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Slide1
Case Review ~Toxicology
Amy Gutman MD ~ Chief of Emergency Medicine
prehospitalmd@gmail.com / amy.gutman@hahv.orgSlide2
Overview
Role of case review is to review interesting cases with unexpected outcomes, examine “root causes”, management & outcome successes or concerns
Great example of a BLS service appropriately utilizing ALS after recognizing a potentially life-threatening condition Slide3
Suicide Attempt
34yo F presents via EMS with suicide attempt. Drove to parking lot of a college, stuffed something in the tailpipe of her car & took an entire bottle of “
tylenol
pm”. Unknown time since ingestion
Found by students
EMT-Bs initially on scene with ALS response
Patient stuporous, combative, crying but hemodynamically stable
Became hypotensive, agitated, tremulous at ED arrival
No other social , family, PMH available from patientSlide4
Physical Exam
GEN’L:
Toxic
HEENT
:
Opithonus
,
mydriasis
, minimally reactive, equal BLPULM: Coarse throughoutCV: Tachy / irregular, S1S2 RRR w/o MRGABD: Soft NT + distended hypoactive BSAQ, heme (-)GU: Lower abd distended
NEURO: Alert to name, “hospital”, DOB; Tremulous, agitated. Moving all extremities, (-) BabinskiDERM: (-) Rashes, lesions, IVDA. Old bruises on shins, old wrist cutting scars. (-) acute trauma. Skin red, hot to touchPSYCH: Agitated, crying
T:
101.1
P:
120
BP:
80/60
O
2
: 92%
ra
CO:
5%Slide5
Labs /
Rads
labs
ABG:
Metabolic Acidosis
HCG:
(-)
TOX:
THC, Opiates; ETOH 138CBC: WBC 14CMP: K
+ 6, bilirubin 4COAGS: Elevated PT/PTT/INRrads
CXR: Congestion BLFAST: (-) except distended bladder (800 cc)Slide6
Initial EKGSlide7
Emergency Management
IV, O2, Monitor
2 large bore IVs, 2 L NS bolus
2 amps NaHCO
3
, NaHCO
3
drip
2 grams MgSO4Partially awake intubation, then vecuroniumVentilation w/ low PEEPDopaminePhysostigmine & N-ACMedFlight transport
Wait a Minute…
Can You Slow Down, Start From the Beginning, & Explain What Just Happened?Slide8
AEIOU-TIPS
AMS DIFFERENTIAL DIAGNOSIS
A:
Alcohol
E:
Endocrine
Electrolytes
Encephalopathy
I: InsulinO: O2 (Hypoxia) Other: ArrhythmiasU: Uremia
T: Toxidromes Trauma TemperatureI: Infection (Sepsis, Encephalopathy)P: Psych
Porphyria PharmacyS: Space Occupying Mass SAH Stroke /Heat Stroke SeizuresSlide9
Acetaminophen Effects
Ubiquitous
>200 products on the market
Analgesic & Antipyretic
Inhibits
hypothamalic
prostaglandin
synthetase
Blocks peripheral pain impulsesSlide10
Pharmacokinetics
Rapid GI absorption, peak plasma levels in 4
hrs
Highly plasma bound (>50% in OD), crosses placenta
½ life 2 hours
Increased if liver dysfunction to >17
hrs
Renal excretion
2% excreted unchangedHepatic Metabolism94% sulfation & glucuronidationCP450 system biotransformationIn OD, liver enzymes saturated, glutathione depletedNAPQI (N-acetyl-p-
benzoquinoneimine) accumulates as cannot be hydroxylated via glutathione, causing hepatic necrosisSlide11
Toxicity
Toxic dose
Adults: 150-250 mg/kg
Children <10 more resistant
Potential liver damage
Adults: > 150 mg/kg (acute); >7.5
gms
in 24
hrs (chronic)Children <10 yrs: >200 mg/kgFactors predicting hepatotoxicityQuantity ingestedTime of total ingestionAge Liver diseaseEnzyme inducing medicationsSerum concentration (
Rumack Nomogram)Slide12
4 Stages of Acetaminophen Poisoning
I (30 mins-4 hrs)
Anorexia, N/V, pallor, diaphoresis, malaise
May appear normal
II (24-48 hours)
“False Recovery”
Mild
abd
painChemistries, LFTs, coags, renal function slowly deteriorate III (3-5 days)N/V, coagulation defects (DIC), jaundice, renal failure, seizures
