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Introduction to Toxicology - Download as PowerPoint

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Introduction to Toxicology - Download as PowerPoint Powered By Docstoc
					Presented by Dr. Levy

Prepared by

Dr. Trey Woods D.O.

Emergency Medicine
St. Joseph’s Health Center
Warren Ohio
   .
Supportive care is main means to decrease
morbidity and mortality
Learn about gastric decontamination
Learn and know all antidotes
Know toxidromes and treatment
   A comprehensive review of all of toxicology
   Though important it will also not cover
    envenomations, medications like oral
    hypoglycemics, blood pressure medications,
    lithium, or caustics
In practice, toxicology makes up 5-30% of
your cases
Inservice and written boards, about 8%
Oral boards, about 15%
   About 2-4 million toxic exposures annually
   Fewer than 1% of overdose patients that
    reach the hospital result in fatality
     But 13-35% mortality if arrive in deep coma
   One fourth of suicide attempts are via drugs
    More than half of exposures, <6 yo
    Toxin-related deaths on the rise
   Ingestions account for 79% of exposures

   Others
       7%    dermal
       6%    ophthalmologic
       5%    inhalations
       3%    stings and bites
       .3%   injection
   Analgesics                                 Alcohols

   Antidepressants                            Gases and Fumes

   Sedative/Hypnotics                         Asthma Therapies

   Stimulants/Street Drugs                    Chemicals

   Cardiovascular Drugs                       Hydrocarbons

   Clinical Toxicology Forum Vol 5 Num 2
   Leading causes of pharmaceutical death
     Analgesics
     Tricyclic antidepressants
     Sedative/hypnotics
     Stimulants and street drugs
     Cardiovascular drugs
     Alcohols
   1. Interfere with O2 transport or tissue
    utilization of oxygen
     (example      cyanide, CO)
   2. Affect CNS
     (example      cocaine, sedatives)
   3. Affect ANS
     (example      organophosphates)
   4. Affect lungs
     (example    paraquat)
   5. Affect cardiovascular system
     (example    TCA, Ca++ channel blockers)
   6. Direct local damage
     (example    acids, bases)
   7. Delayed effects on liver or kidneys
     (example    acetaminophen, metals)
Reduce exposure
Reduce absorption
Increase elimination
Know when to intervene
Give supportive care
Give specific therapy and antidotes when
appropriate
   A basic review of the initial approach to the
    following patient. . .
   29 year old man
     found “down”
     EMS transports
     Reports from scene: “he took something”
     No pill bottles on scene
     No family with him
     Roommates that found him are long gone
   He is now in your ED
   What do I do with him?
     What do I order?
     How do I treat him?
     How do I decontaminate him?
     Do I give him an antidote?
   When can he go to psych?
   Start with the basics
     Airway, breathing, circulation
   Get a better history
     Get EMS to get pill bottles, tell you what they do
      know (found outside, inside, garage…)
     Call friends, family, neighbors
     Call psych or primary MD to see what he is on
      regularly
   Get him to tell you
     Always remember that suicidal patients (just like
      everyone else) can lie so be skeptical of their history
A-Antidotes and alter absorption            (in some
instances prior to airway-decontamination with
organophosphates to protect others, cyanide toxicity where
antidotes are lifesaving)
B-Basics; ABC’s
C-Change metabolism (NAC, ethanol)
D-Distribute differently (calcium gluconate, O2)
E-Elimination (diuresis, dialysis, hemoperfusion)
   Remember the AMPLE history
     Allergies, Medications, Past medical and surgical history,
     Last meal, Events leading to presentation
   When in a jam, remember the P’s
     Paramedics
     Parents
     Pals
     Physicians
     Pharmacists


     History may prove UNRELIABLE
   CNS – level of arousal, GCS, pupils, behaviour,
    neurologic exam
   CVS – rate, rhythm
   Resp – pattern, depth, wheezing
   GI – bowel sounds, distention
   Skin – color, temp, signs of trauma
   Odors
   Vitals (temperature, resp. rate,HR, BP)
   Mental status, bowel sounds, pupillary
    response, skin findings
   Often times no significant physical findings,
    especially if exposure early
   Beware of changes
   Odors may give clue to substance
   Look for easily recognizable toxidromes
   HYPOTHERMIA (COOLS)
       Carbon Monoxide
       Opiates
       Oral Hypoglycemics, insulin
       Liquor
       Sedative Hypnotics

     Emergency Medicine June 1996 79-88
   HYPERTHERMIA (NASA)
       Neuroleptic Malignant Syndrome, nicotine
       Antihistamines
       Salicylates, sympathomimetics
       Anticholinergics, Antidepressants


    Emergency Medicine June 1996 79-88
   Bradycardia (PACED)
       Propanolol (B Blockers), poppies (opiates)
       Anticholinesterase drugs
       Clonidine, calcium channel blockers
       Ethanol, other alcohols
       Digoxin

   Emergency Medicine June 1996
   Tachycardia (FAST)
       Free base (cocaine)
       Anticholinergics, antihistamines, amphetamines
       Sympathomimetics, solvents
       Theophylline



Emergency Medicine June 1996
   Hypotension (CRASH)
       Clonidine, calcium channel blockers
       Reserpine, other antihypertensives
       Antidepressants, aminophylline
       Sedative-hypnotics
       Heroin, other opiates


          ▪ Emergency Medicine June 1996
   Hypertension (CT SCAN)
     Cocaine
     Thyroid supplements
     Sympathomimetics
     Caffeine
     Anticholinergics, amphetamines
     Nicotine

      ▪ Emergency Medicine June 1996
   Hypoventilation (SLOW)
       Sedative-hypnotics
       Liquor
       Opiates
       Weed (marijuana)


   Emergency Medicine June 1996
   Hyperventilation (PANT)
       PCP, paraquat, pneumonitis
       ASA
       Non cardiogenic pulmonary edema
       Toxin-induced metabolic acidosis




    Emergency Medicine June 1996
   Miosis ( COPS)
       Cholinergics, clonidine
       Opiates, organophosphates
       Phenothiazines, pilocarpine, pontine bleed
       Sedative-hypnotics


   Emergency Medicine June 1996
   Mydriasis (AAAS)
       Antihistamines
       Antidepressants
       Anticholinergics
       Sympathomimetics


   Emergency Medicine June 1996
   Flushed/Red Appearance
     Anticholinergics
     Boric Acid
     Carbon Monoxide (rare)
     Cyanide (rare)
   Diaphoretic Skin (SOAP)
       Sympathomimetics
       Organophosphates
       Acetylsalicylic acid
       Phencyclidine

   Dry Skin
     Antihistamines
     Anticholinergics

        ▪ Emergency Medicine June 1996
   Organophosphates                  PCP
   Tricyclic Antidepressants         Benzodiazepine
   Isoniazid, insulin
   Sympathomimetics
                                       withdrawal
   Camphor, cocaine                  Ethanol withdrawal
   Amphetamines                      Lithium, lidocaine
   Methylxanthines                   Lead, lindane

