Salicylates remain one of the most widely used medications, and poisoning – both voluntary and accidental – is common. Aspirin is taken for its analgesic and antipyretic, or antiplatelet effects, but salicylates are also present in drugs in non-aspirin forms, such as methyl salicylate (oil of wintergreen) in liniments, and bismuth sub-salicylate in Pepto Bismol. Salicylates cause toxicity both through ingestion and dermal absorption. Aspirin poisoning is not easy to diagnose and is not always identified, especially in cases of chronic usage, when the symptoms may be atypical or misleading [1].

Salicylates impair the metabolism of all tissues through uncoupling oxidative phosphorylation and inhibiting the function of the Krebs cycle. In addition, drugs based on salicylate have organ-specific physiological responses like stimulation of the respiratory center.

In early stages, patients with acute poisoning most often present with nausea and vomiting because of gastrointestinal irritation and hyperventilation due to stimulation of respiration [3], and tinnitus [2], a characteristic although a non-specific sign of salicylate poisoning. Other signs are diaphoresis, hyperactivity, and tachycardia. Hyperventilation leads to respiratory alkalosis, but not typically in children. Once metabolic disturbances become prominent, the inhibition of aerobic respiration and activation of lipid breakdown lead to accumulation of lactic acid and ketone bodies, and consequently to aciduria and metabolic acidosis. Thus, a mixed acid-base disorder is generated. Late signs are fever, agitation, or conversely, lethargy, convulsions, and stupor. Patients in late stages may be mistakenly diagnosed as suffering from sepsis [4], having a heart attack [5], or being agitated.

Several organ systems are affected, and a variety of signs may be observed. Pulmonary edema is somewhat more frequent in chronic toxicity in the elderly population. Central nervous system (CNS) deterioration can also occur, especially in acidosis, which increases the proportion of uncharged salicylate molecules that are able to cross the blood-brain barrier. CNS toxicity can contribute to vomiting. In severe cases, the condition progresses to cerebral edema, seizures, coma, and death. The inhibition of prostaglandin and thromboxane synthesis is accompanied by increased bleeding times, gastrointestinal (GI) irritation, and, in chronic poisoning, GI bleeding.

Glucose metabolism is also disturbed, leading usually to hypoglycemia, and there is no correspondence between serum glucose levels and cerebrospinal fluid glucose content [6]. Thus, blood glucose levels may not adequately reflect mental responses of the patient. Other blood chemistry changes are dehydration, hypokalemia, and hypocalcemia.

Chronic toxicity may be difficult to recognize, especially in the elderly, because the symptoms are nonspecific (confusion, fever, dehydration and others), and because a confused patient may not remember having taken salicylates. Renal insufficiency exacerbates salicylate poisoning since most of the drug is eliminated by the kidneys [7].

• Fever

  Salicylate poisoning also causes ketosis, fever, and, even when systemic hypoglycemia is absent, low brain glucose levels. [merckmanuals.com]

  OTC drugs were the first-line treatment in 188 (74 percent) of 254 fever episodes during the 2 weeks before the cross-sectional survey. [ncbi.nlm.nih.gov]

  Late signs are fever, agitation, or conversely, lethargy, convulsions, and stupor. Patients in late stages may be mistakenly diagnosed as suffering from sepsis, having a heart attack, or being agitated. [symptoma.com]

• Pain

  An 81-year-old woman with unintentional salicylate intoxication presented with features of sepsis, abdominal pain, and tenderness. Laparotomy was performed to rule out acute cholecystitis. [ncbi.nlm.nih.gov]

  Salicylate Poisoning Potential of Topical Pain Relief Agents: From Age Old Remedies to Engineered Smart Patches. Medicines 2017, 4, 48. [mdpi.com]

  […] or inhalation of large amounts of nicotine paraquat poisoning poisoning caused by ingestion of paraquat parathion poisoning a toxic condition resulting from inhalation or ingestion of the insecticide parathion; characterized by nausea and abdominal pains [vocabulary.com]

  Over-the counter salicylates are used as needed or regularly to reduce pain, fever, and inflammation. [labtestsonline.org]

