[CPX] 약물중독 drug intoxication

 

Definition

     Poisoning 

: To injury or kill with poison, a substance that through its chemical action usually kills, injuries, or impairs an organism (by Webster’s dictionary)

1) accidental (ex. an elderly pt who misreads a label) 
2) unintentional (an inquisitive toddler or a child who gives drugs to a sibling when playing "doctor") 
3) unknown to the pt (the victim of an intended homicide)

     Overdose

: Intentional toxic exposure either in the form of  a suicide attempt or as an inadvertent overdose secondary to intentional drug abuse

Dose/Time principle

독성의 severity 결정인자

(1) 얼마나 많은 양을? (Dose)

(2) 얼마나 많은 시간 동안 체내에 머물러 있는가? (Function of the length of time)

 

이럴 때 의심해 보자!

poisoning or overdose should always be considered in the following:

- an unexplained change in mental status

- head injury / a trauma victim

- psychiatric patient with sudden decompensation

  (especially a young individual or when other circumstances do not offer a plausible cause for a MVA or fall)

- Pts rescued from a fire or found symptomatic in a work environment with chemicals or othertoxins

- metabolic acidosis of unknown etiology

- children : unexplained lethargy, neurologic Sx, bizarre behavior, and other puzzling presentations

- a young patient : chest pain or life -threatening arrhythmia

 

7 phases for general approach

 

1. Emergency management

2. Clinical evaluation

3. Elimination of poison from the GI, skin, eyes, or the site of exposure in inhalation poisoning

 

4. Admin. of a specific antidote (if available)

5. Elimination of the absorbed substance

6. Supportive therapy

7. Observation and disposition

 

 

1. Emergency Management

(1) General Management

1) adequate ventilation and perfusion

2) IV infusion - normal saline 

3) monitoring (ECG for arrhythmia, arrest, shock)

4) oxygen following blood gas determination

(2) Coma or altered mental status : General antidote administration (DONT)

1) glucose 1ml/kg of 50% DW (infant or children  25%, 2ml/kg ) 

2) naloxone hydrochloride (2mg in adult, up to 0.1mg/kg in a child) IV 

3) thiamine 100mg IM (alcoholism Hx)

- 의식 떨어진 환자에서 blood sugar 떨어져 있으면 dextrose 바로 준다

(3) Use drugs to treat emergent conditions, ie:

1) Seizures : anticonvulsants (Benzodiazepine)

2) Cardiac dysrhythmias: anti-arrhythmics (lidocaine)    

3) Agitation ; anxiolytics (benzodiazepine)

 

2. Clinical Evaluation

(1) History

1) The primary goal : ID the toxic agent

① prior medical and psychiatric Hx,  current medications, and allergy  

② prior Hx of drug overdose

③ occupational or vocational Hx

④ source of information : first responders (any Hx, empty bottles, trauma or  inhalation exposure)

2) two simultaneous disorders : accident – overdose

- 사고가 있을 때는 사고만 보지 말고 약물 과다복용도 함께 생각해 줄 것! 

3) The 5W’s of toxicology

Who : pt’s age, weight, relation to others

What : name and dose of medication, coingestants and amount ingested

When : time of ingestion, single vs. multiple ingestions

Where : route of ingestion, geographical location

Why : intentional vs. unintentional

(2) Physical examination

(3) Assessment of major toxic signs 

The acute toxicologic patient may present in one of five major modes
1) Coma 

2) Cardiac arrhythmia 

3) Metabolic acidosis   

4) GI disturbances   
5) Seizures

(4) Laboratory Evaluation

1) Routine Lab : CBC, Electrolytes, BUN, Glucose, ABG, PT, and  12-lead ECG

2) Drug screen : Urine (1st choice), Blood/serum, Gastric contents

: no drug screen is ever complete → " Treat the patient, not the lab "

 

Major toxic signs 

1) Coma  

a) Level of consciousness    

b) pupils : most helpful

① midpoint fixed or unilateral dilated : structural lesion

② pinpoint : 

* overdose - opiate, clonidine, organophosphate, chloral fibrate, phenothiazine, or nicotine             

* use of pilocarpine eye drops

* structural pontine lesion  

③ dilated : nonspecific

c) respiration

compensatory hyperventilation : methanol, ethylene glycol, or other toxin producing metabolic acidosis

d) ocular movements  

e) motor function 

2) Cardiac Arrhythmia

a) ECG as diagnostic clues :

① prolonged QT interval – phenothiazine (CPZ)

② Widened QRS interval - TCA, quinine or quinidine

3) Metabolic Acidosis

a) high anion gap metabolic acidosis (MUDPILES)

: Methanol, Uremia, DKA, Paracetamol, Propylene glycol, Iron, Isoniazid, Lactic acidosis, Ethanol, Salicylates

b) serum osmolality

osmolal gap : osmometer measure - calculated = 10 mosm ↑

  → the presence of osmotically active substances
  : ethyl alcohol, methanol, isopropyl alcohol, ethylene glycol, glycerol or mannitol

