Download Decontamination

Highlights of Toxicology
Mark Kostic, MD
Acetaminophen (APAP)
 Metabolism:
o Glucuronidation and sulfation
o CYP 2E1  NAPQI (toxic metabolite)
 Therapeutic doses  reduced by glutathione
 Toxicity in OD
o NAPQI  hepatocellular necrosis
 Dx: 4 hr level on Rumack-Matthews nomogram
 Tx: N-acetylcysteine (NAC)
o 140 mg/kg then 70 mg/kg q4
 po or IV
 treat x 24 hrs if no toxic effect, if LFTs increased, treat til better
o Acetadote – FDA approved IV NAC – 21 hr continuous infusion
 Load 150 mg/kg over 1 hr; then 50 mg/kg over 4 hrs (12.5
mg/kg/hr); then 100 mg/kg over 16 hrs (6.25 mg/kg/hr)
o Unknown time of ingestion  NAC x 12-24 hrs and re-assess
o Repeated supertherapeutic  if LFTs up  tx til better
 Transplant criteria:
o Arterial pH < 7.3 (after IV fluids) OR
o INR >6 + Cr > 3.4 + Gr III or IV encephalopathy
o Also Lactate > 3.0 after IVF
Alcohols
 Consider MeOH or EG in any patient with unexplained increased anion gap
metabolic acidosis (esp if does not improve with IVF)
 EtOH in a child may cause hypoglycemia
 All may cause an osmol gap, but a normal Osm gap does not rule out
intoxication
 Toxicity takes time, all removed by dialysis
Level
AG
End organ
Rx
of
Metabolites
Antidote
acidosis
toxicity
Adjuncts
intox
Retina,
Formic
optic
Fomepizole,
Methanol
+
+++
Folate
acid
nerve,
EtOH
brain
None
Ethanol
++
(except Acetic acid
AKA)
Glycolic
acid,
Ethylene
Fomepizole, Thiamine,
++
+++
Oxalic acid Kidneys
Glycol
EtOH
B6
(Ca
Oxalate)
Isopropanol +++
Acetone
1
Anticonvulsants
 Most work through CNS Na channel inactivation
 Nystagmus  ataxia  mental status depression
 Phenytoin: low levels  first order kinetics
Higher levels  zero order kinetics
 Carbamazepine: can rarely see paradoxical sz, alternating mental status
 Valproic Acid: hyperammonemia, incr LFTs, carnitine deficiency
 Enterohepatic circulation
Antihistamines/Anticholinergics (antimuscarinics)
 Toxidrome
o Peripheral: hot/dry skin, dry mucous membranes, dec GI motility, flushed,
urinary retention, mydriasis
o Central: agitated delirium, sedation/coma, sz, mild hyperthermia
o *patients rarely manifested all symptoms*
 Diphenhydramine  Quinidine (Na ch blocking/”membrane stabilizing”) effects
o Looks like TCA OD
o Tx  bicarb
 Dx: Physostigmine: 1-2 mg IV over 4 minutes (atropine at bedside, monitors)
o May seize
o Avoid with TCA effect on ECG
Antipsychotics
 Dopamine (D2) receptor antagonists
 Typical: Phenothiazines, Butyrophenones (haloperidol, droperidol)
o Higher rate of akathesia, dystonia, parkinsonism
o Cardiac: Na and K ch blockade  QTc prolongation, toursades
 Esp thioridazine, mesoridazine, haldol, droperidol
o Neuroleptic Malignant Syndrome (NMS)
 Hyperthermia + rigidity + mental status change + autonomic
instability
 A spectrum
 Tx: benzos, support, intubate if needed, treat rhabdo
 Atypical
o Clozapine, Olanzapine, Quetiapine, Risperidone, etc
 Sedation, tachycardia, orthostatic hypotension, prolonged QTc
Botulism
 Mech: presynaptic blockade of ACH release
 Sx: dizzy, fatigue, sore throat  GI sxs  diplopia, dysarthria, dysphagia 
ptosis, ataxia, descending paralysis, resp failure
 Foodborne (ingestion of pre-formed toxin): Type A (West of Mississippi); Type B
(East of Mississippi); Type E (Pacific northwest)
 Infantile (spore ingestion): floppy, constipated baby
o Associated with honey prior to age 1 yr
2