• Hyperthermia

  CNS: Agitation, lethargy, seizures, coma Other: Hyperthermia Features on investigation Blood gases may indicate severity of poisoning Phase 1: Respiratory stimulation - hyperventilation and respiratory alkalosis with alkaluria Phase 2: Paradoxical aciduria [rch.org.au]

  She manifested more aggravated hyperthermia with NSAIDs that was an intravenous aspirin administration to control hyperthermia before we knew she was in a state of methyl salicylate intoxication. [e-jnc.org]

  Salicylate poisoning can cause vomiting, tinnitus, confusion, hyperthermia, respiratory alkalosis, metabolic acidosis, and multiple organ failure. [merckmanuals.com]

  […] preceded by relatively asymptomatic period often gradual and insidious (ingestion over > 12 hrs) Symptoms Initial Anorexia, nausea and vomiting Tinnitus and decreased hearing (early) Hyperpnea/respiratory alkalosis Hyperglycaemia Later Metabolic acidosis Hyperthermia [emedsa.org.au]

• Gastric Lavage

  Treatment options include induction of emesis or diuresis, gastric lavage, administration of activated charcoal, and surgery. [ncbi.nlm.nih.gov]

  After examination, the patient was prescribed urine alkalinisation, gastric lavage and saline to correct hydroelectrolytic alterations, and admitted to the intensive care unit. [revistanefrologia.com]

• Fatigue

  Drowsiness Headache (severe) Unsteadiness, problems moving Skin: Rash Stomach and intestines: Diarrhea Heartburn Nausea, vomiting (sometimes bloody) Stomach pain (possible bleeding in the stomach and intestines) Symptoms of chronic overdose may include: Fatigue [nlm.nih.gov]

  Post-intubation mismanagement : Patients with severe salicylate toxicity may be at risk for respiratory decompensation due to respiratory muscle fatigue, altered mental status from CNS toxicity, or acute lung injury. [emdocs.net]

  100 mg% at 6 hr in acute, 60 in chronic 6) maintain low PCO2 - avoid precipitous rise in PCO2 without giving bicarb due to risk of more ASA shifting into brain; if sedate ( BZ ) without maintaining PCO2 they will die; if patient crashes due to resp fatigue [mcgill.ca]

• Tachypnea

  CLINICAL REPORT A 6-week-old infant, with no prior history, was admitted to the pediatric intensive care unit for treatment of severe disorders of consciousness associated with significant tachypnea. [unboundmedicine.com]

  GI: Nausea Vomiting Epigastric pain Hematemesis Pulmonary: Tachypnea Noncardiogenic pulmonary edema CNS: Tinnitus Deafness Delirium Seizures Coma In suspected overdose settings, medication bottles must be brought in for review Initial Stabilization/Therapy [5minuteconsult.com]

  In general, this should occur regardless of the dose reported (Grade D). 2) The presence of typical symptoms of salicylate toxicity such as hematemesis, tachypnea, hyperpnea, dyspnea, tinnitus, deafness, lethargy, seizures, unexplained lethargy, or confusion [ncbi.nlm.nih.gov]

  The initial physical findings and laboratory data in patients not diagnosed on admission did not markedly differ from the findings in patients diagnosed on admission, and included tachypnea and acid-base disturbances as well as the frequent occurrence [annals.org]

  "Sudden-onset tachypnea and confusion in a previously healthy teenager". Ther Drug Monit. vol. 32. 2010. pp. 700-703. Glisson, JK, Vesa, TS, Bowling, MR. "Current management of salicylate-induced pulmonary edema". [clinicaladvisor.com]

• Hyperpnea

  […] decreased protein, often dehydrated, poor nutrition) Chronology may be preceded by relatively asymptomatic period often gradual and insidious (ingestion over > 12 hrs) Symptoms Initial Anorexia, nausea and vomiting Tinnitus and decreased hearing (early) Hyperpnea [emedsa.org.au]

  In general, this should occur regardless of the dose reported (Grade D). 2) The presence of typical symptoms of salicylate toxicity such as hematemesis, tachypnea, hyperpnea, dyspnea, tinnitus, deafness, lethargy, seizures, unexplained lethargy, or confusion [ncbi.nlm.nih.gov]

