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Extracorporeal drugs overdose &toxin removal in icu

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Extracorporeal drugs overdose & toxin removal

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Extracorporeal drugs overdose &toxin removal in icu

  1. 1. Extracorporeal Toxin removal (ECT) Definition / It is a removal of drugs & toxins from blood via an artificial methods. In 1950 >>> Doolan demonstrated Salicylate can be removed with dialysis Thereafter, Jorgensen published a paper on dialyzable poisons. Up to date, there are 142 dialyzable toxins
  2. 2. A Common case scenario 22 years old F arrived unconscious to ER , her mother found an empty bottle of Tegretol table (200mg ) beside her. after being urgently resuscitated ,she shifted to ICU for further management .
  4. 4. 1st) Indications of ECT There are no clear guidelines for ECT starting . However, there are certain situations where it is absolutely & urgently indicated.
  5. 5. Progressive clinical deterioration (in spite of intensive therapy ) Hemodynamic instability (including depression of mid-brain function) Prolonged coma grades III and IV, prolonged assisted ventilation for more than 48h. Acute renal failure caused by sever nephrotoxic overdose. Impairment of natural excretion of the toxin (hepatic, cardiac or renal failure) Intoxication with agents with metabolic and/or delayed effects, such as methanol, ethylene glycol and paraquat. highly toxic (potentially lethal) dose (best determined after gastric decontamination).
  6. 6. 2nd) Is it dialyzable ? >>Dailyzability It is the capacity of drugs or toxins to be removed by a dialysis membrane  Affected by drug/toxin kinetics & extracorporeal related factors
  7. 7. drug/toxin kinetics  Molecular Weight  Volume distribution  protein binding  endogenous clearance  Rebound phenomena ECTR-Related Factors  Dialysis membrane  Flow rate  Dialysate rate  Ultrafiltration rate  Cartidge saturation Dialyzibility
  8. 8. Drug/toxin kinetics : 1. Molecular weight (MW) [<500 daltons D] solutés diffuse easily [>1000 D] in the case of low-flux membranes) diffuse difficulty. Most toxins are less than 500 D so easily removed by hemodialysis. With the advent of high-flux and high-efficiency dialyzers,even larger MW substances can now be dialyzed (< 15,000 Da) New high-cutoff and middle-cutoff membranes remoev poisons up to 50,000 Da,( availability restricted) As the MW increases, the removal decreases.
  9. 9. 2.Protein binding  Highly protein-bound drugs include: Drugs with minimal protein binding include : Calcium channel blockers, phenytoin, salicylate and (NSAIDs), thyroxine antidepressants (TCAs). Arsenic, Alcohols (methanol,ethylene glycol,isopropanol, ethanol), Aminoglycosides Lithium. toxins & drugs with high PB are difficult to dialysate
  10. 10. 3. Volume of distribution (Vd) dose of the drug in the body VD = ------------------------------------------ serum level of drug  a large VD (>2 L/kg), overall removal by ECTR will be low. Widely distributed drugs& toxins are difficultly to collect
  11. 11.  Toxins with a large Vd are not ideally suitable for removal by ECT,  Drugs with a large Vd include digoxin easily crosses the dialyzer; however, because of its high VD (5–7 L/kg), Less than 5 % of total body of digoxin will be removed in a 6-h dialysis session Drugs with a small Vd are ‘ Digoxin CCB ß-blockers . TCAs barbiturates, chloroquine, colchicines, quinidine,, phenothiazines Alcohols lithium salicylates, paracetamol, aminoglycosides
  12. 12. Rebound phenomenon  Drugs with a large Vd are liable for rebound phenomenon. because ECTR will only remove the toxin from the intravascular compartment due to which the levels fall, causing a diffusion of the drug back into the intravascular compartment from the extravascular compartmen causing more toxicity. IVC INTERSTATIAL toxin ECTR toxin
  13. 13. Endogenous Clearance Removal of toxin via natural ways eg.kidney liver Endogenous clearance kidney ,liver Exogenous clearance like ECTR No ECTR because the hepatic clearance of lidocaine (>1,000 mL/min) greatly exceeds the clearance with dialysis (150 mL/min), ECTR of lidocaine is never indicated. Thisis also true of many street drugs. Any impairment in endogenous metabolic and elimination route wil lower the decisional threshold to initiate dialysis,
