POTD: Lithium Toxicity (Toxicology Thursday)

Lithium has been used to treat patients with bipolar disorder since the 1870s and is still widely used today, but has a very narrow therapeutic index! Toxicity can due to acute deliberate ingestions (18%) or, more commonly, chronic ingestions.

There are three categories of toxicity:

Acute: due to ingestion in a lithium naive patient, generally, an ingestion of > 7.5mg/kg of elemental lithium or 40 mg/kg of lithium carbonate. Prognosis tends to be better in acute poisoning because there is not sufficient time for distribution, which decreases the risk of neurotoxicity.

Acute-on-Chronic: an acute ingestion in a patient chronically on lithium

Chronic poisoning: occurs when chronic ingestion exceeds elimination. Highest risk of neurotoxicity because there is sufficient time to accumulate. Also the half life of lithium in chronic toxicity is prolonged due to underlying renal impairment.

Etiology 

Toxicity from chronic ingestions occur from impaired excretion due to:

• Reduced GFR (NSAIDs, ACE inhibitors)

• Increased renal tubular reabsorption (thiazides, spironolactone)

• Calcium channel blockers (unknown mechanism)

 Renal processing is similar to that of sodium – meaning if the kidneys find any reason to retain sodium, it will also retain lithium! A major example is dehydration.

Serum lithium levels may be high, but the patient may be asymptomatic because effects only occur when moved intracellularly.

Manifestations:

Neurological:

• Coarse tremor

• Hyperreflexia

• Nystagmus

• Ataxia

• Altered mental status

• Seizures/non-convulsive status epilepticus

Renal:

• Nephrogenic diabetes insipidus

• Sodium losing nephritis

• Nephrotic syndrome

Cardiovascular (usually mild)

• Wandering atrial pacemaker

• Sinus bradycardia

• ST-segment elevation

• Prolonged QT syndrome

• T-wave flattening

Gastrointestinal

• Nausea/vomiting

• Diarrhea

• Ileus

**this can worsen toxicity due to increased renal reabsorption of sodium and lithium

Endocrine

• Hypothyroidism (inhibition of hormone synthesis)

  • Also worsens lithium toxicity

Evaluation:

Labs including TFTs, renal function, calcium, serum lithium level, EKG, cardiac monitoring. Make sure the tube was not treated with lithiated heparin. Remember, the serum level does not reflect the intracellular level, so a patient may be asymptomatic with high levels and normal levels do not exclude toxicity!!

However, generally:

• Mild intoxication (1.5-2.5 mEq/L): nausea/vomiting, lethargy, tremor

• Moderate intoxication (2.5-3.5 mEq/L): confusion, agitation, delirium, tachycardia, hypertonia

• Severe intoxication (> 3.5 mEq/L): coma, seizures, hyperthermia, hypotension 

Treatment

Symptomatic treatment (e.g. benzos for seizures, magnesium for torsades).

IVF – the goal is to preserve GFR so that lithium does not get reabsorbed!

Activated charcoal does not work, but you may consider gastric lavage or whole-bowel irrigation for acute ingestions.

Hemodialysis for severe toxicity or renal failure

Patient should be admitted to a monitored setting. Admit to ICU for severe symptoms!! If patients are asymptomatic with a lithium level < 1.5 mEq/L, they may be discharged.

References:
https://emcrit.org/wp-content/uploads/2016/09/Lithium-Toxicity.pdf
https://www.ncbi.nlm.nih.gov/books/NBK499992/
https://www.uptodate.com/contents/lithium-poisoning

POTD: Alcoholic Ketoacidosis

Today’s topic will be for the people who used this 3-day weekend for a bender:

Alcohol Ketoacidosis (AKA)

Clinical Scenario:

Someone who has been on a bender and shows up to your ED after two days of vomiting, has a low bicarb, elevated anion gap, elevated lactate, urine ketones, and an elevated BHB level...probably has AKA. 

