toxicology 2 Flashcards
toxic alcohols
-Order of increasing alcohol toxicity -> Ethanol < isopropyl alcohol < ethylene glycol < methanol
-Toxic metabolites produced by alcohol dehydrogenase which can be inhibited by ethanol or fomepizole -> These all cause inebriation.
-Consider toxic alcohol if there is an unexplained anion gap or ↑ osmolar gap
-Methanol and Ethylene glycol will produce an anion gap. Isopropyl alcohol will NOT.
minding the gap: osmolal gap calculation
-This may be the only clue in an isopropyl alcohol ingestion
-!Osmolal Gap = measured osmolarity – calculated osmolarity
-Measured is given to you on a BMP
-Calculated = (2 Na) + (BUN/2.8)+ (Glu/18) + (ETOH/4.6)
-IF OSM GAP IS >10-20 consider:
-!Toxic alcohols: Isopropyl alcohol, methanol, ethylene glycol
-Ethanol [ketoacidosis]
-Mannitol
-DKA/HHS
-Drunk + Anion gap metabolic acidosis + osmolol gap = ethylene glycol or methanol poisoning
Drunk + osmol gap = isopropyl
ethylene glycol and methanol
osmolar and anion gaps
methanol poisoning
-Sources: paint thinner, car window washing solvent, wood alcohol, gas tank additive
-Methanol itself is nontoxic, but alcohol dehydrogenase forms the toxic metabolite
-Formaldehyde -> formic acid
-!!Anion gap metabolic acidosis + increased osmolal gap
-Symptoms are often delayed 12-18 hours: !Blindness from disc hyperemia!, seizures, resp failure, N/V, pancreatitis, visual changes, ataxia, AMS
-Treatment:
-!Fomepizole (4-methylpyrazole) (antizol)
-An alcohol dehydrogenase inhibitor
-Allows methanol to be excreted intact via the kidneys without being broken down into its toxic metabolites
-Usually, a temporizing measure until you can get dialysis
-Ethanol
-Occupies alcohol dehydrogenase to limit breakdown of methanol into its toxic metabolites
-Ethanol is preferentially metabolized by alcohol dehydrogenase over methanol and ethylene glycol
-Supplement: Folinic acid (cofactor to degradation of formic acid)
-!!Dialysis and bicarbonate if severe acidosis refractory to 4-MP or ethanol therapy
ethylene glycol poisoning
-Ingestion of antifreeze!, moonshine, paints, solvents, windshield wiper fluid
-Ethylene glycol metabolizes into !oxalic acid! -> combines with calcium -> forms calcium oxalate crystals -> acidosis and kidney injury
-3 phases of intoxication
-<12 hours: Intox + CNS depression without odor
-12-24 hours: Cardiopulmonary sxs: Tachycardia, heart failure/pulm edema
-24-72 hours: Acute tubular necrosis, anuria, flank pain, hypocalcemia
-Labs: !Anion gap acidosis, increased osmolar gap!, hypocalcemia, renal failure, hematuria
Wood’s lamp might show green glowing urine, d/t calcium oxalate crystals (low sensitivity and specificity)
-Treatment:
-!FOMEPIZOLE loading dose of 15 mg/kg IV
-Fomepizole inhibits alcohol dehydrogenase activity
-!HEMODIALYSIS if severe
-THIAMINE 10 mg IV & PYRIDOXINE 50 mg IV
-Both are consumed in the metabolism of ethylene glycol and need supplementation
-Pearl:*The absence of a strong odor of alcohol in a patient who appears intoxicated should raise the suspicion of ethylene glycol ingestion
isopropyl alcohol poisoning
-!Rubbing alcohol, disinfectant, hand sanitizer, mouthwash, ginseng shots, NyQuil
-CNS depression greater than ethanol
-Metabolism: in liver >50% metabolized to acetone
-!Hallmark: !Normal anion gap, increased osmolar gap!, Ketosis with normal glucose
-!Hemorrhagic gastritis, pulmonary edema, hypoglycemia
-Severe hypotension
-Supportive care, don’t give alcohol, fatal doses are rare
-Hemodialysis (if severe)
-Isopropyl alcohol poisoning differs from the other two toxic alcohol in that is has a normal anion gap, and is treated with supportive care
summary toxic alcohol chart
A middle-aged appearing man is brought after being found down on a sidewalk. He was found next to an empty bottle of vodka. On examination, he is disheveled and his clothes smell of urine. He has the strong odor of ethanol on his breath. On neurological examination, he is unable to follow commands and is incoherent, making only groaning sounds. After a period of resuscitation and observation in the emergency department, his condition appears to worsen and he becomes less responsive. After endotracheal intubation, an emergent CT head reveals bilateral isodense crescent-shaped lesions.