  N/V, tinnitus, vertigo, hyperpnea, diarrhea Describe the following for moderate ASA toxicity: 1. amount ingested 2. manifestations 1. 200-300mg/kg 2. [quizlet.com]

  15 mg per deciliter [1.1 mmol per liter] and 30 mg per deciliter [2.2 mmol per liter] are considered to be therapeutic for inflammatory conditions), clinical manifestations of salicylate intoxication include tinnitus, vertigo, nausea, vomiting, and hyperpnea [clinlabnavigator.com]

  Hyperpnea is an early finding of toxicity, as salicylates can act directly on the medullary respiratory center leading to hyperventilation leading to a respiratory alkalosis. [ukidney.com]

• Vomiting

  For 24 hour advice, contact the Victorian Poisons Information Centre on 13 11 26 Background Acute intoxication presents with classical symptoms of vomiting, tinnitus, hyperventilation, respiratory alkalosis and metabolic acidosis. [rch.org.au]

  […] conditions (decreased renal function, large Vd, decreased protein, often dehydrated, poor nutrition) Chronology may be preceded by relatively asymptomatic period often gradual and insidious (ingestion over > 12 hrs) Symptoms Initial Anorexia, nausea and vomiting [emedsa.org.au]

  CNS toxicity can contribute to vomiting. In severe cases, the condition progresses to cerebral edema, seizures, coma, and death. [symptoma.com]

  Ringing in the ears (tinnitus), nausea, vomiting, and diaphoresis are other common symptoms. Severe intoxications produce hyperthermia, mental status changes, and pulmonary edema. [medical-dictionary.thefreedictionary.com]

• Nausea

  […] rheumatological conditions (decreased renal function, large Vd, decreased protein, often dehydrated, poor nutrition) Chronology may be preceded by relatively asymptomatic period often gradual and insidious (ingestion over > 12 hrs) Symptoms Initial Anorexia, nausea [emedsa.org.au]

  […] uncoupling of oxidative phosphorylation with inhibition of production of high energy phosphates; disordered glucose metabolism; paradoxical CSF hypoglycaemia clinical features Symptoms and signs may not become apparent for many hours; There may be: nausea [ozemedicine.com]

  Severity Mild (150 mg/kg) Moderate (150–300 mg/kg) Severe (300–500 mg/kg) Toxicity No toxicity expected Mild to moderate toxicity expected Life-threatening toxicity expected Symptoms Nausea, vomiting, dizziness Nausea, vomiting, ringing in the ears, headache [en.wikipedia.org]

  […] caused by the ingestion or inhalation of large amounts of nicotine paraquat poisoning poisoning caused by ingestion of paraquat parathion poisoning a toxic condition resulting from inhalation or ingestion of the insecticide parathion; characterized by nausea [vocabulary.com]

  Aspirin is also known to irritate the gastric mucosa by means of inhibiting cyclooxygenase, leading to nausea and vomiting, sometimes severe enough to cause hemorrhagic gastritis. [ukidney.com]

• Abdominal Pain

  An 81-year-old woman with unintentional salicylate intoxication presented with features of sepsis, abdominal pain, and tenderness. Laparotomy was performed to rule out acute cholecystitis. [ncbi.nlm.nih.gov]

  pains and headache and convulsions and sweating food poisoning illness caused by poisonous or contaminated food late-ripening of plants that ripen in the fall disillusioning freeing from illusion or false belief ptomaine poisoning a term for food poisoning [vocabulary.com]

  Home | CCC | Salicylate Poisoning by, last update April 2, 2019 OVERVIEW mechanisms of toxicity: acid-base disturbance, uncoupling of oxidative phosphorylation, disordered glucose metabolism aspirin CLINICAL FEATURES nausea, vomiting, abdominal pain, [lifeinthefastlane.com]

  Patients with mild intoxication frequently have nausea and vomiting, abdominal pain, lethargy, ringing in the ears, and dizziness. [en.wikipedia.org]

• Hematemesis

  GI: Nausea Vomiting Epigastric pain Hematemesis Pulmonary: Tachypnea Noncardiogenic pulmonary edema CNS: Tinnitus Deafness Delirium Seizures Coma In suspected overdose settings, medication bottles must be brought in for review Initial Stabilization/Therapy [5minuteconsult.com]

