1. Extracorporeal techniques in poisoning Ben Creagh-Brown SHO Anaesthetics October 2003

2. Overview Case report Haemodialysis, filtration, perfusion – what’s the difference? When is it necessary? Complications

3. 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

4. Treatment on ITU 1.Haemofilter with a polyamide filter (1.4 m 2 ) 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).

5. 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

6. PUMP AIR TRAP DIALYSATE IN WASTED DIALYSATE ARTERIAL VENOUS How HD works counter current ab

7. 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

8. HD GoodBad Clears small molecules Rapid elimination Haemodynamic effects Usually only available in renal units

9. 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

10. 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

11. PUMP AIR TRAP ARTERIAL VENOUS How HF works a b ULTRAPURE WATER

12. HF GoodBad Available Cheap Removes higher MW substances than HD Poor clearance of poisons

13. 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

14. PUMP WASTED DIALYSATE ARTERIAL VENOUS How HP works CHARCOAL DIALYSATE IN counter current ab

15. HP GoodBad Very effective at clearing some poisons (inc. theophylline) Rarely available Potential complications

16. 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

17. 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.

18. 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.

19. 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.

20. 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

21. 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

22. 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

23. 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