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ICU Detoxification Protocols: Identifying and Treating Toxic Syndromes

Learn about general measures, common toxidromes, laboratory evaluations, detoxification methods such as gastric lavage, activated charcoal, urinary pH manipulation, and extracorporeal toxin removal. Discover specific protocols for acetaminophen and alcohol poisoning.

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ICU Detoxification Protocols: Identifying and Treating Toxic Syndromes

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  1. Toxicology in the ICU

  2. General Measures • Know your ABCs • Coma cocktail: • Dextrose 50 mg • Thiamine 100mg I.V • Naloxone 0.2-0.4mg up to 10 mg • Flumazenil 0.2 mg up to 3mg • Oxygen

  3. General Measures • Rx Agitation/ seizures • Alteration in temperature • Diagnosis: • History • Identify Toxidrome

  4. Common Toxidromes • Anticholinergic: • “hot as a hare, dry as a bone, red as a beet, mad as a hatter” • seizures, myoclonus • mydriasis, tachycardia • urinary retention, ileus • blurred vision, coma • Cholinergic: • SLUDGE • salivation, lacrimation, urination, diarrhea, GI cramps, emesis • wheezing, diaphoresis, miosis • bronchorrhea, bradycardia

  5. Common Toxidromes • Serotonin: • irratability, hypereflexia • flushing, fever • diaphoresis, trismus • tremor, myoclonus • diarrhea • Narcotic: • slow, shallow breaths • altered mental status • miosis • bradycardia • hypothermia • hypotension • ileus

  6. Common Toxidromes • Sedative, hypnotic: • stupor, coma • confusion • slurred speech • apnea • Salicyclates: • hyperthermia • tachycardia • metabolic acidosis • respiratory alkalosis

  7. Common Toxidromes • Solvents: • lethargy, confusion • headache • incoordination • restlessness • depersonalization • derealization • Hallucinogenics: • hallucinations • psychosis, panic • fever, mydriasis • hyperthermia • synesthesia

  8. Laboratory Evaluation • Anion Gap - > 20 • may be falsely narrowed with hypoalbuminemia • 1 gm decrease in albumin lowers gap by 2.5 • Osmolal Gap • difference between measured & calculated > than 10 • calc. osm. – 1.86(Na) + BUN/2.8 + glucose/18 + ethanol/4.6 • O2 saturation gap • > 5% difference between the calc. sat. from ABG & sat measured by co-oximetry • Toxicology screening • Poison Control center

  9. Detoxification • Gastric lavage: • Maximum benefit within 1 hr • Ensure airway protection • Do not use: • Alkali ingestion • Bleeding diathesis • Non toxic doses of toxic substances • Non toxic substances • Kerosene/petroleum ingestion

  10. Detoxification • Activated Charcoal: • Irreversibly binds intraluminal, high molecular weight drugs • Single dose- 1g/kg • Multi dose regimen – gut dialysis • carbamazapine, dapsone, phenobarbitol, quinine, theophylline • amitriptyline, digoxin, phenytoin, sotalol, piroxicam, phenylbutazone

  11. Detoxification • Whole Bowel Irrigation: • Colyte / Golytely 1-2L/hr • May take 3 – 5 hours • Indicated in: • Sustained release tablets • Iron • Body packing

  12. Urinary pH manipulation • Urinary alkalinization (pH > 7) is most often used to eliminate salicylates, phenobarbital • Hypokalemia will prevent excretion of alkaline urine by promoting distal tubular potassium reabsorption in exchange for hydrogen ion – risking a severe metabolic alkalosis • Urinary acidification has more risk than benefit

  13. Detoxification • Extracorporeal Removal Of Toxins: • Unstable patient • Delayed Clearance • Toxic metabolites • Delayed toxicity

  14. Detoxification • Hemodialysis • Water solubility • Low molecular weight <500d • Low protein binding • Small volume of distribution • Intrinsic clearance 5-100 ml/min • Alcohols, salicylates, lithium

