suits and cases: potential pitfalls in the management of poisoned patients
DESCRIPTION
Suits and Cases: Potential Pitfalls in the management of Poisoned Patients. John Kashani DO St. Josephs Regional Medical Center New Jersey Poison Center. Case 1. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/1.jpg)
Suits and Cases: Potential Pitfalls in the management of
Poisoned Patients
John Kashani DOSt. Josephs Regional Medical Center
New Jersey Poison Center
![Page 2: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/2.jpg)
![Page 3: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/3.jpg)
Case 1
• An 18 year old female, with a past medical history significant for asthma and depression, presents to the ED for shortness of breath
• She has a respiratory rate of 34, is diaphoretic, is actively vomiting and appears confused
![Page 4: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/4.jpg)
Case 1
• Her blood pressure is 90/54, Heart rate is 150 and a rectal temperature is 102.
farenheit and pulse oximetry is 99% on supplemental oxygen
• Her mother states that this is the worst asthma attack she has ever had
• She is emergently intubated
![Page 5: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/5.jpg)
Case 1
• Shortly after being intubated she seizes and develops ventricular fibrilation
• Despite your best efforts she dies• An autopsy is requested by the family• A post mortem salicylate level was
150mg/dL
![Page 6: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/6.jpg)
Introduction
• Salicylates are the most widely used analgesic, anti-pyretic and anti-inflamatory and is the standard for the comparison and evaluation of others
• Because salicylates are so widely available the potential for misuse is often underappreciated
![Page 7: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/7.jpg)
Introduction
• The physician taking care of the salicylate intoxicated patient must be familiar with the pathophysiology, pharmakokinetics, potential pitfalls, and treatment options
![Page 8: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/8.jpg)
Sources of Salicylates• Found in Willow bark (Salix alba vulgaris)• Available in a multitude of
formulas/preparations– Over-the-counter (pepto-bismol)– Topical preparation (wart removal)– Combinations (excedrin, fiorinal,
percodan)– Other (oil of wintergreen)
![Page 9: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/9.jpg)
Pharmakokinetics• Peak levels
– Regular preparations – Enteric coated– Liquids preparations– Overdose
• Distribution• Metabolism• Excretion
![Page 10: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/10.jpg)
Distribution• Volume of distribution (Vd)
– Apparent volume the drug is dissolved in– Measured in Liters or Liters/Kg
• not a real volume
![Page 11: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/11.jpg)
![Page 12: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/12.jpg)
Salicylates: Toxic Dose
• Therapeutic Range: 10–20 mg/kg• Mild Toxicity: 150 mg/kg• Moderate Toxicity: 150-300 mg/kg• Severe Toxicity: > 300 mg/kg
![Page 13: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/13.jpg)
Inflamatory Mediators
• Inhibits cyclooxygenase– Decrease in prostaglandins– Increase leukotrienes
• Increases microvascular permeability
![Page 14: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/14.jpg)
acetyl-CoA
oxaloacetate citrate
isocitrate
-ketoglutarate
succinyl-CoAsuccinate
fumarate
malateNAD+
NADH
NAD+
NADH
NAD+
NADH
FAD
FADH2
pyruvate
CO2
CO2
CO2
NAD+
NADH
matrix
![Page 15: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/15.jpg)
Glucose
Pyruvate Lactate2 ATP
ALT
Muscle
Alanine
Liver
Alanine
Pyruvate
Glucose
NH2
Urea 6 ATP4 ATP
X
![Page 16: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/16.jpg)
Respiration• Uncouples oxidative phosphorylation
– Disrupts hydrogen ion gradient– Unable to generate ATP using electron
transport• Increased oxygen consumption,
increased heat production, increased metabolic rate, decreased ATP production, increased CO2 production
![Page 17: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/17.jpg)
R-COOH
matrix
intermembrane space
H+ H+ H+ H+ H+ H+ H+ H+
H+ H+
H+
R-COOHR-COO-
R-COO-
![Page 18: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/18.jpg)
I
matrix
intermembrane space
II
Q
4H+
4H+
III
4H+