o Antitoxin not effective
o BabyBIG (Bolulism Immune Globulin Intravenous [human])
Contact local health dept or CDC for either antidote
Neither antidote removes toxin already bound to the nerve terminal
Wound (spores grow and release toxin in an anaerobic environment)
Beta Blockers
 Usually well tolerated if no baseline heart disease
 Propranolol: lipid soluble (crosses BBB  sz, MS change), membrane stabilizing
activity (prolonged QRS)
 Sx: bradycardia, hypotensive, hypoglycemia in kids
 Tx:
o Judicious IV fluids
o Atropine (likely won’t work)
o Vasopressors (may not work)
o Glucagon (5 mg doses q 15 min, then drip)
o Hi-dose Insulin and glucose
o IABP
o Lipids
o Pacers may increase rate, but don’t improve BP
o Decontaminate (consider WBI)
Calcium Channel Blockers
 Typically more dangerous than most BBs
 Selectivity lost in OD
 Hypotensive, bradycardic, hyperglycemic with normal mental status
 Treatment similar to BBs except:
o Calcium early (several amps to raise total Ca to mid to hi teens)
o Glucagon less helpful, insulin/glucose more helpful (better studied)
Carbon Monoxide
 Main source: incomplete combustion of fossil fuels
 Presents with flu-like illness
 200x greater affinity for hemoglobin
 Also shifts Oxy-Hgb dissociation curve to left
 Tx: 100% O2
o Hyperbaric O2 may reduce incidence of delayed neurologic sequelae
 Indications:
 Definite: LOC, COHgb>25%, Age >50, metabolic acidosis,
cerebellar dysfunction
 Relative: pregnancy, persistent neuro deficit, cardiac
ischemia, hi levels
Caustic Ingestion
 Amount of injury is pH, concentration, and volume dependent
3


Endoscopy recommended between 12-24 hrs
Button batteries must be removed ASAP if lodged in esophagus
Clonidine
 Central alpha2 (inhibitory) agonist  decreased sympathetic outflow
 Mimics opioid OD
 1-2 pills toxic in toddlers
 Tx: support, alpha agonist for hypotension, narcan
Cyanide
 “bitter almonds” smell (50%)
 Blocks oxidative phosphorylation
 Metabolic acidosis, “arteriolization” of venous blood, AMS, sz
 Closed space fires
 Tx:
o Lilly antidote kit
 Amyl Nitrite pearls, Sodium Nitrite, Sodium thiosulfate
o Hydroxocobalamin
Dextromethorphan
 Optical isomer of levorphanol (an opioid), but has no analgesic activity
 Binds to PCP site on NMDA receptor
o Abused for its potential euphoria and hallucinogenic qualities
o Nystagmus, AMS
 Blocks pre-synaptic serotonin reuptake
Decontamination
 Not a benign procedure!
 Activated Charcoal – 1 gm/kg
o Repeat dose
 Whole Bowel Irrigation
o Sustained release products, packers, things not bound by AC
 Gastric lavage
o Life threatening OD, no antidote, airway protected, soon after ingestion
(rarely indicated)
Digoxin (Cardiac Glycosides)
 Inhibits Na+/K+ ATPase  raised intracellular Na+  increased gradient at
Na+//Ca++ exchanger  raised intracellular Ca++
 Increases vagal tone
 Decrease conduction through SA and AV nodes
 Glycosides in plants: oleander, foxglove, lily of the valley, red squill
 Presentation  any dysrhythmia except afib/flutter with RVR
o Acute  hyperkalemia, n/v, higher levels
o Chronic  more common, K nl/hi/low,
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 Typically: dehydration and renal insuff  inc levels
o Classic ECG: bidirectional Vtach, PAT with block
 Tx: Digibind
o Acute OD and crashing – 10-20 vials
o Chronic OD: #vials = level(ng/ml) x wt (kg)
100
Enhanced Elimination
 Sodium bicarbonate – urine alkalinization
 Multi-dose activated charcoal
 Hemodialysis
Hydrocarbons
 Aliphatics (gasoline, kerosene, mineral spirits)
o Aspiration  pneumonitis  ARDS
o Pediatric mortality
o Most dangerous  low viscosity, hi volatility
 Aromatics (benzene, toluene, xylene)
o Sniffing, huffing, bagging
o Highly addictive
 Halogenated (methylene chloride, carbon tet, TCE)
o Myocardial sensitization
Hydrofluoric Acid
 Ingestion
o Mech: binds intracellular Calcium and Mag  hypocalcemia  efflux of
K+  hyperkalemia  dysrhythmias/death
o Highly lethal
o Tx: Ca++ chloride IV(central line)
 Dermal
o Classic: pt presents with severe hand pain and redness several hrs after
using rust remover, or doing glass etching
o Severe tissue burns/necrosis due to binding with Ca++
o Tx: Decontaminate, Ca++ gluconate gel, Ca++ gluconate local infiltration,
Ca++ infusion via Bier block or intra-arterial
Hydrogen Sulfide
 Sewer gas, “knock down gas”, multiple victims
 Colorless, odor of rotten eggs
 Permanently binds to hemoglobin and inhibits oxidative phosphorylatioin
 Tx: Hi flow O2
Iron