  Possible gastrointestinal manifestations induced by salicylate poisoning include oropharyngeal burns, peptic ulcers accompanied by perforation or bleeding, hematemesis, vomiting and abdominal pain. [ic.steadyhealth.com]

  In general, this should occur regardless of the dose reported (Grade D). 2) The presence of typical symptoms of salicylate toxicity such as hematemesis, tachypnea, hyperpnea, dyspnea, tinnitus, deafness, lethargy, seizures, unexplained lethargy, or confusion [ncbi.nlm.nih.gov]

  […] with multiple medical problems). signs & symptoms General Tachypnea Tachycardia Diaphoresis Hyperthermia Neurologic Tinnitus, vertigo, ataxia, deafness Delirium, agitation, lethargy Seizure, coma GI Nausea/vomiting Diarrhea Can cause gastritis with hematemesis [emcrit.org]

  Five minute evaluation 1) abnormal VS - increased RR,increased Vt, Temp 2) mental status - tinnitus, lethargy, AMS, confusion 3) noncardiogenic pulmonary edema 4) abdominal Sx - n,v, pain, blood-tinged vomitus, gross hematemesis 5) urine - FeCl3, ketones [mcgill.ca]

• Tachycardia

  Other signs are diaphoresis, hyperactivity, and tachycardia. Hyperventilation leads to respiratory alkalosis, but not typically in children. [symptoma.com]

  Dizziness tachycardia and hyperventilation also occur. More severe poisoning can lead to delirium, agitation and convulsions. [gcs3.co.uk]

  Cardiovascular Cardiovascular symptoms of salicylate poisoning include the following: Tachycardia, generally with minimal hemodynamic or clinical significance Hypotension Dysrhythmias - Eg, ventricular tachycardia, ventricular fibrillation, multiple premature [emedicine.medscape.com]

  Earliest Sign of Salicylate Toxicity Nausea and vomiting Tinnitus Diaphoresis or sweating Other Early Sypmtoms Tachycardia Vertigo Hyperventilation Hyperactivity Symptoms occurring as the toxicity or poisoning progresses: Agitation Delirium Disorientation [nursingcrib.com]

• Hypotension

  They include subtle confusion, changes in mental status, fever, hypoxia, noncardiogenic pulmonary edema, dehydration, lactic acidosis, and hypotension. [merckmanuals.com]

  A physical examination revealed sustained arterial hypotension with a systolic blood pressure (SBP) of 80-90mm Hg and diastolic blood pressure (DBP) of 50-60mm Hg. [revistanefrologia.com]

  Coma, and Death Coagulopathy Pylorospasm, decreased gastro intestinal motility (acute) Gastric erosions, Iron deficiency anaemia (in chronic) ARDS (chronic severe toxicity) Renal tubular damage (rare) Haemolysis (rare) HYPERSENSITIVITY Bronchospasm, hypotension [emedsa.org.au]

• Blurred Vision

  Airways and lungs: Rapid breathing Slow, labored breathing Wheezing Eyes, ears, nose, and throat: Ringing in the ears Blurred vision Nervous system: Agitation, confusion, incoherence (not understandable) Collapse Coma (lack of responsiveness) Seizures [nlm.nih.gov]

  She did not have chest pain, abdominal pain, vomiting, diarrhea, fever, cough, rhinorrhea, dysuria, headache, rash, blurred vision, or lymph node swelling. [jucm.com]

• Visual Impairment

  (In chronic renal failure acidosis is uncommon if creatinine is < 0.30 mmol/l ) Methanol Suggested if visual impairment and CNS depression or intoxication. A bdominal pain is common. Check the osmolar gap. [anaesthesiamcq.com]

• Petechiae

  Petechiae (tiny red or purplish spots on the skin caused by bleeding under the skin). Subconjunctival hemorrhage. Lethargy. Coma. Agitation. Confusion. Seizures. Hypotension or low blood pressure. Heart block. Pulmonary edema. Cerebral edema. [healthhype.com]