   Emergency Medicine June 1996
   Acetone                 acetone, acidosis
   Alcohol           NOT with ethylene
                     glycol
   Bitter almonds          cyanide
   Hemp (burnt rope) marijuana
   Garlic            arsenic
   Rotten eggs       disulfiram, H2SO4
   Want to evaluate
       Acid base status
       Renal function
       Liver function
       Cardiac conduction
        ▪ EKG
     Drug levels
      ▪ Based on history or clinical findings
     Any toxin specific findings
      ▪ CK for cocaine, NH3 for valproate, etc
Calculate the anion gap
AG=Na-(HCO3+Cl)
   M:methanol,metoformin,massive ingestions
   U: uremia
   D: DKA
   P: paraldehyde
   I: iron, INH
   L: lactic acidosis (CO,CN)
   E: ethylene glycol
   S: salicylates, strychnine
    Osmolar gap=measure serum osmolality-
    calculated serum osmolality
    Calculated=2Na+glucose/18+BUN/2+ethanol/6
      Normal gap <10 (nl 285-295)
    Causes Osmolar Gap:
    ME DIE (methanol, mannitol, ethanol, diuretic,
    isopropyl, ethylene glycol)
   Comatose          Tox screen, glu, NH4,
                      CT scan, CSF analysis
   Respiratory toxin ABG, CXR,
                      spirometry, pulse ox
   Cardiac toxin     EKG, ECHO, cardiac
                      enzymes, hemodynamic
                      monitoring
   An ECG should be performed on all patients who are
    symptomatic or who have been exposed to potentially
    cardiotoxic agents
   Evaluate QRS and QTC, presence of blocks, rhythm
     QTc > 450 and a QRS > 100 can be concerning for
      toxin induced (eg TCAs) cardiac abnormalities
   Limited usefulness
   CHIPES
       Chloral hydrate, Ca
       Heavy metals
       Iron, iodides
       Phenothiazines
       Enteric coated
       Slow release
   Packers/ stuffers
   Aspiration
                        Tox Screens
Toxic screening is rarely necessary when patients
with a non-intentional ingestion are asymptomatic
or have clinical findings that are consistent with
the medical history.
However, screening for acetaminophen and
salicylates is strongly recommended for patients
with an uncertain history or intentional poisoning;
few early signs may be present following lethal
doses of these agents, and specific treatments are
available and highly effective if implemented early.
   Quantitative urine specimens are superior to
    blood specimens since drug metabolites can
    be detected 2-3 days post exposure
   Urine screen specifically designed for drugs of
    abuse
   A positive or negative screen does not
    necessarily rule in or rule out an overdose
   False Positives
     Amphetamines: pseudoephdrine
     TCAs: cyclobenzaprine, carbazepine,
      phenothiazines, diphenhydramine
     PCP: ketamine, detromethorphan
   False Negatives
     Dilute urine
     Methadone: opiod screens
     MDMA: amphetamines
   Quantitative blood tests should be limited to
    those drugs for which levels can predict
    subsequent toxicity or guide specific therapy
   E.g., iron, lithium, acetaminophen, ASA,
    theophylline, digoxin
                          Toxic Timebombs
Acetaminophen
Mushrooms
Toxic alcohols
Sustained released preps (calcium channel
      blockers, beta blockers, lithium)
Drug packet ingestion (heroin, cocaine)
Oral hypoglycemic agents
Fat soluble organophosphates
Enteric coated preps
MAOs
Heavy metals
   Establish a pattern to his symptoms
     Toxic syndrome
     Also known as a:



                 TOXIDROME
   Not every drug fits into a broad based category
     Lots of meds have unique effects not easily grouped
    “Physiologic fingerprints” that occur in the form of syndromes or
    groups of symptoms which are observed to occur together in
    response to exposure to one of a pharmacologically similar group
    of agents
    Useful in determining the class of agents involved in an unknown
    poisoning
   5 Basic Toxidromes
       Sympathomimetic
       Opiate
       Anticholinergic
       Cholinergic
       Seditive Hypnotic
   Cocaine
   Methamphetamine/Amphetamines
     Ecstasy (MDMA)
     ADHD meds like ritalin, adderal
   Ephedrine
   Caffeine
Excessive SYMPATHETIC stimulation
involving epinephrine, norepinephrine and
dopamine

Excessive stimulation of alpha and beta
adrenergic system
   Tachycardia +/- arrythmias
   Hypertension +/- ICH
   Hyperthermia,
   mydriasis,
   convulsions, diaphoresis, seizure,
   central nervous system (CNS) excitation
   psychosis,
   Rhabdomyolysis
   Mimics Anticholinergic except WET compared to DRY
          Diaphoresis and normal bowel sounds with sympathomimetic
          toxidrome
          Dry skin and absent bowel sounds with anticholinergic
          toxidrome
   Supportive care
     Monitor airway, diagnose ICH,
      rhabdo
     IVF for insensible loses and
      volume repletion
                                        CNS                     Behavioral

   Benzos, benzos,                   excitation                 Agitation



    benzos, benzos
   BP mgmt if severe
   NEVER GIVE BETA                                 Cardiac
                                                   excitation
    BLOCKERS
   Opiate: derived directly from the opium poppy
     morphine and codeine
   Opioids: much broader class of agents that are
    capable of producing opium-like effects or of
    binding to opioid receptors
       Heroin
       Methadone
       meperidine
       Hydrocodone
       oxycodone
   Triad of:
     Coma
     Miosis (not always seen; demerol actually dilates)
     Respiratory depression
   Peripheral vasodilation, hypotension
   Flushing (histamine)
   Bronchospasm
   Pulmonary edema
   Seizures (meperidine, propoxyphene)
   Hypothermia
   Bradycardia
   Competitive opioid antagonist: Naloxone
     Goal of return of spontanous respirations sufficient
      to ventilate the patient appropriately
     May have to re-dose as opiates may act longer than
      antagonist
   There are other longer acting opioid
    antagonists such as nalmefene and naltrexone
    but these are not often used
   Hot as Hades - Fever
   Fast as a Hare - Tachycardia
   Dry as a Bone – Lack of diaphoresis
   Red as a Beet – Flushed skin
   Mad as a Hatter – Delerium
   Full as a Tick – Urinary retention
   Blind as a Bat – Mydriasis
   Supportive care
     IVF to replace insensible losses from agitation,
      hyperthermia
   Benzos to stop agitation
   Physostigmine
     Induces cholinergic effects
     Short acting
     May help with uncontrollable delirium
     Do not use if ingestion not known
      ▪ Danger with TCAs
      ▪ Don’t use in patients with CHB
   Block
    acetylcholinesterase
    from working
   End up with excess of
    acetylcholine in synapses
   Leads to excess
    stimulation of the
    muscarinic and nicotinic
    systems



