Salicylate Overdose DS 3-11
describe the pathophysiology of the acid/base disorder seen in salicylate overdose
- stimulation of resp center -> increased breathing rate -> loss of CO2 -> respiratory alkalosis - uncoupling of Ox phos -> increase in glycolysis -> lactic acid accumulation -> metabolic acidosis - inhibition of TCA cycle enzymes -> accumulation of TCA polycarboxylic acids -> metabolic acidosis
Describe the following for mild ASA toxicity: 1. amount ingested 2. manifestations
1. 150-200mg/kg 2. N/V, tinnitus, vertigo, hyperpnea, diarrhea
Describe the following for moderate ASA toxicity: 1. amount ingested 2. manifestations
1. 200-300mg/kg 2. N/V, tinnitus, hyperpnea, tachycardia, fever, lethargy, electrolyte disturbances, dehydration, confusion
Describe the following for severe ASA toxicity: 1. amount ingested 2. manifestations
1. 300-500mg/kg 2. delerium, hallucinations, convulsions, coma, hypotension, respiratory arrest
Describe the following for very severe ASA toxicity: 1. amount ingested 2. manifestations
1. >500mg/kg 2. potentially fatal
What values are considered toxic for adults?
40 to 50 mg/dL (2.9 to 3.6 mmol/L)
list the clinical and lab manifestations of salicylate toxicity
Acid-Base and Electrolyte Disturbances: ↑ Anion Gap Metabolic acidosis Metabolic alkalosis (vomiting) Respiratory alkalosis (predominates early) Respiratory acidosis (late grave prognosis) Hyponatremia Hypernatremia Hypokalemia CNS: Tinnitus ↓ auditory acuity Vertigo Hallucinations Agitation Hyperactivity Delirium Stupor Coma Lethargy Convulsions Cerebral edema SIADH Coagulation abnormalities: Hypothrombinemia Inhibition of factors V, VII, X Platelet dysfunction GI: Nausea Vomiting Hemorrhagic gastritis ↓ motility Pylorospasm Hepatic: Abnormal liver enzymes Altered glucose metabolism Volume status: Nausea Vomiting perspiration Metabolic: Hyperthermia Hypoglycemia Hyperglycemia Hypoglychorrhachia Ketonemia Ketonuria Pulmonary: Hyperpnea Tachypnea Acute lung injury ( non-cardiogenic pulmonary edema, salicylate-induced pulmonary edema) Renal: Tubular damage Proteinuria NaCl and water retention Hypo- or Hyperuricemia
What precautions should clinicians consider when treating patients with salicylate toxicity?
Administer supplemental oxygen as needed Volume resuscitate unless cerebral or pulmonary edema is present Administer multiple doses of activated charcoal (first dose: 1 g/kg orally up to 50 g) Administer supplemental glucose in patients with altered mental status, even if serum glucose concentration is normal: IV dextrose 50 g as 100 mL of 50 percent dextrose Alkalinize with sodium bicarbonate Alert nephrology team early in the patient's clinical course
what should be included on a differential diagnosis for salicylate toxicity
Alcohol and Substance Abuse Evaluation Anxiety disorders Asthma Diabetic ketoacidosis Lactic acidosis Alcoholic ketoacidosis Metabolic acidosis due to any cause Acute respiratory distress syndrome: adult and pediatric Meningitis and encephalitis: especial in pediatric and elderly Reye syndrome Sepsis and septic shock Withdrawal syndrome
what is the treatment of salicylate poisoning
Basic resuscitation: Airway, Breathing, Circulation, hydration and supportive measures Obtunded pts might require intubation for airway protection and ventilation— try to avoid! Activated charcoal: give as soon as possible 1 mg of charcoal binds about 550 mg salicylate Temperature control: tepid sponging, fanning, cooling blanket, ice-water emersion, colonic lavage Rapidly gain control of seizures and agitation After volume and electrolyte abnormalities corrected need to alkalinize the urine Ideally want urine pH between 7.5-8.0 Goal urine output: 1-2 mL/kg/hr Alkaline diuresis is indicated for any patient with symptoms of poisoning and should not be delayed until salicylate levels are determined This intervention is safe and exponentially increases salicylate excretion Hypokalemia prevents adequate urinary alkalinization unless corrected Give a solution consisting of 1 liter of D5W, 3 amps NaHCO3, and 40 mEq KCl at 1.5-2 times the maintenance iv fluid rate Do NOT use acetazolamide
What was the Done nomogram and why is it no longer used?
Developed to correlate serum salicylate levels with toxicity, the Done nomogram fails to predict toxicity based upon the serum concentration alone
what are the causes of elevated anion gap?
Methanol Uremia DKA Paraldehyde Isoniazid Lactic acidosis Ethanol Rhabdomyolysis Salicylates
how do you calculate anion gap?