• Arthralgia

  A previously healthy 15-year-old girl presented with intermittent fever (up to 39°C), migratory polyarthritis, arthralgia, orthopnea and progressive dyspnea in the last 30 days that led to dyspnea at rest and a new heart murmur requiring hospitalization [oatext.com]

  Chronic salicylism may be insidious; elderly individuals may consume an increasing amount over several days to alleviate arthralgias, subsequently becoming confused, as salicylate pharmacokinetics change at higher concentrations. [emedicine.medscape.com]

• Tinnitus

  For 24 hour advice, contact the Victorian Poisons Information Centre on 13 11 26 Background Acute intoxication presents with classical symptoms of vomiting, tinnitus, hyperventilation, respiratory alkalosis and metabolic acidosis. [rch.org.au]

  […] decreased renal function, large Vd, decreased protein, often dehydrated, poor nutrition) Chronology may be preceded by relatively asymptomatic period often gradual and insidious (ingestion over > 12 hrs) Symptoms Initial Anorexia, nausea and vomiting Tinnitus [emedsa.org.au]

  Minimal Toxicity Patients do not require decontamination or referral to hospital except in cases of deliberate overdose Mild to moderate intoxication Nausea, vomiting Hearing disturbance, tinnitus Increased respiratory rate Primary respiratory alkalosis [kidshealthwa.com]

  Observe for signs of tinnitus, hearing loss, agitation, restlessness, diaphoresis and CNS disturbance Any significant changes should be reported immediately to the medical team Continual cardiac monitoring Fluid input and output Blood glucose level – [pch.health.wa.gov.au]

• Anuria

  […] urinary alkalinization) *Criteria for impaired kidney function include any of the following: estimated glomerular filtration rate < 45 mL/min per 1.73 m 3 creatinine > 2 mg/dL in adults or > 1.5 mg/dL in elderly or patients with low muscle mass oliguria/anuria [thepoisonreview.com]

  Adult Dose 30-150 mL PO of a 70% solution Pediatric Dose 2-11 years: 2 mL/kg PO of 70% solution >12 years: Administer as in adults Contraindications Documented hypersensitivity, anuria Interactions Reduces effectiveness of other drugs when administered [angelfire.com]

• Seizure

  Life-threatening consequences of salicylate overdose include: Seizures Cerebral and pulmonary oedema. [kidshealthwa.com]

  /Tetany Seizures, Cerebral oedema, Coma, and Death Coagulopathy Pylorospasm, decreased gastro intestinal motility (acute) Gastric erosions, Iron deficiency anaemia (in chronic) ARDS (chronic severe toxicity) Renal tubular damage (rare) Haemolysis (rare [emedsa.org.au]

  CNS: Agitation, lethargy, seizures, coma Other: Hyperthermia Features on investigation Blood gases may indicate severity of poisoning Phase 1: Respiratory stimulation - hyperventilation and respiratory alkalosis with alkaluria Phase 2: Paradoxical aciduria [rch.org.au]

• Confusion

  Salicylate poisoning can cause vomiting, tinnitus, confusion, hyperthermia, respiratory alkalosis, metabolic acidosis, and multiple organ failure. [merckmanuals.com]

  Chronic toxicity may be difficult to recognize, especially in the elderly, because the symptoms are nonspecific (confusion, fever, dehydration and others), and because a confused patient may not remember having taken salicylates. [symptoma.com]

  […] warrants referral to an emergency department for evaluation (Grade C). 3) Patients who exhibit typical symptoms of salicylate toxicity or nonspecific symptoms such as unexplained lethargy, confusion, or dyspnea, which could indicate the development of [ncbi.nlm.nih.gov]

• Agitation

  Late signs are fever, agitation, or conversely, lethargy, convulsions, and stupor. Patients in late stages may be mistakenly diagnosed as suffering from sepsis, having a heart attack, or being agitated. [symptoma.com]

  More severe poisoning can lead to delirium, agitation and convulsions. Salicylates stimulate the respiratory centre of the brain and uncouple oxidative phosphorylation Aspirin is rapidly hydrolysed to salicylate in the GI tract and blood. [gcs3.co.uk]

