View source for Salicylate toxicity

==Background==
*Fatal dose: 
**~10-30g by adult 
**~3g by child 

===Salicylate Sources===
*[[Aspirin]]
*Oil of Wintergreen
**Oil of Wintergreen is very concentrated - 5mL contains equivalent of 7.5g of aspirin.<ref>[https://online.epocrates.com/u/29311129/Salicylate+poisoning Epocrates - Salicylate Poisoning] Accessed 06/20/15.</ref>
*[[Bismuth subsalicylate|Pepto-Bismol]]
*Wart removers
*[[Bismuth subsalicylate|Maalox]]
*Alka-Seltzer

===Pathophysiology===
''Uncouples oxidative phosphorylation → increased metabolic rate and hyperthermia''
*As level rises, switches from hepatic to renal clearance (slower) 
*[[Nausea/vomiting]]
**Stimulates chemoreceptor trigger zone
**May cause metabolic alkalosis (contraction alkalosis)
*Respiratory alkalosis
**Activates respiratory center of medulla 
**If have respiratory acidosis, consider: pulmonary edema, co-ingestion of respiratory depressant or fatigue
**Leads to compensatory alkaluria: urinary excretion of potassium and sodium bicarb
*[[Metabolic Acidosis|Anion gap metabolic acidosis]]
**Interferes with cellular metabolism 
**Normal AG does not exclude ASA toxicity in patient with an unknown ingestion (mixed picture)
*[[Hyperthermia]]
**Uncouples oxidative phosphorylation
**As pH drops more ASA is uncharged; able to cross BBB
*[[Altered mental status]] 
**Direct toxicity of salicylate species in the CNS 
**Cerebral edema 
**Neuroglycopenia 
***Salicylate toxicity increases CNS utilization of glucose, serum glucose levels may not reflect CNS levels. 
*[[Pulmonary edema]] 
**Usually occurs in elderly 
**Due to increased pulmonary vascular permeability
*[[Fetal Effects in pregnancy]]
**Increased fetal morbidity and mortality
**Un-ionized salicylate cross the placenta due to higher fetal pH, where it becomes ionized and accumulates in the fetus
**Due to fetal inability to hyperventilate leads to worsening acidosis 
**There can be displacement of bilirubin from protein binding sites allowing it  to cross the blood brain barrier, which can lead to kernicterus.
**Due to inhibition of prostaglandin synthesis, can lead to premature closure of the ductus arteriosus

==Clinical Features==
===Mild (<150mg/kg)===
*[[Tinnitus]]
**Tinnitus is early sign - providers used to dose ASA to onset of tinnitus.
*Hearing loss
*[[Dizziness]]	
*[[Nausea and vomiting]]
**Common with acute toxicity

===Moderate (150-300mg/kg)===
*[[Tachypnea]]	
*[[Hyperpyrexia]]	
*[[Diaphoresis]]
*[[Ataxia]]	
*[[Anxiety]]	

===Severe (>300mg/kg)===
*[[Altered mental status]]
*[[Seizure]]
*[[Coma]]
*Cerebral edema
*Acute lung injury
*[[Nausea and vomiting]]
*[[Acute renal failure]]
*Cardiac [[arrhythmias]]
*[[Shock]]

===Chronic Toxicity===
*Usually neurologic abnormalities, especially in elderly
**[[Agitation]]
**Paranoia
**Memory deficits
**[[Confusion]]
**Stupor
*Hyperventilation
*[[Tremor]]
*[[Papilledema]]
*Higher morbidity ([[pulmonary edema]], [[seizures]], [[renal failure]]) and mortality rate compared with acute toxicity

==Differential Diagnosis==
{{Anion gap metabolic acidosis}}

==Evaluation==
===Work-Up===
*[[ASA]] level
*Acetaminophen level (possible co-ingestant)
*Metabolic panel
**Renal failure prevents ASA clearance
**Hyperglycemia in periphery (CSF will have low glucose due to CNS hypermetabolic state)
**Hypokalemia requires aggressive repletion - this differentiates from [[DKA]] which tends to have hyperkalemia or normokalemia at initial presentation
***Urinary alkalinization inhibited by excretion of H+ in order to reabsorb K+
*Mag and phos
*[[Urine toxicology screen]]
*[[Urinalysis]]
*VBG
*CBC
*PTT, PT/INR
*LFTs
*[[ECG]]
*Chest and abdominal radiographs