                                Normal
   D - Diarrhea
   U - Urination
   M - Miosis
   BBB – Bradycardia, Bronchorrhea, Bronchospasm
   E - Emesis
   L - Lacrimation
   S – Salivation, Seizures
   S - Salivation
   L - Lacrimation
   U - Urination
   D - Diaphoresis
   G - Gasterointestinal upset
     vomiting, diarrhea
   E - Eye
     miosis
   Nicotinic effects
     M- Mydriasis
     T - Tachycardia
     W - Weakness
     (t) H - Hypertension
     F -Fasiculations
 Antagonize muscarinic symptoms
   Atropine
 Stop aging of enzyme blockade
   2-PAM
 Prevent and terminate seizures
   Diazepam
 Supportive care
   Different agents have different
    mechanisms
   Many interfere in the GABA system
   CNS depression, lethargy
   Can induce respiratory depression
   Can produce bradycardia or hypotension
   Supportive care
   Be wary of the benzo “antidote” Flumazinil
     Is an antagonist at the benzo receptor
     RARELY INDICATED
     If seizures develop either because of benzo
      withdrawal, a co-ingestant or metabolic
      derangements, have to use 2nd line agents,
      barbiturates, for seizure control
   Agitated, pupils 8 mm, sweaty, HR 140’s, BP 230/130
     Sympathomimetic
   Unarousable, RR 4, pupils pinpoint
     Opiate
   Confused, pupils 8mm, flushed, dry skin, no bowel sounds,
    1000 cc output with Foley
     Anticholinergic
   Vomiting, urinating uncontrollably, HR 40, Pox 80% from
    bronchorrhea, pupils 2 mm
     Cholinergic
   Lethargic, HR 67, BP 105/70, RR 12, pupils midpoint
     Sedative Hypnotic
   Most toxic exposures will get better simply with meticulous
    supportive care
   Not everybody needs the full court press
   Issues to address
     frequent assessment
     decontamination
     enhancement of elimination
     Antidotes
     disposition
   Do they need to be here at all?
   Beware of the “Stable” patient
   Consider possible polysubstance exposures
   Be prepared for deterioration
     IV access
     Cardiac monitor
     Pulse oximetry
   Airway, breathing, circulation
   Establish IV, O2 and cardiac monitor
   Consider coma cocktail
     Thiamine, D50, Narcan
   Evaluate history and a thorough physical exam
     Look at vitals, pupils, neuro, skin, bowel sounds. . .
     Gives you hints regarding the general class of toxins
     Guides your supportive care
   Draw blood / urine for testing
   Time to consider decontamination options
   Induce vomiting – Ipecac
   Take out pills from the stomach – Lavage
   Adsorb the toxins in the gut – Charcoal
   Flush out the system – Whole Bowel
 Aim is to prevent absorption and minimize exposure
 Many “standard” practices now virtually extinct
     Forced emesis, forced lavage, charcoal “anytime”
   Removal of contaminated clothing, substances on skin or in
    eyes
   Charcoal
   Gastric lavage
   Whole Bowel Irrigation
   Emetine and Cephaeline
   Induces emesis
   Rarely if ever still recommended
    for HOME use
   DOES NOT HAVE A
    ROLE IN ED CARE
   Gastric lavage
     Used far less now than in past
     Having your “stomach pumped,” with large tube
      inserted into stomach, suctioned, and lavaged
     Risk of perforation, aspiration, and simply not
      working
     Contraindicated in comatose or seizing patients,
      unprotected airways, extended release
      preparations
   Can be a brutal
    procedure
   Indication: life
    threatening ingestions
    that occurred within one
    hour
   Airway protection is key
   Limited indications
   Lots of complications
 Basically, everybody gets a dose
 Works to adsorb substances to its matrix
   Not for metals, caustics
 Generally safe, few contraindications
   Aspiration, bowel obstruction
 Dosing 1g/kg po dose, +/- single dose of
  cathartic
   Works by substances being adsorbed to the
    surface, which is size dependent
   Window of opportunity around one hour post
    ingestion
   Has some indications for multiple dosing
     drugs that have enterohepatic circulation
     drugs that can be eliminated by “gut dialysis”
   Charcoal doesn’t bind CHARCOAL
       Caustics and corrosives
       Heavy metals
       Alcohols
       Rapid absorption (cyanide, strychnine)
       Chlorine and iodine
       Other agents insoluble in water
       Aliphatics (petroleum distillates)
       Laxatives (Mg, K, Na)
   Loss of protective reflexes
   drugs likely to cause rapid depressed
    consciousness or early seizures
   infants < 6 months of age
   ingested foreign body
   neurologically impaired
   absent bowel sounds or obstruction
   unstable patients
   Chloral hydrate             NSAIDS
   colchicine                  phencyclidine
   digitalis preparations      phenothiazines
   glutethimide                phenytoin
   isoniazid                   salicylates
   methaqualone                TCA’s
   “Pretty Damn Short QTc
     Phenobarbital
     Dapsone
     Salicylates
     Quinine
     Theophylline
     Carbemazepine
   Isotonic polyethylene glycol electrolyte solutions
    (GoLytely)
   Large volumes ingested “wash” the substances through
    the bowel
     cleanses gut of intoxicants
     PEG solutions at 2 Liters/hour
     effective for use in LA preparations, body packers/stuffers, and
      some substances poorly absorbed by charcoal (ex iron)
     contraindicated if hematemesis, ileus, obstruction, perforation,
      or peritonitis

   Dose in volume sufficient to create clear rectal effluent
   Dosing:
     1-2 LITERS/HOUR
     Have to use an NG tube
In other words, get rid of the toxin faster

   Cathartics - used, but no study showing
    benefit
   Alkalinization – salicylates
   Hemodialysis
   Hemoperfusion
   Invasive, time consuming procedure
   Patients unstable despite supportive
    treatment
   Drugs must be amenable to hemodialysis
     Must have small volume of distribution (ie, drug
      must be in plasma, not tissues)
     Low protein binding, low molecular weight
     Water-soluble
   LET ME SAV P
     Lithium
     Ethylene glycol
     Theophylline