Acute on chronic bilateral subdural hematoma in a patient with acute alcohol intoxication
ethanol (alcohol)
-Alcohol is involved in nearly half of all trauma related deaths
-2.7 million ED visits a year = $8.7 billion
-NOT A TOXIC ALCOHOL
-Found in: Wines, spirits, beers, mouthwash, cologne, perfume
-CNS depressant / GABA agonist = Downregulates GABA and upregulates NMDA
-Many presentations:
-Intoxication
-Withdrawal
-Physical changes: liver disease, varices, SBP, cirrhosis, trauma!
ethanol (alcohol)- intoxication
-Intoxication begins: !80-100mg/dL (0.08 - 0.100 g/dL)
-!Ataxia, slurred speech, horizontal nystagmus, alcohol on breath (AOB)
-!Supportive care management
-Always search for other causes of AMS
-Check blood glucose
-Consider CT head and c-spine
-Look for fractures or other trauma
-Look for other evidence of drug use
-Evaluate for electrolyte abnormalities
-Ethanol serum level, ammonia levels, CBC, BMP+LFTs, VBG, CPK, consider levels for other drugs such as Tylenol or salicylates
-Always REASSESS for improvement ,withdrawal, missed traumatic injuries -> CT head for trauma
-Discharge home based on cognitive measures, not ETOH number (verify transportation)- BAC is not really used bc everyone has diff tolerance
-dont let them drive home
fatal withdrawals
-Withdrawal will cause CNS hyperexcitation!
-!Tachycardia, hypertension, agitation!, diarrhea, mydriasis, insomnia, cramps, diaphoresis, piloerection
-!Alcohol, barbiturates, benzodiazepines!
-CNS depressants
-Abuse, dependence, and acquired tolerance
-Drug intake abruptly stopped = withdrawal symptoms
-People die from withdrawal of benzos/booze/barbs
-Treatment: benzodiazepines!!, clonidine
-Overdose with benzos, booze and barbs is rarely life threatening unless associated with co-ingestion of other CNS depressants such as alcohol, opioids, barbiturates, first-generation antihistamines
CIWA scores
-clinical institute for withdrawal assessment (alcohol, revised)
-Validated scoring tool for alcohol withdrawal
-Done hourly
-Asks about various areas including nausea, vomiting, anxiety, tremors, hallucinations
-High scores = severe withdrawal
alcohol withdrawal syndrome timeline
-6-12hrs- early uncomplication withdrawal- minor symptoms- anxiety, tremors, insomnia
-12-24hrs- alcohol hallucinosis- hallucinations (tactile > auditory or visual) in 7%
-24-48hrs- alcohol withdrawal seizures- generalized tonic-clonic convulsions in up to 15%
-48-72hrs- delirium tremens- disorientation/confusion, hallucinations, hyperthermia, tachycardia (3-5%), mortality up to 50%
EARLY alcohol withdrawal
-Ask- WHY did they stop drinking?
-Tremulous, anxious, agitated
-!Intention hand tremor, that is constant! and does not fatigue
-!Tongue fasciculations are more sensitive
-Early as 6 hours, Peaks at 24-36 hours, resolves at 2-3 days
-Treatment:
-!Benzodiazepines (alternative phenobarb)
-Assess readiness for rehab
-Reassess with CIWA score - <8 can be managed outpatient
alcohol withdrawal seizures
-1-48 hours after decrease/cessation of alcohol consumption
-Usually 1-6 seizure episodes
-Generalized tonic-clonic w/ shorter post-ictal time (few minutes)
-Prolonged seizures, localizing findings, focal seizure, or status epilepticus – look for other cause!!!
-Low threshold to scan, and look for other trauma
-Usually chronic alcoholics (not binge drinkers)
-Treat with benzos! to reduce recurrent AWDS
-No role for antiepileptics unless hx of epilepsy
-Differentials for new onset seizures!