  14. 14. Low MW Low VD Low protein binding Low lipid soluble Low rebound Easy dialyzable High MW High VD High protein binding High lipid soluble High rebound Difficult / non dialyzable
  15. 15. ECTR-Related Factors  dialysis membrane (i.e., material, surface area, porosity),  the concentration gradient  the blood flow rate ,  the dialysate/ultrafiltrate flow rates.  hemoperfusion cartridges saturaturation
  16. 16. • Hemodialysis • Hemoperfusion • Hemofiltration • Hemodialysis + hemoperfusion • Continuous renal replacement therapy(CRRT) • Sustained low-efficiency dialysis (SLED) • Plasmapheresis • Peritoneal dialysis ECTR Modilties
  17. 17.  principle  Diffusion of the toxin through semi-permeable membrane into the dialysate.  The removal is directly proportional to the surface area of the dialyzer used, the porosity and the dialysate and blood flow rate  complications  most common acute complications of hemodialysis are systemic hypotension, between 15% and 30%  risk of rebound toxicity  practical solutions for hypotension during HD. sodium modeling, ultrafiltration modeling,  lowering dialysate temperature to 35°C,  increasing dialysate calcium concentration, α1-adrenergic agonist midodrine)  Notes  Drugs with a low MW, low protein binding, small Vd and low lipid solubility are easily dialyzed.  Such drugs include salicylates, methanol, ethylene glycol and theophylline  the high flux membrane have the capacity for removal of larger molecules and highly protein-bound poisons such as carbamazepine and phenytoin which was exclusively removed by hemoperfusion Hemodialysis
  18. 18. Hemoperfusion The principle  the adsorption of the drug to the adsorbent, which is usually activated charcoal or an ion exchange resin.  Adsorption means the binding of the toxin by hydrogen bonds to the adsorbent.  Activated charcoal is the most common adsorbent used. Hemoperfusion, >> more effective in case of high protin pinding toxins ( activated carbon) competes with plasma proteins for binding the toxin.
  19. 19. Teqhnique (priming) flow of anti-coagulated blood through the cartridge at a flow rate of 150–200 mL/min.not > 340 ml/m. to avoid the risk of hemolysis.  The anti-coagulation is maintained with heparin  Adsorba 300c advocates priming with 500cc dextrose to reduced incidence of hypoglycemia.  followed by heparinized (c2500 iu heparin) in 1000c n/s to prevent hemolysis.  For termination of HP session start with inversion of cartridge up side down then follow usual steps of standard termination protocol .
  20. 20. CRTT&HD TMC TEAM
  21. 21. Complication  Hypersensitivity duo to complement system activation  newer devices with charcoal that is coated with an ultrathin film are available .  limited experience with most centers.  SATURATION The hemoperfusion cartridge usually gets saturated after 3–4 h, more thane one cartridge has to be inserted if the patient requires prolonged hemoperfusion  does not correct the acid–base disturbances, electrolyte imbalance and fluid status .  1. Thrombocytopenia (30%)  2. Leucopenia (10%)  3. Hypocalcemia  4. Hypoglycemia  5. Reduction of fibrinogen  6. Hypothermia
  22. 22. Hemodialysis vs. hemoperfusion in a case where hemoperfusion and hemodialysis are indicated, hemodialysis is usually preferred because There are certain case reports where both the dialyzer and the hemoperfusion device are used together in this case, the blood should first pass through the dialyzer and thereafter the hemoperfusion cartridge so that there is minimal saturation of the cartridge that increases its life span which used in cases of sever phenobarbitol and tegertol posing associated with acid base balance abnormality..wich it is cheaper, corrects acid–base abnormalities fluid and electrolyte imbalances easily available
  23. 23. A frequently asked question is whether HD or HP is superior for treatment of poisoning? Early clinical experience with HP suggested that it was more effective than HD or PD for poison removal. recent studies have shown comparable results with the newer high-flux, high-efficiency dialyzers . HP is preferred when the toxin is lipid-soluble or significantly protein-bound poisons with a large Vd are not likely to be efficiently removed by HP. HP is associated with more frequent complications and higher cost, particularly since the cartridges need to be replaced regularly because of saturation.