“Toxic dose” > 40 mg/kg of elemental iron
Stages (for board exams only!)
o 1 – GI
5



o 2 – quiescent
o 3 – systemic toxicity (hypotension, acidosis, coma, sz)
o 4 – hepatic failure
o 5 – late complications (SBO, GOO)
Mech:
o direct caustic
o disrupts oxidative phosphorylation
o free radical formation, lipid peroxidation
o inhibits thrombin formation
o periportal hepatic necrosis
Dx: Fe levels, +/- KUB
Tx:
o Volume
o Deferoxamine 15 mg/kg/hr (100 mg DFO binds 9 mg Fe)
Isoniazid
 Mech: interferes with pyridoxine (cofactor needed for GABA synthesis)
 Sx: persistent seizures with subsequent metabolic acidosis
 Tx: Pyridoxine
o Gram for gram of INH ingested
o Unknown amount ingested  5 gm (70 mg/kg peds)
Lithium
 Unknown mechanism
 Renal clearance (handled like sodium)
 Sx:
o Acute: GI > neuro, higher levels needed to be toxic
o Chronic: neuro > GI, lower levels
 Other effects: nephrogenic DI (rare), flattened T waves
 Tx: IV fluids (saline), hemodialysis
Local Anesthetics
 AmIdes (LIdocaine, BupIvicaine, MepIvicaine, PrIlocaine); Esters (Procaine,
Benzocaine, cocaine, Tetracaine)
 More allergic rxns to esters (PABA)
 CNS toxicity (seizures) well before cardiac (mostly from inadvertent IV)
 Potential for methemoglobinemia (benzocaine)
 Lidocaine max doses:
o Without epi: 4.5 mg/kg (31 ml of 1% for 70 kg pt)
o With epi: 7 mg/kg (49 ml of 1% for 70 kg pt)
MAO Inhibitors
 Inhibits Monoamine Oxidase  increased pre-synaptic levels of NE, DA, 5HT
 Symptoms from OD of MAOI or its interaction with other meds (e.g. serotonin
syndrome) or foods containing tyramine
o Hemodynamic instability, altered mental status, rigidity, tremor,
hyperthermia, etc
6

Tx: cooling, BZDs, alpha agonist (not dopamine) for hypotension, Nipride for
HTN, paralysis if needed
Metals





- Acute  severe GI effects unless the elemental form ingested
- reacts with sulfhydryl groups (inactivating enzymes)
Arsenic, Thallium
o Diffuse systemic toxicity
o ARDS, ARF, shock, pancreatitis
o Painful neuropathy, alopecia
o Carcinogen
Mercury
o Elemental
 Only toxic if inhaled  ARDS
o Salt
 GI, ARF
o Organic
 CNS
Lead
o Neurotoxicity, esp kids
o Anemia, abdominal pain, constipation, HTN, renal insufficiency
Urine levels for As, Hg; whole blood for Pb
Tx: po Succimer, IM BAL
Methemoglobinemia
 Nitrites (well water, kids < 6mo), aniline dyes, dapsone, pyridium, benzocaine
 Ferrous iron (Fe2+) oxidized to Ferric (Fe3+) which can’t carry O2
 Shifts O2 dissociation curve to left
 “chocolate blood”, SOB, MS change, central cyanosis not responsive to O2,
measured O2 Sat – 85%, calculated sat – normal
 Tx: Methylene blue 1-2 mg/kg IV
o Do not give if G6PD def
Methylxanthines
 Theophylline, Caffeine (hi doses)
 Acute vs Chronic
 Mech:
o Blockade of adenosine receptors, increases glutamate --> seizures
o Increases catecholamine release
 Presentation
o N/V (more if acute OD), persistent sz, very tachycardic
 Theo levels
o Acute danger if > 80-100, chronic if > 40
 Tx: BZDs, IVF, MDAC, dialysis
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Mushrooms
Species
Amanita
phalloides
Toxin
Onset
of Sx
(hr)
Effects
Tx
AC, pcnG,
Silibinin,
hemoperfusion,
?NAC
Pyridoxine,
BZDs
-
Cyclopeptides
(amatoxin)
5-24
Hepatic failure
Monomethylhydrazine
5-10
CNS (sz)
Coprine
0.5-2
Amanita
muscaria
Ibotenic acid,
muscimol
0.5-2
Psilocybe
Psilocybin
0.5-1
Orelline
> 24
ARF
GI irritants
0.5-3
N/V/D
IVF
Muscarine
0.5-2
SLUDGE
atropine
Gyrometra
escuelenta
Coprinus
atramentaruis
Cortinarius
orellanus
Chlorphyllum
Clitocybe,
Inocybe