     MEthanol

     Salicylates
     Atenolol
     Valproic acid

     Potassium, paraquat
   Bleeding at venous puncture site
   hypotension
   DVT
   Bleeding due to systemic anticoagulation
   Infection
   Air embolus
   I STUMBLE (the common ones)
       Isoniazid
       Salicylates
       Theophylline
       Uremia
       Methanol
       Barbiturates
       Lithium
       Ethylene glycol
   Very limited number of antidotes given the
    vast array of pharmaceuticals and chemicals
   “Coma Cocktail”
     glucose
     thiamine
     naloxone
     ** NOT flumazenil**
   Toxin                             Antidote
       APAP                              N acetylcysteine
       Tricyclics                        Na bicarbonate
       Opiates                           Naloxaone
       Organophosphates                  2 PAM
       Heavy metals                      BAL
       Iron                              Desferoxamine
       Digoxin                           Dig Fab (Digibind)
       Beta-blocker                      Glucagon
       Calcium channel blockers          Calcium, glucagon, gluc/insulin
       Cyanide                           Sodium nitrite, sodium thiosulfate,
                                           hydroxycobalamine
   Toxin                            Antidote
     Methanol, ethylene glycol        Fomepizole (Antizole)
     Methemoglobinemia                Methylene blue
     Anticholinergics                 Physostigmine
     Isoniazid                        Pyridoxine
     Snakebites                       Antivenom
   Normal labs, normal EKG, normal exam, no
    history of extended release drug
     Approximately 6 hours
   Extended release medications, buprorion,
    oral hypoglycemics involved
     Depending on agent, 12-24 hours
 Needs circulatory or respiratory support
 altered mental status > 3 hours
 seizures
 arrhythmia
 second or third degree heart block
 widened QRS
 unresponsive to verbal stimuli
 arterial pCO2 > 45 mmHg
   Home if stable after appropriate evaluation
    and observation period, unintentional or
    simple gesture with support structure
   Psychiatry evaluation if intentional, or risk to
    harm self or others
   Admission if unstable, long-acting or
    sustained release, needing therapies
   How do I treat him
     Good supportive care, good physical examination
   How do I decontaminate him
     Charcoal as long as he is not an aspiration risk
   What do I order
     Chem, ASA, APAP, EKG at a minimum
   Do I give him an antidote
     Coma cocktail, others as indicated by labs
   When can he go to psych?
     Observe for 6 hours and re-evaluate
   .
   24 year old male brought in by family

   3 day history of confusion, not eating

   Vitals : T 38.5C HR96/min BP 100/50 RR 20
   What else do we need to know ??
     History of presenting illness
     Meds/All/Imm
     Past medical/surgical history
     Other


   Physical exam
   What is going on ?

   WHY ?

   What do we need to do ?
   Rare, life-threatening
   Reaction to neuroleptic medication

   All anti-psychotics may precipitate
        - typical or atypical
        - potent neuroleptics most frequent
   Classic Symptoms
     Fever
     Altered Mental Status
     Muscle Rigidity
     Autonomic Dysfunction
   Heterogeneous syndrome
   Average onset 4-14 days after initiation of therapy
     May occur at any time
   Pathophysiology
     Dopamine D2 receptor antagonists
     Nigrostriatum : muscle rigidity
     Hypothalamus : altered thermoregulation


     Sympathetic nervous system activation or dysfunction

      ▪ J Neurol Neurosurg Psychiatry 1995 Mar 58(3) : 271-3
   Frequency
     0.07-0.2%
   Mortality
     5-11.6%
      ▪ Respiratory failure, CV collapse, arrhythmias, renal failure, DIC
   Sex
     Male : female 2:1
   Age
     No age predilection

      ▪ Benzer Jan 18 2002
   Recent treatment with neuroleptics
     Within past 1-4 weeks
     Chronic use, increased dose, newly instituted

   Fever
     Above 38 C

   Muscle Rigidity
At Least 5 of the Following
  ▪   Change in mental status
  ▪   Tremor
  ▪   Tachycardia
  ▪   Hypertension/Hypotension
  ▪   Diaphoresis/sialorrhea
  ▪   Incontinence
  ▪   Leukocytosis
  ▪   Increased CK or urine myoglobin
  ▪   Metabolic acidosis

  ▪ EXCLUSION OF OTHER SYSTEMIC DISEASE
   Altered Mental Status
   Hyperthermia
   Autonomic Instability
     Tachycardia, hypertension, hypotension
   Generalized Muscle Rigidity
   Tremor
   Laboratory
       CBC, electrolytes, BUN, creatinine
       Calcium, magnesium, phosphate
       Liver Function
       PT, PTT
       CK
       Blood cultures
       Urine : urinalysis, urine myoglobin
       ABG
       Toxicology screening
   Imaging Studies
     Chest X-ray
     CT Head


   Procedures
     Lumbar Puncture
      ▪ Rule out meningitis
   ABC’S
   Stop all neuroleptics
   IV fluid rehydration
   Reduce Temperature
     Cooled IV fluids
     Cooling blankets
     Ice packs
   Pharmacotherapy
   Benzodiazepines
   Dopamine Agonists
     Bromocriptine
     Levodopa/Carbidopa
     Reverse dopamine blockade
   Skeletal Muscle Relaxants
     Dantrolene
      ▪ Inhibits calcium release from sarcoplasmic reticulum
     Neuromuscular blockade
   Consider the diagnosis

   Institute prompt therapies

   Patient/family education
     Risk for recurrence
   24 year old female brought in by family
   GCS 13/15
   HR 110/min BP 100/52 RR 12/min T 36C

   Able to indicate she took overdose
   Suicidal
   What else do we need to know ??



   What do we need to do ??
   What else do we need to know ??
       Who
       What
       When
       Where
       Why
       How
       How much ?
   What do we need to do ??
       O2/IV/monitors
       A
       B
       C
       D
        ▪ Disability
        ▪ Decontaminate
     E
        ▪ Exposure
     Head to Toe Exam
   Investigations
       CBC
       Electrolytes, BUN, creatinine
       Liver Function
       ASA, acetaminophen, ETOH
       Serum osmolality
       BHCG
       EKG
   Wide usage
     Depression, sleep, chronic pain, enuresis
   Most prevalent in females
   Age prevalence 20-29 years

   2-3% in hospital mortality
   70% out of hospital mortality
       Biittner Dec 11 2001
   Pharmacokinetics
     Peak levels 2-6 hours post ingestion
     Highly lipophilic
      ▪ Crosses blood-brain barrier
      ▪ Large tissue levels
     Elimination : hepatic oxidation
     Average t1/2 : 24 hours
      ▪ Up to 72 hours in overdose
   Toxicity
     10mg/kg : life-threatening
     1 gram : commonly fatal


     Desipramine
      ▪ Most potent sodium channel blocker
   Pathophysiology
       Antihistaminic
       Antimuscarinic
       Inhibit alpha-adrenergic receptors
       Inhibit amine uptake
       Sodium channel blockade
       Potassium channel blockade
       GABA receptor antagonist
   Physical Findings
       Confusion, hallucinations, seizures
       Hypotension
       Tachycardia
       Mydriasis
       Dry mucous membranes and skin
       Decreased bowel sounds
       Urinary retention
   RAD of terminal 40 ms of QRS in limb leads
     Sign of TCA exposure and toxicity

   R wave in aVR 3mm or greater
     Sign of toxicity and potential adverse outcome

   AV blocks

   Bundle branch blocks
           J Emerg Med 1990 Sep-Oct 8(5): 597-605
   Widening of QRS > 100ms
     Predictor of adverse outcome
     Indication for treatment