4) Gastrointestinal Disturbance

a) toxic causes of vomiting or diarrhea or both

: iron, mercury, lithium, phosphorus, mushrooms, theophylline, fluoride, and organophosphate

b) management : IV fluid with N/S Parenteral antiemetics

5) Seizures

 

 

3. Elimination of poison from the eyes, skin, and GI tract
 

(1) Eyes

- Caustic alkalis and acids: copious irrigation for no less than 30 min with N/S

- Caustic alkali exposure: ophthalmologic consultation

(2) Skin : by copious irrigation or shower

(3) Gastrointestinal Tract : Elimination of unabsorbed toxins

Gastric  lavage	Procedure  1) tracheal intubation : unconscious or seizing pts  2) the head down, left lateral decubitus position   3) the proper length of the tube  4) saline lavage solution    Contraindication  1) strong acid or alkali ingestion  2) significant hemorrhagic diathesis (relative CIx)  3) nontoxic ingestion    - gastric lavage: most effective within 1hour of ingestion,  - delayed gastric emptying time with certain agents (salicylates,  TCA, and anticholinergics)      → GL. may remove drugs several hours after ingestion
Activated  charcoal	Dose  1) adult and child : initial dose 1g/kg → 2g/kg                                  2) Repetitive doses : 0.5 to 1g/kg every 2 to 6 h     Contraindication  1) caustic acids or alkali (ineffective, accumulate in burned areas, making      endoscopy difficult)  2) ileus (for repetitive dosing) → vomiting  3) a risk of aspiration and an unprotected airway    * Drugs or toxins not effectively absorbed by charcoal     : Alkali, Cyanide, Ethanol & other alcohol, Ethylene glycol, Lithium, Iron, Potassium
Whole  bowel  irrigation	Procedure  1) Admin. of PEG-ELS (polyethylene glycol) at 25 to 40 ml/kg/h  2) Duration : passage of a clear rectal effluent    Indications  1) excessive ingestions of iron, lithium, and sustained release resin-form tab/cap  2) possible acute ingestion of heavy metals (eg, paint chips containing Pb)
	* Deterioration of the patient`s condition after the charcoal appears in the stool suggests  8 possible problems.  1) enterohepatic recirc. of toxin or its metabolites  2) concretion or large number of pills  3) significant desorption of drug from charcoal  4) a medical complication (aspiration pneumonia, or endorgan failure)  5) a surgical emergency masked by the overdose ( ruptured spleen or CNS trauma)  6) a toxin not adsorbed by charcoal  7) delayed toxin effects  8) ingestion of additional substances during or after initial management by the patient

 

 

4. Antidote Administration

(1) Physiologic or specific antidote

(2) general or nonspecific antidote : sodium bicarbonate

(3) drug-binding antibodies :

- bezodiazepine - flumazenil / cyanide - hydroxycobalamin / heavy metal poisoning - DMSA

 

5. Enhancing the elimination of a toxic compounds

 

(1) Clinical indications

1) signs of severe poisoning

2) deteriorating progressively despite full supportive care

3) serious morbidity or mortality: acetaminophen, ethylene glycol, lithium, mercury chloride methanol,

   paraquat, salicylate,  theophylline.

4) impaired normal route of elimination

 

(2) Methods available to enhance elimination of toxic compounds

1) Forced diuresis

2) Manipulation of urinary pH

ionized molecules – relatively impermeable / nonioized form - cross membrane easily

Alkalization of urine : NaHCO3 1- 2mEq/kg every 3 to 4 hr

urinary pH 7 and 8 – goal
K replacement
Salicylate, phenobarbital

3) Hemodialysis : toxins removed by diffusion 
    Hemoperfusion : toxins removed by adsorption

* Substances amenable to hemodialysis or hemperfusion : “LET ME SAV P”

    Lithium, Ethylene glycol, Theophylline, Methanol, Salicylates, Atenolol, Valproic acid,

    Potassium, paraquat
* CIX for dialysis

① markedly protein-bound (eg,TCA)
② the action of agent is irreversible (eg, cyanide) 
③ Pt is in shock

 

6. Supportive Therapy

    : axioms of supportive care for the overdose

1) frequent V/S assessment (including temp.)

2) hypo- or hyperthermia assessed and treated

3) multiple system monitoring

4) IV fluid

5) frequent ABG

6) indiscriminate use of drugs or antidotes should be avoided if not indicated or necessary

 

7. Observation and Disposition

1) some drugs that have a laten phase : from initial insult only to decompensate 

24 to 72 hr post-ingestion ; iron, mercury, APAP, paraquat, Amanita Phalloides toxin

2) underlying disease that may be exacerbated (eg. DKA)

3) to evaluate and treat complications (skull Fx, aspiration pneumonia, or interstitial pulm.edema)

 

 

(References)

강의록

http://synapse.koreamed.org/Synapse/Data/PDFData/0119JKMA/jkma-56-1067.pdf