  24. 24.  A double-lumen central catheter is required  A temporary femoral catheter is preferred,  To maximize efficacy, the largest surface area dialyzer should be used.  Heparinization of the circuit is favored to prevent clotting.  The blood flow and dialysate/effluent flow should be maximized for optimal clearance .  Adjustment of the dialysate concentration of calcium, phosphate, magnesium, potassium, and/or bicarbonate is essential.  A single 6-h extracorporeal treatment will usually sufficient to lower blood levels of most toxins .  (hemoperfusion cartridges may need to be replaced because of saturation in cases of sever toxicity which need prolonged session ).
  25. 25. 3. Hemofiltration Principle removes toxins by convection across a membrane techinque Water-like substances move out from the plasma through the membrane, and this fluid is replaced with isotonic fluids. The rate of removal of the toxin is influenced by The hemofiltration efficiently removes high MW toxins up to 40,000 D. methotrexate  vancomycin, methanol,  procainamide, thallium, lithium the degree of protein binding . the ultrafiltration (UF) the sieving coefficient, which is the ability of the solute to cross a membrane by convection
  26. 26. 4. Continuous renal replacement therapy (CRRT)  The role of continuous therapies in poisoning is not well established.  Principle (convective transport , filtration) or both.  CRRT has a distinct advantage in hemodynamically unstable patients.  CRRT also be effective for the slow, continuous removal of substances with  tight tissue binding  large volumes of distribution,  slow “rebound phenomenon” (e.g., lithium, procainamide and methotrexate).  Continuous methods are useful for intoxicants such as paraquat, lithium, thallium, methotrexate, procainamide and methanol.  They are useful even if the treatment is initiated many hours or days after exposure.
  27. 27. HD HP HF+CRTT PRINCIPLE DIFFUSION ADSORBTION Convectiotion+/filtration ADVANTAGES Less cost Easier Correct other metabolic electrolyte imbalance Suitable for most drugs over dose More effective especially in case of toxin with high protein bindings Lipid soluble. More suitable in hemodynamic unstable patients Poisons with prolong metabolic effect (methanol) Large MW>40000 Da DISADVANTAGES Heamodynamic unstability less effective inDrugs with high protin binding large vd Cost effective Need expert Thrombocytopenia Cost effective Full time staff Common examples Salicylate Alcholol methanol&ethnel glycol Lithium Valproate Thiophyline Phenobaribtol Thiophyline Gluthemide crbimazine Methotroxate Ethylen glycol Lithim valproate Metformin paracetamol
  28. 28. 5. Slow low efficiency dialysis (SLED)  It is a new technique that is described as an alternative to IHD and CRRT.  SLED combines the advantages of both IHD and CRRT by using conventional hemodialysis machines at  slower blood flow rates of 200mL/min,  slower dialysate flow rates of 300–350 mL/min  prolonged periods of 8–12 h on a daily basis.  In hemodynamiccally unstable, critically ill patients, SLED is better tolerated, results in high solute clearance and fluid removal and does not entail the same level of complexity or costs associated with continuous therapies.
  29. 29. 6 Plasmapheresis and plasma exchange  The role of plasma exchange is not well defined in acute poisoning but has been used for toxins that are highly protein bound (>80%) withlow volumes of distribution (< 0.2 L/kg body weight)  Poisonings complicated by massive hemolysis(e.g., hemolytic anemia from sodium chloratepoisoning) or methemoglobinuria  Large MW > 50,000 D eg cisplatin other chemotherapy  Adverse outcomes from plasma exchange involve  vascular access placementcomplications  , bleeding and hypersensitivity
  30. 30. 7. Peritoneal dialysis (PD)  The role of PD is limited in poisoning as it is not an effctive method for ECTR  PD can be useful in situations such as pediatric poisoning.