   Seizure/Dysrhythmia risk
     QRS<100ms : low
     QRS>100ms : moderate
     QRS>160ms : high

      ▪ Tintinalli ( 5th Edition)
   Normal

   Sinus Tachycardia

   Prolongation PR, QRS, QT intervals

   Ventricular dysrhythmias
   A
   B
   C
   D
     Decontaminate
      ▪ Charcaol
      ▪ Gastric Lavage
   Cardiovascular Agents
     Sodium Bicarbonate
      ▪   QRS > 100 ms
      ▪   Dysrhythmias
      ▪   Cardiac arrest
      ▪   Hypotension
          ▪ Also:
             Seizures
             Acidosis (pH<7.0)

             J Emerg Med11:336 1993
   Cardiovascular Agents
     Norepinephrine
      ▪ Beta 1 and Alpha agonist
     Dopamine
     Avoid Type Ia (quinidine, procainaminde, disopyramide) and
      Type IC (ecainide, flecainide, propafenone)
      ▪ Inhibit fast sodium channels
   Anticonvulsants
     Benzodiazepines
      ▪ Lorazepam
      ▪ Midazolam
      ▪ Diazepam
     Phenobarbital
      ▪ Seizures refractory to benzodiazepines
     Propofol

     Avoid Phenytoin
   .
   3 year old male brought in by his mother

   8 hour history of intractable nausea and
    vomiting
   History
       Visiting friends earlier in the day
       Acute onset : completely asymptomatic prior
       No fever, no URI symptoms, no rash
       Multiple episodes of vomiting and diarrhea
        ▪ No Blood
       No travel history, infectious contacts
       Healthy
       Immunizations UTD
       No medications, allergies
   REMEMBER :
     Ask about potential toxicologic exposure
      ▪ Prescription medications
      ▪ Herbal preparations
      ▪ Vitamins
      ▪ Cleaners, detergents, solvents, paints
      ▪ Plants
      ▪ Etc.
   Leading cause of toxicologic deaths < 6 years old
          ▪ Pediatr Ann 1996
   Pathophysiology
     Corrosive Toxicity
      ▪ GI tract
      ▪ Hypovolemia : fluid and blood loss


     Cellular Toxicity
      ▪ Uncouples oxidative phosphorylation
      ▪ Mitochodrial dysfunction and cell death
      ▪ Liver significantly affected
      ▪ Also : heart, lungs, kidneys, hematologic system
   Toxic Doses
       Non-toxic <20 mg/kg
       Moderate : 20-60 mg/kg
       Severe : > 60 mg/kg
       Lethal : 180-300 mg/kg

   Peak Levels
     Chewable : 4-6 hours
     Enteric coated : erratic
   Maintain High Index of Suspicion
     Vomiting and diarrhea
      ▪ Especially hemorrhagic


     Hyperglycemia and metabolic acidosis
      ▪ During/following episode of abdominal pain and
        gastroenteritis
   Five Stages of Iron Toxicity

   Stage One
     0-12 hours
     GI symptoms
      ▪   Abdominal pain
      ▪   Vomiting, diarrhea
      ▪   Shock
      ▪   +/- Leukocytosis, Hyperglycemia
   Stage Two
     6-24 hours
     Quiescent stage
      ▪ BEWARE !
   Stage Three
     24-72 hours
     Multiple Organ Failure
      ▪   Altered LOC
      ▪   Respiratory failure
      ▪   Cardiovascular Collapse
      ▪   Liver Failure
   Stage Four
     2-5 days
     Hepatic Failure
      ▪ Hypoglycemia
      ▪ Coagulopathy
   Stage Five
     Days
     Obstructions
      ▪ Gastric outlet
      ▪ intestinal
   CBC, electrolytes, Bun, creatinine
   Glucose
   Liver function, PT, PTT
   ABG
   Lipase
   Type and Screen, Crossmatch
   Abdominal xray
     Iron is radiopaque
   Serum iron level
     3 – 5 hours post ingestion
      ▪ < 350 ug/dl : minimal
      ▪ 350-500 ug/dl : moderate
      ▪ 500 ug/dl : severe
     Repeat at 6-8 hours
      ▪ Erratic absorption
   ABC’s
   Fluid resuscitation
   Decontamination
     Charcaol
      ▪ Ineffective
     Whole bowel irrigation
     Exchange transfusion
      ▪ severe
   Deferoxamine
     Binds elemental iron
     100mg to 9.35mg elemental iron
     15 mg/kg/hr
     Renal excretion
     Urine turns “vin rose” color
     Infusion usually for 24 hours
   Serum iron > 500 ug/dL
   Rising serum iron levels
   Sustained GI symptoms
   Metabolic acidosis
   Hypotension

         J Toxicol Clin Toxicol 1996 34 (5) 485-89
   17 year old female
   Nausea, vomiting, diarrhea
   Blurred vision, seeing yellow and green halos

   Took grandmother’s “ heart pills”
   Monitored room
   O2/IV Monitor

   Vitals : T 36 C, HR 50/min BP: 90/60 RR:
    18/min O2 sats 96 % room air

   EKG
   First described in 1785
        ▪ Ellenhorn’s Medical Toxicology 2nd Ed 1997 451-456


   Medication error and toxic effects account for 44%
    of preventable cardiac arrests
     Digoxin most common
        ▪ JAMA 265: 2815, 1991.
   Therapeutic effects
     Inhibits Na/K Pump
      ▪ Increase intracellular sodium and calcium
      ▪ Increase extracellular potassium
        ▪ Increases myocardial contraction
     Direct and indirect effects on SA and AV nodes
      ▪ Increase vagal and decrease sympathetic actvity
     Purkinje Fibers
      ▪ Slow phase 0 depolarization and conduction velocity
      ▪ Decrease action potential duration
      ▪ Enhanced automaticity

           Rosen 5th edition
   Toxic Levels
     Paralyze Na/K pump
      ▪ Hyperkalemia
     Depress generation of SA node impulses
     Decrease conduction through AV node
     Myocardium very sensitive
      ▪ Electrical and mechanical stimuli

     Virtually any dysrhythmia or conduction block

        ▪ Rosen 5th Edition
   Acute overdose
   Deteriorating renal function, dehydration
   Electrolyte disturbances
     Toxic effects on Na/K pump
       ▪ Hyperkalemia most common exacerbant
   Acidosis
     Depresses Na/K pump
   Myocardial Ischemia
     Suppresses Na/K pump
     Alters myocardial automaticity



          Schreiber May 23 2001
   Constitutional Symptoms
   CNS
     Headache, confusion, dizziness, delerium, agitation, paresthesias,
      seizures (rare)
   CVS
     Palpitation, syncope
   Gastrointestinal
     Nausea, vomiting, anorexia, diarrhea
   Ocular
     Disturbances of color vision
      ▪ Tendency to yellow-green
      ▪ Halos and scotomas
      ▪ Blurred vision
      ▪ photophobia
   ABC’S
   Decontamination
     In overdose
     Charcoal
   Correct electrolyte and acid-base disturbances
     Potassium, sodium, magnesium
     Calcium contraindicated unless profoundly hypocalcemic
   Atropine
     For bradydysrhythmias
   Pacing
     External may be safer than transvenous
      ▪ Irritable myocardium
      ▪ May induce tachydysrhythmias