-Head trauma
-Intracranial bleed
-Metabolic derangement
-Acute poisoning
-Epilepsy
-CNS infection
delirium tremens
-Late occurrence: 2-4 days after stopping/decreasing alcohol
-1-15% mortality rate (up to 50 in some studies)
-Symptom complex:
-!Must have disturbance in CONCIOUSNESS or COGNITION
-(if they are awake and alert its not DT)
-Accompanied by tremor, agitation, delusions, hallucinations, fever, tachycardia, diaphoresis, seizures, hyperreflexia
-Respiratory alkalosis from hyperventilation
-Hypovolemia common
-Hypokalemia and hypomagnesemia common
alcohol withdrawal management
-R/O other causes of AMS
-head bleed, infxn, GIB, Liver dz, neuro
-General measures (can be applied to any AUD):
-IVF
-Thiamine 100mg IV
-Multivitamin PO/IV
-Magnesium 2-4g IV
-Dextrose if needed
delirium tremens management
-1st line medical option: Benzodiazepines! (used for all alcohol withdrawals)
-GABA agonist -> sedates the patient
-!Valium (diazepam)
-Fastest onset 1-5 minutes
-5-10mg IV diazepam
-!Ativan (lorazepam)
-!Versed (midazolam)
-!Librium (chlordiazepoxide).
-PO only, 50-100mg, slow onset and long half life, ideal for outpatient setting
-!Phenobarbital: Barbiturate for benzo-resistant alcohol withdrawal
-Propofol is preferred induction agent if intubating
-For severe withdrawals, titrate the benzodiazepines to achieve a state of sedation with arousability to minimal stimulation
A 19-year-old woman arrives at the ED 3 hours after taking “a handful” of over-the-counter pain relievers in the midst of a personal crisis. She is alert with normal vital signs and an unremarkable physical examination. Her APAP concentration at 4 hours after ingestion is 220 μg/mL (1,462 μmol/L).
APAP is the most common agent in pharmaceutical poisoning in North America: 5% of all calls to U.S. poison centers involve APAP, and over 10% of poisoning-related deaths reported to U.S. poison centers each year involve APAP.
acetaminophen (paracetamol) overdose
-!Toxic dose: Single ingestion >150mg/kg or >10g in adult
-MC pill overdose
-Mechanism:
-Hepatic metabolism via CYP450 -> NAPQI, a highly toxic free radical that causes damages liver
-In normal doses, NAPQI combines with thiols to produce non-toxic metabolites
-In overdoses, thiol stores are depleted, and NAPQI accumulates
-Predisposing factors: chronic alcohol use, malnutrition, older age, meds that utilize the CYP450 pathway (anticonvulsants, anti-TB meds)
acetaminophen overdose 4 stages of injury
-!APAP toxicity has no characteristic physical exam findings
-stage 1- first 24 hours -> N/V, abdominal pain
-Stage 2 (latent)- 24-48hrs -> GI sx, resolve (asymptomatic!), hepatic/renal dysfunction begins (Increase AST/ALT bilirubin INR)
-Stage 3- 3-4 days -> LFTs peak, coagulopathy, renal failure, hepatic failure, encephalopathy, sepsis, coma, death
-fulminant liver failure, sepsis
-Stage 4- 4 days - 2wks -> recovery phase for those who survive stage 3
acetaminophen labs
-Serum Studies
-!LFTs (serial)
-Coagulation profile (PT/PTT/INR)
-CBC baseline and calculate anion gap acidosis
-ABG/VBG to confirm acidosis levels
-Renal study
-APAP LEVEL- !Serum concentration >140u/mL 4 hours after ingestion! is considered TOXIC and treatment with NAC should be initiated
-Rumack- Mathew Normogram
-!Acute single ingestion ONLY
-4 hours after ingestion –window 4-24hrs post ingestion
-Does not apply to patient with !multiple-dose! ingestions or !extended-release ingestions!
-Can only do if you know both !exact timing of ingestion and ingestion is not chronic (over hours to days)
acetaminophen overdose management
-ABCs
-Decontamination with activated charcoal within 8-12 hours
-Antidote: !N-acetyl-cysteine (NAC)!
-Dose: 140mg/kg! of NAC
-Detoxifies and decreases production of NAPQI
-Oral and IV versions available
-Safe in pregnancy
-Charcoal does not inhibit effectiveness
-Very effective when given EARLY – !within 8 hours of ingestion!