  31. 31. GUIDE LINE
  32. 32. Common drugs toxicity Acetaminophen. although it is not efficiently extracted by.ECTR but it is dialyzable . Early and prolonged use of N-acetylcysteine (NAC) remains the therapy of choice . ECTR is recommended only in patients with excessively large overdoses with features of mitochondrial dysfunction manifested by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. IHD is the preferred ECTR modality in acetaminophen poisoning .  Narcotics and “street” drugs. A common cause of overdose and death,  narcotics and other street drugs are not amenable to extraction by ECTR  antagonists and supportive therapy are the mainstays of treatment.  Nonbarbiturate hypnotics, sedatives, and tranquilizers.  they have high apparent Vd and lipid solubility and therefore are not removed well by ECTR Other miscellaneous toxins. This group includes paraquat, amanita mushroom toxin, there is little evidence that ECTR are clinically effective for the t their reatment paraquat and procainamide are tightly tissue bound and released slowly, CRRT may be efficacious . the effectiveness of other ECTR modilities remains debatable Organophsophorus poisoning is common . no wide agreement about the ECTR modality of choice but many expertise recommend HP in cases of lethal OP poisoning.
  33. 33. Sever methanol poisoning 1 coma 2 seizures 3 new vision deficit Sever metabolic acidosis IHD Is the ECTR Of choice CRTT Is an alternative mode especially in case of late presentation . HD is indicated in the patient intoxicated with long-acting barbiturates and who have poor renal function. four key recommendations. (a) ECTR should be restricted to cases of severe long-acting barbiturate poisoning.(phenoparb) (b) The indications for ECTR are the presence of prolonged coma, respiratory depression necessitating mechanical ventilation, shock, persistent toxicity, or increasing or persistently elevated serum barbiturate concentrations despite treatment with MDAC. (c) Intermittent HD is the preferred mode of ECTR, and MDAC treatment should be continued during ECTR. (d) Cessation of ECTR is indicated when clinical improvement is apparent ).
  34. 34. clinically non dialyzable drugs Tricyclic antidepressants&.digoxin  have a high Vd .high lipid solubility.  The fraction of drug available for extraction from the circulation is minuscule.  The EXTRIP workgroup concluded that TCAs are not dialyzable and stated that ECTR is not recommended in severe TCA poisoning because poisoned patients with TCAs are not likely to have a clinical benefit from extracorporeal removal . Barbiturates. The short-acting barbiturates are highly lipid- bound and poorly dialyzable.  On the other hand, longer acting barbiturates, especially phenobarbital, are more water-soluble
  35. 35. The Future The future lies in hemoperfusion devices coated with drug-specific antibodies or the antidote of the toxin instead of activated
  36. 36. Our reference EXTRIP group is an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, pharmacology and supported by over 30 professional societies A group of experts in 2010 met to discuss the reference to develop guidelines on the use of ECTR in severe poisoning based on systematic reviews of the literature combined with multidisciplinary expert consensus
  37. 37. Important EXTRIP recommendation  Recommendations for salicylates, lithium, theophylline, valproate, or thallium provide indications for ECTR based on specific cutoff plasma concentrations irrespective of the signs or symptoms.  ECTR mainly reduces the overall cost of antidote therapy and length of hospital stay in the case of early methanol poisoning prior to the development of acidosis.  The workgroup also provided criteria for ECTR cessation, which usually noticeable clinical improvement of toxic symptoms,  targets of surrogate parameters of toxicity (e.g., pH or lactate),  or a specific poison concentration below which toxicity is no longer expected.  recommendations include the preferred type of ECTR for every reviewed poison (favoring intermittent HD in all circumstances)  specific recommendations regarding anticoagulation, special populations, and antidotal dose.  For tricyclic antidepressants and digoxin, the adverse effects of ECTR outweigh any potential benefit of ECTR, and thus the recommendations are not to perform ECTR.
  38. 38. The executive summaries of all EXTRIP recommendations are published at http://www.extrip- workgroup.org/recommendations
  39. 39. Our recent experience
  40. 40. 26 years old women presented with palpitation after intentionally ingested 180 tablet (36 g ) of caffeine in a suicide attempt . her HR 160 bpm . BP 80/60 during initial evaluation she has seizures and develops a wide complex tachycardia which degenerates into multiple pulseless cardiac arrest. In between she retained sinus tachy cardiac rhythm 180 she received isopronalol infusion she circulatory support without any beneficent Real case
  41. 41. ECTR modality of choice IHD IHD started and tachycardia resolved bp restored and weaned from MV discharged to home. Dialyzable Kinetics of caffeine revealed to MW 340d low protein binding and low vd
  42. 42. Thank you .