       ▪ Clin Tox 31: 261 1993
   Digoxin-Fab Fragments (Digibind)
     Digoxin-specific antibody fragments
     From IgG of sheep immunized with digoxin
     One vial = 40 mg of digoxin-specific antibodies

     Doses
      ▪ Chronic Toxicity
        ▪ digoxin level (ng/mL) x weight (kg) / 100 = number of vials
      ▪ Acute Toxicity
        ▪ Amount ingested (mg) x 0.8 /0.5 = number of vials

      ▪ Schreiber May 23, 2001
   Indication for Digitalis Antibody Fragments
     Severe ventricular dysrhythmias
     Hemodynamically significant bradydysrhythmias
         ▪ Unresponsive to atropine
       Serum potassium > 5.0 mEq/L or rising levels
       Rapidly progressive rhythm disturbances
       Coingestion of cardiotoxic drugs
         ▪ B blockers, TCA’s etc.
       Ingestion of plants containing cardiac glycosides plus dysrhythmias
       Acute ingestion > 10 mg plus any of the above
       Level > 6 ng/mL plus ant of the above

        ▪ Rosen 5th Edition
   CHRONIC                          ACUTE
     Higher mortality                 Lower mortality
     Potassium low/normal             Potassium normal/high
     Ventricular dysrhythmias         Bradycardia/AV block
      ▪ More common                     ▪ More common
     Usually elderly                  Usually younger
     Often need Fab                   Often do well without Fab
     Underlying heart disease         Absence of heart disease
      ▪ Increases morbidity and         ▪ Decreases morbidity and
        mortality                         mortality
   A 21-year-old female is brought to the ED by her
    boyfriend when he learned that she had
    ingested approximately 30 X 325 mg tabs of
    acetaminophen in an attempted suicide.
   He was unaware of any prior medical or
    psychiatric problems but reports that she was
    seen in another ED several days earlier for
    persistent headaches.
   The patient provided some history stating that
    she wanted to kill herself but denies any co-
    ingestion. She c/o stomach ache
   On physical exam the patient was
    diaphoretic, pale and suffering from
    abdominal distress.
   VS: BP: 95/70 mm Hg; P: 100/min; RR:
    20/min, and T:98.6 F
   The exam was otherwise unremarkable
    except for mid-epigastric abdominal
    tenderness.
   She was given charcoal and a 4-hour
    acetaminophen level was 215 mcg/mL
   Name 4 metabolic pathways of APAP and the
    proportion of APAP metabolized by each
    pathway in a normal adult host with a
    therapeutic ingestion.
   Hepatic glucuronide conjugation(40-65%)
             90%
   Hepatic sulfate conjugation(20-45%)
     inactive metabolites excreted in the urine.
   Excretion of unchanged APAP in the urine (5%).
   Oxidation by P450 cytochromes (CYP 2E1, 1A2,
    and 3A4) to NAPQI (5-15%)
       GSH combines with NAPQI
        nontoxic cysteine/mercaptate conjugates
        excreted in urine.
   Most absorption 2º, even after OD

   Peak concentration 4º then hepatic metabolism

   90% elimination 3 routes; conjugation w/ gluconroide
    (40-67%) or sulphate (20-46%), or oxidation via CP450
    or similar enzyme then conjugation

   Oxidation by CP450 or subfamily CYP2E1--> very
    reactive electrophile; NAPQI (aka N-acetyl-p-
    benzoquinoeimine)
   It is the toxic metabolite that causes liver
    injury
     See saturation of glucoronidation and sulfonation
      pathways (major pathways)
     Metabolism shifts to minor pathways cytochrome
      P450 metabolism requires glutathione, which
      depletes rapidly
     Toxic metabolite accumulates
     Direct hepatocellular toxicity
Use the nomogram to help
    decide who needs
        treatment
  Must be between 4-24
  hours from single acute
ingestion of non-extended
     release product
   Stage 1: pre-injury; 1st 24º, no specific Sx; N/V,
    anorexia, diaphoresis, malaise... common in 1st 8º

   Stage 2: onset Liver injury 24º (12 to 36º after
    OD). If sever may be 8º; N/V, RUQ/mid-epigastric
    pain

   Stage 3; Max liver injury; 3-4 days. Sx vary;
    fulminant hepatic failure; encephalopathy, coma,
    coagulopathy, hypoglycemia, metab acidosis,
    haemorrhage, ARDS

   Risk renal injury   ↑ 25% w/ severe toxicity vs.
   Stage 4; Recovery Liver Enzymes to baseline 5-7 days,
    longer w/ severe injury. Histologicly- months

   Regeneration of liver is complete w/o chronic dys-fxn
   Toxic ingestion: 140 mg/kg (7-10 g in adults)
   4 hr level > 140 potentially toxic
   N-acetylcysteine (NAC)         Prevents binding of
    BNAPQI to heaptic macromolecules)
   May also reduce NAPQI back to acetaminophen
   Oral and IV preps available
   Safe in pregnancy
   Charcoal does not limit effectiveness
   Still indicated in presentations > 24 hrs
NAC provides a cofactor needed to make inert metabolites of
APAP/Lack of this cofactor results in the production of
hepatotoxic intermediary metabolites
   Tx with NAC if:
     4, 6 or 8h level above the R-M tx line  full course NAC.
     If all levels are below the tx line and the 8h APAP level is
      less than 50% of tx line  D/C home (NYPC).
     If the 8h APAP line is btw 50% of tx line and tx line  NAC.
      for 24-36h and D/C once APAP <10 or transaminases
      normal (NYPC).
     If the 6-hour level is greater than the 4-hour level, begin
      NAC therapy.

    * More prolonged monitoring of levels may be necessary if
      the patient has food in the stomach or co-ingestants that
      delay gastric emptying.
   What percent of pts whose APAP level falls
    above the upper line of the Rumack-Matthew
    normogram will develop hepatotoxicity?

