2 - General Methods for Overdose

Question 1

How can you prevent absorption?

Answer 1

• Gastric emptying (emesis, gastric lavage)
• Adsorption (activated charcoal)
• Catharsis
• Dilution

Question 2

When is emesis used?

Answer 2

• Rarely used

- Only recommended if a recent ingestion or no other option (can cause aspiration)

Question 3

When is gastric lavage recommended?

Answer 3

When you know the agent is still in the stomach

Question 4

Contraindications to emesis

Answer 4

• Drowsiness
• Coma
• Convulsions
• No gag reflex (ex: children)
• Corrosive/ caustic agents in the stomach

Question 5

Complications of emesis

Answer 5

• Aspiration pneumonitis
• Bleedings
• GI rupture

Question 6

What is used to induce emesis?

Answer 6

Syrup of ipecac

Question 7

Contraindications to gastric lavage

Answer 7

• Corrosive/ caustic agents

- Petroleum distillate

Question 8

Complications of gastric lavage

Answer 8

• Cardiac arrhythmias
• Low pO2
• Laryngospasm
• Pharyngeal injury
• Esophageal or gastric perforation

Question 9

What method of absorption prevention can be combined w/ gastric lavage?

Answer 9

Activated charcoal

Question 10

Can gastric lavage cause aspiration?

Answer 10

Less risk than emesis, but still possible so must protect the airways

Question 11

How does activated charcoal work?

Answer 11

• Pyrolysis (oxidizing agents)
• Hydrogen bonding, dipole, and Van der Waals’ forces
• Large surface (generally administered in large amounts)
• Decreases systemic absorption of poisons
• Binds poisons that have left the stomach

Question 12

Which poisonings can not be treated w/ activated charcoal?

Answer 12

• Corrosive agents (acids, alkalis)
• Methanol, ethanol
• Ethylene glycol
• Heavy metals
• Tobramycin

Question 13

Contraindications to activated charcoal

Answer 13

• Ingestion of caustic substances

- Presence of ileus or bowel obstruction

Question 14

Complications of activated charcoal

Answer 14

• Vomiting
• Aspiration pneumonitis
• Constipation (more likely w/ larger amounts)
• GI obstruction
• Charcoal empyema (charcoal goes into abdominal cavity)

Question 15

How is activated charcoal administered?

Answer 15

• PO or by gastric tube
• Adult dose = 30-100 g as a slurry in water
• Child dose based on weight (1-2 g/kg in < 10 y/o; 15-20 g in 10-12 y/o)

Question 16

Benefit of MDAC (multiple dose activated charcoal)

Answer 16

• May help prevent reabsorption of drug in the GI tract
• Increases clearance of drugs excreted w/ the feces
• Ensures that there is a marked serum to GI lumen concentration gradient (which increases elimination of the drug)
• Helpful if route of administration of poison is other than oral
• Effective for a number of agents (ex: analgesics, sedatives, beta-blockers, anticonvulsants, etc.)

Question 17

Problems w/ MDAC

Answer 17

Same as single-dose regimens (vomiting, constipation, GI obstruction)

Question 18

Adult dose of MDAC

Answer 18

25 g over 2 h or 50 g over 4-6 h

Question 19

Whole-bowel irrigation indications

Answer 19

• Ingestion of iron or zinc salts
• Ingestion of SR medications
• Ingestion of drug packets – “body packers”
• Ingestion of “crack” vials – “body stuffers”

Question 20

Whole-bowel irrigation contraindications

Answer 20

• Uncooperative px
• Presence of ileus or GI obstruction
• GI bleeding or perforation

Question 21

Whole-bowel irrigation complications

Answer 21

• Abdominal cramping
• Vomiting
• Profuse diarrhea
• Hyperchloremia – essential to monitor electrolytes

Question 22

Whole-bowel irrigation technique

Answer 22

• Administer large volumes of isotonic, non-absorbable polyethylene glycol/ electrolyte solution over 40 minutes to several hours
• Note: wait for a rectal discharge that looks like the fluid administered (can take 6-12 h to appear)

Question 23

What is the purpose of cathartics? Contraindications and complications? Examples?

Answer 23

• Used to move the poison or poison/ charcoal complex through GI tract
• Can help remove poison and/ or decrease absorption
• Can help prevent formation of concretions of drug or drug/ charcoal complex
• Same contraindications and complications as w/ whole-bowel irrigation
• Ex: sorbitol (typically added to activated charcoal mixtures), magnesium citrate, magnesium/ sodium sulfate

Question 24

Describe the process of dilution. Indication and contraindications

Answer 24

• Fluid administration (water or milk) first few minutes after ingestion
• Value in some ingestions of corrosive agents
• Contraindicated in coma or convulsions

Question 25

What methods can be used to enhance elimination?

Answer 25

* *MDAC, hemodialysis, hemoperfusion - Diuresis - Peritoneal dialysis - Hemofiltration - Plasmapheresis and exchange transfusion

Question 26

What are indications for enhancement of elimination?