4H+
IV
CytC
O2 H2O
2H+
2H+
succinate
NADH + H+
ATP + H2O
ADP + Pi + H+
3H+
3H+
R-0H
R-0H
R-0- + H+
H+
R-0-
H+
heat
![Page 19: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/19.jpg)
Metabolic
• Increased lipolysis• Increased production of ketones
– Ketonuria present in almost all overdose patients
![Page 20: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/20.jpg)
Ketone bodies
Acetyl CoA
Fatty Acids
![Page 21: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/21.jpg)
Metabolic
• Hyperglycemia in acute setting– Glycogenolysis– May cause glucosuria
• Hypoglycemia may subsequently develop
![Page 22: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/22.jpg)
Metabolic• Causes a respiratory alkalosis
– Due to respiratory center stimulation– Increase in respiratory rate and depth
![Page 23: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/23.jpg)
Hematologic• Platelet dysfunction• Inhibition of Vitamin K dependent
clotting factors• II, VII, IX, X, Protein C, Protein S
• Hypoprothrombinemia
![Page 24: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/24.jpg)
Gastrointestinal Effects
• Nausea• Vomiting• Gastritis• Pylorospasm
![Page 25: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/25.jpg)
Neurologic• Occurs from metabolic derangements and
salicylate CNS levels– Agitation, irritability– Tinnitus
• Occurs at levels of 20-45 mg/dL– Lethargy
![Page 26: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/26.jpg)
Laboratories
• Salicylate Level– An Level of 100 mg/dL is extremely
worrisome (impending doom)– Chronic Levels of > 30 mg/dL are
concerning• Difficulty in interpretation due to variable Vd
![Page 27: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/27.jpg)
Laboratories• Levels should be obtained every 1 to 2
hours until downward trend is observed• Do not rely on a single level• Levels < 20mg/dl and a downward trend
can be medically cleared
![Page 28: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/28.jpg)
Case 2• A 35 year old male presents to the
emergency department for profound weakness, bradycardia and emesis
• An I stat potassium is 8.5mg/dL and an EKG show a sine wave pattern
• IV Calcium chloride is administered and he develops ventricular fibrilitation shortly thereafter
![Page 29: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/29.jpg)
Case 2
• Despite your best efforts he dies• The wife said he has no medical
problems, but was recently doing a “cleansing diet” that included herbal teas
![Page 30: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/30.jpg)
Introduction
• Digitalis and digitalis like cardiac glycosides (DG’s) are found in a variety plants, toads and pharmaceutical agents
• Dried powders and extracts have been used for centuries for medicinal agents and as arrow poisons
![Page 31: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/31.jpg)
![Page 32: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/32.jpg)
![Page 33: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/33.jpg)
![Page 34: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/34.jpg)
![Page 35: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/35.jpg)
![Page 36: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/36.jpg)
![Page 37: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/37.jpg)
![Page 38: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/38.jpg)
Pharmacokinetics• Peak serum concentrations occur in
minutes with IV dosing and 1-2 hours after an oral dose
• The VD is initially small and increases following a two phase compartment model– Higher in infants and neonates and
lower in the elderly
![Page 39: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/39.jpg)
Pharmacokinetics
• Tissue distribution takes 6-12 hours• Digoxin crosses the placenta with fetal
levels approaching that of the mother• Elimination
– Hepatic metabolism– Urinary excretion of unchanged drug
![Page 40: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/40.jpg)
Pathophysiology
• Cardiac glycosides inhibit the sodium potassium atp-ase – Responsible for pumping two sodium
ions out of the cell for every two potassium ions in to the cell
![Page 41: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/41.jpg)
3 Na+
2 K+
Na-KATPase Na+
Ca++
SR
Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Ca++
Ca++Ca++