  CNS: Agitation, lethargy, seizures, coma Other: Hyperthermia Features on investigation Blood gases may indicate severity of poisoning Phase 1: Respiratory stimulation - hyperventilation and respiratory alkalosis with alkaluria Phase 2: Paradoxical aciduria [rch.org.au]

  Earliest Sign of Salicylate Toxicity Nausea and vomiting Tinnitus Diaphoresis or sweating Other Early Sypmtoms Tachycardia Vertigo Hyperventilation Hyperactivity Symptoms occurring as the toxicity or poisoning progresses: Agitation Delirium Disorientation [nursingcrib.com]

• Altered Mental Status

  In conclusion, we report the first elderly patient who presented with an altered mental status and hyperthermia after oral ingestion of a topical salicylate. [e-jnc.org]

  This progressive acidosis can promote the influx of salicylic acid into the central nervous system leading to altered mental status, confusion and agitation. [ukidney.com]

  mental status (1D), with acute respiratory distress syndrome requiring supplemental oxygen (1D), and for those in whom standard therapy is deemed to be failing (1D) regardless of the salicylate concentration. [ncbi.nlm.nih.gov]

• Dizziness

  Dizziness tachycardia and hyperventilation also occur. More severe poisoning can lead to delirium, agitation and convulsions. [gcs3.co.uk]

  You feel: Sleepy Confused Like you're seeing or hearing things that aren’t there (hallucinations) Dizzy or light-headed Like it's hard to breathe or your breathing is too fast Doctors will take a blood sample to measure the amount of aspirin in your blood [msdmanuals.com]

  Patients with mild intoxication frequently have nausea and vomiting, abdominal pain, lethargy, ringing in the ears, and dizziness. [en.wikipedia.org]

  Symptoms Mild cases may be involved in dizziness, lethargy, tinnitus, nausea and vomiting. [ic.steadyhealth.com]

The “Done nomogram” [8] was developed in 1960 for predicting salicylate toxicity after a single dose of ingestion [1]. Although successful in many cases, the premises used in its formulation restrict its general applicability [9], and it is not recommended for general use.

Serum salicylate levels do not always reflect the severity of poisoning. A general guide specifies 30 mg/dL above which symptoms usually appear, and 100 mg/dL above which the effects of poisoning may be fatal. Serial salicylate and arterial blood gas levels are more important for the better evaluation of the situation and for following acid-base alterations. A peak value may not be reached up to 4-6 hours after ingestion. Some salicylate tablets have a tendency to form a concretion in the stomach [10], in which case the serum concentrations will keep increasing for a longer time.

Levels of serum electrolytes, creatinine, blood urea nitrogen, and potassium (which may become very low if the patient is alkalinized), should be followed until salicylate concentrations start declining and anomalies are resolved. Urine pH should also be monitored. An abdominal radiograph or other imaging may be necessary if the formation of a concretion is suspected.

• Hypoglycemia

  Salicylate markedly impairs gluconeogenesis and increases glucose utilization, resulting in hypoglycemia. To our knowledge, this is the first article on hypoglycemia due to the application of topical salicylate. (Arch Intern Med. 1991;151:591-593) [jamanetwork.com]

  Abnormalities include: Respiratory alkalosis accompanied by progressive metabolic acidosis Hyperpyrexia GI, renal, pulmonary, and skin losses of body fluids and electrolytes Initial hyperglycemia followed by hypoglycemia, particularly CNS hypoglycemia [unboundmedicine.com]

  Intoxication is characterized by rapid breathing, vomiting, headache, irritability, ketosis, hypoglycemia, and, in severe cases, seizures and respiratory failure. salicylate poisoning Poisoning caused by aspirin or one of its derivatives. [medical-dictionary.thefreedictionary.com]

  Glucose should be added to the intravenous fluid (IVF) because both hypoglycemia and low CNS glucose levels without systemic hypoglycemia are common in salicylate poisoning and can worsen its CNS toxicity. [renalandurologynews.com]

  Glucose metabolism is also disturbed, leading usually to hypoglycemia, and there is no correspondence between serum glucose levels and cerebrospinal fluid glucose content. [symptoma.com]