Na - (Cl + HCO3) normally ~12 ... > 15 indicates high gap
describe the approach to diagnosing chronic salicylate poisoning
Need a high index of suspicion Most common in the elderly and very young Occurs when > 100 mg/kg/d ingested for 2 or more days In elderly can occur with therapeutic doses Presentation atypical - mimics other disease states -May include any sign consistent with acute ingestion -Non-cardiogenic pulmonary edema (35%) -Hyperpyrexia -Altered mental status: delirium, dementia -Encephalopathy of unknown origin -Congestive heart failure Initial key to diagnosis: unexplained high anion gap Serum salicylate level Treatment same as for acute ingestion
what are the goals of treatment for salicylate poisoning?
Rapid assessment and stabilization of airway, breathing, circulation Labs/Tests: CBC, PT/INR, PTT, lytes, Mg⁺⁺, Ca⁺, BUN/Creat, LFT's, ABG's, lactate, salicylate level, acetaminophen level, urine drug screen, ECG, consider CXR Provide supportive care Correct fluid deficits Correct electrolyte abnormalities, esp hypokalemia Prevent further GI absorption of the drug Prevent its entry into the CNS Enhance removal of the drug from the CNS Increase elimination of the drug from the body
What are the primary mechanisms of salicylate toxicity?
Salicylates stimulate the respiratory center, leading to hyperventilation and respiratory alkalosis. In addition, they are weak acids and impair renal function, which leads to accumulation of inorganic acids. Salicylates also interfere with the Krebs cycle and uncouple oxidative phosphorylation, resulting in lactic acidemia and the generation of heat. Finally, the induction of fatty acid metabolism generates ketone bodies. The net result of these metabolic processes is a wide (high) anion gap metabolic acidosis. respiratory alkalosis of salicylate poisoning is not merely compensatory for the metabolic acidosis, but that acutely poisoned adults characteristically present with two primary acid-base disturbances.
what are indications for dialysis?
Serum salicylate level > 100 mg/dL after acute ingestion Serum salicylate level > 60 after chronic ingestion Serum acidosis or other electrolyte disturbance refractory to optimal supportive care (regardless of serum aspirin concentration) Evidence of end-organ injury Seizures, pulmonary edema, renal failure, persistent neurological dysfunction Consider for patients who require intubation unless the indication for mechanical ventilation is respiratory depression secondary to coingestant Progressive deterioration despite standard treatment Inability to tolerate NaHCO₃ secondary to renal insufficiency, pulmonary edema, or congestive heart failure
What lab findings (separate from the salicylate level) might suggest salicylate toxicity?
hypokalemia elevated PT/INR (rarely) elevated serum lactate elevated anion gap, but may be normal w/metabolic acidosis mixed primary respiratory alkalosis-primary metabolic acidosis
Fatal ingestion of aspirin can occur after what dose in adults and what dose in children?
ingestion of *10 to 30 gm by adults* and as little as 3 gm by children
What is considered the therapeutic level of salicylate for adults?
is 10 to 30 mg/dL (0.7 to 2.2 mmol/L)
What forms of salicylates are there and which form is considered most toxic?
oral topical oil liquid - including in combo w/bismuth (ie bismuth subsalicylate [pepto bismol, kaopectate]) the oil form (methyl salicylate, in Oil of Wintergreen) is the most toxic
What arterial blood gas findings might there be and why and in what order do they occur?
primary respiratory alkalosis first b/c of the stimulation of the respiratory center, then wide (high) anion gap metabolic acidosis d/t accumulation of salicylate (which is a weak acid), impairing renal function -> accumulation of inorganic acids & a lactic acidemia d/t uncoupling of oxidative phosphorylation by salicylate. in children b/c of limited respiratory reserve, they present w/metabolic & respiratory alkalosis, but are typically acidemic.
How is salicylate toxicity treated and why?
rapid assessment and stabilization of the airway, breathing, and circulation. This should be followed by gastrointestinal decontamination if indicated and the initiation of specific therapies designed to mitigate the effects of the toxin, which in the case of aspirin consists of alkalinization of the plasma and urine, and in some cases hemodialysis.
What are the signs and symptoms of salicylate toxicity?
typically present w/in 1-2hrs after single acute ingestion (depending on multiple ingestions separated in time, ingestion of enteric coated preparations, and coingestants.) with: - *tinnitus, vertigo, nausea, vomiting, and diarrhea* - hyperpnea is often seen too, as is tachycardia subsequent symptoms portending a more severe intoxication include altered mental status (ranging from agitation to lethargy), hyperpyrexia, noncardiac pulmonary edema, and coma
How does chronic salicylate toxicity differ from acute toxicity in terms of presentation and diagnosis?
typically seen in young children or elderly d/t excessive therapeutic administration of salicylate products - clinical findings are difficult to diagnose b/c no clear history of ingestion & the symptoms are milder & often attributed to other dz processes - ie difficulty breathing d/t cardiac or pulmonary illness
describe the distribution of salicylate
weak acids that cross cell membranes relatively easily. Thus they are more toxic when blood pH is acidic. Dehydration, hyperthermia, and chronic ingestion increase salicylate toxicity because they result in greater distribution of salicylate to tissues Excretion of salicylates increases when urine pH increases