ATPase
Ca++
myocardium
-90 mv
K+
Na+
Na+
Na+
Ca++
Na+
![Page 42: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/42.jpg)
3 Na+
2 K+
Na-KATPase Na+
Ca++
SR
Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Ca++
Ca++Ca++
ATPase
Ca++
myocardium
-90 mv
K+
Na+
Na+
Na+
Na+
Na+
Na+
Na+Na+
Na+
Na+
Na+
Ca++
Na+
![Page 43: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/43.jpg)
3 Na+
2 K+
Na-KATPase Na+
Ca++
SR
Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Ca++
Ca++Ca++
ATPase
Ca++
myocardium
-90 mv
K+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+Na+
Na+
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Na+
![Page 44: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/44.jpg)
3 Na+
2 K+
Na-KATPase Na+
Ca++
SR
Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Ca++
Ca++Ca++
ATPase
Ca++
myocardium
-90 mv
K+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+Na+
Na+
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++Ca++
[Ca++]Ca++
Na+
![Page 45: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/45.jpg)
Inhibition of Na-K-ATPase
[Nai+]
[Cai++]
heart
contractility
![Page 46: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/46.jpg)
3 Na+
2 K+
Na-KATPase Na+
Ca++
SR
Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Ca++
Ca++Ca++
ATPase
Ca++
muscle
-90 mv
K+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+Na+
Na+
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++Ca++
[Ca++]
[K+]
Ca++
Na+
![Page 47: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/47.jpg)
Inhibition of Na-K-ATPase
[Nai+]
[Ko+]
hyperkalemia
[Cai++]
skeletal muscleheart
contractility
![Page 48: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/48.jpg)
3 Na+
2 K+
Na-KATPase Na+
Ca++
SR
Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Ca++
Ca++Ca++
ATPase
Ca++
myocardium
-90 mv
K+
Na+
Na+
Na+
Ca++
Na+
![Page 49: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/49.jpg)
3 Na+
2 K+
Na-KATPase Na+
Ca++
SR
Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Ca++
Ca++Ca++
ATPase
Ca++
myocardium
-90 mv
K+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+Na+
Na+
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++Ca++
Ca++ Ca++
Ca++
Ca++
Na+
![Page 50: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/50.jpg)
3 Na+
2 K+
Na-KATPase Na+
Ca++
SR
Ca++
Ca++
Ca++
Ca++Ca++
Ca++
Ca++
Ca++
Ca++Ca++
ATPase
Ca++
myocardium
-90 mv
K+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+Na+
Na+
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++Ca++
Ca++ Ca++
Ca++
Ca++
Na+
![Page 51: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/51.jpg)
-90 mv
premature beat or ectopic focus
increased automoticity
late afterdepolarizations
![Page 52: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/52.jpg)
Inhibition of Na-K-ATPase
[Nai+]
[Ko+]
hyperkalemia
[Cai++]
skeletal muscleheart
contractility
automoticity
premature beatsescape rhythmsV-tach, V-fib
rise in Nai+
and Cai++
![Page 53: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/53.jpg)
BaroreceptorsCarotidsinus
receptorsCN IX Vagus Nerve
Aortic arch
receptors
Vagal Tone
Bradycardia AV blocksAsystole
Vagus Nerve
![Page 54: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/54.jpg)
Increasedbaroreceptor
firing
CNSParasympathetic
Sympathetic
SVRCO
IncreasedArterial
Pressure
(-)(-)
Baroreceptors
![Page 55: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/55.jpg)
Inhibition of Na-K-ATPase
[Nai+]
[Ko+]
hyperkalemia
[Cai++]
skeletal muscleheart
contractility
premature beatsescape rhythmsV-tach, V-fib
firing
baroceptors
vagal tone
bradycardia, AV blocks, asystole
automoticity
rise in Nai+
and Cai++
rise in Nai+
and Cai++
![Page 56: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/56.jpg)
Devils Advocate
• Treatment of Hyperkalemia in a patient with unrecognized digitalis toxicity– 80 yr old female presents to the ED
with AMS, hyperkalemia and bradycardia
– Treated with intravenous pacing and IV calcium chloride
J Toxicol Clin Toxicol. 2003;41(4):373-6
![Page 57: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/57.jpg)
Devils Advocate
• A toxicological Surprise– A 42 year old man was admitted to a
medical service for CP, nausea and vomiting
– Heart rate was 35, EKG showed total AV block
– Potassium was 5.7mmol/LLancet. 2000 Oct 21;356(9239):1406.