Answer 26

- Failure to respond adequately to full supportive care (intractable hypotension, HF, seizures, metabolic acidosis, or dysrhythmias) - Px in whom the normal route of elimination of the toxin is impaired (renal or hepatic dysfunction, pre-existent or caused by the overdose) - - Remember it takes a while to set up dialysis and takes time for it to start working; not an immediate fix - Px in whom amount of toxin absorbed or the plasma concentration indicate high risk of morbidity or mortality - Px who have concurrent disease or are in age group at particular risk (elderly, infants) - Px overdosed w/ a drug that is known to be successfully removed by such methods

Question 27

What is diuresis? What is the objective?

Answer 27

- Manipulation of pH - Increase renal clearance (works only if poison or active metabolites are excreted in urine; based on concept of "ion-trapping")

Question 28

What is the difference between acid and alkaline diuresis?

Answer 28

- Alkaline diuresis – give NaHCO3 IV to increase urinary pH to 7-8 (increases renal excretion of salicylate, isoniazid, phenobarbital) - Acid diuresis – give NH4Cl IV to reduce urinary pH to 4.5-5.5 (claimed to work w/ weak bases; ex: amphetamines and phencyclidine; however, no evidence of efficacy)

Question 29

What is forced diuresis? What are the risks?

Answer 29

- Volume expansion w/ sodium-containing solutions (valid if glomerular filtration is important determinant of excretion) - Risks – volume overload manifested by pulmonary and cerebral edema

Question 30

What must be monitored when you give a diuretic?

Answer 30

- Electrolytes, fluid balance, acid-base balance, and response to diuretic - Risk of metabolic alkalosis and hypokalemia

Question 31

When can peritoneal dialysis be used?

Answer 31

- Theoretically can be performed to enhance elimination of water soluble, low MW, poorly protein bound compounds w/ a low Vd (ex: alcohols, lithium, salicylates, theophylline) - High clearance can be obtained for molecules w/ MW < 500 Daltons - Relatively simple method, but too slow; rarely used

Question 32

What is the formula for MDAC?

Answer 32

dC/dt = [D*A*K (C1-C2)] / h

Question 33

Which overdoses is MDAC effective in?

Answer 33

- Phenobarbital - Theophylline - Valproic acid

Question 34

What is required when hemodialysis is done?

Answer 34

Anticoagulation with heparin

Question 35

Indications for hemodialysis

Answer 35

- Poison is dialysable - Pt deteriorating despite care - Severe electrolyte problems - Potentially lethal blood levels are present - Risk from prolonged coma, or risk of renal failure - Specific poisonings (methanol, ethylene glycol, salicylate, theophylline, ethanol)

Question 36

Hemodialysis complications

Answer 36

- Clotting and leaking of blood from around connections (thrombosis, bleeding) - Embolus (rare) - Hypotension, arrhythmias - Convulsions - Infections

Question 37

Describe charcoal hemoperfusion

Answer 37

- Compounds adsorbed by activated charcoal - Cartridge containing a sorbent w/ very large surface area (no direct contact) - Usually performed for 4-6 hours; cartridge changed as often as every 2-4 hours - Not limited by plasma protein binding (hemodialysis is)

Question 38

Which drugs is charcoal hemoperfusion used for?

Answer 38

- Carbamazepine - Phenobarbital - Phenytoin - Theophylline

Question 39

Complications of charcoal hemoperfusion

Answer 39

Similar to hemodialysis

Question 40

Describe hemofiltration

Answer 40

- Movement of plasma across a semipermeable membrane in response to hydrostatic pressure gradient - No dialysate solution on the other side of the membrane - Smaller solutes transported across the membrane following the water (bulk flow) while larger solutes, depending on permeability characteristics of membrane, are excluded

Question 41

Advantages of hemofiltration

Answer 41

- Continue therapy for 24 h - Remove drugs like lithium and procainamide that distribute slowly from tissue binding sites and from intracellular compartment - Ultrafiltrate flows of 100-600 mL/min can be achieved

Question 42

Disadvantages of hemofiltration

Answer 42

- Rate of removal of drugs may not be sufficient to benefit the critically ill px - Complexity, experienced ICU staff required for monitoring (4-6 h) - Clearances achieved are significantly lower than those achieved w/ hemodialysis

Question 43

Describe plasmapheresis and exchange transfusion. Indication?

Answer 43

- Used to eliminate molecules w/ large MW (MW > 15,000 Daltons; ex: immunoglobulins) - Both techniques remove plasma proteins (benefit of removing protein-bound molecules, digoxin-digoxin antibody complexes, thyroxine) - Exchange transfusion appropriate in management of small infants or neonates

Question 44

Disadvantages of plasmapheresis and exchange transfusion

Answer 44

- Risk of infections and allergic reactions (replacement of plasma) - Expensive

Question 45

When is lipids rescue used?

Answer 45

- Local anesthetics (lidocaine, bupivacaine) - TCAs - CCBs

Question 46

Formula for clearance

Answer 46

Cl = Q * ER ER = [(Cin - Cout)/ Cin] * 100