  15. Detoxification • Hemodialysis complications • Access • Hypophosphatemia • Alkalemia • Disequilibrium syndrome • Hemodynamic compromise

  16. Detoxification • Hemoperfusion: • Removes both protein-bound & lipid soluble drugs • theophylline, phenobarbital, gluthimide • Clearance 200-400ml/min • Complications • Cartridge saturation • Thrombocytopenia • Hypoglycemia • Hypocalcemia • Technical

  17. Detoxification • CRRT: • CVVHD – good clearance of small solutes, fluids, relies on diffusion, can worsen lactic acidosis in liver patients • CVVHF – relies on convection, removes larger substances, won’t worsen lactic acidosis, hypocalcemia • CVVHDF – best of both worlds, relies on convection & diffusion

  18. Acetaminophen • Toxic metabolite NAPQI • Plasma levels correlate to toxicity • Ingestion> 10gm potentially toxic • Risk higher in • Alcoholics • Induced cytochrome p450 enzymes • Acute on chronic use

  19. Acetaminophen • Phase 1: (first 24hrs) • Nausea, vomiting, anorexia, malaise, pallor • Phase II: (24-72 hrs) • RUQ pain,mild increase LFT, PT, bilirubin • Phase III: (72-96hrs) • Liver necrosis,hepatic encephalopathy, DIC, jaundice, extreme elevation of LFTs • Phase IV: (4days-2 weeks) • Recovery or fulminant hepatic failure

  20. Rumack Mathew Nomogram

  21. Acetaminophen • Gastric Lavage • Activated charcoal • N-acetylcysteine • Oral 140mg/kg followed by 70mg/kg q4hrs • IV 300mg/kg over 20 hrs • Hemoperfusion • Transplant • Poor outcome with late presentation

  22. Alcohols • High index of suspicion • Increased osmolar gap • Toxicity from • Formic acid – methanol • Oxalic and glycolic acid – ethylene glycol

  23. Alcohols • Methanol: • paint thinners, windshield washing fluid • Toxicity: visual loss, optic nerve swelling • Ethylene glycol: • Anti-freeze, industrial solvent • Toxicity: ARF due to crystalluria, hypocalcemia, myocardial dysfunction • Isopropyl alcohol: • Rubbing alcohol • Toxicity: ketonemia without metabolic acidosis, hemorrhagic gastritis, shock, coma

  24. Alcohols • No role for activated charcoal • Ethanol: • Target serum level of 100 -200 mg/dl • 0.6 g/kg load then 66 mg/kg/h continuous • Need to increase infusion as enzymes induced • Fomepizole: • inhibitor of alcohol dehydrogenase • 15 mg/kg load then 10 mg/kg q12hours • Hemodialysis: • visual impairment, renal failure, pulmonary edema, refractory acidosis, coma

  25. Amphetamines • Cause: • CNS stimulation • Peripheral release of catecholamines • Inhibition of catecholamine re-uptake • Inhibition of MAO • Features: • Confusion, tremor,anxiety, agitation • Tachyarrythmias, hypertension, hyperreflexia, hyperthermia, RF due to rhabdo, DIC, seizure,

  26. Amphetamines • Activated charcoal • Supportive • Benzodiazepine, haloperidol • Beta blockers • Cooling measures for hyperthermia • No role for dialysis/ hemoperfusion

  27. Cardiac complications of cocaine • Increased myocardial oxygen demand with limited oxygen supply • Vasoconstriction • Accelerated atherosclerosis & thrombosis • Wide QRS ventricular dysrhytmias • Heart block due to inhibition of conduction

  28. Treatment of cocaine related myocardial ischemia • Standard: oxygen, aspirin, nitrogylcerin, benzodiazepines • Infarctions: verapamil, phentolamine, labetalol. Propranolol may exacerbate ischemia. Possibly thrombolytics/ angioplasty if occluded coronary artery seen on angiography • Arrythmias: correct metabolic abnormalities, bicarb, lidociane

