Case 4 – Feeling Fatigued

Case #4: Feeling Fatigued
Author: Michael Gottlieb, MD
Peer Reviewer: Jenny Lu, MD

A 26 year old male with a past medical history of Bipolar Disorder is brought to the ED by family members after they noted he has had decreased memory and concentration over the past week. On further prompting, he also notes that he has felt increasingly fatigued and has not been eating or drinking much over the past two weeks. He is currently on medication for his Bipolar Disorder, but denies any additional medications (including herbal and over-the-counter medications), as well as any recent changes in his medication. The exam is significant only for a mild resting tremor of both hands.

Vitals: Temp: 98.0, HR: 62, BP: 110/72, RR: 8, O2 Sat: 98% on RA

What is the most likely etiology of this patient’s presentation?
There could be many causes for his current symptoms. However, in a young male with a history of psychiatric illness without other comorbidities, medication side effects and overdoses should be high on the differential. In this case, Lithium (resting tremor is seen in up to 65% of patients taking Lithium) is the most likely culprit. Other bipolar and antipsychotic medications are also possible, though less likely, and should be pursued.

Common precipitants to Lithium overdose include: Fever/Hyperthermia, Volume Depletion (as in this case), Infection, CHF, DM, Renal Failure, and Surgery. As Lithium is 95% eliminated by the kidneys, any causes leading to renal dysfunction or failure can precipitate Lithium toxicity. Dehydration causes reabsorption of both sodium and Lithium due to both molecules possessing a 1+ charge.

What other clinical symptoms might you expect to see with this patient?
CNS: Resting hand tremor, Fatigue, Decreased memory, Decreased concentration, Dysphoria, Ataxia, Dysarthria, Seizure, Coma
HEENT: Eye burning/tearing
CV: Bradycardia, PR and QT prolongation, ST and T wave changes.
Pulm: Respiratory Failure
GI: Anorexia, N/V, Diarrhea, Abdominal pain
GU: Polyuria, CKD, Nephrogenic DI, Inhibition of ADH
Endocrine: HYPOthyroidism, HYPERparathyroidism, Weight gain, Elevated blood glucose
Skin: Rashes
What is the initial treatment for this patient?
This patient requires volume replacement and monitoring. For less severe toxicity, consider giving sodium polystyrene sulfonate as a cation exchanger (similar to its use for elevated potassium). For more severe case, consider hemodialysis.

If the patient develops seizures, treat with benzodiazepines, followed by phenobarbital. Avoid Phenytoin, as it decreases lithium excretion and is often ineffective in controlling Lithium-induced seizures.

Is this medication dialyzable?
Lithium is a low weight molecule with a small Volume of distribution (Vd), poor protein binding, and high water solubility, making it a highly dialyzable drug.

Dialyzable drug criteria:
-Small Vd
-Poor protein binding
-Highly water soluble
-Low molecular weight

What laboratory error can cause a falsely elevated level of this medication?
Serum Lithium levels may be falsely elevated by up to 4 mEq/L if collected in a Green-Top Lithium-Heparin tube.
What is the disposition for these patients?
Monitor the patient for six hours after arrival. If the patient is still symptomatic, Serum Lithium level >1.5mEq/L, or acutely ingested ANY sustained-release preparation, he should be admitted.


Boltan DD, Fenves AZ. Effectiveness of normal saline diuresis in treating lithium overdose. Proc (Bayl Univ Med Cent). 2008 Jul;21(3):261-3.

Ghannoum M, Lavergne V, Yue CS, et al. Successful treatment of lithium toxicity with sodium polystyrene sulfonate: a retrospective cohort study. Clin Toxicol (Phila). 2010 Jan;48(1):34-41.

Groleau G. Lithium toxicity. Emerg Med Clin North Am. 1994 May;12(2):511-31.

Okusa MD, Crystal LJ. Clinical manifestations and management of acute lithium intoxication. Am J Med. 1994 Oct;97(4):383-9.

Wills BK, Mycyk MB, Mazor S, et al. Factitious lithium toxicity secondary to lithium heparin-containing blood tubes. J Med Toxicol. 2006 Jun;2(2):61-3.

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