Transcript Toxic Ingestion - Creighton University

OVERDOSE
&
TOXIC INGESTIONS
What is an Overdose?
Exposure to excessive amounts of a
substance normally intended for
consumption.
Poisoning is the development of harmful
effects following exposure to chemicals.
Pharmaceuticals are responsible for 41%
of poisonings and 75% of fatal poisonings.
Treatment Overview
Supportive Care
Prevention of toxin absorption
Enhancement of drug elimination
Administration of antidote
Initial Measures
Airway
– Establish patent airway by positioning and
suctioning.
– Intubate if obtunded, comatose, no gag reflex .
Breathing
– Assess depth and rate .
– Pulse ox in all.
– ABG if suspicious .
Initial Measures
Circulation
– Treat with NS or pressors if hypotensive
– Assess for arrhythmias
-D-Drugs (give all three)
Dextrose 50%,
Thiamine 100mg.
Naloxone0.4 to 2mg &
consider Flumazenil
(do not give flumazenil in TCA overdose, BZD dependency
and seizure disorder)
Prevention of Toxin Absorption
Emesis:
-Now not performed. Replaced by lavage/charcoal
-Contraindicated in corrosive poisonings/aspiration risk.
Gastric Lavage:
-
-
-
Indications:
Removal of gastric contents (within the first hour). Examination of gastric contents.
Facilitate charcoal.
Contraindications:
Do not do if patient comatose unless intubated. Also do not use if corrosives are
ingested. (controversial)
Technique:
Place patient in left lateral head down position if not intubated. Insert a soft lubricated
tube through mouth or nose into stomach. Aspirate and save contents and then
lavage repeatedly with 50-100ml of fluid until returns are clear .Use luke warm water
or saline.
Prevention of Toxin Absorption
Activated Charcoal
– Adsorbs almost all drugs and poisons. Poorly adsorbed substances are Lithium, Potassium,
alcohol, iron, cyanide.
Indications:
•
All poisonings.
Contraindications:
• Comatose or obtunded unless given by gastric tube or intubated as drinking
cause emesis.
•
Ileus or intestinal obstruction. (delays expulsion of charcoal)
•
Corrosive poisonings where endoscopy is planned .
charcoal can
Technique:
60-100grams orally or via gastric tube .Repeat doses 20-30mg every 3-4 hours may be used
to hasten the elimination of some drugs (digoxin, theophylline and phenobarbitol) by
adsorbing drug excreted into the gut lumen (entero hepatic circulation).
Prevention of Toxin Absorption
Whole Bowel Irrigation: Cleanses the GI tract
Indications:
-Used for “body stuffers/packers” (People who swallow packets of drugs
for smuggling.)
- Massive iron ingestion
Technique:
2 Liters/hour of go-lytely electrolyte soln. Given via gastric tube at rate of 12L/hour until rectal effluent is clear. Patient must be able to sit to pass
contents.
Increased drug removal
 Urinary manipulation
Alkalization of urine: Salicylates, Phenobarbitol.
Forced diuresis: No longer recommended as it causes
electrolyte imbalances.
 Dialysis
 Known dialyzable drugs.
 Severe states :coma, refractory hypotension,
hypothermia for quick effect
 Hepatic or renal failure where excretion of the drug may
be compromised.
Diagnosis of Overdose
History:
Dependent upon history obtained and
reliability of history.
Paramedics/Police will usually bring in pill
bottles: Calculate the amount taken, and
always assume the worst case scenario.
Diagnosis of Overdose
Physical examination
5P’s :Pressure, Pulse rate , perspiration, pupils peristalsis .
Based on above three syndromes:
Sympathomimetic syndrome :
Amphetamines, cocaine, ephedrine, psuedoephidrine, PCP (pupils
may be small)
Sympatholytic syndrome:
Benzo, Barbiturates, other sedative hypnotics, opioids, clonidine.
Cholinergic:
Nicotine, organophosphates, physostigmine.
Initial Laboratory Evaluation
EKG
Basic Chemistry
– Calculate anion gap
• ABG
Drug Screen
Serum Osmolality
(calculate osmolar
gap)
Quantitative Drug
Levels
Acetaminophen
Pathophysiology
Acetaminophen is metabolized by the