Hepatic encephalopathy from centrilobular liver necrosisIV (4 days-2 weeks)If liver “heals”, may have complete resolutionOtherwise hepatorenal failure followed by deathSlide13
ED / Hospital Treatment
Supportive
ABCs, IV, O2, Monitor
Treat symptoms (i.e. N/V)
Labs: CBC, CMP,
Coags
,
Tox
, PregnancyGI decontaminationCharcoal only if ingestion within 1-2 hoursCathartics increase transit timeExtracorporeal elimination (hemodialysis) of limited benefitN-Acetyl CysteineTylenol levels at presentation, 4 hrs & every 4 hrs until “normalizes”
Glutathione substitute supplies inorganic sulfur, alters tylenol metabolismGive N-AC if ANY suspicion of ODSmells (literally) like assSlide14
Remember…This Patient Took “Tylenol PM”
What ELSE is going On?Slide15
Diphenhydramine Hydrochloride
Ethanolomine
Antihistamine
H1 receptor antagonists competitively inhibit histamine & muscarinic receptors causing anticholinergic
toxidrome
Diphenhydramine also blocks neurotransmission through a Na
+
blockade causing CNS effects (i.e. sedation)
Antihistamines 11th overall cause of US drug toxicity Diphenhydramine #1 antihistamine associated with death from ODSlide16
Diphenhydramine OD Levels
Therapeutic level depends on age
Adults: 150-300mg in divided doses (25-50mg q6
hrs)
Pediatrics: 75-150mg in divided doses (12.5-25mg q6
hrs
)
Lethal levels of diphenhydramine
Adults: >19 mg/LChildren: >7 mg/L Infants: >1.5 mg/L1 bottle Tylenol PM contains 25–35 tablets, each with 500mg acetaminophen & 25mg diphenhydraminePatient’s tylenol total ingestion: 12,500mgPatient’s diphenhydramine total ingestion: 625mgSlide17
Overdose Symptoms
Anti-cholinergic
Dry mucous membranes
Flushed, dry, hot skin
Fever
Absence of sweating
Dilated pupils, Blurred Vision
Ileus
Sinus tachycardiaUrinary retentionDelirium: Agitation, confusion, limited short-term memory, meaningless motor movements, incoherent
cns
SeizuresSomnolenceLethargyStuporComaPsychosis
Anxiety
Extrapyramidal symptoms
Withdrawal-like symptoms:
Insomnia, restless, excessive blinking, irritabilitySlide18
Anticholinergic OD
Rapid onset of CNS & CV effects
Unlikely to develop life-threatening events 6 hrs post ingestion
May appear to have a pure anticholinergic toxidrome
vs
mixed syndrome (poly-pharmacy ingestions)Slide19
Arrhythmias
Sinus tachycardia 1
st
sign of toxicityClass 1A antiarrhythmic effect decreases Na+ influx through fast Na
+
channels
Decreased phase “O” slope prolongs QRS / QT / PR
Delays myocardial & conducting tissue depolarizationSlide20
Wide QRS W / R-R Prime
QRS
>
0.16 predicts seizures / arrhythmias > drug levels>130 msec
: 90% require ETI
>120
msec
: 1/3 seized
>160 msec: 75% VT / VFaVR terminal R >3mm better predictor of seizures or arrhythmias than QRS duration
Right axis shift in last 40ms of QRS, deep S wave in lead 1, large R wave in
aVr
suggestive of anticholinergic
cardiotoxitiySlide21
Hypotension
TCA anti–
a
adrenergic effectsNegative inotropy
Peripheral vasodilatation (decreased PVR)
Inhibition of Na
+
flux into myocardium depresses
inotropySlide22
Clinical SSX
CARDIOVASCULAR
CNS
ANTICHOLINGERGIC
Sinus
Tachycardia
Drowsiness
Dry Mouth
Prolonged PR/ QRS/
QT
Opthalmoplegia
Blurred Vision
ST Wave Abnormalities
Seizures*
Dilated Pupils
Heart Blocks
Pyramidal
SSX
Urinary Retention
Vasodilation
Rigidity
Absent Bowel Sounds
Hypotension
Delirium
Pyrexia
Cardiogenic Shock
Respiratory Depression
Myoclonic Twitching
VT
/ VF
Coma
Asystole
*Serotonin or norepinephrine mediated effectsSlide23
Management
ABC, IV x 2, O2, monitor, EKG
Correct hypotension, hypoxia, acidosis
Alkalinize to reduce cardiotoxicity & arrhythmias
Unlike pure anticholinergic toxicity, no
physostigmine
Decreases seizure threshold, arrythmogenic)