  29. Methemoglobinemia • Formed by the oxidation of reduced ferrous hemoglobin to the ferric state • Methemoglobin is incapable of binding & transporting oxygen • Auto-oxidation produces a small amount that is reduced by cytochrome b5 • which is restored by NAD cytochrome b5 reductase in RBCs • Etiologies include : hereditary, dietary, idiopathic but most commomly from oxidant drugs or toxins

  30. Methemoglobinemia • < 15 % of total hemoglobin – patients are generally asymptomatic despite evidence of cyanosis unless anemic or have CAD • 15 - 50% concentrationcan result in dyspnea, headache, weakness • > 60% is associated with confusion, seizures & death • Pulse oximetry ( if > 35%) regresses to 85% & is unreliabe

  31. Methemoglobinemia • Measure by co-oximetry • or note chocolate colored venous blood that does not change color on exposure to air • Selected drugs/ toxins associated with acquired methemoglobinemia: • Dapsone • Amyl nitrates, isosorbide dinitrate, silver nitrate, NTG, nitroprusside • Chloroquine, primaquine • Benzocaine, lidocaine • Herbicides, pesticides • Metoclopramide • Sulfonamides • Nitric oxide

  32. Methemoglobinemia treatment • DC drug, gastric lavage, charcoal • Methylene blue ( 1-2mg/kg ) converts methemoglobin to hemoglobin • Contraindications to methylene blue include G6PD deficiency, renal failure, CN poisoning • Additional therapies include exchange transfusion & possibly hyperbaric oxygen

  33. Benzodiazepines • Enhance inhibitory effects of GABA • Generalized depression of CNS • Rx • Activated Charcoal • Flumazenil • No role for dialysis, hemoperfusion

  34. Barbiturates • Decreased MS, slurred speech, ataxia • Hypothermia, bradycardia, hyporeflexia…coma • Myocardial depression… hypotension • Respiratory depression • Rx • Activated charcoal • Alkaline diuresis • Hemoperfusion

  35. bBlocker • Bradycardia • Myocardial depression… hypotension • Rx • Glucagon 2-3 mg followed 2-5mg/hr • Transvenous pacing • Dopamine, Isoprotrenol, atropine

  36. Calcium channel blocker • Inhibits calcium influx by blocking voltage-sensitive calcium channels • Decreases vascular smooth muscle tone • Negative inotropic effect on myocardium • Inhibits SA AV nodal function • Treatment of toxicity: • Calcium salts, glucagon, atropine, cardiac pacing • Insulin / glucose – stressed myocytes switch to glucose as preferred substrate & CCBs have diabetogenic effect with decreased insulin release & systemic insulin resistance

  37. Carbon Monoxide • Odorless,colorless, tasteless,nonirritating: • Exposure: • Incomplete combustion of carbon containing materials • Attempted suicide from automobile exhaust • Poorly ventilated charcoal/gas stoves • Metabolism of dichloromethane – a component of paint & varnish removers • Affinity 240 times greater than oxygen for hemoglobin • Toxicity results from tissue hypoxia & cytochrome oxidase blockade inhibiting cellular respiration

  38. Carbon Monoxide • Severity depends on the concentration of CO, duration of exposure & minute ventilation • Carboxyhemoglobin levels up to 5% are well tolerated • Mild exposures (5-10%) may result in headache & mild dyspnea – heavy smokers & commuters in congestion • 10 – 30% cause headache, dizziness, dyspnea, nausea, irritability & weakness – like the flu • > 50% results in coma, seizures, cardiovascular collapse & death • Carboxyhemoglobin levels do not always correlate with severity • 10 – 30% of survivors acquire delayed neuropsychiatric sequelae (DNS)

  39. Carbon Monoxide - DNS • DNS can occur 3 – 240 days after apparent recovery • No accurate way of predicting who acquire DNS • Variable manifestations include: • Persistent vegetative state • Parkinsonism • Short term memory loss • Behavioral changes • Hearing loss • Incontinence • Psychosis • After one year 50 – 75% of patients with DNS experience a full recovery