cytochrome P450 pathway to a toxic
intermediate that is detoxified by glutathione.
With acute acetaminophen overdose
hepatocellular glutathione is depleted allowing
the toxic intermediate to attack cell proteins and
cause cell necrosis. Patients with enhanced
cytochrome P450 activity like alcoholics and
anticonvulsant users are at greater risk of
hepatotoxicity.
Acetaminophen
Dose:
Acute ingestion: >7.5 grams/24 hours is toxic – just a guideline!
Chronic ingestion: >4 grams a day.
Symptoms:
1st 24 hours to 48 hours-Asymptomatic.
24-48 hours – Rise of aminotransfersases, jaundice,
encephalopathy.
Treatment:
Lavage & Activated Charcoal indicated.
Rumack-Matthew Nomogram utilized to decide whether treatment
with N-acetylcysteine is required.
Acetaminophen
N-Acetylcysteine increases the availability of
glutathione, decreasing hepatic toxicity.
If patient has a toxic level, give the full course
(usually 17 doses). 140mg/kg orally followed by
70mg/kg.
May be helpful even up to 36 hours after ingestion
If uncertain about the timing of ingestion and at high
risk patients (alcoholics, CytP450 inducing drug
takers, liver disease) use lower line.
Remember: Nomogram not useful for chronic
overdoses and for overdoses that may be associated
with ingestion of another drug that delays GI motility.
The Alcohols
Methanol
Found in windshield wipers .Methanol is
metabolized to formaldehyde and formic acid
which acts as toxin.
Symptoms may not appear for 12-18 hours
because toxins must accumulate, may be
longer if ingested with ethanol because EtOH
inhibits metabolism
Symptoms: CNS depression, visual changes
with blurring/blindness, abdominal pain, N/V
Labs: Wide anion gap metabolic acidosis with
osmolar gap >10
The Alcohols
Ethylene Glycol
Found in antifreeze.
3 distinct clinical phases due to the toxic
metabolites glycolate, glyoxalate, and oxalate
– First 12 hours: CNS effects
appears intoxicated
– 12-24 hours: Cardiopulmonary effects
Increased HR, RR and BP
CHF, respiratory distress syndrome, circulatory collapse
– 24-72 hours: Renal effects
ATN with ARF
Wide anion gap metabolic acidosis with osmolar
gap >10
Metabolized to oxalic acid. Calcium oxalate crystals
seen in urine 33% of the time
The Alcohols
Ethylene Glycol
Oxalate crystals
The Alcohols
Treatment of Methanol and Ethylene Glycol
Ingestion
Rapid Diagnosis
– Hx suspicious for use
– Wide anion gap with a wide osmolar gap, then order serum
level and begin:
Ethanol infusion (not used as much) to keep blood
alcohol >100.
– Competitively inhibits metabolism of MeOH and EG by
alcohol dehydrogenase, has a 10-20 greater affinity than
MeOH and 100 times that of EG
– Is continued until measured levels are zero
Fomepizole (4-methylpyrazole) – more common
– A competitive inhibitor of alcohol dehydrogenase
– Is an alternative to EtOH infusion.
Dialysis for severe cases (serum level > 50mg/dl, refractory
acidosis)
The Alcohols
Isopropyl Alcohol
Found in rubbing alcohol and paint thinners
CNS effects are twice as potent and twice as
long acting as EtOH
Symptoms are similar to EtOH intoxication,
severe posioning causes early onset coma,
respiratory depression, and hypotension
Hemorrhagic gastritis is a characteristic
finding
Ketosis without acidosis
– Metabolized to acetone
– Ketonemia/ketonuria and osmolol gap with
minimal or no acidosis is unique characteristic
Treatment is supportive with dialysis if patient
continues to deteriorate.
Tricyclic Antidepressants
Most dangerous of overdoses.
(25% of fatalities occur in patients who are awake, alert, and in
NSR at time of presentation)
Clinical findings & Treatments
(1) Anticholinergic:
Tachycardia, dry mouth, flushed skin, decreased peristalsis.
(2) Cardiotoxicity:
Quinidine like effect. Blocks sodium channels. Therefore
widening of the QRS interval , ventricular arrhythmias, AV nodal
block.
Tricyclic Antidepressants
Rx:



•
Admit in Telemetry.
Alkalinization either using sodium bicarbonate and
hyperventilation if intubated to a pH of 7.45-7.55. The sodium in
the NaHCO3 alleviates depression of the sodium channels. Also
acidosis impairs sodium channels so alkalinization beneficial.
Manage arrhythmias with lidocaine, magnesium, isoproterenol,
and pacing
Neurologic:
Seizures. ( Note due to absence of sweating and seizures
hyperthermia can occur)
Rx: benzodiazepines.
Salicylates
Aspirin, methyl salicylate (various OTC drugs)
Pathophysiology:

Uncouple cellular oxidative phosphorylation and
cause anaerobic metabolism (lactic acidosis) and
heat production.

Salicylates directly stimulate respiratory centers in
the brainstem.

Mixed respiratory alkalosis with metabolic acidosis.
(wide anion gap).
 Coagulopathy present secondary to platelet
dysfunction and decreased synthesis of coagulation
factors (salicylate induced hypoprothrombinemia).
Salicylates
Symptoms:
Dose dependant
acute ingestion (> 200mg/kg) or chronic excessive
dosing .
Severe: Agitation, Coma, CV collapse,
pulmonary edema, hyperthermia &
death.
Labs:
Suspect in any anion gap metabolic acidosis
Salicylate level elevated salicylate level.
ABG : Shows mixed Met acidosis & resp alkalosis.
Salicylates
Therapy:
General:
Activated charcoal( 10:1 by weight).
NaHCO3: Critical for therapy as acidosis
promotes the entry of salicylic acid into the cells.
(keep>7.4).
Specific:
Urinary alkalization .
Hemodialysis ( >1000-2000mg/L after acute
overdose or> 60-70mg/dl with sub acute or
chronic overdose).
Beta Blockers
Most toxic is Propranolol
Symptoms:
Cardiac: Bradycardia, AV blockade, hypotension.
Rx: Atropine or Isoproterenol if no
response give Glucagon. May need
temporary pacing.
CNS: Delerium, coma, or seizures.
Rx:Ativan for seizures
Electrolyte: Hyperkalemia and hypoglycemia
Ca Channel Blockers
Symptoms include bradycardia, conduction
delays, impaired contractility, and
hypotension
Gastric lavage and activated charcoal
– May consider whole bowel irrigation for sustained
release preparations
May respond to atropine, isoproterenol, or
pacing IVF
If no response IV calcium chloride or calcium
gluconate to treat hypotension and
conduction defects.
Glucagon is occasionally beneficial in severe
toxicity
Digitalis
Pathophysiology: 2 main effects: Blocks AV node & blocks Na/K ATPase. The blockade
of Na/K ATPase increases intracellular Ca and causes delayed after depolarizations
(which can cause VPC and VT). Toxic: Therapeutic ratio is very narrow.
Acute overdose: GI: Nausea, vomiting.
Cardiac: Bradycardia, cardiac arrhythmias mostly ventricular.
Electrolyte: Hyperkalemia.
Chronic: Hypokalemia, hypomagnesemia as patients are on diuretics. Hypokalemia
aggravates dig toxicity.
Treatment:
Bradycardia can be controlled with atropine or temporary pacing
Lidocaine for ventricular arrhythmias
Digibind (digoxin-specific Fab antibody fragments) is effective in rapidly reversing lifethreatening intoxications
– Is cleared via renal excretion
– 40 mg vial neutralizes ~0.6 mg of digoxin
Atropine & Anticholinergics
Drugs with anticholinergic effects:
 Atropine
 Antihistamines: Benadryl
 Mushrooms
 TCA
Effects:
Symptoms: Dry mouth, thirst, blurring of vision,
constipation.
Signs: Psychosis, dilated pupils, fever, ileus, urinary
retention.
Rx:
Charcoal (can give late as there is delayed gut emptying)
Physostigmine (with ECG monitoring).
Cyanide
Situations:

Fires-HCN gas is a component of smoke in fires

Apricot pits

Nitroprusside infusion
 Acetonitrile (finger nail glue removers) has CN
Pathophysiology:
Rapidly absorbed by any route (GI, skin, inhalation)
Inhibits cytochrome oxidase , cellular respiration. Switches to
anaerobic metabolism and therefore lactic acidosis occurs.
Cyanide
Symptoms:
Headache, dizzinness, abdominal pain, nausea. Followed quickly
by syncope, shock and coma.
Labs:
Unexplained lactic acidosis
High Venous O2 sats (>90%) as tissues fail to take up oxygen.
Treatment:
 Remove from site of exposure
 Charcoal: CN is poorly adsorbed ,therefore larger doses.
 “Pack” available consists of Amylnitrite, Sodium nitrite and Na
thiosulfate.
Overview of Antidotes
Drug
Antidote
Acetaminophen
N-Acetylcysteine
Organophosphates
Opioids
Atropine/Pralidoxim
e
Naloxone
Benzodiazepines
Flumazanil
Ethylene Glycol
Fomepizol
Methanol
Fomepizol