-Equally effective at 1 hour post-ingestion, or 7 hours post ingestion
-But still indicated in late presentations >24 hours, decreases mortality even after liver failure ensures
-Dialysis (NAC is so good we rarely do this)- recommended in severe APAP poisoning (>1000mg/L), AMS, metabolic acidosis, elevated lactate (specific recommendations can be looked up)
-Transplant = liver failure
when to give NAC
-If someone walked into your ER and told you they just took an entire bottle of Tylenol, you have two options: Wait for four hours and check a level, or, knowing that this a toxic dose, you could start treating with NAC.
-Can start giving NAC
-Significant reported ingestions (single ingestion >150mg/kg)
-4 hour level (or more) APAP lies above the nomogram cutoff (>140mcg/mL)
-APAP ingestion presenting close to the 8hr cut off
-Evidence of hepatotoxicity presumed to be from APAP
-A serum APAP >10mcg/mL and unknown ingestion time
-There is technically no “cut off” time to start NAC
acetaminophen overdose
-Can consider liver transplant if worsening function
-Can discharge if unintentional ingestion, no hepatotoxicity, down trending APAP levels and in non-toxic range after treatment
-Discharge patients with APAP concentration <150 μg/mL (1,000 μmol/L) at 4 hours or below Rumack-Matthew nomogram treatment line after 4 hours following a single acute poisoning.
An 18-year-old woman is brought to the ED by her mother. The patient is diaphoretic and vomiting. Her mom states that she thinks her daughter tried to commit suicide. The patient admits to ingesting a few handfuls of acetaminophen (Tylenol) approximately 3 hours ago. Her temperature is 99.1 °F, BP is 105/70 mm Hg, HR is 92 beats per minute, RR is 17 breaths per minute, and oxygen saturation is 99% on room air. On examination, her head and neck are unremarkable. Cardiovascular and pulmonary examinations are within normal limits. She is mildly tender in her right upper quadrant, but there is no rebound or guarding. Bowel sounds are normoactive. She is alert and oriented and has no focal deficits on neurologic examination. You administer 50 g of activated charcoal. At this point, she appears well and has no complaints. Her serum acetaminophen (APAP) concentration 4 hours after the reported time of ingestion returns at 350 μg/mL. You plot the level on the nomogram seen below. Which of the following is the most appropriate next step in management?
a. Discharge home with instructions to return if symptoms return.
b. Observe for 6 hours and, if the patient still has no complaints, discharge her home.
c. Repeat the acetaminophen level 4 hours after the patient arrived in the ED. Treat only if this level is above the line.
d. Admit to the psychiatry unit and keep on suicide watch while performing serial abdominal examinations.
e. Begin NAC and admit to the hospital!!!!!!
A 15-year-old female adolescent is brought into the emergency department by her mother with a history of ingesting an unknown number of acetaminophen tablets within the past hour. Neither the mother nor the daughter had any idea how many pills had previously been used or were ingested. The daughter stated she took a lot of pills. The mother stated her daughter had no other medical problems. Both the mother and daughter said that no other medications were being taken.
What is the most appropriate time to evaluate an acetaminophen level after the reported ingestion in this patient to determine if therapy is indicated?
8 hours
4 hours!!!
12 hours
24 hours
2 hours
A 54-year-old man come to the ED because shortness of breath, headache, and ringing in his ears. He usually takes an aspirin a few times a day for his joint pain. He comes to the ED the day after an intentional overdose with a bottle of aspirin.
PMH: Alcoholism, 10 years sober, depression
Vitals: BP: 124/82 mm Hg; HR 114 beats/minute; T: 101°F; RR 24 breaths/minute
Exam: Confused, uncomfortable appearing, sitting up on edge of bed and holding his head. RRR. CTAB. Abd soft NTND.
LABS:
Salicylate level: 70 μg/mL (markedly elevated)
Acetaminophen level: none detected
ABG: pH 7.42; PCO2 22 mm Hg; PO2 68 mm Hg
Serum bicarbonate 18 mEq/L (decreased)
LFTs: normal
BUN 22 g/dL (elevated); creatinine 1.9 mg/dL (elevated)
Anion gap 20 mmol/L (normal 6–12 mmol/L)
UA before bicarb: pH 5.4
ORDERS:
Bicarbonate IV
Dextrose 5% in water (D5W)
Urinalysis (UA): recheck after bicarb!
Chest x-ray: Pulmonary edema and ARDS
Dispo: ICU
The patient’s mental status starts to improve with the start of IV glucose-containing fluids. Dyspnea improves as well. Repeat the salicylate level measurement every 2 hours and do an Interval History to check mental status.