• Hyponatremia

  Skip to main content General Medicine Michele Zell- Kanter Reviewed 06/2017 Respiratory alkalosis and metabolic acidosis: Secondary to inhibition of Krebs cycle and uncoupling of oxidative phosphorylation Dehydration, hyponatremia or hypernatremia, hypokalemia [5minuteconsult.com]

  These risk factors included ventricular arrhythmias/cardiac arrest, respiratory failure, age ≥30, Asian/Pacific Islander race, hyponatremia, diabetes mellitus, kidney failure, and neurological failure. [mdpi.com]

  Other manifestations of salicylate poisoning may include hyperthermia, acute renal failure, rhabdomyolysis, hematemesis, hypokalemia, hyponatremia, hypernatremia, hypocalcemia, thrombocytopenia, abnormal blood coagulation, disseminated intravascular coagulation [ic.steadyhealth.com]

   Acid-base disturbances (respiratory alkalosis, metabolic acidosis)  Dehydration  Electrolyte imbalance (hypokalemia, hyponatremia)  Altered glucose levels (elevated, normal, or low; CNS glucose concetrations may be low despite normal or even high [slideshare.net]

• Hypocapnia

  No significant difference of Pco(2) between the two groups was found, and hence no simple relationship exists between hypocapnia and the development of acidaemia in salicylate poisoning. [ncbi.nlm.nih.gov]

  On admission to the intensive care unit, his clinical condition was unchanged; arterial blood gas analysis revealed a metabolic acidosis, hypoxia and hypocapnia. [journals.lww.com]

  In experimental animals, lactate accumulation is minimal if the initial fall in PCO2 is prevented, but it gradually becomes more prominent as hypocapnia is allowed to occur [12]. [prep4usmle.com]

• Hypercapnia

  This may push patients into the Salicylate Hypercapnia-Acidosis Death Spiral (figure above). Indications for intubation might include: Frank loss of airway protection with active vomiting or ongoing seizures. [emcrit.org]

  The issue with intubation is the inability to keep up with the hyperventilation necessary to avoid hypercapnia and worsening acidosis, both of which can lead to cardiac arrest. [rebelem.com]

The indications for extracorporeal treatments such as hemodialysis are poorly defined. [ncbi.nlm.nih.gov]

See Treatment of salicylate poisoning Overview Contained in aspirin, sodium salicylate, methyl salicylate, oil of wintergreen Found in analgesic products (also in keratolytics and heat rubs) Chronic toxicity frequently missed diagnosis (up to 50%) Mortality [emedsa.org.au]

In this manner, patients with haemodynamic alterations, acute renal failure, severe neurological alterations, and/or severe metabolic acidosis that do not respond to conservative treatment should be started on extra-corporeal depuration treatment. [revistanefrologia.com]

Acidaemia is shown to be associated with impaired consciousness and to carry a grave prognosis. [ncbi.nlm.nih.gov]

The prognosis depends on prompt recognition and treatment. Delayed diagnosis results in increased morbidity and mortality, particularly in the elderly. [go.drugbank.com]

Prognosis  The prognosis in patients with acute salicylate poisoning is very good: the mortality rate is 1%, and the morbidity rate is 16%  The prognosis is worse in patients with chronic salicylate poisoning: the mortality rate is 25%, and the morbidity [slideshare.net]

Incidence/prevalence in the United States >11,100 single-substance ingestions of acetylsalicylic acid or ASA-combination products reported by poison control centers in 2011 22 deaths in 2011, none in children Occurs in children and adults at any age Etiology [unboundmedicine.com]

Regardless of etiology, this is very scary because these patients aren't defending their pH. Acidemia promotes entry of salicylate into the brain, worsening the intoxication. [emcrit.org]

If difficulty in achieving urinary alkalinization occurs, hypokalemia, volume depletion, or excretion of organic acids are possible etiologies. [mcgill.ca]

Etiology and Pathophysiology After ingestion, acetylsalicylic acid is rapidly converted to salicylic acid, its active moiety. Salicylic acid is readily absorbed in the stomach and small bowel. [emedicine.medscape.com]