    (defined as elevation of the plasma transaminases above
    1,000 U/L)
 60%
   N-acetylcysteine (NAC) serves as both glutathione
    precursor & substitute


   NAC may ↓ NAPQI formation & ↑ non-toxic sulfation

   NAC improves survival in pts w/ acetaminophen-
    induced fulminant liver failure, even long after initial
    metabolism

   Possible MOA for survival benefit; ↑ oxygen
    delivery/uptake by tissues, change in microcirculation,
    scavenging ROS & ↓ cerebral edema
   Oral NAC
     The FDA approved oral dosing regimen is 140 mg/kg as the loading
      dose, then 70 mg/kg every 4 hours for 17 doses starting 4 hours
      after the loading dose.
     Oral NAC is irritating to the gastrointestinal track and should be
      diluted to a final concentration of no more than 5% to reduce the
      risk for vomiting.
     The oral form of NAC has an unpleasant odor and taste that can
      also affect compliance with administration.
   IV NAC (Acetadote®)
     adult dosage regimen for the IV formulation is a loading dose of
      150 mg/kg in 200 mL of 5% dextrose given over 15 to 30 minutes.
      The maintenance dose follows at 50 mg/kg in 500 mL of 5%
      dextrose given IV over 4 hours then 100 mg/kg in 1000 mL of 5%
      dextrose given IV over 16 hours2.
     Adjustments are required for children and patientsat risk for fluid
      overload
   Contact poison control center

   Fulminant Hepatic failure, need ICU, frequent Neuro
    checks, glucose measurements, VS monitoring

   Early contact Liver transplant center if Liver failure

   Serum PH < 7.3 after resuscitation likely to die w/o
    transplant.
   Setting: Mid-March 2006 @ RAH ER, sidekick to Dr. Rabin,
    called to T3
   61 yr old obese female who looks unwell, slumped in bed,
    with some increased work of breathing
   Patient’s eyes are closed, she’s not answering questions, but
    responds to commands
   While trying to take some history, she states: “I’ll tell you if
    you tell me…”
   Your initial reaction is?
   1. Here we go again- another patient for Kendra to laugh at
    me about…

   2. I bet she’d open her eyes to look at me if I was Tom Griffin

   3. Where the hell is Bob Moosally when you need him…

   4. This patient is “sick” and ?confused       vitals, chemstrip,
    IV, O2, monitor.
  Initial management
Vitals: T 37°, HR 117, RR 26, BP 109/55,
        Sats 86% on RA, c/s 6.2
Treatment
o O2 NRM
o IV NS TKVO
o Intubation kit at bedside

Investigations
o CBC and diff, lytes, BUN, Cr, LFTs, Troponin, Lactate
o Toxicology Screen, serum osmolarity
o Blood culture & urine cultures
o ABG
o ECG
o CXR (portable)
   Daughter-in-law states patient seldomly seeks medical
    attention
   Unwell X 3d with nausea and emesis and increasing SOB
    and WOB
   Big smoker, but not known to be ETOH/drug abuser
   Longstanding problems with sore back that she was
    taking Tylenol for with increased dosing over the last
    few days
   No history of trauma
   Brought her to hospital because today she was having
    trouble breathing, confused, slurring her speech, and
    ataxic
   Preliminary DDx?
     COPD Exacerbation
     CNS problem
     Sepsis
     GI problem
     Toxidrome
                        SHx:
o PmHx:
                          1-3 ppd smoker/ 75 p.yr.hx
   o COPD
                          No Etoh/recreational drugs
   o HTN
   o DM II
                          o Meds (NKDA):
   o Low back pain          o Indapamide 1.25 mg OD
   o Depression             o Altace 10 mg OD
                            o Lipitor 20 mg OD
   o Constipation           o Metformin 500 mg TID
                            o Advair 250 mcg PRN
                            o Ativan 2 mg BID
                            o Zoloft 200 mg OD
                            o Tylenol PRN
   Emesis non-bloody, non-bilious

   Gradually became fatigued, unsteady on her feet,
    occasionally slurring her speech

   Pertinent negatives…
     Ø fever
     Ø change in cough
     Ø abdo pain or diarrhea/change in stools
     Ø chest pain
     Ø motor symptoms/sensory symptoms
     Ø travel or contacts
   Vitals: T 37°, HR 117, RR 26, BP 109/55,
           Sats 86% on RA, c/s 6.2
   Neuro: GCS 13-14, PERL 5mm, moves all 4 strongly, speech ?slurred, Ø
    facial droop, sensory №

   Resp: ↓ BS with diffuse wheezing, ↑WOB, Ø cyanosis

   CVS: Faint HS, Ø Mx/EHS, JVP ?, no edema, ppp X4 strong, MM dry

   Abdo: BS +, obese, non-tender

   MSK/Derm: Nil, Ø rash

   HEENT: Neck №, Ø lymphadenopathy
   What do you think is most likely?
     COPD exacerbation ± ? something else



   Possible DDX
     Sepsis
     CNS problem
     GI problem
     Toxidrome
Treatment
 O2 NRM
 IV NS bolus 500cc
 Ventolin/Atrovent nebs
 Solumedrol 125 mg IV
 MgS04 2 g IV
 Trial of bipap if deteriorates, intubation kit at
  bedside
   pH 7.24 /41 / 74 / 16.8 / 92% at @ 11:05

   Interpretation of ABG?
     Uncompensated MA

   Winter’s formula
     Expected pC02= 1.5(HCO3) + 8

   Any new intervention now?
     BIPAP!

   pH 7.24 / 39 / 133 / 16.1/ 98% @ 12:00 on bipap
   HGB 127
   WBC 8.1
   PLT 206
   Na 139 / K 3.9 / Cl 108 / C02 16 / ↑AG = 15
   Creatinine 106 / Urea 14.2
   INR 1.4 / PTT 26
   LFTs: AST 42, ALP 54, T. bili 2
   Recap…

   61 yr old smoker, unwell X3 days with flu-like illness,
    now confusion and uncompensated AGMA on ABG

   Treated so far as COPD exacerbation

   Any other thoughts?
   Troponin #1 <0.15

   Lactate 0.5

   Toxicology Screen
     Tylenol –ve
     Etoh –ve
     ASA 105 mg/dL ↑
   Does this change anything? What would you do now?

   1 amp NaHCO3 IV

   NaHCO3 infusion (3 amps NaHCO3 in 1 L D5W at 150cc/hr;
    urine ph q 30 mins, goal pH ≥ 8)

   Dialysis

   ICU consult
   ABCs

   Activated charcoal in acute ingestion

   Urine Alkalinization

   Fresh frozen plasma

   Hemodialysis
     ASA levels and dialysis – is this the only guide?
       ▪ Acute (within 6 hr) >100 mg/dL
       ▪ Chronic >40 mg/dL
   Salicylic Acid salts absorbed rapidly GI tract; serum
    concentrations ½ º, 2/3 of dose in 1º & peak 2-4º


   Absorption to 12º post large ingestion or coated tabs


   ASA hydrolyzed to free Salicylic acid via RBC, Liver,
    Intestinal wall & reversibly binds albumin


   Free Salicylate & conjugates excretion is Renal
   Therapeutic dose is 1st order kinetics, but > 30mg/dL has Zero
    order Kinetics w/ constant Metabolic Rate

   Ph-sensitive urinary excretion of ASA det half-life…toxic
    doses may be 15-30º

   Salicylate stim medullary respiratory center to PH and CO2
    partial pressure.

    amts ASA depress respiratory center. Loss bicarb,
    metabolic acidosis; 2º buffering respiratory alkalosis.
   patient age
   Comorbidities
   serum concentration
   mental status
   hydration status
   mortality.
Inhibition of Krebs cycle   amts lactic & pyruvic acid.