![Page 58: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/58.jpg)
Devils Advocate
• He was treated for a myocardial infarction
• A transvenous pacer was inserted with an increase in his heart rate to 70 BPM
• A serum digoxin level was 365ng/mL (therapeutic range 10-30)
Lancet. 2000 Oct 21;356(9239):1406.
![Page 59: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/59.jpg)
Digoxin in herbal Supplements
• Digoxin Toxicity in a 26 year-old woman taking a herbal dietary supplement– Presented to an ED with chest pain– Initially her heart rate was 70 BPM
and BP was 112/59– Her heart rate dropped to 39 and BP
dropped to 59/36J Am Osteopath Assoc. 2001 Aug;101(8):444-6
![Page 60: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/60.jpg)
Digoxin in herbal Supplements
• EKG showed the absence of P waves• She was given a NS fluid bolus and
placed in the trendelenberg position• Her BP and heart returned to her
original baseline• A digoxin level was 0.9ng/mL
J Am Osteopath Assoc. 2001 Aug;101(8):444-6
![Page 61: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/61.jpg)
Digoxin in herbal Supplements
• She confessed to consuming a tea that contained:– Skullcap herb, wood betony herb,
black cohosh root, hops flowers, valerian root and cayenne pepper fruit
J Am Osteopath Assoc. 2001 Aug;101(8):444-6
![Page 62: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/62.jpg)
Case 3• A 36 year old female, with a past
medical history for depression and chronic back pain, presents to the ED for back pain
• She states that Demerol is the only medication that relieves her pain
• Reluctantly, you write an order for Demerol
![Page 63: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/63.jpg)
Case 3
• Two hours after the administration of Demerol she develops tachycardia, AMS and myoclonus
• You believe that she developed serotonin syndrome
• A NGT is placed in preparation for the administration of cyproheptadine
![Page 64: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/64.jpg)
Case 3 • She has a self limited seizure, vomits
and has a decrease in her O2 sat• She is intubated using etomidate and
succinylcholine• A post intubation x-ray shows a right
upper lobe consolidation• She dies on hospital day 6 from
complications of aspiration pneumonia
![Page 65: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/65.jpg)
Serotonin Syndrome• Drug Induced Disorder• Variable alterations in
– cognition-behavior– neuromuscular activity– autonomic nervous system function
• Increased CNS serotonin neurotransmission at 5-HT1A and 5-HT2A receptors
![Page 66: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/66.jpg)
Serotonin Receptors• The largest and most diverse of all
neurotransmitter systems– 5HT1 – 5HT7
• Each receptor class may contain many subclasses
• 5HT1A - presynaptic and postsynaptic• 5HT1D - presynaptic and postynaptic 5HT2A
- postsynaptic
![Page 67: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/67.jpg)
Serotonin Syndrome
• No gender predilection• Idiosyncratic in nature• Patients are not more likely to develop
SS following an overdose than they are while taking therapeutic doses
• SS is a diagnosis of exclusion
![Page 68: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/68.jpg)
Precipitants
– Addition of second serotonergic drug usually at therapeutic doses
– Increasing primary drug• Inherited / Acquired
– Reduction in endothelial MAOA activity
– Genetic variation
![Page 69: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/69.jpg)
Serotonergic Agents
• Inhibit 5-HT uptake• Enhances 5-HT release• Inhibits 5-HT breakdown• Metabolized to 5-HT• 5-HT1A agonist
• Enhances 5-HT receptor response to stimulation
![Page 70: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/70.jpg)
L-tryptophan
5-hydroxytrytophan
5-HT
TPH
AAD
5-HT
5-HT receptors 1-7
MAO
5-HIAA
5-HT1A, D
-
X
X
![Page 71: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/71.jpg)
Inhibit 5-HT Uptake• Specific SRIs• Non-specific SRIs - clomipramine, trazodone• TCAs• Meperidine• Dextromethorphan• Pentazocine• Tramadol• Dexfenfluramine
![Page 72: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/72.jpg)
Enhance 5-HT Release
• Lithium• Levodopa, dopamine• MDMA• Cocaine• Amphetamines• Fenfluramine• Dexfenfluramine
![Page 73: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/73.jpg)
5-HT1 Agonists
• LSD • Buspirone• Sumatriptan• Dihydroergotamine
