|
mcg/ml |
mMol/L |
|
|
therapeutic level |
10 to 20 |
55.5 to 111 |
|
toxic level |
>20 |
>111 |
|
action levels |
||
|
MDAC |
>20 |
>111 |
|
HP (acute od) |
>90 |
>500 |
|
HP (chronic od) |
>40 |
>222 |
Approach
1) Hx - Is it possible ?
total amt (mg/kg) = dose / (kg) (Vd) = 9000 mg / (60 kg) (.5 L/kg) = 300 mg/L
assumes 100 % bioavalability and asorption, no immediate metabolism
good for ic boluses, overestimates po dose
2) Are the signs and symptoms suggestive ?
- GI-nausea, vomiting because stimulates Chemotactic Trigger Zone; good marker,if no Sx then question the diagnosis
- Tachycardia,dysrhythmias, hypotension
- Tremors, Seizures
Mechanism of Action
1) phosphodiesterase inhibitor - increases cAMP in overdose only, not with therapeutic doses - smooth muscle relaxant, CNS excitation
2) adenosine antagonist - adenosine modulates histamine release to cause bronchoconstriction
3) catecholamine release - increases circulating catecholamines (EPI > NE )
4) diuretic
5) stimulates diaphraghm
Clinical Effects
- nausea, protracted vomiting
- Seizures - phosphodiesterase inhibition, adenosine antagonist, catecholamine release
- CNS - anxiety, hyperventilation, tremor, agitation, hypereflexia
- hypotension - phosphodiesterase sm relaxation, catecholamine (B2) release, diuretic
intravascular vol depleted - n,v, diuretic, diaphoresis
- tachycardias - sinus, SVT, VT - if absent question Dx or consider mixed od
- cardiac - catecholamines, hypoK, hypoPO4, acidosis
- lytes - hypoK, hypoMg, hypoPO4, increase/decrease Ca++
hyperglycemia
Anion Gap Metabolic Acidosis (lactate)
respiratory alkalosis (confused with ASA)
increase WBC
- K+ shifts intracellularly
K pump stimulus is cAMP and B receptor
Treatment
- stabilize ABC’s
- consider DONT for AMS
- cardiac monitor, NIBP
- no Ipecac - have vomited enough, leads to protracted vomiting
- lavage - if have not vomited, tablets don’t fit but a little removal may be beneficial
- Charcoal - require 10:1, large doses often require (500 g), may not keep down due to nausea and vomiting
- MDAC - multi-dose activated charcoal (may need antiemetic, ng drip)
50 g (without sorbitol) Q1H if significant Sx or rising serum levels
50 g Q2H if clinically stable
GI dialysis effect - trapping with back diffusion or sink effect with passive diffusion, creates diffusion gradient from blood to bowel lumen
- Whole Bowel Irrigation (WBI) - if worsening with increasing levels despite charcoal, or with sustained release tabs
Hemodialysis/ Hemoperfusion
Serum theophylline levels Q1H
Persistant vomiting
- common with theophylline
- metochlorpromide
does not decrease Sz threshold
promotility in small bowel
up to 1 mg/kg may be required (dystonia at higher doses)
- phenothiazines - avoid due to decrease in Sz threshold, decrease in GI motility
- Zofran (Odansetron) - 5-HT inhibitor
- slow charcoal ng drip for MDAC
-WBI
- HP indicated after 3rd dose of metochlorpromide
SVT
1) Beta blocker - esmolol relatively B1, less likely to cause bronchospasm
2) CCB
3) Adenosine generally ineffective in therapeutic doses (adenosine inhibitor)
- check lytes and correct K+, Mg++
Seizures
- chemstrip and D50W if low
- Benzo - Benzo - barbs -Propafol - GA - NMB
- avoid Dilantin - doesn’t work in toxic induced Sz (increased Sz in mouse model, not effective in a rabbit model)
- Hemoperfusion
- intubate and lavage
Persistant hypotension
1) volume
2) vasodilation - pure alpha agonist (may decrease HR) theophylline already has excessive beta activity
3) trial of B blocker (? due to predominantly B2 effects) - works in dog model
use SG monitoring (vasodilation, negative ionotrope, volume depletion, rate)
4) Hemoperfusion, lavage, ETT
Dysrhythmias
- correct hypoK,
- CCB for SVT, lidocaine for VT
Hemoperfusion
- indications - level of 40 mcg/ml(mg%)with following
Sz
hypotension
rhythym disturbance
level of 90 mg%
level > 70 mg% four hours after ingestion of sustained release
rising levels despite Rx (4 doses), can’t tolerate charcoal, severe underlying disease
protracted vomiting despite antiemetics
- must be hemodynamically stable and able to tolerate heparin, if you wait until dysrhythmias and hypotension then you have waited too long
- may require fluids and vasopressors to maintain BP
- charcoal cartridge will remove 33 % of PLT (monitor them)
- hypoCa++ common with HP
- continue oral charcoal q1h (continued absorption from the gut)
- HP > HD > PD
- complications - hypotension, hemolysis, thrombocytopenia, charcoal embolus, local line complications
- arrange for early transfer if in peripheral hospital
Indications for ICU Admission
- large quantity ingested, potentially lethal quantity
- Seizures
- ventricular dysrhythmia
- hypotension
- abnormal Vital Signs or Mental Status
- theophylline level not declining
- clinical symptoms cannot be explained solely by theophylline level
Chronic intoxication
- sicker at lower levels (40 - 60 mcg/ml)
- MAT, A fib due to underlying disease
- Seizures at lower levels
- lack of electrolyte abnormalities (K, acidosis)
- cardiac toxicity due to overstimulation of myocardium, hypoxia, lytes