irrigated with water only.

Gastric lavage might be indicated in stable patients who ingested contaminated fluids

Is an Antimuscarinic agent which competes with ACh for receptor binding

GOAL: Atropinization, that is, drying of bronchial secretions with normalized oxygen saturation (which may require 10 to 100 times of usually common atropine doses):

1.A heart rate > 80 bpm2.A systolic BP > 80 mm Hg The initial adult dose is 1 to 3 mg IV as a bolus.

Then titrate according to persistence of bronchorrhea by giving the double of the previously used dose every 5 minutes until atropinization achieved

forms a complex with OPs that are bound to AChE. The pralidoxime-OP complex is then released from the enzyme and thus regenerates AChE function.

Once the AChE bound OPs start aging, pralidoxime is rendered ineffective. Therefore it is crucial to start pralidoxime therapy early.

Dose : 1 to 2 g of pralidoxime in 100 mL NS IV over 20 minutes, then infusion of 500 mg/hr

Cardiac and respiratory failure have been reported after administration of pralidoxime

1- Intermediate syndrome (IMS):◦This syndrome is a post-acute paralysis from persistent ACh excess after the acute cholinergic phase has been controlled.

◦occurs hours to days after treatment of acute OP. 2- OP-induced delayed neurotoxicity (OPIDN):◦OPs also inhibit other neurotoxic esterases, resulting in polyneuropathy or spinal cord damage due to demyelination of the long nerve fibers.

◦OPIDN usually occurs several days to weeks after acute OP poisoning leading to temporary, chronic or recurrent motor or sensory dysfunctions

Generally speaking, benzodiazepines have a wide safety margin so its overdose rarely represent a medical problem.

The typical presentation of a pure oral benzodiazepine overdose is coma with normal vital signs.

Respiratory depression is exceedingly unusual in oral overdose of benzodiazepines.

The differential diagnosis includes barbiturate overdose, hypoglycemia, ethanol intoxication, CNS, and other metabolic causes of coma.

Supportive care with observation is the mainstay of therapy.

In patients with co-ingestions and respiratory depression, intubation and ventilation may be required.

Since this is a benign overdose, gastric lavage and AC are not necessary.

These interventions may cause aspiration in an otherwise stable patient.

Traditional recommendations include the use of flumazenil; however, given the propensity to precipitate seizures and acute benzodiazepine withdrawal in patients on long-term benzodiazepine therapy, this therapy should be avoided.

In special cases such as reversal of iatrogenically induced respiratory depression, reversal of sedation, flumazenil may be given as a 0.1 mg/min dose intravenously.

Repeat injections may be given as resedation occasionally reoccurs.

Multiple TCAs are on the market, including Amitriptyline, Clomipramine, Doxepin, Imipramine, Trimipramine, Desipramine, Nortriptyline, and Amoxapine.

TCAs interact with a wide variety of receptors with many consequent effects

It has a:1.Anticholinergic effect : dry mouth , urinary retention, and GI motility and mydriasis.

2.Antihistaminic effect : sedation 3.Central sympatholytic effect : hypotension and reflex tachycardia

4.Anti serotoninergic effect5.Antagonism of CNS gamma-aminobutyric acid (GABA) A receptors

In one classic study, one-third patients with a QRS of ≥100 milliseconds developed seizures.

Fifty percent of patients with a QRS of ≥ 160 milliseconds developed ventricular dysrhythmias

Prolongation of the QT interval.

After the patient's airway is protected, a dose of AC 1 g/kg is warranted .Sodium bicarbonate has been demonstrated to narrow the QRS, A bolus of 1 to 2 mEq/kg every 3 to 5 minutes ,continuous ECG monitoring until the QRS narrows or the BP improves. Serial VBGs should be obtained with a goal of maintaining the blood pH at 7.50 to 7.55.

Norepinephrine is the pressor of choice in hypotensive patients who do not respond to alkalinization because of its direct effects on the vasculature.

Lidocaine may be considered in the presence of ventricular dysrhythmias precipitated by TCA toxicity. However, class Ia and Ic antidysrhythmics are contraindicated in the management of TCA-poisoned patients.

Benzodiazepines are the mainstay of treatment for seizures. Phenytoin should be avoided.

The toxicity associated with an overdose of β-blockers is largely due to the effects of antagonism at catecholamine receptors.

In general, selectivity is lost in overdose, so bronchospasm may occur in the setting of β1-selective antagonists.

Patients with a significant ingestion of an immediate-release product will exhibit signs of toxicity within 6 hours.

The exception to this rule is sotalol, which in overdose, can have delayed toxicity and prolonged effects

With the exception of propranolol and sotalol, β-blocker overdose in healthy people tends to be benign, with significant number of patients remaining asymptomatic after ingestion

Patients with significant ingestions present with:

1.Bradycardia 2.CHF. 3.Patients with propranolol ingestions may develop coma, seizures, and hypotension.

4.Propranolol overdoses have a high mortality

In patients with symptomatic bradycardia also consider overdose of CCB, clonidine, or digoxin.

The ECG may reveal sinus bradycardia or atrioventricular block.

In propranolol ingestions, a wide QRS manifesting sodium channel blockade may be present.

With sotalol, QTc prolongation may appear as a delayed presentation and torsades de pointes may develop.

Patient should have an IV placed, and continuous cardiac monitoring should be instituted.

Hypoglycemia should be treated with 50 mL of 50% dextrose.

Consider AC if patients present within 1 hour of ingestion.

Intubation and ventilation should be instituted in patients with altered mental status.

Atropine 1 mg IV may be given up to 3 mg for symptomatic bradycardia; however, this is usually ineffective as the bradycardia is not vagally mediated.

A fluid bolus of 20 mL/kg should be given and may be repeated; monitor for the development of fluid overload.

Glucagon 2 to 4 mg IV may be given over 1 to 2 minutes. Then start infusion of 2 to 5 mg/hr—not to exceed 10 mg/hr.

Calcium gluconate 3 to 9 g IV may be given through a peripheral line in patients with hypotension.

Any patient with hypotension is a candidate for high-dose insulin euglycemia therapy.

This involves a bolus of 1 U/kg of regular insulin, followed by an infusion of 0.5 to 1 U/kg/hr of regular insulin. This should be accompanied by a dose of 50 mL of 50% dextrose and a dextrose drip at 1 g/kg/hr of dextrose.

Glucose should be obtained every 30 minutes, and potassium levels should be followed every 2 hours

Catecholamines should be approached with caution in these patients because α-stimulation in conjunction with β-blockade may precipitate acute heart failure.

Therefore, hemodynamic monitoring should be instituted with careful titration of epinephrine at 0.02 mcg/kg/min or norepinephrine at 0.1 mcg/kg/min.

Isoproterenol at 0.1 mcg/kg/min may be useful as well

QUESTIONS ??

Most of poisoning events pass uneventfully without significant harm.

The most important clinical approach is to try to classify the patients toxidromes

ABCDE approach is the first priority in management of poisoned pt.

Gastric lavage is ineffective if done after one hour of exposure.

AC is an effective mode of decontamination but not in all overdoses

ECG is important investigation in poisoned pat.

Paracetamol poisoning is a common cause of drug overdoses and is the most common cause of acute hepatic failure in western countries.

The use of paracetamol nomogram is the best mode to determine the need for NAC use

The goal of GOAL of Atropinization is 1.A heart rate > 80 bpm2.A systolic BP > 80 mm Hg but not dilated pupils.

The classic presentation of Benzodiazepine overdoses is sedation with normal vital signs

Thank you