Uncoupling ETC;  metabolism &Temp, thus  CO2 production
  & O2 use,  glycolysis risk  BS. Less common  BS due
  to adrenaline


K+; Vomiting,  Renal Na+K+HCO3 loss,  Renal Tubercle
  permeability, Intracellular H2O, Na+ retention

Uncoupling ETC also  K+ by inhibiting active transport

   Renal Blood flow; ARF & secretion inappropriate ADH
ETC= electron transport chain, arrows; increase or dec, 3 dots; therefore
   MOA unknown


    Risk Adults; smoking, 30+ y/o, chronic use, metabolic
    acidosis, Neuro Sx, Salicylate > 40mg/dL


    Risk Peds; High salicylate level, large anion gap, K+
    level, CO2 concentration
   Measure level 6º post ingestion, then 2nd sample in 2º


   If 2nd sample > 1st sample; do serial; caution w/ coated
    preps, or chronic ingestion


   Frequently monitor PH


   Death by CNS depression & Cardiovascular collapse
   ASX; occasionally none

   Mild; Mild-mod hyperpnea, Tinnitus, may get lethargy

   Moderate; Severe Hypernea, marked lethargy or
    excitable, NO COMA, NO Convulsions

   Severe; Severe Hypernea, COMA, Semi-coma, may get
    convulsions
Characteristics:                       More dangerous

Features     Acute                Chronic
Age           Young adult         Older adult/infants
Etiology      OD                  Therapeutic misuse
Co-ingest.    Frequent            Rare
Past history OD or psych          Comorbidities/pain/RF
Presentation Early                Late
Dehydration Moderate              Severe
Mental status Normal(initially)   Altered
Serum [conc] 40 - ≥120 mg/dL      30 to ≥80 mg/dL
Mortality     Low w/ treatment    High
   Early: tinnitus, n/v, diaphoresis + hearing loss (a
    bit later)
   Vertigo, hyperventilation, hyperactivity,
    agitation, delirium, hallucinations, Sz, lethargy
    and stupor.
   Late: coma (after massive ingestions  levels
    >100mg/dL or co-ingestions)
   Severe hyperthermia from uncoupling of
    oxidative phosphorylation is a preterminal event.
   Urine output 2-3mL/kg/hr w/ D5NS or D5LR, but No
    Forced diuresis. D5 w/ 100mEq bicarb/L

   Fix K+ & Monitor pH, avoid systemic alkalosis

   Alkalize Urine; ABG; 1-2meq/kg Bicarb, then as needed
    (50ml Bicarb  pH by 0.1)

   DIALYSIS IF; Coma/Seizure, Hepatic failure, Pulm
    edema, Severe acid-base imbalance, Deteriorating
    Status, level > 100mg/dl & 40mg/dL if chronic
   VS; especially respiratory rate, assess minute Volume,
    skin temp, ABG

   Activated Charcoal reduces absorption; consider if
    ingestion w/in 1º NO Evidence of benefit of outcome

   IVF; dehydration occurs early, correct K+ use dextrose,
    accu check frequently. CNS glu maybe low even if serum
    euglycemic

   Alkalize urine especially if salicylates > 35mg/dL, urine pH
    7.5-8 necessary to  excretion

   Consider exchange transfusion in young or dialysis
   Pregnancy; greater concentration on fetal side of placenta,
    fetal distress, associated w/ fetal demise

   Deliver distressed fetus if possible

   If acute intoxication; pulmonary edema, acidosis, electrolyte
    abnormality, renal insufficiency, CNS Sx other than Tinnitus;
    ADMIT

   Mortality Rate of chronic toxicity 25% vs 1% for acute

   DO a Psych EVAL
   Urine dip: ketones
   CBGM: hypoglycemia
 The Done normogram was derived from predominantly pediatric
  data for a level 6hrs post ingestion from a single, acute ingestion
  of non-enteric coated tablets. Also, it is only applicable for levels
  from a blood pH >7.4. It is notoriously unreliable.
 Better way of monitoring:
   ASA levels a 2-4 hourly intervals, looking for the direction
    of change.
       Careful in interpreting a decreasing level: this can indicate
        increased clearance with decreasing toxicity OR increased tissue
        distribution with lower pH and increased toxicity.
       Even a lowering [ASA] with a decreasing pH may be ominous.
   Serial ABG monitoring.
   Monitor the mental status.
    the more acidotic the compartment the
    more SA will be NONionized because SA is a
    weak acid (the stronger acids will dissociate
    and give off their H+ first.)
the more basic a compartment the more
    IONIZED SA will be because there is a relative
    lack of H+  so because SA is an acid it will
    give off its H+ and be ionized, i.e. “trapped” in
    that milieu.
   >40mg/dL in an acute OD
   >30mg/dL in a chronic OD
   Renal failure
   CHF
   Pulmonary edema or acute lung injury
   Refractory acidosis or electrolyte imbalance
    despite maximal therapy
   Persistent CNS symptoms
   Progressive vital sign deterioration
   Acute OD with level >100mg/dL
   Liver failure with coagulopathy
 Age > 30
 Smoking
 Chronic salicylate ingestion
 Presence of neurologic symptoms on
  presentation.
 Hypoxia (increase in pulmonary vasomotor tone)
 Degree of acidosis independent of serum [SA] is
  associated with ALI: it is unclear whether this is a
  causative factor or a consequence of ALI.
   Pt went to ICU and was dialyzed for ASA toxicity (2.92 → <
    0.07 and № pH)

   A few hours after arriving in ICU, ↓ LOC and Sp02 , intubated
    overnight

   Weaned from vent next day, extubated, to medicine

   Left AMA post ICU transfer day 1-2
   Consider chronic ASA toxicity in patients with CNS
    dysfunction.

   Pepto Bismol and oil of wintergreen contain salicylate too!
    Patients taking carbonic anhydrase inhibitors may also have
    ASA toxicity at therapeutic levels.

   Non-cardiogenic pulmonary edema, renal failure,
    neuroglycopenia and seizures can occur in significantly
    poisoned patients.

   Despite CNS stimulation of the medulla by salicylates, you
    may not see respiratory alkalosis in patients with poor lung
    function (i.e. COPD)
   Long-term ASA poisoning occurs most commonly in the
    elderly who regularly take doses of aspirin. In such cases, the
    dx is often overlooked!
   Classic ABG picture of AGMA and respiratory alkalosis- think
    ASA!
   In patients with COPD you may not see the respiratory
    alkalosis because of their underlying lung disease.
   In ASA toxicity, ASA levels should not be the sole
    determinant of management decisions.
   24 hours a day
   Anywhere in the United
    States
   Poison Specialists and
    Medical Toxicologists are
    available

				
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