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Extracorporeal techniques in poisoning
Ben Creagh-BrownSHO Anaesthetics
October 2003
Overview
Case report Haemodialysis, filtration, perfusion –
what’s the difference? When is it necessary? Complications
Case report from Thorax 2000 53 year old woman was admitted to hospital with severe
theophylline toxicity after taking 22.4 g (56 × 400 mg) of slow release theophylline tablets
Persistent sinus tachycardia (250 beats/min) resulting in left ventricular failure
Intractable vomiting with haematemesis Hypokalaemia (K+ 2.6 mmol/l) Tremor Serum theophylline levels continued to increase during
the first 24 hours after admission so she was transferred to the intensive care unit (ICU) where she had a tonic-clonic seizure, aspirated, and required intubation and ventilation
Treatment on ITU
1. Haemofilter with a polyamide filter (1.4 m2) was used, with an average ultrafiltration rate of 25 ml/min. Primed with 5000 units heparin and clotting was subsequently prevented with 1000 units heparin per hour
2. Twelve hours after the onset of haemofiltration the patient's vomiting had settled and she was started on oral activated charcoal (50 g four hourly).
Haemodialysis
Diffusion of solutes across a semi-permeable membrane down a concentration gradient
Rate of diffusion proportional to temperature, inversely proportional to viscosity and size of molecule
Increased flow through HD unit maintains concentration gradient and increases clearance, particularly of small molecules
High flux systems have thin membranes and large pores – more diffusion
PUMP
AIR TRAP DIALYSATE IN
WASTED DIALYSATE
ARTERIAL
VENOUS
How HD works
counter current
a b
Drugs that can be eliminated
Easy:•Low Molecular weight < 500 Da
•Low protein binding
•Water soluble
•Small volume of distribution < 1l/kg
•Enhanced clearance by HD than native clearance
Difficult:•Large MW
•Protein bound
•Lipid soluble
HD
Good Bad
Clears small moleculesRapid elimination
Haemodynamic effectsUsually only available in renal units
Haemofiltration Haemofiltration involves the passage of blood
down one side of a semipermeable membrane which allows water and solutes with a molecular weight up to 40 000 to pass across the membrane by convective flow, as in glomerular filtration
The rate of removal of such a solute is proportional to its concentration in the blood and independent of its size
Can be performed for long periods in haemodynamically unstable patients
Ultrafiltration
Is the process that HF uses to work Convective flow of water and solutes
down a pressure gradient. Pressure gradient caused by hydrostatic and osmotic forces. Water ‘drags’ solutes
PUMP
AIR TRAP
ARTERIAL
VENOUS
How HF works
a
b
ULTRAPURE WATER
HF
Good Bad
AvailableCheapRemoves higher MW substances than HD
Poor clearance of poisons
Haemoperfusion
Passage of blood through a circuit containing an adsorbent such as activated charcoal, carbon or polystyrene resin.
Some drugs bind to the adsorbent more effectively than they would be cleared by HD or HF
Eliminates protein-bound and lipophilic dugs and toxins
PUMP
WASTED DIALYSATE
ARTERIAL
VENOUS
How HP works
CHARCOAL
DIALYSATE IN
counter current
a b
HP
Good Bad
Very effective at clearing some poisons (inc. theophylline)
Rarely availablePotential complications
Extracorporeal techniques in ITU
1. Enhance elimination of poison
2. Correct electrolyte and metabolic disturbance Haemodialysis is only available in a limited
number of hospitals and requires complex machines, equipment and trained staff
Haemofiltration can be done in most ITUs Haemoperfusion can be done where HD or
HF is done if a charcoal column is available
Use in poisoning
0.05% of all poisoning need extracorporeal techniques.
HD is used in 90% of cases. HF not recommended as less effective but
better than nothing.
Which drugs need HD/HF?
Methanol and ethylene glycol
Remove alcohol and metabolites (formate, glycolate, oxalate). Add ethanol to dialysate to maintain blood levels at 110mg/dl. HP ineffective.
Lithium Common, ppt by dehydration. Toxic levels >2 mg/dl. Consider if >2.5 or neuro signs. Levels rebound after HD so give >12 hr or repeated HD.
Aspirin Usually controlled with oral charcoal, gastric lavage, alkaline diuresis, however if levels> 80mg/dl
Theophylline Toxic levels > 20 ug/ml. Well removed by dialysis.
Barbiturates Rare. Phenobarbitol levels> 3mg/dl. HD for prolonged coma or complications.
Which drugs need HP?
Theophylline More effectively removed than with HD
Phenytoin Well removed despite being highly protein bound.
Digoxin Well removed by HP, not removed by HD. Can be used instead of digibind.
Paraquat HP or HD for prolonged periods.
Amanita mushrooms
Benefit of either HD/HP controversial
Others: carbamazepine, chloramphenicol, dapsone, disopyramide, methotrexate, paracetamol, quinine and valproate. All been successfully treated with HP/HD.
Complications
Of HD/HF:• Disequilibrium syndrome
• Hypophosphataemia (none in dialysate)
• Hypokalaemia (little in dialysate)
• Metabolic alkalosis (bicarb in dial.) Extra ones of HP:
• Charcoal emboli
• Hypocalcaemia
• Hypoglycaemia
• Leucopenia and Thrombocytopenia
Which one to use? In general, if a compound is adsorbed by
charcoal, the clearance by haemoperfusion will be higher than that achieved by haemodialysis.
Similarly, if a compound is amenable to removal by haemodialysis, its clearance will be greater than that achieved by haemofiltration
In practice, the compounds for which extracorporeal elimination is used most frequently are the alcohols, lithium and salicylate (haemodialysis) and theophylline (haemofiltration
When should you use it?
1. Severe clinical intoxication
2. Clinical deterioration
3. Coma
4. Drugs with delayed actions or toxic metabolites
5. Impaired native clearance (liver/renal)
6. Known toxic levels of dialyzable drug
Bibliography Continuous venovenous haemofiltration for the treatment of theophylline
toxicity J H Henderson, C A McKenzie, P J Hilton, R M Leach Department of Critical Care Medicine, St Thomas' Hospital, London SE1 7EH, UK
Oxford Handbook of dialysis Oxford handbook of anaesthesia