Download caffeine toxicity - Calgary Emergency Medicine

INTERESTING
CASE ROUNDS
Alyssa Morris
Emergency Medicine R3
Objectives
 DDX for toxin induced seizures
 DDX for toxin induced status epilepticus
 Indications for pyridoxine
 Review methylxanthine toxicity
 Review MDAC
CASE
 19M took an unknown ingestion and had a
seizure.
 What is your quick ddx for drugs that cause
seizure?
DDX Drug induced Seizure
OTIS CAMPBELL
 C- camphor, cocaine
 A- anticholinergic,
 O- organophosphates
 T- TCA

 I- Isoniazid, insulin

 S- sympathomimetics




amphetamines,
anticholinergic,
antidepressants
M- Methylxanthines
P- PCP
B- Benzo w/d
E- EtOH w/d
L- Lithium, lidocaine
L- lead, lindane
DDx-Toxin induced Status
 INH
 Insulin/hypoglycemic agents
 TCA
 Theophylline
 Wellbutrin
 CO
Pyridoxine Indications
 INH
 Ethylene glycol
 Gyromitra Mushrooms
 Methylxanthines*
CASE
 19M who ingested 112 caffeine tablets
(100mg/tab) who was brought in by friend for
intractable nausea and vomiting
• Total ingestion >11g (175mg/kg)
 O/E: P=131,BP= 164/67, T= 37.6, 02= 98%,
agitated, vomiting ++
CASE
 Labs:
• APAP/ASA –
• CK 14
• Na 140, K 2.2, Cl 101, CO2 17, AG: 22
• Lactate 8.8
• pH 7.23
• Caffeine level 429mmol/L
 ECG: Sinus tach, no dysrhythmias
CASE CONT
 Continued to be tachy, ++ vomitting, no seizure and
no dysrhythmias
 Course in ED:
• zofran 12mg
• Maxeran 10g (still vomiting)
• Stemitil 10mg (still vomiting)
• MDAC
• Central line to replace K+
• Zantac 50mg
• Ativan 2mg IV x 2
CASE CONT
 Labs in am
• CK- 2280
• PO4 0.29
• K- 3.1
• Caffeine level 295mmol/L
• Lactate 3.9
 Still vomiting and agitated
CAFFEINE
 Methylxanthine
 Similar to theophylline
 Cause release of endogenous catecholamines
 Stimulates B1 and B2 R
 Structural analogue of Adenosine
 NE and epinephrine release
 Inhibit phosphodiesterase (degrades cAMP)
 Effects like adrenergic stimulation
PHARMACOKINETICS
 Routes: oral, IV, SC, IM, rectal
 Oral almost 100% bioavailability
 Peak concentration 30-60min
 Diffuses readily into total body water and all
tissues
 Readily crosses BBB
 Metabolized by Cytochrome P450 system
 Active metabollite is theophylline
TOXICOKINETICS
 Range of toxicity varies greatly
 No definite conclusions from serum levels can be
drawn
 Lethal dose estimated: 150-200mg/kg or 5-10g
 Death associated serum levels >80mm0l/L
 Fatalities <200mmol/L
 Survivial >400mmol/L
OUR PT: 175mg/kg,
serum 429mmol/L
CLINCIAL EFFECTS
 Occur as a result of:
1
2
3
Adenosine antagonism
Release of endogenous catecholamines
Phosphodiesterase inhibiton
 Toxicity affects:
 GI system
 Cardiovascular system
 CNS
 MSK
GI
 Nausea and protracted emesis
• Severe and difficult to control despite use of
multiple anti-emetics
 Increase in gastric acid secretion and smooth
muscle relaxation
• Gastritis and esophagitis (more common with
chronic use)
 Transiently elevated liver enzymes
CARDIOVASCULAR
 Tachydysrhythmias






Sinus tach
SVT
MAT
Afib
PVCs
VT
 MI
 Peripheral vasodilation (wide pulse pressure)
 Hypertension or hypotension
PULMONARY
 Stimulates CNS respiratory centre
 Increased RR
 Resp Alkalosis
 Respiratory failure
 Acute lung injury
CNS
 H/A
 Tremor
 Anxiety
 Irritability
 Agitation
 Hallucinations
 Insomnia
 Seizures*
MSK
 Increases intracellular Ca++
 Smooth muscle relaxation
 Tremor
 Fasiculations
 Myoclonus
 Rhabdomyolysis
METABOLIC
 HypoK
 Shift into cells from B2 stimulation
 HypoMg
 HypoPO4
 HypoNa
 Hyperglycemia
 AGMA (lactate)
MANAGEMENT
 Basics: IV, monitored bed
 Labs to follow
 extended electrolytes
 Lactate
 CK
 +/- Serum caffeine level
 CXR, ECGs
TREATMENT
 MDAC*
 Emesis
 Zofran, maxeran
 Dysrhythmias
 Benzos
 Esmolol
 Lidocaine
 Rhabdo
 Fluids and monitor u/o
TREATMENT
 Electrolytes
 Replace, but careful b/c will become hyperK
when shift back out of cell
 Hypotension
 Fluids
 Not dopamine
 Seizures
 Benzos
 Phenobarb
 Pyridoxine
MDAC
 Definition: more than 2 sequential doses of AC
• In many cases, the number of doses administered is
substantially greater
 MDAC serves 2 purposes:
1
Prevent ongoing absorption of a drug that persists
in the GIT
1
Enhance elimination by either disrupting
enterohepatic recirculation or by enteroenteric
recirculation
General Indications
 GI decontamination for drug or poison ingestion
associated with significant risk of toxicity, where
supportive care/antidote alone is insufficient to
ensure a satisfactory outcome
 The toxin must be able to bind to AC
 Must believe that a significant amount of agent is
unabsorbed and is amenable to removal
AACT Position Statement
 Position statement states use MDAC only for
ingestions of
 Carbamazepine
 Dapsone
 Phenobarbital
 Quinine
 Theophylline /Methylxanthines
Other Drugs
 Shown to increase
elimination of:
 Digoxin
 Phenobarbital
 Carbamazepine
 Phenylbutazone
 Dapsone
 Nadolol







Theophylline
Salicylate
Quinine
Cyclosporine
Propoxyphene
Nortriptyline
Amitriptyline
Contraindications
 Any contraindication to single-dose activated
charcoal
• AC known not to adsorb
• Airway protective reflexes are absent or
expected to be lost and pt is not intubated
• GI perf (esp caustic ingestion)
• Increases severity of injury (hydrocarbons)
• Endoscopy for dx/mx anticipated
 Presence of ileus
Administration
 Initial dose
• 1g/kg or 10:1 ratio of ACT:toxin, whichever is >
 Repeat dose
• 0.25-0.5mg/kg every 1-6hrs
 Procedure
• Can be administered with cathartic for the 1st
dose only
• If pt vomits, repeat the dose
• Can use oral, NG or OG route
*Sxn tube before removal to reduce aspiration
risk
SUMMARY
 DDX for toxin induced seizures
 OTIS CAMPBELL
 Refractory seizures in toxic ingestion
 Think about pyridoxine
 Caffeine is a methylxanthine
 Adrenergic stimulation
 Can get refractory seizures
 MDAC is indicated