-metabolic acidosis compensatory respiratory alkalosis
salicylate overdose
-Found in: Aspirin, Oil of wintergreen, Bengay, Air fresheners, mouthwash
-Toxic dose = 300mg/kg
-!Acute toxicity: N/V, tachycardia, tachypnea!, fever
-!Chronic toxicity: Tinnitus, GI irritation, altered mental status
-Severe: Cerebral and pulmonary edema, CNS hypoglycemia causing seizure
-Labs: ABG/VBG!!!, ASA level, Acetaminophen level, BMP, LFTs
-!!Primary respiratory alkalosis + Anion gap metabolic acidosis
-E.g. ↑ pH 7.44 | ↓ PCO2 26 | ↓ HCO3 18
-Salicylate level ≥ 30mg/dL
-Cause of death: Cerebral edema (seizure), pulmonary edema (ARDS), metabolic acidosis / resp alkalosis
salicylate overdose management
-ABCs, IV, O2 PRN, monitor
-IV fluids with glucose for CNS hypoglycemia
-!Decon: Activated charcoal
-!Urine alkalinization with !sodium bicarbonate! infusion (urine pH > 8)
-Inject 3 amp of NaCO3 into 1L bag of 5% dextrose to create isotonic solution, infuse at 200mL/hr
-Pay attention to potassium, hypokalemia prevents alkalinization
-NOT to do in CHF or renal failure pts because of volume load
-Titrated to a goal serum pH of 7.45 to 7.55 or a urine pH of 7.50 to 8.0.
-Indications for Hemodialysis!: pulmonary edema, cerebral edema (evidenced by severe confusion/AMS, seizure, coma), renal failure, acidemia, level >100mg/dL (acute) or > 60mg/dL (chronic)
60 year old male with history of HTN presents with altered mental status. His HR is 34bpm, BP 80/65mmHg
Meds: Metoprolol, diltiazem, atorvastatin, aspirin
Management starts with decontamination (AC or WBI)
GLUCAGON
Used for beta-blocker and CCB overdoses, and hypoglycemia
Induces vomiting (give anti-emetic first)
High dose insulin infusion
Increases heart rate by bypassing beta and calcium channels
Monitor potassium!
IV lipid therapy
Works on: TCAs, cocaine, beta blockers, CCBs, local anesthestics
Pulls lipophlic drugs out of the blood system
beta blocker overdose
-Hypotension, bradycardia, AV block, HYPOglycemia
-cardiogenic shock!
-Antidotes:
-Glucagon 5-10mg IV
-Insulin + dextrose
-Intralipid fat emulsion therapy if refractory to previous
-Other treatments: atropine, vasopressors, pacemakers, ECMO
-Timolol eye drops can cause systemic toxicity
irone (1) toxicity heavy metals
-MCC of poisoning death in children
-Free circulating iron:
-Damages blood vessels
-Hepatotoxic
-Direct corrosive to GI tract
->40mg/kg of elemental iron is considered a severely toxic dose
-Prescence of GI symptoms indicates significant exposure
-If no vomiting after 6 hours of ingestion, unlikely a toxic dose
iron (2) toxicity heavy metals
-Workup
-CBC/BMP = ↑ AG, ↑ glucose, ↑ WBCs
-Lactate
-!Iron (Fe) level @ 4 hours = >500 if toxic (dont mem #)
-KUB
-Treatment:
-No role for activated charcoal
-IV crystalloid resuscitation
-Antiemetics
-Consider whole bowel irrigation
-!!DEFEROXAMINE 15/mg/kh/hr chelating agent
-Indications: Severe symptoms, acidosis, serum iron 350-500, significant ingestion, +KUB
rat poison
=warfarin
-50 year old male presents after taking an entire bottle of warfarin. He has no complaints. What do you do?
-Warfarin- PT/INR increases over 8-24 hours, peaks at 32 hours, lasts as long as 5 days
-Rat poison:
-Duration as long as 6-8 weeks
-Usually, suicidal attempts
-Blocks synthesis of vitamin-K dependent clotting factors
-Check a baseline PT/INR (usually normal in first 6 hours)
-Treatment; Lavage, activated charcoal, vitamin K!, FFP, PCC
-If accidental ingestion patient can be reversed, give Vit K PO and have him follow up in 48 hours for repeat level check
intentional overdoses
-1:1 constant observation
-Psychiatry consultation
-Substance use counseling
-Medication reconciliation
