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