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Toxicology in the ICU. 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. General Measures. Rx Agitation/ seizures Alteration in temperature Diagnosis: History Identify Toxidrome.
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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
General Measures • Rx Agitation/ seizures • Alteration in temperature • Diagnosis: • History • Identify Toxidrome
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
Common Toxidromes • Serotonin: • irratability, hypereflexia • flushing, fever • diaphoresis, trismus • tremor, myoclonus • diarrhea • Narcotic: • slow, shallow breaths • altered mental status • miosis • bradycardia • hypothermia • hypotension • ileus
Common Toxidromes • Sedative, hypnotic: • stupor, coma • confusion • slurred speech • apnea • Salicyclates: • hyperthermia • tachycardia • metabolic acidosis • respiratory alkalosis
Common Toxidromes • Solvents: • lethargy, confusion • headache • incoordination • restlessness • depersonalization • derealization • Hallucinogenics: • hallucinations • psychosis, panic • fever, mydriasis • hyperthermia • synesthesia
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
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
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
Detoxification • Whole Bowel Irrigation: • Colyte / Golytely 1-2L/hr • May take 3 – 5 hours • Indicated in: • Sustained release tablets • Iron • Body packing
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
Detoxification • Extracorporeal Removal Of Toxins: • Unstable patient • Delayed Clearance • Toxic metabolites • Delayed toxicity
Detoxification • Hemodialysis • Water solubility • Low molecular weight <500d • Low protein binding • Small volume of distribution • Intrinsic clearance 5-100 ml/min • Alcohols, salicylates, lithium
Detoxification • Hemodialysis complications • Access • Hypophosphatemia • Alkalemia • Disequilibrium syndrome • Hemodynamic compromise
Detoxification • Hemoperfusion: • Removes both protein-bound & lipid soluble drugs • theophylline, phenobarbital, gluthimide • Clearance 200-400ml/min • Complications • Cartridge saturation • Thrombocytopenia • Hypoglycemia • Hypocalcemia • Technical
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
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
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
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
Alcohols • High index of suspicion • Increased osmolar gap • Toxicity from • Formic acid – methanol • Oxalic and glycolic acid – ethylene glycol
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
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
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,
Amphetamines • Activated charcoal • Supportive • Benzodiazepine, haloperidol • Beta blockers • Cooling measures for hyperthermia • No role for dialysis/ hemoperfusion
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
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
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
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
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
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
Benzodiazepines • Enhance inhibitory effects of GABA • Generalized depression of CNS • Rx • Activated Charcoal • Flumazenil • No role for dialysis, hemoperfusion
Barbiturates • Decreased MS, slurred speech, ataxia • Hypothermia, bradycardia, hyporeflexia…coma • Myocardial depression… hypotension • Respiratory depression • Rx • Activated charcoal • Alkaline diuresis • Hemoperfusion
bBlocker • Bradycardia • Myocardial depression… hypotension • Rx • Glucagon 2-3 mg followed 2-5mg/hr • Transvenous pacing • Dopamine, Isoprotrenol, atropine
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
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
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)
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
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
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.
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
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
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
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
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
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
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
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
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