  40. Carbon Monoxide - Diagnosis • High index of suspicion esp. with cohabitants having similar symptoms & cold weather • Pulse oximetry will be normal, need co-oximetry or venous carboxyhemoglobin levels • Cherry red lips

  41. Carbon Monoxide - treatment • Supportive Care • 100% supplemental O2 • Decrease half life from 5-6 hrs. to to 40-90 min • Add 4.5% CO2 to circuit allows pts. To maintain normocapnia while hyperventilating • Hyperbaric O2 • 2.8 atm. within 6 hrs. of exposure • Decrease half life to 15-30 min • New data demonstrated that 3 hyperbaric session at intervals of 6-12 hrs. within a 24 period of exposure significantly reduced DNS at 6wks & 12 mos.

  42. Cyanide • Rapidly acting poison • Oral ingestion • - various seeds & plants • Inhalation of hydrogen cyanide gas • – a combustion byproduct of cyanide-containing products: plastics, wool, nylons, silks • Absorption of cyanide-containing solutions or gas through the skin • Sodium nitroprusside infusions > 10mcg/kg/min • Absorption of cyanide through skin • Binds to cellular cytochrome oxidase & resultant interference with aerobic oxygen utilization

  43. Cyanide • Early manifestations :Anxiety, dyspnea, HA, confusion, tachycardia, hypertension • Followed quickly by stupor, coma, seizures, fixed & dilated pupils, hypoventilation, hypotension , bradycardia, VT, heart block & finally cardiopulmonary collapse • Diagnose in the setting of smoke inhalation • Blood levels > 0.5 mg/L considered toxic • Severe metabolic acidosis due to lactic acidosis • Elevated mixed venous oxyhemoglobin sats. due to blocking of aerobic oxygen utilization • Arteriolization of retinal veins on funduscopic exam • Bitter almond smell

  44. Cyanide Detoxification • Enzymatic conversion to less toxic, renally excreted thiocyanate by rhodenase • Chelated to the B12 precursor hydroxycobalmin to form cyancobalmin • Cyanide has high affinity for the ferric iron contained in methemoglobin –which can act as a scavenger for unbound cyanide

  45. Cyanide • Rx: • Amyl nitrite IH or sodium nitrate IV ( 300 mg. over 3min.) can induce methemoglobinemia <20% • Sodium thiosulfate (12.5 g IV over 10 min.) can act as a sulfur donor to rhodenase • Hydroxycobalamin – 4-5 g IV • 100 % oxygen • No role for HD or hemoperfusion except to clear high levels of thiocyanate

  46. Cyclic Antidepressants • Develop symptoms within 6 hrs ingestion • Anticholinergic effects & inhibition of neural re-uptake of norepinephrine/serotonin • Cardiovascular: • tachycardia/ VT/ heart block • prolonged QRS, QTc, PR • hypotension due to myocardial depression & venodilatation • Seizures

  47. Cyclic Antidepressants • Activated charcoal • ileus can increase risk for obstruction with multidose • Alkalinization of blood • decreases fraction of free drug • continued until QRS narrowed or serum pH > 7.55 • Lidocaine for ventricular arrythmias • Benzodiazepines for seizures

  48. MDMA - methylenedioxymethamphetamine (Ecstasy) • Rapid Onset –15min • Binds the GABA receptors • Inhibition of dopamine release at low dose • Increased dopamine release at high dose • Agitation despite respiratory depression • Hypothermia, bradycardia • Coma ,Respiratory depression • Supportive care • Recovery in 2-96 hrs

  49. Lithium • Levels > 1.5 associated with toxicity • Nausea/Vomiting/Diarrhea • Confusion, tremor, ataxia, nystagmus, dysarthria • Seizure, coma • Low anion gap • Hypo/hyperthermia • Mortality 25% in acute toxicity • Permanent deficits in 10% survivors

  50. Lithium • Oral charcoal not of benefit • Kayexalate/ Colyte • Especially for sustained release lithium • Severe toxicity occurs at lower levels in chronic users • Hemodialysis • levels > 4, or patients with renal insufficiency • large ingestion anticipating rising levels • CVVHD

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