Many meds have “TCA-Like” toxicitySlide24
Alkalinization with Na
+
HCO
3QRS >100ms, seizures, acidosis, hypotension, ventricular arrhythmias, cardiac arrest
Correct acidosis by increasing extracellular Na
+
Narrows QRS
Stabilizes Na
+ channelsRaises BP even if no acidosisIncreases TCA plasma protein bindingImproves inotropy Slide25
Overdose Symptoms
cardiopulmonary
Sinus tachycardia
Cardiogenic shock
Ventricular tachycardia
Hypotension
Decreased myocardial contractility
Heart block (slowed sodium conduction)
Pulmonary edema
MS / SKIN / otherRhabdomyolysisRare skin eruptions
DiarrheaNauseaAbdominal painSlide26
Other OD Effects
Heart blocks
Causes most deaths from diphenhydramine OD
Na+ pump blockade slows myocardial contractility leading to cardiac arrest
Seizure
Death from respiratory arrest or cerebral anoxia
Coma
Nerve impulse transmission blockade causes slowed brain neural activity causing lethargy to stupor to comaSlide27
Emergency Management
Prehospital
IV, O2, monitor, airway
Anticipate cardiac collapse & seizure managementTreat arrhythmias
Hospital
Aggressive airway & hemodynamic management (ETI & fluid resuscitation)
Activated charcoal (if alert) or through NGT to decrease absorption
Physostigmine
: anticholinesterase inhibitor, crosses blood-brain barrier to increase ACh levels, reversing anticholinergic effects Sodium Bicarbonate: improves cardiac contraction, narrows QT to prevent VTBenzodiazepines: seizure managementN-Acytl Cysteine
*: binds “free” tylenol, reverses liver toxicityIntralipids: Binds protein-bound toxins & increases excretionsSlide28
Disposition
Patient stabilized for “ground”
MedFlight
critical care transportAt tertiary care hospital, placed on epinephrine
gtt
, Swan-Ganz placed,
intralipids
started. Liver & kidneys began to fail day 2 (“
hepato-renal syndrome”)Hemodialysis initiated when creatinine bumped to 5 with hyperkalemia and tachyarrythmias & seizuresWas on transplant list for a liver; lost to follow-upSlide29
References
www.emedicine.com~“INRReversal”, “Sulfonylurea Toxicity”, “TCA Overdose” 2011.
Leissinger
CA, Blatt PM, Hoots WK, et al. Role of prothrombin
complex concentrates in reversing warfarin anticoagulation: A review of the literature. Am J
Hematol
. 2008;83:137-43
Weber JE,
Jaggi FM, Pollack, CV. Anticoagulants, antiplatelet agents, and fibrinolytics. In: Tintinalli JE, Kelen GD, Stapczynski JS, eds. Emergengy Medicine: A Comprehensive Study Guide. 6th ed. McGraw-Hill; 2004: 1354-60Hirsh J, Guyatt
G, Albers GW, et al. Executive Summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2008;133:72S-3SPoison Control Center Data. 2010 AHA Cardiovascular Care Recommendations; Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis & Haemostasis. Circulation. 2010.Baker R. Wood; the Warfarin Reversal Consensus Group recommendations. MJA 2004; 181 (9): 492-497Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with
valvular heart disease”. Circulation 2008; 118(15):e523-661.Tintanelli. “Emergency Medicine”. 2009.www.cdc.gov~Poisoning statistics 2010. www.aapcc.org~American Association of Poison Control Website. 2011.
www.toxicology.org~Toxicologyand Critical Care Management Updates. 2011
Carr D. Successful resuscitation of a doxepin overdose using intravenous fat emulsion (IFE).
Clinical Toxicology
2009; 47(7): 710.
www.nlm.nih.gov/medlineplusSlide30
Conclusionsprehospitalmd@gmail.com / amy.gutman@hahv.org
Review of epidemiology, pathophysiology, differential diagnosis & emergency management of acetaminophen & diphenhydramine overdoses
Importance of broad differential diagnosis for AMS & early recognition & aggressive emergency management
Questions?