Ald DH
disulfiramlike
CNS GABAergic,
delirium,
hallucinations
CNS hallucinations
BZD
BZD
HD
“6 hr rule”
o N/V < 6 hrs from ingestion --> less likely to be hepatotoxic species
o N/V > 6 hrs from ingestion --> hepatotoxic
o Caution: may have mixed ingestion
Mustard Gas
 Alkylating agent, forming cross-links between purine bases
 Powerful irritant and vesicant (blisters)
 Dermal symptoms and pulmonary effects often delayed several hours
 Tx: support, early decon
Nicotine
 Potentially toxic ingestion in a kid:
o 1 whole cigarette
o 3 cigarette butts
o 1 transdermal patch
 Sx: nausea, vomiting, diarrhea; initial tachycardia and hypertension followed by
bradycardia and hypotension, fasciculations followed by paralysis
8

Tx: supportive
Opioids
 Narcan indication – to prevent intubation
 Narcan drip: 2/3 the dose required to wake the pt, given per hr
 Seizures: norproxyphene, normeperidine
 Propoxyphene may have quinidine-like effects
o May also be relatively resistant to narcan
 Methadone – cardiotoxicity (prolonged QT with doses > 300 mg/d)
 Buprenorphine – partial agonist/antagonist, highly potent; replacing methadone in
heroin maintenance therapy; Significant toxicity to the opiate naive
 Immunoassays check for morphine and codeine (less sensitivity for semisynthetics; does not assay for synthetics)
 Withdrawal: not life-threatening, very uncomfortable
Organophosphates/Carbamates/Nerve Agents
 OP – permanently disable acetylcholinesterase (AchE)
 Carbamates – reversible bind AchE
 Nerve agents – highly potent OPs that rapidly and irreversibly bind to AchE
 Sx: SLUDGE or DUMBELLS (cholinergic excess)
 Death typically a combination of respiratory and CNS toxicity
 Decontamination (esp dermal)
 Tx:
o Atropine – overcomes muscarinic overload
 goal is drying of secretions
o Pralidoxime (2-PAM)
 Rejuvenates the enzyme
 1 gm IV over 10-5 min, then 500 mg/hr (peds 25 mg/kg bolus, 20
mg/kg/hr)
o Valium
 Even if not seizing
 Found to be synergistic with 2-PAM in improving survival
Plants




Vast majority of pediatric exposures are non-toxic
Nausea and vomiting most common effect
Toxic plants often require a tea to concentrate toxin
Example of often abused plant: Jimson Weed  persistent anticholinergic effects
Ricin

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

Made from ground castor bean husks
Toxicity from chewing castor beans
Potential weapon
Toxalblumin
9

o 2 subunits – one binds to the cell wall, allowing the other to enter and
disable the 60s ribosome
high lethality, no tx except support
Salicylates
 Absorption: erratic, often delayed (esp if enteric coated)
 Mech:
o Uncouples oxidative phosphorylation
o Central stimulation of respiratory center
o Enhance lipolysis
o GI irritation
o Inc cap permeability --> pulmonary and cerebral edema
 Presentation
o Mixed acid/base – prim resp alk with prim metab acidosis (inc anion gap)
o N/v, hyperdynamic, some hyperthermia
 Acute vs Chronic
o Chronic – sicker at lower levels
 Levels: need to be repeated often (q2hrs)
o Underestimate body burden if acidemic
 Tx:
o Decontamination (extra dose of charcoal)
o Volume
o Urine alkalinization
 Increase clearance of ASA
 Prevent acidemia
o Hemodialysis
Scorpion Envenomation
 Most cause only pain
 Bark scorpion (AZ) – neurotoxin
o Tx – benzos, opiates, antivenom if available
Sedative-Hypnotics (BZDs, Barbs, GHB, “muscle relaxants”, chloral hydrate)
 Most enhance effects of GABA
 OD rarely life threatening with supportive care
 Benzos – sedation; GHB – deep coma with agitated awakenings
 Dangerous withdrawal syndrome
o Benzos, GHB, barbs
 Flumazenil rarely, if ever, indicated
 Chloral hydrate
o Effects enhanced with EtOH = “mickey finn”
SSRIs
 Sedation
10