![Page 74: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/74.jpg)
Serotonergic Agents
• Inhibits 5-HT breakdown– MAOIs
• Metabolized to 5-HT– Tryptophan
• Enhances 5-HT1A receptor response to stimulation– Lithium
![Page 75: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/75.jpg)
Drug Combinations
• All MAOI combinations• Dextromethorphan and SSRI• Lithium and SSRI• Trazodone and SSRI• Tramadol and SSRI• Trazodone and Buspirone• Selegiline and SSRIs or TCAs• Switching from 1 SSRI to another SSRI
![Page 76: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/76.jpg)
Serotonin Syndrome Associated with Monotherapy
• Clomipramine• Fluvoxamine• Venlafaxine• MDMA• Sertraline
![Page 77: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/77.jpg)
Clinical Manifestations
• Cognitive and behavioral– Confusion (54%)– Agitation (35%)– Coma (28%) – Hypomania (15%) – Seizures (14%)– Hallucinations (6%)
Mills K. Serotonin Syndrome A Clinical Update. Critical Care Clinics, Volume 13:4 Oct 1997
![Page 78: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/78.jpg)
Clinical Manifestations
• Autonomic Dysfunction– Blood Pressure Lability (47%)– Hyperthermia (46%)– Diaphoresis (46%)– Tachycardia (41%)– Mydriasis (26%)– Diarrhea (12%)
Mills K. Serotonin Syndrome A Clinical Update. Critical Care Clinics, Volume 13:4 Oct 1997
![Page 79: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/79.jpg)
Clinical Manifestations• Neuromuscular Abnormalities
– Myoclonus (57%) – Hyperreflexia (55%) – Rigidity (49%)– Tremor (49%) – Incoordination (38%) – Shivering (25%) – Nystagmus (13%)– Seizures (14%)
Mills K. Serotonin Syndrome A Clinical Update. Critical Care Clinics, Volume 13:4 Oct 1997
![Page 80: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/80.jpg)
Sternbach’s Suggested Diagnostic Criteria
• Coincidental with the addition of or increase in known serotonergic agents to an established medications regimen - at least 3 of the following– agitation, diaphoresis, diarrhea, fever,
hyperreflexia, incoordination, MS changes, myoclonus, shivering, tremor
• Other etiologies (infections, metabolic, withdrawal) have been ruled out
• A neuroleptic agent has not been started or increased in dosage
![Page 81: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/81.jpg)
Other Criteria
• Hegerl Criteria• Dursun Criteria• Randomski Criteria• Mills Criteria• Hunters Decision Rules• MOFO Criteria
![Page 82: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/82.jpg)
Time course
• Usually abrupt• Occurring within hours after initiation of
new serotonergic agent• 2/3 of cases resolves within 24 hours
![Page 83: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/83.jpg)
Treatment
• Five basic management principles– Supportive care– Discontinue serotinergic agents– Anticipate potential complications– Administer antiserotinergic agents– Reassess the need for reinstituting
pharmacotherapy
![Page 84: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/84.jpg)
Treatment
• Antipyretics are generally ineffective• Benzodiazepines are the initial choice
for relieving muscle spasm• No specific antidotes for SS• Most symptoms resolve in 12 – 24
hours
![Page 85: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/85.jpg)
Cyproheptadiene
• Cyproheptadine (periactin)– Most consistently effective– Blocks postsynaptic 5HT1A and 5HT2
receptors– Only available orally (syrup, tablet)– Also has antimuscarinic and
antihistaminc properties
![Page 86: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/86.jpg)
Case 4 • A 54 year old male presents to the ED
with a rash that has been getting progressively worse over that past week and a half
• He also offers complaints of chills, nausea, vomiting and diarrhea
• Past medical history is significant for seizure disorder and hypertension
![Page 87: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/87.jpg)
![Page 88: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/88.jpg)
![Page 89: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/89.jpg)
Case 4
• His medications include phenytoin and lisinopril
• He is febrile with a temperature of 102.c, tachycardic at a ventricular rate of 130, hypotensive with a sys BP of 80, RR 24
• His white count is 28,000 with a left shift, HG: 19, HCT: 45, Platelets 52
![Page 90: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/90.jpg)
Case 4