===Evaluation===
*Triple-mixed acid-base disturbance
**Respiratory alkalosis (earliest sign), AG metabolic acidosis, metabolic (contraction) alkalosis 
**Only other entity that produces this pattern is sepsis
*Elevated ASA level
**Obtain levels q1-2hr until levels decline and patient's clinical status stabilizes
**May be deceptively low early after ingestion and with chronic toxicity

===Levels===
*Therapeutic: 10-30mg/dL 
*Toxicity: >40-50mg/dL 
*Rapidly absorbed - measurable levels in 30 minutes
*Peak occurs ~6hr after absorption (up to 60hr if enteric-coated or extended release)

;Unit Conversion: 100mg/dL = 1000mg/L = 7.24 mmol/L

==Management==
===Airway===
*Avoid intubation unless absolutely necessary! 
**Very difficult to achieve adequate minute ventilation on vent
***Inadequate minute ventilation → ↑ respiratory acidosis → ↑ ASA crossing BBB
***While on ventilator, adjust RR to maintain goal serum pH 7.5 - 7.59 
**Indications for intubation: hypoxemia or hypoventilation 
**Give [[sodium bicarbonate]] 50-100 meq prior to intubating

===Breathing===
*Acute lung injury may lead to high O2 requirements

===Circulation===
*[[Hypotension]] is common due to systemic vasodilation 
*IVF +/- K+ (if no cerebral edema, no pulmonary edema)
**If these are present consider pressors

===Decontamination===
*[[Charcoal]] 1g/kg up to 50g PO 
**Effectively absorbs ASA 
**Give multiple doses if tolerated 
***25g PO q2hr x 3 doses '''OR''' 50g q4hr x 2 doses after initial dose
*[[Whole-bowel irrigation]]
**Consider for ingestion of large amount of enteric-coated or extended-release forms

===Glucose===
*Give [[dextrose|D50]] to altered patients regardless of serum glucose concentration 
*Except for fluids used for initial resuscitation, all IVF should be D5W
**ASA toxicity impairs glucose metabolism

===Alkalinization of plasma and urine===
*Not a substitute for dialysis in severe salicylism
*Continuous IV infusion of [[sodium bicarbonate]] is indicated even in the presence of mild alkalemia from the early respiratory alkalosis per 2013 ACMT guidelines
*Alkalemia from respiratory alkalosis is NOT a contraindication to NaHCO3 treatment
*Mechanism
**Traps ASA in blood and in renal tubules 
***Increases elimination; prevents diffusion across BBB 
*Indications
**ASA>35 or suspect serious toxicity 
*Goals
**Blood pH goal: = >7.5, <7.6 
**Urine pH goal: 7.5-8 
*Monitor serum electrolytes (to include potassium and magnesium) q2-4hrs during urine alkalinization<ref>Waseem M et al. Salicylate Toxicity. eMedicine. Dec 5, 2015. http://emedicine.medscape.com/article/1009987-workup.</ref>
**HCO3 will drive potassium into cells during drip
**Ensure replacement of magnesium and potassium, as urine will not alkalinize otherwise
*Dosing
**NaHCO3 1-2mEq/kg IV bolus; then 3amp bicarb in 1L D5W at 2-3mL/kg/hr
***Maintain urine pH >7.5
 
*Bolus during intubation
**If intubation is required, consider administration of sodium bicarbonate by IV bolus at the time of intubation to maintain a blood pH of 7.45-7.5 over the next 30 minutes

===Dialysis===
Indicated for: 
*[[Altered mental status]] 
*[[Seizure]] 
*[[Pulmonary edema]] 
*[[Coagulopathy]]
*Inability to tolerate volume load from bicarb drip (e.g. [[CHF]])
*New [[hypoxemia]]
*pH ≤7.20
*High ASA levels<ref>Juurlink DN, et al. Extracorporeal treatment for salicylate poisoning: Systematic review and recommendations from the EXTRIP workgroup.Ann Emerg Med. 2015; 66 (2):165-81.
.</ref>
**Initial levels
***>7.2 mmol/L (100mg/dL)
***>6.5 mmol/L (90mg/dL) in the setting of AKI
**After standard therapy
***>6.5 mmol/L (90mg/dL)
***>5.8 mmol/L (80mg/dL) in the setting of AKI

==Disposition==
*Admit all patients who have ingested enteric-coated or extended-release preprarations

==See Also==
*[[Toxicology (Main)]]
*[[General Psych Workup]] 
*[[Acetaminophen (Tylenol)]] 
*[[Antidotes]]
*[[Aspirin]]

==References==
<references/>

[[Category:Toxicology]]