May see Serotonin Syndrome if used in combination with another serotonergic
med
o Mental status change, rigidity (tremor, fasciculations, clonus),
hyperthermia, autonomic instability, hi CPK
o Indistinguishable from NMS except by history
o Tx: BZDs, cyproheptadine (periactin – serotonin blocker)
Snake Envenomation
 Crotalid – pit vipers
o Rattlesnakes, copperheads, cottonmouths
o Local necrosis, hematoxins
o Tx – antivenom – “Crofab”
 Not fasciotomy!!!
 Elapids
o Coral snakes, cobras
o Neurotoxin --> respiratory failure, Tx – antivenom
Spider envenomation
 Black widow
o Mech: opening of cation channels  Ca entry  persistent depolarization
and release of ACH at NMJ
o Sx: pain/paresthesias at bite site (may see local diaphoresis)  migration
 severe abdominal, back or chest pain with hypertension, diaphoresis
o Tx: benzos, opiates, antivenom
 Brown recluse
o Necrotic ulcers, slow to heal, supportive care
o Rare systemic effects (fevers, chills, hemolysis)
Sulfonylureas
 Mech: increase insulin release
 Hypoglycemia within 4 - 8 hrs of OD
 All asymptomatic ingestions need to observed for at least 12 hrs
 Tx if hypoglycemic (no prophylactic glucose!)
o IV dextrose
 Paradoxically causes more insulin release
o Octreotide
 Prevents insulin release from pancreas
Sympathomimetics
 Cocaine, amphetamines, ecstasy, PCP, ketamine, ephedra, etc.
 Tachycardia, HTN, mydriasis, diaphoresis, agitation
 CVAs
 Cocaine
o Sodium channel blocker (like a TCA)
o Cardiac ischemia (up to 72 hrs out)
 TX: Benzos, benzos, benzos
11
o Cocaine MI – treat like any other MI, except no BBs if acutely intoxicated
(benzos)
TCAs
 Presentation
o Altered MS, seizures, tachycardia, widened QRS, hypotension
 TX:
o Sz – BZDs
o Altered MS – early intubation
o Hypotension –norepinephrine
o Widened QRS/Ventricular dysrhythmia – multiple amps of Bicarb
 Give for QRS > 120 ms
Activated Charcoal not useful with:
 Metals (including Li and Fe) – any molecule with a charge
 Caustics
 Hydrocarbons
 Alcohols
Potentially Radio-opaque substances
 Metals
 Cocaine/heroin packets
 Chloral hydrate
 Possibly enteric coated products
Persistent Seizures – think of:
 INH
 Theophylline
Pediatric “One Pill Can Kill” (or at least injure)
 Sulfonylureas
 TCAs
 Calcium Channel Blockers
 Cocaine
 Alcohols
 Opiates
 Quinine
 Hydrocarbon aspiration
 Clonidine
 Methyl salicylate (“oil of wintergreen”)
 OP insecticides
Most common Tox-related causes of death
 Pediatric
o Hydrocarbon aspiration
o CO
o APAP
12

Adult
o APAP
Supportive Care is the KEY!!!
 Protect the airway
 Support the BP (Norepinephrine)
 Treat seizures and/or agitation with benzodiazepines
o Beware of using antipsychotics in the undifferentiated psychotic patient!!
 Check CPK if any down time
 Consider the indications for decontamination
 Standard tox workup:
o Chem 7, APAP, ECG
o Do you really need that Urine Drug Screen?
 If febrile, consider:
o NMS, SS
o Malignant hyperthermia
o Sympathomimetic, anticholinergic, ASA
o Infection (esp aspiration)
Remember to call your regional Poison Control Center!!!!!
1-800-222-1222
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