• Na+ 156, K+ 5.4, Cl- 92, NaHco3- 12,• BUN: 60, CR 5.2 and glucose is 220• His LFTS are markedly elevated and he
has a creatinine of 3.2• His phenytoin level 0.5mcg/mL• He is loaded with IV phenytoin in the ED
![Page 91: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/91.jpg)
Case 4
• One hour after the administration of phenytoin he drops his blood pressure and becomes apneic
• He is subsequently intubated and is transferred to the ICU
• He dies on Hospital day 7 from multi-system organ failure
![Page 92: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/92.jpg)
Introduction
• Anticonvulsant hypersensitivity syndrome (ACHS) is a rare, potentially fatal multisystem disorder that occurs after exposure to phenytoin, carbamazepine, phenobarbital, felbamate and lamotrigine
![Page 93: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/93.jpg)
![Page 94: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/94.jpg)
Signs and Symptoms
• ACHS commonly begins within one to four weeks after starting therapy, but may present as late as three months
• ACHS may occur within hours of a previously sensitized individual
• ACHS is not related to the dose or serum concentration
![Page 95: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/95.jpg)
Signs and Symptoms
• Most commonly ACHS begins with a fever, followed by a rash and variable degrees of lymphadenopathy
• The fever usually ranges from 38 – 40.C • The Rash may develop concurrently or
shortly after the fever
![Page 96: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/96.jpg)
Signs and Symptoms
• The Rash is commonly described as an exanthem with or without pruritus
• The upper extremities, face and trunk are usually first affected
• Periorbital edema, exudative tonsillitis, pharyngitis, oral ulcerations and conjunctivitis may be seen
![Page 97: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/97.jpg)
Signs and Symptoms
• Rarely, more severe skin reactions may occur (SJS, TEN, EM)– Usually in the setting of repeated
exposures or continued use• Tender lymphadenopathy is commonly
seen
![Page 98: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/98.jpg)
Signs and Symptoms
• The Liver is the most common organ involved
• The CNS, heart, lungs, renal system and thyroid gland may be involved– Patients may present with elevated
transaminases, alkaline phosphatase, PT and bilirubin
• The hepatitis is usually mild and anicteric
![Page 99: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/99.jpg)
Signs and Symptoms
• The degree of hepatitis is related to the time between the onset of symptoms and the discontinuation of the offending agent
• Liver biopsies reveal periportal inflammation with or without necrosis
• The majority of patients recover within a few weeks
![Page 100: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/100.jpg)
Signs and Symptoms• Hematologic abnormalities
– Lymphocytosis – Leukocytosis– Eosinophilia– Anemia– Leukopenia – Thrombocytopenia– Aplastic anemia
![Page 101: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/101.jpg)
Pathophysiology
• The anticonvulsants implicated in ACHS all have in common an aromatic benzene ring that is metabolized by cytochrome p450 to an arene oxide
• Arene oxides are highly electrophilic and covalently bind to macromolecules to disrupt cellular function
![Page 102: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/102.jpg)
Pathophysiology
• Arene oxides may also form neoantigens that trigger an immunologic response
• These metabolites are highly unstable and under normal conditions can be detoxified by one of several routes
![Page 103: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/103.jpg)
![Page 104: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/104.jpg)
Diagnosis
• Usually based on history of drug exposure and clinical examination– Atypical lymphocytes – Eosinophilia– Elevated liver enzymes– hyperbilirubinemia
![Page 105: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/105.jpg)
Treatment
• The mainstay of treatment is discontinuation of the offending agent and supportive care
• Severe skin reactions are best managed in a burn center
• Strict attention must be paid to maintaining fluid and electrolyte balance
![Page 106: Suits and Cases: Potential Pitfalls in the management of Poisoned Patients](https://reader035.vdocuments.us/reader035/viewer/2022062810/56815c2e550346895dca0fa5/html5/thumbnails/106.jpg)
Thank You