Background

• Alcoholic ketoacidosis (AKA) is a starvation state in an alcoholic or binge drinker

• Alcohol + No Food + Dehydration = AKA

• Most often associated with acute cessation of alcohol consumption after chronic alcohol abuse

• Can also be associated with first-time alcohol binge

• one of the causes of anion-gap metabolic acidosis 

Clinical Features

• episode of heavy drinking followed by vomiting and an acute decrease in alcohol consumption

• N/V, nonspecific abdominal pain

• can have associated gastritis or pancreatitis

• normal mental status, but if patient is altered, look for toxic alcohol ingestion, postictal states from withdrawal seizures, or occult head injury

• exam with acetone odor on breath

• tachypnea (Kussmaul respiration), tachycardia, and signs of dehydration

Pathophysiology

Nicotinamide adenine dinucleotide (NAD, or “Needs Additional Dextrose”) is depleted by ethanol metabolism, leading to inhibition of the Kreb’s cycle (or aerobic metabolism) in favor of ketone formation, depletion of glycogen stores, and suppression of insulin secretion  

Diagnosis

• low, normal, or slightly elevated glucose

• binge-drinking that ends in N/V and decreased intake

• wide AG metabolic acidosis, especially one without an alternative diagnosis

• (+) serum ketones

• can have associated hypophosphatemia, hyponatremia, and hypokalemia

Treatment

• Sugar and water!

• Glucose stimulates insulin production, which stops lipolysis and halts further ketone formation. Glucose also increases oxidation of NADH to NAD, thereby further stopping ketone production. 

• Start with 5% dextrose in NS. Once fluid and electrolyte losses are replaced, change fluids to 5% dextrose in 1/2 NS until oral intake is assured.

• Give 100 mg thiamine (facilitates Krebs cycle)

• Correct electrolytes

• Repeat Chem7 to see if bicarb improving. If it’s not, consider ethylene glycol or methanol poisoning. This is the time for fomepizole and a call to your local toxicologist or poison center!

Disposition

Discharge if tolerating PO!

References

https://emcrit.org/toxhound/aka-aka/

https://lifeinthefastlane.com/ccc/alcoholic-ketoacidosis/

Tintanelli’s

Cyanide Toxicity Distilled

Public service announcement: Don’t drink the Koolaid® (google Jonestown mass suicide)  Cyanide Toxicity

After a lecture today with our fantastic Maimo paramedics today, Dr. Lobel had insightful and nuanced feedback regarding treatment of cyanide toxicity and the current REMAC protocol.

Exposure: 

Typically, it is due to combustion of nitrogen containing polymers (think couches and kevlar)

Metallurgists, jewelers, and those working with electrolysis may have vats of liquid cyanide laying around; so, be wary. 

IV nitroprusside can also cause cyanide toxicity, even when administered in therapeutic doses. 

Also, apparently the hydrolysis of Amygdalin, which is present in cassava beans, peach pits, and apples seeds produces cyanide. So, depending on the quantity ingested, toxicity may become apparent. For the purposes of this POD, we will not go into the details of chronic CN toxicity. 

Mechanism: 

Cyanide inhibits: superoxide dismutase, carbonic anydrase, CYTOCHROME OXIDASE, succinic acid dehydrogenase.

Obviously, this causes inhibition of cellular metabolism, specifically the-critical-to-cellullar-survival Mitochondrion. 

Syptoms: 

Unfortunately they are non-specific, and overlap with CO toxicity. 

They can include:

Headache, anxiety, ams, lethargy

Cardiovascular collapse

Progressing to the seizure, coma, death pathway

Any unexplained lactic acidosis > 8 mmol/dL, CN toxicity should be considered. 

Treatment: 

As per Goldfrank’s Emergency Toxicology, 74% of confirmed cyanide cases did not receive an appropriate antidote. 

Past treatments included amyl nitrites (aka the “popper”), but this induces methemoglobinemia; therefore this should be avoided at all costs in a patient whose presumed exposure to cyanide gas could also be a concomitant carbon monoxide exposure. 

Hydroxycobalamin is probably the best go to if you only have one antidote available because when administered IV, it directly binds CN with high avidity. Therefore, when CN concentration in the plasma decreases, the CN inside the cells equilibrates down the gradient and shifts CN out of the cells, restoring the mitochondrial electron transport chain. 

This is where LOBEL’S ADVICE was really helpful:

Sodium thiosulfate is a useful adjunct because it recycles Cyano-met-Hgb to met-Hgb. It does not create more met-Hgb like the amyl-nitrites do. So, sodium thiosulfate can be safely administered along with cyanokit to create an additive effect. 

Of note, there are numerous case reports of patients being pulled from fires in cardiac arrest who achieve ROSC only after cyanokit has been administered. 

With that being said, I have a attached a case report from 1970 he gave me. It is a fantastic read and quite hilarious regarding the description of the patient’s tragic tattoos, so definitely give it 2 minutes.