Clinical Manifestations Salicylate toxicity should be suspected in any patient with fever, hyperventilation, seizures or coma of uncertain etiology.(5) It is not uncommon for salicylate poisoning to be misdiagnosed initially as diabetic ketoacidosis. [drplace.com]

[…] frequently missed diagnosis (up to 50%) Mortality/Morbidity - particularly high if untreated Appropriate treatment involves good supportive care, adequate re-hydration with urinary alkalisation and potassium replacement ACUTE TOXICITY CHRONIC TOXICITY Epidemiology [emedsa.org.au]

He has since completed further training in emergency medicine, clinical toxicology, clinical epidemiology and health professional education. [lifeinthefastlane.com]

[…] odsalicylates epidemiology salicylate (eg. aspirin (acetylsalicylic acid), teething gels) poisoning has steadily declined over the past 10-15 yrs in parallel with the declining use of aspirin particularly in children, and the use of child resistant packaging [ozemedicine.com]

PubMed CrossRef Google Scholar Epidemiology Sibert JR, Craft AW, Jackson RH. Child-resistant packaging and accidental child poisoning. Lancet 1977; ii: 289–90. CrossRef Google Scholar Pharmacokinetics Levy G. Clinical pharmacokinetics of aspirin. [link.springer.com]

Increased risk of ante- and intrapartum hemorrhage Epidemiology Incidence/prevalence in the United States >11,100 single-substance ingestions of acetylsalicylic acid or ASA-combination products reported by poison control centers in 2011 22 deaths in 2011 [unboundmedicine.com]

Pathophysiology of aspirin overdosage toxicity, with implications for management. Pediatrics 1978; 69: Suppl. 873–6. Google Scholar Pulmonary Oedema Bowers RE, Brigham KL, Owen PJ. [link.springer.com]

The above-mentioned triad has trapped many clinicians (including this writer) into a mistaken diagnosis of metabolic acidosis, when in reality it is respiratory alkalosis.The time-honored concept of salicylate pathophysiology discussed by the authors, [jamanetwork.com]

[…] ph stomach contents concurrent ingestions Aspirin (acetylsalicylate, pka 3.5) is quickly hydrolysed to salicylic acid (pka 3.0) which is further metabolised by enzymes that are readily saturable and thus in OD the metabolites are eliminated slowly; pathophysiology [ozemedicine.com]

[…] prevalence in the United States >11,100 single-substance ingestions of acetylsalicylic acid or ASA-combination products reported by poison control centers in 2011 22 deaths in 2011, none in children Occurs in children and adults at any age Etiology and Pathophysiology [unboundmedicine.com]

[…] so testy in here... off of merck's own website: " Pathophysiology Salicylates impair cellular respiration by uncoupling oxidative phosphorylation. [forums.studentdoctor.net]

If a case of salicylate poisoning is to be treated with hemodialysis, treatment with alkalinization should still be given without delay, in order to prevent acidemia and to promote elimination of as much salicylate as possible via the kidneys. [ncbi.nlm.nih.gov]

If ventilated, maintain alkalaemia (pH 7.45 – 7.5) to prevent redistribution of salicylate into the CNS. This may require setting the initial ventilator respiratory rate to the pre-intubation respiratory rate. [rch.org.au]

This can counter the salicylate anions within the tubules of the kidney and prevent spread into systemic circulation and ultimately prevent further crossing into the blood brain barrier. Salicylates can be removed via ECTR. [ukidney.com]

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3. Proudfoot AT. Toxicity of salicylates. Am J Med. 1983 Nov 14;75(5A):99-103.
4. Chalasani N, Roman J, Jurado RL. Systemic inflammatory response syndrome caused by chronic salicylate intoxication. South Med J. 1996 May;89(5):479-482.
5. Paul BN. Salicylate poisoning in the elderly: diagnostic pitfalls. J Am Geriatr Soc. 1972 Aug;20(8):387-390.
6. Yip L, Dart RC, Gabow PA. Concepts and controversies in salicylate toxicity. Emerg Med Clin North Am. 1994 May;12(2):351-364.
7. Chin RL, Olson KR, Dempsey D. Salicylate toxicity from ingestion and continued dermal absorption. Cal J Emerg Med. 2007 Feb;8(1):23-25.
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