Expert Commentary
This is a great summary of the causes, symptoms, work-up, and treatment of two relatively common medications that cause toxicity. In fact, these (along with carbamazepine) are levels I routinely recommend checking in patients with a history of bipolar disorder who come to the emergency department with altered mental status even if they do not report a history of being on these medications. That is because these three medications are very commonly used in the treatment of bipolar disorder and all have quite different treatment courses. In addition to the great summary above, below are some of my usual teaching points about these medications in overdose.
Let's tackle them separately as they are quite different toxicities.
First let's talk about lithium. In almost all medical texts, the tissue distribution of lithium is appropriately identified as being "complex." The easiest way I communicate that with patients, families, and medical learners is that in chronic therapy, lithium forms "stores" of drug in the body and intracellularly. Clinically that is relevant because after performing hemodialysis (HD) for lithium toxicity, you will reliably see an initial drop in lithium concentration followed by elevation approaching pre-dialysis levels if routine HD is performed. Although that could make one feel ambivalent about routinely recommending HD for lithium toxicity, there is suggestion of an alternate advantage of performing HD for lithium toxicity. Vodovar et al published a study in 2016 showing that patients who met their institutional criteria for HD and had HD performed had significantly fewer neurologic side effects from their toxicity than those who met criteria but did not have HD. So even though it did not impact usual measurements that we would expect HD to influence -- mortality and ICU length of stay -- its performance in this study seems to have been clinically beneficial.
The other big thing to discuss with lithium toxicity is that there are many known medication interactions with lithium. In short, any medications that impair renal function should not be used in someone on chronic lithium therapy. The main list of those medications includes NSAIDs, ACE inhibitors, ARBs, and thiazide diuretics.
Most of the unique aspects of valproate toxicity focus on its diagnosis and treatment. In the setting of acute intentional overdose of valproate, one of the most important things for emergency physicians to be aware of is that there can be a delay of peak valproic acid level. There are cases of patients presenting to an emergency department with stated valproate ingestion, initial negative level, then repeat level hours later being in the toxic range. So I recommend serial valproate levels until both down-trending and non-toxic. For treatment, there is a great summary of recommendations by the Extracorporeal Treatments in Poisoning Workgroup (EXTRIP) published online (https://www.extrip-workgroup.org/valproic-acid). In short, consult nephrology for dialysis if the patient is super sick.
As always, I recommend you consult your regional poison center when you are worried your patient is experiencing medication toxicity. But I hope this infographic and some of my comments helps you understand their recommendations.
References
Vodovar V, et al. Lithium poisoning in the intensive care unit: predictive factors of severity and indications for extracorporeal toxin removal to improve outcome. Clin Tox (Phila) 2016 Sep; 54(8): 615-23.
Lank P and Bryant S. "Valproic Acid" In: Wolfson A, Hendey G, Ling L, Rosen C, Schaider J, Cloutier R (eds.): Harwood-Nuss’ Clinical Practice of Emergency Medicine, 6th edition. Lippincott Williams & Wilkins 2014.
Patrick Lank, MD, MS
Assistant Professor of Emergency Medicine
Medical Toxicologist
Department of Emergency Medicine
How To Cite This Post
[Peer-Reviewed, Web Publication] Ko J, Dhake S. (2020, July 13). Mood Stabilizer Toxicities [NUEM Blog. Expert Commentary by Lank P. Retrieved from http://www.nuemblog.com/blog/mood-stabilizer-tox